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2.
BMC Neurol ; 20(1): 207, 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32450808

RESUMO

BACKGROUND: Homozygous frameshift mutation in RUBCN (KIAA0226), known to result in endolysosomal machinery defects, has previously been reported in a single Saudi family with autosomal recessive spinocerebellar ataxia (Salih ataxia, SCAR15, OMIM # 615705). The present report describes the clinical, neurophysiologic, neuroimaging, and genetic findings in a second unrelated Saudi family with two affected children harboring identical homozygous frameshift mutation in the gene. It also explores and documents an ancient founder cerebellar ataxia mutation in the Arabian Peninsula. CASE PRESENTATION: The present family has two affected males (aged 6.5 and 17 years) with unsteady gait apparent since learning to walk at 2.5 and 3 years, respectively. The younger patient showed gait ataxia and normal reflexes. The older patient had saccadic eye movement, dysarthria, mild upper and lower limb and gait ataxia (on tandem walking), and enhanced reflexes in the lower limbs. Cognitive abilities were mildly impaired in the younger sibling (IQ 67) and borderline in the older patient (IQ 72). Nerve conduction studies were normal in both patients. MRI was normal at 2.5 years in the younger sibling. Brain MRI showed normal cerebellar volume and folia in the older sibling at the age of 6 years, and revealed minimal superior vermian atrophy at the age of 16 years. Autozygome and exome analysis showed both affected have previously reported homoallelic mutation in RUBCN (NM_014687:exon18:c.2624delC:p.A875fs), whereas the parents are carriers. Autozygosity mapping focused on smallest haplotype on chromosome 3 and mutation age analysis revealed the mutation occurred approximately 1550 years ago spanning about 62 generations. CONCLUSIONS: Our findings validate the slowly progressive phenotype of Salih ataxia (SCAR15, OMIM # 615705) by an additional family. Haplotype sharing attests to a common founder, an ancient RUBCN mutation in the Arab population.


Assuntos
Proteínas Relacionadas à Autofagia/genética , Mutação da Fase de Leitura/genética , Ataxias Espinocerebelares , Adolescente , Cerebelo/diagnóstico por imagem , Criança , Disfunção Cognitiva , Marcha Atáxica , Humanos , Imagem por Ressonância Magnética , Masculino , Ataxias Espinocerebelares/diagnóstico , Ataxias Espinocerebelares/genética
3.
BMC Neurol ; 20(1): 136, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293309

RESUMO

BACKGROUND: Spinocerebellar ataxia type 31 (SCA31) is not usually associated with dementia, and autopsy in a patient with both conditions is very rare. CASE PRESENTATION: An 87-year-old male patient presented with ataxia and progressive dementia. Genetic testing led to a diagnosis of SCA31. Fifteen years after his initial symptoms of hearing loss and difficulty walking, he died of aspiration pneumonia. A pathological analysis showed cerebellar degeneration consistent with SCA31 and abundant argyrophilic grains in the hippocampal formation and amygdala that could explain his dementia. CONCLUSIONS: This is the first autopsy report on comorbid argyrophilic grain disease with SCA31.


Assuntos
Demência/etiologia , Ataxias Espinocerebelares/diagnóstico , Idoso de 80 Anos ou mais , Tonsila do Cerebelo/patologia , Autopsia , Encéfalo/patologia , Humanos , Masculino
4.
J Clin Neurosci ; 71: 150-152, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31540857

RESUMO

Spinocerebellar ataxia type 10 (SCA10) is a rare dominantly inherited neurodegenerative disorder characterized by cerebellar ataxia, dysarthria, ocular dysmetria, and seizures in some populations. Fatigue has been described in SCA1, SCA3, but has not been objectively investigated in SCA10. Our aim is to investigate the presence and related causal factors of fatigue among SCA10 patients. Twenty-eight patients with SCA10 and matched healthy controls were included and assessed using the Scale for the Assessment and Rating of Ataxia (SARA), Modified Fatigue Impact Scale (MFIS), Beck Inventory Depression (BDI) and Epworth Sleepiness Scale (ESS). Fatigue was evidenced in 32% of SCA10 versus 3.6% for the control group (p = 0.005). The following independent variables were not significant predictors for MFIS-BR: duration of disease, SARA and BSS. Age at onset of disease (r = -0.307, p = 0.021) and EDS (r = -0.347, p = 0.014) were mild to moderate predictors of fatigue. Similar to other SCAs, fatigue is common in SCA10 patients, suggesting a possible role of a common topographic degenerative pattern in its pathophysiology.


