Characterization of the Focal Cooling Necessary to Suppress Spontaneous Epileptiform Activity

2007 ◽  
Author(s):  
Reynaldo G. Guerra ◽  
Van Carey ◽  
Boris Rubinsky ◽  
Mitchel Berger
Keyword(s):  
Penetration Depth ◽  
Epileptiform Activity ◽  
Intractable Epilepsy ◽  
Blood Perfusion ◽  
Thermal Parameters ◽  
Heat Transfer Analysis ◽  
Brain Response ◽  
Surface Cooling ◽  
Cold Saline ◽  
Focal Cooling

It has been established that focal cooling to suppress epileptiform activity has become a real and viable option. However, the specific thermal parameters necessary to suppress epileptiform activity have only begun to be quantitatively defined. In 2002 it was reported that a 41 year-old man with medically intractable epilepsy undertook surgery to remove his tumor and resect adjacent epileptogenic tissue. Electrocorticography was performed before resection. Cold saline was impinged on the resulting interictal spike foci resulting in transient, complete cessation of spiking. We present a transient post-operative heat transfer analysis of the cold saline impingement on the surface of brain. An approximate temporal and spatial temperature distribution of the perfused human brain response to surface cooling was developed. The realistic extent of cooling below the brain surface due to impinging saline was quantified. The sensitivity of cooling penetration depth to (a) saline exit velocity from the syringe, and (b) syringe inside diameter, was evaluated. A parametric study was performed to characterize the effects of brain metabolism and blood perfusion on surface cooling. The required thermal parameters necessary to suppress epileptiform activity through focal cooling are here quantitatively approximated, i.e. heat flux removal and maximum and realistic cooling penetration depths. The relatively shallow penetration depth suggests that the spreading depolarization associated with epileptiform activity may be abolished through focal cooling without affecting the deeper neurons responsible for motor activity.

scholarly journals Focal Cooling Suppresses Spontaneous Epileptiform Activity without Changing the Cortical Motor Threshold

Epilepsia ◽  
2002 ◽  
Vol 43 (8) ◽  
pp. 932-935 ◽  
Author(s):  
Kameel M. Karkar ◽  
Paul A. Garcia ◽  
Lisa M. Bateman ◽  
Matthew D. Smyth ◽  
Nicholas M. Barbaro ◽  
...  
Keyword(s):  
Epileptiform Activity ◽  
Motor Threshold ◽  
Cortical Motor ◽  
Focal Cooling

scholarly journals Ring chromosome 20 syndrome – A rare chromosomal cause of refractory epilepsy in children

2017 ◽  
Vol 04 (01) ◽  
pp. 087-089 ◽  
Author(s):  
Umesh Kalane ◽  
Chaitanya Datar ◽  
Shilpa Kalane
Keyword(s):  
Chromosomal Abnormalities ◽  
Refractory Epilepsy ◽  
Genetic Disorders ◽  
Epileptiform Activity ◽  
Intractable Epilepsy ◽  
Ring Chromosome ◽  
Normal Karyotype ◽  
Epileptiform Discharges ◽  
Chromosome 20 ◽  
Work Up

AbstractGenetic disorders and chromosomal abnormalities have been shown to represent 2–3% of all cases of epilepsy. Ring chromosome 20 syndrome is a rare chromosomal abnormality and a rare cause of intractable epilepsy. Exact prevalence of ring chromosome 20 is not known. We report a case of a 10-year old boy who had had intractable epilepsy since 2 years of age. Birth history was insignificant and there was no obvious dysmorphism. His motor milestones were normal but cognition and speech were delayed. Electroencephalography showed progressive worsening from initial bi-frontal epileptiform activity to generalized discharges. Neuroimaging and metabolic work up was normal. Karyotype study showed ring chromosome 20. Diagnosis of ring chromosome 20 or r(20) syndrome was made. Ring chromosome 20 syndrome is a rare cause of refractory epilepsy A patient who present with intractable epilepsy with frontal epileptiform discharges, mental developmental delay, without dysmorphic features should be suspected of chromosomal abnormalities especially ring chromosome 20.

