Public awareness and experiences associated with epilepsy in Japan, 2013-2017.

BACKGROUND: Public attitudes and stigma toward epilepsy may limit people with epilepsy (PWE) in seeking treatment and participating in social activities. The prevalence of epilepsy is approximately 0.8% in Japan, similar to rates reported in other countries. Although epilepsy is relatively common, few studies have investigated public awareness about epilepsy in Japan. Recently, several serious car accidents in Japan involving PWE resulted in pedestrian fatalities. Traffic accidents involving PWE have been reported extensively and repeatedly in the media since 2011. In 2013 and 2017, our research group conducted a large investigation of awareness about epilepsy targeting the general public. Previous studies have reported that knowledge is one of the factors involved in improving attitudes and reducing stigma. The aim of the current study was to compare survey results, especially regarding knowledge of epilepsy, and capture changes in public awareness between 2013 and 2017. METHODS: A total of 2160 people (1080 in each year) participated, with a total of 540 women in each year, aged 20-79 years. Participants lived in the greater Tokyo area as well as the Tohoku and Kansai regions of Japan. All participants answered survey questions online in January 2013 and April 2017. We analyzed five questions regarding the participants' demographic data, nine questions regarding knowledge about epilepsy, and five questions regarding experiences with epilepsy. For questions investigating the respondents' knowledge about epilepsy, we counted only the correct answers and scored these for each respondent. RESULTS: Knowledge scores decreased from 2013 to 2017, demonstrated by statistical analysis. However, the effect size was very small. Knowledge scores among the following groups were higher in both 2013 and 2017: people who had read or heard about epilepsy, those who had witnessed people having an epileptic seizure, people who had acquaintances who were PWE, those who had PWE in their family, and people who had studied medicine or worked in a medical profession. CONCLUSION: We revealed that participants who had some experience with epilepsy had higher knowledge levels in both 2013 and 2017. This suggests that such experiences could be important for motivating people to seek appropriate and accurate knowledge about epilepsy, and could result in a reduction of stigma. Greater awareness is needed among the general public in Japan about various aspects of epilepsy.

Longitudinal investigation into implicit stigma of epilepsy among Japanese medical students before and after mass media coverage of car accidents associated with people with epilepsy.

OBJECTIVE: Public attitudes and stigma toward epilepsy may limit patient motivation for treatment and participation in social activities. Stigma research requiring individuals to report personal beliefs is useful but is subject to social desirability bias. Self-reporting methods often do not capture implicit attitudes; therefore, in this study, implicit stigma was measured using the implicit association test (IAT), which is a word sorting task to minimize this bias. Recently, in Japan, several serious car accidents caused by people with epilepsy (PWE) resulted in pedestrian fatalities. Traffic accidents involving PWE have been reported extensively and repeatedly in the media since 2011. The present study aimed to examine differences in implicit stigma toward epilepsy among medical students in 2010, 2013, and 2016. METHODS: We recruited 41 medical students in 2010, 44 medical students in 2013 and 42 medical students in 2016. We investigated the strength of conceptual associations between the words "Epilepsy" or "Hypertension", and "Safety" or "Danger" in the IAT. RESULTS: The association between the words "Epilepsy" and "Danger" was stronger in 2013 compared with that in 2010; however, the association was weaker in 2016 compared with that in 2013. There was no significant difference between 2010 and 2016. CONCLUSION: The change in IAT results between 2010 and 2013 might be due to the traffic accident involving PWE in Japan. However, the result in 2016 might indicate that the implicit attitudes toward epilepsy were improved to the same level as those in 2010.

Assessment of vascular autonomic function using peripheral arterial tonometry.

