Enfermedad de Creutzfeldt-Jakob de origen genético: serie de casos en la Patagonia Argentina / Creutzfeldt-Jakob syndrome of genetic origin: series of cases in the Argentinian Patagonia

La enfermedad de Creutzfeldt-Jakob (CJD) es un desorden neurodegenerativo poco frecuente con una incidencia estimada en 1 por cada 1.000.000 por año, típicamente caracterizado por demencia rápidamente progresiva, ataxia, mioclonus y cambios de comportamiento. Las enfermedades genéticas priónicas se desarrollan debido a mutaciones en el gen de proteína priónica PRNP. Entre el 10 y el 15% corresponden a formas familiares que se transmiten con patrón autosómico dominante con alta penetrancia. La mutación más frecuente a nivel mundial es la E200K (glutamato por lisina). Se reportan cuatro familias con CJD que fueron atendidas en el Hospital Provincial Neuquén en el año 2018. Tres de los cuatro casos índice tenían historia familiar de trastornos neurológicos y psiquiátricos pero estos datos no fueron jerarquizados en la evaluación inicial del caso. Se consideró la consulta genética por la edad temprana de presentación de la enfermedad. En todos los casos la consulta fue solicitada por el neurólogo. Los síntomas iniciales que presentaron los pacientes fueron insomnio pertinaz y depresión con pobre respuesta a la medicación psiquiátrica habitual. En todos los casos la progresión de la enfermedad fue rápida con desórdenes visuales, mioclonías, ataxia, demencia y pérdida del lenguaje. El análisis de los pedigrees permitió identificar ciento cuarenta personas que potencialmente podrían portar el gen y desarrollar la enfermedad en algún momento de la vida adulta. En todos los casos se identificó la mutación E200K. En la región existe una frecuencia aumentada de CJD. Debe ser investigada en los pacientes con síntomas neuropsiquiátricos e historia familiar sospechosa. Los estudios genéticos confirman el diagnóstico en los pacientes y permite identificarlos en individuos en etapa presintomática. Esto plantea un desafío para el asesoramiento genético familiar y para evitar la transmisión iatrogénica del trastorno.

Creutzfeldt-Jakob disease (CJD) is an uncommon neurodegenerative disorder with an incidence of 1 per 1,000,000 in humans per year, typically characterized by rapidly progressive dementia, ataxia, myoclonus and behavioral changes. Genetic prion diseases, which develop due to a mutation in the prion protein gene (PRNP), account for an estimated 10 to 15% of all CJD cases. Familial CJD is transmitted with an autosomal dominant inheritance pattern with high penetrance. Worldwide, the most common mutation is E200K (glutamate to lysine). We report four families with CJD assisted in Neuquén Hospital in 2018. Three of the four index cases had family history of neurological and psychiatric illness, though data was not taken into consideration at the moment of evaluation of the new cases. The most significant data recorded for a genetic consultation was when the problem had started, and it was required by a neurologist. The initial symptoms were persistent insomnia and depression with poor response to habitual psychiatric medication. Impoverishment is fast with visual disorder, myoclonias, ataxia, dementia and loss of language. Pedigree analysis allowed the identification of 144persons with the gene potential, who can develop the disease at any time in their adulthood. In all cases, mutation E200K was identified. There is a region of increased frequency of CJD. There must be suspicion on patients with neuropsychiatric symptoms and suspected family history(familiar background). Finding of the mutation confirms the diagnosis in patients and allows the identification on pre-symptomatic individuals. Challenge is posed on gene advice and to avoid iatrogenic disorder transmission.