Magnetoencephalography in Neurosurgery

Neurosurgery ◽  
2006 ◽  
Vol 59 (3) ◽  
pp. 493-511 ◽  
Author(s):  
Jyrki P. Mäkelä ◽  
Nina Forss ◽  
Juha Jääskeläinen ◽  
Erika Kirveskari ◽  
Antti Korvenoja ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Diffusion Tensor ◽  
Brain Plasticity ◽  
Epileptiform Activity ◽  
Intractable Epilepsy ◽  
Imaging Data ◽  
Resonance Imaging ◽  
Cortical Areas ◽  
Neurosurgical Patients

Abstract OBJECTIVE: To present applications of magnetoencephalography (MEG) in studies of neurosurgical patients. METHODS: MEG maps magnetic fields generated by electric currents in the brain, and allows the localization of brain areas producing evoked sensory responses and spontaneous electromagnetic activity. The identified sources can be integrated with other imaging modalities, e.g., with magnetic resonance imaging scans of individual patients with brain tumors or intractable epilepsy, or with other types of brain imaging data. RESULTS: MEG measurements using modern whole-scalp instruments assist in tailoring individual therapies for neurosurgical patients by producing maps of functionally irretrievable cortical areas and by identifying cortical sources of interictal and ictal epileptiform activity. The excellent time resolution of MEG enables tracking of complex spaciotemporal source patterns, helping, for example, with the separation of the epileptic pacemaker from propagated activity. The combination of noninvasive mapping of subcortical pathways by magnetic resonance imaging diffusion tensor imaging with MEG source localization will, in the near future, provide even more accurate navigational tools for preoperative planning. Other possible future applications of MEG include the noninvasive estimation of language lateralization and the follow-up of brain plasticity elicited by central or peripheral neural lesions or during the treatment of chronic pain. CONCLUSION: MEG is a mature technique suitable for producing preoperative “road maps” of eloquent cortical areas and for localizing epileptiform activity.

Palliative hemispherotomy in children with bilateral seizure onset

2012 ◽  
Vol 9 (4) ◽  
pp. 381-388 ◽  
Author(s):  
Michael Anthony Ciliberto ◽  
David Limbrick ◽  
Alexander Powers ◽  
Jeffrey B. Titus ◽  
Rebecca Munro ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Mr Imaging ◽  
Seizure Control ◽  
Epileptiform Activity ◽  
Intractable Epilepsy ◽  
Retrospective Chart Review ◽  
Seizure Onset ◽  
Significant Burden

Object Intractable epilepsy is a significant burden on families and on the cognitive development and quality of life (QOL) of patients. Periinsular hemispherotomy (PIH) for medically intractable epilepsy can benefit patients who qualify for this procedure. The ideal hemispherotomy candidate has ipsilateral ictal and interictal epileptiform activity, unilateral MR imaging abnormalities, contralateral hemiplegia, and a normal contralateral hemisphere. However, certain patients present with a mixed picture of bilateral electroencephalography (EEG) findings and severe intractable epilepsy, prompting consideration of a more aggressive treatment approach. This report introduces the possibility of surgery for patients who normally would not meet criteria for this treatment modality. Methods In this retrospective chart review, the authors report on 7 patients with bilateral seizure onset noted on routine or video-EEG monitoring. A QOL phone questionnaire, based on the Quality of Life in Childhood Epilepsy tool, was administered to a parent. The authors reviewed each patient's chart for surgical complications, changes in examination, QOL, limited neuropsychological outcomes, and seizure outcomes. They also investigated each chart for MR imaging and EEG findings as well as the patient's epilepsy clinic notes for seizure semiology and frequency. Results All patients enjoyed a decrease in seizure frequency and a subjective increase in QOL after PIH. Five patients (71%) achieved Engel Class I or II seizure control. The mean follow-up was 3.64 years (2–5.3 years). One patient is now off all antiseizure medication. No patient had a decrement in Full Scale IQ on postsurgical testing, and 2 (28.5%) of 7 individuals had increased adaptive and social functioning. Postsurgical examination changes included hemiplegia and homonymous hemianopia. Conclusions Hemispherotomy in patients with intractable epilepsy is generally reserved for individuals with unilateral epileptiform abnormalities or lesions on MR imaging. Seven patients in this study benefited from surgery despite bilateral seizure onset with improvement in seizure control and overall QOL. Thus, bilateral ictal onset does not necessarily preclude consideration for hemispherotomy in selected patients with severe medically refractory epilepsy.

scholarly journals Heat transfer model to characterize the focal cooling necessary to suppress spontaneous epileptiform activity (Invited Paper)

