Movement Disorders in Chronic Kidney Disease - A Descriptive Review.

OBJECTIVES: The objective of this study is to describe the mechanism of damage to subcortical structures in chronic kidney disease (CKD) and to describe the range of movement disorders associated with CKD. MATERIALS AND METHODS: We have reviewed the Medline literature up to January of 2020 using key words movement disorders and chronic kidney disease. The reviewed articles were studied for mechanisms of subcortical damage in CKD as well as type of the reported movements, their frequency and updated treatment. RESULTS: The search revealed 183 articles most of them dealing with restless legs syndrome. The damage to basal ganglia in CKD resulted from several mechanisms including accumulation of nitro tyrosine caused by reactive oxygen species and action of uremic toxins leading to endothelial damage and dysfunction of blood-brain barrier. Involuntary movements in CKD include restless legs syndrome (RLS), myoclonus, asterixis, dystonia, chorea, tremor, and Parkinsonism. CONCLUSIONS: Chronic kidney disease can cause several abnormal involuntary movements via damaging basal ganglia and subcortical structures. The most common movement disorders in CKD are RLS, myoclonus and asterixis. Restless legs syndrome and myoclonus when severe, need and respond to treatment. Movement disorders in CKD improve with improvement of kidney function.

Long-term safety and efficacy of deutetrabenazine for the treatment of tardive dyskinesia.

OBJECTIVE: To evaluate the long-term safety and efficacy of deutetrabenazine in patients with tardive dyskinesia (TD). METHOD: Patients with TD who completed the 12 week, phase 3, placebo-controlled trials were eligible to enter this open-label, single-arm study. The open-label study consisted of a 6 week dose-escalation phase and a long-term maintenance phase (clinic visits at Weeks 4, 6 and 15, and every 13 weeks until Week 106). Patients began deutetrabenazine at 12 mg/day, titrating up to a dose that was tolerable and provided adequate dyskinesia control, based on investigator judgement, with a maximum allowed dose of 48 mg/day (36 mg/day for patients taking strong cytochrome P450 2D6 (CYP2D6) inhibitors). Safety measures included incidence of adverse events (AEs) and scales used to monitor parkinsonism, akathisia/restlessness, anxiety, depression, suicidality and somnolence/sedation. Efficacy endpoints included the change in Abnormal Involuntary Movement Scale (AIMS) score (items 1 to 7) from baseline and the proportion of patients rated as 'Much Improved' or 'Very Much Improved' on the Clinical Global Impression of Change. RESULTS: A total of 343 patients enrolled in the extension study, and there were 331 patient-years of exposure in this analysis. The exposure-adjusted incidence rates of AEs with long-term treatment were comparable to or lower than those observed in the phase 3 trials. The mean (SE) change in AIMS score was -4.9 (0.4) at Week 54 (n = 146), - 6.3 (0.7) at Week 80 (n = 66) and -5.1 (2.0) at Week 106 (n = 8). CONCLUSIONS: Overall, long-term treatment with deutetrabenazine was efficacious, safe, and well tolerated in patients with TD. TRIAL REGISTRATION NUMBER: NCT02198794.

Trihexyphenidyl for dystonia in cerebral palsy.

