OBJECTIVES: Studies have suggested intrapulmonary shunts may contribute to hypoxemia in COVID-19 ... more OBJECTIVES: Studies have suggested intrapulmonary shunts may contribute to hypoxemia in COVID-19 acute respiratory distress syndrome (ARDS) with worse associated outcomes. We evaluated the presence of right-to-left (R-L) shunts in COVID-19 and non-COVID ARDS patients using a comprehensive hypoxemia workup for shunt etiology and associations with mortality. DESIGN: Prospective, observational cohort study. SETTING: Four tertiary hospitals in Edmonton, Alberta, Canada. PATIENTS: Adult critically ill, mechanically ventilated, ICU patients admitted with COVID-19 or non-COVID (November 16, 2020, to September 1, 2021). INTERVENTIONS: Agitated-saline bubble studies with transthoracic echocardiography/transcranial Doppler ± transesophageal echocardiography assessed for R-L shunts presence. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were shunt frequency and association with hospital mortality. Logistic regression analysis was used for adjustment. The study enrolled 226 patients (182 COVI...
ImportanceStudies have suggested intra-pulmonary shunts may contribute to hypoxemia in COVID-19 A... more ImportanceStudies have suggested intra-pulmonary shunts may contribute to hypoxemia in COVID-19 ARDS and may be associated with worse outcomes.ObjectiveTo evaluate the presence of right-to-left (R-L) shunts in COVID-19 and non-COVID ARDS patients using a comprehensive hypoxemia work-up for shunt etiology and associations with mortality.Design, Setting, ParticipantsWe conducted a multi-centre (4 Canadian hospitals), prospective, observational cohort study of adult critically ill, mechanically ventilated, ICU patients admitted for ARDS from both COVID-19 or non-COVID (November 16, 2020-September 1, 2021).InterventionContrast-enhanced agitated-saline bubble studies with transthoracic echocardiography/transcranial Doppler (TTE/TCD) ± transesophageal echocardiography (TEE) assessed for the presence of R-L shunts.Main Outcomes and MeasuresPrimary outcomes were shunt incidence and association with hospital mortality. Logistic regression analysis was used to determine association of shunt p...
OBJECTIVEDiffusion tensor imaging (DTI) tractography is commonly used in neurosurgical practice b... more OBJECTIVEDiffusion tensor imaging (DTI) tractography is commonly used in neurosurgical practice but is largely limited to the preoperative setting. This is due primarily to image degradation caused by susceptibility artifact when conventional single-shot (SS) echo-planar imaging (EPI) DTI (SS-DTI) is acquired for open cranial, surgical position intraoperative DTI (iDTI). Readout-segmented (RS) EPI DTI (RS-DTI) has been reported to reduce such artifact but has not yet been evaluated in the intraoperative MRI (iMRI) environment. The authors evaluated the performance of RS versus SS EPI for DTI of the human brain in the iMRI setting.METHODSPre- and intraoperative 3-T 3D T1-weighted and 2D multislice RS-iDTI (called RESOLVE [readout segmentation of long variable echo-trains] on the Siemens platform) and SS-iDTI images were acquired in 22 adult patients undergoing intraaxial iMRI resections for suspected low-grade glioma (14; 64%), high-grade glioma (7; 32%), or focal cortical dysplasia....
OBJECTIVE The aim of this study was to investigate long-term seizure outcome, rate of reoperation... more OBJECTIVE The aim of this study was to investigate long-term seizure outcome, rate of reoperation, and postoperative neuropsychological performance following selective amygdalohippocampectomy (SelAH) or anterior temporal lobectomy (ATL) in pediatric patients with medically refractory temporal lobe epilepsy (TLE). METHODS The authors performed a retrospective review of cases of medically refractory pediatric TLE treated initially with either SelAH or ATL. Standardized pre- and postoperative evaluation included seizure charting, surface and long-term video-electroencephalography, 1.5-T MRI, and neuropsychological testing. RESULTS A total of 79 patients treated initially with SelAH (n = 18) or ATL (n = 61) were included in this study, with a mean follow-up of 5.3 ± 4 years (range 1-16 years). The patients' average age at initial surgery was 10.6 ± 5 years, with an average surgical delay of 5.7 ± 4 years between seizure onset and surgery. Seizure freedom (Engel I) following the init...
