Tardive dyskinesia in Asia- current clinical practice and the role of neurologists in the care pathway.

Tardive dyskinesia (TD) is a movement disorder that can arise as a side effect of treatment with dopamine receptor-blocking agents (DRBAs), including antipsychotic drugs (APDs) used to manage psychotic illnesses. Second-generation APDs (SGAs) are often preferred to first-generation drugs due to their lower propensity to cause TD, however many SGAs-treated patients still develop the condition. Although TD is a global health concern, evidence regarding the occurrence of TD and how it is managed in Asian countries is currently limited. This article reports the results of a systematic review of the published literature on TD focusing on its prevalence, types of patients, knowledge of the condition, causative factors, and usual treatment pathways in clinical practice in Asian countries. Epidemiological data suggest that the prevalence of TD is increasing globally due to an overall rise in APD use, contributing factors being polypharmacy with multiple APDs, the use of higher than necessary doses, and off-label use for non-psychotic indications. Although exact prevalence figures for TD in Asian countries are difficult to define, there is a similar pattern of rising APD use which will result in increasing numbers of TD patients in this region. These issues need to be addressed and strategies developed to minimize TD risk and manage this disabling condition which impacts patients' quality of life and daily functioning. To date, both research into TD has been predominantly psychiatry focused and the perspectives from neurologists regarding the clinical management of this challenging condition are scarce. However, neurologists have an essential role in managing the movement disorders manifestations that characterize TD. Optimum management of TD, therefore, should ideally involve collaboration between psychiatrists and neurologists in joint care pathways, wherever practical. Collaborative pathways are proposed in this article, and the challenges that will need to be addressed in Asian countries to improve the care of people with TD are highlighted, with a focus on the neurologist's viewpoint and the implications for the management of TD globally.

Neuroimaging Pearls from the MDS Congress Video Challenge. Part 2: Acquired Disorders.

The MDS Video Challenge continues to be the one of most widely attended sessions at the International Congress. Although the primary focus of this event is the presentation of complex and challenging cases through videos, a number of cases over the years have also presented an unusual or important neuroimaging finding related to the case. We reviewed the previous Video Challenge cases and present here a selection of those cases which incorporated such imaging findings. We have compiled these "imaging pearls" into two anthologies. The first focuses on pearls where the underlying diagnosis was a genetic condition. This second anthology focuses on imaging pearls in cases where the underlying condition was acquired. For each case we present brief clinical details along with neuroimaging findings, the characteristic imaging findings of that disorder and, finally, the differential diagnosis for the imaging findings seen.

Access and Attitudes Toward Palliative Care Among Movement Disorders Clinicians.

BACKGROUND: Neuropalliative care is an emerging field for those with neurodegenerative illnesses, but access to neuropalliative care remains limited. OBJECTIVE: We sought to determine Movement Disorder Society (MDS) members' attitudes and access to palliative care. METHODS: A quantitative and qualitative survey instrument was developed by the MDS Palliative Care Task Force and e-mailed to all members for completion. Descriptive statistics and qualitative analysis were triangulated. RESULTS: Of 6442 members contacted, 652 completed the survey. Completed surveys indicating country of the respondent overwhelmingly represented middle- and high-income countries. Government-funded homecare was available to 54% of respondents based on patient need, 25% limited access, and 21% during hospitalization or an acute defined event. Eighty-nine percent worked in multidisciplinary teams. The majority endorsed trigger-based referrals to palliative care (75.5%), while 24.5% indicated any time after diagnosis was appropriate. Although 66% referred patients to palliative care, 34% did not refer patients. Barriers were identified by 68% of respondents, the most significant being available workforce, financial support for palliative care, and perceived knowledge of palliative care physicians specific to movement disorders. Of 499 respondents indicating their training in palliative care or desire to learn these skills, 55% indicated a desire to gain more skills. CONCLUSIONS: The majority of MDS member respondents endorsed a role for palliative care in movement disorders. Many members have palliative training or collaborate with palliative care physicians. Although significant barriers exist to access palliative care, the desire to gain more skills and education on palliative care is an opportunity for professional development within the MDS. © 2021 International Parkinson and Movement Disorder Society.

The impact of COVID-19 on palliative care for people with Parkinson's and response to future pandemics.

