Sejal Jain - Academia.edu (original) (raw)
Papers by Sejal Jain
Cancer Epidemiology, Biomarkers & Prevention
Many studies show racial and ethnic survival disparities in lung squamous cell carcinoma (LSCC), ... more Many studies show racial and ethnic survival disparities in lung squamous cell carcinoma (LSCC), and self-identified African-Americans have significantly lower overall survival and progression-free survival than self-identified Caucasians. However, survival models based on genetic ancestry, rather than self-identified race, are needed to assess whether genetic ancestry influences this survival disparity or whether the cause of the disparity is largely socioeconomic. Using clinically annotated genomic data from 501 LSCC tumor samples in the Cancer Genome Atlas (TCGA), we compared clinical data, gene expression profiles, mutations, and copy number changes of tumors across ancestral groups to identify significantly differential events. We then applied the Cox Proportional Hazards model to predict overall survival as a function of genetic ancestry alongside other genetic, molecular, and clinical variables. We found a significant difference in metastatic stage between tumors from patient...
Sleep
This study was aimed to evaluate the yearly incidence of pediatric narcolepsy prior to and follow... more This study was aimed to evaluate the yearly incidence of pediatric narcolepsy prior to and following the 2009 H1N1 pandemic and to evaluate seasonal patterns of narcolepsy onset and associations with H1N1 influenza infection in the United States. This was a multicenter retrospective study with prospective follow-up. Participants were recruited from members of the Pediatric Working Group of the Sleep Research Network including 22 sites across the United States. The main outcomes were monthly and yearly incident cases of childhood narcolepsy in the United States, and its relationship to historical H1N1 influenza data. A total of 950 participants were included in the analysis; 487 participants were male (51.3%). The mean age at onset of excessive daytime sleepiness (EDS) was 9.6 ± 3.9 years. Significant trend changes in pediatric narcolepsy incidence based on EDS onset (p < .0001) occurred over the 1998–2016 period, peaking in 2010, reflecting a 1.6-fold increase in narcolepsy i...
Additional file 1: Supplementary Methods. Supplementary Table 1. LFA commercial kit information, ... more Additional file 1: Supplementary Methods. Supplementary Table 1. LFA commercial kit information, sample requirements, and protocol details. Supplementary Table 2. IFU clarity rubric. Supplementary Table 3. Usability ratings and description of kit components. Supplementary Table 4. Clinical information for the COVID-positive individuals whose plasma was used in this study. Supplementary Table 5. LFA Limits of detection estimated from anti-spike antibodies concentrations measured by Simoa.
BMC Infectious Diseases, 2021
Cancer Research, 2021
Aneuploidy, which we define as whole chromosome or chromosome arm copy number imbalance, is a nea... more Aneuploidy, which we define as whole chromosome or chromosome arm copy number imbalance, is a near-universal characteristic of human cancers. Cancer subtypes are often characterized by tumor specific patterns of chromosome arm copy number alterations; for example, squamous cell carcinomas (SCCs) from different tissues of origin (including lung, head and neck, esophagus, and bladder) have a pattern of chromosome 3p loss and chromosome 3q gain. Although these alterations are frequent, they are not well understood due to difficulty in modeling specific aneuploidy alterations in the matching cell type. However, recent advances in genome engineering allow generation of large chromosomal alterations. We used the CRISPR-Cas9 system to delete one copy of chromosome 3p in human immortalized lung epithelial cells most similar to upper airway basal cells. Deletion of chromosome 3p was validated by whole genome sequencing and karyotyping. Consistent with patient data, expression of 3p genes was...
BMC Infectious Diseases, 2021
Background COVID-19 has resulted in significant morbidity and mortality worldwide. Lateral flow a... more Background COVID-19 has resulted in significant morbidity and mortality worldwide. Lateral flow assays can detect anti-Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) antibodies to monitor transmission. However, standardized evaluation of their accuracy and tools to aid in interpreting results are needed. Methods We evaluated 20 IgG and IgM assays selected from available tests in April 2020. We evaluated the assays’ performance using 56 pre-pandemic negative and 56 SARS-CoV-2-positive plasma samples, collected 10–40 days after symptom onset, confirmed by a molecular test and analyzed by an ultra-sensitive immunoassay. Finally, we developed a user-friendly web app to extrapolate the positive predictive values based on their accuracy and local prevalence. Results Combined IgG + IgM sensitivities ranged from 33.9 to 94.6%, while combined specificities ranged from 92.6 to 100%. The highest sensitivities were detected in Lumiquick for IgG (98.2%), BioHit for both IgM (96.4%)...