BACKGROUND: Cerebral palsy occurs in up to 2.1 of every 1000 live births and encompasses a range of motor problems and movement disorders. One commonly occurring movement disorder amongst those with cerebral palsy is dystonia: sustained or intermittent involuntary muscle spasms and contractions that cause twisting, repetitive movements and abnormal postures. The involuntary contractions are often very painful and distressing and cause significant limitations to activity and participation.Oral medications are often the first line of medical treatment for dystonia. Trihexyphenidyl is one such medication that clinicians often use to treat dystonia in people with cerebral palsy. OBJECTIVES: To assess the effects of trihexyphenidyl in people with dystonic cerebral palsy, according to the World Health Organization's (WHO) International Classification of Functioning, Disability and Health (ICF) domains of impairment, activity and participation. We also assessed the type and incidence of adverse effects in people taking the drug. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, eight other databases and two trials registers in May 2017, and we checked reference lists and citations to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials comparing oral trihexyphenidyl versus placebo for dystonia in cerebral palsy. We included studies in children and adults of any age with dystonic cerebral palsy, either in isolation or with the associated movement disorders of spasticity, ataxia, chorea, athetosis and/or hypotonia. We included studies regardless of whether or not the study authors specified the method used to diagnose dystonia in their study population. Primary outcomes were change in dystonia and adverse effects. Secondary outcomes were: activity, including mobility and upper limb function; participation in activities of daily living; pain; and quality of life. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We identified one study, which was set in Australia, that met the inclusion criteria. This was a randomised, double-blind, placebo-controlled, cross-over trial in 16 children (10 boys and 6 girls) with predominant dystonic cerebral palsy and a mean age of 9 years (standard deviation 4.3 years, range 2 to 17 years). We considered the trial to be at low risk of selection, performance, detection, attrition, reporting and other sources of bias. We rated the GRADE quality of the evidence as low.We found no difference in mean follow-up scores for change in dystonia as measured by the Barry Albright Dystonia Scale (BADS), which assesses eight body regions for dystonia on a 5-point scale (0 = none to 4 = severe), resulting in a total score of 0 to 32. The BADS score was 2.67 points higher (95% confidence interval (CI) -2.55 to 7.90; low-quality evidence), that is, worse dystonia, in the treated group. Trihexyphenidyl may be associated with an increased risk of adverse effects (risk ratio 2.54, 95% CI 1.38 to 4.67; low-quality evidence).There was no difference in mean follow-up scores for upper limb function as measured by the Quality of Upper Extremity Skills Test, which has four domains that collectively assess 36 items (each scored 1 or 2) and produces a total score of 0 to 100. The score in the treated group was 4.62 points lower (95% CI -10.98 to 20.22; low-quality evidence), corresponding to worse function, than in the control group. We found low-quality evidence for improved participation (as represented by higher scores) in the treated group in activities of daily living, as measured by three tools: 18.86 points higher (95% CI 5.68 to 32.03) for the Goal Attainment Scale (up to five functional goals scored on 5-point scale (-2 = much less than expected to +2 = much more than expected)), 2.91 points higher (95% CI 1.01 to 4.82) for the satisfaction subscale of the Canadian Occupational Performance Measure (COPM; satisfaction with performance in up to five problem areas scored on a 10-point scale (1 = not satisfied at all to 10 = extremely satisfied)), and 2.24 points higher (95% CI 0.64 to 3.84) for performance subscale of the COPM (performance in up to five problem areas scored on a 10-point scale (1 = not able to do to; 10 = able to do extremely well)).The study did not report on pain or quality of life. AUTHORS' CONCLUSIONS: At present, there is insufficient evidence regarding the effectiveness of trihexyphenidyl for people with cerebral palsy for the outcomes of: change in dystonia, adverse effects, increased upper limb function and improved participation in activities of daily living. The study did not measure pain or quality of life. There is a need for larger randomised, controlled, multicentre trials that also examine the effect on pain and quality of life in order to determine the effectiveness of trihexyphenidyl for people with cerebral palsy.

Non-antipsychotic catecholaminergic drugs for antipsychotic-induced tardive dyskinesia.