Peripheral autonomic function is impaired in diabetic polyneuropathy. However, it is difficult to evaluate it due to the lack of non-invasive quantitative assessment. We aimed to establish a novel index to evaluate vascular autonomic function using reactive hyperemia peripheral arterial tonometry (RH-PAT), a widely performed endothelial function test. Sixty-five subjects were enrolled, including healthy subjects, cases with sympathetic nerve blockers, and diabetic patients. RH-PAT was performed with 5-min blood flow occlusion in unilateral arm. We calculated the reduction ratio of the post-occlusion pulse amplitude to the baseline in the non-occluded arm (RPN), with 1-min sliding window. In healthy subjects, RPN gradually increased with time-dependent manner. However, this phenomenon was eliminated in cases with sympathetic nerve blockers. Plasma concentration of norepinephrine was measured before and after the blood flow occlusion, which showed a significant increase. We then compared RPNs with the change in heart rate variability (HRV) parameters. RPN calculated at 5 min after the reperfusion had the highest correlation with the change in sympathetic HRV parameter, and thus, we named sympathetic hypoemia index (SHI). Finally, we studied the relationship between SHI and diabetes. SHI was significantly lower in diabetic patients than matched controls. SHI, a novel index derived from RH-PAT, represented the peripheral sympathetic activity. SHI may be useful for assessing the vascular autonomic activity in diabetic patients.

Can anti-AQP4 antibody damage the blood-brain barrier?

BACKGROUND: Aquaporin 4 (AQP4) is a water-channel protein predominantly expressed in astrocyte end feet that make up the blood-brain barrier (BBB). Recently, anti-AQP4 antibody has been identified as a specific biomarker of neuromyelitis optica (NMO). However, whether anti-AQP4 antibodies damage the BBB is unclear. METHODS: We evaluated BBB damage in patients with NMO and multiple sclerosis by measuring albumin leakage (AL) and studied its correlation with anti-AQP4 antibody. RESULTS: No obvious difference in AL was observed between patients with and without anti-AQP4 antibodies. In the multivariate analysis, anti-AQP4 antibody was not associated with BBB damage. Of the anti-AQP4-positive patients, 58.0% had normal AL values, and the degree of BBB damage was unrelated to the anti-AQP4 antibody titer. In addition, 41.9% of anti-AQP4-positive patients showed no gadolinium enhancement of the MRI. CONCLUSION: These results indicate that the presence of anti-AQP4 antibody alone in plasma is insufficient to disrupt the BBB.

Detailed magnetoelectric analysis of a nerve impulse propagation along the brachial plexus.

OBJECTIVE: To visualize impulse conduction along the brachial plexus through simultaneous electromagnetic measurements. METHODS: Neuromagnetic fields following median nerve stimulation were recorded above the clavicle with a superconducting quantum interference device biomagnetometer system in 7 healthy volunteers. Compound nerve action potentials (CNAPs) were obtained from 12 locations. Pseudocolor maps of equivalent currents reconstructed from magnetic fields and isopotential contour maps were superimposed onto X-ray images. Surface potentials and current waveforms at virtual electrodes along the brachial plexus were compared. RESULTS: In magnetic field analysis, the leading axonal current followed by a trailing backward current traveled rostrally along the brachial plexus. The spatial extent of the longitudinal intra-axonal currents corresponded to the extent of the positive-negative-positive potential field reflecting transmembrane volume currents. The peaks and troughs of the intra-axonal biphasic current waveforms coincided with the zero-crossings of triphasic CNAP waveforms. The amplitudes of CNAPs and current moments were linearly correlated. CONCLUSIONS: Reconstructed neural activity in magnetic field analysis visualizes not only intra-axonal currents, but also transmembrane volume currents, which are in good agreement with the surface potential field. SIGNIFICANCE: Magnetoneurography is a novel non-invasive functional imaging modality for the brachial plexus whose performance can surpass that of electric potential measurement.

Specific electroencephalogram features in the very early phases of sporadic Creutzfeldt-Jakob disease.

