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10.9. Drug Induced Neuropathies
- General features:
- Most drugs cause a distal axonopathy after prolonged use
- Discontinuation of the drug or decreasing the dose may initiate recovery or prevent further damage
- Pathologic changes may occur in the dorsal root ganglion, the cell body (neuronopathy) or the myelin sheath (myelinopathy)
- Deterioration of nerve function may continue after cessation of the drug (coasting)
- Specific fiber sizes may be differentially affected (C, A-alpha, AB, or autonomic)
Infectious Disease Drugs
Antituberculous Drugs
- Isoniazid
- General features:
- Metabolized by acetylation; slow acetylator may have high blood levels
- Tbc (tuberculosis) therapy
- Toxic effects are caused by interference with vitamin B6 (pyridoxine, pyridoxal and pyridoxamine); inhibits pyridoxal phosphokinase
- Clinical presentation:
- Slowly progressive
- Burning sensory neuropathy
- At 3–5 mg/day a 2% incidence of neuropathy; 6 mg/day a 17% incidence of distal axonopathy
- Loss of vibration, pain and temperature sense greater than position and deep pain sensibility
- Aching cutaneous calf pain
- Late effects are distal muscle atrophy ataxia and severe sensory loss; fasciculations
- Recovery starts within weeks of withdrawal and may be prolonged
- Risk factors are:
- Alcohol abuse
- Liver disease
- Pregnancy
- Poor nutrition
- EMG:
- Pathology:
- Axonal degeneration and loss of both myelinated and unmyelinated fibers
- Ethambutol:
- Sensory-motor polyneuropathy
- Optic neuropathy with loss of green color detection
- Ethionamide:
- Distal paraesthesias
- Reversible neuropathy
- Slow recovery
Antiretroviral Agents
- General features:
- Risk factors:
- Coexistent diabetes
- Nutritional deficiency
- Weight loss
- Advanced HIV
- Clinical presentation:
- Painful distal sensory neuropathy
- Intrinsic foot muscle weakness begins 7–9 weeks after therapy initiated
- Dose related; median onset at 16 weeks
- Rash, fever, headaches and stomatitis are side effects
- 10% of patients develop granulocytopenia
- Rare pancreatic and cardiac toxicity that carries an increased risk in diabetic patients
- Decreased pin prick, hyperpathia and loss of ankle jerks
- Loss of vibration sensibility in 1/3 of patients
- Coasting for 2–3 weeks after discontinuance of therapy
- EMG:
- Increased F-wave latency, low sural nerve SNAP
- Quantitative sensory testing is the best technique to follow neuropathy
- Zalcitabine (Dideoxycytidine):
- Nucleotide analog to block HIV infection
- Alternate agent is Didanosine (ddI)
- Associated risk factors for developing neuropathy:%
- Low cobalamine levels
- Alcohol abuse
- Toxic heavy metal exposure
- AZT use
- Renal insufficiency
- 80% of HIV patients are on 0.06 mg/day
- Stavudine and Didanosine (ddI)
- General features:
- Similar clinical feature to ddC
- Stavudine:
- 2 mg/kg/day <40% of patients develop neuropathy
- 4 mg/kg/day – 60% develop neuropathy
- Pathology of ddI:
- Intra myelin edema
- Myelin infolding
- Differential Diagnosis from HIV neuropathy:
- HIV neuropathy:
- Progression over months rather than weeks
- Distal, symmetrical, small fiber
- CIDP
Antibiotics and Antimicrobials
Chloramphenicol
- General features:
- Rare; is seen in children with cystic fibrosis who have taken an average of 225 grams for a mean of 300 days
- Potentiated by renal failure
- Associated agranulocytosis and bone marrow failure
- Clinical presentation:
- Calf pain and tenderness followed by decreased distal pain and touch
- Loss of knee and ankle deep tendon reflexes; retained upper extremity reflexes
- Optic neuropathy may occur concomitantly before or after the neuropathy
- Possible interference with B12 metabolism
Dapsone
- General features:
- Sulfone derivative
- Used to treat leprosy and dermatological conditions
