Ventriculostomy-Related Infections: Reduced Incidence by Terminating Cerebrospinal Fluid Screening.

BACKGROUND: The external ventricular drain (EVD) is an important instrument in managing patients in neurointensive care (NICU). A frequent and sometimes severe complication is ventriculostomy-related infection (VRI). This study aimed to evaluate the effects of biweekly VRI screening by CSF sampling on the clinical course and rate of VRI. METHODS: Patients with implanted EVDs were retrospectively identified and a cohort screened twice per week was compared with a cohort sampled only on clinical indication. VRI was defined either as a suspected case or a culture-confirmed case. Length of stay in the NICU and CSF shunt dependency were used as outcome parameters. RESULTS: A total of 562 patients were included. The overall proportion of patients treated for VRI was 22% and was not affected by screening (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.57-1.54). Screening was associated with a higher proportion of patients with culture-confirmed VRI (OR, 2.86; 95% CI, 1.36-6.73). The main risk factor for VRI was the number of days with EVD. Positive bacterial culture was associated with both a longer time in the NICU (ß = 3.6; P < 0.01) and higher risk for shunt surgery (OR, 1.95; 95% CI, 1.04-3.64). CONCLUSIONS: Screening was associated with a higher number of culture-confirmed VRI cases. In addition, screening did not detect VRI at an earlier stage and was not associated with a reduction in the rate of permanent hydrocephalus. No clinical benefit of screening was found. Frequent CSF sampling might contribute to infection. Based on these findings, CSF screening for VRI cannot be recommended.

The impact of previous health on the mortality after aneurysmal subarachnoid hemorrhage: analysis of a prospective Swedish multicenter study.

PURPOSE: There is an an increasing awareness of the importance of health and lifestyle for stroke diseases like spontaneous subarachnoid hemorrhage (SAH). However, the importance of pre-existing medical conditions for clinical course and mortality after SAH has not been studied. The aim of the present study was to identify pre-existing conditions contributing to mortality after SAH. METHODS: Data were extracted from a Swedish national prospective study on patients with SAH. Variables were defined for age, sex, body mass index (BMI), clinical condition at admission, and for 10 pre-existing medical conditions. Models predicting mortality in three time intervals with all possible subsets of these variables were generated, compared and selected using Akaike's information criterion. RESULTS: 1155 patients with ruptured aneurysms were included. The mortality within 1 week was 7.6%, 1 month 14.3%, and 1 year 18.7%. The most common pre-existing medical conditions were smoking (57.6%) and hypertension (38.7%). The model's best predicting mortality within 1 week and from 1 week to 1 month included only the level of consciousness at admission and age, and these two variables were present in all the models among the top 200 in Akaike score for each time period. The most predictive model for mortality between 1 month and 1 year added previous stroke, diabetes, psychiatric disease, and BMI as predictors. CONCLUSION: Mortality within the first month was best predicted simply by initial level of consciousness and age, while mortality within from 1 month to 1 year was significantly influenced by pre-existing medical conditions.

Prediction of Long-Term Outcome After Intracerebral Hemorrhage Surgery.

BACKGROUND: Surgery for spontaneous primary intracerebral hemorrhage (ICH) remains controversial. Previous surgical trials have primarily focused on short-term mortality while studies on long-term functional outcome are rare. We therefore conducted this retrospective study of long-term outcome on all ICH patients who underwent craniotomy at a single neurosurgical center during a 10-year period. METHODS: We included all patients >15 years of age who underwent evacuation of spontaneous ICH at Skåne University Hospital between 2003 and 2012. Case fatality at 30 days, 1 year, and long-term follow-up (up to 10 years) were analyzed in relation to potential predictors of outcome. Long-term functional outcome was assessed in 2013 by telephone interview using the modified Rankin Scale (mRS). RESULTS: Of 229 operated patients, overall case fatality was 20% at 30 days and 31% at 1 year. For patients with supratentorial ICH, the case fatality was 16% at 30 days and 27% at 1 year, and 29% at 30 days and 41% at 1 year for patients with cerebellar ICH. The most consistent independent predictors of mortality were preictal heart disease and level of consciousness on admission. Of 185 patients with long-term functional outcome available (median follow-up 6.14 years), 44 of them (24%) had a good outcome (mRS score 0-3) and 141 (76%) were severely disabled or dead (mRS score 4-6). CONCLUSIONS: The case fatality in our study was comparatively low, but most survivors lived dependently several years after surgery. Heart disease and level of consciousness were the most consistent predictors of mortality.

