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Podophyllin binds to microtubules similar to colchicine and probably inhibits axoplasmic ow leading to axonal degeneration24
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THALIDOMIDE Clinical Features
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Thalidomide is an immunomodulating agent used to treat multiple myeloma, graft-vs-host disease, leprosy, and other autoimmune disorders25 31 Thalidomide is associated with severe teratogenic effects as well as peripheral neuropathy, which can be dose limiting Most patients who develop the neuropathy have received a cumulative dose of at least 20 g of thalidomide30 Less then 10% of patients receiving less than 20 g of thalidomide develop a polyneuropathy Patients complain of numbness, painful tingling, and burning discomfort in
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Muscle biopsies reveal a vacuolar myopathy, while sensory nerves demonstrate axonal degeneration
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Colchicine inhibits the polymerization of tubulin into microtubules The disruption of the microtubules probably leads to defective intracellular movement of important proteins, nutrients, and waste products in muscle and nerves17
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the feet and hands and less commonly muscle weakness and atrophy Even after stopping the drug for 4 6 years, as many as 50% patients continue to have signi cant symptoms Physical examination demonstrates a reduction in vibration and position sense, hypo- or are exia, and occasionally proximal and distal weakness
Pathogenesis
The neuropathy may be secondary to carbon disul de, which is a metabolite of disu ram39 A similar axonal neuropathy characterized by accumulation of neuro laments occurs with carbon disul de toxicity
Laboratory Features
NCS demonstrate reduced amplitudes or complete absence of the SNAPs with preserved conduction velocities when obtainable25 28,30,31 Motor NCS are usually normal
DAPSONE Clinical Features
Dapsone is used primarily for the treatment of leprosy and for various dermatologic conditions A primarily motor neuropathy can develop as early as 5 days to as long as 5 years after starting the drug40 46 Weakness initially involves the hands and feet and over time progresses to affect more proximal muscles Occasionally, patients complain of sensory symptoms without weakness
Histopathology
Nerve biopsies reveal a loss of large-diameter myelinated bers and axonal degeneration31 Degeneration of dorsal root ganglion cells has been appreciated on autopsies
Pathogenesis
The pathogenic basis of the neuropathy is not known
Laboratory Features
Motor and sensory NCS usually demonstrate reduced amplitudes with normal or only slightly slow conduction velocities40 44 The NCS usually improve after the dapsone is discontinued
DISULFIRAM Clinical Features
Disul ram (antabuse) is used to treat alcoholism It is metabolized to carbon disul de, which is a neurotoxin and can have adverse effects on both the peripheral nervous system (PNS) and the central nervous system (CNS)32 38 A neuropathy with distal weakness (eg, foot drop) and sensory loss may develop as early as 10 days to as long as 18 months after starting the drug
Histopathology
Biopsy of the motor nerve terminal at the extensor brevis muscle has demonstrated axonal atrophy and Wallerian degeneration of the distal motor nerve terminals45 Sural nerve biopsy may reveal a loss of myelinated nerve bers
Laboratory Features
NCS are suggestive of an axonal sensorimotor polyneuropathy with reduced amplitudes or absent SNAPs and CMAPs with normal or only moderately slow conduction velocities32,33,36 38 Needle EMG reveals brillation potentials and positive sharp waves in distal muscles along with decreased recruitment of neurogenic appearing MUAPs
Pathogenesis
The pathogenic basis of the neuropathy is not known
LEFLUNOMIDE Clinical Features
Le unomide is used for the treatment of rheumatoid arthritis It is a prodrug for the active metabolite A77 1726, which reversibly inhibits dihydroorotate dehydrogenase, the rate-limiting step in the de novo synthesis of pyrimidines necessary for lymphocyte production There have been several reports of patients treated with le unomide who developed distal numbness and paresthesia47 51 The median duration of treatment at the onset of neuropathy was 75 months (range 3 weeks to 29 months) in one large study49
Histopathology
Sural nerve biopsy demonstrates a loss of myelinated bers, predominately large-diameter bers, although small-diameter bers can be affected as well32 36 Nerve biopsies demonstrate axonal degeneration and segmental demyelination On EM, one may appreciate the axonal swellings caused by the accumulation of neuro lamentous debris within the myelinated and unmyelinated axons
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