Intraoperative Neurophysiological Monitoring in Syringomyelia Surgery: A Multimodal Approach.

Syringomyelia can be associated with multiple etiologies. The treatment of the underlying causes is first-line therapy; however, a direct approach to the syrinx is accepted as rescue treatment. Any direct intervention on the syrinx requires a myelotomy, posing a significant risk of iatrogenic spinal cord (SC) injury. Intraoperative neurophysiological monitoring (IONM) is crucial to detect and prevent surgically induced damage in neural SC pathways. We retrospectively reviewed the perioperative and intraoperative neurophysiological data and perioperative neurological examinations in ten cases of syringomyelia surgery. All the monitored modalities remained stable throughout the surgery in six cases, correlating with no new postoperative neurological deficits. In two patients, significant transitory attenuation, or loss of motor evoked potentials (MEPs), were observed and recovered after a corrective surgical maneuver, with no new postoperative deficits. In two cases, a significant MEP decrement was noted, which lasted until the end of the surgery and was associated with postoperative weakness. A transitory train of neurotonic electromyography (EMG) discharges was reported in one case. The surgical plan was adjusted, and the patient showed no postoperative deficits. The dorsal nerve roots were stimulated and identified in the seven cases where the myelotomy was performed via the dorsal root entry zone. Dorsal column mapping guided the myelotomy entry zone in four of the cases. In conclusion, multimodal IONM is feasible and reliable and may help prevent iatrogenic SC injury during syringomyelia surgery.

Comparison of cerebral metabolic rate of oxygen, blood flow, and bispectral index under general anesthesia.

Significance: The optical measurement of cerebral oxygen metabolism was evaluated. Aim: Compare optically derived cerebral signals to the electroencephalographic bispectral index (BIS) sensors to monitor propofol-induced anesthesia during surgery. Approach: Relative cerebral metabolic rate of oxygen ( rCMRO 2 ) and blood flow (rCBF) were measured by time-resolved and diffuse correlation spectroscopies. Changes were tested against the relative BIS (rBIS) ones. The synchronism in the changes was also assessed by the R-Pearson correlation. Results: In 23 measurements, optically derived signals showed significant changes in agreement with rBIS: during propofol induction, rBIS decreased by 67% [interquartile ranges (IQR) 62% to 71%], rCMRO 2 by 33% (IQR 18% to 46%), and rCBF by 28% (IQR 10% to 37%). During recovery, a significant increase was observed for rBIS (48%, IQR 38% to 55%), rCMRO 2 (29%, IQR 17% to 39%), and rCBF (30%, IQR 10% to 44%). The significance and direction of the changes subject-by-subject were tested: the coupling between the rBIS, rCMRO 2 , and rCBF was witnessed in the majority of the cases (14/18 and 12/18 for rCBF and 19/21 and 13/18 for rCMRO 2 in the initial and final part, respectively). These changes were also correlated in time ( R > 0.69 to R = 1 , p - values < 0.05 ). Conclusions: Optics can reliably monitor rCMRO 2 in such conditions.

Diagnosis and treatment of Chiari malformation type 1 in children: the International Consensus Document.

BACKGROUND: Chiari malformation type 1 (CM1) is a rare condition where agreed classification and treatment are still missing. The goal of this study is to achieve a consensus on the diagnosis and treatment of CM1 in children. METHODS: A multidisciplinary panel formulated 57 provisional statements based on a review of the literature. Thirty-four international experts (IE) participated in a Delphi study by independently rating each statement on a 4-point Likert scale ("strongly disagree," "disagree," "agree," "strongly agree"). Statements that were endorsed ("agree" or "strongly agree") by < 75% of raters were re-formulated, or new statements were added, and another Delphi round followed (up to a maximum of three). RESULTS: Thirty-five IE were contacted and 34 agreed to participate. A consensus was reached on 30/57 statements (52.6%) after round 1. Three statements were added, and one removed. After round 2, agreement was reached on 56/59 statements (94.9%). Finally, after round 3, which took place during the 2019 Chiari Consensus Conference (Milan, Italy), agreement was reached on 58/59 statements (98.3%) about four main sections (Definition and Classification, Planning, Surgery, Isolated Syringomyelia). Only one statement did not gain a consensus, which is the "definition of radiological failure 24 month post-surgery." CONCLUSIONS: The consensus document consists of 58 statements (24 on diagnosis, 34 on treatment), serving clinicians and researchers following children with CM1. There is a clear need for establishing an international network and registry and to promote collaborative studies to increase the evidence base and optimize the long-term care of this patient population.

