Diagnostic challenge of Creutzfeldt-Jakob disease in a patient with multimorbidity: a case-report.

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and ultimately fatal neurodegenerative condition caused by prions. The clinical symptoms of CJD vary with its subtype, and may include dementia, visual hallucinations, myoclonus, ataxia, (extra)pyramidal signs and akinetic mutism. In the early course of disease however, several clinical symptoms of CJD may mimic those of co-existing morbidities. CASE PRESENTATION: We report a male in his 60s with a history of situs inversus totalis and Churg Strauss syndrome, who presented with speech fluency disturbances, neuropsychiatric symptoms and allodynia, a few months after becoming a widower. Initially presumed a bereavement disorder along with a flare-up of Churg Strauss, his symptoms gradually worsened with apraxia, myoclonic jerks and eventually, akinetic mutism. MRI revealed hyperintensities at the caudate nucleus and thalami, while the cerebrospinal fluid was positive for the 14-3-3 protein and the real-time quick test, making the diagnosis of CJD highly probable. This case illustrates the complexities that may arise in diagnosing CJD when pre-existing multimorbidity may cloud the clinical presentation. We also discuss the potential mechanisms underlying the co-occurrence of three rare conditions (situs inversus totalis, Churg Strauss syndrome, CJD) in one patient, taking into consideration the possibility of coincidence as well as common underlying factors. CONCLUSIONS: The diagnosis of CJD may be easily missed when its clinical symptoms are obscured by those of pre-existing (rare) multimorbidity. This case highlights that when the multimorbidity has neurological manifestations, an extensive evaluation remains crucial to establish the diagnosis, minimize the risk of prion-transmission and provide appropriate guidance to patients and their caregivers.

Misdiagnosis of rarest subtype of sporadic Creutzfeldt Jakob Disease: a case report.

BACKGROUND: Creutzfeldt-Jakob disease (CJD), is a deadly degenerative condition of the central nervous system marked by rapidly progressive dementia. Magnetic resonance imaging (MRI) abnormalities in the cerebral cortex, basal ganglia, thalamus, and cerebellum could indicate severe acute diseases caused by a variety of factors. Although their MRI patterns may resemble those of CJD, clinical history, additional MRI findings, and laboratory testing are all necessary to provide a reliable difference. Here, we report a misdiagnosed case of probable VV1 subtype of sporadic CJD (sCJD) in which follow-up MRI supported the diagnosis. CASE PRESENTATION: A 41-year-old male patient attended the Neuropsychiatry Department with rapidly progressive dementia, akinetic mutism, and difficulty walking and speaking. His problem began with forgetfulness, disorganized behavior, and disorganized speech 7 months earlier which progressed rapidly and was accompanied by aphasia, apraxia, agnosia, and akinetic mutism in the last 2 months. On neurologic examination, hypertonia, hyperreflexia, frontal ataxia, bradykinesia, gait apraxia, and aphasia were noted. Based on clinical features and rapid symptoms progression the likely diagnosis of CJD was suspected. MRI and electroencephalography (EEG) were advised. MRI revealed features of diffuse cortical injury of both cerebral hemispheres also involving bilateral corpus striatum with evidence of cerebral volume loss. EEG showed lateralized periodic theta slow waves on the right side. According to the CDC's diagnostic criteria for CJD, the diagnosis of probable sCJD was established. Supportive care and symptomatic treatment are provided for the patient. After a 1-month follow up the patient's condition deteriorated significantly. The time-lapse from the first reported symptom to death was about 13 months. CONCLUSION: The need of addressing CJD in patients presenting with rapidly progressive dementia is highlighted in this case report. In the early stages of the disease, interpretation of MRI results might cause diagnostic difficulties; therefore, follow-up MRI is critical in obtaining the correct diagnosis.

Akinetic mutism and the story of David.

