Anthony E Lang

..It outlines answers to a series of questions developed to address all aspects of deep brain stimulation preoperative decision-making...

..2013 Movement Disorder Society...

..This review will highlight these and other issues that must be considered when deciding on the early treatment of PD...

..This randomized controlled clinical trial was designed to confirm initial clinical benefits observed in a small, open-label trial using intraputamenal (Ipu) infusion of recombinant human GDNF (liatermin)...

..Knowledge of the widespread, multisystem nature of the neurodegeneration that accounts for these problems suggests that restoration of the nigrostriatal dopamine system should not be the ultimate goal of future research...

..This article will review the current status of premotor symptoms of Parkinson's disease and discuss their potential for early diagnosis and the design of neuroprotective trials...

..Given the personal and societal impact of these problems, further advances in our understanding of their pathogenesis and the subsequent development of effective therapies are sorely needed...

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..Even if they are eventually found to be distinct disorders, treatments that alter the progression of one may have similar ameliorative effects on the other. Each of these issues are discussed in this selective review of CBD...

..This hypothesis has implications for the development of disease-modifying therapy and the interpretation of endpoints of clinical trials evaluating the efficacy of such treatments...

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..The study also suggests that LFP beta oscillatory activity is generated largely within the dorsal portion of the STN and can produce synchronous oscillatory activity of the local neuronal population...

..Whether these findings are associated with the DBS-PPN clinical effect remains to be proven. However, they suggest that PPN modulation may induce functional changes in neural networks associated with the control of lower limb movements...

..These findings suggest that alterations in both firing rate and firing pattern may underlie the differing motor symptoms associated with these two movement disorders...

..The CTC pathway is involved in the preparation of self-paced but not externally cued movements, although the pathway may still be involved in the execution of these movements...

..Different cortico-subcortical circuits may mediate alpha and beta oscillations. During movement preparation, the motor thalamus and the supplementary motor area predominantly interact in the beta band...

..In the combined mutation carriers the age at onset and clinical course was highly variable and not always younger than in the carriers of LRRK2 G2019S mutations alone...

..This represents the first demonstration that DBS can selectively modulate human sleep, and it supports an important role for the pedunculopontine nucleus region in modulating human REM sleep. Ann Neurol 2009;66:110-114...

..We suspect that individuals employed full time may have a lower threshold for requiring dopaminergic therapy because of occupational demands...

..These preliminary findings suggest a role for 4-8 Hz frequency synchronization in the pathophysiology of dystonia...

..1% at 3 years and 19.2% at 5 years). Anti-PD drugs were significantly reduced by 47.9% at 3 years and 39.8% at 5 years. However, the magnitude of the preoperative response to levodopa did not predict DBS benefit at 3 and 5 years...

..These findings suggest that unilateral subdural motor cortex stimulation may be useful for contralateral hand tremor in selected patients with essential tremor but was not effective in improving parkinsonian signs in our series...

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..017, 0.005). There were no side-to-side differences clinically or in the STN neuronal firing rates and patterns. Bilateral STN DBS is safe and efficacious in improving motor symptoms in patients with prior pallidotomy...

..We conclude that while MCS may be a simpler and safer surgical procedure than DBS of STN, it failed to provide evidence of clear effect on motor performance and movement-related activation pattern in patients with advanced PD...

..Alternatively, these findings may represent endophenotypic abnormalities that predispose to both types of dystonia...

..Cortical activation may be related to the clinical effects of STN DBS in PD...

..The increased focus on these important clinical features represents a major advance in the care of PD patients. In this article, we provide an overview of recent developments in the field...

..The paucity of the literature underscores the need for well-designed studies on psychiatric issues investigating both pathophysiology and clinical outcomes...

..In the present study, preoperative psychiatric symptoms were systematically assessed in patients with PD presenting for routine preoperative psychiatric assessment...

..We tested whether M1 or cerebellar stimulation can reset PD tremor, and investigated the excitability of the CTC pathway in PD...

..To our knowledge, the propositus represents the youngest individual with inherited prion disease described to date...

