1
DISORDERS OF PERIPHERAL NERVES
POLYNEUROPATHIES, MONONEUROPATHIES
Eva Vlčková, Department of Neurology, University Hospital Brno
2
PERIPHERAL NEUROPATHIES
Common neurological problems caused by
disordered function and structure of
peripheral motor, sensory, and autonomic
nerves.
The clinical presentations is highly
variable:
̶ Mononeuropathies/ multiple
mononeuropathies/ plexopathies or
radiculopathies/ polyneuropathies
̶ Motor and/or sensory and/or autonomic
The causes are disparate and include:
̶ entrapment and trauma;
̶ inherited disorders;
̶ diabetes, and other metabolic diseases;
̶ inflammatory demyelinating conditons;
̶ vasculitis and rheumatic diseases;
̶ paraneoplastic conditions;
̶ deficiency states;
̶ infections; and toxins.
3
PATHOLOGICAL PROCESSES IN
PERIPHERAL NERVES
̶ Despite the large number of causes for neuropathy, the pathological reactions of peripheral
nerves to various insults remain limited and include:
̶ (1) axonal degeneration or axonopathy (see next slides) including:
̶ wallerian degeneration (degeneration of axons and their myelin sheath distal to the site of transection) =
the response to axonal interruption, recovery depends on the continuity of the nerve sheaths;
̶ primary neuronal (perikaryal) degeneration or neuronopathy (Either lower motor neurons or
dorsal root ganglion cells may be affected leading to motor neuron diseases or sensory neuronopathy. Little or no
recovery takes place particularly in the latter one);
̶ (2) segmental demyelination (see next slides)
̶ in many neuropathies, axonal degeneration and segmental demyelination COEXIST.
̶ Following characteristics help to establish the underlying pathological change:
̶ The patient's symptoms + the pattern of distribution of signs
̶ Nerve conduction studies and needle EMG
Adopted from: Poage C, Roth C, Scott B. Peroneal Nerve Palsy: Evaluation and Management. J Am Acad Orthop Surg. 2016;24(1):1-10..
Öriginally published by: Seddon HJ: A classification of nerve injuries. Br Med J 1942;2(4260):237-239.
Sunderland S: A classification of peripheral nerve injuries producing loss of function. Brain 1951;74(4):491-516.
Picture taken from: Arslantunali D, Dursun T, Yucel D, Hasirci N, Hasirci V. Peripheral nerve conduits: technology update. Med Devices (Auckl). 2014;7:405-24.
4
CLASSIFICATION OF
NERVE INJURIES
Picture taken from: Arslantunali et al.
No need to know the information in detail  - just that it exists
5
PATHOLOGICAL PROCESSES IN
PERIPHERAL NERVE
̶ AXONOPATHY: the most frequent one,
̶ presumably caused by metabolic derangement within neurons – metabolic or toxic,
̶ starts at the most distal part of the nerve fiber and progresses toward the nerve cell body,
hence the term dying-back or length-dependent neuropathy
̶ clinically presents with distal symmetrical polyneuropathy
̶ axonal regeneration proceeds at a maximal rate of 2 to 3 mm per day, recovery may be
delayed and is often incomplete
̶ DEMYELINATION: injury of myelin sheaths or Schwann cells, resulting in breakdown of
myelin with sparing of axons → no major atrophies despite the presence of weakness.
̶ In immune-mediated, some hereditary and compression neuropathies.
̶ Remyelination may occure (even within days or weeks)
6
DIAGNOSTIC APPROACH
A diagnostic approach to neuropathies consists of:
̶ (1) careful history,
̶ (2) detailed physical and neurological examination,
̶ (3) electrophysiological studies, which not only confirm the presence of a
peripheral nerve disorder but also shorten the list of diagnostic possibilities,
̶ (4) later, further laboratory studies to determine a specific diagnosis are usually
performer based on the outcome of the initial evaluation (blood tests, nerve biopsy,
skin biopsy…)
It is possible to establish a specific diagnosis in up to 75% of patients evaluated in
tertiary referral centers by experts in neuromuscular disorders.
7
ELECTROPHYSIOLOGICAL STUDIES
NCS/ EMG
̶ Confirm the presence and clinical
distribution of neuropathy (and disclose
subclinical abnormities)
̶ Distinguish between pure sensory/ pure
motor/ sensory-motor abnormities
̶ Disclose the presence and extent of
axonal/ demyelinating changes (see
next slides)
̶ A needle EMG of distal muscles may
show acute, subacute or chronic
denervation/reinnervation changes
̶ Only LARGE FIBERS (see next slide  )
According to : Misulis KE. CHAPTER 30 – Sensory Abnormalities of the Limbs, Trunk, and Face. In Bradley WG, Daroff RB,
Fenichel GM, Jankovic J. Neurology in Clinical Practice, 5th ed. London: Elsevier 2008.
8
SENSORY NERVE FIBERS – REMINDER 
̶ small myelinated and unmyelinated fibers (A-delta + C) are NOCICEPTIVE and
responsible for thermal perception (both warm and cold) – prominent impairment of these
nerve fibers leads to SMALL FIBER NEUROPATHY (SFN)
̶ large-diameter myelinated fibers (A-alfa, A-beta) are NON-NOCICEPTIVE (proprioception,
vibration sense, discriminative touch, pressure) – impairment leading to LARGE FIBER NEUROPATHY
CLASS (OLDER TERMINOLOGY) DIAMETER CONDUCTION VELOCITY MODALITIES
Ia (Aα) (myelinated) 12-20 μm 70-100 m/sec Proprioception (muscle spindles)
Ib (Aα) (myelinated) 12-20 μm 70-100 m/sec Proprioception (Golgi tendon organs)
II (Aβ) (myelinated) 5-12 μm 30-70 m/sec Touch and pressure from skin; proprioception from muscle spindles
III (Aδ) (myelinated) 2-5 μm 10-30 m/sec Pain and temperature; sharp sensation; joint and muscle pain sensation
IV (C, unmyelinated) 0.5-2.0 μm 0.5-2.0 m/sec Pain, temperature
No need to know it in detail (just to know the basic classification and get some idea about the principles )
MOTOR NERVE CONDUCTION
STUDIES
STIMULATION
ARTEFACT
DML
CMAP
distal
AREA
CMAP
prox.
