Dystonia in Performing Artists: Beyond Focal Hand Dystonia.

Overuse of specific muscles in perfecting movements in performing arts makes an artist prone to many medical conditions. Musicians' hand dystonia is focal task-specific dystonia (FTSD) of hand among musicians that has been extensively studied. However, embouchure, lower limbs, and laryngeal muscles can also be affected among musicians. Embouchure dystonia (ED) refers to dystonia of the perioral and facial muscles that occurs in musicians while playing embouchure instruments. It is essential to identify ED since the dystonia might become persistent and non-task-specific if the musician continues to play the instrument. Task-specific dystonia of lower limbs among musicians has been exclusively reported among drummers. The diagnosis rests on electromyogram (EMG) of the involved muscles during the task. Singer's dystonia (SD) refers to task-specific laryngeal dystonia that occurs only while singing. The diagnosis of SD is based on laryngeal EMG and spectrographic analysis. Cortical hyperexcitability, loss of inhibition, and aberrant plasticity are central to the pathogenesis in both ED and musicians' hand dystonia. The pathophysiological studies in SD are limited. This review aims to discuss the lesser known dystonias among performing artists - ED, FTSD of lower limb, and SD.

Disorders of Tetrahydrobiopterin Metabolism: Experience from South India.

BACKGROUND: Disorders of tetrahydrobiopterin metabolism represent a rare group of inherited neurotransmitter disorders that manifests mainly in infancy or childhood with developmental delay, neuroregression, epilepsy, movement disorders, and autonomic symptoms. METHODOLOGY: A retrospective review of genetically confirmed cases of disorders of tetrahydrobiopterin metabolism over a period of three years (Jan 2018 to Jan 2021) was performed across two paediatric neurology centres from South India. RESULTS: A total of nine patients(M:F=4:5) fulfilled the eligibility criteria. The genetic variants detected include homozygous mutations in the QDPR(n=6), GCH1(n=2), and PTS(n=1) genes. The median age at onset of symptoms was 6-months(range 3-78 months), while that at diagnosis was 15-months (8-120 months), resulting in a median delay in diagnosis of 9-months. The main clinical manifestations included neuroregression (89%), developmental delay(78%), dystonia(78%) and seizures(55%). Management strategies included a phenylalanine restricted diet, levodopa/carbidopa, 5-Hydroxytryphtophan, and folinic acid. Only, Patient-2 afforded and received BH4 supplementation at a sub-optimal dose later in the disease course. We had a median duration of follow up of 15 months (range 2-48 months). Though the biochemical response has been marked; except for patients with GTPCH deficiency, only mild clinical improvement was noted with regards to developmental milestones, seizures, or dystonia in others. CONCLUSION: Tetrahydrobiopterin deficiencies represent a rare yet potentially treatable cause for non-phenylketonuria hyperphenylalaninemia with better outcomes when treated early in life. Screening for disorders of biopterin metabolism in patients with hyperphenylalaninemia prevents delayed diagnosis. This study expands the genotype-phenotype spectrum of patients with disorders of tetrahydrobiopterin metabolism from South India.

Fulminant Reversible Cerebral Vasoconstriction Syndrome in Breakthrough COVID 19 Infection.

COVID 19 infection continues to afflict people worldwide. Neurological complications of COVID infection are common. We report a case of fulminant reversible cerebrovascular constriction syndrome (RCVS) in a patient with breakthrough COVID 19 infection who was fully vaccinated. A 64 year old lady, fully vaccinated 2 months back, presented with headache, drowsiness, partial seizures, visual impairment and quadriplegia. Her nasopharyngeal swab was tested positive for SARS COV2 on real time PCR assay. MRI brain FLAIR images showed multifocal hyperintensities with MR angiogram showing arterial vasoconstriction suggestive of RCVS. Despite initiation of nimodipine, patient's symptoms worsened and she succumbed to sepsis. RCVS following COVID infection has been reported to have a benign outcome. However, despite vaccination, fulminant RCVS following a breakthrough COVID infection was observed in our patient.

A Study to Evaluate Lipid Profile in Treatment Naïve HIV Positive Patients.

