Síndrome retroviral agudo manifestado como encefalitis y ataxia cerebelosa: reporte de caso y revisión de la literatura / Acute retroviral syndrome presenting as encephalitis and cerebellar ataxia: case report and literature review

RESUMEN El síndrome retroviral agudo (SRA) es uno de los escenarios clínicos posibles en los estadios tempranos de la infección por VIH, con presentaciones variables caracterizadas por alta carga viral y manifestaciones sintomáticas inespecíficas. Se describe el caso de un paciente varón de 21 años que presentó encefalitis aguda y ataxia cerebelosa, en cuyo estudio se diagnosticó infección por VIH y se identificó el cuadro de SRA.

ABSTRACT Acute retroviral syndrome (ARS) is one of the possible clinical configurations in the early stages of HIV infection, with varying presentations, characterized by high viral copies and nonspecific symptoms. We describe the case of a 21-year-old man who presented an acute onset encephalitis and cerebellar ataxia which led to the diagnosis of HIV infection and the identification of ARS.

A case of autosomal recessive spinocerebellar ataxia type 16 caused by STUB1 gene variant and literature review / 中华神经科杂志

Objective:To discuss the clinical characteristics of autosomal recessive spinocerebellar ataxia type 16 patients caused by STUB1 gene mutation, in order to improve the clinical doctors′ understanding of the disease. Methods:The clinical manifestations, auxiliary examinations and genetic testing of 1 autosomal recessive spinocerebellar ataxia type 16 patient caused by STUB1 gene variants diagnosed in Qilu Hospital of Shandong University in May 2022 were collected, and the relevant literature was reviewed to summarize the clinical and genetic characteristics of this type of disease. Results:The proband was a 35-year-old male presenting with unsteady walk and dysarthria. Magnetic resonance imaging showed cerebellar atrophy. Next generation sequencing revealed compound heterozygous c.322dupG (p.Glu108Glyfs *4) and c.433A>C (p.Lys145Gln) variants in the STUB1 gene (according to the transcript NM_005861.4), and the c.322dupG (p.Glu108Glyfs *4) variant was a novel variant. Pedigree verification revealed the 2 variants were respectively inherited from the proband′s healthy parents. A total of 12 foreign literatures reported 32 autosomal recessive spinocerebellar ataxia type 16 patients. The main clinical manifestations were ataxia, dysarthria and tendon hyperreflexia. Besides, nystagmus, spasticity, action tremors, and myoclonus can be present. Magnetic resonance imaging predominantly showed cerebellar atrophy. Conclusions:The patient with autosomal recessive spinocerebellar ataxia type 16 caused by STUB1 gene variant is rare in China. The main clinical manifestation is cerebellar ataxia, and brain imaging reveals remarkable cerebellar atrophy. Genetic testing is helpful for definite diagnosis.

Meta-analysis of the correlation between ocular and neurological manifestations in 43 Chinese children with sialidosis type I / 中华眼底病杂志

Objective:To investigate the correlation between macular cherry red spot (CS) and severity of neurological manifestations in Chinese children with sialidosis (SD) type I.Methods:A evidence-based medical study. "China", "Sialidosis" and "Sialidoses" were used as Chinese and English search terms. The literature was searched in CNKI, Wanfang and PubMed. The cases were all from China and matched the diagnostic criteria. According to the presence or absence of CS in the fundus, the SD children were divided into a group with CS (+) and a group without CS (-), and the correlation between the occurrence of ocular CS and neurological manifestations was compared with meta-analysis by RevMan 5.3 software.Results:Sixty-eight studies were initially retrieved according to the search strategy, and 17 studies were finally included, and 5 studies with CS+ and CS- were meta-analyzed. Among the 43 patients, 28 were male and 15 were female, with a median age of 12 years. Visual impairment was observed in 37 cases (90.2%, 37/41, 2 cases not recorded), and CS was present in 24 cases (55.8%, 24/43). The most common neurological manifestation was myoclonus (97.7%, 42/43), followed by cerebellar ataxia (95.1%, 39/41, 2 cases not recorded) and seizures (91.4%, 32/35, 8 cases not recorded). Pathogenic NEU1 gene mutations were detected in 42 cases and one case was undocumented. The incidence of seizure in group CS+ (100%, 20/20) was higher than that in group CS- (80%, 12/15). Meta-analysis showed that there was no statistically significant difference between the incidence of myoclonus or ataxia [relative risk ( RR)=1.13, 95% confidence interval ( CI) 0.79-1.63, P=0.49] and seizure ( RR=1.13, 95% CI 0.84-2.06, P=0.24) among the children in the CS+ and CS- groups. Conclusions:The incidence of ocular CS in Chinese children with type I SD was 55.8%. There was no correlation with neurological manifestations, however the incidence of seizure was significantly higher in patients with CS than in others without CS.

