A Rare Case of Overlapping Durvalumab-induced Myositis, Takotsubo-like Morphological Changes Caused by Myocarditis, and Myasthenia Gravis.

Immune checkpoint inhibitors can cause a range of immune-related adverse events, including myositis, Takotsubo cardiomyopathy, and myasthenia gravis. We herein report a rare case of a 78-year-old man with concurrent durvalumab-induced myositis, Takotsubo-like morphological changes caused by myocarditis, and myasthenia gravis. The patient initially required invasive ventilation and exhibited symptoms of myasthenia gravis after treatment with high-dose steroids. However, he subsequently achieved successful recovery after the administration of intravenous immunoglobulin, plasmapheresis, and high-dose steroids. We advocate vigilant neurological monitoring of patients with immune checkpoint inhibitor-induced myositis, including the assessment of ptosis and other relevant signs, so that prompt treatment can be initiated at the time of emergence or progression of immune checkpoint inhibitor-induced myasthenia gravis.

Meningiomas in patients with neurofibromatosis type 2 predominantly comprise 'immunogenic subtype' tumours characterised by macrophage infiltration.

Although recent molecular analyses revealed that sporadic meningiomas have various genetic, epigenetic, and transcriptomic profiles, meningioma in patients with neurofibromatosis type 2 (NF2) have not been fully elucidated. This study investigated meningiomas' clinical, histological, and molecular characteristics in NF2 patients. A long-term retrospective follow-up (13.5 ± 5.5 years) study involving total 159 meningiomas in 37 patients with NF2 was performed. Their characteristics were assessed using immunohistochemistry (IHC), bulk-RNA sequencing, and copy number analysis. All variables of meningiomas in patients with NF2 were compared with those in 189 sporadic NF2-altered meningiomas in 189 patients. Most meningiomas in NF2 patients were stable, and the mean annual growth rate was 1.0 ± 1.8 cm3/year. Twenty-eight meningiomas (17.6%) in 25 patients (43.1%) were resected during the follow-up period. WHO grade I meningiomas in patients with NF2 were more frequent than in sporadic NF2-altered meningiomas (92.9% vs. 80.9%). Transcriptomic analysis for patients with NF2/sporadic NF2-altered WHO grade I meningiomas (n = 14 vs. 15, respectively) showed that tumours in NF2 patients still had a higher immune response and immune cell infiltration than sporadic NF2-altered meningiomas. Furthermore, RNA-seq/IHC-derived immunophenotyping corroborated this enhanced immune response by identifying myeloid cell infiltration, particularly in macrophages. Clinical, histological, and transcriptomic analyses of meningiomas in patients with NF2 demonstrated that meningiomas in NF2 patients showed less aggressive behaviour than sporadic NF2-altered meningiomas and elicited a marked immune response by identifying myeloid cell infiltration, particularly of macrophages.

Lidocaine as a potential therapeutic option for super-refractory status epilepticus: A case report.

New-onset refractory status epilepticus (NORSE) is a rare and devastating condition and the prognosis is often poor, with half to two-thirds of survivors experiencing drug-resistant epilepsy, residual cognitive impairment, or functional disability, and the mortality rate is 16% to 27% for adults. We describe a patient with cryptogenic NORSE and favorable recovery from drug-resistant super-refractory SE after the use of intravenous lidocaine. The patient experienced fever and presented with refractory generalized tonic-clonic seizures. The cause was not found by performing extensive examinations, including cell surface autoantibodies and rat brain immunohistochemistry evaluations. The refractory SE with unresponsiveness to multiple anti-epileptic and prolonged sedative medications, which are necessary for prolonged mechanical ventilation, were ameliorated by additive treatment with intravenous lidocaine initiating at 1 mg/kg/h and maintaining at 2 mg/kg/h for 40 days, which led to freedom from intravenous sedative medication and mechanical ventilation. The patient was able to return to school. Lidocaine may be an optional treatment for cryptogenic NORSE.

RNF213 p.Arg4810Lys Wild Type is Associated with De Novo Hemorrhage in Asymptomatic Hemispheres with Moyamoya Disease.

