Science topic

Epilepsy - Science topic

A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313)
Questions related to Epilepsy
Question
10 answers
Is there any effective herbal treatment for epilepsy?
Relevant answer
Answer
There is herbal treatment for epilepsy according to Aurvedic tt.
Question
11 answers
Intuitively the response seems to be yes, but I have found little evidence to support this. I wonder what the consensus is across fields?
Relevant answer
Answer
Hi Celia,
As pointed out, it's a difficult question to answer, and would really depend on from which perspective you are looking. Plus, 'Epilepsy' is not one condition; there are many forms, all of which are symptomatic of something problematic going on in the brain (notice the intentional vagueness!).
In the human imaging literature, there is a vast amount of research, primarily quantitative MRI, indicating that, yes, chronic uncontrolled epilepsy is harmful to the brain, and results in progressive further deterioration. This is shown in cross-sectional (a little problematic) and longitudinal studies. This is supported by some animal research. Furthermore, there is a big neuropsychological literature showing that uncontrolled chronic epilepsy causes progressive neurocognitive decline, far beyond what would be expected in neurological healthy people.
The vast majority of this evidence - in humans at least - comes from uncontrolled seizures in chronic focal epilepsy. I don't think that the literature is as clear in generalised / idiopathic epilepsies.
The general thinking in the most common intractable focal epilepsy - temporal lobe epilepsy due to hippocampal sclerosis - is that an early aberrant neurological event causes some alteration in brain physiology / anatomy (e.g. hippocampal pathology), there is then a latent period (can be decades) which supports unnoticed (because it's asymptomatic) epileptogenic processes (e.g. pathological development of anatomy & physiology that would later support the generation of epileptic seizures), habitual epilepsy kicks in, and if uncontrolled will lead to further brain degeneration (both hippocampal and extrahippocampal). I've got to admit, it's probably not as simple as this, and this hasn't been conclusively demonstrated in humans. And it's hard to disentangle the potentially degenerative effects of seizures from the effects of anti epileptic drugs and other factors.
Happy to point you to some relevant studies if you like, but this literature is huge!
Cheers,
Simon.
Question
4 answers
Use of buccal midazolam in children
Relevant answer
Answer
We used buccal midazolam quite frequently in my residency (Mayo Clinic Rochester), and it seems to work quite well.  We dosed it at 0.3mg/kg, max 20mg.  Parents seemed more willing to administer it to older children, and the cost is much lower than Diastat.
Does anyone know how to approach when a VNS device in a child with intractable epilepsy has increased seizures post procedure?
Question
40 answers
I am a GP consulting and researching with a group of manual therapists who work with children with neurodevelopmental issues. I was approached for advice on this child. Child is female with CDKL5 atypical Rett Syndrome. She has had epilepsy since she has been three weeks old. She is now three and a half. Because the epilepsy was diagnosed eventually as intractable (Tegretol, orfiril long, Prednisolone, Sabrilex, Topiramat, Inovelon, Zonegran and ketogenic diet) she was fitted with a VNS device at the end of November 2013. Currently she is on Keppra and Frisium. Since the procedure, she has had an increase in seizure activity, the worst its ever been according to the parents, and she has progressively since that time refused her food and drink and now for the past four weeks refused everything <Food and drink> offered all together. Prior to the implant she was eating normally. She has lost a lot of weight. The treating team chalk the increased seizures up to the fact that she is not eating and lost weight. However, she started refusing food shortly after the device was fitted and this has not been fully explained to the parents. The hospital has excluded infection and constipation. I will post a list of investigations done shortly. The device has been deactivated last week and since then, the parents have seen a small improvement that seems to be getting better day by day. I have been reading the literature and found many studies supporting the safety and efficacy of the VNS implant, especially for children under 12. I have not found anything suggesting that seizures could increase or that esophageal issues ensue. Rather laryngeal function issues, infection and technical issues have been noted. However, all issues started in the weeks post-op, so clearly there is a connection. What can we advise the parents? Its difficult for them to get a second opinion due to the socialized state-provided nature of health care in their country. Should the device be removed? Which special investigations? Any experience with similar cases?
Relevant answer
Answer
Would you then suggest that what we are seeing are related to the Rett Syndrome?
