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Drug-induced ataxia
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Drug-induced ataxia

Contributors: Jennifer Vermilion MD, Christine Osborne MD, Richard L. Barbano MD, PhD
Other Resources UpToDate PubMed

Synopsis

Medications and toxins can lead to a transient or permanent ataxia, which may be cerebellar or sensory in origin. Cerebellar ataxia can present with a wide-based and unsteady gait, impaired dexterity, abnormal eye movements (nystagmus), a scanning dysarthria, or a combination of these findings. A thorough medication history should be obtained in ataxic patients without a readily apparent cause. Commonly implicated medications include:

Antiepileptic drugs
  • Phenytoin – May cause nystagmus at therapeutic doses, but ataxia is common at supratherapeutic levels. Effects are typically reversible with medication cessation, but permanent cerebellar degeneration can occur with chronic administration.
  • Valproic acid – May cause cerebellar ataxia in the setting of hyperammonemia.
  • Benzodiazepines – Most commonly described in children with epilepsy. Ataxia is often mild and reversible. Elderly patients are also susceptible to benzodiazepine ataxia.
  • Others – Carbamazepine, oxcarbazepine, lacosamide, lamotrigine, rufinamide, zonisamide, ezogabine, gabapentin, felbamate, and phenobarbital.
Psychiatric medications
  • Chronic lithium use is associated with ataxia that is often permanent. Symptom onset tends to occur after infection, dehydration, or renal dysfunction.
  • Ataxia secondary to selective serotonin reuptake inhibitor use has been reported.
Chemotherapeutic and immunosuppressive agents
  • Tacrolimus and cyclosporine are associated with mild and transient ataxia.
  • Cytarabine-induced ataxia tends to occur 2-4 days after first dose and typically resolves within weeks.
Antimicrobials – Ataxia typically resolves with removal of the drug.
  • Metronidazole – High doses associated with ataxia and development of cerebellar hyperintensities in T2 sequences on MRI.
  • Piperazine (antihelmintic agent) can cause ataxia in children.
Alcohol
  • Most common toxin producing ataxia in a midline cerebellar pattern, characterized by ataxia of the legs and gait with relative sparing of the arms.
Other toxins and poisons
  • Carbon tetrachloride, heavy metals, phencyclidine (PCP), and toluene may cause cerebellar ataxia.
Sensory ataxia can arise secondary to a peripheral neuropathy. Like cerebellar ataxia, sensory ataxia may present with a wide-based and unsteady gait. In addition, individuals have a positive Romberg sign. They may have a high-stepping gait due to motor weakness or a foot-slapping gait due to loss of sensation.

Medications commonly implicated in peripheral neuropathy include:

Cardiovascular agents
  • Statins and amiodarone may cause a reversible peripheral neuropathy.
Chemotherapeutic agents
  • Chemotherapy-induced peripheral neuropathy (CIPN) is a well-described entity and may be caused by various agents.
  • Vincristine, paclitaxel, cisplatin, and bortezomib are common causes of CIPN.
Antimicrobials
  • Isoniazide can cause a reversible peripheral neuropathy.
  • Metronidazole may cause a reversible peripheral neuropathy.
HIV highly active antiretroviral therapy (HAART)
  • Nucleoside reverse transcriptase inhibitors such as stavudine contribute to polyneuropathy in patients with human immunodeficiency virus (HIV).
Other
  • Vitamin B6 (pyridoxine) in high doses can cause peripheral neuropathy. However, pyridoxine supplementation can prevent neuropathy in patients on isoniazid therapy.

Codes

ICD10CM:
R27.0 – Ataxia, unspecified

SNOMEDCT:
20262006 – Ataxia

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Diagnostic Pearls

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Differential Diagnosis & Pitfalls

Best Tests

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Management Pearls

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Therapy

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Drug Reaction Data

Below is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.

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References

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Last Reviewed:12/19/2018
Last Updated:12/06/2019
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Drug-induced ataxia
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Drug-induced ataxia : Nystagmus
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