Post on 06-Feb-2018
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Classification of Peripheral
Nerve Disease
Mononeuropathy
Plexopathy
Brachial plexopathy
Lumbar plexopathy
Sacral plexopathy
Radiculopathy
Cervical radiculopathy
Thoracic radiculopathy
Lumbosacral radiculopathy
Multiple mononeuropathy (mononeuritis multiplex)
Polyneuropathy
Symmetrical polyneuropathy
Asymmetrical polyneuropathy?
Polyradiculoneuropathy
Eight Patterns of Neuropathies
1. Symmetric proximal and distal weakness with sensory loss
(GBS)
2. Symmetric distal weakness with sensory loss
(metabolic, drugs, toxins, amyloid, hereditary)
3. Asymmetric distal weakness with sensory loss
(vasculitis, leprosy, Lyme sarcoid, HIV, compressive mononeuropathy)
4. Asymmetric distal weakness without sensory loss
(ALS, MMN)
5. Asymmetric proximal and distal weakness with sensory loss (polyradiculopathy and plexopathy due to DM, meningeal carcinomatosis, idiopathic)
6. Symmetric sensory loss without weakness
(cryptogenic sensory polyneuropathy, metabolic, drugs, toxins)
7. Asymmetric proprioceptive sensory loss without weakness
(sensory neuronoapthy - ganglionopathy)
8. Autonomic symptoms and signs
Etiology of Acquired Polyneuropathies
• Dysmetabolic
–Diabetes mellitus
–Renal disease, liver disease
–Vitamin deficiencies (B1, B2, B6, FA, B12)
–B6 toxicity
–Primary amyloidosis
• Immune-mediated
–GBS
–CIDP
–Vasculitis
–Connective tissue disease
–Monoclonal gammopathies , MGUS, MAG, GM1 …
–Plexitis (brachial, lumbosacral)
• Infectious
–Herpes zoster
–Leprosy, Lyme, HIV, sarcoidosis
• Cancer related
–lymphoma, myeloma, carcinoma related,
• Drugs or toxins
• Unknown etiology
–cryptogenic sensory and sensorimotor
Axonopathy dying-back Myelinopathy Neuronopathy
Neuropathies – Traditional classification
Sensory Neuronopathy
(ganglionopathy)
Segmental demyelination
(myelinopathy)
Axonal degeneration
(axonopathy)
Target:
sensory nerve cell bodies
in the dorsal root and
trigeminal ganglia
Target:
myelin sheaths or Schwann cells
Remyelination of demyelinated
segments thinner-than-normal myelin
sheaths and internodes of shortened
length. Repeated episodes of
demyelination and remyelination
produce proliferation of multiple layers
of Schwann cells around the axon,
termed an onion bulb.
Target:
distal axonal breakdown and
progresses toward the nerve
cell body, (dying-back or
length-dependent
polyneuropathy)
Neuronopathy Myelinopathy Axonopathy dying-back
Axonal Advanced axonal Demyelinating Mononeuritis
multiplex
Node of Ranvier
Axon
Myelin
Node Paranode Juxtaparanode Internode Paranode
The nodal axolemma and the paranode can be the focus of the nerve injury, these
immune mediated neuropathies could be more properly classified as
nodo-paranodopathies.
nodo-paranodopathies
The nodes can be exclusively damaged by autoimmune processes, resulting in development of
neuropathies.
Dysfunction and disruption of the nodal region are common mechanisms in acute (and possibly
chronic) neuropathies associated with antibodies to GM1, GD1a and GD1b.
The common mechanism explains the spectrum of severity ranging from reversible conduction failure
( RCF) with prompt recovery to axonal degeneration with poorer outcome in the different neuropathies
and some features of the continuum between AMAN and AMSAN.
Nodo-paranodopathies (neuropathies associated with antibodies to gangliosides)
Autoantibodies GM1 GD1a GT1a GQ1b GD1b
AMAN IgG IgG
AMSAN IgG IgG
ASAN IgG
PCB IgG
FS IgG IgG
MMN IgM
AMAN, acute motor axonal neuropathy;
AMSAN, acute motor-sensory axonal neuropathy;
ASAN, acute sensory ataxic neuropathy;
PCB, pharyngeal-cervical-brachial weakness;
FS, Fisher syndrome;
MMN, multifocal motor neuropathy.