Studies on the very early electroencephalography (EEG) features prior to the emergence of generalized periodic discharges (GPDs, generally known as periodic sharp-wave complexes) in Creutzfeldt-Jakob disease (CJD) are rare. Fourteen patients with sporadic CJD (sCJD) (eight with MM1/classic and six with MM2c) were included in this study. The predominant findings of the first EEG were categorized as 1) lateralized periodic discharges (LPDs), 2) central sagittal sporadic epileptiform discharges (CSSEDs) showing midline predominant generalized spike-and-wave complexes and/or sharp waves in the central sagittal regions, or 3) focal epileptiform discharges. Clinical records, magnetic resonance imaging (MRI), and changes in EEG were compared between three groups (LPD in MM1/classic, CSSED in MM1/classic, and focal epileptiform discharge in MM2c). Three (37.5%) and five (62.5%) patients with MM1/classic sCJD were classified into the LPD and CSSED groups, respectively. Patients in the LPD group were accompanied by cortical hyperintensities at the corresponding areas on MRI, while those in the CSSED group showed hyperintensities on MRI at unassociated cortical areas. Follow-up EEG of three (100%) patients in the LPD group and four (80%) in the CSSED group showed transitions to GPDs. All patients with MM1/classic sCJD showed myoclonus on initial EEG, and the symptomatic side was opposite to the hemisphere showing LPDs or higher-amplitude central sagittal epileptiform activity. The periodicity after these EEGs likely contributes to the diagnostic confidence of physicians when patients are in the very early stages of MM1/classic sCJD.

Assessing carpal tunnel syndrome with magnetoneurography.

OBJECTIVE: To measure the neuromagnetic fields of carpal tunnel syndrome patients after electrical digital nerve stimulation and evaluate median nerve function with high spatial resolution. METHODS: A superconducting quantum interference device magnetometer system was used to record neuromagnetic fields at the carpal tunnel after electrical stimulation of the middle digital nerve in 10 hands of nine patients with carpal tunnel syndrome. The patients were diagnosed based on symptoms (numbness, tingling, and pain) supported by a positive Phalen or Tinel sign. A novel technique was applied to remove stimulus-induced artifacts, and current distributions were calculated using a spatial filter algorithm and superimposed on X-ray. RESULTS: In 6 of the 10 hands, the amplitude of the inward current waveform attenuated to <70% or the nerve conduction velocity was <40 m/s. The results of conventional nerve conduction studies were normal for two of these six hands. All four hands that could not be diagnosed by magnetoneurography had severe carpal tunnel syndrome superimposed on peripheral neuropathy secondary to comorbidities. CONCLUSIONS: Technical improvements enabled magnetoneurography to noninvasively visualize the electrophysiological nerve activity in carpal tunnel syndrome patients. SIGNIFICANCE: Magnetoneurography may have the potential to contribute to the detailed diagnosis of various peripheral nerve disorders.

Motor nerve conduction study in cauda equina with high-voltage electrical stimulation in multifocal motor neuropathy and amyotrophic lateral sclerosis.

In this study we aim to establish a motor nerve conduction study (NCS) for the cauda equina and examine its usefulness in multifocal motor neuropathy (MMN) and amyotrophic lateral sclerosis (ALS). NCS of the tibial nerve proximal to the knee was performed with an optimized high-voltage electrical stimulation (HV-ES) method in 21 normal subjects, 5 with MMN, and 11 with ALS. HV-ES, but not magnetic stimulation, could supramaximally stimulate the cauda equina. Cauda equina motor conduction time determined by HV-ES, but not that with F-waves, correlated well with cauda equina length on magnetic resonance imaging. HV-ES revealed proximal lesions in 4 MMN patients but in none of the ALS patients. Importantly, 1 patient with "MMN without conduction block (CB)" had a CB in the cauda equina. Cauda equina motor conduction is better evaluated by HV-ES than with F-wave study or magnetic stimulation. HV-ES can help to distinguish MMN and "MMN without CB" from ALS.

Sacral dural arteriovenous fistula mimicking multiple mononeuropathy.

A sacral dural arteriovenous fistula (dAVF) is extremely rare, and the pathophysiological and clinical features have not been established. A 70-year-old man developed gradually progressive right-dominant bilateral sensory disorder of the lower limbs. His clinical course and electrophysiological findings were similar to those of multiple mononeuropathy. However, angiography showed a sacral dAVF at the right intervertebral foramen between the fifth lumbar and first sacral vertebrae. Endovascular embolization of the dAVF improved his clinical symptoms and electrophysiological findings. A sacral dAVF can mimic multiple mononeuropathy in terms of its clinical features and electrophysiological findings. A sacral dAVF is a treatable disease and should be considered as a differential diagnosis of lower extremity disorders.

Noninvasive measurement of sensory action currents in the cervical cord by magnetospinography.

