Return to work after aneurysmal subarachnoid hemorrhage.

Introduction: Survivors of aneurysmal subarachnoid hemorrhage (aSAH) often recover without severe physical or cognitive deficits. However, strikingly low levels of engagement in productive employment have also been reported in aSAH patients with good or excellent outcomes. Knowledge about return to work (RTW) after aSAH and predictors of no RTW remain limited and controversial. The study aimed to delineate the return to maximum work capacity up to 5 years after the ictus in a larger number of consecutive aSAH patients from the entire aSAH severity spectrum and to identify demographic and medical predictors of no RTW. Methods: Data were acquired from a prospective institutional database. We included all 500 aSAH survivors aged > 18 years who were treated between January 2012 and March 2018. In addition to gathering data on work status and the type of work at ictus, we retrieved demographical data and assessed aSAH severity based on the quantification of subarachnoid, intraventricular, and intraparenchymal blood (ICH), as well as the World Federation of Neurological Societies (WFNS) grade. We registered the mode of aneurysm repair (endovascular or surgical) and recorded complications such as vasospasm, newly acquired cerebral infarctions, and chronic hydrocephalus. Results: Furthermore, work status and the grade of fatigue at follow-up were registered. RTW was assessed among 299 patients who were employed at ictus. Among them, 63.2% were women, and their age was 51.3 ± 9.4 (20-71) years. Return to gainful employment was 51.2%, with complete RTW accounting for 32.4%. The independent predictors of no RTW at ictus were age, the WFNS grade 3, and active smoking. The strongest independent predictor was the presence of clinically significant fatigue, which increased the risk of not returning to work by 5-fold. The chance to return to gainful employment significantly increased with the individual's years of education prior to their hemorrhage. The mode of aneurysm repair was not relevant with regard to RTW. Patients in the WFNS grades 1-2 more often returned to work than those in the WFNS grades 3-5, but our results indicate that neurological motor deficits are linked closer to no RTW than aSAH severity per se. Conclusion: Fatigue needs to be addressed as an important element on the path to return to work integration.

Empowering early career vascular neurosurgeons in the endovascular Era: Managing intraoperative aneurysm rupture through a systematic algorithmic approach.

Intraoperative aneurysm rupture (IAR) is a feared complication and an unnerving experience for any neurosurgeon. If not managed properly, the consequences may be devastating. Although overall patient outcomes in IAR have been shown to improve with a neurosurgeon's experience, the likelihood of rupture does not necessarily decrease, and the key to success lies in appropriate management. Microsurgical dexterity, remaining calm and acting sensible are important skills that all neurosurgeons need to master early on in order to achieve good patient outcomes. The landscape of cerebrovascular disease management has evolved significantly, with a growing preference for endovascular approaches. Consequently, the case-load of microsurgical procedures available for trainees have been diminished. As microsurgical cases decline and the remaining cases become more complex, the need for a systematic approach to IAR management becomes critical, to ensure a swift and efficient response and to compensate for reduced experience. This video article aims to empower the next generation of neurosurgeons by emphasizing essential skills and a systematic algorithmic approach required to navigate IAR situations successfully. In this video, we present the unedited sequence of IAR management in a posterior communicating artery (PCoA) aneurysm, from rupture to clipping. A 43-year-old female patient presented with headache and diplopia caused by a left oculomotor nerve palsy. Computed tomography (CT) did not show subarachnoid hemorrhage, but CT angiogram revealed a 7-mm left PCoA aneurysm affecting the oculomotor nerve. Patient consent was obtained for surgical management. The predissection phase was uneventful, however during dissection of the aneurysm neck, IAR occurred from the aneurysm dome. One contributing factor to rupture may have been the traction exerted on the aneurysm with the dissector, possibly due to adhesion of the aneurysm dome to the tentorial edge. Additionally, performing intradural drilling of the anterior clinoid process during the approach could have provided better access to proximal control of the internal carotid artery, making clip application easier. By remaining calm and proceeding with the steps illustrated in the decision algorithm (Fig. 1), the right actions were made, and the aneurysm was successfully clipped. In this article, we provide early career vascular neurosurgeons with a systematic strategy for managing IAR, offering guidance that may facilitate the 'right move' during these high-stress situations.