1) Characterize the evolution of microstructural changes in the contralateral, non-operated hippo... more 1) Characterize the evolution of microstructural changes in the contralateral, non-operated hippocampus-using longitudinal diffusion tensor imaging (DTI)-following surgery for temporal lobe epilepsy (TLE). 2) Characterize the downstream extra-hippocampal volumetric changes of the fornix and mammillary bodies after TLE surgery. 3) Examine the relationship between these measures and seizure/cognitive outcome. Serial structural and DTI brain MRI scans were collected in 25 TLE patients pre- and post-surgery (anterior temporal lobectomy, ATL - 13; selective amygdalohippocampectomy, SelAH - 12) and in 12 healthy controls. Contralateral hippocampal fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were computed with manual hippocampal tracings as volumes of interest following co-registration to anatomical images. Fornix and mammillary body volumetry was performed by manual segmentation. After surgery, the non-resected hippocampus showed s...
<p>(<b>A</b>) Deep sequencing of the fetal and surgically resected (Surg) brain... more <p>(<b>A</b>) Deep sequencing of the fetal and surgically resected (Surg) brain samples revealed that HERV-H exhibited the highest tag frequency and median number of tags followed by HERV-K. (<b>B</b>) When analyzing the HERV-K tags, LTR tags were most abundant, followed by <i>gag-pol</i> and then the <i>env</i> region tags (tags were normalized to respective gene lengths) (<b>C</b>) All host genes with transcript expression profiles correlated with HERV-K(II) <i>env</i> tag abundance (r<sup>2</sup><b>≥</b>0.5) were analyzed using the DAVID tools <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097984#pone.0097984-DAVID1" target="_blank">[58]</a> for enriched gene ontology (GO) terms. Genes related to cell cycle functions and chromosomal organization were most strongly associated with HERV-K(II) <i>env</i> expression. With the use of DAVID bioinformatics resources <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097984#pone.0097984-Dennis1" target="_blank">[59]</a>, the predicted target genes were classified according to KEGG functional annotations to identify pathways that were actively regulated by HERV-K(II) <i>env</i> transcripts in brain tissue. The most over-represented GO term belonged to the transcriptional regulation and chromosome organization followed by different stages of cell cycle pathway. (Mann Whitney t test, *<i>p</i><0.05, **<i>p</i><0.01).</p
<p>(<b>A</b>) Individual cell lines displayed differential constitutive HERV-K(... more <p>(<b>A</b>) Individual cell lines displayed differential constitutive HERV-K(II) <i>env</i> expression profiles. (<b>B</b>) Upon treatment of human fetal neurons, db-cAMP did not have any effects on HERV-K(II) <i>env</i> expression but EGF down-regulated HERV-K(II) expression. (<b>C</b>) U937 and (<b>D</b>) HFA showed decreased in HERV-K(II) <i>env</i> expression upon both db-cAMP and EGF exposure. (n = 4 replicates per group across two independent experiments).</p
<p>(<b>A</b>) Transfection of the pHERV-Kenv plasmid into SK-N-SH cells showed ... more <p>(<b>A</b>) Transfection of the pHERV-Kenv plasmid into SK-N-SH cells showed HERV-K(II) Env immunoreactivity at the predicted molecular weight on western blot. (<b>B</b>) Upon treatment with supernatants from SK-N-SH cells transfected with pHERV-Kenv plasmid, HFN showed increases in <i>BDNF</i> and <i>NGF</i> transcript abundance compared to the control vector transfected cells. (n = 3, with technical quadruplicates) (<b>C</b>) βIII-tubulin expression in HFN following 24-hour exposure to supernatants from HFA-transfected with the pHERV-Kenv or the control vector, showing an increase in βIII-tubulin immunoreactivity in cells exposed to HERV-K Env-transfected cells. (n = 2, with technical octuplicates) (Student t test, *<i>p</i><0.05, **<i>p</i><0.01).</p