Case report- a case of Creutzfeldt-Jakob disease

Creutzfeldt-Jakob Disease (CJD) is a rare invariably fatal neurodegenerative disease believed to be caused by an abnormal isoform of cellular infectious glycoprotein called prion protein. Though it is arare disease; yet it is the most common among prion diseases. Clinical presentation consists of rapidly progressive loss of memory, cognitive & visual disturbance, lack of coordination, myoclonus, cerebellar, pyramidal and extra pyramidal signs, akineticmutism & with progression of disease deterioration in higher mental functions become more pronounced. Periodic sharp triphasic wave complexes on EEG, high signal abnormalities in caudate nucleus and putamen on diffusion weighted (DW) or FLAIR MRI of Brain and positive 14-3-3 protein in CSF substantiate the diagnosis of CJD but definitive diagnosis is established by brain biopsy or autopsy materials. We report a case of 58-year old female patient who was admitted with complaints of rapidly progressive dementia, cognitive disturbance, blurring of vision and myoclonic jerks. Initial MRI brain and CSF findings were normal. Differential diagnoses that can present with rapidly progressive dementia and thereby mimic sporadic Creutzfeldt-Jakob disease were considered after review of literature. In EEG triphasic wave complexes were seen, repeat DWMRI after two weeks showed bilateral hyper-intensities in basal ganglia involving caudate nucleus and putamen, suggesting a diagnosis of probable CJD on the basis of center for disease control and prevention (CDC) criteria. The case is reported because of its rarity and also to emphasise that patients with rapidly progressive dementia, associated visual and cognitive disturbances and myoclonus should be investigated with DW MRI, EEG&CSF for diagnosis of CJD.

Surveillance of Creutzfeldt-Jakob diseases cases in Guizhou Province,China, 2010-2015 / 中国人兽共患病学报

We analyze the epidemiology,clinical features,and outcome of the patients with Creutzfeldt-Jakob diseases (CJD) in Guizhou Province from 2010 to 2015.The epidemiology,clinical characteristics and follow-up data of CJD suspected patients obtained from Guizhou CJD surveillance network were analyzed.The testing results of cerebrospinal fluid (CFS) and blood from the patients were also collected and analyzed.Results showed that a total of 11 CJD cases was found from 23 reported CJD suspected patients in Guizhou from 2010 to 2015,including 8 probable sporadic CJD(sCJD) cases,2 possible sCJD cases and 1 genetic CJD(gCJD) case.In 11 cases,rapidly progressive dementia was the major initial symptom,following by mental symptoms,extrapyramidal symptoms,signs and cerebellum cortical blindness.Clinical symptoms of progressive dementia were the main symptoms,following by visual or cerebellar dysfunction,myoclonus,cone system/extrapyramidal dysfunction,and akinetic mutism.Most of cases were abnormal in MRI (45.45％) and 14-3-3 protein detection in CSF(70％).The 14-3-3 blood samples of prion gene 129 amino acids (PRNP)polymorphisms were M/M type,excepting for 1 case gCJD confirmed diagnosis cases with D178N mutation in PRNP gene.Eleven CJD cases did not show season and regional clusterings and vocational tendency.The majority of the cases were male,the median age was 65,and mainly were the Han nationality.For all cases of CJD reported during that year for follow-up,the lost-tofollow-up rate was 27％,and the majority of cases died within one year.The sCJD cases were the majority in CJD cases of Guizhou Province,2010-2015.The epidemiological characteristics were similar to the national monitoring cases in the same period.

Tumor frontal, trastorno afectivo y encefalopatía. Discusión del caso clínico presentado en el volumen 6, número 2 / Brain Tumour, Mood Disorder and Encephalopathy. Discusion of the Clinical Case Presented in Volume 6, Number 2

En el presente artículo se reporta el caso de una paciente de 65 años que ingresó a la clínica con síntomas neurológicos no específicos y que, debido a hallazgos imagenológicos iníciales de masa tumoral extra axial (meningioma del ala del esfenoides), fue llevada a resección quirúrgica completa. La paciente presentó evolución postquirúrgica con deterioro neurológico progresivo, hasta su fallecimiento. El diagnóstico final, dado por biopsia cerebral abierta, fue de encefalopatía espongiforme. La encefalopatía espongiforme, descrita desde hace casi un siglo como Enfermedad de Creutzfeldt- Jakob (ECJ) y pobremente diagnosticada en nuestro medio por su baja frecuencia y presentación poco común, se manifiesta inicialmente con un trastorno en el comportamiento del paciente y luego con una fase demencial, en una trayectoria fatal cuya prueba de oro para confirmar el diagnóstico está centrada en biopsia cerebral o autopsia del cerebro, con tinciones de inmunohistoquímica para la proteína priónica anómala.