Clinical implications of RNF213 genetic variants, other than p.Arg4810Lys, in moyamoya disease (MMD), remain unclear. This study aimed to investigate the association of RNF213 variants with clinical phenotypes in MMD. This retrospective cohort study collected data regarding the clinical characteristics of 139 patients with MMD and evaluated the angioarchitectures of 253 hemispheres using digital subtraction angiography at diagnosis. All RNF213 exons were sequenced, and the associations of clinical characteristics and angiographical findings with p.Arg4810Lys, p.Ala4399Thr, and other rare variants (RVs) were examined. Among 139 patients, 100 (71.9%) had p.Arg4810Lys heterozygote (GA) and 39 (28.1%) had the wild type (GG). Fourteen RVs were identified and detetcted in 15/139 (10.8%) patients, and p.Ala4399Thr was detected in 17/139 (12.2%) patients. Hemispheres with GG and p.Ala4399Thr presented with significantly less ischemic events and more hemorrhagic events at diagnosis (p = 0.001 and p = 0.028, respectively). In asymptomatic hemispheres, those with GG were more susceptible to de novo hemorrhage than those with GA (adjusted hazard ratio [aHR] 5.36) with an increased risk when accompanied by p.Ala4399Thr or RVs (aHR 15.22 and 16.60, respectively). Within the choroidal anastomosis-positive hemispheres, GG exhibited a higher incidence of de novo hemorrhage than GA (p = 0.004). The GG of p. Arg4810Lys was a risk factor for de novo hemorrhage in asymptomatic MMD hemispheres. This risk increased with certain other variants and is observed in choroidal anastomosis-positive hemispheres. A comprehensive evaluation of RNF213 variants and angioarchitectures is essential for predicting the phenotype of asymptomatic hemispheres in MMD.

Clinical and Genetic Characteristics of Patients with Moyamoya Disease who Experienced Both Ischemic and Hemorrhagic Events.

OBJECTIVE: Cerebrovascular events in moyamoya disease are mainly classified into ischemic or hemorrhagic onset. It is rare for one patient to develop both ischemia and hemorrhage in moyamoya disease; detailed clinical course and genetic characteristics of such patients have not been elucidated. We aimed to clarify the clinical features of patients with both ischemic and hemorrhagic cerebrovascular events. METHODS: We analyzed the background factors, radiological features, and genotype of ring finger protein 213 c.14429 G > A (p.Arg4810Lys) of patients with moyamoya disease who visited our hospital between 1996 and 2020, and experienced both ischemic and hemorrhagic cerebrovascular events. Additionally, we analyzed factors that caused subsequent hemorrhage in adult-onset ischemic moyamoya disease. RESULTS: Of 262 patients, 12 presented with both ischemia and hemorrhage, of which, 4 exhibited pediatric onset and 8 had adult onset. In pediatric-onset subjects, ischemia was the initial event in all cases. Hemorrhagic events occurred at a median of 24.7 years postoperatively in patients who had undergone bypass surgery. In adult-onset subjects, ischemia preceded hemorrhage in 7 patients. In males, the interval to subsequent hemorrhage was significantly shorter for adult-onset ischemic moyamoya disease, and the hazard ratio for hemorrhagic events was 5.45. The ring finger protein 213 p.Arg4810Lys heterozygous variant was present in 9 patients. CONCLUSIONS: A majority of patients with moyamoya disease with both ischemia and hemorrhage experience an ischemic event first. Patients who developed ischemia in childhood may develop subsequent hemorrhage in approximately 20-25 years after bypass surgery. Male sex is a risk factor for a subsequent hemorrhagic event in adult-onset ischemic moyamoya disease.

Genetics of brain arteriovenous malformations and cerebral cavernous malformations.

Cerebrovascular malformations comprise abnormal development of cerebral vasculature. They can result in hemorrhagic stroke due to rupture of lesions as well as seizures and neurological defects. The most common forms of cerebrovascular malformations are brain arteriovenous malformations (bAVMs) and cerebral cavernous malformations (CCMs). They occur in both sporadic and inherited forms. Rapidly evolving molecular genetic methodologies have helped to identify causative or associated genes involved in genesis of bAVMs and CCMs. In this review, we highlight the current knowledge regarding the genetic basis of these malformations.

Sequential dependencies of responses in a questionnaire survey and their effects on the reliability and validity of measurement.

The reliability and validity of measurements in questionnaire surveys are affected by the survey design. Previous studies have discussed whether the items on a multidimensional scale should be grouped by subscale or randomized to increase the reliability and validity of the measurement. However, it is not clear what effect item order has on the true reliability and validity and whether the order causes bias in these estimates. Furthermore, it is not clear whether there are sequential dependencies of responses, which refers to the effect of past responses on current responses and, if so, what effects that they have on reliability, coefficient α, and validity. Study 1 empirically revealed that each respondent's previous response had a positive effect on his or her current response. In Study 2, we conducted a theoretical investigation and found that the first-order positive sequential dependencies of responses reduced the reliability, coefficient α, and validity of the subscales. In addition, sequential dependencies were found to render these indicators higher when the items were grouped than when they were randomized and caused an overestimation of reliability by coefficient α. Study 3 confirmed the effects of sequential dependencies and item order on coefficient α using real data. Thus, this study showed the potential impact of sequential dependencies of responses on psychological measurements.

