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Spinocerebellar ataxia, autosomal recessive-17 (SCAR17) is a rare hereditary ataxia characterized by ataxic gait, cerebellar signs and occasionally accompanied by intellectual disability and seizures. Pathogenic mutations in the CWF19L1 gene that code for CWF19 like cell cycle control factor 1 cause SCAR17. We report here two unrelated families with the clinical characteristics of global developmental delay, cerebellar ataxia, pyramidal signs, and seizures. Cerebellar atrophy, and T2/FLAIR hypointense transverse pontine stripes were observed in brain imaging. Exome sequencing identified novel homozygous mutations including a splice acceptor site variant c.1375-2 A > G on intron 12 in a male patient and a single nucleotide variant c.452 T > G on exon 5 resulting in a missense variant p.Ile151Ser in the female patient from two unrelated families, respectively. Sanger sequencing confirmed the segregation of these variants in the family members with autosomal recessive inheritance. Transcript analysis of the splice site variant revealed activation of a novel cryptic splice acceptor site on exon 13 resulting in an alternative transcription with a loss of nine nucleotides on exon 13. Translation of this transcript predicted an in-frame deletion of three amino acids p.(459_461del). We also observed a novel exon 13 skipping which results in premature termination of the protein product. Our study expands the phenotype, radiological features, and genotypes known in SCAR17., (© 2023. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

Background: Genetic literacy refers to an individual's ability to understand the basics of genetic concepts and apply them to health-related decisions. The level of genetic literacy influences attitude towards genetic testing and is, in turn, influenced by several other factors. Clinicians must be aware of the genetic literacy of their patients and their caregivers before advising genetic testing and/or undertaking pre and post-test counseling., Method: A systematic review of literature in PubMed was carried out using keywords "Genetic testing", "Genetic counseling", "Knowledge", "Attitude", "Parkinson's disease" in various combinations., Results: Seven eligible studies with a total of 1837 individuals (patients with PD-1355 and patient caregivers-482) were identified. More than half the participants were well-versed in basic concepts of genetics (57.8%) and risks of inheriting PD (60.5%) while less than 10% were aware regarding the contribution of specific genes (e.g. LRRK2). Interest in diagnosis, treatment, prevention and facilitating PD research were central themes for positive attitude while apprehensions revolving around impact on employment and insurance and non-benefit were associated with negative attitudes. Possible associations included greater knowledge scores with positive attitudes towards genetic testing and older age for negative attitude towards testing. Insufficient data on attitudes toward prenatal testing, presymptomatic testing and clinicians' attitude toward testing was identified., Conclusion: Patients with PD and their caregivers are aware of the role of genetics in the etiopathogenesis of their disease, which contributes to their positive attitude towards testing. Further studies exploring negative attitudes towards testing will help overcome the hurdles in genetic testing and counseling in this cohort of patients., Competing Interests: Declaration of competing interest SK, VVH, NK, RY, and PKP have no financial disclosures or any conflicts of interest to report relevant to this article., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: L-2-Hydroxyglutaric aciduria (L2HGA) is a rare progressive neurometabolic disorder with variable clinical presentation including cerebellar ataxia, psychomotor retardation, seizures, macrocephaly and speech problems. In this study, we aimed at identifying the genetic cause in two unrelated families suspected with L2HGA., Methods: Exome sequencing was performed on two patients from family 1 with suspected L2HGA. MLPA analysis was carried out on the index patient of family 2 to detect deletions/duplications in the L2HGDH gene. Sanger sequencing was carried out to validate the identified variants and to confirm segregation of the variants in the family members., Results: In family 1, a novel homozygous variant c.1156C > T resulting in a nonsense mutation p.Gln386Ter was identified in the L2HGDH gene. The variant segregated with autosomal recessive inheritance in the family. In family 2, a homozygous deletion of exon 10 in the L2HGDH gene was identified in the index patient using MLPA analysis. PCR validation confirmed the presence of the deletion variant in the patient which is not present in the unaffected mother or an unrelated control., Conclusion: This study identified novel pathogenic variants in the L2HGDH gene in patients with L2HGA. These findings contribute to the understanding of the genetic basis of L2HGA and highlight the importance of genetic testing for diagnosis and genetic counseling of affected families., (© 2023. The Author(s) under exclusive licence to Belgian Neurological Society.)

Introduction: Vascular parkinsonism (VaP), type of lower body parkinsonism, occurs in relation to ischemic cerebrovascular disease. It can be associated with cognitive impairment. We aimed to study the cortical excitability changes in these patients using transcranial magnetic stimulation (TMS)., Methods: We included 20 patients with VaP and 22 healthy controls (HC). All subjects underwent TMS over left motor cortex with recording of resting motor threshold (RMT), central motor conduction time (CMCT), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), contralateral and ipsilateral silent period (SP) along with RMT and CMCT in the contralateral lower limb. Cognitive assessments were done using Montreal cognitive assessment (MoCA) and Addenbrooke's cognitive evaluation III (ACE III)., Results: Mean age of patients (63.90 ± 7.36 years) was comparable with controls (59.77 ± 6.94 years; p = 0.07). Duration of disease was 2.58 ± 2.57 years. The upper and lower limb RMT of patients (32.45 ± 4.81%; 57.20 ± 11.54%) was significantly low compared to HC (43.64 ± 7.73%; 69.18 ± 14.27%; p < 0.001). There was a significant reduction in SICI in patients (1.87 ± 2.03) compared to HC (0.38 ± 0.29; p < 0.001). In addition, there was a significant prolongation of ipsilateral SP in patients (48.49 ± 24.49) compared to controls (32.04 ± 12.26, p = 0.01). However, there was no significant difference in contralateral SP (p = 0.66) and ICF (p = 0.25) between the two groups. There was a significant prolongation of lower limb CMCT in patients (p < 0.01). There was a positive correlation of SICI with MoCA (r = 0.45, p < 0.05) and ACE-III (r = 0.33, p < 0.05) scores., Conclusion: Reduction in RMT and SICI in patients with VaP suggests abnormalities in GABAergic neurotransmission that may underlie cognitive impairment observed in them., Competing Interests: Declaration of competing interest None of the authors have any conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Movement disorders are the commonest clinical presentation in patients with neurological Wilson's disease (NWD). There are very few studies evaluating the spectrum, severity and their correlation with magnetic resonance imaging (MRI) changes of movement disorders in NWD., Objective: To study the spectrum, topographic distribution, radiological correlate, temporal course and outcome in our cohort of NWD patients., Methods: Retrospective chart review of the NWD patients having movement disorders was performed and analyzed., Results: Sixty-nine patients (males- 47) with NWD were analysed and the mean age at the onset of neurological symptoms was 13.6 ± 6.6 years (median 13 years; range 7-37 years). The first neurological symptom was movement disorder in 55 (79.7%) patients. Tremor (43.6%) and dystonia (41.8%) was the commonest movement disorder as the first neurological symptom. Dystonia (76.8%) was the most common overall movement disorder followed by parkinsonism (52.1%) and tremors (47.8%). Chorea (10.1%), myoclonus (1.4%) and ataxia (1.4%) were the least common movement disorder. Putamen was the most common affected site (95.6%) followed by caudate nucleus (73.9%), thalamus (60.8%), midbrain (59.4%), internal capsule (49.2%), pons (46.3%). Putamen was the most common area of abnormality in dystonia (98%), tremors (85%). Caudate (75%) and putamen (75%) was the most common areas of abnormality in parkinsonism. Favourable outcome was observed in 42 patients (60.8%) following treatment., Conclusion: Dystonia is the most common movement disorder in NWD in isolation or in combination with parkinsonism and tremors. Putamen is the most common radiological site of lesions and more frequently affected in patients with dystonia and tremors. Favourable outcome does occur with appropriate medical and surgical treatment., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2023 The Author(s).)

