Biomarkers in patients with idiopathic normal pressure hydrocephalus

Idiopathic normal pressure hydrocephalus (iNPH) is a condition affecting a small percentage of the elderly population; however it is the only known treatable cause of dementia. Surgical cerebrospinal fluid (CSF) diversion is the only known treatment for the condition today. However, such a procedure is not to be offered lightly and any expected benefit has to balance the associated surgical risks. The prognosis of a favourable surgical outcome has been problematic since the conception of the syndrome. None of current prognostic tests reaches 100% sensitivity or specificity and it is felt that there might be a need for a combination of tests, rather than a single one to maximize the chances of selecting the right patients to offer a surgical CSF diversion procedure. Biomarkers are biological substances that may act as surrogate markers of response to a treatment or to characterise a disease’s progression over time. The aim of this study was to identify CSF markers of favourable surgical outcome in patients with iNPH undergoing the insertion of a ventriculoperitoneal shunt (VPS). We first describe the effects of external lumbar drainage (ELD) on the CSF biochemistry of these patients. Correlations are made with imaging data obtained from volumetric analysis and neuropsychological tests in order to obtain a complete profile of these patients. The rostrocaudal gradients of the CSF markers examined are reported showcasing the need to understand that commonly reported values from lumbar CSF do not necessarily reflect pathological changes occurring at cerebral level. Finally, we report on the individual as well as combined prognostic value of 7 CSF markers on surgical outcomes at 6 months. The pathophysiological significance of these markers is discussed individually. It is concluded that the combined power of total tau and Aβ 1-42 may be useful in predicting favourable surgical outcomes at 6 months; further studies applying the findings in a larger cohort and correlating findings with longer outcomes are warranted to enhance the clinical application. The biochemical profile of patients with iNPH appears unique and different than patients with Alzheimer’s dementia or control subjects

Rostrocaudal Dynamics of CSF Biomarkers

The rostrocaudal gradient (RCG) of markers present in cerebrospinal fluid (CSF) has not been studied adequately due to lack of appropriate control populations and ethical restrictions. The aim of this study is to understand the rostrocaudal gradient of CSF biomarkers. We contacted a study comparing CSF levels of seven biomarkers from cisternal (rostral) and lumbar (caudal) CSF obtained from patients with trigeminal neuralgia and tension-type headache. The RCGs of CSF/serum albumin ratio, 8-isoprostane. GFAP, total tau and beta amyloid protein were higher than one. The RCGs of lactate, VEGF and the heavy chain of neurofilament protein were lower than one. The study provides new values for several commonly examined markers of cisternal CSF. Knowledge of the RCG gradient of different CSF markers is important in interpreting studies reporting ventricular CSF values. © Springer Science+Business Media, LLC 2010

The management and outcome for patients with chronic subdural hematoma: a prospective, multicenter, observational cohort study in the United Kingdom

Symptomatic chronic subdural hematoma (CSDH) will become an increasingly common presentation in neurosurgical practice as the population ages, but quality evidence is still lacking to guide the optimal management for these patients. The British Neurosurgical Trainee Research Collaborative (BNTRC) was established by neurosurgical trainees in 2012 to improve research by combining the efforts of trainees in each of the United Kingdom (UK) and Ireland's neurosurgical units (NSUs). The authors present the first study by the BNTRC that describes current management and outcomes for patients with CSDH throughout the UK and Ireland. This provides a resource both for current clinical practice and future clinical research on CSDH

Reduced CSF turnover and decreased ventricular Aβ42 levels are related

International audienceBACKGROUND: The appearance of Aβ42 peptide deposits is admitted to be a key event in the pathogenesis of Alzheimer's disease, although amyloid deposits also occur in aged non-demented subjects. Aβ42 is a degradation product of the amyloid protein precursor (APP). It can be catabolized by several enzymes, reabsorbed by capillaries or cleared into cerebrospinal fluid (CSF). The possible involvement of a decrease in CSF turnover in A4β2 deposit formation is up to now poorly known. We therefore investigated a possible relationship between a reduced CSF turnover and the CSF levels of the A4β2 peptide.To this aim, CSF of 31 patients with decreased CSF turnover were studied. These patients presented chronic hydrocephalus communicating or obstructive, which required surgery (ventriculostomy or ventriculo-peritoneal shunt). Nine subjects had idiopathic normal pressure hydrocephalus (iNPH), and the other 22 chronic hydrocephalus from other origins (oCH).The Aβ42 peptide concentration was measured by an ELISA test in 31 ventricular CSF samples and in 5 lumbar CSF samples from patients with communicating hydrocephalus. RESULTS: The 5 patients with lumbar CSF analysis had similar levels of lumbar and ventricular Aβ42. A significant reduction in Aβ42 ventricular levels was observed in 24 / 31 patients with hydrocephalus. The values were lower than 300 pg/ml in 5 out of 9 subjects with iNPH, and in 15 out of 22 subjects with oCH. CONCLUSION: The decrease of CSF Aβ42 seems to occur independently of the surgical hydrocephalus aetiology. This suggests that a CSF reduced turnover may play an important role in the decrease of CSF Aβ42 concentration

Outcomes following surgery in subgroups of comatose and very elderly patients with chronic subdural hematoma

