The neurophysiological effect of mild hypothermia in gyrencephalic brains submitted to ischemic stroke and spreading depolarizations.

Objective: Characterize the neurophysiological effects of mild hypothermia on stroke and spreading depolarizations (SDs) in gyrencephalic brains. Methods: Left middle cerebral arteries (MCAs) of six hypothermic and six normothermic pigs were permanently occluded (MCAo). Hypothermia began 1 h after MCAo and continued throughout the experiment. ECoG signals from both frontoparietal cortices were recorded. Five-minute ECoG epochs were collected 5 min before, at 5 min, 4, 8, 12, and 16 h after MCAo, and before, during, and after SDs. Power spectra were decomposed into fast (alpha, beta, and gamma) and slow (delta and theta) frequency bands. Results: In the vascular insulted hemisphere under normothermia, electrodes near the ischemic core exhibited power decay across all frequency bands at 5 min and the 4th hour after MCAo. The same pattern was registered in the two furthest electrodes at the 12th and 16th hour. When mild hypothermia was applied in the vascular insulted hemispheres, the power decay was generalized and seen even in electrodes with uncompromised blood flow. During SD analysis, hypothermia maintained increased delta and beta power during the three phases of SDs in the furthest electrode from the ischemic core, followed by the second furthest and third electrode in the beta band during preSD and postSD segments. However, in hypothermic conditions, the third electrode showed lower delta, theta, and alpha power. Conclusion: Mild hypothermia attenuates all frequency bands in the vascularly compromised hemisphere, irrespective of the cortical location. During SD formation, it preserves power spectra more significantly in electrodes further from the ischemic core.

Epilepsy and education: A case-control analysis of the impact of an intensive epilepsy training program on undergraduate medical students.

AIMS: To evaluate the knowledge, attitudes, and practical skills of students submitted to a 6-week intensive training in epilepsy compared to students without any training but mandatory neurology classes. METHODS: It is a case-control study. After completing a 6-week intensive Academic, Clinical, and Research Program in epilepsy, TUMSs answered a validated Knowledge Attitudes and Practices (KAP) questionnaire. The control group, composed of undergraduate students who shared the same age, academic year, and compulsory hours for learning about epilepsy as TUMSs, was also assessed through the KAP instrument. Answers from both groups were submitted to Fisher exact and the χ2 test to observe differences among groups. Descriptive statistics were also performed. RESULTS: TUMSs displayed better results in theoretical knowledge such as the definition and causes of epilepsy, and the application of paraclinical studies essential for diagnosing epilepsy. From their perspective, people with epilepsy encounter restricted opportunities for preserving their social life and employment and they are more prone to workplace accidents. They are convinced that facing epilepsy presents a notable risk due to the difficulties linked with diagnosis, considering epilepsy a challenging disease for general practitioners to identify and follow up. Likewise, they exhibited improvement in treatment adjustment and treatment monitoring of patients with epilepsy, mainly in pregnancy cases. Finally, they had greater knowledge about what to do when they witness a person experiencing a seizure. CONCLUSION: Our study showed that a 6-week intensive education program in epilepsy increased the knowledge and practical skills and changed the attitude toward patients with epilepsy of undergraduate students.

Multi-Stage Treatment for Spetzler-Martin Grades III, IV, and V Arteriovenous Malformations: Preoperative Embolization and Microsurgical Resection in a Consecutive Series of 250 Patients.

PURPOSE: The treatment of high-grade brain AVMs is challenging and has no guidelines available to date. This study was aimed at reporting the experience of two centers in treating these AVMs through a multi-stage approach consisting of preoperative embolization and microsurgical resection. METHODS: A retrospective review was performed for 250 consecutive patients with a diagnosis of high-grade brain AVM (Spetzler-Martin grades III, IV, and V) treated in two centers in Germany between January 1989 and February 2023. The analyzed data included demographic, clinical, morphological, and neurological data. RESULTS: A total of 150 cases (60%) were classified as Spetzler-Martin grade III, 82 cases (32.8%) were classified as grade IV, and 18 cases (7.2%) were classified as grade V. Eighty-seven cases (34.8%) presented with hemorrhage. The devascularization percentages achieved were <50% in 24 (9.6%), 50-80% in 55 (22%), and >80% in 171 (68.4%) cases. The average number of sessions was 5.65 ± 5.50 and 1.11 ± 0.32 endovascular and surgical procedures, respectively, and did not significantly differ by rupture status. Death or dependency (mRS score ≥ 3) after the last follow-up was observed in 18.8% of patients and was significantly associated with age > 80 years and poor baseline neurological condition. The complete resection rate was 82.3% and was significantly associated with age > 80 years, large nidus, and deep venous drainage. Permanent disabling neurological deficit after at least 3 months of follow-up was diagnosed in 13.2% of patients and was significantly associated with age > 80 years and infratentorial locations. CONCLUSION: A multi-stage treatment for high-grade AVMs is feasible for selected cases but comes at a functional cost. The devascularization percentage was not associated with the investigated outcomes. Age > 80 years was associated with poor safety and effectiveness outcomes; consequently, this treatment should be offered only in exceptional circumstances.

