Long-Term Follow-Up before and during Riluzole Treatment in Six Patients from Two Families with Spinocerebellar Ataxia Type 7.

BACKGROUND: Currently no curative treatment exists for spinocerebellar ataxias (SCAs). Riluzole repurposing was proposed as a symptomatic treatment in different types of cerebellar ataxia. We report a long-term-follow up under riluzole treatment in SCA type 7. METHODS: Six patients received Riluzole 50 mg twice daily on a compassionate use program for a mean of 4.8 years (range 3.5-9). We measured ataxia onset and progression through the Scale for the Assessment and Rating of Ataxia (SARA), and collected extensive ophthalmological data before and after Riluzole treatment. Electrocardiogram and laboratory profile for drug safety were performed every six months. RESULTS: Riluzole treatment showed no effect on visual function in two patients with an advanced retinal damage. Improvements of visual function occurred in four patients followed by ophthalmologic stability up to 5 years after starting treatment. Two patients had a less steep deterioration of ataxia after treatment compared to pre-treatment, during the first 2,5 years of therapy. One showed soon after therapy an improvement of the SARA score, and then overall stability lasting 3,5 years, followed by ataxia worsening. One visually impaired patient without neurological impairment did not worse until the last visit after 3,5 years of follow-up. The remaining 2 patients showed an improvement of SARA scores soon after therapy, and an overall stability lasting respectively 5 and 3 years. No adverse event was registered during the observation period. DISCUSSION: This study suggests a possible beneficial action of Riluzole in SCA7 and provides a detailed description of the ophthalmologic profile of these patients.

Genetic Epidemiology and Clinical Characteristics of Patients with Spinocerebellar Ataxias in an Unexplored Brazilian State, Using Strategies for Resource-Limited Settings.

Spinocerebellar ataxias (SCAs) have a worldwide average prevalence of 2.7 cases per 100,000 individuals, with significant geographic variability. This study aimed to develop resource-limited strategies to detect and characterize the frequency and genetic-clinical profile of SCAs in an unexplored population from Alagoas State, a low Human Development Index state in northeastern Brazil. Active search strategies were employed to identify individuals with a diagnosis or clinical suspicion of SCAs, and a protocol for clinical and molecular evaluation was applied in collaboration with a reference center in Neurogenetics. A total of 73 individuals with SCAs were identified, with a minimum estimated prevalence of 2.17 cases per 100,000 inhabitants. SCA3 was the most common type (75.3%), followed by SCA7 (15.1%), SCA1 (6.8%), and SCA2 (2.7%). Patients with SCA3 subphenotype 2 were the most predominant. Detailed analysis of patients with SCA3 and SCA7 revealed age at onset and clinical features congruent with other studies, with gait disturbance and reduced visual capacity in SCA7 as the main initial manifestations. The study also identified many asymptomatic individuals at risk of developing SCAs. These findings demonstrate that simple and collaborative strategies can enhance the detection capacity of rare diseases such as SCAs in resource-limited settings and that Alagoas State has a minimum estimated prevalence of SCAs similar to the world average.

Sjögren: unique surname, two men, four syndromes and one disease / Sjögren: sobrenome único, dois homens, quatro síndromes e uma doença

Abstract Henrik and Torsten Sjögren (/'ogrƏn/ or SHOH-grƏn) were two Swedish physicians living in the same period, but completely unrelated, except for their notable contributions to Medicine. The first one described keratoconjunctivitis sicca, afterward called Sjögren's syndrome, and a fishing net aspect retinal pigmentation affecting visual acuity, nowadays known as Sjögren reticular dystrophy. The last one contributed to the understanding of Spielmeyer-Sjögren disease, Marinesco-Sjögren, and Sjögren-Larsson syndromes, all related to genetic disorders and neurological symptoms. In this paper, we aim to describe each disorder, in order to avoid any misunderstanding in diagnosis and for historical record.

Resumo Henrik e Torsten Sjögren (/'ogrƏn/ or SHOH-grƏn) foram dois médicos suecos que viveram na mesma época, mas não tinham nenhuma relação entre si, exceto por suas notáveis contribuições à medicina. O primeiro descreveu a ceratoconjuntivite sicca, posteriormente chamada de síndrome de Sjögren, e uma pigmentação da retina com aspecto de rede de pesca que afeta a acuidade visual, hoje conhecida como distrofia reticular de Sjögren. O último contribuiu para a compreensão da doença de Spielmeyer-Sjögren, das síndromes de Marinesco-Sjögren e Sjögren-Larsson, todas relacionadas a distúrbios genéticos e sintomas neurológicos. Neste artigo, pretendemos descrever cada desordem, a fim de evitar qualquer mal-entendido no diagnóstico e para registro histórico.

