Insular lobe surgery and cognitive impairment in gliomas operated with intraoperative neurophysiological monitoring.

BACKGROUND: For a long time, surgery of insular gliomas was considered at high risk for postoperative cognitive deficits, but recent studies highlighted the feasibility of the surgical approach. The aims of our study were to investigate the presence of language impairment before and after surgery and the relationship between language impairment and tumor volume preoperatively and extent of resection (EOR) 3 months after surgery. METHODS: Thirty-five patients with insular gliomas underwent an extensive language assessment before and few days after surgery, and after 3 months. Intraoperative neurophysiological monitoring (IOM) and brain mapping with direct electrical stimulation (DES) were used in all the cases; 8 patients underwent awake craniotomy. Statistical analysis was performed on the language tests administered. RESULTS: Patients with pure left insular lesion showed language impairment before and after surgery. Overall, patients with a left lesion showed a drop of performance after surgery followed by a partial recovery. Moreover, when the tumor involved the insula and adjacent networks, we observed a more severe deficit. No correlations were found between tumor volume, EOR, and language impairment. CONCLUSIONS: Left insular lobe is an important hub in language networks; its involvement determines pre- and postsurgical deficits, together with the involvement of white matter connections. Tumor volume and EOR are not risk factors per se directly related to language functioning. Surgery of insular gliomas is possible with a pre- and intraoperative extensive study of the patient with IOM and awake surgery, and encouraged by the trend of cognitive recovery highlighted.

Acute flaccid paralysis due to Echovirus 30 in an immunosuppressed transplant recipient.

An Italian 13-year-old boy immunosuppressed due to kidney transplant presented in November 2018 with acute flaccid paralysis with anterior horn cell involvement resembling the clinical, radiological, and laboratory features of poliomyelitis. Enterovirus was molecularly identified in cerebral spinal fluid and stool samples and the sequence analysis of the VP1 gene of enterovirus genome revealed the presence of Echovirus 30 both in CSF and in stool samples. Echovirus 30 is an emerging neurotropic virus able to cause outbreaks of aseptic meningitis and meningoencephalitis all over the world, but acute flaccid paralysis is not a classical manifestation. A 6-month follow-up revealed a poor outcome with severe motor deficits and only slight improvement in disability. Clinicians must be aware of the possible role of Echovirus 30 in acute flaccid paralysis and active surveillance should consider the possible influence of immunosuppression on the symptoms caused by the widening spectrum of enterovirus infections.

Pseudotumour cerebri associated with mycoplasma pneumoniae infection and treatment with levofloxacin: a case report.

BACKGROUND: Idiopathic intracranial hypertension (IIH), also known as pseudotumour cerebri syndrome (PTCS), is characterized by the presence of signs and symptoms of raised intracranial pressure without evidence of any intracranial structural cause and with normal cerebrospinal fluid microscopy and biochemistry. Obesity, various systemic diseases and endocrine conditions, and a number of medications are known to be risk factors for PTCS. The medications commonly associated with PTCS are amiodarone, antibiotics, corticosteroids, cyclosporine, growth hormone, oral contraceptives, vitamin A analogues, lithium, phenytoin, NSAIDs, leuprolide acetate, and some neuroleptic drugs. In relation to antibiotics, quinolones may cause intracranial hypertension, and most reported cases of quinolone-induced intracranial hypertension were associated with nalidixic acid, ciprofloxacin, ofloxacin, or pefloxacin. Literature reports of levofloxacin-induced PTCS are rare. Some authors recently hypothesized that Mycoplasma pneumoniae may trigger PTCS. CASE PRESENTATION: We report on a 14-year-old overweight White Italian boy who suffered headache, diplopia, and severe bilateral papilloedema after a Mycoplasma pneumoniae infection, exacerbated on levofloxacin intake. A spontaneous improvement in headache and a reduction in diplopia was seen during hospitalisation. Oral acetazolamide therapy led to the regression of papilloedema in about five months. No permanent eye damage has been observed in our patient to date. CONCLUSIONS: PTCS pathophysiology may be multifactorial and its specific features and severity may be a consequence of both constitutional and acquired factors interacting synergistically. It may be useful for paediatricians to know that some antibiotics may have the potential to precipitate PTCS in patients who already have an increased CSF pressure due to a transitory imbalanced CSF circulation caused by infections such as Mycoplasma pneumoniae, with headache being the first and most sensitive, but also the least specific, symptom.

