Dottorato di Ricerca in Scienze delle Attività Motorie [619659]
Dottorato di Ricerca in Scienze delle Attività Motorie
XXII ciclo
Coordinatore: Prof. Giovanni Zummo
Dipartimento di Biom edicina Sperimentale e Neuroscienze Cliniche
Triennio 2008 -2010
“CLINICAL AND EXPERIMENTAL STUDY OF
PERIPHERAL NERVE REGENERATION ”
Tesi di Dottorato di :
Dr Bogdan Caraban
Tutor: Chiar.mo Prof. Giovanni Peri
Settore scientifico -disciplinare
BIO/16 – Anatomia Umana
Clinical and experimental study of peripheral nerve regeneration
2
CCOONNTTEENNTTSS
GENERAL PART ………………………….. ………………………….. …………………….. 6
INTRODUCTION ………………………….. ………………………….. …………………….. 7
BIOLOGY OF NERVE REPAIR A ND REGENERATION MORPHOLOGY .. 9
NERVE PHYSIOLOGY ………………………….. ………………………….. ………….. 16
CLASSIFICATION OF NERVE INJURY ………………………….. ……………….. 20
RESPONSE TO INJURY ………………………….. ………………………….. ……….. 23
Ventral Cell Body ………………………….. ………………………….. ……………….. 23
Proximal Nerve Stump ………………………….. ………………………….. ………… 24
The Distal Nerve Stump ………………………….. ………………………….. ………. 25
FACTORS INVOLVED IN NERVE HEALING ………………………….. ………… 28
DIAGNOSIS AND RECOGNITION OF NERVE INJ URIES ………………….. 29
Electrophysiologic Testing ………………………….. ………………………….. …… 30
TREATMENT OF PERIPHERAL NERVE INJURIES ………………………….. . 33
Nerve Repair ………………………….. ………………………….. ……………………… 34
Sutureless Nerve Repair ………………………….. ………………………….. ……… 36
Fascicle -Matching Techniques ………………………….. …………………………. 36
Results of Nerve Repair ………………………….. ………………………….. ………. 37
Nerve Grafting ………………………….. ………………………….. …………………… 38
Nerve Grafting Techniques ………………………….. ………………………….. ….. 39
Graft Material ………………………….. ………………………….. …………………….. 40
Nerve Lesions in Continuity ………………………….. ………………………….. …. 42
Aftercare and Rehabilitation ………………………….. ………………………….. … 43
Clinical and experimental study of peripheral nerve regeneration
3 Sensory Reeducation ………………………….. ………………………….. …………. 44
UPPER LIMB INNERVATION ………………………….. ………………………….. …. 46
Median nerve ………………………….. ………………………….. …………………….. 46
Ulnar nerve ………………………….. ………………………….. ……………………….. 48
Radial nerve ………………………….. ………………………….. ………………………. 50
PERSONAL CONTRIBUTIONS ………………………….. ………………………….. . 52
MATHERIAL AND METHODS ………………………….. ………………………….. … 53
Alternative methods for nerve repair ………………………….. ………………….. 53
Topograph y of peripheral nerves (median nerve, ulnar nerve, radial
nerve, sciatic nerve) – anatomic study on cadavers …………………………. 54
Clinical experience in peripheral nerve repair (FLOREASCA PLASTIC
SURGERY DEPART MENT BUCHAREST, CONSTANTA PLASTIC
SURGERY DEPARTMENT) – retrospective and prospective study …… 55
TOPOGRAPHY OF PERIPHERAL NERVES (MEDIAN NERVE, ULNAR
NERVE, RADIAL NERVE) – ANATOMIC STUDY ON CA DAVERS ………. 57
ALTERNATIVE METHODS FOR NERVE REPAIR ………………………….. … 65
Nerve autografts and allografts ………………………….. …………………………. 65
Use of fibrin glue in nerve repair ………………………….. ……………………….. 66
End to side neurorrhaphy ………………………….. ………………………….. ……. 67
Nerve repair using silicone tube ………………………….. ……………………….. 69
Nerve repair using chopped nerve around the suture ………………………. 73
CLINICAL EXPERIENCE IN PERIPHERAL NERVE REPAIR
(FLOREASCA PLASTIC SURGERY DEP ARTMENT BUCHAREST,
CONSTANTA PLASTIC SURGERY DEPARTMENT) – RETROSPECTIVE
AND PROSPECTIVE STUDY ………………………….. ………………………….. …. 78
Total number of patients ………………………….. ………………………….. ……… 78
Distribution over years ………………………….. ………………………….. ………… 79
Clinical and experimental study of peripheral nerve regeneration
4 Sex ratio ………………………….. ………………………….. ………………………….. .. 80
Distribution over age ………………………….. ………………………….. …………… 82
Smoking ………………………….. ………………………….. ………………………….. .. 84
Alcohol consumption ………………………….. ………………………….. …………… 86
Affected upper limb ………………………….. ………………………….. …………….. 88
Affected nerve ………………………….. ………………………….. ……………………. 89
Accident location ………………………….. ………………………….. ………………… 91
Type of anaesthesia ………………………….. ………………………….. …………… 92
Time of re pair ………………………….. ………………………….. …………………….. 94
Surgical procedure ………………………….. ………………………….. ……………… 95
Hospitalization period ………………………….. ………………………….. …………. 98
DISCUSS IONS ………………………….. ………………………….. ……………………. 111
CONCLUSIONS ………………………….. ………………………….. ………………….. 114
BIBLIOGRAPHY ………………………….. ………………………….. ………………….. 117
Clinical and experimental study of peripheral nerve regeneration
5
I would like to thank my family, Profe ssors
and friends from Palermo Faculty of
Medicine, Professors from Constanta Faculty
of Medicine who made this study possible .
Clinical and experimental study of peripheral nerve regeneration
6
GGEENNEERRAALL PPAARRTT
Clinical and experimental study of peripheral nerve regeneration
7
IINNTTRROODDUUCCTTIIOONN
Surgical repair of peripheral nerve injuries is not a new concept.
Reports o f successful peripheral nerve repair appeared in the literature as
early as 1836. Additional reports of successful case management
punctuated the 19th century. The first controlled study of experimental
injury and subsequent repair was performed in dogs by Howell and Huber
in 1893. This was followed by a similar study performed by Sherren in
1908.
Interest in advancement of knowledge in the area of peripheral nerve
injury was fostered by World War I. Management of extremity wounds
included recognition of th e importance of restoration of nerve function as
part of the process of reconstructive surgery. Numerous reports of
peripheral nerve repair resulted from the experiences of this war. Very few
of the techniques described were compatible with our present
understanding of nerve biology and regeneration after injury.
Working independently, Babcock and Bunnell proposed standardized
surgical techniques for peripheral repair. These principles encompassed
management of injured nerve tissue, surgical techniques for repair of the
injury, and postoperative management. Much of the information presented
in these reports forms the basis for operative management today. It was
recognized that not all nerve injuries were amenable to direct end -to-end
repair. Many injuries r esulted in loss of nerve tissue and thus the formation
of nerve gaps. To restore function after injury, the possibility of nerve tissue
grafting was explored. Nerve grafting was first reported by Philipeaux and
Vulpian in 1870. The first human allograft wa s reported in 1878 by Albert.
Sherren wrote of his experiences with nerve grafting in 1906. Huber
described autologous nerve grafting in the dog with good results as early
as 1920. Grafting gained popularity in 1932 with the work of Ballance and
Duel. Bunn ell and Boyes reported on the use of digital nerve autografts in
1937. No uniform success was reported by these authors. Alternate
Clinical and experimental study of peripheral nerve regeneration
8 experimental methods for lengthening nerve stumps centered around
mobilization and transposition of existing nerve tissue. It was recognized
that regardless of technique used, excessive tension at the suture line
would increase the probability of clinical failure.It was observed at this time
that further advancement in the management of peripheral nerve injuries
could be a produ ct only of greater understanding in basic biology of
peripheral nerves. Research in this area intensified during the 1930s and
was stimulated by the anticipation of an upcoming global conflict. Much
research performed during this time provided a basis for our current
understanding of nerve degeneration, regeneration, and healing of surgical
repair.
The last several decades have evidenced refinement in basic
principles of nerve injury and repair. Based on an improved understanding
of basic nerve biology, adv ances have been made in surgical repair and
management. Continuous research in the area of suture material and
biologic implants has contributed to increased clinical success in the
management of peripheral nerve injuries. Use of the operating microscope
has contributed to the advancement in reconstructive techniques. Suturing
of individual nerve bundles and alternate techniques for macroscopic nerve
repair are an outgrowth of this technology.
An investigation into technology and basic biologic principles h as
accompanied the study of nerve grafting techniques.
Research in autografting, allografting, and heterografting techniques
has helped to provide answers that add to our knowledge of the factors
that Contribute to the success or failure of grafting techn iques. Ongoing
research will provide answers to questions concerning the relationship of
immunologic response to allografting techniques.
Finally, the application of alternate reconstructive techniques is
under study. Transposition of nerve trunks may help to restore activity to
denervated musculoskeletal areas. Direct implantation of nerve stumps into
muscle tissue resulted in return of motor function. Both of these topics are
current areas of research in the quest for answers to
questions related to basi c biology and clinical restoration of peripheral
nerve function.
Clinical and experimental study of peripheral nerve regeneration
9
BBIIOOLLOOGGYY OOFF NNEERRVVEE RREEPPAAIIRR AANNDD
RREEGGEENNEERRAATTIIOONN MMOORRPPHHOOLLOOGGYY
The basic subunit of any peripheral nerve is the axon. The axon is an
extension of the nerve cell body. Histologically, the axon may be seen as
several distinct components. The center of each axon is composed of
axoplasm, which is the cytoplasmic extension of the nerve cell body. As will
be described below, axoplasm comprises several physiologically distinct
zones that aid in transport of nutrients and essential biochemical
components from the nerve cell body to the terminal axon and
neuromuscular terminals. The cell membrane surrounds the axoplasm and
is referred to as the axolemma. Surrounding this axoplasmic unit is the
Schwann cell. The Schwann cell may invest one or more axoplasmic units.
A myelinated nerve has a Schwann cell and associated structures
surrounding one axoplasmic unit (1 u – 15 u diameter).
The plasma membrane of the Schwann cell forms a lamellar spiral
around the axopla sm. The myelin sheath is a double spiral of lipoprotein
that is contiguous to the plasma membrane of the body of the Schwann
cell. The formation of myelin sheath occurs during development of the
Schwann cell and is a product of cytoplasmic extrusion from t he lamellae.
Each Schwann cell and its associated myelin encase a histologically
distinct zone. This area is referred to as an internode zone. Gaps appear
between two internodes and are referred to as nodes of Ranvier.
Branching of axons always occurs at this junction.
Unmyelinated nerves are not as well organized histologically.
Multiple small -diameter nerve fibers (0.2u -2.0u) are invested by
invaginations or pseudopodia of a Schwann cell. Evidence for a feedback
mechanism from the axon to regulate the pr oduction of myelin by the
Schwann cells has been documented experimentally.
Clinical and experimental study of peripheral nerve regeneration
10
Fig. no. 1 – Neuronal structure
In regeneration after injury, the ax on determines the degree and
amount of myelin that the Schwann cell will produce.Enveloping the
Schwann cell -axon unit is the basement membrane. This structure serves
as a histologic demarcation between the neural and connective tissue
elements of the peri pheral nerve. Immediately adjacent to the basement
membrane is the endoneurium. The endoneurium is composed of a
fibrocytic stroma of a double layer of collagen, fibroblasts, and vascular
components. It forms a tubular structure that surrounds the axon uni t. In
instances of injury, it does not degenerate as will axon components. Axons
and associated endoneurium form aggregates that are referred to as nerve
bundles, fascicles, or funiculi. A funiculus is enclosed by a collagenous
envelope of larger diameter termed the perineurium.
The perineurium consists of 7 to 15 lamellae of fibrous connective
tissue compressed into a tubular arrangement. The inner surface of the
perineurium is lined with mesothelial cells. Within the funiculus,
intrafunicular septae sepa rate individual axon units. The function of these
septae is not fully understood. The perineurium acts both as a diffusion
barrier and as a lattice -work for vascular beds. Enclosing the bundles of
funiculi is the outer covering of the nerve, the epineuriu m, which is a loose
network of collagen, elastin, and fibrocytes. Much of the ability of the
Clinical and experimental study of peripheral nerve regeneration
11 peripheral nerve to undergo elastic deformation without rupture can be
attributed to the tensile strength and elastic properties of the epineurium.
Funiculi are no t arranged in simple uninterrupted strands along the
course of a peripheral nerve. Frequent divisions and fusion with other
funiculi form numerous plexuses along the course of the nerve tank.
Redistribution is active along the entire length of the nerve bu t is
particularly prominent in the proximal portion of the nerve trunk. Two types
of funiculi are incorporated into every peripheral nerve. Simple funiculi are
those that are composed of fibers that serve solely a particular muscle or
cutaneous area. Compo und funiculi are composed of axons from several
sources in varying combinations and proportions. This feature allows for
the integration of various funicular components that distribute to innervate
specific anatomical regions. Several important considerati ons arise from
this plexus formation. Unless complete transection of a nerve trunk occurs,
partial function of the nerve may remain in cases of injury. Cross -sectional
morphometric studies have indicated that funicular anatomy changes every
0.5 mm to 15 mm . If neural tissue is lost in the course of traumatic wounds,
funicular continuity and alignment may not be possible at the time of
surgical repair
The vascular supply to peripheral nerves is by small segmental
nutrient arterioles that arborize into an ext ensive capillary network. The
nutrient arterioles arise at irregular intervals and, as they course toward the
peripheral nerve, are enclosed by a delicate connective tissue referred to
as mesoneurium. Mesoneurium is analogous in function and certain
anatom ical features to the mesentery of the small intestine. All vessels
entering the nerve do so at the mesoneurial border. After entry through the
epineurium, vascular arborization and alignment parallel to the funiculi are
noted. The second generation vessel aligns with the funiculus and courses
parallel to the epineurial vessels. Tertiary arborization proceeds to supply
individual axon units by means of an axon -capillary plexus. Multiple
anastomoses between branches of perineurial and axon vessels ensure
adequate collateral vascular supply in instances of segmental interruption.
Peripheral nerve blood flow appears to be unaffected by autoregulation.
Clinical and experimental study of peripheral nerve regeneration
12
Fig. no. 2 – Nerve structure
The origin of the axon is the nerve cell body. The histologic
components of the nerve cell body are the same as those of other cell
types, including a centrally placed nucleus and surround ing substructures.
The Golgi apparatus and mitochondria are histologically prominent within
the cell. Other characteristic cell inclusions are classified as Nissl bodies or
chromophil substance. Nissl bodies represent endoplasmic reticulum and
associated p olyribosomes. As will be discussed below, the role of these
cellular components was misunderstood and improperly interpreted in
much of the early work on the response of the cell body to injury.
Nerve cells may be classified as unipolar, bipolar, or multip olar. The
configuration of the nerve cell can be associated with the function within
the body. Sensory nerve cells of the dorsal root ganglion have a unipolar
configuration in which one process exits from the nerve cell body and then
divides into the dorsa l root and afferent sensory branches, which The
motor nerve is a sum of individual funiculi, which in turn are aggregates of
axon subunits. Each axon is enclosed in a lamellar whorl of condensed
lipoprotein classified as the Schwann cell. The intercellular zone is referred
to as the node of Ranvier. Note the anatomy of regional vascularization
Clinical and experimental study of peripheral nerve regeneration
13 entering through the mesoneurium The neuromuscular junction is directly
confluent with the sarcolemmal membrane. The postsynaptic invaginations
(clefts) are the site of action for the biochemical transmitter
acetylcholine.Bipolar nerve cells have one axon and one dendrite. They
are located in retinal tissue. Motor cells of the ventral horn of the spinal
cord are of the multipolar variety. One axon and multiple dendrite s
characterize this configuration. This cell type predominates in peripheral
motor nerves.
