Epilepsy & Behavior 5 (2004) 792–796 www.elsevier.com/locate/yebeh
Case Report
Sporadic Creutzfeldt–Jakob disease presenting with nonconvulsive status epilepticus David Cohen, Ekrem Kutluay*, Jonathan Edwards, Amanda Peltier, Ahmad Beydoun Department of Neurology, University of Michigan Health System, UH1B300/0036 Ann Arbor, MI 48109, USA Received 14 May 2004; revised 25 June 2004; accepted 25 June 2004 Available online 14 August 2004
Abstract Creutzfeldt–Jakob disease (CJD) is a rare prion disease characterized by a spongiform encephalopathy in humans. Although the characteristic triad of myoclonus, dementia, and periodic EEG activity is easy to recognize, unusual manifestations of the disease may be challenging and create a diagnostic dilemma. We report a case of CJD that occurred in a 26-year-old patient who presented with a receptive (WernickeÕs) aphasia secondary to nonconvulsive status epilepticus. Ó 2004 Elsevier Inc. All rights reserved. Keywords: Creutzfeldt–Jakob disease; Status epilepticus; WernickeÕs aphasia
1. Introduction
2. Case report
Creutzfeldt–Jakob disease (CJD) is the most common transmissible spongiform encephalopathy in humans. Most cases are sporadic, with an average age at onset of 62 years [1]. The typical clinical triad consists of a rapidly progressive dementia, startle myoclonus, and characteristic periodic sharp complexes on the EEG [1,2]. Other presentations include behavioral abnormalities, cortical dysfunction, visual disorders, and extrapyramidal or cerebellar signs. Although the diagnosis may be straightforward in older adults exhibiting the classic symptoms and signs, the diagnosis is challenging when the initial presentation is atypical. We describe a young patient whose initial manifestation of CJD was WernickeÕs aphasia resulting from a focal nonconvulsive status epilepticus.
The patient was a 26-year-old previously healthy man who presented to the University of Michigan Medical Center because of progressive language difficulties and confusion. In retrospect, his initial symptoms began 2 months earlier, when he developed subtle difficulties in spelling. A few days prior to admission, his parents noted odd behavior characterized by getting lost on his way home, forgetting how to start his computer, and having to write simple instructions and his schedule in a notebook. The patient was employed as an electrical technician and had completed 2 years of college. There was no history of illicit drug use, exposure to toxins, or ingestion of venison. On admission, he was fully awake but had a profound dysphasia. His language was characterized by fluent output noted to be paragrammatic and of an empty quality, secondary to omission of substantive words. He had perseveration and committed multiple paraphasic errors. His confrontation naming was impaired. He could repeat single words but had difficulty repeating sentences. He was unable to read or comprehend printed material. The rest of his neurological examination was
*
Corresponding author. Fax: 1 734 936 5520. E-mail address:
[email protected] (E. Kutluay).
1525-5050/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2004.06.019
Case Report / Epilepsy & Behavior 5 (2004) 792–796
normal. He was diagnosed with a receptive (WernickeÕs) aphasia and admitted to the hospital for evaluation. A 30-minute routine EEG obtained on the day of admission was diagnostic for focal nonconvulsive status epilepticus (NCSE) of left temporal origin. Background activity was characterized by diffuse continuous slowing with superimposed intermittent slower activity with a higher amplitude over the left hemisphere (Fig. 1A). In addition, a total of nine electrographic seizures were re-
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corded in this EEG, with a duration ranging from 7 to 106 seconds, and characterized by rhythmic 2- to 4-Hz delta activity intermixed with sharp waves, with a clear amplitude predominance over the left temporal region (Fig. 1B). Treatment with benzodiazepines and a loading dose of fosphenytoin failed to abort the NCSE. Additional intravenous treatment with a loading dose of valproate was unsuccessful. Midazolam-induced coma was initiated under continuous videoEEG moni-
Fig. 1. (A) Interictal EEG shows diffuse slow background intermixed with additional intermittent slowing with a higher amplitude over the left hemisphere. (B) Left temporal electrographic seizure recorded during the initial EEG on the day of admission.
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toring, and every attempt to taper it resulted in resumption of the NCSE. Despite treatment with various AEDs, including topiramate, phenobarbital, oxcarbazepine, and levetiracetam, the NCSE could not be terminated. Over time, the EEG evolved to a pattern characterized by severe generalized background slowing, by bilateral periodic lateralized epileptiform discharges, of maximum amplitude over both temporal regions (Fig. 2), and by frequent focal electrographic seizures starting from the left temporal region or with a bitemporal onset. The patient remained in a deep coma and never regained consciousness, even after discontinuation of midazolam. On admission, a brain MRI scan showed abnormal increased T2, FLAIR, and diffusion signal involving the head of the right caudate and lentiform nuclei and the right insula. Workup for an infectious, inflammatory, or neoplastic etiology was negative. A lumbar puncture revealed absence of white blood cells, a glucose level of 63 mg/dL. and a protein concentration of 28 mg/ dL. The CSF herpes simplex virus PCR, VDRL, and AFB, viral, bacterial, and fungal cultures were negative. In addition, serum antinuclear, antineuronal, antithyroglobulin, and antimicrosomal antibodies, extractable nuclear antigens, EBV IgM, CMV, and arbovirus panels were negative. CT scans of the chest, abdomen, and pelvis were normal. A brain biopsy was performed on the right frontal lobe and the pathology was indicative of a spongiform encephalopathy, with prominent vacuolization (Fig. 3). Based on this result, the patient was empirically treated with quinacrine (200 mg every 6 hours for five doses, then 100 mg three times daily) and chlorpromazine
(50 mg three times daily) [3]. Chlorpromazine was discontinued due to a rash while quinacrine was continued for 21 days. Because of the patientÕs lack of improvement and poor overall prognosis, the family elected for hospice care on hospital day 62. At that time, he was intubated, in a deep coma, with intact corneal and oculocephalic reflexes, and inconsistently withdrawing to noxious stimuli. The patient died 14 days after his discharge from the hospital. A postmortem brain autopsy was diagnostic of sporadic CJD (M/M2 variant), with a nonpathogenic polymorphism at codon 129 of the PrP gene. The autopsy excluded a familial form of CJD and was not consistent with the new variant CJD.