EDX in polyneuropathy
Collective results of nerve conduction studies and electromyography
are useful in defining the polyneuropathy.
EDX of a polyneuropathy requires both motor and sensory
conduction studies of multiple nerves in upper and lower extremities
bilaterally combined with needle EMG.
EDX to demonstrate the characteristic symmetry of abnormality.
Polyneuropathy EDX protocol
NCV 1. To test most involved site when mild or moderate, least involved if severe.
2. Peroneal motor (EDB); stimulate at ankle, fibular head and knee.
If abnormal or no responses: Peroneal motor (TA); stimulate at fibular head and knee.
3. Tibial motor (AH); stimulate at ankle and knee.
4. Ulnar motor (hypothenar); stimulate at wrist, elbow, above elbow, axilla and Erb’s point.
5. Median motor (thenar); stimulate at wrist, elbow, above elbow, axilla and Erb’s point.
6. F responses.
7. SNAP (sural , superficial peroneal, median, ulnar, radial nerve amplitude and conduction velocity).
8. Evaluation of opposite extremity.
9. Evaluation of specific suspected abnormality.
10. If prominent cranial involvement: Facial CMAP, Blink reflex studies
Needle EMG Examination TA, GA, EHL, FDI, paraspinal muscles.
Intrinsic foot muscles can be considered.
Abnormalities should be confirmed by examination of at least one contralateral muscle.
Demyelinating polyneuropathies
A. Uniform demyelination
B. Segmental demyelination
Uniform demyelinating,
mixed sensorimotor polyneuropathy
CMT 1A
CMT 1B
DSD
Metachromatic leukodystrophy
Krabbe’s globoid leukodystrophy
Adrenomyeloneuropathy
Congenital hypomyelinating neuropathy
Tangier disease’
Cockayne’s syndrome
Cerebrotendinous xanthomatosis
Segmental demyelinating,
motor > sensory polyneuropathy
AIDP
CIDP
MMN
POEMS
MGUS
NHPP
CMTX1
Adrenomyeloneuropathy
Refsum
Diphtheria
Acute arsenic polyneuropathy
Pharmaceuticals
Amiodarone
Perhexiline
High dose Ara-C
Lymphoma
Carcinoma
Lyme disease
Acromegaly
Systemic lupus erythematosus
Glue sniffing neuropathy
Cryoglobulinemia
Axonal loss,
motor > sensory polyneuropathy
Porphyria
Axonal Guillain- Barré syndrome
CMT2
CMT4 (some)
Lead neuropathy
Dapsone neuropathy
Vincristine neuropathy
Axonal loss
sensory neuronopathy or neuropathy
HSAN types I- V
Friedreich's ataxia
Spinocerebellar degeneration.
Abetalipoproteinemia
Primary biliary cirrhosis
Acute sensory neuronopathy
Cisplatinum toxicity
Paraneoplastic sensory neuronopathy
Chronic idiopathic ataxic neuropathy
Sjogren's syndrome
Fisher variant GBS
Paraproteinemias
Pyridoxine toxicity
Idiopathic sensory neuronopathy
Styrene-induced peripheral neuropathy
Crohn's disease
Thalidomide
Nonsystemic vasculitic neuropathy
Chronic gluten enteropathy
Vitamin E deficiency.
Axon loss, mixed sensorimotor
polyneuropathy
Amyloidosis
Chronic liver disease
Nutritional diseases
Vitamin B12 deficiency
Folate deficiency
Whipple’s disease
Post-gastrectomy syndrome
Gastric restriction surgery for obesity
Thiamine deficiency
Alcoholism
Sarcoidosis
Connective tissue diseases
Toxic neuropathy
Mixed axon loss and demyelinating sensorimotor
polyneuropathy
Diabetes mellitus
Uremia
Classification of Diabetic Neuropathies
Generalized Symmetrical Polyneuropathies
Distal sensory or sensorimotor polyneuropathy
Small-fiber neuropathy
Autonomic neuropathy
Large-fiber sensory neuropathy
Focal and Asymmetrical Neuropathies
Cranial neuropathy (single or multiple)
Truncal neuropathy (thoracic radiculopathy)
Limb mononeuropathy (single or multiple)
Proximal motor neuropathy (radiculoplexopathy, amyotrophy)
Combinations
Polyradiculoneuropathy
Diabetic neuropathic cachexia
Acquired (segmental) vs Hereditary (uniform)
CIDP produces variable conduction velocities between fibers with
observed dispersion and conduction block.