There is a histologically distinct zone in which peripheral nerve tissue
separates from the central nervous system. In this transitional area, the
axons abruptly cha nge envelope cell types from the central zone
oligodendrocyte to the peripheral zone Schwann cell. The axons are
enclosed by pia mater at this point, then subsequently pass through a dura
mater tunnel and become enclosed in perineurium. This transition occ urs in
both dorsal and ventral roots. Microscopic evaluation of this pia mater –
perineurial junction shows contiguous extension of the pia with the
perineurium in a smooth layer transition. Efferent terminal motor units are
of two types. Large diameter nerv e fibers (alpha motor neurons) innervate
the extrafusal muscle fibers. Alpha motor neurons subdivide at this juncture
to supply innervation to multiple muscle fibers. These muscle fibers
together with the terminal nerve branches are referred to as a motor unit.
Gamma motor units supply intrafusal muscle fibers of the muscle spindle.
Their activity is influenced by basal muscle tone and control of
sensory activity by the muscle spindle. Fine motor control is influenced by
the number of motor unit components . The higher the ratio of motor units to
muscle fibers, the finer control can be effected. This ratio is highest in
extraocular muscles and lowest in skeletal musculature.
The neuromuscular junction is the transition zone from peripheral
nerve to musculosk eletal systems. As the nerve approaches a
neuromuscular junction, the sheath composed of myelin and the Schwann
cell terminates. The cell membrane of the axon expands to form the
terminal neural junction in association with the sarcolemmal membrane. A
gap of 200 nm to 300 nm is noted on histologic evaluation and is referred
to as the synaptic cleft. At the terminal border of the nerve, synaptic
Clinical and experimental study of peripheral nerve regeneration
14 vesicles filled with acetylcholine are opposed by invaginations of the
sarcolemmal membrane classified as secondar y synaptic clefts. From this
area, release of acetylcholine and receptors for this chemical combine to
transmit neural impulses to the musculoskeletal system.
Sensory receptors are the peripheral component of myelinated and
unmyelinated afferent nerve fibe rs. These fibers, in turn, terminate in the
dorsal spinal roots. The sensory receptors arise from skin, muscle
spindles, joints, and other areas in which neural input is important for
maintenance of homeostasis. They transduce various forms of energy into
nerve impulses. These afferent impulses are integrated at the level of the
spinal segment or at higher levels and evoke a response to compensate for
the change in homeostasis. Of clinical importance in diagnosis of
peripheral nerve disorders is the class o f sensory receptors turned
nociceptors. This class provides sensory input for recognition of noxious
stimuli. In carnivores, a subcategory referred to as mechanonociceptors
predominates. These receptors are influenced more strongly by
mechanical damage tha n by thermal changes. When clinically evaluating
peripheral nerve disease or injury, evaluation of nerve deficits by
application of a noxious stimulus to nociceptors can aid in diagnosis of
specific nerve injury.
The topography of cutaneous innervation is well documented for the
hindlimb; however, some disagreement of zone boundaries for the forelimb
still exists. This can be related to overlap of cutaneous nerve function in
certain superficial regions. Cutaneous regions supplied by only one
cutaneous nerve are referred to as autonomous zones. Some areas have a
dual innervation from two or more peripheral nerve branches and are
called intermediate zones. Knowledge of regional distribution is essential
for correct diagnosis.
Mechanoreceptors predominate in jo ints and muscle spindle regions.
Joint receptors detect acceleration in any direction of that joint and thereby
provide input to compensate for gravitational influences. Muscle
mechanoreceptors from the muscle spindle fibers and Golgi tendon organ
at muscu lotendinous insertions represent sites of adherent input. These
Clinical and experimental study of peripheral nerve regeneration
15 receptors, along with alpha and gamma motor neurons and the spinal cord
segment, form the arcade for segmental reflex evaluation.
Clinical and experimental study of peripheral nerve regeneration
16
NNEERRVVEE PPHHYYSSIIOOLLOOGGYY
The axon consists of subunits that provi de the vital functions of
intracellular nutrition and transport of biochemical substances involved in
the regeneration process following nerve injury. The proteins that make up
this cytoskeleton are classified as microtubules, neurofilaments, and
microfila ments. Microtubules are protein structures that possess an axial
alignment with direction of the axion. Neurofilaments are of similar
morphology; however, the internal diameter of the tube is narrower.
Microfilaments have an actin component chemically rel ated to contractile
actin of skeletal muscle. Their orientation is both transverse and
longitudinal with the long axis of the peripheral nerve.
These internal elements are important for the two types of substance
transport within the nerve cell. By far the majority of proteosynthesis and
nutritive substances are produced in the nerve cell body. Early
experimental work in nerve injury and regeneration indicated that the
average growth of the nerve was I mm to 3 mm per day. From this work, it
was inferred tha t axoplasmic migration occurred in the direction from the
nerve cell body to the periphery; this migration was classified as
axoplasmic flow.This concept was accepted until certain observed
phenomena could not be explained by the prevailing theory.
Followi ng experimental constriction of peripheral nerves, swelling
proximal to the constriction site occurred earlier than anticipated by
calculated axoplasmic flow. Radioactive labeling of protein components
using amino acids and tritium revealed migration as ra pid as 410 mm per
day in sciatic nerves. The rapidity of transport and organization provided
the basis for recognition of a second type of motion, axonal transport. The
function of axonal transport is movement of neurotransmitter substances
and axolemmal r eplacement material from the nerve cell body to the
periphery of the nerve. However, it has been deduced that axonal transport
is not unidirectional. Retrograde as well as antegrade flow of materials can
Clinical and experimental study of peripheral nerve regeneration
17 occur in the microtubular network. This observation may aid in the
explanation of retrograde migration from the periphery of central nervous
system agents such as rabies, herpes viruses, and tetanus toxin. The
normal function of retrograde transport is the return of cell membranes to
the cell body for degra dation or resynthesis and return of a portion of
synaptic vesicles to the nerve cell body for recycling. The rate of retrograde
transport is one half to two thirds that of antegrade conduction.
Axonal transport occurs by means of the cytoskeleton network
described above. Although no definitive work has been done, it is
postulated that motion imparted by one of several mechanisms provides
the basis of propulsion down one microtubular or neurofilamentous track.
Tracks probably have polarity so that only unid irectional flow can occur.
The basis for propulsion is probably actin filaments arranged around the
tubulofilamentous network that provide peristaltic waves or plasma flow
changes to propel units up or down this network. Further work is needed to
elucidate the exact transport mechanism and the relationship, if any, to
maintenance or activity of the excitable neural membrane.
Nerve tissue has dynamic properties similar to any excitable
membrane. A peripheral nerve may be thought of as an electrical conduit i n
which impulses are conducted from a central terminal (light switch) to an
effector organ (light). The event that is produced by conduction of this
impulse is referred to as an action potential. An action potential can be
conducted only when the cell memb rane is in an excitable state. This is
achieved by development of concentration differences for sodium and
potassium ions across the cell membranes. Maintenance of this differential
by the sodiumpotassium pump within the cell membrane imparts an
electrical differential across the cell membrane of – 85 mV. The value,
referred to as a resting potential, remains in a stable state until a stimulus
sufficient to create threshold occurs. When the threshold value is reached,
activation of the cell membrane occurs.
Configurational changes in the membrane pore rearrange "gates" to
allow for sodium ion influx. The membrane then depolarizes and transmits
the length of the axon in either direction. This phenomenon is referred to as
the "all -or-nothing" principle and st ates that once depolarization begins at
Clinical and experimental study of peripheral nerve regeneration
18 any point on the nerve, the entire membrane is obligated to depolarize. The
rate of this propagation is referred to as nerve conduction velocity. Factors
commonly involved in the speed of conduction include fiber dia meter,
degree of myelination, and membrane temperature. The effect of these
factors on peripheral nerve conduction will be discussed below.
Repolarization always begins at the same point at which
depolarization occurred. Efflux of potassium ions from cytop lasm to cell
membrane surface allows for re -establishment of appropriate ionic barrier
charge. Potassium ion is then exchanged for sodium ion by the sodium –
potassium pump to reestablish baseline continuity of ion balance.
The velocity of depolarization dep ends upon the presence of
organized myelin structure in the nerve fiber. Myelinated nerves have
concentric layers of Schwann cell membranes interspersed by
sphingomyelin. As noted above, histologic gaps occur at intervals between
the Schwann cell units. Th ese gaps are classified as nodes of Ranvier and
constitute an important element in nerve impulse conduction. Schwann cell
units with associated myelin are analogous to electrical insulation. Owing
to its increased transmembrane potential, impulse conductio n does not
occur along the entire length of the nerve but only at the nodes of Ranvier.
The cell membrane in this area is especially permeable to ion exchange
and can aid in rapid impulse conduction. As an impulse travels along the
surface of the cell memb rane, its transmission occurs at the nodal junction
and jumps from node to node in a manner classified as saltatory
conduction. Because of the jumps in impulse transmission, velocity of
conduction in a myelinated axon is greater than in its unmyelinated
counterpart.
An additional benefit of saltatory conduction is the conservation of
energy for the axon, accomplishing conduction with less of fewer ions than
standard excitable tissue. This allows for more rapid repolarization with
minimal energy expenditure . Unmyelinated nerves have no organized
mechanism of saltatory conduction. Impulse propagation occurs in an
organized sequential manner involving the entire membrane of the axon.
Membrane depolarization is accompanied by an ion -exchange current
across the cell membrane surface. This flow of ion exchange is described
Clinical and experimental study of peripheral nerve regeneration
19 as an eddy current. Speed of depolarization of the cell membrane by eddy
currents is influenced by axon diameter. A larger cross -sectional diameter
of an unmyelinated nerve allows for a larger c urrent flow and faster local
excitation and results in a higher conduction
velocity.
If an electrical impulse is applied to a nerve trunk and an
oscilloscopic recording of this event is made, a characteristic wave form
will be seen. This wave form is a su mmary of individual nerve fiber types
and is termed a compound action potential. An analysis of this compound
potential shows several distinct subunit waveforms. The earliest wave
deflection reflects conduction of the largest -diameter myelinated nerve
fibers. These fibers are classified as type A fibers and include three
subcategories. Alpha waves represent the largest -diameter myelinated
motor fibers and sensory fibers from muscle spindles. Beta waves
represent sensory fibers from skin sensory receptors. G amma waves are
produced by gamma motor fibers arising from intrafusal muscle fibers of
the muscle spindles.
As the impulse reaches the synaptic junctions, acetylcholine is
liberated from storage vesicles, transverses the synaptic cleft, attaches to
recepto r sites on the secondary folds of the synaptic clefts, and initiates
endplate potential formation.
This potential, in turn, initiates sarcolemmal depolarization and
muscle contraction. After diffusion from the receptor site, acetylcholine is
degraded by t he enzyme acetylcholinesterase. The component substances
are then metabolized or recycled to form new acetylcholine.
Sensory conduction is initiated by peripheral receptors and is
conducted centrally to the dorsal spinal root. The impulse then initiates
reflex arcs in the segmental gray matter and may be transmitted for further
integration to the higher centers by internuncial neurons.
Clinical and experimental study of peripheral nerve regeneration
20
CCLLAASSSSIIFFIICCAATTIIOONN OOFF NNEERRVVEE IINNJJUURRYY
As interest in diagnosis and therapy of peripheral nerve injuries
increased, a need ar ose to standardize the description of types of injury
evaluated in clinical practice. The classification presented below is based
on indirect diagnostic methods that include history, physical examination,
including neurologic examination, and ancillary dia gnostic techniques as
represented by electrodiagnostics. The classification acts as a guideline for
clinical assessment and prognostic evaluation related to medical or
surgical management of the injury. The use of this classification can
correlate, in addi tion, changes in neural tissue related to the injury process.
Table no. 1 – Classification of nerve injuries
Severity Description Tinel
Sign Progress
Distally Recovery
Pattern Rate of
Recovery Surgery
First Neurapraxia Demyelination with restoration in weeks — Fast Complete Fast (days to
12 wk) None
Second Axonotmesis Disruption of axon with regeneration and full recovery + + Complete Slow (3
cm/mo) None
Third Disruption of axon and endoneurium causing disorganized
regeneration + + Varies* Slow (3
cm/mo) Varies
Fourth Disruption of axon, endoneurium, and perineurium, with
intact epineurium and no regeneration + — None None Yes
Fifth Neurotmesis Transection of the nerve + — None None Yes
Sixth Neuroma -in-
continuity Mixture of one or more of the a bove conditions Varies by fascicle, depending on injury
*Recovery is at least as good as nerve repair but varies from excellent to poor, depending on the degree of endoneurial scarr ing and the amount of sensory and
motor axonal misdirection within the inj ured fascicle.
The mildest form of nerve injury is classified as neuropraxia. An
acute insult to the peripheral nerve results in interruption of impulse
transmission. Clinical evaluation will show sensory and motor deficits in the
region that is innerva ted by the injured nerve. Partial function may be
noted, with an imbalance between degree of sensory and motor deficits
Clinical and experimental study of peripheral nerve regeneration
21 noted on examination. Evidence of neurogenic atrophy of muscle fibers is
usually not present. Histologic evaluation of tissue shows only minor
morphologic alterations that are of a reversible nature. It has been
proposed that microvascular alteration resulting in transient ischemia
produces this class of injury. Recovery is accomplished with conservative
therapy and occurs over a variable time period but is usually complete
within 21 days of injury. This time is faster than that expected by
regeneration following wallerian degeneration, as will be noted below.
If there is physical disruption of one or more axons without injury to
stromal ti ssue, the injury is described as axonotmesis This type of injury is
generally noted in conjunction with closed long -bone fractures in humans.
In this type of injury, the axoplasm and cell membranes are damaged;
however, the Schwann cell and connective tiss ue elements remain intact.
Clinical evaluation will reveal deficits related to the zones innervated by the
damaged axons. Loss of sensory and motor function will be dependent
upon the number and type of injured axons. After the 90th hour post injury,
no co nduction of electrical potentials past the site of injury will be seen.
Neurogenic atrophy of skeletal muscle will be evident in the injured
autonomous branch.
Neurotmesis refers to complete severance of the peripheral nerve
trunk. Sensory and motor inner vation to all autonomous branches of the
injured nerve is lost . Clinical and diagnostic evaluation will show complete
loss of clinical function of the nerve. Histologically, degeneration of all
axons occurs distal to the site of injury. Axons will also ma nifest
degenerative changes for one to two nodes of Ranvier proximal to the site
of injury. Except in rare cases, spontaneous recovery from lesions of this
class does not occur.As can be noted from the classifications of injuries
described above, certain t ypes of injuries border on more than one
category. In an attempt to improve and further define types of peripheral
nerve injury, an alternate classification by degree of injury was later
proposed. The advantage to this classification is that description of injury to
individual components of the nerve trunk can be accounted for more
accurately. A first -degree injury correlates with neuropraxia. A second –
degree injury is one in which only the axon is disrupted. A third -degree
Clinical and experimental study of peripheral nerve regeneration
22 injury involves the axon and asso ciated endoneurial tube while the nerve
funiculus remains intact. A fourth -degree injury disrupts axons,
endoneurium, and funiculi while the epineurial sheath remains intact. A
fifth-degree injury is evidenced by complete severance of the nerve trunk.
