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1.
Neurology ; 95(9): e1199-e1210, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32611635

RESUMO

OBJECTIVES: With disease-modifying drugs on the horizon for degenerative ataxias, ecologically valid motor biomarkers are highly warranted. In this observational study, we aimed to unravel and validate markers of ataxic gait in real life by using wearable sensors. METHODS: We assessed gait characteristics of 43 patients with degenerative cerebellar disease (Scale for the Assessment and Rating of Ataxia [SARA] 9.4 ± 3.9) compared with 35 controls by 3 body-worn inertial sensors in 3 conditions: (1) laboratory-based walking; (2) supervised free walking; (3) real-life walking during everyday living (subgroup n = 21). Movement analysis focused on measures of spatiotemporal step variability and movement smoothness. RESULTS: A set of gait variability measures was identified that allowed us to consistently identify ataxic gait changes in all 3 conditions. Lateral step deviation and a compound measure of spatial step variability categorized patients vs controls with a discrimination accuracy of 0.86 in real life. Both were highly correlated with clinical ataxia severity (effect size ρ = 0.76). These measures allowed detecting group differences even for patients who differed only 1 point in the clinical SARAposture&gait subscore, with highest effect sizes for real-life walking (d = 0.67). CONCLUSIONS: We identified measures of ataxic gait that allowed us not only to capture the gait variability inherent in ataxic gait in real life, but also to demonstrate high sensitivity to small differences in disease severity, with the highest effect sizes in real-life walking. They thus represent promising candidates for motor markers for natural history and treatment trials in ecologically valid contexts. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that a set of gait variability measures, even if accessed in real life, correlated with the clinical severity of ataxia in patients with degenerative cerebellar disease.


Assuntos
Análise da Marcha/métodos , Ataxias Espinocerebelares/fisiopatologia , Dispositivos Eletrônicos Vestíveis , Adulto , Idoso , Ataxia Telangiectasia/fisiopatologia , Feminino , Análise da Marcha/instrumentação , Humanos , Masculino , Pessoa de Meia-Idade , Equilíbrio Postural , Índice de Gravidade de Doença , Caminhada , Adulto Jovem
2.
Neurology ; 95(2): e194-e205, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32527970

RESUMO

OBJECTIVE: To determine whether objective and quantitative assessment of dysarthria and dysphagia in spinocerebellar ataxia type 2 (SCA2), specifically at pre-ataxic and early disease phases, can act as sensitive disease markers. METHODS: Forty-six individuals (16 with pre-ataxic SCA2, 14 with early-stage ataxic SCA2, and 16 healthy controls) were recruited in Holguin, Cuba. All participants underwent a comprehensive battery of assessments including objective acoustic analysis, clinician-derived ratings of speech function and swallowing, and quality of life assessments of swallowing. RESULTS: Reduced speech agility manifest at the pre-ataxic stage was observed during diadochokinetic tasks, with the magnitude of speech deficit augmented in the early ataxic stage. Speech rate was slower in early-stage ataxic SCA2 compared with pre-ataxic SCA2 and healthy controls. Reduced speech agility and speech rate correlated with disease severity and time to ataxia onset, verifying that speech deficits occur prior to ataxia onset and increase in severity as the disease progresses. Whereas dysphagia was observed in both pre-ataxic and ataxic SCA2, it was not associated with swallowing-related quality of life, disease severity, or time to ataxia onset. CONCLUSIONS: Speech and swallowing deficits appear sensitive to disease progression in early-stage SCA2, with syllabic rate a viable marker. Findings provide insight into mechanisms of disease progression in early-stage SCA2, signaling an opportunity for stratifying early-stage SCA2 and identifying salient markers of disease onset as well as outcome measures in future early-stage therapeutic studies.


