Details of a Researcher - Takizawa, Tsubasa

Papers - Takizawa, Tsubasa

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Optogenetic Functional Activation Is Detrimental During Acute Ischemic Stroke in Mice.

Kazutaka Sugimoto, David Y Chung, Paul Fischer, Tsubasa Takizawa, Tao Qin, Mohammad A Yaseen, Sava Sakadžić, Cenk Ayata

Stroke 55 ( 10 ) 2502 - 2509 2024

ISSN 00392499

BACKGROUND: Functional activation of the focal ischemic brain has been reported to improve outcomes by augmenting collateral blood flow. However, functional activation also increases metabolic demand and might thereby worsen outcomes. Indeed, preclinical and clinical reports have been conflicting. Here, we tested the effect of functional activation during acute ischemic stroke using distal middle cerebral artery occlusion in anesthetized mice. METHODS: Using transgenic mice expressing channelrhodopsin-2 in neurons, we delivered functional activation using physiological levels of transcranial optogenetic stimulation of the moderately ischemic cortex (ie, penumbra), identified using real-time full-field laser speckle perfusion imaging during a 1-hour distal microvascular clip of the middle cerebral artery. Neuronal activation was confirmed using evoked field potentials, and infarct volumes were measured in tissue slices 48 hours later. RESULTS: Optogenetic stimulation of the penumbra was associated with more than 2-fold larger infarcts than stimulation of the contralateral homotopic region and the sham stimulation group (n=10, 7, and 9; 11.0±5.6 versus 5.1±4.3 versus 4.1±3.7 mm3; P=0.008, 1-way ANOVA). Identical stimulation in wild-type mice that do not express channelrhodopsin-2 did not have an effect. Optogenetic stimulation was associated with a small increase in penumbral perfusion that did not explain enlarged infarcts. CONCLUSIONS: Our data suggest that increased neuronal activity during acute focal arterial occlusions can be detrimental, presumably due to increased metabolic demand, and may have implications for the clinical management of hyperacute stroke patients.

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片頭痛の誘発因子についての最新の知見

滝沢翼, 渡邊成美, 伊庭知里, 石川直樹, 梅田聡, 中原仁

Japanese Journal of Headache (The Japanese Headache Society) 51 ( 1 ) 110 - 111 2024

ISSN 13456547

Interictal burden of migraine and its evaluations: a literature review

M.D. Ph.D. Takizawa Tsubasa, Ph.D. Takemura Ryo, M.D. Ph.D. Igarashi Hisaka, M.D. Ph.D. Matsumori Yasuhiko, M.D. Ph.D. Sato Minako, Ph.D. Ueda Kaname

Rinsho Shinkeigaku (Societas Neurologica Japonica) advpub ( 0 ) 8 - 15 2024

ISSN 0009918X

We conducted a targeted literature review on patient burden during the interictal period of migraine. The results of the literature review revealed that: (1) migraine-associated burden persists into the interictal period and is not confined to the headache episodes themselves; (2) anxiety over the possible recurrence of headache episodes is a factor that reduces daily activities and quality of life (QOL); and (3) prophylactic treatment with calcitonin gene-related peptide (CGRP) antibody drugs may reduce the burden during the interictal period. From these findings, it is considered important in migraine treatment to identify the unmet needs of patients, including the burden during the interictal period, and to select an appropriate treatment method based on the burden experienced by individual patients.

The Impact of Migraine on the Whole Life Course of Patients: Results from the OVERCOME (Japan) 2nd Study.

