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3.
Neurosurgery ; 85(suppl_1): S38-S46, 2019 07 01.
Article in English | MEDLINE | ID: mdl-31197342

ABSTRACT

Early recognition and differentiation of acute ischemic stroke from intracranial hemorrhage and stroke mimics and the identification of large vessel occlusion (LVO) are critical to the appropriate management of stroke patients. In this review, we discuss the current evidence and practices surrounding safe and efficient triage in the emergency room. As the indications of stroke intervention are evolving to further improve stroke care, focus has begun to revolve around recognition of LVO and provision of endovascular thrombectomy with or without the administration of tissue plasminogen activator. Systems of stroke care are being organized to achieve this goal without delay. Clinical history is important in determining time of onset or last known well time, but, alone or along with an examination, it cannot reliably predict an LVO or exclude intracranial hemorrhage and stroke mimics. The choice of imaging is influenced mainly by the duration of symptoms. On the basis of recent trials, patients presenting after the 6-h therapeutic window can be considered for endovascular thrombectomy if the computed tomographic or magnetic resonance perfusion imaging shows favorable findings. The Society of NeuroInterventional Surgery has established time metrics for each step of triage and initial management. Hospitals are required to develop multidisciplinary stroke teams and emergency protocols to meet these goals. There also needs to be coordination of the emergency medical services with the emergency facility of an appropriate stroke center (a primary stroke center, comprehensive stroke care center, or a thrombectomy-capable stroke center).


Subject(s)
Emergency Medical Services/methods , Neuroimaging/methods , Stroke/diagnosis , Triage/methods , Brain Ischemia/diagnosis , Brain Ischemia/therapy , Endovascular Procedures/methods , Humans , Stroke/therapy , Thrombectomy/methods , Time-to-Treatment , Tissue Plasminogen Activator/therapeutic use
4.
Neurosurg Focus ; 45(1): E11, 2018 07.
Article in English | MEDLINE | ID: mdl-29961386

ABSTRACT

OBJECTIVE Idiopathic intracranial hypertension (IIH) is a commonly occurring disease, particularly among young women of child-bearing age. The underlying pathophysiology for this disease has remained largely unclear; however, the recent literature suggests that focal outflow obstruction of the transverse sinus may be the cause. The purpose of this study was to report one group's early experience with transverse venous sinus stenting in the treatment of IIH and assess its effectiveness. METHODS The authors performed a retrospective chart review to identify patients who had undergone stenting of an outflow-obstructed transverse venous sinus for the treatment of IIH at Gates Vascular Institute between January 2015 and November 2017. Patient demographic data of interest included age, sex, BMI, and history of smoking, hypertension, obstructive sleep apnea, hormonal contraceptive use, and acetazolamide therapy. Each patient's presenting signs and symptoms and whether those symptoms improved with treatment were reviewed. The average opening lumbar puncture (LP) pressure preprocedure, average pressure gradient across the obstructed segment prior to stenting, treatment failure rate (need for shunt placement), and mean follow-up period were calculated. RESULTS Of the 18 patients who had undergone transverse venous stenting for IIH, 16 (88.9%) were women. The mean age of all the patients was 38.3 years (median 38 years). Mean BMI was 34.2 kg/m2 (median 33.9 kg/m2). Presenting symptoms were headache (16 patients [88.9%]), visual disturbances (13 patients [72.2%]), papilledema (8 patients [44.4%]), tinnitus (3 patients [16.7%]), and auditory bruit (3 patients [16.7%]). The mean opening LP pressure pre-procedure was 35.6 cm H2O (median 32 cm H2O). The mean pressure gradient measured proximally and distally to the area of focal obstruction within the transverse sinus was 16.5 cm H2O (median 15 cm H2O). Postprocedurally, 14 patients (77.8%) continued to have headaches; 6 (33.3%) continued to have visual disturbances. No patients continued to have auditory bruit (0%) or papilledema (0%). One patient (5.6%) had new-onset tinnitus postprocedure. Overall improvement of symptoms was noted in 16 patients (88.9%) postprocedure, with 1 patient (5.6%) requiring shunt placement and 2 other patients (11.1%) requiring postprocedural LP to monitor intracranial pressure to determine candidacy for further surgical interventions to treat residual symptoms. The mean duration of follow-up was 194.2 days. CONCLUSIONS Transverse sinus stenting is a rapidly developing technique that has shown good effectiveness and safety in the literature. Authors of the present study found that stenting a flow-obstructed transverse sinus in patients with IIH was a safe and effective way to treat the condition.


