Pathologic evidence that the T188R mutation in PRNP is associated with prion disease

Human prion diseases can be caused by mutations in the prion protein gene PRNP. Prion disease with mutations at codon 188 has been reported in 6 cases, but only 1 had the T188R mutation and it was not pathologically confirmed. We report the clinical, neuropsychologic, imaging, genetic, and neuropathologic features of a patient with familial Creutzfeldt-Jakob disease, associated with a very rare PRNP mutation at T188R. The patient presented with prominent behavioral changes in addition to the more typical cognitive and motorimpairments seen in sporadic Creutzfeldt-Jakob disease. The autopsy confirmed prion disease pathology. This case supports the pathogenicity of the T188 PRNP mutation, demonstrates the variability of clinical phenotypes associated with certain mutations, and emphasizes the importance of testing for genetic prion disease in cases of apparently sporadic atypical dementia.     

Familial Creutzfeldt-Jakob disease without periodic EEG activity

Four members of a kindred with Creutzfeldt-Jakob disease are reported, in whom myoclonus did not develop and in whom serial electroencephalograms performed late in their illness failed to show periodic sharp wave complexes. Otherwise, the patients' disease duration, clinical features, and neuropathological findings were similar to those described in sporadic cases of Creutzfeldt-Jakob disease. Our findings and those reported by others suggest that periodic electroencephalographic activity may be rare in familial forms of Creutzfeldt-Jakob disease, as it is in other slow transmissible encephalopathies.     

Demyelinating peripheral neuropathy in Creutzfeldt-Jakob disease.

We describe 2 patients of Jewish Libyan descent, who presented with a clinical syndrome compatible with Creutzfeldt-Jakob disease and who were found to have a mutation of codon 200 in the prion protein. The patients developed symptoms and signs of peripheral nerve involvement diagnosed by electrodiagnostic and histopathological studies as demyelinating neuropathy. This may be a rare manifestation of Creutzfeldt-Jakob disease.     

Creutzfeldt-Jakob disease: a case of 16 years' duration

A 46-year-old man with Creutzfeldt-Jakob disease confirmed postmortem had a 16-year course of very slowly progressing incoordination and mental deterioration, suggesting Alzheimer's disease. The disease course transformed abruptly into a 7-week terminal phase of florid Creutzfeldt-Jakob disease. Dementing illnesses of unknown cause were present in the patient's paternal lineage.     

Hashimoto encephalopathy--a difficult differential diagnosis. A case report of reversible dementia and psychosis

INTRODUCTION: Hashimoto encephalopathy is a rare disease that is associated with Hashimoto thyreoiditis. Dementia, disturbances of consciousness and epileptic seizures are the most common features. CASE REPORT: We report a case of Hashimoto encephalopathy in a 74-year-old woman who presented with psychotic episodes, visual hallucinations, dementia, tremor, rigidity and fluctuation of consciousness. After treatment with steroids, cognitive function became normal and other symptoms improved significantly. CONCLUSION: Hashimoto encephalopathy should be considered as a differential diagnosis of psychosis in combination with dementia and other neurological symptoms to dementia with Lewy bodies and Creutzfeldt-Jakob disease.     

Periodic EEG discharges and status spongiosus of the cerebral cortex in anoxic encephalopathy: a necropsy case report.

A periodic EEG pattern very similar to the changes in Creutzfeldt-Jakob disease was seen in a case of anoxic encephalopathy. Necropsy revealed status spongiosus of the cerebral cortex. Generalised repetitive sharp transients in anoxic encephalopathy occur when the patient is comatose and carry a poor prognosis. They are not specific for Creutzfeldt-Jakob disease.     

Creutzfeldt-Jakob disease: a disease overview

Creutzfeldt-Jakob disease (CJD) is the most common form of the human transmissible spongiform encephalopathies, also known as prion diseases. This is a rare neurological disorder which ultimately results in death. Technologists must familiarize themselves with the clinical symptoms and EEG patterns of this disease since appropriate precautions must be taken. This is especially important when running electroneurodiagnostic (END) studies on patients with rapidly progressive dementia or a suspected or known case of CJD. An overview of the various forms of CJD, clinical symptoms, characteristic EEG results, transmission modes, diagnostic tests, and prevention methods are addressed.     

Brain tissue from persons dying of creutzfeldt-jakob disease causes scrapie-like encephalopathy in goats

Two goats became affected with an encephalopathy indistinguishable from scrapie 43 months after they were inoculated intracerebrally with 10% suspensions of brain from two persons dying of Creutzfeldt-Jakob disease. Although this observation does not establish the common identity of Creutzfeldt-Jakob disease virus and scrapie virus, it is thought to provide strong evidence of a close etiological relationship between the two diseases.     