Clinical features of CAPOS syndrome caused by maternal ATP1A3 gene variation: a case report / 临床耳鼻咽喉头颈外科杂志

CAPOS syndrome is an autosomal dominant neurological disorder caused by mutations in the ATP1A3 gene. Initial symptoms, often fever-induced, include recurrent acute ataxic encephalopathy in childhood, featuring cerebellar ataxia, optic atrophy, areflflexia, sensorineural hearing loss, and in some cases, pes cavus. This report details a case of CAPOS syndrome resulting from a maternal ATP1A3 gene mutation. Both the child and her mother exhibited symptoms post-febrile induction,including severe sensorineural hearing loss in both ears, ataxia, areflexia, and decreased vision. Additionally, the patient's mother presented with pes cavus. Genetic testing revealed a c. 2452G>A（Glu818Lys） heterozygous mutation in theATP1A3 gene in the patient . This article aims to enhance clinicians' understanding of CAPOS syndrome, emphasizing the case's clinical characteristics, diagnostic process, treatment, and its correlation with genotypeic findings.

Investigación científica en el campo de las ataxias espinocerebelosas: una mirada bibliométrica / Scientific Research in The Field of Spinocerebellar Ataxias: A Bibliometric View

El objetivo del presente estudio consistió en caracterizar la producción científica relacionada con el campo de las ataxias espinocerebelosas, las cuales constituyen enfermedades neurodegenerativas, manifestadas por cuadros clínicos progresivos e invalidantes. La investigación es de tipo censal-documental y recupera metadatos de Scopus, correspondientes a 5654 investigaciones relacionadas con este problema de salud, durante el período 1961-2020. El procesamiento explora las principales características bibliométricas de los documentos publicados, el ritmo de crecimiento, la paternidad de las obras, el impacto por índice de citas, así como las redes de colaboración y la estructura que sigue el flujo del conocimiento. Se observa un despegue notable de la producción científica desde inicios de los años 90 del siglo pasado, coincidiendo con el desarrollo de investigaciones afines en el campo de la genética. También se constata un predominio en el estudio de los tipos SCA1, SCA2, SCA3, SCA6, y SCA17, donde los cuatro primeros corresponden a las ataxias de mayor prevalencia a escala mundial. El corpus documental refleja la consolidación de grupos de investigación relativamente estables, encabezados por líderes científicos y caracterizados por la ampliación sostenida de la colaboración internacional y por el trabajo colectivo e interdisciplinario. También se aprecia la tendencia hacia el aumento del número de referencias dentro de cada documento. Los mayores volúmenes productivos se concentran en países desarrollados, junto a países en vías de desarrollo donde existen elevados niveles de prevalencia en esta enfermedad(AU)

The objective of the present study was to characterize the scientific production related to the field of spinocerebellar ataxias, which constitute neurodegenerative diseases, manifested by progressive and disabling clinical conditions. The research is census-documentary type and recovers metadata from Scopus, corresponding to 5,654 investigations related to this health problem, during the period 1961-2020. The processing explores the main bibliometric characteristics of the published documents, the pace of growth, the authorship of the works, the impact by citation index, as well as the collaboration networks and the structure that follows the flow of knowledge. A notable takeoff in scientific production has been observed since the beginning of the 90s of the last century, coinciding with the development of related research in the field of genetics. There is also a predominance in the study of the types SCA1, SCA2, SCA3, SCA6, and SCA17, where the first four correspond to the most prevalent ataxias worldwide. The documentary corpus reflects the consolidation of relatively stable research groups, headed by scientific leaders and characterized by the sustained expansion of international collaboration and collective and interdisciplinary work. There is also a trend towards increasing the number of references within each document. The largest productive volumes are concentrated in developed countries, along with developing countries where there are high levels of prevalence of this disease(AU)

Ataxias in Brazil: 17 years of experience in an ataxia center / Ataxias no Brasil: 17 anos de experiência em um centro de ataxias

