Conformation-sensitive antibodies against myelin oligodendrocyte glycoprotein (MOG) are detectable in patients with optic neuritis, myelitis, opticomyelitis, acute or multiphasic disseminated encephalomyelitis (ADEM/MDEM) and brainstem/cerebral cortical encephalitis, but are rarely detected in patients with prototypic multiple sclerosis. So far, there has been no systematic study on the pathological relationship between demyelinating lesions and cellular/humoral immunity in MOG antibody-associated disease. Furthermore, it is unclear whether the pathomechanisms of MOG antibody-mediated demyelination are similar to the demyelination patterns of multiple sclerosis, neuromyelitis optica spectrum disorders (NMOSD) with AQP4 antibody, or ADEM. In this study, we immunohistochemically analysed biopsied brain tissues from 11 patients with MOG antibody-associated disease and other inflammatory demyelinating diseases. Patient median onset age was 29 years (range 9–64), and the median interval from attack to biopsy was 1 month (range 0.5–96). The clinical diagnoses were ADEM (n = 2), MDEM (n = 1), multiple brain lesions without encephalopathy (n = 3), leukoencephalopathy (n = 3) and cortical encephalitis (n = 2). All these cases had multiple/extensive lesions on MRI and were oligoclonal IgG band-negative. Most demyelinating lesions in 10 of 11 cases showed a perivenous demyelinating pattern previously reported in ADEM (153/167 lesions) and a fusion pattern (11/167 lesions) mainly in the cortico-medullary junctions and white matter, and only three lesions in two cases showed confluent demyelinated plaques. In addition, 60 of 167 demyelinating lesions (mainly in the early phase) showed MOG-dominant myelin loss, but relatively preserved oligodendrocytes, which were distinct from those of AQP4 antibody-positive NMOSD exhibiting myelin-associated glycoprotein-dominant oligodendrogliopathy. In MOG antibody-associated diseases, MOG-laden macrophages were found in the perivascular spaces and demyelinating lesions, and infiltrated cells were abundant surrounding multiple blood vessels in and around the demyelinating lesions, mainly consisting of macrophages (CD68; 1814 ± 1188 cells/mm2), B cells (CD20; 468 ± 817 cells/mm2), and T cells (CD3; 2286 ± 1951 cells/mm2), with CD4-dominance (CD4+ versus CD8+; 1281 ± 1196 cells/mm2 versus 851 ± 762 cells/mm2, P < 0.01). Humoral immunity, evidenced by perivascular deposits of activated complements and immunoglobulins, was occasionally observed in some MOG antibody-associated demyelinating lesions, and the frequency was much lower than that in AQP4 antibody-positive NMOSD. Subpial lesions with perivenous demyelination were observed in both ADEM and cortical encephalitis. Our study suggests that ADEM-like perivenous inflammatory demyelination with MOG-dominant myelin loss is a characteristic finding of MOG antibody-associated disease regardless of whether the diagnostic criteria of ADEM are met. These pathological features are clearly different from those of multiple sclerosis and AQP4 antibody-positive NMOSD, suggesting an independent autoimmune demyelinating disease entity.

This study demonstrates that mutant FUS, which is missing the nuclear traffic activity of the C-terminus, is dislocated to cytoplasm and assembled into SGs, indicating that disruption of translational regulation and metabolism of mRNA via inappropriate/excessive SGs may be crucial for FUS proteinopathies. Our findings provide new biological and pathological insights into the FUS protein that should help our understanding of the pathogenesis of ALS/FTLD.

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We report an 18-year-old woman with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, who developed psychiatric symptoms, progressive unresponsiveness, dyskinesias, hypoventilation, hypersalivation and seizures. Early removal of an ovarian teratoma followed by plasma exchange and corticosteroids resulted in a prompt neurological response and eventual full recovery. Serial analysis of antibodies to NR1/NR2B heteromers of the NMDAR showed an early decrease of serum titres, although the cerebrospinal fluid titres correlated better with clinical outcome. The patients' antibodies reacted with areas of the tumour that contained NMDAR-expressing tissue. Search for and removal of a teratoma should be promptly considered after the diagnosis of anti-NMDAR encephalitis.Paraneoplastic encephalitis associated with ovarian teratoma has recently been related to the development of antibodies to the NR1/NR2B heteromers of the N-methyl-D-asparate receptor (NMDAR). 1 The disorder, called anti-NMDAR encephalitis, results in a characteristic syndrome that presents with prominent psychiatric symptoms or, less frequently, memory deficits, followed by a rapid decline of the level of consciousness, central hypoventilation, seizures, involuntary movements and dysautonomia. Despite the severity of symptoms and prolonged clinical course, most patients recover if the disorder is recognised and treated. 1 Immunotherapy, including corticosteroids, intravenous immunoglobulin or plasma exchange, is often effective, and it has been suggested that prompt resection of the teratoma expedites recovery. 1 In most previously reported cases of anti-NMDAR encephalitis, the ovarian teratoma was removed a few months (median: 9 weeks) after neurological symptom presentation, sometimes when symptoms had already partially responded to immunotherapy. 1-5 We report the clinical outcome and follow-up of antibody titres in a Japanese woman whose ovarian tumour was removed early (20 days) after neurological symptom onset. CASE REPORTAn 18-year-old woman without a past medical history of interest developed headache and fever for a few days. She also complained of the sensation that the left half of her body was twisting. She was admitted to our hospital with progressive psychosis, and emotional and behavioural changes. Her temperature was 37.1°C; no meningeal signs were noted. Sustained involuntary movements were observed around her mouth, resembling orofacial dyskinesias. She was disorientated to place and person, and had schizophrenia-like symptoms, such as disorganized 1). She constantly repeated "I'm in the world of Harry Potter!" and "I have no idea who I am!" and knocked her head against the wall. Intravenous administration of acyclovir (1500 mg/day) and dexamethasone (6 mg/day) resulted in no improvement and she became mute and unresponsive to verbal commands. The orofacial dyskinesias gradually worsened, showing sustained bizarre movements such as widely opening and tightly closing of the eyes and mouth, sticking out the tongue and grimacin...

