Francesco Sala

Intraoperative electrical stimulation in awake craniotomy: methodological aspects of current practice.

There is increasing evidence that the extent of tumor removal in low-grade glioma surgery is related to patient survival time. Thus, the goal of resecting the largest amount of tumor possible without leading to permanent neurological sequelae is a challenge for the neurosurgeon. Electrical stimulation of the brain to detect cortical and axonal areas involved in motor, language, and cognitive function and located within the tumor or along its boundaries has become an essential tool in combination with awake craniotomy. Based on a literature review, discussions within the European Low-Grade Glioma Group, and illustrative clinical experience, the authors of this paper provide an overview for neurosurgeons, neurophysiologists, linguists, and anesthesiologists as well as those new to the field about the stimulation techniques currently being used for mapping sensorimotor, language, and cognitive function in awake surgery for low-grade glioma. The paper is intended to help the understanding of these techniques and facilitate a comparison of results between users.

Steady-state activation in somatosensory cortex after changes in stimulus rate during median nerve stimulation.

Passive electrical stimulation activates various human somatosensory cortical systems including the contralateral primary somatosensory area (SI), bilateral secondary somatosensory area (SII) and bilateral insula. The effect of stimulation frequency on blood oxygenation level-dependent (BOLD) activity remains unclear. We acquired 3-T functional magnetic resonance imaging (fMRI) in eight healthy volunteers during electrical median nerve stimulation at frequencies of 1, 3 and 10 Hz. During stimulation BOLD signal changes showed activation in the contralateral SI, bilateral SII and bilateral insula. Results of fMRI analysis showed that these areas were progressively active with the increase of rate of stimulation. As a major finding, the contralateral SI showed an increase of peak of BOLD activation from 1 to 3 Hz but reached a plateau during 10-Hz stimulation. Our finding is of interest for basic research and for clinical applications in subjects unable to perform cognitive tasks in the fMRI scanner.

Intra-operative neurophysiological mapping and monitoring during brain tumour surgery in children: an update

IntroductionOver the past decade, the reluctance to operate in eloquent brain areas has been reconsidered in the light of the advent of new peri-operative functional neuroimaging techniques and new evidence from neuro-oncology. To maximise tumour resection while minimising morbidity should be the goal of brain surgery in children as much as it is in adults, and preservation of brain functions is critical in the light of the increased survival and the expectations in terms of quality of life.DiscussionIntra-operative neurophysiology is the gold standard to localise and preserve brain functions during surgery and is increasingly used in paediatric neurosurgery. Yet, the developing nervous system has peculiar characteristics in terms of anatomical and physiological maturation, and some technical aspects need to be tailored for its use in children, especially in infants. This paper will review the most recent advances in the field of intra-operative neurophysiology (ION) techniques during brain surgery, focussing on those aspects that are relevant to the paediatric neurosurgery practice.

Operative classification of brain arteriovenous malformations.

The first description of brain arteriovenous malformations (AVMs) can be found in the observations of Luschka1 and Virchow2 in the mid 19th century: they were generally categorized as vascular hamartomas. It is believed that the majority of these lesions are congenital in origin, arising between three and eight weeks of gestation3-5. Morphologically, they resemble the normal anastomotic plexuses formed during the early embryogenesis of the brain vascular system. Several recent studies have revealed possible factors involved in the formation and pathogenesis of AVMs. In particular, the gene that results in the production of endothelin-1, the potent vasoconstrictor agent involved in vascular cell growth, has been found to be repressed in cerebral AVMs; this may be the possible cause of the abnormal autoregulation found in AVMs6.

A microRNA signature from serum exosomes of patients with glioma as complementary diagnostic biomarker

Malignant gliomas, the most frequent primary brain tumors, are characterized by a dismal prognosis. Reliable biomarkers complementary to neuroradiology in the differential diagnosis of gliomas and monitoring for post-surgical progression are unmet needs. Altered expression of several microRNAs in tumour tissues from patients with gliomas compared to normal brain tissue have been described, thus supporting the rationale of using microRNA-based biomarkers. Although different circulating microRNAs were proposed in association with gliomas, they have not been introduced into clinical practice so far. Blood samples were collected from patients with high and low grade gliomas, both before and after surgical resection, and the expression of miR-21, miR-222 and miR-124-3p was measured in exosomes isolated from serum. The expression levels of miR-21, miR-222 and miR-124-3p in serum exosomes of patients with high grade gliomas were significantly higher than those of low grade gliomas and healthy controls and were sharply decreased in samples obtained after surgery. The analysis of miR-21, miR-222 and miR-124-3p in serum exosomes of patients affected by gliomas can provide a minimally invasive and innovative tool to help the differential diagnosis of gliomas at their onset in the brain and predict glioma grading and non glial metastases before surgery.

Evaluation of the central sleep apnea in asymptomatic children with Chiari 1 malformation: an open question

IntroductionType I is the most common Chiari malformation in children. In this condition, the lower part of the cerebellum, but not the brain stem, extends into the foramen magnum at the base of the skull leading to intermittent brain hypertension. In symptomatic children, central sleep apneas are shown in polysomnography evaluation. A central apnea index of 1/h or more is considered abnormal, but >5/h is clearly considered pathological. Therefore, central sleep apnea evaluation in pediatric age may show great age-related variability.Method and subjectsWe present three patients who were assessed by polysomnography with two different scores for central sleep apneas published in the literature: the method by Scholle (2011) and the American Academy of Sleep Medicine scoring system (2012).ConclusionsWe speculated that the Scholle scoring system can be more helpful in assessing children with asymptomatic Chiari 1 malformation for a closer follow-up. More studies are needed.