Although not all aspects of the classification systems can be
appreciated on a clinical basis, certain parallels between clinical
presentation of injury and severity of peripheral nerve damage may be
drawn. In cases of blunt compression injury to soft tissue, it is likely that
neuropraxia results from temporary peripheral nerve compression. This
can produce temporary ischemia and loss of neural conduction. A mild
form of injury of this class would be loss of sensation after steady pressure
has been placed on a nerve trunk for a short period of time. Axonotmesis,
or secondand third -degree peripheral nerve injuries, may be the sequel of
closed long -bone fracture and traction injury to peripheral nerves from
altered orthopaedic biomechanics. Neurotmesis, or fourth – and fifth -degree
injury, may be associated with open long -bone fractures, penetrating
wounds, and altered biomechanics resulting from trauma.
Clinical and experimental study of peripheral nerve regeneration
23
RREESSPPOONNSSEE TTOO IINNJJUURRYY
Injury to a peripheral nerve triggers an initiation of a response that
incorporates a s equence of biochemical and morphologic alterations. Each
component of the injured nerve reacts in an individual manner to the injury
process. The effects of injury may be categorized into those that involve :
(1) the spinal cord, particularly the ventral cell b ody;
(2) the proximal nerve stump;
(3) the distal nerve stump and its associated end -organs.
VVeennttrraall CCeellll BBooddyy
After injury, sequential histologic evaluation of the ventral cell body
shows marked changes in response to injury. The size of the nerve cell
body en larges for 10 to 20 days after injury. This "hypertrophy" is visible for
the course of the regenerative process, and "atrophy" back to normal size
occurs once healing is complete. It was once accepted that this change in
cell body size, along with changes in staining characteristics described
below, represented nuclear degeneration of the injured nerve cell. Recent
observations with electron microscopy, along with an improved
understanding of nerve repair biology, now suggest that the alterations
noted repr esent early induction of metabolic processes required for nerve
regeneration.
The degree of cellular change is dependent upon the level of the
lesion in relation to the cell body. If the level of the injury is close to the
nerve cell body, proportionally more axoplasm is lost, and greater
biosynthesis must occur for regeneration to result. A proximal injury may
exceed the biosynthetic capability of the cell, thereby causing failure of
regeneration. Distal nerve lesions do not activate the cell body to a hi gh
degree of biosynthesis. The nerve cell, therefore, is capable of limited
regenerative potential without initiating severe changes in cellular
metabolism.
Clinical and experimental study of peripheral nerve regeneration
24 PPrrooxxiimmaall NNeerrvvee SSttuummpp
If the nerve trunk has been severed, retraction of the stumps occurs
owing to elastic tissue contained within the epineurial sheath. Hemorrhage
and clot projection are evident immediately at the severed ends.
Intraneural swelling due to tissue edema and exudation of acid
mucopolysaccharides may be noted within one hour after injury. Acid
mucopolysaccharides have an affinity for water and an indirect affinity for
plasma, blood, and serum. The swelling and tissue constituents form a clot
that is evident for 7 to 10 days.
The extent of degeneration in the proximal stump is related to t he
etiology of injury. Sharp lacerations or surgical wounds produce minimal
proximal stump degeneration. Traction or jagged laceration injuries result
in extensive degeneration. In either case, within 24 to 72 hours,
neurofibrillar degeneration in a clean wound occurs for a minimum of two to
three nodes of Ranvier proximal to the point of injury. Loss of axoplasmic
components quickly follows during this time. The myelin sheath begins to
lose its defined layered appearance and blends into a homogenous
granul ar tissue that appears as a series of rings surrounding degenerating
axoplasm. These contorted lamellar rings, which form hollow luminal
structures, are classified as digestion chambers. Macrophage invasion
begins to digest and remove degenerated myelin fr om the damaged nerve
tissue. Schwann cells respond vigorously at this time and proliferate to
form dense cords along the axis of the now digested axoplasm. These
cords possess phagocytic properties and ingest clumps of degenerating
axon, myelin fragments, and other cellular debris. Mesenchymal cells
proliferate in response to the inflammatory process and initiate collagen
deposition at the end of the proximal stump. This, in conjunction with fibrin
remnants from the initial hemorrhage, may lead to formation of a neuroma.
Approximately 2 to 20 days after injury, axoplasmic regeneration
may begin. This event is associated with the increased biosynthetic
capabilities of the nerve cell body. Synthesis of new axoplasm is
transported by migration along the remaini ng viable axon to the site of
injury. The flow rate for this process is approximately 1 mm to 3 mm per
day and advances by the intracellular fibrillar network described above. At
Clinical and experimental study of peripheral nerve regeneration
25 the site of injury, cellular proliferation of Schwann cells has already
comme nced. The Schwann cell outgrowth attempts to connect the proximal
stump with the Schwann cell elements of the distal nerve stump. The
Schwann cell attempts to grow concurrently with the axoplasm, thus
providing a framework for axonal growth. If surgical re alignment or nerve
stump approximation does not occur, the migration axoplasm may form a
neuroma, a meshwork of organized clot elements, mainly fibrin strands,
that provides an errant scaffolding framework for axonal migration.
As the Schwann cells migrate distally, their pathway is deviated to
align with the random fibrin clot at the nerve stump. The regenerating
axons follow the Schwann tubules and continue the random growth
pattern. Axoplasm migration in this disorganized tissue produces
multifilamentous branching that attempts to seek the distal nerve stump.
Extraneural connective tissue may also produce ingrowth to the site
of injury and can additionally distort and block the path of axon migration.
In contrast, surgical repair of peripheral nerve inju ry permits smooth,
unbranched axoplasmic migration into the distal stump. It is hypothesized
that axoplasmic branching attempts to compensate for the neuroma
roadblock to ensure axonal migration into the distal stump.
TThhee DDiissttaall NNeerrvvee SSttuummpp
The entire dis tal stump undergoes a process of degeneration first
described by Waller and referred to as wallerian degeneration. Within 24 to
48 hours after injury, axon thickening is evident histologically. An increase
in acid phosphatase and nicotinamide adenine dinuc leotide (NAD)
diaphorase in surrounding myelin reflects increased metabolic activity.
Evidence of axoplasmic fragmentation and clumping is noted at this time.
Four to five days after injury, all axoplasm is absent, and myelin
degeneration and clumping occu r by a process similar to that described for
proximal stump degeneration. Tissue macrophage invasion is noted during
this period. The origin of the macrophage activity is thought to be
connective tissue histiocytes and converted monocytes from the peripher al
blood. This activity may last from 7 to 32 days after injury. After
Clinical and experimental study of peripheral nerve regeneration
26 macrophage and Schwann cell activity diminishes, only Schwann cells and
connective tissue remain. These diminish with time, and total atrophy of the
distal stump may occur 18 months aft er injury owing to the increased
intertubular deposition of collagen, which reduces the diameter of the
lumen of individual neural elements.
The proximal end of the distal stump deserves special note. The
axons in this region tend to enlarge and isolate f rom the other portions of
the degenerating nerve stump. This unit may survive for as long as 2
weeks prior to degeneration. As connective tissue elements proliferate in
the early degenerative phase, endoneural fibroblasts intertwine in this
isolated segmen t. This swelling is referred to as a glioma, schwannoma, or
distal neuroma. Its gross appearance is not as marked as the previously
described neuroma because it is composed solely of connective tissue
elements originating from perineurium, endoneurium, and pleomorphic
Schwann cells. With the passage of time, shrinkage of the glioma will occur
in conjunction with distal stump atrophy.
Regeneration of axons in the distal stump occurs at a rate of 1 mm to
3 mm per day. This rate is variable depending upon the zone in which
regeneration is occurring. Near the site of injury and at the motor endplate
region, growth is slower owing to external factors. More rapid regeneration
occurs in the body of the distal nerve stump. Extension of Schwann cell
and connective ti ssue elements provides a pathway for migration of
axoplasm filaments into the tubules of the distal stump. As regrowth of
axoplasm into the distal stump proceeds, myelination of the Schwann cell
envelope occurs in regions recently recannulated by axoplasmi c elements.
Marked enzymatic activity is present to aid in the myelination process. The
presence of myelin sheaths is evident 6 to 7 days after regeneration has
occurred in any zone Nodes of Ranvier appear after day 14 in the
regenerative process. Appositi on of myelin occurs for as long as one year
following the repair process.
It is important to recognize that even under the best of
circumstances, aberrant recannulation of the distal stump may occur.
Transposition of sensory and motor components in a mixed -function nerve
is a common sequel to injury. As the motor end -plate region is reached by
Clinical and experimental study of peripheral nerve regeneration
27 the advancing axoplasm, rapid division of the axoplasm occurs until a
myoneural junction is formed.
Clinical and experimental study of peripheral nerve regeneration
28
FFAACCTTOORRSS IINNVVOOLLVVEEDD IINN NNEERRVVEE HHEEAALLIINNGG
Numerous reports in the li terature attempt to assess various factors
that contribute to successful nerve healing. Factors may be described as
intrinsic, or those beyond control of the surgeon, and extrinsic, those in
which clinical management may influence return of function.
Intrinsic factors include species, age, state of tissue nutrition, time
since injury, type of injury, nerve or nerves involved,and level at which
injury occurred. This information can be gathered from history and physical
examination and may aid in prognostic e valuation. As has been discussed
earlier, the time since injury, level of injury, and type of injury relate to
factors concerned with nerve biology. Young patients heal more rapidly
and to a more complete recovery, probably related to increased
biosyntheti c capabilities already present and to a greater capacity for
adaptation. Tissue nutrition is important to meet anabolic requirements
related to the regenerative process.
Extrinsic factors relate to surgical and postoperative management of
nerve lesions. At tention to surgical technique and appropriate selection of
instrumentation and suture material can contribute to return of function.
Clinical and experimental study of peripheral nerve regeneration
29
DDIIAAGGNNOOSSIISS AANNDD RREECCOOGGNNIITTIIOONN OOFF NNEERRVVEE
IINNJJUURRIIEESS
A careful history regarding nerve injury provides important
information aid ing in treatment and in predicting outcome. Patient age and
mechanism of injury are well -known to affect outcome after nerve repair.
As part of the medical history, a careful assessment of comorbid conditions
that detrimentally affect the peripheral nervou s system is important.
Table no. 2: Selected Muscle Evaluation for Diagnosis of Motor Nerve
Injury
I. Median nerve: intrinsic
A. Thumb -palmar abduction (abductor pollicis brevis)
II. Median nerve: extrinsic
A. All flexor digitorum sublimi
B. Flexor profundus digitorum to index
C. Flexor pollicis longus
D. Flexor carpi radialis
III. Ulnar nerve: intrinsic
A. First dorsal interosseous muscle
B. Muscles of the hypothenar eminence
IV. Ulnar nerve: extrinsic
A. Flexor digitorum pro fundus, small finger
B. Flexor carpi ulnaris
V. Radial nerve: extrinsic
A. Wrist extension (extensor carpi radialis brevis and longus, extensor
carpi ulnaris)
B. Extension of fingers at metacarpophalangeal joint (extensor
digitorum communis, exte nsor indicis proprius, extensor digiti minimi)
A careful motor examination should indicate whether a specific
muscle is functioning and, if so, how well. Specific muscles are useful in
identifying selected peripheral nerve injuries. Since cross innervati on and
joint motion aided by several muscles are a source of potential confusion, a
Clinical and experimental study of peripheral nerve regeneration
30 working knowledge of the specific muscles that correlate to specific
peripheral nerve function is essential.
Sensory evaluation in the clinical setting requires patient co operation
and interpretation of various stimuli. There are only three objective tests of
sensation: the triketohydrindene hydrate (Ninhydrin) sweat test, the O'Riain
skin wrinkle test, and electrophysiologic testing. None of these is
particularly practical in the initial patient evaluation; therefore, tests that
require patient interpretation are most commonly used.
The most commonly used clinical tools are two -point discrimination
(2-PD) (both moving and static), Semmes -Weinstein monofilaments, and
vibrome ter testing. Initial evaluation of the nerve -injured patient should at
least include assessment of static 2 -PD in the digits and touch sensation in
the cutaneous distribution of potentially injured nerves. Crossover in
sensory territories is normal, and on ly selected areas will provide accurate
information concerning specific nerve injury
Table no. 3: Sensory Evaluation for Specific Peripheral Nerve Injury
I. Median nerve – Pulp of thumb and index finger
II. Palmar cutaneous branch of median nerve – Proximal palm over
thenar eminence
III. Ulnar nerve – Pulp of small finger
IV. Dorsal cutaneous branch of ulnar nerve – Dorsal ulnar surface of
hand
V. Radial nerve – Dorsal radial hand over first web space
VI. Digital nerve – Area of the distal p halangeal joint flexion crease
The available methods of sensory evaluation provide different and
specific information regarding reinnervation.
EElleeccttrroopphhyyssiioollooggiicc TTeessttiinngg
Electrodiagnostic testing is a useful adjunct to evaluation in patients
with nerve injury. It is rarely needed for initial diagnosis but may be helpful
Clinical and experimental study of peripheral nerve regeneration
31 in evaluation after repair and especially in assessing nerve lesions in
continuity. Electrodiagnostic testing includes somatosensory -evoked
potentials, intraoperative nerve -to-nerve stimu lation, nerve conduction
studies, and electromyography.
Nerve conduction studies provide a measure of the speed with which
a nerve carries information over a known distance. The time from which the
stimulus is initiated until it is recorded is called the l atency period. Since
time and distance are known, conduction velocity can be calculated.
Normal values have been established for both latency and nerve
conduction velocity (NCV) for specific nerves and specific locations. In
evaluating nerve injury, as opp osed to compression neuropathy,
determining the presence or absence of response is frequently more
important than learning the latency or NCV.
Fig. no. 3 – Electromyography
Electromyography is distinctly different from nerve conduction
studies and provides different information. A needle electrode is placed into
a specific muscle, and electrical activity is recorded both at rest and with
attempts at muscle contraction. Normal muscle will show a short burst of
insertional activity related to the local trauma of needle insertion. This burst
of activity is brief, and normal muscle at rest will rapidly become electrically
silent.
Clinical and experimental study of peripheral nerve regeneration
32
Abnormal insertional activity is seen in denervated muscle or in
muscle that is being reinnervated. Spontaneous depolarization in
denervated muscle produces fibrillation potentials and positive sharp
waves. These are descriptive terms identifying re cognizable patterns of
electrical activity, as recorded on an oscilloscope.
Electrical activity can also be recorded during active muscle
contraction. Contraction of fibers produces an M wave, indicating electrical
potential change in the muscle. As the fo rce of contraction continues,
multiple M waves are progressively created; these result in a recognizable
sequence called a recruitment pattern. Changes in M -wave amplitude or
recruitment pattern are present with neuropathy and can be helpful in
identifying denervated muscle or in following recovery.
Clinical and experimental study of peripheral nerve regeneration
33
TTRREEAATTMMEENNTT OOFF PPEERRIIPPHHEERRAALL NNEERRVVEE IINNJJUURRIIEESS
The majority of peripheral nerve injuries are best treated by a
thoughtful surgical reconstruction. However, nonoperative treatment is
indicated in several circumstan ces. The first of these is injury to a sensory
nerve innervating a noncritical area. In the digits, this would include the
ulnar border of the ring finger and possibly the middle finger. After
discussion with the patient concerning symptoms, functional nee ds, and
realistic outcomes, other digital sensory areas may occasionally be
considered noncritical.
Other injuries, such as those to the cutaneous nerves of the forearm,
may be treated nonoperatively if agreed on during careful discussion of
options with the patient. It is important to emphasize patient involvement in
the consideration of nonoperative treatment of peripheral nerve injury.
Decreased sensation in an area that might seem trivial to one patient may
be critical to another. In some situations (e g, after injury of the radial
sensory nerve), nerve repair may be indicated primarily to reduce neuroma
symptoms; in these cases, sensory return is a secondary goal.
Realistic expectations for recovery should be considered when
discussing operative versus nonoperative treatment. Patient age, level of
injury, mechanism of injury, and associated medical conditions all influence
outcome and, in certain cases, may make repair or grafting unreasonable.
