alpha-synuclein and Urinary-Incontinence

Dementia with Lewy bodies (DLB) is the second most common cause of neurodegenerative dementia in older people that has only been recognized in the past decade and that remains widely underdiagnosed. At postmortem examination, affected patients show numerous alpha-synuclein-positive Lewy bodies (LB) in many parts of the cerebral cortex, particularly neocortical and limbic areas in addition to the nigral LB degeneration characteristic of Parkinson's disease (PD). Clinical presentation, unlike PD, is with progressive cognitive decline with particular deficits of visuospatial ability as well as frontal executive function accompanied by usually only mildly to moderately severe parkinsonism, which is often akineto-rigid without the classical parkinsonian rest-tremor. Further accompanying features include spontaneous recurrent visual hallucinations and conspicuous fluctuations in alertness and cognitive performance. The two main differential diagnoses are Alzheimer's disease (AD) and Parkinson's disease dementia (PDD). To improve the differential diagnosis of DLB, consensus criteria have been developed that establish possible and probable levels of clinical diagnostic accuracy. Generally, their sensitivity is variable and low but their specificity is high. Current consensus is to restrict a diagnosis of DLB only to patients with parkinsonism who develop dementia within 12 months of the onset of motor symptoms. Using operationalized criteria, DLB can be diagnosed clinically with an accuracy similar to that achieved for AD or PD. Ancillary investigations, particularly neuroimaging, can aid in differential diagnosis. We review the present state of the best practice in the clinical diagnosis of DLB. Future modifications of diagnostic criteria would ideally include the full range of clinical presentations that can be associated with LB disease.

Topics: Accidental Falls; Age Factors; Aged; alpha-Synuclein; Alzheimer Disease; Brain; Cerebral Cortex; Cognition Disorders; Diagnosis, Differential; Dysarthria; Electromyography; Hallucinations; Humans; Hypotension, Orthostatic; Lewy Bodies; Lewy Body Disease; Limbic System; Magnetic Resonance Imaging; Parkinson Disease; Substantia Nigra; Urinary Incontinence

Urinary urgency and frequency are common in α-synucleinopathies such as Parkinson disease, Lewy body dementia, and multiple system atrophy. These symptoms cannot be managed with dopamine therapy, and their underlying pathophysiology is unclear. We show that in individuals with Parkinson disease, Lewy body dementia, or multiple system atrophy, α-synuclein pathology accumulates in the lateral collateral pathway, a region of the sacral spinal dorsal horn important for the relay of pelvic visceral afferents. Deposition of α-synuclein in this region may contribute to impaired micturition and/or constipation in Parkinson disease and other α-synucleinopathies.

Topics: Aged; Aged, 80 and over; alpha-Synuclein; Alzheimer Disease; Brain; Female; Humans; Immunohistochemistry; Lewy Body Disease; Lumbar Vertebrae; Male; Middle Aged; Multiple System Atrophy; Parkinson Disease; Sacrum; Spinal Cord; Spinal Cord Dorsal Horn; Thoracic Vertebrae; Urinary Incontinence; Visceral Afferents

We report the case of an elderly man of Greek background who presented with progressive cognitive decline and motor parkinsonism on a background of a strong family history of Parkinson's disease. Associated symptoms included visual hallucinations, excessive daytime drowsiness, recurrent falls, orthostatic hypotension and urinary incontinence. His major clinical symptoms and signs fulfilled consensus criteria for a clinical diagnosis of dementia with Lewy bodies. An alpha-synuclein gene mutation analysis for the G209A substitution was positive. We conclude that the alpha-synuclein (G209A) gene mutation genotype should be considered in the differential diagnosis of dementia with Lewy bodies, particularly in patients with European ancestry and a family history of Parkinson's disease.

Topics: Accidental Falls; Aged; alpha-Synuclein; Cognition Disorders; Diagnosis, Differential; Disease Progression; DNA Mutational Analysis; Fatal Outcome; Genetic Markers; Genetic Predisposition to Disease; Genotype; Greece; Hallucinations; Humans; Hypotension, Orthostatic; Lewy Body Disease; Male; Mutation; Parkinsonian Disorders; Respiratory Tract Infections; Urinary Incontinence