Assuntos
Transtornos de Deglutição/etiologia , Transtornos de Deglutição/fisiopatologia , Distúrbios da Fala/etiologia , Distúrbios da Fala/fisiopatologia , Ataxias Espinocerebelares/complicações , Ataxias Espinocerebelares/fisiopatologia , Adolescente , Adulto , Biomarcadores , Transtornos de Deglutição/psicologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Testes de Articulação da Fala , Distúrbios da Fala/psicologia , Ataxias Espinocerebelares/psicologia , Adulto Jovem
3.
Int. arch. otorhinolaryngol. (Impr.) ; 24(1): 86-92, Jan.-Mar. 2020. tab
Artigo em Inglês | LILACS | ID: biblio-1090561

RESUMO

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.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Audiometria de Tons Puros , Limiar Auditivo/fisiologia , Potenciais Evocados Auditivos do Tronco Encefálico , Ataxias Espinocerebelares/fisiopatologia , Testes de Impedância Acústica , Estudos Transversais , Estudos Retrospectivos , Ataxias Espinocerebelares/complicações , Transtornos da Audição/diagnóstico , Transtornos da Audição/etiologia
4.
Cerebellum ; 19(2): 235-242, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31925668

RESUMO

In recent years, increasing evidence of the cerebellar role in social cognition has emerged. The cerebellum has been shown to modulate cortical activity of social brain regions serving as a regulator of function-specific mentalizing and mirroring processes. In particular, a mentalizing area in the posterior cerebellum, specifically Crus II, is preferentially recruited for more complex and abstract forms of social processing, together with mentalizing cerebral areas including the dorsal medial prefrontal cortex (dmPFC), the temporo-parietal junction (TPJ), and the precuneus. In the present study, the network-based statistics approach was used to assess functional connectivity (FC) differences within this mentalizing cerebello-cerebral network associated with a specific cerebellar damage. To this aim, patients affected by spinocerebellar ataxia type 2 (SCA2), a neurodegenerative disease specifically affecting regions of the cerebellar cortex, and age-matched healthy subjects have been enrolled. The dmPFC, left and right TPJ, the precuneus, and the cerebellar Crus II were used as regions of interest to construct the mentalizing network to be analyzed and evaluate pairwise functional relations between them. When compared with controls, SCA2 patients showed altered internodal connectivity between dmPFC, left (L-) and right (R-) TPJ, and right posterior cerebellar Crus II.The present results indicate that FC changes affect a function-specific mentalizing network in patients affected by cerebellar damage. In particular, they allow to better clarify functional alteration mechanisms driven by the cerebellar damage associated with SCA2 suggesting that selective cortico-cerebellar functional disconnections may underlie patients' social impairment in domain-specific complex and abstract forms of social functioning.


Assuntos
Cerebelo/fisiopatologia , Mentalização/fisiologia , Rede Nervosa/fisiologia , Vias Neurais/fisiopatologia , Ataxias Espinocerebelares/fisiopatologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
5.
Cerebellum ; 19(2): 165-181, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31898278

RESUMO

Spinocerebellar ataxia type 2 (SCA2), a rare polyglutamine neurodegenerative disorder caused by a CAG repeat expansion in the ataxin-2 gene, exhibits common cellular phenotypes with other neurodegenerative disorders, including oxidative stress and mitochondrial dysfunction. Here, we show that SCA2 patient cells exhibit higher levels of caspase-8- and caspase-9-mediated apoptotic activation than control cells, cellular phenotypes that we find to be exacerbated by reactive oxygen species (ROS) and inhibition of autophagy. We also suggest that oligomerization of mutant ataxin-2 protein is likely to be the cause of the observed cellular phenotypes by causing inhibition of autophagy and by inducing ROS generation. Finally, we show that removal of ataxin-2 oligomers, either by increasing autophagic clearance or by oligomer dissolution, appears to alleviate the cellular phenotypes. Our results suggest that oligomerized ataxin-2 and oxidative stress affect autophagic clearance in SCA2 cells, contributing to the pathophysiology, and that activation of autophagy or clearance of oligomers may prove to be effective therapeutic strategies.