Daisuke Danno, Shiho Suzuki, Tsubasa Takizawa, Ryotaro Ishii, Masayuki Hamakawa, Yoshinori Tanizawa, Satoshi Osaga, Mika Komori

Neurology and therapy 14 ( 1 ) 335 - 356 2024

ISSN 21938253

INTRODUCTION: The impact of migraine on patients' lives, including challenges they face before getting access to appropriate medical management, is not well understood. The ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE [OVERCOME (Japan)] 2nd study was conducted to provide information regarding burden and experience with migraine throughout the life course. METHODS: This cross-sectional, population-based, nationwide online survey was conducted in adults with or without migraine. The migraine group reported their headache features and experiences in medical management since headache onset. Migraine's burden and impact were assessed with various PRO instruments. Migraine and non-migraine groups reported their experiences in life events and answered questions on self-esteem. Subgroup analyses by the number of monthly headache days (MHD) were performed. RESULTS: The migraine group (n = 19,590) was numerically younger [mean (SD) age 40.5 (13.1) years vs. 53.1 (17.8) years] and included more females (68.8% vs. 52.1%) than the non-migraine group (n = 2219). The migraine group had mean (SD) 3.5 (5.2) MHDs; 24.2-56.7% had moderate-to-very severe disease burden per various PRO instruments. Headaches started when respondents with migraine were 17.8 years old; 86.7% started over-the-counter medications at 19.4 years of age. Only 46.4% self-reported migraine diagnosis by a physician and 25.1% received an oral preventive drug, almost a decade after headache onset. Up to 16.8% reported poor support/lack of understanding from either teachers or parents during school life. The migraine group had numerically more frequent job changes and divorce, and lower self-esteem, than the non-migraine group. Across assessments, increased MHDs tended to worsen outcomes. CONCLUSION: Migraine affected many individuals from an early stage, but timely support and medical intervention were insufficient. This may negatively impact important life events, cause long-term impairment, and decrease self-esteem. Hence, improving the social understanding and medical environment for migraine to provide timely support is essential.

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Predicting response to CGRP-monoclonal antibodies in patients with migraine in Japan: a single-centre retrospective observational study.

Keiko Ihara, Seiya Ohtani, Narumi Watanabe, Nobuyuki Takahashi, Naoki Miyazaki, Kei Ishizuchi, Satoko Hori, Ryo Takemura, Jin Nakahara, Tsubasa Takizawa

The journal of headache and pain (Journal of Headache and Pain) 24 ( 1 ) 23 - 23 2023.12

ISSN 11292369

BACKGROUND: Anti-calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) are a favourable option for patients with migraine who experience distressful headache disability and fail to respond to traditional preventive treatment options. However, since CGRPmAb has been available for only 2 years in Japan, the difference between good and poor responders remains unknown. We aimed to investigate the clinical characteristics of patients with migraine in Japan who responded well to CGRPmAb based on real-world data. METHODS: We analysed patients who visited Keio University Hospital, Tokyo, Japan, between the 12th of August 2021 and 31st of August 2022, and were prescribed one of three CGRPmAbs (erenumab, galcanezumab, and fremanezumab) for more than 3 months. We recorded the patients' basic migraine characteristics, such as pain quality, monthly migraine days (MMD)/monthly headache days (MHD), and the number of prior treatment failures. We defined good responders as patients whose MMDs decreased by more than 50% after 3 months of treatment and other patients as poor responders. We compared the baseline migraine characteristics between the two groups and performed logistic regression analysis based on the items that showed statistically significant differences. RESULTS: In total, 101 patients were considered eligible for the responder analysis (galcanezumab: 57 (56%), fremanezumab: 31 (31%), and erenumab: 13 (13%)). After 3 months of treatment, 55 (54%) patients achieved ≥ 50% reduction in MMDs. Comparisons between ≥ 50% responders and non-responders revealed that age was significantly higher (p = 0.003), and MHD and total prior treatment failures were significantly lower (p = 0.027, 0.040, respectively), in responders than in non-responders. Age was a positive predictive factor, and the total number of prior treatment failures and past medical history of immuno-rheumatologic diseases were negative predictive factors of CGRPmAb responsiveness in Japanese patients with migraine. CONCLUSIONS: Patients with migraine who are older, with fewer prior treatment failures and no past history of immuno-rheumatologic disease, may respond well to CGRPmAbs.

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Real-world evidence of fremanezumab for treating migraine in Japan: a retrospective study.