BACKGROUND Microvascular decompression (MVD) is an effective treatment for trigeminal neuralgia (... more BACKGROUND Microvascular decompression (MVD) is an effective treatment for trigeminal neuralgia (TN), but pain recurrence occurs in a substantial minority of patients. Two recently published scoring systems by Hardaway et al. (HR) and Panczykowski et al. (PS) use simple preoperative clinical and imaging features to predict durable pain-relief following MVD, but their predictive performance has not been independently validated. OBJECTIVE To compare predictive performance of HR and PS scores for one-year, three-year, and long-term pain-free outcomes after MVD for TN. METHODS HR and PS scores were computed for a retrospective, single-institution cohort of 68 TN patients who underwent MVD. Primary outcome was pain recurrence post-MVD. Predictive performance of HR and PS scores was evaluated with area under the curve (AUC) sensitivity analysis, and regression models for survival analyses at one-year, three-year, and last follow-up. RESULTS AUC for predicting pain-free outcome was higher for PS versus HR Score at one-year (0.873 versus 0.775) and three-years (0.793 versus 0.704). Cox proportional-hazard models showed that PS score better predicted long-term pain-free outcomes compared to HR score (P < 0.05). One-year pain-free outcome was best predicted by pain type; longer-term outcomes were better predicted by presence and degree of neurovascular compression on preoperative imaging. CONCLUSION PS score is superior to HR score in predicting pain-free outcomes after MVD, which may aid in patient selection and counseling. Overall, more significant neurovascular compression of the trigeminal nerve root, and to a lesser extent classical paroxysmal pain, are good predictors of durable pain relief post-MVD.
Human endogenous retroviruses (HERVs) are differentially expressed depending on the cell type and... more Human endogenous retroviruses (HERVs) are differentially expressed depending on the cell type and physiological circumstances. HERV-K has been implicated in the pathogenesis of several diseases although the functional consequences of its expression remain unknown. Human immunodeficiency virus (HIV) infection causes neuroinflammation with neuronal damage and death. Herein, we investigated HERV-K(II)/(HML-2) envelope (Env) expression and its actions in the brain during HIV/AIDS. HERV-K(II) Env expression was assessed in healthy brain tissues, autopsied HIV HIV- infected (HIV+) and uninfected (HIV-) brains and in neural cell cultures by real time RT-PCR, massively parallel (deep) sequencing, immunoblotting and immunohistochemistry. Neuronal and neural stem cells expressing HERV-K(II) Env were analyzed in assays of host responses including cellular viability, immune responses and neurobehavioral outcomes. Deep sequencing of human brain transcriptomes disclosed that RNA sequences encoded...
Background Medically-refractory trigeminal neuralgia (TN) can be treated successfully with operat... more Background Medically-refractory trigeminal neuralgia (TN) can be treated successfully with operative intervention, but a significant proportion of patients are non-responders despite undergoing technically successful surgery. The thalamus is a key component of the trigeminal sensory pathway involved in transmitting facial pain, but the role of the thalamus in TN, and its influence on durability of pain relief after TN surgery, are relatively understudied. We aimed to test the hypothesis that variations in thalamic structure and metabolism are related to surgical non-response in TN. Methods We performed a longitudinal, peri-operative neuroimaging study of the thalamus in medically-refractory TN patients undergoing microvascular decompression or percutaneous balloon compression rhizotomy. Patients underwent structural MRI and MR spectroscopy scans pre-operatively and at 1-week following surgery, and were classified as responders or non-responders based on 1-year post-operative pain ou...
Introduction: Neurovascular lesions are rare and understudied in the pediatric population. Their ... more Introduction: Neurovascular lesions are rare and understudied in the pediatric population. Their initial presentation can range from seizures to focal neurologic deficits, as well as headaches. The goal of this study was to examine the clinical presentation and natural history of neurovascular lesions in children with epilepsy. Methods: We reviewed all pediatric epilepsy patients with neurovascular lesions diagnosed between 2006 and 2018 at the University of Alberta and the Stollery Children’s Hospital, Edmonton, Canada. Initial clinical presentation and brain imaging, as well as long-term epilepsy and postsurgical outcome, were assessed. Results: Of the 14 patients, 10 patients had an initial presentation of focal seizures with impaired awareness, whereas 2 patients presented with headache, 1 presented with visual field defects as well as chronic headaches, and 1 with decreased level of consciousness. Seven patients had cavernous angiomas, 6 had arteriovenous malformation, and 1 pa...