Assuntos
Apoptose/fisiologia , Ataxina-2/metabolismo , Autofagia/fisiologia , Ataxias Espinocerebelares/metabolismo , Células Cultivadas , Fibroblastos/metabolismo , Humanos , Estresse Oxidativo/fisiologia , Ataxias Espinocerebelares/fisiopatologia
6.
Am J Hosp Palliat Care ; 37(1): 46-51, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31088125

RESUMO

BACKGROUND: Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant progressive neurodegenerative disease. Few studies have been conducted regarding advance care planning in this population. OBJECTIVE: This study explores advance care planning preferences of patients with SCA1 and their association with disease progression and quality of life. METHODS: The study examined 12 Thai patients with SCA1 from 2 families living in Thailand. The advance care plan followed a Gold Standards Framework. The 12 patients were interviewed and recorded in video. The research team evaluated neurocognitive functions as measured by the following tests; Scale for the Assessment and Rating of Ataxia (SARA), Berg Balance Score, Mini-Mental Status Examination, and Digit Span and Category Fluency. The quality of life was measured by a Short-Form Health Survey-36 (SF-36). RESULTS: Seven of 12 patients with SCA1 rated communication ability as most important for their quality of life. Patients identified becoming a burden on their family members and ventilator dependence as the most undesirable situations. Half of the patients preferred a hospital as their last place of care. Comparing patients prefer hospital to home has significantly high median SARA (23 vs 11.5; P = .03) and low SF-36 (41.4 vs 72.4; P = .02). CONCLUSIONS: Those patients preferring a hospital for end-of-life care exhibited more physical disability and lower quality of life than those who preferred home care. Making assisted living health-care services in the home more readily available and affordable may alleviate concerns of patients facing more severe physical challenges.


Assuntos
Planejamento Antecipado de Cuidados/organização & administração , Qualidade de Vida , Ataxias Espinocerebelares/fisiopatologia , Ataxias Espinocerebelares/psicologia , Assistência Terminal/organização & administração , Adulto , Idoso , Comunicação , Estudos Transversais , Progressão da Doença , Família/psicologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Equilíbrio Postural/fisiologia , Respiração Artificial/psicologia , Tailândia
7.
Stereotact Funct Neurosurg ; 97(4): 241-243, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31743916

RESUMO

The beneficial effect of thalamic deep brain stimulation (DBS) on action tremor has been reported in a few cases of spinocerebellar ataxia (SCA); however, several factors should be taken into account regarding the indication for DBS in advanced cases. We performed DBS of the ventral intermediate nucleus (Vim) of the thalamus for treatment of coarse action tremor in a patient with SCA2 (spinocerebellar ataxia type 2) in the wheelchair-bound stage. Although improvement of the tremor of the proximal part was incomplete, the patient regained substantial parts of daily functioning. The effect lasted for more than 6 years, and the suppression of tremor significantly contributed to maintaining the level of the patient's expression into the bedridden stage. Vim DBS can be a treatment option for tremor in SCA patients, even in the advanced stage, as long as the tremor is depriving the patient of behavioral expression. As residual proximal tremor may hamper functional recovery, DBS of other targets or multi-targets should be further explored to attain a better outcome.


Assuntos
Estimulação Encefálica Profunda/métodos , Ataxias Espinocerebelares/diagnóstico por imagem , Ataxias Espinocerebelares/terapia , Tremor/diagnóstico por imagem , Tremor/terapia , Núcleos Ventrais do Tálamo/diagnóstico por imagem , Feminino , Humanos , Pessoa de Meia-Idade , Ataxias Espinocerebelares/fisiopatologia , Fatores de Tempo , Tremor/fisiopatologia , Núcleos Ventrais do Tálamo/fisiopatologia
8.
Medicine (Baltimore) ; 98(46): e17834, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725623

