Miho Miyajima

Epileptic Seizure Prediction Based on Multivariate Statistical Process Control of Heart Rate Variability Features

Objective: The present study proposes a new epileptic seizure prediction method through integrating heart rate variability (HRV) analysis and an anomaly monitoring technique. Methods: Because excessive neuronal activities in the preictal period of epilepsy affect the autonomic nervous systems and autonomic nervous function affects HRV, it is assumed that a seizure can be predicted through monitoring HRV. In the proposed method, eight HRV features are monitored for predicting seizures by using multivariate statistical process control, which is a well-known anomaly monitoring method. Results: We applied the proposed method to the clinical data collected from 14 patients. In the collected data, 8 patients had a total of 11 awakening preictal episodes and the total length of interictal episodes was about 57 h. The application results of the proposed method demonstrated that seizures in ten out of eleven awakening preictal episodes could be predicted prior to the seizure onset, that is, its sensitivity was 91%, and its false positive rate was about 0.7 times per hour. Conclusion: This study proposed a new HRV-based epileptic seizure prediction method, and the possibility of realizing an HRV-based epileptic seizure prediction system was shown. Significance: The proposed method can be used in daily life, because the heart rate can be measured easily by using a wearable sensor.

Abnormal mismatch negativity for pure-tone sounds in temporal lobe epilepsy

Auditory processing abnormalities in temporal lobe epilepsy (TLE) were assessed by investigating mismatch negativity (MMN) in a group of 20 TLE patients and 20 healthy control subjects. MMN is an event-related potential (ERP) component that reflects pre-attentive sensory memory function. A passive oddball paradigm using frequency changes in sinusoidal tones was employed to evoke MMN. MMN at frontocentral sites was enhanced in TLE patients relative to controls, while mismatch signals at mastoid sites (i.e., mismatch positivity; MMP) did not differ between the two groups. In the MMP temporal range, greater positivity at mastoid sites in response to standard stimuli was observed in TLE patients than in controls. Both MMN and MMP were significantly delayed in the TLE group. These findings demonstrate that TLE patients have impaired pre-attentive processing of pure-tone sounds. Enhanced frontocentral MMN may reflect hyperexcitability of the frontal lobes in compensation for dysfunction of the temporal lobes. Larger positivity at the mastoids in response to standard stimuli may be attributed to poor neuronal adaptation in the temporal lobe. Taken together, results suggest that evaluation of MMN/P is a useful physiological tool for identifying pre-attentive auditory memory dysfunction in TLE.

2C-T-4 intoxication: acute psychosis caused by a designer drug

DESIGNER DRUG ABUSE is a serious problem in Japan. Recently we encountered an acute intoxication in an emergency setting involving one such drug, which has never been reported as a clinical case anywhere. A 40-year-old man, with no previous history of mental disorder, although having had experiences of occasional use of street drugs, was brought to the emergency room by his mother. He was in a delusional state with incoherent speech, such as ‘I am a murderer and president’ and ‘Once I close my eyes, all of the world will disappear’. His mother reported that he had been in this state for 3 h. In an admission interview he confessed to ingesting a liquid from a bottle labeled ‘Vanilla aroma’ 9 h earlier to enhance sexual pleasure when engaging in masturbation. Six hours after ingestion he was overtaken by dreadful fear, which resulted in this emergency visit. On neuroleptic medication he recovered from a psychotic state with no neurological deficits 17 h after the ingestion. A urine test in Triage® detected no psychoactive substances, although laboratory analysis of the liquid product named Vanilla aroma, received from a drug dealer, indicated that it contained 2-(2,5-dimethoxy4-isopropylsulfanylphenyl) ethanamine (2C-T-4), which Triage® could not detect. His psychiatric state was considered to meet the criteria for hallucinogen intoxication on DSM-IV. To our knowledge this is the first report of acute psychosis caused by 2C-T-4, which is a phenethylamine analog and is not legally controlled in many countries, including Japan and the USA. This substance has a chemical structure similar to 2,5-dimethoxy-4propylthio-b-phenethylamine (2C-T-7), a strong hallucinogen with potential lethality. The US Drug Enforcement Administration classified 2C-T-7 as a Schedule I substance in 2004. No clinical information on 2C-T-4 has been available except a report on one user, which described that ingesting 8–22 mg of this substance had produced euphoria, visual hallucinations, and motor disturbances for approximately 15 h. This substance also is difficult to detect on screening in Triage®, although it can be detected on gas chromatography– mass spectrometry. The lack of clinical information and available screening may hinder legal actions against 2C-T-4, resulting in increased black market trafficking. Although an accumulation of additional cases should provide more information, prompt action by several government entities is needed.