Mechanisms behind changes of neurodegeneration biomarkers in plasma induced by sleep deprivation.

Acute sleep deprivation has been shown to affect cerebrospinal fluid and plasma concentrations of biomarkers associated with neurodegeneration, though the mechanistic underpinnings remain unknown. This study compared individuals who, for one night, were either subject to total sleep deprivation or free sleep, (i) examining plasma concentrations of neurodegeneration biomarkers the morning after sleep deprivation or free sleep and (ii) determining how overnight changes in biomarkers plasma concentrations correlate with indices of meningeal lymphatic and glymphatic clearance functions. Plasma concentrations of amyloid-ß 40 and 42, phosphorylated tau peptide 181, glial fibrillary acid protein and neurofilament light were measured longitudinally in subjects who from Day 1 to Day 2 either underwent total sleep deprivation (n = 7) or were allowed free sleep (n = 21). The magnetic resonance imaging contrast agent gadobutrol was injected intrathecally, serving as a cerebrospinal fluid tracer. Population pharmacokinetic model parameters of gadobutrol cerebrospinal fluid-to-blood clearance were utilized as a proxy of meningeal lymphatic clearance capacity and intrathecal contrast-enhanced magnetic resonance imaging as a proxy of glymphatic function. After one night of acute sleep deprivation, the plasma concentrations of amyloid-ß 40 and 42 were reduced, but not the ratio, and concentrations of the other biomarkers were unchanged. The overnight change in amyloid-ß 40 and 42 plasma concentrations in the sleep group correlated significantly with indices of meningeal lymphatic clearance capacity, while this was not seen for the other neurodegeneration biomarkers. However, overnight change in plasma concentrations of amyloid-ß 40 and 42 did not correlate with the glymphatic marker. On the other hand, the overnight change in plasma concentration of phosphorylated tau peptide 181 correlated significantly with the marker of glymphatic function in the sleep deprivation group but not in the sleep group. The present data add to the evidence of the role of sleep and sleep deprivation on plasma neurodegeneration concentrations; however, the various neurodegeneration biomarkers respond differently with different mechanisms behind sleep-induced alterations in amyloid-ß and tau plasma concentrations. Clearance capacity of meningeal lymphatics seems more important for sleep-induced changes in amyloid-ß 40 and 42 plasma concentrations, while glymphatic function seems most important for change in plasma concentration of phosphorylated tau peptide 181 during sleep deprivation. Altogether, the present data highlight diverse mechanisms behind sleep-induced effects on concentrations of plasma neurodegeneration biomarkers.

Brain Sagging Dementia.

PURPOSE OF REVIEW: Brain sagging dementia (BSD) is a rare but devastating form of early-onset dementia characterized by intracranial hypotension and behavioral changes resembling behavioral variant frontotemporal dementia. This review aims to provide a comprehensive overview of BSD, highlighting its pathomechanism, diagnostic tools, and available treatment options. RECENT FINDINGS: BSD exhibits a complex clinical manifestation with insidious onset and gradual progression of behavioral disinhibition, apathy, inertia, and speech alterations. Additionally, patients may exhibit brainstem and cerebellar signs such as hypersomnolence and gait disturbance. Although headaches are common, they may not always demonstrate typical orthostatic features. Recent radiological advances have improved the detection of CSF leaks, enabling targeted treatment and favorable outcomes. Understanding the pathomechanism and available diagnostic tools for BSD is crucial for a systematic approach to timely diagnosis and treatment of this reversible form of early-onset dementia, as patients often endure a complex and lengthy clinical course.

