1. PERIPHERAL NEUROPATHY

8. 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.

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

10. 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)

11. 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

12. 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.

19. 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.

21. 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

22. 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.

23. 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.

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

25. 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

26. Sensory symptoms Positive :
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.

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

28. 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.

29. 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.

30. Mononeuropathy
Focal involvement of a single nerve and implies a local process:
Direct trauma
compression or entrapment
vascular lesions
neoplastic compression or infiltration

31. 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.

32. 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

33. 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.

34. Pattern of weakness
Asymmetrical motor weakness without sensory loss suggests motor neuron disease or multifocal motor neuropathy with conduction block

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

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

37. Autonomic dysfunction
GBS
Diabetes
Amyloid sensorimotor polyneuropathy

38. Small-Fiber Neuropathies
Idiopathic small fiber neuropathy
Diabetes mellitus   
Amyloid neuropathy   
HIV-associated distal sensory neuropathy
Hereditary sensory and autonomic neuropathies   

39. Large-fiber Areflexia Pseudoathetosis
Loss of joint position and vibration sense
Positive Romberg's sign

41. Electrodiagnostic studies
(1) Confirming the presence of neuropathy,
(2) Locating focal nerve lesions,
(3) Nature of the underlying nerve pathology

43. Distal motor latency prolonged
Nerve conduction velocity slow
Reduced action potential

44. 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

45. 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

46. 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
                              

47. 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
                                                       

48. 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