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TOXIC NEUROPATHIES


TOXIC NEUROPATHIES: CLINICAL & PATHOLOGICAL FEATURES

Axonal Demyelinating Mixed
Sensory Sensory & Motor Motor  
Almitrine
Benznidazole
Bortezomib
Brentuximab
Chloramphenicol
Dioxin
Doxorubicin
Ethambutol
Ethionamide
Etoposide (VP-16)
Flecanide
Gemcitabine
Glutethimide
Hydralazine
Ifosfamide
Interferon-α
Isoniazid
Ixabepilone
Lead
Leflunomide
Metronidazole
Misonidazole
Nitrous oxide
Nucleosides
  ddC; ddI;
  d4T; 3TC
Phenytoin
Platinum analogs
Propafenone
Pyridoxine
Statins
Thalidomide
Acrylamide
Alcohol (Ethanol)
Allyl chloride
Arsenic
Cadmium
Carbon disulfide
Chlorphenoxy
Ciguatoxin
Cobalt
Colchicine
Cyanide
Dapsone
Dichloroacetate
Dinitrophenol
Disulfiram
DMAPN
Ethylene oxide
Heroin
Ipilimumab
Lithium
Methyl bromide
Nitrofurantoin
Organophosphates
Podophyllin
PCBs
Saxitoxin
Spanish toxic oil
Taxol
Tetrodotoxin
Thallium
Trichloroethylene
TOCP
Vacor (PNU)
Vinca alkaloids
β-bungarotoxin
Botulism
Dimethylamine Borane
Gangliosides
Latrotoxin
  Black widow
Lead
Mercury
Misoprostol
Tetanus
Tick paralysis
Buckthorn
Chloroquine
Diphtheria
FK506 (Tacrolimus)
Hexachlorophene
Muzolimine
Perhexiline
Porcine brain
Procainamide
Tellurium
TNF-α antagonists
Zimeldine
Amiodarone
Diethylene glycol
Ethylene glycol
1,1'-Ethylidinebis
  [tryptophan]
Gold
Hexacarbons
n-Hexane
Na+ Cyanate
Suramin
A B C D E F G H I L M N O P S T V Z
Also see:
  Cerebellar toxins
  Channel toxins
  Muscle toxins
  Snake venom toxins
  Vitamin disorders


Acrylamide

Alcoholic (Ethanol) polyneuropathy 7

Oppenheim 1894

Allyl chloride

Almitrine
Amiodarone

Arsenic (inorganic)

Oppenheim 1894

Benznidazole
Black Widow Spider Venom (Latrotoxin) 53
  • Insect: Lactrodectus mactans (Female)
    • Red hourglass marking on abdomen
    • US geography
      • Most common in Southeast
      • Present in all US states but Alaska
    • Webs located in dark dry spaces
    • Spider bite location
      • Two small red marks: Not easily found
      • Often on buttocks, genitals or exposed areas
      • Not painful
      • No skin necrosis
      • Local sweating & piloerection: 25%
      • Erythema: Occasional
    • Bites most common in Summer or Early Autumn
    • Related dangerous species
      • L. geometricus; L. bishopi; L. hasselti (Australia); L. variolus; L. hesperus
    • Diagnosis
      • By history
      • Lay identification not reliable
  • Venom
    • Absorbed from site of bite
    • Distributed systemically
    • Does not cross blood-brain or blood-nerve barrier
  • Neurotoxin: α-Latrotoxin
    • Homology with glucagon-like peptide-1 (GLP-1) family
      • Insulin secretagogic hormones
      • GLP-1, Glucagon, VIP, Secretin, Pituitary adenyl cyclase activating polypeptide
    • Receptors
      • CIRL
        • Ca++ independent receptor for latrotoxin (Latrophilin)
        • GTP-binding protein-coupled
      • Neurexin I-α : Binds latrotoxin in Ca++-dependent manner
    • Action mediated, in part, by
      • Increased Ca++ flux into presynaptic nerve terminals ® Depolarization
      • Depolarization ® ­ Spontaneous release of transmitter from nerve terminals
        • Acetylcholine from motor axons
        • Catecholamines from adrenergic terminals
    • Late: Degeneration of nerve terminals
  • General Clinical (Latrodectism)
    • Most patients with only local symptoms (66%)
    • Headache
    • Vomiting
    • Hypertension
    • Rhabdomyolysis: Occasional
    • Course
      • Subside within 12 to 72 hours
      • Symptoms may fluctuate
      • Usually not fatal: More likely serious in young or elderly
    • Treatment
      • Anti-venoms: For severe cases; Intramuscular or Intravenous
        • Horse serum: Require sensitivity testing
        • Usually vs venom of all Latrodectus species
        • Benefit not definitely better than placebo
      • Calcium gluconate for muscle spasms
      • Local: Cleansing; Ice packs
  • Neuropathy: Hyperactivation of motor, sensory & autonomic axons
    • Onset
      • 30 to 60 minutes after bite
      • Severe local pain
    • Spontaneous activity
      • Muscle spasms & Cramping: Generalized; Especially proximal
      • Fasciculations
      • Tremor
    • Sensory
      • Pain
        • Initial: Local; Radiating (Proximal); Regional
        • Some patients: Generalized
        • Subsides within hours
        • Abdominal pain & rigidity: Common
      • Paresthesias & Hyperesthesias
    • Autonomic
      • Salivation: Increased
      • Lacrimation
      • Priapism
      • Hyperhidrosis
      • Tachycardia
    • Tendon reflexes: Hyperactive
    • Pathology: Degeneration of very distal axon terminals
From Crew
Black widow spider

