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Mutations in small heat shock protein beta-1 (HspB1) have been linked to Charcot-Marie-Tooth (CMT) disease type 2F and distal hereditary motor neuropathy type 2B. Only four cases with HSPB1 mutations have been reported to date in Japan. In this study between April 2007 and October 2014, we conducted gene panel sequencing in a case series of 1,030 patients with inherited peripheral neuropathies (IPNs) using DNA microarray, targeted resequencing, and whole-exome sequencing. We identified HSPB1 variants in 1.3% (13 of 1,030) of the patients with IPNs, who exhibited a male predominance. Based on neurological and electrophysiological findings, seven patients were diagnosed with CMT disease type 2F, whereas the remaining six patients were diagnosed with distal hereditary motor neuropathy type 2B. P39L, R127W, S135C, R140G, K141Q, T151I, and P182A mutations identified in 12 patients were described previously, whereas a novel K123* variant with unknown significance was found in 1 patient. Diabetes and impaired glucose tolerance were detected in 6 of the 13 patients. Our findings suggest that HSPB1 mutations result in two phenotypes of inherited neuropathies and extend the phenotypic spectrum of HSPB1-related disorders.

Background: Photophobia is a common feature of migraine, which may involve abnormal cortical information processing. In electroencephalograms (EEG), photic driving is known as a reaction to visual stimulation. Both photophobia and photic driving response are present during light stimulation. We hypothesized that cortical response to photic stimulation would differ between migraine patients with and without aura. Methods: We recruited 50 migraine patients (migraine with aura [MWA] = 21; migraine without aura [MWOA] = 29). Spontaneous eyes-closed resting EEG from 20 electrodes on the scalp during the interictal phase was recorded. After recording, each photic stimulation was separately selected. We analyzed EEG by fast Fourier transform and observed the spectrum frequency peaks and topographies in response to photic stimulation. Exact low-resolution electromagnetic tomography (eLORETA) was used to compute the 3-dimensional intracerebral distribution of EEG activity. Results: Photic stimulation at frequencies 5, 8, 15, and 20 Hz showed significant differences between migraine patients with and without aura. MWOA patients consistently had a stronger response to photic stimulation than MWA patients. In all patients, the differential response was located in the visual cortex, except for the stimulation at 20 Hz, where the difference at subharmonic 10 Hz was located in the parietal cortex (Brodmann Area 7). Conclusion: We confirmed high incidences of photic hypersensitivity and photic driving responses in migraine patients. We suggest that repeated occurrences of cortical spreading depression in MWA may suppress cortical function, thus contributing to a weaker visual cortical response to photic stimulation in MWA patients compared with MWOA patients.

Objective: Migraineurs demonstrate abnormal information processing such as photic hypersensitivity. The photic driving response to photic stimulation (PS) is a reaction to the visual stimulation of electroencephalography (EEG). Both the photic driving response and photic hypersensitivity appear during light stimulation. We considered that evaluation of a migraineur's photic driving response may help to elucidate the mechanism of the migraineur's sensitive condition. Our study aimed to investigate EEG photic driving responses with a source-localizing method. Methods: We recorded spontaneous resting EEG with eyes closed from 20 electrodes on the scalp during the interictal phase. After recording, each PS was separately selected. We also analyzed EEG by fast Fourier transform and observed the spectrum frequency peaks and topographies in response to PS. Results: The photic driving response could be observed at a flashing rate of >15 Hz. Patients with photic hypersensitivity tended to show more photic driving regardless of the migraine subtype. Moreover, in topographies, their activated areas were shifted anteriorly from fundamental driving to harmonic driving for each photic frequency. This anterior shift was more evident with a longer duration of illness, although no significant differences were seen between migraine subtypes. The global field power value had a positive correlation with the duration of illness. Conclusion: Photic hypersensitivity and photic driving responses were increased in migraineurs. Photic hypersensitivity might result in sensitization of the limbic system.

