Autosomal dominant cerebellar ataxias: a systematic review of clinical features

Rossi, Malco; Pérez-Lloret, Santiago; Doldan, Leila; Cerquetti, Daniel; Balej, Jorge; Vernetti, Patricio Millar; Hawkes, Maximiliano A.; Cammarota, Angel; Merello, Marcelo

doi:10.1111/ene.12350

Cited by 117 publications

(121 citation statements)

References 18 publications

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“…Two-hertz repetitive nerve stimulation of the facial and spinal accessory nerves showed no evidence of a postsynaptic neuromuscular junction disorder, such as myasthenia gravis. Complete blood cell count, comprehensive metabolic profile, human immunodeficiency virus, copper, vitamin B 12 , homocysteine, methylmalonic acid, quantitative immunoglobulins, antinuclear antibody, aldolase, and creatine kinase test results were all normal.…”

Section: Laboratory and Imaging Studiesmentioning

confidence: 96%

“…If the MRI does not reveal a specific causative abnormality, then the differential is further divided into toxic, nutritional, autoimmune, neurodegenerative, or hereditary etiologies. These would encompass diagnoses such as alcoholic cerebellar degeneration; vitamin B 1 , B 12 , or E deficiency; paraneoplastic cerebellar degeneration; multiple system atrophy; Creutzfeldt-Jakob disease; and many forms of autosomal dominant, recessive, or X-linked ataxias. 1 A 50-year old man presented for evaluation of progressive gait ataxia with a superimposed spastic paraparesis.…”

Section: Laboratory and Imaging Studiesmentioning

confidence: 99%

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A Middle-aged Man With Progressive Ophthalmoparesis, Ataxia, and Spastic Paraparesis

2017

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A 50-year-old man presented for evaluation of progressive clumsiness and unsteady gait. His first symptoms began around age 39 years when he noted progressive difficulty performing calisthenics such as jumping jacks during intramural sports practice. Approximately 8 years later, he reported difficulty using handheld carpentry tools at work and trouble maintaining balance while carrying drywall from room to room. Because of intermittent neck pain, he was referred to a spine surgeon, who noted hyperreflexia with cervical stenosis on imaging. Anterior cervical discectomy and fusion was performed, with no benefit. The patient reported continued difficulty with balance, and around age 48 years, he could no longer participate in sports practice. He denied focal weakness, numbness, or tingling. He began falling, particularly on uneven ground, and at the time of presentation required a walking stick. He had no other medical history and no pertinent family history. His only medication was baclofen, 10 mg, three times a day. He denied alcohol, tobacco, or drug use, and he was disabled owing to his condition. Owing to his progressive gait disorder, he was referred to our neuromuscular clinic for evaluation.On general medical examination, he was a well-appearing man weighing 78.8 kg with a height of 1.8 m. Results of a general medical examination were normal. On neurologic examination, there was significant ptosis, more prominent on the left than the right. He was observed to have slow and limited eye movements while giving his history, and he frequently turned his head to compensate for impaired extraocular movements. This observation prompted additional questions from the examiner, and he denied diplopia, symptomatic ptosis, or ophthalmoplegia. Eye movements were approximately 75% of normal in both horizontal and vertical directions, and the remaining limitation of eye movements could not be overcome by vestibulo-ocular reflex testing. There was gazeevoked nystagmus in the midright and midleft gazes. Saccades were slowed and there was no dysarthria. On detailed motor examination, there was spastic tone in the lower extremities (2 on the Ashworth scale), but power was 5/5 (by Medical Research Council) in all 4 extremities. Quantitative vibratory sense was diminished at the toes, ankles, and knees, but normal in the fingers. There was no sen-sory level to pinprick examination. Romberg examination showed an inability to stand with his feet together, even with eyes open. Reflexes were 2+ at the biceps, 3+ at the knees, and 2+ at the ankles. Mild appendicular ataxia was noted during finger-nose-finger and rapid alternating movements tests. His gait was wide-based, tremulous, and ataxic.

