Recurrent, founder and hypomorphic variants contribute to the genetic landscape of Joubert syndrome.

BACKGROUND: Joubert syndrome (JS) is a neurodevelopmental ciliopathy characterised by a distinctive mid-hindbrain malformation, the 'molar tooth sign'. Over 40 JS-associated genes are known, accounting for two-thirds of cases. METHODS: While most variants are novel or extremely rare, we report on 11 recurring variants in seven genes, including three known 'founder variants' in the Ashkenazi Jewish, Hutterite and Finnish populations. We evaluated variant frequencies in ~550 European patients with JS and compared them with controls (>15 000 Italian plus gnomAD), and with an independent cohort of ~600 JS probands from the USA. RESULTS: All variants were markedly enriched in the European JS cohort compared with controls. When comparing allele frequencies in the two JS cohorts, the Ashkenazim founder variant (TMEM216 c.218G>T) was significantly enriched in American compared with European patients with JS, while MKS1 c.1476T>G was about 10 times more frequent among European JS. Frequencies of other variants were comparable in the two cohorts. Genotyping of several markers identified four novel European founder haplotypes.Two recurrent variants (MKS1 c.1476T>G and KIAA0586 c.428delG), have been detected in homozygosity in unaffected individuals, suggesting they could act as hypomorphic variants. However, while fibroblasts from a MKS1 c.1476T>G healthy homozygote showed impaired ability to form primary cilia and mildly reduced ciliary length, ciliary parameters were normal in cells from a KIAA0586 c.428delG healthy homozygote. CONCLUSION: This study contributes to understand the complex genetic landscape of JS, explain its variable prevalence in distinct geographical areas and characterise two recurrent hypomorphic variants.

New insights into CC2D2A-related Joubert syndrome.

PURPOSE: In this study, we describe the phenotype and genotype of the largest cohort of patients with Joubert syndrome (JS) carrying pathogenic variants on one of the most frequent causative genes, CC2D2A. METHODS: We selected 53 patients with pathogenic variants on CC2D2A, compiled and analysed their clinical, neuroimaging and genetic information and compared it to previous literature. RESULTS: Developmental delay (motor and language) was nearly constant but patients had normal intellectual efficiency in 74% of cases (20/27 patients) and 68% followed mainstream schooling despite learning difficulties. Epilepsy was found in only 13% of cases. Only three patients had kidney cysts, only three had genuine retinal dystrophy and no subject had liver fibrosis or polydactyly. Brain MRIs showed typical signs of JS with rare additional features. Genotype-phenotype correlation findings demonstrate a homozygous truncating variant p.Arg950* linked to a more severe phenotype. CONCLUSION: This study contradicts previous literature stating an association between CC2D2A-related JS and ventriculomegaly. Our study implies that CC2D2A-related JS is linked to positive neurodevelopmental outcome and low rate of other organ defects except for homozygous pathogenic variant p.Arg950*. This information will help modulate patient follow-up and provide families with accurate genetic counselling.

SUFU haploinsufficiency causes a recognisable neurodevelopmental phenotype at the mild end of the Joubert syndrome spectrum.

BACKGROUND: Joubert syndrome (JS) is a recessively inherited ciliopathy characterised by congenital ocular motor apraxia (COMA), developmental delay (DD), intellectual disability, ataxia, multiorgan involvement, and a unique cerebellar and brainstem malformation. Over 40 JS-associated genes are known with a diagnostic yield of 60%-75%.In 2018, we reported homozygous hypomorphic missense variants of the SUFU gene in two families with mild JS. Recently, heterozygous truncating SUFU variants were identified in families with dominantly inherited COMA, occasionally associated with mild DD and subtle cerebellar anomalies. METHODS: We reanalysed next generation sequencing (NGS) data in two cohorts comprising 1097 probands referred for genetic testing of JS genes. RESULTS: Heterozygous truncating and splice-site SUFU variants were detected in 22 patients from 17 families (1.5%) with strong male prevalence (86%), and in 8 asymptomatic parents. Patients presented with COMA, hypotonia, ataxia and mild DD, and only a third manifested intellectual disability of variable severity. Brain MRI showed consistent findings characterised by vermis hypoplasia, superior cerebellar dysplasia and subtle-to-mild abnormalities of the superior cerebellar peduncles. The same pattern was observed in two out of three tested asymptomatic parents. CONCLUSION: Heterozygous truncating or splice-site SUFU variants cause a novel neurodevelopmental syndrome encompassing COMA and mild JS, which likely represent overlapping entities. Variants can arise de novo or be inherited from a healthy parent, representing the first cause of JS with dominant inheritance and reduced penetrance. Awareness of this condition will increase the diagnostic yield of JS genetic testing, and allow appropriate counselling about prognosis, medical monitoring and recurrence risk.