Cancer Research, 2020
Aneuploidy, whole-chromosome or chromosome arm copy number imbalance, is a near-universal charact... more Aneuploidy, whole-chromosome or chromosome arm copy number imbalance, is a near-universal characteristic of human cancers. We previously applied methods that define chromosome arm-level aneuploidy and a global cancer aneuploidy score to 10,522 tumors of 33 types in The Cancer Genome Atlas (TCGA). Aneuploidy level was correlated with TP53 mutation, somatic mutation rate, and expression of proliferation genes. Overall aneuploidy was anti-correlated with expression of immune signaling genes, due to decreased leukocyte infiltrates in high-aneuploidy samples. In contrast, some individual chromosome arm alterations correlated with higher expression of immune signaling genes, including deletion of chromosome 3p, 8p, and 17p. Cancer subtypes are often characterized by tumor specific patterns of arm-level copy number alterations; for example, squamous cell carcinomas (SCCs) from different tissues of origin (including lung, esophagus, and bladder) have a pattern of chromosome 3p loss and chro...
Nature Communications, 2019
Lung cancer shows substantial genetic and phenotypic heterogeneity across individuals, driving a ... more Lung cancer shows substantial genetic and phenotypic heterogeneity across individuals, driving a need for personalised medicine. Here, we report lung cancer organoids and normal bronchial organoids established from patient tissues comprising five histological subtypes of lung cancer and non-neoplastic bronchial mucosa as in vitro models representing individual patient. The lung cancer organoids recapitulate the tissue architecture of the primary lung tumours and maintain the genomic alterations of the original tumours during long-term expansion in vitro. The normal bronchial organoids maintain cellular components of normal bronchial mucosa. Lung cancer organoids respond to drugs based on their genomic alterations: a BRCA2-mutant organoid to olaparib, an EGFR-mutant organoid to erlotinib, and an EGFR-mutant/MET-amplified organoid to crizotinib. Considering the short length of time from organoid establishment to drug testing, our newly developed model may prove useful for predicting p...
Journal of Clinical Sleep Medicine, 2019
STUDY OBJECTIVES Previous studies have shown that non-rapid eye movement (NREM) sleep parasomnias... more STUDY OBJECTIVES Previous studies have shown that non-rapid eye movement (NREM) sleep parasomnias commonly coexist with restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) in children, leading to speculation that RLS/PLMD may precipitate or worsen parasomnias. However, there are limited data about the effect of the treatment of RLS/PLMD on parasomnias in children. Hence, we performed this study to determine whether the treatment of RLS/PLMD with oral iron therapy is associated with improvement of parasomnias in children. METHODS A retrospective database was created for children with RLS/PLMD who were treated with iron therapy. These participants were followed for at least 1 year at Cincinnati Children's Hospital Medical Center. All participants had ferritin level testing and were treated with iron therapy. In addition, all participants underwent polysomnography before starting iron therapy for RLS/PLMD except for one participant who was already on iron but required a higher dose. Most participants underwent polysomnography after iron therapy. RESULTS A total of 226 participants were identified with the diagnosis of RLS/PLMD. Of these, 50 had parasomnias and 30 of them were treated with iron therapy. Of the 30 participants, RLS symptoms improved in 15 participants (50%) and resolution of parasomnias was noted in 12 participants (40%) participants after iron therapy. Repeat polysomnography after iron therapy was performed in 21 participants (70%). After iron therapy, there was a significant decrease in periodic limb movement index (17.2 ± 8.8 [before] versus 6.7 ± 7.3 [after] events/h, P < .001). In addition, there were significant decreases in PLMS (24.52 ± 9.42 [before] versus 7.50 ± 7.18 [after] events/h, P < .0001), PLMS-related arousals (4.71 ± 1.81 [before] versus 1.35 ± 1.43 [after] events/h, P < .0001), and total arousals (11.65 ± 5.49 [before] versus 8.94 ± 3.65 [after] events/h, P < .01) after iron therapy. CONCLUSIONS Parasomnias are common in our cohort of children with RLS/PLMD. Iron therapy was associated with a significant improvement in periodic limb movement index, RLS symptoms, and resolution of a significant proportion of NREM sleep parasomnias, suggesting that RLS/PLMD may precipitate NREM sleep parasomnia.
