Pulsatile versus non-pulsatile tinnitus in idiopathic intracranial hypertension

Acta Neurochirurgica (2018) 160:2025–2029

Tinnitus is a symptom commonly associated with idiopathic intracranial hypertension (IIH) that can have a profound effect on quality of life. We aim to determine tinnitus symptom response after dural venous sinus stenting (DVSS) or CSF diversion with a shunt, in patients with both pulsatile (PT) and non-pulsatile tinnitus (NPT).

Methods: Single-centre cohort of IIH patients (2006–2016) who underwent 24-h ICP monitoring (ICPM). An un-paired t test compared ICP and pulse amplitude (PA) values in IIH patients with PT vs. NPT.

Results: We identified 59 patients with IIH (56 F:3 M), mean age 32.5 ± 9.49 years, 14 of whom suffered from tinnitus. Of these 14, seven reported PT and seven reported NPT. Patients with tinnitus had a mean 24-h ICP and PA of 9.09 ± 5.25 mmHg and 6.05 ± 1.07 mmHg respectively. All 7 patients with PT showed symptom improvement or resolution after DVSS (n = 4), secondary DVSS (n=2) or shunting (n = 1). In contrast, of the 7 with NPT, only 1 improved post intervention (DVSS), despite 2 patients having shunts and 5 having DVSS.

Conclusions: NPT and PT were equally as common in our group of IIH patients. DVSS appears to be an effective management option for IIH patients with a clear history of pulsatile tinnitus. However, non-pulsatile tinnitus was more persistent and did not respond well to either DVSS or CSF diversion.

The predictive value of T-tau and AB1-42 levels in idiopathic normal pressure hydrocephalus

Acta Neurochir (2017) 159:2293–2300

Idiopathic normal pressure hydrocephalus (INPH) has no reliable biomarker to assist in the selection of patients who could benefit from ventriculo-peritoneal (VP) shunt insertion. The neurodegenerative markers Ttau and Aβ1-42 have been found to successfully differentiate between Alzheimer’s disease (AD) and INPH and therefore are candidate biomarkers for prognosis and shunt response in INPH. The aim of this study was to test the predictive value of cerebrospinal fluid (CSF) T-tau and Aβ1-42 for shunt responsiveness. In particular, we pay attention to the subset of INPH patients with raised T-tau, who are often expected to be poor surgical candidates.

Methods: Single-centre retrospective analysis of probable INPH patients with CSF samples collected from 2006 to 2016. Index test: CSF levels of T-tau and Aβ1-42. Reference standard: postoperative outcome. ROC analysis assessed the predictive value.

Results: A total of 144 CSF samples from INPH patients were analysed. Lumbar T-tau was a good predictor of postoperative mobility (AUROC 0.80). The majority of patients with a co-existing neurodegenerative disease responded well, including those with high T-tau levels.

Conclusion: INPH patients tended to exhibit low levels of CSF T-tau, and this can be a good predictor outcome. However levels are highly variable between individuals. Raised T-tau and being shunt-responsive are not mutually exclusive, and such patients ought not necessarily be excluded from having a VP shunt.A combined panel of markers may be a more specific method for aiding selection of patients for VP shunt insertion. This is the most comprehensive presentation of CSF samples from INPH patients to date, thus providing further reference values to the current literature.

Parametric study of ventricular catheters for hydrocephalus

Parametric study of ventricular catheters for hydrocephalus

Acta Neurochir (2016) 158:109–116

To drain the excess of cerebrospinal fluid in a hydrocephalus patient, a catheter is inserted into one of the brain ventricles and then connected to a valve. This so-called ventricular catheter is a standard-size, flexible tubing with a number of holes placed symmetrically around several transversal sections or “drainage segments”. Three-dimensional computational dynamics shows that most of the fluid volume flows through the drainage segment closest to the valve. This fact raises the likelihood that those holes and then the lumen get clogged by the cells and macromolecules present in the cerebrospinal fluid, provoking malfunction of the whole system. In order to better understand the flow pattern, we have carried out a parametric study via numerical models of ventricular catheters.

Methods The parameters chosen are the number of drainage segments, the distances between them, the number and diameter of the holes on each segment, as well as their relative angular position.

Results These parameters were found to have a direct consequence on the flow distribution and shear stress of the catheter. As a consequence, we formulate general principles for ventricular catheter design.

Conclusions These principles can help develop new catheters with homogeneous flow patterns, thus possibly extending their lifetime.

Identification of microRNAs in the cerebrospinal fluid as biomarker for the diagnosis of glioma

Neuro-Oncology DOI:10.1093/neuonc/nor169

Malignant gliomas are the most common and lethal primary intracranial tumors. To date, no reliable biomarkers for the detection and risk stratification of gliomas have been identified. Recently, we demonstrated significant levels of microRNAs (miRNAs) to be present in cerebrospinal fluid (CSF) samples from patients with primary CNS lymphoma. Because of the involvement of miRNA in carcinogenesis, miRNAs in CSF may serve as unique biomarkers for minimally invasive diagnosis of glioma.

The objective of this pilot study was to identify differentially expressed microRNAs in CSF samples from patients with glioma as potential novel glioma biomarkers.

With use of a candidate approach of miRNA quantification by reverse-transcriptase polymerase chain reaction (qRT-PCR), miRNAs with significant levels in CSF samples from patients with gliomas were identified. MiR-15b and miR-21 were differentially expressed in CSF samples from patients with gliomas, compared to control subjects with various neurologic disorders, including patients with primary CNS lymphoma and carcinomatous brain metastases. Receiver- operating characteristic analysis of miR-15b level revealed an area under the curve of 0.96 in discriminating patients with glioma from patients without glioma. Moreover, inclusion of miR-15b and miR-21 in combined expression analyses resulted in an increased diagnostic accuracy with 90% sensitivity and 100% specificity to distinguish patients with glioma from control subjects and patients with primary CNS lymphoma.

In conclusion, the results of this pilot study demonstrate that miR-15b and miR-21 are markers for gliomas, which can be assessed in the CSF by means of qRT-PCR. Accordingly, miRNAs in the CSF have the potential to serve as novel biomarkers for the detection of gliomas.