Role of surgery in the treatment of pediatric low-grade glioma with various degrees of brain stem involvement.

OBJECTIVE: Posterior fossa pediatric low-grade glioma involving the brainstem and cerebellar peduncles (BS-pLGG) are a subgroup with higher risks at surgery. We retrospectively analyzed the role of surgery in the interdisciplinary armamentarium of treatment options in our institutional series of BS-pLGG with various degrees of brainstem involvement. MATERIAL AND METHODS: We analyzed data of 52 children with BS-pLGG after surgical intervention for clinical/molecular characteristics, neurological outcome, factors influencing recurrence/progression pattern, and tumor volumetric analysis of exclusively surgically treated patients to calculate tumor growth velocity (TGV). Tumors were stratified according to primary tumor origin in four groups: (1) cerebellar peduncle, (2) 4th ventricle, (3) pons, (4) medulla oblongata. RESULTS: The mean FU was 6.44 years. Overall survival was 98%. The mean PFS was 34.07 months. Two patients had biopsies only. Fifty-two percent of patients underwent remission or remained in stable disease (SD) after initial surgery. Patients with progression underwent further 23 resections, 15 chemotherapies, 4 targeted treatments, and 2 proton radiations. TGV decreased after the 2nd surgery compared to TGV after the 1st surgery (p < 0.05). The resection rates were significantly higher in Groups 1 and 2 and lowest in medulla oblongata tumors (Group 4) (p < 0.05). More extended resections were achieved in tumors with KIAA1549::BRAF fusion (p = 0.021), which mostly occurred in favorable locations (Groups 1 and 2). Thirty-one patients showed postoperatively new neurological deficits. A total of 27/31 improved within 12 months. At the end of FU, 6% had moderate deficits, 52% had mild deficits not affecting activities, and 36% had none. Fifty percent of patients were free of disease or showed remission, 38% were in SD, and 10% showed progression. CONCLUSION: The first surgical intervention in BS-pLGG can control disease alone in overall 50% of cases, with rates differing greatly according to location (Groups 1 > 2 > 3 > 4), with acceptable low morbidity. The second look surgery is warranted except in medullary tumors. With multimodality treatments almost 90% of patients can obtain remission or stable disease after > 5 years of follow-up. An integrated multimodal and multidisciplinary approach aiming at minimal safe residual disease, combining surgery, chemo-, targeted therapy, and, as an exception, radiation therapy, is mandatory.

Effects of anterior thalamic nucleus DBS on interictal heart rate variability in patients with refractory epilepsy.

OBJECTIVE: Heart rate variability (HRV) changes were investigated by several studies after resective epilepsy surgery/vagus nerve stimulation. We examined anterior thalamic nucleus (ANT)-deep brain stimulation (DBS) effects on HRV parameters. METHODS: We retrospectively analyzed 30 drug-resistant epilepsy patients' medical record data and collected electrocardiographic epochs recorded during video- electroencephalography monitoring sessions while awake and during N1- or N2-stage sleep pre-DBS implantation surgery, post-surgery but pre-stimulation, and after stimulation began. RESULTS: The mean square root of the mean squared differences between successive RR intervals and RR interval standard deviation values differed significantly (p < 0.05) among time-points, showing increased HRV post-surgery. High (0.15-0.4 Hz) and very low frequency (<0.04 Hz) increased, while low frequency (0.04-0.15 Hz) and the LF/HF ratio while awake decreased, suggesting improved autonomic regulation post-surgery. Change of effect size was larger in patients where both activated contacts were located in the ANT than in those where only one or none of the contacts hit the ANT. CONCLUSIONS: In patients with drug-resistant epilepsy, ANT-DBS might positively influence autonomic regulation, as reflected by increased HRV. SIGNIFICANCE: To gain a more comprehensive outcome estimation after DBS implantation, we suggest including HRV measures with seizure count in the post-surgery follow-up protocol.

Increased prevalence of minor physical anomalies in patients with epilepsy.

