Neurophysiological investigations of drug resistant epilepsy patients treated with vagus nerve stimulation to differentiate responders from non-responders

Background and purpose In patients treated with vagus nerve stimulation (VNS) for drug resistant epilepsy (DRE), up to a third of patients will eventually not respond to the therapy. As VNS therapy requires surgery for device implantation, prediction of response prior to surgery is desirable. It is hypothesized that neurophysiological investigations related to the mechanisms of action of VNS may help to differentiate VNS responders from non-responders prior to the initiation of therapy. Methods In a prospective series of DRE patients, polysomnography, heart rate variability (HRV) and cognitive event related potentials were recorded. Polysomnography and HRV were repeated after 1 year of treatment with VNS. Polysomnography, HRV and cognitive event related potentials were compared between VNS responders (>= 50% reduction in seizure frequency) and non-responders. Results Fifteen out of 30 patients became VNS responders after 1 year of VNS treatment. Prior to treatment with VNS, the amount of deep sleep (NREM 3), the HRV high frequency (HF) power and the P3b amplitude were significantly different in responders compared to non-responders (P = 0.007; P = 0.001; P = 0.03). Conclusion Three neurophysiological parameters, NREM 3, HRV HF and P3b amplitude, were found to be significantly different in DRE patients who became responders to VNS treatment prior to initiation of their treatment with VNS. These non-invasive recordings may be used as characteristics for response in future studies and help avoid unsuccessful implantations. Mechanistically these findings may be related to changes in brain regions involved in the so-called vagal afferent network

M & L Jaargang 12/6

GeneriekMiek Goossens Leven in de brouwerij of hoe iets ouds iets nieuws werd. [From old to new: the Christiaen Brewery in Koekelare.]Bijna twee eeuwen lang wist deze organisch gegroeide dorpsbrouwerij het West-Vlaamse Koekelare tegelijk aan werkgelegenheid te helpen, te lessen en te voorzien in burgemeesters. Het kan dan ook niet enkel toeval genoemd worden dat na het stilvallen van de activiteiten in 1968 en een sindsdien voortschrijdend verval, het controversieel industrieel-archeologisch relict vanaf 1984 een nieuwe bestemming tegemoet ging als gemeentelijk en cultureel polyvalent centrum. Terecht bedacht een Prijs dan ook dit eerste Vlaamse Monument.Ann Bergmans Van Lucca naar Brugge. Een Volto Santo in de Speelmanskapel. [From Lucca to Bruges. A Volto Santo in the Speelmanskapel.]Enige verwarring tussen de gekruisigde Christus-voorstelling en de legendarische vrouw-met-de-baard is niet geheel denkbeeldig, gezien de ooit bijzonder populaire aldus getooide Heilige Wilgefortis. De thans verdwenen muurschildering in de Brugse Speelmanskapel leverde alleszins het verrassende bewijs van een vroeg 15de-eeuwse beïnvloeding door het Italiaanse Lucca. Voor de Zuidelijke Nederlanden een unicum.Roger Deneef en Lutgart Vrancken De Hortus Thenensis. [The Hortus Thenensis.]Met merkelijk meer succes wist de Tiense Léon P. Ch. Van den Bossche vanaf 1883 zijn korte diplomatieke carrière te ruilen voor deze van gepassioneerd plantenverzamelaar: tot méér dan 3000 soorten in 1900, op een oppervlakte van nauwelijks 2,5 hectare, van wetenschappelijke geloofsbrieven voorzien door latere Nationale Plantentuindirecteur Emile De Wildeman. Een weelde, waarvan het Stadspark onverhoopt nog tastbare restanten blijkt te hebben bewaard.P. Vissers Mecenaat in de monumentenzorg, een (her)nieuw(d) gegeven. [Sponsoring historic preservation.]Van het 15de-eeuwse Brugse Oosterlingenhuis, pleisterplaats van Duitse Hanze-kooplui, bleven ingevolge brand en ingrijpende verbouwingen, slechts spaarzame fragmenten intact.Onlangs bij renovatiewerken vrij gelegde kinderbalken brachten alvast een zeldzaam overblijfsel aan het licht van persbrokaat, een uiterst fragiele decoratietechniek ... met een geëigende conserverende behandeling.Marjan Buyle Het plafond van het Oosterlingenhuis te Brugge. [The ceiling of the Oriental House in Bruges.]Van bij haar oprichting in 1984 ijverde de Stichting Monumenten- en Landschapszorg onverdroten voor een meer tastbare financiële inzet van de zakenwereld bij de behartiging van het cultureel erfgoed.Welke zijn nu de reeds bereikte resultaten en in welke mate varen àlle betrokken partijen wel bij deze transactie?SummaryM&L Binnenkran