Introduction: Although in some countries, palliative care (PC) still remains poorly implemented, its importance throughout the course of Parkinson's disease (PD) is increasingly being acknowledged. With an emergence of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic, growing emphasis has been placed on the palliative needs of people with Parkinson's (PwP), particularly elderly, frail, and with comorbidities.Areas covered: The ongoing COVID-19 pandemic poses an enormous challenge on aspects of daily living in PwP and might interact negatively with a range of motor and non-motor symptoms (NMS), both directly and indirectly - as a consequence of pandemic-related social and health care restrictions. Here, the authors outline some of the motor and NMS relevant to PC, and propose a pragmatic and rapidly deployable, consensus-based PC approach for PwP during the ongoing COVID-19 pandemic, potentially relevant also for future pandemics.Expert opinion: The ongoing COVID-19 pandemic poses a considerable impact on PwP and their caregivers, ranging from mental health issues to worsening of physical symptoms - both in the short- and long-term, (Long-COVID) and calls for specific, personalized PC strategies relevant in a lockdown setting globally. Validated assessment tools should be applied remotely to flag up particular motor or NMS that require special attention, both in short- and long-term.

More than hemifacial spasm? A case of unilateral facial spasms with systematic review of red flags.

Unilateral facial spasms (UFS) are frequently caused by hemifacial spasm (HFS), a disorder that usually results from vascular loop compression at the root exit zone of the facial nerve. However, UFS can also be a manifestation of other conditions, including brainstem tumours or demyelination, post-Bell's synkinesis, lesions of the facial nerve in the Faloppio canal and the parotid gland, dystonia, epilepsy, psychogenic conditions, tics and hemimasticatory spasm. In this report, we present a case of UFS, not due to HFS, highlighting clinical red flags for an alternative diagnosis. In addition, a systematic review was conducted to provide a comprehensive summary of UFS differential diagnoses with a list of red flags to assist neurologists in the evaluation of patients with UFS.

Defining spasticity: a new approach considering current movement disorders terminology and botulinum toxin therapy.

Spasticity is a symptom occurring in many neurological conditions including stroke, multiple sclerosis, hypoxic brain damage, traumatic brain injury, tumours and heredodegenerative diseases. It affects large numbers of patients and may cause major disability. So far, spasticity has merely been described as part of the upper motor neurone syndrome or defined in a narrowed neurophysiological sense. This consensus organised by IAB-Interdisciplinary Working Group Movement Disorders wants to provide a brief and practical new definition of spasticity-for the first time-based on its various forms of muscle hyperactivity as described in the current movement disorders terminology. We propose the following new definition system: Spasticity describes involuntary muscle hyperactivity in the presence of central paresis. The involuntary muscle hyperactivity can consist of various forms of muscle hyperactivity: spasticity sensu strictu describes involuntary muscle hyperactivity triggered by rapid passive joint movements, rigidity involuntary muscle hyperactivity triggered by slow passive joint movements, dystonia spontaneous involuntary muscle hyperactivity and spasms complex involuntary movements usually triggered by sensory or acoustic stimuli. Spasticity can be described by a documentation system grouped along clinical picture (axis 1), aetiology (axis 2), localisation (axis 3) and additional central nervous system deficits (axis 4). Our new definition allows distinction of spasticity components accessible to BT therapy and those inaccessible. The documentation sheet presented provides essential information for planning of BT therapy.

Systematic review of hardware-related complications of Deep Brain Stimulation: Do new indications pose an increased risk?

INTRODUCTION: Deep Brain Stimulation (DBS) is an effective treatment extended broadly to many neurological and psychiatric disorders. Nevertheless, complications may arise during DBS procedures or following implantation due to implanted hardware. This may result in both minor and major adverse events that may necessitate hardware removal and/or compromise maximal therapeutic benefit for the patient. OBJECTIVES AND METHODS: To identify relevant literature on hardware-related complications from DBS procedures by performing a systematic review, and propose how to identify at-risk group and possible preventive approaches. RESULTS: Of 4592 abstract screened, 96 articles fulfilled the selection criteria and were reviewed. Overall, the most common hardware-related complications were infections (5.12% of patients), followed by lead migration (1.60%), fracture or failure of the lead or other parts of the implant (1.46% and 0.73%, respectively), IPG malfunctions (1.06% of patients), and skin erosions without infections (0.48% of patients). New indications for DBS, including Tourette's syndrome, cluster headache, and refractory partial epilepsy, were found to bear a higher incidence of hardware-related infections than established indications such as Parkinson's disease. The highest rate of lead fracture or failure was found in dystonia patients (4.22%). Ultimately, the highest rate of pain at the implantation sites was found in refractory partial epilepsy patients (16.55%). CONCLUSION: Our analysis identified a variety of potential hardware-related complications among patients who underwent DBS procedures. Patients who were at risk of complications, such as patients with dystonia and off-label indications (e.g. Tourette's syndrome) should be informed prior to surgery and closely followed thereafter.