RESUMO

RATIONALE: Spinocerebellar ataxia 2 (SCA2) is a genetic disease, mainly characterized by ataxia. A number of other neurological symptoms also have been described, such as Parkinsonism, cognitive dysfunction, autonomic dysfunction, even the signs of motor neuron disease and so on. Mostly, In the same family, clinical performance is the same in most cases. Here, we describe a father and his son who suffered from SCA2, but their first manifestations were different. PATIENT CONCERNS: The father exhibited progressive bradykinesia and rigidity, which resulted in the dysfunction of walking and caring himself. He hoped to relieve his symptoms by taking medicine. But the son presented with ataxia which was mild that the discomfort did not affect his daily life with none treated. DIAGNOSIS: Both of them were given SCA2 tests. Briefly, we designed primers around the CAG trinucleotide, repeated the spinal cerebellar ataxia subtype gene, performed PCR expansion, and then calculated the specific number of repetitions by capillary electrophoresis. Abnormal expansion was detected in them through SCA2 sequencing with different repeat numbers of CAG, and then they were diagnosed with SCA2 sequencing. INTERVENTIONS: The father was treated with dopaminergic drugs, but the son was not administered treatment. OUTCOMES: The father's symptoms are improved and he can take care of himself. The son has none difficulty in his daily life. LESSONS: It is rare that different individuals in the same family with SCA2 have different manifestations. The genetic testing is a crucial method to diagnose the disease of SCA2.


Assuntos
Ataxias Espinocerebelares/genética , Ataxias Espinocerebelares/fisiopatologia , Adulto , Dopaminérgicos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Ataxias Espinocerebelares/tratamento farmacológico
9.
Hum Brain Mapp ; 40(16): 4748-4758, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31365181

RESUMO

The cerebellum has been implicated in the feedforward control of speech production. However, the role of the cerebellum in the feedback control of speech production remains unclear. To address this question, the present event-related potential study examined the behavioral and neural correlates of auditory feedback control of vocal production in patients with spinocerebellar ataxia (SCA) and healthy controls. All participants were instructed to produce sustained vowels while hearing their voice unexpectedly pitch-shifted -200 or -500 cents. The behavioral results revealed significantly larger vocal compensations for pitch perturbations in patients with SCA relative to healthy controls. At the cortical level, patients with SCA exhibited significantly smaller cortical P2 responses that were source localized in the right superior temporal gyrus, primary auditory cortex, and supramarginal gyrus than healthy controls. These findings indicate that reduced brain activity in the right temporal and parietal regions are significant neural contributors to abnormal auditory-motor processing of vocal pitch regulation as a consequence of cerebellar degeneration, which may be related to disrupted reciprocal interactions between the cerebellum and cortical regions that support the top-down modulation of auditory-vocal integration. These differences in behavior and cortical activity between healthy controls and patients with SCA demonstrate that the cerebellum is not only essential for feedforward control but also plays a crucial role in the feedback-based control of speech production.


Assuntos
Cerebelo/fisiopatologia , Retroalimentação Sensorial , Fala , Ataxias Espinocerebelares/fisiopatologia , Estimulação Acústica , Adulto , Córtex Auditivo/diagnóstico por imagem , Córtex Auditivo/fisiopatologia , Mapeamento Encefálico , Cerebelo/diagnóstico por imagem , Eletroencefalografia , Potenciais Evocados , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Ataxias Espinocerebelares/diagnóstico por imagem , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/fisiopatologia , Voz , Adulto Jovem
10.
Curr Opin Ophthalmol ; 30(6): 443-448, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31449085

RESUMO

PURPOSE OF REVIEW: Impaired eye movements are frequently seen in ophthalmic and neurologic clinical practice, especially in individuals with movement disorders. Identification of the abnormal movement can aid initial diagnosis and improve understanding of the underlying disease pathophysiology. The present article reviews the ocular motor manifestations and recent research on them in common movement disorders. RECENT FINDINGS: Ocular motor manifestations and their pathophysiologic correlates are being defined. In particular, study of eye movements can help clarify the changing clinicopathologic spectrum of atypical parkinsonian disorders. The pathophysiology and natural history of blepharospasm are being elucidated. Recent research focuses on high-resolution imaging and other technological advances to improve the sensitivity of the ocular motility exam. Eye movements are being studied as biomarkers for diagnosis and progression in clinical care and trials. SUMMARY: The current review summarizes ocular motor manifestations in common movement disorders, and presents recent research investigating their cause and treatment.