HIV infection is associated with lipid abnormalities in treatment naïve patients. CD4 count is used for monitoring the HIV infection. Primary objective was to evaluate and correlate lipid profile and CD4 counts in HIV infection. Secondary objective was to evaluate the feasibility of using Lipid profile to monitor the HIV infected treatment naïve patients instead of CD4 counts. 112 patients were selected based on a criteria from ART center in tertiary care center. CD4 counts were assessed and Lipid profile was evaluated enzymatically. A correlation study was done between the lipid profile and the CD4 count and clinical stages of infection. Cholesterol showed no significant correlation in any stage. HDL-C showed significant correlation (p < 0.05) with stage 2 and 4 disease. LDL-C showed no significant correlation in any stage. TGL showed significant correlation (p < 0.05) at stage 4 disease. Hence, HDL-C and TGL can be used as indicators of lipid status and for infection progression in treatment naive HIV patients, while Cholesterol and LDL-C has no role to play.

Movement Disorders and Other Neurologic Impairment Associated With Hypomagnesemia: A Systematic Review.

Purpose of Review: The objective of this study was to explore the clinical spectrum of movement disorders and associated neurologic findings in hypomagnesemia and challenges in diagnosis and treatment. Recent Findings: Sixty patients were identified in the literature for analysis. Movement disorders observed were postural tremor (23.3%, n = 14), resting tremor (8.3%, n = 5), intention tremor (10%, n = 6), ataxia involving the trunk (48.3%, n = 29) or limbs (25%, n = 15) and dysarthria (21.7%, n = 13), athetosis (8.3%, n = 5), myoclonus (6.7%, n = 4), and chorea (1.8%, n = 1). Symptoms may be accompanied by downbeat nystagmus, tetany, drowsiness, vertigo, and proximal muscle weakness. Residual deficits were noted in 16 (26.67%) patients. Serum magnesium was 1.3 mg/dL or lower in 53 patients (88.3%). Imaging findings include bilateral cerebellar (20%, n = 11) and vermis hyperintensities (9.09%, n = 5) and normal imaging. Proton pump inhibitors are the commonest etiology. Summary: The movement disorders linked with hypomagnesemia can be associated with varied neurologic symptoms. A high degree of suspicion will enable early diagnosis to prevent residual deficits.

An Individualized Multi-Modal Approach for Detection of Medication "Off" Episodes in Parkinson's Disease via Wearable Sensors.

The primary treatment for Parkinson's disease (PD) is supplementation of levodopa (L-dopa). With disease progression, people may experience motor and non-motor fluctuations, whereby the PD symptoms return before the next dose of medication. Paradoxically, in order to prevent wearing-off, one must take the next dose while still feeling well, as the upcoming off episodes can be unpredictable. Waiting until feeling wearing-off and then taking the next dose of medication is a sub-optimal strategy, as the medication can take up to an hour to be absorbed. Ultimately, early detection of wearing-off before people are consciously aware would be ideal. Towards this goal, we examined whether or not a wearable sensor recording autonomic nervous system (ANS) activity could be used to predict wearing-off in people on L-dopa. We had PD subjects on L-dopa record a diary of their on/off status over 24 hours while wearing a wearable sensor (E4 wristband®) that recorded ANS dynamics, including electrodermal activity (EDA), heart rate (HR), blood volume pulse (BVP), and skin temperature (TEMP). A joint empirical mode decomposition (EMD) / regression analysis was used to predict wearing-off (WO) time. When we used individually specific models assessed with cross-validation, we obtained > 90% correlation between the original OFF state logged by the patients and the reconstructed signal. However, a pooled model using the same combination of ASR measures across subjects was not statistically significant. This proof-of-principle study suggests that ANS dynamics can be used to assess the on/off phenomenon in people with PD taking L-dopa, but must be individually calibrated. More work is required to determine if individual wearing-off detection can take place before people become consciously aware of it.

Long-Term Outcome of Hemimasticatory Spasm.

