1. CLINICAL APPROACH TO PERIPHERAL NEUROPATHY
Prof Dr.B.P.Shelley
Department of Neurology
Yenepoya Medical College

2. “Pattern recognition algorithm”
A stepwise approach
“Pattern recognition algorithm”

3. Peripheral Neuropathies
Diagnostic conundrum: Diagnostic challenge, large number of potential causes, literally thousands of possible causes; is potentially frustrating, time consuming and costly
Despite best efforts, it is important to appreciate that a good percentage (~20%) of neuropathies will remain undiagnosed despite an exhaustive evaluation
1/3-genetic; 1/3-acquired; 1/3- idiopathic despite appropriate diagnostic evaluation
“Pragmatists vs. Completists”: Need to set the direction and level of aggressiveness of the evaluation, should not have an umbrella “one size fits all” blanket strategy of evaluation to an all encompasive ‘excludogram’ approach i.e. an unnecessarily expensive “shotgun” approach

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

11. 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)

12. 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

13. 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.

15. Role of nerve fibres in peripheralneuropathy

16. 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

17. Neuronopathy
Dorsal root ganglionopathy (inflammatory; drugnon neoplastic-NISP; Malignant sensory inflmmaory ganglionopathy-MISG)
Primary loss or destruction of nerve cell bodies with resultant degeneration of their entire peripheral and central axons.
Either lower motor neurons (AHC, motor axonopathy) 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 early gait/limb sensory ataxia; pain, paresthesia, numbness, cramps, fatigue, abnormal hot/cold sensations, nocturnal pains in UL/LLs, severe loss of JPS/vibration sense

18. 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.

19. Demyelinating neuropathies
Relative sparing of temperature and pinprick sensation +
1.Early generalized loss of reflexes (large fiber, predominantly motor neuropathy; immune mediated; acute-subacute)
2.Disproportionately mild muscle atrophy but DTRs affected
3.Presence of proximal and distal weakness (P>D/P=D; universal DTRs involvement)
4.Neuropathic tremor (Anti MAG-IgM paraproteinemic neuropathy- CIDP like)
5. Palpably enlarged nerves
6. CSF Albuminocytologic dissociation
7. ElectroDx changes: slowed NCV, CBs, TD (acquired demyelination, segmental demyelination; not uniform demyelination as in genetic determined CMT IA)

20. 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

21. 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.

22. Autonomic dysfunction
Positive or Negative symptoms
Orthostatic lightheadedness
Fainting spells
Sweating reduced or excessive
Heat intolerance
Bladder, Bowel, and Sexual dysfunction
Anorexia, early satiety, nausea, and vomiting
Adie’s pupil
Cardiovascular dysautonomia

23. 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.

24. 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.

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

26. 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.

27. 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

28. 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.

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

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

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

32. Autonomic dysfunction
GBS
Diabetes
Amyloid sensorimotor polyneuropathy

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

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

35. Algorithm
Does the history and examination suggest that the pathological process is localized to the peripheral nerve? Masqueraders-parietal lesion, cervical spondylotic myelopathy, transverse myelitis; certain neuropathies co-exist with CNS disease (myeloneuropathies-vitamin
B12 deficiency, adrenomyeloneuropathy)
Has the presenting complaint been fully described? a thorough & meticulous history taking
Have I obtained adequate past, family, occupational, and drug histories?
What special features of diagnostic help might I pick up from the examination? (Pink urine-porphyria, umbilical angiokeratomas of Fabry’s disease, Mees line of Arsenic toxicity, orange tonsils of Tangier’s disease, ansomia in Refsum’s diase, Optic atrophy, Adie’s pupil for dysautonomia)

36. Algorithm Is the neuropathy focal, multifocal or generalized?
What is the relative extent of motor and sensory nerve involvement?
Is there prominent small fibre and autonomic involvement?
Is the neuropathy axonal or demyelinating on clinical grounds? (demyelinating- widespread DTR loss, proximal & distal in muscle groups that are not particularly weak or wasted, more proximal weakness/ axonal- selective distal/ankle DTRS absent in the presence of distal wasting and weakness, stocking distribution of sensory loss)
What additional information can I expect from a neurophysiologic assessment?
What screening tests should I perform?
When should I do a nerve biopsy?

