The right amygdala and migraine: Analyzing volume reduction and its relationship with symptom severity.

This study aimed to explore the relationship between gray matter volume changes and various clinical parameters in patients with migraine, focusing on symptom severity, quality of life, and states of depression and anxiety. Using a case-control design, we examined 33 patients with migraine, with or without aura, and 27 age-matched healthy subjects. We used magnetic resonance imaging to assess the volumes of 140 bilateral brain regions. Clinical evaluations included the Migraine Disability Assessment, the Migraine Specific Quality of Life Questionnaire, the Center for Epidemiologic Studies Depression scale, Spielberger's State and Trait Anxiety scales, and the Japanese version of the Montreal Cognitive Assessment. We compared the scores of these measures between migraine patients and healthy controls to examine the interplay between brain structure and clinical symptoms. Significant volumetric differences were observed in the pallidum and amygdala between migraine patients and healthy individuals. The reduction in the right amygdala volume correlated significantly with migraine severity as measured by the Migraine Disability Assessment. Path analysis revealed a model where Migraine Disability Assessment scores were influenced by Migraine Specific Quality of Life Questionnaire outcomes, which were further affected by depression, anxiety, and a low right pallidum volume. Our findings suggest that the chronicity and severity of migraine headaches specifically affect the right amygdala. Our path model suggests a complex relationship whereby migraine disability is strongly influenced by quality of life, which is, in turn, affected by psychological states, such as anxiety and depression.

White Matter Lesions May Aid in Differentiating Idiopathic Normal Pressure Hydrocephalus and Alzheimer's Disease.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is often misdiagnosed as Alzheimer's disease (AD) due to overlapping pathophysiology and similar imaging characteristics, including ventricular enlargement and increased white matter lesions (WMLs). OBJECTIVE: To compare the extent and distribution of WMLs directly between iNPH and AD and examine the association with underlying pathophysiology. METHODS: Twelve patients with iNPH (mean age: 78.08 years; 5 females), 20 with AD (mean age: 75.40 years; 13 females), and 10 normal cognition (NC) participants (mean age: 76.60 years; 7 females) were recruited. The extent and distribution of WMLs and the lateral ventricular volume (LV-V) were evaluated on MRI using voxel-based morphometry analysis. Concentrations of cerebrospinal fluid biomarkers, such as amyloid-ß protein (Aß)42, Aß40, Aß38, and tau species, were also measured. Risk factors for small vessel disease (SVD) were assessed by blood examination and medical records. RESULTS: The periventricular WML volume (PWML-V) and deep WML volume (DWML-V) were significantly larger in iNPH than in AD and NC. The DWML-V was dominant in iNPH, while the PWML-V was dominant in AD and NC. GM-V was significantly smaller in AD than in iNPH and NC. The LV-V positively correlated with WML-V in all participants. There was a significant negative correlation between LV-V and Aß38 in iNPH. Furthermore, there was no significant difference in SVD risk factors between the groups. CONCLUSION: The differences in the extent and distribution of WMLs between iNPH and AD, especially predominance of DWML-V over PWML-V in iNPH, may reflect decreased fluid and Aß clearance.

Serum BDNF as a Potential Biomarker of Alzheimer's Disease: Verification Through Assessment of Serum, Cerebrospinal Fluid, and Medial Temporal Lobe Atrophy.