Interrater Reliability of the Scale for the Assessment and Rating of Ataxia, Berg Balance Scale, and Functional Independence Measure Motor Domain in Individuals With Hereditary Cerebellar Ataxia.

OBJECTIVE: To determine the interrater reliability of the Scale for the Assessment and Rating of Ataxia (SARA), Berg Balance Scale (BBS), and motor domain of the FIM (m-FIM) administered by physiotherapists in individuals with a hereditary cerebellar ataxia (HCA). DESIGN: Participants were assessed by 1 of 4 physiotherapists. Assessments were video-recorded and the remaining 3 physiotherapists scored the scales for each participant. Raters were blinded to each other's scores. SETTING: Assessments were administered at 3 clinical locations in separate states in Australia. PARTICIPANTS: Twenty-one individuals (mean age=47.63 years; SD=18.42; 13 male and 8 female) living in the community with an HCA were recruited (N=21). MAIN OUTCOME MEASURES: Total and single-item scores of the SARA, BBS, and m-FIM were examined. The m-FIM was conducted by interview. RESULTS: Intraclass coefficients (2,1) for the total scores of the m-FIM (0.92; 95% confidence interval [CI], 0.85-0.96), SARA (0.92; 95% CI, 0.86-0.96), and BBS (0.99; 95% CI, 0.98-0.99) indicated excellent interrater reliability. However, there was inconsistent agreement with the individual items, with SARA item 5 (right side) and item 7 (both sides) demonstrating poor interrater reliability and items 1 and 2 demonstrating excellent reliability. CONCLUSIONS: The m-FIM (by interview), SARA, and BBS have excellent interrater reliability for use when assessing individuals with an HCA. Physiotherapists could be considered for administration of the SARA in clinical trials. However, further work is required to improve the agreement of the single-item scores and to examine the other psychometric properties of these scales.

Gene Suppression Therapies in Hereditary Cerebellar Ataxias: A Systematic Review of Animal Studies.

INTRODUCTION: Hereditary cerebellar ataxias (HCAs) are a heterogenous group of neurodegenerative disorders associated with severe disability. Treatment options are limited and overall restricted to symptomatic approaches, leading to poor prognoses. In recent years, there has been extensive research on gene suppression therapies (GSTs) as a new hope for disease-modifying strategies. In this article, we aim to perform a review of in vivo studies investigating the efficacy and safety profile of GSTs in HCAs. METHODS: A structured PubMed® search on GSTs in HCAs from January 1993 up to October 2020 was performed. Inclusion and exclusion criteria were defined, and the selection process was conducted accordingly. The screening process was independently carried out by two authors and was initially based on title and abstract, followed by full-text reading. The risk-of-bias assessment was performed with SYRCLE's tool. A data extraction sheet was created to collect relevant information from each selected article. RESULTS: The initial search yielded 262 papers, of which 239 were excluded. An additional article was obtained following reference scrutiny, resulting in a total of 24 articles for final analysis. Most studies were not clear on the tools used to assess bias. In SCA1, SCA2, MJD/SCA3 and SCA7, RNA interference (iRNA) and antisense oligonucleotide (ASO) therapies proved to be well tolerated and effective in suppressing mutant proteins, improving neuropathological features and the motor phenotype. In SCA6, the phenotype was improved, but no investigation of adverse effects was performed. In FRDA, only the suppression efficacy of the electroporation of the clustered regularly interspaced short palindromic repeats associated with Cas9 enzyme system (CRISPR-Cas9) system was tested and confirmed. CONCLUSION: The literature reviewed suggests that GSTs are well tolerated and effective in suppressing the targeted proteins, improving neuropathological features and the motor phenotype in vivo. Nonetheless, there is no guarantee that these results are free of bias. Moreover, further investigation is still needed to clarify the GST effect on HCAs such as FRDA, SCA6 and SCA2.

