Association of mitochondrial DNA haplogroup and hearing impairment with aging in Japanese general population of the Iwaki Health Promotion Project.

Age-related hearing loss (ARHL) is a complex multifactorial disorder. Studies in animals, including mitochondria-mutator mice, and in human suggest that oxidative stress and mitochondrial disturbance play an important role in the pathoetiology of ARHL. Mitochondrial DNA (mtDNA) haplogroups are populations with genetically similar traits, and they have been reported to affect the mitochondrial function of oxidative phosphorylation. To gain further insights into the relationships between mitochondrial haplotypes and the susceptibility to cochlear aging, in this study, we aimed to elucidate how the differences in mtDNA haplogroups may affect ARHL development in Japanese general population. We focused on early onset ARHL, as the same mtDNA haplogroup can show either a negative or positive effect on systemic co-morbidities of ARHL that appear later in life. A total of 1167 participants of the Iwaki Health Promotion Project were surveyed in 2014, and 12 major haplotype groups (D4a, D4b, D5, G1, G2, M7a, M7b, A, B4, B5, N9, and F) were selected for the analysis. A total of 698 subjects aged 30 to 65 years were included in the statistical analysis, and the hearing loss group consisted of 112 males (40.3%) and 111 females (26.4%). Multiple logistic regression analysis showed that the male subjects belonging to haplogroup A had a significantly increased risk of hearing loss, whereas the female subjects belonging to haplogroup N9 had a significantly decreased risk of hearing loss. These results suggested that the mtDNA haplogroup may be an indicator for future risk of morbidity associated with ARHL.

Fatal Cerebral Venous Thrombosis in a Pregnant Woman with Inherited Antithrombin Deficiency after BNT162b2 mRNA COVID-19 Vaccination.

Antithrombin deficiency is a high-risk factor for venous thromboembolism during pregnancy, whereas cerebral venous thrombosis is rare. Cerebral venous thrombosis related to coronavirus disease 2019 (COVID-19) vaccines has been reported; however, there are a few reports of cerebral venous thrombosis after a messenger RNA (mRNA) vaccination. A 25-year-old female in her sixth week of pregnancy presented with headache 24 days after BNT162b2 mRNA COVID-19 vaccination. The following day, she presented with altered sensorium and was diagnosed with severe cerebral venous thrombosis. She demonstrated heparin resistance and was found to have an inherited antithrombin deficiency. A heterozygous missense variant in SERPINC1 (c.379T>C, p.Cys127Arg, 'AT Morioka') was detected by DNA analysis. Despite intensive care with unfractionated heparin, antithrombin concentrate, and repeated endovascular treatments, she died on the sixth day of hospitalization. Cerebral venous thrombosis in pregnant women with an antithrombin deficiency can follow a rapid and fatal course. Treatment with unfractionated heparin and antithrombin concentrate may be ineffective in severe cerebral venous thrombosis cases with antithrombin deficiency. Early recognition of antithrombin deficiency and an immediate switch to other anticoagulants may be required. Although the association between cerebral venous thrombosis and the vaccine is uncertain, COVID-19 vaccinations may require careful evaluation for patients with prothrombic factors.

Visual Impairment due to a large paraclinoid aneurysm treated with parent artery occlusion and bypass: A case report.

INTRODUCTION: Paraclinoid internal carotid artery (ICA) aneurysms can sometimes cause visual field disturbances due to their size, and it is challenging to treat either surgically or using endovascular techniques. Flow diverters generally have positive outcomes, but sometimes in symptomatic aneurysms, we see the thrombosed section becomes enlarged. Therefore, optimal treatment strategies are difficult to determine. CASE: A 68-year-old woman presented with a chief complaint of vision loss in the left eye. A large wide-necked saccular aneurysm was found on the left ICA paraclinoid portion. Under general anesthesia, a Pipeline Flex was inserted along with coil embolization. After treatment, the aneurysm showed thrombotic expansion, and the visual impairment worsened. One year later, aneurysm recanalization was evident; therefore, another Pipeline was inserted to overlap the stent. However, her visual impairment worsened again, and parent artery occlusion with high flow bypass was performed 20 months after her first treatment. Two weeks postoperatively, improved peripheral vision was confirmed. Further, no enlargement of the aneurysm was observed using magnetic resonance imaging 6 months later. CONCLUSION: This case examined a symptomatic, large paraclinoid aneurysm in a patient, which continued to enlarge after Pipeline stent placement, but was later treated successfully using direct parent artery occlusion in combination with high-flow bypass.