Seminars in pediatric neurology, 2015
Sleep and epilepsy are common bedfellows. Sleep can affect frequency and occurrence of interictal... more Sleep and epilepsy are common bedfellows. Sleep can affect frequency and occurrence of interictal spikes and occurrence, timing, and threshold of seizure. Epilepsy can worsen sleep architecture and severity of sleep disorders. Thus, a vicious cycle is set. Certain epilepsy syndromes are so intertwined with sleep that they are considered sleep-related epilepsies. Poor sleep in epilepsy is multifactorial and is worsened by poorly controlled seizures. On the contrary, poor sleep is associated with worsened quality of life, psychological function, and memory. Improving sleep has been noted to improve seizure frequency and an overall well-being in patients with epilepsy. Hence, an emphasis should be given to address sleep in patients with epilepsy. These interactions are discussed in detail in this review.
2012 ICME International Conference on Complex Medical Engineering (CME), 2012
ABSTRACT Magnetoencephalography (MEG) has been shown to be a useful diagnostic tool for presurgic... more ABSTRACT Magnetoencephalography (MEG) has been shown to be a useful diagnostic tool for presurgical evaluation of pediatric medically intractable partial epilepsy. MEG source localization has been shown to improve the likelihood of seizure onset zone (SOZ) sampling during subsequent evaluation with intracranial EEG (ICEEG). We investigated whether frequency-dependent ictal MEG onset source localization further improves results of interictal MEG in defining the SOZ. Source localization analyses were applied using multiple algorithms, both at the beginning of ictal onset and for interictal MEG discharges. Ictal MEG onsets were identified by visual inspection and power spectrum using short-time Fourier transform (STFT). Source localizations were compared with ICEEG, surgical procedure and outcome. Eight patients were included in this study. Five of the 8 patients (63%) had concordant ictal MEG onset source localization and interictal MEG discharge source localizations in the same lobe, but the source of ictal MEG onset was closer to the SOZ defined by ICEEG. The source localization for the earliest ictal MEG onset with patient-specific frequency change proved to be a useful tool for presurgical evaluation in our pediatric population with medically intractable epilepsy.
Journal of Clinical Sleep Medicine, 2013
Pediatric Neurology, 2008
Intravenous tissue plasminogen activator has become a mainstream treatment for ischemic hyperacut... more Intravenous tissue plasminogen activator has become a mainstream treatment for ischemic hyperacute stroke in the adult population. Its safety and efficacy remain undetermined in the pediatric population. We present a teenager who was hospitalized with left-sided paralysis, and with decreased sensations on the left side. Head computed tomography indicated hyperdensity in the middle cerebral artery region, which confirmed the diagnosis of acute ischemic stroke. Her score on the National Institutes of Health stroke scale was 11. She received intravenous tissue plasminogen activator without any complications. At a follow-up visit 5 months after the stroke, the patient manifested mild apraxia in her left hand and mild expressive amusia. This case underscores the need for emergency head imaging in the pediatric population to establish a diagnosis. The excellent recovery in our patient indicates the need to establish thrombolytic treatment as an option for acute stroke in pediatric populations. It also suggests that tissue plasminogen activator can be used safely and effectively, even in pediatric populations. However, further studies are needed to establish the adequate dosage and adverseeffect profile in pediatric populations.
Journal of Child Neurology, 2012
Sleep disorders significantly affect the lives of children with epilepsy. Limited data exist abou... more Sleep disorders significantly affect the lives of children with epilepsy. Limited data exist about provider practices concerning detection and correct diagnosis of sleep problems in epilepsy. The authors conducted this study to identify and correlate sleep screening methods, referral practices, referral reasons and final sleep diagnoses. They identified that 94% of the providers who had referred patients to the sleep center of a major children’s hospital used routine screening and 70% of them used 2 to 3 screening questions. This method, however, underidentified the patients at risk for sleep disorders. Moreover, in 40% of the children, sleep disorder was incorrectly anticipated, based on the initial symptoms. Of these children, 10% had no sleep disorder and 30% had unexpected sleep disorder. The authors conclude that better screening methods should be used for sleep disorders. Once identified, these patients should have formal sleep evaluation and management. Further studies are ne...