Our aim was to investigate the rate and topological profile of minor physical anomalies (MPAs) in adult patients with epilepsy with the use of the Méhes Scale, a comprehensive modern scale of dysmorphology. Consecutive epilepsy patients admitted for outpatient evaluation were included. Patients with comorbidities of neurodevelopmental origin (such as autism, severe intellectual disability, attention deficit hyperactivity disorder, schizophrenia, tic disorder, Tourette syndrome, bipolar disorder, specific learning disorder and specific language impairment) were excluded. All participants underwent physical examination with the use of the Méhes Scale for evaluation of MPAs, including 57 minor signs. The frequency and topological profile of MPAs were correlated to clinical patient data using Kruskal-Wallis, chi2 tests and logistic regression model. 235 patients were included, according to the following subgroups: acquired epilepsy (non-genetic, non-developmental etiology) [N = 63], temporal lobe epilepsy with hippocampal sclerosis (TLE with HS) [N = 27], epilepsy with cortical dysgenesis etiology [N = 29], cryptogenic epilepsy [N = 69] and idiopathic generalized epilepsy (IGE) [N = 47]. As controls, 30 healthy adults were recruited. The frequency of MPAs were significantly affected by the type of epilepsy [H(6) = 90.17; p < 0.001]. Pairwise comparisons showed that all patient groups except for acquired epilepsy were associated with increased frequency of MPAs (p < 0.001 in all cases). Furrowed tongue and high arched palate were more common compared to controls in all epilepsy subgroup except for TLE (p < 0.001 or p = 0.001 in all cases). A positive association was detected between the occurrence of MPAs and antiepileptic drug therapy resistance [Exp(B) = 4.19; CI 95% 1.37-12.80; p = 0.012]. MPAs are more common in patients with epilepsy, which corroborates the emerging concept of epilepsy as a neurodevelopmental disorder. Assessment of these signs may contribute to the clarification of the underlying etiology. Moreover, as increased frequency of MPAs may indicate pharmacoresistance, the identification of patients with high number of MPAs could allow evaluation for non-pharmacological treatment in time.

The importance of MRI quality and reader's experience for detecting an adenoma in Cushing's disease.

Objective: In Cushing's disease (CD), detection of an adenoma by MRI is challenging. The aim of this study is to compare real-life MRI in the initial diagnostic workup of CD with high-quality MRI performed in a tertiary center for pituitary diseases. Design and methods: We retrospectively analyzed 139 patients with CD who underwent primary transsphenoidal surgery (TSS) in our department and had both an MRI conducted at a different institution (external MRI; extMRI) and an MRI conducted at our institution (internal MRI; intMRI). Preoperative interpretation of MRI was performed independently by an external radiologist (extRAD), an internal neuroradiologist (intRAD) and a pituitary surgeon (SURG). Intraoperative detection of an adenoma and endocrinological remission provided proof of the true adenoma localization in 105 patients. Results: Interpretation of extMRI by extRAD and SURG was concordant in only 64% (89/139) of cases, while 74.1% (103/139) concordance was observed for interpretation of intMRI by intRAD and SURG. Based on extMRI, the true localization of the adenoma was correctly predicted in only 46.7% of the patients by extRAD and in 65.7% by SURG. In contrast, the sensitivity to correctly identify the adenoma on intMRI was 80.0% for intRAD and 94.3% for SURG. Conclusion: Both the quality of MRI and the reader's experience are paramount for detection of microadenomas in CD. Every effort should be made to perform high-quality initial MRI according to current standards and to ensure rating by an expert in pituitary imaging.