Endoscopic four-hands technique for pituitary tumours. / Endoskopisk firehåndsteknikk ved hypofysesvulster.

Tumours in the pituitary fossa region can be resected by endoscopic transnasal surgery using a four-hands technique. The technique, which is atraumatic, safe and minimally invasive, should be the first-line treatment for pituitary tumours and certain skull-base tumours.

Plasma neurodegeneration biomarker concentrations associate with glymphatic and meningeal lymphatic measures in neurological disorders.

Clearance of neurotoxic brain proteins via cerebrospinal fluid (CSF) to blood has recently emerged to be crucial, and plasma biomarkers of neurodegeneration were newly introduced to predict neurological disease. This study examines in 106 individuals with neurological disorders associations between plasma biomarkers [40 and 42 amino acid-long amyloid-ß (Aß40 and Aß42), total-tau, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL)] and magnetic resonance imaging measures of CSF-mediated clearance from brain via extra-vascular pathways (proxy of glymphatic function) and CSF-to-blood clearance variables from pharmacokinetic modeling (proxy of meningeal lymphatic egress). We also examine how biomarkers vary during daytime and associate with subjective sleep quality. Plasma concentrations of neurodegeneration markers associate with indices of glymphatic and meningeal lymphatic functions in individual- and disease-specific manners, vary during daytime, but are unaffected by sleep quality. The results suggest that plasma concentrations of neurodegeneration biomarkers associate with measures of glymphatic and meningeal lymphatic function.

The first report on brain sagging dementia caused by a cranial leak: A case report.

Objective: Brain Sagging Dementia (BSD) is an increasingly recognized syndrome for which diagnostic criteria recently were proposed. There have been no reports on BSD caused by a cranial leak. Here we present the first report on a patient with BSD caused by a cranial leak. Case description: A 60-year old male patient was admitted with a 2-year history of orthostatic headache and gradually progressive cognitive and behavioral changes. Traditional treatments for spontaneous intracranial hypotension, including repeated epidural blood patches, failed. Brain imaging showed severe brain sagging, and intracranial pressure monitoring demonstrated intracranial hypotension. No leakage site was found. His past medical history revealed an accident where a ski pole struck his head at age ten. Due to progressive clinical decline, surgery was pursued. A cranial defect with an accompanying cerebrospinal fluid leak site representing the trauma from his childhood was found and repaired. He also was in need of a ventriculoperitoneal shunt. Following surgery, he improved and recovered completely. Discussion: This case report illustrates that a cranial leak may cause BSD, even with a "lucid interval" between trauma and symptom debut spanning many years. Moreover, this report validates well the recently proposed BSD diagnostic criteria.

Population pharmacokinetic modeling of CSF to blood clearance: prospective tracer study of 161 patients under work-up for CSF disorders.

BACKGROUND: Quantitative measurements of cerebrospinal fluid to blood clearance has previously not been established for neurological diseases. Possibly, variability in cerebrospinal fluid clearance may affect the underlying disease process and may possibly be a source of under- or over-dosage of intrathecally administered drugs. The aim of this study was to characterize the cerebrospinal fluid to blood clearance of the intrathecally administered magnetic resonance imaging contrast agent gadobutrol (Gadovist, Bayer Pharma AG, GE). For this, we established a population pharmacokinetic model, hypothesizing that cerebrospinal fluid to blood clearance differs between cerebrospinal fluid diseases. METHODS: Gadobutrol served as a surrogate tracer for extra-vascular pathways taken by several brain metabolites and drugs in cerebrospinal fluid. We estimated cerebrospinal fluid to blood clearance in patients with different cerebrospinal fluid disorders, i.e. symptomatic pineal and arachnoid cysts, as well as tentative spontaneous intracranial hypotension due to cerebrospinal fluid leakage, idiopathic intracranial hypertension, or different types of hydrocephalus (idiopathic normal pressure hydrocephalus, communicating- and non-communicating hydrocephalus). Individuals with no verified cerebrospinal fluid disturbance at clinical work-up were denoted references. RESULTS: Population pharmacokinetic modelling based on 1,140 blood samples from 161 individuals revealed marked inter-individual variability in pharmacokinetic profiles, including differences in absorption half-life (time to 50% of tracer absorbed from cerebrospinal fluid to blood), time to maximum concentration in blood and the maximum concentration in blood as well as the area under the plasma concentration time curve from zero to infinity. In addition, the different disease categories of cerebrospinal fluid diseases demonstrated different profiles. CONCLUSIONS: The present observations of considerable variation in cerebrospinal fluid to blood clearance between individuals in general and across neurological diseases, may suggest that defining cerebrospinal fluid to blood clearance can become a useful diagnostic adjunct for work-up of cerebrospinal fluid disorders. We also suggest that it may become useful for assessing clearance capacity of endogenous brain metabolites from cerebrospinal fluid, as well as measuring individual cerebrospinal fluid to blood clearance of intrathecal drugs.