37. Stepwise approach
Within the peripheral nervous system? Exclude CNS, spinal causes (UMN cause)
What part of the peripheral nervous system? Root, plexus, single nerve, multiple nerves, peripheral neuropathy, radiculoplexopathy, myeloneuropathy; proximal (AIDP, CIDP, Porphyria, DRPN) or distal neuropathiy; cranial or trunkal neuropthy
What is the time course? Acute, subacute, chronic, progressive, relapsing-remitting, event-linked
What nerve fibers are involved? Sensory, motor, autonomic, combinations
What is the primary pathology? Demyelination, axonal, mixed
What are the other pertinent features? Family, medical, social histories, genetic history

38. An easy approach to peripheral neuropathy

39. “WHAT. ”, “WHERE. ”, “WHEN. ” and “WHAT SETTING
“WHAT?”, “WHERE?”, “WHEN?” and “WHAT SETTING?” ‘user friendly approach’  
What: Nerve fiber type- Sensory (S), motor (M), or autonomic (A) (small fiber vs. large fiber; positive vs. negative symptoms; demyelinating vs. axonal (Myelinopathy, Axonopathy, Neuronopathy); Painful vs. painless) SM, Pure M, Pure S, M>S, S>M, pure autonomic; helpful to rank them in order of symptom predominance- predominantly motor-immune mediated neuropathies/ sensory predominant-small fiber, length dependant, dying back (axonal-Wallerian degeneration) neuropathies related to toxic, metabolic, nutritional, or ischemic-vasculitic etiologies. Ranking them by predominance can help direct evaluation of neuropathies (Harrison’s tabular column)

40. Autonomic-Diabetes, Amyloid, GBS, Sjogren’s related neuropathies, Paraneoplastic, HSAN) Sensory neuropathic symptom profile: Patients with acquired polyneuropathies usually complain of positive neuropathic sensory symptoms (PNSS), whereas patients with inherited polyneuropathies only rarely do. Painful neuropathies (allodynia, hyperalgesia) suggest toxic, metabolic, or ischemic/vasculitic causes of neuropathy involving small fibers (small fiber neuropathy). Pure sensory neuropathies or neuronopathies can result from drug toxicity (e.g., thalidomide, cisplatin, paraneoplastic syndromes or nutritional deficiencies-thiamine; uremia. Predominantly motor neuropathies: AIDP, CIDP, MMN, Prophyria, Diptheria, SLE/PAN, TOCP, Lead. Small fiber sensory neuropathies: DM, Hansen’s, Thiamine, Uremia, Amyloid, Paraneoplastic, HSN. Small fiber autonomic neuropathies: Diabetes, amyloid, Fabry’s disease, Tangier’s, Sjogrens, HSAN)
Fiber Types: Myelinated Aα, Aβ (motor); Thinly myelinated Aδ/C (sensory); Unmyelinated (Type C); Pseudo-syringomyelic neuropathy

41. Where:
The distribution of nerve involvement: symmetrical/asymmetrical/multifocal
Proximal or length dependant distal; mono, multiple mononeuritis, polyneuropathies; plexopathy; neuronopathy; radiculoplexopathy; radiculoneuropathy; myeloneuropathy); cranial/trunkal neuropathies
Motor neuronopathies (eg, amyotrophic lateral sclerosis), Sensory neuronopathies (eg, paraneoplastic), polyradiculoneuropathies (Guillain-Barré syndrome, CIDP), and mononeuritis multiplex (caused by vasculitis), Diabetic radiculoplexopathy, Hepatic/Nutritional-Cassava-Konzo-Tropical Myeloneuropathies (TSP). Multifocal: Vasculitis, Amyloid, Diabetes, MMN, HNPP

42. When? , What setting?
When (disease course): The time course of signs and symptoms: acute, subacute, chronic, recurrent & relapsing; Acute/subacute onset often suggests an immune-mediated or infectious process.
What setting (Etiological): Hereditary-inheritance pattern; familial/ Acquired-MINI- Metabolic, Immune, Neoplastic, Infectious: medical history, medications, social and family history, review of systems (Hereditary/genetic; Acquired- infectious, toxic, metabolic, drugs, endocrine, paraneoplastic, immune mediated, infiltrative, inflammatory-vasculitic); with neurocutaneous markers; hammer toes; claw feet; pes cavus; “champagne bottle” legs, trophic painless ulcers-valuable clues for genetical neuropathies; malignancy; bariatric surgeries-Vit B1 B12 deficiencies; gastrectomy related ‘SCD like picture’ with normal Vit B12-copper myeloneuropathy