Cerebellar cognitive affective syndrome due to cerebellar atrophy: case report / Síndrome cerebelar cognitivo-afetiva secundária à atrofia cerebelar: relato de caso

Cerebellar atrophy is a rare and challenging disease with few descriptions in the medical literature. Motor impairment is mild, but behavioral and linguistic alterations stand out, in what is known as the cerebellar cognitive affective syndrome secondary to cerebellar atrophy. We report the case of an older woman with early-onset (age 45) signs and symptoms of this syndrome, including impairment of executive functions and visuospatial cognition, personality changes, and language deficits, who was followed at a geriatric medical center for 14 years. Neuropsychological, imaging, and behavioral aspects during this period are discussed in light of scientific evidence. This case report contributes to the scientific literature by describing the progression of the signs and symptoms of cerebellar atrophy over the years, which can help guide medical management and support advice for patients and their families.

A atrofia cerebelar é uma doença rara, desafiadora e com poucas descrições na literatura médica. O prejuízo motor é discreto, mas as alterações comportamentais e de linguagem se destacam, caracterizando a síndrome cognitivo-afetiva cerebelar secundária à atrofia cerebelar. Apresentamos o relato de caso de uma paciente idosa, que apresentou sinais e sintomas dessa síndrome precocemente (aos 45 anos de idade) ­ tais como déficits na função executiva, prejuízo visuoespacial, alterações de personalidade e déficits de linguagem ­ e foi acompanhada em um centro médico geriátrico por um período de 14 anos. Aspectos neuropsicológicos, de imagem e comportamentais durante esse período são comentados à luz das evidências científicas. O caso relatado contribui com a literatura científica ao descrever a evolução dos sinais e sintomas da atrofia cerebelar ao longo dos anos, balizando as condutas médicas e amparando as orientações ao paciente e seus familiares.

Anesthetic considerations of Joubert syndrome in patients with mitochondrial disease - A case report.

BACKGROUND: Joubert syndrome and mitochondrial disease are rare congenital diseases in which a wide range of symptoms affects multiple organs. Patients with these diseases present characteristic symptoms related to the musculoskeletal, respiratory, and neurological systems, which make it difficult for anesthesiologists to manage the patient's airway and choose appropriate anesthetic drugs. CASE: A 13-year-old male patient with Joubert syndrome and mitochondrial disease underwent elective surgery to insert a continuous ambulatory peritoneal dialysis catheter. Anesthesia was induced and maintained with propofol, remifentanil, and rocuronium. An I-gel was inserted to secure the airway; however, the fitting did not work properly, so the patient was intubated. The operation was completed without any major problems, and the intubated patient was transferred to the intensive care unit. CONCLUSIONS: Anesthesiologists should determine the method of anesthesia and prepare for unintended complications based on a full understanding of these congenital diseases.

Severe Cerebellar Degeneration and Chiari I Malformation - Speculative pathophysiology based on a systematic review

SUMMARY BACKGROUND Symptomatic Chiari Type I Malformation (CM) is treated with posterior fossa decompression with or without duroplasty. We have noticed some cases with concomitant severe cerebellar ataxia due to cerebellar atrophy. The aim of this study is to review the literature of CM associated with severe cerebellar atrophy and discuss its potential physiopathology. METHODS A systematic literature review in the Pubmed Database was performed using the following key-terms: "cerebellar atrophy Chiari", and "cerebellar degeneration Chiari". Articles reporting the presence of cerebellar degeneration/atrophy associated with CM were included. RESULTS We found only six studies directly discussing the association of cerebellar atrophy with CM, with a total of seven cases. We added one case of our own practice for additional discussion. Only speculative causes were described to justify cerebellar atrophy. The potential causes of cerebellar atrophy were diffuse cerebellar ischemia from chronic compression of small vessels (the most mentioned speculative cause), chronic raised intracranial pressure due to CSF block, chronic venous hypertension, and association with platybasia with ventral compression of the brainstem resulting in injury of the inferior olivary nuclei leading to mutual trophic effects in the cerebellum. Additionally, it is not impossible to rule out a degenerative cause for cerebellar atrophy without a causative reason. CONCLUSIONS Severe cerebellar atrophy is found in some patients with CM. Although chronic ischemia due to compression is the most presumed cause, other etiologies were proposed. The real reasons for cerebellar degeneration are not known. Further studies are necessary.

