Optogenetic stimulus-triggered acquisition of seizure resistance.

Unlike an electrical circuit, the hardware of the brain is susceptible to change. Repeated electrical brain stimulation mimics epileptogenesis. After such "kindling" process, a moderate stimulus would become sufficient in triggering a severe seizure. Here, we report that optogenetic neuronal stimulation can also convert the rat brain to a hyperexcitable state. However, continued stimulation once again converted the brain to a state that was strongly resistant to seizure induction. Histochemical examinations showed that moderate astrocyte activation was coincident with resilience acquisition. Administration of an adenosine A1 receptor antagonist instantly reverted the brain back to a hyperexcitable state, suggesting that hyperexcitability was suppressed by adenosine. Furthermore, an increase in basal adenosine was confirmed using in vivo microdialysis. Daily neuron-to-astrocyte signaling likely prompted a homeostatic increase in the endogenous actions of adenosine. Our data suggest that a certain stimulation paradigm could convert the brain circuit resilient to epilepsy without exogenous drug administration.

The Role of Genetic Analysis in Distinguishing Multifocal and Multicentric Glioblastomas: An Illustrative Case.

Introduction: Glioblastomas can manifest as multiple, simultaneous, noncontiguous lesions. We genetically analyzed multiple glioblastomas and discuss their etiological origins in this report. Case Presentation: We present the case of a 47-year-old woman who presented with memory impairment and left partial paralysis. Radiographic imaging revealed three apparently noncontiguous lesions in the right temporal and parietal lobes extending into the corpus callosum, leading to diagnosis of multicentric glioblastomas. All three lesions were excised. Genetic analysis of the lesions revealed a TERT promoter C228T mutation, a roughly equivalent amplification of EGFR, and homozygous deletion of CDKN2A/B exclusively in the two contrast-enhanced lesions. Additionally, the contrast-enhanced lesions exhibited the same two-base pair mutations of PTEN, whereas the non-enhanced lesion showed a partially distinct 13-base pair mutation. The other genetic characteristics were consistent. Rather than each having arisen de novo, we believe that they had developed by infiltration and are therefore best classified as multifocal glioblastomas. Conclusion: Our findings underscore anew the possibility of infiltration by glioblastomas, even within regions devoid of signal alterations on T2-weighted images or fluid-attenuated inversion recovery images. Genetic analysis can play a crucial role in differentiating whether multiple glioblastomas are multifocal or multicentric.

Optimizing perampanel monotherapy for surgically resected brain tumors.

Perampanel (PER) is an antiseizure medication (ASM) with a unique mechanism of action, which was approved in Japan for use in combination therapy in 2016 and as a monotherapy in 2020. It has exerted antitumor effects against several types of tumors in vitro. However, the efficacy of PER monotherapy for seizure control is not well-established in patients with brain tumor. In the present study, 25 patients with brain tumor treated using PER monotherapy at our institution were analyzed and compared with 45 patients treated using the most commonly prescribed ASM, levetiracetam (LEV). The PER group was younger and had a higher frequency of glioma cases. During drug administration, seizures were observed in two patients from the PER group (8.0%) and five patients from the LEV group (11.1%); however, the difference was not significant. The incidence of adverse effects did not significantly differ between the groups (12.0 and 2.2%, respectively). In the PER group, mild liver dysfunction was observed in two patients and drug rash in one. In the LEV group, a drug-induced rash was observed in one patient. PER monotherapy may be safe and effective for seizure treatment or prophylaxis in patients with brain tumor. Further large-scale clinical studies are warranted.

Clinical Effectiveness of Mirogabalin Besylate for Trigeminal Neuropathy after Skull Base Surgery: Illustrative Cases.

BACKGROUND: Postoperative trigeminal neuropathy may be seen after surgery for middle and posterior cranial fossa lesions. Although neuropathic pain is a cause of reduced quality of life, global consensus on postoperative pain management is lacking. Mirogabalin besylate is a selective ligand for the α2δ subunit of voltage-gated calcium channels. Although mirogabalin has been used for patients with postherpetic neuralgia and painful diabetic peripheral neuropathy, few reports have assessed the effect on postsurgical neuropathy. In this report, we describe a clinical effectiveness of mirogabalin for trigeminal neuropathy after skull base surgery. CASE DESCRIPTION: Case 1: A 51-year-old female with right trigeminal schwannoma was operated on via the anterior transpetrosal approach. She had tingling and numb feelings in the right face postoperatively. Mirogabalin was orally administered after the operation. Her continuous facial numbness immediately improved. Case 2: A 55-year-old female with left middle fossa base meningioma extending into the infratemporal fossa was operated on via the infratemporal fossa approach. She had a tingling feeling in the left face postoperatively. Mirogabalin was orally administered for this symptom after the operation, which gradually improved. CONCLUSIONS: Mirogabalin may show significant pain relief for patients with trigeminal neuropathy after skull base surgery. Further studies using a larger number of patients are warranted to confirm these findings.

