Faycal El Majdoub

Pineal Parenchymal Tumors

Purpose:To evaluate the efficacy of interstitial radiosurgery (IRS) for pineal parenchymal tumors (PPTs).Patients and Methods:18 consecutively admitted patients (twelve male and six female, age range 6–68 years, median age 34 years) with PPTs (eight pineocytomas, ten malignant PPTs) were treated at the authors’ institution with IRS using stereotactically guided iodine-125 seed implantation (125I-IRS) as either primary or salvage therapy. The cumulative tumor surface dose ranged from 40 to 64 Gy. Adjuvant radiotherapy of the whole brain or the craniospine was done in patients with grade III and grade IV PPT. The median follow-up period was 57.4 months (range 6–134 months).Results:Overall actuarial 5- and 8-year survival rates after IRS were 100% and 86% for pineocytomas, and the overall actuarial 5-year survival rate was 78% for high-grade PPTs. Follow-up magnetic resonance imaging showed complete remission in 72% (13/18) and partial remission in 28% (5/18) of the cases. One patient developed an out-of-field relapse 4 years after partial remission of a pineocytoma, which had already been treated with IRS. There was no treatment-related mortality. Treatment-related morbidity occurred in two patients only.Conclusion:This study indicates that stereotactic 125I-IRS for the management of PPTs is quite efficient and safe. Due to the low rate of side effects, IRS may develop into an attractive alternative to microsurgery in de novo diagnosed pineocytomas. In malignant PPTs, IRS may be routinely applied in a multimodality treatment schedule supplementary to conventional irradiation.ZusammenfassungZiel:Die Wirksamkeit der stereotaktischen interstitiellen Radiochirurgie (IRS) zur Behandlung von Pinealisparenchymtumoren (PPTs) wurde analysiert.Patienten und Methodik:18 Patienten (zwölf männlich und sechs weiblich, Alter 6–68 Jahre, medianes Alter 34 Jahre) mit einem PPT (acht Pineozytome, zehn maligne PPTs) wurden in der Klinik der Autoren durch eine stereotaktisch geführte interstitielle Radiochirurgie mittels Implantation von Jod-125-Seeds (125I-IRS) behandelt. Die Behandlung erfolgte entweder als Primar- oder als Salvage-Therapie. Die kumulative Tumoroberflächendosis variierte von 40 bis 64 Gy. Adjuvante Ganzhirnbestrahlung oder Bestrahlung der Wirbelsäule wurde bei den Patienten mit malignen PPTs durchgeführt. Die mediane Nachbeobachtungszeit betrug 57,4 Monate (6–134 Monate).Ergebnisse:Die 5- und 8-Jahres-Uberlebensraten nach IRS für Pineozytome betrugen 100% bzw. 86%, und die 5-Jahres-Uberlebensrate nach IRS für die höhergradigen PPTs lag bei 78%. Eine komplette Remission wurde in 72% der Fälle (13/18) und eine partielle Remission in 28% der Fälle (5/18) erzielt. Ein Patient entwickelte 4 Jahre nach partieller Remission eines Pineozytoms ein „out-of-field“-Rezidiv. Dieses Rezidiv wurde ebenfalls mittels stereotaktisch geführter IRS behandelt. Es wurde keine behandlungsbedingte Mortalität beobachtet. Eine behandlungsbedingte Morbidität trat bei zwei Patienten auf.Schlussfolgerung:Die Studie zeigt, dass die Behandlung von PPTs durch stereotaktisch geführte 125I-IRS sicher und effektiv ist. Aufgrund der geringen Nebenwirkungen kann sich diese Behandlung zu einer guten Alternative zur Mikrochirurgie bei de novo diagnostizierten Pineozytomen entwickeln. Bei malignen PPTs kann diese Methode als Ergänzung in ein multimodales Behandlungskonzept einbezogen werden.