- Clinical features:
- Neuropathy occurs after prolonged use
- Weakness is the predominant feature; symmetric and followed by atrophy
- EMG:
- Slowed MNCV with denervation
Metronidazole and Misonidazole
- General features:
- Metronidazole (Flagyl) is used in the treatment of anaerobic bacterial and protozoan infections
- Misonidazole is used as a cell sensitizer for cancer radiotherapy; sensitizes hypoxic cells to X-RT
- Cumulative dose of 50 grams usually necessary for the metronidazole neuropathy
- Clinical presentation:
- Distal symmetrical predominantly sensory polyneuropathy
- Paresthesias
- Burning
- Dose related
- Decreased reflexes
- Encephalopathy
- Slow but good recovery with cessation of the drug
- EMG:
- Decreased SNAP greater than CMAP; normal latencies
- Motor fibers may be affected
- Pathology:
- Axonal degeneration of myelinated and unmyelinated fibers
- Some segmental demyelination
Nitrofurantoin
- General features:
- Used to treat urinary tract infections; exacerbated by failing renal function
- Compounded by uremic neuropathy
- Total toxic dose 20 gram
- Clinical presentation:
- Rapid onset (unusual amongst distal axonopathies); may occur within six weeks after initiation of treatment
- Initiated by numbness in the distal legs; followed by severe distal weakness and profound sensory loss
- Rarely a profound motor neuropathy is seen; may resemble GBS with loss of reflexes
- Fulminant radiculoneuropathy occurs
- Partial recovery with cessation of the drug
- EMG:
- Decreased motor and sensory conduction velocities; distal denervation
- Pathology:
Thalidomide
- General features:
- Used in the treatment of leprosy (blocks the lepra reaction); HIV patients for mucosal ulcerations; treatment of multiple myeloma
- Single dose of 100–200 mg may cause symptoms; neuropathy is dose related
- Clinical presentation:
- Tingling and numbness in feet followed by hands
- Allodynia to touch (mechanoallodynia)
- Hyperalgesia to pin prick
- Vibration and light touch less affected
- Rare weakness
- Variable loss of deep tendon reflexes
- Somnolence
- Severe constipation
- Babinski in some patients
- Recovery is slow
- EMG:
- Reduced SNAP amplitude; normal MNCV
- Pathology:
- Loss of large diameter fibers
Chloroquine (Plaquenil)
- General features:
- Antimalaria agent; used widely as an anti-inflammatory agent
- Neuropathy occurs after several months to years of use
- Vacuolar myopathy is much more common than the neuropathy
- Clinical presentation:
- Maybe a motor neuropathy
- Other patients primarily a sensorimotor neuropathy
- Weakness
- Absent or reduced reflexes
- Improvement with cessation of drug use
- EMG:
- Fibulation potential myotonic discharges; complex repetitive discharges, increased recruitment
- Pathology:
- Segmental and remyelination of peripheral nerves
- EM: abnormal Schwamm cell inclusions similar to amiodarone
Sulfisoxazole (Trimethoprim-Sulfamethoxazole)
- General features:
- Used primarily in HIV patients
- Clinical features:
Cardiovascular Drugs
Amiodarone
- General features:
- Class F anti-arrhythmic
- Iodinated benzo furan derivative
- Neuropathy is dose related; 400 mg/day for one or more years; neuropathy is 6% of patients
- Clinical presentation:
- Several types of neuropathy:
- Motor predominant
- Large fiber sensory neuropathy
- Distal sensory motor findings with associated proximal weakness and gait disturbance
- Associated myopathy, tremor, ataxia and altered mental status
- 800 mg/day-tremor and ataxia in 20% of patients
- Associated complications:
- Corneal deposits
- Dermatitis
- Lung
- Bone marrow depression
- GI and thyroid complications
- Serum levels of 2.4 mg/dl associated with neuropathy
- EMG:
- Demyelinating and axonal features
- Decreased SNAPs
- Pathology:
- Lysosomal inclusion bodies in Schwamm cells, muscle fibers, capillary endothelial cells