Mutations in small heat shock protein beta‐1 (HspB1) have been linked to Charcot‐Marie‐Tooth (CMT) disease type 2F and distal hereditary motor neuropathy type 2B. Only four cases with HSPB1 mutations have been reported to date in Japan. In this study between April 2007 and October 2014, we conducted gene panel sequencing in a case series of 1,030 patients with inherited peripheral neuropathies (IPNs) using DNA microarray, targeted resequencing, and whole‐exome sequencing. We identified HSPB1 variants in 1.3% (13 of 1,030) of the patients with IPNs, who exhibited a male predominance. Based on neurological and electrophysiological findings, seven patients were diagnosed with CMT disease type 2F, whereas the remaining six patients were diagnosed with distal hereditary motor neuropathy type 2B. P39L, R127W, S135C, R140G, K141Q, T151I, and P182A mutations identified in 12 patients were described previously, whereas a novel K123* variant with unknown significance was found in 1 patient. Diabetes and impaired glucose tolerance were detected in 6 of the 13 patients. Our findings suggest that HSPB1 mutations result in two phenotypes of inherited neuropathies and extend the phenotypic spectrum of HSPB1‐related disorders.

Objective Several studies have shown an increased prevalence of right-to-left shunt (RLs) in migraine patients, particularly those with aura. However, the prevalence of RLs and its relation to Japanese patients with migraine are unknown. We investigated the prevalence of RLs in Japanese patients with migraine. Methods In total, 112 consecutive patients with migraine were recruited from our headache outpatient clinic. Migraine with aura (MA) and migraine without aura (MWOA) were diagnosed according to the International Classification of Headache Disorders, 3rd edition (beta-version). Contrast transcranial Doppler ultrasound was used to detect RLs, including patent foramen ovale (PFO). Then, the associations between RLs and patients' backgrounds and presence of aura were assessed. Results The overall prevalence of RLs and PFO in migraine patients was 54.5% and 43.8%, respectively. The prevalence of RLs and PFO in the MA group were significantly higher than in the MWOA group (RLs, 62.9% vs. 44.0%, p=0.046; PFO, 54.8% vs. 30.0%, p=0.008). There were no marked differences in the prevalence of large, middle and small shunts between MA and MWOA patients. Compared with the MWOA patients, the MA patients were younger (p=0.013) and had early onset age (p=0.013) and increased prevalence of photophobia (p=0.008). Conclusion RLs were found in over half of the Japanese patients with migraine. Our study suggests a possible link between RLs and MA.

Recent studies have provided evidence for a positive association between migraine and restless legs syndrome (RLS), although the exact mechanisms and contributing factors remain unclear. A cross-sectional, case-control study was conducted, including patients with migraine (n = 262) and headache-free control subjects (n = 163). Migraine was diagnosed according to International Classification of Headache Disorders II criteria. RLS diagnosis was made based on four essential criteria as described by the International Restless Legs Syndrome Study Group. All patients completed the Migraine Disability Assessment (MIDAS) questionnaire, Beck Depression Inventory (BDI)-II scores, Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS). A total of 210 blood samples were collected to correlate various parameters with RLS. RLS frequency was significantly greater in patients with migraine than in controls (13.7 vs. 1.8%). Migraine patients with RLS had high scores for MIDAS, BDI-II, PSQI, and ESS compared with those without RLS. In addition, migraine patients with RLS had a high rate of smoking and RLS family history, as well as increased levels of serum phosphorus and urea nitrogen compared with those without RLS. However, there was no difference in serum iron and ferritin levels between the groups. In migraine patients, logistic regression analysis revealed that positive RLS family history, BDI-II, ESS, and serum phosphorus levels were significant RLS predictors. Our study confirmed a positive association between RLS and migraine. RLS comorbidity in migraine patients was associated with insomnia, daytime sleepiness, depressive symptoms, headache-related disability, and increased serum phosphorus levels. These findings may provide a better understanding of RLS pathogenesis in migraine.