Stereotactic interstitial radiosurgery for intracranial Rosai-Dorfman disease

Background:Rosai-Dorfman disease is an idiopathic, histoproliferative disorder characterized by massive painless lymphadenopathy. The favorable treatment of Rosai-Dorfman disease affecting the central nervous system is surgical resection. Histological and immunohistochemical confirmation is essential for a definitive diagnosis.Case Report:The authors report on a 10-year-old patient with Rosai-Dorfman disease of the central nervous system who presented with increased intracranial pressure. She was treated by stereotactic interstitial irradiation using iodine-125 seeds (interstitial radiosurgery).Result:Stereotactic surgery was performed without complications. The patient recovered well to a normal neurologic status. MR images showed a complete remission 49 months after treatment.Conclusion:The presented case demonstrates the high efficacy and safety of interstitial irradiation for intracranial Rosai-Dorfman disease. Hence, interstitial radiosurgery could be an appropriate therapeutic option for high-risk resectable intracranial Rosai-Dorfman disease.Hintergrund:Das Rosai-Dorfman-Syndrom ist eine idiopathische, proliferative Erkrankung, welche durch eine schmerzlose Lymphknotenschwellung charakterisiert ist. Bei Befall des zentralen Nervensystems ist die mikrochirurgische Resektion die Therapie der ersten Wahl. Die histologische und immunhistochemische Analyse ist entscheidend für die definitive Diagnose.Fallbericht:Die Autoren berichten über eine 10-jährige Patientin mit erhöhten Hirndruckzeichen und einem zerebralen Rosai-Dorfman-Syndrom. Primär wurde eine stereotaktisch geführte interstitielle Brachytherapie mit Jod-125-Seeds durchgeführt.Ergebnis:Die Behandlung konnte ohne Komplikationen durchgeführt werden. Der neurologische Zustand normalisierte sich. MRT-Veraufskontrollen zeigten 49 Monate nach der Behandlung eine komplette Tumorremission.Schlussfolgerung:Der vorliegende Fall veranschaulicht die Effizienz der stereotaktisch geführten interstitiellen Seedbestrahlung zur Behandlung eines intrakraniellen Rosai-Dorfman-Syndroms und sollte insbesondere bei inoperablen Tumoren als Therapieoption berücksichtigt werden.

Tractography-Guided Stimulation of Somatosensory Fibers for Thalamic Pain Relief

Background: The spinothalamocortical tract (STC) is seen as a neural tract responsible for or involved in the generation or transmission of thalamic pain. Either the thalamus itself or the posterior limb of the internal capsule (PLIC) are targets for deep brain stimulation (DBS) in patients with thalamic pain, but due to its low contrast, conventional MRI cannot visualize the STC directly. Objectives: To show the feasibility of integrating diffusion tensor imaging-based tractography into the stereotactic treatment planning for identification of an object-oriented lead trajectory that allows STC-DBS with multiple electrode contacts. Methods: Diffusion tensor imaging was performed in 4 patients with thalamic pain. The STC was modeled and integrated into the stereotactic treatment planning for DBS. DBS-lead implantation was done according to trajectory planning along the modeled STC at the level of the PLIC. Results: After implantation, electrode stimulation was possible over a length of more than 20 mm with a tractography-based trajectory along the PLIC part of the STC. After a follow-up of 12 months, pain relief of more than 40% was achieved in 3 of 4 patients with rating on a visual analogue scale. In 1 patient, stimulation failed to reach any long-lasting positive effects. Conclusions: Integrating tractography data into stereotactic planning of DBS in thalamic pain is technically feasible. It can be used to identify a lead trajectory that allows for multiple contact stimulation along the STC at the level of the PLIC. Due to long-lasting positive stimulation effect, tractography-guided stimulation of sensory fibers seems to be beneficial for thalamic pain relief.

Deep brain stimulation in the ventrolateral thalamus/subthalamic area in dystonia with head tremor

Pallidal deep brain stimulation (GPi‐DBS) effectively ameliorates idiopathic dystonia, although approximately 15% of patients respond insufficiently. Although various thalamic and subthalamic targets have been suggested for dystonic tremor, no systematic studies have been published on thalamic DBS in dystonic tremor. We assessed the effect of thalamic/subthalamic area DBS (Th‐DBS) on dystonic head tremor and dystonia in a single‐blind design.

Stereotactic LINAC-Radiosurgery for Glomus Jugulare Tumors: A Long-Term Follow-Up of 27 Patients

Background The optimal treatment of glomus jugulare tumors (GJTs) remains controversial. Due to the critical location, microsurgery still provides high treatment-related morbidity and a decreased quality of life. Thus, we performed stereotactical radiosurgery (SRS) for the treatment of GJTs and evaluated the long-term outcome. Methods Between 1991 and 2011, 32 patients with GJTs underwent SRS using a linear accelerator (LINAC) either as primary or salvage therapy. Twenty-seven patients (median age 59.9 years, range 28.7–79.9 years) with a follow-up greater than five years (median 11 years, range 5.3–22.1 years) were selected for retrospective analysis. The median therapeutic single dose applied to the tumor surface was 15 Gy (range 11–20 Gy) and the median tumor volume was 9.5 ml (range 2.8–51 ml). Results Following LINAC-SRS, 10 of 27 patients showed a significant improvement of their previous neurological complaints, whereas 12 patients remained unchanged. Five patients died during follow-up due to old age or other, not treatment-related reasons. MR-imaging showed a partial remission in 12 and a stable disease in 15 patients. No tumor progression was observed. The actuarial overall survival rates after five, ten and 20 years were 100%, 95.2% and 79.4%, respectively. Conclusions Stereotactic LINAC-Radiosurgery can achieve an excellent long-term tumor control beside a low rate of morbidity in the treatment of GJTs. It should be considered as an alternative therapy regime to surgical resection or fractionated external beam radiation either as primary, adjuvant or salvage therapy.

