Approach to peripheral

neuropathyDr. Parag Moon Senior resident

Dept of neurology GMC Kota

Generalized term including disorders of any cause affecting PNS

May involve sensory nerves, motor nerves, or both

May affect one nerve (mononeuropathy), several nerves together (polyneuropathy) or several nerves not contiguous (Mononeuropathy multiplex)

2

Definitions

Further classified into those that primarily affect the cell body (e.g., neuronopathy or ganglionopathy), myelin (myelinopathy), and the axon (axonopathy)

Most common causes

Disease Diabetes1 2

Paraproteinaemia2 3

Alcohol misuse1

Renal failure1

Vitamin B-12 deficiency1

HIV infection1

Chronic idiopathic axonal neuropathy4

Prevalence 11-41% (depending on

duration, type,and control) 9-10% 7% 4% 3.6%

16% (depending on the population studied, usually much lower)

10-40% of different hospital series

BMJ 2010:341:c6100

BMJ 2010:341:c6100

Loss of function“- symptoms”

Disordered function“+ symptoms”

Sensory “Large Fiber”

↓ Vibration↓ ProprioceptionHyporeflexiaSensory ataxia

Paresthesias

Sensory “Small Fiber”

↓ Pain↓ Temperature

DysesthesiasAllodynia

The clinical response to sensory nerve injury

Loss of function“- symptoms”

Disturbed function“+ symptoms”

Motor nervesLarge fibre

WastingHypotoniaWeaknessHyporeflexiaOrthopedic deformity

Fasciculation Cramps

The clinical response to motor nerve injury

Loss of function“- symptoms”

Disturbed function“+ symptoms”

Autonomic nerves ↓ SweatingHypotensionUrinary retentionImpotenceVascular color changes

↑ Sweating Hypertension

The clinical response to autonomic nerve injury

Mononeuropathy

Focal involvement of a single nerve and implies a local process:

Direct trauma compression or entrapment vascular lesions neoplastic compression or infiltration

Mononeuropathy multiplex

simultaneous /sequential damage to multiple noncontiguous nerves.

Ischemia caused by vasculitis Microangiopathy in diabetes mellitus Less common causes : Granulomatous,

leukemic, or neoplastic infiltration, Hansen's disease (leprosy) and sarcoidosis.

Polyneuropathy Characterized by symmetrical, distal motor

and sensory deficits that have a graded increase in severity distally and by distal attenuation of reflexes,

Rarely predominantly proximal:(E.g: acute intermittent porphyria).

The sensory deficits generally follow a length-dependent stocking-glove pattern

Axonopathies

By far the majority of the toxic, metabolic and endocrine causes

NCVs: CMAPs ↓ 80% lower limit of normal w/o or min velocity or distal motor latency change.

Legs>> arms. EMG: Signs of denervation (acute, chronic) and

reinnervation

Myelinopathies

Unusual by comparison with axonopathies Clues: hypertrophic nerves on exam

global arreflexiaweakness without wastingmotor >> sensory deficitsNCS can discriminate inherited from

acquired

NCS: Distal motor latency prolonged (>125% ULN)Conduction velocities slowed (<80% LLN)May have conduction blockEMG: Reduced recruitment w/o much denervation

Clues for diagnosis

Constitutional symptoms

DM hypothyroidism chronic renal failure liver disease intestinal

malabsorption malignancy connective tissue

diseases

[HIV] drug use Vitamin B6 toxicity alcohol and dietary

habits

•Weight loss, malaise, and anorexia.

Conditions Associated withPainful Peripheral Neuropathy Diabetes and Pre-Diabetes Alcohol neuropathy Chemotherapy

◦ Platinum-based Paraproteinemia Vasculitis and Connective Tissue Diseases Heavy metals and other toxins HIV Amyloidosis Porphyria

Medications Causing Neuropathies Axonal

Vincristine Paclitaxel Nitrous oxide Colchicine Probenecid Isoniazid Hydralazine Metronidazole Pyridoxine Didanosine Lithium Alfa interferon Dapsone

Axonal - continued..Phenytoin Cimetidine Disulfiram Chloroquine Ethambutol Amitriptyline

Demyelinating Amiodarone Chloroquine Suramin Gold

Neuronopathy Thalidomide Cisplatin Pyridoxine

Proximal Symmetric Motor Polyneuropathies

◦ Guillain-Barré syndrome◦ Chronic inflammatory demyelinating

polyradiculoneuropathy ◦ Diabetes mellitus ◦ Porphyria ◦ Osteosclerotic myeloma◦ Waldenstrom's macroglobulinemia ◦ Monoclonal gammopathy of undetermined significance◦ Acute arsenic polyneuropathy ◦ Lymphoma ◦ Diphtheria ◦ HIV/AIDS ◦ Lyme disease◦ Hypothyroidism◦ Vincristine (Oncovin, Vincosar PFS) toxicity

History The temporal course of a neuropathy varies,

based on the etiology.

◦ With trauma or ischemic infarction, the onset will be acute, with the most severe symptoms at onset.

◦ Inflammatory and some metabolic neuropathies have a subacute course extending over days to weeks.

◦ A chronic course over weeks to months is the hallmark of most toxic and metabolic neuropathies.

History A chronic, slowly progressive neuropathy

over many years occurs with most hereditary neuropathies or with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

Neuropathies with a relapsing and remitting course include CIDP, acute porphyria, Refsum's disease, hereditary neuropathy with liability to pressure palsies (HNPP), familial brachial plexus neuropathy, and repeated episodes of toxin exposure.

Ischemic neuropathies often have pain as a prominent feature.

