Computational fluid dynamics model to predict the dynamical behavior of the cerebrospinal fluid through implementation of physiological boundary conditions.

Cerebrospinal fluid (CSF) dynamics play an important role in maintaining a stable central nervous system environment and are influenced by different physiological processes. Multiple studies have investigated these processes but the impact of each of them on CSF flow is not well understood. A deeper insight into the CSF dynamics and the processes impacting them is crucial to better understand neurological disorders such as hydrocephalus, Chiari malformation, and intracranial hypertension. This study presents a 3D computational fluid dynamics (CFD) model which incorporates physiological processes as boundary conditions. CSF production and pulsatile arterial and venous volume changes are implemented as inlet boundary conditions. At the outlets, 2-element windkessel models are imposed to simulate CSF compliance and absorption. The total compliance is first tuned using a 0D model to obtain physiological pressure pulsations. Then, simulation results are compared with in vivo flow measurements in the spinal subarachnoid space (SAS) and cerebral aqueduct, and intracranial pressure values reported in the literature. Finally, the impact of the distribution of and total compliance on CSF pressures and velocities is evaluated. Without respiration effects, compliance of 0.17 ml/mmHg yielded pressure pulsations with an amplitude of 5 mmHg and an average value within the physiological range of 7-15 mmHg. Also, model flow rates were found to be in good agreement with reported values. However, when adding respiration effects, similar pressure amplitudes required an increase of compliance value to 0.51 ml/mmHg, which is within the range of 0.4-1.2 ml/mmHg measured in vivo. Moreover, altering the distribution of compliance over the four different outlets impacted the local flow, including the flow through the foramen magnum. The contribution of compliance to each outlet was directly proportional to the outflow at that outlet. Meanwhile, the value of total compliance impacted intracranial pressure. In conclusion, a computational model of the CSF has been developed that can simulate CSF pressures and velocities by incorporating boundary conditions based on physiological processes. By tuning these boundary conditions, we were able to obtain CSF pressures and flows within the physiological range.

The potential of invasive and non-invasive vagus nerve stimulation to improve verbal memory performance in epilepsy patients.

It has been demonstrated that acute vagus nerve stimulation (VNS) improves word recognition memory in epilepsy patients. Transcutaneous auricular vagus nerve stimulation (taVNS) has gained interest as a non-invasive alternative to improve cognition. In this prospective randomized cross-over study, we investigated the effect of both invasive VNS and taVNS on verbal memory performance in 15 patients with drug-resistant epilepsy. All patients conducted a word recognition memory paradigm in 3 conditions: VNS ON, VNS OFF and taVNS (3-period 3-treatment cross-over study design). For each condition, patients memorized 21 highlighted words from text paragraphs. Afterwards, the intervention was delivered for 30 s. Immediate recall and delayed recognition scores were obtained for each condition. This memory paradigm was repeated after 6 weeks of VNS therapy in 2 conditions: VNS ON and VNS OFF (2-period 2-treatment cross-over study design). Acute VNS and taVNS did not improve verbal memory performance. Immediate recall and delayed recognition scores were significantly improved after 6 weeks of VNS treatment irrespective of the acute intervention. We can conclude that the previously described positive effects of invasive VNS on verbal memory performance could not be replicated with invasive VNS and taVNS. An improved verbal memory performance was seen after 6 weeks of VNS treatment, suggesting that longer and more repetitive stimulation of the vagal pathway is required to modulate verbal memory performance.Clinical trial registration number: NCT05031208.

Laryngeal Muscle-Evoked Potential Recording as an Indicator of Vagal Nerve Fiber Activation.