There is an urgent need to establish blood biomarkers for Alzheimer's disease (AD). Although it has been speculated that brain-derived neurotrophic factor (BDNF) is associated with AD, whether it can be used as a blood biomarker has yet to be determined. We used serum, cerebrospinal fluid (CSF), and medial temporal lobe atrophy from patients with AD to evaluate the association of BDNF with AD and assess its severity. For the blood analysis, 66 participants [21 normal controls (NCs) with normal cognitive function, 22 patients with mild cognitive impairment (MCI) due to AD, and 23 patients with AD] were included. For the CSF analysis, 30 participants were included. Magnetic resonance imaging, including a voxel-based specific regional analysis system for AD, and a Mini Mental State Examination were performed. Serum levels of BDNF and CSF levels of amyloid-ß42, total tau, and phosphorylated tau were measured using ELISA. Serum BDNF levels were significantly lower in the MCI due to AD group than in the NC group (p = 0.037). Although there was no significant difference in the AD group, there was a downward trend compared to the NC group. Serum BDNF levels were positively correlated with CSF Aß42 levels (r = 0.49, p = 0.005). There was a significant correlation between serum BDNF levels and medial temporal lobe atrophy. Decreased serum BDNF can potentially be used as a biomarker for early AD detection. Early detection of AD with a less invasive blood test is very beneficial, as it allows for intervention before dementia progresses.

Sex Differences in the Relationship of Serum Vitamin B1 and B12 to Dementia Among Memory Clinic Outpatients in Japan.

Dementia and cognitive impairment are considered to be one of the biggest social and medical problems. While there is a definite relationship between vitamin B and cognitive decline, this has yet to be fully assessed with regard to sex differences. Thus, the present study investigated the relationship of vitamin B1 or vitamin B12 with dementia in accordance with the sex in 188 patients who visited the Memory Clinic at Showa University Hospital in Japan from March 2016 to March 2019. Cognitive function was tested by the Japanese version of the Mini-Mental State Examination (MMSE) and Hasegawa Dementia Scale-Revised (HDS-R). Blood tests were performed to measure the vitamin levels. Logistic regression analysis was used to calculate the odds ratio (OR) for dementia and the 95% confidence interval (CI). Compared to the highest vitamin group (third tertile), the lowest vitamin group (first tertile) exhibited a significantly increased OR for dementia defined by MMSE for vitamin B1 (OR:3.73, 95% CI:1.52-9.16) and vitamin B12 (2.97, 1.22-7.28) among women. In contrast, vitamin levels were not significantly associated with dementia determined by MMSE in men. These findings were similar even when dementia was defined by HDS-R. The present study suggests that vitamin B1 plays a role in preventing development of dementia in women. Future longitudinal studies will need to be undertaken in order to examine whether decreasing vitamin levels occur before or after cognitive impairment, and whether maintaining a higher vitamin level can prevent a worsening of cognitive function and the development of dementia.

Toxic Amyloid-ß42 Conformer May Accelerate the Onset of Alzheimer's Disease in the Preclinical Stage.

BACKGROUND: Toxic amyloid-ß protein (Aß) conformers play an important role in the progression of Alzheimer's disease (AD). The ratio of toxic conformer to total Aß42 in cerebrospinal fluid (CSF) was significantly high in AD and mild cognitive impairment (MCI) due to AD using an enzyme-linked immunosorbent assay kit with a 24B3 antibody. OBJECTIVE: We compared the toxic Aß42, conformer at different stages of AD to identify its contribution to AD pathogenesis. METHODS: We compared 5 patients with preclinical AD, 11 patients with MCI due to AD, 21 patients with AD, and 5 healthy controls to measure CSF levels of total Aß42, total tau, tau phosphorylated at threonine 181 (p-tau), and toxic Aß conformers. All were classified using the Clinical Dementia Rating. Cognitive function was assessed using the Japanese version of the Mini-Mental State Examination (MMSE-J). RESULTS: Toxic Aß conformer level was insignificant between groups, but its ratio to Aß42 was significantly higher in AD than in preclinical AD (p < 0.05). Toxic Aß42 conformer correlated positively with p-tau (r = 0.67, p < 0.01) and p-tau correlated negatively with MMSE-J (r = -0.38, p < 0.05). CONCLUSION: Toxic Aß conformer triggers tau accumulation leading to neuronal impairment in AD pathogenesis.

Cingulate Island Sign in Single Photon Emission Computed Tomography: Clinical Biomarker Correlations in Lewy Body Disease and Alzheimer's Disease.

