Systematic review of current randomised control trials in chronic subdural haematoma and proposal for an international collaborative approach.

BACKGROUND: Chronic subdural haematoma (CSDH) is a pathology that is frequently encountered by neurosurgeons. Nevertheless, there is a lack of guidelines based on solid evidence. There has been a recent and considerable increase in the interest on management and outcomes for CSDH. Therefore, we systematically reviewed all currently running randomised controlled trials (RCTs) in chronic subdural haematoma to understand the areas under investigation and plan future collaborative trials. METHODS: Clinical trials databases (Cochrane Controlled Register of Trials, WHO ICTRP and clinical trials.gov) were searched for trials relevant to chronic subdural haematoma. It was then established which trials were currently running and fulfilled robust research methodology for a RCT. RESULTS: There are 26 currently running RCTs in CSDH, with the most common topics covering application of steroids (7), surgical techniques (5) and tranexamic acid (5). Further to this, there are trials running on other pharmacological agents (4), middle meningeal artery (MMA) embolisation (2) and peri-operative management (3). CONCLUSIONS: Pharmacological agents are a particular focus of CSDH management currently, and a wealth of studies on steroids will hopefully lead to more harmonised, evidence-based practice regarding this in the near future. Surgical techniques and new procedures such as MMA embolisation are also important focuses for improving patient outcomes. There is an on-going need for future RCTs and evidence-based guidelines in CSDH, particularly including low- and middle-income countries, and it is hoped that the establishment of the iCORIC (International COllaborative Research Initiative on Chronic Subdural Haematoma) will help address this.

A snapshot of European neurosurgery December 2019 vs. March 2020: just before and during the Covid-19 pandemic.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or Covid-19), which began as an epidemic in China and spread globally as a pandemic, has necessitated resource management to meet emergency needs of Covid-19 patients and other emergent cases. We have conducted a survey to analyze caseload and measures to adapt indications for a perception of crisis. METHODS: We constructed a questionnaire to survey a snapshot of neurosurgical activity, resources, and indications during 1 week with usual activity in December 2019 and 1 week during SARS-CoV-2 pandemic in March 2020. The questionnaire was sent to 34 neurosurgical departments in Europe; 25 departments returned responses within 5 days. RESULTS: We found unexpectedly large differences in resources and indications already before the pandemic. Differences were also large in how much practice and resources changed during the pandemic. Neurosurgical beds and neuro-intensive care beds were significantly decreased from December 2019 to March 2020. The utilization of resources decreased via less demand for care of brain injuries and subarachnoid hemorrhage, postponing surgery and changed surgical indications as a method of rationing resources. Twenty departments (80%) reduced activity extensively, and the same proportion stated that they were no longer able to provide care according to legitimate medical needs. CONCLUSION: Neurosurgical centers responded swiftly and effectively to a sudden decrease of neurosurgical capacity due to relocation of resources to pandemic care. The pandemic led to rationing of neurosurgical care in 80% of responding centers. We saw a relation between resources before the pandemic and ability to uphold neurosurgical services. The observation of extensive differences of available beds provided an opportunity to show how resources that had been restricted already under normal conditions translated to rationing of care that may not be acceptable to the public of seemingly affluent European countries.

Post-surgical effects on language in patients with presumed low-grade glioma.

OBJECTIVES: Low-grade glioma (LGG) is a slow-growing brain tumour often situated in or near areas involved in language and/or cognitive functions. Thus, language impairments due to tumour growth or surgical resection are obvious risks. We aimed to investigate language outcome following surgery in patients with presumed LGG, using a comprehensive and sensitive language assessment. MATERIALS AND METHODS: Thirty-two consecutive patients with presumed LGG were assessed preoperative, early post-operative, and 3 months post-operative using sensitive tests including lexical retrieval, language comprehension and high-level language. The patients' preoperative language ability was compared with a reference group, but also with performance at post-operative controls. Further, the association between tumour location and language performance pre- and post-operatively was explored. RESULTS: Before surgery, the patients with presumed LGG performed worse on tests of lexical retrieval when compared to a reference group (BNT: LGG-group median 52, Reference-group median 54, P = .002; Animals: LGG-group mean 21.0, Reference-group mean 25, P = 001; Verbs: LGG-group mean 17.3, Reference-group mean 21.4, P = .001). At early post-operative assessment, we observed a decline in all language tests, whereas at 3 months there was only a decline on a single test of lexical retrieval (Animals: preoperative. median 20, post-op median 14, P = .001). The highest proportion of language impairment was found in the group with a tumour in language-eloquent areas at all time-points. CONCLUSIONS: Although many patients with a tumour in the left hemisphere deteriorated in their language function directly after surgery, their prognosis for recovery was good.