Journal of neuropathology and experimental neurology, Mar 1, 2017
Immune mechanisms have been increasingly recognized in the pathogenesis of hippocampal sclerosis ... more Immune mechanisms have been increasingly recognized in the pathogenesis of hippocampal sclerosis (HS), but infiltration of cytotoxic T-cells and its pathological significance in patients with HS has not been explored. We examined 30 cases of surgically resected hippocampi, including 16 International League Against Epilepsy (ILAE) type 1, 9 ILAE type 2, 1 ILAE type 3 HS, and 4 ILAE No-HS, as well as 6 autopsy No-HS hippocampi. The HS hippocampi showed sparse to scattered CD8-positive T-cells, rare CD4-positive T-cells, and a modest increase in CD68-positive microglia/macrophages, which were significantly more numerous than those in the No-HS controls. The infiltration of CD8-positive T-cells was significantly greater in the CA1 subfield than other subfields of type 1 and type 2 HS. The numbers of CD8-positive T-cells positively correlated with those of CD4-positive T-cells; there was a lower ratio of CD4/CD8-positive T-cells. There were positive correlations between these cells and s...
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques, 2009
The objective of the study was to review our experience with selective amygdalohippocampectomy (S... more The objective of the study was to review our experience with selective amygdalohippocampectomy (SAH) in children and adults with intractable temporal lobe epilepsy. A retrospective case series was used in the setting of a tertiary care hospital which provides epilepsy care to both children and adults. All patients underwent a selective amygdalohippocampectomy procedure and had at least one year of follow-up. Adults and children were divided into two groups and the data was compared between children and adults. Twenty three patients, 9 children and 14 adults were studied. Age of surgery varied from 6 to 58 years. Surgical outcome was variable between the two groups. Amongst the children, three patients (33%) were seizure-free (Engel Class I), two patients (22%) had rare seizures (Engel Class II), one patient (11%) had a worthwhile decrease in seizures (Engel class III) and three patients (32%) had refractory seizures that required re-operation with an anterior temporal lobectomy. Thi...
OBJECTIVES: Studies have suggested intrapulmonary shunts may contribute to hypoxemia in COVID-19 ... more OBJECTIVES: Studies have suggested intrapulmonary shunts may contribute to hypoxemia in COVID-19 acute respiratory distress syndrome (ARDS) with worse associated outcomes. We evaluated the presence of right-to-left (R-L) shunts in COVID-19 and non-COVID ARDS patients using a comprehensive hypoxemia workup for shunt etiology and associations with mortality. DESIGN: Prospective, observational cohort study. SETTING: Four tertiary hospitals in Edmonton, Alberta, Canada. PATIENTS: Adult critically ill, mechanically ventilated, ICU patients admitted with COVID-19 or non-COVID (November 16, 2020, to September 1, 2021). INTERVENTIONS: Agitated-saline bubble studies with transthoracic echocardiography/transcranial Doppler ± transesophageal echocardiography assessed for R-L shunts presence. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were shunt frequency and association with hospital mortality. Logistic regression analysis was used for adjustment. The study enrolled 226 patients (182 COVI...
ImportanceStudies have suggested intra-pulmonary shunts may contribute to hypoxemia in COVID-19 A... more ImportanceStudies have suggested intra-pulmonary shunts may contribute to hypoxemia in COVID-19 ARDS and may be associated with worse outcomes.ObjectiveTo evaluate the presence of right-to-left (R-L) shunts in COVID-19 and non-COVID ARDS patients using a comprehensive hypoxemia work-up for shunt etiology and associations with mortality.Design, Setting, ParticipantsWe conducted a multi-centre (4 Canadian hospitals), prospective, observational cohort study of adult critically ill, mechanically ventilated, ICU patients admitted for ARDS from both COVID-19 or non-COVID (November 16, 2020-September 1, 2021).InterventionContrast-enhanced agitated-saline bubble studies with transthoracic echocardiography/transcranial Doppler (TTE/TCD) ± transesophageal echocardiography (TEE) assessed for the presence of R-L shunts.Main Outcomes and MeasuresPrimary outcomes were shunt incidence and association with hospital mortality. Logistic regression analysis was used to determine association of shunt p...
