Functional hemispheric disconnection procedures for chronic epilepsy: history, indications, techniques, complications and current practice in Europe. A consensus statement on behalf of the EANS functional neurosurgery section.

Introduction: The surgical procedure for severe, drug-resistant, unilateral hemispheric epilepsy is challenging. Over the last decades the surgical landscape for hemispheric disconnection procedures changed from anatomical hemispherectomy to functional hemispherotomy with a reduction of complications and stable good seizure outcome. Here, a task force of European epilepsy surgeons prepared, on behalf of the EANS Section for Functional Neurosurgery, a consensus statement on different aspects of the hemispheric disconnection procedure. Research question: To determine history, indication, timing, techniques, complications and current practice in Europe for hemispheric disconnection procedures in drug-resistant epilepsy. Material and methods: Relevant literature on the topic was collected by a literature search based on the PRISMA 2020 guidelines. Results: A comprehensive overview on the historical development of hemispheric disconnection procedures for epilepsy is presented, while discussing indications, timing, surgical techniques and complications. Current practice for this procedure in European epilepsy surgery centers is provided. At present, our knowledge of long-term seizure outcomes primarily stems from open surgical disconnection procedures. Although minimal invasive surgical techniques in epilepsy are rapidly developing and reported in case reports or small case series, long-term seizure outcome remain uncertain and needs to be reported. Discussion and conclusion: This is the first paper presenting a European consensus statement regarding history, indications, techniques and complications of hemispheric disconnection procedures for different causes of chronic, drug-resistant epilepsy. Furthermore, it serves as the pioneering document to report a comprehensive overview of the current surgical practices regarding this type of surgery employed in renowned epilepsy surgery centers across Europe.

Vasospasm in Pediatric Subarachnoid Hemorrhage.

Cerebral vasospasm (CV) is a common severe complication of subarachnoid hemorrhage (SAH), a severe type of intracranial bleeding that is uncommon in children. The purpose of this article is to review the current literature regarding this potentially devastating complication. CV may be asymptomatic and is less common in children compared to adults. Several molecular phenomena, including inflammatory ones, contribute to its pathophysiology. Better collateral circulation and higher cerebral blood flow are protective factors in children. When clinically apparent, CV may manifest as a change in the child's neurologic status or vital signs. CV can be diagnosed using brain vessel imaging, such as computed tomography angiography, magnetic resonance angiography, digital subtraction angiography, transcranial Doppler ultrasonography, and computed tomography perfusion. A reduction of < 50% in the artery's caliber confirms the diagnosis. Besides general supportive measures and causative treatment of SAH, CV management options include the administration of calcium channel blockers and neurointerventional approaches, such as intra-arterial vasodilators and balloon angioplasty. Long-term outcomes in children are usually favorable.

Nucleus accumbens changes in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS), a representative example of motor neuron disease, is a progressive and fatal neurodegenerative disorder. The nucleus accumbens (NA) is the ventral striatum's main part and is considered as a modulator of the human brain's reward network. The purpose of this article is to review the current knowledge regarding NA changes in ALS patients. The NA involvement in ALS includes volumetric, cellular and molecular changes. There are recent imaging and pathological studies revealing NA atrophy in ALS, a finding which seems to be related to neuronal loss and protein deposition in this area. The clinical significance of NA atrophy in these patients is not currently fully understood. Perhaps it could be correlated with apathy, behavioral disturbances and cognitive impairment that ALS patients sometimes manifest.

Lhermitte-Duclos disease with concomitant KCNT2 gene mutation: report of an extremely rare combination.

