Introduction: Severe, often sudden-onset headache is the principal presenting symptoms of aneurysmal subarachnoid hemorrhage (aSAH). We hypothesized that gabapentin would be safe and tolerable for aSAH-induced headaches and would reduce concurrent opioid use. Methods: We performed a single-center, double-blind, randomized, placebo-controlled trial (registered at ClinicalTrials.gov; NCT02330094) from November 24, 2014, to June 24, 2017, where aSAH patients received either dose-escalating gabapentin or oral placebo, both alongside a standard of care pain regimen. After 7 days, patients had the option to continue in an open-label period until 14 days after enrollment or until discharge from the intensive care unit. Our primary endpoint was the efficacy of gabapentin in reducing headache numeric pain scores and opioid usage in patients with aSAH compared to the placebo group. We identified 63 potential patients with aSAH for the study. After applying stringent exclusion criteria, 16 eligible patients were enrolled into one of two arms. Results: The study ended prematurely after reaching a pre-specified funding period and an unexpected drop in aSAH cases. There was a trend toward lower headache numeric pain scores and opioid use in the gabapentin treated arm; however this was not significantly different. Gabapentin was well tolerated by participants and no adverse effects were reported. Conclusions: While there was a trend toward lower pain scores and opioid requirement in the gabapentin group, the study was underpowered to detect a difference. Larger multicenter trials are required to evaluate the efficacy of gabapentin to reduce opioid requirements after aSAH.

BackgroundNonconvulsive status epilepticus (NCSE) is a diagnosis that is often challenging and one that may progress to refractory NCSE. Ketamine is a noncompetitive N-methyl-d-aspartate antagonist that increasingly has been used to treat refractory status epilepticus. Current Neurocritical Care Society guidelines recommend intravenous (IV) ketamine infusion as an alternative treatment for refractory status epilepticus in adults. On the other hand, enteral ketamine use in NCSE has been reported in only 6 cases (1 adult and 5 pediatric) in the literature to date.Case presentationA 33-year-old woman with a history of poorly controlled epilepsy presented with generalized tonic-clonic seizures, followed by recurrent focal seizures that evolved into NCSE. This immediately recurred within 24 h of a prior episode of NCSE that was treated with IV ketamine. Considering her previous response, she was started again on an IV ketamine infusion, which successfully terminated NCSE. This time, enteral ketamine was gradually introduced while weaning off the IV formulation. Treatment with enteral ketamine was continued for 6 months and then tapered off. There was no recurrence of NCSE or seizures and no adverse events noted during the course of treatment.ConclusionThis case supports the use of enteral ketamine as a potential adjunct to IV ketamine in the treatment of NCSE, especially in cases without coma. Introduction of enteral ketamine may reduce seizure recurrence, duration of stay in ICU, and morbidity associated with intubation.

Aim. To evaluate five illustrative cases and perform a literature review to identify and describe a working approach to adult--onset white matter diseases (WMD).State of the art. Inherited WMD are a group of disorders often seen in childhood. In adulthood, progressive WMDs are rare, apart from the common nonspecific causes of hypertension and other cerebrovascular diseases. The pattern of WMDs on neuroimaging can be an important clue to the final diagnosis. Due to the adoption of a combined clinical-imaging-laboratory approach, WMD is becoming better recognised, in addition to the rapidly evolving field of genomics in this area. Clinical implications.While paediatric WMDs have a well-defined and literature-based clinical-laboratory approach to diagnosis, adult-onset WMDs remain an important, pathologically diverse, radiographic phenotype, with different and distinct neuropathologies among the various subtypes of WMD. Adult-onset WMDs comprise a wide collection of both acquired and inherited aetiologies. While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neurological complications are emerging, we are as yet unaware of it causing WMD outside of post-anoxic changes. It is important to recognise WMD as a potentially undefined acquired or genetic syndrome, even when extensive full genome testing reveals variants of unknown significance. Future directions.We propose a combined clinical-imaging-laboratory approach to WMD and continued exploration of acquired and genetic factors. Adult-onset WMD, even given this approach, can be challenging because hypertension is often comorbid. Therefore, we propose that undiagnosed patients with WMD be entered into multicentre National Organisation for Rare Diseases registries to help researchers worldwide make new discoveries that will hopefully translate into future cures.