AREA
PML
DISTAL
STIMULATION
SITE
PROXIMAL
STIMULATION
SITE
The response to the electrical stimulation = ACTION
POTENCIAL (mV) = CMAP (compound muscle AP)
DISTAL
STIMULATION
PROXIMAL
STIMULATION
AMPLITUDE
AMPLITUDE
THE NERVE
CONDUCTION
VELOCITY is
computed from
the difference
between PML
and DML and
the distance
between distal
and proximal
stimulation site
DML = distal motor latency
PML = proximal motor latency
10
MOTOR NCS –
CONDUCTION BLOCK
̶ In acquired demyelination (i.e., inflammatory
or compression demyelination, but not
hereditary myelinopathies) the presence
conduction block and temporal dispersion
of CMAP represent typical abnormity
̶ Conduction block is defined as a reduction of
either amplitude or area of the compound
motor action potential elicited by proximal vs.
distal motor nerve stimulation
̶ The block results in a loss of the ability of the
nerve AP to reach the muscle, thereby
producing weakness, though the axon remains
intact (= little muscle atrophy)
PHYSIOLOGICALLY,
THE RESPONSES HAVE
THE SAME SIZE AND
SHAPE IN DISTAL AND
ANY PROXIMAL
STIMULATION
11
SENSORY NERVE CONDUCTION STUDIES
The response to the electrical stimulation = ACTION
POTENCIAL (mV) = SNAP (sensory nerve AP)
SNAP
AREA
DSL
THE NERVE CONDUCTION VELOCITY is
computed from the DSL and the distance
between the active electrode and the
stimulation site
AMPLITUDE
Picture taken from: https://www.intechopen.com/books/electrodiagnosis-in-new-frontiers-of-clinical-
research/overview-of-the-application-of-emg-recording-in-the-diagnosis-and-approach-of-neurological-disorders
NEEDLE EMG
̶ detects the electric potential generated by
muscle cells at rest or during the activity
(muscle unit potentials – MUPs, MUAPs).
̶ Evaluation of MUP parameters helps to
distinguish between myopathic/ neuropathic
changes (reinnervation)
̶ Evaluation of the presence/ absence of
spontaneous activity at rest may disclose
denervation changes, myotonic discharges,
fasciculations and other specific abnormities
DENERVATION REINNERVATIONNORMA
NEEDLE EMG - AT REST (IN RELAXED MUSCLE)
PHYSIOLOGICAL CONDITIONS
No electrical activity
ACUTE DENNERVATION (AXONAL LESION)
Abnormal spontaneous activity – fibrilations,
positive sharp waves (PSW)
NEEDLE EMG: ABNORMAL SPONTANEOUS ACTIVITY
MYOTONIC DISCHARGE FASCICULATIONS
https://www.youtube.com/watch?v=6-3PP_S-Q8I
NEEDLE EMG – DURING ACTIVITY
The evaluation of MUPs (motor unit potentials) and the interference pattern
Reinnervation (chronic neurogennic changes) Myogennic changes
Force Minimum Moderate Maximum
Force Minimum Moderate Maximum
16
AXONAL NCS/EMG CHANGES
̶ Axonopathies result in low-amplitude sensory
nerve action potentials (SNAPs) and compound
muscle action potentials (CMAPs) with no major
impact on latencies and velocities.
̶ denervation/ reinnervation changes are proven by
needle EMG.
NORMAL FINDING
DEMYELINATION
CHANGES
AXONAL DEGENERATION
17
Demyelination results in:
̶ the reduction of motor and sensory nerve
conduction velocities (NCVs) with relative
preservation of response amplitudes.
̶ marked prolongation of distal motor/sensory
latencies
̶ In acquired demyelination the presence
conduction block (and temporal dispersion
of CMAP) represent typical abnormities
̶ No major needle EMG changes unless there
is secondary axonal damage
DEMYELINATING NCS/EMG
CHANGES
NORMAL FINDING
DEMYELINATION
CHANGES
AXONAL DEGENERATION
CONDUCTION BLOCK
TEMPORAL
DISPERSION
18
LABORATORY TESTS
̶ The clinical neuropathic patterns and the results of electrodiagnostic studies guide
the experienced clinician to select the most appropriate laboratory tests
̶ Some laboratory tests should be obtained routinely in all patients with peripheral
neuropathy. These include:
̶ complete blood count
̶ sedimentation rate (or C-reactive protein)
̶ chemistry profile (fasting blood sugar, thyroid studies, vitamin B12 level, and serum
protein electrophoresis with immunofixation electrophoresis).
̶ If inherited neuropathy is considered, an ever-increasing number of molecular genetic
tests is available.
