Background Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune astrocytopathy with sporadically reported vaccine-associated onset. Several vaccines are implicated as potential triggers; however, observations have been infrequent. Case presentation We present the case of a previously healthy 42-year-old man with human leukocyte antigen (HLA) A༊24:02, B༊52:01:01/55:02:01, C༊12:02/03:03, and DRB1༊04/15, who developed AQP4 IgG–positive NMOSD with area postrema syndrome (APS) temporally associated with the mRNA-1273 (Moderna) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Twenty-one days after the initial dose of SARS-CoV-2 mRNA vaccine, the patient experienced persistent nausea, recurrent vomiting, and hiccups. Nonetheless, he received the second dose on day 28 and developed low-grade fever, cough, and subsequent neurological symptoms 4 days later. Within 5 days, his condition deteriorated to bilateral weakness, dysphagia, and dysarthria. Forty-nine days after vaccination, the patient was hospitalised for respiratory failure and pneumonia. Despite antibiotics, his hiccups worsened, progressing to type II respiratory failure requiring intubation. AQP4 immunoglobulin G (AQP4 IgG)–positive NMOSD with APS was diagnosed and ultimately resulted in respiratory failure and aspiration pneumonia requiring ventilatory support. The treatment included intravenous methylprednisolone, plasma exchange, and oral corticosteroid therapy, and the patient was able to vocalise via tracheostomy on day 54 post-admission. Inebilizumab was initiated as maintenance therapy, and no recurrence was observed during the 3-year follow-up. Conclusions This case illustrates that new-onset NMOSD temporally associated with SARS-CoV-2 mRNA vaccination presents initially as APS and rapidly progresses to respiratory failure.

PURPOSE:Despite advances in diagnostics, many inherited peripheral neuropathies remain genetically unexplained. We investigated whether biallelic variants in FAT3 (FAT Atypical Cadherin 3) are implicated in inherited axonal neuropathies. METHODS:We identified biallelic FAT3 variants in three unrelated individuals among 3315 Japanese patients with inherited peripheral neuropathies. Variants were evaluated by segregation analysis, in silico modeling, and functional studies in Drosophila and mouse models. RESULTS:All patients exhibited progressive distal muscle weakness and cranial nerve involvement, including tongue atrophy, dysarthria, and facial weakness. Two required ventilatory support because of respiratory muscle paralysis. One patient additionally showed central hypomyelination, autonomic dysfunction, and developmental anomalies, such as congenital scoliosis and intestinal pseudo-obstruction. Identified variants were ultrarare, affected conserved residues, segregated with disease, and were predicted to impair domain stability. FAT3 knockdown in Drosophila resulted in rough eye phenotype, shortened lifespan, impaired motor function, and defective motor neuron branching. Fat3 knockout and knockin mice displayed perinatal lethality, sciatic nerve axonal degeneration, and central nervous system abnormalities despite preserved motor performance. CONCLUSION:Our findings establish FAT3 as a novel gene for autosomal-recessive axonal neuropathies and support the concept of a FAT3-related multisystem neurodevelopmental disorder characterized by motor neuron degeneration and systemic abnormalities.

Creutzfeldt-Jakob disease (CJD) is a rare, fatal neurodegenerative disorder that can share clinicoradiologic features with autoimmune cortical encephalitis (CE); however, the pathological significance of myelin oligodendrocyte glycoprotein (MOG)-IgG, which is one of the causes of CE, has not yet been explored in the context of CJD. We herein present the case of a man in his mid-70s with a family history of CJD and rapidly progressive cognitive decline. Genetic testing confirmed the E200K mutation in PRNP. CSF analysis revealed CSF-restricted MOG-IgG that became undetectable after corticosteroid therapy without clinical improvement. This case highlights the need for cautious interpretation of the CSF-restricted MOG-IgG in CJD.

A 73-year-old male who was a compromised host developed bacteremia, pyelonephritis, and bacterial meningitis due to Arcobacter butzleri. To the best of our knowledge, this is the first report of meningitis caused by A. butzleri. The outcome of treatment with meropenem was excellent. We speculate that the ingestion of contaminated chicken meat caused bacteremia via the digestive tract, leading to pyelonephritis and meningitis. A. butzleri is a possible cause of bacterial meningitis even in the absence of severe gastrointestinal symptoms.