Seiya Ohtani, Narumi Watanabe, Keiko Ihara, Nobuyuki Takahashi, Naoki Miyazaki, Kei Ishizuchi, Ryo Takemura, Satoko Hori, Jin Nakahara, Tsubasa Takizawa

BMC neurology (BMC Neurology) 23 ( 1 ) 404 - 404 2023.12

BACKGROUND: There have been very few real-world studies reported in the literature solely focusing on fremanezumab in Asia. This study aimed to evaluate the efficacy and safety of fremanezumab in a real-world setting in Japan. METHOD: This single-centered, observational, retrospective study examined patients with migraines who received four doses of fremanezumab between December 2021 and August 2022 at Keio University Hospital. We assessed the changes in monthly migraine days, responder rates, and migraine-associated symptoms, as well as injection site reactions and adverse events. RESULT: Twenty-nine patients were enrolled, wherein 79.3% were women. Compared with those at baseline, the monthly migraine days decreased by 5.9 days at 4 months. The 50% responder rate was 55.2% at 4 months. A total of 57.9%, 47.8%, and 65.0% of patients showed improvement in the severity of photophobia, phonophobia, and nausea/vomiting, respectively. Moreover, injection site reactions were the most common adverse events (55.2%). CONCLUSION: Fremanezumab is effective and safe for migraine prevention in Japan. Fremanezumab also improved migraine-associated symptoms in half of the patients.

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Systemic lupus erythematosus mimicking retinal migraine: a case report.

Toshiki Tezuka, Mamoru Shibata, Hironari Hanaoka, Yoshikane Izawa, Taku Kikuchi, Kunihiko Akino, Yoko Ozawa, Masataka Saito, Yuko Kaneko, Jin Nakahara, Tsubasa Takizawa

Cephalalgia : an international journal of headache (Cephalalgia) 43 ( 12 ) 3331024231219477 - 3331024231219477 2023.12

ISSN 03331024

BACKGROUND: Retinal migraine is a diagnosis of exclusion and is characterized by repeated episodes of transient monocular blindness associated with migraine. We report a case of systemic lupus erythematosus with acute episodes mimicking retinal migraines. CASE REPORT: A 46-year-old woman with a history of migraine with aura since her 20s and Evans syndrome presented with episodic transient monocular blindness. Retinal migraine was considered as the cause, and migraine prophylaxis initially reduced its frequency. After 5 months, the frequency increased, with chilblain-like lupus lesions on her extremities. Laboratory testing revealed lymphopenia and hypocomplementemia, fulfilling the diagnostic criteria for systemic lupus erythematosus, which may have caused Evans syndrome and transient monocular blindness, mimicking retinal migraines. After intravenous methylprednisolone and rituximab therapy, the transient monocular blindness episodes did not recur. CONCLUSION: Given the clinical presentation, systemic lupus erythematosus should be considered as a cause of transient monocular blindness and should be distinguished from retinal migraine.

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Switching between anti-calcitonin gene-related peptide monoclonal antibodies: A comparison of monthly and quarterly dosing.

Keiko Ihara, Seiya Ohtani, Narumi Watanabe, Nobuyuki Takahashi, Naoki Miyazaki, Ryo Takemura, Satoko Hori, Jin Nakahara, Tsubasa Takizawa

Journal of the neurological sciences (Journal of the Neurological Sciences) 453 120811 - 120811 2023.10

ISSN 0022510X

BACKGROUND: Anti-calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) have dramatically changed preventive treatment options for patients with migraine. Although there is emerging real-world evidence on the use of CGRPmAbs globally, the change in efficacy and safety after switching between CGRPmAbs owing to patients' frequency of hospital visits preference remains unknown. METHODS: We conducted a single-centre, retrospective, real-world study of patients with migraine who first received galcanezumab for 3 or 4 months and then switched to fremanezumab at Keio University Hospital. We investigated changes in monthly migraine days (MMD), responder rate, and adverse effects such as injection site reactions. RESULTS: MMD increased only by 0.7 (95% CI, -4.1-5.5; p = 0.748) after 4 months of treatment with fremanezumab (6.1, 95% CI, 2.3-9.9) compared to before switching (5.4, 95% CI, 2.2-8.6). Furthermore, switching from galcanezumab to fremanezumab produced only minor adverse events, such as injection site reactions. CONCLUSIONS: After switching from galcanezumab to fremanezumab out of the desire to visit the hospital less often, the reduction in MMD compared to baseline was sustained, and no serious adverse effects were observed.