Subject(s)
Pseudotumor Cerebri/diagnostic imaging , Pseudotumor Cerebri/surgery , Stents , Transverse Sinuses/diagnostic imaging , Transverse Sinuses/surgery , Adult , Female , Follow-Up Studies , Humans , Male , Neurosurgical Procedures/methods , Retrospective Studies , Treatment Outcome
5.
J Neurosurg ; 129(5): 1305-1316, 2018 11 01.
Article in English | MEDLINE | ID: mdl-29303442

ABSTRACT

Here, the authors examined the factors involved in the volumetric progression of traumatic brain contusions. The variables significant in this progression are identified, and the expansion rate of a brain bleed can now effectively be predicted given the presenting characteristics of the patient.


Subject(s)
Brain/pathology , Cerebral Hemorrhage, Traumatic/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Disease Progression , Female , Glasgow Coma Scale , Humans , Infant , Infant, Newborn , Male , Middle Aged , Prognosis , Retrospective Studies , Young Adult
6.
J Neurosurg ; 128(1): 236-249, 2018 01.
Article in English | MEDLINE | ID: mdl-28186445

ABSTRACT

OBJECTIVE Early radiographic findings in patients with traumatic brain injury (TBI) have been studied in hopes of better predicting injury severity and outcome. However, prior attempts have generally not considered the various types of intracranial hemorrhage in isolation and have typically not excluded patients with potentially confounding extracranial injuries. Therefore, the authors examined the associations of various radiographic findings with short-term outcome to assess the potential utility of these findings in future prognostic models. METHODS The authors retrospectively identified 1716 patients who had experienced TBI without major extracranial injuries, and categorized them into the following TBI subtypes: subdural hematoma (SDH), traumatic subarachnoid hemorrhage, intraparenchymal hemorrhage (which included intraventricular hemorrhage), and epidural hematoma. They specifically considered isolated forms of hemorrhage, in which only 1 subtype was present. RESULTS In general, the presence of an isolated SDH was more likely to result in worse outcomes than the presence of other isolated forms of traumatic intracranial hemorrhage. Discharge to home was less likely and perihospital mortality rates were generally higher in patients with SDH. These findings were not simply related to age and were not fully captured by the admission Glasgow Coma Scale (GCS) score. The presence of SDH had a much higher sensitivity for poor outcome than the presence of other TBI subtypes, and was more sensitive for these poor outcomes than having a low GCS score (3-8). CONCLUSIONS In these ways, SDH was the most important finding associated with poor outcome, and the authors show that consideration of SDH, specifically, can augment age and GCS score in classification and prognostic models for TBI.


Subject(s)
Brain Injuries, Traumatic/complications , Brain Injuries, Traumatic/diagnostic imaging , Hematoma, Subdural/diagnostic imaging , Hematoma, Subdural/etiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Brain Injuries, Traumatic/epidemiology , Child , Child, Preschool , Female , Glasgow Coma Scale , Hematoma, Epidural, Cranial/diagnostic imaging , Hematoma, Epidural, Cranial/epidemiology , Hematoma, Epidural, Cranial/etiology , Hematoma, Subdural/epidemiology , Humans , Infant , Infant, Newborn , Male , Middle Aged , Prognosis , Retrospective Studies , Subarachnoid Hemorrhage, Traumatic/diagnostic imaging , Subarachnoid Hemorrhage, Traumatic/epidemiology , Subarachnoid Hemorrhage, Traumatic/etiology , Time Factors , Young Adult
7.
Oper Neurosurg (Hagerstown) ; 13(6): E33-E36, 2017 12 01.
Article in English | MEDLINE | ID: mdl-29186599

