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.

Antiretroviral therapy (ART)

• 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.