OBJECTIVE: To obtain magnetic recordings of electrical activities in the cervical cord and visualize sensory action currents of the dorsal column, intervertebral foramen, and dorsal horn. METHODS: Neuromagnetic fields were measured at the neck surface upon median nerve stimulation at the wrist using a magnetospinography system with high-sensitivity superconducting quantum interference device sensors. Somatosensory evoked potentials (SEPs) were also recorded. Evoked electrical currents were reconstructed by recursive null-steering beamformer and superimposed on cervical X-ray images. RESULTS: Estimated electrical currents perpendicular to the cervical cord ascended sequentially. Their peak latency at C5 and N11 peak latency of SEP were well-correlated in all 16 participants (r = 0.94, p < 0.0001). Trailing axonal currents in the intervertebral foramens were estimated in 10 participants. Estimated dorsal-ventral electrical currents were obtained within the spinal canal at C5. Current density peak latency significantly correlated with cervical N13-P13 peak latency of SEPs in 13 participants (r = 0.97, p < 0.0001). CONCLUSIONS: Magnetospinography shows excellent spatial and temporal resolution after median nerve stimulation and can identify the spinal root entry level, calculate the dorsal column conduction velocity, and analyze segmental dorsal horn activity. SIGNIFICANCE: This approach is useful for functional electrophysiological diagnosis of somatosensory pathways.

Distribution of Deep Gray Matter Lesions on Magnetic Resonance Imaging in Lymphomatosis Cerebri.

We herein report the distribution of gray matter lesions on magnetic resonance imaging (MRI) in two patients with lymphomatosis cerebri (LC). In our patients, the fluid-attenuated inversion recovery sequence of brain MRI demonstrated a bilateral and diffuse high signal intensity, not only in the white matter but also in the thalamus, globus pallidus, putamen, and hippocampus. Among the deep gray matter, the caudate head and putamen (striatum) were relatively spared when compared with the globus pallidus, thalamus, and hippocampus. Interestingly, we found seven previous reports of similar MRI findings, with relative sparing of the striatum, in patients with LC. This finding may be characteristic of LC and help facilitate its diagnosis. Further investigations of a larger number of LC patients are necessary to confirm these findings.

Focal sharp waves are a specific early-stage marker of the MM2-cortical form of sporadic Creutzfeldt-Jakob disease.

Periodic sharp wave complexes (PSWCs), identified using electroencephalography, are observed in less than half of patients with the methionine homozygosity type 2 cortical (MM2c) form of sporadic Creutzfeldt-Jakob disease (sCJD), and only at a later stage of the disease. In this study, we identified early and specific markers on the electroencephalograms (EEGs) of patients with MM2c-sCJD. We retrospectively investigated the clinical records, EEGs, and magnetic resonance imaging (MRI) scans of patients diagnosed with sCJD and compared the EEG findings of MM2c-sCJD and MM1/classic sCJD groups. The records of six patients with MM2c-sCJD and eight with MM1/classic sCJD were included. The median ages of onset in the MM2c- and MM1/classic sCJD groups were 75.0 (range, 60-83) and 72.5 (range, 51-74) years, respectively, and the average durations between disease onset and the first EEG were 9.17 (range, 4-15) and 1.88 (range, 1-4) months, respectively. Focal sharp waves and/or focal spike-and-wave complexes in the brain regions corresponding with cortical hyperintensities on MRI scans were identified on the EEGs of patients with MM2c-sCJD in the early stages of disease progression. In contrast, EEGs of patients in the early stages of MM1/classic sCJD showed lateralized or generalized diffuse sharp waves and spike-and-wave complexes, which were not limited to cortical hyperintensities identified with MRI scans. Our findings indicate that focal sharp waves and/or focal spike-and-wave complexes on the EEGs of patients in the early phase of MM2c-sCJD are characteristic of the disease, suggesting the possible usefulness of this characteristic for early diagnosis.

Visualization of electrophysiological activity at the carpal tunnel area using magnetoneurography.