Operative Treatment
In discussing the timing of nerve repair , treatment is commonly
described as primary or secondary. Primary nerve repair includes repairs
carried out within 1 week of injury. Any repair carried out later is termed
secondary. The classification is, arguably, somewhat arbitrary, but a
precise defin ition is extremely useful in discussion of results. Experimental
evidence has shown very clearly that axons regenerate more quickly in the
setting of secondary repair. In spite of the experimental evidence, no
clinical advantage has been shown with seconda ry repair. Primary suture
under appropriate conditions has proven superior in animal models and in
Clinical and experimental study of peripheral nerve regeneration
34 clinical series. Primary repair is preferable, but situations may arise in
which delayed suture is desirable.
Conceptually, nerve repair should result in the appropriately aligned
coaptation of healthy fascicles in a well -vascularized tissue bed under
minimal tension. If any of these goals cannot be achieved in the primary
setting, secondary repair is more appropriate. For crush injury, the extent
of neural in jury cannot initially be accurately determined. Repair under
these circumstances risks joining injured fascicles and thereby severely
compromising the success of the repair. The condition of the patient in
relation to either injury or associated medical co nditions may preclude
primary repair. Appropriate surgical equipment and adequately trained staff
must be available. Every attempt should be made to ensure that the first
nerve repair is carried out under the best possible conditions.
NNeerrvvee RReeppaaiirr
Epineur al repair requires adequate exposure. Anesthesia should be
selected to provide adequate time for careful exposure, assessment,
mobilization, and repair. Use of a pneumatic tourniquet provides a
bloodless field for dissection. Magnification with loupes or, more
commonly, the operating microscope improves the technical quality of the
repair and favorably affects outcome. The nerve ends for repair are gently
mobilized and cleared of soft tissue, which may obscure visualization of the
epineurium at the repair s ite. Hemostasis is obtained with bipolar cautery.
Careful note is made of external nerve markings, which may aid in
appropriate orientation of the repair. In addition, inspection of the internal
neural topography improves correct fascicular alignment. The nerve ends
are then sharply transected perpendicular to the long axis. After
transection, the nerve is carefully inspected with magnification to ensure
that healthy -appearing, uninjured fascicles are exposed for the repair.
Several sequential transections at short intervals (1 to 2 mm) may be
necessary before the nerve endings are appropriate for repair. This step in
the repair cannot be overemphasized. Failure to adequately resect injured
tissue severely compromises the outcome of the repair. If this step results
Clinical and experimental study of peripheral nerve regeneration
35 in a nerve gap so large that grafting becomes necessary, the surgeon
should not hesitate to proceed with grafting instead of direct repair. Nerve
grafting of uninjured nerve tissue over a short distance will provide results
far superior to direct r epair of injured neural tissue.
Fig. no. 4 – Epineural suture
The repair is begun by placing two epineural sutures 180° to each
other . Careful alignment is the critical factor in this first step. Observation of
the repair during the first few minutes provides an interesting illustration of
the speed with which the epineurium can be sealed simply from surface
tension of local fluids. The refore, additional sutures are placed sparingly.
To accomplish group fascicular repair , the initial exposure and
mobilization of the nerve are the same as those described above for
epineural repair. With the aid of an operating microscope, the nerve ends
are inspected to identify fascicular groups amenable to individual repair.
Matching fascicles are identified proximally and distally. The internal
epineurium is then divided between fascicular groups. After mobilization is
complete, the repair process is i nitiated to facilitate the repair – in general,
the least accessible fascicles, which are often farthest from the surgeon,
are repaired first. Repair of the external epineurium may be helpful in
alleviating tension during the repair. The internal epineuri um is sutured with
Clinical and experimental study of peripheral nerve regeneration
36 the fewest sutures necessary (commonly two) to oppose the fascicular
group.
Fig. no. 5 – Group fascicular repair
Individ ual fascicular repair requires isolation of individual fascicles.
The fascicle is the smallest unit of nerve tissue that can be manipulated
surgically. Interfascicular connections occur, and care must be taken to
avoid injury during the dissection. The rep air follows a pattern similar to
that of group fascicular repair.
SSuuttuurreelleessss NNeerrvvee RReeppaaiirr
Coaptation of nerve tissue without suture is appealing and would
potentially eliminate the trauma associated with traditional suturing
technique. The method has the potential to :
be more efficient,
eliminate variables of tension due to sutu re placement and
technique,
improve alignment of fascicles.
FFaasscciiccllee–MMaattcchhiinngg TTeecchhnniiqquueess
The more precisely axons are directed toward their appropriate end
organ, the better t he chance for successful nerve
Clinical and experimental study of peripheral nerve regeneration
37 regeneration. Intraoperative nerve stimulation in the awake patient is a
readily available tool that can aid in this goal. Hakstian provided an early
description of intraoperative nerve stimulation in 1968. The technique has
been modified and improved over the years. Patient response to
stimulation of selected fascicles in the proximal nerve stump can
differentiate motor and sensory groups. However, caution should be
exercised. Awake stimulation requires a high degree of patie nt cooperation
and is not tolerated by all patients. A thorough preoperative discussion,
which outlines the proposed procedure and describes what the patient will
experience, is crucial to the success of the procedure.
Histologic staining methods are avail able to identify motor and
sensory fascicles in the divided nerve. Acetylcholinesterase is found in
myelinated motor axons and in some unmyelinated axons, but not in
myelinated sensory axons. Carbonic anhydrase is found in myelinated
sensory axons. The det ection of these enzymes with available staining
techniques makes fascicle identification possible. Identification in the
proximal nerve is possible indefinitely. Accurate staining in the distal stump
is possible for about 9 days after nerve division. The t ime required for
intraoperative staining (about 1 hour) and the lack of clear evidence that
the technique improves outcome have limited the use of this technique.
RReessuullttss ooff NNeerrvvee RReeppaaiirr
An accurate and reproducible evaluation of results after treatment is
difficult. Multiple variables in injury, patient comorbidity, treatment,
postoperative evaluation, and the reporting of results contribute to this
difficulty. The most accurate information would be gained from a
prospective standardized assessment. Eve n more difficult would be limiting
each group to a certain age, injury type, specific nerve, level of injury, type
of repair, postoperative protocol, and assessment. In spite of these
difficulties, there is a great deal of useful information available rega rding
nerve repair and results.
The objective evaluation of motor and sensory recovery is essential
to accurate assessment. The Medical Research Council provided a basis
Clinical and experimental study of peripheral nerve regeneration
38 for the assessment of motor and sensory function after nerve injury using
the relative ly simple and reproducible system
The recovery of sensory perception is evaluated by static 2 -PD,
moving 2 -PD, and pinprick. Static 2 -PD is perceived primarily through the
Merkel cell, which is slowly adapting and thus well -suited to continuous
pressure. T he Meissner corpuscle, a rapidly adapting receptor, fires at the
beginning of a stimulus and then dissipates, making it more suitable for
relaying information from moving 2 -PD. Free nerve endings transmit painful
stimuli, such as those from a pinprick. Del lon and Clayton[55] reported that
moving 2 -PD best correlates with a patient's ability to identify objects, and
static 2 -PD correlates with the time to identify objects. Both tests are
neede d to accurately assess functional sensation. Threshold density may
be measured with 2 -PD, and innervation density may be measured with
monofilament testing.
NNeerrvvee GGrraaffttiinngg
Reconstruction after peripheral nerve injury may require
management of segmental de fects or "gaps" in the injured nerve. Local
measures to overcome the problem include nerve mobilization, local joint
positioning, nerve transposition, and bone shortening. Risks and benefits of
each strategy must be carefully considered. Paramount to the d ecision –
making process is the understanding that nerve repair under excess
tension does poorly. Nerve grafting is a readily available solution to the
problem of excessive tension at the repair site. With the dependable
outcomes after nerve grafting, extrem es of joint positioning to accomplish
end-to-end repair are not indicated.
Fig. no 6 – Nerve grafting
Clinical and experimental study of peripheral nerve regeneration
39 Under ideal circumstances, the nerve graft will behave as the distal
nerve stump would. Therefore, the graft must also undergo wallerian
degeneration t o provide a conduit for axon regeneration. Schwann cell
survival in the graft is critical to this process. For the Schwann cells to
survive, the graft must be appropriately revascularized. This process
occurs both from the proximal and distal nerve stumps and from the
surrounding tissue bed. In animal models, graft revascularization reaches
supranormal levels in 4 to 5 days.
Initial revascularization occurs through the proximal and distal
stumps and then the surrounding tissue. Ingrowth from local tissue c reates
extensive adhesions, which limit graft excursion. The first few days after
grafting, cellular viability is dependent solely on diffusion from the tissue
bed. As graft size increases, central cellular necrosis occurs, because the
volume of nerve tiss ue increases beyond the limits of perfusion or
revascularization. This limitation contributes to poor outcome with trunk
grafting. Trunk grafts are now used uncommonly, unless harvested as
vascularized nerve grafts.
NNeerrvvee GGrraaffttiinngg TTeecchhnniiqquueess
In group fas cicular grafting , every attempt is made to accurately
deliver regenerating axons through the graft material to a matching
fascicular group in the distal stump. The distal nerve tissue may be marked
and sent for histochemical staining, depending on clinical needs and
laboratory capabilities. After graft harvest and careful hemostasis, grafts
are sutured to individual fascicular groups with the minimally needed
number of sutures. Emphasis again is placed on appropriate fascicular
matching without tension.
Individual fascicular grafting is uncommon. A distal digital nerve
defect is a specific, useful indication for individual fascicular grafting Other
indications may arise when clinically critical single fascicles (eg, the thenar
motor branch) can be identified .
Clinical and experimental study of peripheral nerve regeneration
40 GGrraafftt MMaatteerriiaall
Autogenous nerve graft is the most commonly used material for
bridging nerve gaps. Ideally, the donor nerve provides a suitable
environment for regeneration and results in acceptable donor morbidity.
The sural nerve meets many requiremen ts for nerve tissue quality and
donor site morbidity and has become the standard autogenous graft for
bridging large upper -extremity nerve gaps. Through a longitudinal incision
or sequential small transverse incisions, up to 40 cm of nerve can be
harvested from each leg.
The resulting sensory loss over the lateral aspect of the foot is not
inconsequential; careful preoperative counseling is necessary to avoid
postoperative disappointments. Blocking the nerve preoperatively with local
anesthetic is very help ful in illustrating the resultant defect to the patient. In
addition to the expected sensory loss, neuroma symptoms can produce
morbidity.
In the forearm, cutaneous nerve branches are available as graft
material. Preoperative counseling and local anesthet ic blocks to reproduce
the donor defect are particularly useful here. The medial antebrachial
cutaneous nerve (MACN) may be harvested and provides up to 10 cm of
graft. The resultant sensory deficit lies along the medial aspect of the mid –
forearm.
The late ral antebrachial cutaneous nerve provides significantly more
graft material than the MACN does – up to 20 cm. However, the resultant
sensory loss along the lateral aspect of the forearm can extend onto the
thenar area, making it undesirable for median ner ve defects in general and
thumb digital nerve injuries in particular.
The posterior interosseous nerve may be harvested at the wrist level
and yields approximately 3.5 cm of graft material. The graft may be
particularly useful in digital nerve defects, and there is no donor morbidity
from sensory loss.
The use of vascularized nerve grafts provides several potential
advantages. The initial period of ischemia (2 to 3 days) after
nonvascularized grafting is avoided, the necessity for revascularization via
the recipient bed (which may be severely scarred and poorly vascularized)
Clinical and experimental study of peripheral nerve regeneration
41 is eliminated, and larger sizes of nerve tissue (in cross section) may be
used as graft without the problems of central necrosis.
Table no. 4 – Vascularized Nerve Grafts: Donor Nerves and Associated
Vessels
Nerve Vascular Supply
Superficial radial Radial artery
Ulnar Superior ulnar collateral artery
Sural Superficial sural artery
Anterior tibial Anterior tibial artery
Superf icial peroneal Superficial peroneal artery
Saphenous Saphenous artery
There is experimental evidence that vascularized nerve grafting can
produce superior outcomes, though conclusive evidence is still lacking.
Clinical series reported superior results w ith vascularized nerve grafts,
though none had control groups and follow -up was frequently limited. As
more clinical follow -up becomes available, the indications for this technique
may expand. The most compelling present indication is grafting in a
severel y scarred tissue bed. Situations where transfer of large nerve trunks
is desirable and feasible (eg, brachial plexus reconstruction using the ulnar
nerve) may benefit from this technique, as well.
Ease of harvest and frequently perfect size match make autologous
vein a predictable material for use in bridging nerve defects. Of course, the
advantage of negligible donor morbidity must be offset by acceptable
clinical results. A consideration of nerve regeneration biology suggests the
ideal peripheral nerve fo r this technique would be small in caliber, motor or
sensory only, and have a limited end -organ target area. The technique is
reported in clinical studies for digital nerve repair. Superiority over
conventional nerve grafting has not been established. Howe ver, as our
understanding of nerve regeneration through hollow tubes improves in
general, indications may expand.
The use of allograft nerve material is particularly appealing because
of its available quantity and lack of donor site morbidity. However, the risks
Clinical and experimental study of peripheral nerve regeneration
42 of immunosuppression required to maintain Schwann cell viability limit
clinical implementation of this method. In animal models, if continuous
immunosuppression is used and the Schwann cell population in the graft
survives, then regeneration equival ent to autograft can be expected. Future
improvements in immunosuppression may expand the use of allografts, but
at present, they are not indicated in clinical practice.
Bridging nerve gaps with a hollow tube has been considered for over
a century, utilizi ng a vast array of materials. As our understanding of nerve
regeneration biology has improved, the conduits for regeneration have
been refined considerably. The ideal conduit would allow inflow of
supportive local nutrient factors but prevent escape of sub stances
supportive of regeneration inside the tube. Ultimately, conduits filled with
neurotrophic substances that are resorbable over appropriate periods may
be available.
Lundborg et al reported a prospective clinical series evaluating
median and ulnar n erve lesions in the forearm treated by conventional
nerve suture or tubulation. Similar outcomes were found in the two groups.
Further clinical trials are needed before the technique can be advocated for
routine use.
NNeerrvvee LLeessiioonnss iinn CCoonnttiinnuuiittyy
Nerve lesi ons in continuity are also called a "neuroma in continuity."
This clinical situation presents unique challenges to the surgeon managing
peripheral nerve injury. The goal of management is the reconstruction of
nonfunctioning neural elements without compromi se of existing function.
Regeneration failure can occur in a wide variety of clinical situations,
including that following nerve repair. However, most commonly, crush
injury, stretch injury (as may be seen with certain fractures), or gunshot
wounds leave t he nerve in continuity, but injured to some degree. The
progress of nerve recovery can be followed clinically by assessment of
functional – both sensory and motor – recovery. In addition, an advancing
Tinel's sign is followed. After regeneration commence s, the advancing
axons progress approximately 1 mm/day. This information, coupled with a
Clinical and experimental study of peripheral nerve regeneration
43 thorough understanding of the local peripheral nerve anatomy, allows the
clinician to predict recovery. Partial recovery, anomalous innervation, or
regeneration across long segments of nerve without branching (such as in
the forearm) can challenge even the most careful observer.
When clinical progress is not proceeding as expected,
electrodiagnostic studies can be useful in identifying regeneration before it
is evident by examination. Electromyography provides specific information
about muscle degeneration. Information gained may obviate the need for
surgical treatment of the lesion and may avoid the situation in which
exploration is delayed so long that end -organ degene ration occurs. If
partial recovery is occurring, further management decisions are based on
the critical nature of missing functions. When motor recovery has occurred
but sensory return is lacking, exploration and intraoperative recordings can
be done with a peripheral nerve stimulator, available in most operating
rooms. Mackinnon has described the intraoperative management
sequence in detail. In brief, functioning motor fascicles are identified and
excluded, allowing section and reconstruction of the injure d sensory
fascicles.
