Comparing 2-dimensional versus 3-dimensional MR myelography for cerebrospinal fluid leak detection.

Purpose: We compared cerebrospinal fluid (CSF) leak conspicuity and image quality as visualized using 3D versus 2D magnetic resonance (MR) myelography in patients with spinal CSF leaks. Methods: Eighteen patients underwent spinal MR imaging at 3 Tesla. Three board-certified radiologists independently evaluated CSF leak conspicuity and image quality on a 4-point scale; the latter assessed by scoring fat suppression, venous visualization, and severity of CSF flow artifacts. Additionally, the evaluators ranked the overall performances of 2D versus 3D MR myelography upon completing side-by-side comparisons of CSF leak conspicuity. Inter-reader agreement was determined using the Gwet's AC1. Results: The quality of 3D MR myelography images was significantly better than that of 2D MR myelography with respect to CSF leak conspicuity (mean scores: 3.3 vs. 1.9, p < 0.0001) and severity of CSF flow artifacts on the axial view (mean scores: 1.0 vs. 2.5, p = 0.0001). Inter-reader agreement was moderate to almost perfect for 2D MR myelography (AC1 = 0.55-1.00), and almost perfect for 3D MR myelography (AC1 = 0.85-1.00). Moreover, 3D MR myelography was judged to be superior to 2D acquisition in 78 %, 83 %, and 83 % of the samples per readers 1, 2 and 3, respectively; the inter-reader agreement was almost perfect (AC1: reader 1 vs. 2; 0.98, reader 2 vs. 3; 0.96, reader 3 vs. 1; 0.98). Conclusion: CSF leaks are more conspicuous when using 3D MR myelography than when using its 2D counterpart; therefore, the former is more reliable for identifying such leaks.

Early Effect of Calcitonin Gene-related Peptide Monoclonal Antibodies in Migraine with Medication Overuse: A Single-center Retrospective Study.

Objective Calcitonin gene-related peptide (CGRP)-(receptor) monoclonal antibody (mAb) has been reported to reduce the frequency of medication overuse in patients with migraine. The present study investigated whether or not CGRP-mAb treatment shows early effectiveness for medication overuse headache (MOH) in Japan. Methods We retrospectively reviewed 34 patients with MOH who received preventive treatment with CGRP-mAb from June 2021 to October 2022. The International Classification of Headache Disorders, 3rd edition was used to diagnose MOH. This study was conducted at the Department of Neurology, Saitama Medical University. Patients were recruited from this specialized headache outpatient center. Results In total, 69 patients with migraine had newly introduced CGRP-mAb, and 34 patients had MOH (49.3%). The mean±standard deviation patient age was 44±15.5 years old. The study population included 24 women (70.6%). The types of CGRP-mAb used were galcanezumab in 16 patients (47.0%), fremanezumab in 10 (29.4%), and erenumab in 8 (23.5%). The mean disease duration was 19.6±13.1 years. The types of migraine diagnosis were chronic migraine in 28 patients (82.4%) and migraine with aura in 11 patients (32.4%). The mean number of headache days in the month before administration of CGRP-mAb was 22±7.7 days; 1 month after administration, the MHD was 16.9±9.1 days. The change in MHD was -5.7 days (22.7%), indicating significant improvement (p<0.05). Conclusion CGRP-mAb has been suggested as a preventive treatment for patients with MOH. Further investigation of the long-term efficacy of CGRP-mAb for MOH is needed.

Brain-Derived Major Glycoproteins Are Possible Biomarkers for Altered Metabolism of Cerebrospinal Fluid in Neurological Diseases.

Cerebrospinal fluid (CSF) plays an important role in the homeostasis of the brain. We previously reported that CSF major glycoproteins are biosynthesized in the brain, i.e., lipocalin-type prostaglandin D2 synthase (L-PGDS) and transferrin isoforms carrying unique glycans. Although these glycoproteins are secreted from distinct cell types, their CSF levels have been found to be highly correlated with each other in cases of neurodegenerative disorders. The aim of this study was to examine these marker levels and their correlations in other neurological diseases, such as depression and schizophrenia, and disorders featuring abnormal CSF metabolism, including spontaneous intracranial hypotension (SIH) and idiopathic normal pressure hydrocephalus (iNPH). Brain-derived marker levels were found to be highly correlated with each other in the CSF of depression and schizophrenia patients. SIH is caused by CSF leakage, which is suspected to induce hypovolemia and a compensatory increase in CSF production. In SIH, the brain-derived markers were 2-3-fold higher than in other diseases, and, regardless of their diverse levels, they were found to be correlated with each other. Another abnormality of the CSF metabolism, iNPH, is possibly caused by the reduced absorption of CSF, which secondarily induces CSF accumulation in the ventricle; the excess CSF compresses the brain's parenchyma to induce dementia. One potential treatment is a "shunt operation" to bypass excess CSF from the ventricles to the peritoneal cavity, leading to the attenuation of dementia. After the shunt operation, marker levels began to increase within a week and then further increased by 2-2.5-fold at three, six, and twelve months post-operation, at which point symptoms had gradually attenuated. Notably, the marker levels were found to be correlated with each other in the post-operative period. In conclusion, the brain-derived major glycoprotein markers were highly correlated in the CSF of patients with different neurological diseases, and their correlations were maintained even after surgical intervention. These results suggest that brain-derived proteins could be biomarkers of CSF production.