Assuntos
Blefarospasmo/diagnóstico , Doença de Huntington/diagnóstico , Doença de Niemann-Pick Tipo C/diagnóstico , Transtornos da Motilidade Ocular/diagnóstico , Doença de Parkinson/diagnóstico , Ataxias Espinocerebelares/diagnóstico , Blefarospasmo/fisiopatologia , Movimentos Oculares/fisiologia , Humanos , Doença de Huntington/fisiopatologia , Doença de Niemann-Pick Tipo C/fisiopatologia , Transtornos da Motilidade Ocular/fisiopatologia , Doença de Parkinson/fisiopatologia , Ataxias Espinocerebelares/fisiopatologia
11.
Kaohsiung J Med Sci ; 35(11): 679-685, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31271500

RESUMO

Spinocerebellar ataxia (SCA) type 1 (SCA1) is a rare autosomal dominant disorder that is characterized by worsening of disordered coordination, ataxia of the trunk, and other neurological symptoms. Physical activity improves both mobility and the daily living activities of patients with SCA. Intervention with daily regular treadmill exercise may slow the deterioration of cerebellar neurons in SCA1. Therefore, the signal changes and performance of cerebellar neurons after exercise in SCA1 was investigated in this study. We employed a transgenic mouse model of SCA1, generated by amplifying the cytosine-adenine-guanine trinucleotide repeat expansions, and the mice underwent 1 month of moderate daily treadmill exercise for 1 hour. The rotarod test revealed that the motor function of the SCA1 mice that underwent training was superior to that of the control SCA1 mice, which did not undergo training. Moreover, the cerebellar pathology revealed preserved Purkinje neurons stained by carbindin with an increase of the neuronal Per Arnt Sim domain protein 4, a key regulation in the structural and functional plasticity of neurons, in the excised SCA1 mice relative to the controls. The mechanism was related to an increase of phosphorylation of ribosomal protein S6, a downstream target of the mammalian target of rapamycin pathway, but not to autophagy activation. This study determined that regular treadmill exercise may play a crucial role in the viable support of cerebellar neurons in SCA1.


Assuntos
Cerebelo/patologia , Atividade Motora , Neurônios/patologia , Condicionamento Físico Animal , Ataxias Espinocerebelares/patologia , Ataxias Espinocerebelares/fisiopatologia , Animais , Autofagia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Contagem de Células , Sobrevivência Celular , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Plasticidade Neuronal , Neurônios/metabolismo , Fosforilação , Células de Purkinje/patologia , Proteína S6 Ribossômica/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
12.
Acta Neurol Scand ; 140(5): 350-358, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31343735

RESUMO

OBJECTIVES: To assess the time and frequency domain measures of cardiac autonomic activity/tone in patients of genetically defined spinocerebellar ataxia (SCA) types 1 and 2, as well as to decipher the probable associations among the cardiovascular autonomic parameters and genetic and clinical characteristics. MATERIALS AND METHODS: Simultaneous 5-min recording of RR interval (RRI) and blood pressure (BP) for the calculation of heart rate variability (HRV), blood pressure variability (BPV) and baroreflex sensitivity (BRS) were performed in genotypically confirmed SCA1 (n = 31) and SCA2 (n = 40) patients and healthy controls (n = 40). Additionally, the International Cooperative Ataxia Rating Scale (ICARS) was used for scoring of clinical severity in SCA patients. RESULTS: Time and frequency domain parameters of HRV, BPV and BRS were depressed in SCA1 and SCA2 subtypes as compared to controls, although there was no statistically significant difference in autonomic tone between the two SCA subtypes. On correlation analysis, autonomic tone parameters were found to be associated with the clinical and genetic features of the SCA subtypes. Also, ICARS was associated with the genotype (CAG repeat length) in SCA2 patents. CONCLUSIONS: Cardiac autonomic tone is depressed in both SCA1 and 2 as compared to healthy controls while the two SCA subtypes do not differ in terms of autonomic tone. Also, a typical association exists between disease characteristics and autonomic indices.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Barorreflexo/fisiologia , Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Ataxias Espinocerebelares/fisiopatologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ataxias Espinocerebelares/genética
13.
Muscle Nerve ; 60(3): 271-278, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31228263