We compared 'CIScore' determined by quantitative single photon emission computed tomography studies of the cingulate island sign to cerebrospinal fluid (CSF) biomarkers in Lewy body disease (LBD) and Alzheimer's disease (AD) to assess its usefulness and pathological background. Among the 16 each age-matched LBD and AD patients, the CIScore differed significantly but was not correlated with CSF biomarkers. In LBD, hippocampal atrophy significantly correlated with Clinical Dementia Rating and CSF p-tau and t-tau levels. Our results showed CIS was not related to CSF biomarkers in LBD and high CSF tau levels were related to clinical disease severity and hippocampal atrophy.

Prognostic evaluation of branch atheromatous disease in the pons using carotid artery ultrasonography.

BACKGROUND: Branch atheromatous disease is an ischemic stroke, involving occlusion or severe stenosis of the perforating artery, causing neurologic symptoms and serious sequelae. We aimed to investigate initial morphometric and hemodynamic characteristics of the vertebral artery immediately post-onset to predict lesion expanding. METHODS: This case-control study collected demographic, historical, and physical examination data from 44 patients with branch atheromatous disease in the pons at admission. The maximum ischemic pons area and stenosis rate in the basilar artery were calculated using magnetic resonance images. Diameter, velocity, and flow volume of the vertebral arteries were measured using carotid artery ultrasonography. Correlations between ischemic lesion extent and these parameters were investigated. RESULTS: Patients were assigned to groups of less (Group 1) or more (Group 2) than the median maximum ischemic area in the pons, calculated from magnetic resonance images (121.6 mm2). Modified Rankin scale scores were significantly worse in Group 2. Blood pressure and blood findings were similar between groups. Group 2 showed significantly higher basilar artery stenosis rates. Flow volume, velocity, peak systolic velocity, and end-diastolic velocity in the vertebral artery on both sides were significantly decreased in Group 2. CONCLUSIONS: Deteriorated vertebral artery hemodynamics caused a more extensive ischemic lesion in branch atheromatous disease in the pons. Evaluation of the vertebral using carotid artery ultrasonography in the acute phase may be useful for predicting disease progression.

[Therapeutic Effects of Intranasal Sumatriptan for Cluster Headache].

To clarify the associated factors for negative response to sumatriptan nasal spray in patients with cluster headache, we investigated the involvement of clinical information, such as the characteristics of headaches, before commencing sumatriptan nasal spray treatment. There were 18 male patients and 4 female patients. A total of 17 responders and 5 non-responders to sumatriptan nasal spray participated in the present study. Three factors for negative response to sumatriptan nasal spray, "young age of onset", "psychiatric disorder", and "the headache is not in the orbit," were found. Oxygen inhalation and/or subcutaneous injection were effective for nonresponsive cases. Therefore, these factors are considered to be useful for predicting therapy before applying sumatriptan nasal spray.

Efforts by Pharmacists in Community Pharmacy in Peacetime for Headache Medical Care in Emergencies, Such as Great Earthquake and Disaster.

We herein analyzed the issues that pharmacists in a community pharmacy in peacetime need to prepare for regarding headache medical care in emergencies (the state that supply of medical supplies is difficult) using a questionnaire intended for doctors and pharmacists in a community pharmacy. Recovery rates were 48.0% (96/200) for doctors and 37.3% (112/300) for pharmacists. In order to distinguish between patients for whom pharmacists need to "recommend OTC drugs" and those who need to be encouraged "to consult a hospital or clinic", doctors indicated that pharmacists need to use an "assistance tool to diagnosis headaches, such as a migraine screener" and "guidelines for chronic headaches". However, few pharmacists used these tools. Approximately 66.7% of doctors indicated that it is "meaningful" for pharmacists to distinguish patients with headaches. Moreover, doctors indicated the need for guidance by pharmacists in peacetime regarding headache medical care in emergencies. Although 73.2% of pharmacists instructed the patients with headaches of the importance of medication notebooks in emergencies, guidance ("understanding the triggers of headaches", "understanding the importance of removing the cause of the headache", "standing OTC drugs" and "standing prescription drugs") by pharmacists to prepare for an emergency was insufficient. These results provide useful information to improve the efforts by pharmacists in community pharmacies in peacetime for headache medical care in emergencies.