We report a case of a 65 years old female patient, who was admitted to the hospital with non specific neurological symptoms and who had preliminary imagenological findings of an extra-axial tumor mass (a meningioma of the sphenoid’s wing), which was taken to complete surgical removal. Afterwards, she developed progressive neurologic deterioration until her death. The final diagnosis was acute spongiform encephalophaty, and was obtained by cerebral biopsy. Spongiform encephalopathy was described, almost a century ago, as the Creutzfeldt-Jakob Disease, poorly diagnosed in our environment because of its low frequency and uncommon onset, which starts with a mood disorder followed by a phase of dementia and a final fatal outcome. The gold standard for the diagnosis is based on a biopsy or an autopsy of the brain, with immunohistochemical stains for the prionic abnormal protein.

Thrombolytic Therapy of Pulmonary Thromboembolism in Probable Sporadic Creutzfeldt-Jakob Disease

The effect of intravenous recombinant tissue plasminogen activator for patients with Creutzfeldt-Jakob disease (CJD) has yet to be determined. A woman with rapidly progressive cognitive decline, cerebellar dysfunction, and extrapyramidal symptoms, diagnosed as probable sporadic CJD, was complicated with pulmonary thromboembolism and systemic hypotension. Her vital signs were restored without brain parenchymal hemorrhage after intravenous thrombolysis. The presence of diffuse brain lesions in CJD did not increase the hemorrhagic complications associated with intravenous thrombolysis, which differs from an ischemic vascular event.

Tumor frontal, transtorno afectivo y encefalopatía / Brain tumor, mood disorder and encephalopathy

Se reporta caso de paciente de 65 años, de sexo femenino, que ingresa con síntomas neurológicos indiferenciados, los cuales, por hallazgos imagenológicos iniciales de meningioma del ala del esfenoides, requieren resección tumoral. Presenta evolución tórpida, deterioro neurológico progresivo, hasta su fallecimiento.

We report a case of a patient was 65 years old, who was admitted with neurologic symptoms ill-defined by imaging findings that initial meningioma wing of the sphenoid, tumor resection, is performed. She presented torpid evolution, progressive neurological deterioration, until her death.

A Case of Heidenhain Variant of Sporadic Creutzfeldt-Jakob Disease

PURPOSE: To report a case of the Heidenhain variant of sporadic Creutzfeldt-Jakob disease (CJD), predominantly characterized by visual impairment at onset. CASE SUMMARY: History-taking, ophthalmologic examination, neurologic examination, cerebrospinal fluid examination including 14-3-3 protein analysis, and brain MRI were performed in a 48-year-old man with progressive visual loss and a visual field defect. These symptoms were accompanied by visual illusion and macropsia. Neurologic examination revealed relatively rapidly progressing cognitive impairment, ataxia, aphasia, and myoclonus. The 14-3-3 protein was detectable in otherwise normal CSF samples. The diffusion weighted brain MRI showed increased signal intensity in both occipital lobes, the basal ganglia, the temporal and frontal lobes. He was clinically diagnosed as having a Heidenhain variant of sporadic CJD. CONCLUSIONS: In a patient with a rapidly progressive visual loss, visual field defects, visual illusion, and neurologic abnormalities including progressive dementia, ataxia, aphasia, and myoclonus, the Heidenhain variant of CJD should be considered. Because prions, a cause of CJD, exhibit unusual resistance to conventional chemical and physical decontamination methods, it is necessary to have an appropriate management scheme to prevent the spread of infection.

New Variant Creutzfeldt-Jakob Disease

No abstract available.