(107) Hold the Benztropine: Prion Disease Masquerading as Medication-induced Extrapyramidal Symptoms

‎Background/Significance: There are reports of psychiatric manifestations of prion diseases in the literature, ‎but little is published regarding prion disease in patients with preexisting psychiatric disorders. We describe a case of ‎prion disease occurring in a patient with schizophrenia.‎

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Case: A 67-year-old female with a recent diagnosis of small cell lung cancer was brought to the emergency ‎room after developing rigidity in all extremities, resting hand tremors, confusion, and truncal ataxia over the course of ‎‎2 weeks. Her daughter reported the patient had a history of schizophrenia and had a modest increase in her ‎risperidone dose for several days due to worsening anxiety and insomnia. After contacting her outpatient psychiatrist, ‎she was evaluated and started on benztropine due to concern for extrapyramidal symptoms (EPS). In the emergency ‎room, her sodium was 122, and she was admitted for hyponatremia and medical workup.‎

The neurology team attributed her symptoms to drug-induced parkinsonism, and she was started on ‎carbidopa/levodopa, diphenhydramine, and benztropine without improvement. Her initial MRI showed no ‎abnormalities. The patient rapidly deteriorated to an akinetic mute state and no longer followed commands or tracked ‎movements.‎

An EEG showed epileptiform activity, and the patient was given Depakene without improvement of symptoms. A ‎specialized autoimmune, paraneoplastic, and protein send-out conducted two weeks after admission was ‎indeterminate for real-time quaking induced conversion (RT-QuIC), a marker for Creutzfeld-Jakob disease (CJD), and ‎showed elevated gamma and tau protein. A month into her hospitalization, a repeat MRI revealed restricted diffusion ‎involving the caudate and putamen. Given her clinical picture and MRI findings, the patient was diagnosed with ‎probable CJD.‎

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Discussion: CJD is a progressive neurodegenerative disease caused by misfolded proteins and presents as a ‎rapidly progressive dementia with extrapyramidal/pyramidal symptoms, cerebellar symptoms, and myoclonus (Manix, ‎‎2015). While psychiatric symptoms were thought to be uncommon, one retrospective review looking at 126 cases of ‎CJD reported over 86% had reported psychiatric symptoms around the time of disease onset (Wall, 2005). Our patient ‎was described by her daughter as atypically anxious and refusing an outpatient MRI prior to her risperidone increase.‎

While case reports regarding psychiatric symptoms in CJD are prevalent, little literature exists on CJD patients with a ‎history of primary psychotic disorder. Our patient was diagnosed with schizophrenia for 40 years and had been on ‎antipsychotics. Her psychiatric history had confounded her CJD diagnosis as her motor and cognitive symptoms were ‎attributed to an atypical EPS parkinsonism drug reaction.‎

‎Conclusion/Implications:‎ In psychiatric patients with rapidly progressive neurological symptoms, other autoimmune and neurodegenerative ‎diseases such as CJD should be considered.‎

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References: ‎
‎1. Manix, M., Kalakoti, P., Henry, M., Thakur, J., Menger, R., Guthikonda, B., & Nanda, A. (2015). Creutzfeldt-Jakob ‎disease: updated diagnostic criteria, treatment algorithm, and the utility of brain biopsy. Neurosurgical focus, 39(5), E2. ‎https://doi.org/10.3171/2015.8.FOCUS15328 ‎
‎2. Wall, C. A., Rummans, T. A., Aksamit, A. J., Krahn, L. E., & Pankratz, V. S. (2005). Psychiatric manifestations of ‎Creutzfeldt-Jakob disease: a 25-year analysis. The Journal of neuropsychiatry and clinical neurosciences, 17(4), 489–‎‎495. https://doi.org/10.1176/jnp.17.4.489‎