Clinical utility and safety of a trapezoid-shaped electrode placement for evaluating the mesio-basal temporal lobe during epilepsy surgery.

A trapezoid-shaped electrode (TSE) is used for detecting epileptogenicity in patients with temporal lobe epilepsy (TLE). However, the utility and safety associated with TSE placement have not been reported. In this study, we evaluated the safety and usefulness of TSE by analyzing the seizure detection, surgical outcomes and complications in patients with TLE who underwent intracranial electrodes (ICE) placement. Between April 2000 and August 2019, 50 patients with TLE who underwent 51 ICE placement procedures were examined. A TSE with eight contacts covering the parahippocampal gyrus and basal temporal lobe was used. Among the 37 patients who underwent TSE placement, 26 and 11 patients were diagnosed with mesial TLE (mTLE) and extra-mTLE, respectively. The 14 remaining patients without TSE placement were diagnosed with extra-mTLE. Seizure freedom was achieved in 73% (19/26) of mTLE patients detected by TSE and 50% (14/24) of extra-mTLE patients.Good seizure outcomes (Engel class I and II) were observed in 81% (21/26) patients with mTLE and 67% (16/24) patients with extra-mTLE. Radiographic complications were observed in 20% (10/50) patients who underwent ICE placement. Although 6% (3/50) patients showed transient neurological deficits, none were permanent. The electrodes responsible for the occurrence of complications included nine grid electrodes and one TSE. The complication rate after TSE placement was 3% (1/37). More than 64 electrode contacts and male sex, not TSE placement, were identified as significant risk factors for developing complications. This study demonstrated the usefulness and safety of TSE for evaluating mTLE in patients undergoing ICE placement.

Mechanical Thrombectomy and Parent Artery Occlusion for Acute Basilar Artery Occlusion Due to Vertebral Fracture and Artery Dissection: A Case Report.

Objective: Basilar artery occlusion (BAO) secondary to traumatic vertebral artery (VA) dissection caused by vertebral fracture is a rare cause of acute ischemic stroke, and optimal management, such as antithrombotic agents, surgical fixation, and parent artery occlusion (PAO), has been controversial. We report a case in which mechanical thrombectomy and PAO were performed for a BAO due to right VA dissection caused by a transverse foramen fracture of the axis vertebra. Case Presentation: A patient in her 80s suffered from a backward fall, and a neck CT revealed a fracture and dislocation of the right lateral mass of the axis and a compressed transverse foramen. The patient was instructed to admit and to remain in bed rest; however, she suddenly lost consciousness the following day. The CTA revealed right VA occlusion and BAO; therefore, the patient underwent mechanical thrombectomy and the BAO was successfully reperfused but the VA stenotic dissection remained. PAO of the right VA was performed on the fifth day after the accident to prevent BAO recurrence. Conclusion: Mechanical thrombectomy is an effective treatment for BAO caused by VA dissection, and PAO may contribute to the prevention of stroke recurrence.

Chemogenetic attenuation of cortical seizures in nonhuman primates.

Epilepsy is a disorder in which abnormal neuronal hyperexcitation causes several types of seizures. Because pharmacological and surgical treatments occasionally interfere with normal brain function, a more focused and on-demand approach is desirable. Here we examined the efficacy of a chemogenetic tool-designer receptors exclusively activated by designer drugs (DREADDs)-for treating focal seizure in a nonhuman primate model. Acute infusion of the GABAA receptor antagonist bicuculline into the forelimb region of unilateral primary motor cortex caused paroxysmal discharges with twitching and stiffening of the contralateral arm, followed by recurrent cortical discharges with hemi- and whole-body clonic seizures in two male macaque monkeys. Expression of an inhibitory DREADD (hM4Di) throughout the seizure focus, and subsequent on-demand administration of a DREADD-selective agonist, rapidly suppressed the wide-spread seizures. These results demonstrate the efficacy of DREADDs for attenuating cortical seizure in a nonhuman primate model.

[Electrocorticography for the Evaluation of Focus Resection].