Spinal arachnoid cyst as a cause of isolated, progressive, bilateral C5–C6 radiculopathy

A 41-year-old man presented with bilateral shoulder weakness and pain. The symptoms had been present for 5 years on the left side and for 3 years on the right. His medical history was remarkable for cervical trauma related to a fall 8 years earlier. Neurologic examination showed severe bilateral weakness of shoulder abduction, with atrophy of the deltoid, supraspinatus, and infraspinatus muscles (Fig. 1). Biceps tendon reflexes were decreased bilaterally. Electromyography findings were consistent with bilateral C5–C6 radiculopathy. Magnetic resonance imaging revealed a spinal intradural arachnoid cyst extending from the level of C2 to L3 (Fig. 2), displacing the spinal cord posteriorly. Computed tomography-myelography showed early filling of this cyst with contrast material, suggesting a large communication with the subarachnoid space. The patient underwent an L2–L3 laminotomy with cyst fenestration and shunting. Three months after surgery, a slight improvement of strength was noticed. Radiculopathy or myelopathy resulting from compression by a spinal cyst is rare. Nabors et al. classified spinal cysts as extradural without spinal nerve root involvement (Type I), extradural with spinal nerve root involvement (Type II), and intradural (Type III) [1]. Arachnoid cysts, the most common spinal intradural cysts, are either congenital or acquired. The majority of acquired arachnoid cysts develop after spinal cord trauma, subarachnoid hemorrhage, or infection [2]. These lesions are usually posterior to the spinal cord in the thoracic region. Subarachnoid cysts anterior to the spinal cord, which are less common, generally have greater craniocaudal extension and are often associated with previous trauma [2]. The extensive subarachnoid cyst in this case is very likely related to the reported previous trauma. It is possible that the findings were the result of stretch or compression injuries to the nerve roots.

Pediatric optic nerve sheath meningioma.

W e read with great interest the report by Nabavizadeh et al (1) regarding the rare occurrence and aggressive behavior of optic nerve sheath meningioma in the pediatric population (2,3). We had the opportunity to evaluate a 10-year-old girl with a 2-month history of progressive left proptosis. Brain magnetic resonance image (MRI) demonstrated a left intraorbital mass with thickening of the orbital portion of the optic nerve with intense and heterogeneous contrast enhancement. The provisional diagnosis was optic nerve glioma. Two months later, MRI showed enlargement of the mass with extension to the orbital apex but without evidence of intracranial invasion (Fig. 1). Because of rapid tumor growth, the patient underwent frontotemporal craniotomy for tumor excision. Histopathology of the specimen showed fragments of optic nerve surrounded and infiltrated by round aggregates of cells with eosinophilic cytoplasm, round-to-oval uniform nuclei with some pseudoinclusions. No necrosis and mitotic figures were found. Immunohistochemical staining revealed diffuse cytoplasmic epithelial membrane antigen expression, confirming a meningothelial origin (Fig. 2). Progesterone receptor, glial fibrillary acidic protein, leukocyte common antigen, and S-100 were negative. Ki-67 labeling index was 6%–7%, and Bcl-2 labeling index was 15%–20%. The final diagnosis was meningothelial meningioma, WHO Grade I, with recommendation of careful follow-up because of the Ki-67 index. No recurrence of disease was documented on MRI 3 months later. Clinical behavior of primary optic nerve sheath meningioma seems more aggressive in pediatric patients than in adults, with rapid visual decline and greater likelihood of intracranial extension and recurrence. Although established

Operative Classification of Brain Arteriovenous Malformation Part Two: Validation

The most important issue when dealing with a patient with a brain AVM is the decision whether to treat or not. Only after this decision has been made, taking into consideration a number of factors depending on both the patient and the specific type of AVM, can the best option for treatment be chosen. An operative classification of brain AVMs, previously adopted in the Department of Neuroradiology and Neurosurgery of Verona (Italy) and published in this journal, was subjected to validation in a consecutive group of 104 patients clinically followed for at least three years after completion of treatment. This classification, slightly modified from the original version concerning the importance of some specific items, allowed us to assess the indication to treat in each case, whatever type of treatment was offered to the patient.

Intraoperative identification of the corticospinal tract and dorsal column of the spinal cord by electrical stimulation

Objectives Anatomical identification of the corticospinal tract (CT) and the dorsal column (DC) of the exposed spinal cord is difficult when anatomical landmarks are distorted by tumour growth. Neurophysiological identification is complicated by the fact that direct stimulation of the DC may result in muscle motor responses due to the centrally activated H-reflex. This study aims to provide a technique for intraoperative neurophysiological differentiation between CT and DC in the exposed spinal cord. Methods Recordings were obtained from 32 consecutive patients undergoing spinal cord tumour surgery from July 2015 to March 2017. A double train stimulation paradigm with an intertrain interval of 60 ms was devised with recording of responses from limb muscles. Results In non-spastic patients (55% of cohort) an identical second response was noted following the first CT response, but the second response was absent after DC stimulation. In patients with pre-existing spasticity (45%), CT stimulation again resulted in two identical responses, whereas DC stimulation generated a second response that differed substantially from the first one. The recovery times of interneurons in the spinal cord grey matter were much shorter for the CT than those for the DC. Therefore, when a second stimulus train was applied 60 ms after the first, the CT-fibre interneurons had already recovered ready to generate a second response, whereas the DC interneurons were still in the refractory period. Conclusions Mapping of the spinal cord using double train stimulation allows neurophysiological distinction of CT from DC pathways during spinal cord surgery in patients with and without pre-existing spasticity.