Transnasal transsphenoidal pituitary surgery in a large tertiary hospital, a retrospective study.

OBJECTIVES: Pituitary adenomas (PAs), although being small tumours, can have quite an impact on patients' lives causing hormonal and visual disturbances, for which surgery must be performed. As a large peripheral hospital with specialists in pituitary surgery, an assessment of the efficacy and safety of transnasal transsphenoidal pituitary surgery was made. METHODS: A retrospective analysis of neurosurgical reports as well as pre and postoperative imaging was made to evaluate the presenting symptoms, tumoural variables, peri-operative morbidity, and long-term outcome. RESULTS: This cohort included 105 patients who were operated for PAs over a 9-year period, with a slight male predominance. Adenomas had a mean maximum diameter of almost 25 mm, with one-third of tumours presenting with a Knosp-grade 3 or 4. As expected, most patients presented with either visual (32.4%) or hormonal (40.0%) disturbances. After surgery, 85.3% had complete resolution of visual deficits, and 97.1% had normalisation of hormonal hypersecretion. Postoperative hormonal insufficiency requiring substitution was observed in 43.1% and was significantly more frequent in males and in non-functioning pituitary adenomas (NFAs). Postoperative cerebrospinal fluid (CSF) leakage was observed in 2.9%, and merely one patient developed meningitis. Tumour recurrence was significantly more frequent in patients with partial resection as compared to complete resection (25.6 vs. 7.9%). CONCLUSIONS: This study demonstrates that transnasal transsphenoidal pituitary surgery can be performed safely and effectively in a large non-university hospital, improving visual and/or hormonal disturbances as well as providing long-term tumour control. Patients with larger adenomas are at an increased risk to develop postoperative hypopituitarism.

Altered Circulating Immune Cell Distribution in Traumatic Spinal Cord Injury Patients in Relation to Clinical Parameters.

Following a spinal cord injury (SCI), an inflammatory immune reaction is triggered which results in advanced secondary tissue damage. The systemic post-SCI immune response is poorly understood. This study aimed to extensively analyse the circulating immune cell composition in traumatic SCI patients in relation to clinical parameters. High-dimensional flow cytometry was performed on peripheral blood mononuclear cells of 18 traumatic SCI patients and 18 healthy controls to determine immune cell subsets. SCI blood samples were collected at multiple time points in the (sub)acute (0 days to 3 weeks post-SCI, (s)aSCI) and chronic (6 to >18 weeks post-SCI, cSCI) disease phase. Total and CD4+ T cell frequencies were increased in cSCI patients. Both CD4+ T cells and B cells were shifted towards memory phenotypes in (s)aSCI patients and cSCI patients, respectively. Most profound changes were observed in the B cell compartment. Decreased immunoglobulin (Ig)G+ and increased IgM+ B cell frequencies reflected disease severity, as these correlated with American Spinal Injury Association (ASIA) impairment scale (AIS) scores. Post-SCI B cell responses consisted of an increased frequency of CD74+ cells and CD74 expression level within total B cells and B cell subsets. Findings from this study suggest that post-SCI inflammation is driven by memory immune cell subsets. The increased CD74 expression on post-SCI B cells could suggest the involvement of CD74-related pathways in neuroinflammation following SCI. In addition, the clinical and prognostic value of monitoring circulating IgM+ and IgG+ B cell levels in SCI patients should be further evaluated.

Epidemiology of spinal metastases, metastatic epidural spinal cord compression and pathologic vertebral compression fractures in patients with solid tumors: A systematic review.

