Presentations selected from submitted abstracts
Altered cerebral blood flow before and after 4-weeks of neurostimulation in patients with episodic migraine
Altered cerebral blood flow (CBF) has been observed during migraine attacks. Transcranial direct current stimulation (tDCS) has been used in patients with episodic migraine (EM) and resulted in a reduction of migraine days compared to baseline. Yet, it is unknown abnormal CBF can be modulated by non-invasive brain stimulation. We hypothesized that CBF will be different between sham and repetitive (4 weeks) real tDCS and that neuronal reorganization should be paralleled by a reduction in migraine days. On a 3 Tesla scanner, we examined 17 adult patients with EM by arterial spin labeling MRI using a 2D pseudo-continuous ASL sequence at three time points (baseline, FUP1 (maximally 4 weeks after tDCS), and FUP2 (6 months after baseline)). CBF difference images were achieved by simple subtraction to minimize spurious BOLD contaminations within the CBF signal. We calculated planned contrasts (t-tests, p < .01, corrected) for within-group differences (baseline vs. follow-up) and between-group differences (sham vs. real tDCS). For real tDCS, anodal tDCS was applied over the occipital cortex for 4 weeks (1200 seconds/day). Sham tDCS contained only a low (< 0.1 mA) current. Eight EM received real tDCS and nine EM received sham stimulation and ASL-MRI. Patients did not differ with respect to sex, age, handedness, and migraine attacks at baseline (all p > .05). None of the patients stopped the stimulation or had a migraine attack during stimulation. Only real tDCS lead to a significant (p < 0.05) reduction in migraine days (from 9 to 6.2). Two of the EM were migraine-free at FUP2. For real tDCS, CBF was higher at baseline compared to the FUP1 in pain processing brain regions (e.g. insula, medial prefrontal cortex, and thalamus). Comparing sham to real tDCS (at FUP1), higher CBF was seen for sham tDCS in the medial prefrontal cortex, subgenual anterior cingulate cortex, somatosensory cortex, insula, superior parietal lobe, and cuneus. Our results indicate altered CBF in the untreated group of patients. This was paralleled by the absence of any longitudinal reduction in migraine days. In contrast, real tDCS significantly reduces migraine days in EM and lowers CBF (compared to baseline and sham, respectively) in brain regions associated with pain processing, such as the insula and prefrontal cortex. In addition, brain regions linked to cognitive control showed lower CBF during real tDCS versus sham tDCS.
Pharmacological modulation of 5-ALA-induced PpIX in GBM cells.
Glioblastoma (GBM) is one of the most frequent and most devastating brain tumor. We have previously shown that expression of different status of EGFR in GBM cell lines reduces 5-ALA-induced PpIX fluorescence by influencing the rate limiting enzyme Heme Oxygenase-1 (HO-1). We hypothesized that 5-ALA-induced Protoporphyrin IX (PpIX) fluorescence can be pharmacologically influenced by adding different drugs.
U87MG, U87wtEGFR, U87vIII (GBM cell lines) having different EGFR expression status, were exposed to exogenous 5-ALA (1mM) and different pharmacological conditions such as: exposition to DFO (iron chelator of Fe2+), SnPP (HO-1 inhibitor), Genistein (ABC transporter G2 inhibitor) and stimulation with EGF (epidermal growth factor). Cell lines were exposed to 5-ALA and PpIX fluorescence was monitored over time in the cells and in the cell culture medium (CM). After 24h, the medium was removed and PpIX washout was measured. As regards the treatments, cells were incubated with EGF (10ng/ml) for 18h and in the last 4h cells are co-treated with 5-ALA. Whereas the treatments with 5-ALA plus DFO and/or SnPP and Genistein were performed incubating cells for 8h. All samples were analyzed with the microplate reader.
5-ALA-induced fluorescence was observed in U87MG (low EGFR expression), U87wtEGFR cells (EGFR overexpression) and in U87vIII (EGFR overexpression/EGFRvIII+). We observed a significant increase of PpIX in all the cell lines between 8 and 24 hours of 5-ALA treatment. At the same time, we noticed that GBM cells start to release PpIX in the CM. After removal of the 5-ALA stimulation, there was a significant reduction of PpIX level, in particular in the first hour. Whereas we saw an increased amount of PpIX in the CM at the same time. After 24h the whole amount of PpIX was secreted by all the cell lines. On the contrary, treatment of U87MG cells with EGF lead to reduced cellular fluorescence, by promoting HO-1 transcription and expression. Remarkably, inhibition of HO-1 activity by SnPP treatment was able to restore the fluorescence in all cell lines. We observed a major increase of PpIX fluorescence in U87vIII respect to the other cells when we treat with drugs.
