Andrew Tarnaris

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.

Is there a difference in outcomes of patients with idiopathic intracranial hypertension with the choice of cerebrospinal fluid diversion site: A single centre experience

UNLABELLED The visual and headache outcomes in patients with idiopathic intracranial hypertension (IIH) undergoing cerebrospinal fluid diversion with a lumboperitoneal (LPS) or ventriculoperitoneal shunting (VPS) have not been well reported. The aims of this study were to: (a) to assess outcomes of CSF diversion in IIH, (b) to understand influence of the type of shunt in outcomes, and (c) to understand factors predisposing in shunt failure. METHODS The medical records of 34 patients who underwent cerebrospinal fluid diversion (CSFD) between 1996 and 2007 were retrieved and epidemiological and clinical data was collected. RESULTS The mean age was 35 (±7.9) years. Thirty-four patients underwent 63 shunt placements in total. 85% follow-up was achieved. The mean follow-up for the entire group was 28.9 (±31.8) months. Headaches improved more than visual disturbances. There was no significant difference between the groups that received a VPS and those receiving an LPS in both headache and visual outcomes. The rate of complications was 20.5% and the need for revision was 35% for the whole group. Patients with LPS suffered more complications and first time revisions than patients with VPS. No factor recorded could predict the need for revision or final outcomes. The shunts of patients receiving a VPS tend to survive longer than those receiving primarily an LPS, however the difference is not statistically significant. CONCLUSIONS Predicting which patients will improve is not possible at present. The influence of site diversion is not critical but patients with VPS have less complications and revisions than those receiving a LPS.

Biomarkers in chronic adult hydrocephalus

Awareness of the importance of chronic adult hydrocephalus has been raised again with the recent emergence of epidemiological studies. It is estimated that between 5 and 10% of patients suffering from dementia might, in fact, have chronic hydrocephalus. Although, surgical diversion of the cerebrospinal fluid (CSF) represents the only known procedure able to treat the symptoms of this condition, the selection of surgical patients has always been problematic. In the last 40 years, we have become wiser in using appropriate diagnostic tests for the selection of these patients; however, the area of biological markers has so far been overlooked in this condition, in contrast to that for other neurodegenerative disorders and dementias. Biomarkers are biological substances that may be used to indicate either the onset or the presence, and the progression of a clinical condition, being closely linked to its pathophysiology. In such a setting they might assist in the more appropriate selection of patients for shunt surgery. In this article, we have reviewed research carried out in the last 25 years regarding the identification of serum and CSF biomarkers for chronic hydrocephalus, discussed the potential for each one, and finally discussed the limitations for use, as well as future directions and possibilities in this field. It is concluded that tumour-necrosis factor, tau protein, lactate, sulfatide and neurofilament triple protein are the most promising CSF markers for chronic hydrocephalus. At present however, none of these meet the criteria required to justify a change clinical practice. In the future, collaborative multi-centre projects will be needed to obtain more substantial data that overcome the problems that arise from small individual and uncoordinated studies.

Ongoing search for diagnostic biomarkers in idiopathic normal pressure hydrocephalus

Idiopathic normal pressure hydrocephalus is a syndrome, which typically has a clinical presentation of gait/balance disturbance, often accompanied by cognitive decline and/or urinary incontinence. Its diagnosis is based on relevant history and clinical examination, appropriate imaging findings and physiological testing. The clinical picture of idiopathic normal pressure hydrocephalus may occasionally be difficult to distinguish from that of Alzheimers dementia, subcortical ischemic vascular dementia and Parkinsons disease. The aim of this article is to systematically review the literature from the last 29 years in order to identify cerebrospinal fluid (CSF) or imaging biomarkers that may aid in the diagnosis of the syndrome. The authors concluded that no CSF or imaging biomarker is currently fulfilling the criteria required to aid in the diagnosis of the condition. However, a few studies have revealed promising CSF and imaging markers that need to be verified by independent groups. The reasons that the progress in this field has been slow so far is also commented on, as well as steps required to apply the current evidence in the design of future studies within the field.

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.

Use of cerebrospinal fluid amyloid-β and total tau protein to predict favorable surgical outcomes in patients with idiopathic normal pressure hydrocephalus