RESUMO

INTRODUCTION: Use of peripheral nerve ultrasound alongside standard electrodiagnostic tests may help to gain insight into the pathophysiology of peripheral nerve involvement in type 2 spinocerebellar ataxia (SCA2). METHODS: Twenty-seven patients with SCA2 underwent ultrasound cross-sectional area (CSA) measurement of median, ulnar, sural and tibial nerves, and motor (median, ulnar, tibial) and sensory (median, ulnar, radial, sural) nerve conduction studies. RESULTS: Twenty patients had pathologically small-nerve CSAs, suggestive of sensory neuronopathy. In these patients, electrophysiology showed non-length-dependent sensory neuropathy (14 of 20), "possible sensory neuropathy" (1 of 20), or normal findings (5 of 20). Four different patients had length-dependent sensory neuropathy on electrophysiology, and 1 had enlarged nerve CSAs. Regression analysis showed an inverse relationship between ataxia scores and upper limb nerve CSA (P < 0.03). DISCUSSION: Our findings suggest that a majority of patients with SCA2 (74%) have a sensory neuronopathy and this correlates with disability. A minority of patients have findings consistent with axonal neuropathy (18%). Muscle Nerve, 2019.


Assuntos
Nervos Periféricos/fisiopatologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Ataxias Espinocerebelares/fisiopatologia , Extremidade Superior/fisiopatologia , Adulto , Idoso , Ataxia Cerebelar/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/metabolismo , Condução Nervosa/fisiologia , Doenças do Sistema Nervoso Periférico/diagnóstico , Transtornos das Sensações/fisiopatologia , Ultrassonografia/métodos
14.
Cerebellum ; 18(6): 1130-1136, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31175630

RESUMO

Oculomotor abnormalities are common in the spinocerebellar ataxias (SCAs). In studies of SCAs 1, 2, 3, and 6, eye movement abnormalities correlate with disease severity. Oculomotor abnormalities may be the sole motor manifestation of early and/or premanifest disease; however, not all ataxia rating scales include oculomotor assessment. We sought to identify the prevalence and characteristics of oculomotor abnormalities at first presentation in a large SCA cohort, including those in earlier stages of disease. We performed a retrospective assessment of initial clinical examinations of SCA patients followed in the Massachusetts General Hospital Ataxia Unit and assessed with the Brief Ataxia Rating Scale (BARS). One hundred thirty-four SCA patients were assessed: 17 SCA1, 13 SCA2, 55 SCA3, 2 SCA5, 22 SCA6, 11 SCA7, 9 SCA8, and 5 SCA17, mainly in the early stages of disease (67.2% stage 0-1). Oculomotor abnormalities were present on initial assessment in 94.8%, including 7/9 stage 0 and 77/81 stage 1 patients. Stage 0/1 patients had frequent saccadic intrusions, nystagmus, and hypo/hypermetric saccades. Saccadic slowing was present even in early stage SCA7 and SCA2, eventually leading to ophthalmoplegia. The burden of oculomotor abnormalities correlated with disease stage, duration, and severity, remaining highly significant even when controlling for age. The ubiquitous presence of oculomotor abnormalities in the SCAs, particularly early in the course, underscores the importance of oculomotor assessment in ataxia rating scales such as BARS. These findings highlight the potential for quantitative physiological oculomotor measures as clinical biomarkers in natural history studies and clinical trials.