Following a description about the characteristics of akinetic mutism (AM) and how it differs from locked-in syndrome (LIS) and a disorder of consciousness (DOC), we present the case of David, a 71-year-old man with AM. David sustained a stroke following a middle cerebral artery (MCA) thrombus. A CT scan at the time detected old ischaemic infarcts affecting the right frontal lobe, the left occipital lobe and the left parietal lobe so David had bilateral brain damage. Initially thought to have a DOC, further neuropsychological assessments administered when David had improved a little, resulted in the diagnosis of AM. Although David spoke little, when he did speak, his words and phrases were well articulated, grammatical and with appropriate intonation. He was alert and visually aware and he was not paralysed. We discuss whether the diagnosis was correct and address the difficulties in assessing such patients.

Creutzfeldt-Jakob disease.

This review will explore the clinical and pathological findings of the various forms of Creutzfeldt-Jakob disease (CJD). Clinical findings of CJD are characterized by rapidly progressive cognitive dysfunction, diffusion-weighted magnetic resonance imaging (DWI) hyperintensity, myoclonus, periodic sharp-wave complexes on electroencephalogram and akinetic mutism state. Neuropathologic findings of CJD are characterized by spongiform changes in gray matter, gliosis-particularly hypertrophic astrocytosis-neuropil rarefaction, neuron loss and prion protein (PrP) deposition. The earliest pathological symptom observed by HE staining in the cerebral cortex is spongiform change. This spongiform change begins several months before clinical onset, and is followed by gliosis. Subsequently, neuropil rarefaction appears, followed by neuron loss. Regions showing fine vacuole-type spongiform change reflect synaptic-type PrP deposition and type 1 PrPSc deposition, whereas regions showing large confluent vacuole-type spongiform changes reflect perivacuolar-type PrP deposition and type 2 PrPSc deposition. Hyperintensities of the cerebral gray matter observed in DWI indicate the pathology of the spongiform change in CJD. The cerebral cortical lesions with large confluent vacuoles and type 2 PrPSc show higher brightness and more continuous hyperintensity on DWI than those with fine vacuoles and type 1 PrPSc . CJD cases showing diffuse myelin pallor of cerebral white matter have been described as panencephalopathic-type, and this white matter pathology is mainly due to secondary degeneration caused by cerebral cortical involvement, particularly in regard to neuron loss. In conclusion, clinical and neuroimaging findings and neuropathologic observations are well matched in both typical and atypical cases in CJD. The clinical diagnosis of CJD is relatively easy for typical CJD cases such as the MM1-type. However, even in atypical cases it seems that clinical findings can be used for an accurate diagnosis.

A case of abulia, status/post right middle cerebral artery territory infarct, treated successfully with olanzapine.

Abulia refers to a pathological deficit of willpower. Disruption of frontal-subcortical-mesolimbic circuits caused by lesions in certain central nervous system structures has been associated with abulia. Given the neurobiological link between the dopaminergic reward system and the psychological phenomenon of motivation, it has been speculated that modulating dopaminergic neurotransmission will potentially alter the clinical presentation of abulia. We present a case of abulia S/P right middle cerebral artery, treated successfully with olanzapine.

From juvenile parkinsonism to encephalitis lethargica, a new phenotype of post-streptococcal disorders: case report.

We report the case of a 16-year-old boy presented with a mild akinetic-rigid parkinsonism shortly after a post-streptococcal infection. After stopping corticoids, he had a rapid neurological deterioration to a fatal encephalitis lethargica-like syndrome. Serum analysis demonstrated consistently elevated anti-streptolysin-O. This case illustrates a new severe phenotype in the spectrum of the post-streptococcal disorders. This etiology should be considered in the differential diagnosis of a movement disorder with a rapid detrimental evolution.

Bilateral substantia nigra changes on MRI in a patient with encephalitis lethargica.

A 33-year-old woman admitted for meningoencephalitis had features of encephalitis lethargica develop on her third day of illness. She had ophthalmoplegia, akinetic mutism, and prominent extrapyramidal signs consisting of lip and hand tremors, cogwheel rigidity, and facial bradykinesia.

Parkinsonian syndrome complicating systemic lupus erythematosus.

