Nonmotor Symptoms in Patients with Spinocerebellar Ataxia Type 10.

Nonmotor symptoms (NMS) have been described in several neurodegenerative diseases but have not been systematically evaluated in spinocerebellar ataxia type 10 (SCA10). The objective of the study is to compare the frequency of NMS in patients with SCA10, Machado-Joseph disease (MJD), and healthy controls. Twenty-eight SCA10, 28 MJD, and 28 healthy subjects were prospectively assessed using validated screening tools for chronic pain, autonomic symptoms, fatigue, sleep disturbances, psychiatric disorders, and cognitive function. Chronic pain was present with similar prevalence among SCA10 patients and healthy controls but was more frequent in MJD. Similarly, autonomic symptoms were found in SCA10 in the same proportion of healthy individuals, while the MJD group had higher frequencies. Restless legs syndrome and REM sleep behavior disorder were uncommon in SCA10. The mean scores of excessive daytime sleepiness were worse in the SCA10 group. Scores of fatigue were higher in the SCA10 sample compared to healthy individuals, but better than in the MJD. Psychiatric disorders were generally more prevalent in both spinocerebellar ataxias than among healthy controls. The cognitive performance of healthy controls was better compared with SCA10 patients and MJD, which showed the worst scores. Although NMS were present among SCA10 patients in a higher proportion compared to healthy controls, they were more frequent and severe in MJD. In spite of these comparisons, we were able to identify NMS with significant functional impact in patients with SCA10, indicating the need for their systematic screening aiming at optimal treatment and improvement in quality of life.

Nonneurological Involvement in Late-Onset Friedreich Ataxia (LOFA): Exploring the Phenotypes.

Friedreich's ataxia (FDRA) is the most common inherited ataxia worldwide, caused by homozygous GAA expansions in the FXN gene. Patients usually have early onset ataxia, areflexia, Babinski sign, scoliosis and pes cavus, but at least 25 % of cases have atypical phenotypes. Disease begins after the age of 25 in occasional patients (late-onset Friedreich ataxia (LOFA)). Little is known about the frequency and clinical profile of LOFA patients. One hundred six patients with molecular confirmation of FDRA and followed in three Brazilian outpatient centers were enrolled. General demographics, GAA expansion size, age at onset, cardiac, endocrine, and skeletal manifestations were evaluated and compared between LOFA and classic FDRA (cFDRA) groups. We used Mann-Whitney and Fisher tests to compare means and proportions between groups; p values <0.05 were considered significant. LOFA accounted for 17 % (18/106) and cFDRA for 83 % (88/106) of the patients. There were 13 and 48 women in each group, respectively. LOFA patients were significantly older and had smaller GAA expansions. Clinically, LOFA group had a tendency toward lower frequency of diabetes/impaired glucose tolerance (5.8 vs. 17 %, p = 0.29) and cardiomyopathy (16.6 vs. 28.4 %, p = 0.38). Skeletal abnormalities were significantly less frequent in LOFA (scoliosis 22 vs. 61 %, p = 0.003, and pes cavus 22 vs.75 %, p < 0.001) as were spasticity and sustained reflexes, found in 22 % of LOFA patients but in none of the cFDRA patients (p = 0.001). LOFA accounts for 17 % of Brazilian FDRA patients evaluated herein. Clinically, orthopedic features and spasticity with retained reflexes are helpful tips to differentiate LOFA from cFDRA patients.

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.

Otoneurological findings in spinocerebellar ataxia.

OBJECTIVE: Describe findings observed in ENG of patients with spinocerebellar ataxias. METHOD: Forty-three patients were studied, and the following procedures were carried out: anamnesis, otorhinolaryngological and vestibular evaluation (ENG). RESULTS: The clinical findings in the entire group of patients were: gait disturbances (83.72%), speech difficulties (48.83%), dizziness (41.86%) and dysphagia (39.53%). Vestibular examination disclosed abnormal caloric exam (83.71%) and saccadic movements (69.76%) with the highest rates of abnormality. The overall presence of alterations in vestibular tests was (90.70%), and the most frequent finding was central vestibular disorder in (74.42%) of patients. CONCLUSION: The study showed that alterations in ENG are related to the severity of SCAs or clinical stage of the disease. We emphasize the importance of studying the vestibular system concomitantly to clinical and genetic follow up.

Spinocerebellar ataxia type 10: Frequency of epilepsy in a large sample of Brazilian patients.

