Pediatric movement disorders.

Pediatric movement disorders are commonly encountered clinical entities in the pediatric outpatient department. These disorders are a heterogenous group of disorders and may represent an underlying genetic disorder, a metabolic disorder or a hypoxic-ischemic insult during the perinatal period. Hyperkinetic movement disorders are more common as compared to hypokinetic disorders. This is unlike the situation in adult movement disorders where hypokinetic disorders are more often seen. A child's nervous system is more prone to hypoxic-ischemic insults due to its higher metabolic demands and the presence of an immature blood-brain barrier. The commonest movement disorders seen are tics, dystonia and chorea. Myoclonus is commonly associated with epilepsy syndromes. The aetiology of paediatric movement disorders depends on their course, their static or progressive nature, and whether an isolated symptom or an association with other neurological symptoms is present. The clue to the diagnosis is the proper recognition of the movement prevalent in the disorder.

Diagnostic accuracy of Magnetic Resonance Parkinsonism Index in differentiating progressive supranuclear palsy from Parkinson's disease and controls in Indian patients.

AIMS AND OBJECTIVES: An assessment of the sensitivity and specificity of magnetic resonance (MR) imaging measurements of midbrain, pons, middle cerebellar peduncles (MCPs), and superior cerebellar peduncles (SCPs) and MR Parkinsonism Index (MRPI) in differentiating progressive supranuclear palsy (PSP) from Parkinson's disease (PD) and controls was performed. The correlation of these MR imaging measurements with the duration and severity of disease in the Indian patients using the PSP rating scale (PSPRS) was also performed. MATERIALS AND METHODS: Twenty-six consecutive patients were enrolled in this study, satisfying the diagnostic criteria by the National Institute for Neurological Disorders and Stroke, and the Society for PSP (NINDS-SPSP), along with 13 PD and 30 control patients. All PSP patients were assessed using the PSP rating scale and staging system. Radiologists were blinded to the clinical diagnoses. MRPI was calculated by multiplying the pons area/midbrain area ratio by MCP width/SCP width ratio. The midbrain/pons area (M/P) ratio was measured as the ratio of midbrain area to pons area. RESULTS: Mean MRPI in PSP patients (23.48 ± 9.61) was significantly higher than that in PD patients (9.07 ± 2.23) and controls (9.45 ± 1.87). In this study, MRPI was 100% sensitive, specific, and accurate in differentiating PSP from PD and was 96.3% sensitive, 100% specific, and 98.21% accurate in differentiating PSP from controls. No correlation was found between the duration of disease, PSP rating scale, PSP staging system, and MRPI in the present study. MRPI was only marginally superior to the M/P ratio in differentiating between PSP and PD patients on an individual basis. No overlapping values were observed in the PSP and PD patients. CONCLUSION: Magnetic Resonance Parkinsonism Index is more sensitive, specific, and accurate in differentiating PSP from PD in the early stages on an individual basis.

Non-motor symptoms in an Indian cohort of Parkinson's disease patients and correlation of progression of non-motor symptoms with motor worsening.

AIM: To document the frequency and prevalence of non-motor symptoms (NMS) in an Indian cohort of Parkinson's disease (PD) patients. OBJECTIVES: To validate the non-motor score scale (NMSS) in an Indian cohort of PD patients for recording NMS of the disease, to study the prevalence and frequency of NMS in Indian PD patients using the NMSS, and to compare the progression of NMS with motor worsening. Conclusion and Results: This was a cross-sectional, single-center, open-label, one point in time evaluation study conducted from 2009 to 2011. It validated the NMSS scale in an Indian population. The study has profiled the prevalence and pattern of NMS in an Indian cohort of PD patients. Comparison of NMS scale scores with the Unified PD Rating Scale motor scores demonstrated a correlation between non-motor and motor symptoms in the disease progression, particularly of manifestations related to the cognitive decline, memory disturbances, urinary incontinence and smell.

Association of TOR1A and GCH1 Polymorphisms with Isolated Dystonia in India.

