Objectives To assess the impacts of social situation changes due to the coronavirus disease 2019 (COVID-19) pandemic on headache-related disability and other symptoms in patients with migraine in Japan. Methods We conducted a multicentre, cross-sectional study including 659 outpatients with migraine diagnosed by headache specialists. The participants were asked about the impacts of the first wave of the COVID-19 pandemic on headache-related disability, headache days, headache intensity, stress, physical activity, hospital access and their work and home lives. For headache-related disability, the total Migraine Disability Assessment (MIDAS) score and part A and B scores were analysed. Multivariate stepwise linear regression analysis was performed to identify the clinical predictors of changes in the total MIDAS score before and during the COVID-19 pandemic. Logistic regression analysis was performed to determine the factors related to new-onset headache during the COVID-19 pandemic. Results Finally, 606 migraine patients (73 M/533 F; age, 45.2 ± 12.0 years) were included in the study, excluding those with incomplete data. Increased stress, substantial concern about COVID-19 and negative impacts of the first wave of the COVID-19 pandemic on daily life were reported in 56.8 %, 55.1 and 45.0 % of the participants, respectively. The total MIDAS and A and B scores did not significantly change after the first wave of the COVID-19 pandemic. New-onset headache, which was observed in 95 patients (15.7 %), was associated with younger age and worsened mood and sleep in the logistic regression analysis. The multivariate stepwise linear regression analysis of changes in the total MIDAS score before and during the first wave of COVID-19 pandemic identified worsened sleep, increased acute medication use, increased stress, medication shortages, comorbidities, the absence of an aura and new-onset headache were determinants of an increased total MIDAS score during the first wave of the COVID-19 pandemic. Conclusions In this multicentre study, clinical factors relevant to headache-related disability, such as new-onset headache, stress and sleep disturbances, were identified, highlighting the importance of symptom management in migraine patients during the first wave of the COVID-19 pandemic.

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IntroductionGerstmann–Sträussler–Scheinker disease P105L (GSS105) is a rare variant of GSS caused by a point mutation of the prion protein (PrP) gene at codon 105 (proline to leucine substitution). It is clinically characterized by spastic paraparesis and dementia and histopathologically defined by PrP‐plaques in the brain. This report describes a clinicopathological analysis of three autopsied kindred from a Japanese GSS105 family, plus a topological analysis of PrP, hyperphosphorylated tau (p‐tau), and beta‐amyloid (Aβ).MethodsUsing paraffin‐embedded sections, we applied histology and single‐ and multiple‐labeling immunohistochemistry for PrP, p‐tau, and Aβ to the three cases. Comparative semi‐quantitative analyses of tissue injuries and PrP‐plaques were also employed.ResultsCase 1 (45 years old (yo)) and Case 2 (56 yo) are sisters, and Case 3 (49 yo) is the son of Case 2. Case 1 and Case 2 presented with spastic paraparesis followed by dementia, whereas Case 3 presented, not with spastic paraparesis, but with psychiatric symptoms. In Case 1 and Case 2, the brain showed tissue injuries with many PrP‐plaques in the cerebral cortices, and the pyramidal tract showed myelin loss/pallor. In Case 3, the brain was least degenerated with a number of PrP‐plaques; however, the pyramidal tract remained intact. In addition, p‐tau was deposited in all cases, where p‐tau was present in or around PrP‐plaques. By double‐labeling immunohistochemistry, the colocalization of p‐tau with PrP‐plaques was confirmed. Moreover in Case 2, Aβ was deposited in the cerebral cortices. Interestingly, not only p‐tau but also Aβ was colocalized with PrP‐plaques. In all cases, both three repeat tau and four repeat tau were associated with PrP‐plaques.ConclusionsThe clinicopathological diversity of GSS105, which is possible even in the same family, was ascertained. Not only p‐tau but also Aβ could be induced by PrP (“secondary degeneration”), facilitating the kaleidoscopic symptoms of GSS.

To evaluate the clinical utility of intravenous gadolinium-enhanced heavily T2-weighted 3D fluidattenuated inversion recovery (HT2-FLAIR) imaging for identifying spinal cerebrospinal fluid (CSF) leaks in patients with spontaneous intracranial hypotension (SIH). Methods: Patients with SIH underwent MR myelography and post-contrast HT2-FLAIR imaging after an intravenous gadolinium injection. Two types of CSF leaks (epidural fluid collection and CSF leaks around the nerve root sleeve) at each vertebral level were compared between the 2 sequences. The total numbers of CSF leaks and vertebral levels involved were recorded for the whole spine. The sequence that was superior for the overall visualization of epidural and paraspinal fluid collection was then selected. Results: Nine patients with SIH were included in the present study. HT2-FLAIR imaging was equivalent or superior to MR myelography at each level for detecting the 2 types of CSF leaks. In the 2 types of CSF leaks, the total numbers of CSF leaks and levels involved were higher on HT2-FLAIR images than on MR myelography, while no significant difference was observed for CSF leaks around the nerve root sleeve. In all 9 patients, HT2-FLAIR imaging was superior to MR myelography for the overall visualization of epidural and paraspinal fluid collection. Conclusion:Intravenous gadolinium-enhanced HT2-FLAIR imaging was superior to MR myelography for the visualization of CSF leaks in patients with SIH. This method can be useful for identifying spinal CSF leaks.

Objective The purpose of this study was to clarify the clinical features of ischemic patients for whom cigarette smoking was the sole risk factor for ischemic stroke. Methods Among the 1,329 patients (male, n=833; female, n=496) with acute ischemic stroke who were admitted to our hospital between April 2005 and September 2016, 346 (26%) were smokers [male, n=308 (36.9%); female, 38 (7.6%)]. In 42 (3.1%; male, n=41; female, n=1) cases, cigarette smoking was considered to be the sole risk factor for ischemic stroke. Data regarding gender, age, the clinical type of ischemic stroke, the National Institutes of Health Stroke Scale (NIHSS) score at the admission, the modified Rankin scale (mRS) scores before the onset and at discharge, the progression of symptoms, and the recurrence of infarction were investigated. Results The mean age of the 42 patients was 63.2±12.4 years (range, 26-86 years). The clinical types of ischemic stroke included atherothrombosis (n=19), lacunar (n=17), other type (n=2) and undetermined type (n=4). The median NIHSS score at the time of admission for ischemic stroke was 2 (interquartile range: IQR 1-4.25). The median mRS scores before the onset and at the discharge were 0 (IQR 0-0) and 1 (IQR 0-2), respectively. One patient had symptoms of progression; no patients had recurrence of infarction. Conclusion Our findings suggest that cigarette smoking alone may induce ischemic stroke; moreover, patients for whom smoking was the sole risk factor for ischemic stroke showed milder symptoms in comparison to patients with other risk factors; however, ischemic stroke was induced from youth. Since cigarette smoking has detrimental effects on the central nervous system, we suggest that people be encouraged to quit smoking in order to maintain good health.