Fremanezumab blocks CGRP induced dilatation in human cerebral, middle meningeal and abdominal arteries.

BACKGROUND: Fremanezumab (TEV-48125) is a fully humanized anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) that has shown positive results in the prevention of episodic migraine and chronic migraine. Previous preclinical studies have revealed CGRP antagonistic effects on intracranial arteries (ICA). The aim of the study was to evaluate the in vitro antagonistic effects of fremanezumab on human arteries. METHODS: Arteries were removed in conjunction with neurosurgery (cerebral, CA, and middle meningeal artery, MMA, n = 7) or reconstructive abdominal surgery (abdominal artery, AA, n = 6). Ring segments of the vessels were mounted in a sensitive myograph, the functional responses of vasoactive intestinal peptide (VIP), substance P and CGRP in increasing concentrations (10- 10-10- 7 M) were studied using pre-contraction with 30 mM potassium chloride (KCl). The concentrations of fremanezumab or isotype control antibody (66.7 nM, 0.33 µM, 0.67 µM) were given 30 min prior to CGRP administration. RESULTS: All included arteries responded with a strong stable contraction to the application of 30 mM KCl. During this pre-contraction, CGRP caused a concentration-dependent relaxation which differed slightly in maximum effect (Imax) between the types of arteries (ICA = 100%; AA 80%). Fremanezumab (66.7 nM) showed a shift in the IC50 value of CGRP, but no significant change in Imax. At higher doses there was also a reduction of Imax. For AA, the Imax decreased from 71% at 66.7 nM, to 4.5% with 0.33 µM of fremanezumab. Isotype control antibody did not modify the responses. There was no effect on concentration-dependent relaxation with VIP with 66.7 nM of fremanezumab or isotype control. CONCLUSION: CGRP relaxes pre-contracted human arteries by 80-100%, but with different IC50; the potency range was ICA < AA. The antagonistic effect and potency of fremanezumab was similar, suggesting that there are vasodilatory CGRP receptors present in all studied arteries and that the antibody may have effect in all studied vessels.

Reduced Quality of Life in Patients with Pituitary Dysfunction After Aneurysmal Subarachnoid Hemorrhage: A Prospective Longitudinal Study.

OBJECTIVE: Pituitary dysfunction (PD) after aneurysmal subarachnoid hemorrhage (SAH) has been demonstrated in several studies. Given the similarities between psychological symptoms and reduced quality of life (QoL) in patients with PD and fatigue commonly seen in patients after SAH, we investigated the relationship between QoL and PD after SAH. METHODS: There were 51 patients with aneurysmal SAH prospectively recruited and evaluated for health-related QoL using the Psychological General Well-Being Index. Evaluations were conducted 3-6 months (n = 45), 6-12 months (n = 44), and 12-24 months (n = 44) after SAH, with concomitant assessment of endocrine function. The study protocol also included a magnetic resonance imaging examination 3 months after SAH. RESULTS: Mean general well-being scores showed a positive trend from 97.3 at 3-6 months to 104.3 at 12-24 months for all patients. Multiple regression analysis identified age, sex, Hunt and Hess grade, and PD as independent predictors for general well-being. Patients with PD had significantly lower scores compared with patients with normal pituitary function at 3-6 months (85.4 vs. 101.7) and 6-12 months (90.4 vs. 105.3). This result was due to central hypoadrenalism (score 81.6 at 3-6 months and score 82.2 at 6-12 months) but not other types of PD. The extent of magnetic resonance imaging lesions had a significant negative correlation to Glasgow Outcome Scale score at all follow-up evaluations. All patients with hypothalamic magnetic resonance imaging lesions had evidence of PD at some point during the follow-up period. CONCLUSIONS: The results support PD, and central hypoadrenalism in particular, as a contributing factor for impaired health-related QoL in patients after SAH.

