Possible contribution of cerebellar disinhibition in epilepsy.

OBJECTIVE: We hypothesize that loss of inhibition from the cerebellum can lead to cortical activation and seizures. BACKGROUND: The traditional model for development of seizures purports that the source of seizures is increased electrical activity originating from cerebral cortical neurons. Studies have shown a decrease in inhibition results in a shift of cortical activity to a hyperexcitable state, which may lead to seizures. Interestingly, a 1978 study suggested the term "disorder of disinhibition" as a way to describe epilepsy from studies of chronic cerebellar stimulation. DESIGN/METHODS: Cases and experimental studies in which cerebellar lesions have been implicated in the development of seizures were reviewed. Cases in which cerebellar inhibition has been targeted in the treatment of seizures were also included. Twenty-six studies and case reports are presented for this report. RESULTS: The cases show cerebellar lesions can lead to cortical epileptiform activity. Purkinje cell loss is linked to the occurrence of seizures in animals. The majority of patients with cerebellar lesions were seizure free after complete resection, while less than half of patients were seizure free after partial resection. Novel treatments using deep-brain stimulation targeting cerebellar structures demonstrated therapeutic benefits for seizures. CONCLUSIONS: Although pathophysiology is not well-understood, the cerebellum likely plays an inherent role in inhibiting aberrant cortical epileptogenesis. Cerebellar lesions may cause seizures due to loss of the inhibition of cortical areas or through intrinsic epileptic activity. Treatments enhancing cerebellar stimulation have shown therapeutic benefits in treating seizures, which could potentially provide another avenue for treatment.

Management Strategies for Intracranial Pressure Crises in Subarachnoid Hemorrhage.

Objectives: Standard management strategies for lowering intracranial pressure (ICP) in traumatic brain injury has been well-studied, but the use of lesser known interventions for ICP in subarachnoid hemorrhage (SAH) remains elusive. Searches were performed in PubMed and EBSCO Host to identify best available evidence for evaluation and management of medically refractory ICP in SAH. The role of standard management strategies such as head elevation, hyperventilation, mannitol and hypertonic saline as well as lesser known management such as sodium bicarbonate, indomethacin, tromethamine, decompressive craniectomy, decompressive laparotomy, hypothermia, and barbiturate coma are reviewed. We also included dose concentrations, dose frequency, infusion volume, and infusion rate for these lesser known strategies. Nonetheless, there is still a gap in the evidence to recommend optimal dosing, timing and its role in the improvement of outcomes but early diagnosis and appropriate management reduce adverse outcomes.

Overall severities of gastrointestinal symptoms in pediatric outpatients with and without autism spectrum disorder.

In order to determine the effectiveness of a Gastrointestinal Severity Index to screen for gastrointestinal disorders, the Gastrointestinal Severity Index was administered to 135 children with autism spectrum disorders and 146 comparisons with and without gastrointestinal disorders. The mean Gastrointestinal Severity Index scores of the groups were 3.53 ± 1.78, 3.15 ± 1.99, 0.81 ± 1.25, and 0.29 ± 0.76 (comparative pediatric patients with gastrointestinal disorder = autism spectrum disorder + gastrointestinal disorder > autism spectrum disorder-gastrointestinal disorder > comparative pediatric patients without gastrointestinal disorder, respectively), Ps < 0.05. Receiver operating characteristic curves and areas under the receiver operating characteristic curves were calculated to ascertain which Gastrointestinal Severity Index cutoff scores yielded the highest sensitivity and specificity rates for the diagnosis of gastrointestinal disorders. The area under the receiver operating characteristic curve (0.97) for the comparison group was higher (P < 0.001) than the area under the receiver operating characteristic curve (0.85) for autism spectrum disorder children indicating that the Gastrointestinal Severity Index was more effective in screening for gastrointestinal disorders in comparisons. However, the same Gastrointestinal Severity Index cutoff score of 2 and above yielded, respectively, sensitivity and specificity rates of 92% and 93% for comparisons and 80% and 79% for autism spectrum disorder children. The negative and positive predictive values based on these sensitivity and specificity rates were calculated for a range of prevalences of gastrointestinal disorders and indicated that the Gastrointestinal Severity Index may be useful for screening children with and without autism spectrum disorder for gastrointestinal symptoms.

A Rare Syndrome of GRID2 Deletion in 2 Siblings.

The Glutamate receptor, ionotropic, delta 2 gene codes for an ionotropic glutamate delta-2 receptor, which is selectively expressed in cerebellar Purkinje cells, and facilitates cerebellar synapse organization and transmission. The phenotype associated with the deletion of Glutamate receptor, ionotropic, delta 2 gene in humans was initially defined in 2013. In this case report, the authors describe 2 brothers who presented with developmental delay, tonic upward gaze, nystagmus, oculomotor apraxia, hypotonia, hyperreflexia, and ataxia. They were found to have a homozygous intragenic deletion within the Glutamate receptor, ionotropic, delta 2 gene at exon 2. Our patients serve as an addition to the literature of previously reported children with this rare clinical syndrome associated with Glutamate receptor, ionotropic, delta 2 deletion.

A Case of Brown-Vialetto-Van Laere Syndrome Due To a Novel Mutation in SLC52A3 Gene: Clinical Course and Response to Riboflavin.

Brown-Vialetto-Van Laere syndrome is a rare disorder characterized by motor, sensory, and cranial neuronopathies, associated with mutations in SLC52A2 and SLC52A3 genes that code for human riboflavin transporters RFVT2 and RFVT3, respectively. The authors describe the clinical course of a 6-year-old girl with Brown-Vialetto-Van Laere syndrome and a novel homozygous mutation c.1156T>C in the SLC52A3 gene, who presented at the age of 2.5 years with progressive brain stem dysfunction including ptosis, facial weakness, hearing loss, dysphagia, anarthria with bilateral vocal cord paralysis, and ataxic gait. She subsequently developed respiratory failure requiring tracheostomy and worsening dysphagia necessitating a gastrostomy. Following riboflavin supplementation, resolution of facial diplegia and ataxia, improvements in ptosis, and bulbar function including vocalization and respiration were noted. However, her sensorineural hearing loss remained unchanged. Similar to other cases of Brown-Vialetto-Van Laere syndrome, our patient responded favorably to early riboflavin supplementation with significant but not complete neurologic recovery.

Expanding the treatment window for ischemic stroke through the application of novel system-based technology.

Recent randomized controlled trials have demonstrated the superiority of endovascular treatment (ET) over medical management in the treatment of acute ischemic stroke patients with anterior circulation emergent large vessel occlusions (ELVOs). Due to such accumulating evidence, expanding ET has become of paramount importance. Advancements in modern technology have enabled the use of mobile stroke units, telestroke networks, mobile neuroendovascular teams, and smartphone applications that shorten the time window to treatment and, thus, make patients more amenable to ET. Additionally, modifying stroke-screening tools to make them more accessible to first responders and the creation of stroke registries can provide further opportunities for ET.