- Loss of myelinated fibers
- Putative inhibitor of lysosomal phospholipase
Flecainide (Tambocor)
- General features:
- Reversible sensory neuropathy
- EMG:
- Reduced SNAP; normal nerve conduction velocities
Hydralazine
- General features:
- Resembles INH
- Pathology possibly related to pyridoxine deficiency
- Clinical presentation:
- Distal extremity numbness and paresthesias predominate over leg weakness
- Axonal polyneuropathy
- Increased excretion of xanthurenic acid after a tryptophan load
Enalapril and Captopril
- General features:
- Clinical presentation:
- Reversible motor-sensory neuropathy
- Captopril associated with GBS like syndrome
- EMG:
- Prolonged motor and sensory latencies
- Decreased conduction velocities associated with captopril
Streptokinase
- General features:
- Thrombolytic agent for myocardial infarction
- Made from group C streptococci
- Clinical presentation:
- Associated with GBS-like syndrome
- Permanent median and ulnar neuropathy (bleeding into the nerve)
Perhexiline Maleate
- General features:
- Used for angina treatment in the past
- Risk increased in patients with decreased oxidation of debrisoquin
- Usual toxic dose of 300–400 mg/day for 4–12 months
- Clinical presentation:
- Numbness of the distal extremities followed by loss of all sensory modalities
- Weakness of distal greater than proximal muscles
- Rarely facial diplegia and perioral numbness
- Autonomic neuropathy with postural hypotension may be presenting symptoms
- Reflexes are depressed or absent
- Weight loss
- Bilateral papilledema
- Abnormal liver function
- CSF protein moderately elevated
- Slow recovery with cessation of the drug
- EMG:
- Increased motor and sensory NCVs
Propafenone
- General features:
- IC antiarrhythmic agent; utilized for supra and ventricular tachycardia
- Cardiac conduction defects and decreased blood pressure are concomitant side effects
- Clinical presentation:
- Distal painful neuropathy
- Central complications, dizziness, blurred vision convulsions and vertigo
- EMG:
- Reduced motor and sensory compound action potentials
Lipid Lowering Drugs
Lovastatin (Mevacor)
- General features:
- 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibits
- Cause symptomatic myopathies
- Concomitant use with gemfibrozil (Lopid) myopathy occurs in up to 5% of patients
- Concomitant use with cyclosporin A causes myopathy in 30% of patients
- Clinical presentation:
- Cranial neuropathy
- Peripheral neuropathy
Simvastatin (Mevastatin, Pravastatin)
- General features:
- Reversible metabolic inhibitor of limiting step in cholesterol synthesis (HMG-CoA reductase)
- Fluvastatin is a synthetic cholesterol lowering agent
- Increased risk of developing peripheral neuropathy if used with clofibrate, nicotinic acid; macrolide antibiotics
- Clinical presentation:
- Sensory motor neuropathy
- Proximal and distal muscle weakness
- Fasciculations may be noted
- Associated myositis
- Elevated hepatic transaminase
- Withdrawal of medicine; variable recovery
- Symptoms may be acute; other patients prolonged use
- EMG:
- Reduced SNAPs and CMAPs; normal nerve conduction velocities to mild slowing
- Wide spread chronic denervation
- Pathology:
- Axonal degeneration of both large and small fibers
- Atorvastatin (Lipitor) and Clofibrate have a similar clinical profile:
Neuropathy from Immunosuppressants
Cyclosporine A
- General features:
- Putative mechanism: neuropathy from solvent (chromophore El)
- Clinical presentation:
- Reversible neuropathy
- Associated; tremor, ataxia, seizures, myoclonus, coma, posterior leukoencephalopathy
Tacrolimus (FK506)
- General features:
- An immunosuppressant primarily used in transplant recipients
- Incidence of 0.003% of treated patients
- Clinical presentation:
- Severe multifocal demyelinating neuropathy that resembles CIDP
