An investigation into the clinical impacts of lowering shunt opening pressure in idiopathic normal pressure hydrocephalus: A case series.

INTRODUCTION: Idiopathic normal pressure hydrocephalus (iNPH) is a shunt- reversible syndrome of the elderly. Shunt management is aimed at achieving a balance between clinical improvement and the complications associated with overdrainage. Although clinical improvement occurs at low pressure, these benefits may be negated by the increase in complication rates observed at lower pressures. The addition of gravity-switch devices has been shown to reduce over drainage problems even at a low valve pressure setting. At our centre the Miethke proGAV is used and commonly lowered below 5 cmH2O to gain further clinical improvement. OBJECT: To determine whether lowering the opening pressure to below 5cmH2O using the proGAV valve in iNPH patients results in a) improved clinical features; and b) no significant increase in complication rates. METHODS: A retrospective case series of iNPH patients was undertaken with 24 patients who had the proGAV shunt system inserted with an initial opening pressure of 5cmH2O. Exclusion criteria were secondary NPH, shunt system other than proGAV inserted, no valve adjustment to below 5cmH2O and inadequate follow-up. Outcome measures were clinical improvement (gait, cognition and urinary continence) and complications (subdural haematoma, low-pressure symptoms and valve damage). RESULTS: Patients underwent a total of 29 adjustments to below 5cmH2O. The mean valve opening pressure after the first adjustment was 2.5cmH2O and the mean opening pressure after the second adjustment was 1cmH2O. Overall, outcome after adjustment included 26% no change, 48% improvement and 26% deterioration clinically. One patient (4%) suffered traumatic subdural haematoma that resolved with increasing valve pressure to 20cmH2O. There was no valve damage or low-pressure symptoms after adjustment. CONCLUSION: This study found that lowering the opening pressure of the proGAV shunt system to below 5cmH2O results in clinical improvement and does not significantly increase the complication rate in iNPH patients.

Cerebral venous system and anatomical predisposition to high-altitude headache.

OBJECTIVE: As inspired oxygen availability falls with ascent to altitude, some individuals develop high-altitude headache (HAH). We postulated that HAH results when hypoxia-associated increases in cerebral blood flow occur in the context of restricted venous drainage, and is worsened when cerebral compliance is reduced. We explored this hypothesis in 3 studies. METHODS: In high-altitude studies, retinal venous distension (RVD) was ophthalmoscopically assessed in 24 subjects (6 female) and sea-level cranial magnetic resonance imaging was performed in 12 subjects ascending to 5,300m. Correlation of headache burden (summed severity scores [0-4]≤24 hours from arrival at each altitude) with RVD, and with cerebral/cerebrospinal fluid (CSF)/venous compartment volumes, was sought. In a sea-level hypoxic study, 11 subjects underwent gadolinium-enhanced magnetic resonance venography before and during hypoxic challenge (fraction of inspired oxygen=0.11, 1 hour). RESULTS: In the high-altitude studies, headache burden correlated with both RVD (Spearman rho=0.55, p=0.005) and with the degree of narrowing of 1 or both transverse venous sinuses (r=-0.56, p=0.03). It also related inversely to both the lateral+third ventricle summed volumes (Spearman rho=-0.5, p=0.05) and pericerebellar CSF volume (r=-0.56, p=0.03). In the hypoxic study, cerebral and retinal vein engorgement were correlated, and rose as the combined conduit score fell (a measure of venous outflow restriction; r=-0.66, p<0.05 and r=-0.75, p<0.05, respectively). INTERPRETATION: Arterial hypoxemia is associated with cerebral and retinal venous distension, whose magnitude correlates with HAH burden. Restriction in cerebral venous outflow is associated with retinal distension and HAH. Limitations in cerebral venous efferent flow may predispose to headache when hypoxia-related increases in cerebral arterial flow occur.

Systematic review of the outcome of shunt surgery in idiopathic normal-pressure hydrocephalus.