Cortical Spreading Depression Phenomena Are Frequent in Ischemic and Traumatic Penumbra: A Prospective Study in Patients With Traumatic Brain Injury and Large Hemispheric Ischemic Stroke.

PURPOSE: Spreading depolarization (SD) phenomena are waves of neuronal depolarization, which propagate slowly at a velocity of 1 to 5 mm/minute and can occur in patients with ischemic or hemorrhagic stroke, traumatic brain injury, and migraine with aura. They form part of secondary injury, occurring after spreading ischemia. The purposes of this study were to describe the frequency and characteristics of SD phenomena and to define whether a correlation existed between SD and outcome in a group of patients with TBI and large hemispheric ischemic stroke. METHODS: This was a prospective observational study of 39 adult patients, 17 with malignant middle cerebral artery infarction and 22 with moderate or severe traumatic brain injury, who underwent decompressive craniectomy and multimodal neuromonitoring including electrocorticography. Identification, classification, and interpretation of SDs were performed using the published recommendations from the Cooperative Study on Brain Injury Depolarization group. The outcomes assessed were functional disability at 6 and 12 months after injury, according to the extended Glasgow outcome scale, Barthel index, and modified Rankin scale. RESULTS: Four hundred eighty-three SDs were detected, in 58.9% of the patients. Spreading depolarizations were more common, particularly the isoelectric SD type, in patients with malignant middle cerebral artery infarction (P < 0.04). In 65.21% of patients with SDs on electrocorticography, the "peak" day of depolarization was day 0 (the first 24 hours of recording). Spreading depolarization convulsions were present in 26.08% of patients with SDs. Patients with more SDs and higher depolarization indices scored worse on extended Glasgow outcome scale (6 months) and Barthel index (6 and 12 months) (P < 0.05). CONCLUSIONS: Evidence on SD phenomena is important to ensure continued progress in understanding their pathophysiology, in the search for therapeutic targets to avoid additional damage from these secondary injuries.

Circulating tumour DNA from the cerebrospinal fluid allows the characterisation and monitoring of medulloblastoma.

The molecular characterisation of medulloblastoma, the most common paediatric brain tumour, is crucial for the correct management and treatment of this heterogenous disease. However, insufficient tissue sample, the presence of tumour heterogeneity, or disseminated disease can challenge its diagnosis and monitoring. Here, we report that the cerebrospinal fluid (CSF) circulating tumour DNA (ctDNA) recapitulates the genomic alterations of the tumour and facilitates subgrouping and risk stratification, providing valuable information about diagnosis and prognosis. CSF ctDNA also characterises the intra-tumour genomic heterogeneity identifying small subclones. ctDNA is abundant in the CSF but barely present in plasma and longitudinal analysis of CSF ctDNA allows the study of minimal residual disease, genomic evolution and the characterisation of tumours at recurrence. Ultimately, CSF ctDNA analysis could facilitate the clinical management of medulloblastoma patients and help the design of tailored therapeutic strategies, increasing treatment efficacy while reducing excessive treatment to prevent long-term secondary effects.

Distal catheter lengthening in pediatric patients with hydrocephalus using a guidewire-assisted technique.