False-positive results obtained for immunoglobulin M antibody tests of cerebrospinal fluid for herpes simplex virus in a patient with varicella zoster virus encephalitis.

A 66-year-old man presented with a disturbed consciousness and seizure-like movements, followed by the initial symptoms of herpes zoster. Immunoglobulin (Ig) M antibodies to varicella zoster virus (VZV) as well as herpes simplex virus (HSV) were positive in the cerebrospinal fluid (CSF), whereas polymerase chain reaction of the CSF was positive for VZV-DNA but negative for HSV-DNA. The serum/CSF IgM ratio for VZV and HSV increased in association with a clinical improvement. This is a case report of a rare case of VZV encephalitis demonstrating false-positive results for IgM to HSV in the CSF. The increase in the serum/CSF IgM ratio possibly reflects a recovery from blood-brain barrier breakdown.

[A case of migraine presenting with thunderclap headache associated with posterior reversible encephalopathy syndrome].

We report a 47-year-old woman who developed a thunderclap headache. Head axial, fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR MRI) revealed high signal lesions in the left occipital and right parietal lobes. Apparent diffusion coefficient mapping showed a vasogenic edema pattern. Upon admission, the patient's blood pressure was normal and the neurological examination was unremarkable. As thunderclap headaches are associated with a repeated rise in blood pressure, we considered cerebral vasoconstriction and administered a calcium channel blocker. Thereafter, her headache with high blood pressure eased significantly and the high signal lesions on FLAIR MRI disappeared. We diagnosed the condition as posterior reversible encephalopathy syndrome (PRES). In addition, head magnetic resonance angiogram showed vasoconstriction of the right anterior cerebral artery, left middle cerebral artery, and bilateral posterior cerebral artery. Calcium channel blocker use was continued and vasoconstriction improved by day 70. In this case, the presenting symptom was thunderclap headache, which is a characteristic feature of reversible cerebral vasoconstriction syndrome (RCVS). Therefore, PRES may be caused by RCVS.

[Relationship between callosal lesions and cerebral microhemorrhage in Marchiafava-Bignami disease].

Marchiafava-Bignami disease is a rare alcohol-associated disorder. Clinical features include not only disturbed consciousness, dysarthria, tetraparesis, and astasia-abasia as initial symptom but also cognitive deficits and symptoms of interhemispheric disconnection as clinical outcomes. The clinical significance of cerebral microhemorrhage has been recognized in patients with cognitive deficits. We have recently examined the clinical significance of cerebral microhemorrhage in Marchiafava-Bignami disease and demonstrated that demented patients showed higher severity of cerebral microhemorrhage than patients with normal cognitive function. However, the relationship between callosal lesions and cerebral microhemorrhage in Marchiafava-Bignami disease has not been fully examined. The aim of the present study was to clarify the relationship between callosal lesions and cerebral microhemorrhage in Marchiafava-Bignami disease. For this purpose, we report four patients with Marchiafava-Bignami disease. All cases had a history of chronic alcohol abuse and symmetrical lesions in the corpus callosum. Clinical symptoms include not only coma, dysarthria, and astasia-abasia as initial symptom but also dementia as clinical outcomes. Susceptibility-weighted imaging showed asymmetrical hypointense areas in the multiple cortico-subcortical regions, indicating the presence of cerebral microhemorrhage. There were no apparent relationships between the extension of callosal lesion and the severity of cognitive deficits or cerebral microhemorrhage. Our present report indicates that cerebral microhemorrhage, an important. factor for the severity of dementia in Marchiafava-Bignami disease as clinical outcomes, is independent of the callosal lesion.

Tryptophan hydroxylase 2 gene polymorphisms in Japanese patients with medication overuse headaches.