Frontal ataxia: historical aspects and clinical definition / Ataxia frontal: aspectos históricos e definição clínica

Abstract Frontal ataxia, originally described by Bruns, is characterized by the presence of signs of frontal lobe dysfunction, such as perseveration, paratonia, frontal release signs, cognitive changes, and urinary difficulty, associated with imbalance, slow gait, broad-based, the presence of postural instability and falls, retropulsion, and bradykinesia in the lower limbs. The goal of the present study is to recall the historical aspects of this condition, to draw attention to the importance of this clinical finding for the differential diagnosis of ataxias and to review the main semiological differences between primary ataxias (frontal, cerebellar, and sensory ataxia).

Resumo A ataxia frontal, originalmente descrita por Bruns, caracteriza-se pela presença de sinais de disfunção do lobo frontal, como perseveração, paratonia, sinais de liberação frontal, alterações cognitivas e dificuldade urinária, associados a desequilíbrio, marcha lenta, base ampla, presença de instabilidade postural e quedas, retropulsão e bradicinesia em membros inferiores. O objetivo do presente trabalho é recordar os aspectos históricos desta condição, ressaltar a importância deste achado clínico para o diagnóstico diferencial das ataxias e revisar as principais diferenças semiológicas entre as ataxias primárias (ataxia frontal, cerebelar e sensitiva).

Effects of Intensive Exercise on Cognitive Dysfunction in Patients With Pure Cerebellar Degeneration: A Single-Arm Pilot Study.

OBJECTIVE: To clarify the profile of cognitive dysfunction and the effects of intensive exercise in spinocerebellar degeneration (SCD). METHODS: We enrolled 60 healthy controls and 16 patients with purely cerebellar type SCD without gait disturbance or organic changes other than cerebellar changes. To assess cognitive function, we evaluated the participants using the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and Montreal Cognitive Assessment-Japanese (MoCA-J) at admission and after intensive exercise. RESULTS: Compared to the controls, SCD patients showed significant cognitive decline. As a result of intensive exercise, significant improvements in motor and cognitive functions were observed: the MMSE score improved from 27.7±1.9 to 29.0±1.3 points (p<0.001); the FAB score improved from 14.8±2.2 to 15.8±2.0 points (p=0.002); and the MoCA-J score improved from 24.6±2.2 to 26.7±1.9 points (p<0.001). For sub-scores, significant improvements were noted in serial 7, lexical fluency, motor series, and delayed recall. CONCLUSION: Our study indicates that intensive exercise can be effective not only for motor dysfunction but also for cognitive dysfunction (Clinical Trial Registration No. UMIN-CTR: UMIN000040079).

Simple and clear differentiation of spinocerebellar degenerations: Overview of macroscopic and low-power view findings.

Spinocerebellar degenerations (SCDs) are a diverse group of rare and slowly progressive neurological diseases that include spinocerebellar ataxia type 1 (SCA1), SCA2, SCA3, SCA6, SCA7, dentatorubral-pallidoluysian atrophy (DRPLA) and multiple system atrophy (MSA). They are often inherited, and affect the cerebellum and related pathways. The combination of clinical findings and lesion distribution has been the gold-standard for classifying SCDs. This conventional approach has not been very successful in providing a solid framework shared among researchers because their points of views have been quite variable. After identification of genetic abnormalities, classification was overwhelmed by genotyping, replacing the conventional approach far behind. In this review, we describe a stepwise operational approach that we constructed based only on macroscopic findings without microscopy to classify SCDs into three major groups: pure cerebellar type for SCA6 and SCA31; olivopontocerebellar (OPC) type for SCA1, SCA2, SCA7 and MSA; and dentatorubral-pallidoluysian (DRPL) type for SCA1, SCA3, DRPLA and progressive supranuclear palsy (PSP). Spinocerebellar tract involvement distinguishes SCA1 and SCA3 from DRPLA. Degeneration of the internal segment of the pallidum is accentuated in SCA3 and PSP, while degeneration of the external segment is accentuated in SCA1 and DRPLA. These contrasts are helpful in subdividing OPC and DRPL types to predict their genotypes. Lesion distribution represents disease-specific selective vulnerability, which is readily differentiated macroscopically using our stepwise operational approach. Precise prediction of the major genotypes will provide a basis to understand how genetic abnormalities lead to corresponding phenotypes through disease-specific selective vulnerabilities.