NF2 Alteration/22q Loss Is Associated with Recurrence in WHO Grade 1 Sphenoid Wing Meningiomas.

Sphenoid wing meningiomas account for 11−20% of all intracranial meningiomas and have a higher recurrence rate than those at other sites. Recent molecular biological analyses of meningiomas have proposed new subgroups; however, the correlation between genetic background and recurrence in sphenoid wing meningiomas has not yet been fully elucidated. In this study, we evaluated the clinical characteristics, pathological diagnosis, and molecular background of 47 patients with sphenoid wing meningiomas. Variants of NF2, AKT1, KLF4, SMO, POLR2A, PIK3CA, TRAF7, and TERT were determined using Sanger sequencing, and 22q loss was detected using multiplex ligation-dependent probe amplification. Alterations were localized at NF2 in 11 cases, had other genotypes in 17 cases, and were not detected in 12 cases. Interestingly, WHO grade 1 meningiomas with NF2 alteration/22q loss (p = 0.008) and a MIB-1 labeling index > 4 (p = 0.03) were associated with a significantly shorter recurrence-free survival, and multivariate analysis revealed that NF2 alteration/22q loss was associated with recurrence (hazard ratio, 13.1). The duration of recurrence was significantly shorter for meningiomas with NF2 alteration/22q loss (p = 0.0007) even if gross-total resection was achieved. Together, these findings suggest that NF2 alteration/22q loss is associated with recurrence in WHO grade 1 sphenoid wing meningiomas.

Three Free-Living Marine Nematodes from Sagami Bay, Japan, with a Description of Wiesoncholaimus jambio sp. nov. (Nematoda: Oncholaimidae).

We describe three free-living marine nematode species from Sagami Bay, Japan. Wiesoncholaimus jambiosp. nov. is the second species of this genus. It differs from the type species, Wiesoncholaimus mawsonae Inglis, 1966, by its dorsal tooth, which is as long as the other two teeth; its conico-cylindrical tail, which is as long as 4.6-4.8 cloacal body diameters; and the absence of the gubernaculum. Thalassironus cf. britannicus de Man, 1889 agrees well with a redescription of Thalassironus britannicus de Man, 1889 based on specimens collected near the type locality. However, as it is possible that T. britannicus sensu lato includes two or more species, our species may not be conspecific to T. britannicus sensu stricto. Vasostoma cf. longispicula Huang and Wu, 2010 closely resembles Vasostoma longispicula Huang and Wu, 2010 originally described from China, but minor differentiations are observed in body diameter, body cuticle thickness, and type of precloacal supplements.

RNF213 p.Arg4810Lys Heterozygosity in Moyamoya Disease Indicates Early Onset and Bilateral Cerebrovascular Events.

The relationship between RNF213 c.14429G > A (p.Arg4810Lys) heterozygous variants and clinical manifestation in patients with Moyamoya disease (MMD) remains unclear. We performed a retrospective cohort analysis to clarify the genotype-phenotype correlation of this RNF213 hotspot variant in MMD patients, especially between wild-type (GG) and heterozygous (GA) genotypes. Clinical and genetic data were obtained from patients diagnosed with MMD in our institutions between October 2011 and November 2020. Clinical data included age, sex, neurological status at diagnosis, medical history, smoking history, alcohol intake, and family history. Of the 225 enrolled patients, 160 (71.1%) were symptomatic, 3 (1.3%) had the homozygous variant, and 149 (66.2%) had the heterozygous variant (GA). Analysis of all enrolled patients showed that the GA group was prone to present bilateral symptoms (p = 0.008) and progressive status (Suzuki grade ≥ 4; p = 0.017). Analysis limited to symptomatic patients revealed that the GA group had bilateral symptoms (p = 0.017), younger age at onset (p = 0.043), and, in particular, a higher proportion of onset before 25 years of age (p = 0.021). Multivariate logistic regression analysis of overall patients revealed that earlier age at diagnosis (p < 0.001, OR 0.936, 95% CI 0.914-0.959) and GA group (p = 0.017, OR 3.326, 95%CI 1.237-8.941) were significantly associated with bilateral symptoms. MMD patients diagnosed at a young age with the RNF213 heterozygous variant should be followed up with consideration of possible contralateral stroke if one hemisphere is already symptomatic or of early cerebrovascular events if bilateral hemispheres are asymptomatic.

Ultrasound-guided computed tomography angiography for the diagnosis of rotational vertebral artery occlusion: 2 case reports and technical notes.