Abstract Background Cerebellar ataxias comprise sporadic and genetic etiologies. Ataxia may also be a presenting feature in hereditary spastic paraplegias (HSPs). Objective To report a descriptive analysis of the frequency of different forms of cerebellar ataxia evaluated over 17 years in the Ataxia Unit of Universidade Federal de São Paulo, Brazil. Methods Charts of patients who were being followed from January 2007 to December 2023 were reviewed. We used descriptive statistics to present our results as frequencies and percentages of the overall analysis. Diagnosed patients were classified according to the following 9 groups: sporadic ataxia, spinocerebellar ataxias (SCAs), other autosomal dominant cerebellar ataxias, autosomal recessive cerebellar ataxias (ARCAs), mitochondrial ataxias, congenital ataxias, X-linked ataxias, HSPs, and others. Results There were 1,332 patients with ataxias or spastic paraplegias. Overall, 744 (55.85%) of all cases were successfully diagnosed: 101 sporadic ataxia, 326 SCAs, 20 of other autosomal dominant cerebellar ataxias, 186 ARCAs, 6 X-linked ataxias, 2 mitochondrial ataxias, 4 congenital ataxias, and 51 HSPs. Conclusion This study describes the frequency of cerebellar ataxias in a large group of patients followed for the past 17 years, of whom 55% obtained a definitive clinical or molecular diagnosis. Future demographic surveys in Brazil or Latin American remain necessary.

Resumo Antecedentes Ataxias cerebelares compreendem as etiologias esporádicas e genéticas. Ataxia também pode ser uma característica das paraplegias espásticas hereditárias (HSPs). Objetivo Relatar uma análise descritiva da frequência das diferentes formas de ataxias cerebelares avaliadas ao longo de 17 anos no Setor da Ataxias da Universidade Federal de São Paulo, Brasil. Métodos Prontuários de pacientes acompanhados de janeiro de 2007 a dezembro de 2023 foram revisados. Usamos análise descritiva para apresentar nossos resultados como frequências e percentuais. Os pacientes foram classificados de acordo com os 9 grupos seguintes: ataxias esporádicas, ataxias espinocerebelares (SCA), outras ataxias cerebelares autossômicas dominantes, ataxias cerebelares autossômicas recessivas (ARCA), ataxias mitocondriais, ataxias congênitas, ataxias ligadas ao X, PEH e outros. Resultados Foram avaliados 1.332 pacientes. Desse total, 744 tiveram um diagnóstico definitivo: 101 ataxias esporádicas, 326 SCA, 20 outras ataxias cerebelares autossômicas dominantes, 186 (ARCA), 6 ataxias ligadas ao X, 2 ataxias mitocondriais, 4 ataxias congênitas e 51 HSP. Conclusão Esse estudo descreve a frequência e a etiologia das ataxias em um grande grupo de pacientes acompanhados nos últimos 17 anos, dos quais 55% obtiveram diagnóstico clínico ou molecular definitivos. Estudos demográficos futuros do Brasil ou da América Latina continuam sendo necessários.

Ataxia cerebelosa aguda y COVID-19: presentación de un caso clínico / Ataxia cerebelosa aguda y COVID-19: presentación de un caso clínico

COVID-19 es una enfermedad viral principalmente respiratoria y/o gastrointestinal. Las manifestaciones neurológicas tienen una frecuencia variable en pediatría. Presentamos un varón de 10 años de edad, previamente sano, que presentó una ataxia cerebelosa durante un cuadro agudo de COVID-19. El SARS-CoV-2 fue detectado por hisopado nasofaríngeo por antígeno y RPC. El LCR fue normal y el cultivo bacteriológico y estudio viral fueron negativos. La TC y RM encefálica fueron normales. No requirió tratamiento específico y tuvo una evolución favorable, con resolución completa de los síntomas neurológicos al mes. Debe considerarse la infección por SARS-CoV-2 como un diagnóstico diferencial entre las causas de ataxia cerebelosa aguda, según la situación epidemiológica.

COVID-19 is a disease that mainly produces respiratory and/or gastrointestinal symptoms. Neurological manifestations occur with a variable frequency in children. We present a previously healthy 10-year-old boy who presented acute cerebellar ataxia during an acute COVID-19. SARS-CoV-2 was detected in a nasopharyngeal sample by antigen and PCR. The CSF was normal, the bacteriological culture and the viral PCR were negative. CT of the brain and gadolinium MRI of the brain were normal. He did not require specific treatment and had a favorable evolution, with complete resolution of neurological symptoms at one month. SARS-CoV-2 infection should be considered as a differential diagnosis between the causes of acute cerebellar ataxia, according to the epidemiological situation.

