PERIPHERAL NEUROPATHY

PHYSIOLOGY

• Pain and temperature sensation : unmyelinated and small myelinated A

d

fibers, • Vibratory sense, proprioception, and the afferent limb of the tendon reflex : large myelinated A

a

and A

b

fibers. • Light touch : both large and small myelinated fibers.

FIVE QUESTION APPROACH

1. Fiber type 2. Pattern of distribution 5. Pathology 3. Temporal course 4. Key features

• 1.What is the

fiber type

involved?

(motor, large sensory, small sensory, autonomic, combination) • 2. What is the

pattern of distribution

?

(distal or proximal, symmetric or asymmetric) • 3. What is the

temporal course?

(acute, chronic, progressive, stepwise, relapsing remitting) • 4. Are there any

key features

pointing to a specific etiology? ( toxic/nutritional/malignancy) • 5. What is the

pathology?

(axonal, demyelinating)

Pathological Process

• (1) Wallerian degeneration, which is the response to axonal interruption; • (2) Axonal degeneration or axonopathy; • (3) Primary neuronal degeneration or neuronopathy; • (4) Segmental demyelination

Wallerian degeneration

• Any type of mechanical injury that causes interruption of axons leads to

wallerian degeneration

(degeneration of axons and their myelin sheaths) distal to the site of transection.

Axonal degeneration

• • Most common pathological reaction of peripheral nerve • Caused by :Systemic metabolic disorders, toxin exposure, and some inherited neuropathies

Also called dying-back neuropathy:

or

length-dependent

• The myelin sheath breaks down along with the axon in a process that starts at the most distal part of the nerve fiber and progresses toward the nerve cell body.

Dying-back neuropathy

• Clinically, presents with symmetrical , distal loss of sensory and motor function in the lower extremities that extends proximally in a graded manner.

• The result is sensory loss in a stocking-like pattern , distal muscle weakness and atrophy, and loss of ankle reflexes

Neuronopathy

• Primary loss or destruction of nerve cell bodies with resultant degeneration of their entire peripheral and central axons.

• • Either lower motor neurons or dorsal root ganglion cells may be affected. • When anterior horn cells - poliomyelitis or motor neuron disease: focal weakness without sensory loss

Sensory neuronopathy,

or

polyganglionopathy :

damage to dorsal root ganglion neurons - inability to localize the limb in space, diffuse areflexia, and sensory ataxia.

Segmental demyelination

• The term implies injury of either myelin sheaths or Schwann cells, resulting in breakdown of myelin with sparing of axons • This occurs in immune-mediated demyelinating neuropathies and in hereditary disorders of Schwann cell/myelin metabolism.

Demyelinating neuropathies

• Relative sparing of temperature and pinprick sensation + • 1.Early generalized loss of reflexes, 2.disproportionately mild muscle atrophy 3.presence of proximal and distal weakness, 4.neuropathic tremor 5. palpably enlarged nerves

Diagnostic Clues from the History

• • • • 1.motor 2.sensory 3.autonomic disturbances. Seek both positive and negative symptoms.

A. Motor:

Positive :

Muscle cramps, fasciculations, myokymia, or tremor

Negative

: early distal toe and ankle extensor weakness, resulting in tripping on rugs or uneven ground

Sensory symptoms

• Positive : • • • • prickling, searing, burning, and tight bandlike sensations.

Paresthesia:

Unpleasant sensations arising spontaneously without apparent stimulus

Allodynia:

painful. perception of nonpainful stimuli as

Hyperalgesia:

stimuli Painful hypersensitivity to noxious

Neuropathic pain

neuropathies.

: cardinal feature of many

Autonomic dysfunction

• Orthostatic lightheadedness, • Fainting spells, • Sweating reduced or excessive, • Heat intolerance, • Bladder, Bowel, and Sexual dysfunction. • Anorexia, early satiety, nausea, and vomiting

TEMPORAL CLUES

•

Onset, duration, and evolution

of symptoms • •

Tempo

of disease : acute, subacute, or chronic

Course

: monophasic, progressive, or relapsing • Acute presentations : Guillain-Barré syndrome (GBS), acute porphyria, vasculitis, toxic neuropathies.

• Relapsing course : (CIDP), acute porphyria, Refsum's disease, hereditary neuropathy with liability to pressure palsies (HNPP), familial brachial plexus neuropathy, and repeated episodes of toxin exposure.

Constitutional symptoms

•Weight loss, malaise, and anorexia.

• DM • hypothyroidism • chronic renal failure • liver disease • intestinal malabsorption • malignancy • connective tissue diseases • [HIV] • drug use • Vitamin B6 toxicity • alcohol and dietary habits • exposure to solvents, pesticides, or heavy metals.

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 : Infectious, 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

Motor deficits

Dominate the clinical picture in • 1. AIDP/CIDP • 2. Hereditary motor and sensory neuropathies, • 3. Neuropathies associated with osteosclerotic myeloma, porphyria, lead and organophosphate intoxications, and hypoglycemia.

Pattern of weakness

• Asymmetrical motor weakness without sensory loss suggests motor neuron disease or multifocal motor neuropathy with conduction block

Neuropathies with Facial Nerve Involvement • Guillain-Barré syndrome • Chronic inflammatory polyradiculoneuropathy • Lyme disease • Sarcoidosis • HIV

Predominant Sensory

• Diabetes • Celiac disease • Carcinoma; • Sjögren's syndrome; • Toxicity with cisplatin, thalidomide, or pyridoxine • Dysproteinemia; • AIDS • vitamin B12 deficiency • Inherited and idiopathic sensory neuropathies

Autonomic dysfunction

• GBS • Diabetes • Amyloid sensorimotor polyneuropathy

Small-Fiber Neuropathies

• Idiopathic small fiber neuropathy • Diabetes mellitus • Amyloid neuropathy • HIV-associated distal sensory neuropathy • Hereditary sensory and autonomic neuropathies

• Areflexia

Large-fiber

• Pseudoathetosis • Loss of joint position and vibration sense • Positive Romberg's sign

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

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

Neuropathies + Serum Autoantibodies

Antibodies against Gangliosides

• GM 1 : Multifocal motor neuropathy • GM 1 , 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

SUMMARY

• A. Clinical pattern of neurologic findings Polyneuropathy, Neuronopathy, Mononeuropathy, Multiple mononeuropathy, Plexopathies • B. Functional disturbance : Motor, Sensory, Autonomic, Mixed • • • C. Mode of onset : 1.Acute 2.Subacute 3.Chronic 4.Relapsing

• • • • D. Pathological and electrophysiological criteria : 1.Demyelinating disease vs Axonopathy 2.Wallerian degeneration - trauma 3.Dying back neuropathy - toxic, metabolic • E. Etiology: • • Metabolic, immune mediated, toxic, vasculitis, dysproteinemic, inherited, Nutritional deficiency

• • • • • • • • F. Diagnosis 1.Clinical data 2.Electrophysiologic test : NCS, EMG 3.Biochemical test : metabolic, nutritional, toxic 4.CSF study 5. Nerve & muscle biopsy 6. Measurement of Ig & anti-neural antibody 7. Genetic study