OBJECTIVE: This study aims to identify the demographic, clinical, and therapeutic characteristics of four patients with hemimasticatory spasm (HMS) seen in our outpatient department over a period of 20 years. METHODS: We performed a retrospective chart review of four patients with HMS who visited outpatient services in the Department of Neurology from 2001 to 2020. RESULTS: The follow-up for all patients ranged from 2 years to 9 years. Three patients had facial or bucco-oral morphea. Two patients maintained long-term improvements in symptoms after being treated with botulinum toxin for 4-7 years, while one patient reported improvement in symptoms with treatment of carbamazepine that subsequently remitted after pregnancy. CONCLUSION: This report highlights the long-term outcome of HMS in our patients. Our patients reported a significant reduction or complete resolution of symptoms after treatment, and eventually, two patients were asymptomatic while off treatment.

Brachial monomelic amyotrophy as an initial manifestation of stiff person syndrome.

Stiff person syndrome (SPS) is characterized by rigidity of truncal and proximal muscles. The presence of abdominal and paraspinal rigidity is a defining clinical feature of SPS. It is rarely associated with the lower motor neuron (LMN) features. We report a patient with SPS whose initial clinical presentation was that of brachial monomelic amyotrophy (BMA). A 24-year-old gentleman presented with a history of the left upper limb wasting and weakness. In addition, he reported stiffness of the lower limbs and abdomen while walking. On examination, patient had left upper limb monomelic amyotrophy and hypertonia, exaggerated deep tendon reflexes in all four limbs. He also had abdominal and paraspinal rigidity. Serum was strongly positive for GAD 65 antibodies suggestive of SPS. Patient showed dramatic improvement to immunomodulation. Patient presented with features of BMA. Symptoms related to SPS were mild. Abdominal rigidity was the clue to the diagnosis. LMN features have been reported previously in stiff person plus syndrome with an atypical course and progressive encephalomyelitis with myoclonus and rigidity, but not in classical SPS.

The association of saccadic abnormalities with rem sleep in patients with Huntington's disease.

BACKGROUND: Huntington's disease (HD) is a progressive neurodegenerative disorder characterised by chorea, cognitive impairment, psychiatric and behavioral disturbances. Sleep disturbances including reduced REM sleep have been observed in HD. OBJECTIVES: The aim of the study was to study the polysomnography findings in HD and to assess whether oculomotor abnormalities are associated with poor REM sleep. METHODS: Twenty-nine genetically confirmed HD patients underwent clinical evaluation including extraocular movement and OKN examination. Twenty-six patients and 15 controls underwent overnight video polysomnography (VPSG). RESULTS: VPSG of 23 HD patients and 13 controls were considered for analysis. Compared to controls, HD patients had higher median wake period and higher WASO percentage (p = 0.005). REM sleep percentage was reduced significantly in HD in comparison to controls (p < 0.001). Out of 23 patients, only two patients had REM sleep above 20% while 14 patients had REM sleep percentage less than 15%. Poor horizontal OKN (grades 2 and 3) was associated with the presence of low REM sleep percentage (REM sleep less than 15%) (p = 0.02). Low REM sleep was also associated with severe illness (UHDRS) (p = 0.038). CONCLUSION: An association between decreased REM sleep and OKN abnormalities indicate that EOM abnormalities seen in HD could lead to errors in scoring REM sleep. To understand the actual degree of decreased REM sleep percentage will require additional parameters in AASM guidelines to score REM sleep in patients with EOM abnormalities like that seen in HD.

DNAJC6 mutation causing cranial-onset dystonia with tremor dominant levodopa non-responsive parkinsonism: A novel phenotype.

DNAJC6 mutation causes two types of phenotypes: slowly progressive parkinsonism with levodopa response and rapidly progressive parkinsonism with additional manifestations like intellectual disability, epilepsy etc. We report a new phenotype wherein an adolescent girl developed blepharospasm followed by jaw opening, lingual and cervical dystonia followed by tremors of limbs (rest and action) with rigidity, bradykinesia. The dystonia-parkinsonism phenotype has not been described. She had novel homozygous missense mutation in DNAJC6 gene.

Sleep and other Non-motor Symptoms in Patients with Idiopathic Oromandibular Dystonia and Meige Syndrome: A Questionnaire-based Study.