̶ Cerebrospinal fluid (CSF) examination is helpful in the evaluation of suspected
demyelinating neuropathies and polyradiculopathies related to meningeal carcinomatosis or lymphomatosis
19
NERVE BIOPSY
̶ Not performed routinely
̶ Mainly important in asymmetric forms causing
significant functional disability (weakness or
sensory deficit), deteriorate rapidly and is
not explained by other methods
̶ Most frequently sural nerve (tibial, superficial
peroneal, superficial radial or obturatory)
̶ Used mainly to confirm/ (exclude):
̶ Vasculitis, perineuritis
̶ Systemic disorders (amyloidosis, leprosy, sarcoidosis)
̶ Demyelinating or some hereditary neuropathies
(mostly not needed)
Picture taken from: https://www.sciencedirect.com/topics/medicine-and dentistry/
nerve-biopsy
20
SMALL FIBER
NEUROPATHY TESTING
̶ A gold standard to document small fiber
neuropathy = skin biopsy with the evaluation
of intraepidermal nerve fiber density (IENFD,
loss of small nerve fibers in skin)
̶ Thermal threshold testing (TTT/QST) – see
the presentation on sensory system
̶ Corneal confocal microscopy (CCM) – direct
visualisation of corneal small nerve fibers
QST QST QST
CCM CCM
CCM
IENFD IENFDIENFD
IENFD
21
THE CLINICAL MANIFESTATION
The first step in the examination of patients with neuropathy is to determine the
anatomical pattern and localization of the disease process (see next slides), and
whether motor, sensory, or autonomic nerves are involved.
Both the POSITIVE AND NEGATIVE symptoms may occure.
̶ Positive symptoms of motor dysfunction: muscle cramps, fasciculations, myokymia
̶ Negative motor symptoms include weakness (in polyneuropathies, negative sensory symptoms
usually start with early distal toe and ankle extensor weakness, resulting in tripping on rugs or unevenground. If the
fingers are weak, patients may complain of difficulty in opening jars or turning a key in a lock).
̶ Positive sensory symptoms include paresthesias, dysesthesias, and neuropathic
pain (and possibly allodynia).
̶ Negative sensory symptoms include the numbness and sensory ataxia (which
contributes to the walking difficulty)
22
THE CLINICAL MANIFESTATION –
AUTONOMIC SYMPTOMS
Their presence can be helpful in directing attention toward specific neuropathies that
have prominent autonomic symptoms (HSAN, GBS, some of the diabetic neuropathies).
It is important to ask the patient about:
̶ the symptoms of orthostatic intolerance (lightheadedness), repeated faintness or
fainting spells as symptoms of the cardiovascular autonomic neuropathy,
̶ reduced or excessive sweating, and heat intolerance
̶ well as bladder, bowel, and sexual dysfunction
̶ anorexia, early satiety, nausea, and vomiting are symptoms suggestive of gastroparesis
̶ The degree of autonomic involvement can be documented by noninvasive autonomic
function studies
23
ANATOMIC PATTERNS
̶ MONONEUROPATHY means focal involvement of
a single nerve and implies a local process (most
frequently trauma or compression/entrapment…)
̶ MULTIPLE MONONEUROPATHY, OR MONONEUROPATHY MULTIPLEX,
signifies simultaneous or sequential damage to multiple noncontiguous nerves.
Usually axonal. The most frequent cause is vasculitis or diabetic microangiopathy.
̶ Single nerve root (MONORADICULOPATHY) is a typical manifestation of
spondylogennic disorders and similar to brachial or lumbar PLEXOPATHIES, they
may be caused also by infectious diseases or diabetes mellitus….
̶ POLYNEUROPATHY is most commonly characterized by symmetrical, distal motor
and sensory deficits that have a graded increase in severity distally and by distal
attenuation of reflexes. Wide range of causes should be considered with diabetes
mellitus as the most prominent one in „western world“.
Picture taken from: https://www.lecturio.com/magazine/polyneuropathies/
24
POLYNEUROPATHIES
̶ most commonly characterized by symmetrical deficits
that have a graded increase in severity distally
̶ most polyneuropathies produce mixed sensorimotor
deficits and some degree of autonomic dysfunction.
̶ Typical clinical features:
̶ Distal (or even general) attenuation of reflexes.
̶ The sensory deficits generally follow a length-dependent stocking-glove pattern.
̶ Predominantly small/ large or both types of nerve fibers may be affected (see the
presentation focused on sensory deficits) leading to the dominant impairment of pain +
temperature sensation or vibration sense + proprioception (+ sensory ataxia) or both
̶ Motor weakness is greater in extensor muscles than in corresponding flexors
(walking on heels is affected earlier than toe walking in most polyneuropathies).
̶ Autonomic symptoms mentioned above may also be present in some polyneuropaties
25
POLYNEUROPATHIES
̶ classified according to several criteria. Vice versa, these
aspects may help to establish what´s causing neuropathy.
̶ Classification based on the DURATION OF SYMPTOMS:
̶ acute (the symptoms develop within few days up to 4 weeks)
̶ subacute (4-12 weeks)
̶ chronic (the symptoms develop more than 12 weeks)
̶ Classification based on the COURSE OF THE DISEASE:
̶ monophasic
̶ relapsing
̶ progressive (slowly / rapidly / stepwise)
SLOWLY
PROGRESSIVE
STEPWISE
PROGRESSIVE
RELAPSING-
REMITTING
26
POLYNEUROPATHIES
̶ Classification based on the PREDOMINANT
PATHOLOGICAL PROCESS in peripheral nerves:
̶ Axonal (more frequent, limited treatment options)
̶ Demyelinating = autoimmune inflammatory (less
frequent, treatable) or hereditary
̶ Classification based on the TYPE OF THE NERVE
FIBERS AFFECTED:
̶ Small fiber neuropathies
̶ Large fiber neuropathies (among others most demyelinating
neuropathies, where the small fibers are relatively preserved)
̶ Mixed fiber neuropathies
Sural nerve
biopsy,
transverse
section,
toluidine blue
staining =
55-68% of the
nerve fibers are
small (those
without dark
blue edging)↓↓
27
ACUTE POLYNEUROPATHIES – GBS
The most frequent acute PNP = Guillain-Barré syndrome (GBS)
̶ an immune-mediated rapidly progressive polyneuropathy whose aetiology and
pathogenesis are not yet fully understood
̶ Usually preceeded by infection (campylobacter, viruses) or vaccination, auto-antibodies
against nerve gangliosides are suggested to play a central role in the pathogenesis
incidence of GBS increases linearly with age, peaking at 70-80 years, with a maximum of 4-
5 cases per 100,000 person years
̶ GBS can be subclassified into a number of variants, depending on clinical presentation
and electrophysiological findings:
̶ Demyelinating forms (Acute Inflammatory Demyelinating Polyneuropathy/polyradiculoneuropathy, AIDP).
