MTT and Blood-Brain Barrier Disruption within Asymptomatic Vascular WM Lesions.

BACKGROUND AND PURPOSE: White matter lesions of presumed ischemic origin are associated with progressive cognitive impairment and impaired BBB function. Studying the longitudinal effects of white matter lesion biomarkers that measure changes in perfusion and BBB patency within white matter lesions is required for long-term studies of lesion progression. We studied perfusion and BBB disruption within white matter lesions in asymptomatic subjects. MATERIALS AND METHODS: Anatomic imaging was followed by consecutive dynamic contrast-enhanced and DSC imaging. White matter lesions in 21 asymptomatic individuals were determined using a Subject-Specific Sparse Dictionary Learning algorithm with manual correction. Perfusion-related parameters including CBF, MTT, the BBB leakage parameter, and volume transfer constant were determined. RESULTS: MTT was significantly prolonged (7.88 [SD, 1.03] seconds) within white matter lesions compared with normal-appearing white (7.29 [SD, 1.14] seconds) and gray matter (6.67 [SD, 1.35] seconds). The volume transfer constant, measured by dynamic contrast-enhanced imaging, was significantly elevated (0.013 [SD, 0.017] minutes-1) in white matter lesions compared with normal-appearing white matter (0.007 [SD, 0.011] minutes-1). BBB disruption within white matter lesions was detected relative to normal white and gray matter using the DSC-BBB leakage parameter method so that increasing BBB disruption correlated with increasing white matter lesion volume (Spearman correlation coefficient = 0.44; P < .046). CONCLUSIONS: A dual-contrast-injection MR imaging protocol combined with a 3D automated segmentation analysis pipeline was used to assess BBB disruption in white matter lesions on the basis of quantitative perfusion measures including the volume transfer constant (dynamic contrast-enhanced imaging), the BBB leakage parameter (DSC), and MTT (DSC). This protocol was able to detect early pathologic changes in otherwise healthy individuals.

The Future of Neurocritical Care Research: Proceedings and Recommendations from the Fifth Neurocritical Care Research Network Conference.

The Fifth Neurocritical Care Research Network (NCRN) Conference held in Boca Raton, Florida, in September of 2018 was devoted to challenging the current status quo and examining the role of the Neurocritical Care Society (NCS) in driving the science and research of neurocritical care. The aim of this in-person meeting was to set the agenda for the NCS's Neurocritical Care Research Central, which is the overall research arm of the society. Prior to the meeting, all 103 participants received educational content (book and seminar) on the 'Blue Ocean Strategy®,' a concept from the business world which aims to identify undiscovered and uncontested market space, and to brainstorm innovative ideas and methods with which to address current challenges in neurocritical care research. Three five-member working groups met at least four times by teleconference prior to the in-person meeting to prepare answers to a set of questions using the Blue Ocean Strategy concept as a platform. At the Fifth NCRN Conference, these groups presented to a five-member jury and all attendees for open discussion. The jury then developed a set of recommendations for NCS to consider in order to move neurocritical care research forward. We have summarized the topics discussed at the conference and put forward recommendations for the future direction of the NCRN and neurocritical care research in general.

Hypertension Is Associated with White Matter Disruption in Apparently Healthy Middle-Aged Individuals.

BACKGROUND AND PURPOSE: Traditional cardiovascular risk factors have been associated with white matter disease. Because hypertension results in vascular stiffness and impaired cerebral perfusion, we hypothesized that it would be the most relevant risk factor for microstructural white matter disruption in apparently healthy middle-aged individuals with a family history of early-onset coronary artery disease. MATERIALS AND METHODS: This was a cross-sectional analysis of participants in the Genetic Study of Atherosclerosis Risk with DTI. Regional fractional anisotropy of 181 segmented brain regions was measured using Eve WM Atlas. Risk factors were examined using univariate analysis for 48 regions representing deep WM structures. Minimal multivariable linear regression models adjusting for age, sex, and race and maximal linear regression models adjusting for cardiovascular risk factors were performed for regions meeting the Bonferroni threshold in the initial analysis. RESULTS: Included were 116 subjects (mean age, 49 ± 11 years; 57% men) with a moderate load of cardiovascular risk factors. Subjects with hypertension had significantly lower regional fractional anisotropy in the right cingulum and left stria terminalis in the minimal and maximal regression models. Additionally, there was lower regional fractional anisotropy in the left fornix in the maximal model and right sagittal stratum in the minimal model. Systolic blood pressure values were significantly associated with regional fractional anisotropy in the left superior longitudinal fasciculus in the maximal model. There were no significant differences among regional fractional anisotropy values for other cardiovascular risk factors. CONCLUSIONS: In middle-aged apparently healthy individuals with susceptibility to vascular disease, among all known cardiovascular risk factors, hypertension was associated with microstructural WM disruption.