Bortezomib (Velcade) 31

Brentuximab vedotin (SGN-35)
Buckthorn fruit

Cadmium 4

Carbon Disulfide (CS2)

Chloramphenicol

Chloroquine & Hydroxychloroquine (4-aminoquinolones)

Cobalt 58

Colchicine
  • Uses: Gout
  • Natural source
    • Tubers of Gloriosa superba
    • Distribution: Central Africa & Asia
    • External link: NatureServe
  • Risk
    • Renal failure: High serum levels
    • Chronic treatment
  • Neuropathy
    • Weakness: Distal
    • Sensory loss: All modalities
    • Severity: Generally Mild
    • Incidence: Low
    • Prognosis: Improvement with stopping drug
    • Pathology: Axonal loss
  • Other features
    • Myopathy (Vacuolar)
    • Systemic: GI; Hepatic; Acute gout

Carr, Hawaii
Gloriosa superba

Cyanide

Dapsone

Dichloroacetate 39
  • Use: Lactate lowering
  • Dose: 25 mg/kg/day by mouth
  • Clinical
    • Onset: 3 to 12 months after starting medication
    • Frequency: 86%
    • Paresthesias: Distal limbs
    • Pain
    • Numbness: Distal
    • Gait disturbances & falling
    • Course: Partial or complete improvement aver 6 to 18 months after stopping drug
  • Laboratory: Axonal neuropathy
    • NCV: Reduced CMAP & SNAP amplitudes

Dichloroacetate

Diethylene glycol 42

Dimethylamine Borane 37
  • (CH3)2NHBH3
  • Epidemiology: Case report
  • Exposure
    • Industrial use
      • High-temperature printed circuit boards, thin metal film,
        floppy disks, semiconductors, power transistors.
    • Acute
    • High dose
    • Skin +
  • Polyneuropathy: Motor predominant
    • Onset: Days after exposure
    • Distribution: Distal; Arms & Legs
    • Weakness: Hands & Feet
    • Sensory loss: Pan-Modal; Hands & Feet
    • Course: Partial recovery over years
  • Other clinical
    • Encephalopathy: Acute
    • Skin & mucosal irritation
  • Laboratory
    • EMG: Denervation, Distal & proximal limbs
    • NCV: Small CMAPs
    • Skin innervation: Reduced
  • Pathology: Sural nerve
    • Axon loss: Large & small myelinated
    • Ultrastructure
      • Axonal degeneration
      • Vacuoles
      • Derangement of microtubules & neurofilaments in some axons

DMAB

Dinitrophenol 59

Dioxins & Furans (2,3,7,8-polychlorinated) 5

2,3,7,8-tetrachlorodibenzo-p-dioxin


Bretonneau: Named diphtheria
Diphtheria 8, 11
Disulfiram

Doxorubicin

Ethambutol

Ethionamide

Ethylene Glycol
Ethylene oxide 1

Etoposide (VP-16)

FK506 (Tacrolimus)

Flecanide 57

Gemcitabine

Glutethimide

Gold (Aurothioglucose)

Hexacarbons

Hexachlorophene

Hydralazine

Ifosfamide 22

Interferon-α 13

Anti-programmed cell death 1 (PD-1) antibodies 61

  Ipilimumab
  Nivolumab
  Pembrolizumab

Isoniazid

Ixabepilone 62

Lead 40
Metallic Poisoning
"I was told that it seemed to be a case of ‘simple neurasthenia’. I looked casually at the bed-card and at once my eye was caught by the record of his occupation ‘Painter’. I looked from the bedcard to his gums, and there I saw written in equally distinct characters the record of the effect of his occupation—in a conspicuous lead-line."
Gowers, 1903.

Leflunomide 32

Lithium

Mercury - Inorganic

Methyl bromide (CH3Br)

Metronidazole 38

Misonidazole

Nitrofurantoin

Myelopathy after N2O: Spinal cord

T1 MRI

T2 MRI
from T Schwartz & J Wippold
Nitrous oxide (N2O)

Nucleosides

Organophosphate compounds

Organophosphorous Esters
Triorthocresyl phosphate (TOCP)

Perhexiline

Phenytoin

Platinum analogs 24

General
Carboplatin
Cisplatinum
Oxaliplatin

Platinum analogs: General cis-platinum (Platinol)
<i>cis</i>-platinum
from PDR
cis-platinum
Carboplatin Oxaliplatin
Podophyllin

Polychlorinated biphenyls (PCBs)

Porcine aerosolized brain-associated polyradiculopathy 45

Procainamide

Propafenone

Sodium cyanate

Spanish Toxic Oil 34
Statins 6

Suramin

Taxol (Paclitaxel)
  (Also other taxanes: Docetaxel 10)
Tellurium

Thalidomide 18
Thallium

Tick Paralysis 3,12

Trichloroethylene (TCE)

Tumor Necrosis Factor-α (TNF-α) Antagonists 55
Vacor (N-3-pyridylmethyl-N-p-nitrophenyl urea; PNU; Pyriminil)


 
Catharanthus
roseus
Vinca alkaloids (vincristine, vinblastine, vinorelbine & vindesine)

Zimeldine

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7/17/2016