Cerebellar ataxia after a single day of metronidazole use: Case report

Cerebellar ataxic syndromes, although uncommon, have been reported previously in patients taking metronidazole. However, almost all cases describe instances where patients were taking prolonged or high doses of the drug. We report a 65-year-old man who consumed 400 mg of metronidazole 3 times over 1 day and presented with slurring of speech, imbalance while walking and diplopia. The symptoms developed the day after consumption of metronidazole. Examination showed slurring of speech, gaze-evoked nystagmus, and dysmetria in all limbs. MRI brain revealed symmetric hyperintense lesions in the dentate nucleus and pons on T2-weighted imaging and FLAIR, which have a well-established association with metronidazole-induced central nervous system (CNS) toxicity. On discontinuation of the drug, symptoms improved, and complete recovery was noted at follow-up 2 weeks later. This case indicates that CNS side effects of metronidazole may not necessarily occur only at high doses or after prolonged courses of metronidazole, but may occur as an idiosyncratic reaction to the drug. Reasons for variable susceptibility require further investigation.

Signo de la cruz en una paciente peruana con ataxia espinocerebelosa tipo 2: reporte de un caso / Hot cross bun sign in a Peruvian patient with spinocerebellar ataxia type 2: A case report

RESUMEN La ataxia espinocerebelosa tipo 2 (SCA2) es una enfermedad neurodegenerativa hereditaria autosómica dominante, causada por una expansión anormal del trinucleótido CAG en el gen ATXN2. La SCA2 se presenta habitualmente en la edad adulta, con ataxia progresiva asociada a neuropatía periférica, alteración de movimientos oculares, parkinsonismo, entre otros síntomas. Exámenes auxiliares aplicables incluyen pruebas bioquímicas, neuroimágenes, como resonancia magnética cerebral, y estudio genético molecular. Describimos, por primera vez en la población peruana, el caso de una mujer de mediana edad con diagnóstico confirmado de SCA2, cuya resonancia magnética cerebral muestra el signo de la cruz (o hot cross bun sign).

ABSTRACT Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant inherited neurodegenerative disease, caused by an abnormal CAG trinucleotide expansion in the ATXN2 gene. SCA2 usually occurs in adulthood, with progressive ataxia associated with peripheral neuropathy, impaired eye movements, parkinsonism, and other symptoms. Auxiliary exams include biochemical tests, neuroimaging such as brain MRI, and a molecular genetic study. We describe, for the first time in the Peruvian population, the case of a middle-aged woman with a confirmed diagnosis of SCA2, whose brain MRI shows the "Hot Cross Bun Sign".

CANVAS: una nueva etiología de la ataxia del adulto. La asociación con tos orienta al diagnóstico. Comunicación de 2 pacientes / Late-Onset Cerebellar Ataxia with Neuropathy: Uncovering the Role of RFC1 Gene Mutations

Presentamos dos pacientes no relacionados con ataxia cerebelosa de inicio tardío asociada con neuropatía y tos seca de larga data. Un paciente tenía dos hermanos afectados con neuropatía sensorial y tos. Ambos probandos tuvieron investigaciones extensas que incluyó pruebas genéticas negativas para las ataxias más comunes, así como pruebas paraneoplásicas y otras causas inmunológicas. Ambos pacientes mostraron una expansión intrónica anormal en el pentanucleótido AAGGG del gen RFC1. Esta etiología se informa como causa frecuente de ataxia de inicio en adultos; la presencia de tos puede conducir al diagnóstico correcto.

We report two unrelated patients with late-onset cerebellar ataxia associated with neuropathy and a long-standing dry cough. One patient had two siblings affected with sensory neuropathy and cough. Both probands had extensive investigations including genetics testing negative for most common ataxias as well as testing for paraneoplasic and other immunologic causes. Both patients showed an abnormal intronic expansion in the pentanucleotide AAGGG of the gene RFC1. This etiology is being reported as frequent cause of adult-onset ataxia; the presence of cough may lead to the correct diagnosis.