Assuntos
Fadiga/diagnóstico , Ataxias Espinocerebelares/diagnóstico , Adulto , Idade de Início , Expansão das Repetições de DNA , Fadiga/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Ataxias Espinocerebelares/complicações
5.
Cerebellum ; 19(1): 40-47, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31637587

RESUMO

The clinical spectrum of spinocerebellar ataxia type 2 includes motor manifestations and cognitive disturbances in executive functions, memory, and visuoconstructive skills. The relationships between severity of motor disturbances and altered cognition are poorly known. In this study, we assessed patients with spinocerebellar ataxia type 2 and age- and sex-matched healthy control subjects by a test battery including the Mini-mental State Examination, the Wisconsin Card Sorting test, and the Wechsler Memory Scale-Revised. The correlation between severity of motor ataxia (as assessed by a validated and widely used severity scale, the SARA scale, and by an objective automated computerized system of gait analysis) and altered cognition was then evaluated by Spearman correlation analysis. Patients performed worse than healthy controls in almost all administered neuropsychological tests. Nevertheless, only global intellectual abilities and executive functions significantly correlated with the overall severity of ataxia as assessed by the SARA scale, and impaired executive functions alone correlated with performance on several spatio-temporal gait analysis parameters. Our findings would probably suggest a prominent influence of executive functions on motor abilities in patients with spinocerebellar ataxia type 2 and raise the possibility that cognitive pharmaceutical or rehabilitative interventions may be of benefit in the management of motor problems in these patients.


Assuntos
Cognição/fisiologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Testes Neuropsicológicos , Ataxias Espinocerebelares/diagnóstico , Ataxias Espinocerebelares/psicologia , Adulto , Idoso , Estudos de Casos e Controles , Disfunção Cognitiva/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ataxias Espinocerebelares/epidemiologia
7.
Brain Behav ; 9(10): e01414, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31523939

RESUMO

BACKGROUND: Spinocerebellar ataxia (SCA) presents with variable clinical presentations in addition to ataxia. The aim of this study was to reappraise the diverse nonataxic clinical characteristics of the five most common SCA subtypes in the Asian population. METHODS: The clinical presentations of 90 patients with genetically confirmed SCA1, SCA2, SCA3, SCA6, or SCA17 were assessed retrospectively between November 2008 and September 2018 at a tertiary referral center in Taiwan. RESULTS: Parkinsonism was the most common nonataxic phenotype (21.1%), with a greater prevalence than Caucasian and other Asian SCA carriers. Patients with parkinsonism feature had fewer CAG repeats in SCA2 (31.0 ± 4.5 vs. 36.9 ± 6.0, p = .03) and SCA3 (65.6 ± 7.9 vs. 70.0 ± 4.2, p = .02) compared to those with pure ataxia presentation. The average age of symptom onset was significantly higher in the parkinsonism group of SCA2 (51.5 ± 8.9 vs. 35.3 ± 12.6 years, p = .007) than those with pure ataxia. Focal or segmental dystonia was identified in 4.4% of SCA patients (n = 2 each SCA2 and SCA3). Nonmotor symptoms, including impaired cognition (6.1% of SCA2 and 8.3% of SCA3 patients) and depression (9.1% of SCA2 and 8.3% of SCA3 patients), were also common nonataxic features in our SCA patients. CONCLUSIONS: Parkinsonism, dystonia, and cognitive-psychiatric symptoms are common features in patients with SCA mutations in our population. Our study identifies a different clinical spectrum of SCA1, SCA2, SCA3, SCA6, and SCA17 compared to Caucasians.


