Adriana Moro

Ataxia-telangiectasia — A historical review and a proposal for a new designation: ATM syndrome

The authors review ataxia telangiectasia, emphasizing historical aspects, genetic discoveries, and the clinical presentations of the classical and atypical forms. In fact, ataxia telangiectasia represents a multisystem entity with pleomorphic neurological and systemic manifestations. ATM syndrome is proposed as a more adequate designation for this entity.

Non-motor signs in Parkinson’s disease: a review

During the past decade the view of Parkinsons disease (PD) as a motor disorder has changed significantly and currently it is recognized as a multisystem process with diverse non-motor signs (NMS). In addition to been extremely common, these NMS play a major role in undermining functionality and quality of life. On the other hand, NMS are under recognized by physicians and neglected by patients. Here, we review the most common NMS in PD, including cognitive, psychiatric, sleep, metabolic, and sensory disturbances, discuss the current knowledge from biological, epidemiological, clinical, and prognostic standpoints, highlighting the need for early recognition and management.

Caffeine as symptomatic treatment for Parkinson disease (Café-PD): A randomized trial

Objective: To assess effects of caffeine on Parkinson disease (PD). Methods: In this multicenter parallel-group controlled trial, patients with PD with 1–8 years disease duration, Hoehn & Yahr stages I–III, on stable symptomatic therapy were randomized to caffeine 200 mg BID vs matching placebo capsules for 6–18 months. The primary research question was whether objective motor scores would differ at 6 months (Movement Disorder Society–sponsored Unified Parkinsons Disease Rating Scale [MDS-UPDRS]–III, Class I evidence). Secondary outcomes included safety and tolerability, motor symptoms (MDS-UPDRS-II), motor fluctuations, sleep, nonmotor symptoms (MDS-UPDRS-I), cognition (Montreal Cognitive Assessment), and quality of life. Results: Sixty patients received caffeine and 61 placebo. Caffeine was well-tolerated with similar prevalence of side effects as placebo. There was no improvement in motor parkinsonism (the primary outcome) with caffeine treatment compared to placebo (difference between groups −0.48 [95% confidence interval −3.21 to 2.25] points on MDS-UPDRS-III). Similarly, on secondary outcomes, there was no change in motor signs or motor symptoms (MDS-UPDRS-II) at any time point, and no difference on quality of life. There was a slight improvement in somnolence over the first 6 months, which attenuated over time. There was a slight increase in dyskinesia with caffeine (MDS-UPDRS-4.1+4.2 = 0.25 points higher), and caffeine was associated with worse cognitive testing scores (average Montreal Cognitive Assessment = 0.66 [0.01, 1.32] worse than placebo). Conclusion: Caffeine did not provide clinically important improvement of motor manifestations of PD (Class I evidence). Epidemiologic links between caffeine and lower PD risk do not appear to be explained by symptomatic effects. Clinicaltrials.gov identifier: NCT01738178. Classification of evidence: This study provides Class I evidence that for patients with PD, caffeine does not significantly improve motor manifestations.

Movement disorders in spinocerebellar ataxias in a cohort of Brazilian patients.

Background: Movement disorders (MDs) are well recognized in all subtypes of spinocerebellar ataxias (SCA), but phenomenology and frequency vary widely. Methods: Three hundred seventy-eight patients, from 169 Brazilian families, with SCAs were assessed with neurological examination and molecular genetic testing. Results: Dystonia was the most common movement disorder, found in 5.5% of all patients, particularly in SCA3. We observed Parkinsonian features in 6.6% of SCA3 patients, and myoclonus in two patients of our cohort. Conclusions: Our study demonstrated that MDs are major extracerebellar manifestations of SCA. The observed phenotypes in addition to ataxia may provide significant clues for a particular SCA genotype.

Clinical relevance of "bulging eyes" for the differential diagnosis of spinocerebellar ataxias

OBJECTIVE To investigate the relevance of the clinical finding of bulging eyes (BE) in a large Brazilian cohort of spinocerebellar ataxias (SCA), to assess its importance in clinical differential diagnosis among SCA. METHODS Three hundred sixty-nine patients from 168 Brazilian families with SCA were assessed with neurological examination and molecular genetic testing. BE was characterized by the presence of eyelid retraction. Genetically ascertained SCA3 was detected in 167 patients, SCA10 in 68 patients, SCA2 in 20, SCA1 in 9, SCA7 in 6, and SCA6 in 3 patients. RESULTS BE was detected in 123 patients with SCA (33.3%), namely 109 of the 167 SCA3 patients (65.3%) and in 5 of the others SCA patients (1 SCA10 patient, 2 SCA1 patients and 2 SCA2 patients). CONCLUSION BE was detected in the majority of patients with SCA3 (65.3%) and could be used with a clinical tool for the differential diagnosis of SCA.

Rhombencephalitis caused by Listeria monocytogenes with striking involvement of trigeminal nerve on MR imaging.

The listeria rhombencephalitis is an uncommon and severe infection of the brainstem, usually occurring in healthy adults with a typical biphasic picture. A prodrome of fever, headache, nausea and vomiting followed by abrupt neurological symptoms. A stiff neck is present in half of the cases and positive culture in cerebrospinal fluid (CSF) in about 40% of the cases. Mortality is high and serious sequelae are common. We report a case of a patient with involvement of the brainstem and a favorable outcome.

Spinocerebellar ataxia type 3: subphenotypes in a cohort of Brazilian patients.