Introduction: Spinal metastases (SM) are a frequent complication of cancer and may lead to pathologic vertebral compression fractures (pVCF) and/or metastatic epidural spinal cord compression (MESCC). Based on autopsy studies, it is estimated that about one third of all cancer patients will develop SM. These data may not provide a correct estimation of the incidence in clinical practice. Objective: This systematic review (SR) aims to provide a more accurate estimation of the incidence of SM, MESCC and pVCF in a clinical setting. Methods: We performed a SR of papers regarding epidemiology of SM, pVCF, and MESCC in patients with solid tumors conform PRISMA guidelines. A search was conducted in the PubMed and Web of Science database using the terms epidemiology, prevalence, incidence, global burden of disease, cost of disease, spinal metastas*, metastatic epidural spinal cord compression, pathologic fracture, vertebral compression fracture, vertebral metastas* and spinal neoplasms. Papers published between 1975 and august 2021 were included. Quality was evaluated by the STROBE criteria. Results: While 56 studies were included, none of them reports the actual definition used for MESCC and pVCF, inevitably introducing heterogenity. The overall cumulative incidence of SM and MESCC is 15.67% and 2.84% respectively in patients with a solid tumor. We calculated a mean cumulative incidence in patients with SM of 9.56% (95% CI 5.70%-13.42%) for MESCC and 12.63% (95% CI 7.00%-18.25%) for pVCF. Studies show an important delay between onset of symptoms and diagnosis. Conclusions: While the overall cumulative incidence for clinically diagnosed SM in patients with a solid tumor is 15.67%, autopsy studies reveal that SM are present in 30% by the time they die, suggesting underdiagnosing of SM. Approximately 1 out of 10 patients with SM will develop MESCC and another 12.6% will develop a pVCF. Understanding these epidemiologic data, should increase awareness for first symptoms, allowing early diagnosis and subsequent treatment, thus improving overall outcome.

T3-T4 Disc Herniations: Clinical Presentation, Imaging, and Transaxillary Approach.

OBJECTIVE: To describe a cohort of T3-T4 thoracic disc herniations (TDHs), their clinical and radiologic characteristics, and unique thoracoscopic transaxillary approach (TAA). METHODS: All patients operated on for a T3-T4 TDH with minimal follow-up of 1 year were selected. RESULTS: Eight TAA procedures (6 males and 2 females) were included (1.4%). Six patients reported axial pain, irradiating in 2, 4 sensory changes, 1 objective and 1 merely subjective motor weakness. Only 1 TDH was calcified, none was giant, 2 were accompanied by myelomalacia, and 2 by a small segmental syrinx. A cardiothoracic surgeon helped with exposure through a curved axillary incision using anterior cervical and more recently double-ring wound retractors. All patients were operated on using a 10-mm 30° rigid (three-dimensional) high-definition scope. There were no major complications and a good outcome with symptomatic relief in 7 of 8 patients. CONCLUSIONS: T3-T4 TDHs are infrequent but may be underdiagnosed because they tend to be small and their signs and symptoms may mimic a cervical problem involving the shoulders and even the arms. There may be a male predominance. The TAA is straightforward, safe, efficacious, and well tolerated despite the supposed vulnerability of the upper thoracic spinal cord. Dissection between large crowded subpleural veins characteristic for the upper thoracic spine and ensuring adequate dura decompression when the steep angle may partially obscure the tip of the instruments does require some extra time. Thorough knowledge of the unique anatomy of the upper thorax is mandatory and the assistance of a cardiothoracic surgeon is highly recommended.

Transdural Thoracic Disk Herniation with Longitudinal Slitlike Dural Defect Causing Intracranial Hypotension: Report of 2 Cases.

BACKGROUND: Intracranial hypotension (IH) has a widely variable clinical and radiologic presentation. Secondary IH may be caused by degenerative spine disorders and in particular by thoracic disk herniations (TDHs). METHODS: We present 2 patients with a transdural TDH, a secondary IH, and superficial siderosis in 1. RESULTS: Case 1 presented with headache, cognitive decline, staggering gait, bilateral subdural effusions, cerebral sagging, an extradural spinal cerebrospinal fluid (CSF) collection suggesting secondary IH, and a calcified TDH at T9-T10. Case 2 presented with intermittent pain at the craniocervical junction provoked exclusively by specific physical activities, superficial siderosis mainly in the posterior fossa, an extradural spinal CSF collection, and a calcified TDH at T7-T8 yet no intracranial signs of IH. In both cases, using strict thoracoscopic technique, we removed a transdural TDH and reconstructed an underlying longitudinal slitlike dural defect with smooth lining. Follow-up magnetic resonance imaging scans confirmed a dramatically improved situation without residual extradural intraspinal CSF collection or signs of IH. CONCLUSIONS: This paper adds to the evidence that some cases of IH and even superficial siderosis are caused by transdural erosion of a TDH that may be otherwise asymptomatic. The dura may degenerate due to chronic compression, and a longitudinal slitlike dural defect with smooth lining may develop, causing continuous (Case 1) or intermittent (Case 2) intraspinal CSF leakage. To the best of our knowledge, such dural defects closely resembling the ones observed in idiopathic spinal cord herniation have never been demonstrated on intraoperative endoscopic video in IH patients.

