Chorea-ballism as a dominant clinical manifestation in heteroplasmic mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome with A3251G mutation in mitochondrial genome: a case report.

BACKGROUND: Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes, the most common maternally inherited mitochondrial disease, can present with a wide range of neurological manifestations including both central and peripheral nervous system involvement. The most frequent genetic mutation reported in mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome is A3243G in MT-TL1 gene. Stroke-like episodes, dementia, epilepsy, lactic acidemia, myopathy, recurrent headaches, hearing impairment, diabetes, and short stature constitute the known presentations in this syndrome. Among the abnormal involuntary movements in mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome, myoclonus is the commonest. Other movement disorders, including chorea, are rarely reported in this disorder. CASE PRESENTATION: A 14-year-old South Asian boy from rural Bengal (India), born of a second degree consanguineous marriage, with normal birth and development history, presented with abnormal brief jerky movements involving his trunk and limbs, with recurrent falls for 10 months. We present here a case of heteroplasmic mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome with A3251G mutation, in which the clinical picture was dominated by a host of involuntary abnormal movements including chorea-ballism, myoclonus, and oromandibular dystonia in a backdrop of cognitive decline, seizure, and stroke-like episode. A final diagnosis was established by muscle biopsy and genetic study. Haloperidol was administered to control the involuntary movements along with introduction of co-enzyme Q, besides symptomatic management for his focal seizures. Six months into follow-up his seizures and abnormal movements were controlled significantly with slight improvement of cognitive abilities. CONCLUSION: The dominance of hyperkinetic movements in the clinical scenario and the finding of a point mutation A3251G in MT-TL1 gene make this a rare presentation.

Chorea revealing systemic lupus erythematosus in a 13-year old boy: A case report and short review of the literature.

Among the neurological manifestations of systemic lupus erythematosus (SLE), chorea is rare, presenting in less than 7% of the pediatric SLE patients. It can appear early in the onset of SLE, be the first or even the sole clinical feature of the illness and has strongly been associated with the presence of antiphospholipid antibodies. We report on the case of a 13-year old boy, admitted with acute onset chorea and finally diagnosed with SLE. Subsequently, we present a short review of the literature on the epidemiology, suggested pathogenesis, clinical presentation and treatment of this rare presentation of SLE.

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.

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.

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.

A case of tardive dyskinesia in the last weeks of life.

Tardive dyskinesia (TD) is a chronic and often irreversible movement disorder that usually evolves after years of neuroleptic use but can sometimes develop over a much shorter time frame. Paradoxically, a higher dose of the neuroleptic agent that causes TD can often temporarily suppress the movement disorder. This is generally an inadvisable approach, though, as its effectiveness is probably limited to only a matter of weeks and as it will worsen the problem in the long run. We describe a patient with widely metastatic squamous cell carcinoma of the lung who developed severe TD when treated with chlorpromazine for severe hiccups. As his prognosis was only days to weeks, we were able to effectively suppress his TD with haloperidol. Hospice care emphasizes relief of suffering at the end of life, often at the expense of attention to long-range adverse effects, and this approach may be a viable management strategy for patients with TD and very limited prognosis.

Botulinum toxin for upper oesophageal sphincter dysfunction in neurological swallowing disorders.

BACKGROUND: Adequate upper oesophageal sphincter (UOS) opening is critical to safe and efficient swallowing due to the close proximity of the UOS to the airway entrance. Many people with neurological conditions, progressive and non-progressive, present with UOS dysfunction. The consequences for the person include difficulty swallowing food with subsequent choking and aspiration (passage of material into the trachea beyond the level of the true vocal cords). Clinical complications include aspiration pneumonia, weight loss, dehydration and malnutrition. Tube feeding is often indicated but is associated with increased mortality. Quality of life is also frequently impacted. A range of interventions exist that aim to improve UOS function and swallowing. These include compensatory strategies, rehabilitation techniques, pharmacological interventions and surgery. Over the last two decades, botulinum toxin has been gaining popularity as an intervention for UOS dysfunction, with some evidence to suggest that it is successful in improving swallow function. Despite a number of studies investigating its efficacy, there is a lack of consensus regarding whether this intervention is effective in improving swallowing for individuals with UOS dysfunction associated with neurological disease. OBJECTIVES: To establish the efficacy and safety of botulinum toxin use aimed at improving UOS dysfunction in people with swallowing difficulties (dysphagia) associated with non-progressive and progressive neurological disease. SEARCH METHODS: We searched the following electronic databases for published trials: the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (1950 to 2013); EMBASE (1980 to 2013); AMED (Allied and Complementary Medicine) (1941 to 2013); CINAHL (Cumulative Index to Nursing and Allied Health Literature) (1937 to 2013). We also searched major clinical trials registers: CCT (http://www.controlled-trials.com); Clinical Trials (http://www.clinicaltrials.gov); Chinese Clinical Trial Register (www.chictr.org); ACTR (http://www.actr.org.au/. We examined the reference lists of all potentially relevant studies to identify further relevant trials. We handsearched published abstracts of conference proceedings from both the Dysphagia Research Society and the European Society of Swallowing Disorders. Digestive Disease Week (published in Gastroenterology) was also handsearched. Additionally, we searched ProQuest Dissertations & Theses for dissertation abstracts. SELECTION CRITERIA: Only randomised controlled trials were sought. DATA COLLECTION AND ANALYSIS: Independent searches were completed by JR, AM, MC and MW. Two review authors (JR and MW) independently inspected titles, abstracts and key words identified from the literature search. MAIN RESULTS: No randomised controlled studies were retrieved. Twenty-nine studies were excluded, mainly on the basis of trial design. AUTHORS' CONCLUSIONS: It was not possible to reach a conclusion on the efficacy and safety of botulinum toxin as an intervention for people with UOS dysfunction and neurological disease. There is insufficient evidence to inform clinical practice. Directions for future research are provided.