Background: Long latency reflexes (LLRs) are impaired in a wide array of clinical conditions. We aimed to illustrate the clinical applications and recent advances of LLR in various neurological disorders from a systematic review of published literature., Methods: We reviewed the literature using appropriately chosen MeSH terms on the database platforms of MEDLINE, Web of Sciences, and Google Scholar for all the articles from 1st January 1975 to 2nd February 2021 using the search terms "long loop reflex", "long latency reflex" and "C-reflex". The included articles were analyzed and reported using synthesis without meta-analysis (SWiM) guidelines., Results: Based on our selection criteria, 40 articles were selected for the systematic review. The various diseases included parkinsonian syndromes (11 studies, 217 patients), Huntington's disease (10 studies, 209 patients), myoclonus of varied etiologies (13 studies, 127 patients) including progressive myoclonic epilepsy (5 studies, 63 patients) and multiple sclerosis (6 studies, 200 patients). Patients with parkinsonian syndromes showed large amplitude LLR II response. Enlarged LLR II was also found in myoclonus of various etiologies. LLR II response was delayed or absent in Huntington's disease. Delayed LLR II response was present in multiple sclerosis. Among the other diseases, LLR response varied according to the location of cerebellar lesions while the results were equivocal in patients with essential tremor., Conclusions: Abnormal LLR is observed in many neurological disorders. However, larger systematic studies are required in many neurological disorders in order to establish its role in diagnosis and management.

Objective: aaMutations in the KMT2B gene have been identified in patients previously diagnosed with idiopathic dystonia. Literature on KMT2B-related dystonia is sparse in the Indian and Asian populations., Methods: aaWe report seven patients with KMT2B-related dystonia studied prospectively from May 2021 to September 2022. Patients underwent deep clinical phenotyping and genetic testing by whole-exome sequencing (WES). A systematic literature search was performed to identify the spectrum of previously published KMT2B-related disorders in the Asian subcontinent., Results: aaThe seven identified patients with KMT2B-related dystonia had a median age at onset of four years. The majority experienced onset in the lower limbs (n = 5, 71.4%), with generalization at a median duration of 2 years. All patients except one had complex phenotypes manifesting as facial dysmorphism (n = 4), microcephaly (n = 3), developmental delay (n = 3), and short stature (n = 1). Magnetic resonance imaging (MRI) abnormalities were present in four cases. WES revealed novel mutations in the KMT2B gene in all patients except one. Compared to the largest cohort of patients with KMT2B-related disorders, the Asian cohort, comprising 42 patients, had a lower prevalence of female patients, facial dysmorphism, microcephaly, intellectual disability, and MRI abnormalities. Protein-truncating variants were more prevalent than missense variants. While microcephaly and short stature were more common in patients with missense mutations, facial dysmorphism was more common in patients with truncating variants. Deep brain stimulation, performed in 17 patients, had satisfactory outcomes., Conclusion: aaThis is the largest series of patients with KMT2B-related disorders from India, further expanding the clinico-genotypic spectrum. The extended Asian cohort emphasizes the unique attributes of this part of the world.

Competing Interests: There are no conflicts of interest.

Competing Interests: There are no conflicts of interest.

Psychotic symptoms occur in a majority of schizophrenia patients and in ~50% of all Parkinson's disease (PD) patients. Altered grey matter (GM) structure within several brain areas and networks may contribute to their pathogenesis. Little is known, however, about transdiagnostic similarities when psychotic symptoms occur in different disorders, such as in schizophrenia and PD. The present study investigated a large, multicenter sample containing 722 participants: 146 patients with first episode psychosis, FEP; 106 individuals in at-risk mental state for developing psychosis, ARMS; 145 healthy controls matching FEP and ARMS, Con-Psy; 92 PD patients with psychotic symptoms, PDP; 145 PD patients without psychotic symptoms, PDN; 88 healthy controls matching PDN and PDP, Con-PD. We applied source-based morphometry in association with receiver operating curves (ROC) analyses to identify common GM structural covariance networks (SCN) and investigated their accuracy in identifying the different patient groups. We assessed group-specific homogeneity and variability across the different networks and potential associations with clinical symptoms. SCN-extracted GM values differed significantly between FEP and Con-Psy, PDP and Con-PD, PDN and Con-PD, as well as PDN and PDP, indicating significant overall grey matter reductions in PD and early schizophrenia. ROC analyses showed that SCN-based classification algorithms allow good classification (AUC ~0.80) of FEP and Con-Psy, and fair performance (AUC ~0.72) when differentiating PDP from Con-PD. Importantly, the best performance was found in partly the same networks, including the thalamus. Alterations within selected SCNs may be related to the presence of psychotic symptoms in both early schizophrenia and PD psychosis, indicating some commonality of underlying mechanisms. Furthermore, results provide evidence that GM volume within specific SCNs may serve as a biomarker for identifying FEP and PDP., (© 2023. The Author(s).)

