Clinical Utility of Sleep Recordings During Presurgical Epilepsy Evaluation With Stereo-Electroencephalography: A Systematic Review.

SUMMARY: Although the role of sleep in modulating epileptic activity is well established, many epileptologists overlook the significance of considering sleep during presurgical epilepsy evaluations in cases of drug-resistant epilepsy. Here, we conducted a comprehensive literature review from January 2000 to May 2023 using the PubMed electronic database and compiled evidence to highlight the need to revise the current clinical approach. All articles were assessed for eligibility by two independent reviewers. Our aim was to shed light on the clinical value of incorporating sleep monitoring into presurgical evaluations with stereo-electroencephalography. We present the latest developments on the important bidirectional interactions between sleep and various forms of epileptic activity observed in stereo-electroencephalography recordings. Specifically, epileptic activity is modulated by different sleep stages, peaking in non-rapid eye movement sleep, while being suppressed in rapid eye movement sleep. However, this modulation can vary across different brain regions, underlining the need to account for sleep to accurately pinpoint the epileptogenic zone during presurgical assessments. Finally, we offer practical solutions, such as automated sleep scoring algorithms using stereo-electroencephalography data alone, to seamlessly integrate sleep monitoring into routine clinical practice. It is hoped that this review will provide clinicians with a readily accessible roadmap to the latest evidence concerning the clinical utility of sleep monitoring in the context of stereo-electroencephalography and aid the development of therapeutic and diagnostic strategies to improve patient surgical outcomes.

Intracerebral Dynamics of Sleep Arousals: A Combined Scalp-Intracranial EEG Study.

As an intrinsic component of sleep architecture, sleep arousals represent an intermediate state between sleep and wakefulness and are important for sleep-wake regulation. They are defined in an all-or-none manner, whereas they actually present a wide range of scalp-electroencephalography (EEG) activity patterns. It is poorly understood how these arousals differ in their mechanisms. Stereo-EEG (SEEG) provides the unique opportunity to record intracranial activities in superficial and deep structures in humans. Using combined polysomnography and SEEG, we quantitatively categorized arousals during nonrapid eye movement sleep into slow wave (SW) and non-SW arousals based on whether they co-occurred with a scalp-EEG SW event. We then investigated their intracranial correlates in up to 26 brain regions from 26 patients (12 females). Across both arousal types, intracranial theta, alpha, sigma, and beta activities increased in up to 25 regions (p < 0.05; d = 0.06-0.63), while gamma and high-frequency (HF) activities decreased in up to 18 regions across the five brain lobes (p < 0.05; d = 0.06-0.44). Intracranial delta power widely increased across five lobes during SW arousals (p < 0.05 in 22 regions; d = 0.10-0.39), while it widely decreased during non-SW arousals (p < 0.05 in 19 regions; d = 0.10-0.30). Despite these main patterns, unique activities were observed locally in some regions such as the hippocampus and middle cingulate cortex, indicating spatial heterogeneity of arousal responses. Our results suggest that non-SW arousals correspond to a higher level of brain activation than SW arousals. The decrease in HF activities could potentially explain the absence of awareness and recollection during arousals.

Rapid eye movement sleep affects interictal epileptic activity differently in mesiotemporal and neocortical areas.

OBJECTIVE: Rapid eye movement (REM) sleep reduces the rate and extent of interictal epileptiform discharges (IEDs). Breakthrough epileptic activity during REM sleep is therefore thought to best localize the seizure onset zone (SOZ). We utilized polysomnography combined with direct cortical recordings to investigate the influences of anatomical locations and the time of night on the suppressive effect of REM sleep on IEDs. METHODS: Forty consecutive patients with drug-resistant focal epilepsy underwent combined polysomnography and stereo-electroencephalography during presurgical evaluation. Ten-minute interictal epochs were selected 2 h prior to sleep onset (wakefulness), and from the first and second half of the night during non-REM (NREM) sleep and REM sleep. IEDs were detected automatically across all channels. Anatomic localization, time of night, and channel type (within or outside the SOZ) were tested as modulating factors. RESULTS: Relative to wakefulness, there was a suppression of IEDs by REM sleep in neocortical regions (median = -27.6%), whereas mesiotemporal regions showed an increase in IEDs (19.1%, p = .01, d = .39). This effect was reversed when comparing the regional suppression of IEDs by REM sleep relative to NREM sleep (-35.1% in neocortical, -58.7% in mesiotemporal, p < .001, d = .39). Across all patients, no clinically relevant novel IED regions were observed in REM sleep versus NREM or wakefulness based on our predetermined thresholds (4 IEDs/min in REM, 0 IEDs/min in NREM and wakefulness). Finally, there was a reduction in IEDs in late (NREM: 1.08/min, REM: .61/min) compared to early sleep (NREM: 1.22/min, REM: .69/min) for both NREM (p < .001, d = .21) and REM (p = .04, d = .14). SIGNIFICANCE: Our results demonstrate a spatiotemporal effect of IED suppression by REM sleep relative to wakefulness in neocortical but not mesiotemporal regions, and in late versus early sleep. This suggests the importance of considering sleep stage interactions and the potential influences of anatomical locations when using IEDs to define the epileptic focus.