PURPOSE: The aim of this study was to evaluate the lengthening or replacement of the peritoneal catheter in a ventriculoperitoneal shunt by using a simple guidewire-assisted technique. Here we report on our experience with this methodology, its indications, caveats, and contraindications. METHODS: A prospective study was performed in 59 consecutively shunted children who required elective lengthening of the peritoneal catheter (25 females and 34 males, mean 10.5 + 4.2 years). The procedure required an incision of only 1 cm over the distal catheter. The catheter was sectioned, and a soft hydrophilic guidewire was inserted into the exposed end of it, which serves as a route for the guidewire to reach the intraperitoneal space. The procedure was followed by the replacement of the patient's catheter with one with additional length as considered appropriate, prior to putting additional slots in the last 5 to 8 cm of the new catheter. RESULTS: The technique was used in 62 CSF shunts (3 patients had a double derivative system). Fifty-five of the 62 (89%) procedures performed were effective. A conventional peritoneal opening technique was used in the 7 unsuccessful attempts. One patient presented a migration of the abdominal catheter during the first days after surgery. No incident of peritoneal perforation was associated with this technique, nor were any infections or other early or late complications associated with this surgical procedure. CONCLUSION: The technique we propose permits the peritoneal catheter of a derivative system to be lengthened or replaced in a manner that is simple, fast, and safe.

Molecular Diagnosis of Diffuse Gliomas through Sequencing of Cell-Free Circulating Tumor DNA from Cerebrospinal Fluid.

Purpose: Diffuse gliomas are the most common primary tumor of the brain and include different subtypes with diverse prognosis. The genomic characterization of diffuse gliomas facilitates their molecular diagnosis. The anatomical localization of diffuse gliomas complicates access to tumor specimens for diagnosis, in some cases incurring high-risk surgical procedures and stereotactic biopsies. Recently, cell-free circulating tumor DNA (ctDNA) has been identified in the cerebrospinal fluid (CSF) of patients with brain malignancies.Experimental Design: We performed an analysis of IDH1, IDH2, TP53, TERT, ATRX, H3F3A, and HIST1H3B gene mutations in two tumor cohorts from The Cancer Genome Atlas (TCGA) including 648 diffuse gliomas. We also performed targeted exome sequencing and droplet digital PCR (ddPCR) analysis of these seven genes in 20 clinical tumor specimens and CSF from glioma patients and performed a histopathologic characterization of the tumors.Results: Analysis of the mutational status of the IDH1, IDH2, TP53, TERT, ATRX, H3F3A, and HIST1H3B genes allowed the classification of 79% of the 648 diffuse gliomas analyzed, into IDH-wild-type glioblastoma, IDH-mutant glioblastoma/diffuse astrocytoma and oligodendroglioma, each subtype exhibiting diverse median overall survival (1.1, 6.7, and 11.2 years, respectively). We developed a sequencing platform to simultaneously and rapidly genotype these seven genes in CSF ctDNA allowing the subclassification of diffuse gliomas.Conclusions: The genomic analysis of IDH1, IDH2, TP53, ATRX, TERT, H3F3A, and HIST1H3B gene mutations in CSF ctDNA facilitates the diagnosis of diffuse gliomas in a timely manner to support the surgical and clinical management of these patients. Clin Cancer Res; 24(12); 2812-9. ©2018 AACR.

Target location after deep cerebral biopsies using low-volume air injection in 75 patients. Results and technical note.