BACKGROUND: Vagus nerve stimulation (VNS) is an adjunctive therapy for drug-resistant epilepsy. Noninvasive evoked potential recordings in laryngeal muscles (LMEPs) innervated by vagal branches may provide a marker to assess effective vagal nerve fiber activation. We investigated VNS-induced LMEPs in patients with epilepsy in acute and chronic settings. MATERIALS AND METHODS: A total of 17 of 25 patients underwent LMEP recordings at initiation of therapy (acute group); 15 of 25 patients after one year of VNS (chronic group); and 7 of 25 patients were tested at both time points (acute + chronic group). VNS-induced LMEPs were recorded following different pulse widths and output currents using six surface laryngeal EMG electrodes to calculate input/output curves and estimate LMEP latency, threshold current for minimal (Ithreshold), half-maximal (I50), and 95% of maximal (I95) response induction and amplitude of maximal response (Vmax). These were compared with the acute + chronic group and between responders and nonresponders in the acute and chronic group. RESULTS: VNS-induced LMEPs were present in all patients. Ithreshold and I95 values ranged from 0.25 to 1.00 mA and from 0.42 to 1.77 mA, respectively. Estimated mean LMEP latencies were 10 ± 0.1 milliseconds. No significant differences between responders and nonresponders were observed. In the acute + chronic group, Ithreshold values remained stable over time. However, at the individual level in this group, Vmax was lower in all patients after one year compared with baseline. CONCLUSIONS: Noninvasive VNS-induced LMEP recording is feasible both at initiation of VNS therapy and after one year. Low output currents (0.25-1.00 mA) may be sufficient to activate vagal Aα-motor fibers. Maximal LMEP amplitudes seemed to decrease after chronic VNS therapy in patients.

A novel hybrid 3D endoscope zooming and repositioning system: Design and feasibility study.

BACKGROUND: Manipulation of the endoscope during minimally invasive surgery is a major source of inconvenience and discomfort. This report elucidates the architecture of a novel one-hand controlled endoscope positioning device and presents a practicability evaluation. METHODS AND MATERIALS: Setup time and total surgery time, number and duration of the manipulations, side effects of three-dimensional (3D) imaging, and ergonomic complaints were assessed by three surgeons during cadaveric and in vivo porcine trials. RESULTS: Setup was accomplished in an average (SD) of 230 (120) seconds. The manipulation time was 3.87 (1.77) seconds for angular movements and 0.83 (0.24) seconds for zooming, with an average (SD) of 30.5 (16.3) manipulations per procedure. No side effects of 3D imaging or ergonomic complaints were reported. CONCLUSIONS: The integration of an active zoom into a passive endoscope holder delivers a convenient synergy between a human and a machine-controlled holding device. It is shown to be safe, simple, and intuitive to use and allows unrestrained autonomic control of the endoscope by the surgeon.

Is the Human Brain Capable of Controlling Seven Degrees of Freedom?

BACKGROUND: Conventional rigid laparoscopic instruments offer five degrees of freedom (DOF). Robotic instruments add two independent DOFs allowing unconstrained directional steering. Several nonrobotic instruments have been developed with the additional DOFs, but with these devices, surgeon's wrist movements are not intuitively transmitted into tip movements. In this study, a new articulated instrument has been evaluated. The aim of the study was to compare learning curves and performances of conventional laparoscopic instruments, the da Vinci system and Steerable devices in a crossover study. MATERIALS AND METHODS: A total of 16 medical students without any laparoscopic experience were trained for 27 h to operate all of a rigid, a robotic, and a new Steerable instrument in a random order. Learning curves and ultimate experience scores were determined for each instrument. Strain in wrist and shoulders was assessed with a visual analog score. RESULTS: Performing the suturing task with rigid and robot instruments required 4 h of training, compared with 6 h to master the Steerable instrument. After 9 h of training with each instrument, completing the complex suturing pattern required 662 ± 308 s with rigid instruments, 279 ± 90 s with the da Vinci system, and 279 ± 53 s with the Steerable instrument. Pain scores were significantly higher after using the rigid instruments compared with the Steerable instruments. CONCLUSIONS: Transmission of torque and the presence of additional two DOFs in combination with reduced crosstalk significantly improved the instrument dexterity where the Steerable platform is concerned. Although the learning curve is longer, once mastered, it provides enhanced surgical freedom.

Articulated Instruments and 3D Visualization: A Synergy? Evaluation of Execution Time, Errors, and Visual Fatigue.