47 m/s
30 m/s
43 m/s
5 mV
Molecular Genetics of Charcot-Marie-Tooth Type 1
Locus Name Gene Symbol Chromosomal Locus Protein Name
CMT1A PMP22 17p11.2 PMP22 duplication; 70%-80%
CMT1B MPZ 1q22 Myelin P0 protein 5%-10%
CMT1C LITAF 16p13.3-p12 Lipopolysaccharide-induced tumor necrosis factor-alpha factor
CMT1D EGR2 10q21.1-q22.1 Early growth response protein 2
CMT1E PMP22 17p11.2 PMP22 point mutations; less than 5%
CMT1F NEFL 8p21 Neurofilament light polypeptide
Electrodiagnostic findings suggestive of demyelination
1. Conduction block
2. Conduction velocity slowing greater than can be explained by axonal loss
A. Prolonged distal motor latencies
B. Slow conduction velocity
Motor conduction slowing <30 m/s arm 25 m/s in the leg
C. Prolonged F-wave latency
D. Prolonged H-reflex latency
3. Temporal dispersion
4. Prolongation of the duration of the distal CMAP
Neuropathies associated with
conduction block
• Inflammatory/immune-mediated
Guillain–Barre´ syndrome
Acute motor axonal neuropathy (AMAN)
Chronic inflammatory demyelinating polyneuropathy (CIDP)
Lewis–Sumner syndrome
Multifocal motor neuropathy (MMN)
• Inherited
Hereditary neuropathy with liability to pressure palsies (HNPP)
• Traumatic
Acute compressive neuropathies
• Toxic
Diphtheria
Buckthorn
Fish toxins
Tetrodotoxin, saxitoxin, ciguatera
54 y man presented with:
Several months history of insidious and progressive gait difficulty and clumsy hands
Become bed ridden and incontinent one month prior to the referral
Intermittent and migrating numbness in both legs
PMH: DM-II, smoker, ETOH
Mild neck flexor weakness
0/5 proximal and distal legs
4-/4- proximal arms
3/3 distal arms/ hands
Reduced tone and atrophy of limb muscles
B/L knee contractures (15 degree)
Muscle stretch reflexes absent throughout
CHRONIC INFLAMMATORY DEMYELINATING POLYRADICULONEUROPATHY (CIDP)
1. It is a symmetric polyradiculoneuropathy or polyneuropathy, affecting motor and sensory fibers, proximal and distal limbs, and infrequently cranial nerves and CNS.
2. The characteristic symptoms are weakness and altered sensation and paresthesias.
3. The course is progressive, stepwise progressive, or relapsing.
4. The protein in CSF is usually elevated to 1.5 to 4 times normal and cells are usually less than 5/ml (albuminocytologic dissociation).
5. Slowing of motor and sensory conduction velocities;
6. A therapeutic trial of plasma exchange, IVIG or steroid usually results in improvement
Practical diagnostic criteria for CIDP
1. Progressive symmetrical weakness of arms and legs for at least 2 months
2. Sensory disturbances generally less prominent
3. Low or absent DTR
4. Sometimes cranial nerve palsies
5. CSF protein almost always elevated
6. Delayed NCV
7. Increased Distal latencies
8. Conduction block
9. Dispersion
10. Decreased excitability
Other causes of chronic neuropathy must be ruled out
NCV values needed to be considered “demyelinating”
NCV DL F
If amplitude is >80% <80% >80% <80% >80% <80%
LLN <80% <70% ULN >125% >150% ULN >120% >150%
Median 48 38.4 33.6 4.5 5.6 6.7 31.0 37.2 46.5
Ulnar 48 38.4 33.6 3.6 4.5 5.4 32.0 38.4 48.0
Peroneal 42.0 33.6 29.4 6.6 8.2 9.9 56.0 67.2 84.0
Tibial 42.0 33.6 29.4 6.6 8.2 9.9 58.0 69.6 87.0
CIDP with concurrent disorders
• MGUS (5% polyneuropathy)
• Multiple myeloma (3:100,000/ year)
• Plasmacytoma
• Waldenström’s macroglobulinemia (5% polyneuropathy, IgM chain in 80%)
• POEMS
• HIV
• Chronic Active hepatitis
• Inflammatory bowel disease
• Connective tissue disease
• Bone marrow and organ transplants
• Lymphoma
• Hereditary neuropathy
• Diabetes mellitus
• Thyrotoxicosis
• Nephrotic syndrome
• CNS demyelination
• Seminoma
Chronic Inflammatory Demyelinating Neuropathies:
Clinical features CIDP Distal
