Neurogenic pulmonary edema.

AIM: We report a case of neurogenic pulmonary edema in a patient who sustained a severe traumatic brain injury in a motorbike accident and review the current literature with regards to the management of neurogenic pulmonary edema (NPE). METHODS: A 17 year old male was involved in a motorbike collision into a tree. Copious amounts of pink frothy sputum was noted on scene. Rapid sequence intubation was performed on scene and video laryngoscopy demonstrated profuse frothy secretions welling up from the larynx. RESULTS: The patient underwent emergency external ventricular drain insertion for intracranial pressure (ICP) monitoring. Intracranial pressures remained refractorily high and a decompressive bifrontal craniectomy was performed on the subsequent day. He was tracheostomised on admission day 24 and discharged from ICU on day 34. DISCUSSION: Neurogenic pulmonary edema is defined as acute respiratory distress triggered by severe sympathetic discharge from acute compromise in the central nervous system. Rapid intervention with intubation is often necessary to protect the airways and facilitate diagnostic evaluation. Reduction of ICP and supportive mechanical ventilation to improve oxygenation is necessary. Positive end-expiratory pressure should be carefully applied to balance recruitment of alveoli and minimisation of ICP. Although NPE is estimated to resolve within 72 h in more than half of patients, prognosis is generally poor due to the severity of the underlying brain injury, with estimated mortality rates of between 60 and 100%. CONCLUSION: Neurogenic pulmonary edema is a potentially life-threatening complication of severe brain injury and should be recognised early to facilitate management.

Differences in neurosurgical treatment of intracerebral haemorrhage: a nation-wide observational study of 578 consecutive patients.

BACKGROUND: Supratentorial intracerebral haemorrhage (ICH) carries an excessive mortality and morbidity. Although surgical ICH treatment can be life-saving, the indications for surgery in larger cohorts of ICH patients are controversial and not well defined. We hypothesised that surgical indications vary substantially among neurosurgical centres in Sweden. OBJECTIVE: In this nation-wide retrospective observational study, differences in treatment strategies among all neurosurgical departments in Sweden were evaluated. METHODS: Patient records, neuroimaging and clinical outcome focused on 30-day mortality were collected on each operated ICH patient treated at any of the six neurosurgical centres in Sweden from 1 January 2011 to 31 December 2015. RESULTS: In total, 578 consecutive surgically treated ICH patients were evaluated. There was a similar incidence of surgical treatment among different neurosurgical catchment areas. Patient selection for surgery was similar among the centres in terms of patient age, pre-operative level of consciousness and co-morbidities, but differed in ICH volume, proportion of deep-seated vs. lobar ICH and pre-operative signs of herniation (p < .05). Post-operative patient management strategies, including the use of ICP-monitoring, CSF-drainage and mechanical ventilation, varied among centres (p < .05). The 30-day mortality ranged between 10 and 28%. CONCLUSIONS: Although indications for surgical treatment of ICH in the six Swedish neurosurgical centres were homogenous with regard to age and pre-operative level of consciousness, important differences in ICH volume, proportion of deep-seated haemorrhages and pre-operative signs of herniation were observed, and there was a substantial variability in post-operative management. The present results reflect the need for refined evidence-based guidelines for surgical management of ICH.

Favorable clinical outcome following surgical evacuation of deep-seated and lobar supratentorial intracerebral hemorrhage: a retrospective single-center analysis of 123 cases.