Mild hypothermia reduces spreading depolarizations and infarct size in a swine model.

Spreading depolarizations (SDs) have been linked to infarct volume expansion following ischemic stroke. Therapeutic hypothermia provides a neuroprotective effect after ischemic stroke. This study aimed to evaluate the effect of hypothermia on the propagation of SDs and infarct volume in an ischemic swine model. Through left orbital exenteration, middle cerebral arteries were surgically occluded (MCAo) in 16 swine. Extensive craniotomy and durotomy were performed. Six hypothermic and five normothermic animals were included in the analysis. An intracranial temperature probe was placed right frontal subdural. One hour after ischemic onset, mild hypothermia was induced and eighteen hours of electrocorticographic (ECoG) and intrinsic optical signal (IOS) recordings were acquired. Postmortem, 4 mm-thick slices were stained with 2,3,5-triphenyltetrazolium chloride to estimate the infarct volume. Compared to normothermia (36.4 ± 0.4°C), hypothermia (32.3 ± 0.2°C) significantly reduced the frequency and expansion of SDs (ECoG: 3.5 ± 2.1, 73.2 ± 5.2% vs. 1.0 ± 0.7, 41.9 ± 21.8%; IOS 3.9 ± 0.4, 87.6 ± 12.0% vs. 1.4 ± 0.7, 67.7 ± 8.3%, respectively). Further, infarct volume among hypothermic animals (23.2 ± 1.8% vs. 32.4 ± 2.5%) was significantly reduced. Therapeutic hypothermia reduces infarct volume and the frequency and expansion of SDs following cerebral ischemia.

Cerebrovascular Pressure Reactivity According to Long-Pressure Reactivity Index During Spreading Depolarizations in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Spreading depolarization (SD) has been linked to the impairment of neurovascular coupling. However, the association between SD occurrence and cerebrovascular pressure reactivity as a surrogate of cerebral autoregulation (CA) remains unclear. Therefore, we analyzed CA using the long-pressure reactivity index (L-PRx) during SDs in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: A retrospective study of patients with aSAH who were recruited at two centers, Heidelberg (HD) and Berlin (BE), was performed. Continuous monitoring of mean arterial pressure (MAP) and intracranial pressure (ICP) was recorded. ICP was measured using an intraparenchymal probe in HD patients and was measure in BE patients through external ventricular drainage. Electrocorticographic (ECoG) activity was continuously recorded between 3 and 13 days after hemorrhage. Autoregulation according to L-PRx was calculated as a moving linear Pearson's correlation of 20-min averages of MAP and ICP. For every identified SD, 60-min intervals of L-PRx were averaged, plotted, and analyzed depending on SD occurrence. Random L-PRx recording periods without SDs served as the control. RESULTS: A total of 19 patients (HD n = 14, BE n = 5, mean age 50.4 years, 9 female patients) were monitored for a mean duration of 230.4 h (range 96-360, STD ± 69.6 h), during which ECoG recordings revealed a total number of 277 SDs. Of these, 184 represented a single SD, and 93 SDs presented in clusters. In HD patients, mean L-PRx values were 0.12 (95% confidence interval [CI] 0.11-0.13) during SDs and 0.07 (95% CI 0.06-0.08) during control periods (p < 0.001). Similarly, in BE patients, a higher L-PRx value of 0.11 (95% CI 0.11-0.12) was detected during SDs than that during control periods (0.08, 95% CI 0.07-0.09; p < 0.001). In a more detailed analysis, CA changes registered through an intraparenchymal probe (HD patients) revealed that clustered SD periods were characterized by signs of more severely impaired CA (L-PRx during SD in clusters: 0.23 [95% CI 0.20-0.25]; single SD: 0.09 [95% CI 0.08-0.10]; control periods: 0.07 [95% CI 0.06-0.08]; p < 0.001). This group also showed significant increases in ICP during SDs in clusters compared with single SD and control periods. CONCLUSIONS: Neuromonitoring for simultaneous assessment of cerebrovascular pressure reactivity using 20-min averages of MAP and ICP measured by L-PRx during SD events is feasible. SD occurrence was associated with significant increases in L-PRx values indicative of CA disturbances. An impaired CA was found during SD in clusters when using an intraparenchymal probe. This preliminary study validates the use of cerebrovascular reactivity indices to evaluate CA disturbances during SDs. Our results warrant further investigation in larger prospective patient cohorts.

Spatial and temporal frequency band changes during infarct induction, infarct progression, and spreading depolarizations in the gyrencephalic brain.