Journal of Child Neurology, 2012
Sleep-related breathing disruptions in children with epilepsy are common and can range from prima... more Sleep-related breathing disruptions in children with epilepsy are common and can range from primary snoring to obstructive sleep apnea. Untreated obstructive sleep apnea can lead to significant morbidity. This study aimed to identify factors associated with its occurrence and severity in children with epilepsy. Children with epilepsy and sleep disruption were evaluated with polysomnography and diagnosed with obstructive sleep apnea or primary snoring. Statistical analyses were done to identify differences within both the groups and among the subjects in the obstructive sleep apnea group. Uncontrolled epilepsy was a risk factor for obstructive sleep apnea (80%) compared with primary snoring (47%, P = .02). Obstructive index increased with increasing number of antiepileptic drugs. In children with epilepsy and disturbed sleep, obstructive sleep apnea is associated with uncontrolled epilepsy and is more severe with polytherapy use. Children with uncontrolled seizures on antiepileptic p...
Journal of Child Neurology, 2012
Central sleep apnea is not uncommon in children with neurologic disorders. The mechanisms include... more Central sleep apnea is not uncommon in children with neurologic disorders. The mechanisms include increased ventilatory chemosensitivity to carbon dioxide level. Conventional treatments include oxygen, noninvasive ventilation, and in patients with heart failure, improving cardiac output. Here, we present a case of a 9-year-old male with Angelman syndrome, epilepsy, insomnia, and central sleep apnea. The patient was initially evaluated for nighttime awakenings and pauses in breathing. Sustained-release melatonin was used to improve his nighttime awakenings. A polysomnography confirmed central sleep apnea. We saw a reduction in arousals and improvement in insomnia with sustained-release melatonin. On a repeat study, central sleep apnea was improved. We hypothesize that sustained-release melatonin, by improving sleep continuity and reducing arousals, might improve central sleep apnea. Studies are needed to test the hypothesis.
Epilepsy Research, 2012
Purpose-Magnetoencephalography (MEG) has been shown a useful diagnostic tool for presurgical eval... more Purpose-Magnetoencephalography (MEG) has been shown a useful diagnostic tool for presurgical evaluation of pediatric medically intractable partial epilepsy as MEG source localization has been shown to improve the likelihood of seizure onset zone (SOZ) sampling during subsequent evaluation with intracranial EEG (ICEEG). We investigated whether ictal MEG onset source localization further improves results of interictal MEG in defining the SOZ. Methods-We identified 20 pediatric patients with one habitual seizure during MEG recordings between October 2007 and April 2011. MEG was recorded with sampling rates of 600 Hz and 4000 Hz for 10 and 2 minutes respectively. Continuous head localization (CHL) was applied. Source localization analyses were applied using multiple algorithms, both at the beginning of ictal onset and for interictal MEG discharges. Ictal MEG onsets were identified by visual inspection and power spectrum using short-time Fourier transform (STFT). Source localizations were compared with ICEEG, surgical procedure and outcome. Key findings-Eight patients met all inclusion criteria. Five of the 8 patients (63%) had concordant ictal MEG onset source localization and interictal MEG discharge source localizations in the same lobe, but the source of ictal MEG onset was closer to the SOZ defined by ICEEG. Significance-Although the capture of seizures during MEG recording is challenging, the source localization for ictal MEG onset proved to be a useful tool for presurgical evaluation in our pediatric population with medically intractable epilepsy.
Acta Neurologica Scandinavica, 2011
Obstructive sleep apnea (OSA) is prevalent in adults with epilepsy, especially refractory, but li... more Obstructive sleep apnea (OSA) is prevalent in adults with epilepsy, especially refractory, but limited data exist in children with epilepsy. We conducted a prospective pilot study in children with epilepsy to identify the prevalence of OSA and its relationship to the use of antiepileptic drugs (AEDs) and epilepsy types. We used Michigan Pediatric Sleep Questionnaire (PSQ) in children with epilepsy. Patients were classified by seizures frequency as mild (0-1 seizure/month) or severe, refractory epilepsy (> 1 seizures/month). We used PSQ ≥ 0.33 as a cutoff point to assess the risk of OSA. Of 84 children, 52 were classified as mild and 32 as severe. Prevalence of OSA was significantly higher in the severe (43.8%) vs the mild group (30.7%, P < 0.05). Children on >1 AED had significantly higher prevalence of OSA (45.8%) than children on ≤1 AED (30.6%, P < 0.05). There was no significant correlation between the prevalence of OSA and seizure types. OSA is more prevalent in refractory epilepsy and in children who are on multiple AEDs. While further studies are needed to confirm these findings and to assess the consequences of OSA, we believe it is important to screen the children with epilepsy for OSA.