RESUMO OBJETIVO A Malformação de Chiari (MC) tipo I sintomática é tratada através da descompressão da fossa posterior com ou sem duroplastia. Observamos alguns casos com ataxia cerebelar grave concomitante devido à atrofia cerebelar. O objetivo deste estudo é revisar a literatura sobre MC associada à atrofia cerebelar grave e discutir sua possível fisiopatologia. METODOLOGIA Conduzimos uma revisão sistemática da literatura no banco de dados Pubmed utilizando as seguintes palavras-chave: "cerebellar atrophy Chiari", e "cerebellar degeneration Chiari". Artigos sobre a presença de degeneração/atrofia cerebelar associada à MC foram incluídos. RESULTADOS Encontramos apenas seis estudos que discutiam diretamente a associação entre atrofia cerebelar e MC, com um total de sete casos. Nós adicionamos um caso da nossa própria prática para ampliar a discussão. Apenas causas especulativas foram descritas para justificar a atrofia cerebelar, entre elas: isquemia cerebelar difusa devido à compressão crônica de pequenos vasos (a causa especulativa mais citada), pressão intracraniana elevada crônica devido ao bloqueio de LCR, hipertensão venosa crônica e associação com platibasia com compressão ventral do tronco cerebral, resultando em lesão do núcleo olivar inferior e levando a efeitos tróficos mútuos no cerebelo. Além disso, não é possível descartar uma causa degenerativa para atrofia cerebelar sem motivos claros. CONCLUSÃO A atrofia cerebelar grave é encontrada em alguns pacientes com MC. A isquemia crônica causada por compressão é a causa mais apontada como suspeita, porém outras etiologias foram propostas. As reais causas da degeneração cerebelar não são conhecidas. Mais estudos são necessários.

Acute cerebellar ataxia: differential diagnosis and clinical approach / Ataxia cerebelar aguda: diagnóstico diferencial e abordagem clínica

ABSTRACT Cerebellar ataxia is a common finding in neurological practice and has a wide variety of causes, ranging from the chronic and slowly-progressive cerebellar degenerations to the acute cerebellar lesions due to infarction, edema and hemorrhage, configuring a true neurological emergency. Acute cerebellar ataxia is a syndrome that occurs in less than 72 hours, in previously healthy subjects. Acute ataxia usually results in hospitalization and extensive laboratory investigation. Clinicians are often faced with decisions on the extent and timing of the initial screening tests, particularly to detect treatable causes. The main group of diseases that may cause acute ataxias discussed in this article are: stroke, infectious, toxic, immune-mediated, paraneoplastic, vitamin deficiency, structural lesions and metabolic diseases. This review focuses on the etiologic and diagnostic considerations for acute ataxia.

RESUMO A ataxia cerebelar é um achado comum na prática neurológica e tem uma grande variedade de causas, desde a degeneração cerebelar crônica e lentamente progressiva à lesão cerebelar aguda devido a infarto, edema ou hemorragia, configurando uma verdadeira emergência neurológica. Ataxia cerebelar aguda é uma síndrome que ocorre em menos de 72 horas em indivíduos previamente saudáveis. A ataxia aguda geralmente resulta em hospitalização e extensa investigação laboratorial. Os clínicos são frequentemente confrontados com a decisão sobre a extensão e o momento dos testes de rastreio iniciais, em particular para detectar as causas tratáveis. O principal grupo de doenças que podem causar ataxias agudas discutidas neste artigo são: acidente vascular cerebral, infecciosas, tóxicas, imunomediadas, paraneoplásicas, deficiência de vitaminas, lesões estruturais e doenças metabólicas. Esta revisão enfoca a etiologia e considerações diagnósticas para a ataxia aguda.

Anti-Yo-Associated Paraneoplastic Cerebellar Degeneration Manifesting as Acute Cerebellitis with Posterior Cranial Fossa Hypertension.

BACKGROUND: Paraneoplastic cerebellar degeneration (PCD) is a rare complication of some malignant cancers. It is most commonly described in women with gynecologic or breast malignancies; however, there have been reports in other types of cancers. Symptoms include ataxia, dysarthria, and tremors, which could be the first manifestations of an underlying malignancy. CASE DESCRIPTION: A 50-year-old woman had an acute PCD with anti-Yo antibodies from an underlying breast invasive ductal carcinoma. She presented with intracranial hypertension in the posterior cranial fossa that required an emergent decompressive craniectomy. CONCLUSIONS: PCD is an uncommon disease that may manifest initially as posterior cranial fossa hypertension and subsequent acute hydrocephalus owing to diffuse cerebellar swelling. To our knowledge, this is the first described case of an anti-Yo PCD that has manifested as acute posterior cranial fossa hypertension owing to diffuse cerebellar edema. Early diagnosis and treatment should be pursued to improve long-term outcomes.