Electrocorticography(ECoG)with intracranial electrodes has a higher spatial resolution and higher sensitivity than conventional electroencephagrahy. Chronic VIDEO-ECoG with subdural grid electrodes has been used to determine the resection border of epileptic focus, and to evaluate cortical function prior to resective surgery. Recording multiple seizures is necessary to determine whether they are the same as habitual seizures and whether they are reproducible, to allow subsequent identification of the seizure onset zone. It is also necessary to understand the ictal ECoG patterns of various seizure onsets. Recent advances in engineering technology have made wideband(0.01 Hz-600Hz)analysis possible. The resection of the area with the ictal DC shift and high frequency oscillation is reported to improve surgical outcome. Although the procedure of subdural grid insertion is technically easy, high rates of complications, such as infections and bleeding, have been reported. Intraoperative acute ECoG was used to validate the extent of resection area. Overall, intraoperative ECoG is greatly affected by anesthetics, and the interictal epileptic discharge should be evaluated carefully.

Validity of intraoperative ECoG in the parahippocampal gyrus as an indicator of hippocampal epileptogenicity.

PURPOSE: Intraoperative electrocorticography (ECoG) in the parahippocampal gyrus is sometimes used as a substitute for intraoperative ECoG in the hippocampus. This study aimed to elucidate the validity of parahippocampal ECoG as an indicator of hippocampal epileptogenicity. METHODS: We retrospectively identified 10 patients with drug-resistant unilateral mesial temporal lobe epilepsy who achieved Engel class I or II after anteromedial temporal lobectomy. Intraoperative ECoG was recorded in the parahippocampal gyrus and hippocampal alveus at sevoflurane concentrations of 1.5-3.0%. We sought to identify the sevoflurane proconvulsant effects on spikes and high-frequency oscillations (HFOs) on spikes in the epileptogenic area. The number of spikes and number of HFOs superimposed on spikes were counted in ECoG recordings of the parahippocampal gyrus, hippocampal alveus, and lateral temporal lobe, and analyzed using two-way repeated-measures analysis of variance. RESULTS: The number of spikes and number of HFOs superimposed on spikes significantly increased as the sevoflurane concentration increased in both the hippocampal alveus and parahippocampal gyrus (spike, p < 0.001; ripple, p < 0.001; Fast ripple (FR), p < 0.001), and the pattern of increase was similar in these two areas. The number of spikes and number of HFOs on spikes were statistically higher in the hippocampal alveus than in the parahippocampal gyrus (spike, p = 0.004; ripple, p = 0.005; FR, p = 0.001). There were almost no spikes or HFOs on spikes in the lateral temporal lobe at sevoflurane concentrations in the range of 1.5-2.5%. CONCLUSIONS: Intraoperative ECoG in the parahippocampal gyrus can serve as an indicator of hippocampal epileptogenicity.

Neurodegenerative processes accelerated by protein malnutrition and decelerated by essential amino acids in a tauopathy mouse model.

Protein malnutrition is epidemiologically suggested as a potential risk factor for senile dementia, although molecular mechanisms linking dietary proteins and amino acids to neurodegeneration remain unknown. Here, we show that a low-protein diet resulted in down-regulated expression of synaptic components and a modest acceleration of brain atrophy in mice modeling neurodegenerative tauopathies. Notably, these abnormal phenotypes were robustly rescued by the administration of seven selected essential amino acids. The up-regulation of inflammation-associated gene expression and progressive brain atrophy in the tauopathy model were profoundly suppressed by treatment with these essential amino acids without modifications of tau depositions. Moreover, the levels of kynurenine, an initiator of a pathway inducing neuroinflammatory gliosis and neurotoxicity in the brain, were lowered by treatment through inhibition of kynurenine uptake in the brain. Our findings highlight the importance of specific amino acids as systemic mediators of brain homeostasis against neurodegenerative processes.

Recovery of Visual Loss Following Internal Trapping of Anterior Cerebral Artery (A1 Segment) for Partially Thrombosed Large Anterior Communicating Artery Aneurysm: A Case Report.