[Genetic diagnosis for epilepsy].

Very few epilepsy phenotypes have been associated with causative genes; nevertheless, it is becoming possible, for some epilepsy phenotypes, to predict the most efficacious anti-epileptic drugs for patients based on their genetic makeup. The development of individualized medicine based on genetic information and the genetic diagnosis of epilepsy are expected to greatly improve the diagnosis and treatment of epilepsy. We developed DNA array(resequencing-array) for genetic diagnosis of epilepsy, and successfully identified epilepsy mutations in patients. This finding indicates that this DNA array is likely to be a useful tool in clinical settings at least for screening purposes, because it can simultaneously and efficiently detect several gene mutations in a patient.

Concurrent delayed recurrence of peripheral primitive neuroectodermal tumors in orbital and sellar/suprasellar regions in an older adult.

BACKGROUND: Peripheral primitive neuroectodermal tumors (pPNETs) are rare and aggressive small round cell tumors, tending to occur in the thoracic and paravertebral soft tissues in children and young adults. This report describes an exceptionally rare case of concurrent delayed recurrence of pPNET in the orbital and sellar/suprasellar regions in an older adult, with a discussion supported by a literature review. CASE PRESENTATION: We report an 82-year-old woman with a history of orbital pPNETs resection at age 62, followed by gamma knife radiosurgery for local recurrence at age 66. She presented left eye pain, left eye protrusion, decreased vision in the right eye, and right homonymous hemianopia. MRI revealed extensive lesions in the left orbital cavity and sellar/suprasellar region, contiguous through the optic canal. The recurrent tumor was treated through a two-stage resection via transcranial and transsphenoidal approaches, which resulted in symptom improvement and a pathologic diagnosis of pPNETs. CONCLUSION: This case highlights a highly rare instance of late-onset orbital pPNETs recurrence in an elderly patient, with evidence suggesting tumor progression into the sellar/suprasellar regions through the optic canal.

Ultra-High-Molecular-Weight Polyethylene Merlon Shape: Novel Fixation of Artificial Bone for Cranioplasty.

BACKGROUND: Cranioplasty is a surgical procedure widely performed for repairing cranial defects caused by external decompression surgery for cerebrovascular disease or traumatic brain injury. We devised a new cranioplasty method using artificial bone made up of ultra-high molecular-weight polyethylene, with serrated wings on the edge. We named this newly designed artificial bone as Merlon shape. OBJECTIVE: To describe our initial experience with the Merlon shape and evaluate its usefulness and safety in cranioplasty. METHODS: The serrated wings of the Merlon shape were preoperatively designed for solid fixation and improving cosmetic results by reducing the thickness of the artificial bone. We evaluated 25 patients who underwent cranioplasty with the Merlon shape between December 2018 and December 2021. The causes of bone defects in these patients (male: 9, female: 16; median age: 62 years) were subarachnoid hemorrhage (n = 14), cerebral infarction (n = 8), and traumatic brain injury (n = 3). RESULTS: There were no postoperative adverse events such as infection, bone resorption, implant exposure, or graft sinking in 24 patients during an average follow-up period of 19 months. One patient experienced acute epidural hemorrhage and required reoperation. CONCLUSION: This is the first report on the use of the ultra-high molecular-weight polyethylene Merlon shape. Our initial 4-year case series showed good outcomes with this method.

A case of autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) coexisting with pervasive developmental disorder harboring SCN1A mutation in addition to CHRNB2 mutation.

