Optimizing High-Resolution MR Angiography: The Synergistic Effects of 3D Wheel Sampling and Deep Learning-Based Reconstruction.

OBJECTIVE: The aim of this study was to assess the utility of the combined use of 3D wheel sampling and deep learning-based reconstruction (DLR) for intracranial high-resolution (HR)-time-of-flight (TOF)-magnetic resonance angiography (MRA) at 3 T. METHODS: This prospective study enrolled 20 patients who underwent head MRI at 3 T, including TOF-MRA. We used 3D wheel sampling called "fast 3D" and DLR for HR-TOF-MRA (spatial resolution, 0.39 × 0.59 × 0.5 mm3) in addition to conventional MRA (spatial resolution, 0.39 × 0.89 × 1 mm3). We compared contrast and contrast-to-noise ratio between the blood vessels (basilar artery and anterior cerebral artery) and brain parenchyma, full width at half maximum in the P3 segment of the posterior cerebral artery among 3 protocols. Two board-certified radiologists evaluated noise, contrast, sharpness, artifact, and overall image quality of 3 protocols. RESULTS: The contrast and contrast-to-noise ratio of fast 3D-HR-MRA with DLR are comparable or higher than those of conventional MRA and fast 3D-HR-MRA without DLR. The full width at half maximum was significantly lower in fast 3D-MRA with and without DLR than in conventional MRA (P = 0.006, P < 0.001). In qualitative evaluation, fast 3D-MRA with DLR had significantly higher sharpness and overall image quality than conventional MRA and fast 3D-MRA without DLR (sharpness: P = 0.021, P = 0.001; overall image quality: P = 0.029, P < 0.001). CONCLUSIONS: The combination of 3D wheel sampling and DLR can improve visualization of arteries in intracranial TOF-MRA.

Very late onset neuromyelitis optica spectrum disorders.

BACKGROUND AND PURPOSE: Neuromyelitis optica spectrum disorder (NMOSD) often presents in the elderly with an insidious onset of symptoms and aggressive progression. There have been anecdotal cases of very late onset (VLO)-NMOSD, but case series reports are rare. The aim of this retrospective study was to clarify the clinical features of VLO-NMOSD. METHODS: According to the age at onset, we classified patients with NMOSD into three subgroups: ≤49 years, early onset NMOSD (EO-NMOSD); 50-69 years, late onset NMOSD (LO-NMOSD); and ≥70 years, VLO-NMOSD. We evaluated the clinical characteristics, magnetic resonance imaging (MRI) findings, laboratory data, and immunotherapies of the groups. RESULTS: Overall, 12 men and 64 women with a median (interquartile range) age at onset and duration of disease of 42.0 (29.0-55.8) years and 70.0 (16.3-143.0) months, respectively, were included. Eight (11%) patients had VLO-NMOSD, 22 (29%) had LO-NMOSD, and 46 (61%) had EO-NMOSD. Patients with EO-NMOSD had a significantly longer interval between episodes as well as time between the first symptom and diagnosis of NMOSD than did those with VLO-NMOSD and LO-NMOSD (p = 0.046). Optic neuritis and nerve lesions on MRI were significantly less frequent in patients with VLO-NMOSD than in those with LO-NMOSD and EO-NMOSD (p = 0.002 and p = 0.028, respectively). In contrast, patients with VLO-NMOSD had higher nadir Expanded Disability Status Scale and Nurick scale scores and a significantly longer spinal lesion length than did those with LO-NMOSD and EO-NMOSD (p = 0.029, p = 0.049, and p = 0.032, respectively). CONCLUSIONS: Patients with VLO-NMOSD tend to develop severe myelitis with long cord lesions but not optic neuritis.

A comprehensive analysis of the clinical characteristics and laboratory features in 179 patients with autoimmune autonomic ganglionopathy.

