Roongroj Bhidayasiri

Expanding use of botulinum toxin.

Botulinum toxin type A (BTX-A) is best known to neurologists as a treatment for neuromuscular conditions such as dystonias and spasticity and has recently been publicized for the management of facial wrinkles. The property that makes botulinum toxin type A useful for these various conditions is the inhibition of acetylcholine release at the neuromuscular junction. Although botulinum toxin types A and B (BTX-A and BTX-B) continue to find new uses in neuromuscular conditions involving the somatic nervous system, it has also been recognized that the effects of these medications are not confined to cholinergic neurons at the neuromuscular junction. Acceptors for BTX-A and BTX-B are also found on autonomic nerve terminals, where they inhibit acetylcholine release at glands and smooth muscle. This observation led to trials of botulinum neurotoxins in various conditions involving autonomic innervation. The article reviews the emerging use of botulinum neurotoxins in these and selected other conditions, including sialorrhea, primary focal hyperhidrosis, pathological pain and primary headache disorders that may be of interest to neurologists and related specialists.

Evidence-based guideline: Treatment of tardive syndromes Report of the Guideline Development Subcommittee of the American Academy of Neurology

Objective: To make evidence-based recommendations regarding management of tardive syndromes (TDS), including tardive dyskinesias (TDD), by addressing 5 questions: 1) Is withdrawal of dopamine receptor blocking agents (DRBAs) an effective TDS treatment? 2) Does switching from typical to atypical DRBAs reduce TDS symptoms? 3) What is the efficacy of pharmacologic agents in treating TDS? 4) Do patients with TDS benefit from chemodenervation with botulinum toxin? 5) Do patients with TDS benefit from surgical therapy? Methods: PsycINFO, Ovid MEDLINE, EMBASE, Web of Science, and Cochrane were searched (1966–2011). Articles were classified according to a 4-tiered evidence-rating scheme; recommendations were tied to the evidence. Results and recommendations: Clonazepam probably improves TDD and ginkgo biloba probably improves TDS (both Level B); both should be considered as treatment. Risperidone may improve TDS but cannot be recommended as treatment because neuroleptics may cause TDS despite masking symptoms. Amantadine and tetrabenazine might be considered as TDS treatment (Level C). Diltiazem should not be considered as TDD treatment (Level B); galantamine and eicosapentaenoic acid may not be considered as treatment (Level C). Data are insufficient to support or refute use of acetazolamide, bromocriptine, thiamine, baclofen, vitamin E, vitamin B6, selegiline, clozapine, olanzapine, melatonin, nifedipine, fluperlapine, sulpiride, flupenthixol, thiopropazate, haloperidol, levetiracetam, quetiapine, ziprasidone, sertindole, aripiprazole, buspirone, yi-gan san, biperiden discontinuation, botulinum toxin type A, electroconvulsive therapy, α-methyldopa, reserpine, and pallidal deep brain stimulation as TDS treatments (Level U). Data are insufficient to support or refute TDS treatment by withdrawing causative agents or switching from typical to atypical DRBA (Level U).

Management of non-motor symptoms in advanced Parkinson disease

Progress in pharmacology has markedly improved the treatment of early Parkinsons disease. The management of advanced Parkinsons symptoms, however, remains a challenge. These symptoms are divided into motor and non-motor symptoms. Non-motor symptoms may appear early or late in the disease and sometimes even before the onset of the first motor symptoms confirming the diagnosis. The spectrum of non-motor symptoms encompasses autonomic dysfunctions, sleep disorders, mood disorders, impulse control disorders, cognitive dysfunction, dementia, paranoia and hallucinations. They are often less appreciated than motor symptoms but are important sources of disability for many PD patients. This review describes these non-motor symptoms and their managements.