Increasing age and lower pre-operative Glasgow coma score (GCS) are associated with worse outcome after surgery for chronic subdural haematoma (CSDH). Only few studies have quantified outcomes specific to the very elderly or comatose patients. We aim to examine surgical outcomes in these patient groups. We analysed data from a prospective multicentre cohort study, assessing the risk of recurrence, death, and unfavourable functional outcome of very elderly (≥ 90 years) patients and comatose (pre-operative GCS ≤ 8) patients following surgical treatment of CSDH. Seven hundred eighty-five patients were included in the study. Thirty-two (4.1%) patients had pre-operative GCS ≤ 8 and 70 (8.9%) patients were aged ≥ 90 years. A higher proportion of comatose patients had an unfavourable functional outcome (38.7 vs 21.7%; p = 0.03), although similar proportion of comatose (64.5%) and non-comatose patients (61.8%) functionally improved after surgery (p = 0.96). Compared to patients aged < 90 years, a higher proportion of patients aged ≥ 90 years had unfavourable functional outcome (41.2 vs 20.5%; p < 0.01), although approximately half had functional improvement following surgery. Mortality risk was higher in both comatose (6.3 vs 1.9%; p = 0.05) and very elderly (8.8 vs 1.1%; p < 0.01) groups. There was a trend towards a higher recurrence risk in the comatose group (19.4 vs 9.5%; p = 0.07). Surgery can still provide considerable benefit to very elderly and comatose patients despite their higher risk of morbidity and mortality. Further research would be needed to better identify those most likely to benefit from surgery in these groups

The management and outcome for patients with chronic subdural hematoma: A prospective, multicenter, observational cohort study in the United Kingdom

OBJECTIVESymptomatic chronic subdural hematoma (CSDH) will become an increasingly common presentation in neurosurgical practice as the population ages, but quality evidence is still lacking to guide the optimal management for these patients. The British Neurosurgical Trainee Research Collaborative (BNTRC) was established by neurosurgical trainees in 2012 to improve research by combining the efforts of trainees in each of the United Kingdom (UK) and Ireland's neurosurgical units (NSUs). The authors present the first study by the BNTRC that describes current management and outcomes for patients with CSDH throughout the UK and Ireland. This provides a resource both for current clinical practice and future clinical research on CSDH.METHODSData on management and outcomes for patients with CSDH referred to UK and Ireland NSUs were collected prospectively over an 8-month period and audited against criteria predefined from the literature: NSU mortality &lt; 5%, NSU morbidity &lt; 10%, symptomatic recurrence within 60 days requiring repeat surgery &lt; 20%, and unfavorable functional status (modified Rankin Scale score of 4–6) at NSU discharge &lt; 30%.RESULTSData from 1205 patients in 26 NSUs were collected. Bur-hole craniostomy was the most common procedure (89%), and symptomatic recurrence requiring repeat surgery within 60 days was observed in 9% of patients. Criteria on mortality (2%), rate of recurrence (9%), and unfavorable functional outcome (22%) were met, but morbidity was greater than expected (14%). Multivariate analysis demonstrated that failure to insert a drain intraoperatively independently predicted recurrence and unfavorable functional outcome (p = 0.011 and p = 0.048, respectively). Increasing patient age (p &lt; 0.00001), postoperative bed rest (p = 0.019), and use of a single bur hole (p = 0.020) independently predicted unfavorable functional outcomes, but prescription of high-flow oxygen or preoperative use of antiplatelet medications did not.CONCLUSIONSThis is the largest prospective CSDH study and helps establish national standards. It has confirmed in a real-world setting the effectiveness of placing a subdural drain. This study identified a number of modifiable prognostic factors but questions the necessity of some common aspects of CSDH management, such as enforced postoperative bed rest. Future studies should seek to establish how practitioners can optimize perioperative care of patients with CSDH to reduce morbidity as well as minimize CSDH recurrence. The BNTRC is unique worldwide, conducting multicenter trainee-led research and audits. This study demonstrates that collaborative research networks are powerful tools to interrogate clinical research questions.Society of British Neurological Surgeons. PJH supported by NIHR Research Professorship and NIHR Cambridge Biomedical Research Centre.This is the author accepted manuscript. It is permanently embargoed to comply with the publisher’s copyright terms. The final version is available via https://doi.org/10.3171/2016.8.JNS1613

Outcomes following surgery in subgroups of comatose and very elderly patients with chronic subdural hematoma

Increasing age and lower pre-operative Glasgow coma score (GCS) are associated with worse outcome after surgery for chronic subdural haematoma (CSDH). Only few studies have quantified outcomes specific to the very elderly or comatose patients. We aim to examine surgical outcomes in these patient groups. We analysed data from a prospective multicentre cohort study, assessing the risk of recurrence, death, and unfavourable functional outcome of very elderly (≥ 90 years) patients and comatose (pre-operative GCS ≤ 8) patients following surgical treatment of CSDH. Seven hundred eighty-five patients were included in the study. Thirty-two (4.1%) patients had pre-operative GCS ≤ 8 and 70 (8.9%) patients were aged ≥ 90 years. A higher proportion of comatose patients had an unfavourable functional outcome (38.7 vs 21.7%; p = 0.03), although similar proportion of comatose (64.5%) and non-comatose patients (61.8%) functionally improved after surgery (p = 0.96). Compared to patients aged < 90 years, a higher proportion of patients aged ≥ 90 years had unfavourable functional outcome (41.2 vs 20.5%; p < 0.01), although approximately half had functional improvement following surgery. Mortality risk was higher in both comatose (6.3 vs 1.9%; p = 0.05) and very elderly (8.8 vs 1.1%; p < 0.01) groups. There was a trend towards a higher recurrence risk in the comatose group (19.4 vs 9.5%; p = 0.07). Surgery can still provide considerable benefit to very elderly and comatose patients despite their higher risk of morbidity and mortality. Further research would be needed to better identify those most likely to benefit from surgery in these groups