Calcitonin gene-related peptide (CGRP) is present virtually throughout the human body and found extensively in the central nervous system (CNS) , peripheral nervous, cardiovascular, and gastrointestinal systems. CGRP receptors are highly expressed in the trigeminovascular system and have been demonstrated in various sites such as the cell body of neurons and satellite glial cells of the trigeminal ganglion, meningeal mast cells as well as in the meningeal vasculature. CGRP and its receptor have also been demonstrated in the CNS in areas such as the trigeminal nucleus caudalis, brainstem nuclei, periaqueductal grey, thalamus, hypothalamus, and cerebellum. The significance of CGRP in the pathogenesis of migraine is evident by numerous experiments. Elevated levels of CGRP demonstrated in internal as well as external jugular venous blood during an episode of migraine and its normalization following administration of sumatriptan with alleviation of pain, suggested possibility of CGRP being crucial to the generation of migraine headache.　
　Recent development of anti-CGRP drugs and their substantial efficacy in the treatment and prophylaxis of migraine has facilitated in consolidating all the data obtained from previous research. The evolution of anti-CGRP antibodies has been a revolutionary step with significant implications in the field of migraine. The site of action of these drugs remains uncertain but it has been proposed that as monoclonal antibodies are large molecules that cannot cross the blood-brain barrier, they probably have a peripheral rather than central site of action in the nervous system. Potential sites would be the dura mater and the trigeminal ganglion where prominent actions of CGRP such as neurogenic inflammation and peripheral sensitization may be suppressed by the anti-CGRP monoclonal antibodies (mAbs) .
　Although speculation still surrounds the site of action of the anti-CGRP mAbs, with potential sites being the meninges and trigeminal ganglion, all clinical trials have consistently demonstrated the mAbs to be extremely efficacious in the prophylaxis of episodic as well chronic migraine by causing a significant decrease in the number of monthly migraine days, with negligible side-effects, which make these drugs more suitable than currently used drugs. The success of these drugs in migraine prophylaxis treatment has encouraged researchers in further investigating the pathophysiology of migraine.

　In clinical practice, we sometimes experience migraine patients with early morning headaches. We investigated the characteristics and relationship between early morning headache and obstructive sleep apnea syndrome (OSAS）in eight migraine patients with morning headaches who visited Headache Clinic of Keio University Hospital. Seven of eight patients had OSAS. Six patients had mild OSAS and one patient had moderate OSAS. There was tendency of positive correlation between AHI and percentage of morning headache. There is the possibility that OSAS may exacerbate migraine, and the treatment of migraine patients with early morning headache and OSAS may be a subject of future research．

　The effect of 10 mg propranolol during premonitory symptoms was assessed in 56 patients (43 without aura and 13 with aura）. Propranolol successfully prevented migraine attack at least some of the time in 54 (96%） patients, with 29 (52%） patients reporting > 50% prevention frequency. Further, pain alleviation was reported by 44 (79%） patients. Prophylactic treatment may be highly desirable for cases in which daily life is adversely affected despite acute treatment. It is critical to select a therapeutic strategy suitable for the frequency and time course of migraine attacks, such as conventional daily prophylactic treatment, preventive treatment during premonitory symptoms, or a combination of the two treatments as applicable.

　Objective : The ownership rates of devices with visual display terminals, particularly those of smartphones, have increased prominently. To date, the aggravation of headaches due to these devices has been reported only in one study that analyzed the relationship between migraines and smartphones. The present study aimed to investigate the effects of various devices on the different types of headaches.
　Methods and Patients : All patients with headaches who visited the Trinity Neurology Clinic between January 1 and February 28, 2019 were diagnosed based on the International Classification of Headache Disorders, 3rd edition. They were also asked with interview form about the frequency and duration of usage of those devices and other factors aggravating headaches.
　Results : This study included 106 patients (19 men, 87 women; average age 48.2 years) who had 45 migraines (average 42.0 years) , 41 tension-type headaches (average 53.4 years) , 1 cluster headache (55 years) , 10 medication-overuse headaches (average 41.3 years) , 16 painful lesions of the cranial nerves and other facial pains (average 50.8 years) , and 10 other headaches (average 57.9 years) . Of all patients with headaches, 75% used smartphones, 45% used personal computers, 3% used tablets, and 45% had other factors aggravating headaches. Patients with migraines or medication-overuse headaches were younger than those with tension-type headaches (p＜0.005 and p＜0.05) and other headaches (p＜0.01 and p＜0.05) , respectively. Smartphone users complained more frequently of migraines and medication-overuse headaches than other types of headaches (p＜0.01) . Tension-type headaches were more common among smartphone users than among non-users (p＜0.05) .
　Conclusions : Smartphone users have more headaches in patients with migraines and tension-type headaches. Smartphone users with migraines tend to aggravate their headaches and complicate medication-overuse headaches. This study is the first to analyze relations between several devices and various types of headaches.