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant disorder caused by an ATTCT repeat intronic expansion in the SCA10 gene. SCA 10 has been reported in Mexican, Brazilian, Argentinean and Venezuelan families. Its phenotype is overall characterized by cerebellar ataxia and epilepsy. Interestingly, Brazilian patients reported so far showed pure cerebellar ataxia, without epilepsy. Here, authors provide a systematic analysis of the presence, frequency and electroencephalographic presentation of epilepsy among 80 SCA10 patients from 10 Brazilian families. Overall, the frequency of epilepsy was considered rare, been found in 3.75 % of the cases while this finding in populations from other geographic areas reaches 60% of SCA10 cases.

NMO-IgG positive neuromyelitis optica in a patient with myasthenia gravis but no thymectomy.

Here we report on a 44-year old woman presenting with both myasthenia gravis (MG) and neuromyelitis optica (NMO). MRI showed transverse myelitis extending from C2 to T4, multifocal demyelinating lesions in the supratentorial white matter, and left optic neuritis. Serological analysis demonstrated antibodies to acetylcholine receptors as well as NMO-IgG. To our knowledge, this is the first case of NMO-IgG positive NMO in a patient with MG but no history of thymectomy or immunosuppression.

Vestibular findings in relapsing, remitting multiple sclerosis: a study of thirty patients.

Our objective was to describe vestibular abnormalities in patients with relapsing and remitting multiple sclerosis. Thirty patients (6 men and 24 women) between 27 and 64 years of age underwent neurological and otolaryngological examinations, complete anamnesis, and electronystagmography. Patients with psychological or oculomotor paresis (or both), internuclear ophthalmoparesis, severe visual disturbances, or locomotion restrictions were excluded. The difference-of-proportion test was used to compare affected patients with controls, with a significance level of 5%. Vestibular alterations were found in 26 (86%) of the evaluated patients, from which 25 presented peripheral etiology and only 1 presented a problem of central origin. There was a prevalence of bilateral peripheral irritative vestibulopathy (20%), followed by bilateral peripheral deficit vestibulopathy (20%) and left peripheral deficit vestibulopathy (17%). The high incidence of vestibular disorders observed in this study indicates that this population might benefit from specific rehabilitation programs. Studies with larger samples are still required and may contribute to the understanding of this pathology.

Reduced penetrance in a Brazilian family with spinocerebellar ataxia type 10.

OBJECTIVE: To describe reduced penetrance associated with early onset in a Brazilian family with spinocerebellar ataxia type 10. DESIGN: Clinical examination and molecular analysis for the ATTCT repeat responsible for spinocerebellar ataxia type 10 in a patient and family members through 3 generations. SETTING: Ambulatory care. Patients A 28-year-old female Brazilian patient who presented with early-onset cerebellar ataxia and epilepsy, and her 9 asymptomatic relatives. Main Outcome Measure Genotype-phenotype correlation. RESULTS: Molecular testing on this patient showed an expansion of approximately 850 ATTCT repeats at the SCA10 locus. Similar SCA10 expansions of approximately 850 repeats were identified in 6 of 8 asymptomatic paternal relatives examined. CONCLUSION: The stably transmitted pentanucleotide expansion of approximately 850 repeats may represent a mutant SCA10 allele with reduced penetrance that may express an early-onset, severe phenotype.

The history of spinocerebellar ataxia type 10 in Brazil: travels of a gene.

The authors report the history of spinocerebellar ataxia 10 (SCA10), since its first report in a large Portuguese-ancestry family with autosomal dominant pure cerebellar ataxia, till the final identification of further families without Mexican ancestry. These families present a quite different phenotype from those SCA10 families described in Mexico.

High-frequency hearing threshold in adult women with multiple sclerosis.

Our objective was to determine the high-frequency hearing thresholds of women with multiple sclerosis (MS) and to investigate the presence of side dominance for high-frequency perception. We submitted 19 affected and 106 nonaffected women (controls) to high-frequency audiometry and classified them in subgroups according to their age (30-40, 40-50, and 50-60 years). We analyzed data through selected statistical tests. We could detect no consistent effect of side dominance and observed a general increase in the hearing sensitivity for high frequencies in MS patients. We concluded that high-frequency sounds seemed to be detected more easily by MS patients than by controls.

Cerebellum and Cognition Henrietta Leiner's contribution. Historical note.

The authors present the scientific contribution of Professor Henrietta C. Leiner, one of the pioneering scientists in the study of cognitive function of the cerebellum.

Os autores apresentam a contribuição científica da Professora Henrietta C. Leiner, um dos cientistas pioneiros no estudo da função cognitiva do cerebelo.

Statin-associated cerebellar ataxia. A Brazilian case series.