Question
5 answers
Ketogenic diet & childhood epilepsy
Relevant answer
Answer
"Gastrointestinal (GI) disturbances, such as nausea/vomiting, diarrhea, and constipation, also were frequently noted, sometimes associated with gastritis and fat intolerance. Other early-onset complications, in order of frequency, were hypertriglyceridemia, transient hyperuricemia, hypercholesterolemia, various infectious diseases, symptomatic hypoglycemia, hypoproteinemia, hypomagnesemia, repetitive hyponatremia, low concentrations of high-density lipoprotein, lipoid pneumonia due to aspiration, hepatitis, acute pancreatitis, and persistent metabolic acidosis. Late-onset complications also included osteopenia, renal stones, cardiomyopathy, secondary hypocarnitinemia, and iron-deficiency anemia. 22 (17.1%) patients ceased the KD because of various kinds of serious complications, and four (3.1%) patients died during the KD, two of sepsis, one of cardiomyopathy, and one of lipoid pneumonia"
"A high-fat ketogenic diet produced significant increases in the atherogenic apoB-containing lipoproteins and a decrease in the antiatherogenic HDL cholesterol"
"The body weight, height, body mass index, serum levels of triglyceride, total cholesterol, and low-density lipoprotein increased significantly at month 6 when compared to baseline values (P < .05)"
"Subjects treated with the ketogenic diet had higher arterial stiffness parameters, including AIx and β-index and higher serum levels of cholesterol or triglycerides compared to those who had never been on the diet (control group). Arterial stiffness is increased in children and young adults treated with the ketogenic diet, before the increase of the intima media thickness. This supports that arterial stiffness is an early marker of vascular damage"
"Despite its positive effects in some patients, there are potential adverse effects. Two complications related to the ketogenic diet are selenium deficiency, which has been associated with impaired myocardial function, and QT prolongation as documented on electrocardiography. Reported here are two cases of death in a child on the ketogenic diet for seizure control. In case 1, the child who died of complications related to torsade de pointes, with documented QT prolongation; post mortem examination revealed selenium-deficiency cardiomyopathy. In case 2, a child experienced QT prolongation while on the ketogenic diet and later died suddenly at home. Both children exhibited selenium deficiency. These two cases suggest that patients on the ketogenic diet require monitoring of the QT interval by electrocardiography, myocardial function by echocardiography, and selenium levels before and during the ketogenic diet"
"The index case had no detectable whole-blood selenium. Cardiac physical examination and ECG were normal, but the echocardiogram revealed cardiomyopathy.Eight had selenium levels below the normal range (six initially, and two developed low selenium levels on serial testing).The nutrient adequacy of the currently used KD has not been fully evaluated. The nutrient content of KD with usual supplements may not meet Recommended Dietary Allowances (RDA) for selenium and may not provide other trace minerals in adequate amounts. At our center, selenium deficiency was found in 20% of the patients evaluated"
"Our patient, a 5-year-old boy on a ketogenic diet for intractable seizures, had a normal selenium level before starting the diet, but he shortly thereafter developed acute reversible cardiomyopathy and ventricular tachycardia.His cardiomyopathy was suspected to be secondary to a selenium-deficient state and was confirmed by way of a markedly low serum selenium level and supported by rapid improvement with the initiation of selenium supplementation and cessation of the ketogenic diet. We suggest that all patients initiated on a ketogenic diet should have a preoperative electrocardiogram (EKG), an echocardiogram, and selenium level determined before any elective surgery. These steps would prevent unnecessary perioperative morbidity and mortality"
Question
11 answers
Recent high profile reports of Cannabidiol (a natural non-psychoactive component of marijuana) being very effective in treating otherwise intractable seizure disorders have led to families of severely affected children demanding access, but current laws in most countries make both access and controlled research difficult. How can this be better managed both clinically and for research?
Relevant answer
Answer
Happily I work in the Netherlands and can prescribe 'Nederwiet', medical Flos Cannabis, and the patient gets it at the pharmacy. The same I believe in Canada.
There is only one way to get Cannabis on your prescription pad:
make it a high priority of your local pain chapter of the IASP,
then write a commentary and statement in your medical journal,
then get your medical association to lobby in your political system,
and then finally you will be able to help your patients.
Mark this: there has NEVER been a fatal side effect of Cannabis...How many death are there in your country as a side effect of opioids??? Why are opioids free to prescribe and a compound as Flos Cannabis is criminalized?