Case Report: Effect of Targeted Therapy With Carbamazepine in KCNQ2 Neonatal Epilepsy.

We present a family case of neonatal-onset KCNQ2-related epilepsy due to a novel intronic mutation. Three members of an Italian family (father and offspring) presented with neonatal-onset asymmetric tonic and clonic seizures with peculiar video-electroencephalography and aEEG features referring to sequential seizures. The father and the first son underwent standard of care treatments in line with current neonatal intensive care unit protocols, with a prolonged hospitalization before reaching full seizure control with carbamazepine. After the experience acquired with her family and the latest advances in the literature, the younger daughter was directly treated with carbamazepine, obtaining rapid seizure control and short hospitalization. They all had normal development. Carbamazepine is rarely administered as a first-line option in neonatal seizures. Recent evidence suggests that neonatal intensive care unit protocols should implement a trial with sodium channel blockers such as carbamazepine as first-option anti-seizure medication and a fast access to genetic testing in neonates with sequential seizures without structural brain injury or acute causes. Moreover, we report and discuss the laboratory studies performed on a novel causative intronic mutation in KCNQ2 (c.1525+5 G>A in IVS13), since pathogenicity may be difficult to prove for intronic variants.

Indication and eligibility of glioma patients for awake surgery: A scoping review by a multidisciplinary perspective.

Background: Awake surgery (AS) permits intraoperative mapping of cognitive and motor functions, allowing neurosurgeons to tailor the resection according to patient functional boundaries thus preserving long-term patient integrity and maximizing extent of resection. Given the increased risks of the awake scenario, the growing importance of AS in surgical practice favored the debate about patient selection concerning both indication and eligibility criteria. Nonetheless, a systematic investigation is lacking in the literature. Objective: To provide a scoping review of the literature concerning indication and eligibility criteria for AS in patients with gliomas to answer the questions:1) "What are the functions mostly tested during AS protocols?" and 2) "When and why should a patient be excluded from AS?". Materials and methods: Pertinent studies were retrieved from PubMed, PsycArticles and Cochrane Central Register of Controlled Trials (CENTRAL), published until April 2021 according to the PRISMA Statement Extension for Scoping Reviews. The retrieved abstracts were checked for the following features being clearly stated: 1) the population described as being composed of glioma(LGG or HGG) patients; 2) the paper had to declare which cognitive or sensorimotor function was tested, or 2bis)the decisional process of inclusion/exclusion for AS had to be described from at least one of the following perspectives: neurosurgical, neurophysiological, anesthesiologic and psychological/neuropsychological. Results: One hundred and seventy-eight studies stated the functions being tested on 8004 patients. Language is the main indication for AS, even if tasks and stimulation techniques changed over the years. It is followed by monitoring of sensorimotor and visuospatial pathways. This review demonstrated an increasing interest in addressing other superior cognitive functions, such as executive functions and emotions. Forty-five studies on 2645 glioma patients stated the inclusion/exclusion criteria for AS eligibility. Inability to cooperate due to psychological disorder(i.e. anxiety),severe language deficits and other medical conditions(i.e.cardiovascular diseases, obesity, etc.)are widely reported as exclusion criteria for AS. However, a very few papers gave scale exact cut-off. Likewise, age and tumor histology are not standardized parameters for patient selection. Conclusion: Given the broad spectrum of functions that might be safely and effectively monitored via AS, neurosurgeons and their teams should tailor intraoperative testing on patient needs and background as well as on tumor location and features. Whenever the aforementioned exclusion criteria are not fulfilled, AS should be strongly considered for glioma patients.

Diffusion tensor imaging, intra-operative neurophysiological monitoring and small craniotomy: Results in a consecutive series of 103 gliomas.

