Biomedical Engineering - Research Publications
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ItemP015 The effects of cathodal transcranial direct current stimulation in patienst with focal epilepsy (a pilot study)‘(Elsevier, 2017-03)Introduction: Over 65 million people live with epilepsy worldwide. Unfortunately, seizures can not be adequately controlled in a third of the affected individuals. Therefore, there is a definite need for adjunctive or alternative therapeutic approaches in this group of patients to control the recurrence of seizure attacks. Modulation of dysfunctional electrical brain activity by transcranial direct current stimulation (tDCS) seems to be a potentially valuable non-invasive alternative for epilepsy treatment in this population. Objectives: This pilot study aimed to assess the effects of a novel protocol called within-session repeated c-tDCS (9 min treatment - 20 min rest - 9 min treatment) on patients with focal epilepsy. Method: We conducted a small pilot study in patients admitted to the Video-EEG Monitoring Unit at the Royal Melbourne Hospital and as out patients at this hospital or St Vincent Hospital. Thirty patients have participated in this study to date. Twenty patients with focal epilepsy received one session of c-tDCS (9–20-9 protocol) over the temporal lobe in the affected hemisphere. One participant received c-tDCS on two consecutive days. The other nine patients received one session of sham tDCS with the same electrode montage and protocol. Short interval intracortical inhibition or SICI was measured with paired-pulse transcranial magnetic stimulation (TMS) before and after the tDCS intervention in 18 participants. Motor evoked potentials were recorded from first dorsal interosseous muscle in these participants. Participants were asked to record the time and the number of their seizures post tDCS treatment for 4 weeks in a seizure diary. Twenty-four participants returned their diaries. Results: All patients tolerated the c-tDCS protocol very well. One-way ANOVA showed that SICI was increased significantly in the experimental group compared to the sham group (F = 10.3, p = 0.005) (Fig. 1). The mean response ratio was −48.4 (SD = 54) for the experimental group vs. −8.3 (SD = 16.7) for sham group
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ItemThree-dimensional neural cultures produce networks that mimic native brain activity(WILEY, 2018-02)Development of brain function is critically dependent on neuronal networks organized through three dimensions. Culture of central nervous system neurons has traditionally been limited to two dimensions, restricting growth patterns and network formation to a single plane. Here, with the use of multichannel extracellular microelectrode arrays, we demonstrate that neurons cultured in a true three-dimensional environment recapitulate native neuronal network formation and produce functional outcomes more akin to in vivo neuronal network activity.
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ItemDeep brain stimulation for drug-resistant epilepsy(WILEY, 2018-02)OBJECTIVES: To review clinical evidence on the antiepileptic effects of deep brain stimulation (DBS) for drug-resistant epilepsy, its safety, and the factors influencing individual outcomes. METHODS: A comprehensive search of the medical literature (PubMed, Medline) was conducted to identify relevant articles investigating DBS therapy for drug-resistant epilepsy. Reference lists of these articles were used to source further articles. RESULTS: Stimulation of the anterior nucleus of the thalamus (ANT) and hippocampus (HC) has been shown to decrease the frequency of refractory seizures. Half of all patients from clinical studies experienced a 46%-90% seizure reduction with ANT-DBS, and a 48%-95% seizure reduction with HC-DBS. The efficacy of stimulating other targets remains inconclusive due to lack of evidence. Approximately three-fourths of patients receiving ANT, HC, or centromedian nucleus of the thalamus (CMT) stimulation are responders-experiencing a seizure reduction of at least 50%. The time course of clinical benefit varies dramatically, with both an initial lesional effect and ongoing stimulation effect at play. Improved quality of life and changes to cognition or mood may also occur. Side effects are similar in nature to those reported from DBS therapy for movement disorders. Several factors are potentially associated with stimulation efficacy, including an absence of structural abnormality on imaging for ANT and HC stimulation, and electrode position relative to the target. Certain seizure types or syndromes may respond more favorably to specific targets, including ANT stimulation for deep temporal or limbic seizures, and CMT stimulation for generalized seizures and Lennox-Gastaut syndrome. SIGNIFICANCE: We have identified several patient, disease, and stimulation factors that potentially predict seizure outcome following DBS. More large-scale clinical trials are needed to explore different stimulation parameters, reevaluate the indications for DBS, and identify robust predictors of patient response.