Tau aggregates represent a key pathologic feature of Alzheimer’s disease and other neurodegenerative diseases. Recently, PET probes have been developed for in vivo detection of tau accumulation; however, they are limited because of off-target binding and a reduced ability to detect tau in non-Alzheimer’s disease tauopathies. The novel tau PET tracer, [18F]PI-2620, has a high binding affinity and specificity for aggregated tau; therefore, it was hypothesized to have desirable properties for the visualization of tau accumulation in Alzheimer’s disease and non-Alzheimer’s disease tauopathies. To assess the ability of [18F]PI-2620 to detect regional tau burden in non-Alzheimer’s disease tauopathies compared with Alzheimer’s disease, patients with progressive supranuclear palsy (n = 3), corticobasal syndrome (n = 2), corticobasal degeneration (n = 1), or Alzheimer’s disease (n = 8), and healthy controls (n = 7) were recruited. All participants underwent MRI, amyloid β assessment, and [18F]PI-2620 PET (Image acquisition at 60–90 minutes post-injection). Cortical and subcortical tau accumulations were assessed by calculating standardized uptake value ratios using [18F]PI-2620 PET. For pathologic validation, tau pathology was assessed using tau immunohistochemistry and compared with [18F]PI-2620 retention in an autopsied case of corticobasal degeneration. In Alzheimer’s disease, focal retention of [18F]PI-2620 was evident in the temporal and parietal lobes, precuneus, and cingulate cortex. Standardized uptake value ratio analyses revealed that patients with non-Alzheimer’s disease tauopathies had elevated [18F]PI-2620 uptake only in the globus pallidus, as compared to patients with Alzheimer’s disease, but not healthy controls. A head-to-head comparison of [18F]PI-2620 and [18F]PM-PBB3, another tau PET probe for possibly visualizing the 4-repeat tau pathogenesis in non-Alzheimer’s disease, revealed different retention patterns in one subject with progressive supranuclear palsy. Imaging-pathology correlation analysis of the autopsied patient with corticobasal degeneration revealed no significant correlation between [18F]PI-2620 retention in vivo. High [18F]PI-2620 uptake at 60–90 minutes post-injection in the globus pallidus may be a sign of neurodegeneration in four-repeat tauopathy, but not necessarily practical for diagnosis of non- Alzheimer’s disease tauopathies. Collectively, this tracer is a promising tool to detect Alzheimer’s disease-tau aggregation. However, late acquisition PET images of [18F]PI-2620 may have limited utility for reliable detection of four-repeat tauopathy because of lack of correlation between postmortem tau pathology and different retention pattern than the non-Alzheimer’s disease-detectable tau radiotracer, [18F]PM-PBB3. A recent study reported that [18F]PI-2620 tracer kinetics curves in four-repeat tauopathies peak earlier (within 30 minutes) than Alzheimer’s disease; therefore, further studies are needed to determine appropriate PET acquisition times that depend on the respective interest regions and diseases.

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Background Electroconvulsive therapy (ECT) is a well‐established treatment for psychiatric disorders, including depression and psychosis. ECT has been reported to be effective in treating such psychiatric symptoms in patients with Parkinson's disease (PD) and has been also reported to be effective in treating motor symptoms. The aim of the study is to summarize previous clinical studies investigating the efficacy of ECT for symptoms in patients with PD. Methods A systematic review and meta‐analysis of any study designs assessing motor and/or non‐motor symptoms in patients with PD before and after ECT. Co‐primary outcomes were set as motor manifestations assessed using the Unified Parkinson's Disease Rating Scale or other rating scales, and non‐motor symptoms included depression and psychosis. Secondary outcomes were wearing‐off phenomenon and cognitive function. The impact of ECT on those symptoms was examined by comparing the severity of the symptoms before and after ECT using a random effect model and was expressed in standardized mean difference. Results Of 1219 identified citations, 14 studies (n = 129; 1 randomized controlled study, 9 prospective observational studies, and 4 retrospective studies) were analyzed. The findings were as follows: ECT significantly improved motor manifestations in patients with PD, and the improvement was significant in the subpopulation without psychiatric symptoms; ECT significantly improved depression and psychosis; and ECT significantly relieved wearing‐off phenomenon and did not worsen cognitive functioning. Conclusion The current meta‐analysis suggests the potential benefit of ECT on motor and non‐motor symptoms in presumably complicated and difficult‐to‐treat subgroups. © 2020 International Parkinson and Movement Disorder Society

Camptocormia is uncommon in PD and is associated with disease severity, higher L-dopa dose and higher frequencies of autonomic symptoms.