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Spreading Depolarizations Suppress Hematoma Growth in Hyperacute Intracerebral Hemorrhage in Mice.

Paul Fischer, Isra Tamim, Kazutaka Sugimoto, Andreia Morais, Takahiko Imai, Tsubasa Takizawa, Tao Qin, Frieder Schlunk, Matthias Endres, Mohammad A Yaseen, David Y Chung, Sava Sakadzic, Cenk Ayata

Stroke (Stroke) 54 ( 10 ) 2640 - 2651 2023.10

Accepted, ISSN 00392499

BACKGROUND: Spreading depolarizations (SDs) occur in all types of brain injury and may be associated with detrimental effects in ischemic stroke and subarachnoid hemorrhage. While rapid hematoma growth during intracerebral hemorrhage triggers SDs, their role in intracerebral hemorrhage is unknown. METHODS: We used intrinsic optical signal and laser speckle imaging, combined with electrocorticography, to investigate the effects of SD on hematoma growth during the hyperacute phase (0-4 hours) after intracortical collagenase injection in mice. Hematoma expansion, SDs, and cerebral blood flow were simultaneously monitored under normotensive and hypertensive conditions. RESULTS: Spontaneous SDs erupted from the vicinity of the hematoma during rapid hematoma growth. We found that hematoma growth slowed down by >60% immediately after an SD. This effect was even stronger in hypertensive animals with faster hematoma growth. To establish causation, we exogenously induced SDs (every 30 minutes) at a remote site by topical potassium chloride application and found reduced hematoma growth rate and final hemorrhage volume (18.2±5.8 versus 10.7±4.1 mm3). Analysis of cerebral blood flow using laser speckle flowmetry revealed that suppression of hematoma growth by spontaneous or induced SDs coincided and correlated with the characteristic oligemia in the wake of SD, implicating the vasoconstrictive effect of SD as one potential mechanism of action. CONCLUSIONS: Our findings reveal that SDs limit hematoma growth during the early hours of intracerebral hemorrhage and decrease final hematoma volume.

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IV. Primary Headache: Migraine-diagnosis and Treatment

Takizawa Tsubasa

Nihon Naika Gakkai Zasshi (The Japanese Society of Internal Medicine) 112 ( 8 ) 1350 - 1358 2023.08

ISSN 00215384

片頭痛は，Quality of life（QOL）を著しく低下させ得る「脳の病気」であり，我が国では約1,000万人もの患者がいる．急性期治療薬としてはトリプタン製剤が従来使用されており，2022年からはラスミジタンも加わった．予防療法については，2021年に登場したカルシトニン遺伝子関連ペプチド（calcitonin gene-related peptide：CGRP）関連抗体薬が著効し「人生が変わる」ような症例も経験する．片頭痛は緊張型頭痛と誤診されているケースも多いが，片頭痛と適切に診断し，片頭痛に特化した治療を提供していくことが重要である．

Calcitonin Gene-Related Peptide mRNA Synthesis in Trigeminal Ganglion Neurons after Cortical Spreading Depolarization.