INTRODUCTION: Early surgical series of shunt insertion for idiopathic normal-pressure hydrocephalus reported a low rate of short-term improvement with a relatively high rate of mortality and morbidity; subsequently shunt insertion was recommended for patients in whom there is favourable risk-to-benefit ratio. METHODS: Bibliographic search for studies that objectively assessed the outcome following shunt insertion in idiopathic normal-pressure hydrocephalus was done; the aim was to estimate the outcome of shunt insertion in terms of improvement rates and associated mortality and morbidity. RESULTS: A total of 64 studies of 3,063 patients were reviewed. Positive improvement following shunt insertion was reported in an average of 71 % of patients with an average 1 % mortality. Results from studies published in the last 5 years showed 82 % improvement following shunt insertion, mortality of 0.2 %, and combined common complications rate of 8.2 %. CONCLUSION: When patients are properly selected, shunt insertion is a safe and effective management of idiopathic normal-pressure hydrocephalus with a prolonged positive outcome.

The prognostic value of brain extracellular fluid nitric oxide metabolites after traumatic brain injury.

BACKGROUND: Nitric oxide (NO) is a compound with both protective and damaging effects on neurons. Quantification of NO metabolites in humans is limited by sample contamination with blood. In vivo cerebral microdialysis may offer an alternative approach as sampling of extracellular fluid (ECF) adjacent to neurons becomes possible. We investigate the prognostic value of brain ECF NO metabolites in patients with traumatic brain injury (TBI). METHODS: A prospective case cohort of 195 ECF samples collected from 11 cases over 4 days following TBI was collected. Nitrate and nitrite concentrations ([NO x ]) were quantified using a vanadium-based colorimetric assay. RESULTS: Early ECF [NO x ] (<48 h post TBI) were significantly higher in non-survivors (median 59.2 µmol/l, n = 7) compared to survivors (23.3 µmol/l, n = 4) (P = 0.04). Late (48-96 h) ECF [NO x ] remained higher in non-survivors (47.9 µmol/l) compared to survivors (23.0 µmol/l) but this was not significant (P = 0.29). Receiver operator characteristic analysis shows an optimized cutoff level for ECF [NO x ] of 26.5 µmol/l measured <48 h post TBI for predicting non-survival (sensitivity 100%, specificity 75%). CONCLUSION: Early ECF NO x concentrations are of prognostic value after TBI. ECF NO x may be a useful biomarker for treatment trials targeted at nitric oxide metabolism.

Early years neurosurgical training in the era of the European Working Time Directive.

The past decade has seen significant changes to the face of neurosurgical training in the United Kingdom, driven in part by an increasing focus on patient safety and the introduction of Modernising Medical Careers and the European Working Time Directive (EWTD). Recent reforms to neurosurgical training over the past few years have resulted in creation of an 8-year 'run-through' training programme. In this programme, early years (ST1 and ST2) trainees often lack dedicated time for elective theatre lists and outpatient clinics. Further, any time spent in theatre and clinics is often with different teams. Here we describe a training model for early years trainees at the National Hospital for Neurology and Neurosurgery, who are given the responsibilities traditionally associated with a more senior trainee including dedicated weekly theatre and clinic time under the supervision of a single consultant, in addition to out of hours experience. The advantages and considerations for implementing this model are discussed, including the benefit of guidance under a single consultant in the early stages of training, along with key educational concepts necessary for understanding its utility. We feel that this is an effective model for junior neurosurgical training in the EWTD era, expediting the trainee's development of key technical and non-technical skills, with potentially significant rewards for patient, trainee and trainer. National implementation of this model should be considered.

Early single centre experience of flow diverting stents for the treatment of cerebral aneurysms.

