Concept: Neurological disorders
Anomalous Brain Development Is Evident in Preschoolers With Attention-Deficit/Hyperactivity Disorder
- Journal of the International Neuropsychological Society : JINS
- Published over 2 years ago
Attention-deficit/hyperactivity disorder (ADHD) is a common neurological disorder with symptom onset early in childhood. Growing evidence suggests anomalous brain development across multiple brain regions is evident in school-aged children; however, few studies have examined whether such differences are notable in the preschool years when symptom onset typically occurs.
Hereditary sensory and autonomic neuropathies (HSANs) encompass a group of genetically inherited disorders characterized by sensory and autonomic dysfunctions. Familial dysautonomia (FD), also known as HSAN type III, is an autosomal recessive disorder that affects 1/3600 live births in the Ashkenazi Jewish population. The disease is caused by abnormal development and progressive degeneration of the sensory and autonomic nervous systems and is inevitably fatal, with only 50% of patients reaching the age of 40. FD is caused by a mutation in intron 20 of the Ikbkap gene that results in severe reduction in the expression of its encoded protein, inhibitor of kappaB kinase complex-associated protein (IKAP). Although the mutation that causes FD was identified in 2001, so far there is no appropriate animal model that recapitulates the disorder. Here, we report the generation and characterization of the first mouse models for FD that recapitulate the molecular and pathological features of the disease. Important for therapeutic interventions is also our finding that a slight increase in IKAP levels is enough to ameliorate the phenotype and increase the life span. Understanding the mechanisms underlying FD will provide insights for potential new therapeutic interventions not only for FD, but also for other peripheral neuropathies.
Abstract There has been only one reported case of neuromuscular scoliosis following chronic inflammatory demyelinating polyneuropathy (CIDP). However, no cases of scoliosis that were treated with surgery secondary to CIDP have been previously described. A 16-year-old boy with CIDP was consultant due to the progression of scoliosis with the coronal curve of 86° from T8 to T12. Posterior correction and fusion with segmental pedicle screws were performed under intraoperative spinal cord monitoring with transcranial electric motor-evoked potentials. Although the latency period was prolonged and amplitude was low, the potential remained stable. Coronal curve was corrected from 86° to 34° without neurological complications. We here describe scoliosis associated with CIDP, which was successfully treated with surgery under intraoperative spinal cord monitoring.
The prevalence of autism spectrum disorders (ASDs) has increased 20-fold over the past 50 years to >1% of US children. Although twin studies attest to a high degree of heritability, the genetic risk factors are still poorly understood. We analyzed data from two independent populations using u-statistics for genetically structured wide-locus data and added data from unrelated controls to explore epistasis. To account for systematic, but disease-unrelated differences in (non-randomized) genome-wide association studies (GWAS), a correlation between P-values and minor allele frequency with low granularity data and for conducting multiple tests in overlapping genetic regions, we present a novel study-specific criterion for ‘genome-wide significance’. From recent results in a comorbid disease, childhood absence epilepsy, we had hypothesized that axonal guidance and calcium signaling are involved in autism as well. Enrichment of the results in both studies with related genes confirms this hypothesis. Additional ASD-specific variations identified in this study suggest protracted growth factor signaling as causing more severe forms of ASD. Another cluster of related genes suggests chloride and potassium ion channels as additional ASD-specific drug targets. The involvement of growth factors suggests the time of accelerated neuronal growth and pruning at 9-24 months of age as the period during which treatment with ion channel modulators would be most effective in preventing progression to more severe forms of autism. By extension, the same computational biostatistics approach could yield profound insights into the etiology of many common diseases from the genetic data collected over the last decade.
Transthyretin-related familial amyloid polyneuropathy (TTR-FAP) typically arises as an autonomic neuropathy primarily affecting small fibres and it occurs in adult patients in their second or third decades of life. It progresses rapidly and can lead to death in approximately 10 years. Other phenotypes have been described in non-endemic areas.
Dystonic storm is a frightening hyperkinetic movement disorder emergency. Marked, rapid exacerbation of dystonia requires prompt intervention and admission to the intensive care unit. Clinical features of dystonic storm include fever, tachycardia, tachypnea, hypertension, sweating and autonomic instability, often progressing to bulbar dysfunction with dysarthria, dysphagia and respiratory failure. It is critical to recognize early and differentiate dystonic storm from other hyperkinetic movement disorder emergencies. Dystonic storm usually occurs in patients with known dystonia, such as DYT1 dystonia, Wilson’s disease and dystonic cerebral palsy. Triggers such as infection or medication adjustment are present in about one-third of all events. Due to the significant morbidity and mortality of this disorder, we propose a management algorithm that divides decision making into two periods: the first 24 h, and the next 2-4 weeks. During the first 24 h, supportive therapy should be initiated, and appropriate patients should be identified early as candidates for pallidal deep brain stimulation or intrathecal baclofen. Management in the next 2-4 weeks aims at symptomatic dystonia control and supportive therapies.
This study aimed to assess the safety and effectiveness of peripheral neurostimulation of the sphenopalatine ganglion (SPG) in the treatment of refractory chronic cluster headache.
Relatively little is known about the stability of a diagnosis of episodic migraine (EM) or chronic migraine (CM) over time. This study examines natural fluctuations in self-reported headache frequency as well as the stability and variation in migraine type among individuals meeting criteria for EM and CM at baseline.
Cluster headache (CH) is a disabling primary headache disorder characterized by severe periorbital pain. A subset of patients does not respond to established pharmacological therapy. This study examines outcomes of a cohort of mainly chronic CH patients treated with sphenopalatine ganglion (SPG) stimulation.
The recent spread of Zika virus (ZIKV) and its association with increased rates of Guillain Barre and other neurological disorders as well as congenital defects that include microcephaly has created an urgent need to develop animal models to examine the pathogenesis of the disease and explore the efficacy of potential therapeutics and vaccines. Recently developed infection models for ZIKV utilize mice defective in interferon responses. In this study we establish and characterize a new model of peripheral ZIKV infection using immunocompetent neonatal C57BL/6 mice and compare its clinical progression, virus distribution, immune response, and neuropathology with that of C57BL/6-IFNAR KO mice. We show that while ZIKV infected IFNAR KO mice develop bilateral hind limb paralysis and die 5-6 days post-infection (dpi), immunocompetent B6 WT mice develop signs of neurological disease including unsteady gait, kinetic tremors, severe ataxia and seizures by 13 dpi that subside gradually over 2 weeks. Immunohistochemistry show viral antigen predominantly in cerebellum at the peak of the disease in both models. However, whereas IFNAR KO mice showed infiltration by neutrophils and macrophages and higher expression of IL-1, IL-6 and Cox2, B6 WT mice show a cellular infiltration in the CNS composed predominantly of T cells, particularly CD8+ T cells, and increased mRNA expression levels of IFNg, GzmB and Prf1 at peak of disease. Lastly, the CNS of B6 WT mice shows evidence of neurodegeneration predominantly in the cerebellum that are less prominent in mice lacking the IFN response possibly due to the difference in cellular infiltrates and rapid progression of the disease in that model. The development of the B6 WT model of ZIKV infection will provide insight into the immunopathology of the virus and facilitate assessments of possible therapeutics and vaccines.