We report a case of autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) with several characteristics distinct from previously reported cases, in which genetic studies identified mutations in two different genes. This case differed from typical ADNFLE with respect to the following: (1) slightly younger onset and refractory to antiepileptic drugs and (2) borderline intellectual functioning and coexistence of pervasive developmental disorder from infancy. Genetic testing revealed a novel mutation and a silent substitution in SCN1A (c.4285G>T, A1429S and c.4371G>C, silent) in addition to a known mutation in CHRNB2 (c.1200C>G, I312M). SCN1A is a gene that codes for the voltage-dependent sodium channel α1 subunit and has been implicated in generalized epilepsy with febrile seizures plus and severe myoclonic epilepsy in infancy. However, the relation between SCN1A and ADNFLE is unknown. We report the clinical course and symptomatic characteristics of this case although the relationship between ADNFLE mutation and SCN1A mutation remains to be elucidated.

Tandem Lesions of the Vertebrobasilar System Treated by Thrombectomy and Vertebral Artery Stenting: A Case Report.

Objective: There are few reports on endovascular treatment of tandem lesions in the posterior circulation and no consensus on treatment strategies has been reached. We report a case of tandem lesions of basilar artery occlusion and vertebral artery stenosis treated by thrombectomy and vertebral artery stenting. Case Presentation: We present the case of a 73-year-old man who developed consciousness disorder and tetraplegia. Head and neck CTA revealed tandem left vertebral artery stenosis and basilar artery occlusion. The patient was treated using a reverse technique, which involves performing thrombectomy first and then vertebral artery stenting, along with Carotid Guardwire PS. Postoperative impairment of consciousness and improvement of tetraplegia were achieved. Conclusion: The reverse technique combined with Carotid Guardwire PS may be a useful treatment strategy for tandem lesions in the posterior circulation.

A low score on the National Institutes of Health Stroke Scale with eye movement disorder may indicate a good candidate for acute mechanical thrombectomy for posterior circulation large vessel occlusion: illustrative cases.

BACKGROUND: Basilar artery occlusion (BAO) accounts for 1% of all strokes, and its natural prognosis is extremely poor. There is no consensus on the treatment strategy for mild BAO. OBSERVATIONS: Between August 2015 and May 2021, 429 patients received mechanical thrombectomy (MT) in the authors' hospital. Three patients had a BAO with a National Institutes of Health Stroke Scale (NIHSS) score of ≤6 and showed eye movement disorder as the main symptom. MT immediately improved ocular symptoms in all three cases, and the patients were discharged with a modified Rankin Scale ≤2. LESSONS: Lesions responsible for the eye movement disorder are distributed from the midbrain to the pontine tegmentum. These lesions are supplied by the arteries of the interpeduncular fossa, which is impaired by BAO. Symptoms due to problems with the arteries of the interpeduncular fossa can be rapidly improved by MT, and it is useful for preventing neurological deterioration in mild cases. BAO with a low NIHSS score in the presence of eye movement disorder as the main symptom may be a good indication for MT.

Repeat stereotactic radiosurgery in the management of brain metastases from non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is characterized by brain metastases that occur in about 30 to 50% of patients. To control tumor growth potential with maintaining neurocognitive function is important in the recent radiotherapy against brain metastases. From this viewpoint, we investigated the utility of repeat stereotactic radiosurgery (SRS) with a linear accelerator in the management of brain metastases from NSCLC. Between October 1998 and May 2010, 28 patients harboring brain metastases received repeat SRS (20 men and 8 women, with the age ranged from 51 to 79). The total number of SRS sessions ranged from 2 to 5, and the total number of lesions in one patient ranged from 1 to 8. Neurological decline due to uncontrolled brain lesions was identified in 9 of 28 patients after the repeat SRS, while the remaining 19 patients showed no neurological decline. Out of the 28 patients, 18 patients died by July 1, 2010; 12 patients died of active extracranial disease and 6 patients died from progressive brain lesions, considered neurological death. The 2-year and 4-year overall survival rates were 51% and 23%, respectively, and the median survival time was 26 months. In conclusion, repeat SRS is a preferred option to manage brain metastases from NSCLC, leading to a long survival with a decreased neurological decline. Repeat SRS is promising to preserve neurocognition, because the convergent dose distribution decreases the unfavorable influences from radiation on germinal niches, thereby preserving neural stem cells that are responsible for the nervous system repair.