Intrathecal Contrast-Enhanced Magnetic Resonance Imaging of Cerebrospinal Fluid Dynamics and Glymphatic Enhancement in Idiopathic Normal Pressure Hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH) is a neurodegenerative disease, characterized by cerebrospinal fluid (CSF) flow disturbance. Today, the only available treatment is CSF diversion surgery (shunt surgery). While traditional imaging biomarkers typically assess CSF space anatomy, recently introduced imaging biomarkers of CSF dynamics and glymphatic enhancement, provide imaging of CSF dynamics and thereby more specifically reveal elements of the underlying pathophysiology. The biomarkers address CSF ventricular reflux grade as well as glymphatic enhancement and derive from intrathecal contrast-enhanced MRI. However, the contrast agent serving as CSF tracer is administered off-label. In medicine, the introduction of new diagnostic or therapeutic methods must consider the balance between risk and benefit. To this end, we performed a prospective observational study of 95 patients with iNPH, comparing different intrathecal doses of the MRI contrast agent gadobutrol (0.10, 0.25, and 0.50 mmol, respectively), aiming at the lowest reasonable dose needed to retrieve diagnostic information about the novel MRI biomarkers. The present observations disclosed a dose-dependent enrichment of subarachnoid CSF spaces (cisterna magna, vertex, and velum interpositum) with dose-dependent ventricular reflux of tracer in iNPH, as well as dose-dependent glymphatic tracer enrichment. The association between tracer enrichment in CSF and parenchymal compartments were as well dose-related. Intrathecal gadobutrol in a dose of 0.25 mmol, but not 0.10 mmol, was at 1.5T MRI considered sufficient for imaging altered CSF dynamics and glymphatic enhancement in iNPH, even though 3T MRI provided better sensitivity. Tracer enrichment in CSF at the vertex and within the cerebral cortex and subcortical white matter was deemed too low for maintaining diagnostic information from a dose of 0.10 mmol. We conclude that reducing the intrathecal dose of gadobutrol from 0.50 to 0.25 mmol gadobutrol improves the safety margin while maintaining the necessary diagnostic information about disturbed CSF homeostasis and glymphatic failure in iNPH.

Brain Sagging Dementia-Diagnosis, Treatment, and Outcome: A Review.