INTRODUCTION: The flow diverting stent (FDS) is a relatively new endovascular therapeutic tool specifically designed to reconstruct the parent artery and divert blood flow along the normal anatomical course and away from the aneurysm neck and dome. METHODS: Retrospective review of prospectively built clinical and imaging database of patients treated with FDS at the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK was done. RESULTS: Between 18/03/2008 and 10/11/2011, 80 patients underwent 84 FDS insertion procedures for various indications. Mean duration of clinical follow-up was 11.3 ± 9.3 months and of imaging follow-up was 10.6 ± 9.3 months. Sixty-seven had anterior circulation aneurysms while 17 had posterior circulation aneurysms. Seven (8.3%) patients died (two probably not related, giving a procedure-related mortality of 5.9%), eight had permanent new deficit (9.5%), 20 had transient deficit (23%) and 49 (58%) had no complications. There was a trend towards bad outcome with larger posterior circulation aneurysms. Angiographic follow-up showed 38% cure rate at 6 months and 61% at 12 months. CONCLUSION: FDS should only be used following multidisciplinary discussion in selected patients. Further data is required regarding long-term safety, efficacy and indications.

Conservative versus surgical management of idiopathic normal pressure hydrocephalus: a prospective double-blind randomized controlled trial: study protocol.

There is no level I evidence to indicate whether placement of a shunt is effective in the management of idiopathic normal pressure hydrocephalus (INPH), because no trial has as yet compared the placement of a shunt versus no shunt in a randomized controlled manner. We started recruiting patients into a prospective double-blind randomized controlled study aiming to provide class I evidence supporting or refuting the role of surgical management in INPH. Inclusion criterion was the diagnosis of probable INPH plus objective improvement of walking speed following 72 h of extended lumbar drainage. Patients with concomitant Alzheimer's disease or vascular dementia were excluded. All patients included in the trial were to have a shunt placed with proGAV(®) adjustable valve. Patients were randomly assigned into two groups: group A was to have the shunt immediately adjusted to function, and group B was to have the shunt valve adjusted to the highest setting for 3 months then adjusted to function. Assessment of gait, cognitive function, and urinary symptoms were done before shunt insertion and at 3 months. Primary end point was to be an improvement in gait. Secondary end points were improvement in mental function or urinary function and incidence of complications. Final results are expected mid 2011.

Secondary normal pressure hydrocephalus in a patient with isolated frontal dilatation--an insight into pathophysiology?

Current theories of the pathophysiology of normal pressure hydrocephalus suggest the classical symptoms are a consequence of disruption of normal frontal function. We present the case of a 70-year-old patient with an isolated, frontal dilatation of his lateral ventricles in the presence of a complete triad as supportive of these theories.

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.

Natural history of idiopathic normal-pressure hydrocephalus.

Natural history of idiopathic normal-pressure hydrocephalus (INPH) is not clear. We performed a literature search for studies that looked into the outcome of unshunted INPH patients trying to answer the following questions: Do all INPH patients deteriorate without shunt? If yes, at what rate? Do some NPH patients improve without shunt? If yes, to what extent? Six studies objectively described the outcome of 102 INPH patients. Result shows that without surgery, most INPH patients had measurable deterioration as early as 3 months following initial assessment. A small number of patients might improve without shunt, however the extent of improvement is not clear. The homogeneity of the findings of the cohort studies provided high evidence supporting the rule of shunt surgery in INPH patients.

Working towards patient oriented outcome assessment in normal pressure hydrocephalus, what is the most important?

OBJECTIVE: To date, there is no standard outcome assessment scale for shunt treatment in normal pressure hydrocephalus (NPH). In designing such scale, the relative weight of each of the common presentations of the condition from the patient's or his/her carer's point of view should be taken into consideration. METHODS: A questionnaire was sent to 24 patients treated for NPH and their family/carer, assessing the patient and carer categorization of the preoperative main complaint, the weight they give to each of the common presentations of NPH and their satisfaction with treatment. RESULTS: Twenty-two patients and 20 carers replied. Gait disturbance was the main complaint from both patient's (86%) and carer's (75%) point of view. Similarly, gait disturbance was considered as the most important problem that needs improvement by both patients (77%) and carers (65%). Incontinence was considered the second most important area by 11 (50%) patients and seven (35%) carers. When asked to quantify their satisfaction out of 10, patients had a mean of 7.2 while carers gave a mean of 7.5. Comparing subjective perspective of improvement with that of objective improvement on 10 m walking test and neuropsychological assessment, all patients who improved objectively were perceived as improved to a satisfactory degree by carers. CONCLUSION: Walking/balance should be given far greater weight than other components of the NPH triad in future outcome assessment scales in accordance with patient/family perception.