acquired
demyelinating
symmetric
(MAG)
Lewis–
Sumner
syndrome
MMN POEMS
Weakness and
sensory loss
Symmetric, distal and
proximal (legs>arms)
M>S
Symmetric, mild
distal (legs>arms)
S>M
Asymmetric, mostly
distal, pain, Tinel’s
(arms>legs)
Pure motor,
asymmetric,
mostly distal
(arms>legs)
Symmetric, distal and
proximal (legs>arms)
Painful feet
M>S
CSF protein Elevated Elevated Elevated No Elevated
M protein Uncommon IgM Uncommon Uncommon Lambda light chain
Antineural
antibodies
Uncommon Anti MAG Uncommon Anti GM1
VEGF
Systemic Uncommon
(MGUS, MM, WM
Connective tissue
disease …)
No No No Osteosclerotic myeloma
Organomegaly
Endocrinopathy
Skin changes
edema, ascites
Motor NCV Demyelination Demyelination Demyelination Demyelination Demyelination, more uniform
slowing, greater
axonal loss in LE,
higher terminal latency index
Sensory NCV Abnormal Abnormal Abnormal Normal Abnormal
Treatment Prednisone, IVIG,
PLEX,
immunosuppressants
?Rituxan
?IVIG
IVIG
Immunosuppressants
Prednisone
IVIG
?cyclophosphamide
Stem cell, dexamethasone
Melphalan, Lenalidomide ,
Thalidomide, Bortezomib,
anti-VEGF antibody
(bevacizumab)
Classification of Guillain-Barré syndrome and typical
antiganglioside antibodies
- Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) Unknown
- Acute motor and sensory axonal neuropathy (AMSAN) GM1, GM1b, GD1a
- Acute motor axonal neuropathy (AMAN) GM1, GM1b, GD1a, GalNac-GD1a
- Acute motor conduction block neuropathy (AMCBN)
- Acute sensory neuronopathy GD1b
- Acute pandysautonomia
- Regional variants
Fisher’s syndrome GQ1b, GT1a
Oropharyngeal –cervical-brachial GT1a
- Overlap
Fisher’s syndrome/ GBS overlap syndrome GQ1b, GM1, GM1b, GD1a,
Antibodies Clinical variants
GBS
- GBS is a rare but important disease that can lead to life threatening respiratory failure
- Structural similarities between a triggering infectious organism and peripheral nerve
tissue are important in its pathogenesis
- Treatment consists of rapid administration of intravenous immunoglobulin or plasma
exchange, which shortens the time to recovery
- Around 10% of patients die from respiratory failure, pulmonary emboli, or infection
- Around 20% of patients have residual disability, with weakness or persistent sensory
disturbance
- GBS should be considered in any patient developing rapidly progressive limb weakness
- Absent reflexes are a “red flag” for GBS in patients with rapidly progressive weakness
- Patients with suspected GBS should be referred to hospital as an emergency
- A history of weakness preceded by respiratory or GI infection suggests GBS
Diagnostic criteria for GBS
Required Supportive Doubtful
Prog. Weakness
of >1 limb
Areflexia
Progression<4 weeks
Symmetric weakness
Mild sensory symptoms
Cranial nerve (VIIth)
Autonomic dysfunction
protein in CSF
CSF cells <10
NCV demyelination*
Recovery
Asymmetry
B/B dysfunction*
>50 cells in CSF
Polys in CSF
Sensory level
Motor Nerve Conduction: Peroneal Nerve.R(EDB) absent
Peroneal Nerve.R (TA) absent
Tibial Nerve.R absent
Ulnar Nerve.L absent
Ulnar Nerve.R absent
Median Nerve.R Latency-ms Amplitude -mV Conduction velocity m/s
Wrist 3.7 0.7
Elbow 11.0 0.5 Wrist-Elbow 47
Axilla 14.4 0.5 Elbow-Axilla 44
Median Nerve.L
Wrist 4.1 0.6
Elbow 10.9 0.5 Wrist-Elbow 46
Axilla 14.7 0.5 Elbow-Axilla 43
Sensory Nerve Conduction: Nerve and Site Latency -ms Amplitude -µV Conduction velocity m/s
Sural Nerve.R 3.5 6.6 39
Superficial Peroneal.R 2.5 7.7 46
Radial Nerve.R 1.9 17.3 56
Median Nerve.R 2.5 19.3 52
Ulnar Nerve.R 2.5 11.5 48
Radial Nerve.L 1.8 17.9 54
Median Nerve.L 2.6 15.6 48
Ulnar Nerve.L 2.4 15.3 52
Needle EMG Examination:
Muscle Insert. Fibs Pos. Fascs Poly Dur Amp Pattern Effort
Tibialis anterior.R Increased 2+ 2+ None None Max.