BACKGROUND: In spontaneous supratentorial intracerebral hemorrhage (ICH), the role of surgical treatment remains controversial, particularly in deep-seated ICHs. We hypothesized that early mortality and long-term functional outcome differ between patients with surgically treated lobar and deep-seated ICH. METHOD: Patients who underwent craniotomy for ICH evacuation from 2009 to 2015 were retrospectively evaluated and categorized into two subgroups: lobar and deep-seated ICH. The modified Rankin Scale (mRS) was used to evaluate long-term functional outcome. RESULT: Of the 123 patients operated for ICH, 49.6% (n = 61) had lobar and 50.4% (n = 62) deep-seated ICH. At long-term follow-up (mean 4.2 years), 25 patients (20.3%) were dead, while 51.0% of survivors had a favorable outcome (mRS score ≤ 3). Overall mortality was 13.0% at 30 days and 17.9% at 6 months post-ictus, not influenced by ICH location. Mortality was higher in patients ≥ 65 years old (p = 0.020). The deep-seated group had higher incidence and extent of intraventricular extension, younger age (52.6 ± 9.0 years vs. 58.5 ± 9.8 years; p < 0.05), more frequently pupillary abnormalities, and longer neurocritical care stay (p < 0.05). The proportion of patients with good outcome was 48.0% in deep-seated vs. 54.1% in lobar ICH (p = 0.552). In lobar ICH, independent predictors of long-term outcome were age, hemorrhage volume, preoperative level of consciousness, and pupillary reaction. In deep-seated ICHs, only high age correlated significantly with poor outcome. CONCLUSIONS: At long-term follow-up, most ICH survivors had a favorable clinical outcome. Neither mortality nor long-term functional outcome differed between patients operated for lobar or deep-seated ICH. A combination of surgery and neurocritical care can result in favorable clinical outcome, regardless of ICH location.

Predictors of 30-Day Mortality for Surgically Treated Patients with Spontaneous Supratentorial Intracerebral Hemorrhage and Validation of the Surgical Swedish Intracerebral Hemorrhage Score: A Retrospective Single-Center Analysis of 136 Cases.

OBJECTIVE: We aimed to identify independent risk factors of 30-day mortality in patients with surgically treated spontaneous supratentorial intracerebral hemorrhage (ICH), validate the Surgical Swedish ICH (SwICH) score within Polish healthcare system, and compare the SwICH score to the ICH score. METHODS: We carried out a single-center retrospective analysis of the medical data juxtaposed with computed tomography scans of 136 ICH patients treated surgically between 2008 and 2022. Statistical analysis was performed using the same characteristics as in the SwICH score and the ICH score. Backward stepwise logistic regression with both 5-fold crossvalidation and 1000× bootstrap procedure was used to create new scoring system. Finally predictive potential of these scales were compared. RESULTS: The most important predictors of 30-day mortality were: ICH volume (P < 0.01), Glasgow Coma Scale at admission (P < 0.01), anticoagulant status (P = 0.03), and age (P < 0.01). The SwICH score appears to have a better predictive potential than the ICH score, although this did not reach statistical significance [area under the curve {AUC}: 0.789 (95% confidence interval {CI}: 0.715-0.863) vs. AUC: 0.757 (95% CI: 0.677-0.837)]. Moreover, based on the analyzed characteristics, we developed our score (encompassing: age, ICH volume, anticoagulants status, Glasgow Coma Scale at admission), [AUC of 0.872 (95% CI: 0.815-0.929)]. This score was significantly better than previous ones. CONCLUSIONS: Differences in health care systems seem to affect the accuracy of prognostic scales for patients with ICH, including possible differences in indications for surgery and postoperative care. Thus, it is important to validate assessment tools before they can be applied in a new setting and develop population-specific scores. This may improve the effectiveness of risk stratification in patients with ICH.

Multiple meningiomas: Epidemiology, management, and outcomes.