Cancer Epidemiology, Biomarkers & Prevention
Many studies show racial and ethnic survival disparities in lung squamous cell carcinoma (LSCC), ... more Many studies show racial and ethnic survival disparities in lung squamous cell carcinoma (LSCC), and self-identified African-Americans have significantly lower overall survival and progression-free survival than self-identified Caucasians. However, survival models based on genetic ancestry, rather than self-identified race, are needed to assess whether genetic ancestry influences this survival disparity or whether the cause of the disparity is largely socioeconomic. Using clinically annotated genomic data from 501 LSCC tumor samples in the Cancer Genome Atlas (TCGA), we compared clinical data, gene expression profiles, mutations, and copy number changes of tumors across ancestral groups to identify significantly differential events. We then applied the Cox Proportional Hazards model to predict overall survival as a function of genetic ancestry alongside other genetic, molecular, and clinical variables. We found a significant difference in metastatic stage between tumors from patient...
Sleep
This study was aimed to evaluate the yearly incidence of pediatric narcolepsy prior to and follow... more This study was aimed to evaluate the yearly incidence of pediatric narcolepsy prior to and following the 2009 H1N1 pandemic and to evaluate seasonal patterns of narcolepsy onset and associations with H1N1 influenza infection in the United States. This was a multicenter retrospective study with prospective follow-up. Participants were recruited from members of the Pediatric Working Group of the Sleep Research Network including 22 sites across the United States. The main outcomes were monthly and yearly incident cases of childhood narcolepsy in the United States, and its relationship to historical H1N1 influenza data. A total of 950 participants were included in the analysis; 487 participants were male (51.3%). The mean age at onset of excessive daytime sleepiness (EDS) was 9.6 ± 3.9 years. Significant trend changes in pediatric narcolepsy incidence based on EDS onset (p < .0001) occurred over the 1998–2016 period, peaking in 2010, reflecting a 1.6-fold increase in narcolepsy i...
Additional file 1: Supplementary Methods. Supplementary Table 1. LFA commercial kit information, ... more Additional file 1: Supplementary Methods. Supplementary Table 1. LFA commercial kit information, sample requirements, and protocol details. Supplementary Table 2. IFU clarity rubric. Supplementary Table 3. Usability ratings and description of kit components. Supplementary Table 4. Clinical information for the COVID-positive individuals whose plasma was used in this study. Supplementary Table 5. LFA Limits of detection estimated from anti-spike antibodies concentrations measured by Simoa.
BMC Infectious Diseases, 2021
Cancer Research, 2021
Aneuploidy, which we define as whole chromosome or chromosome arm copy number imbalance, is a nea... more Aneuploidy, which we define as whole chromosome or chromosome arm copy number imbalance, is a near-universal characteristic of human cancers. Cancer subtypes are often characterized by tumor specific patterns of chromosome arm copy number alterations; for example, squamous cell carcinomas (SCCs) from different tissues of origin (including lung, head and neck, esophagus, and bladder) have a pattern of chromosome 3p loss and chromosome 3q gain. Although these alterations are frequent, they are not well understood due to difficulty in modeling specific aneuploidy alterations in the matching cell type. However, recent advances in genome engineering allow generation of large chromosomal alterations. We used the CRISPR-Cas9 system to delete one copy of chromosome 3p in human immortalized lung epithelial cells most similar to upper airway basal cells. Deletion of chromosome 3p was validated by whole genome sequencing and karyotyping. Consistent with patient data, expression of 3p genes was...
BMC Infectious Diseases, 2021
Background COVID-19 has resulted in significant morbidity and mortality worldwide. Lateral flow a... more Background COVID-19 has resulted in significant morbidity and mortality worldwide. Lateral flow assays can detect anti-Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) antibodies to monitor transmission. However, standardized evaluation of their accuracy and tools to aid in interpreting results are needed. Methods We evaluated 20 IgG and IgM assays selected from available tests in April 2020. We evaluated the assays’ performance using 56 pre-pandemic negative and 56 SARS-CoV-2-positive plasma samples, collected 10–40 days after symptom onset, confirmed by a molecular test and analyzed by an ultra-sensitive immunoassay. Finally, we developed a user-friendly web app to extrapolate the positive predictive values based on their accuracy and local prevalence. Results Combined IgG + IgM sensitivities ranged from 33.9 to 94.6%, while combined specificities ranged from 92.6 to 100%. The highest sensitivities were detected in Lumiquick for IgG (98.2%), BioHit for both IgM (96.4%)...