A 36-year-old man developed polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome after conversion from solitary plasmacytoma of bone to multiple myeloma. Twenty-four days following the neurological onset, he lost his independent walking ability. The level of serum vascular endothelial growth factor (VEGF) at diagnosis was 5,250 pg/mL. Three months after initiating treatment, he regained his independent walking ability in line with a reduction in the elevated serum VEGF level. Due to their genomic instability gained during conversion, myeloma cells may overproduce humoral factors and cytokines, possibly contributing to the development of neuropathy as well as the production of VEGF.

Autoantibodies against 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and the signal recognition particle (SRP) are representative antibodies causing immune-mediated necrotizing myopathies (IMNM), called as anti-HMGCR and anti-SRP myopathies, respectively. Here, we analyzed the differences in routine blood test results between 56 anti-HMGCR and 77 anti-SRP myopathy patients. A higher alanine transaminase (ALT) level and a lower aspartate transaminase (AST)/ALT ratio were observed in anti-HMGCR myopathy patients [ALT, 265.7 +/- 213.3 U/L (mean +/- standard deviation); AST/ALT ratio, 0.88 +/- 0.32] than in anti-SRP-myopathy patients (ALT, 179.3 +/- 111.2 U/L, p < 0.05; AST/ALT ratio, 1.28 +/- 0.40, p < 0.01). In the active phase, anti-HMGCR myopathy often showed ALT predominance, whereas anti-SRP myopathy often showed AST predominance. In addition, there were differences in erythrocyte sedimentation rate (ESR), total cholesterol (TChol) level, and high-density lipoprotein (HDL) level between anti-HMGCR and anti-SRP myopathies (ESR: HMGCR, 24.4 +/- 20.8 mm/1 h; SRP, 35.7 +/- 26.7 mm/1 h, p = 0.0334; TChol: HMGCR, 226.7 +/- 36.6 mg/dL; SRP, 207.6 +/- 40.8 mg/dL, p = 0.0163; HDL: HMGCR, 58.4 +/- 13.9 mg/dL; SRP, 46.2 +/- 17.3 mg/dL, p < 0.01). Additional studies on the differences in routine blood test results may further reveal the pathomechanisms of IMNM. (C) 2021 Elsevier B.V. All rights reserved.

Immune thrombocytopenic purpura (ITP) can increase the risk of not only hemorrhagic incidents but also thrombotic events. Although several patients with ITP who developed cerebral infarction have been reported, concurrence of spinal cord infarction and ITP has not been reported. We report the case of a female patient who developed spinal cord infarction during the exacerbation of her ITP. This case suggests a possible association between spinal cord infarction and ITP, which can cause paradoxical thrombosis.

•PML can occur in patients with hematologically well-controlled AL amyloidosis.•Plasma cell dyscrasia, chemotherapy, and end-stage renal disease, can cause immunosuppression in these patients.•PML should be considered when neurological symptoms occur in AL amyloidosis patients.

Objective Epidemic myalgia associated with human parechovirus type 3 (EM-HPeV3) is characterized by severe muscle pain and weakness on the limbs and trunk with a fever. No outbreak of EM-HPeV3 has been reported since 2016, and its clinical characteristics have not been sufficiently clarified. We herein report a series of EM-HPeV3 cases during the summer of 2019 and clarify the clinical characteristics of EM-HPeV3. Methods The diagnosis of EM-HPeV3 was established when the patients met both of the following criteria: (1) Patients developed severe muscle pain and weakness with a fever within a week, and those symptoms resolved within a month; and (2) HPeV3 was detected in either a throat swab or fecal specimen of the patient by polymerase chain reaction. We reviewed the medical records of these patients retrospectively. Results Seven patients met the criteria (6 men and 1 woman, age 34 to 47 years old). Myalgia was observed on the thigh, lower legs, upper arms, and forearms in seven, five, two, and five patients, respectively. Four patients showed distal dominant weakness on the arms, while none of the patients showed proximal dominant weakness on the arms. Of the six patients examined, five showed reduced tendon reflexes on all four limbs. One patient showed slight myogenic change and increased insertion activities on needle electromyography. Conclusion We observed seven cases of EM-HPeV3 during the summer of 2019. Reduced tendon reflexes and distal dominancy of muscle pain and weakness on the arms are considered its distinct clinical features.