This approach could be used to determine the optimal time point for the PpIX visualization after 5-ALA induction. Moreover, it could be very interesting to test different combination of these drugs to better improve the accumulation of PpIX in GBM tumor cells and their visualization during the surgery.
IS AWAKE DEEP BRAIN STIMULATION SURGERY OUTDATED? ON THE IMPORTANCE OF INTRAOPERATIVE MICROELECTRODE RECORDING AND MACROSTIMULATION.
Aim: Deep brain stimulation (DBS) has become an established treatment for diverse neurological diseases. Nevertheless, the technique of lead implantation differs widely among functional neurosurgeons. During recent years classical aids such as intraoperative microelectrode recording (MER) and macrostimulation (MS) in the awake patient were challenged. Our aim was to investigate the relevance of these techniques according to lead trajectory adjustment rates and comparing intraoperative response to stimulation between anatomically planned (PSP) and definite stimulation points (DSP), along with follow-up outcome.
Methods: We conducted a retrospective analysis of prospectively collected datasets of Parkinson’s disease (PD) patients that had bilateral lead placement in the subthalamic nucleus for DBS. The implantation was performed awake with MER and MS in all patients. Intraoperative motor outcomes between the stimulation sites were compared along with the lead trajectory adjustment rate. The outcome at six months according to the Unified PD Rating Scale-III (UPDRS-III), levodopa equivalent daily dose (LEDD) and DBS related adverse events (AE) was analyzed.
Results: In 47 of 101 patients and 59 of 202 leads intraoperative lead adjustment was performed respectively. 29% of the leads were adjusted due to MS but only 3% solely due to MER results. The mean response to MS improved significantly between PSP and DSP (37.07 ± 2.18% vs. 41.38 ± 2.15%; p < 0.001) with a more pronounced effect in initially poor responding electrodes (18.08 ± 3.78 % vs. 31.47 ± 2.78 %; p < 0.001), leading to a number needed to treat of 9.6 per electrode. After 6 months, follow-up UPDRS-III (23.3 ± 1.1 vs. 15.6 ± 0.8; p < 0.001) and LEDD (1262.3 ± 60.9 mg/d vs. 487.7 ± 39.2 mg/d; p < 0.001) showed significant improvement. The optimal intraoperative stimulation site covered the active electrode contact in 87% of leads. 15 stimulation or surgery related adverse events occurred.
Conclusion: The use of MER and MS have an important influence on the intraoperative lead placement. The intraoperatively identified stimulation site corresponds to the chronically active contact. Poor DBS outcome is prevented in a subgroup of leads. Follow-up UPDRS-III results, LEDD reductions and DBS related AE correspond to previously published data.
To Scan or Not to Scan: The Role of Follow-up CT Scanning for Management of Chronic Subdural Hematoma After Neurosurgical Evacuation (TOSCAN) – a randomised, controlled trial
Chronic subdural hematoma has a high recurrence rate after surgery and postoperative scans often show substantial residuals, eventually leading to a higher rate of reoperation. However, the benefit of post-surgical imaging for patient outcome remains unknown. The aim of this study was to investigate the value of post-operative CT scans for outcome after surgical evacuation of chronic subdural hematoma.
We randomly assigned 368 patients with newly diagnosed chronic subdural hematoma within 48 hours after surgery to either a combined radiological and clinical follow up (CT arm) or a clinical follow up with scans only in case of neurological deterioration (No-CT arm). The primary outcome was the modified Rankin scale (mRS) score at 90 days; this categorical scale measures functional outcome, with scores ranging from 0 (no symptoms) to 6 (death).
A follow-up protocol with CT imaging did not improve the primary outcome; there was no significant between-arm difference for mRS as a categorical variable (p=0.79) or as numerical variable (p=0.37). The proportion of patients who survived without severe disability (mRS 0-3) was 89% in the CT arm and 93% in the No-CT arm (odds ratio 1.4, 95% confidence interval 3.72-0.82, p=0.15). Death occurred in 12 patients in the CT arm and in 8 patients in the No-CT arm (p=0.5). Re-operation for recurrent hematomas was performed in 59 patients in the CT arm and in 39 patients in the No-CT arm ( p=0.055). Complications were seen in 26 patients in the CT-Arm and in 19 patients in the No-CT arm (p=0.34).