Objective. The introduction of advanced endoscopic systems, such as the Storz Image1S and the Olympus Endoeye, heralds a new era of 3-dimensional (3D) visualization. The aim of this report is to provide a comprehensive overview of the neurophysiology of 3D view, its relevance in videoscopy, and to quantify the benefit of the new 3D technologies for both rigid and articulated instruments. Method. Sixteen medical students without any laparoscopic experience were trained each for a total of 27 hours. Proficiency scores were determined for rigid and articulated instruments under 2D and 3D visualization conditions. Results. A reduction in execution time of 14%, 28%, and 36% was seen for the rigid instruments, the da Vinci, and Steerable instruments, respectively. A reduction in errors of 84%, 92%, and 87% was seen for the rigid instruments, the da Vinci, and Steerable instruments, respectively. Conclusion. 3D visualization greatly augments endoscopic procedures. The advanced endoscopic systems employed in the recent study caused no visual fatigue or discomfort. The benefit of 3D was most distinct with articulated instruments.

A new dynamic model for in vitro evaluation of intravascular devices.

INTRODUCTION:: A dynamic model to evaluate thrombus formation on intravascular catheters in vitro is presented. The model enables fluid infusion, variation in the catheter orientation, and variable flow conditions. It was applied on a catheter used to shunt cerebrospinal fluid to a vein, a dural venous sinus, for the treatment of hydrocephalus. METHODS:: Fresh human blood-filled circuits were circulated in a non-occlusive roller pump. A catheter infused either with cerebrospinal fluid, Ringer's lactate, or no fluid (control) was inserted through each circuit's wall. Sixteen circuits (six cerebrospinal fluid, six Ringer's lactate, four control) ran for 60 min. Qualitative assessment was performed by measuring viscoelastic properties of blood at the start and end of the experiment; quantitative evaluation of clot formation by scanning electron microscope. RESULTS:: Average blood velocity was 79 mm/s, with a pressure wave between 5 and 15 mm Hg. At the experiment's end, the infused fluid represented 5.88% of the blood/infusion volume in the circuit. The control circuits showed no statistical difference between the start and end for viscoelastic testing, whereas both Ringer's lactate and cerebrospinal fluid enhanced coagulation, most pronounced for the latter. Most thrombus material was observed on catheters in the cerebrospinal fluid group. Clot formation was less pronounced on the surface of the catheter facing the blood flow. DISCUSSION:: A dynamic model for intravascular catheter testing mimics better clinical conditions when evaluating blood-material interaction. Catheter position, blood flow around the catheter, and infusion fluid all have a potential impact on the hemocompatibility of a given catheter.

Hydroxyapatite cranioplasty: a retrospective evaluation of osteointegration in 17 cases.

BACKGROUND: Cranial reconstruction with autologous bone is still the gold standard although several biomaterials are available to re-establish the integrity of the cranial vault. Due to their biological and morphological characteristics, hydroxyapatite implants show promising results in small clinical cohort studies, especially within the paediatric population. Its biocompatibility and osteoconductivity should allow the formation of osseous bridging at the skull-prosthesis interface. OBJECTIVE: To examine the possible occurrence of osteointegration and to quantify it. METHODS: A retrospective study of patients with a hydroxyapatite implant from 2010 to 2014 at our neurosurgical department was conducted. Demographic, surgical and radiological data were studied. A senior neuroradiologist, a staff member neurosurgeon and a resident neurosurgeon independently performed the radiological evaluation. A new software analysis technique was developed to objectively quantify the degree of osteointegration. RESULTS: Seventeen implants were evaluated with an average patient age of 39 years and a mean follow-up of 155 weeks. Through radiologic evaluation, osseous bridging was deemed higher than 50% in six prostheses and higher than 75% in three. In five patients, no osteointegration could be seen. The remaining patients exhibited sparse signs of osteointegration, estimated between 10 and 50%. Software analysis showed an average osteointegration ratio of 37.4% with a 400-HU filter and 27.3% with a 700-HU filter. CONCLUSION: In this small retrospective study of cranial hydroxyapatite implants, osteointegration did occur and to a degree of more than 50% in 1/3 of the patients.

Treating Hydrocephalus with Retrograde Ventriculosinus Shunt: Prospective Clinical Study.