̶ Axonal forms (Acute Motor or Motor/Sensory Axonal Neuropathy – AMAN or AMSAN)
28
ACUTE POLYNEUROPATHIES - GBS
AIDP x AMAN/AMSAN clinical picture:
̶ rapid progression (over days to 4 weaks)
̶ symmetrical weakness of both legs and arms (flaccid para- or tetraparesis)
̶ in the peak phase of the disease, about 75% of patients can no longer walk
unaided, 30% are tetraparetic, 35-50% show cranial nerve involvement, and 15-
20% have respiratory failure and/or autonomic dysfunction.
̶ up to 70% suffer from neuropathic pain
Recovery begins 2-4 weaks after progression ceases
even in non-treated patients (sooner in treated patients)
Picture taken from:
Pieter A. van Doorn. Diagnosis, treatment and prognosis of
Guillain-Barré syndrome (GBS). La Presse Médicale 2013: 42(6).
29
ACUTE POLYNEUROPATHIES - GBS
̶ Diagnosis: clinical picture, NCS/EMG (AIDP/AMAN) and CSF (albuminocytological dissociation)
̶ Treatment:
̶ Immunomodulatory therapy with plasmapheresis (PE) or intravenous
immunoglobulins (IVIG) has been proven effective in GBS, namely by accelerating
the improvement of weakness.
̶ No response to corticosteroids
̶ Improvement follows a plateau phase that ranges from days to weeks and runs an
extremely variable course, regardless of whether a specific therapy has been applied or not
̶ Physical therapy, venous thromboembolism prophylaxis, nursing
30
ACUTE POLYNEUROPATHIES - OTHER
̶ Other acute neuropathies (very
rare!!!)
̶ Acute porphyria
̶ Some types of diabetic neuropathy
or some toxic neuropathies
̶ Vasculitic neuropathy can cause
hyperacute (multiple)
mononeuropathies usually
occurring by 24–72 h
Vasculitic neuropathy, picture taken from Gwathmey KG,
Burns TM, Collins MP, Dyck PJB. Vasculitic neuropathies.
Lancet Neurology. 2014;13(1):67-82
31
CHRONIC POLYNEUROPATHIES - CAUSES
̶ diabetes mellitus – the most common cause in the western world (see next slides);
̶ other metabolic diseases (thyroid disorders, liver or kidney diseases);
̶ inflammatory demyelinating conditons
Chronic inflammatory demyelinating polyneuropaty (CIDP);
Multifocal motor neuropathy (MMN)
̶ vasculitis and rheumatic diseases (mostly asymmetric, nerve biopsy needed);
̶ paraneoplastic (S-M, axonal, ⁓5% of cancer patients, or autonomic or sensory neuronopathy), antibodies in some);
̶ deficiency states (B12 – posterior columns dysfunction, folic acid, B1, B2, B6);
̶ infections (leprosy, lyme disease, varicella zoster virus, HIV, hepatitis C, Zika - AMAN);
̶ toxins (see next slides);
̶ inherited polyneuropathies (see next slides).
32
CHRONIC INFLAMMATORY DEMYELINATING
POLYNEUROPATHY (CIDP)
̶ Rare neurological disorder, suspected autoimmune basis
̶ Caused by the inflammation of nerve roots and peripheral nerves and destruction of
the myelin sheath of the nerve fibers = demyelinating
̶ The prevalence of CIDP ranges from 1 to 2 per 100,000
̶ Seen at all ages, with the peak incidence in the fifth and sixth decades
̶ Similar to GBS (AIDP), but:
̶ (1) the clinical course is more protracted in CIDP
̶ (2) CIDP is rarely associated with preceding infections
̶ (3) there is a response to corticosteroids in CIDP patients
33
CIDP: CLINICAL PICTURE
̶ symmetrical weakness of both legs and arms (flaccid para- or tetraparesis)
Muscle wasting is rarely pronounced, generalized hyporeflexia/areflexia is the rule
Proximal limb weakness is almost as severe as distal limb weakness, indicating a
nonlength dependency of the neuropathy (note difference from other types of PNP!)
̶ sensory disturbance is frequent (but some cases with predominantly motor involvement)
Numbness or tingling in stocking-glove distribution, pain occurs less frequently
̶ The degree of severity and the course of disease may vary from person to person.
̶ Two patterns of temporal evolution of CIDP can be seen:
̶ continuous or stepwise progressive course over months to years (> 60%)
̶ relapsing course with partial or complete recovery between recurrences (1/3)
34
CIDP: DIAGNOSTICS
̶ clinical picture
̶ NCS/EMG (demyelination!!!)
