Differential Diagnosis in Neurology

10.20. Differential Diagnosis of Neuropathy by Pathology, Evolution Overtime and Precipitating Cause

• Axonal necropathies:
  • Acute onset:
    • Acute demyelinating axonal neuropathy (AIDP)
    • Acute intermittent porphyria
    • Variegate porphyria
    • Coproporphyria
    • Tick paralysis
  • Acute intoxications (axonal destruction):
    • Heavy metals ( lead , arsenic, mercury, thallium, gold, antimony, zinc, bismuth)
    • Organic solvents (n-hexane; methyl-N-butyl ketone; organophosphates, toluene)
    • Toxins:
      • Antineoplastics
      • Sedative/hypnotics
      • Antibiotics
      • Nutritional deficiency
      • Medicines
  • Subacute and chronic axonal neuropathies associated with systemic disease:
    • Diabetes mellitus
    • Hypothyroidism
    • Liver failure
    • Chronic obstructive lung disease
    • Acromegaly
    • Critical care neuropathy
    • Celiac disease (gluten enteropathy)
    • Crohn's disease
    • Pancreatitis
    • Uremia
    • Sarcoid
    • Paraneoplastic (antiHu, MA, TA)
    • Myeloma
    • Congestive heart failure
    • Primary biliary cirrhosis
    • Hyperlipidemia
    • Amyloidosis (acquired, TTR-met 30; familial)
    • Hyperoxaluria
    • Ethylene oxide
    • Hexocarbons
    • Acrylamide
    • Vitamin B12 (most often demyelinating)
    • Vitamin E
    • Pyridoxine
    • Thiamine
    • Lead
    • Vincristine
    • Fabry's disease
    • Cisplatin
    • Thallium
    • Colchicine
    • Phenytoin
    • Disulfiram
    • Lithium
    • Vasculitis
    • HIV
    • Sjögren's
    • Scleroderma
    • Rheumatoid arthritis
    • Lead poisoning

Charcot–Marie–Tooth Type 1 (HSMNI)

• CMT – 1A – chromosome: 17 p11.2–12 – gene: PMP 22
• CMT – 1B – chromosome: 1 q 22–q23 – gene PO
• CMT – 1C – chromosome: same locus for CMT-2I; 2J) – gene: Po
• CMT – 1D – chromosome: 10q 21–q22 – gene: EGR-2

Charcot–Marie–Tooth Type 2 (HSMN-II)

• CMT-2A - Chromosome: 1p35–p36
• CMT-2B - Chromosome: 3q13–q22
• CMT-2C
• CMT-2D - Chromosome: 7p14
• CMT-2E - Chromosome: 8p21
• CMT-2G
• CMT-2L - Chromosome: 12q24
• CMT-2H
• CMT-2I
• CMT-2K
• CMT-2J

Dejerine Sottas (CMT 3, HSMN III)

• DSD - Chromosomes: 17p11, 2–12 (EGR2); 1q22–23; 10q21–q22

Charcot–Marie–Tooth

• CMT-X- Chromosome:Xq13.1 (CX32)
• CMT-4A - Chromosome: 8q13–q21
• CMT-4B - Chromosomes: 5q23–q33 (MTMR-2); 11q22

Congenital Hypomyelinating Neuropathy

• CHN - Chromosome: 10q22–23 (EGR2); 1q22–23

Hereditary Neuropathy with Liability to Pressure Palsy

• HNPP - Chromosome: 17p11.2–12 (PMP22)

Inherited Axonal Neuropathies

• Hereditary sensory motor neuropathy II:
  • CMT 1–17
• Hereditary sensory motor neuropathy type IV (with optic atrophy)
• Hereditary sensory motor neuropathy type VI (II and spastic paraparesis)
• Hereditary sensory neuropathy (autonomic neuropathy):
  • Type I – AD
  • Type II – AR
  • Type III – Rily Day
  • Type IV
• Leigh's disease (mtDNA)
• NARP (neuropathy, ataxia, retinitis pigmentosa)
• Porphyrias (AIP, variegate)
• Coproporphyrinuria
• Fabry's disease
• MNGIE (mtDNA) myopathy, neurogastrointestinal, encephalopathy
• Ataxia telangiectasia
• Giant axonal neuropathy
• Associated with spinocerebellar degeneration
• Friedreich's variant's; SCA 3
• Amyloidosis-TTR-met 30 (transthyretin); familial amyloid