Mamoru Shibata, Satoshi Kitagawa, Miyuki Unekawa, Tsubasa Takizawa, Jin Nakahara

International journal of molecular sciences (International journal of molecular sciences) 24 ( 14 ) 2023.07

ISSN 16616596

Migraine is a debilitating neurovascular disorder characterized by recurrent headache attacks of moderate to severe intensity. Calcitonin gene-related peptide (GGRP), which is abundantly expressed in trigeminal ganglion (TG) neurons, plays a crucial role in migraine pathogenesis. Cortical spreading depolarization (CSD), the biological correlate of migraine aura, activates the trigeminovascular system. In the present study, we investigated CGRP mRNA expression in TG neurons in a CSD-based mouse migraine model. Our in situ hybridization analysis showed that CGRP mRNA expression was observed in smaller-sized neuronal populations. CSD did not significantly change the density of CGRP mRNA-synthesizing neurons in the ipsilateral TG. However, the cell sizes of CGRP mRNA-synthesizing TG neurons were significantly larger in the 48 h and 72 h post-CSD groups than in the control group. The proportions of CGRP mRNA-synthesizing TG neurons bearing cell diameters less than 14 μm became significantly less at several time points after CSD. In contrast, we found significantly greater proportions of CGRP mRNA-synthesizing TG neurons bearing cell diameters of 14-18 μm at 24 h, 48, and 72 h post-CSD. We deduce that the CSD-induced upward cell size shift in CGRP mRNA-synthesizing TG neurons might be causative of greater disease activity and/or less responsiveness to CGRP-based therapy.

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Dysautonomia associated with immune checkpoint inhibitors.

Toshiki Tezuka, Shinichi Okuzumi, Chiho Nakashima, Toshihiro Ide, Shungo Imai, Satoru Mitsuboshi, Yuki Kuwahara, Tsubasa Takizawa, Morinobu Seki, Naoto Minematsu, Naoko Aragane, Jin Nakahara, Satoko Hori, Shunya Nakane, Shigeaki Suzuki

Journal of neurology (Journal of Neurology) 270 ( 7 ) 3413 - 3423 2023.07

ISSN 03405354

OBJECTIVE: The purpose of this study is to report the clinical characteristics of dysautonomia associated with immune checkpoint inhibitors (ICIs). METHODS: We reported two patients with autoimmune autonomic ganglionopathy (AAG) occurring as immune-related adverse events (irAEs). We also performed a review of previous case reports presenting dysautonomia during ICI therapy. Moreover, we conducted pharmacovigilance analyses using the US Food and Drug Administration Adverse Events Reporting System (FAERS) to investigate dysautonomia associated with ICI. RESULTS: Two patients in our care developed both AAG and autoimmune encephalitis following ICI therapy for lung cancers. We comprehensively reviewed 13 published cases (M:F = 11:2, mean onset age of 53 years) with ICI-associated dysautonomia including AAG (n = 3) and autonomic neuropathy (n = 10). Of these, ICI monotherapy was performed in seven and combination ICI use in six. In 6 of 13 patients, dysautonomia appeared within one month after the start of ICIs. Orthostatic hypotension was observed in 7 and urinary incontinence or retention in five. All patients except three showed gastrointestinal symptoms. Anti-ganglionic acetylcholine receptor antibodies were undetectable. All but two patients received immune-modulating therapy. Immuno-modulating therapy was effective in three patients with AAG and two patients with autonomic neuropathy, but ineffective in the others. Five patients died, of either the neurological irAE (n = 3) or cancer (n = 2). The pharmacovigilance analyses using FAERS showed that ipilimumab monotherapy and the combination of nivolumab and ipilimumab constituted significant risks for developing dysautonomia, consistent with the review of literature. CONCLUSION: ICIs can cause dysautonomia including AAG, and autonomic neuropathy is a neurological irAE.

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Anti-N-methyl-D-aspartate receptor encephalitis with concurrent human herpes virus-6A deoxyribonucleic acid detection: An autopsy case.