Peroneus longus.R Increased 2+ 3+ None None Max.
Gastroc (Medial head).R Increased 1+ 2+ None None Max.
Vastus medialis.R Increased 1+ 2+ None None Max.
Rectus femoris.R Increased 2+ 3+ None Unstable Unstable Single unit Max.
Deltoid.R Normal 1+ 2+ None Many Normal Normal Reduced Max.
Triceps brachii.R Normal 2+ 2+ None Many Sl. Incr. Normal Single unit Max.
Biceps brachii.R Normal 1+ 1+ None Few Normal Normal Single unit Max.
Extensor dig communis.R Normal 2+ 2+ None Many Unstable Unstable Single unit Max.
1st dorsal interosseous.R Increased 2+ 3+ None None Max.
67-year-old man AMAN
The interpretation of NCS in GBS is not straightforward.
Conduction block is considered supportive of demyelination and AIDP
Short-lasting conduction block that resolves without temporal dispersion has
also been observed in early stages of a GBS subtype associated with
antiganglioside antibodies that resembled AMAN. This suggests that the block
is due to nodal Na channel dysfunction rather than demyelination.
Therefore, the finding of conduction block in itself cannot be attributed simply
to a particular subtype.
Classification depends on the timing of NCS relative to disease onset. Serial
NCS lead to reclassification in as many as 40% of patients (from AIDP to an
axonal form)
GBS
Acute Chronic
AIDP: no antibody CIDP: no antibody
AMAN: IgG anti-GM1 MMN: IgM anti-GM1
Fisher syndrome: IgG anti-GQ1B CANOMAD: IgM anti-GQ1B and GT1A
Antecedent event in 70% No antecedent event
Monophasic Requires continued Rx
Steroids ineffective Steroids effective in CIDP
Both axonal and demyelinating forms Axonal forms not as well described
Parallels and differences between GBS and CIDP
CANOMAD: Chronic Ataxic Neuropathy Ophtalmoplegia IgM paraprotein Cold Agglutinins Disialosyl antibodies
57 y man presented with:
Four months progressive proximal and distal symmetrical arm
and leg weakness leading to wheelchair bound state
No sensory symptoms
Absent DTR in the legs, trace in the arms
NCV-conduction block in motor fibers
Normal SNAP
IgM spike
anti-GM1 = 1:58000 (repeated 1:100000)
BM = low grade B-cell lymphoma
(Waldenström's macroglobulinemia)
Multifocal Motor Neuropathy-MMN
• Age of onset is generally between 20 and 75
• Men are affected somewhat more commonly than women
• Weakness:
• Distal > Proximal
• Asymmetric
• Upper > Lower extremity
• Weakness in muscles with relatively normal bulk
• No upper motor neuron signs
• Sensory: Normal or minimal subjective symptoms
• Tendon reflexes: Preserved in proportion to strength
• Time course: Slowly progressive (years)
• High IgM vs GM1 ganglioside
Neurophysiology of conduction block
Conduction block (CB) – failure of a nerve impulse to propagate in a
segment of an intact axon
Temporal dispersion (TD) – excessive desynchronization of the
impulse (duration >15%)
In clinical practice, CB is suspected when proximal amplitude or area
are smaller than distal
No universally accepted criteria for parameters of CMAP are present
(range of amplitude difference 14- 50%)
CB and TD have been considered characteristic of acquired segmental
demyelinating neuropathies
CB and TD are absent in hereditary neuropathies
Partial conduction block cannot be reliably recognized in the context
of severe axon loss.