OBJECT The prognostic value of CSF biomarkers in patients with idiopathic normal pressure hydrocephalus (iNPH) has not been adequately studied to date. The aim of this study was to identify CSF markers of favorable surgical outcome in patients with iNPH undergoing the insertion of a ventriculoperitoneal shunt. METHODS Ventricular CSF was collected intraoperatively from 22 patients with iNPH and enzyme-linked immunosorbent assay was used to analyze the levels of amyloid-β 1-42 (Aβ(1-42)) and total tau protein. The Black grading scale was used to assess outcomes at 6 months. Receiver operating characteristic (ROC) curves were obtained and discriminant function analysis was undertaken to provide sensitivity and specificity figures for each marker as well as their combination. RESULTS The mean age of the patients was 71.45 years (± 9.5 years [SD]). Follow-up was achieved in 21 patients. Seventeen patients had a favorable outcome and 4 patients had unfavorable outcome at 6 months. An Aβ(1-42) level of 180 pg/ml had a sensitivity of 35% and a specificity of 20% for predicting a favorable outcome at 6 months. A total tau level of 767 pg/ml will have a sensitivity of 17% and a specificity of 20% for predicting a favorable outcome at 6 months. A combination of Aβ(1-42) and total tau levels predicted favorable outcomes with a sensitivity of 80% and specificity of 82.4%. CONCLUSIONS In this pilot study a combination of Aβ(1-42) levels and total tau protein levels predicted favorable surgical outcomes at 6 months with adequate accuracy to be of clinical use. Further study in a larger group with longer follow-up is warranted.

Does conservative management for brain stem cavernomas have better long-term outcome?

There has been a controversy in the last 15 years on the correct management of brain stem cavernomas. We have reviewed our experience of the last 10 years in a single Institution and reviewed related literature published in the last 15 years. We recorded the demographics, clinical presentation, rebleeding episodes, incidence of neurological events and outcome assessed by recording the change of the modified Rankin scale in 21 cases. Univariate analysis was applied to test the effect of demographics, and presentation on the incidence and timing of rebleeding, chance of having a new neurological event, the number of subsequent neurological events and outcomes. Six cases were treated with surgery and 15 cases were managed conservatively. We obtained follow-up data in 20 patients (95%). Mean follow-up period was 79.7 months (range: 6–244, median 70 months). There were 0.05 rebleeding events per patient-year and 0.1 episodes of neurological deterioration per patient-year. No mortality was noted in either the surgical or the non-surgical group. Three of the six surgical cases had a reoperation. The outcome was improved in one patient, unchanged in 1, and worse in 3 surgical patients. In the case of conservative management the outcome was improved in two patients, unchanged in five patients, and worse in eight patients. Outcome was worse in the case of multiple cavernomas (p = 0.012). Our findings suggest that conservative management may be appropriate in individual cases when compared with surgery, but this difference was not statistically significant enough in order to support a change in practice. The natural history of brain stem cavernomas appears more benign than previously thought.

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

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.

Endovascular treatment of ruptured intracranial aneurysms during pregnancy: Is this the best way forward? Case report and review of the literature

OBJECTIVE AND IMPORTANCE Subarachnoid haemorrhage in pregnancy has traditionally been treated by surgical clipping however lately cases of successful coiling have been reported. Nevertheless, the long-term outcome of coiling is not well known in pregnant women. Mortality due to rebleeding of an incompletely treated aneurysm remains high. Only 15 cases of successful endovascular coiling during pregnancy have been reported so far. CLINICAL PRESENTATION We report the case of a pregnant woman who presented with aneurysmal subarachnoid hemorrhage (WFNS Grade III) due to rupture of a right posterior communicating artery aneurysm. INTERVENTION The patient underwent endovascular coiling successfully followed by an elective caesarian section and delivery of a healthy baby. However, during the course of a 2-year follow up the patient had suffered two relapses of the coiled aneurysm which required additional treatment. These events have affected her choice of extending her family. CONCLUSION The small risk of recurrence and the potential impact on future pregnancies should be explicitly communicated to patients in cases of endovascular coiling.

Use of the proGAV shunt valve in normal-pressure hydrocephalus.

BACKGROUND: Overdrainage is a common complication associated with shunt insertion in normal-pressure hydrocephalus (NPH) patients. Using adjustable valves with antigravity devices has been shown to reduce its incidence. The optimal starting setting of an adjustable shunt valve in NPH is debatable. OBJECTIVE: To audit our single-center practice of setting adjustable valves. METHODS: We performed a retrospective review of clinical records of all NPH patients treated in our unit between 2006 and 2009 by the insertion of shunts with a proGAV valve, recording demographic and clinical data, shunt complications, and revision rates. Radiological reports of postoperative follow-up computed tomography scans of the brain were reviewed for detected subdural hematomas. RESULTS: A proGAV adjustable valve was inserted in 50 probable NPH patients between July 2006 and November 2009. Mean ± SD age was 76 ± 7 years. Mean follow-up was 15 months. The initial shunt setting was 6 ± 3 cm H2O, and the final setting was 4.9 ± 1.9 cm H2O. Nineteen patients required 24 readjustment procedures (readjustment rate, 38%; readjustment number, 0.48 times per patient). One patient (2%) developed delayed bilateral subdural hematoma after readjustment of his shunt valve setting as an outpatient. CONCLUSION: Starting with a low opening pressure setting on a proGAV adjustable shunt valve does not increase the chances of overdrainage complications and reduces the need for repeated readjustments.