PURPOSE: We investigated whether tryptophan hydroxylase 2 (TPH2) gene polymorphisms were involved in the aggravation of migraines due to the overuse of medication. METHODS: Forty-seven migraine patients (6 males and 41 females; 36.4 10.3 years) and 22 MOH patients (1 male and 21 females; 39.6 9.9 years) who had migraines participated in this study. The genotypes for the TPH2 gene polymorphisms (rs4565946, rs4570625, and rs4341581) were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. RESULTS: The rs4565946, rs4570625, and rs4341581 genotypes were similarly distributed between migraine patients and MOH patients. CONCLUSION: The results of this study showed no association between tryptophan TPH2 gene polymorphisms and the complication of MOH in patients with migraines.

Association between the G252A Tumor Necrosis Factor-ß Gene Polymorphism and Medication-Overuse Headache.

BACKGROUND AND PURPOSE: Migraine patients are particularly prone to the complication of medication-overuse headache (MOH). Although it has been shown that A allele carriers for the tumor necrosis factor (TNF)-ß gene G252A polymorphism are at high risk of the development of migraine without aura, the relationship between the TNF-ß gene G252A polymorphism and MOH is unknown. We investigated whether the TNF-ß gene G252A polymorphism is involved in the aggravation of migraine by overuse of medications. METHODS: Forty-seven migraine patients (6 males and 41 females; age 36.4±10.3 years, mean±SD) and 22 MOH patients (1 male and 21 females; age 39.6±9.9 years) who had migraine were included in this study. The genotype for the TNF-ß gene G252A polymorphism was determined by polymerase-chain-reaction restriction-fragment-length polymorphism analysis. RESULTS: The distribution of TNF-ß gene G252A genotype frequency differed significantly between migraine and MOH patients (p=0.013). The G/G genotype was carried by 23% of the migraine patients but it was absent in MOH patients. CONCLUSIONS: G/G genotype carriers appear to be less susceptible to the aggravation of migraine by overuse of medications. The G252A TNF-ß gene polymorphism may be one of the factors contributing to the complications of MOH in patients with migraine.

Sharing breathlessness: investigating respiratory change during observation of breath-holding in another.

Studies of empathy show that seeing another person in pain, fear or disgust elicits the same brain activations associated with pain, fear or disgust in oneself. Our interest is to know whether respiratory change can be observed in empathy, that is, whether respiration can be altered when observing emotions in others. A discomfort associated with respiration can be breathlessness. We investigated respiratory pattern and metabolic response during observation of a breath-holding subject. We found that breathlessness occurred in participants who observed breath-holding in another person. It is interesting to note that observers felt more breathlessness after breath-holding ended with an increase in respiratory rate consistent with the breath-holder's respiratory pattern. In addition, observers with high trait anxiety felt more breathlessness accompanied with an increase in respiratory rate. An increase in respiratory rate may be involved in the perception of breathlessness, in addition to the effect of observing breath-holding, indicating shared negative emotion.

Impairment of odor recognition and odor-induced emotions in type 1 myotonic dystrophy.

This study aimed to test whether type 1 myotonic dystrophy (DM1) patients who have a lower sensitivity to emotional facial expressions have an abnormal olfactory threshold or recognition level. We measured DM1 patients' performances in an olfactory acuity test and respiratory responses to odor stimuli, and compared their results to those of healthy controls (HCs). We found that DM1 patients exhibited a significantly reduced odor detection sensitivity compared with that in HCs. Three out of seven DM1 patients exhibited impaired odor recognition, while other four patients had significantly lower odor recognition compared with HCs. Even when patients were able to identify the type of odor, the levels of pleasantness they reported experiencing in response to a pleasant odor were significantly lower than those reported by HCs. These subjective data in DM1 patients were reflected in the respiratory responses (RRs). In the current study, one patient showed impairments in both odor detection and odor recognition. Abnormalities of the olfactory limbic areas might have been the cause of the olfactory impairments observed in the DM1 patients.