The Differing Effects of Sleep on Ictal and Interictal Network Dynamics in Drug-Resistant Epilepsy.

OBJECTIVE: Sleep has important influences on focal interictal epileptiform discharges (IEDs), and the rates and spatial extent of IEDs are increased in non-rapid eye movement (NREM) sleep. In contrast, the influence of sleep on seizures is less clear, and its effects on seizure topography are poorly documented. We evaluated the influences of NREM sleep on ictal spatiotemporal dynamics and contrasted these with interictal network dynamics. METHODS: We included patients with drug-resistant focal epilepsy who underwent continuous intracranial electroencephalography (iEEG) with depth electrodes. Patients were selected if they had 1 to 3 seizures from each vigilance state, wakefulness and NREM sleep, within a 48-hour window, and under the same antiseizure medication. A 10-minute epoch of the interictal iEEG was selected per state, and IEDs were detected automatically. A total of 25 patients (13 women; aged 32.5 ± 7.1 years) were included. RESULTS: The seizure onset pattern, duration, spatiotemporal propagation, and latency of ictal high-frequency activity did not differ significantly between wakefulness and NREM sleep (all p > 0.05). In contrast, IED rates and spatial distribution were increased in NREM compared with wakefulness (p < 0.001, Cliff's d = 0.48 and 0.49). The spatial overlap between vigilance states was higher for seizures (57.1 ± 40.1%) than IEDs (41.7 ± 46.2%; p = 0.001, Cliff's d = 0.51). INTERPRETATION: In contrast to its effects on IEDs, NREM sleep does not affect ictal spatiotemporal dynamics. This suggests that once the brain surpasses the seizure threshold, it will follow the underlying epileptic network irrespective of the vigilance state. These findings offer valuable insights into neural network dynamics in epilepsy and have important clinical implications for localizing seizure foci. ANN NEUROL 2023.

Primary headache types in adult epilepsy patients.

BACKGROUND: Headache is among the most common comorbidities in epilepsy. This study examined the distribution of different primary headache disorders in a large cohort of patients with diagnosed epilepsy. Headache types were analysed with regard to gender, type of epilepsy and antiepileptic drugs (AEDs). METHODS: In this prospective single-centre study, 500 patients with epilepsy (250 female, mean age: 45.52 ± 17.26 years) were evaluated with regards to primary headache types using a validated German headache questionnaire categorizing for migraine (MIG), tension-type headache (TTH) or trigeminal autonomic cephalalgias (TAC), their combinations and unclassifiable headache. Data regarding type of epilepsy, seizure-associated headache, AED treatment and seizure freedom were collected. RESULTS: Of 500 patients with epilepsy, 163 (32.6%) patients (108 female and 55 male) reported suffering from headaches at least 1 day per month. MIG (without aura, with aura) and TTH were the most frequent headache type (MIG 33.1%, TTH 33.1%). Female epilepsy patients reported headaches significantly more often than male patients (x2 = 8.20, p = 0.0042). In contrast, the type of epilepsy did not significantly affect headache distribution. Of 163 patients with headache, 66 (40.5%) patients reported seizure-associated headache and AEDs were used by 157 patients. Of importance, patients with AED monotherapy suffered from MIG less often when compared to patients on polytherapy (x2 = 4.79, p = 0.028). CONCLUSION: MIG and TTH are the most common headache types in epilepsy patients and headache is more frequent among female epilepsy patients. Monotherapy in AEDs might have a beneficial effect on the frequency of headache compared to polytherapy.

Imaging slow brain activity during neocortical and hippocampal epileptiform events with electrical impedance tomography.