Lhermitte-Duclos disease (LDD) refers to cerebellar dysplastic gangliocytoma, a slow-growing tumor. Pathogenic variants of voltage-gated potassium channels have been associated with epilepsy of variable severity. These include the sodium-activated potassium channel subfamily T member 2 (KCNT2) gene, which encodes for pore-forming alpha subunits. KCNT2 gene mutations have been recently described to cause developmental and epileptic encephalopathies (DEEs). The purpose of the present article is to describe an extremely rare case of a young child who has both LDD and KCNT2 mutation. Our patient is an 11-year-old boy who presented with an absence episode, and his investigations revealed electroencephalography (EEG) abnormalities, LDD, and a heterozygous KCNT2 mutation. Regarding LDD patients, epileptic seizures have been reported in very few cases. Reports of patients with mutated KCNT2 variants are also extremely rare. It is for sure that LDD and KCNT2 mutation is an extremely rare combination. Although further follow-up is mandatory in order to draw safe conclusions for our case, the available data support that our patient is either the first reported case of a subclinical KCNT2 mutation or the first case of its clinical expression in late childhood so far.

Nucleus accumbens atrophy in Parkinson's disease (Mavridis' atrophy): 10 years later.

Parkinson's disease (PD) is a common neurodegenerative disorder associated with gray matter atrophy. The human nucleus accumbens (NA) is a major part of the ventral striatum and modulator of the reward network of the brain. It plays an important role in several cognitive and emotional functions. In patients with PD, dysfunction of this nucleus is correlated not only with movement disorders but also with various neuropsychological deficits and psychiatric symptoms. The human NA suffers atrophy in PD, which is called Mavridis' atrophy (MA), a well established characteristic of PD that was first described 10 years ago. The purpose of this article is to review the current knowledge regarding the clinical significance of MA. We currently know that it begins in early-stage PD patients, precedes clinical phenotype, and is part of the degeneration of the dopaminergic nigrostriatal system in these patients. MA has several clinical consequences. It is, more specifically, associated with the expression (and severity) of specific neuropsychiatric PD symptoms, namely cognitive impairment, apathy, disinhibition, and impulsive behavior, while its association with motor symptoms remains unclear. MA was recently suggested as a marker of global dysfunction in the mesocorticolimbic network. With new research data, new questions about MA emerge and further research is obviously necessary in order to effectively apply MA, as an imaging finding, to clinical practice.

Discovery of Selective Nanomolar Inhibitors for Insulin-Regulated Aminopeptidase Based on α-Hydroxy-ß-amino Acid Derivatives of Bestatin.

The oxytocinase subfamily of M1 zinc aminopeptidases comprises emerging drug targets, including the ER-resident aminopeptidases 1 and 2 (ERAP1 and ERAP2) and insulin-regulated aminopeptidase (IRAP); however, reports on clinically relevant inhibitors are limited. Here we report a new synthetic approach of high diastereo- and regioselectivity for functionalization of the α-hydroxy-ß-amino acid scaffold of bestatin. Stereochemistry and mechanism of inhibition were investigated by a high-resolution X-ray crystal structure of ERAP1 in complex with a micromolar inhibitor. By exploring the P1 side-chain functionalities, we achieve significant potency and selectivity, and we report a cell-active, low-nanomolar inhibitor of IRAP with >120-fold selectivity over homologous enzymes. X-ray crystallographic analysis of IRAP in complex with this inhibitor suggest that interactions with the GAMEN loop is an unappreciated key determinant for potency and selectivity. Overall, our results suggest that α-hydroxy-ß-amino acid derivatives may constitute useful chemical tools and drug leads for this group of aminopeptidases.

Pineal region tumors: pathophysiological mechanisms of presenting symptoms.

Pineal region tumors (PRTs) affect all ages, with a remarkable proportion of cases occurring in children. They are mainly classified into three categories, namely germ cell tumors (GCTs), pineal parenchymal tumors (PPTs), and other tumors such as gliomas and tumors of the surrounding structures. The purpose of this article is to review the current literature regarding pathophysiological mechanisms of the presenting clinical features of patients with PRT. The usual presentation of PRTs is the symptoms of obstructive hydrocephalus and intracranial hypertension, such as headache and vomiting. However, there is a remarkable spectrum of clinical findings that can be caused by such lesions. These include ophthalmologic and endocrinologic disturbances, motor and sensory abnormalities, and cognitive and psychiatric symptoms. The unique anatomic location of the pineal gland, which is close to many vital brain structures, is crucial for the explanation of most of those findings. In rare cases, manifestations of intracranial bleeding may be the presenting feature of a PRT. Tumor histology and patient's age can affect the clinical presentation. Hydrocephalus is the most common clinical syndrome of a PRT because of the location of the pineal gland. Presenting symptoms also include ophthalmologic, endocrinologic, motor, sensory, cognitive, and psychiatric symptoms. Clinicians should be aware of the initial symptoms of PRTs, including the misleading ones, in order to avoid delay in the diagnosis and management of these life-threatening lesions.