G-protein coupled receptor 6 deficiency alters striatal dopamine and cAMP concentrations and reduces dyskinesia in a mouse model of Parkinson's disease.

The orphan G-protein coupled receptor 6 (GPR6) is a constitutively active receptor which is positively coupled to the formation of cyclic adenosine-3',5'-monophosphate (cAMP). GPR6 is predominantly expressed in striatopallidal neurons. Here, we investigated neurochemical and behavioural effects of Gpr6 deficiency in mice. Gpr6 depletion decreased in vivo cAMP tissue concentrations (20%) in the striatum. An increase of striatal tissue dopamine concentrations (10%) was found in Gpr6(-/-) mice, whereas basal extracellular dopamine levels were not changed compared with Gpr6(+/+) mice, as shown by in vivo microdialysis. Western blot analyses revealed no alteration in the expression and subcellular localisation of the dopamine D2 receptor in the striatum of Gpr6(-/-) mice, and the number of tyrosine hydroxylase positive neurons in the substantia nigra was unchanged. DARPP-32 (dopamine and cAMP-regulated phosphoprotein of 32kDa) expression in the striatum of Gpr6(-/-) mice was not altered, however, a twofold increase in the phosphorylation of DARPP-32 at Thr34 was detected in Gpr6(-/-) compared with Gpr6(+/+) mice. Gpr6(-/-) mice showed higher locomotor activity in the open field, which persisted after treatment with the dopamine D2 receptor antagonist haloperidol. They also displayed reduced abnormal involuntary movements after apomorphine and quinpirole treatment in the mouse dyskinesia model of Parkinson's disease. In conclusion, the depletion of Gpr6 reduces cAMP concentrations in the striatum and alters the striatal dopaminergic system. Gpr6 deficiency causes an interesting behavioural phenotype in the form of enhanced motor activity combined with reduced abnormal involuntary movements. These findings could offer an opportunity for the treatment of Parkinson's disease beyond dopamine replacement.

[Description of a case of hyperkinetic movement disorder in neonatal onset multisystem inflammatory disease or chronic infantile neurologic cutaneous and articular syndrome]. / Descripcion de un caso de trastorno del movimiento hipercinetico en la enfermedad inflamatoria multisistemica de inicio neonatal o sindrome cronico infantil neurologico, cutaneo y articular.

TITLE: Descripcion de un caso de trastorno del movimiento hipercinetico en la enfermedad inflamatoria multisistemica de inicio neonatal o sindrome cronico infantil neurologico, cutaneo y articular.

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.

Tic disorders.

PURPOSE OF REVIEW: Primary tic disorders are complex, multifactorial disorders in which tics are accompanied by other sensory features and an array of comorbid behavioral disorders. Secondary tics are proportionally much less frequent, but their etiology is diverse. This review aims to guide clinicians in the recognition of the phenomenology, pathophysiology, and treatment of these disorders. RECENT FINDINGS: Advances include greater phenomenologic insights, particularly of nonmotor (sensory) features; increased knowledge of disease mechanisms, particularly coming from neuropsychological, functional imaging, pathologic, and animal model studies; growing evidence on the efficacy of alpha-2 agonists and the newer generation of dopamine-modulating agents; and recent strides in the evaluation of cognitive-behavioral therapy and deep brain stimulation surgery. SUMMARY: The correct diagnostic approach to tic disorders requires accurate historical gathering, a thorough neurologic examination, and detailed definition of the patient's psychopathologic profile. Treatment should always begin with individualized psychoeducational strategies. Although pharmacologic treatments remain beneficial for most patients, cognitive-behavioral treatments have thus far shown promising efficacy. Deep brain stimulation surgery should still be limited to adult patients refractory to pharmacotherapy and cognitive-behavioral therapy.

