Improvement trend for individual health guidance intervention according to Japan clinical guidelines by public health nurses for type 2 diabetes mellitus who visited for medical checkups regularly: a case-control preliminary report.

We conducted a retrospective case-control study to assess the efficacy of personalized health guidance interventions on individuals with type 2 diabetes mellitus and obesity. A selection was made of individuals in regular visits to the Takagi Hospital for medical checkups between January 2017, and October 2021. Totally, 108 subjects (cases) with health guidance were divided into 2 groups: one group without pharmacotherapy for diabetes mellitus in medical institutions (n = 92) and another group with pharmacotherapy (n = 116). Cases were provided with personalized health guidance interventions by public health nurses for 30 min, in accordance with the Japanese clinical guidelines for the prevention of lifestyle-related diseases. Sex- and age-matched controls were chosen from individuals with diabetes mellitus without health guidance. The intervention without pharmacotherapy resulted in improvements in health indicators, including body weight, waist circumference, diastolic blood pressure, triglyceride levels, and γ-glutamyl trans-peptidase. These positive effects were not observed in the control group without health guidance. The therapeutic effects of health guidance were observed in cases where pharmacotherapy was administered. In conclusion, the implementation of individual health guidance interventions may prove to be effective for individuals with type 2 diabetes mellitus and obesity who regularly attend medical checkups.

Prevalence of adult epilepsy in a general Japanese population: The Hisayama study.

The aim of the present study was to examine the prevalence and causes of adult epilepsy in a general Japanese population. We examined a total of 3333 Japanese residents in the town of Hisayama aged ≥40 years in 2012-2013. The examination was performed mainly at the municipal center for health promotion, but some subjects were examined in their homes, hospitals, or nursing homes. Twenty-three subjects had a diagnosis of epilepsy. The prevalence (95% confidence interval [CI]) of epilepsy per 1000 was 6.9 (4.1-9.7) in total, 4.9 (1.3-8.5) in men, and 8.4 (4.3-12.5) in women (P = 0.23 between sexes). The prevalence of epilepsy was significantly higher in the elderly (aged ≥65 years; 10.3 per 1000 [95% CI 5.4-15.1]) than in the middle-aged (aged 40-64 years; 3.6 per 1000 [95% CI 0.7-6.4]; P = 0.02). The major cause of epilepsy was cerebrovascular diseases (n = 11; 48% of the epilepsy patients). More than half of the epilepsy patients experienced the first episode of seizure in older age (≥65 years; n = 13; 57%). The findings of this study suggest the clinical importance of the prevention of cerebrovascular diseases to reduce the burden of epilepsy in the future.

Outcome of vagus nerve stimulation for drug-resistant epilepsy: the first three years of a prospective Japanese registry.

Vagus nerve stimulation (VNS) is an established option of adjunctive treatment for patients with drug-resistant epilepsy, however, evidence for long-term efficacy is still limited. Studies on clinical outcomes of VNS in Asia are also limited. We report the overall outcome of a national, prospective registry that included all patients implanted in Japan. The registry included patients of all ages with all seizure types who underwent VNS implantation for drug-resistant epilepsy in the first three years after approval of VNS in 2010. The registry excluded patients who were expected to benefit from resective surgery. Efficacy analysis was assessed based on the change in frequency of all seizure types and the rate of responders. Changes in cognitive, behavioural and social status, quality of life (QOL), antiepileptic drug (AED) use, and overall AED burden were analysed as other efficacy indices. A total of 385 patients were initially registered. Efficacy analyses included data from 362 patients. Age range at the time of VNS implantation was 12 months to 72 years; 21.5% of patients were under 12 years of age and 49.7% had prior epilepsy surgery. Follow-up rate was >90%, even at 36 months. Seizure control improved over time with median seizure reduction of 25.0%, 40.9%, 53.3%, 60.0%, and 66.2%, and responder rates of 38.9%, 46.8%, 55.8%, 57.7%, and 58.8% at three, six, 12, 24, and 36 months of VNS therapy, respectively. There were no substantial changes in other indices throughout the three years of the study, except for self/family-accessed QOL which improved over time. No new safety issues were identified. Although this was not a controlled comparative study, this prospective national registry of Japanese patients with drug-resistant epilepsy, with >90% follow-up rate, indicates long-term efficacy of VNS therapy which increased over time, over a period of up to three years. The limits of such trials, in terms of AED modifications and during follow-up and difficulties in seizure counting are also discussed.