Rotational vertebral artery occlusion is a rare cause of ischemic stroke in the vertebrobasilar arteries. While computed tomography angiography (CTA) is less invasive for the diagnosis of rational vertebral artery occlusion than digital subtraction angiography and more useful for elucidating the correlation between vertebrobasilar arteries and the surrounding structure, carotid ultrasound is noninvasive and more beneficial for the real-time evaluation of the hemodynamic change with neck rotation compared to CTA. Here, we reported 2 cases of rotational vertebral artery occlusion in patients aged 81 and 38 years and proposed a novel technique for its diagnosis using ultrasound-guided CTA. We suggest that the combination of ultrasound and CTA is useful for diagnosing rotational vertebral artery occlusion, which would compensate for the disadvantages of CTA alone.

Anti-programmed cell death-1 (PD-1) monoclonal antibodies involve reversible cranial dura matter.

This case is the first document to describe a patient receiving anti-programmed cell death 1 (PD-1) antibodies which showed cranial dura matter involvement. According to the increasing use of anti-PD-1 monoclonal antibodies, adverse effects can occur in several organs since its ligand PD-L1 and PD-L2 are expressed in a wide variety of tissues. The estimated rate of neurological complications is 1-4.2% of patients, and neuromuscular disorders are the most common. Adverse effects on the central nervous system including encephalitis are less frequent. Here, a patient receiving anti-PD-1 antibodies showed cranial dura matter involvement, and the dura enhancement on MRI was resolved by withdrawal of the treatment with anti-PD-1 antibodies only.

First report of marine horsehair worms (Nematomorpha: Nectonema) parasitic in isopod crustaceans.

Nectonema, the only horsehair worm (Nematomorpha) genus found in marine environments, was previously known to be parasitic only in decapod crustaceans. We report Nectonema sp. as the first record of a marine nematomorph parasitic in isopod crustaceans. This is also the third record of marine nematomorphs from the North Pacific. Six infected isopods (Natatolana japonensis) collected from 1425 m of depth in the Sea of Japan each contained one to seven (mean 2.33) nematomorphs in the body cavity in the pereon. There was no correlation between the host body length and number of parasites. For Nectonema sp., we describe and illustrate morphological features of the parasitic juvenile stage and present nucleotide sequences for the cytochrome c oxidase subunit I gene (COI or cox1; 451 nt), 18S rRNA gene (1777 nt), and region spanning the internal transcribed spacer 1 (ITS1) and the 28S rRNA gene including the 5.8S rRNA gene and ITS2 (1218 nt in total). In an 18S maximum-likelihood tree that included 24 nematomorph species, Nectonema sp. grouped with N. agile from the northwestern Atlantic; the 18S gene from these two taxa was divergent by 11.8% K2P distance, suggesting that they are different species. Nectonema species may have a broader range of host groups than previously suspected, but may have been previously misidentified as nematode parasites.

Three new species of free-living marine nematodes (Nematoda: Enoplida) from the Clarion-Clipperton Fracture Zone (CCFZ), North Pacific.

Three new species of free-living marine nematodes, Phanodermopsis dordi sp. nov., Halalaimus shinkai sp. nov., and Oxystomina hakureiae sp. nov. are described from the abyssal sediments of the Clarion-Clipperton Fracture Zone, North Pacific. Phanodermopsis dordi sp. nov. differs from the congeners by having papilliform anterior sensilla and a long conical tail with an acute tip. Halalaimus shinkai sp. nov., belonging to Keppner's group 2 based on the presence of caudal alae and the absence of precloacal sensillum or pore, can be distinguished from all of the members of this group by the presence of lateral pieces of gubernacula. Oxystomina hakureiae sp. nov. differs from the congeners by the short setiform anterior sensilla, the amphid located posterior to cephalic sensilla, the conico-cylindrical tail in both sexes, the spicules with a velum and a capitulum, the presence of the gubernacula and the precloacal setae, and the diorchic and monodelphic reproductive systems. The amended dichotomous keys to the species of Phanodermopsis, Halalaimus group 2, and Oxystomina are provided. A new combination Nemanema arenaria (Bussau, 1990) comb. nov. transferred from Oxystomina is also provided.

Two new and one known species of Phanodermatidae (Nematoda: Enoplida) from Sagami Bay, Japan.