- Associated; asterixis and posterior reversible leukoencephalopathy
- Some improvement with dose reduction, IVIG, plasmapheresis (probably associated autoimmune neuropathy)
- EMG:
- Conduction block
- Focal slowing
Interferon Alpha
- General features:
- Immunomodulating agent primarily used in cancer patients
- Severe respiratory and systemic effects
- Clinical presentation:
- Mild sensory-motor neuropathy
- Associated: encephalopathy, asterixis, myoclonus, coma
- Interleukin 2
- Used as an immunomodulator preventing HIV progression to an AIDS diagnosis
Neuropathy from Antineoplastic Drugs
Paclitaxel (Taxol)
- General features:
- Derived from bark of Taxus brevifolia
- Dose-dependent; necessary cumulative dose of 200–250 mg/m2
- Incidence of neuropathy increase with concurrent use of cis-platinum
- Primarily used for breast cancer
- Polymerization of microtubules; blocks depolymerization
- Clinical presentation:
- Predominantly a sensory neuropathy
- Paraesthesias of the hands and feet followed by numbness
- Symptoms may begin 1–3 days after therapy is initiated
- Motor involvement in 17% of patients
- Autonomic involvement is rare
- Paraesthesias of the hands and face may occur before the feet and trunk
- May have acute burning pain necessitating narcotics
- Stocking and glove sensory loss of both large and small fiber modalities
- Decreased or absent reflexes
- Weakness is rare; if it occurs it is of rapid onset and with burning pain
- variable degree of recovery of motor, sensory and reflex loss
- EMG:
- Low amplitude SNAPs; slowed motor and sensory conduction velocities
- Denervation present
- Pathology:
- Aggregates of microtubules in axons, Schwamm cells, and dorsal root ganglia
- Axonal atrophy, nerve fiber loss, secondary demyelination
Docetaxel (Taxotere)
- General features:
- Derived from the European Yew tree (Taxus baccata)
- Greater potency than paclitaxel, used to treat breast, ovarian and lung cancer
- Neuropathy may occur at 50 mg/m2; usual cumulative dose for toxicity is 400 mg/m3
- Approximate 10% peripheral neuropathy with its use
- Docetaxel and cis-platinum greater than 50% of patients suffer neuropathy
- Clinical presentation:
- Small fiber symptoms of burning pain
- Improvement after cessation of drug treatment
- Antihistamines may help pain
- EMG:
- Denervation and reinnervation of distal leg muscles
- Pathology:
- Axonal degeneration; large myelinated fiber loss
- Muscle biopsy demonstrates neurogenic atrophy
Vinorelbine (Navelbine)
- General features:
- Used to treat solid tumors
- In combination with paclitaxel a mild sensory neuropathy occurs in 44% of patients and a severe sensory neuropathy in 28%
Cytarabine (Cytosar)
- General features:
- Neuropathy occurs with doses greater than 200 mg/m2/day; 0.6% of treated patients
- Clinical presentation:
- CNS complications are usual
- Painful paresthesias
- Pure sensory neuropathy
- GBS-like syndrome
- Onset may occur hours after the first dose
- Complete recovery is rare
- Pathology:
- Axonal loss and demyelination on sural nerve biopsy
Suramin
- General features:
- Used as an anti-parasitic drug, antiretroviral and to treat refractory neoplasms
- Toxicity related to high serum drug levels and not cumulative dose; neuropathy in 40% of patients at greater than 350 μg/ml
- Clinical presentation:
- Paraesthesias followed by weakness
- GBS like syndrome in two patients
- EMG:
- Pathology
Unusual Drug Induced Neuropathies
- Chlorambucil: Associated with sensory neuropathy
- Etoposide: High dose repeated therapy causes a mild peripheral neuropathy
- Ifosfamide: Alkylating agent, peripheral neuropathy
- Procarbazine: Structurally similar to INH; high doses necessary to cause mild sensory peripheral neuropathy
- Combination of interferon, melphalan infusion:
- Used in melanoma
