Infratentorial Cerebral Cavernous Malformation May be a Risk Factor for Symptomatic Bleeding and Precocity of Symptoms: A Multicenter, Propensity Score Matched, Case-Control Study.

BACKGROUND: Cerebral Cavernous Malformation (CCM) is one of the most common types of vascular malformation of the central nervous system. Intracerebral hemorrhage, seizures, and lesional growth are the main clinical manifestations. Natural history studies have tried to identify many risk factors; however, the clinical course remains highly unpredictable. OBJECTIVE: Here, we have analyzed a multicenter CCM cohort looking for the differential clinical data regarding the patients harboring supra and/or infratentorial cavernous malformations in order to better understand risk factors involved in the anatomical location of the unique neurosurgical disease. METHODS: We have presented a multicenter, Propensity Score Matched (PSM), case-control study including 149 consecutive CCM cases clinically evaluated from May 2017 to December 2022 from three different neurosurgical centers. Epidemiological data were defined at each clinical assessment. Logistic regression was used to identify the independent contribution of each possible risk factor to the bleeding risk. To balance baseline covariates between patients with and without symptoms, and specifically between those with and without symptomatic bleeding, we used a PSM strategy. The Kaplan-Meier curve was drawn to evaluate if patients with infratentorial lesions had a greater chance of bleeding earlier in their life. RESULTS: The presence of infratentorial lesions was a risk factor in the multivariate analysis comparing the bleeding risk with pure asymptomatic individuals (OR: 3.23, 95% CI 1.43 - 7.26, P = 0.005). Also, having an infratentorial CCM was a risk factor after PSM (OR: 4.56, 95% CI 1.47 - 14.10, P = 0.008). The presence of an infratentorial lesion was related to precocity of symptoms when the time to first bleed was compared to all other clinical presentations in the overall cohort (P = 0.0328) and in the PSM group (P = 0.03). CONCLUSION: Here, we have provided some evidence that infratentorial cerebral cavernous malformation may have a more aggressive clinical course, being a risk factor for symptomatic haemorrhage and precocity of bleeding.

First Report of Concomitant Pathogenic Mutations Within MGC4607/CCM2 and KRIT1/CCM1 in a Familial Cerebral Cavernous Malformation Patient.

BACKGROUND: Familial cerebral cavernous malformations (CCM) are among the most common vascular malformations of the central nervous system (CNS) and are linked to mutations on the specific genes CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10. We present the first report in the literature of a pharmaco-resistant epileptic patient harboring co-occurring pathogenic mutations within CCM2/MGC4607 and CCM1/KRIT1. CASE DESCRIPTION: A 51-year-old patient first presented at age of 33 years with episodes of seizures. Magnetic resonance imaging including a susceptibility-weighted imaging sequence had shown multiple cerebral cavernous malformation lesions. She had partial response of symptoms and remained in routine follow-up needing progressive pharmacological improvement. Direct sequencing allowed the detection of 1 nonsense pathogenic mutation in CCM2/MGC4607 (c.118C>T; p.Arg40Ter) and 1 unclassified frameshift insertion variant in CCM1/KRIT1 (c.1687_1688insT; p.Tyr563LeufsTer5). CONCLUSIONS: Although the CCM2/MGC460 variant seems to be the major contributor for the patient's CCM phenotype, the mutated CCM1/KRIT1 seems to act as a booster to CCM overall pathogenicity.

Doença de Creutzfeldt-Jakob: forma esporádica: relato de caso em paciente de 81 anos / Creutzfeldt-Jacob disease-sporadic form: case report of 81-year-old patient

As doenças priônicas são neurodegenerativas e possuem longo período de incubação, progredindo inexoravelmente, assim que os sintomas clínicos aparecem. A doença de Creutzfeldt-Jakob é a mais frequente das doenças priônicas, embora ainda seja rara. O quadro clínico dela é caracterizado por uma demência rapidamente progressiva, sintomas cerebelares e extrapiramidais, e a ressonância magnética, o eletroencefalograma e a análise do líquido cefalorraquidiano possuem achados típicos. Relatamos o caso de um paciente de 81 anos que se apresentou com declínio cognitivo rapidamente progressivo seguido, posteriormente, de mutismo acinético. Proteína 14-3-3 foi detectada no líquido cefalorraquidiano. A ressonância magnética revelou hipersinal do núcleo caudado e putâmen em imagem em difusão, T2 e FLAIR.(AU)

Prion diseases are neurodegenerative, and have long incubation periods, progressing inexorably once clinical symptoms appear. Creutzfeldt-Jakob disease (CJD) is the most frequent of the human prion diseases, although being still rare. The clinical picture of this disease is characterized by a rapidly progressing dementia, cerebellar and extrapyramidal symptoms, and rather specific magnetic resonance (MR), electroencephalography and cerebrospinal fluid (CSF) findings. We report the case of an 81-year-old patient who presented with rapidly progressive cognitive decline followed by akinetic mutism. Protein 14-3-3 in cerebrospinal fluid was detected. Magnetic resonance imaging findings revealed hyperintensity of the caudate and putamen in diffusion-weighted imaging, T2 Weighted sequences and FLAIR images. Patients who have progressive dementia should be evaluated by means of magnetic resonance imaging and cerebrospinal fluid analysis for Creutzfeldt-Jakob.(AU)