BACKGROUND: Since the 1950s, hydrocephalus has been be treated with cerebrospinal fluid (CSF) shunts, usually to the peritoneal cavity or to the right cardiac atrium. However, because of their siphoning effect, these shunts lead to nonphysiologic CSF drainage, with possible comorbidity and high revision rates. More sophisticated shunt valve systems significantly increase costs and technical complexity and remain unsuccessful in a subgroup of patients. In an attempt to obtain physiologic CSF shunting, many neurosurgical pioneers shunted towards the dural sinuses, taking advantage of the physiologic antisiphoning effect of the internal jugular veins. Despite several promising reports, the ventriculosinus shunts have not yet become standard neurosurgical practice. METHODS: In this single-center prospective clinical study, we implanted the retrograde ventriculosinus shunt, as advocated by El-Shafei, in 10 patients. This article reports on our operation technique and long-term outcome, including 4 patients in whom this shunt was implanted as a rescue operation. RESULTS: Implantation of a ventriculosinus shunt proved to be feasible, warranting physiologic drainage of CSF. However, in only 3 of 14 patients, functionality of the retrograde ventriculosinus shunt was maintained during more than 6 years of follow-up. In our opinion, these shunts fail because present venous access devices are difficult to implant correctly and become too easily obstructed. After discussion of possible causes of this frequent obstruction, a new dural venous sinus access device is presented. CONCLUSION: An easy-to-implant and thrombogenic-resistant dural venous sinus access device needs to be developed before ventriculosinus shunting can become general practice.

The influence of cerebrospinal fluid on blood coagulation and the implications for ventriculovenous shunting.

OBJECTIVE: The effect of CSF on blood coagulation is not known. Enhanced coagulation by CSF may be an issue in thrombotic complications of ventriculoatrial and ventriculosinus shunts. This study aimed to assess the effect of CSF on coagulation and its potential effect on thrombotic events affecting ventriculovenous shunts. METHODS: Two complementary experiments were performed. In a static experiment, the effect on coagulation of different CSF mixtures was evaluated using a viscoelastic coagulation monitor. A dynamic experiment confirmed the amount of clot formation on the shunt surface in a roller pump model. RESULTS: CSF concentrations of 9% and higher significantly decreased the activated clotting time (ACT; 164.9 seconds at 0% CSF, 155.6 seconds at 9% CSF, and 145.1 seconds at 32% CSF). Increased clot rates (CRs) were observed starting at a concentration of 5% (29.3 U/min at 0% CSF, 31.6 U/min at 5% CSF, and 35.3 U/min at 32% CSF). The roller pump model showed a significantly greater percentage of shunt surface covered with deposits when the shunts were infused with CSF rather than Ringer's lactate solution (90% vs 63%). The amount of clot formation at the side facing the blood flow (impact side) tended to be lower than that at the side facing away from the blood flow (wake side; 71% vs 86%). CONCLUSIONS: Addition of CSF to blood accelerates coagulation. The CSF-blood-foreign material interaction promotes clot formation, which might result in thrombotic shunt complications. Further development of the ventriculovenous shunt technique should focus on preventing CSF-blood-foreign material interaction and stagnation of CSF in wake zones.

A non-hydrocephalic goat experimental model to evaluate a ventriculosinus shunt.

The ventriculosinus shunt is a promising treatment for hydrocephalus. Currently, different shunt techniques exist, and it is not clear whether one is preferable. This pilot study reports on a non-hydrocephalic goat model (Saanen breed) that provides opportunities to evaluate and optimize several aspects of the ventriculosinus shunt technique. Analysis of the coagulation properties of 14 goats by a viscoelastic coagulation monitor showed that goats have a hypercoagulable state compared to humans. This property can be partially counteracted by antiplatelet drugs. During implantation of a ventriculosinus shunt, a pulsatile reflux of blood was observed. After implantation, the animals recovered to their preoperative state, and none of them developed a superior sagittal sinus thrombosis. Evaluation of the shunts after 16 days showed an obstructing luminal clot. Several model-related factors may have promoted this obstruction: the absence of hydrocephalus, the hypercoagulability of caprine blood and the smaller dimensions of the caprine superior sagittal sinus. However, the pulsatile reflux of blood, which is caused by the compliance of the shunt system distal to the valve, may have been an important factor as well. In conclusion, the non-hydrocephalic goat model limits animal suffering and simplifies the study protocol. This model allows researchers to evaluate their implantation technique and shunt hardware but not the efficacy of the treatment or shunt survival.

Automatic detection of oesophageal intubation based on ventilation pressure waveforms shows high sensitivity and specificity in patients with pulmonary disease.