BACKGROUND: Stereotactic biopsy is a minimally invasive technique that allows brain tissue samples to be obtained with low risk. Classically, different techniques have been used to identify the biopsy site after surgery. OBJECTIVE: To describe a technique to identify the precise location of the target in the postoperative CT scan using the injection of a low volume of air into the biopsy cannula. METHODS: Seventy-five biopsies were performed in 65 adults and 10 children (40 males and 35 females, median age 51 years). Frame-based biopsy was performed in 46 patients, while frameless biopsy was performed in the remaining 29 patients. In both systems, after brain specimens had been collected and with the biopsy needle tip in the center of the target, a small volume of air (median 0.7 cm3) was injected into the site. RESULTS: A follow-up CT scan was performed in all patients. Intracranial air in the selected target was present in 69 patients (92%). No air was observed in two patients (air volume administered in these 2 cases was below 0.7 cm3), while in the remaining four patients blood content was observed in the target. The diagnostic yield in this series was 97.3%. No complications were found to be associated with intracranial air injection in any of the 75 patients who underwent this procedure. CONCLUSIONS: The air-injection maneuver proposed for use in stereotactic biopsies of intracranial mass lesions is a safe and reliable technique that allows the exact biopsy site to be located without any related complications.

Brain activation during speech perception in a patient with a massive left hemisphere infarction.

BACKGROUND: Little is known about the regions involved in recovery from global aphasia in patients with malignant infarction after decompressive hemicraniectomy. This study reports a case of brain activation during speech perception in a right-handed patient with a massive left hemispheric infarction. METHODS: Decompressive hemicraniectomy was performed in a 20-year old woman with space-occupying infarction of the speech dominant hemisphere. Complete anterior, middle and part of the posterior cerebral artery territories of the left hemisphere, as well as posterior regions of the right middle cerebral artery territory, were affected. Neuropsychological testing and functional magnetic resonance imaging (fMRI) during speech perception were performed 10 months after stroke. RESULTS: The patient was able to walk, go up and down stairs independently and perform simple tasks at home. She was also well able to match visually and orally presented words with their corresponding pictures, despite large bilateral lesions in the posterior regions. fMRI revealed strong activation of the left temporo-occipital and parieto-occipital areas. In the right hemisphere was observed a small area of activation in the posterior part of the superior and middle temporal gyrus. CONCLUSIONS: In aphasic patients, the activation of posterior bilateral associative areas might be used to support language perception.

Cognitive disturbances and neuropsychological changes after surgical treatment in a cohort of 185 patients with idiopathic normal pressure hydrocephalus.

Although idiopathic normal pressure hydrocephalus (iNPH) is considered a treatable dementia, there is still some controversy regarding the cognitive improvement in these patients. The main aims of this study were to analyze baseline cognitive status and to study the neuropsychological changes after surgical treatment in a sample of 185 consecutive iNPH patients. An additional aim was to identify the variables that influenced the cognitive outcome. Specific tests assessing memory, attention, visual scanning, executive functions (EFs), and motor speed were used before and 6 months after shunting. The cognitive domains most affected at baseline were memory, EFs, attention, and psychomotor speed. After shunting, significant differences in the group as a whole were found in all tests except Digits Forward and Trail Making Part B. However, less than 50% of patients showed a significant improvement when analyzed individually. Previous global cognitive status assessed by Mini-Mental State Examination baseline scores was the best predictor for the cognitive outcome.

Intracranial pressure monitoring with the Neurodur-P epidural sensor: a prospective study in patients with adult hydrocephalus or idiopathic intracranial hypertension.

OBJECT: Continuous intracranial pressure (ICP) monitoring using an epidural sensor is a common technique used in selected neurosurgical patients. The aim of this study was to assess the safety and accuracy of the Neurodur-P epidural sensor in the clinical setting. METHODS: The zero drift, as well as the medical and technical complications, of using the Neurodur-P sensor placed in the epidural space was evaluated in 106 patients with hydrocephalus of varying causes or with suspected intracranial hypertension. RESULTS: The median duration of ICP monitoring was 8 days (interquartile range [IQR] 6-12 days). In 78 (73.6%) of the 106 patients the pressure reading was recorded at sensor removal. No zero drift was observed in 28 sensors. The median drift was 0 mm Hg with an IQR of -1 to 1 mm Hg. No significant differences were found between patients monitored for < or = 5 days and those monitored for > 5 days (t = 535, p = 0.100). No correlation was found between zero drift and monitoring time (r = 0.153, p = 0.181). Of the 83 patients with a follow-up computed tomography scan, 3 showed a < 1 ml collection of blood at the catheter tip. No clinical infections could be attributed to the devices. Only 1 sensor malfunctioned. CONCLUSIONS: Continuous ICP monitoring using the Neurodur-P sensor is safe, reliable, and easy to perform. At present, using this device is the authors' standard method for the long-term monitoring of patients with alterations in complex cerebrospinal fluid dynamics or with implanted shunts.