Owing to the presence of multiple enzymatic domains, LRRK2 has been associated with a diverse set of cellular functions and signaling pathways. It also has several pathological mutant-variants, and their incidences show ethnicity biases and drug-response differences with expression in dopaminergic-neurons and astrocytes. Here, we aimed to assess the cell-intrinsic effect of the LRRK2-I1371V mutant variant, prevalent in East Asian populations, on astrocyte yield and biology, involving Nrf2-mediated glutathione machinery, glutamate uptake and metabolism, and ATP generation in astrocytes derived from LRRK2-I1371V PD patient iPSCs and independently confirmed in LRRK2-I1371V-overexpressed U87 cells. Astrocyte yield (GFAP-immunopositive) was comparable between LRRK2-I1371V and healthy control (HC) populations; however, the astrocytic capability to mitigate oxidative stress in terms of glutathione content was significantly reduced in the mutant astrocytes, along with a reduction in the gene expression of the enzymes involved in glutathione machinery and nuclear factor erythroid 2-related factor 2 (Nrf2) expression. Simultaneously, a significant decrease in glutamate uptake was observed in LRRK2-I1371V astrocytes, with lower gene expression of glutamate transporters SLC1A2 and SLC1A3. The reduction in the protein expression of SLC1A2 was also directly confirmed. Enzymes catalyzing the generation of γ glutamyl cysteine (precursor of glutathione) from glutamate and the metabolism of glutamate to enter the Krebs cycle (α-ketoglutaric acid) were impaired, with significantly lower ATP generation in LRRK2-I1371V astrocytes. De novo glutamine synthesis via the conversion of glutamate to glutamine was also affected, indicating glutamate metabolism disorder. Our data demonstrate for the first time that the mutation in the LRRK2-I1371V allele causes significant astrocytic dysfunction with respect to Nrf2-mediated antioxidant machinery, AT -generation, and glutamate metabolism, even with comparable astrocyte yields.

Objective: The objective was to evaluate oral health-related knowledge, and to compare the effectiveness of three different oral health education interventions (OHEI) on plaque removal in a cohort with Parkinson disease., Method and Materials: The three-arm, parallel-group, randomized controlled trial included 63 Parkinson disease stage 1 and 2 patients aged ≥ 40 years and scores ≥ 26 in both Montreal Cognitive Assessment test and Mini-Mental State Exam. These patients were allocated to three OHEI groups: lectures, presentation, and demonstration. The validated questionnaire assessed knowledge level at baseline (0), 1, 2, and 3 months. Oral hygiene at 0 and 3 months was assessed by the Plaque Index and the Patient Hygiene Performance Index (PHPI). Unstimulated whole saliva was collected to assess the salivary flow rate., Results: Pairwise comparison using ANOVA showed a significant decrease in mean percentage knowledge 0, 1, 2, and 3 months in all three groups (P < .001). After Tukey post-hoc analysis the presentation group had significantly higher knowledge (P = .030). ANOVA showed that the percentage of knowledge decreased as time passed (P = .001). Comparison of means of Plaque Index and PHPI scores by MANOVA followed by Tukey post-hoc analysis showed significant decrease in Plaque Index scores from 0 to 3 months (P = .001). No significant change in the salivary flow rate was noted., Conclusion: Pictorial representation of OHEI is a better mode of intervention compared to lectures and demonstrations in Parkinson disease stage 1 and 2 patients. Despite the decline in knowledge with time, Plaque Index scores reduced significantly, implying that this form OHEI offers positive benefits.

Background: Creutzfeldt-Jakob disease (CJD) is a rare neuro degenerative disease that is mainly characterized by rapidly progressive dementia along with a varying combination of myoclonus, visual, cerebellar, pyramidal/extrapyramidal and akinetic mutism. Several movement disorders phenomenologies can occurs either at onset, as presenting symptom or during the course of illness. Present study aims to characterize the clinical, radiological features and the outcome of patients with CJD with movement disorders as the forthcoming manifestation., Methods: Chart review of patients with CJD with movement disorders. Demographic, clinical and radiological details of the patients were reviewed., Results: 25 patients (13 males) of sCJD with median age at presentation of 58 years and median duration of illness of 5 months were included in the study. According to revised CDC diagnostic criteria 1 patient was classified as definite sCJD, 20 as probable and 2 as possible CJD. Myoclonus, ataxia and parkinsonism were the most common movement disorder and chorea was the least common. Magnetic resonance imaging of brain was performed in all and basal ganglia abnormality and cortical ribboning was seen in more than two-third of cases. Electroencephalographic abnormality was noted in 21 patients with triphasic waves and periodic sharp waves seen in 7 and 6 patients respectively. Cerebrospinal fluid 14-3-3 assay was abnormal in 2 out of 4 patients. Atypical presentations were noted in the form of ataxic presentation, CBS like presentation and choreiform presentation., Conclusion: Myoclonus, ataxia and parkinsonism are the most frequent movement disorders phenomenology observed in patients with sCJD., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2023 The Author(s).)

Background: About 70-90% of Parkinson's disease (PD) patients have olfactory deficits which is considered as pre-motor symptom of PD. Lewy bodies have been demonstrated in the olfactory bulb (OB) in PD., Objective: To assess the OB volume (OBV), olfactory sulcus depth (OSD) in PD and compare with progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and vascular parkinsonism (VP) patients and determine the cut-off volume of OB that will aid in the diagnosis of PD., Methods: This was a cross-sectional, hospital based, single-center study. Forty PD, 20 PSP, 10 MSA, 10 VP patients and 30 controls were recruited. OBV and OSD was assessed using 3-T magnetic resonance imaging (MRI) brain. Olfaction was tested using Indian Smell Identification test (INSIT)., Results: The mean total OBV in PD was 113.3 ± 79.2 mm 3 and 187.4 ± 65.0 mm 3 in controls ( P  = 0.003) which was significantly lower in PD. The mean total OSD in PD was 19.4 ± 8.1 and 21.1 ± 2.2 mm in controls ( P  = 0.41) with no difference. The mean total OBV was significantly lower in PD as compared to that of PSP, MSA and VP patients. There was no difference in the OSD among the groups. The total OBV in PD had no association with age at onset, duration of disease, dopaminergic drugs dosage, motor and non-motor symptoms severity but had positive correlation with cognitive scores., Conclusion: OBV is reduced in PD patients as compared to PSP, MSA, VP patients and controls. OBV estimation by MRI adds to the armamentarium in the diagnosis of PD., (© 2023 International Parkinson and Movement Disorder Society.)

PSP and CBD are usually multi system sporadic disorders characterized by tau inclusions in neurons and glia. The clinical and neuroimaging features are different .However in some cases overlapping of features are noted. Here we present a case of a 65 years old female patient, presenting a 3 years history of insidious onset of asymmetric right upper and lower limb dystonia, followed by slowness, falls and injuries to the back, Parkinsonism, urinary incontinence and cognitive dysfunction and upward gaze palsy. MRI findings were suggestive of moderate cerebral and cerebellar atrophy with prominent ventricular system, reduced antero-posterior midline midbrain diameter, at the level of superior colliculus on axial imaging (morning glory sign was positive) on the left side. PET showed asymmetric hypo metabolism noted in the left superior and middle frontal gyrus, superior temporal and mid temporal gyrus in addition to striatum and thalamus, as well as midbrain, pons and right cerebellar hemisphere. Overall MR/PET was suggestive of unilateral PSP (left) and it corroborated with clinical history of unilateral dystonia and supranuclear gaze palsy. Based on MRI the differential considered was also CBD, but PET showed metabolic activity in the motor cortex. Additionally based on the hummingbird sign and morning glory sign a rare diagnosis of unilateral PSP could be made which also corroborated with the clinical picture.The case report emphasizes the utility of PETMRI simultaneously in situations like these to pick atypical variants or cases with overlapping pathology to reach a diagnosis with in vivo imaging methods., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Nuclear Medicine.)