A 60-year-old woman, who experienced progressive right visual loss, was diagnosed with an unruptured large cerebral aneurysm. Magnetic resonance imaging (MRI) and angiography revealed a large partially thrombosed anterior communicating artery (Acom) aneurysm. The aneurysmal neck was located at the junction of the left A1-A2 segments, and the aneurysmal dome communicated with the right A1-A2 junction by the Acom. Endovascular treatment using the flow alteration technique was selected. Following an oral antiplatelet therapy for 9 days, balloon test occlusion (BTO) of the medial portion of the left A1 segment was performed under local anesthesia. After confirming the tolerance of the BTO, internal trapping of the medial portion of the left A1 segment by detachable coils was performed following intra-aneurysmal coil embolization. Oral antiplatelet treatment was continued for 19 days postoperatively. Within 3 months following the operation, her right visual acuity dramatically improved to the original level. Owing to aneurysmal recanalization and the disappearance of the thrombus, the second and third embolization was performed through the Acom route, 4 months and 3 years following the first embolization, respectively, and followed up for an additional 7 years by MRI; no deterioration of her visual acuity and no aneurysmal recanalization was observed. Thus, endosaccular embolization combined with flow alteration is considered a useful alternative treatment for large and partially thrombosed Acom aneurysms.

Effects of sevoflurane anesthesia on intraoperative high-frequency oscillations in patients with temporal lobe epilepsy.

PURPOSE: This is a cross-sectional study without an unexposed group. We elucidated the effects of sevoflurane anesthesia on high-frequency oscillations (HFOs) to examine the usefulness of assessing intraoperative HFOs. METHODS: We recorded electrocorticography in seven patients with medication-resistant temporal lobe epilepsy (TLE) caused by unilateral hippocampal sclerosis who were seizure-free after temporal lobectomy. We analyzed the number of intraoperative spikes and HFOs on spikes in the epileptogenic parahippocampal gyrus and nonepileptogenic superior temporal gyrus with sevoflurane concentrations of 1.5%, 2.0%, 2.5%, and 3.0%. RESULTS: The number of spikes and HFOs in the epileptogenic area significantly increased with an increase in the sevoflurane concentration. In the nonepileptogenic area, spikes and HFOs did not significantly increase with increases in the sevoflurane concentration. However, 2.5% sevoflurane markedly induced spikes and ripples but no fast ripples (FRs) in one patient, and 3.0% sevoflurane induced marked increases in both ripples and FRs in two patients. CONCLUSIONS: The proconvulsant effect of sevoflurane on intraoperative HFOs in patients with TLE depends on the concentration. While HFOs induced by higher sevoflurane concentrations may be a useful biomarker for epileptogenic areas, careful interpretation is also needed because a higher sevoflurane concentration can also induce false-positive HFOs in nonepileptogenic areas.

Rab27a targeting to melanosomes requires nucleotide exchange but not effector binding.

Rab GTPases are important determinants of organelle identity and regulators of vesicular transport pathways. Consequently, each Rab occupies a highly specific subcellular localization. However, the precise mechanisms governing Rab targeting remain unclear. Guanine nucleotide exchange factors (GEFs), putative membrane-resident targeting factors and effector binding have all been implicated as critical regulators of Rab targeting. Here, we address these issues using Rab27a targeting to melanosomes as a model system. Rab27a regulates motility of lysosome-related organelles and secretory granules. Its effectors have been characterized extensively, and we have identified Rab3GEP as the non-redundant Rab27a GEF in melanocytes (Figueiredo AC et al. Rab3GEP is the non-redundant guanine nucleotide exchange factor for Rab27a in melanocytes. J Biol Chem 2008;283:23209-23216). Using Rab27a mutants that show impaired binding to representatives of all four Rab27a effector subgroups, we present evidence that effector binding is not essential for targeting of Rab27a to melanosomes. In contrast, we observed that knockdown of Rab3GEP resulted in mis-targeting of Rab27a, suggesting that Rab3GEP activity is required for correct targeting of Rab27a. However, the identification of Rab27a mutants that undergo efficient GDP/GTP exchange in the presence of Rab3GEP in vitro but are mis-targeted in a cellular context indicates that nucleotide loading is not the sole determinant of subcellular targeting of Rab27a. Our data support a model in which exchange activity, but not effector binding, represents one essential factor that contributes to membrane targeting of Rab proteins.