Routinely scheduled CT scans after neurosurgical evacuation of chronic subdural haematoma have no benefit on outcome.
A classification and microsurgical strategy to seal CSF-leaks at the 360° dural circumference via a posterior approach and spinal cord release in spontaneous intracranial hypotension.
BACKGROUND: Spinal cerebrospinal fluid (CSF) leaks are the cause of spontaneous intracranial hypotension (SIH).
OBJECTIVE: To report the results of a large surgical series and to propose a surgical strategy, stratified on anatomical location of the leak, for sealing all CSF leaks around the 360° circumference of the dura through a single tailored posterior approach.
METHODS: All consecutive patients undergoing spinal surgery between February 2013 and October 2017 were included. All patients were refractory to conservative treatment and to epidural blood patching and workup had exactly localized the anatomical site of the leak. We used a posterior approach via a tailored hemilaminectomy or interlaminar fenestration and intra-operative electrophysiological monitoring in all cases. To seal the CSF leak either a mere extradural, foraminal, or transdural microsurgical trajectory was chosen. Neurological status was assessed before, at day 1, 30 and 90 after surgery, as well as mRS and working status at 3 months.
RESULTS: Forty-seven SIH patients had a neuroradiologically identified spinal CSF leak between the levels C6 and L1. Micorsurgically, we could localize (anterior n=35, lateral n=9, foraminal n=2) and seal all dural tears via a transdural (n=28), a direct extradural (n=16), or a foraminal (n=2) trajectory. The transdural trajectory necessitated cutting the dentate ligament accompanied by elevation and rotation of the spinal cord under continuous neuromonitoring (spinal cord release maneuver, SCRM). No patient experienced a permanent neurological deficit; 4 patients had transient deficits. We propose an anatomical stratification of CSF leaks into I ventro-medial, i.e. anterior to the spinal cord, II ventro-lateral, lateral and dorsal, and III foraminal. All CSF-leaks can be sealed via a single tailored fenestration and a respective transdural (I), direct extradural (II) and foraminal (III) microsurgical approach.
CONCLUSION: With the posterior microsurgical (tailored fenestration) strategy, it is possible to seal all defects around the 360° surface of the dura via 3 surgical trajectories, that are selected according to the exact anatomical location of the leak. Intraoperative neuromonitoring is mandatory for the SCRM.
The Swiss Pituitary Registry - SwissPit
BACKGROUND: The treatment of sellar lesions demands an interdisciplinary network consisting of endocrinologists, neurosurgeons, radiooncologists, radiosurgeons, ophthalmologists, otorhinolarngylogists, neuropathologists and neuroradiologists. Each of these specialists contributes valuable information to optimize treatment of these patients; however, a multicentre registry to collect the resulting biomedical data was lacking in Switzerland. While in other European Countries established centers provided the base for nationwide databases, this was not the case in our country. While due to the low incidence representative numbers of patients are hard to find for retrospective data analysis, this is automatically provided by a structured database, resulting in resourceful scientific contributions. Furthermore, it may be used as a base for prospective multicentric trials.
METHODS: Founded at the Kantonsspital Aarau in cooperation with the Clinical Trial Unit of the University Hospital of Basel with approval of the ethics comitee of the northwestern part of Switzerland, the Swiss Pituitary Registry (SwissPit) has been designed as an online electronic data capture system. All patients with lesions in the sellar region are eligible for inclusion in the database. Data generated by routine clinical follow-up and standard therapies, as well as details about adverse events and outcomes is entered by medical staff. In each participating center, a designated neurosurgeon and/or endocrinologist acts as a local investigator and helds responsibility for the quality of the entered data. Each centre is free to conduct single centre trials, while multicentric studies with exchange of data are coordinated by the project leaders after appropriate approval. After a thourough test of the database by the founders, a step-wise growth by inviting other centres is planed.
RESULTS: The SwissPit is online since January 2016. After the Kantonsspital Aarau, the University Hospital of Basel, the Kantonsspital Lucerne, the Kantonsspital St. Gallen and lately the University Hospital of Zurich have joined. Detailed data of more than 700 patients have since then been entered.
CONCLUSION: The SwissPit is the first multicentric Swiss database on sellar lesions working by the standards of Good Clinical Practice and in concordance with the revised Swiss laws. The members of SwissPit look forward to invite further investigators in other centres to join in 2018!