BACKGROUND: Unrecognised endotracheal tube misplacement in emergency intubations has a reported incidence of up to 17%. Current detection methods have many limitations restricting their reliability and availability in these circumstances. There is therefore a clinical need for a device that is small enough to be practical in emergency situations and that can detect oesophageal intubation within seconds. In a first reported evaluation, we demonstrated an algorithm based on pressure waveform analysis, able to determine tube location with high reliability in healthy patients. The aim of this study was to validate the specificity of the algorithm in patients with abnormal pulmonary compliance, and to demonstrate the reliability of a newly developed small device that incorporates the technology. MATERIALS AND METHODS: Intubated patients with mild to moderate lung injury, admitted to intensive care were included in the study. The device was connected to the endotracheal tube, and three test ventilations were performed in each patient. All diagnostic data were recorded on PC for subsequent specificity/sensitivity analysis. RESULTS AND DISCUSSION: A total of 105 ventilations in 35 patients with lung injury were analysed. With the threshold D-value of 0.1, the system showed a 100% sensitivity and specificity to diagnose tube location. CONCLUSION: The algorithm retained its specificity in patients with decreased pulmonary compliance. We also demonstrated the feasibility to integrate sensors and diagnostic hardware in a small, portable hand-held device for convenient use in emergency situations.

The use of the trendelenburg position in the surgical treatment of extreme cerebellar slump.

BACKGROUND: State-of-the-art treatment for Chiari Malformation I (CM-I) consists of decompression by posterior fossa craniectomy. A rare but severe complication that develops over months to years after this procedure is cerebellar slump. Treatment options for this condition are limited. We present a new and promising approach to treat this rare condition. METHODS: The patients were placed in the Trendelenburg position to facilitate ascent of the cerebellum. After almost complete dissolution of neurologic symptoms, surgical reconstruction was performed by tonsillar resection and the creation of a new structural support using a bone graft. RESULTS: Both patients experienced good clinical and morphological outcomes immediately after surgery, and for two years thereafter. CONCLUSIONS: Neurological symptoms related to cerebellar or brainstem slump can be adequately reversed by placing the patient in the Trendelenburg position. After uneventful gravitational reversal of the slump, safe surgical reconstruction of the cerebellar support can be performed to securely preserve the anatomical reversal.

Endoscopic Treatment of Temporal Arachnoid Cysts in 34 Patients.

INTRODUCTION: Arachnoid cysts are lesions present in 1% of the population and usually found in the temporal fossa. Clinical and radiologic presentations can differ greatly. Despite intensive research, it is still debatable which patients will benefit from surgery. OBJECTIVE: This study aims to investigate the pretreatment parameters influencing the outcome after neuroendoscopic treatment of temporal arachnoid cysts. MATERIALS AND METHODS: A retrospective analysis of 34 patients who underwent an endoscopic fenestration of a temporal arachnoid cyst between July 1991 and December 2013 was performed. RESULTS: In symptomatic patients, there was a clinical improvement in 76.4% of cases. The best results were found in treating symptoms related to intracranial hypertension, acute neurologic defects, and macrocrania. Patients with temporal lobe epilepsy improved after cyst fenestration in 33.3% of cases. Behavioral problems and psychomotor retardation remained largely unchanged. Patients with a complex neurologic presentation, often from a congenital syndrome and combined with an intellectual disability, had the least benefit from endoscopic surgery. Radiologic follow-up showed a cyst volume decrease in 91.2% of cases. Complications were present in 29.4%, but were mostly minor and transient. CONCLUSION: This study demonstrates that patients with symptoms related to intracranial hypertension, acute neurologic deficits, and macrocrania have the best postoperative outcome. Also, patients with ipsilateral temporal lobe epilepsy seem to be good candidates for endoscopic arachnoid cyst fenestrations. In complex neurologic disorders without one of the previously mentioned symptoms, endoscopy remains less successful.

A novel design for steerable instruments based on laser-cut nitinol.