Spectrum of findings on magnetic resonance imaging of the brain in patients with neurological manifestations of dengue fever / O espectro de achados de ressonância magnética do encéfalo em pacientes com manifestações neurológicas de dengue

Abstract Objective: To describe the spectrum of magnetic resonance imaging (MRI) findings in patients with neurological manifestations of dengue. Materials and Methods: We included nine patients with dengue fever (three females and six males; age range, 9-30 years), all of whom presented with neurological manifestations. The MRI examinations, performed in 1.5 T or 3 T scanners, included T1-weighted, T2-weighted, and fluid-attenuated inversion recovery (FLAIR) sequences. Diffusion-weighted imaging with apparent diffusion coefficient mapping was also employed. Fast low-angle shot and susceptibility-weighted gradient-recalled echo sequences, as well as contrast-enhanced T1-weighted scans, were also obtained in order to assess parenchymal enhancement. MRI scans were analyzed for lesion distribution and imaging features. Results: All patients showed areas of altered signal intensity that appeared as hyperintensity on T2-weighted and FLAIR sequences. The most commonly affected site was the basal ganglia-thalamus complex. Other affected sites were the cerebellum, cerebral cortex, white matter, and brainstem. In all cases, we observed patchy areas of restricted diffusion and focal areas of hemorrhage. Conclusion: Dengue encephalitis commonly affects the basal ganglia, thalamus, cerebellum, cerebral cortex, and white matter. Therefore, MRI should be an indispensable part of the evaluation of patients with neurological complications of dengue fever.

Resumo Objetivo: Descrever o espectro dos achados de ressonância magnética (RM) em pacientes com manifestações neurológicas de dengue. Materiais e Métodos: Foram incluídos nove pacientes com dengue (três do sexo feminino e seis do sexo masculino; faixa etária: 9-30 anos), todos com manifestações neurológicas. Os exames de RM, realizados em aparelhos de 1,5 T ou 3 T, incluíram sequências ponderadas em T1 e em T2, assim como fluid-attenuated inversion recovery (FLAIR). Também foi empregada a imagem ponderada em difusão com mapeamento de coeficientes de difusão aparente. Além disso, foram obtidas sequências gradiente-eco ponderadas por suscetibilidade e em fast low-angle shot, bem como imagens ponderadas em T1 pós-contraste, para avaliar o realce parenquimatoso. As imagens de RM foram analisadas quanto à distribuição de lesões e características de imagens. Resultados: Todos os pacientes apresentaram áreas de intensidade de sinal alteradas que apareceram como hiperintensidade em sequências ponderadas em T2 e sequências FLAIR. O local mais comumente afetado foi o complexo gânglios basais-tálamo. Outros locais afetados foram o cerebelo, o córtex cerebral, a substância branca e o tronco encefálico. Em todos os casos observamos áreas irregulares de difusão restrita e áreas focais de hemorragia. Conclusão: A encefalite por dengue geralmente afeta os gânglios basais, o tálamo, o cerebelo, o córtex cerebral e a substância branca. Portanto, a RM deve ser uma parte indispensável da avaliação de pacientes com complicações neurológicas da dengue.

Cryptococcal cerebellitis in no-VIH patient / Cerebelitis criptococócica en paciente VIH negativo

Abstract Introduction: Cryptococcosis is an opportunistic fungal infection whose etiology is Cryptococcus neofromans / C. gattii, complex which affects immunocompromised patients mainly. Meningeal infection is one of the most common presentations, but cerebellar affection is rare. Case Description: Male patient with 65 old years, from an area of subtropical climate with chronic exposure to poultry, without pathological antecedents, who presented clinical picture consistent with headache, fever, seizures and altered mental status. Clinical findings and diagnostic methods: Initially without menigeal signs or intracranial hypertension and normal neurological examination. Later, the patient developed ataxia, dysdiadochokinesia and limb loss. By lumbar punction and image of nuclear magnetic resonance (NMR) cerebellitis cryptococcal was diagnosticated. Treatment: Antifungal therapy with amphotericin B and fluconazole was performed, however the patient died. Clinical Relevance: The cryptococcosis has different presentations, it´s a disease whose incidence has been increasing since the advent of the HIV / AIDS pandemy, however the commitment of the encephalic parenchyma and in particular the cerebellum is considered rare. In this way we are facing the first case of cryptococcal cerebellitis in our midst.