Cognitive, biochemical, and imaging profile of patients suffering from idiopathic normal pressure hydrocephalus.

INTRODUCTION: It has still not been clearly established whether the cognitive deficits of idiopathic normal pressure hydrocephalus (iNPH) are caused by a disturbance in cerebrospinal fluid (CSF) dynamics or an underlying metabolic disturbance. OBJECTIVE: To identify the possible associations between biochemical markers, the neuroimaging characteristics, and cognitive deficits of patients undergoing investigations for possible iNPH. METHODS: A CSF sample obtained during a lumbar puncture from 10 patients with iNPH was analyzed for several biochemical markers (lactate, 8-isoprostane, vascular endothelial growth factor [VEGF], neurofilament heavy protein, glial fibrillary acidic protein, amyloid beta 1-42, and total tau). All patients underwent a battery of neuropsychological testing and imaging as part of their selection process for their suitability for CSF diversion surgical procedure. Volumetric analysis of imaging was carried out measuring the ventricular volume (VV), intracranial volume (ICV), periventricular lucencies, deep white matter hyperintensities, and white matter (WM) volume, as well as their ratios. RESULTS: A significant negative correlation of preoperative symptom duration and total tau levels (R = -0.841, P = .002) was found. There was a significant positive correlation (R = 0.648, P = .043) between the levels of VEGF and the VV/ICV ratio. There was a significant positive correlation of the levels of glial fibrillary acidic protein and the VV/deep white matter hyperintensities ratio (R = 0.828, P = .006). A significant negative correlation was observed between the levels of neurofilament heavy protein and the VV/ICV ratio (R = -0.657, P = .039) and the WM volume (R = -0.778, P = .023). Lactate levels were lower for patients performing in the normal range on the Recognition Memory Test for faces. Patients who performed better in the Recognition Memory Test words test had higher ICV volumes. All the patients in this study showed below normal performance when the subcortical function was assessed. CONCLUSION: The positive correlation of VEGF with the severity of ventriculomegaly may indicate that this is because of the transmantle pressure gradient; this response may not be because of hypoxia but represents an attempt at neuroregeneration. The degree of reactive gliosis correlates inversely with the severity of WM lesions. Neuronal degeneration is negatively correlated with the volume of the WM in these patients. The small association of volumetry and the cognitive profile of these patients may be consistent with a direct biochemical disturbance being responsible for the cognitive deficit observed. Ongoing studies with set protocols for neuropsychological assessment and volumetric analysis are warranted to further elucidate on the preliminary results of the current study.

Ventriculosinus shunt.

Hydrocephalus can be managed successfully with cerebrospinal fluid shunting to extracranial compartments, most commonly the peritoneum. However, current shunt systems are not ideal with high revision rates on long-term follow-up. Draining the cerebrospinal fluid from the cerebral ventricles to the cerebral venous sinuses could mimic the physiological conditions with the added advantages of avoiding overdrainage and extracranial recipient site complications. A literature search was carried out using the keywords hydrocephalus, shunt, venous sinus and sagittal sinus. Seven clinical series of ventriculosinus shunts with a total of 265 patients were found. None of the patients developed venous sinus thrombosis, air embolism or intra-operative sinus bleeding. Ventriculosinus shunt is a potential alternative that can be done under local anaesthetic in ill patients where traditional shunts recipient sites are not feasible. However, further studies with extended follow-up period would provide better understanding of the suitability and indications of this technique.