Purpose: Psychiatric comorbidity in Parkinson's disease (PD) and atypical parkinsonian syndromes (APS) has been consistently associated with poor outcomes. However, the co-occurrence of multiple psychiatric disorders has been sparsely studied. This study examines the prevalence, patterns, and correlates of psychiatric comorbidity and multimorbidity among in-patients hospitalised with PD/APS., Methods: Patients (N-110 [PD-71, APS-39]) underwent a single cross-sectional assessment. Psychiatric comorbidity was examined using the Mini International Neuropsychiatric Interview. Other domains assessed include sleep disorders, quality of life, and caregiver burden., Statistical Analysis: In addition to descriptive statistics, multinomial logistic regression was used to examine the effect of sociodemographic and clinical factors on comorbidities., Results: The prevalence of psychiatric comorbidity in patients with PD and APS was 77.00% and 71.79%, with approximately half of those having co-occurrence of multiple psychiatric disorders. In both disorders, depression was the most common, followed by anxiety disorder. The two commonest patterns of multimorbidity reported in PD were the combination of depression and anxiety disorder, followed by the combination of psychosis, depression, and anxiety, with the order being reversed in APS. When compared to those without, those with single psychiatric comorbidity had higher odds of having REM sleep behaviour disorder and caregiver stress. Those with multiple psychiatric comorbidities had higher odds of being female, higher UPDRS part-1 scores, REM sleep behaviour disorder, poor sleep quality, and caregiver stress., Conclusion: Psychiatric illness is highly comorbid among patients with PD/APS, with most having multiple co-occurring psychiatric illnesses. Clinicians must be aware to ensure early detection and intervention.

Background: Recent studies have shown various neurological adverse events associated with COVID-19 vaccine., Objective: We aimed to retrospectively review and report the neurological diseases temporally associated with COVID-19 vaccine., Methods: We performed a retrospective chart review of admitted patients from 1st February 2021 to 30th June 2022. A total of 4672 medical records were reviewed of which 51 cases were identified to have neurological illness temporally associated with COVID-19 vaccination., Results: Out of 51 cases, 48 had probable association with COVID-19 vaccination while three had possible association. Neurological spectrum included CNS demyelination (n = 39, 76.5 %), Guillain-Barré-syndrome (n = 3, 5.9 %), stroke (n = 6, 11.8 %), encephalitis (n = 2, 3.9 %) and myositis (n = 1, 2.0 %). Female gender had a greater predisposition (F:M, 1.13:1). Neurological events were more commonly encountered after the first-dose (n = 37, 72.5%). The mean latency to onset of symptoms was 13.2 ± 10.7 days after the last dose of vaccination. COVIShield (ChAdOx1) was the most commonly administered vaccine (n = 43, 84.3 %). Majority of the cases with demyelination were seronegative (n = 23, 59.0 %) which was followed by anti-Myelin oligodendrocyte-glycoprotein associated demyelination (MOGAD) (n = 11, 28.2 %) and Neuromyelitis optica (NMOSD) (n = 5, 12.8 %). Out of 6 Stroke cases, 2 cases (33.3 %) had thrombocytopenia and coagulopathy. At discharge, 25/51 (49.0 %) of the cases had favourable outcome (mRS 0 to 1). Among six patients of stroke, only one of them had favourable outcome., Conclusion: In this series, we describe the wide variety of neurological syndromes temporally associated with COVID-19 vaccination. Further studies with larger sample size and longer duration of follow-up are needed to prove or disprove causality association of these syndromes with COVID-19 vaccination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Occasionally, movement disorders can occur following interventional procedures including but not limited to radiotherapy, dental procedures, and cardiac, cerebral and spinal surgeries. The majority of these disorders tend to be unexpected sequelae with variable phenomenology and latency, and they can often be far more disabling than the primary disease for which the procedure was performed. Owing to poor knowledge and awareness of the problem, delays in diagnosing the condition are common, as are misdiagnoses as functional movement disorders. This narrative review discusses the phenomenology, pathophysiology, and potential treatments of various movement disorders caused by interventional procedures such as radiotherapy and neurological and non-neurological surgeries and procedures.

Introduction: Vascular Parkinsonism (VaP) is characterized by symmetric, predominantly lower limb bradykinesia and rigidity and no significant improvement with levodopa. We aimed to describe the clinical and radiological features of patients with VaP and the factors that determine levodopa responsiveness., Methods: This is a retrospective chart review of patients with VaP . The study included 44 patients (36 men) with VaP . The diagnosis was based on Zijlman's criteria. Demographic and clinical details were recorded from the case files. MRI data were available for all the patients. However, the motor severity scores assessed in the OFF and ON states using the unified Parkinson's disease rating scale (UPDRS) part III were available for 17 patients only. Based on the Magnetic Resonance Imaging (MRI) finds, patients were categorized into isolated periventricular ischemic (PVI) changes, isolated basal ganglia (BG)/thalamic infarcts, and both combined., Results: The mean age at the diagnosis was 65.2 ± 7.4 years. Further, the age at the onset of symptoms was 61.8 ± 8.1 years and the total disease duration was 3.5 ± 2.5 years. Hypertension was the most common risk factor and was observed in 88.6% of patients. Symmetrical lower body parkinsonism was observed in 88.6%. The mean UPDRS part III OFF score was 33.76 ± 12.7 and ON score was 30 ± 13.98. PVI changes were the most common MRI abnormality detected. Patients with isolated BG/thalamic infarcts had better mini-mental status examination scores and better levodopa responsiveness compared to other groups., Conclusions: Hypertension was the most common risk factor seen in patients with VaP. Those with isolated BG/thalamus infarcts demonstrated better levodopa responsiveness., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Annals of Indian Academy of Neurology.)

Competing Interests: There are no conflicts of interest.