[Participation of People with Epilepsy in Sports].

People with epilepsy (PWE) have been discouraged from participating in exercise and sports because of the fear of inducing seizures or increasing seizure frequency, risks associated with such activities, stigma, and overprotection. Recently, there has been a shift in the medical recommendations toward encouraging, rather than restricting, participation. Cases of exercise-induced seizures are rare. Physical activity can exert beneficial actions, such as a reduction in seizure susceptibility and the number of seizures, improvement in quality of life (QOL), and better social integration. The antiepileptogenic and neuroprotective effects of exercise in epilepsy have been shown. The majority of sports are safe for PWE to participate in when special attention is paid to seizure control, direct supervision, etc. Human and animal studies have supported the use of exercise as a therapy for epilepsy, complementary to standard treatments. The International League Against Epilepsy (ILAE) Task Force on Sports and Epilepsy offers general guidelines concerning the participation of PWE in sports activities. Sports are divided into three categories based on the potential risk of injury or death. Engaging in physical exercise and sports activities has positive effects for PWE. The ILAE propose to use the regulations governing the issuance of fitness certificates for driving as a possible guide. The decision to participate in sports is based on whether the benefit outweighs the risk.

Internal structures of the globus pallidus in patients with Parkinson's disease: evaluation with quantitative susceptibility mapping (QSM).

OBJECTIVES: The aim of this study was to assess the susceptibility change in medial and lateral globus pallidus (GPm and GPl) related to age separately, using quantitative susceptibility mapping (QSM) and to determine whether QSM can depict GPm in Parkinson's disease (PD) patients. METHODS: QSM was performed in 19 PD patients and in 41 normal control (NC) subjects. First, we quantitatively analysed age-related changes in QSM value in NC for GPl and GPm by a manual region of interest (ROI) technique. Then, in PD patients and age-matched NC subjects, we evaluated the depiction of GPm on QSM images qualitatively. RESULTS: In NC, the QSM value within GPl significantly increased gradually with age (r = 0.32, p = 0.04), whereas it did not change with age in GPm. The average QSM value was significantly larger for GPl than for GPm (205 vs 191, p < 0.05). In both PD patients and age-matched NC, the depiction of GPm on QSM images was good in most cases (87 %, 33 of 38 sides in PD patients) mainly because of the differences in susceptibility between GPm and GPl. CONCLUSIONS: The QSM value in GPl increases gradually with age, which allows for the identification of GPm in elderly PD subjects.

[Professor Hans Otto Lüders].

Professor Lüders has made significant contributions to Clinical Neurology and particularly to Epilepsy and Clinical Neurophysiology. Some of his most important contributions include the following: 1.He pioneered the use of chronically implanted, large plates of subdural electrodes in the presurgical evaluation of patient who were candidates for epilepsy surgery. These electrodes were used to record epileptic seizures and by electrical stimulation to establish the location of eloquent cortex. Lately he has also advocated the use in the USA of stereotactically implanted depth electrodes for presurgical evaluation of epilepsy patients who had deep seated epileptic foci which were impossible to assess with subdural electrodes. These techniques were imported from Europe. 2.Mapping studies with subdural electrodes led to the discovery of a number of cortical eloquent areas that had not been described before: a. The basal temporal language area located in the dominant fusiform gyrus. b. The "negative motor areas" located in the caudal region of the inferior frontal gyrus (bilaterally) and immediately in mesial frontal pre-SMA region (also bilaterally). He concluded that these "negative motor areas" most likely correspond to praxis regions. c. The dominant posterior fusiform gyrus which plays a crucial role in processing reading material. Stimulation of that area produces "alexia without agraphia". 3.He developed a new classification of epileptic seizures based exclusively on semiological ictal characteristics. With the development of the semiological seizure classification he also defined several new seizure types: a. Dialeptic seizures, b. Hypnopompic seizures, c. Hypomotor seizures. 4.Working with general epilepsy principles, he established the existence of 6 zones that characterize the epilepsies: the epileptogenic zone, the irritative zone, the seizure onset zone, the epileptogenic lesion, the symptomatogenic zone and functional deficit zone. 5.He described the ictal DC (direct current) shift seen at the beginning of focal seizures and its value for localization of the seizure onset zone.

Proposal: different types of alteration and loss of consciousness in epilepsy.