BACKGROUND: Tardive dyskinesia (TD) is a disabling movement disorder associated with the prolonged use of antipsychotic medication. Several strategies have been examined in the treatment of TD. Currently, however, there is no clear evidence of the effectiveness of these drugs in TD and they have been associated with many side effects. One particular strategy would be to use pharmaceutical agents which are known to influence the catecholaminergic system at various junctures. OBJECTIVES: 1. To determine the effects of any of the following drugs for antipsychotic-induced TD in people with schizophrenia or other chronic mental illnesses.i. Drugs which influence the noradrenergic system.ii. Dopamine receptor agonists.iii. Dopamine receptor antagonists.iv. Dopamine-depletor drugs.v. Drugs that increase the production or release of dopamine.2. To examine whether any improvement occurred with short periods of intervention (less than 6 weeks) and, if this did occur, whether this effect was maintained at longer periods of follow-up.3. To examine if there was a differential effect for the various compounds.4. To examine whether the use of non-antipsychotic catecholaminergic drugs are most effective in those with more recent onset TD (less than five years). SEARCH METHODS: We retrieved 712 references from searching the Cochrane Schizophrenia Group Trials Register (July 2015 and April 2017). We also inspected references of all identified studies for further trials and contacted authors of trials for additional information. SELECTION CRITERIA: We selected studies if they were randomised controlled trials focusing on people with schizophrenia or other chronic mental illnesses and antipsychotic-induced tardive dyskinesia. We compared the use of catecholaminergic interventions versus placebo, no intervention, or any other intervention for the treatment of antipsychotic-induced tardive dyskinesia. DATA COLLECTION AND ANALYSIS: We independently extracted data from these trials and we estimated risk ratios (RRs) with 95% confidence intervals (CIs). We assumed that people who left the studies early had no improvement. MAIN RESULTS: There are 10 included trials (N = 261) published between 1973 and 2010; eight are new from the 2015 and 2017 update searches. Forty-eight studies are excluded. Participants were mostly chronically mentally ill inpatients in their 50s, and studies were primarily of short (2 to 6 weeks) duration. The overall risk of bias in these studies was unclear, mainly due to poor reporting of allocation concealment and generation of the sequence. Studies were also not clearly blinded and we are unsure if data are incomplete or selectively reported, or if other biases were operating.One small, three-arm trial found that both alpha-methyldopa (N = 20; RR 0.33, 95% CI 0.14 to 0.80; low-quality evidence) and reserpine (N = 20; RR 0.52 95% CI 0.29 to 0.96; low-quality evidence) may lead to a clinically important improvement in tardive dyskinesia symptoms compared with placebo after 2 weeks' treatment, but found no evidence of a difference between alpha-methyldopa and reserpine (N = 20; RR 0.60, 95% CI 0.19 to 1.86; very low quality evidence). Another small trial compared tetrabenazine and haloperidol after 18 weeks' treatment and found no evidence of a difference on clinically important improvement in tardive dyskinesia symptoms (N = 13; RR 0.93, 95% CI 0.45 to 1.95; very low quality evidence). No study reported on adverse events.For remaining outcomes there was no evidence of a difference between any of the interventions: alpha-methyldopa versus placebo for deterioration of tardive dyskinesia symptoms (1 RCT; N = 20; RR 0.33, 95% CI 0.02 to 7.32; very low quality evidence), celiprolol versus placebo for leaving the study early (1 RCT; N = 35; RR 5.28, 95% CI 0.27 to 102.58; very low quality evidence) and quality of life (1 RCT; N = 35; RR 0.87, 95% CI 0.68 to 1.12; very low quality evidence), alpha-methyldopa versus reserpine for deterioration of tardive dyskinesia symptoms (1 RCT; N = 20; not estimable, no reported events; very low quality evidence), reserpine or carbidopa/levodopa versus placebo for deterioration of tardive dyskinesia symptoms (2 RCTs; N = 37; RR 1.18, 95% CI 0.35 to 3.99; very low quality evidence), oxypertine versus placebo for deterioration of mental state (1 RCT; N = 42; RR 2.20, 95% CI 0.22 to 22.45; very low quality evidence), dopaminergic drugs (amantadine, bromocriptine, tiapride, oxypertine, carbidopa/levodopa) versus placebo for leaving the study early (6 RCTs; N = 163; RR 1.29, 95% CI 0.65 to 2.54; very low quality evidence), and tetrabenazine versus haloperidol for deterioration of tardive dyskinesia symptoms (1 RCT; N = 13; RR 1.17, 95% CI 0.09 to 14.92) and leaving the study early (1 RCT; N = 13; RR 0.23, 95% CI 0.01 to 4.00). AUTHORS' CONCLUSIONS: Although there has been a large amount of research in this area, many studies were excluded due to inherent problems in the nature of their cross-over designs. Usually data are not reported before the cross-over and the nature of TD and its likely response to treatments make it imprudent to use this data. The review provides little usable information for service users or providers and more well-designed and well-reported studies are indicated.

Functional activity of the sensorimotor cortex and cerebellum relates to cervical dystonia symptoms.