ABSTRACT

BACKGROUND AND IMPORTANCE: Cerebrospinal fluid shunt placement is used to treat the various causes of hydrocephalus by redirecting the cerebrospinal fluid to the body, most commonly from the ventricle to the peritoneum. Distal catheter displacement from the peritoneal cavity can occur as a complication, necessitating reoperation. CLINICAL PRESENTATION: We report 2 such cases in obese patients involving retropulsion of the distal tubing. To address this complication, we implanted a T-connector to the distal catheter construct. CONCLUSION: This study supports the use of a T-connector catheter construct to decrease and prevent the possibility of distal peritoneal catheter retropulsion in cases of elevated intra-abdominal pressure, both prophylactically and in revisions.


Subject(s)
Equipment Failure , Reoperation/instrumentation , Reoperation/methods , Ventriculoperitoneal Shunt/adverse effects , Catheters, Indwelling/adverse effects , Female , Follow-Up Studies , Humans , Hydrocephalus/diagnostic imaging , Hydrocephalus/surgery , Male , Middle Aged , Peritoneum/surgery , Tomography Scanners, X-Ray Computed , Ventriculoperitoneal Shunt/instrumentation , X-Rays
8.
Surg Neurol Int ; 8: 112, 2017.
Article in English | MEDLINE | ID: mdl-28680731

ABSTRACT

BACKGROUND: Animals held in captivity tend to live longer than do their wild counterparts, and as such, are prone to developing age-related degenerative injuries. Here, we present a case of an adult female polar bear with symptomatic lumbar stenosis. There is a paucity of literature on large mammalian spine surgery, and anatomical differences between humans and other vertebrates must be taken into consideration. CASE DESCRIPTION: A 24-year-old female polar bear residing at the zoo was found to have decreased motor function in her hind legs. Diagnostic myelography performed at the L7/S1 level demonstrated lumbar stenosis at L5/6 for which a laminectomy was performed. Postoperatively, she returned to premorbid functional level, with no apparent associated adverse sequelae. CONCLUSIONS: To our knowledge, this is the first reported case of spine surgery in a polar bear and demonstrates that neurosurgical diagnostic and operative techniques developed for humans can also be applied to large mammals with successful results.

10.
Clin Neurol Neurosurg ; 146: 152-5, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27259283

ABSTRACT

We present an unusual case of a 59year old male patient who presented with acute, bilateral lower extremity weakness and was found to have non-traumatic spinal subarachnoid hemorrhage. Diagnostic workup including MRI and angiography revealed an aneurysm of the artery of Ademkiewicz. This was managed conservatively and the patient has had marked clinical improvement. We present the details of this unusual case as well as a literature review related to aneurysms of the artery of Ademkiewicz.


Subject(s)
Aneurysm, Ruptured/diagnostic imaging , Dura Mater/blood supply , Magnetic Resonance Imaging/methods , Spinal Cord/blood supply , Subarachnoid Hemorrhage/diagnostic imaging , Aneurysm, Ruptured/etiology , Aneurysm, Ruptured/therapy , Humans , Male , Middle Aged , Subarachnoid Hemorrhage/therapy
11.
Surg Neurol Int ; 7(Suppl 10): S259-62, 2016.
Article in English | MEDLINE | ID: mdl-27213112

ABSTRACT

BACKGROUND: Management of penetrating cranial trauma remains a high acuity and imaging intense neurosurgical disorder. Imaging of vital structures, including angiography, is typically conducted to understand the proximity of vital structures in comparison to a foreign body and prepare for intraoperative complications such as hemorrhage. Preservation of function following initial injury in cases where minimal neurological deficit exists is essential. CASE DESCRIPTION: Here, we present a case using intraoperative computed tomography to assist in early detection and resolution of hemorrhage in the surgical management of an intact patient with self-inflicted penetrating cranial trauma. CONCLUSIONS: This method may aid in early detection of hemorrhage and prevention of consequential neurological deterioration or emergent need for secondary surgery.