There are at least five types of alterations of consciousness that occur during epileptic seizures: auras with illusions or hallucinations, dyscognitive seizures, epileptic delirium, dialeptic seizures, and epileptic coma. Each of these types of alterations of consciousness has a specific semiology and a distinct pathophysiologic mechanism. In this proposal we emphasize the need to clearly define each of these alterations/loss of consciousness and to apply this terminology in semiologic descriptions and classifications of epileptic seizures. The proposal is a consensus opinion of experienced epileptologists, and it is hoped that it will lead to systematic studies that will allow a scientific characterization of the different types of alterations/loss of consciousness described in this article.

[Clinical guidelines for epilepsy].

Many international guidelines for epilepsy from the countries in Europe, USA and Asia have been published since the introduction of evidence-based medicine. In Japan, the clinical guidelines for epilepsy management were published by the Japanese Society of Neurology (JSN) in 2002 and 2010. The clinical guideline for epilepsy 2010 primarily targets general practitioners treating epilepsy patients. The Japan Epilepsy Society has been publishing 16 guidelines for several topics since 2005. The clinical guideline for epilepsy 2010 recommends that carbamazepine can be regarded for new onset partial epilepsy and sodium valproate is for new onset generalized epilepsy as anti-epileptic drug (AED) monotherapy. The new AEDs received approval by the Ministry of Health, Labour and Welfare, Japan, mainly in the add-on treatment of adults with partial epilepsy. The clinical guideline for epilepsy 2010 will contribute to improvement in the management of epilepsy in Japan.

[Treatment of epilepsy in the elderly].

As the elderly constitute the most rapidly growing population, epilepsy in this group is an important health issue worldwide. We identified 70 patients who developed epilepsy after the age of 65 years at our institution. Complex partial seizures (CPS) without secondarily generalization were most frequent. The most frequent diagnosis was temporal lobe epilepsy. Etiological diagnosis was possible in nearly 50% patients, including those with cerebrovascular disease. Interictal EEG revealed focal epileptiform discharges in 66.7% of patients. Forty-two patients were on antiepileptic monotherapy and 52 patients had been seizure-free for more than 1 year. Epileptogenecity was relatively low in elderly patients and they responded well to antiepileptic medication.

Limbic encephalitis associated with anti-voltage-gated potassium channel complex antibodies as a cause of adult-onset mesial temporal lobe epilepsy.

Recently, some reports have indicated that limbic encephalitis associated with anti-voltage-gated potassium channel complex antibodies (VGKC-Ab) is a cause of adult-onset mesial temporal lobe epilepsy (MTLE). We report a 53-year-old woman who had her first epileptic seizure at the age of 50 years old. Examination by 3-Tesla brain MRI revealed left hippocampal high signal intensity and swelling on fluid-attenuated inversion recovery (FLAIR) and T2-weighted imaging at 2 months after her first seizure. The patient received intravenous methylprednisolone and carbamazepine 300 mg/day. One month later, MRI revealed improvement of her left hippocampal abnormalities. Thereafter, she had no seizures, however, three years after her first seizure, EEG revealed a seizure pattern in the left temporal region. Brain MRI revealed left hippocampal high signal intensity and brain fluorodeoxyglucose positron emission tomography revealed hypermetabolism. Her serum VGKC-Ab levels were 118 pM(normal < 100 pM). Intravenous methylprednisolone therapy was reinitiated. Two months later, her hippocampal abnormalities had improved and 3 months later her VGKC-Ab levels decreased to 4.4 pM. Remission of the epileptic seizures was also observed. This MTLE in the middle age was considered as limbic encephalitis associated with anti- VGKC-Ab. In cases of unexplained adult-onset MTLE, limbic encephalitis associated with anti-VGKC-Ab, which responds well to immunotherapy, should be considered in the differential diagnosis.

Longitudinal changes of motor cortical excitability and transcallosal inhibition after subcortical stroke.

OBJECTIVE: A general lack of longitudinal studies on interhemispheric interactions following stroke led us to use transcranial magnetic stimulation (TMS) to examine changes in corticospinal/intracortical excitability and transcallosal inhibition over a 1-year period following subcortical stroke. METHODS: We measured TMS parameters such as motor threshold (MT), short-interval intracortical inhibition (SICI), and ipsilateral silent period (iSP) and evaluated clinical scores at three time-points (T1, T2, and T3) in 24 patients and 25 age-matched healthy subjects. RESULTS: At T1, we observed reduced MTs and SICIs with prolonged iSPs in the unaffected hemisphere (UH). In contrast, increased MTs and reduced SICIs were observed in the affected hemisphere (AH). These abnormalities gradually reduced and no MEP response to TMS at T1 predicted a worse prognosis. The prolonged iSP at T1 was associated with more severe impairments, but it did not necessarily predict a worse prognosis after 1year. CONCLUSIONS: UH excitability was increased at the post-acute time-period, which may have resulted in enhanced transcallosal inhibition to the AH. However, it is unclear whether there was a causal relationship between the enhanced transcallosal inhibition and the extent of clinical recovery. SIGNIFICANCE: This is the first study to demonstrate changes in transcallosal inhibition over a longitudinal period following stroke.