Cervical dystonia (CD) is the most common type of focal dystonia, causing abnormal movements of the neck and head. In this study, we used noninvasive imaging to investigate the motor system of patients with CD and uncover the neural correlates of dystonic symptoms. Furthermore, we examined whether a commonly prescribed anticholinergic medication in CD has an effect on the dystonia-related brain abnormalities. Participants included 16 patients with CD and 16 healthy age-matched controls. We collected functional MRI scans during a force task previously shown to extensively engage the motor system, and diffusion and T1-weighted MRI scans from which we calculated free-water and brain tissue densities. The dystonia group was also scanned ca. 2 h after a 2-mg dose of trihexyphenidyl. Severity of dystonia was assessed pre- and post-drug using the Burke-Fahn-Marsden Dystonia Rating Scale. Motor-related activity in CD was altered relative to controls in the primary somatosensory cortex, cerebellum, dorsal premotor and posterior parietal cortices, and occipital cortex. Most importantly, a regression model showed that increased severity of symptoms was associated with decreased functional activity of the somatosensory cortex and increased activity of the cerebellum. Structural imaging measures did not differ between CD and controls. The single dose of trihexyphenidyl altered the fMRI signal in the somatosensory cortex but not in the cerebellum. Symptom severity was not significantly reduced post-treatment. Findings show widespread changes in functional brain activity in CD and most importantly that dystonic symptoms relate to disrupted activity in the somatosensory cortex and cerebellum. Hum Brain Mapp 38:4563-4573, 2017. © 2017 Wiley Periodicals, Inc.

Status dystonicus in childhood.

PURPOSE OF REVIEW: Dystonia is a common paediatric neurological condition. At its most severe, dystonia may lead to life-threatening complications, a state termed status dystonicus. This review provides an update on the definition, causes, management and outcome of childhood status dystonicus. RECENT FINDINGS: High-quality studies in childhood status dystonicus are lacking, though an increasing number of case series have been published. Status dystonicus appears to occur more frequently in children compared with adults, with a clear precipitant identified in around two-thirds of cases. Although febrile illness remains the commonest trigger for status dystonicus, unplanned interruption to deep brain stimulation (DBS) is increasingly reported as a precipitant. In parallel with this, neurosurgical intervention for status dystonicus appears to have become more widely used, though optimum timing and patient selection remains unclear. In most cases, a multistaged approach is required; we propose an 'ABCD' approach - Addressing precipitants, Beginning supportive measures, Calibrating sedation and Dystonia specific medications. Outcomes following status dystonicus appear to have slightly improved in recent years, potentially as a consequence of increasing use of DBS, though mortality has remained around 10%. SUMMARY: Future work is needed to inform evidence-based guidelines for the management of status dystonicus. One of many pressing questions is the precise indication, and timing of interventions such as DBS.

Advances in pharmacotherapies for movement disorders in children: current limitations and future progress.

PURPOSE OF REVIEW: In childhood, movement disorders are generated by a very large number of disorders of the nervous system, and the very different developmental ages at which these occur make studies of pharmacotherapy efficacy extremely difficult. In most clinical practices, medication used in management is by trial and error, and limited by lack of efficacy and/or adverse drug reactions leading to drug intolerance. Nevertheless, symptom reduction using polypharmacy must be balanced against any accompanying comorbidities such as poor attention and concentration, constipation, ileus, urinary retention, blurred vision sedation and respiratory depression. RECENT FINDINGS: A 'personalised medicine' approach may lead to specific management breakthroughs that are beneficial to a wider number of children. At present, neuromodulation with implantable devices offers greater proven efficacy for dystonia, myoclonus and dystonic-choreoathetosis, but enteral, intravenous and, more recently, transdermal medication strategies with clonidine patches and enteral gabapentin may provide important relief for both home management and critical care settings. SUMMARY: The current review brings the clinician up-to-date with the latest, albeit limited, thinking on the pharmacological management of movement disorders in children by focussing on goal-directed outcome measures to improve clinical decision-making in an evidence-light clinical setting.

Delayed onset diabetic striatopathy: Hemichorea-hemiballism one month after a hyperglycemic episode.

Diabetic striatopathy is an uncommon and life threatening manifestation of diabetes mellitus. It has a tendency to occur in the elderly, female and people of Asian descent. Patients usually present with hemichorea-hemiballism caused by non-ketotic hyperglycemia. However, patients could develop diabetic striatopathy weeks after the hyperglycemic event, even when blood sugar has been well controlled. Herein, we report a case of delayed onset diabetic striatopathy and discuss the importance of detailed history and brain magnetic resonance imaging for making prompt and accurate diagnosis.

[Therapy of Hemifacial Spasm with Botulinum Toxin]. / Therapie des Spasmus hemifacialis mit Botulinumtoxin.

