D. Van Roost

Anatomical and physiological basis and mechanism of action of neurostimulation for epilepsy

Neurostimulation is an emerging treatment for neurological diseases. Different types of neurostimulation exist mainly depending of the part of the nervous system that is being affected and the way this stimulation is being administered. Vagus nerve stimulation (VNS) is a neurophysiological treatment for patients with medically or surgically refractory epilepsy. Over 30,000 patients have been treated with VNS. No clear predictive factors for responders have been identified. 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 better to VNS and may guide the search for optimal stimulation parameters and finally improve clinical efficacy. Deep brain stimulation (DBS) has been used extensively as a treatment for movement disorders. Several new indications such as obsessive compulsive behaviour and cluster headache are being investigated with promising results. The vast progress in biotechnology along with the experience in other neurological diseases in the past ten years has led to a renewed interest in intracerebral stimulation for epilepsy. Epilepsy centers around the world have recently reinitiated trials with deep brain stimulation in different intracerebral structures such as the thalamus, the hippocampus and the subthalamic nucleus.

Neurosurgical aspects of temporal deep brain stimulation for epilepsy.

Deep brain stimulation (DBS), which mimics the effect of ablative surgery in movement disorders, is considered by analogy as potentially useful in the epileptic temporal lobe as an alternative to resection. It could be applied to patients in whom resective surgery is less beneficial, e.g. cases without memory impairment or with bilateral hippocampal involvement. In patients who undergo invasive presurgical analysis, the necessary intrahippocampal leads can serve for the application of DBS, provided that they are suited for chronic use. The hippocampus, in which the focus of epilepsy is detected, is stimulated continuously using high-frequency square-wave pulses. The reduction of interictal spike activity during a period of acute stimulation is the criterion for deciding whether the leads will be connected to an internal pulse generator. We are conducting a pilot study, with 16 patients enrolled so far, ten of whom have been followed up for more than one year. Some theoretical considerations are dedicated to hippocampal DBS.

Experimental and numerical modelling of the ventriculosinus shunt (El-Shafei shunt)

This study assesses malresorptive hydrocephalus treatment by ventriculosinus shunting with the shunt in the antegrade or retrograde position. First, an experimental model of the cerebral ventricles, the arachnoid villi, the cortical veins, and the superior sagittal sinus was built. For this purpose, the compliance of a human cortical vein was measured and then modelled by means of Penrose tubes. The dimensions of the superior sagittal sinus were determined in vivo by measurements on magnetic resonance imaging scans of 21 patients. Second, a numerical model of the cortical veins and the superior sagittal sinus was built. The numerical results were validated with the results from the experimental model. The experimental and numerical pressure difference between the intracranial pressure and the static sinus pressure was small (0–20 Pa) and corresponded to the theoretically expected values. No overdrainage was found in either the antegrade or the retrograde position of the shunt. Blood reflow was only found while mimicking lumbar puncture or changes in position with the experimental model (lowering the intracranial pressure or increasing the sinus pressure rapidly). Optimal results can be obtained with the shunt positioned in the most downstream half of the superior sagittal sinus. The experimental and numerical results confirm the potential of ventriculosinus shunting as therapy for malresorptive hydrocephalus patients. The ventriculosinus shunt thus proves to be a promising technique.

Myelotomies for Chronic Pain

The literature on myelotomy for the treatment of chronic pain was reviewed and a total of 635 published cases scrutinized. Two main modes of myelotomy can be distinguished 1) a longitudinal commissural section tuned to the segmental pain level and 2) a focused central lesion, irrespective of considerations of the metameric pain distribution, mainly carried out at a high cervical level. Of the longitudinal commissural myelotomy, a posteriorly restricted and a complete type can moreover be discerned. The pain relief decays with time after myelotomy of any kind. Central myelotomy scores better than complete commissural section for malignant pain in a statistically significant manner but its superiority over posterior commissurotomy cannot be statistically proven. Except of a girdle-shaped hypo-algesia, which is expected after the section of the decussating spinothalamic fibers in a complete commissurotomy, other--irregular--patterns of hypo-algesia have been observed, especially after central myelotomy. This unusual lesion, provoking unusual hypo-algesia patterns, together with phenomena like a preserved sharp-blunt-discrimination within the hypo-algesic area, points at a different sensory channel that might be severed in a central myelotomy as compared with an anterolateral chordotomy or a complete commissurotomy. This hypothesis is matched with recent physiological evidences.

