A video-based discussion of movement disorders in paediatric anti NMDAR encephalitis: A case series from Eastern India.

PURPOSE: The spectrum of movement disorders associated with anti N-Methyl-d-Aspartate-Receptor (NMDAR) encephalitis is myriad, particularly in children, possibilities of which were investigated from two tertiary care centres. METHODS: A retrospective study was conducted in two tertiary referral centres in Eastern India, analysing data of 8 paediatric patients diagnosed as anti NMDAR encephalitis, presenting with one or more movement disorders (MDs). RESULTS: All the patients were of Bengali ethnicity with a median age of 9 years (3-16 years) and with female predilection (62.5%). CSF pleocytosis was a common feature in all. Seizures were described in 62.5%% of patients with a solitary patient exhibiting abnormalities on brain imaging. 3 out of 8 (37.5%) of patients presented with a single MD while the remaining had more than one type. Oro-linguo-facial dyskinesias and dystonia (37.5% each) were the most common movement type followed by chorea (12.5%). Complex stereotypies, myoclonus and facial tics were noted in one patient each. All patients received pulse methyl prednisolone. Escalation to second line therapy in form of rituximab was done for 5 patients (62.5%). Following immunotherapy, hyperkinetic movements resolved in 50% of patients, with persistence of movements in one (12.5%). A mortality of 37.5% was noted. Median duration of follow up was 26 months, during which none of the patients had evidence of systemic neoplasm. CONCLUSION: MDs are a core feature of anti NMDAR encephalitis, particularly in the paediatric age group, understanding and characterization of which, is the key to early diagnosis and effective therapy.

Cushing's syndrome in early infancy due to isolated sporadic bilateral micronodular adrenocortical disease associated with myosin heavy chain 8 mutation: diagnostic challenges, too many!

Endogenous Cushing's syndrome (CS) is rare in infancy. Bilateral micronodular adrenocortical disease (BMAD), either primary pigmented nodular adrenocortical disease or the non-pigmented isolated micronodular adrenocortical disease is an important aetiology of CS in this age group, which requires bilateral adrenalectomy for cure. BMAD may be isolated, or a component of Carney complex. Isolated sporadic BMAD without other systemic manifestations poses a diagnostic challenge. Paradoxical cortisol response to dexamethasone suggests, while adrenal histopathology and mutational analysis of the culprit genes confirm BMAD. BMAD was suspected in 6-year-old infant with midnormal adrenocorticotrophic hormone, inconclusive adrenal and pituitary imaging and paradoxical increase in cortisol following high dose of dexamethasone. Exome sequencing revealed heterozygous c.354+1G>C (5' splice site) variant in the myosin heavy chain gene (MYH8), located in chromosome 17. This particular variant has not been reported in the literature. In view of suspected phenotype and its absence in the population databases, the variant was classified as pathogenic.

Differentiating 11ß-hydroxylase deficiency from primary glucocorticoid resistance syndrome in male precocity: real challenge in low-income countries.

Congenital adrenal hyperplasia due to 11ß-hydroxylase deficiency (11-BHD) and primary glucocorticoid resistance syndrome (PGRS) are two relatively uncommon causes of gonadotropin-releasing hormone-independent isosexual male precocity; PGRS, however, is considerably rarer than 11-BHD. Other than serum and urinary cortisol, which are elevated in PGRS and low/low-normal in 11-BHD, both of these conditions are indistinguishable by clinical, biochemical or radiological parameters. In 11-BHD, oxidation of 11-deoxycortisol (11-DOC) to cortisol is impaired, resulting in accumulation of 11-DOC and other cortisol precursors. 11-DOC shares structural homology with cortisol, and falsely elevated serum cortisol values are observed in older generation immunoassays (Siemens ADVIA Centaur) due to antibody cross-reactivity. 11-BHD, thus, may be misdiagnosed as PGRS. Structure-based cortisol assays are not widely available in low-income countries. Hence, immunoassays using highly specific antibodies against cortisol are required to ensure assay selectivity. Newer generation analysers probably are effective alternatives to liquid chromatography-tandem mass spectrometry in conditions associated with 11ß-hydroxylase defect.