12.
J Neurosurg Pediatr ; 16(4): 402-5, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26149436

ABSTRACT

OBJECT: Programmable shunts have a valuable role in the treatment of patients with hydrocephalus, but because a magnet is used to change valve settings, interactions with external magnets may reprogram these shunts. Previous studies have demonstrated the ability of magnetic toys and iPads to erroneously reprogram shunts. Headphones are even more ubiquitous, and they contain an electromagnet for sound projection that sits on the head very close to the shunt valve. This study is the first to look at the magnetic field emissions of headphones and their effect on reprogrammable shunt valves to ascertain whether headphones are safe for patients with these shunts to wear. METHODS: In this in vitro study of the magnetic properties of headphones and their interactions with 3 different programmable shunts, the authors evaluated Apple earbuds, Beats by Dr. Dre, and Bose QuietComfort Acoustic Noise Cancelling headphones. Each headphone was tested for electromagnetic field emissions using a direct current gaussmeter. The following valves were evaluated: Codman Hakim programmable valve, Medtronic Strata II valve, and Aesculap proGAV. Each valve was tested at distances of 0 to 50 mm (in 5-mm increments) from each headphone. The exposure time at each distance was 1 minute, and 3 trials were performed to confirm results at each valve setting and distance. RESULTS: All 3 headphones generated magnetic fields greater than the respective shunt manufacturer's recommended strength of exposure, but these fields did not persist beyond 5 mm. By 2 cm, the fields levels were below 20 G, well below the Medtronic recommendation of 90 G and the Codman recommendation of 80 G. Because the mechanism for the proGAV is different, there is no recommended gauss level. There was no change in gauss-level emissions by the headphones with changes in frequency and amplitude. Both the Strata and Codman-Hakim valves were reprogrammed by direct contact (distance 0 mm) with the Bose headphones. When a rotation component was added, all 3 headphones reprogrammed the Strata and Codman-Hakim valves at 0 mm. At all distances above 0 mm, the headphones did not affect the shunts. The proGAV valve was not affected by headphones at any distance. CONCLUSIONS: Although all the headphones studied generated significant gauss fields at distances less than 5 mm, the programmable valve settings only changed at a distance of 0 mm (i.e., with direct contact). Given the subcutaneous location of the valve, the authors conclude that is highly unlikely that commercially available or customary headphones can contribute to the reprogramming of shunts.


Subject(s)
Acoustics/instrumentation , Cerebrospinal Fluid Shunts/adverse effects , Magnetic Fields/adverse effects , Cerebrospinal Fluid Shunts/instrumentation , Equipment Design , Equipment Failure , In Vitro Techniques
14.
J Neurotrauma ; 31(7): 630-41, 2014 Apr 01.
Article in English | MEDLINE | ID: mdl-24195645