Contextualized Filtering for Shared Cyber Threat Information.

Cyber threat information sharing is an imperative process towards achieving collaborative security, but it poses several challenges. One crucial challenge is the plethora of shared threat information. Therefore, there is a need to advance filtering of such information. While the state-of-the-art in filtering relies primarily on keyword- and domain-based searching, these approaches require sizable human involvement and rarely available domain expertise. Recent research revealed the need for harvesting of business information to fill the gap in filtering, albeit it resulted in providing coarse-grained filtering based on the utilization of such information. This paper presents a novel contextualized filtering approach that exploits standardized and multi-level contextual information of business processes. The contextual information describes the conditions under which a given threat information is actionable from an organization perspective. Therefore, it can automate filtering by measuring the equivalence between the context of the shared threat information and the context of the consuming organization. The paper directly contributes to filtering challenge and indirectly to automated customized threat information sharing. Moreover, the paper proposes the architecture of a cyber threat information sharing ecosystem that operates according to the proposed filtering approach and defines the characteristics that are advantageous to filtering approaches. Implementation of the proposed approach can support compliance with the Special Publication 800-150 of the National Institute of Standards and Technology.

Pediatric stereo-electroencephalography: effects of robot assistance and other variables on seizure outcome and complications.

OBJECTIVE: The safety of stereo-electroencephalography (SEEG) has been investigated; however, most studies have not differentiated pediatric and adult populations, which have different anatomy and physiology. The purpose of this study was to assess SEEG safety in the pediatric setting, focusing on surgical complications and the identification of patient and surgical risk factors, if any. The authors also aimed to determine whether robot assistance in SEEG was associated with a change in practice, surgical parameters, and clinical outcomes. METHODS: The authors retrospectively studied all SEEG cases performed in their department from December 2014 to March 2020. They analyzed both demographic and surgical variables and noted the types of surgery-related complications and their management. They also studied the clinical outcomes of a subset of the patients in relation to robot-assisted and non-robot-assisted SEEG. RESULTS: Sixty-three children had undergone 64 SEEG procedures. Girls were on average 3 years younger than the boys (mean age 11.1 vs 14.1 years, p < 0.01). The overall complication rate was 6.3%, and the complication rate for patients with left-sided electrodes was higher than that for patients with right-sided electrodes (11.1% vs 3.3%), although the difference between the two groups was not statistically significant. The duration of recording was positively correlated to the number of implanted electrodes (r = 0.296, p < 0.05). Robot assistance was associated with a higher number of implanted electrodes (mean 12.6 vs 7.6 electrodes, p < 0.0001). Robot-assisted implantations were more accurate, with a mean error of 1.51 mm at the target compared to 2.98 mm in nonrobot implantations (p < 0.001). Clinical outcomes were assessed in the first 32 patients treated (16 in the nonrobot group and 16 in the robot group), 23 of whom proceeded to further resective surgery. The children who had undergone robot-assisted SEEG had better eventual seizure control following subsequent epilepsy surgery. Of the children who had undergone resective epilepsy surgery, 42% (5/12) in the nonrobot group and 82% (9/11) in the robot group obtained an Engel class IA outcome at 1 year (χ2 = 3.885, p = 0.049). Based on Kaplan-Meier survival analysis, the robot group had a higher seizure-free rate than the nonrobot group at 30 months postoperation (7/11 vs 2/12, p = 0.063). Two complications, whose causes were attributed to the implantation and head-bandaging steps, required surgical intervention. All complications were either transient or reversible. CONCLUSIONS: This is the largest single-center, exclusively pediatric SEEG series that includes robot assistance so far. SEEG complications are uncommon and usually transient or treatable. Robot assistance enabled implantation of more electrodes and improved epilepsy surgery outcomes, as compared to those in the non-robot-assisted cases.