What predicts survival in glioblastoma? A population-based study of changes in clinical management and outcome.

Background: Glioblastoma is the most common and most aggressive primary brain tumor in adults. Despite multimodal treatment, the median survival time is 15-16 months and 5-year survival rate 5%-10%. The primary goal of this study was to identify prognostic factors for survival in an unselected population of patients operated for glioblastoma. The secondary goal was to explore changes in outcome and the clinical management of this patient group over time. Methods: We identified 222 consecutive adults operated for glioblastoma between November 2012 and June 2016 at the Department of Neurosurgery, Sahlgrenska University Hospital in Gothenburg, serving a health care region in the western part of Sweden with 1.900.000 inhabitants. Clinical variables were identified and tested as predictors for prognosis in extended Poisson regression models. The results were compared with a previously published cohort from 2004 to 2008, before current standard of care based on molecular tumor diagnosis was fully implemented. Results: Median overall survival was 1.07 years, which was significantly longer than in the 2004-2008 cohort (1.07 vs. 0.73 y, age- and sex adjusted HR = 1.89, p < 0.0001). Variables associated with longer survival in the multivariable model were MGMT promoter hypermethylation, non-central tumor location, complete resection of enhancing tumor, WHO performance status 0-1, unilateral tumor location, fewer lobes involved, younger age and no comorbidities. Conclusion: The median survival for patients with glioblastoma treated according to current standard treatment has moderately but significantly increased, with MGMT promoter hypermethylation as the strongest predictor for survival.

Perioperative risk factors for short term shunt revisions in adult hydrocephalus patients.

OBJECTIVES: The aim of this study was to prospectively study perioperative variables associated with revision after shunt surgery for adult hydrocephalus. METHODS: Two protocols were designed to prospectively study perioperative risk factors during shunt insertion. Over 10 years (1995-2004), 450 adult (age >16 years) patients with first time shunt implantations were studied. Patients who had been treated with endoscopic third ventriculostomy were excluded from the study. All shunts were designated as meeting one of two end points: (1) shunt failure requiring revision within 6 months or (2) no shunt failure within 6 months. Shunt revision within 6 months postoperatively was considered to be related to the shunting procedure. RESULTS: 85 shunt revisions were performed within 6 months after insertion. During the study period the revision rate declined from 21.1% to 9.1%. Revision rates were the same for ventriculoperitoneal (n = 411) and ventriculoatrial (n = 39) shunts. The predictive values of variables related to the patient, operating room, surgical technique and shunt system were analysed to determine shunt outcome. CONCLUSIONS: Right frontal placement of the ventricular catheter was associated with the lowest rate of revisions. Adjustable valves were associated with a lower risk for shunt revision. Shunt revision rates did not differ between ventriculoperitoneal and ventriculoatrial shunts.

Long-term outcome after surgery for Chiari I malformation.

OBJECTIVE: To examine the long-term effects of suboccipito-cervical decompression on an intention-to-treat basis in patients with Chiari I malformation (CMI). PATIENTS AND METHODS: Twenty-four consecutive patients, 14 females and 10 males with a median age of 26 years, underwent decompressive surgery for CMI during 1998-2006. All patients were contacted by an independent examiner and asked to complete a questionnaire regarding headache, other neurological symptoms and negative impact of the disease on the daily life before and after surgery. The median follow-up time after surgery was 3.2 years (range 1.7-9.2 years). Twenty-three patients (96%) completed the questionnaire. RESULTS: On an intention-to-treat basis there was an improvement in headache in 75%, decreased associated neurological symptoms in 88% and less negative impact on daily life in 75% of the 24-operated patients. CONCLUSIONS: More than three-quarters of the patients still considered their situation improved at long-term follow-up after surgery. These results support surgical intervention in symptomatic Chiari I patients.