Impact of the COVID-19 pandemic on migraine in Japan: a multicentre cross-sectional study.

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.

Intravenous enhanced 3D FLAIR imaging to identify CSF leaks in spontaneous intracranial hypotension: Comparison with MR myelography.

PURPOSE: To evaluate the clinical utility of intravenous gadolinium-enhanced heavily T2-weighted 3D fluid-attenuated 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.

Orthostatic Headache in Children Including Postural Tachycardia Syndrome and Orthostatic Hypotension: A Near-Infrared Spectroscopy Study.

BACKGROUND AND AIM: Although head and/or neck pain attributed to orthostatic hypotension is included in international guidelines, its mechanisms and relevance remain unknown. This study examined the term's relevance and aimed to elucidate the associated clinical features. METHODS: An active stand test was performed to evaluate fluctuations in systemic and cerebral circulation in children and adolescents reporting complaints in the absence of a confirmed organic disorder. The subjects were categorized based on orthostatic headache presence/absence, and their characteristics and test results were compared. RESULTS: Postural tachycardia syndrome was observed in 50.0% of children with, and 55.1% without, orthostatic headache. For orthostatic hypotension, the respective values were 31.3% and 30.6%. A history of migraine was more prevalent in children with orthostatic headaches (64.1% vs. 28.6%; p < 0.01). The observed decrease in the cerebral oxygenated hemoglobin level was larger in children with orthostatic headaches (Left: 6.3 (3.2-9.4) vs. 4.1 (0.8-6.1); p < 0.01, Right: 5.3 (3.1-8.6) vs. 4.0 (0.8-5.9); p < 0.01). CONCLUSION: Fluctuations in cerebral blood flow were associated with orthostatic headaches in children, suggesting that the headaches are due to impaired intracranial homeostasis. As orthostatic headache can have multiple causes, the term "head and/or neck pain attributed to orthostatic (postural) hypotension" should be replaced with a more inclusive term.

Small-Bowel Lesions in Patients Taking Direct Oral Anticoagulants Detected Using Capsule Endoscopy.

METHODS: This study was a prospective, open-label, nonblinded, multicenter, and observational study. From September 2013 to March 2017, patients taking DOACs were enrolled. Patients underwent VCE. The type and location of small-bowel lesions were registered. Also, (1) the proportion of lesions detected between types of DOAC was evaluated and (2) the hemoglobin (Hb) and serum ferritin levels were compared between patients with and without small-bowel lesions. RESULTS: 33 patients were enrolled, but 4 patients withdrew their consent, and VCE was performed on 29 patients. Eight, 13, and 8 patients received dabigatran, rivaroxaban, and apixaban, respectively. Small-bowel transit was complete in 27 of 29 patients (93.1%). Small-bowel lesions were detected in 23 (79.3%), redness in 12 (41.4%), erosions in 14 (48.3%), and angioectasia in 3 (10.3%) patients, and 6 patients (20.7%) had no abnormalities. Redness and erosions were detected in the upper, middle, or lower portions, but erosions tended to be less frequent in the middle portion (p = 0.25, 0.06). Angioectasia was not detected in the lower portion. No patients had active bleeding. The findings did not differ according to the drug. The relationships between the endoscopic findings and the Hb and serum ferritin levels were not significant. CONCLUSION: Many patients taking DOACs had small-bowel lesions; however, most lesions were relatively mild. Observing small-bowel lesions over longer periods may be necessary in patients taking DOACs. This trial is registered with UMIN000011527.

An autopsy report of three kindred in a Gerstmann-Sträussler-Scheinker disease P105L family with a special reference to prion protein, tau, and beta-amyloid.