【 PICTURES IN CLINICAL MEDICINE 】 Anti-agalactosyl Immunoglobulin G Antibodies in Probable Rheumatoid Meningitis Keiko Hatano , Kazuto Katsuse , Takeshi Suzuki 2 and Hideji Hashida 1

Anti-myelin oligodendrocyte glycoprotein (MOG) antibodies have been associated with steroid-responsive cortical encephalitis and comorbid generalized epilepsy. A 44-year-old woman developed repeated epilepsia partialis continua (EPC) without generalized seizures and was anti-MOG antibody-positive. Radiological abnormalities were detected in the bilateral medial frontoparietal cortices, but there were no cerebrospinal fluid abnormalities. She achieved remission with anti-epileptic drugs alone. However, encephalitis recurred four months later when pleocytosis appeared, and steroid therapy was effective. Altogether, EPC without typical cerebrospinal fluid features can be an early sign of anti-MOG antibody-positive encephalitis. Thus, patients with EPC of unknown etiology need to be screened for anti-MOG antibodies.

The patient is an 80‐year‐old man. At the age of 76, he presented with acute onset of severe orthostatic hypotension and diarrhea. Anti‐ganglionic acetylcholine receptor (anti‐gAChR) antibodies were positive, and prednisolone was effective. He was diagnosed with autoimmune autonomic ganglionopathy (AAG) based on acute onset autonomic dysfunction, positive anti‐gAChR antibodies, and efficacy of prednisolone. After the event of AAG, he gradually developed Parkinson's disease (PD). Parkinsonism is described as a complication of AAG in the previous literature. Anti‐gAChR antibodies might inhibit dopamine neurotransmission and be associated with the development of PD.

We report a 65-year-old man who was diagnosed with focal status epilepticus generating a dreamy state, delusions with anxiety, complex audiovisual hallucinations, elementary auditory hallucinations, and metamorphopsia with a growing large lateral temporal lobe lesion. After administrating anti-seizure drugs, all the symptoms disappeared, and brain magnetic resonance imaging revealed ipsilateral hippocampal sclerosis. To the best of our knowledge, this is the first report to present all the symptoms in one epilepsy case. On the basis of semiology, electroencephalography, and brain magnetic resonance imaging, we speculated that epileptic activities that have originated from the lateral lesion might have propagated to the ipsilateral mesial temporal lobe, causing hippocampal sclerosis.

The patient was a 64-year-old man who presented with gait disturbance at the age of 58. He was later diagnosed with Parkinson's disease. At the age of 64, he felt severe right abdominal pain because his right abdomen was compressed by his abnormal posture. Neurological examinations showed axial flexion to the anterior and right sides, i.e. a combination of camptocormia and Pisa syndrome, and hypertrophy of the right lumbar paraspinal muscles in addition to parkinsonism. Surface electromyography and body computed tomography suggested axial dystonia, i.e. right dominant hyperactivity and hypertrophy of the lumbar paraspinal muscles. Botulinum toxin was injected into the right lumbar paraspinal muscles. One month later, his abnormal posture improved and his right abdominal pain was also relieved. In general, botulinum toxin treatment of the paraspinal muscles has the potential to improve Pisa syndrome but carries the risk of worsening camptocormia. However, in our case, not only Pisa syndrome but also camptocormia improved. Therefore, we should note that botulinum toxin treatment of paraspinal muscles is able to improve not only Pisa syndrome but also camptocormia. As a plausible explanation, botulinum toxin treatment could control the hyperactivity of the bilateral paraspinal muscles symmetrically, which might improve camptocormia in addition to Pisa syndrome.

We report on a 44-year-old woman who was diagnosed with toxic epidermal necrolysis (TEN) during the recovery phase from autoimmune limbic encephalitis with anti-glutamate receptor antibodies. Both, autoimmune limbic encephalitis and TEN are very rare diseases. The co-existence of the two diseases has not yet been reported. We speculate that the total of 18 drugs needed for the treatment of encephalitis might have increased the risk of TEN. Similar reports would be required to elucidate the pathophysiology of the co-existence.

We describe the case of a 34-year-old woman with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. She developed transient ischemic attack after the introduction of lenalidomide plus dexamethasone (Rd) therapy despite no vascular risk factors. Magnetic resonance and computed tomography angiographies showed bilateral internal carotid artery stenosis. Rd therapy was suspended because of its thromboembolic risk. She had been neurologically stable during the suspension of Rd therapy. After Rd therapy was restarted, however, she repeated ischemic cerebrovascular disease. Rd therapy was switched to carfilzomib plus dexamethasone therapy. Thereafter, she had been neurologically stable. Multivessel stenosis is infrequently seen in POEMS syndrome. Therefore, magnetic resonance angiography should be performed before introducing Rd therapy in POEMS syndrome.