- Isolated extremity perfusion
- Local sensory neuropathy
Vincristine and Vinblastine
- General features:
- Derived from the periwinkle plant (vinca rosea)
- Inhibits microtubular polymerization; blocks axonal transport
- Neuropathy is dose dependent
- Clinical presentation:
- Numbness and tingling in a stocking and glove distribution
- Symmetric distal muscle weakness
- Rare extraocular muscle, vocal cord, pupillary and bowel and bladder; orthostatic hypotension involvement
- Loss of deep tendon reflexes; some only AJ loss
- Hands may be symptomatic; earlier than feet
- Weakness may be severe and of sudden onset; upper extremity extensors and distal lower extremity muscles are involved
- Coasting effect may be seen for months
- EMG:
- Low amplitude SNAPs and CMAPs; mild slowing of NCVs
- Denervation and reinnervation noted on needle EMG; decreased number of motor units
- Pathology:
- Axonal degeneration of large and small fibers; wallerian degeneration; some secondary demyelination
- Intra-axonal filaments may be noted
Cis-Platinum
- General features:
- Nephrotoxic; neuropathy is usually the toxicity that limits dosage
- Primarily used for ovarian carcinoma
- 40 mg/m2 dose cause neuropathy; hypomagnesemia may predispose to neuropathies
- Total cumulative dose of 200–500 mg/m2 usual range for neuropathy
- Clinical presentation:
- Numbness of the distal extremities progressing to a sensory ataxia
- Lhermitte's sign and lancinating pain occur
- Loss of vibration sensibility and reflexes may occur prior to symptoms; progresses to loss of light touch and pin prick sensibility in the lower extremities
- Weakness occurs in severe cases
- Intra-arterial administration causes plexopathies; severe neuropathy in those with hereditary sensory motor neuropathies
- VIIIth nerve involvement
- Autonomic dysfunction
- Recovery incomplete and is protracted
- Doxorubicin and diacetal compound neurotoxicity
- EMG evaluation:
- Low amplitude SNAPs; prolonged distal latencies; slowed conduction velocities
- Needle EMG may demonstrate denervation
- Pathology:
- Axonal degeneration of large greater than small axons
- Segmental demyelination
- Carboplatin: toxicity occurs only in high doses; milder peripheral neuropathy
Neuropathy Associated with Psychiatric Drugs and Seizure Medications
Amitriptyline (Elavil)
- General features:
- Antidepressant; used to treat neuropathic pain
- Rare acute polyradiculoneuropathy
- Severe overdose:
- Quadriplegia, reflexa, bulbar dysfunction, and respiratory compromise
- Elevated CSF protein
- EMG (overdosed patient):
- Decreased MNCVs; denervation
- Decreased motor amplitudes with prolonged F waves
Lithium
- General features:
- Inverse correlation between motor and sensory NCVs and lithium levels
- CNS toxicity of myoclonus tremors convulsions over shadow the peripheral neuropathy
- Clinical presentation:
- Neuropathy may occur shortly after initiation of treatment (noted by EMG)
- Paraesthesias distal lower extremities
- Mild distal muscle weakness
- Depressed or absent reflexes
- Variable recovery with discontinuation of treatment
- Exacerbates diabetic and alcoholic neuropathies
- EMG:
- Decrease CMAPs and SNAPs
- Distal denervation and slow motor and sensory NCVs
- Pathology (sural nerve biopsy):
- Axonal degeneration and loss of myelinated fibers
Phenytoin
- General features:
- Peripheral neuropathy symptoms or EMG abnormalities in 50% of patients taking the drug for 15 years
- Associated slight cerebellar atrophy
- Elevated serum levels predispose to neuropathy
- Lower extremity loss of vibratory and light touch sensibility
- Slow improvement occurs after cessation of therapy
- Possible associated vitamin deficiency (folate, B12)
- EMG:
- Compatible with axonal sensory motor neuropathy
- Decreased SNAPs and CMAP; minimally slowed NCVs.