Abnormal diffusion-weighted magnetic resonance imaging in Creutzfeldt-Jakob disease following corneal transplantations

BACKGROUND: The value of magnetic resonance imaging of the brain in the diagnosis of iatrogenic cases of Creutzfeldt-Jakob disease has been questioned. OBJECTIVE: To illustrate the value of magnetic resonance imaging of the brain in the diagnosis of iatrogenic Creutzfeldt-Jakob disease. METHODS: Case report. RESULTS: A patient with a history of 3 corneal transplantations exhibited the alien hand sign on initial examination. Diffusion-weighted magnetic resonance imaging of the brain revealed prominent cortical diffusion abnormalities. During the following months, the patient developed rapidly progressive dementia. The diagnosis of Creutzfeldt-Jakob disease was proven by brain biopsy. CONCLUSION: Brain magnetic resonance imaging, particularly diffusion-weighted magnetic resonance imaging, can be very helpful in the diagnosis of Creutzfeldt-Jakob disease, even in suspected iatrogenic cases.     

Atypical presentation of Creutzfeldt-Jakob disease: the first Italian case associated with E196K mutation in the PRNP gene

Genetic Creutzfeldt-Jakob disease (gCJD) is caused by a range of mutations in the prion protein gene (PRNP). We describe the first Italian case of gCJD associated with the rare PRNP E196K mutation. The disease showed an atypical presentation featuring dementia without motor signs in a 75-year-old woman. The case lacked both a known family history of a similar neurological disease and the typical EEG pattern; it was misdiagnosed as frontotemporal dementia. The present case emphasizes that vigilance must be kept high to avoid missing gCJD cases falling outside a typical phenotypical presentation and a known family history, especially in the elderly, in whom an alternative, more common, but incorrect diagnosis may be made.     

Hashimoto's encephalitis as a differential diagnosis of Creutzfeldt-Jakob disease

OBJECTIVES: During an epidemiological study of Creutzfeldt-Jakob disease in Germany, Hashimoto's encephalitis was encountered as a differential diagnosis, which has not yet been described in this context. METHODS: The symptoms and findings of seven patients who fulfilled the criteria for "possible" Creutzfeldt-Jakob disease are presented. RESULTS: A Hashimoto's thyroiditis with antibodies against thyroglobulin or thyroid peroxidase, or both and a hypoechoic thyroid ultrasonogram were found in all cases. Analysis of CSF disclosed an increased leucocyte count in three patients, and a raised CSF:serum concentration ratio of albumin (QA1b) in four patients. The 14-3-3 protein, typical of Creutzfeldt-Jakob disease, could not be detected in any of our patients. No periodic sharp wave complexes, which are typical of Creutzfeldt-Jakob disease, were detected on EEG in any of the cases. By contrast with Creutzfeldt-Jakob disease, which leads to death within a few months, the patients with Hashimoto's encephalitis often recover quickly when treated adequately. All the patients improved after administration of corticosteroids. CONCLUSION: The clinical symptomatology of both diseases may be very similar: dementia, myoclonus, ataxia, and personality change or psychotic phenomena are characteristic symptoms.     

Diagnostic difficulties in Creutzfeldt-Jakob disease--case report

The Creutzfeldt-Jakob disease (CJD) is rare spongiform encephalopathy. Its main symptoms are rapidly progressing dementia, myoclonic jerks, visual disturbances, ataxia, and pyramidal and extrapyramidal signs. A case of sporadic form of the CJD is reported, with blurred vision as one of the first symptoms. This symptom occurred shortly after vaccination against influenza, and was accompanied by other signs suggesting postvaccinal encephalitis. However, at a later stage of the disease typical changes were found in EEG recording and in magnetic resonance imaging (MRI). The presence of the 14-3-3 protein was detected in the patient's cerebrospinal fluid. The diagnosis of sporadic Creutzfeldt-Jakob disease was verified neuropathologically.     

Creutzfeldt-Jakob disease: case report with spinal cord involvement]

Creutzfeldt-Jakob disease (CJD) is the most common subacute transmissible spongiform encephalopathy. Approximately 85% of the cases are sporadic. The remaining 15% consist of genetic and iatrogenic forms. We report a sporadic form of CJD with spinal cord involvement and a clinical manifestation characterized by dementia and cerebellar syndrome, myofasciculation with absent reflexes and seizures. The two last manifestations are rare. The clinical hypothesis was probable CJD which was confirmed with autopsy and immunohistochemistry. We conclude that CJD should always be suspected when rapidly progressive dementia occurs and the absence of pyramidal or extrapyramidal signs suggest a spinal cord and/or peripheral nerve involvement.     