..Though sample size was small, there was a trend towards a reduction in LID lasting up to 12 years suggesting that posteroventral pallidotomy may provide sustained benefit in reducing LID...

..19). Nevertheless, it remains to be evaluated whether PINK1 variations contribute to the risk of common late onset sporadic PD...

..Abnormal synaptic plasticity in the motor cortex may play a role in the development of LID...

..These include fluctuations in FD symptoms termed motor fluctuations, as well as non-motor symptoms, termed non-motor fluctuations. Here we review the phenomenology and methods of assessing these levodopa-related complications...

..The similarities in the molecular pathology of these four-repeat tauopathies suggests that important advances in the management of one will have a definite impact on the treatment of the other...

..Our focus in clinical care needs to be broadened beyond assessing and treating Parkinsonism, recognizing the impact of mood, cognition and function on HRQOL...

..Mutations in the PTEN-induced kinase (PINK1) gene located within the PARK6 locus on chromosome 1p35-p36 have recently been identified in patients with recessive early-onset Parkinson disease...

..We sought to determine whether STN stimulation could release endogenous striatal dopamine...

..Levodopa, however, normalized speed to a greater extent than amplitude. Our observations suggest that amplitude and speed impairments may be associated with different functional aspects in PD and deserve separate clinical assessment...

..Later-stage features often contribute markedly to disability and impaired quality of life and, therefore, represent an important future therapeutic challenge...

..Even when the electrode is well positioned in the target, the optimization of clinical results depends on careful programming of electrical parameters and changes in antiparkinsonian drug dosages...

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..We found no evidence of systematic seasonal variation in PD incidence by birth date, or of clustering of birth dates during influenza pandemic years in PD patients...

..Our data demonstrate a task-specific improvement of oculomotor deficits in this HD patient with pallidal DBS, supporting a role of GPi in oculomotor control...

..Adjustment of stimulation parameters in GPi DBS may have the potential to optimize the motor response in HD, improving chorea without aggravating bradykinesia...

..CONCLUSIONS: Our data suggest that motor cortical stimulation using these parameters fails to improve the motor disability in MSA. Worsening of motor scores was likely a function of disease progression...

..Furthermore, the findings did reveal a difference between firing patterns in the HD and PD groups, thereby supporting the role of altered firing patterns in the pathophysiology of these diseases...

..Epidemiologic studies consistently link caffeine, a nonselective adenosine antagonist, to lower risk of Parkinson disease (PD). However, the symptomatic effects of caffeine in PD have not been adequately evaluated...

..In conclusion, CBS patients had deficits in intracortical and interhemispheric inhibition in the representations for both distal and proximal upper limb muscles bilaterally with relative sparing of motor cortical output pathways...

..Here, we review novel non-dopaminergic approaches that are in at least phase II clinical development for the treatment of PD...

..Our findings raise the question of whether pathological gambling may in part stem from an impaired capacity of the OFC to guide behavior when facing negative consequences...

..quot; We describe a patient with OT, with postural tremor of the arms and restless legs syndrome (RLS), who developed features typical of progressive supranuclear palsy (PSP). PSP can be accompanied by OT...

..At present, no controlled prospective studies have evaluated this phenomenon, although they are ongoing...

..This observation also highlights the need to perform tasks of bradykinesia in one limb at a time for best accuracy...

..A substantial body of evidence has also accrued to implicate regions outside the striatum in the generation of tics...

..The authors sought to determine the location of deep brain stimulation (DBS) electrodes that were most effective in treating Parkinson disease (PD)...

..We describe two unrelated cases with PINK1 mutations (homozygous nonsense and heterozygous missense) that highlight issues regarding the role of heterozygous mutations and the utility of genetic screening in patient care...

..Our results demonstrate a marginally significant association of GBA mutations with PD and suggest that variations in the GBA gene may constitute a rare susceptibility factor for PD (P = 0.048)...

..Two of five patients with essential tremor had contralateral tremor improvement after ongoing stimulation for 2 years; two developed marked tolerance to DBS...