Short-term discontinuation of vagal nerve stimulation alters 18F-FDG blood pool activity: an exploratory interventional study in epilepsy patients.

BACKGROUND: Vagus nerve activation impacts inflammation. Therefore, we hypothesized that vagal nerve stimulation (VNS) influenced arterial wall inflammation as measured by 18F-FDG uptake. RESULTS: Ten patients with left-sided VNS for refractory epilepsy were studied during stimulation (VNS-on) and in the hours after stimulation was switched off (VNS-off). In nine patients, 18F-FDG uptake was measured in the right carotid artery, aorta, bone marrow, spleen, and adipose tissue. Target-to-background ratios (TBRs) were calculated to normalize the respective standardized uptake values (SUVs) for venous blood pool activity. Median values are shown with interquartile range and compared using the Wilcoxon signed-rank test. Arterial SUVs tended to be higher during VNS-off than VNS-on [SUVmax all vessels 1.8 (1.5-2.2) vs. 1.7 (1.2-2.0), p = 0.051]. However, a larger difference was found for the venous blood pool at this time point, reaching statistical significance in the vena cava superior [meanSUVmean 1.3 (1.1-1.4) vs. 1.0 (0.8-1.1); p = 0.011], resulting in non-significant lower arterial TBRs during VNS-off than VNS-on. Differences in the remaining tissues were not significant. Insulin levels increased after VNS was switched off [55.0 pmol/L (45.9-96.8) vs. 48.1 pmol/L (36.9-61.8); p = 0.047]. The concurrent increase in glucose levels was not statistically significant [4.8 mmol/L (4.7-5.3) vs. 4.6 mmol/L (4.5-5.2); p = 0.075]. CONCLUSIONS: Short-term discontinuation of VNS did not show a consistent change in arterial wall 18F-FDG-uptake. However, VNS did alter insulin and 18F-FDG blood levels, possibly as a result of sympathetic activation.

Improved seizure control and regaining cognitive milestones after vagus nerve stimulation revision surgery in Lennox-Gastaut syndrome.

We report a child with Lennox-Gastaut syndrome with an increase in seizure frequency and loss of psychomotor skills due to a disintegrated cervical VNS lead, not detected during standard device monitoring. The lead was completely removed and replaced by a new 303 lead on the same nerve segment. After reinitiating VNS, side effects forced us to switch it off, resulting in immediate seizure recurrence. EEG recording demonstrated a non-convulsive status epilepticus that was halted by reinitiating VNS therapy. Thereafter, he remained seizure free for eight months, and regained psychomotor development.

Elevated inflammatory cytokine expression in CSF from patients with symptomatic thoracic disc herniation correlates with increased pain scores.