2005 ◽  
Author(s):  
Reynaldo G. Guerra ◽  
Rafael V. Davalos ◽  
Paul A. Garcia ◽  
Boris Rubinsky ◽  
Mitchel Berger
Keyword(s):  
Heat Transfer ◽  
Epileptiform Activity ◽  
Heat Transfer Model ◽  
Transfer Model ◽  
Focal Cooling

scholarly journals Surgery for Heterotopia: A Second Look

2005 ◽  
Vol 5 (5) ◽  
pp. 197-199
Author(s):  
Paul A. Garcia
Keyword(s):  
Surgical Outcomes ◽  
Grey Matter ◽  
Epileptiform Activity ◽  
Intractable Epilepsy ◽  
Epileptogenic Zone ◽  
Seizure Onset ◽  
Periventricular Nodular Heterotopia ◽  
Nodular Heterotopia ◽  
Temporal Structures

Electroclinical, MRI, and Neuropathological Study of 10 Patients with Nodular Heterotopia, with Surgical Outcomes Tassi L, Colombo N, Cossu M, Mai R, Francione S, Lo Russo G, Galli C, Bramerio M, Battaglia G, Garbelli R, Meroni A, Spreafico R Brain 2005;128:321–337 We present the results of a retrospective study on 10 patients operated on for intractable epilepsy associated with nodular heterotopia, as identified by high-resolution MRI. Seven patients had unilateral heterotopia, one patient had symmetrical bilateral heterotopia, and two patients had asymmetrical bilateral heterotopia. By stereoelectroencephalogram (SEEG; nine patients), interictal activity within nodules was similar in all cases, and ictal activity never started from nodules alone but from the overlying cortex or simultaneously in nodules and cortex. Excellent outcomes (Engel class Ia, 1987) were achieved in the seven patients with unilateral heterotopia, showing that surgery can be highly beneficial in such cases when the epileptogenic zone is carefully located before surgery by MRI and particularly SEEG. For the bilateral cases, surgical outcomes were Engel IIa (one patient) or Engel IIIa (two patients). Histologic/immunohistochemical studies of resected specimens showed that all nodules had similar microscopic organization, even though their extent and location varied markedly. The overlying cortex was dysplastic in nine patients, but of normal thickness. We suggest that nodule formation may be the result of a dual mechanism: ( 1 ) failure of a stop signal in the germinal periventricular region leading to cell overproduction; and ( 2 ) early transformation of radial glial cells into astrocytes, resulting in defective neuronal migration. The intrinsic interictal epileptiform activity of nodules may be due to an impaired intranodular GABAergic system. The Role of Periventricular Nodular Heterotopia in Epileptogenesis Aghakhani Y, Kinay D, Gotman J, Soualmi L, Andermann F, Olivier A, Dubeau F Brain 2005;128:641–651 A temporal resection in patients with periventricular nodular heterotopia (PNH) and intractable focal seizures yields poor results. To define the role of heterotopic grey matter tissue in epileptogenesis and to improve outcome, we performed stereoencephalography (SEEG) recordings in eight patients with uni- or bilateral PNH and intractable focal epilepsy. The SEEG studies aimed to evaluate the most epileptogenic areas and included the allo- and neocortex and at least one nodule of grey matter. Interictal spiking activity was found in ectopic grey matter in three patients, in the cortex overlying the nodules in five, and in the mesial temporal structures in all. At least one heterotopion was involved at seizure onset in six patients, synchronous with the overlying neocortex or ipsilateral hippocampus. Two patients had their seizures originating in the mesial temporal structures only. Six patients had surgery, and the resected areas included the seizure onset, with follow-up from 1 to 8 years. An amygdalohippocampectomy was performed in two (Engel classes Id and III), an amygdalohippocampectomy plus removal of an adjacent heterotopion in two (class Ia), and a resection of two contiguous nodules plus a small rim of overlying occipital cortex in one patient (class Id). One patient with bilateral PNH had three adjacent nodules resected and an ipsilateral amygdalohippocampectomy, resulting in a reduction of the number of seizures by 25 to 50%. The best predictor of surgical outcome is the presence of a focal epileptic generator; this generator may or may not include the PNH. Invasive recording is required in patients with PNH; it improves localization and is the key to better outcome.

