Disaster countermeasures have been implemented by the Japanese Society of Neurology based on the experience of support to the areas affected by the Great East Japan Earthquake on March 11, 2011. The countermeasures activity began at the end of 2011. We, the Committee for Measures Against Disaster, officially started work in 2014. We developed a support network to urgently deal with patients with intractable neurological disease at the time of disaster and strengthen disaster measures, including effective disaster countermeasure training. During the 2016 Kumamoto earthquake, we realized the need to prepare for natural disasters, leading to a state of emergency, at normal times. A list of vulnerable people should be prepared and the individual support plan for disaster should be confirmed during normal times. Furthermore, during disaster, livelihood support is required for patients with intractable neurological disease living in evacuation centers in affected areas. Therefore, we compiled and published the book, titled “The manual of disaster countermeasures,” in 2017. The Committee for Measures Against Disaster in the Japanese Society of Neurology has appointed a liaison officer for patients with intractable neurological disease in each prefecture. The liaison’s role of is gathering and disseminating information on the disaster-hit areas, arranging medical support, and coordinating health activities, when natural disasters occur. It is hoped that the liaison officer will play an active role both at normal times and during disaster, even unforeseen ones. Although we hope for the best, we aim to be prepared for the worst.
Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disease that had been diagnosed by autopsy until recently, but the number of cases has increased since skin biopsy was reported to be useful in 2011. In 2019, the genetical cause of NIID was identified as the extension of the GGC repeat sequence on the NOTCH2NLC gene, and genetic diagnosis became possible. In NIID, there are two groups: a group onset with cognitive dysfunction, and with leukoencephalopathy on head MRI and a high intensity signal at the corticomedurally junction on DWI, and a group with limb weakness. It is necessary to include NIID in the differential diagnosis of leukoencephalopathy and neuropathy, and it is necessary to combine skin biopsy and genetic testing to accurately diagnose of NIID and promote pathological elucidation.
In elderly patients with so-called psychogenic physical symptoms, changes with age of the symptoms were discussed from the standpoint of geriatric psychiatry. In recent years, the diagnostic criteria for psychogenic physical symptoms have been revised and are closer to the definition of psychosomatic disorders. In aging, the aging phenomenon of each body organ progresses, and the brain is no exception. Clinical findings suggest that conventional physical and mental symptoms are alleviated as brain function declines in general. If dementia is added, the speed of relief will increase. In Japan, where super-aging is advancing, the need to focus on the positive aspects of aging is discussed.
Migraine is a common and debilitating neurological disorder characterized by recurrent attacks of moderate to severe throbbing headache accompanied by nausea, vomiting and photophobia/phonophobia. Because of its high prevalence, migraine causes a considerable financial burden on the society as well as impaired quality of life in individual patients. Scientific evidence shows that migraine is a quite complex neurological disorder that involves not only the trigeminovascular and autonomic systems but also the hypothalamus and cerebral cortex. Calcitonin gene-related peptide (CGRP) was originally discovered as a 37-amino acid neuropeptide derived from a calcitonin gene splicing variant. CGRP is found to be expressed in trigeminal ganglion neurons. Much attention has been attracted to this molecule since CGRP was found to be released from trigeminal terminals in animal migraine models. Subsequent studies demonstrated that CGRP administration induced migraine-like headache attacks specifically in migraineurs, thus highlighting a pivotal role of CGRP in the development of migraine attacks. Several CGRP receptor antagonists were shown to be efficacious for the treatment of acute migraine. Among them, telcagepant, was shown to exert a significant migraine prophylactic action as well. Nevertheless, the development of most of these agents were discontinued due to hepatotoxicity. Currently, newer CGRP receptor antagonists are being developed. On the other hand, monoclonal antibodies targeting CGRP and its receptor showed consistent efficacy for migraine prophylaxis with excellent safety profiles in Phase III clinical trials. Furthermore, emerging data support the long-term safety and efficacy of these antibodies. In this review article, the development and perspective of anti-migraine therapeutic strategies using CGRP-related antibodies are discussed.
We report a 74-year-old man with a 2-year history of proximal limb pain, body weight loss of 15 kg, and muscle weakness. Muscle atrophy was evident in the limbs and trunk, as well as the tongue. He was admitted to our hospital with suspected amyotrophic lateral sclerosis (ALS). Although he had no physical manifestations of Basedow disease such as palpitations, hyperhidrosis, hand tremor, exophthalmos, and an enlarged thyroid, he was diagnosed as having thyrotoxic myopathy as laboratory examinations indicated hyperthyroidism and positivity for TSH receptor antibody. The serum level of soluble IL-2 receptor was also elevated. Despite the severe muscle atrophy, the serum CK level was normal. A biopsy from the left quadriceps muscle revealed Type 1 fibers atrophy. Administration of anti-thyroid drugs normalized his thyroid function and the level of soluble IL-2 receptor, leading to improvement of the generalized muscle atrophy.
Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a brainstem predominant lymphocytic inflammatory disease, which often relapses without oral immunosuppressants. This report describes a 37-year-old male case of CLIPPERS without relapse for 1 year after early steroid treatment. He was admitted to our hospital because of sensory disturbance in the left side of his body and ataxic gait. Gadolinium-enhanced T1-weighted MRI revealed multiple punctate and curvilinear enhancements in the pons and right middle cerebellar peduncle. We started treatment with high-dose intravenous methylprednisolone (IVMP) therapy on the 20th day of the illness. His neurological symptoms dramatically improved. Follow-up MRI showed that the enhancing lesions disappeared. We diagnosed him with CLIPPERS based on the clinical course, radiological findings, and steroid response. He did not take any oral immunosuppressant after discharge. However, there was no clinical and radiological relapse for 1 year after the IVMP therapy. Although this case requires careful follow-up because of recurrence risk, early steroid treatment was possibly related to 1-year remission.
