Recommendations for the Management of Initial and Refractory Pediatric Status Dystonicus.

Status dystonicus is the most severe form of dystonia with life-threatening complications if not treated promptly. We present consensus recommendations for the initial management of acutely worsening dystonia (including pre-status dystonicus and status dystonicus), as well as refractory status dystonicus in children. This guideline provides a stepwise approach to assessment, triage, interdisciplinary treatment, and monitoring of status dystonicus. The clinical pathways aim to: (1) facilitate timely recognition/triage of worsening dystonia, (2) standardize supportive and dystonia-directed therapies, (3) provide structure for interdisciplinary cooperation, (4) integrate advances in genomics and neuromodulation, (5) enable multicenter quality improvement and research, and (6) improve outcomes. © 2024 International Parkinson and Movement Disorder Society.

Autosomal Recessive Guanosine Triphosphate Cyclohydrolase I Deficiency: Redefining the Phenotypic Spectrum and Outcomes.

BACKGROUND: The GCH1 gene encodes the enzyme guanosine triphosphate cyclohydrolase I (GTPCH), which catalyzes the rate-limiting step in the biosynthesis of tetrahydrobiopterin (BH4), a critical cofactor in the production of monoamine neurotransmitters. Autosomal dominant GTPCH (adGTPCH) deficiency is the most common cause of dopa-responsive dystonia (DRD), whereas the recessive form (arGTPCH) is an ultrarare and poorly characterized disorder with earlier and more complex presentation that may disrupt neurodevelopmental processes. Here, we delineated the phenotypic spectrum of ARGTPCHD and investigated the predictive value of biochemical and genetic correlates for disease outcome. OBJECTIVES: The aim was to study 4 new cases of arGTPCH deficiency and systematically review patients reported in the literature. METHODS: Clinical, biochemical, and genetic data and treatment response of 45 patients are presented. RESULTS: Three phenotypes were outlined: (1) early-infantile encephalopathic phenotype with profound disability (24 of 45 patients), (2) dystonia-parkinsonism phenotype with infantile/early-childhood onset of developmental stagnation/regression preceding the emergence of movement disorder (7 of 45), and (3) late-onset DRD phenotype (14 of 45). All 3 phenotypes were responsive to pharmacological treatment, which for the first 2 must be initiated early to prevent disabling neurodevelopmental outcomes. A gradient of BH4 defect and genetic variant severity characterizes the 3 clinical subgroups. Hyperphenylalaninemia was not observed in the second and third groups and was associated with a higher likelihood of intellectual disability. CONCLUSIONS: The clinical spectrum of arGTPCH deficiency is a continuum from early-onset encephalopathies to classical DRD. Genotype and biochemical alterations may allow early diagnosis and predict clinical severity. Early treatment remains critical, especially for the most severe patients.

A comparison of various methods of measuring antidepressant medication adherence among children and adolescents with major depressive disorder in a 12-week open trial of fluoxetine.

OBJECTIVE: In this study, we examined antidepressant (fluoxetine) medication adherence in children and adolescents with major depressive disorder (MDD). Using electronic monitoring (EM) as the "reference standard," we compared various methods of measuring antidepressant medication adherence (including EM, pill counts, and medication diaries) among children and adolescents with MDD and examined the relationship between EM medication adherence and depression severity across time. We then suggested recommendations for clinical researchers and practicing clinicians regarding medication adherence assessment. METHOD: Thirty-one child and adolescent outpatients with MDD who enrolled in a 12-week open trial of fluoxetine had their antidepressant medication adherence assessed at each visit, using EM, pill counts, and parent and patient medication diaries. Depression severity was assessed by the Children's Depression Rating Scales-Revised at each visit. RESULTS: Twelve-week least squares mean estimates of medication adherence for the entire sample was high, regardless of the adherence assessment method, although the overall adherence among the four methods (EM, pill, parent diary, patient diary) was significantly different (87.5% vs. 90.6% vs. 93.1% vs. 93.3%, respectively, p=0.0002). Adjusted mean symptom severity was significantly lower for the EM "adherent" group than for the EM "nonadherent" group over the 12 weeks of treatment (35.6 vs. 43.8, p=0.008). CONCLUSION: Overall, EM medication adherence for the depressed youth in this study is high. Compared with EM, there is a tendency of pill counts and medication diaries to overestimate medication adherence. However, pill count adherence better approximates EM adherence, and compliance with returning medication diaries is poor. Youth who are adherent to fluoxetine treatment have lower symptom severity over the course of treatment. Recommendations are provided.