..Improvements in tremor, rigidity, and bradykinesia were more marked and better sustained over time than improvements in axial symptoms. A good preoperative response to levodopa predicted a good response to surgery...

..We sought to identify and characterize human PGO waves...

..The presence of basal ganglia abnormalities on the preoperative magnetic resonance imaging scan is an indicator of a lesser response to pallidal interventions for dystonia...

..Although the surgical targets were not randomized, there was a trend to a better outcome of motor signs in the STN-DBS patients and fewer adverse events in the GPi-DBS group...

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..The results of this study indicate that early skeletal development in rats is not affected by loss of nigrostriatal dopamine per se, but is markedly attenuated by corticospinal lesions sustained during the neonatal period...

..Aetiology and pathogenesis, biomarker directions, and causal treatment opportunities are discussed for each disease, followed by a brief discussion drawing attention to important translational initiatives...

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..The widely accepted pathophysiological models of dystonia that propose global decreases in basal ganglia output need to be viewed with caution in light of these findings...

..Efficient swallows require well-coordinated tongue movements during bolus flow, but little is known about such movements in Parkinson's disease...

..This may relate to changes in philosophies with respect to starting treatment for Parkinson's disease, but the factors underlying this change remain to be elucidated...

..4%) in contrast with previous reports of 14%. Despite the low incidence, this behavior is disruptive and should be carefully elicited by physicians caring for Parkinson's disease patients...

..Typical antipsychotics are still commonly being chosen as first-line agents for older patients, indicating a need for interventions to improve practice...

..We found no evidence for seasonal fluctuation in the UPDRS scores, suggesting that, although considerable day-to-day variation may exist in PD, there is little monthly or seasonal variation...

..Potential mechanisms implicated in the response of psychosis to antidepressants are discussed...

..CONCLUSION: In families with a dominant inheritance, an additional genetic or environmental cause must coexist with the Ex3Delta40 mutation...

..This report summarizes presentations and discussion dealing with these issues from a one-day symposium involving Canadian Movement Disorders neurologists...

..These findings suggest that DAT SPECT may be useful in differentiating parkinsonism from controls and D2 SPECT in further differentiating MSA from Parkinson's disease and possibly PSP...

..Finally, although apraxia results in clear disability in patients with the CBS, it is not clear how milder ideomotor apraxia found on specific testing contributes to patients' overall day-to-day motor disability...

..Our case study adds to the growing literature on the effects of brain damage on artistic expression in the graphic arts...

..This is only the second report of intragenic deletions with SGCE and it highlights the need to include exonic copy number variation when performing mutational analysis of SGCE...

..The recent observation that deep-brain stimulation of the pedunculopontine nucleus improves axial signs, possibly even in those less responsive to levodopa, brings new hope to the management of advanced Parkinson's disease...

..This case expands the clinical and neuropathological spectrum of DRPLA and supports the hypothesis that aggregates may not be intrinsically pathogenic...

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..These data provide an estimate of the magnitude of the treatment effects and emphasize the need for controlled and randomized studies...

..The frequency of these spells and whether driving should be restricted has yet to be established...

..0097). We found no association between mutation type and phenotype...

..Family history and genetic testing were unrevealing. Neuropathological findings were identical to genetic dentatorubral pallidoluysian (DRPLA) except for the lack of intranuclear inclusions...

..To determine whether concentration of serum urate, a purine metabolite and potent antioxidant that has been linked to a reduced risk of Parkinson disease (PD), predicts prognosis in PD...

..LRRK2-associated PD be distinguished from idiopathic PD; which mutations in LRRK2 are pathogenic; and what is the age-specific cumulative risk of PD for individuals who inherit or are at risk of inheriting a deleterious mutation in LRRK2?..

..000002). Compared to the MMSE, the MoCA may be a more sensitive tool to identify early cognitive impairment in PD...

..Early treatment decisions for individual patients depend largely on the anticipated risk of side effects and long-term complications. Both ropinirole and levodopa are viable treatment options in early PD...

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