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Multiple system atrophy (MSA) is a neurodegenerative disorder that presents as parkinsonism, cerebellar ataxia, and autonomic dysfunction. Magnetic resonance imaging (MRI) findings of MSA are reported to be the atrophy of the putamen/pons/cerebellum, hot cross bun sign, and bright middle cerebellar peduncle (MCP) sign. Here, we assessed the sensitivity of detecting the bright MCP sign in patients with MSA cerebellar variant (MSA-C) using a double inversion recovery (DIR) procedure, comparing it to the sensitivity of detection by T2-weighted image (T2WI) and fluid-attenuated inversion recovery (FLAIR) sequences on conventional MRI. We evaluated 6 MSA-C patients and 6 control patients (multiple sclerosis, neuromyelitis optica, and spinocerebellar atrophy). Characteristics of all the patients were collected, and MRI was analyzed. Two neurologists independently evaluated the visualization of the bright MCP sign using a 4-point visual grade from Grade 0 to Grade 3. Differences in grade between DIR and T2WI or FLAIR were statistically analyzed. Also, as a quantitative analysis, the signal intensity of the MCP lesion was compared with that of the ipsilateral thalamus, and the MCP/thalamus ratio was evaluated. As a result, DIR more sensitively showed the bright MCP signs of MSA-C patients than T2WI or FLAIR. Also, the bright MCP sign deteriorated and expanded over time in the cases we followed with MRI. We also evaluated hot cross bun sign in the pons, but the hot cross bun sign in MSA-C patients was not significantly different between the DIR and conventional MRI sequences. The DIR procedure can be a more sensitive method for detecting the involvement of MCP lesions in MSA-C., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Shiraishi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims/hypothesis: Diabetic retinopathy is characterised by neuroinflammation that drives neuronal and vascular degenerative pathology, which in many individuals can lead to retinal ischaemia and neovascularisation. Infiltrating macrophages and activated retina-resident microglia have been implicated in the progression of diabetic retinopathy, although the distinct roles of these immune cells remain ill-defined. Our aim was to clarify the distinct roles of macrophages/microglia in the pathogenesis of proliferative ischaemic retinopathies., Methods: Murine oxygen-induced retinopathy is commonly used as a model of ischaemia-induced proliferative diabetic retinopathy (PDR). We evaluated the phenotype macrophages/microglia by immunostaining, quantitative real-time RT-PCR (qRT-PCR), flow cytometry and scRNA-seq analysis. In clinical imaging studies of diabetic retinopathy, we used optical coherence tomography (OCT) and OCT angiography., Results: Immunostaining, qRT-PCR and flow cytometry showed expression levels of M1-like macrophages/microglia markers (CD80, CD68 and nitric oxide synthase 2) and M2-like macrophages/microglia markers (CD206, CD163 and macrophage scavenger receptor 1) were upregulated in areas of retinal ischaemia and around neo-vessels, respectively. scRNA-seq analysis of the ischaemic retina revealed distinct ischaemia-related clusters of macrophages/microglia that express M1 markers as well as C-C chemokine receptor 2. Inhibition of Rho-kinase (ROCK) suppressed CCL2 expression and reduced CCR2-positive M1-like macrophages/microglia in areas of ischaemia. Furthermore, the area of retinal ischaemia was reduced by suppressing blood macrophage infiltration not only by ROCK inhibitor and monocyte chemoattractant protein-1 antibody but also by GdCl 3 . Clinical imaging studies of diabetic retinopathy using OCT indicated potential involvement of macrophages/microglia represented by hyperreflective foci in areas of reduced perfusion., Conclusions/interpretation: These results collectively indicated that heterotypic macrophages/microglia differentially contribute to retinal ischaemia and neovascularisation in retinal vascular diseases including diabetic retinopathy. This adds important new information that could provide a basis for a more targeted, cell-specific therapeutic approach to prevent progression to sight-threatening PDR., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Perampanel belongs to a novel class of antiseizure medications (ASMs). Studies examining the effect of hemodialysis on perampanel serum levels in clinical settings are lacking. We aimed to evaluate the changes in serum perampanel levels during hemodialysis. We studied patients with seizures who received oral perampanel between April 2020 and March 2023 and whose serum concentration of perampanel was measured before and after hemodialysis. We analyzed the serum concentrations of levetiracetam and lacosamide for comparison. Fourteen patients, with a mean age of 76.1 ± 7.88 years, were included. The dose of perampanel was 2.14 ± 1.27 mg. The hemodialysis clearance rate of perampanel, levetiracetam, and lacosamide was 0 ± 13%, 69 ± 11%, and 59.6 ± 8.2%, respectively. The post-dialysis CD ratio decreased significantly with levetiracetam but not with perampanel. Adverse but acceptable effects of perampanel were observed in two patients. The serum concentrations of several ASMs have been shown to be reduced during hemodialysis. Our study revealed that the serum perampanel concentration does not decrease during hemodialysis. Owing to the low rate of adverse effects and the stability of perampanel serum concentration during hemodialysis, perampanel could be a favorable choice as an ASM for patients with seizures undergoing hemodialysis. PLAIN LANGUAGE SUMMARY: Our study looked at how hemodialysis affects the serum levels of perampanel, a new type of medication for seizures. In 14 patients who started treatment between April 2020 and March 2023, perampanel serum levels did not decrease during hemodialysis, unlike other seizure medications. This shows that perampanel can be a good option for patients with seizures who need hemodialysis, with fewer side effects compared to other medications., (© 2024 The Author(s). Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Hyperglycemia sometimes initially presents with neurological manifestations, including seizures, visual hallucinations, choreoathetosis, hemiballismus, myoclonus, tremor, and consciousness disturbance. Epileptic seizures induced by hyperglycemia are reported to occur predominantly in the occipital lobe, and the epileptic form is mainly epilepsia partialis continua. Of the two patterns of hyperglycemia (ketotic or nonketotic), nonketotic hyperglycemia is more commonly associated with seizures because ketosis has an anticonvulsive effect, so hyperglycemia-induced seizures are generally seen in nonketotic patients. Here, we report a 51-year-old Japanese male with intermittent homonymous hemianopsia who presented high hemoglobin A1c (19.1%). He had been drinking 3 L of the sugared soft beverage every day. After admission, he showed left-sided hemiconvulsion. Anti-seizure medications and insulin treatment were administered, and his seizure was aborted. The magnetic resonance imaging (MRI) showed a high-intensity lesion in the diffusion-weighted image and fluid-attenuated inversion recovery with gadolinium enhancement in the occipital lobe. In hyperglycemic convulsions, MRI sometimes shows leptomeningeal or parenchymal gadolinium enhancement. In addition, most hyperglycemic seizures are associated with nonketotic hyperglycemia and show occipital-dominant imaging abnormalities. We report this case by reviewing the differential diagnosis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Shiraishi et al.)