Background: Oculomotor abnormalities are one of the cardinal clinical features of progressive supranuclear palsy (PSP). Vertical saccadic slowing is an early sign of PSP. The association between oculomotor abnormalities and sleep architecture has not been studied so far., Objectives: To study the association of oculomotor abnormalities of PSP with the sleep stages by using video polysomnography (vPSG)., Methods: This was a cross-sectional single-center study. Twenty-two patients with PSP and 15 age and gender-matched controls were recruited. Saccades, vestibulo-ocular reflex, and optokinetic nystagmus were assessed and graded clinically in all patients and one overnight vPSG was done in all cases., Results: Vertical saccades, upward more than downwards, were affected in all cases. While horizontal saccades were normal only in 41% of cases. Vertical optokinetic nystagmus (OKN) was affected in all cases. Horizontal OKN was normal in 36% of patients. The vertical upward saccades had a negative correlation with N1% and duration (r = -0.418; p = 0.05, r = -0.457; p = 0.03), N3% and duration (r = -0.486; p = 0.02, r = -0.510; p = 0.01), REM% (r = -0.449; p = 0.04), total sleep time (r = -0.487; p = 0.02) and sleep efficiency (r = -0.444; p = 0.04). There was a positive correlation between horizontal OKN and sleep onset latency (r = 0.432; p = 0.05)., Conclusions: Vertical saccadic restriction in PSP has significant negative correlation with total sleep time and sleep efficiency. The oculomotor and sleep abnormalities in PSP are probably interlinked and their assessment is useful in determining the characteristics of the disease., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Niemann-Pick disease type C (NPC) is an autosomal recessive neurovisceral lipid storage disorder caused by mutations in the NPC 1 or 2 genes. Movement disorders can occur as the first symptom and as predominant symptom mainly in juvenile-onset. The frequency and heterogeneity of movement disorders in NPC are not well described. We studied the frequency and spectrum of movement disorders in patients with NPC of different age of onset., Methods: Retrospective chart review of patients with NPC diagnosed based on the Suspicion Index tool and demonstration of foamy macrophages/sea-blue histiocytes in bone marrow aspirate., Results: We report 9 cases of NPC with 2 patients of late-infantile, 4 juvenile-onset and 3 of adult-onset. The mean age at onset of symptoms was 11.7 ± 10.4 (range 4-38 years) and the median duration of illness was 4 years. Vertical supranuclear gaze palsy (VSGP) was noted in 8 patients and VSGP with slowing of saccade in 1 patient. Splenomegaly was seen in 5 patients. Movement disorders as the first symptom occurred in 4 patients. Dystonia was the first symptom in 2 patients and cerebellar ataxia in 2 patients. Cerebellar ataxia occurred during the course of illness in 5 patients, dystonia in 6 patients. One patient with late-infantile NPC had stimulus-sensitive myoclonus., Conclusion: Movement disorders are common in NPC and occur as a presenting symptom. Cerebellar ataxia and dystonia are the most common movement disorder in NPC. Vertical supranuclear gaze palsy along with the movement disorders should lead to clinical suspicion of NPC., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2022 The Author(s).)

Background: Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism. We aimed to study the abnormalities in the retinal layers in patients with WD using optical coherence tomography (OCT)., Methods: The study is a chart review of 16 patients with WD (six females) who underwent OCT at our hospital during follow-up visits. Spectral-domain OCT was performed in all subjects to assess the thickness of macula and retinal nerve fiber layer (RNFL) and the data was compared with 14 healthy controls (three females)., Results: The mean age of the patients was 20.81 ± 7.47 years and controls was 26.86 ± 9.95 years. The mean age at the onset of the illness was 16.25 ± 5.57 years (range 11-28 years) with the mean duration of illness being 4.81 ± 3.31 years at the final follow-up examination. The mean macular thickness was found to be significantly reduced in patients (232.13 ± 19.39) when compared to controls (271.30 ± 17.32 μm; P = 0.01). There was a significant difference in the ganglion cell and inner plexiform (GCIP) layer between the patients (86.83 ± 8.20 μm) and controls (97.72 ± 5.31 μm; P = 0.01). In addition, the outer nuclear layer with the photoreceptor layer (ONL + PRL) thickness was also reduced in WD (93.90 ± 10.23 μm vs. 108.43 ± 10.00 μm; P = 0.01) There was no change in the RNFL thickness, between the two groups ( P = 0.53)., Conclusions: Abnormalities of the retinal layers were observed in the patients with WD. OCT is a non-invasive tool to identify and quantify the abnormalities of the retinal layers., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Annals of Indian Academy of Neurology.)

Background: Sleep disturbances have been reported to occur in progressive supranuclear palsy (PSP). The anatomical regions affected in PSP and those regulating sleep and wake cycle like dorsal raphe nucleus, locus coeruleus (LC), and pedunculopontine nucleus (PPN) overlap. There is a paucity of polysomnographic studies in PSP and they have shown altered sleep architecture., Objective: To study the sleep architecture in patients with PSP using video-polysomnography (vPSG) and correlate it with the disease severity and duration., Methods: This was a prospective, cross-sectional, case-control, single-center study. A total of 22 patients with PSP and 15 age and gender-matched controls were recruited. The cases and controls underwent clinical assessment, face-to-face interviews with sleep questionnaires, anxiety and depression scales, and one overnight vPSG. The sleep architecture was analyzed in detail., Results: The sleep architecture was altered as compared to the controls. The total sleep time, stage N2 duration, stage N3 duration, rapid-eye-movement (REM) sleep duration, sleep efficiency %, and N2%, N3%, and REM% were significantly lesser in PSP patients. The wake duration, wake after sleep onset (WASO) duration, wake%, WASO%, stage N1 duration was significantly greater in PSP patients. The stage N2 and N3 latencies were significantly prolonged in patients. REM sleep without atonia was noted in four patients and no patients had vPSG proven REM sleep behavior disorder., Conclusions: Sleep architecture is altered in PSP even during the early stages of the disease. There is reduced total sleep including both non-REM and REM sleep, sleep efficiency, prolonged sleep latencies, and increased wake duration. This correlates with the neurodegenerative processes affecting the anatomical region regulating the sleep/wake cycle like dorsal raphe nucleus, locus coeruleus (LC), pedunculopontine nucleus (PPN)., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Annals of Indian Academy of Neurology.)

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder. In India, an accurate number of PD patients remains uncertain owing to the unawareness of PD symptoms in the geriatric population and the large discrepancy between the number of PD patients and trained neurologists. Constructing additional neurological care centers along with using technology and integrating it into digital healthcare platforms will help reduce this burden. Use of technology in PD diagnosis and monitoring started in 1980s with invasive techniques performed in laboratories. Over the last five decades, PD technology has significantly evolved where now patients can track symptoms using their smartphones or wearable sensors. However, the use of such technology within the Indian population is non-existent primarily due to the cost of digital devices and limited technological capabilities of geriatric patients especially in rural areas. Other reasons include secure data transfers from patients to physicians and the general lack of awareness of wearables devices. Thus, creating a simple, cost-effective and inconspicuous wearable device would yield the highest compliance within the Indian PD patient population. Implementation of such technology will provide neurologists with wider outreach to patients in rural locations, remote monitoring and empirical data to titrate medication., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Annals of Indian Academy of Neurology.)