A compact CZT γ-ray detector for nuclear applications in medicine

This thesis presents two case studies for the use of a compact CZT γ-ray detector (manufactured by Kromek) in a medical context. The aim is to evaluate the potential of this type of detector for common nuclear applications in medicine. CZT γ-ray detectors are a type of semiconductor detectors, made of Cd$_{0.9}$Zn$_{0.1}$Te. Owing to the particular band structure of the material (Eg = 1.57 eV), CZT detectors can operate at room temperature. This is a major benefit compared to, for example, HPGe detectors, which must be cooled to limit thermal excitation. Moreover, the CZT detectors of Kromek’s GR family, which are considered in this thesis, are compact: the detection crystal and electronics are contained in a 2.5 cm × 2.5 cm × 6.3 cm casing. Therefore, these detectors can be used in remote places that might be inaccessible to other detection systems. In both case studies, the CZT detector is used for γ-spectroscopy. In this technique, energy spectra of γ-ray emitting samples are investigated to identify and quantify the present radioactive isotopes. The first case study for the use of a compact Kromek CZT detector involves the production of terbium radioisotopes for medical applications at CERN MEDICIS (Geneva, CH). The Tb radionuclide family is very promising for nuclear medicine, because it contains four radioisotopes with complementary decay characteristics suitable for both imaging and therapy. For the neutron-rich radioisotope, $^{161}$Tb, large-scale production has been established at SCK CEN (Mol, BE) by neutron irradiation of Gd targets. The neutrondeficient radioisotopes, $^{149}$Tb, $^{152}$Tb and $^{155}$Tb, are predominantly produced at MEDICIS. In this case, a heavy target of Gd or Ta is irradiated by energetic protons up to 1.4 GeV, and the Tb radioisotopes are separated from the other species by the ISOL (Isotope Separation On-Line) method. Finally, the separated isotopes of interest are collected on implantation foils. At MEDICIS, the Tb activity can be monitored during the collection using the Kromek GR1 CZT detector installed in front of the collection chamber. In this thesis, the γ-spectra acquired by the detector during the $^{155}$Tb collections in 2021 are analysed. They show the presence of $^{139}$Ce$^{16}$O as isobaric contaminant that is collected together with $^{155}$Tb. Furthermore, they indicate that (self-)sputtering occurs in the collection chamber, limiting the amount of $^{155}$Tb that stays implanted on the foil. Finally, combined with ion current measurements, the γ-spectra suggest that target conditioning prior to the collection is useful to prevent saturation of the ion source. In the second case study, a Kromek CZT detector is used in the context of radioactive waste management at the proton therapy facility PARTICLE (Leuven, BE). Due to direct irradiation by the proton beam of 230MeV or indirect irradiation by scattered protons, nuclear reactions are induced in the construction elements of the beam-line. A variety of radioisotopes is produced, depending on the composition of the construction material and the energy of the protons. In this manner, radioactive waste is created. To decide on the proper treatment for specific components, the radioisotopes generated in them must be identified and quantified. In this thesis, that is done with a Kromek GR05 CZT detector for 12 parts of the accelerator at PARTICLE. $^{22}$Na, $^{54}$Mn, $^{57}$Co, $^{60}$Co and $^{65}$Zn are identified as common radioisotopes. This is in agreement with FLUKA simulations of the proton irradiation of conventional construction materials. Furthermore, it is observed that higher activities are produced in objects that are directly irradiated. Consequently, it takes longer for these objects to decay to activities below the appropriate clearance level for disposal. In both case studies discussed in this thesis, the Kromek CZT detector presents itself as a suitable device to apply γ-spectroscopy in a medical context. Given its ability to operate at room temperature as well as its compact size and mobility, the detector can be used in remote locations

A pilot trial with modified Atkins' diet in adult patients with refractory epilepsy