The epidemiology and etiology of facial onset sensory and motor neuronopathy (FOSMN), a rare syndrome that initiates with facial sensory disturbances followed by bulbar symptoms, remain unknown. To estimate the prevalence of FOSMN in Japan and establish the characteristics of this disease, we conducted a nationwide epidemiological survey. In the primary survey, we received answers from 604 facilities (49.8%), leading to an estimated number of 35.8 (95% confidential interval: 21.5-50.2) FOSMN cases in Japan. The secondary survey collected detailed clinical and laboratory data from 21 cases. Decreased or absent corneal and pharyngeal reflexes were present in over 85% of the cases. Electrophysiological analyses detected blink reflex test abnormalities in 94.1% of the examined cases. Immunotherapy was administered in 81% of cases and all patients received intravenous immunoglobulin. Among them, 35.3% were judged to have temporary beneficial effects evaluated by the physicians in charge. Immunotherapy tended to be effective in the early stage of disease. The spreading pattern of motor and sensory symptoms differed between cases and the characteristics of the motor-dominant and sensory-dominant cases were distinct. Cases with motor-dominant progression appeared to mimic amyotrophic lateral sclerosis. This is the first nationwide epidemiological survey of FOSMN in Japan. The clinical course of FOSMN is highly variable and motor-dominant cases developed a more severe condition than other types of cases. Because clinical interventions tend to be effective in the early phase of the disease, an early diagnosis is desirable., Competing Interests: Declaration of competing interest RY received honoraria from Teijin Pharma, Ono Pharmaceutical, Takeda Pharmaceutical, Eisai, Novartis, Nihon Pharmaceutical, and CSL Behring. SK received honoraria from CSL Behring, Nihon Pharm, and Japan Blood Product Organization and he is a member of the data and safety monitoring board of Argenx. NI received honoraria from Mitsubishi Tanabe Pharma and research funding from Boehringer Ingelheim. The remaining authors report no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Neuralgic amyotrophy (NA) is a multifocal inflammatory neuropathy accompanied by acute pain and muscle atrophy. NA commonly affects the upper extremities, but rarely affects the phrenic nerve. Here, we report a male with neck pain, orthopnea, difficulty sleeping in the supine position, and inability to slurp. His saturated oxygen level decreased from 97% to 86% in the supine position. His right shoulder showed muscle atrophy. Chest X-ray examination in the supine position and a nerve conduction study showed phrenic palsy. We diagnosed it as bilateral phrenic nerve palsy associated with NA. NA sometimes causes phrenic nerve palsy and may cause slurping difficulty., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Shiraishi et al.)