When sensory recovery is present but motor function is deficient,
nerve -to-nerve recording is required. Specialized equipment for this
process is not commonly available. In this situation, tendon transfers or
referral to centers famili ar with the technique may be appropriate. Happel
and Kline describe the intraoperative technique in detail.
Intraoperative testing, in general, identifies functioning fascicles
before end -organ innervation. This information correlates well with eventual
function and can therefore dependably identify fascicles that may be
reconstructed.
AAfftteerrccaarree aanndd RReehhaabbiilliittaattiioonn
Postoperative management after nerve repair or reconstruction is
directed toward wound healing, maintaining joint mobility, and
reestablishing l ongitudinal excursion of the nerve. Repairs are immobilized
for approximately 3 weeks. Adjacent joints are splinted in a safe position.
Clinical and experimental study of peripheral nerve regeneration
44 Extremes of positioning are not indicated to allow repair without grafting, as
discussed in the introductory section on nerve grafting. After digital nerve
repair, a careful intraoperative assessment of tension on the repair site,
where the metacarpophalangeal (MP) joints are held in flexion and the
interphalangeal joints in extension, provides critical information concerni ng
early postoperative motion after tendon repair. Splinting for specific nerve
injuries should prevent contracture during the months required for
regeneration. After ulnar nerve repair, blocking the MP joints in 30° of
flexion allows active interphalangea l motion but prevents hyperextension
deformity at the MP joints. Abduction splinting prevents contractures of the
first web space when thumb abduction is lost.
SSeennssoorryy RReeeedduuccaattiioonn
After nerve regeneration, a new and confusing set of signals is
relayed fr om the hand to the brain. Innervation density is significantly
reduced. Imperfect topographic specificity results in axon regeneration to
new locations. For example, after median nerve repair, axons once
destined for the middle finger may now innervate the palm. In addition,
end-organ innervation is significantly altered. The resultant signal to the
brain from sensory stimulation may be nearly unrecognizable. Sensory
reeducation is designed to help the patient recognize new input in a useful
manner. The abi lity to change cortical maps of sensory input and alter
them to allow accurate identification of new sensory input is called cortical
plasticity. Children are particularly adept at this process, which probably
contributes greatly to their improved outcome after peripheral nerve injury.
Sensory reeducation is carried out in three stages: desensitization,
early -phase discrimination and localization, and late -phase discrimination
and tactile gnosis. Initial efforts are directed toward helping the patient
under stand the potential risks present with a lack of protective sensation.
As early recovery occurs, desensitization is accomplished by a program of
graded stimuli, which gradually decreases unpleasant stimuli and builds
tolerance for increasing levels of stim ulus.
Clinical and experimental study of peripheral nerve regeneration
45 When a 30 -cps tuning fork can be perceived in the palm, early -phase
discrimination and localization begins. During this stage, the patient is
taught to distinguish between static and moving touch. In addition, false
localization of stimuli is address ed. Sensory stimuli are presented with and
without visual clues. Once moving and constant touch can be dependably
identified, late -phase training begins.
The goal of late -phase training is the reestablishment of tactile
gnosis. Tactile gnosis describes the hand's unique ability to "see" an object
and to provide extraordinary detail concerning its shape, texture, and
temperature.[88]Objects that differ greatly in size, shape, and texture are
presented sequentially to the patient. As perception improves, increasingly
complex objects are used.
Clinical and experimental study of peripheral nerve regeneration
46
UUPPPPEERR LLIIMMBB IINNNNEERRVVAATTIIOONN
MMeeddiiaann nneerrvvee
The median nerve originates in the brachial plexus as branches from
the lateral and medial cords come together. These cords bring fibers from
all roots of the brachial plexus, from C5 to T1. The median nerve runs
through the anteromedial compartment, through the cubital fossa just
medial to the brachial arte ry, and enters the forearm between the heads of
the pronator teres.
The median nerve supplies most of the flexor muscles in the forearm
and a few muscles in the hand. Once in the forearm, the median nerve
splits into a superficial and deep branch. The superficial branch supplies
the pronator teres, flexor carpi radialis, and palmaris longus before the
distal portion supplies the flexor digitorum superficialis.
The deep trunk runs medially down the forearm deep to the muscles
and supplies motor innervation to the flexor pollicis longus, pronator
quadratus, and the portions of flexor digitorum profundus (FDP) that flex
the index and long fingers and sends articulate branches to the radial
carpal j oint via the anterior interosseous. At the wrist, the deep median
branch sits between the palmaris longus and flexor pollicis longus, travels
through the carpal tunnel with the flexor tendons, and splits into 6 branches
once clear of the flexor retinaculum. The recurrent branch of the median
nerve innervates the palmaris brevis and the muscles of the thenar
eminence, namely the abductor pollicis brevis, opponens pollicis, the first
and second lu mbricals, and the superficial head of the flexor pollicis brevis.
The remaining branches are sensory and include 3 common digital nerves
to the second, third, and fourth digits and 2 proper digital nerves to the
thumb.
Clinical and experimental study of peripheral nerve regeneration
47
Fig. no. 7 – Sensorial innervation of the hand
These digital nerves run along the lateral (radial) and medial (ulnar)
sides of the fingers with the digital arteries. The median nerve has 2 other
sensory branches not yet mentioned that supply the elbow and a palmar
cutaneous branch that passes over the top of the flexor retinaculum to
innervate the palm.
Fig. no. 8 – Median nerve branches
Motor targets of the median nerve are as follows:
Pronator teres
Flexor carpi radialis
Clinical and experimental study of peripheral nerve regeneration
48 Palmaris longus
Flexor digitorum superficialis
Flexor digitorum profundus
Flexor pollicis longus
Pronator quadratus
Palmaris brevis
Abductor pollicis brevis
Flexor pollicis brevis – Superficial head
Opponens pollicis
First and second lumbricals
Some notable variations in the pattern of innervation exist in the median
distribution. In the forearm, the median nerve supplies approximately one
half of the FDP muscle, sharing it with the ulnar nerve. However, in 50% of
patients, the median and ulnar nerves overlap and the median nerve
encroaches on the ulnar inne rvation to the FDP. However, in the hand, the
ulnar nerve tends to extend across the palm and innervate a larger portion
of the thenar eminence.
Another clinically important variation is the pr esence of Martin -Gruber
anastomoses in the forearm and Riche -Cannieu anastomoses in the palm.
Martin -Gruber anastomoses are believed to be present in approximately
17% of patients, while Riche -Cannieu anastomoses may be present in as
many as 70%. Because t hese anastomoses allow unique patterns of
innervation, they can mask lesions by changing the symptoms present.
UUllnnaarr nneerrvvee
The ulnar nerve arises from the medial cord and contains fibers from
the C7, C8, and T1 roots. It passes through the arm, behind the medial
epicondyle, and into the flexor compartment. In the forearm, the ulnar
nerve gives off motor branches to the flexor carpi ulnaris and the medial
(ulnar) portion of FDP that supplies the ring and little fingers. Usually, the
ulnar nerve gives a small branch to the ulnar artery, known as the nerve of
Henle, which i s present in approximately 60% of people. The remaining
Clinical and experimental study of peripheral nerve regeneration
49 40% of people have a palmar cutaneous branch.63 At the level of the wrist,
the ulnar nerve passes through the Guyon canal, right next to the hook of
the hamate.
In the hand, the ulnar nerve divides into a deep motor and a
superficial sensory branch. The deep motor branch supplies all of the
intrinsic muscles of the hand: the mus cles of the hypothenar eminence, the
interossei, the third and fourth lumbricals, adductor pollicis, and the deep
head of the flexor pollicis brevis. The superficial sensory nerve supplies
sensation to the little finger and the ulnar side of the ring finge r. The ulnar
nerve also supplies sensation to part of the dorsum of the hand via the
dorsal sensory branch that wraps around to the dorsum near the level of
the dorsal carpal ligament. This provides sensation in the same distribution
as on the volar surfac e.
Fig. no. 9 – Ulnar nerve
Motor targets of the ulnar nerve are as follows:
Flexor carpi ulnaris
Flexor dig itorum profundus
Hypothenar muscles
Clinical and experimental study of peripheral nerve regeneration
50 All interossei
Third and fourth lumbricals
Adductor pollicis
Flexor pollicis brevis – Deep head
RRaaddiiaall nneerrvvee
The radial nerve is a branch off the posterior cord and contains fibers
from roots C7 -T1. This nerve wraps around the humerus in the spiral
groove as it passes through the upper arm, supplying motor innervation to
all 3 heads of the triceps muscle, the anconeus, the brachioradialis, and a
small part of the brachialis muscle before entering the cubital fossa lateral
to the biceps tendon. In the forearm, the nerve supplies motor innervation
to the extensor carpi radialis longus, extensor carpi radialis brevis, and the
supinator before splitting into deep and superficial branches .
Fig. no. 10 – Radial nerve
The deep branch provides motor innervation to the muscles of f inger
and thumb extension before becoming the posterior interosseous nerve
and supplying sensation to the dorsal aspect of the carpal joints. The
superficial sensory branch passes through the anatomic snuffbox on its
Clinical and experimental study of peripheral nerve regeneration
51 way to supply sensation to the dorsum o f the hand, thumb, and first 2.5
fingers. The radial nerve also provides sensation to a portion of the forearm
via the posterior cutaneous nerve and to the elbow.
Motor targets of the radial ne rve are as follows:
Triceps (long, medial, lateral)
Anconeus
Brachioradialis
Extensor carpi radialis longus
Extensor carpi radialis brevis
Supinator
Extensor digitorum communis
Extensor indicis proprius
Extensor digiti minimi quinti
Extensor carpi ulnaris
Abductor pollicis longus
Extensor pollicis longus
Extensor pollicis brevis
Clinical and experimental study of peripheral nerve regeneration
52
PPEERRSSOONNAALL CCOONNTTRRIIBBUUTTIIOONNSS
Clinical and experimental study of peripheral nerve regeneration
53
MMAATTHHEERRIIAALL AANNDD MMEETTHHOODDSS
AAlltteerrnnaattiivvee mmeetthhooddss ffoorr nneerrvvee rreeppaaiirr
Study of nerve regeneration using a silicone tube
Aim of this study is to deter mine alternative methods for nerve repair
to avoid nerve graft.
We randomized 6 Wistar rats, aprox 450g each, in 2 groups:
Control group
Silicone tube group
For control group we used epineural neuroraphy
For Silicone tube group I used a silicone tube with 2mm internal
diameter and wall thickness of 0,18mm
Surgical protocol
We used inhalation anaesthesia with Halotane and O2.
For surgical intervention I used a surgical microscope with
magnification between 10 -40x in aseptic conditions.
We did an oblique in cision in the dorsal part of rat thigh.
We dissected the muscles and I exposed sciatic nerve.
For silicone tube group I used an 1 cm silicone tube and I let
between nerve stump 5mm
For control group I used epineural neuroraphy
Sutureing was done with 9/ 0 Polipropylene suture
New experiment for nerve regeneration
We will use a new experiment to determine nerve regeneration
comparing with suture only control.
Two different experimental groups will be tested;
Suture only
Suture + seeding with chopped nerv e
Clinical and experimental study of peripheral nerve regeneration
54 Protocol
Adult rats (7 animals per group) will be anaesthetised and the left
sciatic nerve exposed .
The sciatic nerve was transected 1 mm segment of nerve will be
excised and the nerve sutured with a perineural technique with 9/0 sutures.
In the stud y group, the segment of nerve will be chopped and
seeded around the nerve suture, while nothing will be done in the control
group .
Two different time -points will be examined, allowing study of the
extent of early stages of nerve regeneration (14 days) and muscle
reinnervation (180 days).
In both studies we used EMG machine for assessing the results:
Protocol for EMG assesing
We will use an EMG machine
We will reexpose the sciatic nerve of the rats
We will stimulate sciatic nerve proximal and distal with 2
electrodes
We will put the electrode for recording in the muscles of the calf
We will put the referent electrode to the calcanean tendon
We will put the closeing electrode subcutaneous between
stimulation and recording electrodes
We will use a pulse 0,2m s, 20mA,10Hz and 6 continous
stimulation
We will record NCV and I will compare the 2 groups
We will compare NCV for the 2 groups with NCV from healthy
thigh of the rats
TTooppooggrraapphhyy ooff ppeerriipphheerraall nneerrvveess ((mmeeddiiaann nneerrvvee,, uullnnaarr
nneerrvvee,, rraaddiiaall nneerrvvee,, sscciiaattiicc nneerrvvee)) –– aannaattoommiicc ssttuuddyy oonn
ccaaddaavveerrss
This anatomical study followed fascicular dissection of main nerves
involved in reconstructive surgery of peripheral nerves of the upper
Clinical and experimental study of peripheral nerve regeneration
55 extremity (median, ulnar radial). Nervous branches are dissected from
distal to pro ximal and followed till were is possible.
We dissected upper extremity of 3 fresh cadaver and individualised
nervous traiect of main nerves.
Material used were standard surgical instruments. We took pictures with
digital camera.
CClliinniiccaall eexxppeerriieennccee iinn ppeerriipphheerraall nneerrvvee rreeppaaiirr ((FFLLOORREEAASSCCAA
PPLLAASSTTIICC SSUURRGGEERRYY DDEEPPAARRTTMMEENNTT BBUUCCHHAARREESSTT,, CCOONNSSTTAANNTTAA
PPLLAASSTTIICC SSUURRGGEERRYY DDEEPPAARRTTMMEENNTT)) –– rreettrroossppeeccttiivvee aanndd
pprroossppeeccttiivvee ssttuuddyy
This study is a retrospective and prospective study concerning the
affections of peripheral nerves in plast ic surgery department of C onstanta
emergency hospital and ―Floreasca‖ emergency hospital B ucharest.
We studied 2 groups of pacients.
First group – 478 patients treated in plastic surgery department of
Constanta emergency hospital between 2006 -2010
Second group – 1742 patients treated in plastic surgery department
of ―Floreasca‖ emergency hospital B ucharest between 2006 -2010.
We studied the following parameters:
Distribution over years
Sex ratio
Distribution over age
Smoking
Alcohol consumption
Upper ext remity involved]
Affected nerve
Accident location
Type of anaesthesia
Clinical and experimental study of peripheral nerve regeneration
56 Time of repair
Surgical procedure
Hospitalization period
For the retrospective study we used patient file and for the
prospective we used anamnestic data. All data were recorded in a
standard worksheet and introduced in a database built in Microsoft Access
2010 software.
All data were transposed in table and graphs using Microsoft Excel
2010 software.
Clinical and experimental study of peripheral nerve regeneration
57
TTOOPPOOGGRRAAPPHHYY OOFF PPEERRIIPPHHEERRAALL NNEERRVVEESS
((MMEEDDIIAANN NNEERRVVEE,, UULLNNAARR NNEERRVVEE,, RRAADDIIAALL
NNEERRVVEE)) –– AANNAATTOOMMIICC SSTTUUDDYY OONN CCAADDAAVVEERRSS
Initially, when Sunderland looked at the fascicular patterns of
peripheral nerves in 1947, he described a pattern of twisting and crossing
fascicles that branched so ofte n that nerve grafting and intraneural
dissection were assumed to be impossible. Fortunately, the pattern
described by Sunderland is only true for the proximal part of the nerve. As
described by Jabaley in 1980, the fascicular pattern in the distal forearm is
much straighter, with less crossing over. Apparently, the crossing over in
the proximal portion sorts the nerve fibers into bundles by function. This
means that by the time the distal forear m is reached, the fascicles contain
nearly pure motor or sensory axons.