Chorea and related disorders

Chorea refers to irregular, flowing, non-stereotyped, random, involuntary movements that often possess a writhing quality referred to as choreoathetosis. When mild, chorea can be difficult to differentiate from restlessness. When chorea is proximal and of large amplitude, it is called ballism. Chorea is usually worsened by anxiety and stress and subsides during sleep. Most patients attempt to disguise chorea by incorporating it into a purposeful activity. Whereas ballism is most often encountered as hemiballism due to contralateral structural lesions of the subthalamic nucleus and/or its afferent or efferent projections, chorea may be the expression of a wide range of disorders, including metabolic, infectious, inflammatory, vascular, and neurodegenerative, as well as drug induced syndromes. In clinical practice, Sydenham’s chorea is the most common form of childhood chorea, whereas Huntington’s disease and drug induced chorea account for the majority of adult onset cases. The aim of this review is to provide an up to date discussion of this disorder, as well as a practical approach to its management.

Spectrum of tardive syndromes: clinical recognition and management

Tardive syndrome (TS) refers to a group of delayed onset disorders characterised by abnormal movements and caused by dopamine receptor blocking agents (DRBAs). Classical tardive dyskinesia is a specific type of oro-buccal-lingual dyskinesia. However, TS may exist in other forms—for example, stereotypy, dystonia, and akathisia—and frequently occur in combination. The onset typically is insidious and after reaching its maximum severity it often stabilises. Frequently reported risk factors are age, dose and duration of neuroleptic exposure, the use of conventional DRBAs, and co-existing mood disorders. This review highlights the broad spectrum of TS, not limited to classical tardive dyskinesia, as well as the clues for its recognition. Despite challenges in the treatment of TS, dictated by the different phenomenology, severity of TS and the need for ongoing neuroleptic treatment, the authors provide evidence based recommendations for patient management, which is not restricted to only withdrawal of the offending neuroleptics or the selection of an alternative medication, such as clozapine. In a minority of cases with significant functional disability, symptomatic or suppressive treatments should be considered. Recently, there has been a resurgence of stereotactic pallidal surgery for the treatment of TS. Although the efficacy of both pallidotomy and pallidal deep brain stimulation in dystonia has been encouraging, the evidence is still limited.

Motor complications in Parkinson disease: clinical manifestations and management.

Long-term dopaminomimetic therapy, not limited to levodopa, is complicated by the emergence of variations of motor response in a majority of Parkinson disease (PD) patients. These variations can occur in different forms, as early wearing off during the initial stage of motor complications, dyskinesias in the intermediate stage, and complex fluctuations in the advanced stage. Considered to be a major source of disability in advanced PD patients, recognition of these complications is critical in order to develop different strategies designed not only to treat these problems when they develop, but also to prevent troublesome complications associated with potential risk factors. In this article, authors classify a wide clinical spectrum of motor complications into different stages as the disease progresses through the treatment. A number of strategies are proposed in order to manage these complications as well as to avoid them. Better understanding of these potential complications will result in better management of these problems and lessen the disability associated with advanced PD.

Dystonia: genetics and treatment update.

Background:Dystonia refers to a syndrome of sustained muscle contractions, frequently causing twisting and repetitive movements or abnormal postures. Although age at onset, anatomic distribution, and family history are essential elements in the evaluation of dystonia, new classification increasingly relies on etiologic and genetic data. In recent years, much progress has been made on the genetics of various forms of dystonia and its pathophysiology underlying the clinical signs. The treatment of dystonia has continued to evolve to include newer medications, different forms of botulinum toxin, and various surgical procedures. Review Summary:In this article, the author reviewed and summarized the history of dystonia, its evolving classification, and recent genetic data, as well as its clinical investigation and treatment. Conclusions:Recent advances in molecular biology have led to the discovery of novel dystonia genes and loci, updating classification schemes, and better understanding of underlying pathophysiology. Treatment strategies for dystonia have significantly been updated with the introduction of different forms of botulinum toxin therapy, new pharmacologic agents, and most recently pallidal deep brain stimulation. A systematic approach to the diagnosis and treatment evaluation of dystonic patients provides optimal care for long-term management.