Superficial siderosis is a disease in which hemosiderin is deposited under the leptomeninges and subpial layers of hindbrain structures, e.g., the cerebellum, brainstem, and eighth cranial nerve. The main symptoms of superficial siderosis are cerebellar ataxia, hearing loss, cognitive decline, and myelopathy. The activities of daily living of patients with superficial siderosis are severely impaired due to the progressive symptoms. Here, we report a patient with superficial siderosis whose symptoms deteriorated after lumbar subarachnoid-peritoneal (L-P) shunt surgery. She received L-P shunt surgery based on the diagnosis of idiopathic normal pressure hydrocephalus at another hospital. The patient had a history of cervical surgery, and a dural defect was identified at the C4-5 level by a detailed magnetic resonance imaging study. We hypothesized that the L-P shunt reduced cerebrospinal pressure and increased bleeding from the fragile vessels in the dural defect, which might have increased hemosiderin deposition., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Ando et al.)

Behçet's disease commonly affects 20-40-year-old men and shows ophthalmo-dermatological manifestations. Here, we report a man in his 70s with acute onset of dysarthria, dysphagia and hemiplegia showing brainstem and subcortical lesions, which responded to steroid and colchicine therapy. He had a history of uveitis and was homozygous for the human leucocyte antigen-B51 allele, and we clinically diagnosed him with acute neuro-Behçet's disease. Old-age onset neuro-Behçet's disease is uncommon, and as far as we know, this is the oldest case of the first attack of neuro-Behçet's disease. Clinicians should consider Behçet's disease even for elderly patients., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Follow-up of aneurysms treated with stent-assisted coil embolization has been performed using digital subtraction angiography (DSA) because in time-of-flight magnetic resonance angiography, metal artifacts from the stent often affect visualization., Objective: To confirm whether ultrashort echo time (TE) MRA may be an alternative for DSA during follow-up., Methods: Patients with unruptured aneurysms initially treated with stent-assisted coil embolization between April 2019 and March 2021 were enrolled. After 3 months of treatment, follow-up DSA and ultrashort TE MRA were performed. All images were independently reviewed by neurosurgeons to evaluate in-stent flow and rated from 1 (not visible) to 4 (excellent). Aneurysmal embolization status was assessed as complete obliteration, residual neck, or residual aneurysm. Ultrashort TE MRA findings were classified as evaluative or nonevaluative state based on the presence of metal artifacts. We investigated the types of aneurysms that were evaluative and the agreement between ultrashort TE and DSA., Results: Overall, 89 aneurysms were examined, of which 74% (n = 66) were classified as evaluative on ultrashort TE. Significant differences were observed in size and stent type. Evaluative cases had an aneurysm size of <7 mm ( P = .0007) and a higher rate of Neuroform Atlas ( P = .0006). The rate of agreement between ultrashort TE with evaluative state and DSA was 95%., Conclusion: Ultrashort TE MRA could evaluate an embolization status treated with stenting, and the findings are in excellent agreement with those of DSA. Aneurysms measuring <7 mm and treated with Neuroform Atlas are evaluative on ultrashort TE, and DSA might not be necessary., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Vitamin B12 deficiency can cause thrombotic microangiopathy (TMA)-like symptoms such as purpura caused by platelet reduction, general fatigue caused by anemia, and renal and hepatic abnormalities caused by malnutrition. TMA-like symptoms are known as metabolism-mediated TMA (MM-TMA). In MM-TMA, blood cell production is altered, and both pancytopenia and schistocytes appear. The initial presentation of MM-TMA makes it challenging to distinguish between primary and secondary TMA when patients do not present risk factors for malnutrition. We encountered an older female patient with a chief complaint of unconsciousness and loss of appetite for two days. Laboratory tests revealed pancytopenia with schistocytes. Moreover, the laboratory data revealed low serum levels of vitamin B12, indicating MM-TMA. The patient was successfully treated with intravenous vitamin B12 supplementation and discharged home. The patient had atrophic gastritis, which could have impeded the absorption of vitamin B12 from food. Among older patients without prolonged appetite loss, TMA-like symptoms should be investigated as MM-TMA induced by vitamin B12 deficiency, and prompt initiation of appropriate treatment is essential to differentiate between MM-TMA and true TMA., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Shiraishi et al.)