Standard intracranial in vivo animal models of delayed cerebral vasospasm.

OBJECT: Animal models provide a basis for clarifying the complex pathogenesis of delayed cerebral vasospasm (DCVS) and for screening of potential therapeutic approaches. Arbitrary use of experimental parameters in current models can lead to results of uncertain relevance. The aim of this work was to identify and analyze the most consistent and feasible models and their parameters for each animal. METHODS: An online search of the MEDLINE PubMed and EMBASE medical databases (1969 to week 21 of 2007) was performed using the key words "canine", "mice", "rabbit", "pig", "rat", "cat", and "primate" in combination with "subarachnoid hemorrhage", "model", and "vasospasm". Cross references of each model were checked. Analysis of identified publications was considered in accordance with predetermined eligibility criteria. RESULTS: 1254 abstracts were reviewed and 516 studies were included in the analysis. Then, 66 models in 7 animals were identified. Most often used blood amounts (ml) lead to degree (% vessel narrowing) and peak onset (day) of DCVS within animal models as follows: mice endovascular puncture (various, day 3, 20-62%); rat single injection (0.3 ml, day 2, 19-29%); rat double injection (2 x 0.3 ml, day 7, 28-47%); rabbit single injection (3 ml, day 3, 19-55%); rabbit double injection (not established, day 5, not established); dog double injection (2 x 4-5 ml, day 7, 45-66%); primate clot placement (5 ml, day 7, 32-52%). CONCLUSIONS: Among the great number of experimental SAH methods and associated parameters only a fistful reliable and consistent models can be identified and recommended. Implementation of more standardized experimental techniques could increase the relevance of future experimental studies.

The operative findings in re-do microvascular decompression for recurrent trigeminal neuralgia.

BACKGROUND: Re-do microvascular decompression (MVD) of the trigeminal nerve occasionally becomes necessary following recurrence of symptoms after a previous MVD. The indications include failure or contraindication of less invasive treatment options such as medication or trigeminal nerve lesioning and when supported by vascular compression on brain MRI scans. PURPOSE: To report on our findings following re-do MVD in the National Hospital for Neurology and Neurosurgery, Queen Square London from July 1995 to July 2008. METHODS: Case note review of all patients who underwent re-do MVD for the above reasons in the senior author's series in the above institution and stated period. The parameters of study interest were pre-operative MRI features, operative findings, and complete pain-free period with regards to the first and re-do MVD. RESULTS: Data analysis showed that 6 underwent a re-do MVD. Neurovascular conflict was confirmed in 5 cases (83.3%) involving the superior cerebellar artery and anterior inferior cerebellar artery in 2 cases each (33.3%) and ectatic basilar artery in 1 case (16.6%). Arachnoid adhesions around the previous teflon felt were also found in 5 cases (83.3%) mostly in association with other findings. Neo-arachnoid cyst formation in the corresponding cerebello-pontine angle, was an unexpected finding in 2 cases (33.3%), though of uncertain significance. CONCLUSION: Redo MVD should be considered as a safe and effective treatment option in recurrent trigeminal neuralgia, which fails to respond to non-surgical means.

Continuous intracranial pressure monitoring in pseudotumour cerebri: Single centre experience.

OBJECTIVE: Investigating pseudotumour cerebri (PTC) patients who do not fulfil the diagnostic criteria, or those presenting post-shunt insertion with recurrent symptoms and signs, with no clear evidence of shunt malfunction, present a diagnostic challenge. PTC patients who underwent continuous intracranial pressure (ICP) monitoring in our unit were reviewed retrospectively. RESULTS: Twenty-six ICP monitoring procedures were done on 20 patients. Eleven patients had normal pressure, 2 overdrainage/low pressure, 11 underdrainage/high pressure and 2 variable pressures. On the basis of these results 12 patients were managed conservatively: 11 patients were referred to headache team and 1 patient had readjustment of an adjustable valve shunt setting; of those 3 patients had improved symptoms on their first post-operative clinic review. On the other hand, 14 patients had surgery: 5 had shunt revision and 9 had shunt insertion; of those 5 patients improved. CONCLUSION: ICP monitoring using an intraparenchymal probe is a safe and effective diagnostic technique in investigating PTC when indicated. A multidisciplinary approach achieves best results in terms of successful management and follow-up.