̶ CSF (albuminocytological dissociation)
̶ ultrasound: nerve enlargement of at least 2
proximal sites and/or the brachial plexus
̶ MRI: enlargement and/or increased signal intensity
of nerve root(s) on T2 MRI
̶ response to treatment (IVIg, plasma exchange,
corticosteroids)
̶ Sural nerve biopsy suggesting demyelination
Lehmann HC, Burke D,
Kuwabara S. Chronic
inflammatory demyelinating
polyneuropathy: update on
diagnosis,
immunopathogenesis and
treatment. J Neurol Neurosurg
Psychiatry 2019;90(9):981-987.
https://www.sciencephoto.com/k
eyword/mri-of-cidp
35
CIDP: TREATMENT
̶ Daily single-dose oral prednisone (started at 60 to 80 mg, improvement can be
anticipated within 2 months; by 3 months 88% improve. Following improvement, the dose
may be converted to an alternate-day, single-dose schedule)
̶ Alternative treatment with high-dose, intermittent, intravenous methylprednisolone
̶ Therapeutic plasma exchange (improvement faster – within days)
̶ IVIG using 0.4 g/kg/day on 5 consecutive days (improvement already during the first
week, maximal in 6 weeks). When secondary deterioration occurs, patients are retreated
with single IVIG infusions (0.4 to 1.0 g/kg), depending on the severity of the relapse
̶ Alternative forms of immunosuppressive treatment should be considered for patients
with CIDP who are refractory to corticosteroids, plasma exchange, and IVIG, or asused
as corticosteroid-sparing, adjunctive agents (no control trial available)
36
DIABETIC NEUROPATHY
̶ Microvascular complication
̶ Earlier and slightly higher prevalence in type 2 DM vs. type 1
̶ Prevalence depends on the confirmatory methods used:
̶ 7.5% at the disease onset
̶ 50% 25 years after onset
̶ Risk factors for developing diabetic neuropathy
̶ Glycemic control: Higher glycosylated hemoglobin
̶ Cardiovascular risk factors = Metabolic syndrome (hypertension, smoking, obesity,
high triglyceride levels)
̶ Presence of the cardiovascular disease
̶ Type 2 diabetes
37
TYPES OF NEUROPATHY IN DM PATIENTS
̶ Symmetric neuropathies
̶ Chronic
Distal sensory/autonomic
Autonomic
Sensory-motor
̶ Acute
Painful
Reversible
̶ Immune PN: predisposition
̶ CIDP
̶ Asymmetric neuropathies
̶ Lumbosacral plexopathy
̶ Radiculopathies
̶ Mononeuropathies (acute e.g cranial or ↑ susceptibility to entrapment)
̶ Mononeuritis multiplex
Distal
symmetric
polyneuropathy
(small/large fibers)
Radiculopathy
(truncal)
Plexopathy
(lumbosacral)
Mononeuropathies
(acute
or
entrapment)
Autonomic
neuropathy
Picture taken from: Feldman EL, Callaghan BC, et al. Diabetic neuropathy. Nat Rev Dis Primers. 2019;5(1):41.
38
TOXIC NEUROPATHIES
̶ Many agents, mostly axonal
̶ Alcoholic = direct toxic effect + nutritional defficiency (mainly B1 - associated also with
Wernicke´s (acute delirium + ataxia + ocular palsy) – Korsakoff´s encefalopathy (chronic
psychosis).
̶ Frequent in anticancer chemotherapy (vinca-alcaloids, taxanes, cisplatine, oxaliplatine,
thalidomide, bortezomib, brentuzumab vendotine…)
̶ Rarely others
̶ including rare side offect of some other medicines (amiodarone, chloroquine, chloramphenicol….)
̶ or metallic poisoning (lead – mostly industrial exposure, motor neuropathy) (lithium, arsenic, cobalt…)
39
HEREDITARY NEUROPATHIES
Heterogeneous group of diseases, which usually share the clinical features of insidious
onset and indolent course over years to decades.
̶ Typical skeletal abnormalities such as hammer toes, high arches, or scoliosis
̶ Common paucity of positive symptoms - may not be aware of any problem for many years
̶ → The diagnosis is frequently established in adulthood
̶ The most frequent types are autosomal dominant
less frequently autosomal recessive or X-linked
̶ Mostly positive family history, sometimes new mutations
̶ Typical electrophysiological abnormities in particular types
(demyelinating x axonal x intermediate)
̶ Diagnosis confirmed by genetic testing
40
HEREDITARY NEUROPATHIES
Charcot-Marie-Tooth Disease (Hereditary Motor and Sensory Neuropathy) (CMT, HSMN)
̶ Type I demyelinating, type II axonal, others rare
̶ Large fibers - common paucity of positive symptoms, peroneal weakness
̶ Frequent skeletal abnormities (hammer toes, high arches, or scoliosis)
Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) - quite frequent, AD
̶ condition leading to increased peripheral nerve susceptibility to mechanical traction or compression
̶ Patients have recurrent episodes of isolated mononeuropathies, typically affecting, in order of
decreasing frequency, the common peroneal, ulnar, brachial plexus (painless!), radial, and median nerves.
Hereditary Sensory and Autonomic Neuropathy (HSAN)
̶ Rare!!!, affects small fibers - pain or paresthesias in some (not all) patients
̶ Sensory loss: initially pain + temperature (with progression to all modalities)
̶ unnoticed, recurrent trauma, leading to neuropathic (Charcot) joints,
nonhealing ulcers, infections, and osteomyelitis resulting in acral mutilations
Definujte zápatí - název prezentace / pracoviště41
CURRENT
LIST OF
HSMN TYPES
̶ With particular genetic
defects
̶ No need to know – just
to get an idea, how
heterogennic the
disease is .
Adopted from:
https://neuromuscular.wustl.edu/
time/hmsn.html
42
OTHER INHERITED DISEASES PRESENTING
(AMONG OTHERS) WITH NEUROPATHY
Mostly the storage diseases – mutisystem involvement (cardiac, renal, ocular… etc.)
̶ Some of them treatable! (enzyme replacement therapy – mainly prevents further
progression, partial regression of the symptoms/signs is also possible)
Some examples:
̶ Familiar transthyretin (TTR) amyloid neuropathy (AD,
polyneuropathy (frequent autonomic symptoms) + CTS +
̶ Fabry disease (XR, α-Galactosidase deficiency,
males afected, painful feet, precipitated by fever
or hot weather or physical aktivity + other organs→→→)
43
TREATMENT OPTIONS IN POLYNEUROPATHIES
̶ In demyelinating inflammatory neuropathies: corticosteroids, IVIG, plasmaferesis,
other immunosupressive drugs (see above)
̶ In axonal neuropathies – management of the underlying disease (if possible)
̶ In DM: good compensation + lifestyle interventions + vascular risk factor management
̶ In others: substitution of vitamine deficiency, cessation of toxine exposure,
treatment of particular infecious disease (leprosis, HIV, lyme….)….