Background: Progressive multifocal leukoencephalopathy (PML) is a devastating demyelinating disorder of the central nervous system caused by opportunistic infection of the JC virus (JCV)., Case Presentation: A 58-year-old Japanese woman was admitted to our hospital for aphasia. She had a 5-year history of untreated sarcoidosis and was a human T cell lymphotropic virus-1 (HTLV-1) carrier. Serum angiotensin-converting enzyme, soluble interleukin-2 receptor, lysozyme, and calcium levels were elevated. JCV-DNA was not detected in cerebrospinal fluid by PCR testing. Skin biopsy revealed noncaseating granuloma formation. Bilateral multiple nodular lesions were present on chest X-ray. Brain magnetic resonance imaging showed left frontal and temporal lesions without gadolinium enhancement. As we suspected that systemic sarcoidosis had developed into neurosarcoidosis, we started steroid and infliximab administration. After treatment, the chest X-ray and serum abnormalities ameliorated, but the neurological deficits remained. At 1 month after immunotherapy, she developed right hemiparesis. Cerebrospinal fluid was positive for prototype (PML-type) JCV on repeated PCR testing. Brain biopsy revealed demyelinating lesions with macrophage infiltration, atypical astrocytes, and JCV antigen-positive cells. We diagnosed her with PML and started mefloquine, leading to partial remission., Conclusions: Sarcoidosis and HTLV-1 infection both affect T cell function, especially CD4 + T cells, and may developped the patient's PML. The comorbidity of sarcoidosis, PML, and HTLV-1 infection has not been reported, and this is the world's first report of PML associated with HTLV-1 infection and sarcoidosis., (© 2023. The Author(s).)

Competing Interests: None

Intraretinal hyperreflective foci (HRF) are significant biomarkers for diabetic macular edema. However, HRF at the vitreoretinal interface (VRI) have not been examined in diabetic retinopathy (DR). A prospective observational clinical study with 162 consecutive eyes using OCT imaging showed significantly increased HRF at the VRI during DR progression (P < 0.01), which was reversed by anti-vascular endothelial growth factor (VEGF) therapy. F4/80+ macrophages increased significantly at the VRI in Kimba (vegfa+/+) or Akimba (Akita × Kimba) mice (both P < 0.01), but not in diabetic Akita (Ins2+/-) mice, indicating macrophage activation was modulated by elevated VEGF rather than the diabetic milieu. Macrophage depletion significantly reduced HRF at the VRI (P < 0.01). Furthermore, BrdU administration in Ccr2rfp/+Cx3cr1gfp/+vegfa+/- mice identified a significant contribution of M2-like tissue-resident macrophages (TRMs) at the VRI. Ki-67+ and CD11b+ cells were observed in preretinal tissues of DR patients, while exposure of vitreal macrophages to vitreous derived from PDR patients induced a significant proliferation response in vitro (P < 0.01). Taken together, the evidence suggests that VEGF drives a local proliferation of vitreous resident macrophages (VRMs) at the VRI during DR. This phenomenon helps to explain the derivation and disease-relevance of the HRF lesions observed through OCT imaging in patients., (© 2022 by the American Diabetes Association.)