OBJECTIVE: To establish a noninvasive method to measure the neuromagnetic fields of the median nerve at the carpal tunnel after electrical digital nerve stimulation and evaluate peripheral nerve function. METHODS: Using a vector-type biomagnetometer system with a superconducting quantum interference device, neuromagnetic fields at the carpal tunnel were recorded after electrical stimulation of the index or middle digital nerve in five healthy volunteers. A novel technique for removing stimulus-induced artifacts was applied, and current distributions were calculated using a spatial filter algorithm and superimposed on X-ray. RESULTS: A neuromagnetic field propagating from the palm to the carpal tunnel was observed in all participants. Current distributions estimated from the magnetic fields had five components: leading and trailing components parallel to the conduction pathway, outward current preceding the leading component, inward currents between the leading and trailing components, and outward current following the trailing component. The conduction velocity and peak latency of the inward current agreed well with those of sensory nerve action potentials. CONCLUSION: Removing stimulus-induced artifacts enabled magnetoneurography to noninvasively visualize with high spatial resolution the electrophysiological neural activity from the palm to the carpal tunnel. SIGNIFICANCE: This is the first report of using magnetoneurography to visualize electrophysiological nerve activity at the palm and carpal tunnel.

Visualization of electrical activity in the cervical spinal cord and nerve roots after ulnar nerve stimulation using magnetospinography.

OBJECTIVE: To establish a method for magnetospinography (MSG) measurement after ulnar nerve stimulation and to clarify its characteristics. METHODS: Using a 132-channel magnetoneurography system with a superconducting quantum interference device, cervical MSG measurements were obtained for 10 healthy volunteers after stimulation of the ulnar nerve at the elbow and the wrist, and neural current distribution was calculated and superimposed on the cervical X-ray images. RESULTS: Neuromagnetic signals were obtained in all participants after applying the stimulus artifact removal algorithm. The measured magnetic field intensity after elbow stimulation was about twice that after wrist stimulation. Calculated neural currents flowed into the intervertebral foramina at C6/7 to T1/2 and propagated cranially along the spinal canal. The conduction velocity from the peak latency of inward currents at C5-C7 was 73.4 ± 19.6 m/s. CONCLUSIONS: We successfully obtained MSG measurements after ulnar nerve stimulation. The neural currents flowed into the spinal canal from more caudal segments after ulnar nerve stimulation compared with median nerve stimulation, and these MSG measurements were effective in examining the spinal tracts at C5/6/7. SIGNIFICANCE: This is the first report on the use of MSG to visualize electrical activity in the cervical spinal cord and nerve root after ulnar nerve stimulation.

[Malignant lymphoma presented as left trigeminal neuralgia].

A male, 60 years of age, presented with transient left facial pain located within all three divisions of the trigeminal nerve. Magnetic resonance imaging (MRI) revealed a swollen left trigeminal nerve with gadolinium enhancement. Following schwannoma diagnosis, the patient received Gamma Knife radiosurgery, which proved effective against symptoms of neuralgia and enhanced lesions. A relapse of unsteadiness was noted 11 months after initial treatment. Furthermore, while MRI presented a normal trigeminal nerve, multiple enhanced white matter mass lesions around the lateral ventricles were observed. Lastly, pathological examinations revealed diffuse large B cell lymphomas. The administration of high-dose methotrexate followed with whole brain radiation therapy appeared to have remarkable effects. No recurrences were observed in a 30 month duration following secondary treatment. Malignant lymphoma may present as trigeminal neuralgia. The conclusions from our case report and another literature review follow a difficult to near impossible task of establishing a correct diagnosis without biopsy in the initial stages of trigeminal nerve tumors. Therefore, a careful MRI follow-up is necessary even if the tumors show a favorable response towards primary steroid treatment or Gamma Knife radiosurgery.

Nerve conduction study of the association between glycemic variability and diabetes neuropathy.

BACKGROUND: It remains unclear whether glycemic variability is related to diabetes microvascular disease, especially diabetes peripheral neuropathy (DPN). We investigated the association between glycemic variability and DPN with type 1 or 2 diabetes. METHODS: Forty patients (23 males and 17 females; aged 34-79 years) underwent continuous glucose monitoring (CGM) and a nerve conduction study (NCS). Glycemic variability was estimated by mean amplitude of glycemic excursions (MAGE) in CGM. DPN was quantitatively evaluated by NCS in the median, tibial, sural and medial plantar nerves. RESULTS: MAGE had a significantly positive correlation with disease duration and low-density lipoprotein cholesterol level (r = 0.462, p = 0.003; and r = 0.40, p = 0.011, respectively), and a significantly negative correlation with BMI and medial plantar compound nerve action potential amplitude (r = - 0.39, p = 0.012; and r = - 0.32, p = 0.042, respectively). Multivariate linear regression analysis with adjustment for clinical background showed that MAGE (ß = - 0.49, p= 0.007) was independently associated with a higher risk of medial plantar neuropathy. CONCLUSIONS: Glycemic variability may be an independent risk factor for DPN.