Noninvasive biomarkers in normal pressure hydrocephalus: evidence for the role of neuroimaging.

OBJECT: Normal pressure hydrocephalus (NPH) represents a treatable form of dementia. Recent estimates of the incidence of this condition are in the region of 5% of patients with dementia. The symptoms of NPH can vary among individuals and may be confused with those of patients with multi-infarct dementia, dementia of the Alzheimer type, or even Parkinson disease. Traditionally the diagnosis of NPH could only be confirmed postoperatively by a favorable outcome to surgical diversion of CSF. The object of this literature review was to examine the role of structural and functional imaging in providing biomarkers of favorable surgical outcome. METHODS: A Medline search was undertaken for the years 1980-2006, using the following terms: normal pressure hydrocephalus, adult hydrocephalus, chronic hydrocephalus, imaging, neuroimaging, imaging studies, outcomes, surgical outcomes, prognosis, prognostic value, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. RESULTS: The query revealed 16 studies that correlated imaging with surgical outcomes offering accuracy results. Three studies fulfilled the statistical criteria of a biomarker. A dementia Alzheimer-type pattern on SPECT in patients with idiopathic NPH, the presence of CSF flow void on MR imaging, and the N-acetylaspartate/choline ratio in patients with the secondary form are able to predict surgical outcomes with high accuracy. CONCLUSIONS: There is at present Level A evidence for using MR spectroscopy in patients with secondary NPH, and Level B evidence for using SPECT and phase-contrast MR imaging to select patients with idiopathic NPH for shunt placement. The studies, however, need to be repeated by other groups. The current work should act as a platform to design further studies with larger sample sizes.

Incidence of hemorrhagic stroke in black Caribbean, black African, and white populations: the South London stroke register, 1995-2004.

BACKGROUND AND PURPOSE: Data are lacking on the differences in hemorrhagic stroke incidence between black Caribbean (BC), black African (BA), and white ethnic groups. We estimated the incidence for primary intracerebral hemorrhage (PICH) and subarachnoid hemorrhage (SAH) and the associated risk factors for BCs, BAs, and whites. METHODS: First-ever stroke patients were drawn from a prospective community stroke register based in a multiethnic population in South London with 9% BCs, 15% BAs, and 63% whites. Incidence rates were standardized to European and world populations and adjusted for age and sex. Incidence rate ratios (IRRs) relative to whites were calculated by Poisson regression. RESULTS: Between 1995 and 2004, 566 incident stroke patients were registered: 395 PICHs and 171 SAHs. For PICH, age- and sex-adjusted IRRs were higher in BAs (IRR, 2.80; 95% CI, 2.00 to 3.91) than in BCs (IRR, 1.46; 95% CI, 1.07 to 1.99) and were particularly pronounced for patients age 0 to 64 years: IRR=3.95 (95% CI, 2.65 to 5.87) in BAs and 2.38 (95% CI, 1.50 to 3.80) in BCs. For those <65 years, prestroke hypertension was more prevalent in BAs and BCs (P=0.049). For SAH, the IRR was higher in BCs (IRR; 1.62; 95% CI, 1.05 to 2.48) than in BAs (IRR, 0.80; 95% CI, 0.43 to 1.46). CONCLUSIONS: The higher incidence of PICH observed in BCs and BAs could be explained by prestroke hypertension being more common among young blacks. The different incidences of SAH in BCs and BAs suggest that the baseline risk of stroke for distinct black ethnic groups is not homogeneous.