Effects of Nonuniform Tissue Properties on Temperature Prediction in Magnetic Nanohyperthermia

2011 ◽  
Vol 2 (2) ◽  
Author(s):  
Qian Wang ◽  
Zhong-Shan Deng ◽  
Jing Liu
Keyword(s):  
Temperature Distribution ◽  
Heat Source ◽  
Cooling Water ◽  
Blood Perfusion ◽  
Source Distribution ◽  
Surface Cooling ◽  
Temperature Prediction ◽  
Tissue Properties ◽  
Distribution Features ◽  
Em Field

In tumor hyperthermia, effectively planning in advance and thus controlling in situ the heating dosage within the target region are rather critical for the success of a therapy. Many studies have simulated the temperature distribution during hyperthermia. However, most of them are based on fixed and known heat source distributions, which are generally very complex to compute. Besides, there is little information concerned the numerical analysis of temperature during magnetic hyperthermia loading with magnetic nanoparticles (MNPs), which has its specific heat source distribution features. Particularly, the parameters for different human tissues varied very much, which will cause a serious impact on the heat source and temperature distribution. This paper is aimed at investigating the effects of nonuniform tissue properties to the temperature prediction in magnetic nanohyperthermia and other possible effect factors including external EM field, MNP properties, tumor size and depth, surface cooling conditions, etc. It was found that the spatial heat source generated in the nonuniform model appears smaller than that in the uniform model. This is mainly resulted from the energy reflection when transmitting from fat to tumor and muscle under the same condition, while the temperature is higher on account of overall contribution of different parameters including tissue thermal conductivity, blood perfusion, density, heat capacity, and metabolic heat production rate, which also affect the temperature distribution apart from the heat source. Controlling the properties of the external EM field, MNPs and cooling water can acquire different temperature distributions. Tumors with different depths and sizes need specific plannings, which require as accurate as possible temperature prediction. The nonuniform model can be further improved to be applied in magnetic nanohyperthermia treatment planning and thus help optimize the surgical procedures.

VALPROIC ACID EXTENDS LIFESPAN OF THE ZEBRAFISH MODEL OF CLN2 DISEASE (LATE INFANTILE NEURONAL CEROID LIPOFUSCINOSIS)

2015 ◽  
Vol 86 (11) ◽  
pp. e4.153-e4
Author(s):  
Fahad Mahmood ◽  
Anselm Zdebik ◽  
Alexandra Au ◽  
Jennifer Cooke ◽  
Claire Russell
Keyword(s):  
Seizure Activity ◽  
Neuronal Ceroid Lipofuscinosis ◽  
Epileptiform Activity ◽  
Intractable Epilepsy ◽  
Premature Death ◽  
Neuronal Ceroid Lipofuscinoses ◽  
Lysosomal Storage ◽  
Zebrafish Model ◽  
Lysosomal Protease

CLN2 disease is a subtype of the neuronal ceroid lipofuscinoses (NCLs), a group of lysosomal storage disorders causing progressive, untreatable, neurodegeneration, intractable epilepsy and premature death in children. We have developed a permanent genetic zebrafish model of CLN2 disease due to a mutation in tpp1 encoding the lysosomal protease Tripeptidyl-peptidase-1 that replicates the neurodegenerative and storage phenotype. We hypothesize that CLN2 zebrafish display electrical and behavioural evidence of seizure activity that responds to established anti-convulsants and can further be used to develop novel therapeutic approaches.To validate the presence of seizures we performed single electrode electroencephalography showing CLN2 zebrafish had increased spiking activity vs wildtype with Fast-Fourier transform showing significantly increased amplitude about 2–4Hz. This was attenuated by Valproate (p=0.049), but not pentobarbitone. We also demonstrate that Valproate significantly reduces seizure-related movement bouts, thereby correlating movements and epileptiform activity. Lastly, we show exposure to Valproate significantly extends the lifespan of our zebrafish model with mortality between 3–6 days post-fertilization 8.33% in treated vs 33.3% in controls (p=0.01).The CLN2 zebrafish model thus displays electrical and behavioural seizure activity that can be attenuated by Valproate, with associated prolongation in survival. Moreover this model can utilize high-throughput in vivo screening assays to develop novel anti-convulsants.

Local synaptic circuits and epileptiform activity in slices of neocortex from children with intractable epilepsy

1992 ◽  
Vol 67 (3) ◽  
pp. 496-507 ◽  
Author(s):  
J. G. Tasker ◽  
W. J. Peacock ◽  
F. E. Dudek
Keyword(s):  
Electrical Stimulation ◽  
Gabaa Receptor ◽  
Epileptiform Activity ◽  
Intractable Epilepsy ◽  
Pyramidal Cells ◽  
Synaptic Inhibition ◽  
Gamma Aminobutyric Acid ◽  
Total N ◽  
Postsynaptic Potentials ◽  
Synaptic Circuits