Electroencephalographic features of benign adult familial myoclonic epilepsy.

OBJECTIVE: To investigate electroencephalographic (EEG) features of benign adult familial myoclonic epilepsy (BAFME). METHODS: We reviewed interictal EEG features in patients with BAFME treated between April 2005 and November 2012 at a tertiary referral center. The diagnostic criteria for BAFME were the presence of infrequent generalized tonic-clonic seizures, myoclonus or myoclonic seizures, and autosomal dominant inheritance. Interictal EEG findings of epilepsy with generalized tonic-clonic seizure only (EGTCS) were reviewed for comparison. We randomly selected 10 generalized spike/polyspike and wave complexes (GSW) for each BAFME patient and measured the duration of them. Photic stimulation and hyperventilation were performed in all. RESULTS: Nineteen (eight men, 11 women) patients with BAFME were included in this study. The mean frequency of GSW was 4.3±1.0Hz (mean±SD, n=14) in BAFME and 3.2±0.8Hz (n=10) in EGTCS. There was a statistically significant difference (p=0.008) between the two. Photoparoxysmal responses (PPR) were noted in 18 (95%) patients with BAFME but 1 (10%) with EGTCS. CONCLUSION: Faster frequency of GSW, compared with that in EGTCS, accompanied by PPR may be characteristic EEG features of BAFME. SIGNIFICANCE: These findings may lead the diagnosis of BAFME.

[Migraine and epilepsy].

Migraine and epilepsy are both common episodic disorders that share many clinical features and underlying pathophysiological mechanisms. The comorbidity of these two conditions is well known. However, the temporal association between migraine and epilepsy is a controversial issue, since these two conditions may occur in numerous ways. Four types of association between headache and epileptic seizure are recognized: pre-ictal headache, headache as the expression of an epileptic manifestation, post-ictal headache, and inter-ictal headache. The classification of epilepsy by the International League Against Epilepsy did not refer to the epileptic headache. On the other hand, the International Classification of Headache Disorders, 3rd edition (ICHD-3) defines three entities: migraine aura-triggered seizure which sometimes referred to as migralepsy, hemicrania epileptica, and post-ictal headache. However, ICHD-3 mentions that there is a complex and bidirectional association between migraine and epilepsy. Most of the previous reports of migralepsy corresponded to occipital seizures that mimic migraine with aura. The term migralepsy has recently been criticized. Migraine and epilepsy share several pathophysiological mechanisms which involve neurotransmitters and iron channel dysfunctions. There is the hypothesis of a shared genetic susceptibility to migraine and epilepsy. Strong support of a shared genetic basis comes from familial hemiplegic migraine.

[Epilepsy in the elderly].

As the elderly constitute the most rapidly growing population, epilepsy in this group is an important health issue worldwide. We surveyed the prevalence of epilepsy in two hospitals for elderly citizens in Fukuoka, Japan. The study revealed that the prevalence of epilepsy was 11.2% in 743 studied hospitalized patients. We identified 70 patients who developed epilepsy after the age of 65 years at the outpatient clinic in a university affiliated hospital. Complex partial seizures (CPS) without secondarily generalization were most frequent. The most frequent diagnosis was temporal lobe epilepsy. Etiological diagnosis was possible in nearly 50% patients, including those with cerebrovascular disease. Interictal EEG revealed focal epileptiform discharges in 66.7% of patients. Forty-two patients were on antiepileptic monotherapy and 52 patients had been seizure-free for more than 1 year. Epileptogenecity was relatively low in elderly patients and they responded well to antiepileptic medication.

[Cerebral infarction and intracranial aneurysm related to the reactivation of varicella zoster virus in a Japanese acquired immunodeficiency syndrome (AIDS) patient].