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ItemEtiologies and characteristics of refractory status epilepticus cases in different areas of the world: Results from a global audit(WILEY, 2018-10)To describe the demographics, etiologies, types of status epilepticus (SE), and outcomes in people with refractory and super-refractory SE from around the world, we prospectively collected cases of refractory SE (RSE) treated with continuous intravenous anesthetic drugs in an intensive care unit setting through online questionnaires using "active surveillance." We collected information about 776 cases of RSE in 50 countries over 4 years. Control of SE was achieved in 74% of the cases. Neurologic outcomes were poor in 41% of patients, and 24% died. Good outcome was associated with younger age and a history of epilepsy. Etiology strongly influenced the outcome. Patients from Asia were younger, more frequently presented with convulsive SE, and were more frequently affected by infectious etiologies when compared with patients from Europe and the Americas. Despite these differences, outcomes were similar in all countries. Demographics of patients with RSE in a global audit are similar to those in prior single center series, providing evidence of generalizability of those studies. Important differences exist among patients with RSE from different regions of the world, but these do not seem to significantly influence patient outcomes.
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ItemSingle-fiber F waves compared with conventional surface F waves, and their utility in detecting early diabetic neuropathy(WILEY, 2018-11)INTRODUCTION: The single-fiber F-wave (SFF-wave) technique assesses the entire length of single motor fibers using a concentric needle. Herein we investigated the utility of this approach in the detection of early diabetes-related neuropathy, and compared it with the use of conventional surface F waves (CF waves). METHODS: Sixteen patients with diabetes and either no neuropathy or mild neuropathy were assessed and compared with 16 age- and height-matched control participants. RESULTS: Both CF and SFF waves were abnormal in all 5 patients who had mild neuropathy. However, SFF waves demonstrated subclinical abnormalities in 7 of 11 patients (64%) with no neuropathy, whereas only 2 of these patients (18%) had prolonged CF waves. Minimum F-wave latency was comparable between techniques, but maximum SFF-wave latency was more frequently prolonged, as these delayed motor units were better isolated, rather than buried among summated CF-wave responses. DISCUSSION: SFF waves highlight the segmental involvement in diabetic neuropathy, and use of the SFF-wave technique detects more abnormalities than with CF waves. Muscle Nerve 58: 665-670, 2018.
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Item"Truths and roses have thorns about them" - Henry David Thoreau(WILEY, 2018-06)
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ItemPostictal suppression and seizure durations: A patient-specific, long-term iEEG analysis(WILEY, 2018-05)OBJECTIVE: We report on patient-specific durations of postictal periods in long-term intracranial electroencephalography (iEEG) recordings. The objective was to investigate the relationship between seizure duration and postictal suppression duration. METHODS: Long-term recording iEEG from 9 patients (>50 seizures recorded) were analyzed. In total, 2310 seizures were recorded during a total of 13.8 years of recording. Postictal suppression duration was calculated as the duration after seizure termination until total signal energy returned to background levels. The relationship between seizure duration and postictal suppression duration was quantified using the correlation coefficient (r). The effects of populations of seizures within patients, on correlations, were also considered. Populations of seizures within patients were distinguished by seizure duration thresholds and k-means clustering along the dimensions of seizure duration and postictal suppression duration. The effects of bursts of seizures were also considered by defining populations based on interseizure interval (ISI). RESULTS: Seizure duration accounted for 40% of postictal suppression duration variance, aggregated across all patients and seizures. Seizure duration accounted for more than 25% of the variance in postictal suppression duration in 2 patients and accounted for less than 25% in the remaining 7. In 3 patients, heat maps showed multiple distinct postictal patterns indicating multiple populations of seizures. When accounting for these populations, seizure duration accounted for less than 25% of the variance in postictal duration in all populations. Variance in postictal suppression duration accounted for less than 10% of ISI variance in all patients. SIGNIFICANCE: We have previously demonstrated that some patients have multiple seizure populations distinguishable by seizure duration. This article shows that different seizure populations have distinct and consistent postictal behaviors. The existence of multiple populations in some patients has implications for seizure management and forecasting, whereas the distinct postictal behaviors may have implications for sudden unexpected death in epilepsy (SUDEP) prediction and prevention.