Nonconvulsive status epilepticus in the elderly associated with newer antidepressants used at therapeutic doses: A report of three cases☆☆☆★

Classic antidepressants have been known to induce convulsive seizures and nonconvulsive status epilepticus (NCSE). On the other hand, many reports have emphasized the safety of novel antidepressants. However, we encountered three cases of NCSE in the elderly associated with the use of newer antidepressants at therapeutic doses. All three patients were male and were 73 years of age or older. One patient was recently diagnosed with temporal lobe epilepsy and treated with low-dose lamotrigine. In all patients, newer antidepressants were initiated because of depressive symptoms. After titrating to therapeutic doses (paroxetine 20 mg/day, sertraline 50 mg/day, and combination of sertraline 50 mg/day and mirtazapine 30 mg/day in one patient each), impaired consciousness appeared. Electroencephalography (EEG) showed generalized slow waves with intermittent spike–slow-wave complexes. Intravenous injection of antiepileptic drugs improved EEG findings and clinical symptoms. After discontinuance of the abovementioned antidepressants, NCSE did not recur in any of patients. These reports raise the question of whether the newer antidepressants, like classic antidepressants, might also induce NCSE in the elderly, even when used at therapeutic doses. Physicians should consider monitoring for possible NCSE when using newer antidepressants in patients who may have low drug tolerability. Active continuous video-EEG monitoring is essential when behavioral and psychological symptoms or change in consciousness level is suspected.

Real-time heart rate variability monitoring employing a wearable telemeter and a smartphone

A telemetry system for the measurement of heart rate variability (HRV) has been developed with a low-cost manufacturing process and a low-power consumption design. All the components and functions for the RRI measurement were implemented on a wearable telemeter which can operate for up to 10 hours with a rechargeable Li-Polymer battery, and the RRI data is stored into a smartphone via a Bluetooth wireless transmission. In a long-term measurement of a young subject that extended over 48 hours in total, the results showed a 1% probability of recurring errors. The obtained results suggest that the proposed fully-wearable system enables the continuous monitoring of HRV for both clinical care and healthcare operated by a non-expert.

Aroma helps to preserve information processing resources of the brain in healthy subjects but not in temporal lobe epilepsy.

PURPOSE Inhalation of ylang-ylang aroma has been shown to reduce the auditory P300, an event-related potential thought to reflect higher-order processing. Because olfactory function is sometimes disturbed in temporal lobe epilepsy (TLE), the objective of the present study was to determine whether the effect of ylang-ylang aroma on the auditory P300 was impaired in patients with TLE. METHOD Fourteen subjects with TLE and 14 healthy controls participated in this study. Electroencephalograms were recorded during an auditory oddball task, and ylang-ylang aroma or odorless air was delivered through a mask. RESULTS We found that the ylang-ylang aroma prolonged the latencies of P300 in both groups. The ylang-ylang aroma significantly reduced the P300 amplitudes of healthy subjects as described previously. However, in TLE patients, the P300 was unaffected by the aroma. CONCLUSION The current results show that exposure to the ylang-ylang aroma reduced information processing resources in healthy subjects but had limited effects in patients with TLE. We suggest that impaired higher-order olfactory processing in TLE patients may inhibit the effects of the ylang-ylang aroma on the P300.

Heart rate variability features for epilepsy seizure prediction

Although refractory epileptic patients suffer from uncontrolled seizures, their quality of life (QoL) may be improved if an epileptic seizure can be predicted in advance. In the preictal period, an excessive neuronal activity of epilepsy affects the autonomic nerve system. Since the fluctuation of the R-R interval (RRI) of an electrocardiogram (ECG), called heart rate variability (HRV), reflects the autonomic nervous function, an epileptic seizure may be predicted through monitoring HRV data of an epileptic patient. In the present work, preictal and interictal HRV data of epileptic patients were analyzed for developing an epilepsy seizure prediction system. The HRV data of five patients were collected, and their HRV features were calculated. The analysis results showed that frequency HRV features, such as LF and LF/HF, changed at least one minute before seizure onset in all seizure episodes. The possibility of realizing a HRV-based seizure prediction system was shown through these analysis.