Two girls with florid extrapyramidal parkinsonism complicating systemic lupus erythematosus (SLE) are reported. One patient (15 years old) presented with extreme rigidity, irritability, and mutism initially diagnosed as acute psychosis. Examination revealed severe extrapyramidal akinetic mutism, along with marked restlessness. CT and MRI imaging of the brain were unremarkable. EEG revealed moderate generalized disturbance of background activity. 99mTc-HmPAO SPECT cerebral scanning detected decreased regional cerebral blood flow at the basal ganglia. Dopamine-agonist drugs led to complete recovery after 3 months, along with normalization of EEG and SPECT alterations. The second patient (16 years old) was assessed for progressive bradykinesia and apathy impeding her active daily activities, and she was suspected to have developed depression. Neurologic assessment revealed a parkinsonian syndrome that was less severe than that of the first patient. The EEG showed mild disturbance of background activity, and 99mTc-HmPAO SPECT demonstrated impaired regional cerebral blood flow over the basal ganglia. A parkinsonian extrapyramidal syndrome complicating SLE should therefore be taken into account in any patient with SLE presenting with marked behavioral alterations, rigidity, or akinetic mutism.

Akinetic mutism due to diphenylhydantoin toxicity.

Akinetic mutism (AM) is a rare, specific, unconscious state. An AM patient seems to be awake, lacks mental activity, is unable to speak, and does not respond to any environmental stimulus. Cyclical sleep and awake states are maintained, and incontinence is present. Various factors such as tumor, vascular events, drug use and radiotherapy are responsible for the development of AM. A 12-year-old epileptic patient displayed AM and diphenylhydantoin toxicity (DPH). She seemed awake, was unable to speak or to understand, and had no movements with either spontaneous or noxious stimuli. Her serum DPH level was greater than 40 micrograms/ml. Magnetic resonance imaging (MRI) showed mild cerebellar atrophy. All known causes of AM were excluded. The AM state in this patient was considered to be due to toxic DPH levels. She regained her motor and mental activity within two months after carbamazepine was administered to replace DPH. She was symptom-free when examined at the two-year follow-up. No similar adverse effect of DPH has been reported to date.

Peptostreptococcal empyema in akinetic mutism.

Peptostreptococcal empyema occurred in a 54-year-old man who had suffered from diabetes mellitus and had been in akinetic mutism. Ultrasonic tomogram was useful to detect the space of empyema and to identify the decrease in volume of the empyema space with treatment.

[An autopsy case of Parkinson's disease associated clinically with dementia terminating in akinetic mutism and pathologically with multiple Lewy's Bodies in the cerebral cortex].

An autopsy case of a 50 year-old male with Parkinson's disease associated with multiple Lewy bodies in the cerebral cortex was reported. His clinical symptoms began at the age of 26 with the speech and actions indicative of a persecution complex accompanied by irritability and were followed by progressive dementia from the age of 37 and Parkinsonism since the age of 41. He was in a state of akinetic mutism thereafter till his death at the age of 50. Autopsy disclosed in addition to the typical findings of Parkinson's disease in the brain stem multiple intracytoplasmic Lewy bodies in medium-sized neurons of the fifth and sixth layers of the cerebral cortex. They were atypical in the sense that they did not have any haloes. They were especially numerous in the cingulate gyrus. In addition, findings of non-specific neuronal degeneration were obtained in the cerebral cortex such as cellular atrophy with massive deposition of lipofuscin pigments, central chromatolysis, cell loss and cellular gliosis in the third, fifth and sixth layers. These neuronal findings were also prominent in the cingulate gyrus. Such senile changes as senile plaques or granulo-vacuolar degeneration were not found, although there were a few foci of neurofibrillary degeneration in the hippocampal gyrus. Histochemically and electron microscopically, no difference was observed in the constituents of Lewy bodies between the brain stem and the cerebral cortex. Such autopsy findings and a review of the literature indicate that the dementia in this case may be related not only to the presence of Lewy bodies but also to the above-described, non-specific neuronal degeneration in the bilateral cingulate gyri and surrounding frontal gyri. The standpoint of regarding a Parkinson's disease with multiple Lewy bodies in the cerebral cortex as an independent disease entity was criticized.

[The locked-in syndrome. A case report]. / Das locked in-syndrom. Ein kasuistischer Beitrag.

Based on five of our own cases and the literature on hand the etiological, clinical, diagnostic and intensive therapeutic aspects of the syndrome are represented. Special emphasis is placed on the possible role of the oral contraceptives in triggering this syndrome.