Assuntos
Disfunção Cognitiva , Distonia , Transtornos Parkinsonianos , Ataxias Espinocerebelares , Adulto , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Ataxina-2/genética , Ataxina-3/genética , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/genética , Distonia/diagnóstico , Distonia/etiologia , Distonia/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Transtornos Parkinsonianos/diagnóstico , Transtornos Parkinsonianos/genética , Fenótipo , Proteínas Repressoras/genética , Estudos Retrospectivos , Ataxias Espinocerebelares/diagnóstico , Ataxias Espinocerebelares/epidemiologia , Ataxias Espinocerebelares/genética , Ataxias Espinocerebelares/fisiopatologia , Taiwan/epidemiologia
8.
Neurology ; 93(16): e1543-e1549, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31534027

RESUMO

OBJECTIVE: To develop a disease-specific severity index for adults with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) (DSI-ARSACS) that considers the 3 components (pyramidal, cerebellar, neuropathic) of the disease, and to document its content validity, internal consistency, and construct validity. METHODS: The Beta DSI-ARSACS (17 items) was developed based on literature review and expert inputs and then administered to 26 participants. Items reduction was based on Cronbach α and desirable criteria. Performance measures were administered to assess the construct validity of the final version of the DSI-ARSACS. RESULTS: The final DSI-ARSACS have 8 items that can be easily performed during usual medical follow-up. The mean score was 19.6 ± 8.1 (range 6.0-35.5) and the Cronbach α was 0.912. The DSI-ARSACS score increased with disease stage and age (p ≤ 0.001) and was closely correlated with other measures assessing similar construct (9-Hole Peg Test, 10-Meter Walk Test, Scale for the Assessment and Rating of Ataxia, Berg Balance Scale, Barthel Index) (r s = 0.75-0.95, p < 0.01). A moderate but not significant correlation was found with the 6-Minute Walk test (r s = -0.611, p = 0.108). CONCLUSIONS: The DSI-ARSACS is a valid measure of disease severity for the adult ARSACS population that is able to distinguish between patients with different clinical profiles. Further documentation of metrologic properties is necessary, but these first results are promising.


Assuntos
Ataxia/diagnóstico , Ataxia Cerebelar/diagnóstico , Espasticidade Muscular/diagnóstico , Índice de Gravidade de Doença , Ataxias Espinocerebelares/congênito , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Ataxias Espinocerebelares/diagnóstico , Teste de Caminhada , Adulto Jovem
9.
Cerebellum ; 18(5): 849-854, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31377949

RESUMO

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant disorder in which patients have a slowly progressive cerebellar ataxia, with dysarthria, dysphagia, and epilepsy. The aims of this study were to characterize the phenotypic expression of SCA10 and to examine its genotype-phenotype relationships. Ninety-one Brazilian patients with SCA10 from 16 families were selected. Clinical and epidemiological data were assessed by a standardized protocol, and severity of disease was measured by the Scale for the Assessment and Rating of Ataxia (SARA). The mean age of onset of symptoms was 34.8 ± 9.4 years. Sixty-two (68.2%) patients presented exclusively with pure cerebellar ataxia. Only 6 (6.6%) of the patients presented with epilepsy. Patients with epilepsy had a mean age of onset of symptoms lower than that of patients without epilepsy (23.5 ± 15.5 years vs 35.4 ± 8.7 years, p = 0.021, respectively). All cases of intention tremor were in women from one family. This family also had the lowest mean age of onset of symptoms, and a higher percentage of SCA10 cases in women. There was a positive correlation between duration of disease and severity of ataxia (rho = 0.272, p = 0.016), as quantified by SARA. We did not find a statistically significant correlation between age of onset of symptoms and expansion size (r = - 0.163, p = 0.185). The most common clinical presentation of SCA10 was pure cerebellar ataxia. Our data suggest that patients with epilepsy may have a lower age of onset of symptoms than those who do not have epilepsy. These findings and the description of a family with intention tremor in women with earlier onset of symptoms draw further attention to the phenotypic variability of SCA10.