Objective: The current study sought to develop a new indicator for disease progression rate in amyotrophic lateral sclerosis (ALS)., Methods: We used a nonparametric method to score diverse patterns of decline in the percentage of predicted forced vital capacity (%FVC) in patients with ALS. This involved 6317 longitudinal %FVC data sets from 920 patients in the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database volunteered by PRO-ACT Consortium members. To assess the utility of the derived scores as a disease indicator, we examined changes over time, the association with prognosis, and correlation with the Risk Profile of the Treatment Research Initiative to Cure ALS (TRICALS). Our local cohort (n = 92) was used for external validation., Results: We derived scores ranging from 35 to 106 points to construct the FVC Decline Pattern scale (FVC-DiP). Individuals' FVC-DiP scores were determined from a single measurement of %FVC and disease duration at assessment. Although the %FVC declined over the disease course (p < 0.0001), the FVC-DiP remained relatively stable. Low FVC-DiP scores were associated with rapid disease progression. Using our cohort, we demonstrated an association between FVC-DiP and the survival prognosis, the stability of the FVC-DiP per individual, and a correlation between FVC-DiP scores and the TRICALS Risk Profile (r 2  = 0.904, p < 0.0001)., Conclusions: FVC-DiP scores reflected patterns of declining %FVC over the natural course of ALS and indicated the disease progression rate. The FVC-DiP may enable easy assessment of disease progression patterns and could be used for assessing treatment efficacy., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Giant cell arteritis (GCA) generally affects extracranial large and medium-sized vessels. It rarely causes intracranial vessel stenosis, presenting as cerebral infarction (CI). Consequently, accurate diagnosis of CI induced by GCA is often challenging. Improved motion-sensitized driven-equilibrium (iMSDE) is one of the advanced high-resolution magnetic resonance (MR) vessel wall imaging techniques that enables direct visualization of the vessel wall because of a strong reduction in blood flow artifacts, leading to higher quality images. Herein, we effectively used gadolinium-enhanced MR iMSDE imaging to diagnose a patient presenting with recurrent CI due to right intracranial internal carotid artery (ICA) stenosis as GCA., Case Description: A 64-year-old man with polymyalgia rheumatica for several years and who had experienced CI due to moderate intracranial ICA stenosis one year ago, presented to the emergency room with dysarthria and left hemiparesis. Diffusion-weighted MR imaging showed high signals in the right centrum ovale, and MR angiography revealed severe stenosis of the right intracranial ICA. Gadolinium-enhanced MR iMSDE imaging showed marked concentric enhancement in the vessel wall of the right stenosed ICA, which led to a definitive diagnosis of GCA via biopsy from the right superficial temporal artery. The patient's symptoms gradually improved after initiation of steroid treatment. Three months later, gadolinium-enhanced MR iMSDE imaging revealed improvement in the contrast enhancement in the vessel wall and vascular stenosis., Conclusion: Gadolinium-enhanced MR iMSDE imaging is useful to diagnose and evaluate GCA with intracranial vessel involvement., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Paraneoplastic tumefactive demyelination (TD) is a rare disorder of the central nervous system that can be challenging to diagnose. Here, we describe a 32-year-old Japanese man with a TD associated with testicular seminoma. He presented with symptoms of right-sided motor and sensory impairment 2 days after vaccination for coronavirus disease 2019 (COVID-19). Brain magnetic resonance imaging (MRI) showed a high-intensity lesion in the left internal capsule. He had a 3-year history of enlargement of the left testicle. Blood examination showed tumor marker elevation and the presence of anti-amphiphysin antibodies. Whole-body computed tomography (CT) revealed mass lesions in the left testicle and enlargement of the retroperitoneal lymph nodes. Radical orchiectomy was performed. As the pathology showed testicular seminoma, chemotherapy was administered. After surgery, his neurological symptoms deteriorated. MRI revealed that the brain lesion had enlarged and progressed to a tumefactive lesion without gadolinium enhancement. The cerebrospinal fluid (CSF) examination was normal without pleocytosis or protein elevation. Steroid pulse therapy was added; however, his symptoms did not improve. A brain stereotactic biopsy was performed and the sample showed demyelinating lesions without malignant cells. As the initial corticosteroid therapy was ineffective, gamma globulin therapy was administered in parallel with chemotherapy, and the clinical symptoms and imaging findings were partially ameliorated. TD seldom appears as a paraneoplastic neurological syndrome. In addition, there are few reports of COVID-19 vaccination-associated demyelinating disease. Clinicians should recognize paraneoplastic TD, and the further accumulation of similar cases is needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shiraishi, Umemura, Nakayama, Yamada, Shijo and Hashimoto.)