Amplitude below 20% of the lower limit of normal at the most distal
stimulation site is sufficiently small to preclude the confident
recognition of partial conduction block.
Conduction block
Normal CMAP
ms
mV
Distal
Proximal
Conduction block
ms
mV
Distal
Proximal
Temporal dispersion
ms
mV
Distal
Proximal
MMN ALS CIDP Lewis Sumner
Asymmetrical +++ + - ++
Distal > proximal +++ ++ +/- ++
UL>LL +++ +/- - +
Atrophy +/- +++ ++ ++
Fasciculations + ++ - -
Bulbar - +++ - -
Diaphragm - +++ - -
Sensory - - ++ ++
Cold worsening ++ ++ - -
Reflexes Asymmetric
reduced
Brisk Symmetric
reduced
Reduced
Course Slowly/ stepwise
progressive/
Treatable
Progressive/
invariably fatal
Subacutely
progressive/
treatable
Subacute/stepwise
progressive/treata
ble
Conduction
block
+++ - ++ ++
GM1 ++ - - -
CSF protein - - ++ +
IVIG response +++ - +++ +++
Steroids/PLEX - - +++ +++
Differential diagnosis of MMN
40 y man presented with:
Progressive proximal and distal weakness (legs> arms)
Distal dysesthesias and sensory loss
Absent DTR
Absent SNAP
Slow NCV
LP- albuminocytologic dissociation
Monoclonal spike on IE
Neuropathies and autoantibodies
Disease Antigen Antibody % positive
MMN
GBS
Miller-Fisher
MAG-pn
Sensory neuronopathy
Sensory-chronic
CIDP
GM1
GM1, GD1a
GQ1b
MAG
Hu
Sulfatide
Tubulin
Poly IgM
Poly IgG, IgM
Poly IgG
Mono IgM
Poly IgG
Mono IgM
Poly IgM, IgG
Anti tubulin
50%
20-30%
95%
50%
>95%
?
?
60%
Disorder Neuropathy Systemic Paraprotein EMG
MM Symmetric, distal S, SM Anemia, fatigue, bone pain IgM- or IgG-
> 3g/dl
A
WM Symmetric distal S, SM,
(CIDP-like)
Fatigue, weight
encephalopathy
IgM- D
OM Symmetric, prox, dist,
SM (CIDP-like)
POEMS IgG- or IgA- D
AL Symmetric, painful,
small fiber, autonomic
CHF, CRI, HSM, weight
macroglossia,
IgG- or IgA-
A
Cryo. Symmetric or
multifocal, distal
painful, autonomic
HSM, purpura, arthralgias,
Raynaud’s, leg ulcers
IgM or IgG A
Lymph S, SM, MND, CIDP,
GBS
Fatigue, weight … IgM or IgG A, D?
Paraproteinemic disorders associated with
neuropathy
• Younger age, mostly man
• Osteosclerotic myeloma (3% of myeloma)
– Axial skeleton (spine, pelvis, ribs)
• Polyneuropathy (CIDP-like)
• Organomegaly (HSM)
• Endocrinopathy
– (gynecomastia, impotence, amenorrhea, DM, hypothyroidism)
• M-protein (lambda-chain)
• Skin changes
– (hyperpigmentation, hypertrichosis, thickening, hemangiomas)
• Pitting edema, ascites, pleural effusion, clubbing
POEMS
Sensory neuronopathy vs length
dependent sensory neuropathy
Sensory neuronopathy
(non- length dependent)
Sensory predominant polyneuropathy
(length dependent)
Symmetric or asymmetric Symmetric
Proximal and distal, UE, LE, truncal nerves Distal sensory nerves, feet usually
Profound proprioceptive loss (all modalities) Rare to no proprioceptive loss
No motor weakness In severe cases distal motor deficit
Generalized areflexia Distal areflexia (ankle jerks)
Absent SNAP LE and UE SNAP abnormal LE
Motor NCV normal Distal decreased amplitude CMAP
High signal posterior columns - Present High signal posterior columns - Absent
DRG - positive pathology DRG - normal
Motor Nerve Conduction:
Nerve and Site Latency ms Amplitude mV CV m/s F-waves:
Peroneal Nerve.R
Ankle 4.0 4.7
Fibular head 11.1 4.3 44 53.7 ms