BACKGROUND: The pathophysiology of pain in patients with symptomatic thoracic disc herniation (TDH) remains poorly understood. Mere mechanical compression of the spinal cord and/or the exiting nerve root by a prolapsed disc cannot explain the pathogenesis of pain in all cases. Previous studies report a direct correlation between the levels of proinflammatory cytokines in disc biopsies and the severity of leg pain in patients with lumbar disc herniation. A similar correlation in patients with TDH has not been investigated. PURPOSE: To correlate the cerebrospinal fluid (CSF) expression of cytokines and pain-related amino acids with preoperative pain scores in patients with symptomatic TDH. STUDY DESIGN: A prospective human study of CSF samples and clinical outcome scores. METHODS: Using enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC), we determined inflammatory cytokine levels (TNF-α, IL-1ß, and IL-10) and amino acid levels (glutamate, aspartate, gamma-aminobutyric acid, glycine, and arginine) in CSF samples from 10 patients with TDH and 10 control subjects who did not suffer an inflammatory disease nor pain related to spinal cord compression and subsequently correlated these levels with preoperative pain scores. Differences between both groups were evaluated by a Mann-Whitney U test. In order to estimate the correlation between cytokine or amino acid expression and pain scores, data were analyzed using a linear regression analysis. RESULTS: No inflammatory cytokines were found in CSF samples from control subjects, whereas TNF-α, IL-1ß, and IL-10 were detectable by ELISA in all CSF samples from patients with TDH. TNF-α and IL-10 but not IL-1ß levels moderately correlated with preoperative pain scores. Elevated TNF-αlevels positively correlated with high pain scores; elevated IL-10 levels negatively correlated with high pain scores. Amino acids were detectable in all samples from both groups. There were no significant differences between the groups in any of the amino acids measured with HPLC. CONCLUSION: Increased proinflammatory cytokine expression is associated with elevated pain scores in patients with symptomatic TDH. On the other hand, there is no conclusive correlation between the intensity of pain and the local or systemic presence of amino acids associated with pain transmission.

Multilayer Dura Reconstruction After Thoracoscopic Microdiscectomy: Technique and Results.

BACKGROUND: Anterior transthoracic approaches, including thoracoscopic microdiscectomy (TMD), are the preferred techniques for central, broad-based, calcified thoracic disc herniations (TDHs). Dural defects due to manipulation or transdural extension may create a potentially life-threatening subarachnoid-pleural fistula. We evaluate a fast, sutureless technique for reconstructing the dura. METHODS: We analyzed 476 anterior transthoracic approaches for TDHs (437 TMDs, 31 mini-thoracotomies, 7 transaxillary approaches, and 1 sternotomy). Dural defects were closed using an onlay dura substitute, fibrin glue, an autologous fat graft, and another layer of fibrin glue topped by an absorbable gelatin sponge. A chest tube was used to provide a water seal, and the use of external lumbar drains (ELDs) was discontinued in recent years. RESULTS: We encountered 35 dural defects (7.35%), including 27 in 279 procedures (9.67%) in the first 10 years and 8 in 197 (4.06%) in the past 6 years. Five defects were large, 23 were relatively small, and 5 had an intact arachnoid layer, likely preventing cerebrospinal fluid (CSF) egress. Two CSF leaks in the early series were overlooked intraoperatively; 1 patient died following widespread cortical venous thrombosis, whereas the other merely had a headache that disappeared within 1 week. Overall, an ELD was inserted in 3 of 5 large defects and in 17 of 23 small defects; however, in the past 6 years, an ELD was inserted in no large defects and in only 1 of 5 small defects. The technique was successful in all but 1 patient, who underwent reoperation using a larger fat graft. CONCLUSIONS: Dural defects encountered during anterior transthoracic approaches to TDHs can be reconstructed endoscopically, while avoiding the use of an ELD in most cases.

Anterior Transthoracic Surgery with Motor Evoked Potential Monitoring for High-Risk Thoracic Disc Herniations: Technique and Results.

OBJECTIVE: To present our experience with anterior transthoracic surgery for high-risk thoracic disc herniations (TDHs) using motor evoked potential monitoring (MEPm). METHODS: We estimated surgical risk based on clinical and radiologic characteristics, including anteroposterior (AP) spinal canal occupation (SCO), AP spinal cord compression (SCC), residual AP spinal cord diameter (RSCD), and intramedullary signal changes (ISC). We analyzed Anand, ASIA, and Nurick scores, anesthesiologic, neurophysiological, and surgical reports. We considered >50% MEP signal deterioration significant. RESULTS: Out of 435 anterior transthoracic procedures, 77 concerned high-risk TDH(s): 69 single-level, 8 multilevel, 61 with clinical myelopathy, 6 with merely ISC. Mean SCO and SCC were 55.4% and 54.0% for single-level, 31.8% and 33.9% for multilevel cases. ISC were present in 64% of single-level and 50% of multilevel cases, calcifications in 87% of single-level and 84% of multilevel TDHs. We initially performed 23 mini-transthoracic approaches (mini-TTAs) and 24 thoracoscopic microdiscectomies (TMDs), more recently 29 TMDs (23 giant TDHs) and 1 transaxillary mini-TTA. Overall, 72 patients had reliable MEP signals. Isolated lower extremity MEP signal deteriorations (n = 21) correlated with maximal TDH AP diameter, SCO, SCC, and ISC. ASIA and Nurick scores improved in 45% and 66% respectively. One patient became paraplegic. MEP signal deterioration had 100% sensitivity, 75% specificity, and 19% positive predictive value during and 44% at the end of surgery. CONCLUSIONS: Maximal TDH AP diameter, SCO, SCC, (sub)total calcification, and ISC correlate with lower extremity MEP signal deterioration. In experienced hands, TMD with MEPm support is a safe, efficient procedure for high-risk TDHs.