43. Pearls for classification of peripheral neuropathies A suggested construct for the approach to neuropathy, using the “what, where, when, and what setting” approach to characterizing the neuropathy and placing the neuropathy into a presumed etiologic ...
Figure Pearls for classification of peripheral neuropathies A suggested construct for the approach to neuropathy, using the “what, where, when, and what setting” approach to characterizing the neuropathy and placing the neuropathy into a presumed etiologic category. PNSS = positive neuropathic sensory symptoms; CMT = Charcot-Marie-Tooth; HMSN = hereditary motor and sensory neuropathies; HNPP = hereditary neuropathy with liability to pressure palsy; GBS = Guillain-Barré syndrome; CIDP = chronic inflammatory demyelinating polyradiculoneuropathy; MMN = multifocal motor neuropathy; PAN = polyarteritis nodosa; SLE = systemic lupus erythematosus; RA = rheumatoid arthritis. Modified and reprinted with permission from Mauermann ML, Burns TM. The evaluation of acquired neuropathies. Semin Neurol 2008;28:133–151.6
Mauermann M, Burns T. Neurology 2009;72:e28-e31
©2009 by Lippincott Williams & Wilkins

44. Electrodiagnosis
ElectroDx: Electrodiagnostic testing assists in characterizing the neuropathic process as sensory, motor or sensorimotor (What?). Electrodiagnostic testing helps characterize a neuropathy as primarily demyelinating, primarily axonal, or mixed demyelinating and axonal; help localize the neuropathic process (the “where”-symmetrical, asymmetrical, proximal, distal, localization to roots, plexus, nerve, radiculoplexopathy, radiculoneuropathy); help gauge the severity of neuropathy; help assess treatment response

45. Algorithm showing a stepwise approach to the assessment and investigation of a possible neuropathy. CIDP, chronic inflammatory demyelinating polyradiculoneuropathy; CMT, Charcot-Marie-Tooth; EMG, electromyography; GBS, Guillain-Barre syndrome; HNPP, hereditary neuropathy with liability to pressure palsies; NCS, nerve conduction studies.
Willison, H. J et al. J Neurol Neurosurg Psychiatry 2003;74:3-8ii
Copyright ©2003 BMJ Publishing Group Ltd.

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

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

49. 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

50. 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

51. 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
                             

52. 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  
Laboratory Tests: Serology, CSF, Blood sugar, Liver function tests, Vitamin B12, Paraprotein screen, Thyroid function, Full blood count, Erythrocyte sedimentation rate, vasculitic screen                                                    
4.CSF study
     5. Nerve & muscle biopsy Nerve biopsy: helpful in very specific cases to diagnose vasculitis, leprosy, amyloid neuropathy, leukodystrophies, sarcoidosis and, occasionally, CIDP
     6. Measurement of Ig & anti-neural antibody
     7.  Genetic study
                                                      

53. History taking; Pertinent question (Pearls & Oysters)
Time frame/Onset: Acute (0-4 weeks), Sub acute (4-8 weeks), Chronic (> 8 weeks)
Course: Monophasic; Multifocal; Progressive; Relapsing/Recurrent (CIDP/Refsum’s disease; porphyria; beri-beri; Tangier’s disease; Toxic: HIV)
Distribution: Focal or Multifocal (MADSAM; HNPP; Vasculitic; Entrapment); Diffuse/Generalised; Symmetrical or Asymmetrical (mononeuritis multiplex-DM; vasculitic, PAN, SLE; Wegner’s; Churg- Strauss; cryogloulinemia; Sjogren’s; HNPP; HIV; lymphoma; carcinoma)
Fiber Type: Type A alpha; Type A beta (myelinated); Type A delta (thinly myelinated); Type C (unmyelinated); Large fiber vs. Small fiber neuropathy
Positive and Negative Symptoms Associated with Nerve Damage