Sho Shimohama, Takahiro Iizuka, Tsubasa Takizawa, Narumi Watanabe, Toshiki Tezuka, Kosuke Matsuda, Kazuhiro Yamanoi, Naomi Kanazawa, Yoshiki Kawamura, Tetsushi Yoshikawa, Tadaki Suzuki, Masaki Takao, Jin Nakahara, Yoshikane Izawa

Neuropathology : official journal of the Japanese Society of Neuropathology (Neuropathology) 43 ( 3 ) 257 - 261 2023.06

ISSN 09196544

We report an autopsy case of anti-N-methyl-D-aspartate (NMDA) receptor (NMDAR) encephalitis with concurrent human herpes virus-6 (HHV-6) A deoxyribonucleic acid (DNA) detection in cerebrospinal fluid (CSF). A 38-year-old previously healthy Japanese man presented with a generalized seizure. Brain magnetic resonance imaging (MRI) findings were unremarkable, but CSF revealed pleocytosis. On Day 11, HHV-6 DNA was detected in CSF, and IgG antibodies against the NR1 subunit of the NMDAR (GluN1) were subsequently detected. Since HHV-6 encephalitis was initially suspected, the patient was treated with foscarnet and ganciclovir, but the HHV-6A copy number increased from 200 (Day 22) to 2000 copies/mL (Day 47), and the therapy was ineffective. As typical symptoms of anti-NMDAR encephalitis developed, we changed the patient's treatment to combat anti-NMDAR encephalitis. He was repeatedly treated with first-line immunotherapy, and GluN1 antibody titer decreased. He was not treated with second-line immunotherapy because of recurrent infections; he died on Day 310. Postmortem examinations did not show systemic tumors. Microscopic examination of the brain revealed only severe neuronal rarefaction in the hippocampal cornu ammonis (CA) 3-4 areas with gliosis. Early initiation of aggressive immunotherapy may be required in a refractory case of anti-NMDAR encephalitis, even with HHV-6A DNA detection, because the significance of this concurrent detection in autoimmune encephalitis remains unclear.

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COVID-19 vaccination elicited de novo and recurrence of cluster headache: A case series.

Shih-Pin Chen, Tsubasa Takizawa, Koji Sekiguchi, Jin Nakahara, Shuu-Jiun Wang

Cephalalgia : an international journal of headache (Cephalalgia) 43 ( 5 ) 3331024231173354 - 3331024231173354 2023.05

ISSN 03331024

BACKGROUND: Recent pharmacovigilance studies suggested that cluster headache could be a potential adverse effect after coronavirus disease-2019 (COVID-19) vaccination; however, the possibility of coincidence could not be excluded. Detailed case studies might help elucidate their potential link and implicate potential pathogenic mechanisms. METHODS: Patients who developed cluster headache in close temporal relationship to COVID-19 vaccination were identified from two tertiary medical centers in Japan and Taiwan respectively through 2021-2022. Detailed characteristics of the headaches and time between the onset of the index cluster episode and antecedent COVID-19 vaccination were reported. In patients with previous cluster headaches, the duration from previous bout was also recorded. RESULTS: Six patients with new cluster headache bout 3-17 days after COVID-19 vaccination were identified. Two of them were de novo cases. The others either had been attack-free for a long time or developed new cluster bout in seasons atypical to prior bouts. The vaccines included mRNA, viral vector, or protein subunit vaccines. CONCLUSIONS: COVID-19 vaccines, regardless of vaccine types, may elicit de novo or relapse of cluster headache. Future studies are needed to confirm the potential causality and explore the potential pathogenic mechanism.

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Optogenetic Spreading Depolarizations Do Not Worsen Acute Ischemic Stroke Outcome.

Kazutaka Sugimoto, Joanna Yang, Paul Fischer, Tsubasa Takizawa, Inge A Mulder, Tao Qin, Taylan D Erdogan, Mohammad A Yaseen, Sava Sakadžić, David Y Chung, Cenk Ayata