Assuntos
Ataxina-10/genética , Epilepsia/epidemiologia , Epilepsia/genética , Testes Genéticos/métodos , Ataxias Espinocerebelares/epidemiologia , Ataxias Espinocerebelares/genética , Adolescente , Adulto , Brasil/epidemiologia , Expansão das Repetições de DNA/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ataxias Espinocerebelares/diagnóstico , 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.
Sci Rep ; 9(1): 11878, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31417125

RESUMO

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare early-onset neurological disease caused by mutations in SACS, which encodes sacsin. The complex architecture of sacsin suggests that it could be a key player in cellular protein quality control system. Molecular chaperones that operate in protein folding/unfolding and assembly/disassembly patterns have been described as essential modulators of selectivity during the autophagy process. We performed RNA-sequencing analysis to generate a whole-genome molecular signature profile of sacsin knockout cells. Using data analysis of biological processes significantly disrupted due to loss of sacsin, we confirmed the presence of decreased mitochondrial function associated with increased oxidative stress, and also provided a demonstration of a defective autophagic pathway in sacsin-depleted cells. Western blotting assays revealed decreased expression of LC3 and increased levels of p62 even after treatment with the lysosomal inhibitor bafilomycin A1, indicating impairment of the autophagic flux. Moreover, we found reduced co-immunolocalization of the autophagosome marker LC3 with lysosomal and mitochondrial markers suggesting fusion inhibition of autophagic compartments and subsequent failed cargo degradation, in particular failed degradation of damaged mitochondria. Pharmacological up-regulation of autophagy restored correct autophagic flux in sacsin knockout cells. These results corroborate the hypothesis that sacsin may play a role in autophagy. Chemical manipulation of this pathway might represent a new target to alleviate clinical and pathological symptoms, delaying the processes of neurodegeneration in ARSACS.


Assuntos
Autofagia/genética , Perfilação da Expressão Gênica , Predisposição Genética para Doença , Proteínas de Choque Térmico/genética , Espasticidade Muscular/genética , Ataxias Espinocerebelares/congênito , Transcriptoma , Sistemas CRISPR-Cas , Células Cultivadas , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Técnicas de Inativação de Genes , Ontologia Genética , Estudos de Associação Genética , Humanos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Espasticidade Muscular/diagnóstico , Espasticidade Muscular/metabolismo , Fosforilação Oxidativa , Complexo de Endopeptidases do Proteassoma/metabolismo , Ataxias Espinocerebelares/diagnóstico , Ataxias Espinocerebelares/genética , Ataxias Espinocerebelares/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Ubiquitina/metabolismo
12.
Neurocase ; 25(5): 195-201, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31423897

RESUMO

Autosomal recessive spinocerebellar ataxia type 10 (SCAR10) caused by a homozygous c.132dupA mutation in the anoctamin 10 gene is infrequent and little is known about its cognitive profile. Three siblings (1 male) with this mutation were assessed with a neuropsychological battery measuring multiple cognitive domains. The deficits observed in one patient were in executive functions whereas the other two patients showed deficits in practically all the functions. Cognitive impairment seems to be a characteristic of the SCAR10 produced by this mutation, with a range from mild impairment, especially involving prefrontal systems, to a severe cognitive impairment suggesting widespread cerebral involvement.


Assuntos
Anoctaminas/genética , Cognição , Ataxias Espinocerebelares/genética , Ataxias Espinocerebelares/psicologia , Adulto , Expansão das Repetições de DNA/genética , Feminino , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Testes Neuropsicológicos , Tempo de Reação , Ataxias Espinocerebelares/diagnóstico
13.
Cerebellum ; 18(5): 841-848, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31342269

RESUMO

Spinocerebellar ataxia type 10 (SCA10) is a repeat expansion disease occurring mostly in Latin America, suggesting that the mutation spread with the peopling of the Americas, or that Amerindian populations, have a higher ATXN10 mutability. High frequency of large normal alleles is associated with prevalence and relative frequency of other repeat expansion diseases. To test whether the allele distribution of the SCA10-causing ATXN10 microsatellite in an Amerindian Peruvian population differs from that of other populations. The ATXN10 allele distribution in a Quechua Peruvian population from Puno, Peru, is similar to that of Finland. Mean allele size and mode were also similar to those of Mexico, Japan, and white Europeans. ATXN10 allele distribution in a healthy Amerindian population from Peru does not differ from that of other populations.