Rovatirelin ameliorates motor dysfunction in the cytosine arabinoside-induced rat model of spinocerebellar degeneration via acetylcholine and dopamine neurotransmission.

Thyrotropin-releasing hormone (TRH) and the TRH mimetic taltirelin have been used in Japan for the treatment of spinocerebellar degeneration (SCD), a type of progressive ataxia. A TRH mimetic, rovatirelin, ameliorates ataxia symptoms in the rolling mouse Nagoya, a hereditary SCD model. The aim of this study was to verify the effects of oral administration of rovatirelin on a cytosine arabinoside (Ara-C)-induced ataxia rat model, a sporadic SCD model characterized by gait abnormalities and falls because of cerebellar atrophy and investigate the central nervous system mechanism associated with rovatirelin-mediated amelioration of motor dysfunction in these rats. Rovatirelin at ≥3 mg/kg significantly decreased the fall index, which is a primary endpoint of improved motor function calculated by dividing the number of falls by the locomotor activity, in both male and female rats with Ara-C-induced ataxia. Furthermore, rovatirelin caused a significant increase in locomotor activity in a dose-dependent manner. Taltirelin at ≥30 mg/kg ameliorated motor dysfunction in ataxic rats. Moreover, rovatirelin significantly increased acetylcholine (ACh) levels in the medial prefrontal cortex (mPFC) and dopamine (DA) levels in the nucleus accumbens (NAc) at ≥3 mg/kg and significantly increased DA levels in the dorsal striatum at ≥10 mg/kg in normal rats. In conclusion, oral administration of rovatirelin ameliorates motor dysfunction in rats with Ara-C-induced ataxia, owing to its ACh-increasing effects in the mPFC and DA-increasing effects in the dorsal striatum and NAc. Furthermore, the effects of rovatirelin were more potent than those of taltirelin.

Ataxia telangiectasia: a diagnostic challenge. case report

ABSTRACT Introduction: Ataxia-telangiectasia (AT) is a neurodegenerative syndrome with low incidence and prevalence worldwide, which is caused by a mutation of the ATM gene. It is an autosomal recessive disorder that is associated with defective cell regeneration and DNA repair mechanisms. It is characterized by progressive cerebellar ataxia, abnormal eye movements, oculocutaneous telangiectasias and immunodeficiency. Early diagnosis is critical to initiate a timely interdisciplinary treatment, improve acute symptoms, and control the multiple comorbidities of the disease. The following is the case of a patient who presented with the aforementioned characteristics and had an adequate response to the established medical treatment. Case presentation: A 7-year-old female patient from Bogotá, who presented clinical signs of global neurodevelopmental delay, cerebellar ataxia, frequent respiratory infections and ocular telangiectasias. Symptoms were associated with elevation of alpha fetoprotein and immunodeficiency, which allowed for a diagnosis of AT and the initiation of a timely interdisciplinary treatment. Conclusion: AT is a chromosomal instability syndrome with characteristic signs and symptoms. It is essential to know the etiopathogenesis, clinical manifestations, diagnostic criteria, and therapeutic options, emphasizing that early detection and clinical suspicion could favor the proper management of the comorbidities and improve the progressive course of the disease.

RESUMEN Introducción. La ataxia-telangiectasia (AT) es un síndrome neurodegenerativo con baja incidencia y prevalencia mundial que es causado por una mutación del gen ATM, es de herencia autosómica recesiva y se asocia a mecanismos defectuosos en la regeneración y reparación del ADN. Este síndrome se caracteriza por la presencia de ataxia cerebelosa progresiva, movimientos oculares anormales, telangiectasias oculocutáneas e inmunodeficiencia. El diagnóstico oportuno de la AT es muy importante para poder iniciar un manejo interdisciplinario temprano, mejorar la sintomatología aguda y controlar las múltiples comorbilidades que causa. A continuación se presenta el caso de una paciente con las características clásicas de esta enfermedad y una adecuada respuesta y evolución al manejo médico instaurado. Presentación de caso. Paciente femenina de 7 años de edad, procedente de Bogotá, quien presentó cuadro clínico inicial de retraso global del neurodesarrollo, ataxia cerebelosa, infecciones respiratorias frecuentes y telangiectasias oculares. La sintomatología se asoció a elevación de alfa fetoproteína e inmunodeficiencia, lo que permitió plantear el diagnóstico de AT e iniciar de manera oportuna el manejo interdisciplinario. Conclusión. La AT es un síndrome de inestabilidad cromosómica con signos clínicos y síntomas característicos, por lo que es primordial conocer la etiopatogenia, el cuadro clínico, los criterios diagnósticos y las propuestas terapéuticas, pues la detección y la sospecha clínica temprana pueden favorecer el manejo precoz de las diferentes comorbilidades y mejorar el curso progresivo.