Vagus nerve stimulation lead removal or replacement: surgical technique, institutional experience, and literature overview.

BACKGROUND: With the growing use of vagus nerve stimulation (VNS) as a treatment for refractory epilepsy, there is a growing demand for complete removal or replacement of the VNS system. We evaluate the safety and efficacy of complete removal or replacement of the VNS system and provide an extensive description of our surgical technique. METHODS: We retrospectively reviewed our patient registry for all VNS surgeries performed between January 2007 (the year of our first complete removal) and May 2014. In order to assess patient satisfaction, a written questionnaire was sent to patients or their caregivers. Additionally, we reviewed all literature on this topic. RESULTS: The VNS system was completely removed in 22 patients and completely replaced in 13 patients. There were no incomplete removals. Revision surgery was complicated by a small laceration of the jugular vein in two patients and by vocal cord paralysis in one patient. Seizure frequency was unaltered or improved after revision surgery. Electrode-related side effects all improved after revision surgery. Twenty-one studies reported a total of 131 patients in whom the VNS system was completely removed. In 95 patients, the system was subsequently replaced. The most frequently reported side effect was vocal cord paresis, which occurred in four patients. CONCLUSIONS: Complete removal or replacement of the VNS system including lead and coils is feasible and safe. Although initial results seem promising, further research and longer follow-up are needed to assess whether lead replacement may affect VNS effectiveness.

Crippling upper back pain after whiplash and other motor vehicle collisions caused by thoracic disc herniations: report of 10 cases.

STUDY DESIGN: Retrospective analysis of a prospectively collected database of thoracoscopic microdiscectomies performed at the Maastricht University Medical Center. OBJECTIVE: Many victims of a motor vehicle collision (MVC) report crippling upper back pain resistant to conservative treatment. Although this pain is often regarded as nonspecific or related to a whiplash type of cervical spine injury, this study demonstrates it may be caused by a thoracic disc herniation. SUMMARY OF BACKGROUND DATA: Recent literature on bodily pain after whiplash and other MVCs has shown that most patients rather than pain confined to the posterior neck area (0.4%) report pain in multiple body areas, the most frequently affected region being the posterior trunk region, including the posterior neck, posterior shoulder, upper back, lumbar, and buttock areas. Although several patterns determining most variance in pain localization in these patients have been identified, different pathoanatomical and pathophysiological substrates underlying these patterns have not been identified. However, a high incidence of posterior shoulder pain (75%) and upper back pain (66%) is striking. METHODS: In a series of 326 thoracoscopic microdiscectomies for one or more symptomatic TDHs, we identified 10 patients whose symptoms had started after an MVC. We analyzed their clinical and radiological presentation, intraoperative findings, and postoperative outcome. RESULTS: All patients (7 females, 3 males; age, 26-58 yr, including 4 with typical whiplash complaints) had reported substantial improvement of their complaints except for their upper back pain. Most hernias were small or medium sized (n = 8), at the apex of the kyphotic curvature (n = 6), and to some extent calcified (n = 7). One year postoperatively, results were excellent in 7, good in 2, and poor in 1. CONCLUSION: Crippling upper back pain after MVCs may be caused by a (previously asymptomatic) thoracic disc herniation. Although the exact pathophysiological mechanism has not been elucidated, results after thoracoscopic microdiscectomy are quite encouraging.