Sporadic Creutzfeldt-Jakob disease presenting with nonconvulsive status epilepticus

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 (Wernicke's) aphasia secondary to nonconvulsive status epilepticus.     

Akinetic mutism as a classification criterion for the diagnosis of Creutzfeldt-Jakob disease

OBJECTIVES—Among the classification criteria for the diagnosis of Creutzfeldt-Jakob disease, akinetic mutism is described as a symptom which helps to establish the diagnosis as possible or probable. Akinetic mutism has been anatomically divided into two forms—the mesencephalic form and the frontal form. The aim of this study was to delimit the symptom of akinetic mutism in patients with Creutzfeldt-Jakob disease from the complex of symptoms of an apallic syndrome and to assign it to the individual forms.
METHODS—Between April and December 1996, 25 akinetic and mute patients with Creutzfeldt-Jakob disease were consecutively examined. The patients were classified according to the definition of akinetic mutism by Cairns and secondly in accordance with the features constituting the complete picture of an appalic syndrome (defined by Gerstenbrand).
RESULTS—From 25 patients with definite Creutzfeldt-Jakob disease, 24 patients showed impoverishment of speech and, after a mean duration of four (range 1.1-11.2) months, almost complete absence of voluntary movements and speech. Seven patients were classified as being mute and akinetic and assigned to the mesencephalic form whereas 13 patients were classified as apallic. One patient was mute without being akinetic and four patients were comatose.
CONCLUSION—Diffuse brain damage underlies akinetic mutism in patients with Creutzfeldt-Jakob disease. The term can be used as a classification criterion for the diagnosis of Creutzfeldt-Jakob disease; however, it should be applied very carefully and delimited clearly from the apallic syndrome.

     

Generalized convulsive status epilepticus in Creutzfeldt-Jakob disease.

We report a patient who was referred to our department because of generalized status epilepticus. His condition deteriorated rapidly and he died 1 month after admission. Autopsy confirmed the clinical diagnosis of Creutzfeldt-Jakob disease (CJD). CJD should be added to the list of rare but possible causes of generalized status epilepticus.     

Familial myoclonic dementia masquerading as Creutzfeldt-Jakob disease

We describe a kindred with 7 confirmed and 2 probable cases of subacute dementia accompanied by myoclonus. The inheritance pattern is consistent with autosomal dominance and shows anticipation. The pathological changes involve marked gliosis with neuronal loss of the dorsomedial and midline thalamic nuclei, with lesser involvement of the anterior, lateral, and posterior thalamic nuclei. Medullary olivary hypertrophy is prominent. Spongiform change is minimal or absent. Attempted disease transmission to primates from 3 affected family members has been unsuccessful; Western immunoblot tests have likewise failed to detect the presence of specifically reactive 27-30 kD Mr proteins in brain tissue from 2 of these patients. We conclude that this family has a rare inherited neurological systems degeneration with associated thalamic dementia, the clinical course of which is very similar to Creutzfeldt-Jakob disease.     

Creutzfeldt-Jakob disease with unusually extensive neuropathology in a child treated with native human growth hormone

We report a case of iatrogenic Creutzfeldt-Jakob disease(iCJD) in a child with a neonatal growth hormone (GH) deficiency that was treated with native human growth hormone (hGH) between the ages of 9 months and 7 years. Three years after the end of treatment a progressive neurological syndrome consistent with Creutzfeldt-Jakob disease (CJD) developed, leading to death within a year, at age 11. Neuropathological examination showed an unusual widespread form of CJD, notably characterized by (i) involvement of the cerebellar white matter, (ii) cortico-spinal degeneration and (iii) ballooned neurons. A transitional form of the disease between common iatrogenic and panencephalopathic CJD is suggested.     

Creutzfeldt-Jakob disease in England and Wales, 1980-1984: a case-control study of potential risk factors.

An attempt was made to ascertain all cases of Creutzfeldt-Jakob disease occurring in England and Wales during the 5 year period 1980-1984. The mean annual mortality rate was 0.49/million; women were more frequently affected than men. The age-specific mortality rate reached a peak in the seventh decade. A case-control study involving 92 of the 122 definite and probable cases ascertained failed to confirm the reality of previously suspected aetiological agents in the environment. Although there was no confirmed instance of familial Creutzfeldt-Jakob disease in the case-control study, dementia in close relatives was significantly more common than in controls.     

Creutzfeldt-Jakob disease: familial clustering among Libyan-born Israelis.

Creutzfeldt-Jakob disease was studied among Libyan-born Israelis, in whom the disease appears with unusual frequency. Interviews with relatives of deceased victims revealed statistically significant clustering within families. The results suggest either a common source of exposure or a genetic influence on susceptibility to the virus.