Chyloperitoneum following open myelomeningocele repair: dealing with an extremely rare finding.

PURPOSE: Chyloperitoneum is an extremely rare finding following myelomeningocele (MMC) repair in neonates. We aimed to describe the characteristics of such a case and explore its clinical significance. CASE REPORT: A male baby born at term with open MMC and hydrocephalus underwent MMC repair surgery with rotational flaps on the first postnatal day. The procedure was uneventful. Three days later, he underwent a right ventriculoperitoneal shunt (VPS) insertion. On opening the peritoneum, a remarkable amount of yellowish opaque fluid was observed. Chyloperitoneum was suspected, but the VPS procedure was completed as planned. Biochemical analysis was consistent with that of chyle. DISCUSSION: Neonatal chylous ascites is a rare condition; hence, available data on pathophysiology and therapy in the literature are scarce. It is postulated that the MMC repair in neonates causes abdominal tautness, which leads to rupture of small lymphatics and raised intraportal pressure. The combination of these two processes results in extravasation of chyle from the gastrointestinal tract. Presence of chyloperitoneum is not a contraindication for VPS insertion. CONCLUSION: Chyloperitoneum is an extremely rare sequela of MMC repair in neonates. Pediatric neurosurgeons should be aware of it, especially when a VPS procedure is to follow a repair, in order to know how to deal with it and avoid unnecessary abandonment of the shunt.

Nervous system involvement in Pfeiffer syndrome.

Pfeiffer syndrome (PS) is a rare autosomal dominant craniofacial disorder characterized by primary craniosynostosis, midface hypoplasia, and extremities' abnormalities including syndactyly. The purpose of this article was to review the current knowledge regarding how PS affects the nervous system. Methodologically, we conducted a systematic review of the existing literature concerning involvement of the nervous system in PS. Multiple-suture synostosis is common, and it is the premature fusion and abnormal growth of the facial skeleton's bones that cause the characteristic facial features of these patients. Brain abnormalities in PS can be primary or secondary. Primary anomalies are specific developmental brain defects including disorders of the white matter. Secondary anomalies are the result of skull deformity and include intracranial hypertension, hydrocephalus, and Chiari type I malformation. Spinal anomalies in PS patients include fusion of vertebrae, "butterfly" vertebra, and sacrococcygeal extension. Different features have been observed in different types of this syndrome. Cloverleaf skull deformity characterizes PS type II. The main neurological abnormalities are mental retardation, learning difficulties, and seizures. The tricky neurological examination in severely affected patients makes difficult the early diagnosis of neurological and neurosurgical complications. Prenatal diagnosis of PS is possible either molecularly or by sonography, and the differential diagnosis includes other craniosynostosis syndromes. Knowing how PS affects the nervous system is important, not only for understanding its pathogenesis and determining its prognosis but also for the guidance of decision-making in the various critical steps of its management. The latter necessitates an experienced multidisciplinary team.

The Promotion of Eating Behaviour Change through Digital Interventions.

Diet-related chronic disease is a global health epidemic giving rise to a high incidence of morbidity and mortality. With the rise of the digital revolution, there has been increased interest in using digital technology for eating behavioural change as a mean of diet-related chronic disease prevention. However, evidence on digital dietary behaviour change is relatively scarce. To address this problem, this review considers the digital interventions currently being used in dietary behaviour change studies. A literature search was conducted in databases like PubMed, Cochrane Library, CINAHL, Medline, and PsycInfo. Among 119 articles screened, 15 were selected for the study as they met all the inclusion criteria according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) search strategy. Four primary digital intervention methods were noted: use of personal digital assistants, use of the internet as an educational tool, use of video games and use of mobile phone applications. The efficiency of all the interventions increased when coupled with tailored feedback and counselling. It was established that the scalable and sustainable properties of digital interventions have the potential to bring about adequate changes in the eating behaviour of individuals. Further research should concentrate on the appropriate personalisation of the interventions, according to the requirements of the individuals, and proper integration of behaviour change techniques to motivate long-term adherence.