Vagus nerve stimulation increases energy expenditure: relation to brown adipose tissue activity.

BACKGROUND: Human brown adipose tissue (BAT) activity is inversely related to obesity and positively related to energy expenditure. BAT is highly innervated and it is suggested the vagus nerve mediates peripheral signals to the central nervous system, there connecting to sympathetic nerves that innervate BAT. Vagus nerve stimulation (VNS) is used for refractory epilepsy, but is also reported to generate weight loss. We hypothesize VNS increases energy expenditure by activating BAT. METHODS AND FINDINGS: Fifteen patients with stable vns therapy (age: 45 ± 10 yrs; body mass index; 25.2 ± 3.5 kg/m(2)) were included between January 2011 and June 2012. Ten subjects were measured twice, once with active and once with inactivated VNS. Five other subjects were measured twice, once with active VNS at room temperature and once with active VNS under cold exposure in order to determine maximal cold-induced BAT activity. BAT activity was assessed by 18-Fluoro-Deoxy-Glucose-Positron-Emission-Tomography-and-Computed-Tomography. Basal metabolic rate (BMR) was significantly higher when VNS was turned on (mean change; +2.2%). Mean BAT activity was not significantly different between active VNS and inactive VNS (BAT SUV(Mean); 0.55 ± 0.25 versus 0.67 ± 0.46, P = 0.619). However, the change in energy expenditure upon VNS intervention (On-Off) was significantly correlated to the change in BAT activity (r = 0.935, P<0.001). CONCLUSIONS: VNS significantly increases energy expenditure. The observed change in energy expenditure was significantly related to the change in BAT activity. This suggests a role for BAT in the VNS increase in energy expenditure. Chronic VNS may have a beneficial effect on the human energy balance that has potential application for weight management therapy. TRIAL REGISTRATION: The study was registered in the Clinical Trial Register under the ClinicalTrials.gov Identifier NCT01491282.

Diagnostic radiation exposure in children with spinal dysraphism: an estimation of the cumulative effective dose in a cohort of 135 children from The Netherlands.

OBJECTIVE: Based on the assumption that children with spinal dysraphism are exposed to a large amount of ionising radiation for diagnostic purposes, our objective was to estimate this exposure, expressed in cumulative effective dose. DESIGN: Retrospective cohort study. SETTINGS: The Netherlands. PATIENTS: 135 patients with spinal dysraphism and under 18 years of age treated at our institution between 1991 and 2010. RESULTS: A total of 5874 radiological procedures were assessed of which 2916 (49.6%) involved ionising radiation. Mean cumulative effective dose of a child with spinal dysraphism during childhood was 23 mSv, while the individual cumulative effective dose ranged from 0.1 to 103 mSv. Although direct radiography accounted for 81.7% of examinations, the largest contributors to the cumulative effective dose were fluoroscopic examinations (40.4% of total cumulative effective dose). CONCLUSIONS: Exposure to ionising radiation and associated cancer risk were lower than expected. Nevertheless, the use of ionising radiation should always be justified and the medical benefits should outweigh the risk of health detriment, especially in children.

Infections of the spinal subdural space in children: a series of 11 contemporary cases and review of all published reports. A multinational collaborative effort.

INTRODUCTION: Positioned anatomically between the spinal epidural space and the intramedullary compartment, the spinal subdural space remains the least common area of localized infection in the central nervous system. Infectious processes of the subdural spinal space include subdural spinal empyema, subdural spinal abscess, infected spinal subdural cyst, and infectious spinal subdural cyst. To date, there has been no systematic review of these entities in children, with the cumulative knowledge of the pathophysiologic, microbiologic, and demographic characteristics of these infections relegated solely to few small series and case reports. METHODS: A series of 11 recent cases culled from the collaboration of international authors are presented. In addition, an exhaustive MEDLINE search and manual review of the international literature was performed, identifying a total of 73 cases of spinal subdural infections in patients under the age of 21. Data of interest include the age, sex, signs, and symptoms at presentation, spinal location of infection, presence of spinal dysraphism, and other comorbidities, offending organism, treatment, outcome, and follow-up. RESULTS: Patients ages ranged from 4 weeks to 20 years (mean, 6.5 years). Males outnumbered females by a ratio of 2:1. Over half (53 %) of spinal subdural infections in children were associated with spinal dysraphism or other congenital abnormalities of the spine. The commonest organism to infect the spinal subdural space in children is mycobacterium tuberculosis and the thoracic spinal region was most commonly infected. CONCLUSIONS: The disease is usually treated surgically, although a more expectant approach consisting of antibiotics and observation has also been proposed.