Use of Contralateral Trans-Anterior Communicating Artery Snare to Rescue Lost Access to a Pipeline Embolization Device Unsheathed in an Aneurysm.

Objective: A pipeline embolization device (PED; Medtronic, Minneapolis, MI, USA) is a new vascular reconstruction device used to treat large internal carotid artery (ICA) aneurysms in Japan. We herein present a PED-related complication and describe its rescue strategy. Rescue therapy using a snare via the posterior communicating artery from the contralateral side has already been reported. However, this is the first report of therapy via the anterior communicating artery (AcomA). Case Presentation: A 49-year-old woman underwent vascular reconstruction with a PED for a large cavernous ICA aneurysm. During the placement of the PED, the proximal side of the PED slipped into the aneurysm. It was impossible to enter the true lumen of the PED from the proximal side because the orifice of the stent faced the aneurysmal wall. Contralateral trans-AcomA access to the PED was obtained through the distal ICA. The microwire from the distal ICA was connected with Goose Neck snares (Medtronic) from the proximal ICA. Pulling the snares to the proximal side, the PED was straightened and distal access was regained. Another PED was deployed such that it overlapped with the first PED to achieve vascular reconstruction. The patient finally recovered from aphasia, but paralysis of the right upper limb remained after rehabilitation. Conclusion: If the stent slips into the aneurysm, distal access through the true stent lumen may be very difficult. We presented a rescue technique for this complication, through the AcomA from the contralateral side.

Effect of Preoperative Administration of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor on Carotid Artery Stenting.

BACKGROUND: Perioperative embolic stroke is one of the most serious complications during carotid artery stenting (CAS). Proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) is a low-density lipoprotein-lowering drug that inhibits proprotein convertase subtilisin/kexin type 9, which normally binds to the low-density lipoprotein cholesterol (LDL-C) receptor. Its combination with statin significantly decreases LDL-C levels. PCSK9i is expected to achieve lower LDL-C levels than single use of statin. This study aimed to investigate whether perioperative PCSK9i administration stabilizes carotid artery plaque and reduces perioperative complications of CAS. METHODS: Nine patients with symptomatic stenosis (North American Symptomatic Carotid Endarterectomy Trial [NASCET] 50%) or asymptomatic stenosis (NASCET ≥ 80%) were included. PCSK9i was administered at least twice (once in 2 weeks) in the outpatient clinic before CAS. Perioperative complications; results from blood tests, magnetic resonance imaging (MRI), magnetic resonance angiography, and carotid ultrasonography (US); and modified Rankin scale score at discharge were assessed. RESULTS: High intensity on diffusion-weighted imaging was not observed in 8 patients. Changes in carotid plaque characteristics were found with MRI and/or carotid US in 7 patients. The plaque to muscle ratio decreased in 3 patients. The carotid plaque became hyperechoic in 2 patients, and the fibrous cap was seen more clearly on carotid US. Two patients had findings of stabilized plaque on MRI and carotid US, which indicates that plaque transformation was more stable. CONCLUSIONS: Lowering LDL-C level could reduce ischemic complications, and low LDL-C level affects plaque stability and antithrombus formation. PCSK9i can possibly stabilize carotid plaque and reduce perioperative complications of CAS.

Regulation of muscle protein degradation, not synthesis, by dietary leucine in rats fed a protein-deficient diet.

The aim of this study was to elucidate the effects of long-term intake of leucine in dietary protein malnutrition on muscle protein synthesis and degradation. A reduction in muscle mass was suppressed by leucine-supplementation (1.5% leucine) in rats fed protein-free diet for 7 days. Furthermore, the rate of muscle protein degradation was decreased without an increase in muscle protein synthesis. In addition, to elucidate the mechanism involved in the suppressive effect of leucine, we measured the activities of degradation systems in muscle. Proteinase activity (calpain and proteasome) and ubiquitin ligase mRNA (Atrogin-1 and MuRF1) expression were not suppressed in animals fed a leucine-supplemented diet, whereas the autophagy marker, protein light chain 3 active form (LC3-II), expression was significantly decreased. These results suggest that the protein-free diet supplemented with leucine suppresses muscle protein degradation through inhibition of autophagy rather than protein synthesis.