OBJECTIVEDiffusion tensor imaging (DTI) tractography is commonly used in neurosurgical practice b... more OBJECTIVEDiffusion tensor imaging (DTI) tractography is commonly used in neurosurgical practice but is largely limited to the preoperative setting. This is due primarily to image degradation caused by susceptibility artifact when conventional single-shot (SS) echo-planar imaging (EPI) DTI (SS-DTI) is acquired for open cranial, surgical position intraoperative DTI (iDTI). Readout-segmented (RS) EPI DTI (RS-DTI) has been reported to reduce such artifact but has not yet been evaluated in the intraoperative MRI (iMRI) environment. The authors evaluated the performance of RS versus SS EPI for DTI of the human brain in the iMRI setting.METHODSPre- and intraoperative 3-T 3D T1-weighted and 2D multislice RS-iDTI (called RESOLVE [readout segmentation of long variable echo-trains] on the Siemens platform) and SS-iDTI images were acquired in 22 adult patients undergoing intraaxial iMRI resections for suspected low-grade glioma (14; 64%), high-grade glioma (7; 32%), or focal cortical dysplasia....
OBJECTIVE The aim of this study was to investigate long-term seizure outcome, rate of reoperation... more OBJECTIVE The aim of this study was to investigate long-term seizure outcome, rate of reoperation, and postoperative neuropsychological performance following selective amygdalohippocampectomy (SelAH) or anterior temporal lobectomy (ATL) in pediatric patients with medically refractory temporal lobe epilepsy (TLE). METHODS The authors performed a retrospective review of cases of medically refractory pediatric TLE treated initially with either SelAH or ATL. Standardized pre- and postoperative evaluation included seizure charting, surface and long-term video-electroencephalography, 1.5-T MRI, and neuropsychological testing. RESULTS A total of 79 patients treated initially with SelAH (n = 18) or ATL (n = 61) were included in this study, with a mean follow-up of 5.3 ± 4 years (range 1-16 years). The patients' average age at initial surgery was 10.6 ± 5 years, with an average surgical delay of 5.7 ± 4 years between seizure onset and surgery. Seizure freedom (Engel I) following the init...
1) Characterize the evolution of microstructural changes in the contralateral, non-operated hippo... more 1) Characterize the evolution of microstructural changes in the contralateral, non-operated hippocampus-using longitudinal diffusion tensor imaging (DTI)-following surgery for temporal lobe epilepsy (TLE). 2) Characterize the downstream extra-hippocampal volumetric changes of the fornix and mammillary bodies after TLE surgery. 3) Examine the relationship between these measures and seizure/cognitive outcome. Serial structural and DTI brain MRI scans were collected in 25 TLE patients pre- and post-surgery (anterior temporal lobectomy, ATL - 13; selective amygdalohippocampectomy, SelAH - 12) and in 12 healthy controls. Contralateral hippocampal fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were computed with manual hippocampal tracings as volumes of interest following co-registration to anatomical images. Fornix and mammillary body volumetry was performed by manual segmentation. After surgery, the non-resected hippocampus showed s...