OBJECTIVE: Electrical impedance tomography (EIT) is an imaging technique that produces tomographic images of internal impedance changes within an object using surface electrodes. It can be used to image the slow increase in cerebral tissue impedance that occurs over seconds during epileptic seizures, which is attributed to cell swelling due to disturbances in ion homeostasis following hypersynchronous neuronal firing and its associated metabolic demands. In this study, we characterised and imaged this slow impedance response during neocortical and hippocampal epileptiform events in the rat brain and evaluated its relationship to the underlying neural activity. APPROACH: Neocortical or hippocampal seizures, comprising repeatable series of high-amplitude ictal spikes, were induced by electrically stimulating the sensorimotor cortex or perforant path of rats anaesthetised with fentanyl-isoflurane. Transfer impedances were measured during ≥30 consecutive seizures, by applying a sinusoidal current through independent electrode pairs on an epicortical array, and combined to generate an EIT image of slow activity. MAIN RESULTS: The slow impedance responses were consistently time-matched to the end of seizures and EIT images of this activity were reconstructed reproducibly in all animals (p < 0.03125, N = 5). These displayed foci of activity that were spatially confined to the facial somatosensory cortex and dentate gyrus for neocortical and hippocampal seizures, respectively, and encompassed a larger volume as the seizure progressed. Centre-of-mass analysis of reconstructions revealed that this activity corresponded to the true location of the epileptogenic zone, as determined by EEG recordings and fast neural EIT measurements which were obtained simultaneously. SIGNIFICANCE: These findings suggest that the slow impedance response presents a reliable marker of hypersynchronous neuronal activity during epileptic seizures and can thus be utilised for investigating the mechanisms of epileptogenesis in vivo and for aiding localisation of the epileptogenic zone during presurgical evaluation of patients with refractory epilepsies.

Optimised induction of on-demand focal hippocampal and neocortical seizures by electrical stimulation.

BACKGROUND: Epilepsy is a common neurological disorder affecting over 60 million people globally, approximately a third of whom are refractory to pharmacotherapy. Surgical resection of the epileptogenic zone is frequently unsuitable or ineffective, particularly for individuals with focal neocortical or mesial temporal lobe epilepsy. Therefore, there is a need to develop animal models for elucidating the mechanisms of focal epilepsies and evaluating novel treatment strategies. NEW METHOD: We present two adapted in vivo seizure models, the neocortical and hippocampal epileptic afterdischarge models, that enable stereotyped seizures to be induced on demand by electrical stimulation in anaesthetised, neurologically intact rats. The stimulation parameters and anaesthetic were optimised to generate electrographically reproducible, self-sustaining seizures with a well-defined focal origin. RESULTS: Neocortical or hippocampal seizures were consistently generated under fentanyl-isoflurane anaesthesia by stimulating the sensorimotor cortex or perforant path, respectively, with 100 Hz trains of biphasic square-wave pulses. The induced seizures were suppressed by propofol, an established antiseizure anaesthetic, thus validating the clinical responsiveness of the developed models. COMPARISON WITH EXISTING METHODS: The high degree of reproducibility in seizure presentation, predictable seizure induction and ability to operate in anaesthetised animals renders these models overall less laborious and more cost-effective than most conventionally used seizure models. CONCLUSIONS: The proposed models provide an efficient method for the high-throughput screening of novel antiseizure therapies, including closed-loop stimulation paradigms, and are well-suited to in vivo investigations that require tight regulation of seizure timing under anaesthetised conditions, particularly neuroimaging studies aimed at understanding the development of epileptogenic networks.

In vivo imaging of deep neural activity from the cortical surface during hippocampal epileptiform events in the rat brain using electrical impedance tomography.

Electrical impedance tomography (EIT) is a medical imaging technique which reconstructs images of the internal impedance changes within an object using non-penetrating surface electrodes. To date, EIT has been used to image fast neural impedance changes during somatosensory evoked potentials and epileptiform discharges through the rat cerebral cortex with a resolution of 2 â€‹ms and <300 â€‹µm. However, imaging of neural activity in subcortical structures has never been achieved with this technique. Here, we evaluated the feasibility of using EIT to image epileptiform activity in the rat hippocampus using non-penetrating electrodes implanted on the cortical surface. Hippocampal epileptiform events, comprising repetitive 30-50 â€‹Hz ictal spikes, were induced by electrically stimulating the perforant path of rats anaesthetised with fentanyl-isoflurane. For each of ≥30 seizures, impedance measurements were obtained by applying 100 â€‹µA current at 1.4 â€‹kHz through an independent pair of electrodes on a 54-electrode planar epicortical array and recording boundary voltages on all remaining electrodes. EIT images of averaged ictal spikes were reconstructed using impedance recordings from all seizures in each animal. These revealed a focus of neural activity localised to the dentate gyrus which was spatially and temporally aligned to local field potential (LFP) recordings and could be reconstructed reproducibly in all animals with a localisation accuracy of ≤400 â€‹µm (p â€‹< â€‹0.03125, N â€‹= â€‹5). These findings represent the first experimental evidence of the ability of EIT to image neural activity in subcortical structures from the surface of the cortex with high spatiotemporal resolution and suggest that this method may be used for improving understanding of functional connectivity between cortico-hippocampal networks in both physiological and pathophysiological states.