Thermodynamic integration methods, infinite swapping, and the calculation of generalized averages.

In the present paper we examine the risk-sensitive and sampling issues associated with the problem of calculating generalized averages. By combining thermodynamic integration, stationary phase Monte Carlo, and infinite swapping techniques, we develop an approach for such problems and explore its utility for a prototypical class of applications.

Management of infections associated with neurocritical care.

The reported incidence of hospital-acquired infections (HAIs) in the neurointensive care unit (NICU) ranges from 20% to 30%. HAIs in US hospitals cost between $28 and $45 billion per year in direct medical costs. These infections are associated with increased length of hospital stay and increased morbidity and mortality. Infection risk is increased in NICU patients due to medication side-effects, catheter and line placement, neurosurgical procedures, and acquired immune suppression secondary to steroid/barbiturate use and brain injury itself. Some of these infections may be preventable but many are not. Their appearance do not always constitute a failure of prevention or physician error. Neurointensivists require indepth knowledge of common nosocomial infections, their diagnosis and treatment, and an approach to evidence-based practices that improve processes of care and reduce HAIs.

Complement levels before and after dives with a high risk of DCS.

BACKGROUND: Previously, complement activation has been associated with decompression sickness (DCS). However data, both in humans and in animals, are controversial. HYPOTHESIS: Complement activation and depletion occurs after exposure to the hyperbaric environment and is associated with increasing risk of DCS. METHODS: We obtained serological samples from 102 dives (120-300 feet of seawater) with a constant partial pressure of O2 set at 1.3 ATA in thirty-five U.S. Navy diver volunteers. Blood was obtained within one hour of diving and within one hour of surfacing. Plasma was extracted and analyzed for complement depletion. The risk of DCS was estimated using a validated model of DCS risk. RESULTS: Pre-post dive concentrations of C3a were significantly related to estimated risk of DCS (Figure 1), but the variation in predicted DCS explained by C3a was small (correlation co-efficient (r2 = 0.19, p < 0.0001). CONCLUSIONS: There was a reduction in total Ca3 levels in divers after exposure to dives with a high estimated risk of DCS. This decomplementation appeared to increase as the estimated risk of DCS increased.

Wyburn-Mason syndrome associated with thyroid arteriovenous malformation: a first case report.

A 31-year-old woman with a prior history of Wyburn-Mason syndrome, complicated previously by a left thalamic intracerebral hemorrhage at age 21, complained of sudden left vision loss due to a central retinal vein occlusion. Angiography revealed a left thyroid arterio-venous malformation (AVM) in addition to ones found intracerebrally. The pathogenesis and embryogenesis of this finding including the management of AVMs in Wyburn-Mason syndrome are discussed.

Seizures in patients with multiple sclerosis seen at Mayo Clinic, Rochester, Minn, 1990-1998.

