A 67-year-old man is brought to the office due to progressively worsening insomnia and impaired concentration and judgment for 2 months. Medical history is significant for early-stage non-small cell lung cancer that was resected 5 years ago. The patient currently takes no medications. Vitals signs are within normal limits. On examination, he is alert and oriented. The patient has limited language and difficulty remembering objects and names. Horizontal nystagmus is present. Mild spasticity, myoclonus, and hyperreflexia are present. Gait is wide based and unsteady. Cardiopulmonary and abdominal examinations show no abnormalities. MRI of the head reveals cerebral atrophy and diffuse bright signals in the cortical white matter and portions of the basal ganglia; there are no mass lesions. Which of the following is the most likely diagnosis?

Question

A 67-year-old man is brought to the office due to progressively worsening insomnia and impaired concentration and judgment for 2 months.  Medical history is significant for early-stage non-small cell lung cancer that was resected 5 years ago.  The patient currently takes no medications.  Vitals signs are within normal limits.  On examination, he is alert and oriented.  The patient has limited language and difficulty remembering objects and names.  Horizontal nystagmus is present.  Mild spasticity, myoclonus, and hyperreflexia are present.  Gait is wide based and unsteady.  Cardiopulmonary and abdominal examinations show no abnormalities.  MRI of the head reveals cerebral atrophy and diffuse bright signals in the cortical white matter and portions of the basal ganglia; there are no mass lesions.  Which of the following is the most likely diagnosis?

Quizplus · Accepted Answer

Explanation: 11ec25c8_d5c6_b86c_bc81_9f1479588976_MD0003_00 This patient's rapid neurologic decline is concerning for Creutzfeldt-Jakob disease, a fatal transmissible spongiform encephalopathy caused by a prion. Prions induce protein misfolding that leads to the accumulation of neurotoxic fibrils. This results in spongiform neurodegeneration with widespread neuronal loss. Clinical manifestations of Creutzfeldt-Jakob disease are diverse and often include: Neuropsychiatric decline: behavioral abnormalities, personality changes, sleep disturbances (eg, insomnia, hypersomnia), and rapidly progressive dementia. This may progress to a loss of speech and inability to care for oneself. Myoclonus: classically provoked by a startle Cerebellar signs: nystagmus, ataxia (wide-based gait) Upper motor neuron signs (eg, hyperreflexia, upgoing Babinski) due to degeneration of the corticospinal tracts Extrapyramidal signs: hypokinesia, dystonia MRI of the brain often reveals hyperintensity of the cerebral cortex (ie, cortical ribboning), putamen, and head of the caudate (ie, hockey stick sign). Electroencephalogram classically shows sharp, triphasic, and synchronous discharges. (Choice A) Some patients with significant prior carbon monoxide (CO) poisoning can present with neuropsychiatric symptoms (cognitive dysfunction, personality changes, movement disorders). MRI can show hemorrhagic infarction of the basal ganglia, although this is typically limited to the globus pallidus. Cerebellar signs (eg, nystagmus) are uncommon. (Choice B) Leptomeningeal carcinomatosis can also present with subacute cognitive impairment; infiltration into the cerebellum can also lead to ataxia. However, most patients present with headache and demonstrate cranial nerve deficits. Focal cortical signs such as aphasia and hemiparesis are uncommon. In addition, MRI would show enhancement of the meninges, not cortical ribboning and enhancement of the basal ganglia. (Choice D) Wernicke encephalopathy due to thiamine deficiency can also present with confusion and ataxia (often with nystagmus). However, myoclonus is less typical; and MRI classically reveals mamillary body atrophy and periaqueductal gray matter hyperintensity. (Choice E) Wilson disease can also cause subacute, progressive dementia with movement disorders and MRI can show basal ganglia changes. However, it typically presents in children or adolescents and is accompanied by liver dysfunction. Educational objective: Creutzfeldt-Jakob disease is a rapidly fatal prion disease that presents with rapidly progressive dementia, myoclonus, mood symptoms, and sleep disturbances. MRI of the brain often reveals hyperintensity of the cerebral cortex (ie, cortical ribboning) and the putamen and caudate head (ie, hockey stick sign).

A 67-Year-Old Man Is Brought to the Office Due to Progressively