Because our society is afraid for mildly mind altering substances...guess why?
Question
6 answers
Can anyone please let me know the frequency range of epilepsy seizure activities from Scalp EEG analysis? I have found a range from the literature which is 0.5 Hz to 29 Hz. Is this applicable to all types of epilepsy seizures? Would appreciate if someone answers this confusion. Thank you in advance.
Relevant answer
Answer
There's a growing body of literature on high-frequency oscillations (HFO) in various epilepsies, that you'll want to review (see also, 'gamma', 'high gamma', 'ripple', and 'high ripple', as terms used to describe higher frequency events or oscillations). Historically, there's been a focus on activity <40 Hz or so, which reflects a belief that higher frequency activity is poorly resolved on scalp EEG (due to contamination with muscle artifact, temporal smearing related to our physiology, etc.). With intracranial recordings, or magnetoencephalography (MEG), we have increased access to high frequency activity. HFOs may be coincident or predictive of interictal and ictal spikes.
Question
1 answer
Many brain insults, including TBI, stroke and encephalitis, may be associated with “early seizures” in the first week after the insult. These seizures are not spontaneous (unprovoked), but are directly caused by the initial insult. Late unprovoked (i.e., spontaneously recurrent seizures), may follow weeks, months or years later.
Our question is: May such early seizures also occur after a status epilepticus and is there literature on this (both for patients and SE models)?
We do typically observe early seizures in different SE models (e.g., pilocarpine, kainate) in rats. They occur with a peak frequency at 3-5 days following SE (if the SE was effectively interrupted after 60-120 min) and then subside. Late seizures occur earliest after about 7 days but often later.
Relevant answer
Answer
This depends how you define epilepsy. A SE followed by a seizure some days later will qualify for most epilepsy definitions.
For a classic publication on recurrence of nonconvulsive seizures/SE see:
Neurology. 2001 Sep 25;57(6):1036-42. Continuous EEG monitoring and midazolam infusion for refractory nonconvulsive status epilepticus. Claassen J, Hirsch LJ, Emerson RG, Bates JE, Thompson TB, Mayer SA.
Question
1 answer
Ceiling concentration of extracellular potassium. The lower limit as per my knowledge is 3.5 mM.
Relevant answer
Answer
According to Lothman et al., 1975 (J Physiol. 1975 Oct;252(1):115-36) the upper normal level is 12 mM, with higher concentrations leading to spreading depression.
Leif Hertz
Question
5 answers
Expression of NKCC1 and KCC2 appears crucial in triggering seizures in immature rats through breakdown of Cl- homeostasis, which apparently seem to stabilize with maturation. However, can induction of seizures, using High K+ model (or) Zero Mg2+ model (or) 4-AP model, regulate NKCC1 expression in adult brain (6-8wks old rats) ?
Also, if such changes do occur, can these be studied using acute hippocampal slice preparations?
Relevant answer
Answer
Dear Deepak,
I would like to add a word of caution. The opposite mode of regulation of KCC2 and NKCC1 by kinases, pointed out by Pavel Uvarov, is just one aspect of a probably more complex regulation of these two key transporters. Conceivably the developmental switches (e.g. release of KCC2 expression from NRSF suppression or reversal of DNA methlyation in case of NKCC1) may be kind of reset. However, in human epileptogenic tissues we find also a decline in bumetanide-sensitive i.e. NKCC1-mediated chloride extrusion. On average NKCC1 is reduced by 60 % but KCC2 decreased by 80%.
(Deisz et al. 2011, J. Physiol).
Best regards
Rudolf
Question
7 answers
We are currently testing out the best way to do fMRI studies in patients with epilepsy. It would great if you could recommend some of the established tests for auditory comprehension paradigm.
Relevant answer
Answer
I am assuming you're looking to lateralize language for presurgical planning? One simple test, that has been fairly successful includes flashing a description of an object for the patient to read. His/her response will be to silently name the object to themselves while in the MRI. The control portion of the test could be nearly anything, but usually staring at a cross on the screen of their goggles works well. A good description of the task can be found in "Language dominance in partial epilepsy patients identified with an fMRI reading task" Neurology (2002) 59, 256-265. Hope this helps!
Question
4 answers
Looking for human or animal model evidence of neuronal/physical damage to assess the impact of poorly controlled partial onset seizures.