Comparison of Xpert MTB/RIF with AFB smear and AFB culture in suspected cases of paediatric tuberculosis in a tertiary care hospital, Karachi.

OBJECTIVE: To evaluate the sensitivity, specificity, positive predictive and negative predictive values of Xpert mycobacterium tuberculosis and resistance to rifampicin by comparing it with acid-fast bacilli smear and culture in suspected tuberculosis patients. METHODS: The retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised patient data from January 2013 to December 2016. Data related to children with clinical suspicion of pulmonary and extra-pulmonary tuberculosis based on Modified Kenneth Jones criteria, aged 1 month to 18 years whose samples (respiratory or non-respiratory) were sent for Xpert mycobacterium tuberculosis and resistance to rifampicin and acid-fast bacilli smear and culture con currently. Analysis was carried out by STATA 12 and Med Calc softwares . RESULTS: Of the 91 cases, 50(54.9%) related to females. The overall median age of the patients was 12.5 years (interquartile range: 8 years). Overall, 42(46.2%) cases had extra-pulmonary tuberculosis. The Xpert test had 66.7% sensitivity compared to smear microscopy 47.6%. Overall sensitivity, specificity, positive predictive value and negative predictive value were 95.7%, 72%, 51.2% and 98.3% respectively when the two tests were compared. CONCLUSIONS: Xpert mycobacterium tuberculosis was found to be more sensitive than acid-fast bacilli smear and culture in both pulmonary and extra-pulmonar y tuberculosis in children.

Investigating the safety of fast neural electrical impedance tomography in the rat brain.

OBJECTIVE: Electrical impedance tomography (EIT) can be used to image impedance changes which arise due to fast electrical activity during neuronal depolarisation and so holds therapeutic potential for improving the localisation of epileptic seizure foci in patients with treatment-resistant epilepsy to aid surgical resection of epileptogenic tissue. Prolonged cortical stimulation may, however, induce neural injury through excitotoxicity and electrochemical reactions at the tissue-electrode interface. The purpose of this work was to assess whether current levels used in fast neural EIT studies induce histologically detectable tissue damage when applied continuously to the rat cerebral cortex. APPROACH: A 57-electrode epicortical array was placed on one or both hemispheres of adult Sprague Dawley rats anaesthetised with isoflurane. In an initial series of experiments, current was injected simultaneously at 10, 25, 50, 75 and 100 µA for 1 h at 1.725 kHz through five electrodes across two epicortical arrays to provide a preliminary indication of the safety of these current levels. Since no obvious cortical damage was observed in these rats, the current level chosen for further investigation was 100 µA, the upper-bound of the range of interest. In a separate series of experiments, 100 µA was applied through a single electrode for 1 h at 1.725 kHz to verify its safety. Following termination of stimulation, brain samples were fixed in formalin and histologically processed with Haematoxylin and Eosin (H&E) and Nissl stains. MAIN RESULTS: Histological analysis revealed that continuous injection of 100 µA current, equating to a current density of 354 Am-2, into the rat cortex at 1.725 kHz does not cause cortical tissue damage or any alterations to neuronal morphology. SIGNIFICANCE: The safety of current injections during typical EIT protocols for imaging fast neural activity have been validated. The current density established to be safe for continuous application to the cortex, 354 Am-2, exceeds the present safety limit of 250 Am-2 which has been complied with to date, and thus encourages the application of more intensified fast neural EIT protocols. These findings will aid protocol design for future clinical and in vivo EIT investigations aimed at imaging fast neural activity, particularly in situations where the signal-to-noise ratio is considerably reduced.

Imaging fast electrical activity in the brain during ictal epileptiform discharges with electrical impedance tomography.