Introduction: Movement disorders can present in emergency services in an acute severe form which can be life threatening if not recognized. The relative frequency and spectrum of movement disorder emergencies have not been studied extensively. We studied the frequency, spectrum, and outcome of patients presenting with movement disorders emergencies., Methods: This was a prospective, descriptive single center study. Patients presenting with acute movement disorders to the neurology emergency services of the institute during the study period from April 2019 to June 2021 were analyzed., Results: A total of 71 patients presented with acute movement disorders during the study period. Out of them, 65 patients had hyperkinetic and 6 patients had hypokinetic movement disorders emergencies. Fifteen patients were below the age of 18 years. Chorea (59.1%) was the most common movement disorder emergencies followed by dystonia and myoclonus in adults. Dystonia (33.3%) was the common movement disorder emergencies in children. Hyperglycemia followed by stroke was the most common etiology of acute movement disorders., Conclusion: This study brings out some novel findings on the movement disorders emergencies in Indian scenario. Chorea was the most common movement disorder emergencies presenting to the neurology emergency services. Early recognition and management of movement disorders emergencies help in reducing morbidity., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Annals of Indian Academy of Neurology.)

Background: PLA2G6-Associated Neurodegeneration, PLAN, is subdivided into: Infantile neuroaxonal dystrophy, atypical neuroaxonal dystrophy, and adult-onset dystonia parkinsonism [1]. It is elicited by a biallelic pathogenic variant in phospholipase A2 group VI (PLA2G6) gene. In this study we describe new cases and provide a comprehensive review of previously published cases., Methods: Eleven patients, from four different institutions and four different countries. All underwent a comprehensive chart review., Results: Ages at onset ranged from 1 to 36 years, with a median of 16 and a mean of 16.18 ± 11.91 years. Phenotypic characteristics were heterogenous and resembled that of patients with infantile neuroaxonal dystrophy (n = 2), atypical neuroaxonal dystrophy (n = 1), adult-onset dystonia parkinsonism (n = 1), complex hereditary spastic paraparesis (n = 3), and early onset Parkinson's disease (n = 2). Parental genetic studies were performed for all patients and confirmed with sanger sequencing in five. Visual evoked potential illustrated optic atrophy in P4. Mineralization was evident in brain magnetic resonance imaging of P1, P2, P4, P5, P7, and P11. Single photon emission computed tomography was conducted for three patients, revealed decreased perfusion in the occipital lobes for P10. DaTscan was performed for P11 and showed decreased uptake in the deep gray matter, bilateral caudate nuclei, and bilateral putamen. Positive response to Apomorphine was noted for P10 and to Baclofen in P2, and P3., Conclusions: PLAN encompasses a wide clinical spectrum. Age and symptom at onset are crucial when classifying patients. Reporting new variants is critical to draw more attention to this condition and identify biomarkers to arrive at potential therapeutics., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Hyperkinesias are heterogeneous involuntary movements that significantly differ in terms of clinical and semeiological manifestations, including rhythm, regularity, speed, duration, and other factors that determine their appearance or suppression. Hyperkinesias are due to complex, variable, and largely undefined pathophysiological mechanisms that may involve different brain areas. In this chapter, we specifically focus on dystonia, chorea and hemiballismus, and other dyskinesias, specifically, levodopa-induced, tardive, and cranial dyskinesia. We address the role of neurophysiological studies aimed at explaining the pathophysiology of these conditions. We mainly refer to human studies using surface and invasive in-depth recordings, as well as spinal, brainstem, and transcortical reflexology and non-invasive brain stimulation techniques. We discuss the extent to which the neurophysiological abnormalities observed in hyperkinesias may be explained by pathophysiological models. We highlight the most relevant issues that deserve future research efforts. The potential role of neurophysiological assessment in the clinical context of hyperkinesia is also discussed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Charcot-Marie-Tooth disease, type 4D (CMT4D) is a progressive, autosomal recessive form of CMT, characterized by distal muscle weakness and atrophy, foot deformities, severe motor sensory neuropathy, and sensorineural hearing impairment. Mutations in NDRG1 gene cause neuropathy in humans, dogs, and rodents. Here, we describe clinical and genetic features of a 17-year-old male with wasting of hand muscle and foot and severe motor neuropathy. Whole exome sequencing was carried out on the patient and his unaffected parents. We identified a novel deletion of nine nucleotides (c.537 + 2&#95;537 + 10del) on the splice donor site of intron 8 in NDRG1 gene. The Sanger sequencing confirmed the segregation of this mutation in autosomal recessive inheritance. Furthermore, transcript analysis confirmed a splice defect and reveals using of an alternate cryptic splice donor site on the downstream intronic region. It resulted in an insertion of 42 nucleotides to exon 8 of NDRG1. Translation of the resulting transcript sequence revealed an insertion of 14 amino acids in-frame to the existing NDRG1 protein. This insertion is predicted to disrupt an alpha helix which is involved in protein-protein interactions in homologous proteins. Our study expands the clinical and genetic spectrum of CMT4D. The splice defect we found in this patient reveals a novel splice isoform of NDRG1 as the potential cause for the neuropathy observed in this patient., (© 2022. Fondazione Società Italiana di Neurologia.)

This review is part of the series on the clinical neurophysiology of movement disorders. It focuses on Parkinson's disease and parkinsonism. The topics covered include the pathophysiology of tremor, rigidity and bradykinesia, balance and gait disturbance and myoclonus in Parkinson's disease. The use of electroencephalography, electromyography, long latency reflexes, cutaneous silent period, studies of cortical excitability with single and paired transcranial magnetic stimulation, studies of plasticity, intraoperative microelectrode recordings and recording of local field potentials from deep brain stimulation, and electrocorticography are also reviewed. In addition to advancing knowledge of pathophysiology, neurophysiological studies can be useful in refining the diagnosis, localization of surgical targets, and help to develop novel therapies for Parkinson's disease., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Robert Chen received honoraria from Abbvie, Merz and Ipsen, outside of the submitted work. Alfonso Fasano received honoraria for his work as consultant for Abbvie, Abbott, Boston Scientific, Ipsen, Medtronic, and Sunovion; he sits in the advisory board for Abbvie, Boston Scientific, Ceregate, and Inbrain; received speaker fees from Abbvie, Abbott, American Academy of Neurology, Boston Scientific, Brainlab, Ipsen, Medtronic, Merz, Movement Disorders Society, Sunovion, Paladin Labs, and UCB; he received royalties from Springer and has received research grants from Abbvie, Boston Scientific, Dystonia Medical Research Foundation, University of Toronto, Michael J Fox Foundation, Medtronic, and the MSA coalition. Rick Helmich has served as a consultant for Roche Pharma. William D. Hutchison has received honoraria and travel support from Medtronic Inc. Andrea A. Kuhn: Personal fees from Medtronic, personal fees from Boston Scientific, personal fees from Abbott, personal fees from Ipsen Pharma, personal fees from Teva, outside the submitted work. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V.)