1. Single and dual intracellular recordings were performed in neocortical slices obtained from tissue samples surgically removed from children (8 mo to 15 yr) for the treatment of intractable epilepsy. Electrical stimulation and glutamate microapplication were used to study local synaptic inputs to pyramidal cells. 2. In recordings with potassium-acetate electrodes, activation of presynaptic neocortical neurons with glutamate microdrops did not elicit a clear increase in postsynaptic potentials (PSPs) but did suppress current-evoked repetitive spike firing in recorded neurons. Bicuculline (10 microM) blocked this effect, suggesting it was caused by the activation of presynaptic gamma-aminobutyric acid (GABA) cells. In recordings with KCl electrodes, glutamate microdrops elicited an increase in the frequency and amplitude of depolarizing PSPs. Bicuculline (5-10 microM) blocked the glutamate-evoked PSPs, suggesting they were reversed GABAA-receptor-mediated inhibitory postsynaptic potentials (IPSPs). In one cell recorded with a KCl electrode (total n = 8), current-evoked spike trains elicited afterdischarges of reversed IPSPs, thus revealing a recurrent inhibitory circuit. Therefore local inhibitory synaptic circuits were robust and could be observed in tissue from patients as young as 11 mo. 3. In addition to short-latency (10-25 ms), monosynaptic excitatory postsynaptic potentials (EPSPs), electrical stimulation at low intensities sometimes elicited delayed EPSPs (20-60 ms). When GABAA-receptor-mediated synaptic inhibition was partially reduced in bicuculline (5-10 microM), electrical stimulation evoked large EPSPs at long and variable latencies (100-300 ms). Glutamate microapplication caused an increase in the frequency and amplitude of EPSPs; preliminary results suggest that glutamate microdrops were less likely to evoke EPSPs in tissue from younger patients (8-12 mo) than in slices from patients greater than 4 yr. Evidence for local excitatory synaptic circuits was thus found when synaptic inhibition was partially reduced. 4. After further reduction of inhibition in bicuculline (5-50 microM), electrical stimulation elicited epileptiform bursts. In pairs of simultaneously recorded neurons, bursts were generated synchronously from long-latency EPSPs (100-300 ms) in slices from patients as young as 8 mo. Reflected EPSPs at very long and variable latencies (500-1,100 ms) and repetitive epileptiform bursts could be evoked synchronously in pairs of cells. Glutamate activation of local presynaptic neurons elicited robust epileptiform events in recorded cells. This was seen in slices from patients as young as 16 mo. 5. These data provide physiological evidence for the presence of local inhibitory and excitatory synaptic circuits in human neocortex at least as early as 11 and 8 mo, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Clinical characteristics and electroencephalography features of intractable childhood epilepsy - A case series

2010 ◽  
Vol 50 (3) ◽  
pp. 133
Author(s):  
Irawan Mangunatmadja ◽  
Eva Devita Harmoniati
Keyword(s):  
Clinical Characteristics ◽  
Age Of Onset ◽  
Epileptiform Activity ◽  
Intensive Therapy ◽  
Case Series ◽  
Intractable Epilepsy ◽  
Neurological Impairment ◽  
Childhood Epilepsy ◽  
Complex Partial Seizures ◽  
Eeg Features

Background The majority of epilepsy patients have good prognosis, but lOAO% will develop intractable epilepsy. Early identification of patients v.ith risks of developing intractable epilepsy allows more intensive therapy to be performed.Objective To study clinical characteristics and electroencephalography (EEG) features of intractable childhood epilepsy.Methods We reviewed children \\lith intractable epilepsy attending the Pediatric Neurology and Growth and Development Clinic in Child Health Department, Cipto Mangunkusumo Hospital from 2005􀁏2008. EEG examination was perfonned in epilepsy patients who had consumed two or more antiepileptic drugs for at least 18 months but still experienced seizure at least once per month. Data of clinical characteristics were collected from the medical records and information provided by the parents.Results There were 41 subjects. Age of onset between o􀁏 1 year old was found in 50% subjects, neurological impainnent in 80%, microcephaly in 50%, and abnonnal neuroimaging in 14 of 24 subjects. Seizure manifestations were mostly generalized tonic clonic, tonic, my oclonic, and complex partial seizures. AbnonnalEEG features were found in 88% subjects and the majority showed generalized sloMng of the background activity. Focal and multifocal epileptifonn activity was found in 31 % and 28% subjects, respectively. Epileptifonn activity was located mostly in the frontal and temporal lobe.Conclusions Most patients Mth intractable epilepsy haveage of onset before the age of 1 year. A substantialpoportionof them have neurological impairment, microcephaly,abnonnal neuroimaging, and abnormal EEG features. Seizure manifestation ismostlygeneralized seizure. Epileptiform activity in intractable childhood epilepsy is often found in the frontal and temporal lobe. 

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