Biochemical and clinical effects of Whey protein supplementation in Parkinson's disease: A pilot study.

BACKGROUND: Parkinson's disease (PD) is an oxidative stress-mediated degenerative disorder. Elevated plasma homocysteine (Hcy) is frequently found in the levodopa-treated PD patients, is associated with disease progression and is a marker of oxidative stress. Whey protein is a rich source of cysteine, and branched-chain amino acids (BCAA). It has been shown that supplementation with Whey protein increases glutathione synthesis and muscle strength. OBJECTIVES AND METHODS: In this study, we conducted a placebo-controlled, double-blind study (NCT01662414) to investigate the effects of undenatured Whey protein isolate supplementation for 6months on plasma glutathione, plasma amino acids, and plasma Hcy in PD patients. Clinical outcome assessments included the unified Parkinson's disease rating scale (UPDRS) and striatal L-3,4-dihydroxy-6-(18)F-fluorophenylalanine (FDOPA) uptake were determined before and after supplementation. 15 patients received Whey protein, and 17 received Soy protein, served as a control group. RESULTS: Significant increases in plasma concentration of reduced glutathione and the ratio of reduced to oxidized glutathione were found in the Whey-supplemented patients but not in a control group. This was associated with a significant decrease of plasma levels of Hcy. The plasma levels of total glutathione were not significantly changed in either group. Plasma BCAA and essential amino acids (EAA) were significantly increased in the Whey-supplemented group only. The UPDRS and striatal FDOPA uptake in PD patients were not significantly ameliorated in either group. However, significant negative correlation was observed between the UPDRS and plasma BCAA and EAA in the pre-supplemented PD patients. CONCLUSION: This study is the first to report that Whey protein supplementation significantly increases plasma reduced glutathione, the reduced to oxidized glutathione ratio, BCAAs and EAAs in patients with PD, together with a concomitant significant reduction of plasma Hcy. However, there were no significant changes in clinical outcomes. Long-term, large randomized clinical studies are needed to explore the benefits of Whey protein supplementation in the management of PD patients.

Factors influencing secondary non-response to botulinum toxin type A injections in cervical dystonia.

BACKGROUND: The development of secondary non-response (SNR) to botulinum neurotoxin type-A (BoNT-A) is considered a key issue in the management of cervical dystonia (CD). This case-controlled study was performed to systematically identify factors influencing SNR during BoNT-A therapy. METHODS: This was a retrospective, international, non-interventional study of CD patients. Patients with SNR were matched with up to three responder patients (control) on the basis of duration of therapy and number of injection cycles. Factors influencing the development of SNR were screened using a univariate logistic regression model and confirmed using a multivariate conditional logistic regression model. RESULTS: 216 patients were enrolled, and 201 (SNR = 52; responder = 149) were matched and subdivided into blocks (doublets, triplets or quadruplets). At baseline, a significantly higher proportion of SNR patients had received previous or concomitant therapies (p = 0.038) and surgery for CD (p = 0.007) compared with controls. Although disease severity at onset was similar between groups, a significantly higher proportion of SNR patients experienced severe CD at the time of SNR compared with controls at the last documented visit. Multivariate analyses identified five factors that were significantly associated in predicting SNR (odds ratio [OR] > 1 indicated higher chances for being SNR): previous surgical procedure for CD (OR 9.8, p = 0.013), previous BoNT-A related severe adverse event (AE) (OR 5.6 p = 0.027), physical therapy (OR 4.6, p = 0.028), neuroleptic use (OR 3.3, p = 0.019) and average BoNT-A dose (OR 2.7, p = 0.010). CONCLUSIONS: These findings suggest that SNR may not reflect true pharmacological resistance to BoNT-A therapy, but may be related to underlying disease severity.

Transplacental transfer of NMDA receptor antibodies in an infant with cortical dysplasia.

A confused and agitated 18-year-old woman presented to the emergency unit with orolingual movements, eye deviation, and a temperature of 38°C. The symptoms had begun 2 weeks prior to the admission when she developed a severe headache associated with pathologic laughing and intermittent episodes of upgaze deviation. A urine pregnancy test was positive and a transvaginal ultrasonography showed a 9-week-old fetus. An MRI of the brain was unremarkable and results of the CSF analysis were also unremarkable apart from a CSF pleocytosis (62 lymphocytes) and slightly elevated protein (55 mg/dL; normal range 0-45 mg/dL). Extensive microbiologic and serologic studies with CSF were all negative. She gradually lost consciousness, experienced respiratory failure, and was intubated. There were semirhythmic movements consisting of complex patterns of mouth opening, chewing, facial grimacing, synchronous flexion-extension, and supination-pronation limb movements, which persisted during the period of unresponsiveness. She also had generalized hyperreflexia, persistent hyperthermia, and a full bladder. Three EEGs showed diffuse slow waves with no epileptic discharges. A diagnosis of anti-NMDA receptor (NMDAR) encephalitis was made on clinical grounds and strongly positive serum NMDAR antibodies.