The clinical importance of autoantibodies against the ganglionic acetylcholine receptor (gAChR) remains to be fully elucidated. We aimed to identify the clinical characteristics of autoimmune autonomic ganglionopathy (AAG) in patients with gAChR autoantibodies. For this cohort investigation, serum samples were obtained from patients with AAG between 2012 and 2018 in Japan. We measured the levels of autoantibodies against gAChRα3 and gAChRß4 and evaluated clinical features, as well as assessing the laboratory investigation results among the included patients. A total of 179 patients tested positive for antibodies, including 116 gAChRα3-positive, 13 gAChRß4-positive, and 50 double antibody-positive patients. Seropositive AAG patients exhibited widespread autonomic dysfunction. Extra-autonomic manifestations including sensory disturbance, central nervous system involvement, endocrine disorders, autoimmune diseases, and tumours were present in 118 patients (83%). We observed significant differences in the frequencies of several autonomic and extra-autonomic symptoms among the three groups. Our 123I-metaiodobenzylguanidine myocardial scintigraphy analysis of the entire cohort revealed that the heart-to-mediastinum ratio had decreased by 80%. The present study is the first to demonstrate that patients with AAG who are seropositive for anti-gAChRß4 autoantibodies exhibit unique autonomic and extra-autonomic signs. Decreased cardiac uptake occurred in most cases, indicating that 123I- metaiodobenzylguanidine myocardial scintigraphy may be useful for monitoring AAG. Therefore, our findings indicate that gAChRα3 and gAChRß4 autoantibodies cause functional changes in postganglionic fibres in the autonomic nervous system and extra-autonomic manifestations in seropositive patients with AAG.

A Randomized Phase 2 Trial of Antibiotic Prophylaxis Versus No Intervention for Muscle Biopsy in A Neurology Department.

Muscle biopsy can be used to confirm the diagnosis of neuromuscular diseases. However, it is unclear whether antibiotic prophylaxis prior to muscle biopsy is needed to prevent surgical site infection (SSI). We are conducting a phase 2, single-center, open-labeled, prospective randomized trial to clarify the need for antibiotic prophylaxis in patients at low risk for SSI undergoing muscle biopsy. Patients will be randomized to an antibiotic prophylaxis group or a control group, and the incidence of SSI will be compared between the groups. Our findings will clarify the need for antibiotic prophylaxis in this patient population.

Is 123I-MIBG Scintigraphy Beneficial or Excessive for the Diagnosis of Parkinson's Disease in the Early Phase?

INTRODUCTION/OBJECTIVE: In most cases, abnormal cardiac 123I-meta-iodobenzylguanidine (MIBG) scintigraphy increases the probability of a diagnosis of Parkinson's disease (PD) in patients with parkinsonian features. In our study, we validated the additional value of 123I-MIBG scintigraphy beyond providing information on neurological findings and response to dopaminergic therapy for the diagnosis of PDin the early phase. METHODS: We investigated 77 cases of PD (Hoehn and Yahr Stages I-III) and 73 cases of atypical parkinsonian disorder (APD), including 35 patients with multiple system atrophy, 19 with corticobasal syndrome, and 19 with progressive supranuclear palsy. Two multiple logistic regression models were developed to predict the probability of PD based on APD. Common covariates were resting tremor, vertical supranuclear palsy, apraxia, cerebellar symptoms, and response to dopaminergic therapy with MIBG scintigraphy (reference model) or without it (MIBG-added model). The net reclassification index (NRI) was examined and net benefit using decision curve analysis was performed to examine the additional clinical value of MIBG scintigraphy. Finally, we estimated the cost-effectiveness of MIBG scintigraphy. RESULTS: The MIBG-added model significantly improved the ability to classify PD or APD compared with the reference model (NRI index 1.390, p < 0.001). However, the decision curve of the reference model ranked equally with the MIBG-added model up to a risk threshold of 0.8. In addition, MIBG scintigraphy was not cost-effective. CONCLUSIONS: Although MIBG scintigraphy has statistical usefulness for PD diagnosis, there may be little additional benefit in the early phase of PD beyond the neurological findings and response to dopaminergic therapy regarding clinical effectiveness and cost-effectiveness. It may be of greatest value when neurological findings that do not match PD are observed during the clinical course.

A 23-Year-Old Woman with Sudden-Onset Blindness of the Right Eye.

A 23-year-woman was presented for sudden-onset monocular blindness. Branch retinal artery occlusion in the right eye and multiple brain embolism were detected. Trousseau syndrome due to bilateral ovarian cancer was diagnosed; no embolic events were observed after anticoagulant therapy and surgical resection.

A Novel Mutation of VPS13D-related Disorders with Parkinsonism.