Diffusion tensor imaging (DTI) allows visualization of the main white matter tracts while intraoperative neurophysiological monitoring (IONM) represents the gold standard for surgical resection of gliomas. In recent years, the use of small craniotomies has gained popularity thanks to neuronavigation and to the low morbidity rates associated with shorter surgical procedures. The aim of this study was to review a series of patients operated for glioma using DTI, IONM, and tumor-targeted craniotomies. The retrospective analysis included patients with supratentorial glioma who met the following inclusion criteria: preoperative DTI, intraoperative IONM, tumor-targeted craniotomy, pre- and postoperative MRI, and complete clinical charts. The DTI was performed on a 3T scanner. The IONM included electroencephalography (EEG), transcranial (TC) and/or cortical motor-evoked potentials (MEP), electrocorticography (ECoG), and direct electrical stimulation (DES). Outcomes included postoperative neurological deficits, volumetric extent of resection (EOR), and overall survival (OS). One hundred and three patients (61 men, 42 women; mean age 54 ± 14 years) were included and presented the following WHO histologies: 65 grade IV, 19 grade III, and 19 grade II gliomas. After 3 months, only three patients had new neurological deficits. The median postoperative volume was 0cc (IQR 3). The median OS for grade IV gliomas was 15 months, while for low-grade gliomas it was not reached. In our experience, a small craniotomy and a tumor resection supported by IONM and DTI permitted to achieve satisfactory results in terms of neurological outcomes, EOR, and OS for glioma patients.

Epilepsy features in ARID1B-related Coffin-Siris syndrome.

Coffin-Siris syndrome (CSS) is a rare congenital malformation syndrome, caused by mutations in the ARID1B gene in over half of the cases. While the clinical characteristics of the syndrome have been increasingly described, a detailed evaluation of the epileptic phenotype in patients with ARID1B alterations and CSS has not been approached yet. We report seven patients with ARID1B-related CSS, focusing on epilepsy and its electroclinical features. The evolution of epilepsy and EEG findings of children with CSS are described and compared with patients previously reported in the literature. The patients described here reveal common features, consistent with those of patients previously described in the literature. The epilepsy phenotype of CSS due to ARID1B pathogenic variants may be described as focal epilepsy with seizures, variable in frequency, arising from motor areas, with onset in the first years of life and susceptibility to fever, and interictal perisylvian (centrotemporal) epileptiform abnormalities that are enhanced during sleep with possible evolution to an EEG pattern of continuous spike and wave during sleep (without documented developmental regression). Additional information emerging from other patients is needed to confirm this definition.

Botulinum neurotoxin-A does not spread to distant muscles after intragastric injection: A double-blind single-fiber electromyography study.

The purpose of this study was to perform a careful neurophysiological examination to identify subclinical signs of botulinum toxin spread distant to the injection site following intragastric injection for obesity treatment. Single-fiber electromyography of extensor digitorum communis and repetitive stimulation of abductor digiti minimi were performed before and 8 days after multiple intragastric injections of botulinum toxin A (Botox, 200 U per patient) or placebo. The study was performed in a randomized double-blind fashion. No patient in either group displayed results indicative of neuromuscular dysfunction either before or after the treatment. No significant change in muscle jitter was observed when comparing baseline with the after-treatment evaluation in either group, and no significant differences between groups were observed. After intragastric botulinum toxin injection no subclinical sign of distant spread was observed.

Therapeutic effect of Anakinra in the relapsing chronic phase of febrile infection-related epilepsy syndrome.

Febrile infection-related epilepsy syndrome (FIRES) is a severe epileptic encephalopathy with presumed inflammatory origin and lacking effective treatments. Anakinra is the human recombinant interleukin 1 receptor antagonist clinically used in autoinflammatory or autoimmune conditions. We report a case of FIRES for which the spatial and temporal match between electroencephalography (EEG) and magnetic resonance imaging (MRI) focal alterations provides support for the detrimental synergic interplay between seizures and inflammation that may evolve to permanent focal lesions and progressive brain atrophy in weeks to months. Brain biopsy showed aspects of chronic neuroinflammation with scarce parenchymal lymphocytes. We report the novel evidence that anakinra reduces the relapse of highly recurrent refractory seizures at 1.5 years after FIRES onset. Our evidence, together with previously reported therapeutic effects of anakinra administered since the first days of disease onset, support the hypothesis that interleukin 1ß and inflammation-related factors play a crucial role in seizure recurrence in both the acute and chronic stages of the disease.