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ItemCommon data elements for epilepsy mobile health systems(WILEY, 2018-05)OBJECTIVE: Common data elements (CDEs) are currently unavailable for mobile health (mHealth) in epilepsy devices and related applications. As a result, despite expansive growth of new digital services for people with epilepsy, information collected is often not interoperable or directly comparable. We aim to correct this problem through development of industry-wide standards for mHealth epilepsy data. METHODS: Using a group of stakeholders from industry, academia, and patient advocacy organizations, we offer a consensus statement for the elements that may facilitate communication among different systems. RESULTS: A consensus statement is presented for epilepsy mHealth CDEs. SIGNIFICANCE: Although it is not exclusive, we believe that the use of a minimal common information denominator, specifically these CDEs, will promote innovation, accelerate scientific discovery, and enhance clinical usage across applications and devices in the epilepsy mHealth space. As a consequence, people with epilepsy will have greater flexibility and ultimately more powerful tools to improve their lives.
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ItemRing and peg electrodes for minimally-Invasive and long-term sub-scalp EEG recordings(Elsevier, 2017-09-01)OBJECTIVE: Minimally-invasive approaches are needed for long-term reliable Electroencephalography (EEG) recordings to assist with epilepsy diagnosis, investigation and more naturalistic monitoring. This study compared three methods for long-term implantation of sub-scalp EEG electrodes. METHODS: Three types of electrodes (disk, ring, and peg) were fabricated from biocompatible materials and implanted under the scalp in five ambulatory ewes for 3months. Disk electrodes were inserted into sub-pericranial pockets. Ring electrodes were tunneled under the scalp. Peg electrodes were inserted into the skull, close to the dura. EEG was continuously monitored wirelessly. High resolution CT imaging, histopathology, and impedance measurements were used to assess the status of the electrodes at the end of the study. RESULTS: EEG amplitude was larger in the peg compared with the disk and ring electrodes (p<0.05). Similarly, chewing artifacts were lower in the peg electrodes (p<0.05). Electrode impedance increased after long-term implantation particularly for those within the bone (p<0.01). Micro-CT scans indicated that all electrodes stayed within the sub-scalp layers. All pegs remained within the burr holes as implanted with no evidence of extrusion. Eight of 10 disks partially eroded into the bone by 1.0mm from the surface of the skull. The ring arrays remained within the sub-scalp layers close to implantation site. Histology revealed that the electrodes were encapsulated in a thin fibrous tissue adjacent to the pericranium. Overlying this was a loose connective layer and scalp. Erosion into the bone occurred under the rim of the sub-pericranial disk electrodes. CONCLUSIONS: The results indicate that the peg electrodes provided high quality EEG, mechanical stability, and lower chewing artifact. Whereas, ring electrode arrays tunneled under the scalp enable minimal surgical techniques to be used for implantation and removal.
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ItemIs seizure frequency variance a predictable quantity?(WILEY, 2018-02)BACKGROUND: There is currently no formal method for predicting the range expected in an individual's seizure counts. Having access to such a prediction would be of benefit for developing more efficient clinical trials, but also for improving clinical care in the outpatient setting. METHODS: Using three independently collected patient diary datasets, we explored the predictability of seizure frequency. Three independent seizure diary databases were explored: SeizureTracker (n = 3016), Human Epilepsy Project (n = 93), and NeuroVista (n = 15). First, the relationship between mean and standard deviation in seizure frequency was assessed. Using that relationship, a prediction for the range of possible seizure frequencies was compared with a traditional prediction scheme commonly used in clinical trials. A validation dataset was obtained from a separate data export of SeizureTracker to further verify the predictions. RESULTS: A consistent mathematical relationship was observed across datasets. The logarithm of the average seizure count was linearly related to the logarithm of the standard deviation with a high correlation (R2 > 0.83). The three datasets showed high predictive accuracy for this log-log relationship of 94%, compared with a predictive accuracy of 77% for a traditional prediction scheme. The independent validation set showed that the log-log predicted 94% of the correct ranges while the RR50 predicted 77%. CONCLUSION: Reliably predicting seizure frequency variability is straightforward based on knowledge of mean seizure frequency, across several datasets. With further study, this may help to increase the power of RCTs, and guide clinical practice.