A simple combined approach using anterior transpetrosal and retrosigmoid approach: A case report.

Background: A combined transpetrosal approach (CTP) is often used for large lesions in the posterior cranial fossa (PCF). Although CTP provides a wide surgical corridor, it has complex and time-consuming bony work of mastoidectomy and cosmetic issues. Here, we describe a simple combined surgical technique to approach the supratentorial region, anterolateral surface of the brainstem, petroclival region, and foramen magnum by drilling only the petrous apex with a combination of retrosigmoid approach (RA). Clinical presentation: A 27-year-old female was referred with extra-axial left cerebellopontine angle space-occupying epidermoid cyst extending to the prepontine cistern, anterior to the basilar artery, superior to the chiasma, and caudally to the foramen magnum. A one-stage surgical procedure using the anterior transpetrosal approach (ATP) and RA was performed after one-piece temporal-suboccipital craniotomy. These two approaches complemented each other well. Near-total removal was achieved. Conclusion: A one-stage surgical procedure using ATP and RA provides the wider viewing and better visualization of the PCF with minimal technical difficulty.

Case report: meningeal lymphangiogenesis around ependymoma forming along the dura matter.

Recently, there has been growing interest in the presence and function of meningeal lymphatic vessels, with no direct evidence linking these vessels to primary brain tumors. We report a unique case of recurrent ependymoma in the dura mater, showing histopathological signs of lymphatic proliferation at the tumor attachment site. The patient initially presented with a headache, and was diagnosed with ZFTA fusion-positive supratentorial ependymoma, central nervous system WHO Grade 3. Following multiple dura mater recurrences and surgery, the fifth procedure revealed numerous tumors contralateral to the original site, with genetic testing confirming ZFTA fusion positivity, indicating recurrent ependymoma. Immunohistochemical analysis showed D2-40+ lymphatic vessel proliferation around tumor attachment sites within the dura mater. Elevated expression of ZEB1, which is an epithelial-to-mesenchymal transition factor, was also observed, implicating potential involvement in the unique pathophysiology. The present case suggests a new process of metastasis through meningeal lymphatic vessels, although we were unable to visually confirm tumor cell infiltration into the lymphatic vessels. This case is the first report suggesting ependymoma metastasis through dural lymphatic vessels, underlining the need for further case accumulation and study to understand the mechanisms of this phenomenon.

Odontogenic Pericarotid Abscess after Carotid Endarterectomy.

Carotid endarterectomy (CEA) and carotid artery stenting (CAS) for internal carotid artery (ICA) stenosis have specific risks. Therefore, the accurate evaluation and management of each risk factor are important, especially for patients who are at high risk for both CEA and CAS. We report the case of a 77-year-old man with right ICA stenosis that progressed despite optimal medical treatment. In addition, he had several risk factors for both CEA and CAS, including previous cervical radiation therapy, contralateral ICA occlusion, chronic kidney insufficiency, and severe aortic valve stenosis. CEA was performed with priority given to aortic valve stenosis without complications, and the patient was discharged 10 days postoperatively, without neurological sequelae. However, a pericarotid cervical abscess was detected by carotid echo, computed tomography (CT), and magnetic resonance imaging (MRI) 1 month after CEA that required surgical drainage. The infection was thought to be odontogenic because the pathogen was identified as normal oral bacterial flora, and a wound infection was not apparent. Teeth extraction and abscess drainage, in combination with antibiotic therapy, successfully cured the infection without additional complications. Odontogenic cervical abscesses after CEA can occur, especially if the patient is at risk of infection. Therefore, both preoperative and postoperative dental evaluation and management are recommended. As in this case, a cervical abscess can occur without wound infection, and the abscess diagnosis is sometimes difficult from wound inspection alone. Cervical echocardiogram and CT were useful for detecting fluid collection, whereas MRI was useful for qualitatively evaluating the lesion.

Idiopathic unilateral oculomotor nerve palsy: A case report.

Cranial nerve III palsy, also known as oculomotor nerve palsy, may result from various causes; however, the etiology remains unknown in some instances. The aim of this case report is to present the authors' experience with two cases of idiopathic cranial nerve III palsy, together with a review of the literature. Case 1 is a 78-year-old woman and case 2 is a 75-year-old man, both having no history of trauma and no vascular risk factors. They presented to the authors' hospital with diplopia and palpebral ptosis and were diagnosed with idiopathic unilateral cranial nerve III palsy. They received oral steroids for treatment. One patient recovered completely within 3 months, while the other patient did not recover regardless of long-term follow-up. Idiopathic cranial nerve III palsy can occur in otherwise healthy individuals and often recover in several months. Careful examinations to rule out other causes and then steroid treatment should be considered after early diagnosis.