Safety and timing of early therapeutic anticoagulation therapy after craniotomy.

Background: To date, there are few guidelines and studies to guide the timing of initiation of therapeutic anticoagulation (AC) after craniotomy. The goal of this study was to assess the timing, safety, and outcomes of patients following the administration of therapeutic AC after craniotomy. Methods: A retrospective case-control study was performed evaluating all craniotomy patients from August 2017 to July 2021. Cases were selected if they received therapeutic AC within ten days of craniotomy. Nineteen out of 1013 craniotomy patients met the inclusion criteria. Indications for therapeutic AC were diverse, including deep venous thrombosis, pulmonary embolism, dural venous sinus thrombosis, mechanical heart valve, and left ventricular thrombus. Results: The mean and median time to therapeutic AC were 5.35 and 5 days, respectively. Three patients developed intracerebral hemorrhage (ICH) that was stable on repeat imaging and did not require any surgical intervention or result in new neurologic deficits. There was no significant association between therapeutic AC and postoperative ICH (P = 0.067). Conclusion: This study demonstrated that the initiation of therapeutic AC in postoperative craniotomy patients from postoperative days 2 to 10 did not result in any major complications. A prospective study is warranted to clarify the indications and safety of therapeutic AC after craniotomy.

Cytomegalovirus and varicella zoster virus coinfection-associated central hypoventilation syndrome (Ondine's Curse).

Central hypoventilation syndrome (CHS) is a rare condition resulting from damage to the respiratory centers in the central nervous system (CNS). It can be congenital or acquired and can cause hypoventilation, inadequate gas exchange, and respiratory failure, often during sleep but sometimes even while awake. CHS can lead to respiratory failure and life-threatening complications if not identified promptly. In this report, we present a rare case of a patient with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), who developed CHS likely due to an opportunistic infection by cytomegalovirus (CMV) and varicella zoster virus (VZV), manifesting as a lesion in the medullary respiratory nuclei. After treatment with ganciclovir, the patient showed clinical improvement, and his medullary lesion resolved.

The Impact of Drug and Alcohol Intoxication on Glasgow Coma Scale Assessment in Patients with Traumatic Brain Injury.

BACKGROUND: The effect of intoxicating substances on assessment of Glasgow Coma Scale (GCS) in the trauma setting has not been completely elucidated. METHODS: A trauma registry was queried for patients with blunt head trauma in 2013-2017. Initial GCS score and toxicology screening from the database were reviewed. Next recorded GCS score from the neurosurgery evaluation and change in GCS score (ΔGCS) were compared. RESULTS: We reviewed 468 patients. In 217 (46.4%) patients, no toxic substances were found, whereas >1 toxic substance was found in 104 (22.2%) patients. Alcohol level above the legal limit was found in 109 (23.3%) patients, marijuana was found in 105 (22.4%) patients, benzodiazepines were found in 94 (20.1%) patients, opiates were found in 48 (10.3%) patients, and cocaine was found in 41 (8.8%) patients. Mean change in GCS score was significantly higher in impaired patients compared with patients with a negative screening test (1.74 ± 2.4 vs. 0.75 ± 2.7, P < 0.001); this is despite both groups having a similar initial GCS score (6.23 ± 3.86 in impaired group vs. 6.47 ± 3.52 in sober group, P = 0.677). Initial GCS score was 3 in 187 patients, of whom 150 had a positive toxicology screen. Change in GCS score was significantly higher in the impaired group (2.75 ± 2.7 vs. 1.19 ± 1.8, P < 0.001). CONCLUSIONS: Intoxicating substances can confound GCS assessment in trauma patients. This can have effects on patient care as well as performance metrics and predictive analytics. These patients should be screened, and intoxicating substances should be reversed or allowed to wear off before GCS score is recorded for benchmarking or quality reporting.

Impact of premorbid hypertension on haemorrhage severity and aneurysm rebleeding risk after subarachnoid haemorrhage.

OBJECTIVE: Arterial hypertension (HTN) is a risk factor for subarachnoid haemorrhage (SAH). We aimed to assess the impact of premorbid HTN on the severity of initial bleeding and the risk of aneurysm rebleeding after SAH. DESIGN: Retrospective analysis of a prospective cohort study of all SAH patients admitted to Columbia University Medical Center between 1996 and 2012. RESULTS: We enrolled 1312 consecutive patients with SAH; 643 (49%) had premorbid HTN. Patients with premorbid HTN presented more frequently as Hunt-Hess Grade IV or V (36% vs 25%, p<0.001) and World Federation of Neurosurgical Societies (WFNS) Grade 4 or 5 (42.6% vs 28.2%, p<0.001), with larger amounts of subarachnoid (Hijdra Sum Score 17 vs 14, p<0.001) and intraventricular blood (median IVH sum score 2 vs 1, p<0.001), and more often with intracerebral haemorrhage (20% vs 13%, p=0.002). In multivariate analysis, patients with premorbid HTN had a higher risk of in-hospital aneurysm rebleeding (11.8% vs 5.5%, adjusted OR 1.67, 95% CI 1.02 to 2.74, p=0.04) after adjusting for age, admission, Hunt-Hess grade, size and site of the ruptured aneurysm. CONCLUSIONS: Premorbid HTN is associated with increased severity of the initial bleeding event and represents a significant risk factor for aneurysm rebleeding. Given that aneurysm rebleeding is a potentially fatal-but preventable-complication, these findings are of clinical relevance.