Knee 13.6 4.2 50
Peroneal Nerve (TA).R
Fibular head 5.1 3.0
Knee 7.3 3.1 52
Tibial Nerve.R
Ankle 6.3 8.1
Pop. fossa 15.9 8.3 4 3 58.9 ms
Peroneal Nerve.L
Ankle 4.7 5.0
Fibular head 11.5 4.7 43 50.7 ms
Knee 13.7 4.9 48
Peroneal Nerve (TA).L
Fibular head 4.3 3.4
Knee 6.2 3.4 58
Tibial Nerve.L
Ankle 4.8 3.9
Pop. fossa 14.6 3.5 42 56.9 ms
Median Nerve.L
Wrist 3.1 10.4
Elbow 8.6 9.9 56 29.0 ms
Axilla 11.2 10.4 60
Ulnar Nerve.L
Wrist 2.4 10.1
Below Elbow 6.3 9.6 53 28.4 ms
Above Elbow 8.2 9.4 61
Axilla 11.2 8.6 58
Median Nerve.R
Wrist 3.2 11.6
Elbow 8.1 11.6 53 28.2 ms
Ulnar Nerve.R
Wrist 2.2 10.5
Below Elbow 6.2 8.2 59 29.8 ms
Above Elbow 8.7 8.1 54
Axilla 11.1 7.1 54
Needle EMG Examination:
Spontaneous ActivityVolitional Activity Maximal Effort
Muscle Insert. Fibs Pos. Fascs Poly Dur Amp Pattern Effort
Tibialis anterior.R Normal None None None Few Normal Normal Full Max.
Gastroc (Medial head).R Normal None None None Few Normal Normal Full Max.
Extensor dig communis.R Normal None None None Few Normal Normal Full Max.
1st dorsal interosseous.R Normal None None None Few Normal Sl. Incr. Full Max.
Extensor digitorum brevis.R Normal None None None Few Normal Normal Full Max.
50 y. patient Sensory Neuronopathy
Sensory Nerve Conduction:
Sural Nerve.R Absent
Superficial Peroneal.R Absent
Sural Nerve.L Absent
Superficial Peroneal.L Absent
Radial Nerve.L Absent
Median Nerve.L Absent
Ulnar Nerve.L Absent
Median Nerve.R Absent
Ulnar Nerve.R Absent
Radial Nerve.R Absent
Causes of sensory neuronopathy
• Cancer (paraneoplastic)
• Sjögren syndrome and other inflammatory dss.
• Idiopathic sensory
• Cisplatinum, Paclitaxel
• Vitamin B6 toxicity
• HIV-related sensory
Cryptogenic sensory polyneuropathy • Decreased sensation, paresthesias, dysesthesias, allodynia and
pain in length dependent fashion
• At least 3 months duration and no symptoms of weakness
• Symptoms of gait unsteadiness and autonomic dysfunction are
allowable
• Sensory signs in symmetrical fashion (vibration,
proprioception, light touch, pain, temperature
• ± reflexes (AJ)
• Minimal weakness of the toes allowable
• ± EMG/NCV changes (axonal)
• ± QST abnormalities
• ± Skin biopsy
• ± QSART
• ± Autonomic testing
• Stable course, no functional disability
Painful Polyneuropathies
• Cryptogenic
• Paraproteinemic
• In malignancies
• Diabetes mellitus
• Vasculitis
• GBS
• Amyloidosis
• Toxic (arsenic, thallium)
• HIV-related
• Fabry’s disease
Useful Blood Studies
• CBC, SMA, LFT, U/A, ESR,A1C, TFT?
• Immunofixation, Quant. Ig
• B12, B6, B1, Folate, MMA, homocysteine
• VDRL, RF, ANA, ANCA, Lyme, HIV
• Anti-MAG, GM1, GD1B, GQ1B
• SS-A, SS-B, ANNA-1
• Heavy metal screen (urine, blood)
• Hepatitis screen, cryoglobulins
Investigations
• EMG/NCV – large fibers
• S Q – proprioception, pain, temperature
• QSART – postganglionic sudomotor
• Autonomic reflex testing (DB, Valsalva, Tilt) • Cardiovagal, cardiovascular adrenergic
• Sympathetic skin response
• Thermoregulatory sweat test - TST
• Skin or salivary gland biopsy, abdominal fat aspiration
• Skeletal survey, LP
• Imaging (chest, abdomen, pelvis)
Nerve Biopsy is useful in:
• Vasculitis
• Sarcoidosis
• Amyloidosis
• Leprosy
• Tumor infiltration
• CIDP?