A2A receptor antagonists do not induce dyskinesias in drug-naive or L-dopa sensitized rats.

L-dopa, the precursor to dopamine, is currently the gold standard treatment for Parkinson's disease (PD). However, chronic exposure is associated with L-dopa-induced dyskinesias (LIDs), a serious side effect characterized by involuntary movements. Adenosine A2A receptor antagonists have been studied as a novel non-dopaminergic PD treatment. Because A2A receptor antagonists do not act on dopamine receptors, it has been hypothesized that they will not induce dyskinesias characteristic of L-dopa. To test this hypothesis in a rodent model, the A2A receptor antagonists SCH 412348 (3 mg/kg), vipadenant (10 mg/kg), caffeine (30 mg/kg), or istradefylline (3 mg/kg) were chronically (19-22 days) administered to Sprague Dawley rats, and dyskinetic behaviors were scored across this chronic dosing paradigm. Unlike L-dopa, there was no evidence of dyskinetic activity resulting from any of the four A2A receptor antagonists tested. When delivered to animals previously sensitized with L-dopa (6 mg/kg), SCH 412348, vipadenant, caffeine or istradefylline treatment produced no dyskinesias. When administered in combination with L-dopa (6 mg/kg), SCH 412348 (3 mg/kg) neither exacerbated nor prevented the induction of LIDs over the course of 19 days of treatment. Collectively, our data indicate that A2A receptor antagonists are likely to have a reduced dyskinetic liability relative to L-dopa but do not block dyskinesias when coadministered with L-dopa. Clinical studies are required to fully understand the dyskinesia profiles of A2A receptor antagonists.

Medical treatment of dystonia.

Medications such as anticholinergic drugs, dopamine modulators, baclofen, muscle relaxants, and other pharmacologic agents have been used for a long time to treat dystonia, but the introduction of botulinum toxin and deep brain stimulation clearly revolutionized the symptomatic treatment of this neurological movement disorder. Therapy of dystonia can be divided into the following categories: (1) physical, supportive, and ancillary therapy; (2) pharmacologic treatment; (3) chemodenervation with botulinum toxin; and (4) peripheral and central surgery (deep brain stimulation). Except in some cases of secondary dystonia, pathogenesis-targeted or disease-modifying therapy is currently not available. This review focuses on evidence-based medical treatment of dystonia, highlighting recent advances, with emphasis on individualized approach. © 2013 Movement Disorder Society.

Clinical case of anti-N-methyl-D-aspartate receptor encephalitis in an 8-month-old patient with hyperkinetic movement disorder.

This article describes an 8-month-old boy with the full clinical spectrum anti-N-methyl-d-aspartate receptor encephalitis. He was admitted to the hospital with involuntary orofacial head movements, behavioral changes, and fluctuation in consciousness. His examination showed tongue thrusting, decreased responsiveness, and hypotonia without fever. Analysis of the cerebrospinal fluid revealed increased protein levels (62 mg/dL). The next day he developed oral dyskinesia and choreoathetosis. Video-electroencephalogram polygraphy showed coreo-dystonic movements without electrographic correlation. A putative diagnosis of autoimmune encephalopathy was made, and treatment with intravenous immunoglobulin and methylprednisolone was started, with improvement in the abnormal movements. Antibodies to the N-methyl-d-aspartate receptor were identified in the cerebrospinal fluid and blood. He began receiving immunoglobulin once a month for a year. Two months after the treatment had started, the involuntary movement disappeared and his development has been normal. N-methyl-d-aspartate receptor encephalitis is a recently identified disorder. This is the youngest case reported. Prompt diagnosis and treatment are important to obtain full recovery.

Botulinum toxin for conditions of the female pelvis.

INTRODUCTION AND HYPOTHESIS: Botulinum toxin has recently been approved by the Food and Drug Administration (FDA) for the treatment of urinary incontinence associated with neurogenic detrusor overactivity. However, it has also been used off-label for a multitude of other conditions in the female pelvis, including urological, gynecological, and colorectal. This article reviews the most recent data regarding its efficacy and safety, and administration techniques for those conditions. METHODS: A literature review of the most relevant reports published between 1985 and 2012. RESULTS: Urinary incontinence related to neurogenic detrusor overactivity is currently the only approved indication in the female pelvis. Other supported off-label uses include: idiopathic detrusor overactivity, interstitial cystitis/bladder pain syndrome, detrusor sphincter dyssynergia, high-tone pelvic floor dysfunction, anal fissure, anismus, and functional anal pain. CONCLUSIONS: Botulinum toxin may effectively and safely be used in many conditions of the female pelvis. More high quality research is needed to better clarify its role in the therapeutic algorithm for those indications.