　In the treatment of medication-overuse headache （MOH）, discontinuation of the causative drug often results in rebound headache and subsequent difficulty in withdrawing from the causative drug. Prophylactic drugs are not fast-acting and do not counteract rebound headache. We investigated the efficacy of traditional Japanese Kampo medicines, which can be taken in combination with regular medication and at the time of headache, in 298 first-time headache outpatients from 2017 to 2020; 54 patients were diagnosed with MOH, and 47 of these patients with concomitant symptoms were treated with Kampo medicines. Primary endpoints included the success rate of withdrawal from the causative medication and course of treatment, and secondary endpoints were the Kampo medicine prescription, age, sex, underlying headache disorder, and use of prophylactic medication. The male to female ratio was 7：40, and the median age was 43 years. Successful withdrawal was the complete resolution of chronic headache and analgesic use<10 days/month within 2 months after discontinuation of overuse medication. The successful withdrawal rate was 89%. Migraine was the most common underlying cause of headache. The prescriptions were “goreisan”, “keishibukuryogan”, and “tokishakuyakusan”. Concomitant use of Kampo medicines contributes to successful withdrawal from the causative drug in MOH.

　Trigeminal neuralgia is an ancient human disease that causes pain in the face and is characterized by sudden, intense pain lasting from a few seconds to several minutes. In 1962, Gardner succeeded for the first time in treating trigeminal neuralgia by releasing the blood vessels that were compressing the root entry zone of the trigeminal nerve. In 1970, Jannetta established Micro Vascular Decompression (MVD) by performing surgery using a microscope. As for medical treatment, carbamazepine was successful in trigeminal neuralgia, but did not provide adequate pain control due to pain tolerance or side effects. Today, the primary etiology of trigeminal neuralgia is not trauma, neurodegeneration, or viruses, but compression of the trigeminal nerve origin by intracerebral blood vessels. In patients with the root entry zone of the trigeminal nerve compression, external factors such as washing the face, shaving, smoking, talking, or brushing the teeth are thought to induce overexcitement of the nerve, resulting in paroxysmal, severe pain.
　MVD is a functional neurosurgery, the goal of which is to achieve complete resolution of trigeminal neuralgia symptoms and avoid complications of surgery. The goal of MVD is to achieve complete resolution of trigeminal neuralgia symptoms without complications from surgery and to prevent recurrence over time. In Review I, we will discuss the pathogenesis, epidemiology, diagnosis, imaging, and treatment strategies.

　The goal of MVD is the complete elimination of trigeminal neuralgia, which of course should be free of recurrence and complications. MVD is a radical treatment that eliminates the cause and can be a blessing for patients with trigeminal neuralgia. However, as MVD has become more widespread, it has also resulted in an increase in medical disputes due to unsatisfactory surgical outcomes and complications. We believe that it is the responsibility of physicians involved in MVD to learn the correct surgical methods and techniques for the permanent relief of pain in patients with trigeminal neuralgia. In Review 2, we will discuss the standard MVD treatment, the practice of MVD, possible postoperative complications, healing results, characteristics of postoperative recurrence, and measures to prevent recurrence.