We herein report a case of VPS13D-related disorder with a novel homogeneous variant. A 58-year-old Japanese woman was referred to our hospital with slowly progressive gait disturbance and cognitive impairment. A neurological examination revealed decreased spontaneity, recent memory impairment, Parkinsonism, cerebellar ataxia, pyramidal signs, and autonomic dysfunction. Dopamine transporter single-photon-emission computed tomography showed a markedly reduced uptake in the striatum bilaterally. Whole-exome sequencing revealed a novel homozygous missense variant of the VPS13D gene (Arg3267Pro). Our case suggests that mutations in VPS13D may cause parkinsonism, in addition to the previously reported cerebellar ataxia and spastic paraplegia.

Autoimmune Polyglandular Syndrome with Refractory Gait Disturbance.

Autoimmune polyglandular syndrome (APS) causes autoimmune diseases of multiple organs and can also present with neurological symptoms. We here report a 58-year-old man who presented with progressive gait disturbance that had started 7 years ago. He had spasticity, reduced deep sensations, and truncal cerebellar ataxia. Laboratory examinations revealed autoantibody-related cobalamin deficiency and the presence of anti-thyroid antibodies and anti-glutamic acid decarboxylase antibodies. His gait worsened after cobalamin replenishment, but additional steroid therapy was effective. APS can cause refractory gait disturbance that requires not only cobalamin replenishment but also immunotherapy.

Gut microbiota of Parkinson's disease in an appendectomy cohort: a preliminary study.

In patients with Parkinson's disease (PD), α-synuclein pathology is thought to spread to the brain via the dorsal motor nucleus of the vagus nerve. The link between the gut microbiome and PD has been explored in various studies. The appendix might play an important role in immunity by maintaining the microbiota as a reservoir. In recent times, appendectomy has been linked to a lower risk of PD, possibly owing to the role of the appendix in altering the gut microbiome. We aimed to elucidate whether the gut microbiota affects PD development in the appendectomy cohort. We analyzed the fecal microbial composition in patients with PD and healthy controls with and without a history of appendectomy. The abundance of microbes from the family Enterobacteriaceae was higher in feces samples from patients with Parkinson's disease compared to that in samples collected from healthy controls. Furthermore, there was a significant phylogenetic difference between patients with PD and healthy controls who had undergone appendectomy. There was a significant phylogenetic difference between patients with PD and HCs who had undergone APP. These results suggest the correlation between gut microbiota and PD in patients who have undergone APP.

Miller Fisher Syndrome Following Vaccination against SARS-CoV-2.

After BNT162b2 messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccination, a 30-year-old man developed bilateral lateral gaze palsy, diplopia, absent tendon reflexes, and ataxic gait. Serum anti-GQ1b and anti-GT1a immunoglobulin G (IgG) antibodies were strongly positive. Based on those findings, he was diagnosed with Miller Fisher syndrome (MFS). Intravenous immunoglobulin therapy was administered, and his symptoms fully recovered within approximately 3 months. To the best of our knowledge, this is the first report to describe the development of MFS after COVID-19 mRNA vaccination.

Histopathological Features of Gerhardt Syndrome in a Patient With Multiple System Atrophy: An Autopsy Case Report.

Multiple system atrophy (MSA) is a progressive neurodegenerative disease characterized by autonomic failure, parkinsonism, and cerebellar ataxia. Gerhardt syndrome, which is inspiratory dyspnea with laryngeal stridor associated with dysfunction of the vocal folds, is a frequent and fatal complication of MSA. A 59-year-old man with a six-year history of MSA presented with ataxia and dysarthria. He also had dyspnea and stridor, which had worsened in the last three months, and died from respiratory distress. Autopsy revealed neurogenic group atrophy of the posterior cricoarytenoid (PCA) muscle, which suggested that laryngeal nerve damage caused abductor vocal fold paralysis in addition to cerebellar and brainstem atrophy with glial cytoplasmic inclusions. Our histopathological findings suggest that Gerhardt syndrome may be associated with neurogenic atrophy of the laryngeal abductor muscle (PCA muscle) of the vocal folds.

Detection of Vascular Notch3 Deposits in Unfixed Frozen Skin Biopsy Sample in CADASIL.