ABSTRACT

Predictive modeling of emergent behavior, inherent to complex physiological systems, requires the analysis of large complex clinical data streams currently being generated in the intensive care unit. Brain tissue oxygen protocols have yielded outcome benefits in traumatic brain injury (TBI), but the critical physiological thresholds for low brain oxygen have not been established for a dynamical patho-physiological system. High frequency, multi-modal clinical data sets from 29 patients with severe TBI who underwent multi-modality neuro-clinical care monitoring and treatment with a brain oxygen protocol were analyzed. The inter-relationship between acute physiological parameters was determined using symbolic regression (SR) as the computational framework. The mean patient age was 44.4±15 with a mean admission GCS of 6.6±3.9. Sixty-three percent sustained motor vehicle accidents and the most common pathology was intra-cerebral hemorrhage (50%). Hospital discharge mortality was 21%, poor outcome occurred in 24% of patients, and good outcome occurred in 56% of patients. Criticality for low brain oxygen was intracranial pressure (ICP) ≥22.8 mm Hg, for mortality at ICP≥37.1 mm Hg. The upper therapeutic threshold for cerebral perfusion pressure (CPP) was 75 mm Hg. Eubaric hyperoxia significantly impacted partial pressure of oxygen in brain tissue (PbtO2) at all ICP levels. Optimal brain temperature (Tbr) was 34-35°C, with an adverse effect when Tbr≥38°C. Survivors clustered at [Formula: see text] Hg vs. non-survivors [Formula: see text] 18 mm Hg. There were two mortality clusters for ICP: High ICP/low PbtO2 and low ICP/low PbtO2. Survivors maintained PbtO2 at all ranges of mean arterial pressure in contrast to non-survivors. The final SR equation for cerebral oxygenation is: [Formula: see text]. The SR-model of acute TBI advances new physiological thresholds or boundary conditions for acute TBI management: PbtO2≥25 mmHg; ICP≤22 mmHg; CPP≈60-75 mmHg; and Tbr≈34-37°C. SR is congruous with the emerging field of complexity science in the modeling of dynamical physiological systems, especially during pathophysiological states. The SR model of TBI is generalizable to known physical laws. This increase in entropy reduces uncertainty and improves predictive capacity. SR is an appropriate computational framework to enable future smart monitoring devices.


Subject(s)
Algorithms , Brain Injuries/physiopathology , Brain/blood supply , Models, Neurological , Oxygen/metabolism , Adult , Female , Humans , Intracranial Pressure/physiology , Male , Middle Aged
16.
J Neurosurg ; 113(6): 1314-6, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20617878

ABSTRACT

Despite the varied sources of hydrocephalus, all shunt-treated conditions involve redirection of CSF to the body, commonly the peritoneum. Migration of the distal catheter tip out of the peritoneal space can occur, leading to the need for reoperation. Although uncommon, the authors have recently had 3 such cases in obese patients involving distal tubing retropulsion in otherwise uncomplicated surgeries. In addressing this issue, the authors performed anchoring of the distal catheter tubing through a small abdominal mesh, which is commonly used for hernia repair to increase catheter tube friction without compromising CSF flow. The results suggest this method may mitigate the chance of peritoneal catheter displacement in patients with higher than normal intraabdominal pressure.


Subject(s)
Foreign-Body Migration/prevention & control , Herniorrhaphy , Hydrocephalus/surgery , Obesity/complications , Ventriculoperitoneal Shunt/adverse effects , Adult , Aged , Female , Hernia/etiology , Humans , Male , Peritoneal Cavity , Surgical Mesh
17.
J Neurosurg ; 111(4): 672-82, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19463048