Assuntos
Alelos , Ataxina-10/genética , Repetições de Microssatélites/genética , Vigilância da População , Ataxias Espinocerebelares/epidemiologia , Ataxias Espinocerebelares/genética , Expansão das Repetições de DNA/genética , Europa (Continente)/epidemiologia , Humanos , Japão/epidemiologia , México/epidemiologia , Peru/epidemiologia , Vigilância da População/métodos , Ataxias Espinocerebelares/diagnóstico
14.
Ophthalmic Genet ; 40(3): 282-285, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31269856

RESUMO

Background: Spinocerebellar ataxia Type 7 (SCA7) is an autosomal dominant, progressive neurodegenerative disorder, primarily characterized by cerebellar ataxia. The disease is caused by the expansion of a CAG trinucleotide repeat within the ataxin-7 gene when its CAG repeat sequences are extended beyond 38. The degree of retinopathy can vary from pigment change in the fovea to foveal atrophy and is correlated with the number of CAG repeats. The present study describes a case of SCA7 with a retinal presentation similar to occult macular dystrophy (OMD) which is an inherited macular dystrophy characterized by presenting with a normal fundus and fluorescein angiography but with progressive central visual loss. Materials and Methods: Report of a case. Results: In this case, no specific abnormality was found on fundus examination, fluorescein angiography, full-field electroretinography and infrared autofluorescence. Spectral-domain optical coherence tomography showed foveal thinning, focal disruption of the ellipsoid zone, and central loss of the outer segment-retinal pigment epithelium interdigitation zone that were well matched with the multifocal electroretinography finding. Thirty-nine CAG repeats in ataxin-7 gene were identified through genetic testing. Conclusions: SCA7 can present with a very mild form of retinal degeneration similar to the classic phenotype of RP1L1-negative OMD in case of the lower number of CAG repeats.


Assuntos
Proteínas do Olho/genética , Degeneração Macular/diagnóstico , Mutação , Distrofias Retinianas/diagnóstico , Ataxias Espinocerebelares/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Degeneração Macular/genética , Pessoa de Meia-Idade , Fenótipo , Distrofias Retinianas/genética , Ataxias Espinocerebelares/genética
16.
Parkinsonism Relat Disord ; 67: 74-89, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31272925

RESUMO

Juvenile parkinsonism is arbitrarily defined as parkinsonian symptoms and signs presenting prior to 21 years of age. Levodopa-responsive juvenile parkinsonism that is consistent with diagnostic criteria for Parkinson's disease is most often caused by mutations in the PARK-Parkin, PARK-PINK1, or PARK-DJ1 genes. However, many other genetic and acquired parkinsonian disorders presenting in childhood or young adulthood are being reported, often with atypical features, such as presence of other movement disorders, cognitive decline, and psychiatric symptoms. The genetic landscape of juvenile parkinsonism is rapidly changing with the discovery of new genes. Although the mainstay of treatment remains levodopa, other symptomatic therapies such as botulinum toxin for focal dystonia, supportive medical therapies, and deep brain stimulation in select cases, may also be used to provide the most optimal long-term outcomes. Since the topic has not been reviewed recently, we aim to provide an update on genetics, differential diagnosis, evaluation, and treatment of juvenile parkinsonism.