UNLABELLED Spinocerebellar ataxia type 3 (SCA3) involves cerebellar, pyramidal, extrapyramidal, motor neuron and oculomotor systems with strong phenotypic heterogeneity, that lead us to classify the disorder into different clinical subtypes according to the predominantly affected motor systems. METHOD The series comprises 167 SCA3 patients belonging to 68 pedigrees, studied from 1989-2013. These patients were categorized into seven different subphenotypes. RESULTS SCA3 cases were clustered according to the predominant clinical features. Three most common forms were subphenotype 2, characterized by ataxia and pyramidal symptom was observed in 67.5%, subphenotype 3 with ataxia and peripheral signs in 13.3%, and subphenotype 6 with pure cerebellar syndrome in 7.2%. CONCLUSION Our study was the first to systematically classify SCA3 into seven subphenotypes. This classification may be particularly useful for determination of a more specific and direct phenotype/genotype correlation in future studies.

SPG4-related hereditary spastic paraplegia: frequency and mutation spectrum in Brazil

To the Editor : Hereditary spastic paraplegia (HSP) is a heterogeneous group of neurodegenerative disorders characterized by progressive lower limb spasticity and weakness. Mutations in SPAST /SPG4 are the major cause of autosomal dominant (AD-HSP) in Europe accounting for 40–50% of all patients (1). However, there are few studies on SPG4-HSP from Latin America (2), which has a distinctive ethnic background (populations from European, African and Native American descent). Therefore, our aim was to investigate the frequency and mutation spectrum of SPG4-HSP in a cohort of 55 Brazilian patients with AD-HSP from 34 unrelated families. Patients were recruited from three centers in the south and southeast of Brazil: Universidade Estadual de Campinas (23 families), Universidade Federal do Paraná (7) and Universidade Federal do Rio Grande do Sul (4). This study was approved by our institution Ethics Committee and written informed consent was obtained from all participants. Genomic DNA was used in polymerase chain reactions with primers designed to cover the 17 exons of SPAST /SPG4 (3). Mutation screening was performed by automatic Sanger sequencing and multiplexligand probe amplification (MLPA). All variants found were checked in human single nucleotide polymorphism (SNP) and mutation databases: Ensembl (www.ensembl.org), Human Gene Mutation Database

Spinocerebellar ataxia type 10 in the South of Brazil: the Amerindian-Belgian connection

Spinocerebellar ataxia type 10 (SCA10) is a rare form of autosomal dominant ataxia found predominantly in patients from Latin America with Amerindian ancestry. The authors report the history of SCA10 families from the south of Brazil (the states of Paraná and Santa Catarina), emphasizing the Belgian-Amerindian connection.

Acute onset of cerebellar ataxia in a spinocerebellar ataxia type 10 patient after use of steroids

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant disorder caused by an expansion of a pentanucleotide (ATTCT) repeat in intron 9 of the ATXN10 gene on chromosome 22q13.31,2. SCA10 gene encodes a 475 KD protein of largely undetermined function. The pathogenic number of ATTCT repeat units ranges from 800 to 4,500 repeats. SCA10 represents a rare form of SCA, described only in Latin America1,2. While clinical manifestations of families described in Brazil are those of a predominantly “pure” cerebellar syndrome, it is often accompanied by epilepsy and occasionally peripheral neuropathy in the Mexican ones1,2. Here, we presented the case of a patient with genetically confirmed SCA10, who developed sudden onset of cerebellar ataxia after a course of corticosteroid therapy. A 34-year-old previously asymptomatic Brazilian woman suddenly developed gait ataxia and dysarthria two weeks after a pulse therapy with methylprednisolone for the treatment of idiopathic thrombocytopenic purpura. The patient was admitted with a clinical picture of body petechiae, gingival bleeding, and hematochezia, which started four days earlier. She had a platelet count of 1,000, which improved with the use of corticosteroids. Neurological assessment revealed gait ataxia, dysarthria, and ocular dysmetria. The Scale for the Assessment and Rating of Ataxia (SARA) was 7.5. Brain magnetic resonance imaging (MRI) showed moderate cerebellar atrophy. Family history was positive for SCA10, including previously reported relatives (aunt and two cousins), whose symptoms were initially manifested during pregnancy3. Interestingly, this same family has also reported the occurrence of cerebellar symptoms triggered by ingestion of small amounts of alcohol, which was previously also published by the authors4. SCA10 is the second most common autosomal dominant cerebellar ataxia in Brazil (after SCA type 3) and in Mexico (after SCA 2). To our knowledge, there is no report of acute cerebellar ataxia development after steroid therapy in patients with SCAs. Based on the case reported here and on family history of onset of symptoms during pregnancy and on postpartum period3, the authors hypothesized that hormonal factors may have a role in the emergence of SCA10 clinical symptoms and signs in previously asymptomatic patients in this family. The mechanisms by which hormones act on cerebellar function and its afferent and efferent connections remain unknown. Previously established genetic variables could be responsible for a lower threshold for manifestation of SCA10 in the course of steroid therapy, and additional studies are necessary to confirm this finding. On the other hand, it is widely known that stress seems to cause acute neuronal death or dysfunction5. Therefore, another possibility is that factors related to stress, involved in acute medical situations, such as pregnancy and postpartum period, could have a pivotal role in the development of acute symptoms of cerebellar ataxia in patients with asymptomatic cerebellar atrophy due to SCA10.