Objective: With the use of next-generation sequencing in clinical practice, several genetic etiologies of dystonia have been identified. This study aimed to ascertain the utility of clinical exome sequencing (CES) in dystonia and factors suggestive of a genetic etiology., Methods: This study was a retrospective chart review of patients with dystonia who had undergone CES for the evaluation of dystonia., Results: Forty-eight patients (35 males, 46 families) with dystonia were studied, with a mean age at onset of 16.0 ± 14.1 (1-58) years. A pathogenic/likely pathogenic variant was found in 20 patients (41.7%) among which 14 patients (29.2%) carried a novel variant. CES was more likely to detect a genetic diagnosis in patients with an early age at onset, i.e., ≤ 20 years., Conclusion: CES is a useful tool in the diagnostic evaluation of dystonia, with a yield of close to 40%. Patients with an earlier age at onset have a higher likelihood of having dystonia due to a genetic cause than those with a later age at onset.

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: We aimed to study the cortical and intracortical functions in patients of ET using transcranial magnetic stimulation (TMS) and to evaluate the effect of continuous theta burst stimulation (cTBS) on the tremor characteristics., Methods: Ten ET and 20 healthy controls were included in the study. All the participants were evaluated with TMS with recording of resting motor threshold (RMT), central motor conduction time, contralateral silent period (cSP), short interval intracortical inhibition (SICI) and intracortical facilitation (ICF). Subsequently only ET patients underwent cTBS of the motor cortex (M1) followed by repeat TMS., Results: The mean age of the patients (46.5 ± 17.2 years) was comparable to healthy controls (55.4 ± 9.2 years; p = 0.16). There was a non-significant increase in RMT in ET patients (44 ± 12.5%) when compared to healthy controls (40.9 ± 6.9%; p = 0.48). There was a significant reduction of cSP in the ET group (102.03 ± 15.26 msec) compared to healthy controls (116.1 ± 15.2, p = 0.03). In addition, a significant reduction in ICF was observed in ET patients (0.9 ± 0.7) compared to healthy controls (1.8 ± 0.8, p = 0.01). Following cTBS there was a significant reduction in the tremor scores [FTMRS (Pre-cTBS: 29.3 ± 18.7, Post-cTBS: 25.3 ± 16.8; p < 0.001) and TETRAS (pre-cTBS: 34.4 ± 16.2, post-cTBS: 29.8 ± 12.1; p = 0.01)] and improvement (increase) of the duration of cSP (pre-cTBS: 102.03 ± 15.3 msec., post-cTBS: 119.4 ± 12.03 msec; p = 0.05)., Conclusions: Patients with ET have GABAergic and glutaminergic dysfunction as demonstrated by reduced cSP and ICF. However, only the cSP improved following cTBS of M1 region, with a corresponding improvement of tremor severity suggesting the effect of cTBS on the cerebello-thalamo-cortical network., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Joubert syndrome (JS) is a rare syndrome characterized by ataxia and the molar tooth sign (MTS) on imaging. The present study aims to explore the clinical and radiological features in a cohort of patients with JS., Methods: This was a retrospective chart review of patients with JS evaluated by movement disorder specialists., Results: Nine patients were included in the study. All patients had facial dysmorphism and ocular abnormalities, and 4 patients had dystonia. Ocular tilt reaction and alternate skew deviation (66%) were the most common ocular abnormalities. Horizontally aligned superior cerebellar peduncles were observed in all four patients with diffusion tensor imaging, with a lack of decussation in three. Exome sequencing performed in four patients revealed novel variants in the MKS1, CPLANE1, and PIBF1 genes., Conclusion: Facial dysmorphism, ocular abnormalities and classical imaging findings were observed in all patients with JS. Apart from ataxia, dystonia and myoclonus are other movement disorders observed in JS.

Background: Parkinson's disease (PD) is characterized by bradykinesia, tremor, rigidity, postural instability and cognitive deficits in attention, executive functions, learning and memory. Motor speed, measured using Finger Tapping Test (FTT), is an important indicator and predictor of cognitive and motor functions. Deficits in motor speed have significant impact on performance on other neuropsychological tests., Objective: This study aimed to understand and compare the cognitive profile of patients with and without deficits in motor speed as evaluated on the FTT., Method and Material: A detailed neuropsychological evaluation using the NIMHANS Neuropsychological Battery was carried out on 70 PD patients. The PD patients were divided into patients with (n = 46) and without (n = 24) motor speed deficits. The two groups were comparable with regard to age (P = 0.591), years of formal education (up to 10 th - 24.3, above 10 th - 75.7) duration of illness (P = 0.703) and age of onset (P = 0.721)., Results: Across the various cognitive domains such as executive functions, verbal recognition, visuospatial functions, visual learning and memory, the group without deficits in motor speed performed significantly better in comparison to patients with motor symptoms., Conclusion: A short and simple test such as FTT may be helpful in predicting the range and severity of cognitive deficits across other cognitive domains in patients with PD. Future studies on larger cohort examining the intricate role and association of FTT and other motor functions such as dexterity may be helpful in understanding the nature and severity of other cognitive functions in this clinical population., Competing Interests: None

Background and Aims: Myelin oligodendrocyte glycoprotein (MOG) is an oligodendrocytopathy resulting in demyelination. We aimed to determine the frequency of MOG-associated disorders (MOGAD), its various clinical phenotypes, and imaging characteristics., Methods: All patients with MOGAD were included. Description of the various clinical phenotypes, investigation profile, therapeutic response, differences between pediatric and adult-onset neurological disorders, determination of poor prognostic factors was done., Results: The study population consisted of 93 (M:F = 45:48) (Pediatric:40, Adult-onset:47, Late-onset:7) patients with a median age of 21 years. Among the 263 demyelinating episodes; 45.8% were optic neuritis (ON), 22.8% were myelopathy, 17.1% were brainstem, 7.6% were acute demyelinating encephalomyelitis(ADEM), 4.2% were opticomyelopathy and 2.3% with cerebral manifestations. There was exclusive vomiting in 24.7% prior to onset of clinical syndrome, none of them had area postrema involvement. ADEM was exclusively seen in pediatric patients. Poor prognostic indicators included: (i) incomplete recovery from an acute attack, (b) brainstem syndrome, (c) ADEM with incomplete recovery, (d) MRI suggestive of leukodystrophy pattern, (e) severe ON, (f) ADEMON., Conclusions: The Spectrum of MOG-associated disorders is wider affecting the brain (grey and white matter) and the meninges. There are various clinical phenotypes and MRI patterns, recognition of which may help in the determination of therapeutic strategies, and long-term prognosis.