PN with autonomic involvement
• Diabetes mellitus
• Amyloidosis
• GBS
• Vincristine
• Porphyria
• HIV-related
• PAF
A partial list of clinical characteristics and treatments for six common
forms of systemic vasculitis affecting small and/or medium-sized vessels
of nerve
Characteristic Wegener
Granulomatosis
Churg-Strauss
syndrome
Polyarteritis
nodosa
Microscopic
polyangiitis
Rheumatoid
vasculitis
Mixed
Cryoglobulinemia
Peripheral
nerve
disease
40% – 50% 65% – 80% 35% – 75% 60% –
70%
50% (of cases
of rheumatoid
vasculitis
-- a secondary
vasculitis that
occurs
in 5% - 15% of
cases of RA
20% - 90%
Vessel size
involved
small to medium
vessels (eg,
capillaries, venules,
arterioles, arteries)
small to medium
vessels
medium to small
arteries (not
arterioles,
capillaries or
venules)
small vessels
(eg, capillaries,
arterioles,
venules)
Medium to
small arteries
(histologically
indistinguishable
from polyarteritis
nodosa)
Small (eg,
capillaries,
arterioles, venules)
Pitfalls in EDX in polyneuropathy – I
The primary sources are errors of omission, ie, drawing conclusions based upon a limited
database.
Another common error is overemphasizing the value of conduction velocity. This measure
is sensitive to demyelination but may remain normal in the setting of axon degeneration.
Similarly, distal latencies, another barometer of conduction rate, are markedly prolonged
only in demyelination, moderately prolonged in association with entrapment, and only
mildly prolonged in axonal degeneration.
Failure to exclude from interpretation focal slowing of conduction velocity due to specific
entrapment mononeuropathies before concluding that a generalized process of reduced
conduction exists.
Markedly reduced motor evoked amplitudes (CMAP) with normal sensory responses
(SNAP) are unusual in polyneuropathy; further investigation usually demonstrates a
polyradiculopathy, motor neuron disease, or defective neuromuscular transmission (LEMS)
Sensitivity of conduction velocity, distal latency, and amplitude to change in temperature
Pitfalls in EDX in polyneuropathy – II
Difficulties in obtaining supramaximal stimulation proximally (Erb’s point, tibial nerve in the
posterior knee, radial nerve in the axilla).
The longer the nerve segment the greater the area/ amplitude reduction required for CB.
Excessive stimulation distally - Particularly an issue with median nerve stimulation at the wrist.
Excessive stimulation can recruit ulnar innervated motor units. For all cases of median CB in the
forearm, one needs to stimulate the ulnar nerve at the wrist and record over the thenar eminence. If a
CMAP is obtained, median nerve stimulation at the wrist needs to be done with gradual increments to
make sure that ulnar stimulation does not occur.
Martin–Gruber anastomosis Ulnar CMAP on proximal stimulation can appear reduced if there is
median-ulnar anastomosis. In all cases of suspected ulnar CB in the forearm, one needs to stimulate
the median nerve at elbow recording at Abductor Digiti Minimi to check.
CB cannot be reliably recognized in the context of severe axon loss.
Amplitude below 20% of the lower limit of normal at the most distal stimulation site is sufficiently
small to preclude the confident recognition of CB.
Electrophysiology
-At the onset of acute demyelinating neuropathy small decrease in proximal CMAP amplitude is valid
indicator of conduction block
-In chronic demyelinating neuropathy abnormal temporal dispersion is likely to be responsible for prox/ dist
amplitude discrepancy
-Acute Wallerian degeneration in the first few days may have appearance of CB since some of the fibers
distal to the lesion will preserve their excitability for few days
CB parameters are nerve dependent
peroneal = median = ulnar 25% p-p amplitude reduction
25%d 19%d 19%d 30% -p amplitude reduction
tibial nerve 36% p-p amplitude reduction
33%d 41% -p amplitude reduction
CB criteria are also distance dependent (longer distance- more strict
criteria)
Temperature dependent