Cancer Research, 2020
Aneuploidy, whole-chromosome or chromosome arm copy number imbalance, is a near-universal charact... more Aneuploidy, whole-chromosome or chromosome arm copy number imbalance, is a near-universal characteristic of human cancers. We previously applied methods that define chromosome arm-level aneuploidy and a global cancer aneuploidy score to 10,522 tumors of 33 types in The Cancer Genome Atlas (TCGA). Aneuploidy level was correlated with TP53 mutation, somatic mutation rate, and expression of proliferation genes. Overall aneuploidy was anti-correlated with expression of immune signaling genes, due to decreased leukocyte infiltrates in high-aneuploidy samples. In contrast, some individual chromosome arm alterations correlated with higher expression of immune signaling genes, including deletion of chromosome 3p, 8p, and 17p. Cancer subtypes are often characterized by tumor specific patterns of arm-level copy number alterations; for example, squamous cell carcinomas (SCCs) from different tissues of origin (including lung, esophagus, and bladder) have a pattern of chromosome 3p loss and chro...
Nature Communications, 2019
Lung cancer shows substantial genetic and phenotypic heterogeneity across individuals, driving a ... more Lung cancer shows substantial genetic and phenotypic heterogeneity across individuals, driving a need for personalised medicine. Here, we report lung cancer organoids and normal bronchial organoids established from patient tissues comprising five histological subtypes of lung cancer and non-neoplastic bronchial mucosa as in vitro models representing individual patient. The lung cancer organoids recapitulate the tissue architecture of the primary lung tumours and maintain the genomic alterations of the original tumours during long-term expansion in vitro. The normal bronchial organoids maintain cellular components of normal bronchial mucosa. Lung cancer organoids respond to drugs based on their genomic alterations: a BRCA2-mutant organoid to olaparib, an EGFR-mutant organoid to erlotinib, and an EGFR-mutant/MET-amplified organoid to crizotinib. Considering the short length of time from organoid establishment to drug testing, our newly developed model may prove useful for predicting p...
Journal of Clinical Sleep Medicine, 2019
STUDY OBJECTIVES Previous studies have shown that non-rapid eye movement (NREM) sleep parasomnias... more STUDY OBJECTIVES Previous studies have shown that non-rapid eye movement (NREM) sleep parasomnias commonly coexist with restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) in children, leading to speculation that RLS/PLMD may precipitate or worsen parasomnias. However, there are limited data about the effect of the treatment of RLS/PLMD on parasomnias in children. Hence, we performed this study to determine whether the treatment of RLS/PLMD with oral iron therapy is associated with improvement of parasomnias in children. METHODS A retrospective database was created for children with RLS/PLMD who were treated with iron therapy. These participants were followed for at least 1 year at Cincinnati Children's Hospital Medical Center. All participants had ferritin level testing and were treated with iron therapy. In addition, all participants underwent polysomnography before starting iron therapy for RLS/PLMD except for one participant who was already on iron but required a higher dose. Most participants underwent polysomnography after iron therapy. RESULTS A total of 226 participants were identified with the diagnosis of RLS/PLMD. Of these, 50 had parasomnias and 30 of them were treated with iron therapy. Of the 30 participants, RLS symptoms improved in 15 participants (50%) and resolution of parasomnias was noted in 12 participants (40%) participants after iron therapy. Repeat polysomnography after iron therapy was performed in 21 participants (70%). After iron therapy, there was a significant decrease in periodic limb movement index (17.2 ± 8.8 [before] versus 6.7 ± 7.3 [after] events/h, P < .001). In addition, there were significant decreases in PLMS (24.52 ± 9.42 [before] versus 7.50 ± 7.18 [after] events/h, P < .0001), PLMS-related arousals (4.71 ± 1.81 [before] versus 1.35 ± 1.43 [after] events/h, P < .0001), and total arousals (11.65 ± 5.49 [before] versus 8.94 ± 3.65 [after] events/h, P < .01) after iron therapy. CONCLUSIONS Parasomnias are common in our cohort of children with RLS/PLMD. Iron therapy was associated with a significant improvement in periodic limb movement index, RLS symptoms, and resolution of a significant proportion of NREM sleep parasomnias, suggesting that RLS/PLMD may precipitate NREM sleep parasomnia.