Ventricular cerebrospinal fluid neurofilament protein levels decrease in parallel with white matter pathology after shunt surgery in normal pressure hydrocephalus.

Normal pressure hydrocephalus (NPH) is characterized by disturbed cerebrospinal fluid (CSF) dynamics and white matter lesions (WML). Although the morphology of these lesions is described, little is known about the biochemistry. Our aim was to explore the relationship between ventricular CSF markers, periventricular WML and postoperative clinical outcome in patients with NPH. We analysed lumbar and ventricular concentrations of 10 CSF markers, 12 clinical symptoms and signs, magnetic resonance imaging (MRI) periventricular white matter hyperintensities (PVH) and ventricular size before and 3 months after shunt surgery in 35 patients with NPH. Higher ventricular CSF neurofilament protein (NFL), an axonal marker, correlated with more extensive PVH. A larger postoperative reduction in NFL correlated with larger reduction in PVH and a more pronounced overall improvement. Albumin ratio, HMPG, NPY, VIP and GD3 increased postoperatively whereas NFL, tau and HVA decreased. Variations in ventricular size were not associated with CSF concentrations of any marker. We conclude that NPH is characterized by an ongoing periventricular neuronal dysfunction seen on MRI as PVH. Clinical improvement after shunt surgery is associated with CSF changes indicating a restitution of axonal function. Other biochemical effects of shunting may include increased monoaminergic and peptidergic neurotransmission, breakdown of blood brain barrier function, and gliosis.

How effective is endoscopic third ventriculostomy in treating adult hydrocephalus caused by primary aqueductal stenosis?

OBJECTIVE: To evaluate the long-term efficacy of third ventriculostomies for adult patients with hydrocephalus caused by primary aqueductal stenosis. METHODS: Eighteen of 64 patients who underwent endoscopic third ventriculostomies (ETVs) between June 1991 and July 1995 were treated because of primary aqueductal stenosis. All of these patients accepted follow-up investigations, which were performed 3 months to 5 years after surgery. If hydrocephalic symptoms persisted, the patency of the ventriculostomy was investigated; in cases of open ventriculostomies, the patients were offered shunt surgery. The effects of the shunt surgery were evaluated after 3 months. RESULTS: After ETV, nine of the patients exhibited excellent improvements, two exhibited slight improvements, one displayed no change, and six demonstrated temporary improvements. The ventriculostomies were patent in all nine patients who experienced less than excellent results. Subsequent ventriculoperitoneal shunt placement produced improvements for all seven patients who accepted the surgery. CONCLUSION: In our experience, the long-term effectiveness of ETVs for adult patients with noncommunicating hydrocephalus was sufficient in only 50% of the cases. One-third of the patients exhibited temporary improvements, lasting 1 to 12 months (average duration, 5 mo) after the ETVs, and then demonstrated deterioration to even worse clinical conditions, despite patent ventriculostomies. All patients who did not exhibit permanent improvements after the ETVs benefited from shunt surgery. Efforts should be made to establish methods for the selection of patients for ETV or ventriculoperitoneal shunt surgery.

[Incidence of surgery for hydrocephalus in adults surveyed: same number afflicted by hydrocephalus as by multiple sclerosis]. / Operationsincidensen för hydrocefalus hos vuxna kartlagd: lika många insjuknar i hydrocefalus som i multipel skleros.

The incidence of surgical treatment for adult hydrocephalus (older than 18 years) in Sweden from 1996 to 1998 was surveyed. The number of operations was 891 and the average incidence 3.36 operations per 100,000 inhabitants and year, varying regionally from 2.3 to 6.3. The mean age was 60 years (range 18-92), with no sex difference. Normal pressure hydrocephalus (47%) was most common, followed by communicating high pressure hydrocephalus (27%) and aqueductal stenosis (11%). 804 shunt operations (90%) and 67 ventriculostomies (7.5%) were performed, 2% were unclassified.