The clinical motto is always that one seizure is a seizure too many, but is there any physical pointer for this? I find this crucial to evaluate the burden of AED polytherapy on patients and the importance of trying new therapies in unsatisfactorily controlled patients.
Relevant answer
Answer
1: Fuerst D, Shah J, Shah A, Watson C. Hippocampal sclerosis is a progressive
disorder: a longitudinal volumetric MRI study. Ann Neurol. 2003 Mar;53(3):413-6.
PubMed PMID: 12601713.
Question
3 answers
Few publications showed a limited effect of cannabinoids for epilepsy. Gloss D. Cochrane Database Syst Rev. 2014. but what are your experiences?
Relevant answer
Answer
I ve startet in oneof my patients with Nieman Pick disease with THC. Not because of seizures but because of pain, his muscular spasticity and trouble with sleep. all of this problems improved right from the beginning and most important, the quality of live improved very much. unfortunately is the norwegian health system not willing to pay for the treatment.
Question
1 answer
A number of prospective studies have attempted to identify risk factors that predict the risk of drug-resistant epilepsy {DRE}. These studies have varied somewhat in their sampling (population-based versus hospital-based) and whether they included children, adults, or both. No single factor has been found to be uniquely useful in making accurate predictions.
Relevant answer
Answer
Usually children with congenital brain structure abnormal (especially in MRI) are easily to develop into drug-resistant epilepsy. Children with infantile spasms not reacting well to ACTH are also prone to have drug resistant, In addition, some epileptic syndromes, such as Alpers syndrome, Rasmussen's syndrome, are also risk factors for drug resistant
Question
7 answers
Melatonin is a chronobiotic hormone secreted by pineal gland - regulates circadian rhythm, it may improve myoclonic and nocturnal seizures.
Relevant answer
Answer
Dimah Sweis. THE USES OF MELATONIN. Arch Dis Child Educ Pract Ed 2005; 90.
Melatonin was first reported to improve significantly clinical electroencephalogram (EEG) patterns in untreatable epileptic patients with different aetiologies by Anton Tay et al in 1974. There are several explanations for the effect of melatonin on epilepsy. It is known to have a neuroprotective role, due to its ability to inhibit glutamate receptors and potentiate GABA-benzodiazepine receptors. Melatonin is also known as an antioxidant, scavenging highly toxic free radicals that are generated during seizures. Finally, it is known that epilepsy is exacerbated by lack of sleep, therefore improved sleep patterns would lead to fewer seizures.
Many investigations have been carried out examining the effect of melatonin on children with epilepsy. These studies have shown very contrasting results, whereby some have found significant improvement, while others reported remarkable deterioration. Several studies have found contrasting results within the same investigation, reporting random cases of worsening and improvement. One studydescribed worrying results that seizure frequency increased with melatonin administration, in spite of improved sleep patterns. Discontinuation of treatment led to the return of seizure activity to baseline, and re-challenge with melatonin caused a recurrence of seizures. It must be noted that this study only included six children, which is not a representative sample, and there have been no other studies that reported similar results. Alternatively, several studies have reported significant decreases in seizure frequency confirming the anticonvulsant action of melatonin, particularly for myoclonus seizures and nocturnal seizures. Melatonin has also been investigated as adjunctive treatment to valproate and phenobarbital. Such studies showed favourable effects of melatonin, leading to lower anticonvulsant doses, thereby reducing the side effects.
Several studies on children with epilepsy were conducted using varying doses of melatonin. One recommendation was that fast release melatonin is administered one hour before bedtime using the following doses12:
• 6 mg for children younger than 9 years or weighing < 30 kg
• 9 mg for children older than 9 years or weighing > 30 kg
In another study, children were started on 5 mg and if there was no improvement after 3–5 days the dose was slowly increased to a maximum of 10 mg.
One particular study attempted to initiate melatonin in an untreatable child with severe myoclonic epilepsy as an adjunctive to anticonvulsant therapy. In this particular study, the child was given an initial dose of 500 mg which triggered a convulsive seizure lasting three hours. After one week, another attempt was made to start melatonin with a dose of 50 mg, resulting in a notable decrease in the number of seizures. After much experimentation, the optimal dosing regimen for this child was 120 mg/day (20 mg at 9 am and 100 mg at 9 pm). When the melatonin dose was reduced, seizures were more likely to occur, and the melatonin concentrations were to be maintained high throughout the entire day.