Resumen Introducción: La Criptococosis es una infección micótica oportunista cuya etiología es el complejo Cryptococcus neofromans/C. gattii, el cual principalmente afecta pacientes inmunocomprometidos. La afección meníngea es una de las formas más frecuentes pero el compromiso cerebeloso es raro. Descripción del Caso: Paciente masculino de 65 años, procedente de un área rural con exposición crónica a aves de corral, sin antecedentes patológicos, con cuadro clínico inicial consistente en cefalea crónica, fiebre, convulsiones y alteración del estado mental. Hallazgos clínicos y métodos diagnósticos: Al principio sin signos de hipertensión intracraneana ni meníngeos y examen neurológico normal, con posterior desarrollo de ataxia, disdiadococinesia y dismetría. Se diagnosticó Cerebelitis Criptocococica con ayuda de repetidos estudios de LCR y resonancia magnética nuclear. Tratamiento: Se inició terapia antifúngica con Anfotericina B y Fluconazol, con respuesta tórpida y el paciente fallece. Relevancia clínica: La Cerebelitis Criptocococica es una presentación clínica infrecuente que requiere sospecha clínica y recursos diagnósticos para definir el tratamiento de forma temprana. La inmunosupresión no es requisito para padecer esta infección.

Síndrome cerebeloso por mesalamina: reporte de un caso / Cerebellar syndrome for mesalamine: a case report

El cerebelo proviene del latín "pequeño cerebro", es aproximadamente una décima parte del cerebro en tamaño y peso, se encuentra en la fosa craneal posterior. está conectado directamente o indirectamente a una variedad de estructuras, incluyendo el tronco cerebral, la columna vertebral, las regiones corticales y subcorticales. El cerebelo contiene casi el 80 % del total de las neuronas del cerebro y se compone de formas diferenciadas de unidades neuronales, cada una compartiendo microcircuitos cerebelosos básicos. El cerebelo está formado por dos hemisferios laterales y una porción media o vermis . El cerebelo tiene varias funciones: coordinar los movimientos voluntarios especializados al influir en la actividad muscular y controlar el equilibrio, el tono muscular a través de conexiones con el sistema vestibular, la médula espinal y sus neuronas motoras alfa. Dentro de la corteza del cerebelo existe una organización somatotópica de las partes del cuerpo. El cerebelo es una pieza clave para el procesamiento de la información y participa en numerosas actividades motoras y no motoras, gracias a las características anatómicas de sus circuitos, las enormes capacidades de análisis y la alta conectividad con otras áreas del cerebro, puede verse afectado por diferentes factores como: anormalidades en el desarrollo embrionario, tóxicos, enfermedades autoinmunes, inflamatorias, vasculares y metabólicas, infecciones, tumores primarios y secundarios, traumas, iatrogénicos, enfermedades genéticas, esporádicas, dando origen a signos y síntomas que causan un síndrome cerebeloso de acuerdo al área anatómica comprometida. En la literatura científica no hay reportes de casos de síndrome cerebeloso por mesalamina (mesalazina). A continuación presentamos el primer caso.

Cerebellum is Latin for "little brain" is about a tenth of the brain in size and weight, is in the posterior cranial fossa. It connects directly or indirectly to a variety of structures, including brainstem, spinal cord, cortical and subcortical regions. The cerebellum contains almost 80% of all neurons in the brain and consists of different forms of neuronal units, each sharing basic cerebellar microcircuits. The cerebellum is formed by two lateral hemispheres and vermis or a middle portion . The cerebellum has several functions: coordinate movements specialized volunteers to influence muscle activity and control the balance, muscle tone through connections with the vestibular system, the spinal cord and alpha motor neurons. Within the cerebellar cortex somatotopic organization exists a body part. The cerebellum is a key to information processing and participates in numerous motor and non-motor activities, thanks to the anatomical characteristics of its routes, huge analysis capabilities and high connectivity with other brain areas, can be affected by different factors such as abnormalities in embryonic development, toxic, autoimmune, inflammatory, vascular and metabolic, infections, primary and secondary tumors, trauma, iatrogenic, genetic diseases, sporadic, giving rise to signs and symptoms that cause cerebellar syndrome according to compromised anatomical area. In the scientific literature no reported cases of cerebellar syndrome mesalamina (mesalazina), we report the first case.