This study aimed to evaluate the utility of immunohistochemical staining of vascular Notch3 deposits in biopsied unfixed frozen skin samples from patients with suspected cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We analyzed vascular Notch3 deposits in unfixed frozen skin biopsy samples obtained from 43 patients with suspected CADASIL by immunohistochemistry using antibodies against the extracellular domain (ECD) of Notch3. We also sequenced the NOTCH3 gene in all patients, as well as evaluated their symptoms and neuroimages. We found granular Notch3 ECD deposits in the vessel walls of unfixed frozen skin biopsy samples in 10 of the 43 suspected patients with CADASIL. All 10 cases with skin Notch3 ECD deposits also carried reported pathogenic variants in the NOTCH3 gene associated with CADASIL. NOTCH3 variants of unknown significance were found in the other four patients without vascular Notch3 ECD or granular osmiophilic material deposits in biopsied skin samples. The remaining 29 cases without vascular Notch3 ECD deposits did not have variants in the NOTCH3 gene. Immunohistochemical evaluation of vascular Notch3 ECD deposits in unfixed frozen biopsied skin samples may be useful for detecting Notch3 deposits in CADASIL.

[A case of a syndrome resembling PSP after aortic arch replacement under deep hypothermic circulatory arrest].

A 57-year-old man presented with acute signs and symptoms mimicking PSP (bradykinesia, supranuclear ocular palsy, dysphagia, neck dystonia, and apraxic gait) on the day after a graft replacement surgery, which was performed for aortic arch aneurysm under deep hypothermic circulatory arrest (rectal temperature, 18 degrees C). Dysphagia improved temporarily, but relapsed after a few months. Symptoms did not change during 2 years of antiparkinsonian drug administration. Brain images obtained before the surgery revealed slight atrophy of the midbrain tegmentum and frontal lobes, but the patient was asymptomatic. No findings of cerebral vascular disease and hypoxic encephalopathy were observed on brain images after the surgery. These clinical features resembling PSP might have been caused by deep hypothermia and the patient's predisposition for PSP. This is the first case report in Japan of a syndrome resembling PSP that occurred after aortic arch replacement under deep hypothermic circulatory arrest.

gAChR antibodies in children and adolescents with acquired autoimmune dysautonomia in Japan.

OBJECTIVE: Patients with acquired autonomic dysfunction may have antibodies specific to the ganglionic nicotinic acetylcholine receptor (gAChR). However, the clinical features of children and adolescents with acquired autonomic dysfunction (AAD) remain unclear. This study aimed to determine the clinical features of pediatric patients with acquired autonomic dysfunction. METHODS: This study retrospectively examined a series of patients of AAD with serum gAChR antibodies who were referred to our laboratory for antibody testing between January 2012 and April 2019. The study included 200 patients (<20 years, 20 cases; ≥20 years, 175 cases) with clinical features of AAD. RESULTS: Upon comparing pediatric and adult patients, we found that antecedent infection and autonomic symptoms at onset with gastrointestinal symptoms occurred more frequently in children with AAD. We confirmed that four children (20.0%) met the diagnostic criteria for postural orthostatic tachycardia syndrome (POTS). A significantly higher number of children than adults had POTS (P = 0.002). In addition, upper GI dysfunction was more prevalent in children than in adults (P = 0.042). In particular, nausea and vomiting occurred in 60.0% of children with AAD and in 21.1% of adults (P < 0.001). The frequency of paralytic ileus was significantly higher in children with AAD (20.0%) relative to adults (6.3%) (P = 0.030). Regarding extra-autonomic manifestations, encephalopathy was more frequent in children (15.0%) than in adults (1.1%) (P < 0.001). INTERPRETATION: Pediatric AAD patients have their own clinical characteristics, and these features may be unique to children and adolescents.

Diagnostic accuracy of MRI parameters in pure akinesia with gait freezing.

