Dissecting the Phenotype and Genotype of PLA2G6-Related Parkinsonism.

BACKGROUND: Complex parkinsonism is the commonest phenotype in late-onset PLA2G6-associated neurodegeneration. OBJECTIVES: The aim of this study was to deeply characterize phenogenotypically PLA2G6-related parkinsonism in the largest cohort ever reported. METHODS: We report 14 new cases of PLA2G6-related parkinsonism and perform a systematic literature review. RESULTS: PLA2G6-related parkinsonism shows a fairly distinct phenotype based on 86 cases from 68 pedigrees. Young onset (median age, 23.0 years) with parkinsonism/dystonia, gait/balance, and/or psychiatric/cognitive symptoms were common presenting features. Dystonia occurred in 69.4%, pyramidal signs in 77.2%, myoclonus in 65.2%, and cerebellar signs in 44.6% of cases. Early bladder overactivity was present in 71.9% of cases. Cognitive impairment affected 76.1% of cases and psychiatric features 87.1%, the latter being an isolated presenting feature in 20.1%. Parkinsonism was levodopa responsive but complicated by early, often severe dyskinesias. Five patients benefited from deep brain stimulation. Brain magnetic resonance imaging findings included cerebral (49.3%) and/or cerebellar (43.2%) atrophy, but mineralization was evident in only 28.1%. Presynaptic dopaminergic terminal imaging was abnormal in all where performed. Fifty-four PLA2G6 mutations have hitherto been associated with parkinsonism, including four new variants reported in this article. These are mainly nontruncating, which may explain the phenotypic heterogeneity of childhood- and late-onset PLA2G6-associated neurodegeneration. In five deceased patients, median disease duration was 13.0 years. Brain pathology in three cases showed mixed Lewy and tau pathology. CONCLUSIONS: Biallelic PLA2G6 mutations cause early-onset parkinsonism associated with dystonia, pyramidal and cerebellar signs, myoclonus, and cognitive impairment. Early psychiatric manifestations and bladder overactivity are common. Cerebro/cerebellar atrophy are frequent magnetic resonance imaging features, whereas brain iron deposition is not. Early, severe dyskinesias are a tell-tale sign. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Dopa-Responsive Dystonia: An Early Presentation of Ataxia-Telangiectasia.

Ataxia-telangiectasia (AT) is a complex genetic neurodegenerative disease with autosomal recessive inheritance. The typical initial features of ataxia telangiectasia include ataxia, cutaneous telangiectasia, and immune deficiency with recurrent infections. Usually, movement disorder occurs late in the course of the disease. A diagnosis of variant or atypical ataxia-telangiectasia (variant AT) is considered in case of any deviation from the normal course of illness giving rise to variable presentations of the disease. Only a few cases of variant AT with predominant movement disorder have been reported worldwide. A knowledge of atypical presentations helps in early diagnosis and thus to initiate management and counselling of the family at the earliest. Here, we report a case of genetically confirmed ataxia-telangiectasia with an initial presentation of dopamine responsive dystonia.

Subacute Sclerosing Panencephalitis (SSPE): Experience from a Tertiary-Care Pediatric Center.

Introduction Subacute sclerosing panencephalitis (SSPE) is a devastating neurodegenerative disease occurring as a complication of measles infection that is still prevalent in low-resource countries. Clinical and electrographical variability in SSPE can lead to diagnostic delays. Methods Children diagnosed with SSPE in a tertiary care pediatric hospital in India in a period of 8 years were included in the study. The diagnosis was established on the basis of Dyken's criteria. The demographic data, clinical presentations, investigations, treatment approaches, and outcomes were reviewed and recorded. Results Thirty-four patients were included in the analysis. Average age at symptom onset was 7 years, 5 months. Majority of the children were not vaccinated for measles. Most patients (80%) presented with stage 2 of illness. Nearly 25% presented with atypical clinical features. Myoclonus was the most predominant feature seen after diagnosis. Electroencephalography (EEG) was the most useful investigation for suspecting the diagnosis. All patients showed deterioration in neurological status with time and 20% died during follow-up. Conclusion Atypical presentations of SSPE must be recognized in areas with high incidence to institute timely treatment and establish prognosis. EEG findings were found to be the most important indicator for diagnosis. Measles eradication will pave the way for elimination of this dreaded disease.

Designing and Validation of a Hindi-language Parent Self-report Developmental Screening Tool.

AIM: To design and validate Hindi-language parent self-report developmental screening questionnaires for 9-month and 18-month-old Indian children. DESIGN: Cross-sectional study. SETTING: Tertiary-care pediatric hospital from April 2014 to March 2016. PARTICIPANTS: In each age group (9-month and 18-month), 45 children were enrolled for designing of questionnaires (30 for obtaining parental observations of current development and 15 for pre-testing). For validation of tool, 100 children (60 low risk and 40 high risk) were enrolled in each age group. METHODS: For designing, observations regarding current developmental milestones were obtained from parents and a list of all enumerated milestones was prepared. After detailed discussion by a team of developmental pediatricians, pediatric resident, clinical psychologist and language specialist, milestones were chosen for drafting of questionnaires. In each age group, drafts were pre-tested and required modifications were done. The final questionnaires contained 20 items each to be scored on a Likert scale (total score ranging from 20 to 60, a lower score indicating a higher risk of developmental delay). These questionnaires were validated against Developmental Assessment Scale for Indian Infants (DASII), a gold standard instrument. RESULTS: On ROC analysis, the 9-month and 18-month screening tool had area under curve of 0.988 and 0.953, respectively, for detecting developmental delay. Score ≤50 on the 9-months questionnaire had sensitivity of 100% and specificity of 87.2%. Score ≤49 on the 18-months questionnaire had sensitivity of 91.4% and specificity of 88.7%. CONCLUSION: The new questionnaires have a promising role in developmental screening of children at the time of routine immunizations in our country.