- Pathology (sural nerve biopsy):
- Axonal degeneration
- Segmental demyelination; increase small myelinated fibers
Sansert
- General features:
- Pulmonary, cardiac, and retroperitoneal fibrosis
- Severe migraine and chronic daily headache patients
- Ischemic neuropathy; monomelic (one extremity)
Methaqualone
- General features:
- Sedative; drug of abuse often taken with cannabis and diphenhydramine
- Sensory motor neuropathy
Drugs Utilized in Treatment of Rheumatological Disease
Gold
- General features:
- Treatment of rheumatic arthritis
- Neuropathy not dose dependent
- Associated cutaneous and renal involvement
- Sodium aurothiomalate used
- Clinical presentation:
- Subacute progressive sensory loss in the legs and cutaneous hyperesthesia; loss of all sensory modalities
- Distal muscle weakness:
- Rheumatoid arthritis has particular intrinsic hand muscle weakness and atrophy
- Rapid motor and sensory polyneuropathy that may resemble GBS (rare)
- Symptoms may occur after first injection
- Elevated CSF protein
- Weakness may be asymmetric
- Discontinuation of drug causes improvement which is not complete in severely affected patients
- EMG:
- Moderate slowing of MNCV and SNCV
- Decreased SNAP and CMAP amplitude
- Denervation and myokymia demonstrated
- Pathology (sural nerve biopsy):
- Axonal and segmental demyelination
Indomethacin
- General features:
- Primarily used for its anti-inflammatory and analgesic properties
- Blocks synthesis of inflammatory prostaglandins
- Clinical presentation:
- Sensorimotor neuropathy
- Ataxia
- Distal extremity weakness
- Paresthesias of upper and lower extremities
- Recovery usually complete after cessation of drug use
- EMG:
- Decreased MNCVs
- Normal sensory latencies
Colchicine
- General features:
- Used in treatment of acute gout; familial Mediterranean fever
- Putative mechanism; inhibition of polymerization of tubulin and decreased axonal transport
- Higher incidence of neuropathy in patients with renal failure
- Associated vacuolar myopathy
- 0.18 mg/day associated with neuropathy
- Clinical presentation:
- Mild distal sensory loss and paresthesias
- Associated myopathy (proximal with elevated CK
Allopurinol
- General features:
- Used in the treatment of gout and secondary hyperuricemia
- Clinical presentation:
- Delayed sensory-motor polyneuropathy
- Dysesthesias and distal extremity weakness
- Stocking glove sensory loss
- Absent reflexes
- Improvement occurs after discontinuation of the drug
- EMG:
- Decreased SNAPs and CMAP
- Mildly decreased NCVs
- Pathology (sural nerve biopsy):
- Axonal degeneration
- Segmental demyelination
Rare Agents
Disulfiram
- General features:
- Adjunct in treatment of alcohol abuse
- Occurs after long standing treatment at doses of 250–500 mg/day
- Putative mechanism: carbon disulfide a metabolite
- Clinical features:
- Affects pain, temperature and vibration sensibility in the feet
- Gait on steadiness
- Optic neuropathy
- Foot dorsiflexors affected prior to hand weakness
- Absent ankle deep tendon reflexes
- EMG:
- Mild slowing of MNCV
- Decreased SNAPs
- Denervation
- Pathology (sural nerve biopsy):
- Axonal degenerative
- Loss of myelinated fibers neurofilament accumulation
Nitrous Oxide
- General features:
- Used as dental anesthetic and food propellants; abused as euphoric
- Neuropathy and myelopathy occurs must frequently in B12 deficient patients
- Mechanisms of pathology may be methionine synthetase inhibition
- Clinical presentation:
- Initial systems are numbness of the distal arms and legs with poor finger dexterity; leg weakness and gait imbalance
- Early stage of the neuropathy is accompanied by depressed reflexes impairment of fibration and pain sensibility
- Lhermitte's sign may be noted
- Severe intoxication causes lower extremity spasticity, severe loss of vibration, pain and position sensibility, hyperreflexia and Babinski signs are noted