Pure-Tone Hearing Thresholds and Brainstem Auditory Evoked Potentials in Sporadic Ataxia

Abstract Introduction Spinocerebellar ataxia (SCA) is part of a genetic and clinical heteroge- neous group of neurodegenerative diseases characterized by progressive cerebellar ataxia. Objective To describe the results of audiological and electrophysiological hearing evaluations in patients with sporadic ataxia (SA). Methods A retrospective cross-sectional study was carried out with 11 patients submitted to the following procedures: anamnesis, otorhinolaryngological evaluation, tonal and vocal audiometry, acoustic immittance and brainstem auditory evoked potential (BAEP) tests. Results The patients presented with a prevalence of gait imbalance, of dysarthria, and of dysphagia; in the audiometric and BAEPs, four patients presented with alterations; in the acoustic immittance test, five patients presented with alterations, predominantly bilateral. Conclusion The most evident alterations in the audiological evaluation were the prevalence of the descending audiometric configuration between the frequencies of 2 and 4 kHz and the absence of the acoustic reflex between the frequencies of 3 and 4 kHz bilaterally. In the electrophysiological evaluation, the patients presented changes with a prevalence of increased I, III and V wave latencies and the interval in the interpeak I-III, I-V and III-V. In the present study, it was observed that auditory complaints did not have a significant prevalence in this type of ataxia, which does not occur in some types of autosomal recessive and dominant ataxia.

Pure-Tone Hearing Thresholds and Brainstem Auditory Evoked Potentials in Sporadic Ataxia.

Introduction Spinocerebellar ataxia (SCA) is part of a genetic and clinical heterogeneous group of neurodegenerative diseases characterized by progressive cerebellar ataxia. Objective To describe the results of audiological and electrophysiological hearing evaluations in patients with sporadic ataxia (SA). Methods A retrospective cross-sectional study was carried out with 11 patients submitted to the following procedures: anamnesis, otorhinolaryngological evaluation, tonal and vocal audiometry, acoustic immittance and brainstem auditory evoked potential (BAEP) tests. Results The patients presented with a prevalence of gait imbalance, of dysarthria, and of dysphagia; in the audiometric and BAEPs, four patients presented with alterations; in the acoustic immittance test, five patients presented with alterations, predominantly bilateral. Conclusion The most evident alterations in the audiological evaluation were the prevalence of the descending audiometric configuration between the frequencies of 2 and 4 kHz and the absence of the acoustic reflex between the frequencies of 3 and 4 kHz bilaterally. In the electrophysiological evaluation, the patients presented changes with a prevalence of increased I, III and V wave latencies and the interval in the interpeak I-III, I-V and III-V. In the present study, it was observed that auditory complaints did not have a significant prevalence in this type of ataxia, which does not occur in some types of autosomal recessive and dominant ataxia.

The Classification of Autosomal Recessive Cerebellar Ataxias: a Consensus Statement from the Society for Research on the Cerebellum and Ataxias Task Force.

There is currently no accepted classification of autosomal recessive cerebellar ataxias, a group of disorders characterized by important genetic heterogeneity and complex phenotypes. The objective of this task force was to build a consensus on the classification of autosomal recessive ataxias in order to develop a general approach to a patient presenting with ataxia, organize disorders according to clinical presentation, and define this field of research by identifying common pathogenic molecular mechanisms in these disorders. The work of this task force was based on a previously published systematic scoping review of the literature that identified autosomal recessive disorders characterized primarily by cerebellar motor dysfunction and cerebellar degeneration. The task force regrouped 12 international ataxia experts who decided on general orientation and specific issues. We identified 59 disorders that are classified as primary autosomal recessive cerebellar ataxias. For each of these disorders, we present geographical and ethnical specificities along with distinctive clinical and imagery features. These primary recessive ataxias were organized in a clinical and a pathophysiological classification, and we present a general clinical approach to the patient presenting with ataxia. We also identified a list of 48 complex multisystem disorders that are associated with ataxia and should be included in the differential diagnosis of autosomal recessive ataxias. This classification is the result of a consensus among a panel of international experts, and it promotes a unified understanding of autosomal recessive cerebellar disorders for clinicians and researchers.