Brain sagging dementia (BSD), caused by spontaneous intracranial hypotension (SIH), is a rare syndrome that is only recently recognized, mimicking the clinical findings of behavioral variant frontotemporal dementia (bvFTD). Being aware of its signs and symptoms is essential for early diagnosis and treatment in this potentially reversible form of dementia. Our objective was to identify cases of BSD in the literature and present its clinical characteristics, diagnostic workup, treatment options, and outcome. The review was reported according to PRISMA guidelines and registered with the PROSPERO database (CRD42020150709). MEDLINE, EMBASE, PsychINFO, and Cochrane Library were searched. There was no date restriction. The search was updated in April 2021. A total of 983 articles were screened and assessed for eligibility. Twenty-nine articles (25 case reports and 4 series) and 70 patients were selected for inclusion. No cranial leak cases were identified. BSD diagnosis should be made based on clinical signs and symptoms and radiologic findings. There is a male predominance (F:M ratio 1:4) and a peak incidence in the 6th decade of life. The main clinical manifestation is insidious onset, gradually progressive cognitive and behavioral changes characteristic for bvFTD. Headache is present in the majority of patients (89%). The presence of brain sagging and absence of frontotemporal atrophy is an absolute criterion for the diagnosis. CSF leak is identified with myelography and digital subtraction myelography. The treatment and repair depend on the etiology and extent of the dural defect, although an epidural blood patch is the first-line treatment in most cases. With treatment, 81% experienced partial and 67% complete resolution of their symptoms. This review highlights the most important clinical aspects of BSD. Due to the sparse evidence and lack of BSD awareness, many patients are likely left undiagnosed. Recognizing this condition is essential to provide early treatment to reverse the cognitive and behavioral changes that may otherwise progress and fully impair the patient. Moreover, patients with longstanding SIH must be assessed carefully for cognitive and behavioral changes.

Trigeminal neuralgia and genetics: A systematic review.

Trigeminal neuralgia (TN) is a severe facial pain disease of unknown cause and unclear genetic background. To examine the existing knowledge about genetics in TN, we performed a systematic study asking about the prevalence of familial trigeminal neuralgia, and which genes that have been identified in human TN studies and in animal models of trigeminal pain. MedLine, Embase, Cochrane Library and Web of Science were searched from inception to January 2021. 71 studies were included in the systematic review. Currently, few studies provide information about the prevalence of familial TN; the available evidence indicates that about 1-2% of TN cases have the familial form. The available human studies propose the following genes to be possible contributors to development of TN: CACNA1A, CACNA1H, CACNA1F, KCNK1, TRAK1, SCN9A, SCN8A, SCN3A, SCN10A, SCN5A, NTRK1, GABRG1, MPZ gene, MAOA gene and SLC6A4. Their role in familial TN still needs to be addressed. The experimental animal studies suggest an emerging role of genetics in trigeminal pain, though the animal models may be more relevant for trigeminal neuropathic pain than TN per se. In summary, this systematic review suggests a more important role of genetic factors in TN pathogenesis than previously assumed.

Clinical application of intrathecal gadobutrol for assessment of cerebrospinal fluid tracer clearance to blood.

BACKGROUNDMethodology for estimation of cerebrospinal fluid (CSF) tracer clearance could have wide clinical application in predicting excretion of intrathecal drugs and metabolic solutes from brain metabolism and for diagnostic workup of CSF disturbances.METHODSThe MRI contrast agent gadobutrol (Gadovist) was used as a CSF tracer and injected into the lumbar CSF. Gadobutrol is contained outside blood vessels of the CNS and is eliminated along extravascular pathways, analogous to many CNS metabolites and intrathecal drugs. Tracer enrichment was verified and assessed in CSF by MRI at the level of the cisterna magna in parallel with obtaining blood samples through 48 hours.RESULTSIn a reference patient cohort (n = 29), both enrichment within CSF and blood coincided in time. Blood concentration profiles of gadobutrol through 48 hours varied between patients diagnosed with CSF leakage (n = 4), idiopathic normal pressure hydrocephalus dementia (n = 7), pineal cysts (n = 8), and idiopathic intracranial hypertension (n = 4).CONCLUSIONAssessment of CSF tracer clearance is clinically feasible and may provide a way to predict extravascular clearance of intrathecal drugs and endogenous metabolites from the CNS. The peak concentration in blood (at about 10 hours) was preceded by far peak tracer enhancement at MRI in extracranial lymphatic structures (at about 24 hours), as shown in previous studies, indicating a major role of the spinal canal in CSF clearance capacity.FUNDINGThe work was supported by the Department of Neurosurgery, Oslo University Hospital; the Norwegian Institute for Air Research; and the University of Oslo.