54. History taking; Pertinent question (Pearls & Oysters)
Clinical pattern: Motor, Sensory, SM, Autonomic; Cranial neuropathies
Painful [Neuropathic pain] vs. Painless neuropathies/ Painful neuropathies are axonal secondary to toxic, metabolic, nutritional causes
Recurrent/Relapsing neuropathies
Mononeuropathy, Mononeuritis multiplex, Polyneuropathy, Autonomic, Myeloneuropathies, Radiculoneuropathies
Polyneuropathy with clinical combinations/associations: skin changes; eye lesions; ear lesions; pyramidal deficits; ataxia; mental- cognitive-behavioural-neuropsychiatric disorders; orange tonsils; dwarfism; thickened Achilles tendon

55. History taking; Pertinent question (Pearls & Oysters)
Polyneuropathies with “the company it keeps”
Skin: Refsum’s disease/Abetalipoproteinemia (icthyosis); xeroderma pigmentosum, Cockayne syndrome; Varigate porphyria (UV light hypersensitivity); Fabry’s disease (angiokeratoma corporis diffusum)
Curly reddish hair: Giant axonal neuropathy (alopecia-Thallium neuropathy)
Eye: Refsum’s disease; Cockayne syndrome; Abetalipoproteinemia; NARP (Retinitis pigmentosa); ALD (retinal degenartion); HMSN (Optic atrophy); Fabry’s disease, Tangier’s disease; Familial amyloid neuropathy Type 4 (corneal dystrophy); Refsum’s disease/abetalipoproteinemia (night blindness); Marinesco-Sjogren’s syndrome (cataract)
Ear: Fabry’s disease
Cardiac: Refsum’s disease, Refsum’s disease (ataxia; neuropathy; cardiomyopathy; phytanic acid elevated; cataract; SN deafness; icthyosis)

56. History taking; Pertinent question (Pearls & Oysters)
GI symptoms: Whipple’s disease; Malabsorption syndromes; Celiac disease; Arsenic neuropathy (abdominal pain, diarrhea, vomiting
Adrenal insuffiency: ALD
Pyramidal: Krabbe, Metachromatic leucodystrophy; HMSN type 5; SCD-anemia/Vit E/Copper myeloneuropathies; HSP; TSP; Tropical Myeloneuropathies
Ataxia: Mitochondrial cytopathies; Ataxia telangiectasia; Abetalipoproteinemia (LDL C low); Refsum’s disease; Xeroderma pigmentosum; Cockayne syndrome, SCD, Friederich’s ataxia; Roussy Levy Disease
Mental retardation: Leucodystrophy; Cockayne syndrome; ADL
Neuropsychiatry: Porphyria
Yellow Orange tonsils: Tangier’s disease (HDL C low)
Short stature/Dwarfism: Cockayne syndrome; mitochondrial cytopathies
Thickened TA tendon: Cerebrotendinous xanthomatosis

57. History taking; Pertinent question (Pearls & Oysters)
Upper limb/Bibrachial neuropathies: Lead neuropathy, brachial neuritis, amyloid neuropathy type II, Porphyria, AIDP/GBS, MMNCB, ALS, Hirayama’s diasease, Bibrachial amyotrophic diplegia, HypoK paralysis
Neuropathies with cranial nerve involvement:AIDP/GBS, CIDP, Hansen’s disease; Diabetes mellitus, HIV, Sarcoidosis, Diptheria
Asymmetrical neuropathies:Mononeuritis multiplex, Vasculitic PAN, SLE, Wegeners’ granulomatosis, Cryoglobulinemia, Sjogren’s syndrome, HNPP, HIV, Lymphoma, Carcinoma

58. Evaluation of PN; Pearls & Oysters
Pathology:
Fiber type: Small (Pseudosyringomyelic-Leprosy; DM; Tangier’s; Amyloid; Alcoholic ;) vs. Large fiber neuropathy (Positive & Negative symptoms); Burning feet syndrome/Gopalan syndrome-pantothenate deficiency; alcoholic; nutritional neuropathies; toxic-Arsenic/Thallium; HIV
Small fiber: DTRs retained
Positive: fasciculations; minipolymyoclonus; cramps; myokymia; neuromyotonia; dystonia; pseudoathetosis; tremors (CIDP/Anti MAG paraproteinemic neuropathy); paraesthesia; dysesthesia; allodynia; hyperpathia; hyperalgesia; restless leg syndrome/Ekbom’s syndrome; sensory ataxic neuropathies/ganglionopathies (pseudoathetosis-dancing fingers; pseudotabes-DM)
Negative: Numbness; loss of temperature sensations
Myelinopthy/Demeylination (segmental), Axonal-dying back neuropathy/Axonopathy, Mixed demyelinating-axonal; Neuronopathy (DRG/AHC)
Demyelinating neuropathy: proximal > distal weakness; proximal DTRs affected; no atrophy; thickened nerves; CSF: AB cytologic dissociation; NCV changes & F latency
Axonopathies: Distal weakness; distal areflexia; muscle atrophy; NCV changes; EMG DN pattern