Cáncer de mama y mutación del gen ataxia telangiectasia: reporte de caso

Entre las mujeres, el cáncer de mama es el más frecuente en el mundo, con el 25,7 %, lo cual hace que sea un tema de interés en salud pública. El cáncer de mama es una enfermedad genética compleja, heterogénea y, en la gran mayoría de los casos, de etiología desconocida. Alrededor del 7 % de los casos de cáncer de mama en la población general presentan alteraciones en un gen de susceptibilidad de herencia mendeliana. La mutación del gen de ataxia telangiectasia (ATM) se encuentra en menos del 1 % de la población general, y los estudios de asociación con controles han demostrado que estos alelos se caracterizan por conferir un riesgo moderado (RR: 2‐4) de padecer cáncer hereditario. Las mutaciones en ATM cosegregan de manera incompleta la enfermedad, y se estima que un 15 % de las portadoras de mutación en este gen desarrollarán el cáncer. La penetrancia incompleta de ATM, y otros genes de riesgo moderado, apoya que estos actúen siguiendo un modelo poligénico de susceptibilidad al cáncer. Se reporta el caso de una mujer de 35 años, con diagnóstico de carcinoma de mama bilateral metacrónico estadio clínico IIIB cT4b N1 M0 mama izquierda y estadio clínico I cT1c N0 mama derecha, con subtipo intrínseco luminal B y sobreexpresión HER2, y con la variante patogénica del gen ATM c.7913 G>A, p. Trp2638*. La paciente fue tratada con quimioterapia neoadyuvante, seguida de mastectomía, ganglio centinela y radioterapia. El objetivo es describir las características clínico‐patológicas y la asociación del cáncer de mama con mutaciones de genes de riesgo moderado.

Among women, breast cancer is the most common cancer in the world, accounting for 25.7 % of all cancers and thus making it a topic of interest in public health. Breast cancer is a complex, heterogeneous genetic disease and, in the vast majority of cases, of unknown etiology. Around 7 % of breast cancer cases in the general population present a susceptibility gene mutation of Mendelian inheritance. The ataxia telangiectasia mutated (ATM) gene mutation is found in less than 1 % of the general population, and association studies conducted with controls have shown that these alleles are characterized by a moderate risk (RR: 2 ‐ 4) for hereditary cancer. Mutations in ATM incompletely cosegregate the disease, with an estimated 15 % of mutation carriers in this gene developing cancer. The incomplete penetrance of ATM, as well as other moderate‐risk genes, supports that they follow a polygenic model of cancer susceptibility. We report the case of a 35‐year‐old woman diagnosed with metachronous bilateral breast carcinoma-T4b N1 M0 stage IIIB left breast and T1c N0 stage I right breast, intrinsic luminal B subtype, HER2 overexpression and pathogenic variant of ATM gene c.7913 G>A, p. Trp2638*-who was treated with neoadjuvant chemotherapy, followed by mastectomy, sentinel node biopsy and radiotherapy. The objective of this case report is to describe the clinicopathological characteristics of breast cancer and its association with moderate‐risk gene mutations.

Ataxia de Friedreich, revisión y actualización de la literatura con búsqueda sistemática de casos en Latinoamérica / Friedreich's ataxia, review and literature update with a systematic search for cases in Latin America

La Ataxia de Friedreich (AF) es una enfermedad neurodegenerativa autosómica recesiva con compromiso multisistémico. En esta revisión, se actualizan aspectos epidemiológicos, fisiopatológicos y clínico-terapéuticos y se conduce una búsqueda sistemática de casos de AF reportados en Latinoamérica. La prevalencia de AF en poblaciones caucásicas es estimada entre 2 y 5 casos por 100 000 habitantes. En Latinoamérica se han publicado 35 estudios que reúnen 1481 casos en 6 países. Causada por la expansión anormal de repeticiones GAA en el gen FXN, la etiopatogenia está asociada a una reducción en los niveles de la proteína frataxina (que altera el metabolismo energético) y el acúmulo de hierro mitocondrial. El fenotipo clásico de AF suele comenzar antes de los 25 años, aunque hay otros de inicio tardío y retención de reflejos. La sintomatología se caracteriza por ataxia progresiva, alteración sensitiva, arreflexia, disartria, y alteraciones oculomotoras, además de compromiso cardiaco, endocrino y musculoesquelético. El diagnóstico requiere evaluación neurológica detallada, estudios neurofisiológicos, neuroimágenes y pruebas bioquímicas pero el enfoque determinante es el estudio genético que demuestre variantes genéticas bialélicas en el gen FXN. El manejo es multidisciplinario, orientado a aminorar los síntomas, prevenir complicaciones y brindar asesoramiento genético apropiado. Recientemente se ha aprobado el primer tratamiento farmacológico para AF con varios más en fases de experimentación.