We report two cases of transthyretin familial amyloid polyneuropathy (ATTR-FAP) from non-endemic areas. Both cases showed chronic progressive distal limb numbness and weakness. Due to nonspecific symptoms, they were not diagnosed for a long period of time. A nerve conduction study revealed axonal neuropathy in the lower limbs and carpal tunnel syndrome. An echo test showed thickness of the left ventricle, one of the red flag symptom clusters of ATTR-FAP. Genetic analysis revealed a mutation in the transthyretingene. In cases with chronic progressive neuropathy, it is important to consider a differential diagnosis of ATTR-FAP.
We report the case of a 66-year-old female with hemiplegia cruciata and severe facial pain due to infarction of the cervicomedullary junction. She presented to the hospital with complaints of acute-onset left facial pain and gait disturbance. Neurological examination revealed narrow left palpebral fissure, severe left facial pain and hypothermoesthesia, weakness predominantly in the left upper and right lower extremities, decreased pain and temperature sensation in the right lower extremity, decreased vibration sensation in the left lower extremity, hyperreflexia in the left upper extremity, and mild ataxia in the left upper and lower extremities. Brain MRI revealed a high-intensity lesion in the left cervicomedullary junction on diffusion-weighted and fluid-attenuated inversion recovery images. Hemiplegia cruciata due to the pyramidal tract injury at the cervicomedullary junction is an uncommon clinical manifestation. However, in patients with hemiplegia cruciata, identifying the lesion location may be difficult. Clinicians should consider the possibility of pyramidal decussation lesions. Anatomical differences, in the course of pyramidal tract fibers between the upper and lower limbs have been considered in the pyramidal decussation. Hemiplegia cruciata in this case was primarily caused by the impairment of the left upper limb pyramidal fibers after the pyramidal decussation and the right lower limb pyramidal fibers before the pyramidal decussation.
A 75-year-old woman developed low back pain, weakness of the lower extremities, and urinary retention. On day 7 after the onset of symptoms, she was brought to the emergency department of our hospital by an ambulance because of progressive weakness of both lower extremities. Spine MRI showed longitudinally extensive spinal cord lesion (LESCL) at the Th8–Th11 spinal cord level and flow voids around the lesions. Lumbar puncture revealed a normal opening pressure, yellowish appearance, pleocytosis with polymorphonuclear predominance, and decreased cerebrospinal fluid (CSF) glucose levels. Based on the rapidly progressing myelopathy, LESCL, and CSF findings, we initially diagnosed the patient with myelitis and administered acyclovir and high-dose intravenous immunoglobulin on day 7. Spine MRI with gadolinium-enhancement showed longitudinally extending flow voids of the thoracic cord, and digital subtraction arteriogram (DSA) revealed arteriovenous shunt on the dura with dilated and tortuous intradural veins. We finally diagnosed her with spinal dural arteriovenous fistula (SDAVF). Cases of SDAVF might be initially misdiagnosed as myelitis because of showing rapid progressive myelopathy, pleocytosis with polymorphonuclear predominance, and decreased CSF glucose levels. Lumbar puncture and steroid administration for the cases of SDAVF could aggravate the patient’s neurological symptoms. Therefore, lumbar puncture and initiation of immunotherapy should be avoided until SDAVF is completely excluded in patients with suspected myelitis on spine MRI without gadolinium-enhancement, even if their neurological symptoms progress rapidly.
During the COVID-19 pandemic in 2020, an 81-year-old afebrile woman was transported to our institute at 44 minutes after she was found to have global aphasia and weakness of the right extremities. The onset time was unclear. CT showed an occlusion of the left middle cerebral artery without early ischemic changes. MRI revealed a negative fluid-attenuated inversion recovery (FLAIR) pattern, in which several small acute infarcts were seen in diffusion-weighted images with no corresponding hyperintensity lesions on FLAIR. Accordingly, intravenous thrombolysis with alteplase (0.6 mg/kg, the dose approved in Japan) was administered at 1,660 minutes after the last known well and 116 minutes after the symptom recognition. An immediate internal carotid angiogram showed severe stenosis at the distal end of the horizontal portion of the left middle cerebral artery. In the follow-up angiogram at 164 minutes after the symptom recognition, the stenotic lesion almost resolved with the restoration of quick and nearly complete antegrade flow. Her symptoms also resolved promptly. Although the use of MRI is recommended to be minimized in the emergency stroke management during the COVID-19 pandemic, MRI is occasionally mandatory for patient selection, such as cases with unclear onset to perform intravenous thrombolysis. The individualized protected code stroke is essential and must be well considered by each institute for diagnosing patients by selecting appropriate modalities.
A 50-year-old woman developed gait disturbances and dysarthria since the past 2 years. She also presented with dystonia and hypokinesia of her left lower limb, and orthostatic hypotension. The dopamine transporter SPECT with 123I ioflupane showed abnormal scans in bilateral striatum. Cerebral MRI revealed atrophy and signal changes in the medulla and spinal cord, from which Alexander disease (AxD) was suspected. Consequently, we checked the Glial fibrillary acidic protein (GFAP) gene. The analysis of the gene detected a heterozygous c.219G>T mutation, which was the first mutation reported in Japan, and finally she was diagnosed with AxD. Dystonia is relatively rare in AxD patients, but this case demonstrated that AxD should be listed in the differential diagnosis of extrapyramidal syndromes with abnormalities of the medulla and spinal cord on MRI.