Trichloroethylene
- General features:
- Industrial uses: dry cleaning, rubber production; degreasing agent
- Clinical presentation:
- Acute industrial exposure:
- Dysfunction of the Vth, VIIth and optic nerve
- Usually cranial neuropathy occurs after a period of high exposure
- Trigeminal neuropathy affects all divisions of the nerve and is accompanied by weakness of muscles of mastication
- Recovery occurs over months
Perazine
- General features:
- Phenothiazine derivative
- Sun exposure causes cell damage by a lipid peroxidation mechanism
- Clinical Presentation:
- Sun burn induced sensory neuropathy
- Bilateral facial palsies
- Monophasic illness with recovery
- EMG:
- Denervation of the VIIth nerve decreased
- Sural nerve conduction velocities
- Normal MNCV
Pyridoxine (B6)
- General features:
- Occurs at doses of 2–6 grams/day
- Often used to prevent INH neuropathy; and al tunnel syndrome
- Neuropathy may occur with small dose
- Clinical presentation:
- Numb feet and unsteady gait
- Clumsiness of hands
- Perioral numbness
- Stocking and glove sensory loss of large > small fibers
- Sensory ataxia from decreased proprioception
- Decreased or absent reflexes
- Normal strength
- Slow improvement with discontinuation of the drug
- EMG:
- Normal motor NCVS
- Absent SNAPs
- Pathology (sural nerve biopsy):
- Loss of large and small axons
- Normal CSF
Amphetamines
- General features:
- Weight loss and hyperexcitability
- CNS arteries (usually large vessel):
- Acute increase of blood pressure with ICH
- Clinical presentation:
- Necrotizing hypersensitivity angiitis with distal motor sensory neuropathy
- Mononeuritis multiplex
Heroin
- General features:
- Neuropathy and CNS manifestations probably secondary to autoimmune reaction to adulterants (quinine, librium)
- Acute pulmonary edema with second exposure
- Clinical presentation:
- Painful plexopathy; lower extremity greater than upper extremity
- Associated transverse myelopathy
Etretinate (Tegison)
- General features:
- Used for treatment of psoriasis
- Clinical presentation:
- EMG:
- Normal motor NCVs
- Decreased or absent SNAPs
- Pathology:
- Axonal degeneration of small and large fibers
Ammoniated Topical Mercury
- Clinical presentations:
- Burning distal paraesthesias
- Stocking glove sensory loss; small fibers greater than large fibers
- Absent lower extremity reflexes
- Pathology:
- Axonal polyneuropathy with secondary demyelination
Podophyllin
- General features:
- Used for the treatment of candidemia acuminata; absorption through the skin
- Multiorgan failure is associated with significant absorption
- CNS manifestations include: hallucinations, seizures, ataxia, autonomic dysregulation
- Pancytopenia
- Clinical presentation:
- Stocking glove sensory loss
- Distal weakness
- Loss of ankle deep tendon reflexes
- Associated CNS signs and symptoms
- EMG:
- Decreased sensory and motor nerve potentials; increased distal latencies
- Denervation
- Pathology:
- Loss of small and large axons
- CSF demonstrates elevated protein
Acetazolamide
- General features:
- Used for increased intracranial pressure migraine and seizure prophylaxis; some channelopathies
- Clinical presentation:
- Painful distal extremity paresthesia
- Distal sensory loss
Sodium Cyanate
- General features:
- Sickle cell crisis prevention
- Clinical presentation:
Stilbamidine
- General features:
- Used in treatment of blastomycosis
- Clinical presentation:
- Involvements of the Vth cranial nerve
- Distal sensory paresthesias
L-Tryptophan-Induced Eosinophilia-Myalgia Syndrome
- General features
- Clinical presentation:
- Associated myopathy
- Stocking glove sensory loss all modalities; distal weakness
- Pathology: severe axonal large and small fiber neuropathy
Tagamet
- General features:
- Reversible motor neuropathy