Objectives: At Ghent University Hospital, the feasibility and efficacy of the modified Atkins' diet was evaluated in adult patients with refractory epilepsy. The Atkins' diet restricts carbohydrate intake and was originally designed for weight loss. Patients and methods: During a 6-month trial period, a carbohydrate restriction of 20 g/day was in place. During a 36 h hospital admission, patients were instructed about the diet. Patients underwent clinical neurological testing, EEG, ECG, blood and urine analyses and mood evaluation before and during the trial. Seizure frequency and side effects were recorded in seizure diaries and followed up at monthly clinic visits. Results: Eight patients were included in the study. Three out of eight patients followed the diet for 6 months. One out of three patients showed a >50% seizure reduction, 1/3 > 30%, and 1/3 < 30%. Side effects such as constipation and diarrhoea were mild and occurred mainly during, the initial week of the diet. Patients reported improved concentration and well being. This was confirmed by improved scores on the Beck Depression Inventory Scale. Conclusion: This pilot Study shows that the modified Atkins' diet is feasible in an adult population, and that seizure frequency reduction is possible. The results need to be confirmed in larger prospective, controlled studies with comparison groups

Severe autonomic nervous system imbalance in Lennox-Gastaut syndrome patients demonstrated by heart rate variability recordings

Objective: Patients diagnosed with Lennox Gastaut syndrome (LGS), an epileptic encephalopathy characterized by usually drug resistant generalized and focal seizures, are often considered as candidates for vagus nerve stim-ulation (VNS). Recent research shows that heart rate variability (HRV) differs in epilepsy patients and is related to VNS treatment response. This study investigated pre-ictal HRV in generalized onset seizures of patients with LGS in correlation with their VNS response. Methods: In drug resistant epilepsy (DRE) patients diagnosed with LGS video-electroencephalography recording was performed during their pre-surgical evaluation. Six HRV parameters (time and-, frequency domain, non-linear parameters) were evaluated for every seizure in epochs of 10 min at baseline (60 to 50 min before seizure onset) and pre-ictally (10 min prior to seizure onset). The results were correlated to VNS response after one year of VNS therapy. Results: Seven patients and 31 seizures were included, two patients were classified as VNS responders (>= 50 % seizure reduction). No difference in pre-ictal HRV parameters between VNS responders and VNS non-responders could be found, but high frequency (HF) power, reflecting the parasympathetic tone increased significantly in the pre-ictal epoch in both VNS responders and VNS non-responders (p = 0.017, p = 0.004). Significance: In this pilot data pre-ictal HRV did not differ in VNS responders compared to VNS non-responders, but showed a significant increase in HF power - a parasympathetic overdrive -in both VNS responders and VNS non-responders. This sudden autonomic imbalance might have an influence on the cardiovascular system in the ictal period. Generalized tonic-clonic seizures are regarded as the main risk factor for SUDEP and severe seizure-induced autonomic imbalance may play a role in the pathophysiological pathway

Pre-ictal heart rate variability alterations in focal onset seizures and response to vagus nerve stimulation

Purpose: Vagus nerve stimulation (VNS) is an effective and well-known treatment for drug resistant epilepsy (DRE) patients since 1997, yet prediction of treatment response before implantation is subject of ongoing research. Neuroimaging and neurophysiological studies investigating the vagal afferent network in resting state documented that differences in between epilepsy patients were related to treatment response. This study investigated whether an event-related parameter, pre-ictal heart rate variability (HRV) is associated with response to VNS therapy. Methods: DRE patients underwent video-electroencephalography (EEG) recording before VNS implantation. HRV parameters (time, non-linear and frequency domain) were assessed for every seizure during two 10 min time frames: baseline (60 min before seizure onset) and pre-ictal (10 min before seizure onset). Pre-ictal HRV parameter alterations were correlated with VNS response after one year of VNS therapy and seizure characteristics (temporal/extratemporal, left/right or bilateral). Results: 104 seizures from 22 patients were evaluated. Eleven patients were VNS responders with a seizure frequency reduction of > 50 % after one year of VNS. In VNS responders no changes in HRV parameters were found while in VNS non-responders the time domain and non-linear HRV variables decreased significantly (p = 0.024, p = 0.005, p = 0.005) during the pre-ictal time frame. 10/11 VNS non-responders had a seizure lateralization to the left compared to 4/11 VNS responders. Conclusion: VNS non-responders were characterized by a significant decrease of pre-ictal HRV (time domain/nonlinear variables) suggesting a sudden autonomic imbalance probably due to an impaired central autonomic function that makes it at the same time unlikely to respond to VNS

Epilepsy surgery: diagnosis, techniques, outcome

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