Hemifacial spasm (HFS) is a frequent disorder characterized by involuntary contractions of those muscles innervated by the facialis nerve on one side of the face. The symptoms can appear as tonic or clonic, intermittent or permanent. Diagnosis is based purely on clinical observation. Differential diagnosis should rely on cranial MRI, which can demonstrate a pathological contact between the nerves and vessels and exclude alternative causation. Often, the symptoms are not marked so that therapy may not be necessary. The therapy of choice is an injection of botulinum toxin to reduce the underlying pathological activity. As an alternative, decompression operation according to Jannetta can be considered, although it is frequently rejected by patients.

[Treatment of laryngeal dystonia with botulinum toxin]. / Die Behandlung der laryngealen Dystonie mit Botulinumtoxin.

The treatment of laryngeal dystonias with botulinum toxin is successful. Every patient suffering from a laryngeal dystonia should be assured of high quality therapeutic intervention. Therefore it is important to establish general standards by experts in this field. In this connection, we want to focus here on different relevant aspects of laryngeal dystonias. This includes new aspects in etiology, anatomical landmarks for the injection, standards in diagnostics and therapy and finally open issues needing discussion.

Multimodal Drug Therapy and Physical Rehabilitation in the Successful Treatment of Capture Myopathy in a Lesser Flamingo (Phoeniconaias minor).

A wild-caught lesser flamingo (Phoeniconaias minor) from the Fort Worth Zoo (Fort Worth, TX, USA) presented with moderate lameness that progressed to the inability to stand 2 days after restraint and handling. Results of blood tests showed severely elevated creatine phosphokinase (CPK) and aspartate aminotransferase (AST) activities, confirming suspected capture myopathy. Intensive supportive therapy, consisting of intravenous fluids and muscle relaxants, along with physical rehabilitation therapy, nutritional support, and anxiolytics, were instituted to aid in relaxation and muscle regeneration. After 2 weeks of intensive therapy, the bird showed substantial improvement and could remain standing throughout the day after being assisted to a standing position. By day 23, the bird was able to stand independently and walk completely unassisted, with no discernible lameness. The bird has subsequently remained healthy since it was returned to the flock approximately 27 days after it was first presented for treatment. Although anecdotal communications of successful treatment of this condition in flamingos exist, this is the first report, to our knowledge, that describes in detail the successful treatment of capture myopathy in any flamingo species. Success in this case is attributed to the combination of early fluid and drug therapy, intensive physical rehabilitation therapy, and anxiolytics to counteract the hyperexcitable nature of this wild-caught bird.

Ultrasound-guided botulinum toxin A injection in the treatment of belly dancer's dyskinesia.

BACKGROUND: Belly dancer's dyskinesia is an extremely rare condition. It manifests as semicontinuous, slow, writhing, sinuous abdominal wall movements that are bothersome to the patient. Management of this condition is extremely difficult and challenging. METHODS: We describe four patients with belly dancer's dyskinesia who were treated with Botulinum Toxin A (BTX) injections under ultrasound guidance. RESULTS: All patients underwent the same BTX injection procedure using an aseptic technique under ultrasound guidance. The patients responded well to the BTX injections after an unsatisfactory course of medical treatment. The patients reported complete abolishment of abnormal abdominal movements with no side effects. CONCLUSIONS: We report a cohort of patients with belly dancer dyskinesia treated successfully with BTX injections. Ultrasound guidance for injections increases the accuracy and reduces the risk of the complications. BTX injection under ultrasound guidance is a safe and effective treatment modality that should be employed as a first-line in the management of patients with belly dancer's dyskinesia.

Hemichorea with unilateral MRI striatal hyperintensity in a Saudi patient with diabetes.

Hemichorea is a disorder characterized by abnormal, continuous, nonrhythmic, jerky, and distal movement involving one side of the body. It may result from cerebrovascular insult to basal ganglia, or from other causes including neoplasm, infection, and non-ketotic hyperglycemia. We report the clinical, laboratory, and neuroimaging data with treatment response of a Saudi woman who has diabetes with left side hemichorea, involving the face, and upper and lower extremities, with unilateral right striatal hyperintense signal changes in T1 weighted MRI, and a hyperglycemic state of longstanding uncontrolled diabetes. Literature review suggested a syndrome with a triad of symptoms: non-ketotic hyperglycemia, hemichorea, and T1 MRI striatal hyperintensities. As the number of internationally reported cases is still modest, reporting more patients will highlight aspects pertaining to the diagnosis and treatment of this condition. We present a patient who had a sustained therapeutic result from haloperidol and clonazepam.