OBJECTIVE: Omnidirectional articulated instruments enhance dexterity. In neurosurgery, for example, the simultaneous use of 2 instruments through the same endoscopic shaft remains a difficult feat. It is, however, very challenging to manufacture steerable instruments of the requisite small diameter. We present a new technique to produce such instruments by means of laser cutting. Only 3 coaxial tubes are used. The middle tube has a cutting pattern that allows the steering forces to be transmitted from the proximal to the distal end. In this way the steering part is concealed in the wall of the tube. Large diameter articulated instruments such as for laparoscopy might benefit from the excellent tip stability provided by the same economical technology. METHOD: Coaxial nitinol tubes are laser-cut with a Rofin Stent Cutter in a specific pattern. The 3 tubes are assembled by sliding them over one another, forming a single composite tube. In a surgical simulator, the neurosurgical microinstruments and laparoscopic needle drivers were evaluated on surgical convenience. RESULTS: Simultaneous use of 2 neurosurgical instruments (1.5 mm diameter) through the same endoscopic shaft proved to be very intuitive. The tip of the steerable laparoscopic instruments (10 mm diameter) could resist a lateral force of more than 20 N. The angle of motion for either instrument was at least 70° in any direction. CONCLUSIONS: A new design for steerable endoscopic instruments is presented. It allows the construction in a range from microinstruments to 10-mm laparoscopic devices with excellent tip stability.

A novel implantable vagus nerve stimulation system (ADNS-300) for combined stimulation and recording of the vagus nerve: pilot trial at Ghent University Hospital.

PURPOSE: Vagus nerve stimulation (VNS) is an established treatment for refractory epilepsy. The ADNS-300 is a new system for VNS that includes a rechargeable stimulus generator and an electrode for combined stimulation and recording. In this feasibility study, three patients were implanted with ADNS-300 for therapeutic VNS. In addition, compound action potentials (CAPs) were recorded to evaluate activation of the vagus nerve in response to VNS. METHODS: Three patients were implanted with a cuff-electrode around the left vagus nerve, that was connected to a rechargeable pulse generator under the left clavicula. Two weeks after surgery, therapeutic VNS (0.25-1.25 mA, 500 µs, 30s on, 10 min off and 30Hz) was initiated and stimulus-induced CAPs were recorded. RESULTS: The ADNS-300 system was successfully implanted in all three patients and patients were appropriately stimulated during six months of follow-up. A reduction in seizure frequency was demonstrated in two patients (43% and 40% in patients 1 and 3, respectively), while in patient 2 seizure frequency remained unchanged. CAPs could be recorded in patients 1 and 2, proving stimulation-induced activation of the vagus nerve. CONCLUSION: This feasibility study demonstrates that the ADNS-300 system can be used for combined therapeutic stimulation (in 3/3 patients) and recording of CAPs in response to VNS (in 2/3 patients) up to three weeks after surgery. Implantation in a larger number of patients will lead to a better understanding of the electrophysiology of the vagus nerve, which in turn could result in more adequate and individualized VNS parameter choice.

Evolution in VNS therapy for refractory epilepsy, experience with Demipulse devices at Ghent University Hospital.

RATIONALE: Vagus nerve stimulation (VNS) is a frequently used treatment for patients with refractory epilepsy who are unsuitable candidates for epilepsy surgery. There has been a steady evolution in VNS technology, as generators' volumes have become smaller and battery life expectancy longer. This pilot study is an open-label retrospective study that describes our experience with the latest commercially available generator, i.e. the VNS Therapy Demipulse Model 103. Treatment efficacy and side effects, as well as technical and practical enhancements useful for the patient and for the medical staff are discussed in this study. METHODS: Twenty patients (11F/9M) with a mean age of 40 years (range 8-61), who were considered unsuitable candidates for resective surgery, were implanted with a VNS Therapy Demipulse Model 103. Mean monthly seizure frequency reduction and side effects were evaluated 1 year after implantation. RESULTS: Mean monthly seizure frequency decreased significantly from 54 seizures/month (SEM 30; range 1-555) before treatment to 33 (SEM 24, range 0-445) following 12 months of treatment (p<0.05). Seven patients (39%) were considered responders with a reduction in seizure frequency of more than 50%. One of those seven patients became seizure free. Side effects were stimulation-related tingling sensation in the throat and/or hoarseness, a painful sensation in the left neck or ear region and a lead breakage In addition; one case of SUDEP was reported. CONCLUSION: Patients treated with VNS Therapy Demipulse generators proved to have a significant decrease in seizure frequency. In this patient group, VNS was well tolerated. The main technical advances are the decrease in size and improved options for battery life follow-up.