ABSTRACT

OBJECT: Cerebral ischemia is the leading cause of preventable death in cases of major trauma with severe traumatic brain injury (TBI). Intracranial pressure (ICP) control and cerebral perfusion pressure (CPP) manipulation have significantly reduced the mortality but not the morbidity rate in these patients. In this study, the authors describe their 5-year experience with brain tissue oxygen (PbtO(2)) monitoring, and the effect of a brain tissue oxygen-directed critical care guide (PbtO(2)-CCG) on the 6-month clinical outcome (based on the 6-month Glasgow Outcome Scale score) in patients with TBIs. METHODS: One hundred thirty-nine patients admitted to Creighton University Medical Center with major traumatic injuries (Injury Severity Scale [ISS] scores >or= 16) and TBI underwent prospective evaluation. All patients were treated with a PbtO(2)-CCG to maintain a brain oxygen level > 20 mm Hg, and control ICP < 20 mm Hg. The role of demographic, clinical, and imaging parameters in the identification of patients at risk for cerebral hypooxygenation and the influence of hypooxygenation on clinical outcome were recorded. Outcomes were compared with those in a historical ICP/CPP patient cohort. Subgroup analysis of severe TBI was performed and compared to data reported in the Traumatic Coma Data Bank. RESULTS: The majority of injuries were sustained in motor vehicle crashes (63%), and diffuse brain injury was the most common abnormality (58%). Mechanism of injury, severity of TBI, pathological entity, neuroimaging results, and trauma indices were not predictive of ischemia. Factors affecting death included gunshot injury, poor trauma indices, subarachnoid hemorrhage, and coma. After standard resuscitation, 65% of patients had an initially low PbtO(2). Data are presented as means +/- SDs. Treatment with the PbtO(2)-CCG resulted in a 44% improvement in mean PbtO(2) (16.21 +/- 12.30 vs 23.65 +/- 14.40 mm Hg; p < 0.001), control of ICP (mean 12.76 +/- 6.42 mm Hg), and the maintenance of CPP (mean 76.13 +/- 15.37 mm Hg). Persistently low cerebral oxygenation was seen in 37% of patients at 2 hours, 31% at 24 hours, and 18% at 48 hours of treatment. Thus elevated ICP and a persistent low PbtO(2) after 2 hours represented increasing odds of death (OR 14.3 at 48 hours). Survivors and patients with good outcomes generally had significantly higher mean daily PbtO(2) and CPP values compared to nonsurvivors. Polytrauma, associated with higher ISS scores, presented an increased risk of vegetative outcome (OR 9.0). Compared to the ICP/CPP cohort, the mean Glasgow Outcome Scale score at 6 months in patients treated with PbtO(2)-CCG was higher (3.55 +/- 1.75 vs 2.71 +/- 1.65, p < 0.01; OR for good outcome 2.09, 95% CI 1.031-4.24) as was the reduction in mortality rate (25.9 vs 41.50%; relative risk reduction 37%), despite higher ISS scores in the PbtO(2) group (31.6 +/- 13.4 vs 27.1 +/- 8.9; p < 0.05). Subgroup analysis of severe closed TBI revealed a significant relative risk reduction in mortality rate of 37-51% compared with the Traumatic Coma Data Bank data, and an increased OR for good outcome especially in patients with diffuse brain injury without mass lesions (OR 4.9, 95% CI 2.9-8.4). CONCLUSIONS: The prevention and aggressive treatment of cerebral hypooxygenation and control of ICP with a PbtO(2)-directed protocol reduced the mortality rate after TBI in major trauma, but more importantly, resulted in improved 6-month clinical outcomes over the standard ICP/CPP-directed therapy at the authors' institution.


Subject(s)
Brain Injuries/drug therapy , Brain/metabolism , Monitoring, Physiologic/methods , Oxygen/metabolism , Oxygen/therapeutic use , Adolescent , Adult , Brain Injuries/metabolism , Brain Injuries/physiopathology , Critical Care/methods , Female , Glasgow Outcome Scale , Humans , Intracranial Pressure/physiology , Male , Middle Aged , Prospective Studies , Retrospective Studies , Trauma Severity Indices , Treatment Outcome , Young Adult
19.
Exp Physiol ; 93(2): 213-22, 2008 Feb.
Article in English | MEDLINE | ID: mdl-17911358