Long-term outcome in 109 adult patients operated on for hydrocephalus.

To examine the long-term effects of surgery in adult hydrocephalus we conducted a cross-sectional questionnaire study assessing both the patients' sense of well-being, and changes in gait, living conditions, daily need of sleep and bladder function. One-hundred-and-nine consecutive patients operated for non-communicating hydrocephalus (N-CH) (22) and communicating normal pressure hydrocephalus (NPH), both idiopathic (38) and secondary (49) were included. For survival analyses, three reference groups were selected from the general population and from the Northern Sweden MONICA Project. At long-term follow-up, 29 (27%) patients had died. Sixty-eight patients (62%) returned the questionnaire, while 12 (11%) patients did not reply. The median follow-up time was 4.2 years (range 2.3 - 6.2 years). Fifty-four (79%) of these patients reported that they still felt improved and 60% had persisting observable improvement of gait, living conditions, bladder function and need of sleep. Intention-to-treat analyses revealed that 54 (50%) of the patients still felt better and 37% remained functionally improved. The standardized mortality ratio (observed/expected) was 3.01 (CI: 2.01 - 4.32).

How should primary aqueductal stenosis in adults be treated? A review.

In 10% of adult patients with hydrocephalus, the cause is because of aqueductal stenosis (AS), causing enlargement of the lateral and third ventricles. There are currently two alternate forms of surgical treatment for AS; shunt surgery and ventriculostomy. Shunt surgery is associated with high complication rates and many patients need revisions, but the effectiveness is high. Endoscopic third ventriculostomy (ETV), re-establishing a physiological route of CSF dynamics, has become the treatment of choice for AS in most neurosurgical centers. ETV has fewer complications and revisions are rare, but some patients need shunt surgery to improve despite a patent ventriculostomy. There are today no common criteria for patient selection to either ETV or ventriculo-peritoneal shunt surgery.

National and regional incidence of surgery for adult hydrocephalus in Sweden.

In Sweden, the annual incidence of surgery for hydrocephalus was 3.4 per 100,000 adults between the years 1996 and 1998. The most common indication for surgery was normal pressure hydrocephalus (NPH; 47%), followed by high-pressure hydrocephalus (27%). Seventy-three percent of the patients had communicating hydrocephalus, of which 63% had NPH. Twenty percent of the patients had non-communicating hydrocephalus, of which half resulted from aqueduct stenosis. The annual incidence of operations varied between regional clinics from 2.3 to 6.3 per 100,000 inhabitants.

Objective B wave analysis in 55 patients with non-communicating and communicating hydrocephalus.

BACKGROUND: B waves, slow and rhythmic oscillations in intracranial pressure (ICP), are claimed to be one of the best predictors of outcome after surgery for normal pressure hydrocephalus (NPH). OBJECT: To determine the relation between the percentage of B waves and outcome in patients with hydrocephalus, and also the diurnal variation of B waves. METHODS: ICP and patient behaviour were recorded overnight (17 to 26 hours) in 29 patients with non-communicating hydrocephalus and 26 with NPH. The B wave activity, measured with an amplitude threshold of 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, and 5.0 mm Hg, was estimated as the percentage of total monitoring time (% B waves) using a computer algorithm, and correlated with postoperative outcome, defined as changes in 12 standardised symptoms and signs. RESULTS: There was no linear correlation between improvement after surgery in the 55 patients and total % B waves, but a correlation was found between improvement and % B waves during sleep (r = 0.39, p = 0.04). The percentage of B waves was the same during sleep and wakefulness, and patients with NPH had the same proportion of B waves as the non-communicating patients. CONCLUSIONS: B waves are commonly observed in patients with both communicating and non-communicating hydrocephalus, but are only weakly related to the degree of postsurgical improvement.

Differences in cerebrospinal fluid dynamics do not affect the levels of biochemical markers in ventricular CSF from patients with aqueductal stenosis and idiopathic normal pressure hydrocephalus.