SUMMARY Friedreich Ataxia (FA) is an autosomal recessive neurodegenerative disease with multisystemic involvement. This update of epidemiological, pathophysiological, and clinico-therapeutic aspects of FA, includes a systematic review of cases in Latin America. The estimated FA prevalence in Caucasian populations is between 2 to 5 cases per 100 000. In Latin America, 1481 cases have been published in 35 articles from six different countries. Caused by an abnormally repeated expansion of GAA trinucleotide inside the FXN gene, FA's etiopathogenesis is associated with reduced levels of the frataxin protein, which disturb the energy metabolism and result in mitochondrial iron accumulation. The classic phenotype usually shows symptoms before the age of 25, although there are others with a later onset. The main symptoms of AF are progressive ataxia, sensory disturbances, areflexia, dysarthria, and oculomotor alterations, in addition to cardiac, endocrine, and musculoskeletal compromise. Diagnostic workup requires a detailed neurological examination, neuroconduction studies, neuroimaging, and biochemical tests. The definitive diagnosis is provided by genetic testing showing biallelic variants within the FXN gene. The management is multidisciplinary, aimed at reducing symptoms, preventing complications, and providing an appropriate genetic counseling. Recently, the first pharmacological treatment for AF has been approved, with several others in clinical assessment trials.

Ataxia-telangiectasia: una revisión desde la etiopatogenia al manejo actual con descripción de casos reportados en Perú / Ataxia telangiectasia: A review from etiopathogenesis to current management with a description of reported cases in Peru

La Ataxia-Telangiectasia (AT) es una rara enfermedad de herencia autosómica recesiva y de afección multisistémica, caracterizada por ataxia progresiva, inmunodeficiencia variable con infecciones recurrentes, riesgo incrementado de neoplasias con o sin telangiectasias óculo-cutáneas. La AT es causada por variantes patogénicas bialélicas en el gen ATM. Su diagnóstico se basa en la sospecha de un cuadro clínico compatible, niveles elevados de alfafetoproteína, atrofia cerebelosa y estudios genéticos. No existe tratamiento curativo de AT y su manejo se basa en medidas de soporte y prevención de complicaciones y asesoramiento genético. En esta revisión, actualizamos la epidemiología, manifestaciones clínicas, diagnóstico y tratamiento de AT incluyendo una búsqueda de casos publicados en el Perú.

Ataxia-Telangiectasia (AT) is a rare autosomal recessive disease with multisystemic involvement, characterized by slowly progressive ataxia, variable immunodeficiency with recurrent infections, increased risk of neoplasms with or without oculocutaneous telangiectasias. AT is caused by biallelic pathogenic variants within the ATM gene. Its diagnosis is based on suspicion of a compatible clinical symptomatology, increased levels of alpha-fetoprotein, cerebellar atrophy, and genetic testing. There is no curative treatment for AT and its management is based on supportive and preventive measures of eventual complications and genetic counseling. This review updates the epidemiology, clinical manifestations, diagnosis, and treatment of AT, including a search for cases published in Peru.

Diagnostic Value of Structural MRI in Spinocerebellar Ataxia Type 3 / 中山大学学报(医学科学版)

ObjectiveTo explore the role of structural MRI in the diagnosis of spinocerebellar ataxia type 3 （SCA3） and further evaluate its correlation with disease severity and disease duration. MethodsWe prospectively enrolled 81 genetically diagnosed SCA3 patients ［59 symptomatic （sym-SCA3） and 22 pre-symptomatic （pre-SCA3）］ and 35 age- and sex-matched healthy controls （HCs）. MRI structural images （3D T1 MPRAGE） and clinical data of all subjects were collected. Three observers with different radiological experience measured the width of the superior， middle and inferior cerebellar peduncle （SCP， MCP and ICP）， the anterior-posterior diameters of the pons and spinal cord at the levels of the foramen magnum and upper edge of the 3rd-5th cervical vertebra. One observer performed the measurements again 2 months later to assess for the intra- and inter-observer reliability， respectively. One-way ANOVA， rank-sum test， ROC curve and Random Forest were used to evaluate the diagnostic value of the above metrics for SCA3， and the correlation between the metrics and clinical variables was analyzed. ResultsNot depending on the radiological experience， the metrics based on morphological MRI showed high intra- and inter-observer reliability， among which bilateral superior and middle cerebellar peduncles performed best. The diameters of bilateral SCP， MCP， ICP， pons and spinal cord （except spinal cord at the level of the upper edge of the 5th cervical vertebra） decreased successively in HCs， pre-SCA3 and sym-SCA3 with a statistical difference （P<0.017）. ROC analysis revealed that the left MCP had the highest diagnostic value for pre-SCA3 （AUC=0.911）， with sensitivity， specificity and a cut-off value of 85.7%， 95.5% and 10.15 mm， respectively. In contrast， the right SCP had the highest diagnostic value for sym-SCA3 （AUC=0.999）， with sensitivity， specificity and a cut-off value of 100%， 98.3% and 2.62 mm， respectively. The Random Forest model based on the above metrics also had high diagnostic efficiency （AUC= 0.970， specificity=93.1%）， and the left MCP contributed the most. Correlation analysis showed that the above metrics had a significantly or moderately negative correlation with the Scale for the Assessment and Rating of Ataxia （SARA） and disease duration （P<0.05）. ConclusionNot depending on radiological experience， measurements of brain structure based on morphological MRI are reliable， which can help diagnose SCA3 and predict disease severity and duration. The left MCP and the right SCP perform best for predicting pre-SCA3 and sym-SCA3， respectively. Therefore， the structural MRI is recommended for assisting the clinical diagnosis of SCA3.