Objective Barometric pressure has been reported as a triggering and exacerbating factor in migraine headaches, although there are few reports concerning the association of weather change and migraine headache. The relationship between barometric pressure changes and migraine headaches was prospectively examined. Methods A total of 28 migraine patients who lived within 10 km of the Utsunomiya Local Meteorological Observatory kept a headache diary throughout the year. Daily and monthly mean barometric pressure data of the Utsunomiya Local Meteorological Observatory were obtained via the homepage of the Meteorological Office. Results The correlation between headache frequency obtained by the headache diaries for 1 year and changes in the barometric pressure during the period of 2 days before and 2 days after the headache onset were evaluated. The frequency of migraine increased when the difference in barometric pressure from the day the headache occurred to the day after was lower by more than 5 hPa, and decreased when the difference in barometric pressure from the day the headache occurred to 2 days later was higher by more than 5 hPa. Of 28 patients, weather change was associated with migraine headache development in 18 (64%) patients, 14 of which reported low barometric pressure to be a cause of headache. There was no association between the monthly mean barometric pressure and headache frequency throughout the year. Conclusion Barometric pressure change can be one of the exacerbating factors of migraine headaches.

The aim of the present study is to provide effective tools for monitoring hemodynamic changes in the cortical and scalp surface during migraine attack and treatment. Using near-infrared spectroscopy system (NIRS) and laser Doppler skin blood flow (SkBF) devices in combination, we monitored changes in extra- and intra-cranial vasculature states upon sumatriptan injection during spontaneous migraine attack. We examined 4 control subjects and 4 migraine patients. Multi-channel NIRS probes were placed over the temporoparietal area bilaterally and oxygenated hemoglobin (oxy-Hb) was analyzed. Laser Doppler SkBF was simultaneously recorded to measure scalp surface blood flow changes. All patients were treated with a sumatriptan injection (3 mg), and all control subjects received a saline injection as a control for oxy-Hb/SkBF signals caused by injection pain over the monitoring period. There was a marked reduction of oxy-Hb/SkBF in all patients after sumatriptan injection, consistent with pain relief. Moreover, the changes in oxy-Hb/SkBF were significantly correlated. By contrast, saline injection did not cause any significant changes. These data suggest that sumatriptan induces blood vessel contraction at both cortical and scalp surfaces. Simultaneous oxy-Hb/SkBF recording enables real-time continuous monitoring of the effects of sumatriptan treatment in clinical situations.

The Japanese Headache Society and the Japanese Society of Neurology has published the 2013 guidelines for the diagnosis and treatment of chronic headache. A new CQ has been set up in the guidelines on the topic of "How to treat chronic migraine." In the past, lomerizine was the only prophylactic medication of migraine that was eligible under insurance coverage. However, afterward in 2010, valproate was added to the list of antimigraine medications approved under insurance coverage, followed by propranolol, amitriptyline, and verapamil, with rapid advances in the treatment of migraine. Valproate, topiramate (not approved under insurance coverage until date), and amitriptyline could potentially be used in the treatment of chronic migraine in Japan; further, considering the clinical outcomes thus far, lomerizine could also be added to the list. As a drug for migraine prophylaxis, valproate is contraindicated in pregnant women and needs to be used with caution.

The pathophysiology of migraine includes the vascular theory, the trigeminovascular theory, and cortical spreading depression; however, the pathophysiology of a spontaneous migraine attack has not yet been clarified. The vascular theory became negative, and it was considered that the pain of migraine was not associated with vascular expansion. However, recent studies have again attracted attention toward the vascular theory of migraine. The aim of the present study was to provide effective tools for monitoring hemodynamic changes in the cortical and scalp surface during migraine attack and treatment. Using a near-infrared spectroscopy system and laser doppler skin blood flow (SkBF) monitoring device in combination, we monitored changes in extra- and intracranial vasculature upon sumatriptan injection during spontaneous migraine attack. There was a marked reduction of oxy-Hb/SkBF in all patients after sumatriptan injection, and this was consistent with pain relief. Moreover, the changes in oxy-Hb and SkBF were significantly correlated. In contrast, saline injection did not cause any significant changes. These data suggest that sumatriptan induces the vasoconstriction of the vascular bed region, including the arteriovenous anastomosis in the scalp and cortex. On the basis of these data, we suggest that it is now justifiable to reconsider the vascular theory of migraine.