Seminars in pediatric neurology, 2015
Sleep and epilepsy are common bedfellows. Sleep can affect frequency and occurrence of interictal... more Sleep and epilepsy are common bedfellows. Sleep can affect frequency and occurrence of interictal spikes and occurrence, timing, and threshold of seizure. Epilepsy can worsen sleep architecture and severity of sleep disorders. Thus, a vicious cycle is set. Certain epilepsy syndromes are so intertwined with sleep that they are considered sleep-related epilepsies. Poor sleep in epilepsy is multifactorial and is worsened by poorly controlled seizures. On the contrary, poor sleep is associated with worsened quality of life, psychological function, and memory. Improving sleep has been noted to improve seizure frequency and an overall well-being in patients with epilepsy. Hence, an emphasis should be given to address sleep in patients with epilepsy. These interactions are discussed in detail in this review.
2012 ICME International Conference on Complex Medical Engineering (CME), 2012
ABSTRACT Magnetoencephalography (MEG) has been shown to be a useful diagnostic tool for presurgic... more ABSTRACT Magnetoencephalography (MEG) has been shown to be a useful diagnostic tool for presurgical evaluation of pediatric medically intractable partial epilepsy. MEG source localization has been shown to improve the likelihood of seizure onset zone (SOZ) sampling during subsequent evaluation with intracranial EEG (ICEEG). We investigated whether frequency-dependent ictal MEG onset source localization further improves results of interictal MEG in defining the SOZ. Source localization analyses were applied using multiple algorithms, both at the beginning of ictal onset and for interictal MEG discharges. Ictal MEG onsets were identified by visual inspection and power spectrum using short-time Fourier transform (STFT). Source localizations were compared with ICEEG, surgical procedure and outcome. Eight patients were included in this study. Five of the 8 patients (63%) had concordant ictal MEG onset source localization and interictal MEG discharge source localizations in the same lobe, but the source of ictal MEG onset was closer to the SOZ defined by ICEEG. The source localization for the earliest ictal MEG onset with patient-specific frequency change proved to be a useful tool for presurgical evaluation in our pediatric population with medically intractable epilepsy.
Journal of Clinical Sleep Medicine, 2013
Pediatric Neurology, 2008
Intravenous tissue plasminogen activator has become a mainstream treatment for ischemic hyperacut... more Intravenous tissue plasminogen activator has become a mainstream treatment for ischemic hyperacute stroke in the adult population. Its safety and efficacy remain undetermined in the pediatric population. We present a teenager who was hospitalized with left-sided paralysis, and with decreased sensations on the left side. Head computed tomography indicated hyperdensity in the middle cerebral artery region, which confirmed the diagnosis of acute ischemic stroke. Her score on the National Institutes of Health stroke scale was 11. She received intravenous tissue plasminogen activator without any complications. At a follow-up visit 5 months after the stroke, the patient manifested mild apraxia in her left hand and mild expressive amusia. This case underscores the need for emergency head imaging in the pediatric population to establish a diagnosis. The excellent recovery in our patient indicates the need to establish thrombolytic treatment as an option for acute stroke in pediatric populations. It also suggests that tissue plasminogen activator can be used safely and effectively, even in pediatric populations. However, further studies are needed to establish the adequate dosage and adverseeffect profile in pediatric populations.
Journal of Child Neurology, 2012
Sleep disorders significantly affect the lives of children with epilepsy. Limited data exist abou... more Sleep disorders significantly affect the lives of children with epilepsy. Limited data exist about provider practices concerning detection and correct diagnosis of sleep problems in epilepsy. The authors conducted this study to identify and correlate sleep screening methods, referral practices, referral reasons and final sleep diagnoses. They identified that 94% of the providers who had referred patients to the sleep center of a major children’s hospital used routine screening and 70% of them used 2 to 3 screening questions. This method, however, underidentified the patients at risk for sleep disorders. Moreover, in 40% of the children, sleep disorder was incorrectly anticipated, based on the initial symptoms. Of these children, 10% had no sleep disorder and 30% had unexpected sleep disorder. The authors conclude that better screening methods should be used for sleep disorders. Once identified, these patients should have formal sleep evaluation and management. Further studies are ne...