Type Ⅰ sialidosis:four case reports / 中国神经精神疾病杂志

Sialidosis is a rare autosomal recessive disorder which is classified into type Ⅰ and Ⅱ according to the age of onset and severity of the disease.Type I,also known as mucolipidosis,is often manifested as myoclonus,ataxia,general tonic clonic seizure,and bilateral cherry-red spots in eye examination.Four cases of type Ⅰ sialidosis were reported in order to improve the diagnosis and treatment of this disease.Patients were mainly manifested as myoclonus and ataxia.Whole exon gene sequencing of the four patients all showed the mutation c.544A＞G in the NEU1 gene.Meanwhile,the new mutation c.596G＞A carried was found in case 2 and its pathogenicity was also analyzed.Finally,we summarized the clinical characteristics of type Ⅰ patients in China,noting that most patients develop all the core symptoms as the disease progresses.

Clinical analysis of adult oculomoclonus-myoclonus syndrome with vertigo / 中华内科杂志

The clinical manifestation, physical and laboratory examination, electrophysiological, and imaging data of 2 female adult OMS patients with vertigo were analyzed at the Department of Neurology of the First Medical Center of Chinese PLA General Hospital from February 2021 to March 2022. The treatment strategy and clinical outcome were followed up. The two female patients were aged 42 and 66 years. Anti-NMDA receptor antibody and anti-GABAB receptor antibody were detected in serological screening, respectively. The two patients met the diagnostic criteria for OMS, and one was screened for breast tumor. The clinical symptoms of the two patients were relieved after immunomodulation therapy. OMS is a group of rare clinical syndromes; its clinical evaluation process should be standardized and the etiology should be actively searched for.

A family study of Zellweger spectrum disorders due to mutations in the PEX10 gene and literature review / 中华神经科杂志

Objective:To report a family of Zellweger spectrum disorders (ZSD) caused by mutations in the PEX10 gene and to increase the level of awareness of the disease among clinicians. Methods:The clinical and genetic data of a brother-sister co-morbidity family with ZSD due to PEX10 gene mutation admitted to the Department of Neurology, Qilu Hospital of Shandong University in July 2022 were collected and a literature review was performed. Results:The proband was a 24-year-old female who was admitted to the Qilu Hospital of Shandong University due to unstable walking for 8 years and aggravated for 1 year with squatting effort. Cranial magnetic resonance imaging (MRI) showed cerebellar atrophy, electromyography suggested peripheral neuropathy with motor and sensory involvement, and pure tone hearing threshold measurement showed neurogenic deafness. The 15-year-old brother of the proband presented with "unsteadiness in walking and difficulty in squatting for 2 years". His cranial MRI and electromyography were similar to those of the proband, and his laboratory results suggested abnormal liver function. The whole exon sequencing results of the proband suggested a compound heterozygous mutation in the PEX10 gene with c. 992G>A(p. R331Q) and c. 988T>C(p. C330R) mutations and both were likely pathogenic mutations and respectively from her parents. And her brother also carried the above variants. A total of 9 case reports in English literature (1 of which was published by domestic scholars) were retrieved from major domestic and international databases on PEX10 gene mutations causing ZSD, with a total of 15 patients, most of whom had childhood and adolescent onset. The most common initial symptom was slowly progressed ataxia. The majority of patients showed cerebellar atrophy on cranial MRI and peripheral neuropathy was found in the most patients.The 2 patients were suggested to have phytic acid-free food, at the same time, they bagan taking L-arginine and ursodeoxycholic acid. Fortunately,both the ataxia symptom and liver function of them were dramatically alleviated 3 months later. Conclusions:For the patients with unexplained ataxia with polyneuropathy and abnormal liver function,the possibility of ZSD should be considered. Phytic acid-free food, L-arginine and ursodeoxycholic acid supplement may be beneficial for the ZSD patients.