While the arrangement varies by individual and by nerve, generally,
the sensory fascicles are considered to sit more sup erficially and the motor
fibers more dorsal.
Fig. no. 11 – 12: Fascicular pattern of sciatic nerve
Clinical and experimental study of peripheral nerve regeneration
58
Fig. no. 13: Fascicular pattern of ulnar nerve
Fig. no. 14 – 15 – Branches of ulnar nerve
The ulnar nerve arises from the medial cord of the brachial plexus.
The ulnar nerve travels posterior to the brachial artery and remains within
the flexor compartment of the upper extremity until it reaches the medial
epicondyle. The nerve travels behind the medial epicondyle back into the
flexor co mpartment underneath the flexor musculature. Above the elbow,
the ulnar nerve lies on the long head and then the medial head of the
triceps muscle, directly posterior to the medial intermuscular septum
between the brachialis and the triceps muscles.
The fa scial bands over the median nerve constitute the Struthers
arcade. The nerve passes within the cubital tunnel posterior to the medial
epicondyle. It is directly underneath a tight fascial roof known as the
Osborne band, which is contiguous with the leading fascial heads of the
flexor carpi ulnaris (FCU) muscle. Just above the elbow branches, the
Clinical and experimental study of peripheral nerve regeneration
59 nerve branches to the superficial head of the FCU. The nerve lies directly
over the top of the FDS muscle and beside the FDP muscle at the elbow.
As the ulnar nerve travels down the forearm, it is wedged between the FDS
and the FDP muscle bellies to exit in the distal forearm just ulnar to the
ulnar artery and the FDP tendons. The FCU tendon protects the nerve on
its ulnar aspect. The ulnar nerve travels within the G uyon canal at the wrist
to supply the hypothenar muscles, including the opponens digiti quinti and
the abductor digiti quinti. It also supplies the 2 ulnar lumbrical muscles and
the interossei to the hand and the deep branch to the flexor pollicis brevis
muscle. The ulnar ne rve supplies sensation to the 1 -5 digits of the ulnar
aspect. The dorsal cutaneous branch of the ulnar nerve supplies sensation
to the dorsal ulnar half of the hand and fingers. This nerve arises from the
main ulnar nerve approximately 6 cm proximal to the wrist.
Fig. no. 16 – Fascicular pattern of digital nerve
In the hand, the common digital nerves are derived from the median
and ulnar nerves and divide in the distal palm into paired volar (or palmar)
branches. These run with the di gital vessels on either side of the flexor
tendon sheath of each finger and supply the lateral and palmar aspect of
each finger together with the tip and nail bed area. The smaller dorsal
digital nerves, derived from the radial and ulnar nerves, run on the
dorsolateral aspect of each finger and supply sensation to the back of the
finger.
Clinical and experimental study of peripheral nerve regeneration
60 In the palm of the hand the median nerve is covered by the skin and
the palmar aponeurosis , and rests on the tendons of the Flexor muscles .
Immediately after emerging from under the transverse carpal
ligament the median nerve becomes enlarged and flattened and splits into
a smaller, lateral, and a larger, medial portion.
The lateral portion supplies a short, stout branch to certain of the
muscles of the ball of the thumb, v iz., the Abductor brevis, the Opponens,
and the superficial head of the Flexor brevis, and then divides into
three proper palmar digital nerves of median nerve (proper volar digital
nerves):
two of these supply the sides of the thumb,
while the third gives a twig to the first Lumbricalis and is distributed
to the radial side of the index finger.
Each proper digital nerve , opposite the base of the first phalanx,
gives off a dorsal branch which joins the dorsal digital nerve from
the superficial branch of th e radial nerve , and supplies
the integument on the dorsal aspect of the last phalanx.
At the end of the digit, the proper digital nerve divides into two
branches,
one of which supplies the pulp of the finger,
the other ramifies around and beneath the nail.
The proper digital nerves, as they run along the fingers, are placed
superficial to the corresponding arteries
Clinical and experimental study of peripheral nerve regeneration
61
Fig. no. 17 – 20: Terminal branches of median nerve
The nerve is superficial to the brachialis muscle and usually lies in a
groove with the brachial artery, between the brachialis and biceps muscle.
It travels across the antecubital fossa, underneath the bicipital
aponeurosis, and between the biceps tendon and the pronator teres. At
this level, the median nerve is on the distal as pect of the brachialis muscle.
The nerve then travels underneath the 2 heads of the flexor digitorum
sublimis (FDS) muscle to lie between this muscle and the flexor digitorum
profundus (FDP) muscle. The median nerve emerges between these 2
muscles in the d istal forearm to then travel ulnar to the flexor carpi radialis
and radial to the sublimis tendons, usually directly underneath the palmaris
longus tendon, and enters the carpal tunnel in a more superficial plane to
the flexor tendons.
The motor branch eme rges at variable sites but most frequently at
the distal aspect of the carpal ligament to service the thenar musculature.
Just beyond the end of the carpal ligament, the median nerve trifurcates to
Clinical and experimental study of peripheral nerve regeneration
62 become the common digital sensory nerves to the fingers. T he palmar
cutaneous branch of the median nerve is a sensory branch that comes
from the main body of the nerve approximately 6 inches above the rest of
the nerves and services an elliptical area at the base of the thenar
eminence. This superficial nerve doe s not lie within the carpal tunnel.
Just distal to the antecubital fossa, the median nerve branches into
the anterior interosseous nerve, which travels on the interosseous
membrane and innervates the flexor pollicis longus (FPL), the FDP to the
radial 2 di gits, and the pronator quadratus at its termination. The nerve
innervates the pronator teres, flexor capri radialis, the FDS, and the 2
radial FDP tendons. It also supplies the FPL and the pronator quadratus.
Within the hand, the motor branch of the median nerve supplies the
opponens pollicis, the flexor pollicis brevis, and the abductor pollicis brevis
musculature. It also supplies the 2 radial lumbrical muscles in the hand.
The median nerve supplies sensation to the 3.5 digits on the radial aspect.
In the distal half of the arm, the branches of the median nerve
consistently collect into three fascicular groups, which are located at the
anterior, middle, and posterior parts of the median nerve trunk. The
anterior fascicular group is composed of the branches to the pronator teres
and the flexor carpi radialis, the posterior fascicular group is composed
mainly of the anterior interosseous nerve and the branches to the palmaris
longus, and the middle fascicular group is made up mostly of the branches
to the han d and the flexor digitorum superficialis.
Clinical and experimental study of peripheral nerve regeneration
63
Fig. no. 21 – 24: Branches of radial nerve
The radial nerve emerges from the posterior aspect of the humerus
in the spiral groove between the brachialis and brachioradialis muscles
above the elbow. It leaves the extensor compartment to travel in front of
the elbow underneath the brachioradialis muscle, sending branches of
innervation to it just above the elbow. The radial nerve divides at the level
of the radial capitellar joint into the deep motor branch of the radial nerve
(ultimately becoming the posterior interosseous nerve) and the superficial
radial nerve. At this point, it branches to the extensor carpi radialis brevis.
The superficial radial nerve continues to travel underneath the
brachiorad ialis muscle to ultimately emerge between that muscle and the
extensor carpi radialis longus tendon. The superficial radial nerve supplies
sensation to the radial half of the dorsum of the hand. The deep motor
branch of the radial nerve travels within the fat pad and runs below the
supinator muscle to emerge the supinator and become the posterior
interosseous nerve in the distal dorsal aspect of the forearm. The posterior
Clinical and experimental study of peripheral nerve regeneration
64 interosseous nerve travels at the level of the interosseous membrane to
ultimately pro vide sensation to the posterior aspect of the wrist. This nerve
innervates the extensor indicis proprius, extensor digiti quinti, extensor
carpi ulnaris, abductor pollicis longus, extensor pollicis brevis, and extensor
digitorum communis muscles.
Clinical and experimental study of peripheral nerve regeneration
65
AALLTTEERRNNAATTIIVVEE MMEETTHHOODDSS FFOORR NNEERRVVEE RREEPPAAIIRR
In recent past there have been significant developments in the
management of peripheral nerve injuries. The advent of microsurgical
techniques with use of magnification, micro -sutures and micro instruments
has considera bly improved the results in nerve repairs. Many advances
have been made in the area of neurobiology of nerve injury and
regeneration, and increasing attempts are being made in the use of nerve
allografts and nerve conduits for bridging the gaps.
NNEERRVVEE AAUUTTOOGGRRAAFFTTSS AANNDD AALLLLOOGGRRAAFFTTSS
Nerve autografts are considered the gold standard technique for the
peripheral nerve lesions. The nerve grafting technique was first reported
between the years 1870 and 1900, but it was Millessi who worked
extensively on the nerve grafting techniques. He made it clear that nerve
grafting without tension was superior to epineural suture under tension.
Tension across a direct suture repair decreases blood flow and excessive
tension will cause the repair to break down. The sural ner ve is by far the
most commonly used donor nerve, others being the cutaneous nerves of
arm and forearm, dorsal sensory branch of radial nerve and distal portion
of anterior interosseous nerve.
One current practice that accounts for the success of nerve gra fts is
the use of small, thin grafts which get vascularized faster than the large
and thick grafts. For bridging the long gaps (greater than 20 cm) with
associated soft tissue loss over the repaired area, current recommendation
is to use free vascularized nerve grafts 2,3 In global brachial plexus palsy
with C8 . and T1 root avulsions, pedicled vascularized ulnar nerve has
been used for a contralateral C7 root transfer to the median nerve.
Clinical and experimental study of peripheral nerve regeneration
66 The use of allografts has been experimented in nonhuman primates
and later practiced by Mackinnon et al in the humans and the groups
involved in hand Transplantation Nerve allografts act as a temporary
scaffold across which host axons regenerate. Ultimately, the allograft
tissue is completely replaced with host materi al. Once regeneration has
occurred through the graft,immunosuppression may be discontinued. A
new immunosuppressant FK 506, also known as tacrolimus, has greater
potential and fewer side effects than other immunosuppressants. It has
been established th at FK 506 has neuroregenerative and neuroprotective
effects regardless of its immunosuppressive activity.
Fig. no.25 – 28 – Rat sciatic nerve autograft
UUSSEE OOFF FFIIBBRRIINN GGLLUUEE IINN NNEERRVVEE RREEPPAAIIRR
Synthetic nerve suture may induce considerable fibrot ic and
inflammatory reactions at the coaptation site which could seriously hamper
regeneration of nerve fibres.
Clinical and experimental study of peripheral nerve regeneration
67 Young and Medawar devised a method by which the nerve stumps
were held together with concentrated coagulated blood plasma. In 1988
Narakas revi ved the use of fibrin in nerve repair. Since then, its use has
steadily gained popularity amongst the peripheral nerve surgeons.
A recent study has compared the use of fibrin glue and microsutures
in the repair of rat median nerve and found that nerve re pairs performed
with fibrin sealants produced less inflammatory response and fibrosis,
better axonal regeneration, and better fiber alignment than the nerve
repairs performed with microsuture alone. In addition, the fibrin sealant
techniques were quicker and easier to use. Bozorg at al have reported
promising results with fibrin glue in he repair of facial nerve in human
beings.
EENNDD TTOO SSIIDDEE NNEEUURROORRRRHHAAPPHHYY
In last two decades, there has been a volume of research evaluating
end-to-end versus end -to-side rep airs but it is generally accepted that end –
to-side will provide only limited sensory recovery .
The technique seems most successful when the epineurium is
opened and there has been a small amount of damage to the enclosed
fascicles during the placement of a distal nerve stump to the whole nerve.
An end -to-side repair will allow motor reinnervation through collateral
sprouting only when there has been a direct nerve injury at the repair site,
such as a partial neurectomy
NERVE GUIDANCE CONDUIT
Nerve guid ance conduit (also referred to as an artificial nerve
conduit or artificial nerve graft, as opposed to an autograft) is an artificial
means of guiding axonal regrowth to facilitate nerve regeneration and is
one of several clinical treatments for nerve inju ries. When direct suturing of
the two stumps of a severed nerve cannot be accomplished without
tension, the standard clinical treatment for peripheral nerve injuries is
autologous nerve grafting. Due to the limited availability of donor tissue and
function al recovery in autologous nerve grafting, neural tissue
Clinical and experimental study of peripheral nerve regeneration
68 engineering research has focused on the development of bioartificial nerve
guidance conduits as an alternative treatment, especially for large defects.
Similar techniques are also being explored for n erve repair in the spinal
cord but nerve regeneration in the central nervous system poses a greater
challenge because its axons do not regenerate appreciably in their native
environment.
Despite some limited improvements in surgical technique, for more
than 5 decades we have continued to use autologous nerve grafts to
reconstruct nerve lesions, consequently creating donor site morbidities
leading to non sensitive areas or even ulcers or pressure sores. This
project will aim to show how seeding cells aroun d a nerve suture could be
of therapeutic use for the treatment of nerve injury, a nerve cells may serve
as a stimulus to nerve regeneration.
Scientifically, the project will serve as the bases for the future use of
ADSC, differentiated to a Schwann cell ph enotype for the treatment of
nerve lesions. Since nerve lesions are common within the population we
expect this research to have widespread health and socioeconomic
consequences. Division of a peripheral nerve results in impaired sensation,
reduced motor function and sometimes pain. Such injuries have a profound
and permanent impact of the patient’s life as they do not regain normal
function. There are also serious economic implications for both the
individual patient and society as a whole as a result of the intensive period
of rehabilitation required and a mean time off work ranging from 21.4 to
31.3 weeks, with just 59 – 69% of patients back in full time work 1 year
after injury. The total expense per patient is estimated to be EUR 51,238
for median and ulnar nerve injuries.
The results of this project will define a new clinical possibility, using
cells, to easily repair nerves without implanting non human derived
substances, allowing surgeons to address nerve gap lesions in a fast and
easy way. The reco mmendations derived from this study will result in
improved outcome of nerve lesions without the drawback of a de -sensitised
area either at the donor site or at the reconstructed area. The project also
aims to prove the positive effect of modified neural repair on reinnervation
and consequently muscle tone and activity. The results could have
Clinical and experimental study of peripheral nerve regeneration
69 beneficial effects on muscle restitution after trauma with or even without
nerve damage. In summary, these experiments will examine the extent of
nerve regeneration i n combination with analysis of muscle morphology and
biochemistry to evaluate fully the effectiveness of using nerve cells around
the neural suture for nerve repair. This could allow new ways of treating
nerve lesions providing a better outcome and minimal morbidity.
Fig. no. 29 – 32: Microsurgery lab of Floreasca Emergency Hospital
NNEERRVVEE RREEPPAAIIRR UUSSIINNGG SSIILLIICCOONNEE TTUUBBEE
Aim of this study is to determine alternative methods for nerve repair
to avoid nerve graft.
We randomized 6 Wistar rats, aprox 450g each, in 2 groups:
Control group
Silicone tube group
For control group we used epineural neuroraphy
Clinical and experimental study of peripheral nerve regeneration
70 For Silicone tube group we used a silicone tube with 2mm internal
diameter and wall thickness of 0,18mm
SURGICAL PROTOCOL
We used inhalation anaesthesia with Halotane and O2.
For surgical intervention we used a surgical microscope with
magnification between 10 -40x in aseptic conditions.
We did an oblique incision in the dorsal part of rat thigh.
We dissected the muscles and expos ed sciatic nerve.
For silicone tube group we used an 1 cm silicone tube and we let
between nerve stumps 5mm.
For control group we used epineural neuroraphy.
Sutureing was done with 9/0 Polipropylene suture.