INTRODUCTION: Non-motor symptoms are an essential cause of comorbidity in generalized and focal dystonia. However, there are few studies on dystonia involving the craniofacial regions. METHODS: We studied non-motor symptoms in patients with oromandibular dystonia (OMD) and Meige syndrome using a questionnaire, and validated instruments for depression, anxiety, REM behaviour disorder, restless leg syndrome, sleep quality, excessive daytime sleepiness, and self-esteem. The severity of dystonia and blepharospasm was also studied. RESULTS: Nineteen patients with OMD were recruited into the study. Among patients with OMD, depression was seen in 63.6% (n = 7), sleep impairment in 27.3% (n = 3), excessive daytime sleepiness in 27.3% (n = 3), and poor self- esteem in 18.2% (n = 2) of the patients. Among patients with Meige syndrome, depression was seen in 37.5% (n = 3), sleep impairment in 12.5% (n = 1), excessive daytime sleepiness in 25% (n = 2), low self-esteem in 25% (n = 2) of the patients. CONCLUSION: This study highlights the significant frequency of depression and sleep disturbances in patients with idiopathic OMD and Meige syndrome.

Clinical spectrum of pediatric drug refractory epilepsy secondary to parieto-occipital gliosis.

BACKGROUND: Parieto-occipital (PO) gliosis secondary to perinatal insult, is often associated with neurologic sequelae such as epilepsy, which can be drug resistant. OBJECTIVE: To evaluate the spectrum of epilepsy among patients presenting with seizures in association with PO gliosis and to determine factors that influence the development of epileptic encephalopathy (EE) in these patients. METHODS: We retrospectively evaluated patients aged < 16 years with drug refractory epilepsy and PO gliosis who underwent video electroencephalography (Video EEG). We evaluated the clinical, electrophysiological and radiological profile including treatment responsiveness of subjects with EE. RESULTS: One hundred one patients (M: F=3:1) with mean age of onset of epilepsy at 28.9 ± 33.1 months were recruited into the study. Based on video EEG findings, Based on video EEG findings, the commonest type of focal onset ictus was tonic seizures with impaired awareness (n = 26, 29.9%). Myoclonic jerks (n = 20, 23%) were the commonest type of generalised onset seizures. Ictal onset from parieto occipital region were observed in 28 patients. Ictal onset from frontal, temporal and fronto temporal region were observed in 6 (6.8%), 7(7.9%) and 9 (8.9%) patients, respectively. Comparison of the seizure types and ictal onset among subgroups of patients with occipital gliosis, parieto-occipital gliosis and parieto-occipital with frontal gliosis revealed that the extent of gliosis did not significantly affect seizure semiology or ictal onset. EE was significantly associated with presence of neonatal seizures (p = 0.04), hypoglycaemia (p = 0.005), longer duration of ICU stay (Z score = -3.55, p < 0.001) and younger age of onset of seizures (Z score = - 2.97, p = 0.03). Eleven out of eighteen (64.7%) subjects with EE showed greater than 50% improvement in seizure frequency following three months of pulse intravenous methylprednisolone therapy. CONCLUSIONS: Among subjects with PO gliosis on MRI, the seizure semiology is unaffected by laterality, radiologic extension beyond the occipital cortex or presence of ulegyria. Patients with PO gliosis can have florid interictal epileptiform discharges anteriorly and can have seizures with ictal onset from frontal and temporal region. Development of EE is strongly related to the age of onset of seizures, neonatal seizures, prolonged NICU admission, rather than the radiological findings. Subjects with EE and PO gliosis show good response to intravenous pulse methylprednisolone.

Altered REM sleep architecture in patients with Myotonic dystrophy type 1: is related to sleep apnea?

