Vascular Parkinsonism: deconstructing a syndrome.

Progressive ambulatory impairment and abnormal white matter (WM) signal on neuroimaging come together under the diagnostic umbrella of vascular parkinsonism (VaP). A critical appraisal of the literature, however, suggests that (1) no abnormal structural imaging pattern is specific to VaP; (2) there is poor correlation between brain MRI hyperintensities and microangiopathic brain disease and parkinsonism from available clinicopathologic data; (3) pure parkinsonism from vascular injury ("definite" vascular parkinsonism) consistently results from ischemic or hemorrhagic strokes involving the SN and/or nigrostriatal pathway, but sparing the striatum itself, the cortex, and the intervening WM; and (4) many cases reported as VaP may represent pseudovascular parkinsonism (e.g., Parkinson's disease or another neurodegenerative parkinsonism, such as PSP with nonspecific neuroimaging signal abnormalities), vascular pseudoparkinsonism (e.g., akinetic mutism resulting from bilateral mesial frontal strokes or apathetic depression from bilateral striatal lacunar strokes), or pseudovascular pseudoparkinsonism (e.g., higher-level gait disorders, including normal-pressure hydrocephalus with transependimal exudate). These syndromic designations are preferable over VaP until pathology or validated biomarkers confirm the underlying nature and relevance of the leukoaraiosis. © 2015 International Parkinson and Movement Disorder Society.

The genetics of the dystonias--a review based on the new classification of the dystonias.

The definition and classification of the dystonias was recently revisited. In the new 2013 classification, the dystonias are subdivided in terms of their etiology according to whether they are the result of pathological changes or structural damage, have acquired causes or are inherited. As hereditary dystonias are clinically and genetically heterogeneous, we sought to classify them according to the new recently defined criteria. We observed that although the new classification is still the subject of much debate and controversy, it is easy to use in a logical and objective manner with the inherited dystonias. With the discovery of new genes, however, it remains to be seen whether the new classification will continue to be effective.

The genetics of the dystonias – a review based on the new classification of the dystonias / A genética das distonias – uma revisão baseada na nova classificação das distonias

The definition and classification of the dystonias was recently revisited. In the new 2013 classification, the dystonias are subdivided in terms of their etiology according to whether they are the result of pathological changes or structural damage, have acquired causes or are inherited. As hereditary dystonias are clinically and genetically heterogeneous, we sought to classify them according to the new recently defined criteria. We observed that although the new classification is still the subject of much debate and controversy, it is easy to use in a logical and objective manner with the inherited dystonias. With the discovery of new genes, however, it remains to be seen whether the new classification will continue to be effective.

O conceito e a classificação das distonias foram recentemente revisados. Na nova classificação de 2013, quanto à etiologia, as distonias podem ser subdividas em relação às alterações patológicas, aos danos estruturais, às causas adquiridas e à hereditariedade. Como as distonias hereditárias são clínica e geneticamente heterogêneas, buscamos classifica-las segundo os novos critérios estabelecidos recentemente. Observamos que apesar da nova classificação das distonias ainda ser objeto de discussões e controvérsias, ela pode usada com facilidade, de uma maneira lógica e objetiva, no contexto das distonias hereditárias. Com a descoberta de novos genes poderemos observar se essa classificação continuará sendo efetiva.

Atypical unclassifiable parkinsonism on Guadeloupe: an environmental toxic hypothesis.

We characterize the clinical features of Parkinson's syndrome on Guadeloupe and describe possible environmental causes. Consecutive patients who were referred to the University Hospital at Pointe a Pitre with parkinsonism from September 1996 to May 2002 were included. All cases were examined in a standardized manner by a neurologist with a special interest in movement disorders and independently by 3 external movement disorders specialists, using standard operational clinical diagnostic criteria. The subjects were 265 patients with Parkinson's syndrome living on Guadeloupe, four fifths of whom had been referred by primary care physicians and one fifth by neurologists. The levodopa response was assessed after a minimum period of 1 month of continuous treatment. All patients had brain computed tomography or brain magnetic resonance imaging scans and detailed neuropsychological examinations. Of 265 patients, only 66 were classified as Parkinson's disease, whereas 58 fulfilled the National Institute of Neurological Disorders and Stroke (NINDS) and Society for Progressive Supranuclear Palsy (SPSP) criteria for progressive supranuclear palsy, 100 had unclassifiable parkinsonism, characterized by dopa-unresponsiveness, marked axial rigidity, relative symmetry of parkinsonian features, early dysarthria, and frontolimbic cognitive impairment. Within this group, early postural instability, dysarthria, a frontal behavior disorder, cortical or subcortical atrophy, pyramidal signs, axial rigidity, and family history of neurodegenerative disorders were associated with poorer prognosis. A very large number of unclassifiable cases of atypical parkinsonism that do not fulfill operational criteria for Parkinson's disease or other defined motor neurodegenerations has been observed on Guadeloupe. Most patients closely resemble descriptions of bodig from Guam. In both geographic isolates, an environmental cause has been discussed. Annonaceae fruits and herbal teas are consumed on both islands. These plants contain several neurotoxins, particularly acetogenins, which induce dopaminergic neuron loss in animals. Neuronal death involves cholinergic and dopaminergic cells of the substantia nigra and GABAergic neurons of the striatum, associated with microglial proliferation. The development of atypical parkinsonism in Guadeloupe and probably elsewhere, could result from synergistic toxicity, but acetogenins are probably the most potent neurotoxin, acting as mitochondrial complex I inhibitor.