Efeitos de ensino envolvendo equivalência entre palavra ditada, palavra escrita e objeto sobre a inteligibilidade da fala em adolescente com hipoplasia cerebelar / Effects of teaching equivalent relations between dictated words, written words, and objects on speech intelligibility in adolescents with cerebellar hypoplasia

Dentre as muitas estruturas cerebrais envolvidas na linguagem, o ceberelo cumpre um papel importante na coordenação dos movimentos responsáveis pela fala, de modo que qualquer alteração nesta estrutura pode comprometer o desenvolvimento da linguagem oral. Considerando o planejamento do ensino e as intervenções enquanto um fator que pode alterar as expressões fenotípicas impostas pela hipoplasia cerebelar, este estudo de caso teve como objetivo verificar os efeitos de um programa de ensino (envolvendo equivalência entre palavra ditada, palavra escrita e objeto) sobre a inteligibilidade da fala de um adolescente com doze anos, gênero masculino, com hipoplasia cerebelar. As sessões foram conduzidas em contexto clínico e com uso de brinquedos de preferência do participante. O programa consistiu em etapas de avaliação, ensino, pós-testes e retenção, no qual eram apresentadas tarefas de seleção, vocalização, escrita e composição de palavras. Durante a avaliação, observou-se um baixo desempenho em todas as tarefas, especialmente na nomeação de objetos; no decorrer do ensino, as vocalizações foram monitoradas, constatando-se uma gradativa melhora na inteligibilidade da fala quando o participante nomeava objetos, chegando à precisão no pós-testes e retenção. Pode-se concluir que, para o caso apresentado, o fortalecimento da rede de relações entre estímulos e estímulos-ações verbais promovido pelo programa de ensino, favoreceu melhorias na inteligibilidade da fala.

Within these many brain structures involved in language, the cerebellum fulfill an important role in coordinating the movements responsible for speech, so that any alteration in this structure may compromise the development of oral language. Considering the planning of teaching and intervention while a factor that can alter the phenotypic expression imposed by cerebellar hypoplasia, this case study aimed to verify the effects of an teaching program (involving equivalence between dictated word, written word and object) on the intelligibility of speech in a teenager twelve year old, male gender, with cerebellar hypoplasia. The sessions were conducted in the clinical setting and with use of preference toys participant’s. The program consisted of phases of assessment, teaching, post-test and retention, on which were presented selection tasks, vocalization, writing and composition of words. During the assessment, observed a low performance in all tasks, especially in objects naming; in the course of teaching, the vocalizations were monitored, indicating a gradual improvement in speech intelligibility when the participant named objects, reaching accuracy in post-test and retention. This suggests that, for the case presented, strengthening the network of relationships between stimulus and stimuli-verbal actions promoted by teaching program, favored improvements in speech intelligibility.

Neurotoxicidad secundaria a metronidazol: un efecto adverso reversible. Caso clínico / Reversible neurotoxicity secondary to metronidazole report of one case

Metronidazole can cause adverse effects both in the central and peripheral nervous system. We report a 34-year-old female who presented a reversible cerebellar syndrome and peripheral neuropathy as an adverse effect associated with the use of metronidazole. Brain magnetic resonance imaging (MRI) showed hyperintense T2 and FLAIR bilateral symmetrical cerebellar lesions, without contrast enhancement or mass effect, isointense in diffusion-weighted imaging and hypointense in apparent diffusion coefficient sequences. Also, electrophysiological evaluation was consistent with axonal polyneuropathy. She had received metronidazole for a liver abscess during 49 days. After discontinuation of metronidazole, she had rapid regression of cerebellar symptoms and normalization of MRI, with subsequent disappearance of peripheral symptoms. The brain MRI, electromyography and nerve conduction studies performed at 35 months later showed complete resolution of the lesions. Although metronidazole neurotoxicity is a rare event, it must be borne in mind because the prognosis is usually favorable after stopping the drug.

Cerebelite aguda por Cryptococcus em paciente imunocompetente. Relato de caso / Acute cerebellitis caused by Cryptococcus in an immunocompetent patient. Case report

A cerebelite aguda é uma condição neurológica que pode ocorrer principalmente em associação à infecção viral, bem como a outros agentes infecciosos. A criptococose cerebral é a infecção que ocorre mais comumente em pacientes imunossuprimidos, principalmente na forma de meningoencefalite. O objetivo deste estudo foi relatar um caso de cerebelite fúngica em paciente imunocompetente, condição não relatada na literatura até omomento. Paciente do gênero masculino, 30 anos, foi encaminhado para investigação de quadro agudo de náuseas, vômitos, cefaleia intensa, vertigem e ataxia da marcha. A ressonância nuclear magnética de encéfalo demonstrou imagem hipodensaisolada em cerebelo. A análise liquórica evidenciou Criptococcus em fase de gemulação. Houve melhora completa do quadro após tratamento com anfotericina B e fluconazol. A infecção fúngica por Criptococcus é condição incomum em pacientes imunocompetentes. Casos previamente relatados de criptococose não seapresentaram de forma isolada em cerebelo. De acordo com o presente estudo, quando o quadro clínico do paciente for compatível com cerebelite, é importante atentar para outras possibilidades etiológicas, que não apenas vírus ou bactérias...