[Focal dystonia in musicians: Phenomenology and musical triggering factors]. / Distonía del músico: fenomenología y desencadenantes vinculados a la ejecución musical.

Dystonias are defined as a joint sustained and involuntary contraction of agonist and antagonist muscles, which can cause torsion, repetitive abnormal involuntary movements, and/or abnormal postures. One special group of dystonias are those known as occupational, which include dystonia disorders triggered by a repetitive motor activity associated with a specific professional activity or task. Musicians are a population particularly vulnerable to these types of dystonia, which are presented as a loss of coordination and voluntary motor control movements highly trained in musical interpretation. Our aim is to describe a clinical series of focal dystonias in musicians evaluated and treated in our centre. PATIENTS AND METHODS: Data is presented on a clinical series of 12 musicians with occupational dystonia. Their history and phenomenology are described, as well as well as their outcome after therapy. RESULTS: Demographic details: Mean age 34.8 ± 11.8 years, 10 males (83.3%) and 2 females (16.7%). CLINICAL HISTORY: History of trauma in dystonic segment, 6 patients (50%); family history of neurological diseases in first-degree relatives, 6 patients (50%); occupational history according to music category, 8 patients (66.6%) were classical musicians and 4 patients (33.3%) were popular musicians. PHENOMENOLOGY: The dystonia syndrome was characterised by having a mean age of onset of 28.2 ± 11.3 years (range 18-57 years). The segment affected was the hand (91.7%) in 11 patients. Of all the musicians seen in the clinic, 9 of them (75%) received therapy. The majority of patients appeared to have triggering factors specific to musical execution and linked to the requirement of fine motor control. It should be mentioned that 50% of the musicians treated maintained their professional activity or position in the orchestra to which they belonged. CONCLUSIONS: The majority of our phenomenological findings are consistent with those reported in the current literature. However, it is worth mentioning the presence of triggering factors attributed to the specific requirements of performing music, linked to the participation of fine motor control.

The anti-dyskinetic effect of dopamine receptor blockade is enhanced in parkinsonian rats following dopamine neuron transplantation.

Graft-induced dyskinesia (GID) is a serious complication induced by dopamine (DA) cell transplantation in parkinsonian patients. We have recently shown that DA D2 receptor blockade produces striking blockade of dyskinesia induced by amphetamine in grafted 6-OHDA-lesioned rats, a model of GID. This study was designed to investigate whether blockade of DA D1 receptors could produce similar outcome, and to see whether the effect of these treatments in grafted rats was specific for dyskinesia induced by amphetamine, or could also influence L-DOPA-induced dyskinesia (LID). L-DOPA-primed rats received transplants of fetal DA neurons into the DA-denervated striatum. Beginning at 20weeks after transplantation rats were subjected to pharmacological treatments with either L-DOPA (6mg/kg) or amphetamine (1.5mg/kg) alone, or in combination with the D1 receptor antagonist SCH23390, the D2 receptor antagonist eticlopride, and the 5-HT1A agonist/D2 receptor antagonist buspirone. Grafted rats developed severe GID, while LID was reduced. Both eticlopride and SCH23390 produced near-complete suppression of GID already at very low doses (0.015 and 0.1mg/kg, respectively). Buspirone induced similar suppression at a dose as low as 0.3mg/kg, which is far lower than the dose known to affect LID in non-grafted dyskinetic rats. In agreement with our previous results, the effect of buspirone was independent from 5-HT1A receptor activation, as it was not counteracted by the selective 5-HT1A antagonist WAY100635, but likely due to D2 receptor blockade. Most interestingly, the same doses of eticlopride, SCH23390 and buspirone were found to suppress LID in grafted but not in control dyskinetic rats. Taken together, these data demonstrate that the DA cell grafts strikingly exacerbate the effect of DA D1 and D2 receptor blockade against both GID and LID, and suggest that the anti-GID effect of buspirone seen in patients may also be due to blockade of DA D2 receptors.

Oleoylethanolamide reduces L-DOPA-induced dyskinesia via TRPV1 receptor in a mouse model of Parkinson´s disease.