Hereditary Demyelinating Neuropathies

• HSMN I, III, IV
• Krabbe's globoid leukodystrophy
• Tangiers's disease
• Metachromatic leukodystrophy
• Adrenomyeloneuropathy
• Cockayne's syndrome

Segmental Demyelinating Neuropathies

• AIDP
• CIDP
• Arsenic
• Carcinoma
• Lymphoma
• Hereditary neuropathy with sensitivity to pressure palsy (HNNP-chromosome 17)
• Hypothyroidism
• Ulcerative colitis
• Amiodarone
• Perhexiline
• Arabinoside (Ara-C)
• Waldenström's macroglobulinemia
• Monoclonal gammopathy of undetermined significance (IgM, IgG, IgA)
• Diphtheria
• Leprosy
• Diabetes
• HIV
• Lyme's disease
• SLE
• Cryoglobulinemia
• Osteosclerotic myeloma

Asymmetric Single or Multiple Neuropathies

• Diabetic proximal asymmetric neuropathy
• Polyarteritis
• Vasculitides
• Entrapment
• Compression
• Traumatic neuropathy
• Autoimmune (primarily lower extremity)

Acute Demyelinating Neuropathy

• AIDP (GBS)
• Diphtheria
• HIV
• Lyme

Chronic Demyelinating Neuropathy

• Hypomyelinating neuropathy (CHN)
• HSMN (I, III)
• Refsum's (IV)
• Metachromatic leukodystrophy
• HNPP (deletion chromosome 17)
• Hypothyroidism
• Diabetes
• Uremia
• Perhexiline
• Sodium cyanate
• Allergic (vasculitis)
• HIV
• Paraproteinemia
• CIP/CDIP/multifocal
• Waldenström's macroglobulinemia
• Osteosclerotic myeloma
• Monoclonal gammopathy of unknown significance (MGUS)
• SLE
• Melanoma (immunotherapy)
• Plasma cell dyscrasia
• Inflammatory bowel disease
• MAG, SGPG-autoimmune epitopes
• SICCA complex
• CID-codon 200
• MtDNA neuropathy 3243

Toxic Neuropathies

• Heavy metals:
  • Thallium
  • Zinc
  • Bismuth
  • Mercury
  • Gold
  • Lead
  • Arsenic
  • Platinum
• Organic solvents (hexocarbons):
  • M-hexane
  • Methyl-n-butyl ketone
  • Organophosphates
  • Acrylamide
  • Toluene
  • Carbon disulfide
  • Vacor
• Drugs:
  • Vincristine
  • Vinblastine
  • Nitrogen mustard
  • Taxol
  • Cis-platinum
  • Docetaxel
  • Paclitaxel

Antiretroviral Agents

• Stavudine
• Dideoxycytidine (ddc)
• HAART drugs

Miscellaneous Drugs

• Penicillin
• Fe injection
• FK-506 (tacrolimus)
• Lithium
• Amiodarone
• Interferon-a
• Methylbromide
• Tegretol/Dilantin
• Colchicine
• Allopurinol

Antibiotics

• Amphotericin B
• Chloramphenicol
• Clioquinol
• Streptomycin
• Ethambutol
• INH
• Nitrofurantoin
• Sulfonamide
• Pyridoxine
• Stilbamidine
• Dapsone

Sedative/Hypnotic/Antidepressants

• Amitriptyline
• Imipramine
• Meprobamate
• MAO inhibitors
• Glutethimide

Nutritional Deficiencies

• Alcohol (associated with multiple vitamin deficiency)
• Thiamine (Wernicke's)
• Pyridoxine
• Pantothenic acid (associated with chronic alcoholism)
• Riboflavin
• Vitamin B12
• Vitamin B6
• Vitamin E