A 35-years-old right-handed man admitted to our hospital with a worsening of dysarthria, left facial palsy and left hemiparesis for 2 days. Acquired immunodeficiency syndrome (AIDS) was diagnosed when he was 28 years old. At that time, he also was treated for syphilis. After highly active antiretroviral treatment (HAART) was introduced at the age of 35 years old, serum level of human immunodeficiency virus (HIV) was not detected, but the number of CD4+ T cells was still less than 200/µl. He had no risk factors of atherosclerosis including hypertension, diabetes and hyperlipidemia. He had neither coagulation abnormality nor autoimmune disease. Magnetic resonance imaging (MRI) showed acute ischemic infarction spreading from the right corona radiate to the right internal capsule without contrast enhancement. Stenosis and occlusion of intracranial arteries were not detected by MR angiography. Although argatroban and edaravone were administered, his neurological deficits were worsened to be difficult to walk independently. Cerebrospinal fluid (CSF) examination showed a mild mononuclear pleocytosis (16/µl).　Oligoclonal band was positive. The titer of anti-varicella zoster virus (VZV) IgG antibodies was increased, that indicated VZV reactivation in the central nervous system (CNS), although VZV DNA PCR was not detected. Therefore, acyclovir (750 mg/day for 2 weeks) and valaciclovir (3,000 mg/day for 1 month) were administered in addition to stroke therapy. He recovered to be able to walk independently 2 month after the admission.Angiography uncovered a saccular aneurysm of 3 mm at the end of branch artery of right anterior cerebral artery, Heubner artery, 28 days after the admission. We speculated that VZV vasculopathy caused by VZV reactivation in CNS was involved in the pathomechanism of cerebral infarction rather than HIV vasculopathy in the case.

Clinical characteristics and treatment responses in new-onset epilepsy in the elderly.

PURPOSE: Epidemiologic studies have shown that the incidence of epilepsy is the highest in the elderly population. Because the elderly constitutes the most rapidly growing population, epilepsy in this group is an important health issue worldwide. To identify the characteristics of epilepsy in the elderly, we reviewed our experience at a tertiary referral center in Japan. METHODS: We searched all electronic medical records of the past 6 years at the epilepsy clinic of the hospital affiliated to our University-affiliated hospital. We defined an elderly person as an individual aged 65 years and above. All patients underwent history and physical examinations, 3T magnetic resonance imaging and/or computer tomography, and electroencephalogram (EEG). The diagnosis of epilepsy, age of onset, etiology, and antiepileptic medication were recorded. RESULTS: We identified 70 patients who developed epilepsy after the age of 65 years. The mean age of seizure onset was 73.1 years and 52.9% patients were males. Complex partial seizures (CPS) without secondarily generalization (n=33, 47.1%) were most frequent. The most frequent diagnosis was temporal lobe epilepsy (n=50, 71.4%). Etiological diagnosis was possible in nearly 50% patients, including those with cerebrovascular disease. A clear cause of epilepsy was not found (i.e., non-lesional epilepsy) in 52.8% patients. Interictal EEG revealed focal epileptiform discharges in 72.9% (n=51) patients. Of the 54 patients who were followed more than 1 year, 42 patients (77.8%) were on antiepileptic monotherapy and 52 patients (96.3%) had been seizure-free for more than 1 year. CONCLUSION: The most frequent diagnosis in our cohort of elderly persons with new-onset epilepsy was temporal lobe epilepsy. Non-lesional temporal lobe epilepsy was not uncommon. Epileptogenecity was relatively low in elderly patients and they responded well to antiepileptic medication.

A more realistic approach, using dynamic stimuli, to test facial emotion recognition impairment in temporal lobe epilepsy.

To explore potentially impaired social functioning in patients with mesial temporal lobe epilepsy (MTLE), we evaluated facial emotion recognition (FER) using dynamic facial stimuli. We evaluated FER in 88 patients with MTLE, including 25 posttemporal lobectomy (PTL) patients, when they watched videos of actors expressing the six basic emotions of happiness, sadness, anger, fear, surprise, and disgust. Thirty-two healthy subjects were examined as controls. The relationships between task, performance, and neurophysiological and radiological variables potentially affecting the ability to recognize moving facial emotions were examined by multivariate analysis. Both the patients with MTLE and the PTL subset demonstrated significantly impaired FER compared with healthy controls. Of the six emotions, they showed impaired recognition of sadness, fear, and disgust. Facial emotion recognition was impaired in patients with chronic MTLE, particularly those with bilateral damage. Failure to recognize emotional expressions, particularly fear, disgust, and sadness, may contribute to difficulties in social functioning and relationship building.