Assuntos
Movimentos Oculares/fisiologia , Transtornos da Motilidade Ocular/diagnóstico , Transtornos da Motilidade Ocular/fisiopatologia , Ataxias Espinocerebelares/diagnóstico , Ataxias Espinocerebelares/fisiopatologia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos da Motilidade Ocular/epidemiologia , Estudos Retrospectivos , Ataxias Espinocerebelares/epidemiologia
15.
Cerebellum ; 18(4): 817-822, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31111429

RESUMO

While heterozygous mutations in the AFG3L2 gene have been linked to spinocerebellar ataxia 28 (SCA28), homozygous mutations in the same gene can cause spastic ataxia 5 (SPAX5). AFG3L2 encodes a mitochondrial ATP-dependent metalloprotease. We here report a SCA28 patient with biallelic AFG3L2 variants and his heterozygous mother. The patient and his mother underwent a detailed neurological examination and fibroblast lines were established. The effect of the two missense variants on mitochondria was assessed by form factor analysis and quantification of mitochondrial proteins (TOMM70, complex V). The 39-year-old index patient presented with a slowly progressive cerebellar gait disorder for 19 years, bilateral ptosis, and dysarthria. A cranial MRI showed mild cerebellar atrophy. He carried two compound-heterozygous, rare, missense variants (c.1847A>G [p.Y616C], c.2167G>A [p.V723M]) in AFG3L2, while his mother was heterozygous for the first change that had previously been described in SPAX5. Altered mitochondrial morphology and interconnectivity, together with reduced protein levels of TOMM70 and complex V (ATPase), suggest mitochondrial structural defects in the patient's fibroblasts. No significant abnormalities were found in his mother's fibroblast cultures albeit all measurements were slightly below the control level. We here present a SCA28 patient with compound-heterozygous AFG3L2 variants and demonstrate mitochondrial abnormalities in skin fibroblast cultures from this patient. Thus, AFG3L2 variants should be considered in both slowly progressive ataxias and phenotypes with clinical features reminiscent of mitochondrial disease. Of note, ptosis was present in both mutation carriers and may serve as a red flag in the diagnosis of SCA28.


Assuntos
Proteases Dependentes de ATP/genética , ATPases Associadas a Diversas Atividades Celulares/genética , Ataxias Espinocerebelares/congênito , Adulto , Atrofia , Progressão da Doença , Fibroblastos/patologia , Heterozigoto , Humanos , Imagem por Ressonância Magnética , Masculino , Mitocôndrias/patologia , Proteínas Mitocondriais/genética , Mutação/genética , Mutação de Sentido Incorreto/genética , Exame Neurológico , Ataxias Espinocerebelares/diagnóstico por imagem , Ataxias Espinocerebelares/genética , Ataxias Espinocerebelares/fisiopatologia
17.
Brain Dev ; 41(7): 630-633, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30898343

RESUMO

BACKGROUND: Spinocerebellar ataxia type 5 (SCA5), a dominant spinocerebellar ataxia is caused by spectrin beta nonerythrocytic 2 gene (SPTBN2) mutation. It typically consists of a slow progressive cerebellar ataxia with an onset principally in adulthood. Here, we report on the first Japanese patient with infantile-onset SCA5 associated with a novel heterozygous SPTBN2 mutation. CASE REPORT: The patient, a 6-year-old girl, developed delayed motor development and unsteady arm movement during infancy. She also showed gaze-evoked nystagmus, saccadic eye pursuit, dysarthria, dysmetria, intention tremor and mild intellectual disability. Brain MRI revealed moderate cerebellar atrophy and mild pontine atrophy. Comprehensive target capture sequencing to identify the causative gene identified a novel missense mutation in SPTBN2 (c.1309C