̶ In inherited neuropathies only symptomatic
In some storage diseases (TTR amyloidosis, Fabry) enzyme replacement therapy
̶ Symptomatic treatment
̶ Neuropathic pain treatment (antiepileptics or antidepressants or opioids)
̶ Physical therapy (to restore, or maintain muscle strength, and prevent muscle shortening and deformity)
̶ Orthotic management (angle-foot orthosis in peroneal palsy), orthopedic surgery (CMT)
̶ The prevention of painless traumas in SFN
44
MONONEUROPATHIES
̶ THE MOST COMMON CAUSES:
̶ direct trauma,
̶ compression or entrapment,
̶ vascular lesions,
̶ neoplastic compression or infiltration.
̶ SYMPTOMS AND SIGNS limited to
the distribution of one peripheral nerve
̶ ELECTROPHYSIOLOGICAL STUDIES:
̶ provide a more precise localization of the lesion than may be possible by clinical examination
̶ can separate axonal loss from focal segmental demyelination.
̶ may reveal a more widespread change, indicating an underlying neuropathy that has
made the nerve susceptible to entrapment as occurs in diabetes mellitus,
hypothyroidism, acromegaly, alcoholism, and HNPP.
Source:
https://www.spineorthoc
enter.com/conditions/car
pal-tunnel-syndrome/
Poage C, Roth C, Scott B. Peroneal Nerve Palsy: Evaluation
and Management. J Am Acad Orthop Surg 2016;24(1):1-10.
45
ENTRAPMENT NEUROPATHY
̶ defined as a focal neuropathy caused by restriction or mechanical distortion of a
nerve within a fibrous or fibro-osseous tunnel (or less commonly by other structures
such as bone, ligament, other connective tissues, blood vessels, or mass lesions).
̶ Far the most frequent cause of peripheral mononeuropathies
̶ compression, constriction, angulation, and stretching are important mechanisms
that produce nerve injury at certain vulnerable anatomical sites (see next slides).
̶ In chronic entrapment, mechanical distortion of the nerve fibers leads to focal
demyelination or, in severe cases, to wallerian degeneration
̶ In contrast, ischemia plays a more significant role in nerve injury associated with acute
compression secondary to space-occupying lesions such as hematoma or
compartment syndromes.
46
ENTRAPMENT NEUROPATHIES OF UPPER LIMBS
NERVE SITE OF COMPRESSION PREDISPOSING FACTORS MAJOR CLINICAL FEATURES
Median Wrist (carpal tunnel syndrome) Tenosynovitis, arthritis, etc. Paresthesia, pain, thenar atrophy
Anterior interosseous Strenuous exercise, trauma Abnormal pinch sign, normal sensation
Elbow (pronator teres syndrome) Repetitive elbow motions Tenderness of pronator teres, sensory loss
Ulnar Elbow (cubital tunnel syndrome) Elbow leaning, trauma Clawing and sensory loss of fourth and fifth
fingers
Guyon's canal Mechanics, cyclists Hypothenar atrophy, variable sensory loss
Radial
Axilia Crutches Wrist drop, triceps involved, sensory loss
Spiral groove Abnormal sleep postures Wrist drop, sensory loss
Posterior interosseous Elbow synovitis Paresis of finger extensors, radial wrist
deviation
Superficial sensory branch Wrist bands, hand cuffs Paresthesias in dorsum of hand
Suprascapular Suprascapular notch Blunt trauma Atrophy of supraspinatus and infraspinatus
muscles
Dorsal scapular Scalene muscle Trauma Winging of scapula on arm abduction
Lower trunk of the brachial
plexus or C8/T1 roots
Thoracic outlet Cervical rib, enlarged C7
transverse process
Atrophy of intrinsic hand muscles,
paresthesias of hand and forearm
No need to know all of them - just those in the blue boxes (will be described more in detail later)
47
ENTRAPMENT NEUROPATHIES OF LOWER LIMBS
NERVE SITE OF COMPRESSION PREDISPOSING FACTORS MAJOR CLINICAL FEATURES
Sciatic Sciatic notch Endometriosis, intramuscular
injections
Pain down thigh, footdrop,
absent ankle jerk
Hip Fracture dislocations
Piriformis muscle
Popliteal fossa Popliteal Baker's cyst
Fibular Fibular neck Leg crossing, squatting Footdrop, weak levators, sensory
loss in dorsum of foot
Anterior compartment Muscle edema Footdrop
Posterior tibial Medial malleolus (tarsal tunnel
syndrome)
Ankle fracture, tenosynovitis Sensory loss over sole of foot
Femoral Inguinal ligament Lithotomy position Weak knee extension, absent
knee jerk
Lateral femoral cutaneous Inguinal ligament (meralgia
paresthetica)
Tight clothing, weight gain, utility
belts
Sensory loss in lateral thigh
Ilioinguinal Abdominal wall Trauma, surgical incision Direct hernia, sensory loss in the
iliac crest, crural area
Obturator Obturator canal Tumor, surgery, pelvic fracture Sensory loss in medial thigh,
weak hip adduction
No need to know all of them - just those in the blue boxes (will be described more in detail later)
48
ENTRAPMENT NEUROPATHIES
̶ DIAGNOSIS – mainly based on history + neurological examination
̶ Confirmed by NCS/EMG - either short segment conduction slowing or conduction
block across the site of entrapment. Secondary axonopathy is frequently present.