Two new and one known species of free-living marine nematode belonging to the family Phanodermatidae are described. They were collected during the 12th Japanese Association for Marine Biology (JAMBIO) Coastal Organism Joint Survey off Jogashima, Japan in Sagami Bay, North Pacific Ocean. Phanodermopsis kohtsukai sp. nov. differs from the congeners by the shape of the tail, the longer spicules, and the absence of the gubernaculum. Micoletzkyia nakanoi sp. nov. differs from the congeners by the absence of a circle of cervical setae, the proportion of the tail, the cylindrical gubernaculum without projection, and the position of the vulva. Crenopharynx caudata (Filipjev, 1927) comb. nov. is transferred from the genus Phanodermopsis based on the presence of the long spicules. The morphological characters of the newly collected specimens of C. caudata comb. nov. are in excellent agreement with those shown in the original description of the specimens from Arctic Russia and the previous redescription of the specimens from Skagerrak. The new diagnoses and species lists for these three genera and two dichotomous keys to the males of Micoletzkyia and Crenopharynx are provided.

[A case of antiphospholipid syndrome associated with recurrent brain infarction and diffuse hypertrophy of the arachnoid membrane].

A 55-year-old man presented with recurrent brain infarction which had increased multifocally mainly in the cerebral white matter over the course of one year. Antibodies associated with antiphospholipid syndrome (APS) were initially negative. The patient was admitted to our department because of the thickened meninges shown on gadolinium enhanced brain MRI, mimicking hypertrophic pachymeningitis. However, blood and cerebrospinal fluid analysis revealed no significant inflammatory changes. On histopathological examination of the biopsied meninges, the arachnoid membrane was thickened with fibrosis, and arachnoidal microvessels were enlarged without significant inflammatory changes. The dura mater was not thickened, and no inflammation or microvessel enlargement were revealed. Finally, serum IgG anticardiolipin antibody testing was positive twice at an interval of more than 12 weeks, confirming the diagnosis of APS. Since initiating antithrombotic therapy with warfarin, brain infarction has not recurred. Without inflammation in the arachnoid membrane, the congestion of blood flow caused by thrombosis of microvessels in the arachnoid membrane might have increased the thickness of the arachnoid membrane.

Checklist of the subfamily Adoncholaiminae Gerlach and Riemann, 1974 (Nematoda: Oncholaimida: Oncholaimidae) of the world: genera, species, distribution, and reference list for taxonomists and ecologists.

BACKGROUND: Adoncholaiminae is one of the seven subfamilies in the free-living aquatic nematode family Oncholaimidae. Nematodes in Adoncholaiminae are found from various water environment of the world. However, a checklist of all Adoncholaiminae species including full literature, especially information of experimental (not taxonomic) works, has not been updated for more than 40 years. NEW INFORMATION: A revised checklist of the subfamily Adoncholaiminae of the world is provided. It contains 31 valid and 13 invalid species names in four genera with synonyms, collection records, and full literature from 1860's to 2015 for each species. A literature survey of total 477 previous papers was conducted in this work, and 362 of them are newly added to checklist.

Indications and Timings of Re-operation for Residual or Recurrent Hemifacial Spasm after Microvascular Decompression: Personal Experience and Literature Review.

We reviewed reports about the postoperative course of hemifacial spasm (HFS) after microvascular decompression (MVD), including in our own patients, and investigated treatment for delayed resolution or recurrence of HFS. Symptoms of HFS disappear after surgery in many patients, but spasm persists postoperatively in about 10-40%. Residual spasm also gradually decreases, with rates of 1-13% at 1 year postoperatively. However, because delayed resolution is uncommon after 1 year postoperatively, the following is advised: (1) In patients with residual spasms after 1 year postoperatively (incomplete cure) or who again experience spasm ≥ 1 year postoperatively (recurrence), re-operation is recommended if the spasms are worse than before MVD. (2) When re-operation is considered, preoperative magnetic resonance imaging (MRI) findings and intraoperative videos should be reviewed to ensure that no compression due to a small artery or vein was missed, and to confirm that adhesions with the prosthesis are not causing compression. If any suspicious findings are identified, the cause must be eliminated. Moreover, because of the risk of nerve injury, decompression of the distal portion of the facial nerve should be performed only in patients in whom distal compression is strongly suspected to be the cause of symptoms. (3) Cure rates after re-operation are high, but complications such as hearing impairment and facial weakness have been reported in 10-20% of cases, so surgery must be performed with great care.

Nickel-catalyzed ring-opening alkylative coupling of enone with methylenecyclopropane in the presence of triethylborane.

Nickel-catalyzed alkylative coupling of an enone or enal with methylenecyclopropane in the presence of triethylborane was achieved via stereospecific proximal C-C bond cleavage of methylenecyclopropane. With the use of methylenecyclopropane possessing an acyclic alkyl substituent, this reaction was also accompanied by the ß-hydrogen elimination.