Meningiomas are the most common nonmalignant brain tumor in adults, with an increasing incidence of asymptomatic meningiomas diagnosed on more ubiquitous neuroimaging. A subset of meningioma patients bear 2 or more spatially separated synchronous or metachronous tumors termed "multiple meningiomas" (MM), reported to occur in only 1%-10% of patients, though recent data indicate higher incidence. MM constitute a distinct clinical entity, with unique etiologies including sporadic, familial and radiation-induced, and pose special management challenges. While the pathophysiology of MM is not established, theories include independent origin in disparate locations through unique genetic events, and the "monoclonal hypothesis" of a transformed neoplastic clone with subarachnoid seeding precipitating numerous distinct meningiomas. Patients with solitary meningiomas carry the risk of long-term neurological morbidity and mortality, as well as impaired health-related quality of life, despite being a generally benign and surgically curable tumor. For patients with MM, the situation is even less favorable. MM should be regarded as a chronic disease, and in many cases, the management goal is disease control, as cure is seldom possible. Multiple interventions and lifelong surveillance are sometimes necessary. We aim to review the MM literature and create a comprehensive overview, including an evidence-based management paradigm.

Glucose-6-phosphate dehydrogenase and 8-iso-prostaglandin F2α as potential predictors of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Delayed cerebral ischemia (DCI) is a serious complication of aneurysmal subarachnoid hemorrhage (aSAH), which is responsible for significant death and disability. The dynamic balance between the production and elimination of reactive oxygen species (ROS) in patients with DCI is suspected be shifted to favor ROS formation. The authors assessed the relationship between F2-isoprostanes (F2-IsoPs), oxidative stress biomarkers, and glucose-6-phosphate dehydrogenase (G6PD), which are responsible for nicotinamide adenine dinucleotide phosphate (NADPH) production for glutathione system function, with post-aSAH DCI. METHODS: The authors assessed 45 aSAH patients for F2-IsoP and G6PD concentration using commercial ELISA on days 2, 4, and 6 after aSAH. The authors examined the correlation between plasma F2-IsoP and G6PD concentrations and clinical factors with DCI occurrence and aSAH outcome. RESULTS: Expectedly, the most important clinical predictors of DCI were Hunt and Hess grade and modified Fisher (mFisher) grade. Plasma F2-IsoP and G6PD concentrations were greater in aSAH patients than the control group (p < 0.01). F2-IsoP concentrations were greater and G6PD concentrations were lower in patients with DCI than those without (p < 0.01). Plasma F2-IsoP and G6PD concentrations on day 2 were correlated with DCI occurrence (p < 0.01). Plasma F2-IsoP concentrations on days 2 and 6 were correlated with outcome at 1 and 12 months (p < 0.01). CONCLUSIONS: Decreased G6PD indirectly informs the reduced antioxidant response, especially for the glutathione system. G6PD concentration was lower in patients with DCI than those without, which may explain the increased F2-IsoP concentrations. mFisher grade, plasma F2-IsoP concentration, and G6PD concentration on day 2 after aSAH, in combination, may serve as predictors of DCI. Further research is necessary to investigate the therapeutic utility of F2-IsoPs and antioxidants in clinical practice.

Long-Term Functional Outcome and Quality of Life After Surgical Evacuation of Spontaneous Supratentorial Intracerebral Hemorrhage: Results from a Swedish Nationwide Cohort.

OBJECTIVE: To investigate long-term survival, neurologic outcome, and quality of life in patients with spontaneous supratentorial intracerebral hemorrhage (ICH) treated with craniotomy and hematoma evacuation. METHODS: A nationwide multicenter retrospective analysis of 341 patients who underwent craniotomy and evacuation of supratentorial ICH between January 1, 2011, and December 31, 2015, was performed. Baseline characteristics associated with 6-month mortality and long-term mortality were investigated. Survivors received a questionnaire about their state of health from which EuroQol 5D (EQ-5D) and modified Rankin scale (mRS) were obtained. Predictors of mortality, unfavorable outcome, and life quality were analyzed. RESULTS: The mean follow-up time was 55.2 months. Predictors of 6-month mortality in multiple regression analysis were age ≥75 years, previous myocardial infarction, lower level of consciousness, and mechanical ventilation. Predictors of long-term mortality were higher age and mechanical ventilation. At follow-up, 49.5% of survivors had a favorable neurologic outcome (mRS ≤3). Predictors of an unfavorable functional outcome were higher age and ICH volume ≥50 mL. The mean EQ-5D health index was 0.719, and the mean EQ-5D visual analog scale score was 53.9. In multiple regression, only a higher mRS score was significantly associated with worse life quality. CONCLUSIONS: Knowledge about survival, functional outcome, and life quality as well as their predictors in this specific patient group is previously primarily described in short-term follow-up. This multicenter study provides novel information in the long-term perspective, which is important for improved surgical decision-making and prognostication.

