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