Isolated dystonia is a common movement disorder often caused by genetic mutations, although it is predominantly sporadic in nature. Common variants of dystonia-related genes were reported to be risk factors for idiopathic isolated dystonia. In this study, we aimed to analyse the roles of previously reported GTP cyclohydrolase (GCH1) and Torsin family 1 member A (TOR1A) polymorphisms in an Indian isolated dystonia case-control group. A total of 292 sporadic isolated dystonia patients and 316 control individuals were genotyped for single-nucleotide polymorphisms (SNPs) of GCH1 (rs3759664:G > A, rs12147422:A > G and rs10483639:C > G) and TOR1A (rs13300897:G > A, rs1801968:G > C, rs1182:G > T and rs3842225:G > Δ) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by direct Sanger sequencing. The statistical significance of allelic, genotypic and haplotypic associations of all of the SNPs were evaluated using the two-tailed Fisher exact test. The minor allele (A) of rs3759664 is significantly associated with isolated limb dystonia as a risk factor (p = 0.005). The minor allele (C) of rs1801968 is strongly associated with isolated dystonia (p < 0.0001) and most of its subtypes. The major allele of rs3842225 (G) may act as a significant risk factor for Writer's cramp (p = 0.03). Four different haplogroups comprising of either rs1182 or rs3842225 or in combination with rs1801968 and rs13300897 were found to be significantly associated with isolated dystonia. No other allelic, genotypic or haplotypic association was found to be significant with isolated dystonia cohort or its endophenotype stratified groups. Our study suggests that TOR1A common variants have a significant role in isolated dystonia pathogenesis in the Indian population, whereas SNPs in the GCH1 gene may have a limited role.

Paroxysmal Asymmetric Dystonic Arm Posturing-A Less Recognized but Characteristic Manifestation of ATP1A3-related disease.

BACKGROUND: ATP1A3 mutations cause a wide clinical spectrum, and are one of the "commoner rare diseases". METHODS: Case series of four patients with ATP1A3 mutations. RESULTS: The patients displayed characteristic episodes of dystonic arm posturing, involving a dystonic, flexed arm held in front of the body or close to the body, but with the hand raised upwards. Other attacks manifested with arm extension, either beside the body or reaching upwards. Dystonic posturing occurred paroxysmally, with no neurological signs between attacks, or combined with other signs like chorea, ataxia, and hypotonia. CONCLUSIONS: While previous diagnostic criteria have not included paroxysmal or episodic dystonia, recent expert consensus has proposed to include alternating or paroxysmal dystonia as major feature calling for ATP1A3 genetic testing. Attacks of marked arm flexion posturing, either paroxysmal or as episodic exacerbation of mild pre-existent dystonia, are a characteristic clue to ATP1A3-related disease.

Genetic screening of THAP1 in primary dystonia patients of India.

BACKGROUND: Primary Dystonia is a common movement disorder manifested by dystonic symptoms only. DYT6, a major genetic factor, plays a significant role in primary pure dystonia pathogenesis. In this study we analyzed THAP1 (DYT 6) gene in primary pure dystonia patients, which has been widely studied in other populations but not in Indians. METHODS: The study cohort contained 227 index primary pure dystonia patients with the involvement of cervical region and 254 neurologically control individuals collected from East Indian population. All three exons of THAP1 and their flanking sequences, including exon-intron boundaries, were screened by PCR, DNA sequencing and/or RFLP analysis. RESULTS: A total of three nucleotide variants were detected, which include a reported missense mutation (c.427 A>G; p.Met143Val) in a juvenile onset generalized dystonia patient, a novel frameshift deletion mutation (c.208-209 ΔAA; p.K70VfsX15) in a juvenile onset cervical dystonia patient and a rare variant in 3' UTR of THAP1 (c.*157 T>C) in an adult-onset blepharospasm patient. In addition, two SNPs (rs71521601 and rs111989331) were detected both in the patients and controls with the major allele of the latter being significantly over represented in the patients. CONCLUSIONS: Our study suggests that the THAP1 is likely to have a causative role in the pathogenesis of Indian primary pure dystonia patients. Though the phenotypic spectrum is extensively diverse, the cervical involvement with dystonic tremor and speech problem is common amongst the patients harboring mutations.