Background: Recent studies have suggested a strong link between migraines and restless legs syndrome (RLS). It is possible that these disorders share a dopaminergic dysfunction in the hypothalamic A11 nucleus that contributes to this association. However, there have been no clinical studies to evaluate the effect of dopaminergic treatment on migraine symptoms in patients with concomitant migraines and RLS. Methods: We present an illustrative patient with concomitant RLS and migraine who showed improvement in her headache frequency and RLS symptoms following immediate‐release pramipexole (P‐IR) treatment and provide review results from the medical records of patients who experienced both migraines and RLS in our previous cross‐sectional study. Results: Ten patients (nine patients from the previously completed single‐center study) received P‐IR treatment were included in the study. RLS symptoms improved markedly in all of the subjects. Five out of the 10 patients (50%) reported improvement in migraine headaches. Of these five patients, four (80%) had reported morning headaches before P‐IR treatment. Discussion: Our results indicate that the identification of RLS in migraine patients is clinically significant and that dopaminergic treatment may improve both migraines, particularly morning headache (80% improvement in this study), and RLS symptoms. However, further clinical studies are warranted to verify our results., Tremor and Other Hyperkinetic Movements, Tremor and Other Hyperkinetic Movements

Background Sleep disorders, nightmares and visual hallucinations have been reported in migraine patients, which may suggest the involvement of rapid eye movement (REM) sleep regulation in migraine. However, the relationship between migraine and REM sleep behaviour disorder (RBD) remains unclear. Methods To investigate the clinical correlates of dream-enacting behaviours (DEB) in migraine patients, we assessed episodic migraine patients ( n = 161, mean age 33.1 years) and headache-free control subjects ( n = 140, mean age 33.1 years) under 50 years of age in a cross-sectional, case-control study. The Japanese version of the RBD screening questionnaire was used, and subjects scoring 5 or higher were defined as having DEB. Results A significantly increased frequency of DEB was observed in migraine patients compared to controls (24.2% vs. 14.3%). Migraine patients with DEB presented higher scores on the Migraine Disability Assessment and Pittsburgh Sleep Quality Index and an increased rate of smoking compared to those without DEB. Duration of migraine and headache frequency and intensity were not different between migraine patients with or without DEB. Conclusion DEB was associated with impaired sleep and severe headache-related disability in migraine patients and may reflect brainstem dysfunction and increased brain excitability in migraine patients.

Parkinson's disease is a chronic, progressive and common disease of neurological disorders. Motor complication in parkinson's disease (PD) is resting tremor, slow movement, rigidity and postural instability. The motor symptoms of PD respond well to bilateral deep brain stimulation (DBS). Recent study, there are also reports of worsened verbal fluency, executive dysfunction, and processing speed with DBS. Whether subthalamic nuclei (STN) stimulation worsens there are under debate. The aim of this study was to explore the effects of STN stimulation verbal fluency as assessed with clinical neuropsychological tests. Eight patients treated with deep brain stimulation were enrolled, and some of the patients continued anti-PD medications. Assessments were done both with the STN stimulation turned OFF and ON. In both test conditions, the following were assessed: speech, word fluency A, and B. The score of the word fluency test of all patients have undergone DBS surgery significantly worsened as compared with before surgery. Five patients speech ware worsened, but three patients were improved when the STN stimulation was turned OFF. On the other hand, five patients were reduced the word fluency's total score when the STN stimulation was turned OFF. In this sample, STN stimulation significantly worsened the result of the word fluency test. When the STN stimulation was turned OFF, it was reduced. These finding suggests that STN-DBS might be worse speech conditions and verbal fluency.