Background and Purpose: In patients with ischemic stroke, DWI lesions can occasionally be reversed by reperfusion therapy. This study aimed to ascertain the relationship between ADC levels and DWI reversal in patients with acute ischemic stroke who underwent recanalization treatment., Materials and Methods: We conducted a retrospective cohort study in patients with acute ischemic stroke who underwent endovascular mechanical thrombectomy with successful recanalization between April 2017 and March 2021. DWI reversal was assessed through follow-up MR imaging approximately 24 hours after treatment., Results: In total, 118 patients were included. DWI reversal was confirmed in 42 patients. The ADC level in patients with reversal was significantly higher than that in patients without reversal. Eighty-three percent of patients with DWI reversal areas had mean ADC levels of ≥520 × 10 -6 mm 2 /s, and 71% of patients without DWI reversal areas had mean ADC levels of <520 × 10 -6 mm 2 /s. The mean ADC threshold was 520 × 10 -6 mm 2 /s with a sensitivity and specificity of 71% and 83%, respectively. In multivariate analysis, the mean ADC level (OR, 1.023; 95% CI, 1.013-1.033; P < .0001) was independently associated with DWI reversal. Patients with DWI reversal areas had earlier neurologic improvement (NIHSS at 7 days) than patients without reversal areas ( P < .0001)., Conclusions: In acute ischemic stroke, the ADC value is independently associated with DWI reversal. Lesions with a mean ADC of ≥520 × 10 -6 mm 2 /s are salvageable by mechanical thrombectomy, and DWI reversal areas regain neurologic function. The ADC value is easily assessed and is a useful tool to predict viable lesions., (© 2022 by American Journal of Neuroradiology.)

Several cases of posterior reversible encephalopathy syndrome (PRES) after blood transfusion have been reported, but the long-term prognosis is unknown. Here, we report two cases of blood transfusion-associated PRES with severe brain atrophy at 1 year after onset. We report the case with a discussion of pathological mechanisms., Competing Interests: The authors state that they have no conflicts of interest to declare., (© 2022 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

The most common neurological manifestation of eosinophilic granulomatosis with polyangiitis (EGPA), formerly called Churg-Strauss syndrome, is mononeuritis multiplex caused by small-vessel vasculitis. In contrast, central nervous system involvement is rare. Among EGPA-associated central nervous system disorders, there are only a few reported cases of hypertrophic pachymeningitis (HP). Here, we report a patient with EGPA with headache and ophthalmoplegia who presented with HP and had a dural biopsy. The biopsy specimen showed lymphocytic inflammatory cell infiltration without EGPA-specific findings, that is, eosinophilic infiltration, granuloma or angiitis. To the best of our knowledge, there are no previous reports of EGPA-associated HP pathology. Here, we report the first case presentation of a patient with EGPA-associated HP with pathological findings., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Macrophages expressing C-C chemokine receptor type 2 (CCR2) infiltrate the central and peripheral neural tissues of amyotrophic lateral sclerosis (ALS) patients. To identify the functional role of CCR2 + macrophages in the pathomechanisms of ALS, we used an ALS animal model, mutant Cu/Zn superoxide dismutase 1 G93A (mSOD1)-transgenic (Tg) mice. To clarify the CCR2 function in the model, we generated SOD1 G93A /CCR2 Red fluorescence protein (RFP)/Wild type (WT) /CX3CR1 Green fluorescence protein (GFP)/WT -Tg mice, which heterozygously express CCR2-RFP and CX3CR1-GFP, and SOD1 G93A /CCR2 RFP/RFP -Tg mice, which lack CCR2 protein expression and present with a CCR2-deficient phenotype. In mSOD1-Tg mice, mSOD1 accumulated in the sciatic nerve earlier than in the spinal cord. Furthermore, spinal cords of SOD1 G93A /CCR2 RFP/WT /CX3CR1 GFP/WT mice showed peripheral macrophage infiltration that emerged at the end-stage, whereas in peripheral nerves, macrophage infiltration started from the pre-symptomatic stage. Before disease onset, CCR2 + macrophages harboring mSOD1 infiltrated sciatic nerves earlier than the lumbar cord. CCR2-deficient mSOD1-Tg mice showed an earlier onset and axonal derangement in the sciatic nerve than CCR2-positive mSOD1-Tg mice. CCR2-deficient mSOD1-Tg mice showed an increase in deposited mSOD1 in the sciatic nerve compared with CCR2-positive mice. These findings suggest that CCR2 + and CX3CR1 + macrophages exert neuroprotective functions in mSOD1 ALS via mSOD1 clearance from the peripheral nerves., (© 2021. The Author(s).)