Objective: Atlantoaxial instability, although rarely reported in the literature, can be associated with cervical dystonia (CD) and may lead to compression of the cord at the craniovertebral junction. We present a case series of 4 patients of longstanding CD with neurologic complications. Treatment strategies and challenges are discussed., Methods: Retrospective analysis of 4 cases of longstanding CD with complications of myelopathy or radiculopathy., Results: The average age at onset of complications was 28 years (range, 17-37). The average duration of CD was 23.75 years. Narrowing of the craniovertebral junction was seen in 3 patients, of which 2 had os odontoideum, and 1 had rotational malalignment at the atlantoaxial joint. One patient had disc desiccation with bulge and intramedullary signal changes in the cord at C3-4 level. Medical treatment was not satisfactory, but botulinum toxin was partly useful in all. One patient had sequelae of myelopathy and did recover partially after deep brain stimulation. Of the 2 patients who underwent surgical fixation with a fusion of the spine, one improved, and the other had no improvement due to irreversible cord damage. The overall outcome was satisfactory only in 2 patients., Conclusions: Early-onset CD can lead to cord complications at a young age and at higher levels of the cervical spine and at the cervicovertebral junction. Comprehensive management by a multidisciplinary team is crucial to prevent complications early., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Despite anti-cholinergics being the oldest type of medication used for the treatment of Parkinson's disease (PD), the mechanism of action and exact benefit is unclear. This study compared the effectiveness of trihexyphenidyl (THP) and levodopa (LD) on motor symptoms in patients with PD. Patients with PD who are currently taking or had taken THP were recruited. UPDRS-III was done following overnight medication OFF state and 30 min, 60 min, 90 min, and 120 min after THP (4 mg). After a forty-eight-hour interval, UPDRS-III was assessed one hour after Levodopa/carbidopa (200/50 mg) in an overnight OFF state. Twenty patients with a mean age of 57.9 ± 7.8 years and mean duration of illness of 5.1 ± 3.6 years were recruited. UPDRS-III score reduction (%) with THP was maximum in the tremor sub-score (53.8 ± 22.8) and was significantly better compared to improvement in total-UPDRS-III (27.0 ± 14.7), bradykinesia-UPDRS-III (22.2 ± 27.2), rigidity-UPDRS-III (29.5 ± 28.0) and axial-UPDRS-III (8.1 ± 13.3) sub-score. In comparison, respective LD improvement was 67.1 ± 22.9 (tremor-UPDRS-III), 61.3 ± 14.4 (total-UPDRS-III), 67.9 ± 32.1 (bradykinesia-UPDRS-III), 65.3 ± 25.5 (rigidity-UPDRS-III) and 50.7 ± 16.0 (axial-UPDRS-III). Improvement (%) in tre-UPDRS-III post-THP was comparable to that of post-LD (53.8 ± 22.8 vs. 67.1 ± 22.9, p = 0.057). Those with same or better tremor response with THP had significantly milder baseline tremor severity than those who had better response with LD (tre-UPDRS-III-OFF, 10.0 ± 2.8 vs. 5.8 ± 4.0, p = 0.013). Both THP and LD showed significant improvement in UPDRS-III. With THP, the maximum degree of improvement was in the tremor sub-score and not significantly different to that obtained by LD. Those with better tremor response on THP had milder tremor severity.

Background: The COVID-19 pandemic has compelled countries to impose lockdowns to curb the spread. As a result of the lockdown and need for health care services to cater to acute diseases on priority, patients with chronic illnesses such as Parkinson's disease (PD) may be facing several difficulties., Aims: This study aimed to explore the effects of prolongation of lockdown on patients with PD by evaluating possible problems faced during a lockdown and worsening of symptoms if any., Materials and Methods: One hundred patients with PD and their caregivers were contacted., Results: We observed a significant increase in problems faced due to this pandemic, specifically, the inability to access health care, and difficulty procuring medication. Patients also reported worsening of motor symptoms., Conclusions: The present findings highlight the need for health care systems to consider a plan of action for chronic neurological diseases like PD, which are worsening in the absence of regular hospital visits., Competing Interests: None

Background: Huntington's disease (HD), an inherited, often late-onset, neurodegenerative disorder, is considered to be a rare, orphan disease. Research into its genetic correlates and services for those affected are inadequate in most low-middle income countries, including India. The apparent 'incurability' often deters symptomatic and rehabilitative care, resulting in poor quality of life and sub-optimal outcomes. There are no studies assessing disease burden and outcomes from India., Methods: We attempted to evaluate individuals diagnosed to have HD at our tertiary-care center between 2013 and 2016 for clinical symptoms, functionality, mortality, follow up status through a structured interview, clinical data from medical records and UHDRS-TFC scoring., Results: Of the 144 patients, 25% were untraceable, and another 17 (11.8%) had already died. Mean age at death and duration of illness at the time of death, were 53 years and 7 years respectively, perhaps due to suicides and other comorbidities at an early age. The patients who could be contacted (n = 81) were assessed for morbidity and total functional capacity (TFC). Mean CAG repeat length and TFC score were 44.2 and 7.5 respectively. Most individuals (66%) were in TFC stage I and II and could perhaps benefit from several interventions. The TFC score correlated inversely with duration of illness (p < 0.0001). The majority were being taken care of at home, irrespective of the physical and mental disability. There was a high prevalence of psychiatric morbidity (91%) including suicidal tendency (22%). Three of the 17 who died had committed suicide, and several other families reported suicidal history in other family members. Only about half the patients (57%) maintained a regular clinical follow-up., Conclusions: This study demonstrates the poor follow-up rates, significant suicidality and other psychiatric symptoms, sub-optimal survival durations and functional outcomes highlighting the need for holistic care for the majority who appear to be amenable to interventions.

Introduction: Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder pathologically characterized by localized neuronal loss, and presence of eosinophilic intranuclear inclusions in neurons and glial cells., Case Report: A 50-year-old man presented with rapidly progressive dementia, behavioral changes, gait disturbances, and incontinence of 3 months duration. His brain magnetic resonance imaging showed diffuse T2/FLAIR hyperintensity of basal ganglia, thalami, cerebral peduncles, ventral pons, and supratentorial white matter with a frontal predominance. Hyperintensity was noted along the corticosubcortical junction on diffusion-weighted images. NIID was suspected and the patient underwent triple biopsy of the sural nerve with adjacent skin and biceps biopsy. Biopsy revealed ubiquitin-positive intranuclear inclusions surrounding the myofibers, and vascular smooth muscles suggestive of NIID., Conclusions: NIID is a rare neurodegenerative disorder usually diagnosed postmortem. The rectal and skin biopsy had proved helpful in antemortem diagnosis. We have increased the diagnostic armamentarium by showing the presence of intranuclear inclusions in smooth muscle cells of the muscle. Hence, a high degree of suspicion, magnetic resonance imaging features, with nerve/muscle/skin biopsy can help in diagnosis of NIID.