peripheral neuropathy. physiology pain and temperature sensation : unmyelinated and small myelinated...

PERIPHERAL NEUROPATHY

PHYSIOLOGY• Pain and temperature sensation :

unmyelinated and small myelinated Ad fibers,

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

• Light touch : both large and small myelinated fibers.

FIVE QUESTION APPROACH

2. Pattern of distribution

3. Temporal course

1. Fiber type

4. Key features

5. Pathology

• 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 or length-dependent neuropathy:

• 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 symptomsPositive :• prickling, searing, burning, and tight bandlike

sensations.• Paresthesia: Unpleasant sensations arising

spontaneously without apparent stimulus• Allodynia: perception of nonpainful stimuli as

painful. • Hyperalgesia: Painful hypersensitivity to noxious

stimuli • Neuropathic pain: cardinal feature of many

neuropathies.

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

• 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.

•Weight loss, malaise, and anorexia.

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 deficitsDominate 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

• Carcinoma;

• Sjögren's syndrome;

• Dysproteinemia;

• AIDS

• vitamin B12 deficiency

• Celiac disease

• Toxicity with cisplatin, thalidomide, or pyridoxine

• 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  

Large-fiber• Areflexia

• 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• 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

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