Sporadic adult onset ataxia of unknown etiology

Abele, Michael; Minnerop, Martina; Urbach, Horst; Specht, Karsten; Klockgether, Thomas

doi:10.1007/s00415-007-0556-1

Cited by 48 publications

(15 citation statements)

References 29 publications

(33 reference statements)

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“…Abele and colleagues report that the median AO of ILOCA was 56 years in their 2002 study, 35 and 47 years in their 2007 study. 33 These differing AO may reflect the fact that the understanding of ILOCA continues to evolve as new genetic findings sculpt out genetic-ataxia syndromes from what was previously regarded as idiopathic ataxia. 38–48 Even in our own ILOCA cohort, the finding of possibly pathogenic VUS in dominant ataxia genes (SCA5, 13, 14, 28, 35) in five cases is intriguing, but not yet established with certainty.…”

Section: Discussionmentioning

confidence: 99%

“…The problem for the clinician is that ILOCA and MSA-C both present in mid-life, and it has been suggested that both disorders include extra-cerebellar symptoms such as erectile dysfunction, bladder urgency, dysphagia, snoring, restless leg syndrome, and rapid eye movement sleep behavior disorder. 33,34 The natural histories of MSA-C and ILOCA are quite different, however, as MSA-C has an average survival of 7 to 9 years, 4,5 whereas ILOCA patients can have a normal lifespan. 35,36 Making the correct diagnosis early in the course is therefore of paramount importance for patient management, and for research initiatives into early intervention and treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

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The Diagnosis and Natural History of Multiple System Atrophy, Cerebellar Type

2015

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OBJECTIVE To identify key features differentiating Multiple System Atrophy Cerebellar type (MSA-C) from Idiopathic Late-Onset Cerebellar Ataxia (ILOCA). METHODS We reviewed records of patients seen in the Massachusetts General Hospital Ataxia Unit between 1992 and 2013 with consensus criteria diagnoses of MSA-C or ILOCA. 12 patients had Definite MSA-C, 53 had Possible/Probable MSA-C, and 12 had ILOCA. RESULTS Autonomic features, specifically urinary urgency, frequency, and incontinence with erectile dysfunction in males, differentiated MSA-C from ILOCA throughout the disease course (p = 0.005). Orthostatic hypotension developed later and differentiated MSA-C from ILOCA (p < 0.01). REM sleep behavior disorder (RBD) occurred early in Possible/Probable MSA-C (p < 0.01). Late MSA-C included pathologic laughing and crying (PLC, p < 0.01), bradykinesia (p = 0.01), and corticospinal findings (p = 0.01). MRI distinguished MSA-C from ILOCA by atrophy of brainstem (p < 0.01) and middle cerebellar peduncles (MCP, p = 0.02). MSA-C progressed faster than ILOCA: by 6 years, MSA-C walker dependency was 100%, ILOCA 33%. MSA-C survival was 8.4 ± 2.5 years. Mean length of ILOCA illness to date is 15.9 ± 6.4 years. CONCLUSIONS A sporadic onset, insidiously developing cerebellar syndrome in mid-life, with autonomic features of otherwise-unexplained bladder dysfunction with or without erectile dysfunction in males, and atrophy of cerebellum, brainstem, and MCP points strongly to MSA-C. RBD and postural hypotension confirm the diagnosis. Extrapyramidal findings, corticospinal tract signs and PLC are helpful but not necessary for diagnosis. Clarity in early MSA-C diagnosis can prevent unnecessary investigations and facilitate therapeutic trials.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Diagnosis and Natural History of Multiple System Atrophy, Cerebellar Type

2015

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“…The recognition that the non‐motor manifestations often precede the cerebellar or parkinsonian motor features of MSA has led some to label these manifestations as premotor signs and symptoms . However, ILOCA also presents with extra‐motor features, many of which overlap with those observed in MSA‐C.…”

Section: Multiple System Atrophy: a Moving Targetmentioning

confidence: 95%

“…Additional terms have now been applied to this group. For example, Abele and colleagues coined the term “sporadic adult onset ataxias of unknown etiology” (SAOA) to denote a non‐genetic, adult‐onset, sporadic ataxia distinct from MSA . Currently, ILOCA, SAOA, and a host of other terms (Table ) are used to refer to this same group of patients.…”

Section: Multiple System Atrophy: a Moving Targetmentioning

confidence: 99%

“…Abele and colleagues report that the median age of onset of SAOA is 56 years, very similar to MSA‐C, which also presents in the mid‐50s. SAOA also presents with a number of extra‐cerebellar symptoms that overlap with features of MSA, including erectile dysfunction, bladder urgency, dysphagia, snoring, restless leg syndrome, and rapid eye movement sleep behavior disorder . Two independent studies found that adult patients presenting with idiopathic (at the time of presentation) sporadic ataxia evolved to develop MSA approximately 30% of the time (29% in one study and 33% in the other).…”

Section: Multiple System Atrophy: a Moving Targetmentioning

confidence: 99%

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Multiple system atrophy of the cerebellar type: Clinical state of the art

2014

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Multiple system atrophy (MSA) is a late-onset, sporadic neurodegenerative disorder clinically characterized by autonomic failure and either poorly levodopa-responsive parkinsonism or cerebellar ataxia. It is neuropathologically defined by widespread and abundant central nervous system α-synuclein-positive glial cytoplasmic inclusions and striatonigral and/or olivopontocerebellar neurodegeneration. There are two clinical subtypes of MSA distinguished by the predominant motor features: the parkinsonian variant (MSA-P) and the cerebellar variant (MSA-C). Despite recent progress in understanding the pathobiology of MSA, investigations into the symptomatology and natural history of the cerebellar variant of the disease have been limited. MSA-C presents a unique challenge to both clinicians and researchers alike. A key question is how to distinguish early in the disease course between MSA-C and other causes of adult-onset cerebellar ataxia. This is a particularly difficult question, because the clinical framework for conceptualizing and studying sporadic adult-onset ataxias continues to undergo flux. To date, several investigations have attempted to identify clinical features, imaging, and other biomarkers that may be predictive of MSA-C. This review presents a clinically oriented overview of our current understanding of MSA-C with a focus on evidence for distinguishing MSA-C from other sporadic, adult-onset ataxias.

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