Investigation of synapses in the cortical white matter in human temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is one of the most common focal pharmacotherapy-resistant epilepsy in adults. Previous studies have shown significantly higher numbers of neurons in the neocortical white matter in TLE patients than in controls. The aim of this work was to investigate whether white matter neurons are part of the neuronal circuitry. Therefore, we studied the distribution and density of synapses in surgically resected neocortical tissue of pharmacotherapy-resistant TLE patients. Neocortical white matter of temporal lobe from non-epileptic patients were used as controls. Synapses and neurons were visualized with immunohistochemistry using antibodies against synaptophysin and NeuN, respectively. The presence of synaptophysin in presynaptic terminals was verified by electron microscopy. Quantification of immunostaining was performed and the data of the patients' cognitive tests as well as clinical records were compared to the density of neurons and synapses. Synaptophysin density in the white matter of TLE patients was significantly higher than in controls. In TLE, a significant correlation was found between synaptophysin immunodensity and density of white matter neurons. Neuronal as well as synaptophysin density significantly correlated with scores of verbal memory of TLE patients. Neurosurgical outcome of TLE patients did not significantly correlate with histological data, although, higher neuronal and synaptophysin densities were observed in patients with favorable post-surgical outcome. Our results suggest that white matter neurons in TLE patients receive substantial synaptic input and indicate that white matter neurons may be integrated in epileptic neuronal networks responsible for the development or maintenance of seizures.

[Postoperative outcome of surgical interventions for epilepsy between 2005 and 2016 at the Epilepsy Center of Pécs]. / Epilepsziasebészeti beavatkozások eredményei a Pécsi Epilepszia Centrumban 2005 és 2016 között.

INTRODUCTION: Epilepsy as a chronic, severe neurologic disease significantly influences the quality of life of the epileptic patients. In candidates well selected for surgery, the seizure freedom is realistically achievable, and the quality of life can be further improved with complex individual rehabilitation. AIM: We aimed to evaluate the postoperative outcome of patients who underwent epilepsy surgery between 2005 and 2016 at the Epilepsy Center at Pécs. METHOD: We evaluated seizure status at regular follow-up visits after surgery and the quality of life using questionnaires focusing on employment and social status. RESULTS: 76% of the 72 patients who underwent surgical resection for epilepsy were free from disabling seizures , and 10% had rare disabling seizures (almost seizure-free), 7% experienced worthwhile improvement and 7% had no worthwhile improvement. Comparing the employment status of patients free from disabling seizures to patients not free from disabling seizures, we found that the employment status is significantly influenced by seizure freedom (p<0.01, Fisher's exact test). While 67% of seizure-free patients were employed, only 19% of patients not free from disabling seizures were hired. CONCLUSION: Our results resemble the international tendencies and success rate, proving epilepsy surgery as an available, valid and effective treatment in well selected patients. Orv Hetil. 2019; 160(7): 270-278.

Vascular Anatomy and Not Age is Responsible for Increased Risk of Complications in Symptomatic Elderly Patients Undergoing Carotid Artery Stenting.

BACKGROUND: Various studies have suggested that age ≥80 years is associated with a higher rate of complications after carotid artery stenting (CAS). The Buffalo Risk Assessment Scale (BRASS) predicts complications in symptomatic patients undergoing CAS. Application of the BRASS has shown the ability to improve patient selection. We used the BRASS system to evaluate whether the higher rate of complications associated with CAS in the elderly is related to vascular anatomy. METHODS: A retrospective review of CAS was performed at our institution over 7 years. Demographic information, anatomic characteristics, BRASS categorization, and outcome measures were compared between elderly (≥80 years) and younger patients (<80 years). RESULTS: The study included 447 patients: 335 patients (75%) <80 years and 112 patients (25%) ≥80 years. There were significantly more elderly patients in the high-risk BRASS category (P < 0.01), and more young patients in the low-risk BRASS category (P = 0.04). The complication rates in the 2 groups were similar. Older patients were more likely to harbor complex vascular anatomy: they had significantly higher rates of types II and III aortic arches (P = 0.01 and P < 0.01, respectively), higher percentage of tortuous carotid vessels (P < 0.01), and higher rates of hostile anatomy for deployment of distal embolic protection devices (P = 0.02). CONCLUSIONS: Complex vascular anatomy, rather than age, is the key factor behind the higher CAS-associated complication rate in the elderly. Complications can be avoided through proper patient selection and stratifying patients based on anatomic characteristics, which can be achieved through the BRASS scoring system.