Impaired mitochondrial respiration and decreased fatigue resistance followed by severe muscle weakness in skeletal muscle of mitochondrial DNA mutator mice.

Mitochondrial dysfunction can drastically impair muscle function, with weakness and exercise intolerance as key symptoms. Here we examine the time course of development of muscle dysfunction in a mouse model of premature ageing induced by defective proofreading function of mitochondrial DNA (mtDNA) polymerase (mtDNA mutator mouse). Isolated fast-twitch muscles and single muscle fibres from young (3-5 months) and end-stage (11 months) mtDNA mutator mice were compared to age-matched control mice. Force and free myoplasmic [Ca(2+)] ([Ca(2+)](i)) were measured under resting conditions and during fatigue induced by repeated tetani. Muscles of young mtDNA mutator mice displayed no weakness in the rested state, but had lower force and [Ca(2+)](i) than control mice during induction of fatigue. Muscles of young mtDNA mutator mice showed decreased activities of citrate synthase and ß-hydroxyacyl-coenzyme A dehydrogenase, reduced expression of cytochrome c oxidase, and decreased expression of triggers of mitochondrial biogenesis (PGC-1α, PPARα, AMPK). Muscles from end-stage mtDNA mutator mice showed weakness under resting conditions with markedly decreased tetanic [Ca(2+)](i), force per cross-sectional area and protein expression of the sarcoplasmic reticulum Ca(2+) pump (SERCA1). In conclusion, fast-twitch muscles of prematurely ageing mtDNA mutator mice display a sequence of deleterious mitochondrial-to-nucleus signalling with an initial decrease in oxidative capacity, which was not counteracted by activation of signalling to increase mitochondrial biogenesis. This was followed by severe muscle weakness in the end stage. These results have implication for normal ageing and suggest that decreased mitochondrial oxidative capacity due to a sedentary lifestyle may predispose towards muscle weakness developing later in life.

Mechanical and Geometric Analysis of Fenestration Design for Polymethylmethacrylate-Augmented Pedicle Screw Fixation.

BACKGROUND: The practice of cement augmentation in pedicle screw fixation is well established. However, there is a lack of consensus regarding the optimal screw design or cement type. This remains a clinically important question given the incidence of cement augmentation-associated complications. While fenestrated screws have become widely used in clinical practice, the relationship between fenestration placement along the screw axis and cement plume geometry and pullout strength have yet to be clarified. This study was designed to evaluate the mechanical and geometric properties of different fenestrated screw designs and cement viscosities in pedicle screw fixation. METHODS: Three different screw fenestration configurations and 2 different cement viscosities were examined in this study. Axial pullout tests were conducted in both foam blocks and cadaveric vertebrae. All vertebral specimens underwent tests of bone mineral density. In the foam blocks, 6 tests were conducted for each augmentation combination and also for nonaugmented controls. In the cadaveric testing, 36 lumbar vertebrae were instrumented with a cemented and uncemented control screw to compare features of fixation. Computed tomography (CT) images were taken to assess the geometric profile of the cement plumes in both the foam blocks and the cadaveric vertebrae. RESULTS: In both foam blocks and vertebral specimens, cementation was shown to confer a significant increase in pullout strength. Significant correlations existed between the anterior-posterior and lateral cement plume diameters and pullout strength in cadaveric vertebra and foam blocks, respectively. Within instrumented vertebra, variables such as the width of the vertebral body and screw insertion were found to significantly correlate with enhanced fixation. CT analysis of the instrumented vertebra demonstrated that a centrally distributed pattern of fenestrations was found to result in a cement plume with consistently predictable distribution within the vertebral body, without evidence of leak. CONCLUSION: Cementation of fenestrated pedicle screws increases overall pullout forces; however, there is an unclear relationship between the geometric properties of the cement plume and the overall strength of the screw-bone interface. This study demonstrates that the plume diameter, vertebral body width, and angle of screw insertion are correlated with enhanced pullout strength. Furthermore, varying the fenestration design of injectable screws resulted in a set of predictable plume patterns, which may be associated with fewer complications. Further investigation is required to clarify the optimal geometric and biomechanical properties of injectable pedicle screws and their role in establishing the cement-bone interface. CLINICAL RELEVANCE: This study is relevant to currently practicing spinal surgeons and biomechanical engineers.

