Post on 18-Dec-2015
Jieli Li
12/07/05
Overview
The most common presentation is distal symmetric sensorimotor dysfunction
Developed countries: DM and alcoholism are the most common etiologies
Worldwide: Leprosy is the most common treatable cause The underlying cause of axonal neuropathies can
frequently be treated Demyelinating neuropathies are generally managed with
the assistance of a neurologist
Anatomy
Peripheral nerves include– Cranial nerves (except the second)– Spinal nerve roots– Dorsal root ganglia– The peripheral nerve trunks and their terminal branches– Peripheral autonomic nervous system
Types of Axons
Large myelinated axons (associated with large-fiber neuropathies)
– Motor nerves– Sensory nerves for vibration, proprioception and light touch
Small myelinated axons (associated with small-fiber neuropathies)
– Autonomic nerves– Sensory nerves for light touch, pain and temperature
Small unmyelinated axons (associated with small-fiber neuropathies)
– sensory nerves for pain and temperature
Pathophysiology
Axonopathies – at the level of the axon– Wallerian degeneration– “Dying-back”
Neuronopathies – at the level of the motor neuron or dorsal root ganglion– With subsequent degeneration of their peripheral and central processes– Recover is usually incomplete
Myelinopathies – at the level of the myelin sheath– Inflammatory (acquired) – recovery is often rapid and complete– Hereditary – usually diffuse, slowly progressive course
Wallerian Degeneration and “Dying Back”
After division of the same single nerve fiber, Wallerian degeneration occurs distal to the division. Degeneration will also occur for a variable distance proximal to the nerve division.
Diagnostic Approach
Is there a neuropathy? What is the pattern of nerve involvement?
– Focal – Multifocal – Symmetric
If the neuropathy is symmetric, is it proximal or distal? What is the fiber type?
– Motor– Sensorimotor– Sensory only– Small fiber/autonomic
Any cranial nerve involvement?
Is There a Neuropathy?
Differential diagnosis include:– Motor neuron disease– Disorders of the neuromuscular junction – myopathy– Myelopathy– Syringomyelia– Dorsal column disorders (e.g., tabes dorsalis)– Hysterical symptoms
Neuropathies by Pattern of Involvement
Focal Entrapment
– Common sites of compression– Myxedema– RA– Amyloidosis– Acromegaly
Compressive neuropathies Trauma Ischemic lesions
– DM– Vasculitis
Leprosy Sarcoidosis Neoplastic infiltration or compression
Multifocal DM Vasculitis
– Polyarteritis Nodosa– SLE– Sjögren's syndrome
Sarcoidosis Leprosy HIV/AIDS Multifocal variant of CIDP Hereditary predisposition to pressure palsies
If the Neuropathy is Symmetric, is it Proximal or Distal?
Most toxic and metabolic neuropathies present as a distal symmetric or dying-back process
Proximal sensory neuropathies are rare– Porphyria
Predominantly motor neuropathies are often proximal – Guillain-Barré syndrome – Exception: lead neuropathy
Is There Cranial Nerve Involvement?