Assuntos
Antiparkinsonianos/uso terapêutico , Estimulação Encefálica Profunda , Transtornos Parkinsonianos/genética , Transtornos Parkinsonianos/terapia , Adolescente , Criança , Pré-Escolar , Síndrome de DiGeorge/genética , Diagnóstico Diferencial , Distúrbios Distônicos/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/genética , Humanos , Doença de Huntington/diagnóstico , Doença de Huntington/genética , Levodopa/uso terapêutico , Transtornos Parkinsonianos/diagnóstico , Proteína Desglicase DJ-1/genética , Proteínas Quinases/genética , Ataxias Espinocerebelares/diagnóstico , Ataxias Espinocerebelares/genética , Ubiquitina-Proteína Ligases/genética , Adulto Jovem , alfa-Sinucleína/genética
18.
Neurogenetics ; 20(3): 161-164, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31190316

RESUMO

Autosomal dominant spinocerebellar ataxia (SCA) type 12 is a rare SCA characterized by a heterogeneous phenotype. Action tremor of the upper limbs is the most common presenting sign and cerebellar signs can appear subsequently. In many cases, minor signs, like dystonia, can be predominant even at onset. Laryngeal dystonia (spasmodic dysphonia) has been observed only in one case of SCA12 and never reported at disease onset. We present a 61-year-old female who developed spasmodic dysphonia followed by dystonic tremor and subsequent ataxia diagnosed with SCA12. Thus, spasmodic dysphonia can be a presenting symptom of SCA12.


Assuntos
Disfonia/diagnóstico , Distúrbios Distônicos/diagnóstico , Ataxias Espinocerebelares/diagnóstico , Alelos , Encéfalo/diagnóstico por imagem , Feminino , Transtornos Neurológicos da Marcha/genética , Heterozigoto , Humanos , Doenças da Laringe/diagnóstico , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Fenótipo , Tremor
19.
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
20.
Ophthalmic Genet ; 40(3): 267-275, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31135245

RESUMO

Purpose: To confirm the pathogenic role of a novel mutation in PNPLA6 and detail the phenotype of a patient presenting with choroideremia-like chorioretinal degeneration. Methods: A 40-year-old man with presumed choroideremia underwent a complete ophthalmic examination, full-field electroretinography (ERG), kinetic fields and two-color automated static perimetry and retinal imaging with spectral domain optical coherence tomography (SD-OCT) and near-infrared (NIR) and short wavelength (SW) fundus autofluorescence (FAF). Results: Visual acuity was 20/200 and 20/40 for the right and left eye, respectively, with a ~ 5D myopic correction. Small cone-mediated ERG responses were detectable. The visual field by kinetic perimetry (V-4e stimulus) was limited to small (<5°) central islands separated from large peripheral islands of vision by an absolute midperipheral scotoma. There were minute islands of apparently spared retina near the foveal center separated from large peripheral islands of better appearing retina by severe pericentral and midperipheral chorioretinal atrophy. SD-OCT confirmed detectable photoreceptors near the center and in nasal midperipheral retina despite severe outer segment loss. Central photoreceptor loss was associated with disproportionately severe retinal pigment epithelium (RPE) depigmentation and choroidal atrophy. NIR- and SW-autofluorescence was widely hypoautofluorescent with the exception of residual autofluorescence along peripheral regions of relative RPE preservation. Gene screening revealed biallelic mutations (p.Arg1031GlnfsTer38/p.Arg1183Gln) in PNPLA6. Hypogonadotropic hypogonadism and cerebellar vermis hypoplasia by MRI confirmed a diagnosis of Boucher-Neuhäuser syndrome. Conclusions: PNPLA6-associated retinal degenerations can present with predominantly retinal findings and subtle systemic abnormalities and should be considered in the differential diagnosis of diffuse chorioretinal atrophies.


Assuntos
Coroideremia/diagnóstico , Hipogonadismo/diagnóstico , Mutação , Fosfolipases/genética , Distrofias Retinianas/diagnóstico , Ataxias Espinocerebelares/diagnóstico , Adulto , Coroideremia/genética , Diagnóstico Diferencial , Humanos , Hipogonadismo/genética , Masculino , Fenótipo , Prognóstico , Distrofias Retinianas/genética , Ataxias Espinocerebelares/genética , Acuidade Visual
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