Synucleinopathies from bench to bedside.

Accumulation of alpha-synuclein is a pathological feature in several neurological diseases. Its characterization has allowed for a re-grouping of diseases according to the expected pathology. The clinical syndrome of PD can now be classified into forms with and without alpha-synuclein pathology. DLB and PDD are synucleinopathies, and MSA shows alpha-synuclein pathology with glial inclusions. ADHD symptoms commonly occur in persons that will subsequently develop DLB. A similar phenomenon may be the early personality changes and frontotemporal atrophy in patients with SNCA multiplication. RLS is not known to have alpha-synuclein pathology, but as PD and ADHD, involves a hypodopaminergic state. Furthermore, PD and RLS co-occur in families in a way that suggests common inheritance. A proportion of patients with ET have brainstem Lewy body pathology. Gaucher disease and other lysosomal storage disorders also have alpha-synuclein pathology. Alpha-synuclein is a naturally unfolded protein. Non-fibrillar oligomeres may be the toxic species, and Lewy body formation may in fact be protective. Inhibiting alpha-synuclein toxicity seems to be an attractive novel treatment strategy and several approaches are being developed. When such treatments become available, clinicians will need to be familiar with the clinical features that distinguish the synucleinopathies from their look-alikes.

Treatment of dystonia.

Dystonia may be a sign or symptom, that is comprised of complex abnormal and dynamic movements of different etiologies. A specific cause is identified in approximately 28% of patients, which only occasionally results in specific treatment. In most cases, treatment is symptomatic and designed to relieve involuntary movements, improve posture and function and reduce associated pain. Therapeutic options are dictated by clinical assessment of the topography of dystonia, severity of abnormal movements, functional impairment and progression of disease and consists of pharmacological, surgical and supportive approaches. Several advances have been made in treatment with newer medications, availability of different forms of botulinum toxin and globus pallidus deep brain stimulation (DBS). For patients with childhood-onset dystonia, the majority of whom later develop generalized dystonia, oral medication is the mainstay of therapy. Recently, DBS has emerged as an effective alternative therapy. Botulinum toxin is usually the treatment of choice for those with adult-onset primary dystonia in which dystonia usually remains focal. In patients with secondary dystonia, treatment is challenging and efficacy is typically incomplete and partially limited by side effects. Despite these treatment options, many patients with dystonia experience only partial benefit and continue to suffer significant disability. Therefore, more research is needed to better understand the underlying cause and pathophysiology of dystonia and to explore newer medications and surgical techniques for its treatment.

Prevalence and risk factors of Parkinson's disease in retired Thai traditional boxers

Boxing is often believed to be a frequent cause for parkinsonism caused by chronic repetitive head injury, with Muhammad Ali frequently cited as an example. The purpose of this study is to determine the prevalence of Parkinsons disease (PD) in retired Thai traditional boxers. Two standardized screening questionnaires were sent to all registered Thai traditional boxers. Subjects who screened positive for parkinsonism were invited for clinical examinations by two independent neurologists. Among 704 boxers (70%) who completed the questionnaires, 8 boxers (1.14%) had parkinsonism: 5 with PD, 1 with progressive supranuclear palsy and 2 with vascular parkinsonism. Boxers with PD were found to have an older mean age than those without PD (P = 0.003). The analysis of probable risk factors disclosed an association between the number of professional bouts (>100 times) and PD (P = 0.01). The crude prevalence of PD in Thai boxers was 0.71% (95% CI: 0.09–1.33), with a significant increase with age. The prevalence rate of PD in those aged 50 and above was 0.17% (95% CI: 0.15–0.20), age‐adjusted to the USA 1970 census, which is comparable to that of the general populations. The analysis determined that the number of professional bouts is a risk factor among these boxers, supporting the notion that repetitive head trauma may pose an additional risk to certain individuals who are already susceptible to PD.