The long-term use of levodopa (L-DOPA) in Parkinson's disease (PD) results in the development of abnormal involuntary movements called L-DOPA-induced dyskinesias. Increasing evidences suggest that the endocannabinoid system may play a role in the modulation of dyskinesias. In this work, we assessed the antidyskinetic effect of the endocannabinoid analog oleoylethanolamide (OEA), an agonist of PPARα and antagonist of TRPV1 receptors. We used a hemiparkinsonian model of PD in mice with 6-OHDA striatal lesion. The chronic L-DOPA treatment developed intense axial, forelimb and orolingual dyskinetic symptoms, as well as contralateral rotations. Treatment with OEA reduced all these symptoms without reducing motor activity or the therapeutic motor effects of L-DOPA. Moreover, the OEA-induced reduction in dyskinetic behavior correlated with a reduction in molecular correlates of dyskinesia. OEA reduced FosB striatal overexpression and phosphoacetylation of histone 3, both molecular markers of L-DOPA-induced dyskinesias. We found that OEA antidyskinetic properties were mediated by TRPV1 receptor, as pretreatment with capsaicin, a TRPV1 agonist, blocked OEA antidyskinetic actions, as well as the reduction in FosB- and pAcH3-overexpression induced by L-DOPA. This study supports the hypothesis that the endocannabinoid system plays an important role in the development and expression of dyskinesias and might be an effective target for the treatment of L-DOPA-induced dyskinesias. Importantly, there was no development of tolerance to OEA in any of the parameters we examined, which has important implications for the therapeutic potential of drugs targeting the endocannabinoid system.

Consensus paper: management of degenerative cerebellar disorders.

Treatment of motor symptoms of degenerative cerebellar ataxia remains difficult. Yet there are recent developments that are likely to lead to significant improvements in the future. Most desirable would be a causative treatment of the underlying cerebellar disease. This is currently available only for a very small subset of cerebellar ataxias with known metabolic dysfunction. However, increasing knowledge of the pathophysiology of hereditary ataxia should lead to an increasing number of medically sensible drug trials. In this paper, data from recent drug trials in patients with recessive and dominant cerebellar ataxias will be summarized. There is consensus that up to date, no medication has been proven effective. Aminopyridines and acetazolamide are the only exception, which are beneficial in patients with episodic ataxia type 2. Aminopyridines are also effective in a subset of patients presenting with downbeat nystagmus. As such, all authors agreed that the mainstays of treatment of degenerative cerebellar ataxia are currently physiotherapy, occupational therapy, and speech therapy. For many years, well-controlled rehabilitation studies in patients with cerebellar ataxia were lacking. Data of recently published studies show that coordinative training improves motor function in both adult and juvenile patients with cerebellar degeneration. Given the well-known contribution of the cerebellum to motor learning, possible mechanisms underlying improvement will be outlined. There is consensus that evidence-based guidelines for the physiotherapy of degenerative cerebellar ataxia need to be developed. Future developments in physiotherapeutical interventions will be discussed including application of non-invasive brain stimulation.

Cerebellar and parkinsonian phenotypes in multiple system atrophy: similarities, differences and survival.

Multiple system atrophy (MSA) is a neurodegenerative disease with two motor phenotypes: parkinsonian (MSA-P) and cerebellar (MSA-C). To elucidate whether in addition to the motor abnormalities there are other significant differences between these phenotypes, we performed a retrospective review of 100 patients (61 males, 39 females) with a diagnosis of possible (12 %), or probable (88 %) MSA. Four patients eventually had post-mortem confirmation (i.e., definite MSA). Sixty percent were classified as having MSA-P and 40 % as MSA-C. MSA-C and MSA-P patients had similar male prevalence (60 %), age of onset (56 ± 9 years), and frequency of OH (69 %). Brain MRI abnormalities were more frequent in MSA-C patients (p < 0.001). Mean survival was 8 ± 3 years for MSA-C and 9 ± 4 years for MSA-P patients (p = 0.22). Disease onset before 55 years predicted longer survival in both phenotypes. Initial autonomic involvement did not influence survival. We conclude that patients with both motor phenotypes have mostly similar survivals and demographic distributions. The differences here identified could help counseling of patients with MSA.

Update on treatments for dystonia.

Oral medication, botulinum toxin injections, and deep brain stimulation are the current mainstays of treatment for dystonia. In addition, physical and other supportive therapies may help prevent further complications (eg, contractures) and improve function. This review discusses evidence-based medical treatment of dystonia with an emphasis on recent advances in treatment. We will also review the current treatment approaches and suggest ways in which these therapies can be applied to individuals with dystonia.