Hereditary Ataxia with a Novel Mutation in the Senataxin Gene: A Case Report.

Hereditary ataxias (HA) are a group of inherited neurological disorders caused by changes in genes. At least 115 different mutations in the senataxin (SETX) gene causing ataxia have been identified. There are no reports of any SETX gene mutation among the Iranian population. Here we report on two cases with homozygous and heterozygous mutations in which one patient was affected by HA with oculomotor apraxia type 2, and the other was a carrier of the disorder. In 2016, the affected patient was referred to the Biogene Medical and Genetic Laboratory (Tehran, Iran) suffering from imbalance and tremor of both head and body. The coding regions of 18 genes, including the SETX gene, were screened. The target regions were captured using the NimbleGen chip followed by next-generation sequencing (NGS) technology on the Illumina Hiseq2500 platform. NGS, a DNA sequencing technology, has greatly increased the ability to identify new causes of ataxia; a useful tool for the prevention of primary manifestations and treatment of affected patients. In the present study, a novel mutation in the SETX gene has been identified.

Successful treatment of psychosis in dentatorubral-pallidoluysian atrophy with quetiapine: A case report.

INTRODUCTION: Patients with dentatorubral-pallidoluysian atrophy (DRPLA) sometimes elicit psychosis. First-generation antipsychotic drugs have been reported to be effective in treating psychotic symptoms associated with the disease. However, little information is available on the benefits of second-generation antipsychotic drugs (SGAs). CASE: We report on a 47-year-old man with DRPLA whose psychotic symptoms were effectively treated with quetiapine, one of the SGAs. He suffered from delusions, auditory hallucinations, and disorganized speech. Initially, other antipsychotic drugs were tried, but were withdrawn because of adverse effects before switching to quetiapine. CONCLUSION: Our observations add to the notion that some of the SGAs are useful for ameliorating psychosis in DRPLA.

Twenty-five years since the identification of the first SCA gene: history, clinical features and perspectives for SCA1 / Vinte e cinco anos desde a identificação do primeiro gene das SCAs: história, aspectos clínicos e perspectivas para a SCA1

ABSTRACT Spinocerebellar ataxias (SCA) are a clinically and genetically heterogeneous group of monogenic diseases that share ataxia and autosomal dominant inheritance as the core features. An important proportion of SCAs are caused by CAG trinucleotide repeat expansions in the coding region of different genes. In addition to genetic heterogeneity, clinical features transcend motor symptoms, including cognitive, electrophysiological and imaging aspects. Despite all the progress in the past 25 years, the mechanisms that determine how neuronal death is mediated by these unstable expansions are still unclear. The aim of this article is to review, from an historical point of view, the first CAG-related ataxia to be genetically described: SCA 1.

RESUMO As ataxias espinocerebelares (SCA) são um grupo clínico e geneticamente heterogêneo de doenças monogênicas que compartilham ataxia e herança autossômica dominante como características principais. Uma proporção importante de SCAs é causada por expansões de repetição de trinucleotídeos CAG na região de codificação de diferentes genes. Além da heterogeneidade genética, os aspectos clínicos transcendem os sintomas motores, incluindo aspectos cognitivos, eletrofisiológicos e de imagem. Apesar de todo o progresso feito nos últimos 25 anos, os mecanismos que determinam como se dá a morte neuronal mediada por essas expansões instáveis ainda não estão claros. O objetivo deste artigo é revisar, de um ponto de vista histórico, a primeira ataxia geneticamente relacionada com o CAG descrita: SCA 1.

Successful Treatment with Olanzapine of Psychosis in Dentatorubral-pallidoluysian Atrophy: A Case Report.

Patients with dentatorubral-pallidoluysian atrophy occasionally elicit psychosis. So far, one study reported first generation antipsychotics drugs may provide an effective treatment; however, there is no literature on the benefits of second generation antipsychotics. We report on a 44-year-old man with dentatorubral-pallidoluysian atrophy whose psychotic symptoms were effectively treated with olanzapine. Our observation suggests some second generation antipsychotics provide a therapeutic option for ameliorating psychosis in dentatorubral-pallidoluysian atrophy.

