Spotlight on Multiple system atrophy

Multiple system atrophy is a sporadic degenerative disorder with a highly variable anatomic distribution and clinical picture. It typically features some combination of motor parkinsonism, ataxia, and dysautonomia, along with many other less constant signs. Average age at onset is 53 years, and average survival is only 8 years. Although there is no specific treatment, clinicians can palliate many aspects of the syndrome, particularly the dysautonomia and the sleep disturbances. The defining pathologic feature is aggregates of alpha-synuclein in oligodendroglia.

In this article, Dr. Robert Fekete of New York Medical College describes the essential features of multiple system atrophy, including advances in distinguishing it from the other parkinsonian disorders and in managing its many disabling clinical features.

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Spotlight on Joubert syndrome

Joubert syndrome is a malformation syndrome affecting brainstem and cerebellum, resulting in early hypotonia, subsequent truncal ataxia, delayed milestones, and, finally, cognitive impairment of varying degrees. Although a rare condition, its pathogenetic understanding is likely to contribute significantly to the organization and function of the hindbrain. Molar tooth sign is a characteristic neuroimaging finding on axial cuts through the midbrain/hindbrain region. In this summary, Dr. Eugen Boltshauser, Professor Emeritus of Pediatric Neurology at University Children’s Hospital in Zurich, Switzerland, gives an update of the diagnostic workup, refers to other cerebello-oculo-renal syndromes, and summarizes the actual knowledge about molecular genetics.

The genetic situation is very complex in view of marked genetic heterogeneity and modifier genes. Twenty-four different genes are known; however, in about half of affected individuals, a pathogenic mutation is still unknown. All genes are related to the primary ciliary-basal body apparatus. Joubert syndrome can be grouped among the ciliopathies. Joubert syndrome is now the best-studied hindbrain malformation.

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MedLink Neurology authors are always at work to bring you broad and up-to-date coverage of neurology topics. We are pleased to highlight clinical summaries that have been recently added or updated and to introduce the authors who write these authoritative articles. We hope you enjoy these overviews and appreciate the contributions of our more than 450 authors who keep MedLink Neurology the premier information resource for neurologists.

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Spotlight on Nondominant hereditary ataxias

The autosomal recessive cerebellar ataxias comprise a large group of rare diseases, the most common forms being Friedreich ataxia, ataxia-telangiectasia, and early-onset cerebellar ataxia with retained tendon reflexes. This is a large and expanding group of disorders characterized by degeneration or developmental anomalies of the cerebellum and spinal cord, age of onset prior to 20 years, and autosomal recessive inheritance. Dr. Ryan W Y Lee of Kennedy Krieger Institute and the Johns Hopkins University School of Medicine provides an updated comprehensive review of this disorder and its classifications.

The disorders of X-linked inheritance are also described here. The “Differential Diagnosis” section describes the utility of using associated symptoms as a clinical tool to investigate etiologies. Methods such as in proteomics, molecular and genetic studies, and high-throughput drug screening are allowing researchers to better understand the mechanisms of this group of disorders and arrive at targeted therapy.

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MedLink Neurology authors are always at work to bring you broad and up-to-date coverage of neurology topics. We are pleased to highlight clinical summaries that have been recently added or updated and to introduce the authors who write these authoritative articles. We hope you enjoy these overviews and appreciate the contributions of our more than 450 authors who keep MedLink Neurology the premier information resource for neurologists.

Spotlight on Spinocerebellar ataxia type 3

Spinocerebellar ataxia type 3 (also called Machado-Joseph disease, MJD/SCA3) is 1 of the 2 most common inherited ataxic syndromes in the world. This autosomal dominant disorder includes a fairly wide range of phenotypes that may precede or accompany the ataxia. With more widespread genetic testing, an increasing range of phenotypes has been recognized. Advances in molecular biology are helping to form a better picture of the underlying pathophysiology.

In this clinical summary, Dr. Anelyssa D’Abreu of the State University of Campinas in Sao Paolo, Brazil and Dr. Joseph Friedman of Butler Hospital and the Alpert School of Brown University discuss the clinical aspects of MJD/SCA3, including nonmotor features, the genetics of the disorder, and possible pathologic mechanisms of the toxic gain of function mutant form of ataxin 3.

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MedLink Neurology authors are always at work to bring you broad and up-to-date coverage of neurology topics. We are pleased to highlight clinical summaries that have been recently added or updated and to introduce the authors who write these authoritative articles. We hope you enjoy these overviews and appreciate the contributions of our more than 450 authors who keep MedLink Neurology the premier information resource for neurologists.

Spotlight on Fragile X-associated tremor/ataxia syndrome

Fragile X-associated tremor/ataxia syndrome is a late-onset triplet repeat disorder that leads to dementia, parkinsonism, and neuropathy. Its cause is a restricted triplet repeat expansion mutation in the FMR1 gene, whereas a larger expansion results in fragile X syndrome A in children. In this review Dr. Florian Thomas of Saint Louis University and Dr. Niranjan Singh of the University of Missouri – Columbia focus on fragile X-associated tremor/ataxia syndrome and its relation to fragile X syndrome A.

Fragile X-associated tremor/ataxia syndrome illustrates the importance of obtaining a comprehensive family history that is not limited to clinical questions of the patient. Fragile X-associated tremor/ataxia syndrome is part of the differential diagnosis in patients with varying combinations of the above symptoms with or without a family history of intellectual disability. Some estimates suggest that as many as 1 in 3000 men older than 50 years of age may develop fragile X-associated tremor/ataxia syndrome; such numbers would signify a great impact on healthcare costs. The pathomechanistic evidence of mitochondrial and RNA dysfunction and of a neurodevelopmental component to fragile X-associated tremor/ataxia syndrome is discussed.

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MedLink Neurology authors are always at work to bring you broad and up-to-date coverage of neurology topics. We are pleased to highlight clinical summaries that have been recently added or updated and to introduce the authors who write these authoritative articles. We hope you enjoy these overviews and appreciate the contributions of our more than 450 authors who keep MedLink Neurology the premier information resource for neurologists.