Occurrence and recurrence of spontaneous chronic subdural haematoma is associated with a factor XIII deficiency

OBJECTIVE In some patients, chronic subdural haematoma (cSDH) appears to occur spontaneously with frequent re-bleeding events. The pathophysiology of this phenomenon is still poorly understood. Because coagulation factor XIII (FXIII) is known to be involved in vascular integrity, endothelial barrier function and wound healing, we evaluated the role of FXIII in spontaneous cSDH. METHODS We prospectively scrutinised the origin of cSDH in 117 patients and identified a subgroup of patients suffering from spontaneous cSDH who were included in this study. We analysed the plasma activity of FXIII and standard coagulation parameters and compared these data to age- and sex-matched healthy controls. We assessed the occurrence of re-bleeding events using clinical and imaging data and compared FXIII activity in patients with and without re-bleeding events. RESULTS Out of 117 cSDH patients, 18 individuals suffered from spontaneous cSDH in this study. The patients with spontaneous cSDH showed significantly lower FXIII activity than the control group (65% [52.75, 80.25] (median [IQR]) vs. 93% [81, 111], P=0.001), whereas standard coagulation parameters did not differ significantly between the groups. Six patients developed re-bleeding events after haematoma evacuation, and these patients expressed significantly lower FXIII activity compared to the other 12 patients (47.5% [33.5, 64] vs. 78.5% [58, 87], P=0.005). The patient group with FXIII≤68.5% differed significantly from the group with FXIII>68.5% when categorised by the occurrence of re-bleeding events (n=6/9 vs. n=0/9, P=0.009). This cut-off value predicted the re-bleeding events with a sensitivity of 100% and a specificity of 75% (positive predictive value: 66%, negative predictive value: 100%). CONCLUSION FXIII deficiency may play a pathophysiological role in spontaneous cSDH, so we suggest investigating FXIII activity because it may predict re-bleeding events after treatment. In individuals with considerably low FXIII activity, FXIII substitution may mitigate the chronic nature of this disease.

Pitfalls and fallacies interfering with correct identification of embryonic stem cells implanted into the brain after experimental traumatic injury

Cell-therapy was proposed to be a promising tool in case of death or impairment of specific cell types. Correct identification of implanted cells became crucial when evaluating the success of transplantation therapy. Various methods of cell labeling have been employed in previously published studies. The use of intrinsic signaling of green fluorescent protein (GFP) has led to a well known controversy in the field of cardiovascular research. We encountered similar methodological pitfalls after transplantation of GFP-transfected embryonic stem cells into rat brains following traumatic brain injury (TBI). As the identification of implanted graft by intrinsic autofluorescence failed, anti-GFP labeling coupled to fluorescent and conventional antibodies was needed to visualize the implanted cells. Furthermore, different cell types with strong intrinsic autofluorescence were found at the sites of injury and transplantation, thus mimicking the implanted stem cells. GFP-positive stem cells were correctly localized, using advanced histological techniques. The activation of microglia/macrophages, accompanying the transplantation post TBI, was shown to be a significant source of artefacts, interfering with correct identification of implanted stem cells. Dependent on the strategy of stem cell tracking, the phagocytosis of implanted cells as observed in this study, might also impede the interpretation of results. Critical appraisal of previously published data as well as a review of different histological techniques provide tools for a more accurate identification of transplanted stem cells.