Intra-abdominal pressure: the neglected variable in selecting the ventriculoperitoneal shunt for treating hydrocephalus.

OBJECTIVE: In the selection of a ventriculoperitoneal cerebrospinal fluid shunt, the intra-abdominal pressure (IAP) is traditionally neglected as a result of the idea that its value is close to 0 mmHg. Our aim was to explore the relationship between body mass index (BMI) and IAP with the goal of providing clinically relevant data that could help neurosurgeons to estimate IAP and select the appropriate shunt for patients with hydrocephalus and especially those with normal-pressure hydrocephalus syndrome. METHODS: Sixty patients requiring the placement of a ventriculoperitoneal shunt were included in the study. We determined weight, BMI, and IAP. IAP was measured through an intraperitoneal catheter during the shunt surgery. To determine whether a linear relationship existed between quantitative variables, linear regression analysis was used. RESULTS: BMI was 28.1 +/- 4.8 kg/m2. Eighteen patients (30%) had normal weight, 21 (35%) were moderately overweight, and 21 (35%) were obese. IAP was related to patient BMI. A significant positive linear correlation was identified between BMI and IAP (r = 0.52; P = 0.018) with a slope of 0.31 (P < 0.001) and an intercept of -5.5. CONCLUSION: In our study, we determined that IAP had a strong positive linear relationship with BMI. This correlation was independent of sex. An IAP of 0 mmHg can, therefore, only be assumed for patients with a normal BMI who are recumbent. In obese or overweight patients, neurosurgeons should take IAP into account when selecting both the most adequate differential pressure valve to be implanted and in which distal cavity to place the distal catheter to avoid shunt underdrainage induced by high IAP.

Percutaneous implantation of cerebral microdialysis catheters by twist-drill craniostomy in neurocritical patients: description of the technique and results of a feasibility study in 97 patients.

Cerebral microdialysis is increasingly used to monitor several types of neurocritical patients. This study presents the technique used in our unit for percutaneous implantation of cerebral microdialysis catheters using a small twist-drill craniostomy that can be performed in the intensive care unit (ICU). We also present the results of this technique in 89 head-injured patients and in eight patients with a malignant middle cerebral artery (MCA) infarction. One hundred and twenty-two cerebral microdialysis catheters were implanted in the 97 patients included in this study. One cerebral microdialysis catheter was implanted in the less damaged hemisphere of 67 head-injured patients with a diffuse brain injury. An additional microdialysis catheter was inserted in the pericontusional parenchyma of 22 patients with brain contusions. In five of the eight patients with a malignant MCA infarction, only one microdialysis probe was inserted in the penumbral zone. In the remaining three patients, two cerebral microdialysis catheters were implanted in the same hemisphere (one in the ischemic core and the other in the penumbra). Technical problems were detected in 18 (15%) of the 122 microdialysis catheters implanted and were more frequent during the initial period of using microdialysis in our unit. In four patients (3% of implanted catheters), follow-up computed tomography (CT) scans showed a small intracerebral blood collection (always

Good outcome in patients with normal-pressure hydrocephalus and factors indicating poor prognosis.