OBJECTIVE: To determine the usefulness of MRI measurements in patients with pure akinesia with gait freezing (PAGF), Richardson's syndrome, and Parkinson's disease for diagnosis. METHODS: We obtained MRI measurements for patients with PAGF, Richardson's syndrome, or Parkinson's disease: 9 patients with PAGF, 26 with Richardson's syndrome, and 93 with Parkinson's disease. We measured the area of the pons and midbrain on midsagittal MRIs and the midbrain width on axial MRIs. We also calculated the mean values of the superior cerebellar peduncle, middle cerebellar peduncle, and cerebral crus width; the pons area-to-midbrain area ratio; the middle cerebellar peduncle width-to-superior cerebellar peduncle width ratio; and the magnetic resonance (MR) Parkinsonism index. RESULTS: The Richardson's syndrome group had the highest pons area-to-midbrain area ratio and MR Parkinsonism index; the Parkinson's disease group had the lowest values. The Parkinson's disease group also had the highest midbrain width and cerebral crus width, with the lowest values being seen in the Richardson's syndrome group. The PAGF group had the intermediate values of the pons area-to-midbrain area ratio and MR Parkinsonism index between the Richardson's syndrome group and the Parkinson's disease group, whereas significant differences were found only in the pons area-to-midbrain area ratio. Results from receiver operating characteristic curve analyses showed that the pons area-to-midbrain area ratio has a higher sensitivity, specificity, and accuracy than the MR Parkinsonism index. CONCLUSIONS: The pons area-to-midbrain area ratio is more useful to distinguish PAGF from Richardson's syndrome and Parkinson's disease than the MR Parkinsonism index.

Impact of major earthquakes on Parkinson's disease.

In April of 2016, major earthquakes occurred in Kumamoto, Japan. There is limited information on how major earthquakes affect patients with Parkinson's disease (PD). This study investigates the effect of major earthquakes on patients with PD. The participants were outpatients with PD from hospitals located in areas heavily damaged by the earthquakes. We performed an anonymous survey at nine medical institutions to investigate the condition of these patients during the month following the earthquakes. We collected questionnaires from 335 patients with PD. The mean age was 72.6, and the mean disease duration was 7.4 years. Regarding physical conditions, 29.3% of the patients worsened, 1.5% improved, and 68.1% had no change. The mental health of 35.2% of the patients worsened, 2.4% improved, and 57.9% had no change. The most frequently exacerbated neurologic symptoms included bradykinesia (56.1%), gait disturbance (51.0%), freezing of gait (40.8%), extension of "off" time (38.8%), and constipation (38.8%). The worsening mental conditions included fear of an aftershock (77.1%), anxiety (49.2%), insomnia (47.5%), melancholy feelings (45.8%), and fatigability (38.1%). Patients forced to evacuate reported significantly more physical and mental health symptoms (p < 0.01). The influences of major earthquakes on patients with PD were identified. After major earthquakes, we should consider the care required for patients' physical and mental health especially for those who experienced evacuation.

Autoimmune autonomic ganglionopathy: an update on diagnosis and treatment.

INTRODUCTION: Autoimmune autonomic ganglionopathy (AAG) is an acquired immune-mediated disorder that leads to autonomic failure. The disorder is associated with autoantibodies to the ganglionic nicotinic acetylcholine receptor (gAChR). We subsequently reported that AAG is associated with an overrepresentation of psychiatric symptoms, sensory disturbance, autoimmune diseases, and endocrine disorders. Area covered: The aim of this review was to describe AAG and highlight its pivotal pathophysiological aspects, clinical features, laboratory examinations, and therapeutic options. Expert commentary: AAG is a complex neuroimmunological disease, these days considered as an autonomic failure with extra-autonomic manifestations (and various limited forms). Further comprehension of the pathophysiology of this disease is required, especially the mechanisms of the extra-autonomic manifestations should be elucidated. There is the possibility that the co-presence of antibodies that were directed against the other subunits in both the central and peripheral nAChRs in the serum of the AAG patients. Some patients improve with immunotherapies such as IVIg and/or corticosteroid and/or plasma exchange. 123I-MIBG myocardial scintigraphy may be a useful tool to monitor the therapeutic effects of immunotherapies.

Effect of thymectomy for thymic atrophy in myasthenia gravis: A retrospective study on 93 patients.

To clarify the efficacy of thymectomy among myasthenia gravis (MG) patients with and without thymoma. We classified MG patients who underwent thymectomy into 3 groups, such as thymic atrophy group, thymic follicular hyperplasia (TFH) group and thymoma group. We compared the data of clinical features and postoperative prognosis at very short-term, short-term, and medium-term. The clinical course of MG patients with atrophic thymus after thymectomy was even better than those of TFH or thymoma, in this retrospective study. However, we found no significant differences in the comparison of mean dose of prednisolone between the 3 groups at each time point.