Stroke (Stroke) 54 ( 4 ) 1110 - 1119 2023.04

ISSN 00392499

BACKGROUND: Spreading depolarizations (SDs) are believed to contribute to injury progression and worsen outcomes in focal cerebral ischemia because exogenously induced SDs have been associated with enlarged infarct volumes. However, previous studies used highly invasive methods to trigger SDs that can directly cause tissue injury (eg, topical KCl) and confound the interpretation. Here, we tested whether SDs indeed enlarge infarcts when induced via a novel, noninjurious method using optogenetics. METHODS: Using transgenic mice expressing channelrhodopsin-2 in neurons (Thy1-ChR2-YFP), we induced 8 optogenetic SDs to trigger SDs noninvasively at a remote cortical location in a noninjurious manner during 1-hour distal microvascular clip or proximal an endovascular filament occlusion of the middle cerebral artery. Laser speckle imaging was used to monitor cerebral blood flow. Infarct volumes were then quantified at 24 or 48 hours. RESULTS: Infarct volumes in the optogenetic SD arm did not differ from the control arm in either distal or proximal middle cerebral artery occlusion, despite a 6-fold and 4-fold higher number of SDs, respectively. Identical optogenetic illumination in wild-type mice did not affect the infarct volume. Full-field laser speckle imaging showed that optogenetic stimulation did not affect the perfusion in the peri-infarct cortex. CONCLUSIONS: Altogether, these data show that SDs induced noninvasively using optogenetics do not worsen tissue outcomes. Our findings compel a careful reexamination of the notion that SDs are causally linked to infarct expansion.

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Long-term open-label and real-world studies of lasmiditan, ubrogepant, and rimegepant for the acute treatment of migraine attacks.

Olivia Begasse de Dhaem, Tsubasa Takizawa, David W Dodick

Cephalalgia : an international journal of headache (Cephalalgia) 43 ( 2 ) 3331024221137092 - 3331024221137092 2023.02

ISSN 03331024

BACKGROUND: Long-term data helps assess the consistency of efficacy, tolerability, and safety of acute treatment over repeated use for different attacks. Real-world studies help assess tolerability, safety, and efficacy in patients with possibly refractory chronic migraine, more comorbidities, other diseases such as cardiovascular diseases, and polypharmacy. METHODS: This is a narrative review of the long-term open-label and real-world studies of lasmiditan, ubrogepant, and rimegepant for the acute treatment of migraine. Both manuscripts and abstracts were reviewed. RESULTS: The efficacy and tolerability of lasmiditan, ubrogepant, and rimegepant are maintained over time. No significant cardiovascular adverse events were thought to be related to any of these medications. The rare instances of palpitations and/or tachycardia occurred within 48 hours of lasmiditan. One participant with a history of supraventricular tachycardia had sinus tachycardia thought to be related to ubrogepant which did not recur despite continued use. One case of thrombocytopenia and two cases of increased aspartate aminotransferase and alanine transaminase were thought to be possibly related, but the alanine transaminase and aspartate aminotransferase levels normalized despite continued use of ubrogepant. A case of first-degree atrioventricular block was considered possibly related to rimegepant. Acute use of rimegepant was associated with a decrease in monthly migraine days over time. The three medications were associated with improvement in function and/or productivity. CONCLUSION: Long-term and real-world data of tolerability, safety and efficacy of lasmiditan, ubrogepant, and rimegepant is thus far consistent with prior studies, but more longitudinal data that clarifies long-term safety as well as consistency and predictors of response is needed.

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Headache attributed to SARS-CoV-2 infection, vaccination and the impact on primary headache disorders of the COVID-19 pandemic: A comprehensive review.

Edoardo Caronna, Thomas C van den Hoek, Hayrunnisa Bolay, David Garcia-Azorin, Ana Beatriz Gago-Veiga, Massimiliano Valeriani, Tsubasa Takizawa, Karl Messlinger, Robert E Shapiro, Peter J Goadsby, Messoud Ashina, Cristina Tassorelli, Hans-Christoph Diener, Gisela M Terwindt, Patricia Pozo-Rosich

Cephalalgia : an international journal of headache (Cephalalgia) 43 ( 1 ) 3331024221131337 - 3331024221131337 2023.01