Assuntos
Espectrina/genética , Ataxias Espinocerebelares/genética , Degenerações Espinocerebelares/genética , Criança , Feminino , Humanos , Japão , Imagem por Ressonância Magnética , Mutação , Mutação de Sentido Incorreto , Espectrina/metabolismo , Ataxias Espinocerebelares/fisiopatologia
19.
Med Oral Patol Oral Cir Bucal ; 24(2): e165-e171, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30818308

RESUMO

BACKGROUND: Neurodegenerative diseases that affect the cerebellum, especially in elderly individuals, cause impairment of motor coordination and quality of life. The presente study evaluated the electromyographic activity and thickness of the right and left masseter and temporal muscles, and the maximum molar bite force of individuals with spinocerebellar ataxia. MATERIAL AND METHODS: Twenty-eight individuals were divided into two groups: those with (n=14) and without (n=14) spinocerebellar ataxia. Data on the masticatory muscles obtained from the electromyographic activity (resting, right and left laterality and protrusion), muscle thickness (maximal voluntary contraction and tensile strength) and maximum bite force (right and left) were tabulated and descriptive analysis using Student's t-test (P ≤ 0.05). RESULTS: In the comparison between groups, greater electromyographic activity was demonstrated for individuals with spinocerebellar ataxia, with a statistically significant difference in protrusion and laterality for the temporal muscles (P = 0.05). There was no statistically significant difference between the groups for masticatory muscles thickness in the conditions evaluated. For maximum molar bite force, the group with spinocerebellar ataxia showed lower bite force (P ≤ 0.05). CONCLUSIONS: The data obtained suggest that spinocerebellar ataxia promotes functional reduction in the stomatognathic system, mainly affecting the electromyographic activity and bite force, hindering chewing, with a resultant alteration of nutritional intake and a decrease of quality of life.


Assuntos
Força de Mordida , Ataxias Espinocerebelares/fisiopatologia , Sistema Estomatognático/fisiopatologia , Adulto , Brasil , Estudos de Casos e Controles , Oclusão Dentária , Eletromiografia , Feminino , Lateralidade Funcional , Humanos , Masculino , Mandíbula , Músculo Masseter/fisiopatologia , Mastigação , Músculos da Mastigação/fisiopatologia , Pessoa de Meia-Idade , Dente Molar , Estudos Prospectivos , Qualidade de Vida , Músculo Temporal/fisiopatologia , Transtornos da Articulação Temporomandibular/fisiopatologia
20.
Parkinsonism Relat Disord ; 63: 191-194, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30862453

RESUMO

INTRODUCTION: Spinocerebellar Ataxia 38 (SCA38) is caused by ELOVL5 gene mutation, with significant reduction of serum docosahexaenoic acid (DHA) levels. DHA supplementation has been proven effective at short-term follow-up. In the present paper, we evaluated long-term safety and efficacy of 600 mg/day oral DHA in SCA38 by a 2-year open label extension study. METHODS: Nine SCA38 patients underwent standardised clinical assessment at 62 (T1), 82 (T2) and 104 (T3) weeks, and compared to pre-treatment scores (T0). Brain 18-Fluorodeoxyglucose Positron Emission Tomography and electroneurography were performed at T0 and T3. RESULTS: We found a significant maintenance of clinical symptom improvement at each follow-up time-point (p < 0.001) as compared to T0, a sustained increase of cerebellar metabolism at T3 as compared to T0 (p = 0.013), and no worsening of neurophysiological parameters. No side effect was recorded. CONCLUSIONS: Long-term DHA supplementation is an eligible treatment for SCA38.


Assuntos
Ácidos Docosa-Hexaenoicos/farmacologia , Ataxias Espinocerebelares/tratamento farmacológico , Ataxias Espinocerebelares/fisiopatologia , Adulto , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/efeitos adversos , Estimulação Elétrica , Eletromiografia , Elongases de Ácidos Graxos/genética , Feminino , Fluordesoxiglucose F18 , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Ataxias Espinocerebelares/diagnóstico por imagem , Ataxias Espinocerebelares/genética
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