Superficial siderosis of the central nervous system：A literature analysis and case report / 中风与神经疾病杂志

@#Objective To investigate the etiology，clinical manifestations，imaging features，and treatment of superficial siderosis of the central nervous system （SSCNS）. Methods A patient confirmed with SSCNS was reported.Sixty-one patients confirmed with SSCNS were found through a search of China National Knowledge Infrastructure and Wanfang Data and were analyzed in categories for the epidemiology， etiology， clinical manifestations， and laboratory test results. Results Among the 61 patients with SSCNS reported in the literature， ataxia was the most common clinical symptom （49 cases， 80%）， followed by hearing loss （43 cases，70%） and pyramidal signs（30 cases， 49%）.A probable cause was found in 25 （39%） of these cases. Conclusion SSCNS can last for several years or even decades， with hearing loss， ataxia， and pyramidal signs as its main clinical symptoms.Magnetic resonance imaging is the most valuable basis for diagnosis， and susceptibility-weighted imaging is more sensitive in the diagnosis of microhemorrhage.

Behavioral and pathological characterization of YG8R transgenic mouse models of Friedreich ataxia / 中风与神经疾病杂志

@#Objective This study aimed to compare the motor behavior and pathological changes of YG8R transgenic mouse models of Friedreich ataxia (FRDA). Methods The movement behavior changes between YG8R mice and littermate wild-type (WT) mice were evaluated by the accelerated rotarod test,open field test,grip strength test and gait analysis. Real-time fluorescence-based quantitative PCR (qRT-PCR) was used to detect the Frataxin mRNA in the dorsal root ganglia (DRG) and cerebellum. Immunohistochemical staining was used to evaluate neuronal death in the mouse spinal cord tissue. Results Compared with WT mice,the time-to-fall off on an accelerating rotarod,movement distance,and grip strength of YG8R mice were significantly decreased (P<0.05) from 4 to 6 months. Compared to WT mice,YG8R mice had significantly decreased left and right hindlimb step lengths (P<0.05),increased forelimb and hindlimb step widths (P<0.01),decreased right hind limb swing time (P<0.01),and increased the touchdown time of the left and right hind limbs (P<0.05). The number of neurons in the spinal cord of YG8R mice was significantly decreased (P<0.01). The qRT-PCR results showed that frataxin mRNA levels in the spinal cord and DRG of YG8R mice were significantly decreased compared with the WT group (P<0.0001). Conclusion This study further provides detailed motor characteristics and pathological changes of the YG8R transgenic mouse models of FRDA based on GAA repeat expansion,which will be helpful for follow-up studies on the disease mechanism and treatment of FRDA.

Clinical Features and Mutation Analysis of Gordon Holmes Syndrome Associated with RNF216 Gene Mutation and a Literature Review / 罕见病研究

  Objective  To summarize the clinical characteristics and RNF216 gene mutation of a patient with Gordon Holmes syndrome (GHS), and to improve the understanding of the genetic and clinica characteristics of this disease through literature review.  Methods  We collected the clinical data of the patient with GHS, extracted the DNA from 2 mL peripheral venous blood of the patient and his parents for whole exome gene detection, and then we analyzed the clinical and genetic characteristics of all previously reported patients with RNF216 gene mutation.  Results  The young male patient was short in stature at sixyearsold and was diagnosed growth hormone deficiency.He had no secondary sexual characteristics by the age of 15 and was diagnosed hypogonadal hypogonadism.After the age of 22, he gradually developed abnormal gait and had progressive decline in speech, motor, and cognitive functions.Whole exome sequencing revealed a homozygous, nonsense mutation c.1549C>T (p.R517*) in the RNF216 gene.His parents were consanguineous and were heterozygous carriers of the mutations with phenotypic normality.Combined with literature review and this case report results showed that a total of 21 patients of the disease in the world and among them 15 had pathogenic variants of RNF216 gene mutation.7 of the 15 had truncated mutations, 5 had missense mutations, and 1 synonym mutation, 1 splice mutation, and 1 deletion mutation respectively.RNF216 gene mutation can be seen in neurodegenerative diseases with multiple overlapping symptoms of GHS, Huntington-like disease, and 4H syndrome.The main clinical manifestations are hypogonadotropic hypogonadism and early-onset progressive neurological dysfunction in adolescence or early adulthood.The median age of onset of neurological symptoms is 28 years old, featuring cerebellar ataxia, dysarthria, and cognitive impairment, as well as imaging manifestations of extensive white matter lesions and cerebellar atrophy.  Conclusions  The mutation of RNF216 gene can cause GHS.Genetic testing is helpful to the diagnosis and treatment of rare diseases.