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ABSTRACTBackground:Levodopa is currently the most effective treatment for Parkinson''s disease (PD); however, long-term levodopa therapy often results in motor complications, such as motor fluctuations and dyskinesia. The initial complication is commonly wearing-off, which is the re-emergence of motor and non-motor symptoms before the next scheduled levodopa dose.Objective:The purpose of this article was to review published literature that discusses wearing-off, focusing on the role of the healthcare professional, including the primary care physician, in the effective management of wearing-off.Methods:An electronic literature search was conducted using MEDLINE and EMBASE to find articles discussing wearing-off and its management using the following key words: ‘Parkinson''s disease’; ‘wearing-off’; ‘levodopa’; ‘primary care’.Findings and conclusions:Current evidence indicates that a consistent delivery of levodopa should improve long-term symptomatic efficacy and may prevent or delay motor complications. A number of therapeutic options are available to optimize therapeutic outcome, including modification of the levodopa dose or dosing schedule, switching to another levodopa formulation and the use of adjunct therapies, such as catechol-O-methyl transferase inhibitors, dopamine agonists and monoamine oxidase-B inhibitors. The management of wearing-off is dependent upon the early identification of symptoms and the initiation of effective treatment. Key issues are the need to educate patients and to facilitate good communication with both primary and secondary healthcare professionals. In most cases, patients with PD initially present to primary healthcare professionals who may refer the patient to a neurologist once disease management becomes more complex. However, in many cases, especially in rural areas where neurologists may not be widely available, the primary healthcare professionals may manage the patient throughout the disease course. Limitations of this review include the restricted search criteria and selected search period. [ABSTRACT FROM AUTHOR]

Despite its being one of the most commonly observed neurological disorders, neuropathological studies of essential tremor (ET) are rare. There have been surprisingly few autopsy studies and even fewer case-control comparisons. The primary objective was to describe and quantify the pathological changes in 33 ET and 21 control brains. A secondary objective was to correlate clinical and pathological features. We examined autopsy tissue from the Essential Tremor Centralized Brain Repository. Eight (24.2%) of the 33 ET brains had Lewy bodies in the brainstem, mainly in the locus ceruleus. However, the majority of ET brains (25/33, 75.8%) had no Lewy bodies, but had pathological changes in the cerebellum. The mean number of Purkinje cells per 100× field was reduced in ET cases without Lewy bodies (6.6 ± 2.4 versus 9.6 ± 3.4, P < 0.01), and there were ∼7× more Purkinje cell torpedoes per section (12.6 ± 7.9 versus 1.7 ± 1.4, P < 0.001) compared to controls. ET cases without Lewy bodies also had degeneration of the dentate nucleus (two cases). Other findings in ET cases were Purkinje cell heterotopias and dendrite swellings. Lewy body ET cases were older than ET cases without Lewy bodies. Several trends were observed in ET cases without Lewy bodies, including a younger age of onset of tremor and higher proportions with gait difficulty and family history of ET. The pathological changes of ET seem to be heterogeneous and degenerative. The majority have cerebellar changes without Lewy bodies; a smaller proportion has brainstem Lewy bodies. The clinical differences between cases with versus without Lewy bodies require additional study. [ABSTRACT FROM AUTHOR]