OBJECTIVE: To determine the sleep architecture and sleep respiratory abnormalities and to correlate with sleep symptoms in patients with Myotonic dystrophy type 1 (DM1). METHODS: We recruited a cohort of genetically confirmed patients with DM1, who attended the Neuromuscular clinic between July 2016 and December 2019. Clinical, sleep and whole night polysomnography data were collected. The analysis of sleep architecture, sleep respiratory parameters and comparison with healthy controls (HC) was performed in our sleep laboratory. RESULTS: A total of 59 patients with DM1 underwent sleep evaluation. Hypersomnolence in 42 (77.8%), ESS>10 in 23 (39%), and PSQI>5 in 18 (30.5%) were found in patients with DM1. Thirty-one (68.89%) patients with DM1 and 22 (95.65%) HC had more than 4-h of total sleep time (TST). More than 4 h of TST was taken to compare respiratory and sleep architecture parameters. Patients with DM1 had reduced sleep efficiency, reduced N2 sleep, and increase in N1 sleep, wake index, stage shift index, nocturnal sleep-onset REM periods compared to HC. AHI>15 was found in 16 (51.61%) DM1 and in 3 HC (13.64%). AHI had positive correlation with BMI, but not with age, ESS or disease progression (MIRS). All DM1 with AHI>15; 8(80%) and 1(33.33%) in AHI5to15, and AHI<5 groups, respectively had hypersomnolence. CONCLUSION: In this first study on Indian cohort, daytime hypersomnolence, poor nocturnal sleep quality, sleep architecture irregularities are identified to be common in patients with DM1. These abnormalities may be explained by sleep-related breathing disorders that are highly prevalent in these patients.

Non-Motor Symptoms in Cervical Dystonia: A Review.

Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive movements, postures, or both. Dystonic movements are typically patterned, associated with twisting of body parts, and may have tremulousness. Dystonia is usually initiated or worsened by voluntary action and associated with overflow muscle activation. Cervical dystonia (CD) is the most prevalent form of dystonia. CD is a condition characterized by cranial muscle overactivity leading to abnormal intermittent or continuous posturing of the head. Non-motor symptoms are comorbidity of dystonia, which significantly hampers the quality of life among these patients. The symptoms can be as a result of the dystonia itself. However, studies have highlighted the involvement of cortical-striatal-thalamocortical circuits in primary dystonia that could be the pathophysiological basis for the non-motor symptoms. The non-motor symptoms that are commonly associated with dystonia are anxiety, depression, restless leg syndrome, excessive daytime sleepiness, cognitive disturbances, and poor sleep. This review attempts to summarize the literature on non-motor symptoms in patients with CD.

Status Dystonicus as an Acute Sequelae Following Anoxic Cerebral Damage.

BACKGROUND: Status dystonicus (SD) is the term used for extreme, continuous, generalized muscle contractions that are poorly responsive to treatment. Here, we report a rare case of acute hypoxic ischemic encephalopathy presenting with SD. CASE REPORT: A young male sustained cerebral hypoxia following a cardiac event and presented with opisthotonic posturing and dystonia refractory to medical therapy. His serum creatine phosphokinase was high and his urine tested positive for myoglobin. DISCUSSION: SD as an acute sequelae following acute brain hypoxia is rare. Management of brain anoxia is challenging, even more so when the presentation is compounded by refractory SD.

A clinical TRIAD for early suspicion of autoimmune encephalitis as a possibility in patients presenting with progressive cognitive decline.

Patients with progressive cognitive decline mostly suffer from degenerative disease and carry a relatively poor prognosis. But small groups among these patients have a potentially treatable cause of illness and therefore every patient with dementia needs to be considered treatable unless proved otherwise. This group can be identified only by high degree of suspicion based on clinical clues. We have evaluated the validity of some simple clinical clues which we noticed in our patients with immune mediated dementias. The Panic score, Epsworth sleepiness score, catatonic symptoms and history of seizures were compared between 23 and 11 patients with serologically confirmed anti-NMDA antibody and anti-VGKC antibody associated encephalitis respectively. They were compared with 20 patients with probable behavioral variant of Frontotemporal dementia (bvFTD) and 20 patients with probable Alzheimer's disease (AD). Chi-square test was used to compare across the groups and there was significant difference (P < 0.05) across the 4 groups comprising anti NMDA encephalitis, anti VGKC encephalitis, FTD and AD among the four variables (Panic scores, Catatonic symptoms, Epsworth sleepiness score and seizures) studied. Our study revealed that panic and sleepiness is highly significant when tested across all groups and catatonia showed a trend towards NMDA and when compared with degenerative dementia versus immune mediated syndromes all the 4 parameters were highly significant This simple bedside TRIAD of panic, sleepiness with either of catatonia or seizures if found in patients it is appropriate to order antibody assessment before anything else is planned. This needs to be evaluated in a larger sample.