ARES: Automated Risk Estimation in Smart Sensor Environments.

Industry 4.0 adoption demands integrability, interoperability, composability, and security. Currently, integrability, interoperability and composability are addressed by next-generation approaches for enterprise systems integration such as model-based standards, ontology, business process model life cycle management and the context of business processes. Security is addressed by conducting risk management as a first step. Nevertheless, security risks are very much influenced by the assets that the business processes are supported. To this end, this paper proposes an approach for automated risk estimation in smart sensor environments, called ARES, which integrates with the business process model life cycle management. To do so, ARES utilizes standards for platform, vulnerability, weakness, and attack pattern enumeration in conjunction with a well-known vulnerability scoring system. The applicability of ARES is demonstrated with an application example that concerns a typical case of a microSCADA controller and a prototype tool called Business Process Cataloging and Classification System. Moreover, a computer-aided procedure for mapping attack patterns-to-platforms is proposed, and evaluation results are discussed revealing few limitations.

Spinal angiolipoma: Presentation of two cases and review of the literature for the years 2012-2017 / Angiolipoma espinal: descripción de 2 casos y revisión de la bibliografía durante los años 2012-2017

INTRODUCTION AND OBJECTIVES: Angiolipomas of the spinal canal are a rare condition of unknown origin. They are considered histologically benign; however, some have the potential to infiltrate adjacent structures. The aim of this systematic review was to suggest a potential mechanism for the pathogenesis of spinal angiolipomas, along with a useful approach for their preoperative management. MATERIALS AND METHODS: A literature review of cases of spinal angiolipoma was performed. In addition, two of the cases encountered in our practice are presented. The first case refers to a 35-year-old male patient with a history of spinal fusion because of a T9 fracture, while the second concerns a 46-year-old male patient with an epidural mass extending outside the spinal canal, who underwent fine needle biopsy and embolisation of its feeding vessel. RESULTS: From the review of the literature performed, we were unable to identify any correlation between the infiltrative potential and the patients' demographic and tumour characteristics. CONCLUSIONS: Angiolipomas are considered to be sporadic, yet theories concerning their pathogenesis include reaction to harmful stimuli and congenital malformation of the adipose tissue. Fine needle biopsy may be mistakenly considered non-diagnostic, due to the presence of well-differentiated adipocytes

INTRODUCCIÓN Y OBJETIVOS: Los angiolipomas del canal vertebral son una enfermedad rara de origen desconocido. Se consideran histológicamente benignos, aunque en algunos casos existe la posibilidad de que se infiltren en estructuras adyacentes. El objetivo de esta revisión sistemática es sugerir un posible mecanismo para la patogenia de los angiolipomas espinales, junto con un enfoque útil para su tratamiento preoperatorio. Materiales y métodos: Se realizó una búsqueda bibliográfica de los casos de angiolipomas espinales. Además, se presentan 2 de los casos encontrados en nuestra práctica clínica. El primer caso corresponde a un paciente varón de 35 años con antecedentes de artrodesis vertebral debido a una fractura en T9, mientras que el segundo corresponde a un paciente varón de 46 años con una masa epidural que se extendía fuera del canal vertebral, al que se realizó una biopsia con aguja fina y una embolización del vaso nutricio. RESULTADOS: A partir de la revisión bibliográfica realizada, no pudimos identificar ninguna correlación entre el potencial de infiltración, los datos demográficos y las características de los tumores de los pacientes. CONCLUSIONES: Los angiolipomas se consideran esporádicos, existiendo, no obstante, teorías referentes a su patogenia que incluyen la reacción a estímulos nocivos y la malformación congénita del tejido adiposo. La biopsia con aguja fina puede considerarse erróneamente como no diagnóstica, debido a la presencia de adipocitos bien diferenciados

Toxocariasis of the Nervous System.