A Triphasic Change of Cardiac Autonomic Nervous System During Electroconvulsive Therapy.

Objectives Dynamic autonomic activity changes have been repeatedly reported during electroconvulsive therapy (ECT). However, the specific timing of these changes remains unclear. To clarify whether sympathetic or parasympathetic nervous activity contributes separately to the second stage and the third stage during and after induced seizures by ECT, we examined heart rate (HR) and spectral analysis of variability (HRV) during ECT. Methods Seventeen patients with depression participated in the study and underwent ECT. The R-R intervals (RRI) were recorded and analyzed sequentially for the HRV indices high-frequency (HF) (an index of parasympathetic activity) and low-frequency (LF)/high-frequency (an index of sympathetic activity) for 4 minutes before and after stimulus onset by the maximum entropy method. Averaged HRs were compared between 3 heart beats prestimulus and poststimulus onset. The HRV power in the range of 30 to 80 and 80 to 130 seconds after a seizure was compared between the HF and LF/HF components. Results There was a significant reduction of the averaged HR over 3 HRs just after stimulus onset, suggesting parasympathetic dominance in the first phase. The LF/HF power significantly increased in the 30 to 80 s range after stimulus onset, whereas the HF power significantly increased in the 80 to 130 s range after stimulus onset, reflecting sympathetic activation in the second phase and parasympathetic activation in the third phase, respectively. Conclusions The evaluation of HR and HRV revealed a triphasic change from parasympathetic to sympathetic to parasympathetic cardiac autonomic activity after ECT stimulus onset in depression patients.

Changes in the duration and frequency of deviant stimuli engender different mismatch negativity patterns in temporal lobe epilepsy

Mismatch negativity (MMN) is an event-related potential (ERP) component that reflects preattentive sensory memory functions. Previous research revealed that MMN is generated by distinct sources in the frontal and temporal lobes. Event-related potential abnormalities have been shown in the vicinity of seizure foci in epilepsy. Additionally, no published study has investigated the MMN in response to variations in both frequency and duration deviants in patients with temporal lobe epilepsy (TLE). The aims of this study were to compare MMN changes between the frontocentral sites and the mastoid sites and to compare MMNs related to deviant stimuli with different durations and frequencies in patients with TLE. We recorded MMNs elicited by duration and frequency changes of deviant stimuli from 15 patients with TLE and 15 healthy control subjects. We found that mean MMN amplitudes related to duration deviants were lower in patients with TLE at the mastoid sites relative to controls, whereas the MMN amplitudes at the frontocentral sites did not differ between the two groups. There were no MMN differences related to frequency deviants between TLE subjects and controls at the frontocentral sites or the mastoid sites. Mismatch negativity parameters related to duration deviants did not correlate with those related to deviant frequencies in the group with TLE. The present findings suggest selective impairments among multiple mismatch generators in TLE and suggest that processing of temporal information of auditory stimuli is selectively disturbed in TLE. Changes in MMN amplitudes related to duration deviants at the mastoid sites may represent deficits in time-dependent processing in TLE.

Development of a wearable HRV telemetry system to be operated by non-experts in daily life

A telemetry system for the measurement of heart rate variability (HRV) with automatic gain control has been developed with a low-cost manufacturing process and a low-power consumption design. The proposed automatic gain control technique provided highly reliable RR interval (RRI) detection for subjects of different ages, and enabled the subjects to use the system without any expert knowledge of the electrocardiogram (ECG) measurement. All the components and functions for the RRI measurement were implemented on a wearable telemeter which can operate for up to 440 h with a CR2032 coin battery, and the wirelessly transmitted RRI data is stored into a PC by a receiver via a USB connection. The errors of the RRI detection occurred at less than 2% probability in subjects of five different ages. In a long-term measurement of a young subject that extended over 48 h, the results showed a 0.752% probability of recurring errors. The obtained results suggest that the proposed system enables the long-term monitoring of HRV for both clinical care and healthcare operated by a non-expert.