Electrophysiological registration of phonological perception in the subthalamic nucleus of patients with Parkinson’s Disease

Phonological processing is usually associated with the activation of cortical areas, especially in the left cerebral hemisphere. This study examined if phonologically elicited evoked potentials can be recorded directly from the subthalamic nucleus in patients with Parkinsons Disease (PD). Seven PD patients who had undergone implantation of deep brain electrodes for the stimulation of the subthalamic nucleus were included. Local field potentials were recorded in a pre-attentive auditory phonological task, an attentive auditory phonological discrimination task, and a word recognition task. Auditory evoked potentials related to phonological, but not lexical processing, could be demonstrated in the subthalamic nucleus for all three tasks. Only minor changes were found after levodopa administration. This study demonstrates that the subthalamic nucleus is involved in early phonological perception, which puts the subthalamic nucleus in a position to modify phonological perception in a larger cortico-subcortical network.

Cryptococcoma unresponsive to antifungal treatment in a 63-year-old non-HIV-infected male.

Abstract Cryptococcosis is an invasive fungal infection mainly due to Cryptococcus neoformans which has become increasingly prevalent in immunocompromised patients. The majority of patients with disseminated infection are immunocompromised due to AIDS, prolonged treatment with corticosteroids, organ transplantation, or malignancy. Invasive cryptococcal infection is rare in healthy immunocompetent individuals. We present a case of cerebral cryptococcoma in a previously healthy individual with development of meningitis and multiple intracerebral lesions in spite of persistently negative cultures and refractory to conventional antifungal therapy. The diagnosis was confirmed by two independent anatomopathological examinations.

Amygdalohippocampal Deep Brain Stimulation (Ah-DBS) for Refractory Temporal Lobe Epilepsy

Four patients had a left-sided focal medial temporal lobe onset. Three patients had a right-sided regional medial temporal lobe onset. One patient had a bilateral regional temporal lobe onset with predominant involvement of the left side. Two patients had a leftsided regional medial temporal lobe onset. Nine out of 10 patients had a >50% reduction of interictal spikes during the initial AH-DBS trial period. In one patient who showed very infrequent spiking, seizure frequency that had significantly decreased, was used as a criterion for implantation. One patient did not meet the chronic implantation criterion and underwent a selective amygdalo-hippocampectomy. Nine out of 10 patients were implanted with an internal generator. The mean follow-up in these patients was 16 months (range: 9–25 months). One patient has been free of complex partial seizures (CPS) for 2 years and has been tapered off 2 anti-epileptic drugs (AEDs). Another patient has become seizure-free in the past 9 months; 3/10 patients have a >50% reduction in seizure frequency; 3/4 patients have been taIntroduction

Training charter in epilepsy surgery added competence.

The present Training Charter in Epilepsy Surgery Added Competence constitutes the third stage of a program initiated by the European Society for Stereotactic and Functional Neurosurgery (ESSFN) and substantiated in close collaboration with the Union Européennedes Médecins Spécialists (UEMS) and the European Association of Neurosurgical Societies (EANS). This program aims to raise the standards of clinical practice by guiding education and quality control concepts. The particular sections of this Charter include: definitions and standards of added competence training, relations of the Epilepsy Unit with the Neurosurgical Department, duration of epilepsy surgery fellowship, institution and training program director requirements, operative totals for epilepsy surgery, educational program, individual requirements, and evaluation and qualification of the trainees. The specification of all these requirements is expected to improve harmonisation and quality of epilepsy surgery practice across Europe, and enhance the clinical activity and the scientific productivity of existing neurosurgical centres.

CHORDOID MENINGIOMA IN AN ADULT PATIENT PRESENTING WITH CHRONIC FATIGUE AND SYSTEMIC INFLAMMATION

Abstract We report a 27-year-old woman presenting with chronic fatigue and depressive symptoms. Aspecific neurologic symptoms and biochemical indices of inflammation and anaemia triggered an MRI, revealing a tumor with compression of the medulla oblongata. After neurosurgical resection, anatomopathologic examination showed a chordoid meningioma. All complaints disappeared and inflammatory parameters normalized, suggesting an association with Castleman syndrome. This case demonstrates the importance of a systematic diagnostic approach in patients presenting with unexplained chronic fatigue.