Connexin36 (Cx36) forms gap junctions between neurons, which are called electrical synapses, enabling adjacent neurons to communicate directly. The participation of chemical synapses in neurodegeneration in amyotrophic lateral sclerosis (ALS) has long been indicated, but it remains unclear whether electrical synapses are involved in the pathogenesis of ALS. We performed extensive immunopathological analyses using mutant superoxide dismutase 1 (SOD1 G93A ) transgenic mice and their littermates to investigate whether Cx36-made electrical synapses are affected in motor neuron diseases. We found that in the lamina IX of the lumbar spinal cord from wild type mice, about half of the Cx36 puncta existed independently of chemical synapse markers, while the rest coexisted with chemical synapse markers, such as vesicular glutamate transporter 1 (VGLUT1), which is a glutamatergic axon terminal marker, and/or glutamate decarboxylase 65 (GAD65), which is a GABAergic axon terminal marker. Cx36 single or Cx36/GAD65 double positive puncta, but not VGLUT1-containing puncta, were preferentially decreased on neuronal and dendritic surfaces of the anterior horn cells in the early stage of SOD1 G93A ALS mice. Moreover, in five human autopsied sporadic ALS cases with bulbar or upper limb onset, Cx36 immunoreactivity was diminished in the proximal dendrites and neuropils of well-preserved large motor neurons in the lumbar anterior horns. These findings suggest that downregulation of neuronal and dendritic Cx36 in the spinal anterior horns commonly occurs from the early stage of hereditary and sporadic ALS. Cx36-made electrical synapses without glutamatergic signaling appear to be more vulnerable than other chemical synapses and electrical synapses with glutamatergic signaling in the early stage of motor neuron degeneration, suggesting involvement of Cx36-made electrical synapses in the pathogenesis of human ALS.