Muscle atrophy and regeneration associated with behavioural loss and recovery of function after sciatic nerve crush.

AIM: To resolve timing and coordination of denervation atrophy and the re-innervation recovery process to discern correlations indicative of common programs governing these processes. METHODS: Female Sprague-Dawley (SD) rats had a unilateral sciatic nerve crush. Based on longitudinal behavioural observations, the triceps surae muscle was analysed at different time points post-lesion. RESULTS: Crush results in a loss of muscle function and mass (-30%) followed by a recovery to almost pre-lesion status at 30 days post-crush (dpc). There was no loss of fibres nor any significant change in the number of nuclei per fibre but a shift in fibres expressing myosins I and II that reverted back to control levels at 30 dpc. A residual was the persistence of hybrid fibres. Early on a CHNR -ε to -γ switch and a re-expression of embryonic MyHC showed as signs of denervation. Foxo1, Smad3, Fbxo32 and Trim63 transcripts were upregulated but not Myostatin, InhibinA and ActivinR2B. Combined this suggests that the mechanism instigating atrophy provides a selectivity of pathway(s) activated. The myogenic differentiation factors (MDFs: Myog, Myod1 and Myf6) were upregulated early on suggesting a role also in the initial atrophy. The regulation of these transcripts returned towards baseline at 30 dpc. The examined genes showed a strong baseline covariance in transcript levels which dissolved in the response to crush driven mainly by the MDFs. At 30 dpc the naïve expression pattern was re-established. CONCLUSION: Peripheral nerve crush offers an excellent model to assess and interfere with muscle adaptions to denervation and re-innervation.

A grading scale for surgically treated patients with spontaneous supratentorial intracerebral hemorrhage: the Surgical Swedish ICH Score.

OBJECTIVE: The authors aimed to develop the first clinical grading scale for patients with surgically treated spontaneous supratentorial intracerebral hemorrhage (ICH). METHODS: A nationwide multicenter study including 401 ICH patients surgically treated by craniotomy and evacuation of a spontaneous supratentorial ICH was conducted between January 1, 2011, and December 31, 2015. All neurosurgical centers in Sweden were included. All medical records and neuroimaging studies were retrospectively reviewed. Independent predictors of 30-day mortality were identified by logistic regression. A risk stratification scale (the Surgical Swedish ICH [SwICH] Score) was developed using weighting of independent predictors based on strength of association. RESULTS: Factors independently associated with 30-day mortality were Glasgow Coma Scale (GCS) score (p = 0.00015), ICH volume ≥ 50 mL (p = 0.031), patient age ≥ 75 years (p = 0.0056), prior myocardial infarction (MI) (p = 0.00081), and type 2 diabetes (p = 0.0093). The Surgical SwICH Score was the sum of individual points assigned as follows: GCS score 15-13 (0 points), 12-5 (1 point), 4-3 (2 points); age ≥ 75 years (1 point); ICH volume ≥ 50 mL (1 point); type 2 diabetes (1 point); prior MI (1 point). Each increase in the Surgical SwICH Score was associated with a progressively increased 30-day mortality (p = 0.0002). No patient with a Surgical SwICH Score of 0 died, whereas the 30-day mortality rates for patients with Surgical SwICH Scores of 1, 2, 3, and 4 were 5%, 12%, 31%, and 58%, respectively. CONCLUSIONS: The Surgical SwICH Score is a predictor of 30-day mortality in patients treated surgically for spontaneous supratentorial ICH. External validation is needed to assess the predictive value as well as the generalizability of the Surgical SwICH Score.