ABSTRACT

Rats that had been injected with monosodium glutamate (MSG) neonatally were studied for up to 70 weeks and compared with age-matched control rats to study changes in glucose tolerance and in sympathetic and sensory nerves. At 61 and 65 weeks of age, there were significant differences in glucose tolerance between the MSG and control groups, and the MSG group had raised fasting blood glucose. These changes were not associated with changes in the number of beta-cells in the islets of Langerhans. In addition, the diabetic MSG-treated rats had central obesity and cataracts. Hypoalgesia to thermal stimuli was present in MSG-treated rats as early as 6 weeks and persisted at 70 weeks. However, no differences were observed in the distribution of substance P, the neurokinin-1 receptor or calcitonin gene-related peptide in the dorsal horn of L3-L5 at this age (70 weeks). Diabetic MSG-treated animals at 65 and 70 weeks of age had significantly reduced noradrenaline concentrations in the heart, tail artery and ileum, while concentrations in the adrenal gland and corpus cavernosum were significantly increased. There was also a significant increase in adrenal adrenaline, dopamine and serotonin, largely attributable to changes in weight of the adrenal gland in the MSG-treated animals. The results indicate that MSG-treated animals develop a form of type II diabetes by about 60 weeks of age, and that there are significant changes in amine levels in various tissues associated with these developments.


Subject(s)
Autonomic Nervous System/physiology , Diabetes Mellitus, Type 2/chemically induced , Diabetes Mellitus, Type 2/physiopathology , Diabetic Neuropathies/physiopathology , Neurons, Afferent/physiology , Sodium Glutamate , Aging/physiology , Animals , Blood Glucose/metabolism , Body Weight/physiology , Calcitonin Gene-Related Peptide/metabolism , Chromatography, High Pressure Liquid , Diabetes Mellitus, Type 2/pathology , Diabetic Neuropathies/pathology , Glucose Intolerance/chemically induced , Glucose Intolerance/physiopathology , Glucose Tolerance Test , Hot Temperature , Immunohistochemistry , Insulin/metabolism , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/metabolism , Obesity/complications , Organ Size/physiology , Pain Measurement/drug effects , Physical Stimulation , Radioimmunoassay , Rats , Rats, Wistar , Receptors, Neurokinin-1/metabolism , Substance P/metabolism
20.
Nat Neurosci ; 9(11): 1382-7, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17041593

ABSTRACT

Temporal lobe epilepsy is a common form of drug-resistant epilepsy that sometimes responds to dietary manipulation such as the 'ketogenic diet'. Here we have investigated the effects of the glycolytic inhibitor 2-deoxy-D-glucose (2DG) in the rat kindling model of temporal lobe epilepsy. We show that 2DG potently reduces the progression of kindling and blocks seizure-induced increases in the expression of brain-derived neurotrophic factor and its receptor, TrkB. This reduced expression is mediated by the transcription factor NRSF, which recruits the NADH-binding co-repressor CtBP to generate a repressive chromatin environment around the BDNF promoter. Our results show that 2DG has anticonvulsant and antiepileptic properties, suggesting that anti-glycolytic compounds may represent a new class of drugs for treating epilepsy. The metabolic regulation of neuronal genes by CtBP will open avenues of therapy for neurological disorders and cancer.


Subject(s)
Alcohol Oxidoreductases/physiology , Antimetabolites/pharmacology , Chromatin/physiology , DNA-Binding Proteins/physiology , Deoxyglucose/pharmacology , Epilepsy/drug therapy , Epilepsy/metabolism , Repressor Proteins/physiology , Transcription Factors/physiology , Alcohol Oxidoreductases/genetics , Animals , Chromatin/drug effects , DNA-Binding Proteins/genetics , Diet , Disease Progression , Down-Regulation/drug effects , Energy Metabolism/physiology , Epilepsy/diet therapy , Gene Expression/drug effects , Glycolysis/drug effects , Glycolysis/physiology , Hippocampus/drug effects , Hippocampus/metabolism , Kindling, Neurologic/physiology , NAD/physiology , Neuronal Plasticity/drug effects , Rats , Receptor, trkB/biosynthesis , Receptor, trkB/genetics , Repressor Proteins/genetics , Transcription Factors/genetics
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