Introduction: Facial onset motor and sensory neuronopathy (FOSMN) is a rare disease whose cardinal features are initial asymmetrical facial sensory deficits followed by bulbar symptoms and spreading of sensory and motor deficits from face to scalp, neck, upper trunk, and upper extremities in a rostral-caudal direction. Although bulbar involvement is frequently observed in FOSMN, dysphagia in these patients has not been fully described. In this study, we aimed to characterize dysphagia as a prognostic factor in FOSMN by investigating our institutional case series., Methods: We retrospectively reviewed the medical records, including swallowing function tests, of six patients with FOSMN (three men and three women) who were thoroughly examined at Kyushu University Hospital between 1 January 2005 and 30 November 2017., Results: Average age at onset was 58.5 years; average disease duration was 5.7 years. All patients developed bulbar dysfunction and dysphagia (at an average of 1.8 and 2.6 years from onset, respectively), resulting in choking episodes in three patients, percutaneous endoscopic gastrostomy placement in three, and recurrent aspiration pneumonia in one. Four of five patients evaluated with videofluoroscopic swallowing studies had poor oral retention, leading to bolus flowing into the pharynx before swallowing; the fifth patient showed poor lingual transfer. Fiberoptic endoscopic evaluation of swallowing revealed leakage of blue-dyed water from the mouth to the pharynx in three patients because of poor oral retention, but only mild pharyngeal phase dysphagia in all four cases evaluated., Conclusions: Oral phase dysphagia predominates in the early stage of FOSMN., (© 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Objective: The objective of this study was to identify new causes of Charcot-Marie-Tooth (CMT) disease in patients with autosomal-recessive (AR) CMT., Methods: To efficiently identify novel causative genes for AR-CMT, we analyzed 303 unrelated Japanese patients with CMT using whole-exome sequencing and extracted recessive variants/genes shared among multiple patients. We performed mutation screening of the newly identified membrane metalloendopeptidase (MME) gene in 354 additional patients with CMT. We clinically, genetically, pathologically, and radiologically examined 10 patients with the MME mutation., Results: We identified recessive mutations in MME in 10 patients. The MME gene encodes neprilysin (NEP), which is well known to be one of the most prominent beta-amyloid (Aβ)-degrading enzymes. All patients had a similar phenotype consistent with late-onset axonal neuropathy. They showed muscle weakness, atrophy, and sensory disturbance in the lower extremities. All the MME mutations could be loss-of-function mutations, and we confirmed a lack/decrease of NEP protein expression in a peripheral nerve. No patients showed symptoms of dementia, and 1 patient showed no excess Aβ in Pittsburgh compound-B positron emission tomography imaging., Interpretation: Our results indicate that loss-of-function MME mutations are the most frequent cause of adult-onset AR-CMT2 in Japan, and we propose that this new disease should be termed AR-CMT2T. A loss-of-function MME mutation did not cause early-onset Alzheimer's disease. Identifying the MME mutation responsible for AR-CMT could improve the rate of molecular diagnosis and the understanding of the molecular mechanisms of CMT., (© 2016 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.)

We report a 55 year old Japanese man with a history of alcohol abuse, who was in a near fasting state for the previous few days.He was admitted to our hospital with abrupt disturbance of consciousness. He presented disturbance of consciousness with extreme hypoglycemia and ketoacidosis with high β-hydroxybutyric acid concentration. Taking into account his living history, we diagnosed with alcoholic ketoacidosis (AKA). Symptoms ameliorated with glucose injection and fluid loading. AKA patients show abdominal pain, nausea or vomiting, but they are usually alert and lucid despite the severe acidosis. This case, however, presented comatose status caused by hypoglycemia. Poor oral intake of this patient was assumed to be the cause of hypoglycemia. Alcoholism may cause hypoglycemia accompanying with AKA, due to a low carbohydrate intake, the inhibition of gluconeogenesis, and reduced hepaticglycogen storage as seen in this case. Here, we report a case of AKA that demonstrated hypoglycemia with the literature review.

A 43-year-old woman with a 3-year history of headache, fever, and swelling of the forehead, presented to our hospital. A general examination revealed palmar and plantar pustules. Blood analyses showed an elevated white blood cell count, C-reactive protein level, and erythrocyte sedimentation rate. Brain MRI revealed a partially thickened cranial bone with gadolinium enhancement, and also abnormally enhanced dura mater. Bone scintigraphy showed involvement of the cranial bone and bilateral sternoclavicular joints. Palmar skin biopsy indicated palmoplantar pustulosis. From these results, SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome with associated hypertrophic pachymeningitis was diagnosed. After corticosteroid therapy and tonsillectomy, the clinical symptoms and radiological abnormalities were improved. Clinicians should be aware of SAPHO as a potential unusual cause of hypertrophic pachymeningitis., (Copyright © 2014 Elsevier B.V. All rights reserved.)

We report the first case of definite neuromyelitis optica (NMO) with a pathogenic mitochondrial DNA (mtDNA) mutation for Leber's hereditary optic neuropathy (LHON) (G11778A point mutation). A 36-year-old Japanese woman had experienced recurrent neurological symptoms originating from involvements of the optic nerves and spinal cord. She finally lost her bilateral vision, and spastic paraparesis and sensory disturbances below the T6 level remained despite intensive immunotherapies. Brain and spinal magnetic resonance imaging (MRI) revealed T2-high-intensity lesions in the optic nerves and thoracic spinal cord, but no lesions in the brain. A blood examination revealed positivity for both anti-aquaproin-4 antibodies and an LHON mtDNA mutation.