A 74-year-old woman is brought to the emergency department due to worsening weakness and gait unsteadiness. The patient has a history of ischemic stroke causing right-sided weakness and uses a cane to ambulate. Over the past several days, she has been feeling weak and unsteady, and this morning she fell while getting out of bed. She did not lose consciousness and has had no headache, vomiting, or vision loss. The patient recently has had dysuria and urinary urgency, which have improved after taking trimethoprim-sulfamethoxazole. Other medical conditions include hypertension, type 2 diabetes mellitus, and seizure disorder controlled with phenytoin. Temperature is 37.1 C (98.8 F), blood pressure is 140/86 mm Hg, and pulse is 84/min. Pupils are equal and briskly reactive, and extraocular movements are intact. There is bilateral nystagmus on lateral gaze. Muscle strength is diffusely decreased but more pronounced in the right extremities. Deep tendon reflexes are increased throughout. Dysmetria is present on finger-nose testing, and the gait is wide-based. Which of the following is the most likely cause of this patient's current condition?

Question

A 74-year-old woman is brought to the emergency department due to worsening weakness and gait unsteadiness.  The patient has a history of ischemic stroke causing right-sided weakness and uses a cane to ambulate.  Over the past several days, she has been feeling weak and unsteady, and this morning she fell while getting out of bed.  She did not lose consciousness and has had no headache, vomiting, or vision loss.  The patient recently has had dysuria and urinary urgency, which have improved after taking trimethoprim-sulfamethoxazole.  Other medical conditions include hypertension, type 2 diabetes mellitus, and seizure disorder controlled with phenytoin.  Temperature is 37.1 C (98.8 F), blood pressure is 140/86 mm Hg, and pulse is 84/min.  Pupils are equal and briskly reactive, and extraocular movements are intact.  There is bilateral nystagmus on lateral gaze.  Muscle strength is diffusely decreased but more pronounced in the right extremities.  Deep tendon reflexes are increased throughout.  Dysmetria is present on finger-nose testing, and the gait is wide-based.  Which of the following is the most likely cause of this patient's current condition?

Quizplus · Accepted Answer

Phenytoin is a commonly used, long-acting antiepileptic medication that inhibits voltage-gated sodium channels. Acute toxicity initially manifests with signs of cerebellar dysfunction: horizontal nystagmus (ie, nystagmus on lateral gaze), ataxia (eg, wide-based gait), dysmetria (eg, on finger-nose testing), slurred speech, and nausea/vomiting are common, and hyperreflexia may occur. Severe toxicity results in altered mental status (eg, lethargy, confusion), coma, paradoxical seizures, and death. Rapid intravenous infusions of phenytoin or its prodrug fosphenytoin can also result in hypotension and bradyarrhythmia. Toxicity typically occurs after dosing adjustments or initiation of medications that interfere with the pharmacodynamics of phenytoin. Because phenytoin is highly protein-bound and is hepatically metabolized by the cytochrome p450 system, medications that inhibit the cytochrome p450 system (eg, trimethoprim-sulfamethoxazole [as in this patient], fluconazole) or that displace phenytoin from plasma proteins (eg, valproic acid) increase the risk of drug toxicity. Patients with renal or hepatic dysfunction are also at increased risk. Management involves supportive care with gastric decontamination and possibly hemodialysis. (Choice A) Epidural abscesses (which may result from hematogenous spread of infection) may cause weakness and hyperreflexia; however, patients typically have fever, malaise, and back pain. Lower extremity hyperreflexia is possible, but diffuse hyperreflexia would be unlikely. In addition, epidural abscess is unlikely to cause cerebellar dysfunction and nystagmus. (Choice B) Folate deficiency (which is associated with phenytoin use) typically causes macrocytic anemia and mood disturbances or psychosis but may rarely cause paresthesias and weakness. However, nystagmus and cerebellar dysfunction would be unexpected. (Choice D) Septic encephalopathy is characterized by delirium (waxing and waning altered mentation) and confusion. Focal neurologic deficits, as seen in this patient, would be unexpected. In addition, although the patient likely had a urinary tract infection, symptoms have improved and she does not have fever, tachycardia, tachypnea, or hypotension to suggest sepsis. (Choice E) Acute subdural hematoma usually occurs after trauma (eg, fall) and often causes coma at the time of injury (or shortly thereafter). Chronic subdural hematoma has an indolent course with gradually worsening headache, cognitive impairment, and somnolence that occurs over a period of weeks. This patient's symptoms preceded the fall, and nystagmus would be unexpected. Educational objective: Phenytoin is highly protein-bound and metabolized hepatically by the cytochrome p450 system; medications that inhibit cytochrome p450 (eg, trimethoprim-sulfamethoxazole, fluconazole) or that displace phenytoin from plasma proteins (eg, valproic acid) increase the risk of drug toxicity. Common symptoms of acute phenytoin toxicity include horizontal nystagmus, ataxia, and nausea/vomiting, and significant toxicity can result in altered mental status, coma, and death. References: When less is more: a case of phenytoin toxicity. (http://www.ncbi.nlm.nih.gov/pubmed/23536644)

A 74-Year-Old Woman Is Brought to the Emergency Department Due