Ruptured pseudoaneurysm following Gamma Knife surgery for a vestibular schwannoma.

A 75-year-old woman underwent Gamma Knife surgery (GKS) for a vestibular schwannoma. Eight years after GKS, she suffered sudden onset of headache. Computed tomography revealed diffuse subarachnoid hemorrhage around the cisterns of the posterior fossa. Right vertebral artery angiography showed an aneurysm arising from the lateral pontomedullary segment of the left anterior inferior cerebellar artery. The aneurysm was not located at a branching site. Trapping of the distal anterior inferior cerebellar artery aneurysm was performed, and the aneurysm was removed. The pathological features of this aneurysm are discussed. This aneurysm was diagnosed as a pseudoaneurysm pathologically. This is the first report of aneurysm formation with pathological findings following GKS for a vestibular schwannoma.

A case of multiple pial arteriovenous fistulas associated with dural arteriovenous fistula.

Pial arteriovenous fistulas (AVFs) are known as rare cerebrovascular lesions. They are composed of >/= 1 arterial feeding vessels and a single draining vein that usually has high perfusion pressure and generally occur in infants. Cases involving adults are very rare and the developmental mechanisms and natural history of these lesions remain unknown. The authors present a case of multiple pial AVFs in an adult in whom the lesions developed after radiosurgical treatment of dural AVFs. Direct disconnection of pial arterial supplies was performed, and the abnormal shunts were successfully eliminated. The authors report the clinical course of this case and discuss the characteristics of and treatment strategy for multiple pial AVFs, reviewing the published literature.

Supplementation with dietary leucine to a protein-deficient diet suppresses myofibrillar protein degradation in rats.

Muscle mass is regulated by the synthesis and degradation of muscle protein, which in turn are affected by aging, several catabolic diseases, and malnutrition. Amino acids, particularly leucine, are known to stimulate muscle protein synthesis and suppress muscle protein degradation, although their long-term effects are unclear. The objective of our research was to elucidate whether long-term feeding of a protein-free or low-protein diet supplemented with leucine suppresses myofibrillar protein degradation. The rate of myofibrillar protein degradation was measured by the rate of release of 3-methylhistidine (MeHis) from isolated extensor digitorum longus (EDL) muscle. The weight of gastrocnemius muscle decreased in rats fed a protein-free diet for 7 d; however, a leucine-supplemented (1.5%) diet tended to suppress this decrease. The release of MeHis from EDL muscle was increased by the protein-free diet and decreased by the feeding of a diet supplemented with leucine to the level of a 20% casein diet. When rats were fed a 5% casein diet, the gastrocnemius muscle weight decreased and MeHis release from EDL muscle increased compared to those fed a 20% casein diet. However, feeding of a 5% casein diet supplemented with leucine (1.15%) reduced muscle weight loss and MeHis release. These results suggest that long-term feeding of leucine suppresses the rate of myofibrillar protein degradation and muscle weight loss in rats fed a protein-deficient diet.

Thyroid follicular carcinoma metastasized to the lung, skull, and brain 12 years after initial treatment for thyroid gland--case report.

A 65-year-old woman presented with multiple metastases from thyroid follicular carcinoma to the lung, skull, and brain. The skull and brain tumors had been successfully treated by surgery, thyroxine supplementation, and radiosurgery until she died of sudden intracerebral hemorrhage which had no connection with tumor treatment. The lung tumor was treated by conventional irradiation and radioactive ablation. Well-differentiated thyroid carcinoma is a slowly progressive tumor. Follicular carcinoma is thought to have the most optimistic prognosis even with metastases to the lymph nodes and lung. Radioactive ablation using iodine-131 is widely used to treat the primary and/or metastatic lesion. However, the prognosis for patients with brain metastases is poor. Intracranial metastasis of this tumor is rare, but has a mean posttreatment survival of around 12 months. Surgical excision of the metastatic intracranial lesion may be the only effective treatment.

[A case of bacterial aneurysm that occurred in the external carotid artery].