It is well known that the migraine patients indicate abnormal information processing such as photic supersensitivity. And it is high incidence and an aggravation factor of migraine attack. In addition, it is included in the diagnostic criteria of ICHD-?. However, the underlining mechanism is still open for discussion. Our study aimed to investigate the photic driving responses of the electroencephalogram (EEG) with source localizing method. We recorded spontaneous eyes-closed resting EEG from 20 electrodes on the scalp during their inter-ictal phase. Stroboscope flashes consisting of 3–5–8–10–13–15–18–20 Hz were used. After recording, each photic stimulation was selected respectively. And we examined the relation between clinical backgrounds and the prophylaxis. In addition, we analyzed EEG by FFT and observed the frequency peaks and its topographies responded for photic stimulation. The photic driving response could be observed in higher flashing rate than 15 Hz in addition to lower flashing rate. And the case as having photic supersensitivity tended to show a lot of photic driving regardless of migraine subtypes. Moreover, in topographies, their activated areas were shifted anterior from fundamental driving to harmonic driving for each photic frequency. This anterior shift was more evident for longer duration of illness, although no significant differences between subgroups. And the global field power (GFP) value had a positive correlation between the duration of the illness. We conclude that high incidences of photic hypersensitivity and photic driving response in migraineurs were confirmed. The underlying mechanism of photic hypersensitivity might result in sensitization of limbic system.

It is known that cognitive impairments can be observed in some patients with migraine. To clarify the neurophysiological mechanism of cognitive impairments in migraine patients, we evaluated the relationships between event-related potentials (ERPs) and various behavioral data such as performance, subtype, severity, duration, and usage of preventive medicine. Thirty one patients suffering from migraine without and with aura were enrolled in headache-free periods. Severity of the headache was assessed by headache impact test-6(HIT-6). Two tones counting auditory oddball paradigm was used for the ERPs. EEG was recorded from 20 channels on the scalp and recomputed global field power (GFP) from the all channel. We assessed counting performance and the P3 GFP peak amplitude and latency. Forty four percent of patients (n=15) were classified into the good performance group. There were no differences in age, usage of prophylactic drug, the presence or absence of aura, score of HIT-6, and P3 parameters between the good and poor performance groups. The group of long duration showed decreased P3 GFP peak amplitude and HIT-6 score. The group with preventive treatment significantly had more attacks of the month than the non-medication group. In addition, this group showed prolonged P3 GFP peak latency and decreased P3 GFP peak amplitude. These findings suggest that ERPs abnormalities may reflect abnormal information-processing for the attention preceding target recognition in migraine patients regarding with preventive treatment.

We report the case of a man in his sixties with mucormycosis in whom initial cerebellar infarction progressed into pontine infarction due to basilar artery occlusion. He had received blood transfusions for myelodysplastic syndrome for 1 year and suddenly developed ataxic speech and gait disturbances. On the basis of the diagnosis of cerebellar infarction and pneumonia, he was administered antifungal medications (micafungin sodium, fosfluconazole, and amphotericin B) in addition to glycerin, after which the patient suffered from high fever associated with meningeal irritation and consciousness disturbance. Diffusion-weighted images derived from brain magnetic resonance imaging (MRI) revealed the presence of high-signal intensity lesions extending to the bilateral pons. He died of tonsillar herniation associated with brainstem edema. Autopsy revealed mucormycosis occluding and invading the basilar artery, which caused fatal brainstem infarction. This case highlights the importance of the opportunistic infection, namely, mucormycosis, which is caused by Mucor.

Background There may be a link between right-to-left shunt (RLs) and brain white matter lesions (WMLs) in patients with migraine. In this study, we assessed the relationship between WMLs and RLs in Japanese migraine patients. Methods A total of 107 consecutive patients with migraine with (MA) and without aura (MWOA) were included in this study. Contrast transcranial Doppler ultrasound was used to detect RLs. WMLs were graded using brain magnetic resonance imaging based on well-established criteria. Findings The prevalence of RLs was significantly increased in the WMLs positive group (n = 24) compared with the WMLs negative group (n = 83) (75.0% vs. 47.0%, p = 0.015). In prevalence of WMLs between MA and MWOA patients, there were no statistical differences (p = 0.410). Logistic regression analysis adjusted by age and disease duration of migraine identified an RLs-positive status as the sole determinant for the presence of WMLs (OR = 6.15; 95% CI 1.82–20.8; p = 0.003) Conclusion Our study suggests a possible link between RLs and WMLs in Japanese patients with migraine.