3. Discussion This case is a unique presentation of CJD because of a number of atypical features: clinical onset at the age of 26 years manifested by receptive aphasia resulting from a focal NCSE. The age at onset in our patient is very atypical when one considers that out of 4751 people who died from CJD in the United States between 1979 and 1998, only 10 (0.2%) were younger than 30 [4]. Patients with the new variant CJD have a mean age at onset similar to that of our patient [5]. However, a diagnosis of the sporadic, nonfamilial CJD form was confirmed in our case and the results were inconsistent with the new variant of the disease. Although a recent report raised the possibility of developing CJD after venison consumption, a cau-
Fig. 2. Continuous periodic pattern recurring at a frequency of 0.5–2 Hz.
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Fig. 3. Brain biopsy showing coarse spongiosis (H&E).
sal relationship has not yet been established [6]. In addition, our patient had no history of venison consumption. Another atypical feature in our case was that he presented with a focal NCSE. Although seizures have been reported to occur in up to 15% of patients with CJD [2], they usually occur in the setting of an established diagnosis and are present at onset in only 3% of cases [5]. A few case reports have described status epilepticus in CJD [7–10]. In a series of 21 patients with pathological findings of spongiform encephalopathy, 5 (24%) had seizures and only one had status epilepticus [7]. Two patients with CJD and a previous history of complex partial seizures were reported to be in complex partial status epilepticus, although the EEG was characterized by periodic discharges at 2 Hz, and failed to show temporal and spatial summation [8,9]. A recent article described an elderly woman who developed a change in mental status and who had electrographic features of NCSE. Her postmortem examination was diagnostic of CJD [10]. In our case, the initial EEG was unequivocally diagnostic of focal status epilepticus with focal onset from the left temporal area and subsequent spatial and temporal summations. Subsequent EEGs performed during more advanced stages of the disease were characterized by the periodic sharp wave complexes typical of CJD. The lack of periodic sharp wave complexes on the initial EEG done on our patient is not unusual. The characteristic periodic sharp wave complexes consist of biphasic or triphasic waves and are usually evident within 3 months of the onset of symptoms. A
study of serial EEG recordings in seven patients with CJD showed that the periodic sharp wave complexes on EEGs do not occur when cognitive impairment is the single symptom and that they first appear shortly after the development of akinetic mutism [11]. In addition, WernickeÕs aphasia as the initial presentation of CJD is very rare. We could only find a single case reported in the literature with such an initial presentation. This was a 61-year-old man whose initial presentation of CJD was a progressively worsening receptive aphasia and whose EEG studies were characterized by continuous left temporal slow activity in the theta range with intermixed periodic sharp wave complexes [12]. In addition, aphasia as the manifestation of status epilepticus is a very rare occurrence, as such occurrences have only been reported in individual case reports [13]. The diagnosis of CJD in our patient was delayed because of his unusual presentation. He was only 26 years old and did not exhibit myoclonus, neuropsychiatric abnormalities, extrapyramidal features, or dementia at presentation. It is, however, possible that his aphasia may have obscured some memory impairments. This case demonstrates that CJD can have protean clinical manifestations and should be considered in the differential diagnosis of NCSE of unclear etiology. References [1] Weihl CC, Roos RP. Creutzfeldt–Jakob disease, new variant Creutzfeldt–Jakob disease, and bovine spongiform encephalopathy. Neurol Clin 1999;17:835–59.
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[2] Roos R, Gajdusek DC, Gibbs CJ. The clinical characteristics of transmissible Creutzfeldt–Jakob disease. Brain 1973;96:1–20. [3] Korth C, May BC, Cohen FE, Prusiner SB. Acridine and phenothiazine derivatives as pharmacotherapeutics for prion disease. Proc Natl Acad Sci USA 2001;98:9836–41. [4] Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt–Jakob disease in the United States: 1979–1998. JAMA 2000;284:2322–3. [5] Zerr I, Poser S. Clinical diagnosis and differential diagnosis of CJD and vCJD: with special emphasis on laboratory tests. APMIS 2002;110:88–98. [6] Belay ED, Gambetti P, Schonberger LB, et al. Creutzfeldt–Jakob disease in unusually young patients who consumed venison. Arch Neurol 2001;58:1673–8. [7] Cokgor I, Rozear M, Morgenlander J. Seizures and Creutzfeldt– Jakob disease. NCMJ 1999;60:108–9. [8] Rees JH, Smith SJ, Kullmann DM, Hirsch NP, Howard RS. Creutzfeldt–Jakob disease presenting as complex partial status
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