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Chapter 20: Toxic Neuropathies

INTRODUCTION

This chapter reviews neuropathies associated with various drugs and other environmental exposures (Table 20-1). Toxic neuropathies due to chemotherapeutic agents are discussed in Chapter 19. The associated neuropathy for most of these is an axonal, length-dependent predominantly sensory neuropathy. The history of exposure and sometimes the involvement of other organ systems help to suggest the correct diagnosis. Although we mention features that have been reported on nerve biopsy, this is not typically part of the workup as in most cases the abnormalities are nonspecific.

TABLE 20-1.TOXIC NEUROPATHIES
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TABLE 20-1.TOXIC NEUROPATHIES
Drug Mechanism of Neurotoxicity Clinical Features Nerve Histopathology EMG/NCS
Misonidazole Unknown Painful paresthesias, loss of large and small fiber sensory modalities, and sometimes distal weakness in length-dependent pattern Axonal degeneration of large myelinated fibers; axonal swellings; segmental demyelination Low-amplitude or unobtainable SNAPs with normal or only slightly reduced CMAP amplitudes
Metronidazole Unknown Painful paresthesias, loss of large and small fiber sensory modalities, and sometimes distal weakness in length-dependent pattern Axonal degeneration Low-amplitude or unobtainable SNAPs with normal CMAP
Chloroquine and hydroxychloroquine Amphiphilic properties may lead to drug–lipid complexes that are indigestible and result in accumulation of autophagic vacuoles Loss of large and small fiber sensory modalities and distal weakness in length-dependent pattern; superimposed myopathy may lead to proximal weakness Axonal degeneration with autophagic vacuoles in nerves as well as muscle fibers Low-amplitude or unobtainable SNAPs with normal or reduced CMAP amplitudes; distal denervation on EMG; irritability and myopathic-appearing MUAPs proximally in patients with superimposed toxic myopathy
Amiodarone Amphiphilic properties may lead to drug–lipid complexes that are indigestible and result in accumulation of autophagic vacuoles Paresthesia and pain with loss of large and small fiber sensory modalities and distal weakness in length-dependent pattern; superimposed myopathy may lead to proximal weakness Axonal degeneration and segmental demyelination with myeloid inclusions in nerves and muscle fibers Low-amplitude or unobtainable SNAPs with normal or reduced CMAP amplitudes; can also have prominent slowing of CVs; distal denervation on EMG; irritability and myopathic-appearing MUAPs proximally in patients with superimposed toxic myopathy
Colchicine Inhibits polymerization of tubulin in microtubules and impairs axoplasmic flow Numbness and paresthesia with loss of large fiber modalities in a length-dependent fashion; superimposed myopathy may lead to proximal in addition to distal weakness Nerve biopsies demonstrate axonal degeneration; muscle biopsies reveal fibers with vacuoles Low-amplitude or unobtainable SNAPs with normal or reduced CMAP amplitudes; irritability and myopathic-appearing MUAPs proximally in patients with superimposed toxic myopathy
Podophyllin Binds to microtubules and impairs axoplasmic flow Sensory loss, tingling, muscle weakness, and diminished muscle stretch reflexes in length-dependent pattern; autonomic neuropathy Axonal degeneration Low-amplitude or unobtainable SNAPs with normal or reduced CMAP amplitudes
Thalidomide Unknown Numbness, tingling, burning pain, and weakness in a length-dependent pattern Axonal degeneration; Autopsy studies reveal degeneration of dorsal root ganglia Low-amplitude or unobtainable SNAPs with normal or reduced CMAP amplitudes
Disulfiram Accumulation of neurofilaments and impaired ...

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