Differential Diagnostic of Drug Induced Neuropathy by Seminal Features
Sensory Motor Neuropathy
- Allopurinol (rare associated CTS)
- Amiodarone (skin pigmentation)
- Amitriptyline (depression)
- Atorvastatin (vascular disease)
- Captopril (lacunar stroke)
- Chloroquine (muscle disease/macular degeneration)
- Colchicine (gout, familial Mediterranean fever)
- Disulfiram (acute presentation)
- Docetaxel (breast cancer; paraneoplastic syndrome)
- Ethambutol (green gene dysfunction)
- FK SO6 (myoclonus, tremor, posterior leukoencephalopathy)
- Gold (associated rheumatoid, hand intrinsic muscle wasting)
- Hexamethylamine
- Indomethacin
- Interferon alfa (encephalopathy, fever)
- INH (burning pain)
- Lithium (myoclonus, tremor, movement disorder)
- Lovastatin (CVD; muscle cramps)
- Methaqualone
- Nitrofurantoin
- Pachytene
- Perhexiline (lumbosacral radiculopathy
- Phenytoin (asymptomatic loss of reflexes, mild ataxia)
- Podophyllin
- Pravastatin (muscle cramps)
- Sodium cyanate
- Suramin
- Thalidomide (severe constipation)
- Vincristine (pupillary involvement; bowel and bladder)
Primary Sensory Neuropathy
- Acetazolamide (paresthesias of upper extremities; kidney stone)
- Alma tine
- Clerambault
- Chloramphenicol
- Cisplatinum (Severe sensory ataxia)
- Chlorquinol (optic neuropathy); spinal cord
- Colistin
- Cytarabine-ara (ataxia)
- Dideoxycytidine (burning feet)
- Didanosine (burning feet)
- Ethionamide
- Etretinate
- Flecainide
- Glutethimide
- Hydralazine
- Mercury (basal ganglion dysfunction, cognitive decline)
- Methimazole
- Niacin (flushing)
- Nitrous oxide (spinal cord involvement)
- Paclitaxel (retinopathy)
- Procarbazine
- Propylthiouracil (thyroid storm, atrial fibrillation)
- Pyridoxine (burning feet)
- Stavudine (associated HIV neuropathy)
- Streptomycin (VIIIth nerve dysfunction)
- Thalidomide (small fiber modalities; constipation)
Differential Diagnosis of Primary Sensory Neuropathy
- Chloramphenicol:
- Optic neuropathy
- Anemia (RBC vacuoles)
- Nitrofurantoin:
- Rapidly of onset; may be fulminant resemble GBS; pure motor neuropathy
- Metronidazole:
- INH
- Burning sensory neuropathy; hot coma hypoglycemia
- Ethambutol
- Optic neuropathy; and of green cones
- Vincristine
- Hands earlier than feet
- Pupil/bowel/bladder/orthostasis
- Cis-platin
- Sensory ataxia; VIIIth nerve
- Elavil (overdose)
- Gold
- Acute weakness (may be profound)
- Myokymia
- GBS-like syndrome
- Perazine
- Bilateral facial palsy with recovery
- Photo induced
- Monophasic illness
- Dapone
- Optic neuropathy
- Predominantly motor
- Muscle atrophy hands prominent
- Podophyllin
- Skin absorption
- Seizures
- Sensory loss
- CSF increase (root involvement):
- Strachan's
- Ulcers of cornea; dermatitis; optic neuropathy and polysensory neuropathy
- Vitamin E
- Spinocerebellar ataxia with polyneuropathy (setting of fat malabsorption)
Primary Motor Neuropathy
- Chloroquine (macular degeneration; muscle disease)
- Cimetidine (extremity)
- Dapsone (associated skin rash)
- Imipramine
- Methimazole
- Zimeldine
Drug Induced Axonal Neuropathies
- Allopurinol
- Almititrine
- Amidoxime
- Chloroquine
- Cisplatinum
- Clioquinol
- Colchicine
- Cytarabine
- Dapsone
- Dideoxycytidine (ddC)
- Disulfiram
- Docetaxel
- Ethionamide
- Etretinate
- Flecainide
- Glutethimide
- Gold
- HMG CoA inhibitors
- Hydralazine
- Isoniazid
- Lithium
- L-Tryptophan
- Metronidazole
- Nitrofurantoin
- Nitrous oxide
- Misonidazole
- Paclitaxel
- Perazine
- Perhexiline
- Phenytoin
- Podophyllin
- Pyridoxine
- Sodium cyanate
- Suramin
- Thalidomide
- Vincristine
Ganglioneuropathies
- Cisplatinum
- Paclitaxel
- Pyridoxine
- Simvastatin
- Thalidomide
- Doxorubicin
Demyelinating
- Amiodarone
- Cytarabine
- Chloroquine
- Tacrolimus
- Gold
- Misonidazole
- Perhexiline
- Suramin
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