<p>(<b>A</b>) Deep sequencing of the fetal and surgically resected (Surg) brain... more <p>(<b>A</b>) Deep sequencing of the fetal and surgically resected (Surg) brain samples revealed that HERV-H exhibited the highest tag frequency and median number of tags followed by HERV-K. (<b>B</b>) When analyzing the HERV-K tags, LTR tags were most abundant, followed by <i>gag-pol</i> and then the <i>env</i> region tags (tags were normalized to respective gene lengths) (<b>C</b>) All host genes with transcript expression profiles correlated with HERV-K(II) <i>env</i> tag abundance (r<sup>2</sup><b>≥</b>0.5) were analyzed using the DAVID tools <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097984#pone.0097984-DAVID1" target="_blank">[58]</a> for enriched gene ontology (GO) terms. Genes related to cell cycle functions and chromosomal organization were most strongly associated with HERV-K(II) <i>env</i> expression. With the use of DAVID bioinformatics resources <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097984#pone.0097984-Dennis1" target="_blank">[59]</a>, the predicted target genes were classified according to KEGG functional annotations to identify pathways that were actively regulated by HERV-K(II) <i>env</i> transcripts in brain tissue. The most over-represented GO term belonged to the transcriptional regulation and chromosome organization followed by different stages of cell cycle pathway. (Mann Whitney t test, *<i>p</i><0.05, **<i>p</i><0.01).</p
<p>(<b>A</b>) Individual cell lines displayed differential constitutive HERV-K(... more <p>(<b>A</b>) Individual cell lines displayed differential constitutive HERV-K(II) <i>env</i> expression profiles. (<b>B</b>) Upon treatment of human fetal neurons, db-cAMP did not have any effects on HERV-K(II) <i>env</i> expression but EGF down-regulated HERV-K(II) expression. (<b>C</b>) U937 and (<b>D</b>) HFA showed decreased in HERV-K(II) <i>env</i> expression upon both db-cAMP and EGF exposure. (n = 4 replicates per group across two independent experiments).</p
<p>(<b>A</b>) Transfection of the pHERV-Kenv plasmid into SK-N-SH cells showed ... more <p>(<b>A</b>) Transfection of the pHERV-Kenv plasmid into SK-N-SH cells showed HERV-K(II) Env immunoreactivity at the predicted molecular weight on western blot. (<b>B</b>) Upon treatment with supernatants from SK-N-SH cells transfected with pHERV-Kenv plasmid, HFN showed increases in <i>BDNF</i> and <i>NGF</i> transcript abundance compared to the control vector transfected cells. (n = 3, with technical quadruplicates) (<b>C</b>) βIII-tubulin expression in HFN following 24-hour exposure to supernatants from HFA-transfected with the pHERV-Kenv or the control vector, showing an increase in βIII-tubulin immunoreactivity in cells exposed to HERV-K Env-transfected cells. (n = 2, with technical octuplicates) (Student t test, *<i>p</i><0.05, **<i>p</i><0.01).</p
BACKGROUND Microvascular decompression (MVD) is an effective treatment for trigeminal neuralgia (... more BACKGROUND Microvascular decompression (MVD) is an effective treatment for trigeminal neuralgia (TN), but pain recurrence occurs in a substantial minority of patients. Two recently published scoring systems by Hardaway et al. (HR) and Panczykowski et al. (PS) use simple preoperative clinical and imaging features to predict durable pain-relief following MVD, but their predictive performance has not been independently validated. OBJECTIVE To compare predictive performance of HR and PS scores for one-year, three-year, and long-term pain-free outcomes after MVD for TN. METHODS HR and PS scores were computed for a retrospective, single-institution cohort of 68 TN patients who underwent MVD. Primary outcome was pain recurrence post-MVD. Predictive performance of HR and PS scores was evaluated with area under the curve (AUC) sensitivity analysis, and regression models for survival analyses at one-year, three-year, and last follow-up. RESULTS AUC for predicting pain-free outcome was higher for PS versus HR Score at one-year (0.873 versus 0.775) and three-years (0.793 versus 0.704). Cox proportional-hazard models showed that PS score better predicted long-term pain-free outcomes compared to HR score (P < 0.05). One-year pain-free outcome was best predicted by pain type; longer-term outcomes were better predicted by presence and degree of neurovascular compression on preoperative imaging. CONCLUSION PS score is superior to HR score in predicting pain-free outcomes after MVD, which may aid in patient selection and counseling. Overall, more significant neurovascular compression of the trigeminal nerve root, and to a lesser extent classical paroxysmal pain, are good predictors of durable pain relief post-MVD.
Human endogenous retroviruses (HERVs) are differentially expressed depending on the cell type and... more Human endogenous retroviruses (HERVs) are differentially expressed depending on the cell type and physiological circumstances. HERV-K has been implicated in the pathogenesis of several diseases although the functional consequences of its expression remain unknown. Human immunodeficiency virus (HIV) infection causes neuroinflammation with neuronal damage and death. Herein, we investigated HERV-K(II)/(HML-2) envelope (Env) expression and its actions in the brain during HIV/AIDS. HERV-K(II) Env expression was assessed in healthy brain tissues, autopsied HIV HIV- infected (HIV+) and uninfected (HIV-) brains and in neural cell cultures by real time RT-PCR, massively parallel (deep) sequencing, immunoblotting and immunohistochemistry. Neuronal and neural stem cells expressing HERV-K(II) Env were analyzed in assays of host responses including cellular viability, immune responses and neurobehavioral outcomes. Deep sequencing of human brain transcriptomes disclosed that RNA sequences encoded...
