Electrophysiological and imaging evidence of sustained inhibition in limbic and frontal networks following deep brain stimulation for treatment refractory obsessive compulsive disorder.

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder that arises from a complex interaction of environmental and genetic factors. Despite numerous pharmacological and behavioral interventions, approximately 10% of patients remain refractory. High-frequency deep brain stimulation (HF-DBS) has shown promising results for treatment-refractory OCD. We report the follow-up result of up to 6 years of 4 treatment-refractory OCD patients treated by HF-DBS. Targets of stimulation were the anterior limb of the internal capsule (ALIC) in two cases, and the nucleus accumbens (NAc) in the remaining cohort. The clinical profiles were quantified by the Yale-Brown obsessive-compulsive scale (Y-BOCS). Highly significant reductions in Y-BOCS scores were obtained from all patients during the follow-up period. A greater that 90% reduction in Y-BOCS, observed in the most successful case, was achieved with NAc HF-DBS. Y-BOCS scores in the other patients consistently achieved over 50% reductions in OCD symptoms. FDG-PET imaging indicated post-surgical reductions in metabolism, in not only targeted limbic networks, but also other frontal cortical and subcortical regions, suggesting that large-scale network modulation and inhibitions are associated with functional recovery in OCD. This study demonstrates that HF-DBS targeted to the ALIC and NAc is a safe and effective method for ameliorating intractable, treatment-refractory OCD symptoms. The NAc appeared to be the superior target for symptom reduction, and local inhibition of NAc activity and reduced frontal metabolism are key therapeutic indications.

Nucleus accumbens deep brain stimulation for a patient with self-injurious behavior and autism spectrum disorder: functional and structural changes of the brain: report of a case and review of literature.

The aim of this report was to investigate the clinical outcome of deep brain stimulation (DBS) for autism spectrum disorder (ASD) and the functional and structural changes in the brain after DBS. We present a 14-year-old boy with ASD and self-injurious behavior (SIB) refractory with medical and behavioral therapy. He was treated by bilateral nucleus accumbens (NAc) DBS. Remarkable clinical improvement was observed following NAc DBS. Brain fluorodeoxyglucose-positron emission tomography (FDG-PET) and magnetic resonance imaging (MRI) volumetric studies revealed that the metabolism in the prefrontal and the frontal cortex as well as the occipital cortex was markedly decreased in association with the decreased cortical volumes in those areas 2 years after NAc DBS. The therapeutic potential of NAc DBS is suggested for the clinical improvement of patients with ASD and SIB with structural and functional changes after DBS.

Whole exome sequencing for a patient with Rubinstein-Taybi syndrome reveals de novo variants besides an overt CREBBP mutation.

Rubinstein-Taybi syndrome (RSTS) is a rare condition with a prevalence of 1 in 125,000-720,000 births and characterized by clinical features that include facial, dental, and limb dysmorphology and growth retardation. Most cases of RSTS occur sporadically and are caused by de novo mutations. Cytogenetic or molecular abnormalities are detected in only 55% of RSTS cases. Previous genetic studies have yielded inconsistent results due to the variety of methods used for genetic analysis. The purpose of this study was to use whole exome sequencing (WES) to evaluate the genetic causes of RSTS in a young girl presenting with an Autism phenotype. We used the Autism diagnostic observation schedule (ADOS) and Autism diagnostic interview revised (ADI-R) to confirm her diagnosis of Autism. In addition, various questionnaires were used to evaluate other psychiatric features. We used WES to analyze the DNA sequences of the patient and her parents and to search for de novo variants. The patient showed all the typical features of Autism, WES revealed a de novo frameshift mutation in CREBBP and de novo sequence variants in TNC and IGFALS genes. Mutations in the CREBBP gene have been extensively reported in RSTS patients, while potential missense mutations in TNC and IGFALS genes have not previously been associated with RSTS. The TNC and IGFALS genes are involved in central nervous system development and growth. It is possible for patients with RSTS to have additional de novo variants that could account for previously unexplained phenotypes.

Comparison of lenograstim and filgrastim on haematological effects after autologous peripheral blood stem cell transplantation with high-dose chemotherapy.

OBJECTIVE: To compare the efficacy of lenograstim and filgrastim on haematological recovery following an autologous peripheral blood stem cell transplantation (PBSCT) with high-dose chemotherapy. METHODS: A retrospective case-controlled study. RESULTS: Absolute neutrophil count (ANC) recovery above 0.5 x 10(9)/l and white blood cell (WBC) recovery above 4 x 10(9)/l for 3 consecutive days was achieved earlier with filgrastim than with lenograstim ((13.2 +/- 8.0 vs 19.0 +/- 10.0 days, p = 0.004), (16.9 +/- 9.7 vs 29.9 +/- 16.6 days, p = 0.001), respectively). The platelet recovery above 20 x 10(9)/l was also achieved earlier with filgrastim than with lenograstim (19.5 +/- 11.6 vs 27.2 +/- 13.8 days, p = 0.006). Furthermore, filgrastim-treated patients received fewer days of granulocyte colony simulating factor (G-CSF) administration (12.5 +/- 7.0 vs 18.6 +/- 8.5 days, p = 0.001) and spent less time in hospital (23.7 +/- 10.9 vs 32.0 +/- 17.6 days, p = 0.009). Duration of antibiotic administration was also significantly shorter in the filgrastim group (13.6 +/- 7.6 vs 29.1 +/- 19.8 days, p = 0.001). CONCLUSION: In patients undergoing PBSCT following high-dose chemotherapy, filgrastim significantly reduced the duration of neutropenia, thrombocytopenia and days of G-CSF administration, and led to earlier hospital discharge compared with lenograstim.