INTRODUCTION: Gerstmann-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 (Aß). METHODS: Using paraffin-embedded sections, we applied histology and single- and multiple-labeling immunohistochemistry for PrP, p-tau, and Aß to the three cases. Comparative semi-quantitative analyses of tissue injuries and PrP-plaques were also employed. RESULTS: Case 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, Aß was deposited in the cerebral cortices. Interestingly, not only p-tau but also Aß was colocalized with PrP-plaques. In all cases, both three repeat tau and four repeat tau were associated with PrP-plaques. CONCLUSIONS: The clinicopathological diversity of GSS105, which is possible even in the same family, was ascertained. Not only p-tau but also Aß could be induced by PrP ("secondary degeneration"), facilitating the kaleidoscopic symptoms of GSS.

Fatal Familial Insomnia Initially Developing Parkinsonism Mimicking Dementia with Lewy Bodies.

We report a rare case of fatal familial insomnia in a 58-year-old man who initially developed parkinsonism, secondary dementia, and visual hallucinations that were suspected to be due to dementia with Lewy bodies. We evaluated the function of the striatum via dopamine transporter single-photon emission computed tomography (DAT SPECT) using 123I-ioflupane and found marked presynaptic dopamine dysfunction in the bilateral striatum. This is the first reported case in which the initial symptom of fatal familial insomnia was parkinsonism and in which the dopamine transporter function was evaluated by DAT SPECT.

The Clinical Features of Ischemic Stroke Patients for Whom Smoking Was Considered the Sole Risk Factor for Ischemic Stroke.

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.

Naratriptan in the Prophylactic Treatment of Cluster Headache.

Objective Naratriptan has been reported to reduce the frequency of cluster headache. The purpose of this study was to determine whether naratriptan is effective as a prophylactic treatment for cluster headache in Japan. Methods We retrospectively reviewed all 43 patients with cluster headache who received preventive treatment with naratriptan from April 2009 to April 2015. The International Classification of Headache Disorders, 3rd Edition (beta version) (ICHD-3 beta) was used to diagnose cluster headache. This study was conducted at 3 centers (Department of Neurology, Saitama Medical University; Saitama Neuropsychiatric Institute; Saitama Medical University International Medical Center). Patients were recruited from these specialized headache outpatient centers. Naratriptan was taken before the patient went to bed. Results The study population included 30 men (69.8%) and 13 women (30.2%). Twenty-two cases received other preventive treatments (51.2%), while 21 cases only received naratriptan (48.8%). Among the 43 cases, 37 patients (86.0%) achieved an improvement of cluster headache on naratriptan. Conclusion Naratriptan has been suggested as a preventive medicine for cluster headache because of the longer the biological half-life in comparison to other triptans. The internal use of naratriptan 2 hours before attacks appears to achieve a good response in patients with cluster headache.

[Non-taking oral antithrombotic agents in patients with ischemic stroke].

BACKGROUND: In clinical practice, secondary prevention in patients with ischemic stroke (IS) needs to be continued permanently; however, antithrombotic agents are sometimes stopped by clinicians or the patients themselves. The rate of non-taking oral antithrombotic agents was evaluated in IS patients. METHODS: 266 consecutive patients (154 men and 112 women; age, 73.6 +/- 11.5 years) with first-ever acute IS were studied. Patients with transient ischemic attack (TIA) were also included. Emboligenic heart diseases, frequency of past stroke, oral antithrombotic agent use just before IS, and secondary prevention were evaluated. RESULTS: The number of past strokes was 0 in 182 cases (68.4%), 1 in 66 cases (24.8%), 2 in 14 cases (5.3%), 3 in 3 cases (1.1%), and 9 in 1 case (0.4%; 3 times with stroke, and 6 times with TIA). There were 42 cases (15.8%) with TIA, 47 (17.7%) with lacunar infarction, 69 (25.9%) with atherothrombotic infarction, 62 (23.3%) with cardioembolic infarction, 23 (8.7%) with other types of infarction, and 23 (8.7%) with stroke of unknown etiology. Although 15-26% of patients with their first IS had taken antithrombotic agents just before IS, about 40% of the patients with a previous IS history were not taking antithrombotic agents just before their recurrent IS. CONCLUSION: About 40% of the patients with recurrent IS were not taking antithrombotic agents at the time of their recurrent IS; had they been taking antithrombotic agents at the time, the recurrent IS might have been prevented. Clinicians must recognize the importance of antithrombotic agents in patients with IS, and patients must continue to take antithrombotic agents permanently.