How I do it: endoscopic endonasal resection of tuberculum sellae meningioma.

BACKGROUND: Tuberculum sellae meningiomas (TSMs) adherent to neurovascular structures are particularly challenging lesions requiring delicate and precise microneurosurgery. There is an ongoing debate about the optimal surgical approach. METHOD: We describe technical nuances and challenges in TSM resection using the endoscopic endonasal approach (EEA) in two cases of fibrous tumors with adherence to neurovascular structures. The cases are illustrated with a video (case 1) and figures (cases 1 and 2). CONCLUSION: A dedicated team approach and precise microsurgical technique facilitate safe resection of complex TSMs through the EEA.

Survival and outcome in patients with aneurysmal subarachnoid hemorrhage in Glasgow coma score 3-5.

BACKGROUND: Outcome of early, aggressive management of aneurysmal subarachnoid hemorrhage (aSAH) in patients with Hunt and Hess grade V is hitherto limited, and we therefore present our results. METHODS: Retrospective study analyzing the medical data of 228 aSAH patients in Glasgow Coma Score 3-5 admitted to our hospital during the years 2002-2012. Background and treatment variables were registered. Outcome was evaluated after 3 and 12 months. RESULTS: We intended to treat 176 (77.2%) patients, but only 146 went on to aneurysm repair. Of 52 patients managed conservatively, 27 had abolished cerebral circulation around arrival and 25 were deemed unsalvageable. One-year overall mortality was 65.8% and most (84.7%) of the fatalities occurred within 30 days. One-year mortality was higher in patients > 70 years. Without aneurysm repair, mortality was 100%. After 1 year, 21.9% of all patients lived independently and 4.8% lived permanently in an institution. Outcome in the 78 survivors (34.2%) was favorable in 64.1% in terms of modified Rankin Scale score 0-2, and 85.9% of survivors were able to live at home. Return to work was low for all 228 patients with 14.0% of those employed prior to the hemorrhage having returned to paid work, and respectively, 26.3% in the subgroup of survivors. CONCLUSIONS: Even with aggressive, early treatment, 1-year mortality is high in comatose aSAH patients with 65.8%. A substantial portion of the survivors have a favorable outcome at 1 year (64.1%, corresponding to 21.9% of all patients admitted) and 85.9% of the survivors could live at home alone or aided.

Surgery for Brainstem Cavernous Malformations: Association between Preoperative Grade and Postoperative Quality of Life.

BACKGROUND: Brainstem cavernous malformations (BSCMs) are associated with substantial neurologic morbidity, but the literature on quality of life (QoL) after surgical treatment is limited. There is a need for validating the clinical utility of current grading scales for cavernous malformations. OBJECTIVE: To assess outcome of surgery for BSCMs and validate how outcome is associated with current grading scales for cavernous malformations. METHODS: We retrospectively reviewed a single-surgeon series of patients with BSCM treated surgically during a 10-yr period. Outcome was categorized according to modified Rankin Scale (mRS), and QoL was assessed by interviewing patients using Short Form 36 (SF-36) Health Survey and comparing results with the normative population. The mRS and QoL were correlated with the Lawton BSCM grading scale and with the Zabramski classification of cavernous malformations. RESULTS: The study included 22 patients (12 males and 10 females; median age 58 yr). No mortality related to the BSCM surgery occurred, and none were in vegetative state. In SF-36, 70% of patients reported a physical and mental functioning noninferior compared to the general population of comparative age and gender group. There was a significant positive correlation between the Lawton BSCM grading and the postoperative mRS score and QoL. CONCLUSION: Outcome of surgery for BSCM was good, as assessed by mRS and QoL. The Lawton grading scale for BSCMs correlated significantly with the postoperative mRS score and QoL, suggesting this grading scale may become a useful clinical tool for treatment prognostication at the individual level.