OBJECTIVE: To evaluate seizure type, electroencephalographic findings, and response to antiepileptic drug (AED) treatment in patients with multiple sclerosis (MS) and coexistent seizure activity. PATIENTS AND METHODS: We reviewed the medical records of all patients seen at the Mayo Clinic in Rochester, Minn, with the diagnosis of MS and seizures between 1990 and 1998. RESULTS: During the study period, 5715 patients with MS were identified. Of these 5715 patients, 51 (0.89%) experienced seizure activity. The most common ictal behavior was a generalized tonic-clonic seizure in 35 patients (68.6%). Simple or complex partial seizures occurred in 11 patients (21.6%), and 18 patients (35.3%) had only 1 seizure episode. Focal motor status epilepticus, ie, epilepsia partialis continua, occurred in 3 patients (5.9%) and was associated with cognitive impairment. In 37 patients (72.5%), the initial seizure presentation was after the diagnosis of MS. A seizure resulted in the diagnosis of MS or occurred before the diagnosis of MS but after other symptoms or signs of demyelinating disease in 14 patients (27.4%). Electroencephalography was performed in 43 patients. Electroencephalographic findings included diffuse or localized nonspecific background slowing in 19 patients (44.2%), unilateral or bilateral frontotemporal spike discharges in 9 (20.9%), generalized atypical spike-and-wave or multifocal independent epileptiform alterations in 6 (14.0%), and normal results in 11 (25.6%). Of the 45 patients who received AED therapy, 35 (77.8%) had an excellent response, ie, they were seizure free. Five treated patients (11.1%) had an intractable seizure disorder. CONCLUSION: Most of the patients with MS who experienced seizure activity had a benign and transient disorder that was responsive to AED treatment or required no therapy.

Circadian and seasonal occurrence of subarachnoid and intracerebral hemorrhage.

OBJECTIVE: To determine whether the time of onset of subarachnoid hemorrhage (SAH) or intracerebral hemorrhage (ICH) is associated with a time of day or season of year. BACKGROUND: Prior studies have suggested that there may be a circadian and seasonal pattern of ischemic stroke occurrence, but this is less certain for hemorrhagic stroke. Population-based data have been unavailable. METHODS: All incident ICH and SAH among residents of Rochester, MN, were ascertained. The medical records of patients were reviewed to determine the time of onset and date of occurrence. The day was divided into 8-hour periods, and the year into seasonal quartiles. Each patient was assigned a period based on the time of onset of symptoms. The data were analyzed by chi(2) analysis to determine whether there was a trend toward increased occurrence based on time period or seasonal quartile of onset. RESULTS: From 1960 to 1989, there were 155 cases (48 men, 107 women) of incident SAH. From 1975 to 1989, there were 137 cases (57 men, 80 women) of incident ICH. There was a significant increase in the time of onset for ICH and SAH in the 8 AM to 4 PM period (p = 0.005 and p = 0.03, respectively). The concomitant occurrence of hypertension, gender, and age did not affect the time of day of occurrence. In the analysis of seasonal variation, there was a significant increase in events during December, January, and February in the combined SAH and ICH group (p = 0.032) and a trend for SAH alone (p = 0.07) but not for ICH (p = 0.34). Hypertension and age had no impact on the association between season and the occurrence of SAH and ICH. CONCLUSION: The occurrence of SAH and ICH is increased from 8 AM to 4 PM. The occurrence of hemorrhage is increased during the winter months, but this is likely limited only to SAH.

Novel features of tumors that secrete both growth hormone and prolactin in acromegaly.

The most prominent previously reported clinical features of growth hormone (GH) and prolactin (PRL)-secreting pituitary adenomas associated with acromegaly have included the high incidence of galactorrhea in women and a generally more favorable response to dopamine agonist therapy. The authors analyzed a consecutive series of 62 acromegalic patients treated with transsphenoidal microsurgery. GH-PRL tumors were found in 30% of the patients. There was a significant difference in sex distribution between acromegalics with the GH-PRL tumor subtype and all other acromegalics. Women represented 73% of the GH-PRL immunostain subtype, as compared with the overall sex distribution of 33 women (53%) and 29 men (47%) for the entire series of acromegalic patients. Individuals with the GH-PRL subtype had significantly higher postoperative GH levels than those with the GH subtype, and significantly higher postoperative GH levels when compared with all other acromegalics with a variety of immunostain subtypes. Linear regression analysis of the pre- and postoperative GH data revealed that the increased postoperative GH levels in the GH-PRL immunostain subtype were independent of the invasiveness of the tumor and of sex of the subject. When the same linear regression technique was used, lower preoperative levels of thyroxine and thyroid-stimulating hormone were observed in the GH-PRL subtype. These data suggest inherent differences characteristic of tumors that secrete both growth hormone and prolactin.