High prevalence of pituitary dysfunction after aneurysmal subarachnoid hemorrhage: a long-term prospective study using dynamic endocrine testing.

OBJECTIVE: Impaired systemic hormonal activity caused by hypothalamic and pituitary injury may contribute to neuropsychologic disturbances and poor quality of life after aneurysmal subarachnoid hemorrhage (SAH). This prospective study was designed to longitudinally evaluate long-term clinical outcome and pituitary function after SAH using dynamic tests for adrencorticotropic and somatotropic secretory capacity. METHODS: Endocrine function was assessed by basal hormonal concentrations at 6-12 months and 12-24 months after SAH. At the 12-24 months follow-up, dynamic provocative evaluation of adrenocorticotropic hormone (ACTH) and growth hormone (GH) was performed using the insulin tolerance test (ITT). In patients where ITT was contraindicated, an ACTH stimulation test was used to assess ACTH capacity, and a growth hormone releasing hormone (GHRH)-arginine stimulation test was used to assess GH capacity. RESULTS: Of 60 patients with SAH screened, 51 were included in the study, and 44 remained to be tested at the two follow-up visits. As assessed by basal hormone concentrations alone, the prevalence of pituitary dysfunction was 34% at 6-12 months and 41% at 12-24 months. When using dynamic tests (12-24 months), impaired pituitary function was detected in 43%. The ITT detected more cases of central hypoadrenalism and GH deficiency compared with the ACTH- and GHRH-arginine-stimulation tests, respectively. CONCLUSIONS: Application of dynamic endocrine tests revealed a high frequency of long-term hypothalamic-pituitary dysfunction after aneurysmal SAH. The role of pituitary dysfunction in the recovery after SAH merits further evaluation.

Pituitary dysfunction after aneurysmal subarachnoid hemorrhage is associated with impaired early outcome.

OBJECTIVE: Poor outcome and neuropsychological sequelae after aneurysmal subarachnoid hemorrhage (SAH) is a persistent problem. Pituitary dysfunction has been proposed as a contributing factor. Clinical studies have given variable and conflicting results on its importance and incidence after SAH. The aim of this study was to prospectively examine SAH patients with assessment of endocrine function in the acute stage and at early follow-up and to compare clinical SAH features to endocrine abnormalities indicating pituitary dysfunction. METHODS: Endocrine function was assessed by basal hormonal concentrations at 5 to 10 days and 3 to 6 months after SAH. Growth hormone deficiency also was evaluated by the growth hormone releasing hormone-arginine stimulation test at follow-up. Clinical outcome was assessed and scored according to the Glasgow Outcome Scale. RESULTS: Fifty-one SAH patients were included and assessed in the acute stage after the bleed. Six were lost to follow-up. The overall prevalence of pituitary dysfunction was 37% and 27% in the acute stage and at follow-up, respectively. Patients with evidence of pituitary dysfunction had significantly worse outcome according to Glasgow Outcome Scale at both occasions. The ruptured aneurysm was more commonly located in the circle of Willis among patients with pituitary dysfunction in the acute stage. CONCLUSIONS: The present results support earlier findings that hormonal abnormalities are not infrequent after SAH. Furthermore, our data suggest that pituitary dysfunction is associated with worse clinical outcome and is more common among patients with bleeding sites close to the hypothalamus.