59. Evaluation of PN; Pearls & Oysters
Etiological: MINI (Metabolic; Immune; Neoplastic/Nutritional; Infectious/Inherited) Hereditary/Genetic, Inflammatory, Infectious,Ischemic, Immunological, Nutritional, Metabolic, Toxic, Drug induced; Infiltrative, Paraneoplastic, Critical Illness; Idiopathic (30%)
Topography: Proximal/Distal Neuropathies (length dependant neuropathies) [Proximal neuropathies: AIDP/SIDP/CIDP/Porphyric neuropathy; Diabetic plexoradiculopathy-Garland’s Diabetic amyotrophy]
Genetic neuropathies: AR; AD; X-linked Mendelian inheritance (HMSN; HSAN)
Enlarged peripheral nerves: Hansen’s disease; chronic recurrent/replacing neuropathies; CIDP; HMSN-CMT-1 (hypertrophic neuropathies); Neurofibromatosis; nerve tumors; Djerine Sottas neuropathy; Amyloid neuropathy [greater auricular-middle SSM; supraorbital; suprascapular; supraclavicular; cervical, ulnar; median (wrist); radial (radial groove); CPN; posterior tibial; superficial radial cutaneous-anatomical snuff box]

63. Causes of small fiber neuropathy
Diabetes
Amyloidosis
Fabry's disease
Tangier's disease
Hereditary sensory and autonomic neuropathy
Sjogren's syndrome
Chronic idiopathic small fiber sensory neuropathy

64. Causes of focal-multifocal neuropathies
Entrapment neuropathy: Carpal tunnel syndrome, ulnar nerve at the elbow, common peroneal at the fibular head
Endocrinal: diabetes mellitus, myxedema, acromegaly, Amyloidosis
Hereditary neuropathy susceptible to pressure palsy
Vasculitis
Multifocal motor neuropathy with conduction block

65. Causes of chronic axonal neuropathies
Drugs & Toxins: Alcohol, Vincristine, Phenytoin, TOCP, Organophosporus, Statins
Infections: Leprosy, HIV, Borreliosis
Connective tissue/Vasculitic: Sjogern’s syndrome; SLE; MCTD, RA
Metabolic: DM, CRF
Paraneoplastic: CA lung,ovary
Inherited: CMT 2; CMT-X
Vitamin deficiency: B12, Folate; Cobalamin, Vit E
Endocrine: Hypothyroidism
Paraproteinemia; Waldenstrom’s macroglobulinemia; MGUS; POEMS syndrome 

66. NERVE BIOPSIES
Granulomatous infiltration-Hansen’s disease
Amyloidosis (Rectal biopsy)
Leprosy
Sarcoidosis
Leucodystrophies
Giant axonal neuropathy
Vasculitides
Demyelinating-CIDP (onion bulb formation-Schwann cell hyperplasia)
Tomaculous neuropathy
Mitochondrial neuropathies
Refsum’s disease

67. Learning Key Points Answer “what, when, where, & what setting?”
Perform electrodiagnosis
Use laboratory testing judiciously
Treat as appropriate

74. SCIENTIFIC WISDOM & ROOTS OF LIFE LONG LEARNNG
There are known knowns; there are things we know we know. We also know there are known unknowns; that is to say, we know there are some things we do not know. But there are also unknown unknowns – the ones we don’t know we don’t know. Donald Rumsfeld
STAY HUNGRY [curiosity; critical thinking, self directed learning] STAY FOOLISH [ thirst for knowledge] Steve Jobs
'One thing I only know, & that is, I know nothing' Socrates.

75. THANK YOU