BACKGROUND: Drug-induced cerebellar ataxias (DICA) represent an important group of secondary cerebellar ataxias. Herein, we reported a case series of progressive cerebellar ataxia induced by HMG-CoA reductase inhibitors (statins). METHODS: Observational study with a Brazilian case series of patients with cerebellar ataxia due to statins use. RESULTS: We described four patients with cerebellar ataxia, predominantly gait ataxia, due to statins use. Mean age was 67.5 years old, predominantly male, with several comorbidities, such as dyslipidemia, diabetes mellitus, hypertension, and myocardial revascularization. After statin withdrawal, and treatment with coenzyme Q10 in some patients, progressive improvement of gait ataxia was observed. DISCUSSION: We presented a case series of four patients with cerebellar ataxia due to statins use, which represents a new rare side-effect of statins, probably related to coenzyme Q10 deficiency.

Itajaí, Santa Catarina - Azorean ancestry and spinocerebellar ataxia type 3.

The authors present a historical review of spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD), the most common form of spinocerebellar ataxia in Brazil, and consider the high frequency of cases in families from Itajaí, a city on the coast of the state of Santa Catarina with a large population of Portuguese/Azorean descent.

Rosalie: the Brazilian female monkey of Charcot.

Jean-Martin Charcot, the father of Neurology, a very austere and reserved man that did not express affection freely for human being, had a profound affection to animals, particularly to a small female monkey, called "Rosalie", which came from Brazil and was a gift of Dom Pedro II to Charcot.

Idiopathic very late-onset cerebellar ataxia: a Brazilian case series.

UNLABELLED: The authors present a Brazilian case series of eight patients with idiopathic very-late onset (mean 75.5 years old) cerebellar ataxia, featuring predominantly gait ataxia, associated with cerebellar atrophy. METHOD: 26 adult patients with a diagnosis of idiopathic late onset cerebellar ataxia were analyzed in a Brazilian ataxia outpatient clinic and followed regularly over 20 years. Among them, 8 elderly patients were diagnosed as probable very late onset cerebellar ataxia. These patients were evaluated with neurological, ophthalmologic and Mini-Mental Status examinations, brain MRI, and EMG. RESULTS: 62.5% of patients were males, mean age was 81.9 years-old, and mean age of onset was 75.5 years. Gait cerebellar ataxia was observed in all patients, as well as, cerebellar atrophy on brain MRI. Mild cognitive impairment and visual loss, due to macular degeneration, were observed in 50% of cases. Chorea was concomitantly found in 3 patients. CONCLUSION: We believe that this condition is similar the one described by Marie-Foix-Alajouanine presenting with mild dysarthria, associated with gait ataxia, and some patients had cognitive dysfunction and chorea.

Differential diagnosis of sporadic adult-onset ataxia: The role of REM sleep behavior disorder.

BACKGROUND: Sporadic adult-onset ataxia encompasses a group of degenerative, non-hereditary disorders, including idiopathic adult-onset ataxia and the cerebellar form of multiple system atrophy. Our objective was to analyze the diagnosis at follow-up of 50 sporadic adult-onset ataxia patients. METHODS: Clinical and laboratory findings of 50 adult patients with sporadic adult-onset ataxia were analyzed. Diagnosis of probable REM sleep behavior disorder was based predominantly on clinically accepted criteria. RESULTS: Multiple system atrophy was diagnosed in 48% of cases, the remaining 52% received a diagnosis of sporadic adult-onset ataxia. REM sleep behavior disorder was diagnosed in 46% of the patients. However, among patients with probable multiple system atrophy, the corresponding figure was 83.34% versus 11.53% among those with sporadic ataxia (p < 0.001). CONCLUSIONS: REM sleep behavior disorder is an important aid to the differentiation of multiple system atrophy from sporadic adult-onset ataxia and its use for this purpose should be encouraged.

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.

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.

Pathogenic compound heterozygous ATP7B mutations with hypoceruloplasminaemia without clinical features of Wilson's disease.

The authors report a 44-year-old man with a history of attention deficit and hyperactivity disorder, obsessive compulsive behaviour, vocal tics, depression, and anxiety, in whom a compound heterozygous ATP7B mutation was found, associated with hypoceruloplasminemia, but without clinical or pathological manifestation of Wilson's disease (WD). Genetic testing revealed a compound heterozygous ATP7B mutation already described in WD, p.Met645Arg (C1934TG/c.51+4A→T). Hypoceruloplasminaemia was detected but no clinical manifestations (hepatic or central nervous system) of WD were present. The authors conclude that patients can carry a heterozygous mutation of the ATP7B gene that is associated with hypoceruloplasminaemia and display no overt clinical hepatic and/or central nervous system manifestations of WD.