Changes in behaviors of male C57BL/6J mice across adult life span and effects of dietary restriction.

Behavioral analysis is a high-end read-out of aging impact on an organism, and here, we have analyzed behaviors in 4-, 22-, and 28-month-old male C57BL/6J with a broad range of tests. For comparison, a group of 28-month-old males maintained on dietary restriction (DR) was included. The most conspicuous alteration was the decline in exploration activity with advancing age. Aging also affected other behaviors such as motor skill acquisition and grip strength, in contrast to latency to thermal stimuli and visual placement which were unchanged. Object recognition tests revealed intact working memory at 28 months while memory recollection was impaired already at 22 months. Comparison with female C57BL/6J (Fahlström et al., Neurobiol Aging 32:1868-1880, 2011) revealed that alterations in aged males and females are similar and that several of the behavioral indices correlate with age in both sexes. Moreover, we examined if behavioral indices in 22-month-old males could predict remaining life span as suggested in the study by Ingram and Reynolds (Exp Aging Res 12(3):155-162, 1986) and found that exploratory activity and motor skills accounted for up to 65% of the variance. Consistent with that a high level of exploratory activity and preserved motor capacity indicated a long post-test survival, 28-month-old males maintained on DR were more successful in such tests than ad libitum fed age-matched males. In summary, aged C57BL/6J males are marked by a reduced exploratory activity, an alteration that DR impedes. In light of recently published data, we discuss if a diminishing drive to explore may associate with aging-related impairment of central aminergic pathways.

Behavioral changes in aging female C57BL/6 mice.

Using a range of tests we have studied alterations in behavior with advancing age in female C57BL/6 (of Jackson origin), the golden standard on which most genetically engineered mice are back-crossed. In parallel, growth and survival data were collected. In a protected environment the 90% and 75% cohort survival age was 20 and 25 months, respectively, and the 50% cohort survival was 32 months. In mice, body weight increases continuously until 15-20 months of age, while in advanced age whole body weight drops. The body mass loss in senescence is associated with emergence of other aged phenotype features such as kyphosis, balding and loss of fur-color. Our behavioral data show that aging modulates certain aspects of basic behavior in a continuous manner, like explorative and locomotor activities. Advanced age associates with an acceleration of behavioral impairments evident in most of the tests used, including motor skill acquisition and memory consolidation. However, certain domains of mouse behavior were well preserved also in advanced age such as thermal noxious threshold and working memory as assessed by an object recognition task. The decreased drive to explore is suggested to be a key factor underlying many aspects of reduced performance including cognitive capacity during aging. Behavioral aging affects genetically closely related individuals housed under strictly standardized conditions differentially (Collier, T.J., Coleman, P.D., 1991. Divergence of biological and chronological aging: evidence from rodent studies. Neurobiol. Aging, 12, 685-693; Ingram, D.K., 1988. Motor performance variability during aging in rodents. Assessment of reliability and validity of individual differences. Ann. N.Y. Acad. Sci., 515, 70-96). Consistent with this a subpopulation of the 28-month-old mice showed an explorative activity similar to young-adult mice and a significantly stronger preference for a novel object than aged mice with a less explorative behavior. Thus, subtle environmental factors and epigenetic modifications may be important modulators of aging.