Intracranial Ependymoma: Long-Term Results in a Series of 21 Patients Treated with Stereotactic 125Iodine Brachytherapy

Background We evaluated the long-term outcome in patients harboring intracranial ependymomas treated with interstitial brachytherapy (IBT). Methods Twenty-one patients (M/F = 9/12; median age: 29 years; range: 8–70 years), diagnosed with intracranial ependymoma (1 WHO I, 11 WHO II, 9 WHO III) were treated with IBT using stereotactically implanted 125Iodine seeds between 1987 and 2010, either primarily, as adjuvant therapy following incomplete resection, or as salvage treatment upon tumor recurrence. Sixteen of 21 patients underwent microsurgical resection prior to IBT; in 5 patients, IBT was performed primarily after stereotactic biopsy for histological diagnosis. The cumulative tumor surface dose ranged from 50–65 Gy treating a median tumor volume of 3.6 ml (range, 0.3–11.6 ml). A median follow-up period of 105.3 months (range, 12.7–286.2 months) was evaluated. Results Actuarial 2-, 5- and 10-years overall- and disease-specific survival rates after IBT were each 90% and 100% at all times for ependymomas WHO I/II, for anaplastic ependymomas WHO III 100%, 100%, 70% and 100%, 100%, 86%, respectively. The neurological status of seven patients improved, while there was no change in 12 and deterioration in 2 patients, respectively. Follow-up MR images disclosed a complete tumor remission in 3, a partial remission in 12 and a stable disease in 6 patients. Treatment-associated morbidity only occurred in a single patient. Conclusions This study shows that stereotactic IBT for intracranial ependymomas is safe and can provide a high degree of local tumor control. Due to the low rate of side effects, IBT may evolve into an attractive alternative to microsurgery in ependymomas located in eloquent areas or as a salvage treatment.

Intensity-based 2D 3D registration for lead localization in robot guided deep brain stimulation.

Intraoperative assessment of lead localization has become a standard procedure during deep brain stimulation surgery in many centers, allowing immediate verification of targeting accuracy and, if necessary, adjustment of the trajectory. The most suitable imaging modality to determine lead positioning, however, remains controversially discussed. Current approaches entail the implementation of computed tomography and magnetic resonance imaging. In the present study, we adopted the technique of intensity-based 2D 3D registration that is commonly employed in stereotactic radiotherapy and spinal surgery. For this purpose, intraoperatively acquired 2D x-ray images were fused with preoperative 3D computed tomography (CT) data to verify lead placement during stereotactic robot assisted surgery. Accuracy of lead localization determined from 2D 3D registration was compared to conventional 3D 3D registration in a subsequent patient study. The mean Euclidian distance of lead coordinates estimated from intensity-based 2D 3D registration versus flat-panel detector CT 3D 3D registration was 0.7 mm  ±  0.2 mm. Maximum values of these distances amounted to 1.2 mm. To further investigate 2D 3D registration a simulation study was conducted, challenging two observers to visually assess artificially generated 2D 3D registration errors. 95% of deviation simulations, which were visually assessed as sufficient, had a registration error below 0.7 mm. In conclusion, 2D 3D intensity-based registration revealed high accuracy and reliability during robot guided stereotactic neurosurgery and holds great potential as a low dose, cost effective means for intraoperative lead localization.

Deep Brain Stimulation of Medial Dorsal and Ventral Anterior Nucleus of the Thalamus in OCD: A Retrospective Case Series.

Background The current notion that cortico-striato-thalamo-cortical circuits are involved in the pathophysiology of obsessive-compulsive disorder (OCD) has instigated the search for the most suitable target for deep brain stimulation (DBS). However, despite extensive research, uncertainty about the ideal target remains with many structures being underexplored. The aim of this report is to address a new target for DBS, the medial dorsal (MD) and the ventral anterior (VA) nucleus of the thalamus, which has thus far received little attention in the treatment of OCD. Methods In this retrospective trial, four patients (three female, one male) aged 31–48 years, suffering from therapy-refractory OCD underwent high-frequency DBS of the MD and VA. In two patients (de novo group) the thalamus was chosen as a primary target for DBS, whereas in two patients (rescue DBS group) lead implantation was performed in a rescue DBS attempt following unsuccessful primary stimulation. Results Continuous thalamic stimulation yielded no significant improvement in OCD symptom severity. Over the course of thalamic DBS symptoms improved in only one patient who showed “partial response” on the Yale-Brown Obsessive Compulsive (Y-BOCS) Scale. Beck Depression Inventory scores dropped by around 46% in the de novo group; anxiety symptoms improved by up to 34%. In the de novo DBS group no effect of DBS on anxiety and mood was observable. Conclusion MD/VA-DBS yielded no adequate alleviation of therapy-refractory OCD, the overall strategy in targeting MD/VA as described in this paper can thus not be recommended in DBS for OCD. The magnocellular portion of MD (MDMC), however, might prove a promising target in the treatment of mood related and anxiety disorders.