Fig. no. 33 – 34: Epineural suturing – Control group
Clinical and experimental study of peripheral nerve regeneration
71
Fig. no.35 -39: Silicone tube group
We asses the rats at 6 and 9 months postoperatively
2 rats died from control group
1 rat died from silicone tube group
PROTOCOL FOR EMG ASSESING
We used an EMG machine
We stimulated sciatic nerve proximal and distal with 2 electrodes
We put the electrode for recording in the muscles of the calf
We put the referent electrode to the calcanean tendon
We put the closing electrode subc utaneous between stimulation and
recording electrodes
We used a pulse 0,2ms, 20mA,10Hz and 6 continous stimulation
We recorded NCV
Clinical and experimental study of peripheral nerve regeneration
72 We compared NCV for the 2 groups with NCV from healthy thigh of
the rats
NCV RECOVERY RATE
For unoperated limb NCV wa s between 65,40 – 93,20 m/s
For control group at 6 months p.o NCV was 72 m/s
For control group at 9 months p.o NCV was 49.68 m/s
For silicone tube group at 6months p.o NCV was between 35.97 –
50.32 m/s
For silicone tube group at 9 months p.o NCV was between 37.93 –
55.26 m/s
Table no. 5
Group Unoperated limb 6 months 9 months
Control 72,40 m/s 43.20 m/s 49.68 m/s
Silicone tube –
rat #1 65.40 m/s 35.97 m/s 37.93 m/s
Silicone tube –
rat #2 93.20 m/s 50.32 m/s 55.26 m/s
Chart no. 1 – Ncv recovery rate
Clinical and experimental study of peripheral nerve regeneration
73
Table no. 6
Group UNOPERATED
LIMB 6 MONTHS 9 MONTHS
Control 72,40 m/s 59.66 68.61
Silicone
tube-rat #1 65.40 m/s 55 58.46
Silicone
tube-rat #2 93.20 m/s 54 59.3
Both groups have a difference between unoperated limb and
operated limb at 9 months.
Are not significant differences for nerve recovery between silicone
tube group (54.5%recovery at 6 month, 58.85%at 9 months) and
control group (59.66% at 6 month, 68.61% at 9 months)
We conclude that silicone tube technique is a good technique as an
alternative f or nerve graft.
NNEERRVVEE RREEPPAAIIRR UUSSIINNGG CCHHOOPPPPEEDD NNEERRVVEE AARROOUUNNDD TTHHEE
SSUUTTUURREE
Two different exp erimental groups will be tested:
Suture only
Suture + seeding with chopped nerve
Adult rats (7 animals per group) are anaesthetised useing Ketamin
and Dormicum injecti on.
The sciatic nerve is transected
3 mm segment of nerve is excised and the nerve sutured with a
perineural technique with 9/0 sutures.
Clinical and experimental study of peripheral nerve regeneration
74 In the study group, the segment of nerve is chopped and seeded
around the nerve suture, while nothing will be done in t he control
group
Two different time -points will be examined, 6 months and 9 month
Fig. no. 40 – 44: Nerve repair using chopped nerve around the suture
We asses the rats at 6 and 9 months postoperatively
2 rats died from control group
3 rats died from suture+chopped nerve group
We used an EMG machine
We stimulated sciatic nerve proximal and distal with 2 electrodes
We put the electrode for recording in the muscles of the calf
Clinical and experimental study of peripheral nerve regeneration
75 We put the referent electrode to the calcanean tendon
We put the closing electrode subcutaneous between stimulation and
recording electrodes
We used a pulse 0,2ms, 20mA,10Hz and 6 continous stimulation
We recorded NCV
We compared NCV for the 2 groups with NCV from healthy thigh of
the rats
Table no. 7
UNOPERATED LIMB
(m/s) 6 MONTHS
(m/s) 9 MONTHS
(m/s)
RAT #1 72,50 44.22(61%) 48.75(67%)
RAT #2 78.40 49.39(63%) 54.09(69%)
RAT #3 69.10 41.46(60%) 45.60(66%)
RAT #4 84.60 52.90(62.54%) 56.96(67.34%)
RAT #5 87.30 55.95(64.10%) 60.58(69.40%)
Chart no. 2 – NCV in control group
Clinical and experimental study of peripheral nerve regeneration
76 Table no. 8
UNOPERATED LIMB
(m/s) 6 MONTHS
(m/s) 9 MONTHS
(m/s)
RAT #1 69,50 2.9 3.3
RAT #2 62.40 3.6 3.9
RAT #3 89.10 2.4 2.7
RAT #4 76.30 4.1 4.9
Chart no. 3: NCV in chopped nerve around the suture group
For unoperated limb NCV was between 62,40 – 89,10 m/s with a
medium value of 76,5m/s
For control group at 6 months p.o NCV was between 41.46 -55.9 m/s
with a medium value of 48.78 m/s
For control group at 9 months p.o NCV was between 48.75 -60.58
m/s with a medium value of 53.1 9 m/s
Clinical and experimental study of peripheral nerve regeneration
77 For suture+chopped nerve group at 6 months p.o NCV was between
2.4-4.1 m/s with a medium value of 3.25 m/s
For suture+chopped nerve group at 9 months p.o NCV was between
2.7-4.9 m/s with a medium value of 3.7 m/s
We conclude that seeding chopped n erve in the suture is not a viable
alternative for nerve graft, so we don’t continue this study in the
future
Clinical and experimental study of peripheral nerve regeneration
78
CCLLIINNIICCAALL EEXXPPEERRIIEENNCCEE IINN PPEERRIIPPHHEERRAALL NNEERRVVEE
RREEPPAAIIRR ((FFLLOORREEAASSCCAA PPLLAASSTTIICC SSUURRGGEERRYY
DDEEPPAARRTTMMEENNTT BBUUCCHHAARREESSTT,, CCOONNSSTTAANNTTAA
PPLLAASSTTIICC SSUURRGGEERRYY DDEEPPAARRTTMMEENNTT)) ––
RREETTRROOSSPPEECCTTIIVVEE AANNDD PPRROOSSPPEECCTTIIVVEE SSTTUUDDYY
TToottaall nnuummbbeerr ooff ppaattiieennttss
Table no. 9
0200400600800100012001400160018002000
Constanta Bucharest
Chart no. 4 City No of patients
Constanta 478
Bucharest 1742
Clinical and experimental study of peripheral nerve regeneration
79 DDiissttrriibbuuttiioonn oovveerr yyeeaarrss
Table no.10
Constanta Bucharest %Constanta %Bucharest
2006 90 281 18.83 16.13
2007 110 439 23.01 25.20
2008 121 382 25.31 21.93
2009 89 354 18.62 20.32
2010 68 286 14.23 16.42
Total 478 1742 100 100
Chart no.5
As we see in the previous table and graph in both locations the
peak of frequency is in the year 2007 and 2008.
Clinical and experimental study of peripheral nerve regeneration
80
SSeexx rraattiioo
Table no. 11
Constanta Bucharest %Constanta %Bucharest
Male 362 1352 75.73 77.61
Female 116 390 24.27 22.39
02004006008001000120014001600
Constanta BucharestMale
Female
Chart no. 6
The table and graphs reveal that men present more hand
traumatic lesions than women because of their profes sional and
domestic activities that predispose them to accidents .
Clinical and experimental study of peripheral nerve regeneration
81
Constanta
Male
75.73%Female
24.27%
Chart no. 7
A total number of 478 consecutive patients with nerve injury attended the
Plastic Surgery Clinic of Constanta Emergency Hospital of which 362 were
men and 116 were female. The distribution of hand injury according to the
sex group is seen in table and graph
Bucharest
Male
77.61%Female
22.39%
Chart no. 8
A total number of 1742 consecutive patients with nerve injury attended the
plastic surgery clinic of ―Floreasca‖Emergency Hospital Bucharest of
Clinical and experimental study of peripheral nerve regeneration
82 which 1 352 were men and 390 were female. The distribution of hand injury
according to the sex group is seen in previous table and graph.
DDiissttrriibbuuttiioonn oovveerr aaggee
Age of the patient is the single most critical factor in sensory
recovery after nerve repair, but resul ts are adversely affected by
associated injuries to muscle, arteries, tendons, and bone;
Young patients can recover close -to-normal nerve function. In contrast, a
patient over 60 years old with a cut nerve in the hand would expect to
recover only protecti ve sensation; that is, the ability to distinguish hot/cold
or sharp/dull.
Results of nerve repair begin to decline after second decade (75% good
results in children vs 50% good results in adults) .
Results of nerve repair may be poor after the sixth decade ;
Table no. 12
Decade Constanta Bucharest %Constanta %Bucharest
0 – 10 9 19 1.88 1.09
11 – 20 27 94 5.65 5.40
21 – 30 63 320 13.18 18.37
31 – 40 118 428 24.69 24.57
41 – 50 127 468 26.57 26.87
51 – 60 94 278 19.67 15.96
>60 40 135 8.37 7.75
Clinical and experimental study of peripheral nerve regeneration
83
050100150200250300350400450500
Constanta Bucharest0 – 10
11 – 20
21 – 30
31 – 40
41 – 50
51 – 60
>60
Chart no. 9
The table and graphs lead to the conclusion that the most
exposed subjects are patients between 30 and 50 year because their
involvement in the proces of work. This is very important because this
type of accidents can affect the work capacity needing a long period
of rehabilitation and sometimes can cause the total loss of this work
capacity and profesional reintegration.
Bucharest
0 – 10
1.09%11 – 20
5.40%
21 – 30
18.37%
31 – 40
24.57%41 – 50
26.87%51 – 60
15.96%>60
7.75%
Chart no.10
Clinical and experimental study of peripheral nerve regeneration
84
Constanta
0 – 10
1.88%11 – 20
5.65%
21 – 30
13.18%
31 – 40
24.69%
41 – 50
26.57%51 – 60
19.67%>60
8.37%
Chart no. 11
SSmmookkiinngg
Peripheral nerves have a high metabolic demand and require a continuous
energy supp ly to support impulse transmission and axonal transport. They
are perfused through a rich network of extrinsic and intrinsic blood vessels.
In the event of interruption of this blood flow, high energy phosphates are
rapidly depleted and conduction failure ensues. Nicotine has been shown
to worsen the severity of ischemia/reperfusion injury in experimental
models.
This suggests that cigarette smoking may worsen the damage caused to
peripheral nerves by ischemia and reperfusion. If true, this holds important
implications for cigarette smokers who sustain extremity injuries or who
suffer from nerve damage syndromes. Smoking cessation may prove to be
a useful adjunct in the treatment of patients with nerve injuries
Further, pharmacologic manipulation of the eff ects of nicotine upon
peripheral nerves could prove to be a useful adjunct to the established
treatment modalities for neuropathic conditions.
Clinical and experimental study of peripheral nerve regeneration
85 Table no. 13
Constanta Bucharest %Constanta %Bucharest
Smokers 354 1240 74.06 71.18
Non-
smokers 124 502 25.94 28.82
0200400600800100012001400
Constanta BucharestSmokers
Non-smokers
Chart no. 12
Bucharest
Smokers
71.18%Non-smokers
28.82%
Chart no. 13
Clinical and experimental study of peripheral nerve regeneration
86 Number of smokers in Floreasca‖ Emergency Hospital
Bucharest was 1240 ( 71.18 %) and in Constanta Emergency Hospital 354
(74,06% ). This patients have a poor prognostic campareing with non –
smokers patients.
Constanta
Smokers
74.06%Non-smokers
25.94%
Chart no. 14
AAllccoohhooll ccoonnssuummppttiioonn
Experimental studies show that chronic alcoholism has a negative
influence on peripheral nerve regeneration associated with a
significant decrease in axon number and increased axonal
degeneration.
Table no. 14
Constanta Bucharest %Constanta %Bucharest
Drinkers 220 1014 46.03 58.21
Non-drinkers 258 728 53.97 41.79
Clinical and experimental study of peripheral nerve regeneration
87
020040060080010001200
Constanta BucharestDrinkers
Non-drinkers
Fig. no. 15
Constanta
Drinkers
46.03%
Non-drinkers
53.97%
Fig. no. 16
Bucharest
Drinkers
58.21%Non-drinkers
41.79%
Fig. no. 17
Clinical and experimental study of peripheral nerve regeneration
88 AAffffeecctteedd uuppppeerr lliimmbb
Table no.15
Constanta Bucharest %Constanta %Bucharest
Left 311 1114 65.06 63.95
Right 167 628 34.94 36.05
020040060080010001200
Constanta BucharestLeft
Right
Chart no. 18
The right hand was injured in 167 patients (34.9 %)in Constanta
Emergency Hospital and 628 patients in ―Floreasca‖ Emergency
Hospital Bucharest (36%), the left hand injured in 311 patients
(65.06 %), in Constanta Emergency H ospital and 1114 patients in
―Floreasca‖ Emergency Hospital Bucharest (63.95%) and this reflects
the finding of other reports . Graphs showed the sides involved in
hand injuries . In 99% of patients right hand was dominant hand.
Clinical and experimental study of peripheral nerve regeneration
89
Chart no. 19
Chart no. 20
AAffffeecctteedd nneerrvvee
Table no.16
Constanta Bucharest %Constanta %BucharestR
Median 162 530 33.89 30.42
Ulnar 148 490 30.96 28.13
Radial 17 51 3.56 2.93
Digital 151 671 31.59 38.52
Clinical and experimental study of peripheral nerve regeneration
90
0100200300400500600700800
Constanta Bucharest %Constanta %BucharestMedian
Ulnar
Radial
Digital
Chart no. 21
Chart no. 22
Chart no. 23
Clinical and experimental study of peripheral nerve regeneration
91 Like we saw in previous table and graphs the most affected
nerves were digital nerves (151 in Constanta Emergency Hospital and
671―Floreasca‖ Emergency Hospital Bucharest ) followed by median
and ulnar nerve in the forearm.
AAcccciiddeenntt llooccaattiioonn
Table no. 17
Constanta Bucharest %Constanta %Bucharest
Household 184 571 38.49 32.78
Work 294 1171 61.51 67.22
Chart no. 24
Chart no. 25
Clinical and experimental study of peripheral nerve regeneration
92
0200400600800100012001400
Constanta BucharestHousehold
Work
Chart no. 26
TTyyppee ooff aannaaeesstthheessiiaa
Table no.18
Constanta Bucharest %Constanta %Bucharest
General
anaesthesia 364 1564 76.15 89.78
Local
anaest hesia 114 178 23.85 10.22
Chart no. 27
Clinical and experimental study of peripheral nerve regeneration
93
Chart no. 28
020040060080010001200140016001800
Constanta BucharestGeneral anaesthesia
Local anaesthesia
Chart no. 29
When performing procedures on the hands and upper extremities,
many options are available for anesthesia. General anesthesia techniques
can be applied for hand and upper extremity p rocedures the same as for
procedures on the rest of the body. However,regional anesthetics have a
unique application for procedures of the hand, including axillary,, wrist, and
digital blocks. When used in the proper setting and patient population,
regiona l anesthesia can be applied safely for procedures involving the
upper extremities and the hands. In general, small needles and lower
Clinical and experimental study of peripheral nerve regeneration
94 volumes of local anesthetic should be used in regional anesthesia to
minimize the risk of neurovascular complications. More over, epinephrine
can be used to augment local anesthetics to provide a longer duration of
action, lower risk of adverse systemic effects, and less bleeding at the
surgical site.
