Safety of AADC Gene Therapy for Moderately Advanced Parkinson Disease: Three-Year Outcomes From the PD-1101 Trial.

Background And Objectives: To report final, 36-month safety and clinical outcomes from the PD-1101 trial of NBIb-1817 (VY-AADC01) in participants with moderately advanced Parkinson disease (PD) and motor fluctuations.

Methods: PD-1101 was a phase 1b, open-label, dose escalation trial of VY-AADC01, an experimental AAV2 gene therapy encoding the human aromatic l-amino acid decarboxylase (AADC) enzyme. VY-AADC01 was delivered via bilateral, intraoperative MRI-guided putaminal infusions to 3 cohorts (n = 5 participants per cohort): cohort 1, ≤7.

Detecting autonomic response to pain in Rett syndrome.

Objective: To quantify pain response in girls affected by Rett syndrome (RTT) using electrodermal activity (EDA), a measure of skin conductance, reflecting sympathetic activity known to be modulated by physical and environmental stress.

Methods: EDA increase, heart rate (HR) increase and Face Legs Activity Cry Consolability (FLACC) values calculated during venipuncture (invasive) and vital signs collection (non-invasive) events were compared with values calculated during a prior baseline and a RTT clinical severity score (CSS).

Results: EDA and HR increase were significantly higher than baseline during venipuncture only and not significantly correlated with FLACC or CSS.

Safety, pharmacokinetics, and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome.

Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder mainly affecting females and is associated with mutations in MECP2, the gene encoding methyl CpG-binding protein 2. Mouse models suggest that recombinant human insulin-like growth factor 1 (IGF-1) (rhIGF1) (mecasermin) may improve many clinical features. We evaluated the safety, tolerability, and pharmacokinetic profiles of IGF-1 in 12 girls with MECP2 mutations (9 with RTT).

Monozygotic twins with trisomy 21 and partial agenesis of the corpus callosum.

Trisomy 21 is the most common viable trisomy. Although it is invariably associated with mild to severe developmental delay and intellectual disability, no gross central nervous system malformation has been consistently identified in individuals with trisomy 21. We present the case of a monozygotic twin pregnancy in which both fetuses were identified as having trisomy 21 and partial agenesis of the corpus callosum.

Case of infantile onset spinocerebellar ataxia type 5.

Dominant spinocerebellar ataxias are a rare clinically and genetically heterogeneous group of neurodegenerative disorders. They are characterized by progressive cerebellar ataxia resulting in unsteady gait, clumsiness, dysarthria, and swallowing difficulty. The onset of symptoms is usually in the third or fourth decade of life; however, more subtle clinical manifestations can start in early childhood.

Homozygous PLCB1 deletion associated with malignant migrating partial seizures in infancy.

Malignant migrating partial seizures in infancy (MMPEI) is an early onset epileptic encephalopathy with few known etiologies. We sought to identify a novel cause of MMPEI in a child with MMPEI whose healthy parents were consanguineous. We used array comparative genomic hybridization (CGH) to identify copy number variants genome-wide and long-range polymerase chain reaction to further delineate the breakpoints of a deletion found by CGH.

Translational research: Rett syndrome and tuberous sclerosis complex.

Purpose Of Review: Rare genetic diseases that affect behavior and cognition provide a unique opportunity to study the mechanisms of neurodevelopmental disorders through the examination of animal models, which can lead to development of hypotheses and treatments testable in human beings. Rett syndrome (RTT) and tuberous sclerosis complex (TSC) are both Mendelian disorders that present with autism, epilepsy, and intellectual disability, in which animal model work has been directly translated into clinical treatment trials currently underway. Here, we review the recent advances in our understanding of RTT and TSC pathogenesis and signaling pathways that may be targeted for novel treatments.

Spectrum of neurodevelopmental disabilities in children with cerebellar malformations.

Aim: Advances in perinatal care and neuroimaging techniques have increased the detection of cerebellar malformations (CBMs) in the fetus and young infant. As a result, this has necessitated a greater understanding of the neurodevelopmental consequences of CBMs on child development. The aim of this study was to delineate the impact of CBMs on long-term neurodevelopmental outcomes.

How accurately does current fetal imaging identify posterior fossa anomalies?

Objective: The first objective of our study was to describe the prevalence and spectrum of posterior fossa anomalies over 5 years in a major fetal care center where the referral diagnosis (by fetal sonography) was investigated by fetal MRI and, if confirmed, by postnatal MRI if possible. The second objective was to assess the accuracy with which fetal MRI predicts postnatal MRI findings in this population.

Materials And Methods: We retrospectively identified all cases of suspected fetal posterior fossa anomalies referred to our center from 2002 through 2006.

Basilar meningitis associated with ethmoid and sphenoid cephaloceles.

Nontuberculous causes of basilar meningitis are rare. This study presents the case of a male who developed fever and meningitis caused by Streptococcus pneumoniae. He developed multiple cranial nerve palsies and imaging findings consistent with basilar meningitis and ventriculitis.