OBJECT: The authors set out to describe the outcome in a subgroup of patients with normal-pressure hydrocephalus (NPH) in whom prognostic factors were poor. This subgroup of patients who had received shunts was selected according to strict criteria. METHODS: From a cohort of 56 patients with NPH in whom shunts were placed, the authors selected a subgroup with four of the factors traditionally considered to indicate poor prognosis: idiopathic type, cortical atrophy, longstanding symptoms, and presence of dementia in addition to old age. Twelve patients met the inclusion criteria. After receiving shunts, 92% of the patients showed clinical improvement on the NPH scale; gait improved in 100% of patients, sphincter control in 90%, and dementia in 33%. Improvement was significant for gait and sphincter control, general NPH score, and most daily life activity scales. No significant differences regarding clinical, cognitive, or functional changes following surgery were found in comparison with the rest of patients (the good prognosis subgroup). CONCLUSIONS: The clinical condition of patients with NPH who present with traditionally accepted markers of poor prognosis can improve after surgery, especially as regards gait and sphincter control. The authors assert that the presence of these markers should not be considered to be an absolute criterion for ruling out shunt surgery in cases of NPH syndrome.

Is the placement of shunts in patients with idiopathic normal-pressure hydrocephalus worth the risk? Results of a study based on continuous monitoring of intracranial pressure.

OBJECT: Data from many studies have demonstrated that shunt insertion in patients with idiopathic normal-pressure hydrocephalus (NPH) is associated with high morbidity and a lack of significant improvement; however, the use of strict diagnostic and treatment protocols can improve the results of surgery in these patients. The primary aim in this prospective study was to analyze the results of shunt placement in 43 patients with idiopathic NPH. A secondary aim was to determine the relationship between several clinical and neuroimaging factors, and patient outcome after surgery. METHODS: Thirty men and 13 women with a mean age of 71.1 +/- 6.9 years participated in this study. All patients underwent clinical, neuropsychological, and radiological assessment before and 6 months after surgery. In all patients continuous monitoring of intracranial pressure was performed using a fiberoptic extradural sensor. In 31 patients cerebrospinal fluid dynamics were also determined. Eighty-six percent of patients showed clinical improvement after shunt insertion, 11.6% showed no change, and 2.3% exhibited some worsening. Gait improved in 81.4% of the patients, sphincter control in 69.8%, and cognitive dysfunction in 39.5%. There was no treatment-related death. Early or late postsurgical complications occurred in six patients (14%), although all of these complications were minor or were satisfactorily resolved. The complete clinical triad, cortical sulci size, and periventricular lucencies were related to outcome, whereas patient age, symptom duration, ventricular dilation, and the degree of presurgical dementia were unrelated to outcome. CONCLUSIONS: Given the correct diagnosis, shunt insertion can produce marked improvement in patients with idiopathic NPH syndrome, causing few deaths and few clinically relevant complications.

Postsurgical cerebral perfusion changes in idiopathic normal pressure hydrocephalus: a statistical parametric mapping study of SPECT images.

UNLABELLED: Our goal was to study cerebral blood flow (CBF) changes after surgery in a group of 15 patients with idiopathic normal pressure hydrocephalus (NPH). METHODS: We used hexamethylpropyleneamine oxime SPECT and statistical parametric mapping (SPM), an image analysis method that does not require prior selection of regions of interest. RESULTS: Our study showed areas of significant increase in perfusion in specific regions of both frontal lobes and the right parietal lobe. Regions of increased perfusion were found in the left prefrontal dorsolateral areas (Brodmann's areas 9 and 45 or 47), right frontal premotor area (Brodmann's area 44), right medial prefrontal region (Brodmann's area 10 or 32), right frontal white matter area (superior longitudinalis fasciculus), and right basal ganglia (lenticular nucleus, putamen, and globus pallidus). In the right hemisphere, another region of increased perfusion was found in the inferior parietal lobule (Brodmann's area 40). The 2 areas most related to clinical improvement were Brodmann's area 32 and the frontal part of the left lobule of Reil insula. CONCLUSION: The results obtained with the SPM method of image analysis confirm and expand on previous CBF literature in NPH, with specific CBF regions located in frontal and parietal areas that improve after surgery in idiopathic NPH.