Small-fiber neuropathies often present with burning pain, lightning-like or lancinating pain, aching, or uncomfortable paresthesias (dysesthesias).

History

Dying-back (distal symmetric axonal) neuropathies initially involve the tips of the toes and progress proximally in a stocking-glove distribution.

History

Peripheral neuropathy can present as restless leg syndrome.

Proximal involvement may result in difficulty climbing stairs, getting out of a chair, lifting and bulbar involvement can also be seen

History

The clinical assessment should include:◦ careful past medical history, looking for systemic

diseases that can be associated with neuropathy, such as diabetes or hypothyroidism.

History

All patients should be questioned regarding ◦ HIV risk factors◦ diet (nutrition)◦ vitamin use (especially B6) ◦ possibility of a tick bite (Lyme disease) ◦ Constitutional symtoms (malignancy)

History

Differential Diagnosis of Neuropathies

by Clinical Course Acute onset (within days)

Subacute onset (weeks to months)

Chronic course/ insidious onset

Relapsing/ remitting course

Guillain-Barré syndrome

Maintained exposure to toxic agents/medications

Hereditary motor sensory neuropathies

Guillain-Barré syndrome

Acute intermittent porphyria

Persisting nutritional deficiency

Dominantly inherited sensory neuropathy

CIDP

Critical illness polyneuropathy

Abnormal metabolic state

CIDP HIV/AIDS

Diphtheric neuropathy

Paraneoplastic syndrome

Toxic

Thallium toxicity CIDP Porphyria

Physical Examination A cranial nerve examination can provide

evidence of mononeuropathies.

Funduscopic examination may show abnormalities such as optic pallor, which can be present in leukodystrophies and vitamin B12 deficiency.

Thickened nerves

Physical examination

Assessing Autonomic Nervous System

Cardiovagal◦ Heart rate variability

Adrenergic◦ Valsalva maneuver

Induces BP changes and monitors pulse reaction

Postganglionic sudomotor function◦ QSART

Recommendations for lab testing: Screening laboratory tests may be

considered for all patients with DSP (Level C).

Tests with the highest yield of abnormality:1. blood glucose (fasting)2. serum B12 with metabolites (methylmalonic acid, homocysteine)3. SPEP(serum protein electrophoresis)

(Level C).

Other laboratory studies ANA, RF, Anti-dsDNA, Anti-Ro, Anti-La, ANCA

screen, cryoglobulins Urine for heavy metals, porphyrins IFE/urine IFE/ plasma light chain analysis

Neuropathies + Serum Autoantibodies

Antibodies against Gangliosides GM1 : Multifocal motor neuropathy GM1, GD1a : Guillain-Barré syndrome GQ1b : Miller Fisher variant

Antibodies against Glycoproteins Myelin-associated glycoprotein : MGUS

Antibodies against RNA-binding proteins Anti-Hu, antineuronal nuclear antibody 1: Malignant

inflammatory polyganglionopathy

Electrodiagnostic studies

(1) Confirming the presence of neuropathy,

(2) Locating focal nerve lesions,

(3) Nature of the underlying nerve pathology

Distal motor latency prolonged

Nerve conduction velocity slow

Reduced action potential

The limitations of EMG/NCS should be taken into account when interpreting the findings. ◦ There is no reliable means of studying proximal

sensory nerves. ◦ NCS results can be normal in patients with

small-fiber neuropathies◦ Lower extremity sensory responses can be

absent in normal elderly patients.

EMG/NCS are not substitutes for a good clinical examination.

Laboratory Evaluation

Nerve biopsy In vasculitis, amyloid neuropathy, leprosy,

CIDP, Inherited disorders of myelin, and rare axonopathies

The Sural nerve is selected most commonly The superficial peroneal nerve – alternative;

:advantage of allowing simultaneous biopsy of the peroneus brevis muscle through the same incision.

This combined nerve and muscle biopsy procedure increases the yield of identifying suspected vasculitis

Skin biopsy

“For symptomatic patients with suspected polyneuropathy, skin biopsy may be considered to diagnose the presence of a polyneuropathy, particularly SFSN.”

Slow progression◦ Treat causative factors if possible◦ If rapidly progressing

IVIG Immunomodulating agents

Symptom Management

Treatment

Tricyclic antidepressants◦ Amitryptilin, nortryptilin

Calcium channel alpha-2-delta ligands◦ Gabapentin, pregabalin

Calcium channel blocker• Prialt SNRI’s

◦ Duloxetine, venlafaxine Topical Agents

◦ Lidocaine, Capsaicin

Symptom Management

Antiepileptic Drugs◦ Carbamazepine, phenytoin, lacosamide

SSRI’s Opioid analgesics Tramadol Miscellaneous

◦ Botulinum toxin◦ Mexiletine◦ Alpha lipoic acid

NMDA receptors unsuccessful◦ Namenda, Dextromethorphan

Symptom Management

First line drugs • Lidoderm 5% patch• Tricyclic antidepressants• Gabapentin• Pregabalin p.o.• Duloxetine Second line • Carbamazepine• Phenytoin• Venlafaxine • Tramadol

Physical Therapy ◦ Gait and balance training

Assistive devices Safe environment Footwear at all times Foot hygiene

Thanks

Clinical Approach to Peripheral Neuropathy: Anatomic Localization and Diagnostic Testing Adina R. Alport et al : Continuum Lifelong Learning Neurol 2012;18(1):13–38.

An Approach to the Evaluation of Peripheral Neuropathies;Mark B. Bromberg; SEMINARS IN NEUROLOGY/VOLUME 30, NUMBER 4 2010

References