TTiimmee ooff rreeppaaiirr
Table no.19
Constanta Bucharest %Constanta %Bucharest
Primary repair 392 1521 82.01 87.31
Secondary repair 86 221 17.99 12.69
Chart no. 30
Clinical and experimental study of peripheral nerve regeneration
95
Chart no. 31
Chart no. 32
SSuurrggiiccaall pprroocceedduurree
Table no. 20
Constanta Bucharest %Constanta %Bucharest
Epineural 440 972 92.05 55.80
Fascicular groups 20 420 4.18 24.11
Fascicular 0 220 0.00 12.63
Nerve graft 18 130 3.77 7.46
Clinical and experimental study of peripheral nerve regeneration
96
Chart no. 33
Chart no. 34
020040060080010001200
Epineural Fascicular
groupsFascicular
groupsNerve graftConstanta
Bucharest
Chart no. 35
Clinical and experimental study of peripheral nerve regeneration
97 Nowadays there is no surgical repair technique that can ensure
recovery of tactile discrimination in the hand of an adult patient following
nerve repair while very young individuals usually regain a complete
recovery of functional sensibility. Post -traumatic nerve regeneration is a
complex biological process where the outcome depends on multiple
biological and environmental factors such as surv ival of nerve cells, axonal
regeneration rate, extent of axonal misdirection, type of injury, type of
nerve, level of the lesion, age of the patient and compliance to training. A
major problem is the cortical functional reorganization of hand
representatio n which occurs as a result of axonal misdirection. Although
protective sensibility usually occurs following nerve repair, tactile
discriminative functions seldom recover –a direct result of cortical
remapping. Sensory re -education programmes are routinely applied to
facilitate understanding of the new sensory patterns provided by the hand.
In severe injuries of different causes there may be a defect between
the severed nerve ends after resection of necrotic tissue of the nerve trunk.
As a support for the ax ons such a defect has to be bridged by a nervegraft
. A number of different donor nerves,preferably sensory branches, are
available. The most common donor nerve is the sural nerve. At harvest it is
possible to get a long (from the lateral malleolus up to j ust below the knee)
graft with few branches . Other donor nerves are the medial antebrachial
cutaneous nerve in the forearm and the terminal branch of the posterior
interosseous nerve. The latter two are particularly suitable for digital
nerves. For digita l nerves the use of autologous nerve grafts has been
questioned due to potential sequelae after harvesting. Nerve tubes or other
alternatives may be selected in such situations.
Choice of nerve repair
Epineural
Sutures through the epineural sheath
Used in pure motor or pure sensory nerves, digital, radial and
median nerves, sharply or evenly severed nerves
Clinical and experimental study of peripheral nerve regeneration
98 Group fascicular
Connection of matching groups or bundles of fascicles by
placement of sutures in epi -fascicular epineurium
Used in larger nerves and p artially severed or unevenly
transected or avulsed nerves
Fascicular
Connection of isolated fasciculi, by placement of sutures in the
perineurium
Used in neuroma, in continuity, in small nerves, partially
severed nerve when only a few fascicles are severed
Graft
Nerve grafting is indicated, if gap is 3 – 7 cm or if repair is
impossible without tension
Nerves which can be used as grafts are the lateral cutaneous
nerve of the thigh, the saphenous nerve, the sural nerve, and
the medial cutaneous nerve of the forearm
If ulnar and median nerves are irreparable, a segment of the
ulnar nerve can be used to bridge the median nerve
If the graft nerve diameter is small, several strips may be
needed (cable graft) and grafts should be 15% longer to avoid
tension
HHoossppiittaalliizzaattiioonn ppeerriioodd
Table no. 21
Constanta Bucharest %Constanta %Bucharest
1 – 5 days 287 1342 60.04 77.04
6 – 14 days 178 298 37.24 17.11
>14 days 13 92 2.72 5.28
Clinical and experimental study of peripheral nerve regeneration
99
Chart no.36
The hospitalisation period was in Constanta Emergency Hospital
in 60.0 4% of cases between 1 and 5 days with an average period of 3
days.
Chart no. 37
Clinical and experimental study of peripheral nerve regeneration
100
Chart no. 38
ASSESSMENT CRITERIA
The evaluation of motor and sensitive function was done following
the international criteria:
MOTOR FUNCTION
RADIAL NERVE:
M0 – complete palsy
M1 – visible contraction
M2 – poor forearm muscles contraction against gravitation
M3 – contraction against gravitation gravitation
M4 – contraction against resistance
M5 – normal contraction
Clinical and experimental study of peripheral nerve regeneration
101 MEDIAN NERVE
M0 – complete palsy
M1 – poor forearm muscles contraction
M1* – forearm muscles contraction against gravitation but thenarian muscles
palsy
M2 – forearm muscles contraction against gravitation and poor thenarian
muscles contraction
M3 – forearm and thenarian muscles contraction agains t resistance
M4 – all muscles contraction against hard resistance
M5 – normal contraction
ULNAR NERVE
M0 – complete palsy
M1 – poor forearm muscles contraction
M1* – forearm muscles contraction against gravitation but hand intrinsic
muscles palsy
M2 – forearm muscles contraction against gravitation and poor hipothenarian
muscles contraction, interossei muscles palsy
M3 – forearm, thenarian muscles, and interossei muscles for comisural
space I contraction against resistance
M4 – all muscle contraction again st resistance
M5 – normal contraction
SENSITIVE ASSESSMENT
S0 – loss of sensitivity in entire sensitive area
S1 – deep pain feelling
S2 – poor superficial pain feelling and restore of sensitivity in some areas
S2* – pain feelling and restore of sensitivit y but presence of overreactions
S3 – – pain feelling and restore of sensitivity without overreactions
S3* – pain feelling and restore of sensitivity without overreactions and some
areas of 2 points discriminations
S4 – complete recovery
Clinical and experimental study of peripheral nerve regeneration
102 RESULTS ASSESSMEN T
MEDIAN NERVE
Good : S4 or S3* M3
Poor : S3 M2
Bad : S1 or S2 M1 or M0
CONSTANTA
Table no. 22 – Constanta
Chart no. 39
BUCHAREST
Table no. 23 – Bucharest RESULTS NO. OF CASES PERCENTAGE %
GOOD 96 59.26
POOR 53 32.72
BAD 13 8.02
RESULTS NO. O F CASES PERCENTAGE %
GOOD 396 74.72
POOR 96 18.11
BAD 38 7.17
Clinical and experimental study of peripheral nerve regeneration
103
Chart no. 40
Chart no. 41
ULNAR NERVE
Good : S3 M4
Poor : S2 M3
Bad : S1 or S0, M1 or M2
Clinical and experimental study of peripheral nerve regeneration
104 CONSTANTA
Table no. 24
Chart no. 42
BUCHAREST
Table no. 25
RESULTS NO. OF CASES PERCENTAGE %
GOOD 89 64.19
POOR 42 24.32
BAD 17 11.49
RESULTS NO. OF CASES PERCENTAGE %
GOOD 361 73.67
POOR 84 17.14
BAD 45 9.18
Clinical and experimental study of peripheral nerve regeneration
105
Chart no. 43
Chart no. 44
RADIAL NERVE
Good : M4
Poor : M3
Bad : M2 or M1
Clinical and experimental study of peripheral nerve regeneration
106 CONSTANTA
Table no. 2 6
Chart no.45
BUCHAREST
Table no. 27 RESULTS NO. OF CASES PERCENTAGE %
GOOD 10 58.82
POOR 5 29.41
BAD 2 11.76
RESULTS NO. OF CASES PERCENTAGE %
GOOD 37 72.55
POOR 10 19.61
BAD 4 7.84
Clinical and experimental study of peripheral nerve regeneration
107
Chart no. 46
Chart no. 47
DIGITAL NERVES
Good : S4 or S3*
Poor : S3
Bad : S1 or S2
Clinical and experimental study of peripheral nerve regeneration
108 CONSTANTA
Table no.28
Chart no. 48
BUCHAREST
Table no. 29
RESULTS NO. OF CASES PERCENTAGE %
GOOD 132 87.42
POOR 15 9.93
BAD 4 2.65
RESULTS NO. OF CASES PERCENTAGE %
GOOD 592 88.23
POOR 68 10.13
BAD 11 1.64
Clinical and experimental study of peripheral nerve regeneration
109
Chart no. 49
Chart no. 50
In lesions of the median or ulnar nerves, DASH -score and strength
measured with the vigorimeter correlated significantly . The higher the
DASH -score, the lower the corresponding grip strength and return of
sensibility . Seventy -four percent of patients were satisfied with the
regenerative results.
The Tinel's sign was positive in 50% of the patients. Its prevalence at
the time of examination correlated significantly with an inferior return of
sensitivity .
Clinical and experimental study of peripheral nerve regeneration
110 The median pe riod of disability after nerve reconstruction was 33
days (7 -150 days) for lesions to the digital nerves and 90 days (28 -1,050
days) for those to the ulnar and median nerves. Longer periods were
associated with severe concomitant injuries.
Seventeen percen t of the patients suffered from concomitant
diseases such as diabetes mellitus, coronary heart diseases, or
polyneuropathia. We did not detect significant correlation with the return of
sensibility.
Clinical and experimental study of peripheral nerve regeneration
111
DDIISSCCUUSSSSIIOONNSS
Currently even under perfect conditions , nerve regeneration can
never achieve complete histological and clinical recovery. Thus, recovery is
often disappointing. However, the period of functional improvement
following nerve repair can last for at least 3 to even 5 years. Care should
be taken th at nerve reconstruction is being performed by micro – and hand
surgically experienced physicians to guarantee proper surgical treatment.
Consistent sensory training by the physiotherapist plays a major role in the
postoperative care. But, because of the lim ited evidence available and the
variation between the interventions studied, no specific sensory
reeducation intervention can be recommended yet . The strategy is to
activate the cortical area representing the damaged nerve to maintain the
cortical represe ntation of the affected body part that is increasing with
prolonged denervation
The patient's age is one of the major predictors for recovery. Results
deteriorate with advancing age as was demonstrated in this study. The
best results are seen in children. Furthermore, nerve regeneration seems
to deteriorate after the fifth – to sixth -life decade. No evidence was found
that gender influences recovery .
Delay of nerve reconstruction after transection also has detrimental
effects on functional outcome .In some injuries, for example, with strong
contamination, secondary reconstruction is required. But if possible, nerve
continuity should be re -established primarily. With a delay of 6 months
between injury and reconstruction, the chance of satisfactory recovery
declines slowly.
There is general consent that tension on the nerve coaptation is
substantially detrimental for nerve regeneration. If tensionless coaptation
cannot be achieved, the nerve gap requires reconstruction, usually
performed with a nerve graft. Tu bulization seems to provide comparable
Clinical and experimental study of peripheral nerve regeneration
112 results given a gap length of less than 3 cm. But even if longer distances
can be bridged by autologous nerve grafting, recovery deteriorates with
nerve grafts measuring more than 3 -5 cm in length .
Nerve regeneration also seems to deteriorate with increasing
distance to the innervated organ, which was confirmed in this study. The
reasons for this phenomenon are manifold and not completely understood.
Axons have to reorganize and search for their distal counterparts af ter
complete transection (neurotmesis ). The more proximal the nerve injury,
the lower the chances for the axons to re -innervate adequate terminal
receptors and organs because possible misdirections increase.
In proximal nerve lesions, atrophy of muscle and sensory receptors
may have occurred because of too long a time lapse before re -innervation
can take place .
In experimental settings, different neurotrophic (growth support) and
neurotropic (directional guiding) substances showed abilities to improve
peripheral nerve regeneration when administered systemically or locally,
but for now all these approaches only render rather minor improvements .
Even though there are a multitude of extensive and precise
modalities for documentation of outcome after nerve rep air , for the daily
clinical practice, tools for examination of nerve regeneration have to be fast
and easy to handle, while being highly reproducible and objective.
Retained values should be easily understandable and should allow good
comparability for fo llow-up. 2PD measurement has been the gold standard
for years. It does not need special equipment; a paper clip may be enough.
While m2PD aims at the fast adapting mechanoreceptors, the Pacinian and
Meissner's corpuscles , s2PD indicates the function of th e slowly adapting
receptors, the Merkel's discs . Both values show high correlation, with the
values of the m2PD being usually slightly below those of the s2PD. For
standard clinical examination, the measurement of s2PD seems to be
sufficient.
Some studies argue that monofilament testing provides advantages
in terms of validity, but in general, results show high correlation with 2PD –
measurement. In our experience, s2PD is faster and easier to handle.
Clinical and experimental study of peripheral nerve regeneration
113 Techniques to measure changes in skin structure and funct ion are rather
intricate and generally found no place in the daily clinical practice.
Measurement of grip strength, for example, with the Jamar
dynamometer or vigorimeter is a valuable tool to estimate the return of
motor function that can be easily assess ed with every consultation . All
values should always be compared with the results of the uninjured
contralateral side.
Summing up, for the daily clinical practice, s2PD, location of the
Tinel's sign, and grip strength measurement seem to be fast and
repro ducible tools to follow up nerve regeneration at the upper extremity.
Protection sensibility should be checked if no s2PD can be detected.
Patients should further be asked for the prevalence of disturbing
hyperesthesia or cold intolerance. However, further examinations may be
required for study purposes or detailed medical reports.
Clinical and experimental study of peripheral nerve regeneration
114
CCOONNCCLLUUSSIIOONNSS
1. In recent past there have been significant developments in the
management of peripheral nerve injuries. The advent of
microsurgical techniques with use of magnifi cation, micro -sutures
and micro instruments has considerably improved the results in
nerve repairs. Many advances have been made in the area of
neurobiology of nerve injury and regeneration, and increasing
attempts are being made in the use of nerve allogr afts and nerve
conduits for bridging the gaps.
2. We conclude that silicone tube technique is a good technique as an
alternative for nerve graft
3. Are not significant differences for nerve recovery between silicone
tube group (54.5%recovery at 6 month, 58.85 %at 9 months) and
control group (59.66% at 6 month, 68.61% at 9 months)
4. We conclude that seeding chopped nerve in the suture is not a viable
alternative for nerve graft, so we don’t continue this study in the
future
5. The body of knowledge regarding nerve grafts is extensive, long –
term motor and sensory recovery is not always achieved. Continued
research and experimentation by plastic surgeons can determine the
maximum time for immobilization, time from injury to graft, and
amount of suture tension, as well as the relative importance of these
and other factors in determining outcomes.
Clinical and experimental study of peripheral nerve regeneration
115 6. Repair of a short gap in the nerve by stretch repair with an end -to-
end anastomosis, even with some degree of tension, is followed by
better recovery than by grafting. Howeve r, where a graft is
necessary, a similar level of recovery will result from use of a sural
nerve graft.
7. In this moment microsurgical repair of peripheral nerves remain the
―golden standard‖ for plastic surgery departments.
8. In most of the cases epineural sutureing is enough for a good
peripheral nerve recovery but fascicular groups repair is a good
alternative when is possible. Fascicular repair is limited to selected
cases.
9. Treatment of peripheral nerves injuries is not only a mechanic
problem and surger y cannot solve it . Surgeon can aproximate and
suture nerve fascicles but axon recovery canot be managed surgical
– this is a complex process regulate biological to molecular level.
10. Peripheral nerve injuries requiring surgical intervention will
have bette r results the earlier the nerve is repaired after injury.
Therefore, repairs with or without grafting done immediately after the
injury have better results, with progressively worsening results if
done 3, 6, 9, or 12 months or longer after the injury.
11. Young patients can recover close -to-normal nerve function. In
contrast, a patient over 60 years old with a cut nerve in the hand
would expect to recover only protective sensation; that is, the ability
to distinguish hot/cold or sharp/dull.
12. Smoking may worse n the damage caused to peripheral nerves
by ischemia and reperfusion. This holds important implications for
cigarette smokers who sustain extremity injuries or who suffer from
Clinical and experimental study of peripheral nerve regeneration
116 nerve damage syndromes. Smoking cessation may prove to be a
useful adjunct in th e treatment of patients with nerve injuries.
13. Men present more hand traumatic lesions than women
because of their professional and domestic activities that predispose
them to accidents
14. Results of microsurgical nerve repair depends of many
important factor s: age, level of injury, associated comorbidities,
quality of sirgical technique, patient level of understanding, moment
of repair, postoperative care, rehabilitation program.
Clinical and experimental study of peripheral nerve regeneration
117
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