Neuropathies with Cranial Nerve Involvement – DM– Guillain-Barré syndrome – HIV/AIDS– Lyme disease– Sarcoidosis neoplastic invasion of skull base or
meninges– Diphtheria
Neuropathies by Fiber Type
Small-fiber neuropathies Leprosy DM Alcoholic neuropathy Amyloidosis AIDS Hereditary
Autonomic neuropathies DM Amyloidosis Porphyria Paraneoplastic neuropathy Lymphoma Thallium, arsenic, mercury toxicity Thiamine deficiency Vincristine (Oncovin, Vincosar
PFS) toxicity Guillain-Barré syndrome Alcoholic neuropathy Acute pandysautonomia HIV/AIDS
Pure Sensory Neuropathies
Paraneoplastic Medications Carcinomatous sensory
neuronopahty Lymphomatous sensory
neuronopathy Sjogren’s syndrome Paraproteinemias Nonsystemic vasculitic
neuropathy
Idiopathic sensory neuronopathy Styrene-induced peripheral
neuropathy Primary biliary cirrhoisis Crohn’s disease Chronic gluten enteropathy Vitamin E deficiency Hereditary sensory neuropathy
types I and IV Friedreich’s ataxia
Diabetic Neuropathy
Most commonly causes a distal, symmetric axonal sensorimotor neuropathy
Second most common: a small-fiber, painful neuropathy Autonomic fiber involvement is common in DM but not
Alcoholism or HIV infection Multifocal neuropathies including cranial nerves Asymmetric proximal motor neuropathy (diabetic
amyotrophy) Symmetric proximal motor neuropathy
Clues in History
Temporal course Symptoms and signs PMH
– Systemic diseases such as DM or hypothyroidism
Medications SH
– Drug and alcohol use FH
– Hereditary neuropathy
Exposure to heavy metals and solvents
HIV risk factors Foreign travel (leprosy) Diet (nutrition) Vitamin use (especially
B6) Tick bite (Lyme disease)
Drugs Causing Neuropathies
Axonal Vincristine, Paclitaxel Isoniazid, Pyridoxine, Ethambutol,
Dapsone Metronidazole Didanosine Alfa interferon Chloroquine Lithium Amitriptyline Phenytoin Hydralazine Nitrous Oxide Colchicine Cimetidine Disulfiram (antabuse)
Demyelinating Amiodarone Chloroquine Suramin Gold
Neuronopathy Thalidomide Cisplatin Pyridoxine
Physical Examination
Vitals – May reveal orthostatic hypotension without a compensatory tachycardia
(seen in autonomic involvement) Respiratory rate and vital capacity (in GBS) Evidence of systemic disease
– Skin lesions– HSM– LAD
Cranial Nerve exam Funduscopic exam
– May show optic pallor which can suggest leukodystrophies and Vit B12 deficiency
Physical Exam cont.
Motor exam– fasciculations or loss of
muscle bulk– Muscle tone – Pattern of weakness
Sensory exam– Sensitivity to light touch,
pinprick, temp– Vibration and position sense– Romberg sign– Sensory loss in specific nerve
distributions (mononeuritis multiplex)
DTR Gait
– Foot drops Trophic changes
– Pes cavus (high arch foot)– Kyphoscoliosis– Loss of hair in affected areas– Ulceration
Nerve thickening
EMG/NCS
Often the most useful initial diagnostic study in patients with peripheral neuropathy
Can confirm the presence of a neuropathy Provide information regarding:
– Types of fibers involved Motor vs. sensory vs.both
– Pathophysiology Axonal loss vs. demyelination
– Patterns of involvement Symmetric vs. asymmetric vs. multifocal
Advantages of EMG/NCS
Being able to distinguish between axonal vs. demyelinating disorders
– Axon loss Loss of amplitude of nerve action potentials
– Myelin loss Slowed nerve conduction velocities Dispersion of evoked compound action potentials Conduction block (decreased amplitude of muscle compound action
potentials on proximal compared with distal nerve stimulation) Marked prolongation of distal latencies
Limitations of EMG/NCS
There is no reliable means of studying proximal sensory nerves
NCS can be normal in pts with small-fiber neuropathies
Lower extremity sensory responses can be absent in normal elderly pts
Standard Laboratory Tests?
CBC ESR TSH SPEP Fasting blood glucose, Hgb A1c BUN/Cr Vitamin B12 ANA UA
Autonomic Studies
Determination of heart rate variation with respiration
Orthostatics Blood pressure response to sustained hand grip Measurement of sympathetic skin response
CSF Analysis
Useful in evaluation of myelinopathies and polyradiculopathies
Albuminocytologic dissociation – Elevated total protein with < 5 WBC– Associated with acquired inflammatory neuropathy
(e.g., GBS, CIDP)
Nerve Biopsy
Only useful in specific cases– Vasculitis– Leprosy– Amyloid neuropahty– Leukodystrophies– Sarcoidosis– CIDP
Sural nerve is the most common site Complications
– Infection– Poor wound healing– Painful dysesthesias
References
Poncelet, AN. An Algorithm for the Evaluation of Peripheral Neuropathy. American Family Physician 1998/57: 4.
Rutkove, SB. Overview of Polyneuropathy. Up to Date 2005.