Electrical Impedance Tomography (EIT) is an emerging medical imaging technique which can produce tomographic images of internal impedance changes within an object using non-penetrating surface electrodes. It has previously been used to image impedance changes due to neuronal depolarisation during evoked potentials in the rat somatosensory cortex with a resolution of 2 ms and <200 µm, using an epicortical electrode array. The purpose of this work was to use this technique to elucidate the intracortical spatiotemporal trajectory of ictal spike-and-wave discharges (SWDs), induced by electrical stimulation in an acute rat model of epilepsy, throughout the cerebral cortex. Seizures lasting 16.5 ±â€¯5.3 s with repetitive 2-5 Hz SWDs were induced in five rats anaesthetised with fentanyl-isoflurane. Transfer impedance measurements were obtained during each seizure with a 57-electrode epicortical array by applying 50 µA current at 1.7 kHz to two electrodes and recording voltages from all remaining electrodes. Images were reconstructed from averaged SWD-related impedance traces obtained from EIT measurements in successive seizures. We report the occurrence of reproducible impedance changes during the initial spike phase, which had an early onset in the whisker barrel cortex and spread posteriorly, laterally and ventrally over 20 ms (p < 0.03125, N = 5). These findings, which confirm and extend knowledge of SWD initiation and expression, suggest that EIT is a valuable neuroimaging tool for improving understanding of neural circuits implicated in epileptic phenomena.

Imaging fast neural traffic at fascicular level with electrical impedance tomography: proof of principle in rat sciatic nerve.

OBJECTIVE: Understanding the coding of neural activity in nerve fascicles is a high priority in computational neuroscience, electroceutical autonomic nerve stimulation and functional electrical stimulation for treatment of paraplegia. Unfortunately, it has been little studied as no technique has yet been available to permit imaging of neuronal depolarization within fascicles in peripheral nerve. APPROACH: We report a novel method for achieving this, using a flexible cylindrical multi-electrode cuff placed around nerve and the new medical imaging technique of fast neural electrical impedance tomography (EIT). In the rat sciatic nerve, it was possible to distinguish separate fascicles activated in response to direct electrical stimulation of the posterior tibial and common peroneal nerves. MAIN RESULTS: Reconstructed EIT images of fascicular activation corresponded with high spatial accuracy to the appropriate fascicles apparent in histology, as well as the inverse source analysis (ISA) of compound action potentials (CAP). With this method, a temporal resolution of 0.3 ms and spatial resolution of less than 100 µm was achieved. SIGNIFICANCE: The method presented here is a potential solution for imaging activity within peripheral nerves with high spatial accuracy. It also provides a basis for imaging and selective neuromodulation to be incorporated in a single implantable non-penetrating peri-neural device.

Frequency-dependent characterisation of impedance changes during epileptiform activity in a rat model of epilepsy.

OBJECTIVE: Electrical impedance tomography (EIT) can be used to image impedance changes associated with epileptiform activity and so holds therapeutic potential for improving presurgical localisation of the ictal onset zone in patients with treatment-resistant epilepsy. There are two principal impedance changes which occur during seizures that may be imaged with EIT: (a) a fast, transient impedance decrease over milliseconds due to hypersynchronous neuronal depolarisation in individual ictal discharges; and (b) a larger, slow impedance increase caused by cell swelling over the course of the seizure. The magnitude of these signals is highly dependent on the carrier frequency of applied current used for obtaining impedance measurements. The purpose of this work was to characterise the frequency response of the fast and slow impedance changes during epileptiform activity. APPROACH: Seizures were induced in anaesthetised rats by electrically stimulating the cerebral cortex. During each seizure, impedance measurements were obtained by delivering 50 µA, through two electrodes on an epicortical array, at one of 20 frequencies in the 1-10 kHz range. Recordings were demodulated to determine the magnitude of fast and slow impedance responses at each frequency. MAIN RESULTS: The fast impedance change during averaged ictal discharges reached a maximal amplitude and signal-to-noise ratio (SNR) of -0.36% ± 0.05% and 50.2 ± 11.3, respectively, at 1355 Hz. At this frequency, the slow impedance change had an amplitude of 4.61% ± 1.32% and an SNR of 545 ± 125, which did not significantly change across frequency (p > 0.01). SIGNIFICANCE: We conclude that the optimal frequency for imaging epileptiform activity is 1355 Hz, which maximises the SNR of fast neural changes whilst enabling simultaneous measurement of slow changes. These findings will inform future investigations aimed at imaging epilepsy in subcortical brain structures, where SNR is considerably reduced, and those using parallel, multi-frequency EIT.

Feasibility of imaging evoked activity throughout the rat brain using electrical impedance tomography.