PURPOSE: Toxocariasis is a helminthozoonosis caused by the infection of a human host by the larva of Toxocara spp., predominately involving Toxocara canis and Toxocara cati, which are common nematodes in dogs and cats, respectively. Human transmission occurs through contact with animals or by consumption of food contaminated with parasite's eggs. The purpose of this article is to review the current knowledge regarding human neurotoxocariasis. METHODS: We conducted a systematic review of the existing literature concerning toxocariasis of the nervous system. RESULTS: Clinical spectrum of human toxocariasis varies widely from a subclinical course to significant organ morbidity. Clinical course depends on parasitic load, the migration route of the larvae and host response. Human neurotoxocariasis is a relatively rare entity yet associated with severe sequelae. Manifestations include meningitis (usually eosinophilic), encephalitis, myelitis, cerebellar vasculitis, space-occupying lesion, behavioral abnormalities, and optic neuritis. Even though valid diagnostic criteria are lacking, neurotoxocariasis should be suspected in patients with neurologic symptoms and cerebrospinal fluid (CSF) pleocytosis with eosinophilia, positive serology for anti-Toxocara antibodies, in serum and/or CSF, sterile CSF and clinical improvement after antihelminthic treatment. Neurotoxocariasis is treated by benzimidazole components, most frequently albendazole, corticosteroids, or diethylcarbamazine. CONCLUSION: Parasite larvae migrate through tissues and are able to reach the nervous system causing neurotoxocariasis. Its clinical spectrum varies and includes myelitis, meningoencephalitis, brain abscess, and vasculitis. Neurotoxocariasis should always be suspected in patients with neurologic symptoms accompanied by eosinophilia in blood and/or CSF. Early diagnosis and treatment could prevent long-term neurologic impairment.

D4I - Digital forensics framework for reviewing and investigating cyber attacks.

Many companies have cited lack of cyber-security as the main barrier to Industrie 4.0 or digitalization. Security functions include protection, detection, response and investigation. Cyber-attack investigation is important as it can support the mitigation of damages and maturing future prevention approaches. Nowadays, the investigation of cyber-attacks has evolved more than ever leveraging combinations of intelligent tools and digital forensics processes. Intelligent tools (e.g., YARA rules and Indicators of Compromise) are effective only when there is prior knowledge about software and mechanisms used in the cyber-attack, i.e., they are not attack-agnostic. Therefore, the effectiveness of these intelligent tools is inversely proportional to the number of the never-seen-before software and mechanisms utilized. Digital forensic processes, while not suffering from such issue, lack the ability to provide in-depth support to a cyber-attack investigation mainly due to insufficient detailed instructions in the examination and analysis phases. This paper proposes a digital forensics framework for reviewing and investigating cyber-attacks, called D4I, which focuses on enhancing the examination and analysis phases. First, the framework proposes a digital artifacts categorization and mapping to the Cyber-Kill-Chain steps of attacks. Second, it provides detailed instructing steps for the examination and analysis phases. The applicability of D4I is demonstrated with an application example that concerns a typical case of a spear phishing attack.

Spinal angiolipoma: Presentation of two cases and review of the literature for the years 2012-2017.

INTRODUCTION AND OBJECTIVES: Angiolipomas of the spinal canal are a rare condition of unknown origin. They are considered histologically benign; however, some have the potential to infiltrate adjacent structures. The aim of this systematic review was to suggest a potential mechanism for the pathogenesis of spinal angiolipomas, along with a useful approach for their preoperative management. MATERIALS AND METHODS: A literature review of cases of spinal angiolipoma was performed. In addition, two of the cases encountered in our practice are presented. The first case refers to a 35-year-old male patient with a history of spinal fusion because of a T9 fracture, while the second concerns a 46-year-old male patient with an epidural mass extending outside the spinal canal, who underwent fine needle biopsy and embolisation of its feeding vessel. RESULTS: From the review of the literature performed, we were unable to identify any correlation between the infiltrative potential and the patients' demographic and tumour characteristics. CONCLUSIONS: Angiolipomas are considered to be sporadic, yet theories concerning their pathogenesis include reaction to harmful stimuli and congenital malformation of the adipose tissue. Fine needle biopsy may be mistakenly considered non-diagnostic, due to the presence of well-differentiated adipocytes.