　The purpose of this article is to report the characteristics and treatment of a special type of trigeminal neuralgia that is difficult to diagnose.
　The purpose of this report is to describe the characteristics and treatment of trigeminal neuralgia.
　1. Trigeminal neuralgia due to vertebra-basilar artery vertebrobasilar ectasia.
　2. Trigeminal neuralgia due to venous compression alone.
　3. Trigeminal neuralgia due to arachnoid thickening.
　4. Trigeminal neuralgia caused by compression of the trigeminal nerve by multiple blood vessels.
　5. Trigeminal neuralgia of young onset (age 15) .
　6. Trigeminal neuralgia caused by trigeminocerebellar artery (TCA) . The TCA, a malformation of the superior cerebellar artery, compresses the REZ of the trigeminal nerve as it penetrates the nerve.
　7. Trigeminal neuralgia caused by cerebral arteriovenous malformation. Cerebral arteriovenous malformation compresses the REZ of the trigeminal nerve; AVMs may be small lesions and may be missed in the preoperative diagnosis. Cerebral arteriovenous malformations can be treated with MVD without removal of the lesion, which may result in pain relief.
　8. Trigeminal neuralgia due to venous hemangioma. The outflowing vein of a venous hemangioma may directly contact the trigeminal nerve, or the outflowing vein may dilate and the pyramidal vein may compress the trigeminal nerve, or the superior cerebellar artery and anterior inferior cerebellar artery may simultaneously compress the trigeminal nerve. Treatment includes coagulation and disconnection of the outflow vein, or coagulation and reduction of the outflow vein and MVD.
　9. Trigeminal neuralgia due to supratentorial tubercle.
　10. Trigeminal neuralgia due to brain tumor. The main tumors associated with trigeminal neuralgia symptoms are epithelioma, vestibular schwannoma, and meningioma, each of which has a different surgical approach. Some tumors cause further compression of the trigeminal nerve REZ by the superior cerebellar artery in addition to tumor compression. Trigeminal neuralgia caused by pyriform plateau meningioma should be treated with MVD at an early stage, because even if the tumor is small, the pathology of compression of the superior cerebellar artery and compression of the trigeminal nerve REZ should be recognized.
　11. Postoperative recurrence due to interposition material, transverse pontine. V. Even if paroxysmal pain of trigeminal neuralgia disappears after reoperation, neuropathic pain, which is persistent pain, is likely to remain.
　12. Trigeminal neuralgia after gamma knife therapy. paroxysmal pain of trigeminal neuralgia after MVD may disappear, but persistent neuropathic pain is likely to remain.
　13. Some SUNCT syndromes can be cured by microvascular decompression.
　In cases with typical symptoms of trigeminal neuralgia, trigeminal neuralgia due to rare causes, such as the one presented here, should be taken into consideration.

　Headache disorders are usually not considered as potential causes of motor-vehicle accidents (MVAs) . We report two patients who had life-threatening MVAs caused by migraine symptoms. One patient, a 51-years-old woman, had headache and vertigo while driving causing a MVA on a highway. She was diagnosed with vestibular migraine. The second patient, a 49-years-old woman, had a sudden headache and loss of consciousness while driving causing lumbar fractures. She was diagnosed with migraine with brainstem aura. She was previously diagnosed with migraine without aura, which underlines that auras of different types may appear along the course of migraine initially without aura. Doctors who are treating migraines must be aware of the possibility of severe attacks with neurological symptoms leading to MVAs．

　A 48-year-old female underwent allogeneic bone marrow transplantation for severe aplastic anemia. She complained of thunderclap headache at night after tacrolimus (Tac) administration. Although MRI at symptom onset showed posterior reversible encephalopathy syndrome （PRES）, we suspected reversible cerebral vasoconstriction syndrome （RCVS） from the thunderclap headache. The white matter lesions of PRES improved after transient worsening, despite continuing the transplantation with Tac. But vasospasm appeared a few days later and gradually improved after lomerizine treatment. She was diagnosed as RCVS. Tac often induce PRES, but it’s relationship to RCVS is reported fewer, and uncertain. We could continue Tac with a diagnosis of RCVS. Therefore, symptoms is more important than images in RCVS with PRES.