To compare levels of biochemical markers in ventricular cerebrospinal fluid (vCSF) between patients with aqueductal stenosis (AS) and idiopathic normal pressure hydrocephalus (INPH) and relate these results to clinical outcome after surgery. Neurofilament light protein, tau protein, sulfatide, vasoactive intestinal peptide (VIP), neuropeptide PYY (NPY) and CSF/serum albumin ratio were measured in vCSF from 18 consecutive AS and 19 consecutive INPH patients. Clinical outcome was evaluated after surgery by standardized indices. The levels of markers were related to clinical outcome. No differences in any of the markers were found between AS and INPH patients. The concentration of sulfatide and albumin ratio correlated inversely with psychometric improvement, whilst VIP and NPY correlated inversely with improvement in alertness. The similar levels of biochemical markers in vCSF from AS and INPH patients indicate similarities in pathophysiology and turnover rate of vCSF despite differences in CSF dynamics. High albumin ratio and sulfatide concentrations in vCSF in hydrocephalus patients have negative implications for surgical outcome and might indicate concomitant cerebrovascular disorder.

Neurological symptoms and signs in adult aqueductal stenosis.

OBJECTIVE: To comprehensively describe and compare prospectively (pre/postoperatively) the symptomatology in aqueductal stenosis (AS) vs idiopathic normal pressure hydrocephalus (INPH). METHODS: Twenty-seven patients with AS and 39 patients with INPH were consecutively included. Postural functions, gait, wakefulness, cognitive functions, urinary continence and headache were examined before and 3 months after treatment with shunt operation or endoscopic ventriculostomy. RESULTS: The AS patients had better postural functions, walked faster, performed better cognitively and had a higher wakefulness than INPH patients, but these differences were explained by age differences between groups. The frequency of incontinence was similar in the two patients groups. Headache occurred more frequently in AS, but independently of the other symptoms. Most symptoms and signs improved after surgery. CONCLUSION: Patients with AS had a higher frequency of headaches than INPH patients, but otherwise the symptomology of the two groups was not found to differ after correcting for age differences.

CSF sulfatide distinguishes between normal pressure hydrocephalus and subcortical arteriosclerotic encephalopathy.

OBJECTIVES: To examine the CSF concentrations of molecules reflecting demyelination, neuronal and axonal degeneration, gliosis, monoaminergic neuronal function, and aminergic and peptidergic neurotransmission in a large series of patients with normal pressure hydrocephalus (NPH) or subcortical arteriosclerotic encephalopathy (SAE), to elucidate pathogenic, diagnostic, and prognostic features. METHODS: CSF concentrations of glycosphingolipid (sulfatide), proteins (neurofilament triplet protein (NFL), glial fibrillary acidic protein (GFAP)), neuropeptides (vasoactive intestinal peptide (VIP), 4-aminobutyric acid (GABA)), and monoamines (homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA), 4-hydroxy-3-methoxyphenylglycol (HMPG)) were analysed in 43 patients with NPH and 19 patients with SAE. The diagnoses of NPH and SAE were based on strict criteria and patients with NPH were subsequently operated on. Twelve clinical variables, psychometric tests measuring perceptual speed, accuracy, learning, and memory and a psychiatric evaluation were performed in all patients and before and after a shunt operation in patients with NPH. RESULTS: The CSF sulfatide concentration was markedly increased in patients with SAE (mean 766, range 300-3800 nmol/l) compared with patients with NPH (mean 206, range 50-400 nmol/l) (p<0.001). 5-HIAA, GABA, and VIP in CSF were higher in patients with SAE than in patients with NPH. The patients with NPH with cerebrovascular aetiology had higher sulfatide concentrations and a poorer outcome after shunt surgery than patients with NPH with other aetiologies. CONCLUSIONS: The pathogenesis of the white matter changes in NPH and SAE is different and ischaemic white matter changes can be a part of the NPH state. The markedly increased CSF sulfatide concentrations in patients with SAE indicate ongoing demyelination as an important pathophysiological feature of SAE. The CSF sulfatide concentration distinguished between patients with SAE and those with NPH with a sensitivity of 74% and a specificity of 94%, making it an important diagnostic marker.