Preoperative Predictors of Long-Term Mortality after Elective Endovascular Aneurysm Repair for Abdominal Aortic Aneurysm.

OBJECTIVE: This study aimed to clarify long-term mortality and its predictors in patients with abdominal aortic aneurysm (AAA) who underwent endovascular aneurysm repair (EVAR). MATERIALS AND METHODS: Patients with AAA who underwent elective EVAR at Tokyo Medical and Dental University hospital between 2008 and 2011 were reviewed. The patients' data were retrospectively collected from medical records. RESULTS: Sixty-four patients were identified for this study. In long-term follow-up, the survival rate was significantly lower in patients with high preoperative C-reactive protein (CRP) levels. Patients with obstructive lung disease (FEV1/FVC <70%) or anemia tended to have a poorer prognosis but the association was not statistically significant. Age, concurrent hyperlipidemia, and blood pressure levels were not predictors of mortality rates. DISCUSSION: High CRP level, COPD, and anemia reflect inflammation, which is associated with the pathogenesis of AAA. These inflammatory markers are predictors of long-term mortality after EVAR for AAA as well as for other diseases. CONCLUSIONS: A high preoperative CRP level was a predictor of increased long-term mortality in patients with AAA who underwent EVAR. No specific leading causes of death were identified for this increase in the mortality rate.

Concentrations of Immunoglobulin G Antibodies Against Pertussis Toxin Does Not Decrease Over a Long Period of Time in Japan.

Objective Adult patients with pertussis rarely show typical symptoms, such as paroxysmal coughing, inspiratory "whoop", or post-tussive vomiting. While a culture is regarded as the gold standard for diagnosis, the sensitivity is very low. Therefore, the diagnosis of pertussis in adults in clinical practice is mostly based on single-sample serology using an enzyme-linked immunosorbent assay (ELISA) with the pertussis toxin antigen. Various cut-off values for the anti-pertussis toxin IgG (PT-IgG) have been proposed. It has been reported that concentrations of PT-IgG fall below the defined cut-off about 4.5 months after infection on average, and within 1 year in most patients. We investigated the distribution and time course of the PT-IgG levels. Methods The data were collected from the medical records. Patients The study retrospectively identified subjects who had visited Ikebukuro Otani Clinic, which is a specialized clinic for patients with cough. We retrospectively reviewed 406 patients with PT-IgG measurements to investigate the age distribution of PT-IgG levels. The changes in PT-IgG levels over time were assessed in the 205 patients who had more than one PT-IgG measurement. Results PT-IgG levels were ≥100 EU/mL in more than 15% of subjects. The PT-IgG levels of a few subjects had diminished over a long period of time. Conclusion A PT-IgG level greater than the defined cut-off value simply indicates past infection or immunization in most subjects. As such, a single measurement of PT-IgG using the cut-off values might lead to overdiagnosis of pertussis. Further data collection and analysis are required.

Sphenoid Sinusitis Complicated by Pneumococcal Meningitis and an Infectious Aneurysm in the Intracavernous Carotid Artery.

A 61-year-old Japanese woman presented with a headache and appetite loss lasting for nine days and was admitted to our hospital, where she was diagnosed with pneumococcal meningitis associated with acute sphenoid sinusitis. While the administration of meropenem and dexamethasone ameliorated the meningitis, right third and sixth nerve palsy suddenly developed 10 days after admission. CT angiography subsequently demonstrated an aneurysm in the cavernous portion of the right internal carotid artery. This is the first reported case of sphenoid sinusitis simultaneously complicated by both pneumococcal meningitis and an infectious aneurysm in the intracavernous carotid artery.