Occurrence of a mycotic aneurysm extracranially is extremely rare. We report our experience with a case of mycotic aneurysm that occurred in the external carotid artery accompanying infectious endocarditis. The case was a 33-year-old male. He visited our hospital with principal complaints of weakness in the lower left side and visual difficulty. Multiple cerebral infarctions were noted in a head MRI. In addition, vegetation was noted on the mitral valve in an echocardiogram, and the patient was admitted to cardiology for infectious endocarditis. Aneurysms were noted in the external carotid artery and the posterior cerebral artery in a cerebral angiogram performed before valve replacement. After administration of antibiotics for 5 weeks, radical surgery was performed for the external carotid artery aneurysm that had remained unchanged. With a satisfactory postoperative course, the patient was able to walk independently after mitral valve replacement and was discharged. We have scoured the literature with regard to mycotic aneurysm occurring extracranially and have studied this case because of this characteristic. When performing cerebral angiography to search for a mycotic aneurysm, the area outside the cranium as well as inside must be closely examined.

[A case of primary meningeal melanocytoma of the left middle fossa].

A 29-year-old woman presented with a primary meningeal melanocytoma of the left middle fossa manifesting as headache and nausea. Computed tomography (CT) with contrast medium demonstrated a clearly demarcated, homogeneously enhanced high density area surrounded by a cyst in the left temporal lobe. Magnetic resonance (MR) imaging showed the mass as a slightly high signal intensity area on the T1-weighted image and as a low signal intensity area on the T2-weighted image. Cerebral angiography revealed shift of the middle cerebral artery but no tumor stain. The solid part of the tumor had rapidly increased in size with reduction of the cyst 3 months later. Left frontotemporal craniotomy disclosed a clearly demarcated jet-black tumor attached to the dura. The black-colored lesion in the dura and the bone extended to the skull base, so malignant melanoma was a possibility. The solid part of the tumor was gross totally removed, and the dura and the skull bone were preserved. Histological examination of the tumor specimen revealed meningeal melanocytoma. Melanophages were present in the specimen of the black-colored lesion in the dura and the bone, but no neoplastic infiltration was present. The postoperative course was uneventful, and the patient's headache and nausea disappeared. CT and MR imaging taken 1 month later confirmed total removal of the tumor. No recurrence has been observed for 2.5 years after surgery. Preoperative differentiation of meningeal melanocytoma from malignant melanoma is difficult, but the primary goal of therapy is gross total resection of the solid part of the tumor irrespective of tumor type.

Surgical treatment of spinal extradural arteriovenous fistula with parenchymal drainage: report on 5 cases.

BACKGROUND AND IMPORTANCE: Spinal extradural arteriovenous fistula (SEDAVF) with parenchymal drainage (type A) is a rare clinical entity that causes venous congestive myelopathy. Treatment includes endovascular and open microsurgical interventions. We reviewed the clinical records of patients treated for a type A SEDAVF to evaluate the feasibility of our treatment strategy. CLINICAL PRESENTATION: Between 2004 and 2010, 5 patients with a type A SEDAVF were treated at our institutes (4 men and 1 woman; mean age, 60 years). We performed endovascular transvenous embolization (TVE) when lesions were accessible transvenously; otherwise, microsurgical perimedullary drainer occlusion was performed. Follow-up ranged from 23 to 94 months (mean, 45.8 months). One patient was treated with TVE, and the remaining 4 were treated with microsurgical drainer occlusion. After a simple intradural drainer occlusion, an epidural venous lake was completely thrombosed in 2 patients. In 1 patient, postoperative angiography revealed that a part of the epidural component had persisted; however, the patient has been asymptomatic. In the remaining case with multiple intradural draining veins, sole drainer occlusion was not sufficient. A second surgery was required to meticulously coagulate the venous lake. As a consequence, parenchymal drainers disappeared. Overall, all patients stabilized or improved neurologically and experienced no recurrence. CONCLUSION: To treat a type A SEDAVF, either TVE or microsurgical intradural drainer occlusion can be used for satisfactory long-term results with minimal surgical risks. For a case with multiple intradural draining veins, detachment of the venous lake should be considered.