ISSN 03331024

OBJECTIVE: The objective is to summarize the knowledge on the epidemiology, pathophysiology and management of secondary headache attributed to SARS-CoV-2 infection and vaccination; as well as to delineate their impact on primary headache disorders. METHODS: This is a narrative review of the literature regarding primary and secondary headache disorders in the setting of COVID-19 pandemic. We conducted a literature search in 2022 on PubMed, with the keywords "COVID 19" or "vaccine" and "headache" to assess the appropriateness of all published articles for their inclusion in the review. RESULTS: Headache is a common and sometimes difficult-to-treat symptom of both the acute and post-acute phase of SARS-CoV-2 infection. Different pathophysiological mechanisms may be involved, with the trigeminovascular system as a plausible target. Specific evidence-based effective therapeutic options are lacking at present. Headache attributed to SARS-CoV-2 vaccinations is also common, its pathophysiology being unclear. People with primary headache disorders experience headache in the acute phase of COVID-19 and after vaccination more commonly than the general population. Pandemic measures, forcing lifestyle changes, seemed to have had a positive impact on migraine, and changes in headache care (telemedicine) have been effectively introduced. CONCLUSIONS: The ongoing COVID-19 pandemic is a global challenge, having an impact on the development of secondary headaches, both in people with or without primary headaches. This has created opportunities to better understand and treat headache and to potentiate strategies to manage patients and ensure care.

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Review of anti-CGRP monoclonal antibodies in the real-world in Japan

Ohtani Seiya, Ihara Keiko, Hori Satoko, Nakahara Jin, Takizawa Tsubasa

Japanese Journal of Headache (The Japanese Headache Society) 49 ( 3 ) 578 - 583 2023

Accepted, ISSN 13456547

Migraine is a common disease that significantly negatively affects patients’ quality of life. Previously reported treatments have shown limited efficacy and safety; however, anti-calcitonin gene-related peptide monoclonal antibody (CGRPmAb) has attracted considerable attention as an antimigraine agent. This agent became commercially available in Japan in 2021, only a year before this present review, and research is warranted to gain deeper insight into the outcomes of CGRPmAb treatment in real-world clinical practice. In this review, we discuss the abstracts presented at the 49th Congress of the Japanese Headache Society (November 2021) and the 63rd Annual Meeting of the Japanese Society of Neurology (May 2022)． We identified 13 abstracts that have reported the efficacy and safety of CGRPmAb after greater than 1-month treatment with this agent. These results show that CGRPmAb decreased monthly migraine days and monthly headache days and minimized headache-induced disability without serious adverse effects.

Reversible Splenial Lesion Triggered by Hyperthyroidism

Okusa Shohei, Nakahara Jin, Takizawa Tsubasa

Internal Medicine (The Japanese Society of Internal Medicine) advpub ( 0 ) 2925 - 2926 2023

ISSN 09182918

Migraine triggers in Asian countries: a narrative review.

Chisato Iba, Seiya Ohtani, Mi Ji Lee, Sunjun Huh, Narumi Watanabe, Jin Nakahara, Kuan-Po Peng, Tsubasa Takizawa

Frontiers in neurology (Frontiers in Neurology) 14 1169795 - 1169795 2023

ISSN 1664-2295

BACKGROUND: Migraine is one of the most common neurological disorders worldwide. Clinical characteristics of migraine may be somewhat different across ethnic groups. Although factors such as stress, lack of sleep, and fasting are known as migraine triggers, the discussion about geographical differences of migraine triggers in Asia is lacking. METHODS: In this study, we performed a narrative review on migraine triggers in Asia. We searched PubMed for relevant papers published between January 2000 and February 2022. RESULTS: Forty-two papers from 13 Asian countries were included. Stress and sleep are the most frequently reported migraine triggers in Asia. There were some differences in migraine triggers in Asian countries: fatigue and weather common in Eastern Asia and fasting common in Western Asia. CONCLUSION: Majority of the common triggers reported by patients with migraine in Asia were stress and sleep, similar to those reported globally, thus showing they are universally important. Some triggers linked to internal homeostasis are influenced by culture (e.g., alcohol, food/eating habit), and triggers related to environmental homeostasis, such as weather, are highly heterogenous between regions.

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