Acute cerebellitis is a neurological condition that can occur especially in association with viral infection, as well as other infectious agents. Cerebral criptococcose infection most commonly occurs in immunosuppressed patients, mainly in the form of meningoencephalitis. The objective of this study was to report a case of fungal cerebellitis in an immunocompetentpatient, a condition not reported in the literature. Male patient, 30 years old, was referred for investigation of acutenausea, vomiting, severe headache, vertigo and gait ataxia. The magnetic resonance of the brain showed an isolated hypodense image in cerebellum. The analysis of the cerebral spinal fluidrevealed cryptococcus in the process of budding. There was complete improvement after treatment with anphotericin B and fluconazole. The fungal infection cryptococcus is an uncommon condition in immunocompetent patients. Previously reported cases of criptococcose were not presented in isolation in thecerebellum. According to this study, when the patient’s condition is compatible with cerebellitis, it is important to pay attention to other etiological possibilities, not just viruses or bacteria...

Hyperventilation-induced nystagmus in a large series of vestibular patients.

The Hyperventilation Test is widely used in the "bed-side examination" of vestibular patients. It can either activate a latent nystagmus in central or peripheral vestibular diseases or it can interact with a spontaneous nystagmus, by reducing it or increasing it. Aims of this study were to determine the incidence, patterns and temporal characteristics of Hyperventilation-induced nystagmus in patients suffering from vestibular diseases, as well as its contribution to the differential diagnosis between vestibular neuritis and neuroma of the 8(th) cranial nerve, and its behaviour in some central vestibular diseases. The present study includes 1202 patients featuring, at vestibular examination, at least one sign of vestibular system disorders or patients diagnosed with a "Migraine-related vertigo" or "Chronic subjective dizziness". The overall incidence of Hyperventilation-induced nystagmus was 21.9%. It was detected more frequently in retrocochlear vestibular diseases rather than in end-organ vestibular diseases: 5.3% in Paroxysmal Positional Vertigo, 37.1% in Menière's disease, 37.6% in compensated vestibular neuritis, 77.2% in acute vestibular neuritis and 91.7% in neuroma of the 8(th) cranial nerve. In acute vestibular neuritis, three HVIN patterns were observed: Paretic pattern: temporary enhancement of the spontaneous nystagmus; Excitatory pattern: temporary inhibition of the spontaneous nystagmus; Strong excitatory pattern: temporary inversion of the spontaneous nystagmus. Excitatory patterns proved to be time-dependent in that they disappeared and were replaced by the paretic pattern over a period of maximum 18 days since the beginning of the disorder. In acoustic neuroma, Hyperventilation-induced nystagmus was frequently observed (91.7%), either in the form of an excitatory pattern (fast phases towards the affected site) or in the form of a paretic pattern (fast phases towards the healthy side). The direction of the nystagmus is only partially related to tumour size, whereas other mechanisms, such as demyelination or a break in nerve fibres, might have an important role in triggering the situation. Hyperventilation-induced nystagmus has frequently been detected in cases of demyelinating diseases and in cerebellar diseases: in multiple sclerosis, hyperventilation inhibits a central type of spontaneous nystagmus or evokes nystagmus in 75% of patients; in cerebellar diseases, hyperventilation evokes or enhances a central spontaneous nystagmus in 72.7% of patients. In conclusion the Hyperventilation Test can provide patterns of oculomotor responses that indicate a diagnostic investigation through cerebral magnetic resonance imaging enhanced by gadolinium, upon suspicion of neuroma of the 8(th) cranial nerve or of a central disease. In our opinion, however, Hyperventilation-induced nystagmus always needs to be viewed within the more general context of a complete examination of the vestibular and acoustic system.