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Section: Laboratory and Imaging Studiesmentioning

confidence: 96%

Section: Laboratory and Imaging Studiesmentioning

confidence: 99%

A Middle-aged Man With Progressive Ophthalmoparesis, Ataxia, and Spastic Paraparesis

2017

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“…Characterized by a progressive loss of motor coordination, other symptoms include dysarthria and disturbance of eye movements 1 . Cerebellar ataxias may be acquired or inherited, with hereditary ataxias classified into autosomal dominant, autosomal recessive, X-linked or mitochondrial forms.…”

Section: Cerebellar Ataxiasmentioning

confidence: 99%

Recent advances in modelling of cerebellar ataxia using induced pluripotent stem cells

Wong

Watson

Becker

2017

J Neurol Neuromedicine

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The cerebellar ataxias are a group of incurable brain disorders that are caused primarily by the progressive dysfunction and degeneration of cerebellar Purkinje cells. The lack of reliable disease models for the heterogeneous ataxias has hindered the understanding of the underlying pathogenic mechanisms as well as the development of effective therapies for these devastating diseases. Recent advances in the field of induced pluripotent stem cell (iPSC) technology offer new possibilities to better understand and potentially reverse disease pathology. Given the neurodevelopmental phenotypes observed in several types of ataxias, iPSC-based models have the potential to provide significant insights into disease progression, as well as opportunities for the development of early intervention therapies. To date, however, very few studies have successfully used iPSC-derived cells to model cerebellar ataxias. In this review, we focus on recent breakthroughs in generating human iPSC-derived Purkinje cells. We also highlight the future challenges that will need to be addressed in order to fully exploit these models for the modelling of the molecular mechanisms underlying cerebellar ataxias and the development of effective therapeutics.

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“…Due to the genetic heterogeneity, patients with SCAs can develop impaired vision, dysarthria, pyramidal signs, ophthalmoplegia, extrapyramidal signs, loss of sensory function, dementia, or any combination of these abnormalities (Rossi et al., 2014; van Gaalen, Giunti, & van de Warrenburg, 2011). Among these, spinocerebellar ataxia type 2 (SCA2), one of the most frequent types, is definitely caused by an CAG repeat expansion in the ATXN2 gene (Pulst et al., 1996).…”

Section: Introductionmentioning

confidence: 99%

Voxel‐based meta‐analysis of gray and white matter volume abnormalities in spinocerebellar ataxia type 2

et al. 2018

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ObjectiveTo identify the consistent findings from the whole‐brain voxel‐based morphometry (VBM) studies on spinocerebellar ataxia type 2 (SCA2).MethodsThe whole‐brain VBM studies comparing SCA2 patients and healthy controls (HCs) were systematically searched in PubMed, Embase databases from January 2000 to June 2017. The coordinates with significant differences in gray matter (GM) and white matter (WM) between SCA2 patients and HCs were extracted separately from each cluster. A meta‐analysis was performed using anisotropic effect size‐based signed differential mapping (AES‐SDM) software.ResultsA total of five studies with 65 SCA2 patients and 124 HCs were included in the GM meta‐analysis. Four of the five studies with 50 SCA2 patients and 109 HCs were included in the WM meta‐analysis. Significant and consistent GM volume reductions were detected in bilateral cerebellar hemispheres, cerebellar vermis, the right fusiform gyrus, the right parahippocampal gyrus, and the right lingual gyrus. The WM volume reductions were observed in bilateral cerebellar hemispheres, cerebellar vermis, middle cerebellar peduncles, pons, and bilateral cortico‐spinal projections. The findings of the study remained largely unchanged in jackknife sensitivity analysis.ConclusionsThe consistent findings from our meta‐analysis showed that GM volume reductions in SCA2 patients were not limited in cerebellum while significant WM volume reductions widely existed in cerebellum and pyramidal system. The findings provide morphological basis for further studies on SCA2.

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Autosomal dominant cerebellar ataxias: a systematic review of clinical features

Abstract: Autosomal dominant cerebellar ataxias encompass a broad spectrum of clinical features with high prevalence of non-ataxia symptoms. Certain features distinguish different genetic subtypes. A new algorithm for ADCA classification at disease onset is proposed.

Cited by 117 publications

References 18 publications

A Middle-aged Man With Progressive Ophthalmoparesis, Ataxia, and Spastic Paraparesis

A Middle-aged Man With Progressive Ophthalmoparesis, Ataxia, and Spastic Paraparesis

Recent advances in modelling of cerebellar ataxia using induced pluripotent stem cells

Voxel‐based meta‐analysis of gray and white matter volume abnormalities in spinocerebellar ataxia type 2

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