The low prevalence of primary restless legs syndrome in Thai Parkinson's disease patients at Chulalongkorn University Hospital.

OBJECTIVE: There have been many studies of the prevalence of restless legs syndrome (RLS) in Parkinson's disease (PD). Some studies found a lower prevalence than in comparable groups in the general population while others reported more RLS. The present study was designed to determine the prevalence of primary RLS in Thai PD patients. MATERIAL AND METHOD: PD patients were interviewed for RLS symptoms and were excluded if they had a malignancy, endstage renal disease, neuropathy, a history of spinal cord diseases or were pregnant. Serum ferritin levels were measured. RESULTS: Three out of 183 patients interviewed (1.6%) had symptoms consistent with RLS. When one patient who had a serum ferritin level of 31.9 ng/ml is excluded, the prevalence falls to 0.98%. None of the following variables were significantly different in patients with and without RLS: age, gender age at onset of PD, duration of PD, Hoehn and Yahr stage, serum ferritin level and dose and duration of dopaminergic medication. None of the patients who have had subthalamic nucleus deep brain stimulation (n = 5) had RLS. CONCLUSION: The prevalence of RLS in Thai PD patients was found to be much lower than in most of the previous studies, especially those conducted in Europe and America.

Prevalence of neuroleptic-induced restless legs syndrome in patients taking neuroleptic drugs.

Dopamine deficiency or dopamine dysfunction has been implicated as one of the factors involved in the pathophysiology of restless legs syndrome (RLS). Our objective is to determine the prevalence of primary RLS in patients taking neuroleptic drugs. One hundred patients taking neuroleptic drugs and 100 healthy age- and sex-matched controls were interviewed with the Cambridge-Hopkins diagnostic questionnaire for RLS. Patients with malignancy, end-stage renal disease, neuropathy, history of spinal cord diseases, pregnancy and Parkinson's disease were excluded. Only one patient had symptoms consistent with RLS (1%), similar to one patient in the control group. She was a 40 years old female with a diagnosis of depression. She started having RLS symptoms approximately four years after starting perphenazine. The symptoms persisted after the medications were discontinued but decreased in severity and frequency. Her serum ferritin level was 90.3 ng/ml. The prevalence of primary RLS is low in patients attending the out-patient clinic who are taking neuroleptic drugs. Other factors apart from dopaminergic dysfunction are likely to be involved in the pathogenesis of RLS.

A national registry to determine the distribution and prevalence of Parkinson's disease in Thailand: implications of urbanization and pesticides as risk factors for Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) occurs worldwide but prior to this review of data from the Thailand Parkinson's Disease Registry there had been no nationwide PD registry reported globally. OBJECTIVE: To determine the distribution and prevalence of PD in Thailand and related risk factors in order to more adequately develop and allocate prevention and treatment resources where they are most needed and to ascertain risk factors that are specific to the Thai population. DESIGN: The Thailand Parkinson's Disease Registry is a new resource, and data collection began in March 2008. Data is collected by the Registry from physicians, and a mechanism is also provided for patients to self-report. This data was further analyzed by the capture-recapture methodology (CRM) to assess reporting biases. METHODS: The three main sources of data input to the Registry, i.e. (1) public hospitals, (2) private hospitals and (3) self-registration, require checking for duplicates and also allow estimation of completeness of recording (the degree of underreporting) in this disease registry. There is underreporting because of poor record keeping and administrative procedures in some facilities, and there is an unknown number of persons with PD who are not properly diagnosed because of inadequate facilities and staffing in some areas. Since our data sources should be overlapping in some way, and assuming that the likelihood of being detected in one system is independent of the others, we estimated these data sources' actual coverage and the expected total number of patients utilizing the 'capture-recapture' statistical technique. RESULTS: As of March 2011, the Thailand PD Registry had identified 40,049 PD patients. Employing log-linear modeling, the CRM analysis based on the three data sets estimated underreporting of 20,516 cases. The revised estimated total is thus 60,565 cases, resulting in a crude and age-adjusted prevalence of 95.34 and 424.57 PD cases/100,000 population, respectively. The prevalence of PD was 126.83/100,000 in urban areas and 90.82/100,000 in rural areas (p < 0.001). Preliminary regional comparisons revealed a higher prevalence of PD in residents of the central plain valley of Thailand, an area with a large amount of pesticide use. CONCLUSIONS: The combination of a passive registry and the CRM technique allowed us to derive population prevalence estimates for PD in Thailand. Thai PD prevalence estimates were similar to previous ones published for Asian countries; in addition, they suggested that urbanization and exposure to pesticides may both be risk factors for PD in the Thai population.