̶ Imaging methods (US, MR, CT) may help for exact localisation of the lesion, and a
diagnosis of possible underlying lesions (tumor…), but in typical cases, they are not necessary.
̶ TREATMENT: splints in neutral position, physical therapy, NSAIDs (and possibly
local corticosteroid injection or local anesthetic block of the nerve) often suffice.
̶ Some lesions typically recover spontaneously (radial nerve compression)
̶ In patients with positive sensory symptoms – neuropathic pain treatment
̶ In severe cases surgical nerve release
CARPAL TUNNEL SYNDROME
Source:
https://www.spineorthoc
enter.com/conditions/
carpal-tunnel-syndrome/
̶ by far the most common entrapment neuropathy
̶ lifetime prevalence about 3-5% of the general population
̶ Several predisposing factors had been identified (see next slide)
̶ entrapment occurs at wrist in the tunnel through which the median
nerve and flexor digitorum tendons pass under the transverse
carpal ligament (more frequent in tenosynovitis or arthritis in this area)
̶ Symptoms consist of nocturnal pain and paresthesias, most often
confined to the thumb, index, and middle fingers.
̶ Patients complain of tingling numbness and burning sensations,
often awakening them from sleep.
̶ Referred pain may radiate to the forearm and even to the shoulder.
̶ Symptoms are often worse after excessive use of the hand or wrist
50
CTS – PREDISPOSING FACTORS
̶ Diseases and conditions that have been found to predispose to the development
of CTS include pregnancy, diabetes, obesity, age, rheumatoid arthritis,
hypothyroidism, amyloidosis, gout, acromegaly, certain mucopolysaccharidoses,
arteriovenous shunts for hemodialysis, old fractures at the wrist, and inflammatory
diseases involving tendons or connective tissues at the wrist level.
̶ More frequent in certain in work settings (repetitive forceful grasping or pinching,
awkward positions of the hand and wrist, direct pressure over the carpal tunnel, and
the use of hand-held vibrating tools) – meat packers, butchers, dental hygienists…
̶ Also a familial predisposition.
̶ The syndrome is frequently bilateral and usually of greater intensity in the
dominant hand.
̶ objective sensory changes may be found in the distribution of median nerve
̶ thenar (abductor pollicis brevis muscle) atrophy may be present with prolonged entrapment
̶ Tinel's sign (percussion of the nerve at the wrist causes paresthesias in the distribution of the median nerve)
̶ Phalen´s maneuver (flexing patient's hand at wrist for 1 min. reproduce the symptoms)
̶ reversed Phalen's maneuver (the same with the hyperextension of the wrist)
̶ Diagnosis confirmed by NCS/ EMG (mostly demyelinating for a long time from onset)
CARPAL TUNNEL SYNDROME
̶ In cases with only mild sensory symptoms, treatment with splints in
neutral position, NSAIDs (and possibly local corticosteroid injection) often suffice.
̶ Severe sensory loss and thenar atrophy suggest the need for surgical
carpal tunnel release - fiberoptic techniques are usually performed,
with more than 90% of patients having prompt resolution of pain and
paresthesias (open surgical sectioning of the volar carpal ligament is much less frequent).
Picture adopted from:
https://www.medicalexamprep.co.uk/uppe
r-limb-nerve-lesions-part-4-ulnar-nerve/
ULNAR NERVE ENTRAPMENT
̶ the second most common compression mononeuropathy
̶ Causes: Compression of the nerve by a thickened fibrotic flexor carpi
ulnaris aponeurosis at the entrance of the elbow's cubital tunnel, more
frequent in some occupations + following traumas
̶ External pressure to the nerve (resting of the flexed elbow on a hard surface)
̶ Clinical picture: Prominent atrophy of the first dorsal
interosseous muscle, with clawing of the fourth and fifth
fingers (the result of lumbrical weakness, with secondary hyperextension of the
metacarpophalangeal joints).
̶ Sensory loss or hypoesthesia involves the fifth finger, part of the
fourth finger, and the hypothenar eminence and extends to the
dorsum of the hand (but does not extend above the wrist).
53
̶ The sensory loss may be associated with paresthesias and pain
̶ A Tinel's sign at the elbow may be elicited
̶ The weakness of the flexor carpi ulnaris, flexor digitorum profundus of the IV. and V.
fingers, and the intrinsic hand muscles. Grip strength is reduced. Weakness of the
interossei muscles results in an inability to forcefully extend the interphalangeal joints.
Abduction and adduction of the fingers becomes more difficult.
̶ NCS/EMG: Focal ulnar nerve slowing +/- conduction block in the elbow segment
̶ Mostly also the reduction in the ulnar CMAP amplitude and needle EMG changes –
frequent axonal loss (present together with the demyelinating changes or even predominant)
̶ MRI of the elbow or US may reveal abnormal structures compressing the nerve and/or
thickening of the nerve
ULNAR NERVE ENTRAPMENT
54
̶ Conservative treatment should be attempted in patients with mild symptoms elbow
protectors + avoidance of repetitive elbow flexion and extension or
direct pressure on the elbow may alleviate the symptoms.
̶ Surgical approaches: include simple release of the flexor carpi ulnaris
aponeurosis, anterior transposition of the nerve trunk, and resection of the
medial epicondyle.
̶ Only approximately 60% of patients (especially those with symptoms of less than 1
year's duration), benefit from surgery and some experience worsening of symptoms.