Background Medically-refractory trigeminal neuralgia (TN) can be treated successfully with operat... more Background Medically-refractory trigeminal neuralgia (TN) can be treated successfully with operative intervention, but a significant proportion of patients are non-responders despite undergoing technically successful surgery. The thalamus is a key component of the trigeminal sensory pathway involved in transmitting facial pain, but the role of the thalamus in TN, and its influence on durability of pain relief after TN surgery, are relatively understudied. We aimed to test the hypothesis that variations in thalamic structure and metabolism are related to surgical non-response in TN. Methods We performed a longitudinal, peri-operative neuroimaging study of the thalamus in medically-refractory TN patients undergoing microvascular decompression or percutaneous balloon compression rhizotomy. Patients underwent structural MRI and MR spectroscopy scans pre-operatively and at 1-week following surgery, and were classified as responders or non-responders based on 1-year post-operative pain ou...
Introduction: Neurovascular lesions are rare and understudied in the pediatric population. Their ... more Introduction: Neurovascular lesions are rare and understudied in the pediatric population. Their initial presentation can range from seizures to focal neurologic deficits, as well as headaches. The goal of this study was to examine the clinical presentation and natural history of neurovascular lesions in children with epilepsy. Methods: We reviewed all pediatric epilepsy patients with neurovascular lesions diagnosed between 2006 and 2018 at the University of Alberta and the Stollery Children’s Hospital, Edmonton, Canada. Initial clinical presentation and brain imaging, as well as long-term epilepsy and postsurgical outcome, were assessed. Results: Of the 14 patients, 10 patients had an initial presentation of focal seizures with impaired awareness, whereas 2 patients presented with headache, 1 presented with visual field defects as well as chronic headaches, and 1 with decreased level of consciousness. Seven patients had cavernous angiomas, 6 had arteriovenous malformation, and 1 pa...
Journal of neuropathology and experimental neurology, Mar 1, 2017
Immune mechanisms have been increasingly recognized in the pathogenesis of hippocampal sclerosis ... more Immune mechanisms have been increasingly recognized in the pathogenesis of hippocampal sclerosis (HS), but infiltration of cytotoxic T-cells and its pathological significance in patients with HS has not been explored. We examined 30 cases of surgically resected hippocampi, including 16 International League Against Epilepsy (ILAE) type 1, 9 ILAE type 2, 1 ILAE type 3 HS, and 4 ILAE No-HS, as well as 6 autopsy No-HS hippocampi. The HS hippocampi showed sparse to scattered CD8-positive T-cells, rare CD4-positive T-cells, and a modest increase in CD68-positive microglia/macrophages, which were significantly more numerous than those in the No-HS controls. The infiltration of CD8-positive T-cells was significantly greater in the CA1 subfield than other subfields of type 1 and type 2 HS. The numbers of CD8-positive T-cells positively correlated with those of CD4-positive T-cells; there was a lower ratio of CD4/CD8-positive T-cells. There were positive correlations between these cells and s...
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques, 2009
The objective of the study was to review our experience with selective amygdalohippocampectomy (S... more The objective of the study was to review our experience with selective amygdalohippocampectomy (SAH) in children and adults with intractable temporal lobe epilepsy. A retrospective case series was used in the setting of a tertiary care hospital which provides epilepsy care to both children and adults. All patients underwent a selective amygdalohippocampectomy procedure and had at least one year of follow-up. Adults and children were divided into two groups and the data was compared between children and adults. Twenty three patients, 9 children and 14 adults were studied. Age of surgery varied from 6 to 58 years. Surgical outcome was variable between the two groups. Amongst the children, three patients (33%) were seizure-free (Engel Class I), two patients (22%) had rare seizures (Engel Class II), one patient (11%) had a worthwhile decrease in seizures (Engel class III) and three patients (32%) had refractory seizures that required re-operation with an anterior temporal lobectomy. Thi...
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