Behavioural and cognitive effects during vagus nerve stimulation in children with intractable epilepsy - a randomized controlled trial.

BACKGROUND/AIMS: In addition to effects on seizure frequency in intractable epilepsy, multiple studies report benefits of vagus nerve stimulation (VNS) on behavioural outcomes and quality of life. The present study aims to investigate the effects of VNS on cognition, mood in general, depression, epilepsy-related restrictions and psychosocial adjustment in children with intractable epilepsy, as well as the relation between these effects and seizure reduction. METHODS: We conducted a randomized, active-controlled, double-blinded, add-on study in 41 children (age 4-18) with medically refractory epilepsy. We performed cognitive and behavioural testing at baseline (12 weeks), at the end of the blinded phase (20 weeks) in children receiving either high-output or low-output (active control) stimulation, and at the end of the open label phase (19 weeks) with all children receiving high-output stimulation. Seizure frequency was recorded using seizure diaries. RESULTS: VNS did not have a negative effect on cognition nor on psychosocial adjustment. At the end of the follow-up phase we noted an improvement of mood in general and the depression subscale for the entire group, unrelated to a reduction of seizure frequency. At the end of the blinded phase a ≥50% reduction of seizure frequency occurred in 16% of the high-stimulation group and 21% of the low-stimulation group. At the end of the open-label follow-up phase, 26% of the children experienced a seizure frequency reduction of 50% or more (responders). CONCLUSIONS: VNS has additional beneficial effects in children with intractable epilepsy. As opposed to anti-epileptic drugs, there are no negative effects on cognition. Moreover, we observed an improvement of mood in general and depressed feelings in particular, irrespective of a reduction in seizure frequency. These beneficial effects should be taken into account when deciding whether to initiate or continue VNS treatment in these children.

Vagus nerve stimulation in children with intractable epilepsy: a randomized controlled trial.

AIM: The aim of this study was to evaluate the effects of vagus nerve stimulation (VNS) in children with intractable epilepsy on seizure frequency and severity and in terms of tolerability and safety. METHOD: In this study, the first randomized active controlled trial of its kind in children, 41 children (23 males; 18 females; mean age at implantation 11y 2mo, SD 4y 2mo, range 3y 10mo-17y 8mo) were included. Thirty-five participants had localization-related epilepsy (25 symptomatic; 10 cryptogenic), while six participants had generalized epilepsy (four symptomatic; two idiopathic). During a baseline period of 12 weeks, seizure frequency and severity were recorded using seizure diaries and the adapted Chalfont Seizure Severity Scale (NHS3), after which the participants entered a blinded active controlled phase of 20 weeks. During this phase, half of the participants received high-output VNS (maximally 1.75mA) and the other half received low-output stimulation (0.25mA). Finally, all participants received high-output stimulation for 19 weeks. For both phases, seizure frequency and severity were assessed as during the baseline period. Overall satisfaction and adverse events were assessed by semi-structured interviews. RESULTS: At the end of the randomized controlled blinded phase, seizure frequency reduction of 50% or more occurred in 16% of the high-output stimulation group and in 21% of the low-output stimulation group (p=1.00). There was no significant difference in the decrease in seizure severity between participants in the stimulation groups. Overall, VNS reduced seizure frequency by 50% or more in 26% of participants at the end of the add-on phase The overall seizure severity also improved (p<0.001). INTERPRETATION: VNS is a safe and well-tolerated adjunctive treatment of epilepsy in children. Our results suggest that the effect of VNS on seizure frequency in children is limited. However, the possible reduction in seizure severity and improvement in well-being makes this treatment worth considering in individual children with intractable epilepsy.