Startle syndromes.

Startle refers to a sudden involuntary movement of the body in response to a surprising and unexpected stimulus. It is a fast twitch of facial and body muscles evoked by a sudden and intense tactile, visual, or acoustic stimulus. While startle can be considered to be a protective function against injury, startle syndromes are abnormal responses to startling events, consisting of three heterogeneous groups of disorders. The first is hyperekplexia, characterized by brisk and generalized startle in response to trivial stimulation. The major form of hereditary hyperekplexia has a genetic basis, frequently due to mutations in the α1 subunit of the glycine receptor (GLRA1) on chromosome 5q. In the second group, normal startle induces complex but stereotyped motor and/or behavioral abnormalities lasting several seconds, termed as startle epilepsy. It usually occurs in the setting of severe brain damage, particularly perinatal hypoxia. The third group is characterized by nonhabituating hyperstartling, provoked by loud noises, sudden commands, or gestures. The intensity of startle response tends to increase with frequency of stimulation, which often leads to injury. Interestingly, its occurrence is restricted to certain social or ethnic groups in different parts of the world, such as jumping Frenchmen of Maine among Franco-Canadian lumberjack communities, and Latah in Southeast Asia. So far, no neurological abnormalities have been reported in association with these neuropsychiatric startle syndromes. In this chapter, the authors discuss the clinical presentation, physiology, and the neuronal basis of the normal human startle as well as different groups of abnormal startle syndromes. The aim is to provide an overview of hyperstartling with some diagnostic hints and the distinguishing features among these syndromes.

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.

HIV-related opsoclonus-myoclonus-ataxia syndrome: report on two cases.

Opsoclonus-myoclonus-ataxia (OMA) syndrome is a rare neurological disorder, characterized by a rapid onset of generalized myoclonus in association with chaotic multi-directional eye movements and, less frequently, cerebellar ataxia. OMA is commonly related to a paraneoplastic process, specifically neuroblastoma in children and lung or breast cancer in adults. Nevertheless, OMA may occur in association with various infectious agents, such as Coxsackie virus B3, Epstein-Barr virus, mumps, enterovirus, and streptococcus. We recently encountered two cases of HIV-related OMA syndrome. The first patient developed a sudden onset of OMA at the time of HIV seroconversion. The second patient experienced severe ataxia with a mild degree of myoclonus and opsoclonus, associated with an elevated CD4 count following the initiation of highly active antiretroviral therapy (HAART). We suggest that OMA syndrome may be another rare manifestation of HIV infection at the time of seroconversion or during an immune restoration period.

Extrapontine myelinolysis in preoperative sellar region tumor: report of two cases.

Osmotic demyelination syndrome (ODS) is a well-known disorder caused by rapid correction of serum sodium. Many conditions including hormonal abnormality are associated with this syndrome. The authors describe two cases of preoperative sellar region tumor associated with hypopituitarism and secondary adrenal insufficiency. These two patients had hyponatremia. Neurological manifestations in both of them were generalized dystonia. Magnetic resonance imaging (MRI) revealed a characteristic extrapontine myelinolysis (EPM). The first case was a 35-year-old man with craniopharyngioma who developed generalized dystonia after rapid correction of hyponatremia. The second case was a 24-year-old man with gonadotroph pituitary adenoma who developed generalized dystonia, dysarthria, and dysphagia in the course of hyponatremia. Hormonal changes will cause fluctuation in hyponatremia and correction of hyponatremia, even if the recommended rate may be hazardous and will promote ODS. Patients with sellar region tumors are at risk of developing ODS and correction of hyponatremia in these cases should be closely monitored.

Frameless stereotactic for deep brain stimulation placement: operative technique.

Deep brain stimulation (DBS) has been shown to be a safe and effective method for the treatment of refractory Parkinson's disease and other movement disorders. Traditionally, frame-based stereotactic have been the standard technique commonly used for DBS surgery. With the development of image-guided neurosurgical systems, frameless stereotactic has been increasingly used for tumor resection or biopsy without the use of stereotactic frame. Frameless stereotactic for functional surgery has been recently developed with the accuracy comparable to frame-based stereotactic surgery. The authors report the surgical technique of frameless functional stereotactic for the treatment of movement disorders.