Influence of platelet clumps on platelet function analyser (PFA)‐200® testing

Sir, The platelet function analyser (PFA)-200 is widely used as a simple and rapid screening tool to measure global platelet haemostatic function to detect bleeding disorders as well as to monitor platelet inhibition by several antiplatelet drugs [1]. The PFA-200 simulates the process of platelet adhesion and aggregation triggered by either collagen/epinephrine (coll/EPI) or collagen/ADP (coll/ ADP) in vitro, reporting results as a ‘closure time’ (CT) [2]. The investigation of platelet function by PFA-200 is highly vulnerable to a broad series of pre-analytical variables. Sample collection and transportation may influence the results [3, 4]. Patient characteristics such as a platelet count <100 9 10/L and haematocrit <30% usually results in prolongation of the CT [5, 6], as well as the concentration of von Willebrand factor (vWF) in plasma [7]. The PFA-CT with coll/EPI test cartridge, but not the coll/ADP test cartridge, is usually prolonged by COX-1 inhibitors, such as aspirin [8]. According to manufacturer’s specification, the requirements for processing a specimen for PFA currently include the lack of microthrombi in the sample. Also haemolysed blood for PFA testing is not recommended [9]. Recently, we received a blood sample of a 56-year-old woman, to screen the platelet function before urgently needed neurosurgery; the aspirin (100 mg/day) therapy had been stopped since one day. PFA-200 was performed to evaluate the effect of antiplatelet therapy. The complete blood count revealed a platelet count of 500 9 10/L (normal range, 171–374 9 10/L) and haematocrit value of 32.8% (normal range, 35.8–43.7%). PFA-CT with coll/EPI and coll/ADP were both normal, respectively, 81 s (normal range, 82–150 s) with coll/EPI and 67 s (normal range, 62–100 s) with Coll/ADP in duplicate measurement. Because of the unexpected PFA result with normal CT, light transmission platelet aggregation (LTA) on platelet rich plasma with several agonists (epinephrine 10 lM, adenosine diphosphate (ADP) 2.5 lM and 5 lM, collagen 2.5 lg/mL and 5 lg/mL, ristocetin 0.5 mg/mL and 1.5 mg/mL, arachidonic acid, 0.25 mM and thromboxane A2 analogue U46619 10 lM) was performed on Chrono-log 700 (Chrono-Log, Havertown, PA, USA). The LTA showed normal aggregation with ADP, collagen, ristocetin and U46619. There was no aggregation with arachidonic acid, confirmed in repeated measurement. Although a normal coll/EPI CT the LTA with epinephrine was slightly reduced (an amplitude of 60%); this might be explained by the higher concentration of epinephrine used in the PFA cartridge. The LTA was compatible with the effect of aspirin (Figure 1). The complete blood count on citrated (0.109 mM or 3.2%) blood was performed on Sysmex KX-21N (Sysmex Corporation, Kobe, Japan) haematology analyser, and we noticed a flagging for platelet clumps. A microscopic review of the blood smear confirmed the presence of platelet clumps (Figure 2). This could explain the falsely shortened CT of the PFA with coll/EPI and the discrepancy with LTA. Other possible factors contributing to the short CT of the PFA could be the high platelet count (500 9 10/L) or an elevated vWF (not measured in this patient); however, we had little arguments to conclude to pronounced acute phase because the slightly elevated C-reactive protein (7.3 mg/L, normal range <5 mg/L). Platelet clumps are a frequent cause of flow obstructions and may cause cancellation of the test. We cannot exclude that the false short PFA-CT results in this patients may be due to platelet clumps not indicated as ‘flow obstruction’ by the instrument. In conclusion, we reported a discrepant result in a presurgery platelet function screening between PFA and LTA in a patient taking aspirin. Although variations in test results in regard to aspirin effect on PFA and LTA are described in the literature [10,11], we report another possible cause of false negative results with PFA. Considering the platelet count and haemotocrit is common practice in interpreting PFA-CT results. However, review for platelet clumps is not. Platelet clumps can falsely reduce the CT of the PFA and may lead to misdiagnosis of platelet function disorders, as well as inappropriate perceptions and clinical response related to antiplatelet therapy, as illustrated in this case.