Síndrome de Joubert: reporte de caso / Joubert syndrome: case report

En este artículo se reporta un caso de síndrome de Joubert, patología rara, de la que hay descritos tan sólo un poco más de 100 casos en la literatura mundial. Este síndrome es una rara malformación de la fosa posterior, clínicamente heterogénea, caracterizada por taquipnea neonatal, anormalidades oculomotoras, hipotonía, ataxia, retardo en la maduración, deficiencia mental y algunos rasgos faciales distintivos. Está incluido actualmente en el espectro malformativo de síndromes cerebelo-óculo-renales. Las imágenes de resonancia magnética revelan hipoplasia o aplasia del vermis, prominencia y elongación de los pedúnculos cerebelosos superiores y fosa interpeduncular ensanchada, que simulan la silueta de una muela o “signo del molar”. También se evidencian alteraciones morfológicas del cuarto ventrículo, que adquiere forma de “alas de murciélago”.

A case of Joubert syndrome (JS) is described, it is a rare syndrome of which only a little over 100 cases have been reported in the literature. The JS is a rare posterior fossa malformation, clinically heterogeneous, characterized by neonatal tachypnea, oculomotorabnormalities, hypotonia, ataxia, delayed maturation, mental retardation and certain facial features. It is currently included on the spectrum of cerebellar-oculo-renal malformationsyndromes (CORS). Magnetic Resonance Imaging (MRI) shows hypoplasia or aplasia of the vermis, prominence and elongation of the superior cerebellar peduncles and widened interpeduncular fossa, simulating the shape of a molar tooth. Also shown are morphological alterations of the fourth ventricle, which resemble “bat wings”.

Influência do Wii Fit no equilíbrio de paciente com disfunção cerebelar: estudo de caso / Influence of the Wii Fit on the balance of cerebellar dysfunction patient: case study

Objetivo - O cerebelo possui inúmeras funções, tendo como principal a avaliação e correção dos movimentos iniciados pelas áreas motoras. Este processo é fundamental para a manutenção do equilíbrio. Fugindo da tradicionalidade, a realidade virtual é um recurso que vem se destacando em reabilitações neurológicas, pois com sua interação gráfica pode trazer inúmeros benefícios. O objetivo deste estudo foi verificar a influência da realidade virtual no equilíbrio de paciente com disfunção cerebelar. Métodos - Foi utilizado o vídeo game da marca Nintendo®, denominado Wii, utilizando o jogo Wii Fit, onde os jogos escolhidos estimularam o equilíbrio látero-lateral e ântero-posterior, aplicado em uma paciente com diagnóstico médico de Ataxia Cerebelar Precoce. Para a mensuração foram utilizadas a escala de equilíbrio de Berg, o Índice de Barthel, o qual avalia as atividades da vida diária e a escala de Lawton, a qual avalia as atividades da vida prática, com duração de 9 terapias, 30 minutos cada, realizadas duas vezes por semana. Resultados - Com uma análise comparativa da avaliação pré-protocolo e da avaliação pós-protocolo, foi sugerido que a paciente teve um aumento de 23,21% na escala de equilíbrio de Berg. Em relação ao Índice de Barthel e a escala de Lawton, houve uma melhora na pontuação de 10% e de 25% respectivamente, sugerindo então uma melhora na funcionalidade nas tarefas diárias. Conclusão - Os resultados obtidos neste estudo sugerem que a realidade virtual oferece melhora do equilíbrio de pacientes com disfunções cerebelares, assim como maior independência para realização das tarefas diárias.

Objective - The cerebellum own many functions, having as principal the evaluate of movements initiated by the motor areas. This process is fundamental for the balance maintenance. The virtual reality is a recourse that is standing out in neurological rehabilitation, because with the graphic interaction could bring many improvements. The objective of this study was to verify the influence of virtual reality in the balance of patient with cerebellar disfunction. Methods - It was used a Nintendo's® video game, named Wii, using the game Wii Fit, which the choosen game stimulate the latero-lateral and anterior-posterior balance, applied in a patient with the medical diagnosis of Cerebellar Ataxia Precocious. To measure, it was used the Berg balance scale, the Barthel Index, that evaluates the activies of the daily life and the Lawton scale, that evaluates the activities of practical life, with a duration of 9 treatments, lasting 30 minutes each, 2 times per week. Results - In a comparable analysis of the pre protocol estimate and post protocol estimate, it was suggested that the patient had a increased of 23,21% in the Berg balance scale. In relation of Barthel Index and Lawton scale, there was an improvement of 10% and 25% on the punctuation, respectively, suggering a gain in the daily tasks functionality. Conclusion - The results obtained in this study suggest that the virtual reality offers improvement in the balance of patient with cerebellar disfunction and also more independency to do daily tasks.