Aim: To describe the spatial and temporal electrocorticographic (ECoG) changes after middle cerebral artery occlusion (MCAo), including those caused by spreading depolarization (SD) in the pig brain. Methods: The left middle cerebral arteries (MCAs) were clipped in six pigs. The clipping procedure lasted between 8 and 12 min, achieving a permanent occlusion (MCAo). Five-contact ECoG stripes were placed bilaterally over the frontoparietal cortices corresponding to the irrigation territory of the MCA and anterior cerebral artery (ACA). ECoG recordings were performed around 24 h: 1 h before and 23 h after the MCAo, and SDs were quantified. Five-minute ECoG signal segments were sampled before, 5 min, and 4, 8, and 12 h after cerebral artery occlusion and before, during, and after the negative direct current shift of the SDs. The power spectrum of the signals was decomposed into delta, theta, alpha, beta, and gamma bands. Descriptive statistics, Wilcoxon matched-pairs signed-rank tests, and Friedman tests were performed. Results: Electrodes close to the MCAo showed instant decay in all frequency bands and SD onset during the first 5 h. Electrodes far from the MCAo exhibited immediate loss of fast frequencies and progressive decline of slow frequencies with an increased SD incidence between 6 and 14 h. After 8 h, the ACA electrode reported a secondary reduction of all frequency bands except gamma and high SD incidence within 12-17 h. During the SD, all electrodes showed a decline in all frequency bands. After SD passage, frequency band recovery was impaired only in MCA electrodes. Conclusion: ECoG can identify infarct progression and secondary brain injury. Severe disturbances in all the frequency bands are generated in the cortices where the SDs are passing by.

Evolution and Revolution of Imaging Technologies in Neurosurgery.

We understand only a small fraction of the events happening in our brains; therefore, despite all the progress made thus far, a whole array of questions remains. Nonetheless, neurosurgeons invented new tools to circumvent the challenges that had plagued their predecessors. With the manufacturing boom of the 20th century, technological innovations blossomed enabling the neuroscientific community to study and operate upon the living brain in finer detail and with greater precision while avoiding harm to the nervous system. The purpose of this chronological review is to 1) raise awareness among future neurosurgeons about the latest advances in the field, 2) become familiar with innovations such as augmented reality (AR) that should be included in education given their ready applicability in surgical training, and 3) be comfortable with customizing these technologies to real-life cases like in the case of mixed reality.

Screening spreading depolarizations during epilepsy surgery.

BACKGROUND: Spreading depolarization (SD) is a fundamental pathophysiological mechanism of both pannecrotic and selective neuronal lesions following deprivation of energy. SD with brain injury has been reported including in one patient during an intracranial operation. However, the incidence of SDs in operative resections is unknown. METHODS: We performed (a) retrospective analysis of intraoperative AC-recordings of 69 patients and (b) a prospective study using intraoperative near-DC recording. All patients had the diagnosis of pharmaco-resistant epilepsy. Both studies were designed to determine the incidence and characteristics of SDs intraoperatively. In the retrospective analysis, we used intraoperative electrocorticography (iECoG) recordings obtained from AC-recording of 69 patients. In the prospective analysis, we used an Octal Bio Amp and Power Lab ECoG recorder with near-DC range. RESULTS: In the retrospective study, we included 69 patients with a mean of 1 h 3 min of iECoG recordings. In the prospective study, we recruited 20 patients with near DC recordings. A total of 35 h 41 min of iECoG recordings with mean of 2 h 32 min/patient were analyzed. We did not find SD in either study. CONCLUSIONS: SDs were not detected during intraoperative recordings of epilepsy surgery using AC- or DC-amplifiers.

Fractal anatomy of the hippocampal formation.

PURPOSE: We believed that the hippocampal complex is a fractal, and we try to demonstrate it. METHODS: We selected 12 magnetic resonance (MR) studies from healthy brains. Five women and 7 men without neurological or psychiatric disease were analyzed. The age range was 50-71 years old, with a mean 57.1 ± 7.6 years. Image series of MR were obtained through 3D SPGR in scanner GE Singa 3.0 T (general Electric, USA), matrix acquisition 512 Å-512 Å-120, field size 240 mm, voxel size 0.47 mm Å-0.47 mm Å-1.2 mm, repetition time of 13 ms and eco time of 5.6 ms. The MRI were imported in DICOM format in the OsiriXsoftware where they were contoured. Post processing was done with ImageJ software; Box Counting method for fractal analysis and we also used the Box Counting method of the BoneJ plugin. RESULTS: All of the hippocampus analyzed were a fractal. The fractal dimension analysis distribution of the measurements had a central tendency. The mean of hippocampal fractal dimension was 1.32635, the range was from 1.3373 to 1.5344. We found a short interval of variability in the hippocampal fractal number. CONCLUSIONS: The hippocampal complex is a fractal. The fractal analysis must be an objective measurement that can help us as a descriptive tool in hippocampal anatomy and maybe in a close future in the diagnosis of anatomical alterations.