ULNAR NERVE ENTRAPMENT
55
RADIAL NERVE ENTRAPMENT
̶ compression in the axilla may result from crutches or from
the weight of a sleeping partner's head (honeymoon palsy)
̶ weakness of the triceps brachii, brachioradialis, supinator,
and extensor muscles of the wrist and fingers
Picture adopted from: https://teesneuro.org/2019/09/26/cases-
for-finals-12-examination/
̶ compression at the spiral groove of the humerus (miduppper arm) during drunken
sleep wherein the arm is draped over a chair (Saturdaynight palsy)
̶ the triceps brachii is spared, resulting in weakness confined to the brachioradialis, wrist,
and finger extensors = wrist drop
̶ Hypoesthesia over the dorsum of hand, thumb, index finger, and middle finger in both
̶ Compressive radial nerve lesions caused by pressure lead to a conduction block in
NCS/EMG and usually improve in 6 to 8 weeks.
̶ must be differentiated from radial nerve injury caused by fractures of the humerus,
because the prognosis for recovery is poorer in the latter case (due to axonopathy)
56
COMMON FIBULAR (PERONEAL)
NERVE ENTRAPMENT
̶ the most frequent entrapment neuropathy in the leg
̶ Nerve is vulnerable in the region of the fibular neck as it passes through the origin of
the fibularis (peroneus) longus muscle. Near this opening, the nerve divides into two
main terminal divisions: the superficial and deep fibular nerves
̶ lesion leads to weakness of foot and toe extension and foot eversion, with a footdrop
and steppage gait.
̶ Sensory impairment is found over the lateral aspect of the lower
leg and the dorsum of the foot.
̶ Caused by a direct pressure to the fibular head area (long taking
squatting or kneeling possition, habitual leg crossing, improperly
applied plaster casts or unrecognized pressure on the nerve
in debilitated or unconscious patients) Picture taken from:
http://www.southfloridasportsmedicine.co
m/common-peroneal.html
Picture taken from:
https://clinicalgate.com/peron
eal-neuropathy/
Lateral cutaneous
nerve of the knee (a
branch of the
common peroneal
nerve)
Superficial peroneal
Deep peroneal
57
COMMON FIBULAR (PERONEAL) NERVE ENTRAPMENT
̶ NCS/EMG: frequently focal conduction block or localized conduction slowing in the
region of the fibular head (suggesting demyelinating process)
̶ the most frequent pathophysiological process is axonal loss regardless of the cause.
̶ EMG demonstrates the denervation potentials in anterior (or anterolateral) calf muscles
̶ The prognosis is uniformly good in cases of acute compression
̶ bracing with a custom-made plastic ankle-foot orthosis is
necessary to improve the gait in the presence of severe footdrop.
̶ The few patients who do not improve spontaneously after 3
months, or those who have pain or a slowly progressive fibular
nerve lesion, may require MRI studies and surgical exploration
58
POSTERIOR TIBIAL NERVE ENTRAPMENT
(TARSAL TUNNEL SYNDROME)
̶ occurs behind and immediately below the medial malleolus (in tarsal tunnel).
̶ Burning pain occurs in the toes and the sole of the foot
̶ Examination usually reveals plantar sensory impairment and wasting of the intrinsic
foot muscles + positive Tinel´s sign
̶ Confirmed by NCS/EMG (which also excludes other possible cases – e.g. polyneuropathy)
̶ Local injection with corticosteroids underneath the
laciniate ligament may temporarily relieve the symptoms.
̶ Surgical decompression is mostly needed for
permanent results. Source: wikipedia
Picture taken from: https://www.sciencedirect.com/topics/medicine-and-
dentistry/meralgia-paraesthetica59
LATERAL FEMORAL CUTANEOUS NERVE
ENTRAPMENT (MERALGIA PARESTHETICA)
̶ pure sensory nerve
̶ passes medial to the anterior superior iliac spine
under the inguinal ligament (usual site of
entrapment) to enter the thigh under the fascia
lata that it penetrates to supply the skin of the
anterolateral part of the thigh.
̶ association with obesity, pregnancy, ascites…
̶ patients develop numbness, painful burning,
and itching over the anterolateral thigh.
̶ Treatment consists of rest, analgesics (against
neuropathic pain), and weight loss. Neurolysis
is rarely beneficial.
Source: Wikipedia
60
FEMORAL NERVE LESIONS
LITHOTOMY
POSITION
̶ The lesion leads to the weakness of
m. quadriceps femoris and m. iliopsoas.
̶ Patients complain of difficulty in walking
and of knee buckling (, depending on the severity of injury.
̶ There is also a numbness and/or positive sensory
symptoms in anterior aspect of the thigh and anteromedial
aspect of the calf.
̶ Causes: Sometimes seen as a complication of hip
arthroplasty or other procedures performed in lithotomy
position, or after direct trauma or in diabetic patients…
̶ Prognosis (with the exception of total transections) is quite
good with almost complete recovery
61
OTHER CAUSES OF PERIPHERAL
MONONEUROPATHIES/RADICULO-/PLEXOPATHIES
̶ Much less frequent comparing with entrapment
̶ Direct traumatic nerve injury (exclude from history and clinical examination) – the
prognosis depends on the extent of trauma and nerve continuity – loss of continuity
prevents from recovery
̶ Vasculitis (very rare, consider particularly in multiple mononeuropathy with very
acute development and in patients with other symptoms/signs of autoimmune
disease. Nerve biopsy may be necessary to confirm the diagnosis).
̶ Infectious diseases
̶ Neuroborreliosis – frequently presents with radiculo/neuropathy (Banwarth syndrome lymphocytic
meningoradiculitis) – often facial nerve or nerve roots
̶ Leprosy
̶ Herpes zoster (radiculitis) – may result in postherpetic neuralgia
62
MAIN SOURCES OF INFORMATION
̶ Harati Y, Bosch PE. CHAPTER 80 – Disorders of Peripheral Nerves. In Bradley WG, Daroff
RB, Fenichel GM, Jankovic J. Neurology in Clinical Practice, 5th ed. London: Elsevier 2008.
̶ https://www.lecturio.com/magazine/polyneuropathies
̶ https://neuromuscular.wustl.edu/
THANKS FOR YOUR ATTENTION 