The importance of central auditory evaluation in Friedreich's ataxia / A importância da avaliação auditiva central na ataxia de Friedreich

ABSTRACT Objective To assess central auditory function in Friedreich's ataxia. Methods A cross-sectional, retrospective study was carried out. Thirty patients underwent the anamnesis, otorhinolaryngology examination, pure tone audiometry, acoustic immittance measures and brainstem auditory evoked potential (BAEP) assessments. Results The observed alterations were: 43.3% in the pure tone audiometry, bilateral in 36.7%; 56.6% in the BAEP test, bilateral in 50%; and 46.6% in the acoustic immittance test. There was a significant difference (p < 0.05) in the comparison between the tests performed. Conclusion In the audiological screening, there was a prevalence of the descending audiometric configuration at the frequency of 4kHz, and absence of the acoustic reflex at the same frequency. In the BAEP test, there was a prevalence of an increase of the latencies in waves I, III and V, and in the intervals of interpeaks I-III, I-V and III-V. In 13.3% of the patients, wave V was absent, and all waves were absent in 3.3% of patients.

RESUMO Objetivo Avaliar a função auditiva central na ataxia de Friedreich (AFRD). Métodos Foi realizado um estudo retrospectivo de corte transversal. 30 pacientes realizaram anamnese, avaliações otorrinolaringológica, audiológica, imitanciométrica e do potencial evocado auditivo de tronco encefálico (PEATE). Resultados As alterações observadas foram: 43,3% no exame audiométrico sendo 36,7% dos casos, bilateralmente; 56,6% na avaliação do PEATE com 50% dos casos, bilateralmente e 46,6% no exame imitanciométrico. Houve diferença significativa (p < 0,05) na comparação entre os exames realizados. Conclusão No exame audiológico, ocorreu uma preponderância maior da configuração audiométrica descendente a partir da freqüência de 4kHz e ausência do reflexo acústico na mesma frequência. No exame do PEATE, houve prevalência do aumento das latências nas ondas I, III e V, e nos intervalos dos interpicos I-III, I-V e III-V. Em 13,3% dos casos, a onda V estava ausente, e em 3,3% dos casos, todas as ondas estavam ausentes.

Successful Treatment with Olanzapine of Psychosis in Dentatorubral-pallidoluysian Atrophy: A Case Report

Patients with dentatorubral-pallidoluysian atrophy occasionally elicit psychosis. So far, one study reported first generation antipsychotics drugs may provide an effective treatment; however, there is no literature on the benefits of second generation antipsychotics. We report on a 44-year-old man with dentatorubral-pallidoluysian atrophy whose psychotic symptoms were effectively treated with olanzapine. Our observation suggests some second generation antipsychotics provide a therapeutic option for ameliorating psychosis in dentatorubral-pallidoluysian atrophy.

Novel compound heterozygous mutations of ATM in ataxia-telangiectasia: A case report and calculated prevalence in the Republic of Korea

Ataxia-telangiectasia (AT; OMIM 208900) is a rare autosomal recessive inherited progressive neurodegenerative disorder, with onset in early childhood. AT is caused by homozygous or compound heterozygous mutations in ATM (OMIM 607585) on chromosome 11q22. The average prevalence of the disease is estimated at 1 of 100,000 children worldwide. The prevalence of AT in the Republic of Korea is suggested to be extremely low, with only a few cases genetically confirmed thus far. Herein, we report a 5-year-old Korean boy with clinical features such as progressive gait and truncal ataxia, both ankle spasticity, dysarthria, and mild intellectual disability. The patient was identified as a compound heterozygote with two novel genetic variants: a paternally derived c.5288_5289insGA p.(Tyr1763*) nonsense variant and a maternally derived c.8363A>C p.(His2788Pro) missense variant, as revealed by next-generation sequencing and confirmed by Sanger sequencing. Based on claims data from the Health Insurance Review and Assessment Service Republic of Korea, we calculated the prevalence of AT in the Republic of Korea to be about 0.9 per million individuals, which is similar to the worldwide average. Therefore, we suggest that multi-gene panel sequencing including ATM should be considered early diagnosis.