Intracranial hemorrhage in patients with cancer.

Intracranial hemorrhage (ICH) is a common neurological emergency in patients with cancer, typically occurring late in the disease course, although it occasionally heralds the cancer diagnosis. ICH in these patients often occurs from unique mechanisms, especially intratumoral hemorrhage or coagulopathy, whereas hypertensive hemorrhage is rare. Lung, melanoma, breast, and glioblastoma multiforme are the most commonly associated solid tumors, partly because of their ubiquity and frequent brain involvement, whereas leukemia is the most commonly associated hematological cancer. Patients typically present with focal neurological deficits, headache, and encephalopathy, and their initial diagnostic evaluation and management should follow standard guidelines, although steroids and/or surgical resection should be strongly considered in those with intratumoral hemorrhage. Short-term outcomes are comparable to ICH in the community, whereas long-term outcomes are generally poor, corresponding to the prognosis of the underlying cancer. This review focuses on the recent advances and special considerations in cancer-related intracranial hemorrhage.

Conditional ablation and recovery of forebrain neurogenesis in the mouse.

Forebrain neurogenesis persists throughout life in the rodent subventricular zone (SVZ) and hippocampal dentate gyrus (DG). Several strategies have been employed to eliminate adult neurogenesis and thereby determine whether depleting adult-born neurons disrupts specific brain functions, but some approaches do not specifically target neural progenitors. We have developed a transgenic mouse line to reversibly ablate adult neural stem cells and suppress neurogenesis. The nestin-tk mouse expresses herpes simplex virus thymidine kinase (tk) under the control of the nestin 2nd intronic enhancer, which drives expression in neural progenitors. Administration of ganciclovir (GCV) kills actively dividing cells expressing this transgene. We found that peripheral GCV administration suppressed SVZ-olfactory bulb and DG neurogenesis within 2 weeks but caused systemic toxicity. Intracerebroventricular GCV infusion for 28 days nearly completely depleted proliferating cells and immature neurons in both the SVZ and DG without systemic toxicity. Reversibility of the effects after prolonged GCV infusion was slow and partial. Neurogenesis did not recover 2 weeks after cessation of GCV administration, but showed limited recovery 6 weeks after GCV that differed between the SVZ and DG. Suppression of neurogenesis did not inhibit antidepressant responsiveness of mice in the tail suspension test. These findings indicate that SVZ and DG neural stem cells differ in their capacity for repopulation, and that adult-born neurons are not required for antidepressant responses in a common behavioral test of antidepressant efficacy. The nestin-tk mouse should be useful for studying how reversible depletion of adult neurogenesis influences neurophysiology, other behaviors, and neural progenitor dynamics.

Medial frontal hyperactivity in reality distortion.

BACKGROUND: Schizophrenia/schizoaffective disorder involves reality distortion (RD), which impairs the ability to process socioemotional information. Because this psychological capacity maps to the medial prefrontal cortex (MPFC) and schizophrenia involves abnormal MPFC function, we tested the hypothesis that treated schizophrenic/schizoaffective patients with persistent RD (RD+) would exhibit greater MPFC dysfunction than patients without significant RD (RD-). The amygdala interacts with MPFC, also carries out socioemotional processing, and has been implicated in schizophrenia; thus, we also tested the hypothesis that patients would exhibit aberrant amygdala activity. METHODS: Eleven RD+ patients, 12 RD- patients, and 15 healthy control subjects (HC) viewed emotionally salient pictures with neutral, aversive, and positive content during the acquisition of blood oxygenation level-dependent (BOLD) sensitive functional magnetic resonance imaging. RESULTS: All groups had similar behavioral responses to the pictures. The RD+ subjects had greater BOLD responses (compared with the RD- and HC groups) to the aversive pictures in the anterior MPFC. Both patient groups showed reduced activation in MPFC and the left amygdala (compared with HC) for neutral pictures (compared with blank condition), although this effect could be explained by medication. CONCLUSIONS: Reality distortion is associated with hyperactivity of the MPFC in schizophrenic/schizoaffective patients whose symptoms persist in spite of antipsychotic treatment.

Versatile asymmetric synthesis of the kavalactones: first synthesis of (+)-kavain.

[reaction: see text] Three asymmetric pathways to the kavalactones have been developed. The first method is chiral auxiliary-based and utilizes aldol reactions of N-acetyl thiazolidinethiones followed by a malonate displacement/decarboxylation reaction. The second approach uses the asymmetric catalytic Mukaiyama additions of dienolate nucleophile equivalents developed by Carreira and Sato. Finally, tin-substituted intermediates, prepared by either of these routes, can serve as advanced general precursors of kavalactone derivatives via Pd(0)-catalyzed Stille couplings with aryl halides.