Electrical Impedance Tomography (EIT) is an emerging technique which has been used to image evoked activity during whisker displacement in the cortex of an anaesthetised rat with a spatiotemporal resolution of 200 µm and 2 ms. The aim of this work was to extend EIT to image not only from the cortex but also from deeper structures active in somatosensory processing, specifically the ventral posterolateral (VPL) nucleus of the thalamus. The direct response in the cortex and VPL following 2 Hz forepaw stimulation were quantified using a 57-channel epicortical electrode array and a 16-channel depth electrode. Impedance changes of -0.16 ±â€¯0.08% at 12.9 ±â€¯1.4 ms and -0.41 ±â€¯0.14% at 8.8±1.9 ms were recorded from the cortex and VPL respectively. For imaging purposes, two 57-channel epicortical electrode arrays were used with one placed on each hemisphere of the rat brain. Despite using parameters optimised toward measuring thalamic activity and undertaking extensive averaging, reconstructed activity was constrained to the cortical somatosensory forepaw region and no significant activity at a depth greater than 1.6 mm below the surface of the cortex could be reconstructed. An evaluation of the depth sensitivity of EIT was investigated in simulations using estimates of the conductivity change and noise levels derived from experiments. These indicate that EIT imaging with epicortical electrodes is limited to activity occurring 2.5 mm below the surface of the cortex. This depth includes the hippocampus and so EIT has the potential to image activity, such as epilepsy, originating from this structure. To image deeper activity, however, alternative methods such as the additional implementation of depth electrodes will be required to gain the necessary depth resolution.

Characterising the frequency response of impedance changes during evoked physiological activity in the rat brain.

OBJECTIVE: Electrical impedance tomography (EIT) can image impedance changes associated with evoked physiological activity in the cerebral cortex using an array of epicortical electrodes. An impedance change is observed as the externally applied current, normally confined to the extracellular space is admitted into the conducting intracellular space during neuronal depolarisation. The response is largest at DC and decreases at higher frequencies due to capacitative transfer of current across the membrane. Biophysical modelling has shown that this effect becomes significant above 100 Hz. Recordings at DC, however, are contaminated by physiological endogenous evoked potentials. By moving to 1.7 kHz, images of somatosensory evoked responses have been produced down to 2 mm with a resolution of 2 ms and 200 µm. Hardware limitations have so far restricted impedance measurements to frequencies <2 kHz. The purpose of this work was to establish the optimal frequency for extending EIT to image throughout the brain and to characterise the response at frequencies >2 kHz using improved hardware. APPROACH: Impedance changes were recorded during forepaw somatosensory stimulation in both cerebral cortex and the VPL nucleus of the thalamus in anaesthetised rats using applied currents of 1 kHz to 10 kHz. MAIN RESULTS: In the cortex, impedance changed by -0.04 ± 0.02 % at 1 kHz, reached a peak of -0.13 ± 0.05 % at 1475 Hz and decreased to -0.05 ± 0.02 % at 10 kHz. At these frequencies, changes in the thalamus were -0.26 ± 0.1%, -0.4 ± 0.15 % and -0.08 ± 0.03 % respectively. The signal-to-noise ratio was also highest at 1475 Hz with values of -29.5 ± 8 and -31.6 ±10 recorded from the cortex and thalamus respectively. Signficance: This indicates that the optimal frequency for imaging cortical and thalamic evoked activity using fast neural EIT is 1475 Hz.

Thalassemia and premarital screening: potential for implementation of a screening program among young people in Pakistan.

Pakistan has a high prevalence of ß-thalassemia (ß-thal) but lacks a screening program for its prevention. This questionnaire-based cross-sectional study was conducted in six randomly chosen non medical universities to assess the students' knowledge of ß-thal and premarital screening, and their attitude towards such a program. Comparison was made between the respondents' attitude towards premarital screening before and after providing them some information regarding the disease. Only 54.5% (207) of 380 students had heard of ß-thal, with a mean knowledge score of 13.0 ± 4.4 out of 27 questions. Most respondents were aware of the concept of premarital screening. Out of 207 students, 60.4% wanted to know if they were carriers, 69.1% wanted to know their spouse's carrier status and 59.4% wanted premarital screening to be made mandatory in Pakistan. These figures increased to 72.5, 78.3 and 67.6%, respectively after provision of written information (p values: 0.03, 0.02, and 0.01, respectively). The positive attitude towards premarital screening with low background knowledge of the disease highlights the need of a mass awareness campaign and subsequent implementation of a premarital screening program.