Journal of Child Neurology, 2012
Sleep-related breathing disruptions in children with epilepsy are common and can range from prima... more Sleep-related breathing disruptions in children with epilepsy are common and can range from primary snoring to obstructive sleep apnea. Untreated obstructive sleep apnea can lead to significant morbidity. This study aimed to identify factors associated with its occurrence and severity in children with epilepsy. Children with epilepsy and sleep disruption were evaluated with polysomnography and diagnosed with obstructive sleep apnea or primary snoring. Statistical analyses were done to identify differences within both the groups and among the subjects in the obstructive sleep apnea group. Uncontrolled epilepsy was a risk factor for obstructive sleep apnea (80%) compared with primary snoring (47%, P = .02). Obstructive index increased with increasing number of antiepileptic drugs. In children with epilepsy and disturbed sleep, obstructive sleep apnea is associated with uncontrolled epilepsy and is more severe with polytherapy use. Children with uncontrolled seizures on antiepileptic p...
Journal of Child Neurology, 2012
Central sleep apnea is not uncommon in children with neurologic disorders. The mechanisms include... more Central sleep apnea is not uncommon in children with neurologic disorders. The mechanisms include increased ventilatory chemosensitivity to carbon dioxide level. Conventional treatments include oxygen, noninvasive ventilation, and in patients with heart failure, improving cardiac output. Here, we present a case of a 9-year-old male with Angelman syndrome, epilepsy, insomnia, and central sleep apnea. The patient was initially evaluated for nighttime awakenings and pauses in breathing. Sustained-release melatonin was used to improve his nighttime awakenings. A polysomnography confirmed central sleep apnea. We saw a reduction in arousals and improvement in insomnia with sustained-release melatonin. On a repeat study, central sleep apnea was improved. We hypothesize that sustained-release melatonin, by improving sleep continuity and reducing arousals, might improve central sleep apnea. Studies are needed to test the hypothesis.
Epilepsy Research, 2012
Purpose-Magnetoencephalography (MEG) has been shown a useful diagnostic tool for presurgical eval... more Purpose-Magnetoencephalography (MEG) has been shown a useful diagnostic tool for presurgical evaluation of pediatric medically intractable partial epilepsy as MEG source localization has been shown to improve the likelihood of seizure onset zone (SOZ) sampling during subsequent evaluation with intracranial EEG (ICEEG). We investigated whether ictal MEG onset source localization further improves results of interictal MEG in defining the SOZ. Methods-We identified 20 pediatric patients with one habitual seizure during MEG recordings between October 2007 and April 2011. MEG was recorded with sampling rates of 600 Hz and 4000 Hz for 10 and 2 minutes respectively. Continuous head localization (CHL) was applied. Source localization analyses were applied using multiple algorithms, both at the beginning of ictal onset and for interictal MEG discharges. Ictal MEG onsets were identified by visual inspection and power spectrum using short-time Fourier transform (STFT). Source localizations were compared with ICEEG, surgical procedure and outcome. Key findings-Eight patients met all inclusion criteria. Five of the 8 patients (63%) had concordant ictal MEG onset source localization and interictal MEG discharge source localizations in the same lobe, but the source of ictal MEG onset was closer to the SOZ defined by ICEEG. Significance-Although the capture of seizures during MEG recording is challenging, the source localization for ictal MEG onset proved to be a useful tool for presurgical evaluation in our pediatric population with medically intractable epilepsy.
Acta Neurologica Scandinavica, 2011
Obstructive sleep apnea (OSA) is prevalent in adults with epilepsy, especially refractory, but li... more Obstructive sleep apnea (OSA) is prevalent in adults with epilepsy, especially refractory, but limited data exist in children with epilepsy. We conducted a prospective pilot study in children with epilepsy to identify the prevalence of OSA and its relationship to the use of antiepileptic drugs (AEDs) and epilepsy types. We used Michigan Pediatric Sleep Questionnaire (PSQ) in children with epilepsy. Patients were classified by seizures frequency as mild (0-1 seizure/month) or severe, refractory epilepsy (> 1 seizures/month). We used PSQ ≥ 0.33 as a cutoff point to assess the risk of OSA. Of 84 children, 52 were classified as mild and 32 as severe. Prevalence of OSA was significantly higher in the severe (43.8%) vs the mild group (30.7%, P < 0.05). Children on >1 AED had significantly higher prevalence of OSA (45.8%) than children on ≤1 AED (30.6%, P < 0.05). There was no significant correlation between the prevalence of OSA and seizure types. OSA is more prevalent in refractory epilepsy and in children who are on multiple AEDs. While further studies are needed to confirm these findings and to assess the consequences of OSA, we believe it is important to screen the children with epilepsy for OSA.