Progressive supranuclear palsy (PSP) is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common being Alzheimer’s disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 PSP cases and 3,247 controls (Stage 1) followed up by a second stage where 1,051 cases and 3,560 controls were genotyped for Stage 1 SNPs that yielded P ≤ 10−3. We found significant novel signals (P < 5 × 10−8) associated with PSP risk at STX6, EIF2AK3, and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response, and for a myelin structural component.

Levodopa-induced dyskinesias (LID) are common and difficult to treat. This review focuses on three issues related to LID: clinical features, classification and rating, pathophysiology and pathogenesis, and management. The three primary clinical syndromes are OFF-period dystonia, peak-dose dyskinesia, and diphasic dyskinesia. Several other forms also occur, making the evaluation and choice of treatment complicated. A core component of the pathophysiology of LID is overactivity of the direct striatal output pathway. This pathway provides a direct GABAergic connection by which the striatum inhibits the output regions of the basal ganglia, i.e., the internal globus pallidus and the substantia nigra pars reticulata. Altering dopaminergic dosing and timing can abate dyskinesias, but usually impact the control of parkinsonism. Putative therapies to reduce the problem of dyskinesias could focus on the glutamatergic, GABAergic, alpha2 adrenergic, serotonergic (5HT1A, 5HT2A), opioid, histamine H3, adenosine A2A receptors, the monoamine transport or cannabinoid CB1 receptors systems. The only currently available drug with an evidence-based recommendation on efficacy for dyskinesia is amantadine. Therapy goals include the prevention of dyskinesia and treatment of dyskinesias that are troublesome clinically. New rating measures to assess severity and disability related to dyskinesia are in the process of development and clinimetric testing.

Objective: To summarize the 2010 EFNS/MDS-ES evidence-based treatment recommendations for the management of Parkinson's disease (PD). This summary includes the treatment recommendations for early and late PD. Methods: For the 2010 publication, a literature search was undertaken for articles published up to September 2009. For this summary, an additional literature search was undertaken up to December 2010. Classification of scientific evidence and the rating of recommendations were made according to the EFNS guidance. In cases where there was insufficient scientific evidence, a consensus statement ('good practice point') is made. Results and Conclusions:: For each clinical indication, a list of therapeutic interventions is provided, including classification of evidence.

PINK1 homozygous mutations are a relevant cause of disease among Italian sporadic patients with early-onset parkinsonism. The role of mutations found in single heterozygous state is difficult to interpret. Our study suggests that, at least in some patients, these mutations are disease causing, in combination with additional, still unknown factors.

We confirm that ATP13A2 homozygous mutations are associated with human parkinsonism, and expand the associated genotypic and clinical spectrum, by describing a homozygous missense mutation in this gene in a patient with a phenotype milder than that initially associated with ATP13A2 mutations (Kufor-Rakeb syndrome). Our data also suggest that ATP13A2 single heterozygous mutations might be etiologically relevant for patients with YOPD and further studies of this gene in Parkinson disease are warranted.

Unilateral cranial autonomic symptoms (UAs) such as lacrimation, conjunctival injection, eyelid oedema and nasal congestion, which are the hallmark of trigeminal autonomic cephalgias, may also occur in an as yet undetermined proportion of migraine patients. We studied 177 consecutive migraineurs to assess the frequency of UAs and the clinical characteristics of such patients. UAs were reported by 81 patients (45.8%), ocular symptoms alone or in combination with nasal symptoms being the most frequent. The headache was more severe (P<0.0002) and more strictly unilateral (P<0.0004) in patients who reported UAs than in those without. Thus, the presence of UAs suggests an activation of the trigeminal-autonomic reflex, probably related to an over-activation of the trigeminal afferent arm. These findings could have therapeutic implications, given the potential large-scale recruitment of peripheral neurovascular 5-HT(1B/1D) receptors (the target of acute migraine treatment) in such patients.

27 patients with essential tremor (ET) were studied to determine the cognitive feature of this condition. 15 familial cases and 12 cases with a family history Parkinson's disease (PD) were identified. Performances on frontal lobe tasks of ET patients were compared with those of 15 patients with PD and 15 healthy control subjects. The ET patients showed significant impairments both in attentional and conceptual thinking tasks, similar to those observed in the PD group. Despite the nosographic independence of the two conditions, data showed that the frontal lobe feature of ET was similar to those of PD, thus possibly suggesting a common dysregulation of dopamine pathways.

To determine whether pain is more frequent among people with Parkinson disease (PD) than among age-matched controls.