Deep brain stimulation in patients with refractory temporal lobe epilepsy.

PURPOSE: This pilot study prospectively evaluated the efficacy of long-term deep brain stimulation (DBS) in medial temporal lobe (MTL) structures in patients with MTL epilepsy. METHODS: Twelve consecutive patients with refractory MTL epilepsy were included in this study. The protocol included invasive video-EEG monitoring for ictal-onset localization and evaluation for subsequent stimulation of the ictal-onset zone. Side effects and changes in seizure frequency were carefully monitored. RESULTS: Ten of 12 patients underwent long-term MTL DBS. Two of 12 patients underwent selective amygdalohippocampectomy. After mean follow-up of 31 months (range, 12-52 months), one of 10 stimulated patients are seizure free (>1 year), one of 10 patients had a >90% reduction in seizure frequency; five of 10 patients had a seizure-frequency reduction of > or =50%; two of 10 patients had a seizure-frequency reduction of 30-49%; and one of 10 patients was a nonresponder. None of the patients reported side effects. In one patient, MRI showed asymptomatic intracranial hemorrhages along the trajectory of the DBS electrodes. None of the patients showed changes in clinical neurological testing. Patients who underwent selective amygdalohippocampectomy are seizure-free (>1 year), AEDs are unchanged, and no side effects have occurred. CONCLUSIONS: This open pilot study demonstrates the potential efficacy of long-term DBS in MTL structures that should now be further confirmed by multicenter randomized controlled trials.

Are psychotic symptoms related to vagus nerve stimulation in epilepsy patients?

Four patients with refractory epilepsy presented with psychotic symptoms following treatment with vagus nerve stimulation (VNS) to control seizures. Besides its anti-epileptic effect VNS has been shown to have an effect on various cognitive and behavioural functions. VNS is known to increase alertness and reduce sedation, which is independent from seizure control. VNS has also been shown to positively affect cognition and to exert strong antidepressant effects. Co-morbidity in epilepsy often comprises psychiatric illnesses. Increased psychiatric symptoms have mainly been described in association with successful outcome following epilepsy surgery as a result of 'forced normalisation'. Different hypotheses on the underlying aetiology of VNS-induced psychotic symptoms other than the previously described 'forced normalisation' are discussed.

Neurostimulation for refractory epilepsy.

Neurostimulation is an emerging treatment for refractory epilepsy. To date the precise mechanism of action remains to be elucidated. Better insight in the mechanism of action may identify seizure types or syndromes that respond to such a treatment and may guide the search for optimal stimulation parameters and finally improve clinical efficacy. In the past ten years some progress has been made through neurophysiological, neuroanatomical, neurochemical and cerebral blood flow studies in patients and animals undergoing vagus nerve stimulation (VNS). Interesting results have been found in VNS-treated patients that underwent evoked potential measurements, cerebrospinal fluid investigation, neuropsychological testing and PET, SPECT and fMRI testing. Desynchronisation of abnormal synchronous epileptic activity is one of the hypotheses on the mode of action that might primarily be responsible for an anti-seizure effect. There is however increasing evidence from research and clinical observation that VNS might establish a true and long-term anti-epileptic effect. It has been shown that VNS influences neurotransmission in the brain and provokes long-term changes in cerebral blood flow in areas crucial for epileptogenesis such as the thalamus and medial temporal lobe structures. Deep brain stimulation (DBS) for epilepsy has regained interest. Central nervous system structures known to play a key role in the epileptogenic network such as the thalamus and subthalamic nucleus have been targeted. Another approach is to target the ictal onset zone such as the medial temporal lobe. At Ghent University Hospital 10 patients have been treated with long-term amygdalohippocampal DBS. Several hypotheses have been raised for the mechanism of action of DBS for refractory seizures. Seizure reduction may be due to a microlesion caused by electrode insertion or by provoking a reversible functional lesion due to the effect of electrical current on hyperexcitable tissue. Neurophysiological techniques such as evoked potentials monitoring and intraoperative single unit potential recordings may guide correct electrode placement, individual DBS titration and elucidation of the mechanims of action of DBS for epilepsy.