Question
5 answers
Herbal medicine in epilepsy
Relevant answer
Answer
Thanks all for answers
Question
6 answers
This patient started with generalized tonic-clonic seizure, associated with severe absence seizures per day, all together with myoclonic seizures, he was refractory to Ethosuximide, Valproic Acid, he´s actually with Clobazam and levetiracetam. As he was refractory, we conducted an MRI and found bilateral periventricular nodular heterotopia.
Relevant answer
Answer
Thanks again, our patient was initiated with CBZ before coming to our Epilepsy clinic, nevertheless, he was postulated as a possible candidate for Vigabatrin as well, but we preferred starting a add on therapy with LEV and VPA. In your case, was the patient a female o a male? and another question is how old was he/she at the moment of the onset of epilepsy?
Question
3 answers
Patients with epilepsy whose seizures do not successfully respond to antiepileptic drug (AED) therapy are considered to have drug-resistant epilepsy (DRE). This condition is also referred to as intractable, medically refractory, or pharmacoresistant epilepsy. As many as 20 to 40 percent of patients with epilepsy (roughly 400,000 Americans) are likely to have refractory epilepsy.
Relevant answer
Answer
Neurosurgery when possible is the only treatment for these drug-resistant patients. Numerous Epileptic center are using EcoG or iEEG to investigate intractable epilepsy in order to drive surgical treatment by localizating the epileptic zones. I am not sure there is more simple way...
Question
9 answers
Dravet syndrome, also known as Severe Myoclonic Epilepsy of Infancy (SMEI), is a rare and catastrophic form of intractable epilepsy that begins in infancy. Initial seizures are most often prolonged events and in the second year of life other seizure types begin to emerge. Development remains on track initially, with plateaus and a progressive decline typically beginning in the second year of life. Dravet syndrome is refractory to many anti-epileptic medications.
Relevant answer
Answer
In our institute first choice is combination of valproate with clonazepam or clobazam. We have also used topiramate in some cases.
Question
8 answers
We have been studying audiogenic reflex seizures in cats. The phenotype seems to be older cats (usually >14years old) suffering myoclonic twitches and generalised tonic-clonic seizures in response to sound. Many of the cats have concurrent renal and cardiac abnormalities with a smaller proportion having hearing difficulties. However, these conditions may simply reflect the older population that are affected with this syndrome. The stimulus is generally a high pitch noise (e.g. a spoon tapping against a ceramic bowl, rustling of paper and crinkling of foil etc) but can be quite variable. We are looking to see if this relates to a similar late onset myoclonic reflex epilepsy in humans. I have become familiar with juvenile myoclonic epilepsy which seems to fit our model well but is obviously different in terms of the age of the patients affected. If any one has thoughts on analogous syndromes this would be extremely helpful in the planned genotyping of this feline condition. Thank you in advance of any help or insight people may have.
Relevant answer
Answer
Question
5 answers
I am currently working on artifact removal from ambulatory EEG for seizure detection of an epilepsy patient. I have gone through some literature related to this topic but found almost all of it to use some kind of motion sensors; e.g. accelerometer, gyroscope, etc. to track the movement/motion artifacts and hence use suitable techniques to remove them. However, I am wondering if I can do this without using the sensors, since not every ambulatory EEG recorder would come with such sensors. I would like to work fully from the signal processing point of view in digital domain and I don't want to interfere/modify the recording setups. Hope I made it simple to understand. Thanks in advance.
Relevant answer
Answer
A way to significantly reduce (actually remove) motion artifacts in ambulatory EEG is to use amplifiers with active shielding technology. We use Mobita amplifiers from TMS-international (http://www.tmsi.com/)
We recently reported on our experiences in this paper:
Mobile EEG in Epilepsy.
Jessica Askamp, Michel J A M van Putten
International journal of psychophysiology: official journal of the International Organization of Psychophysiology (Impact Factor: 3.05). 09/2013; DOI:10.1016/j.ijpsycho.2013.09.002
Is health related quality of life has any impact on family members of adolescents living with idiopathic epilepsy?
Question
12 answers
Idiopathic epilepsy is most commonly identified in early adolescence. Does having adolescents with idiopathic epilepsy affect the health related quality of life of family members?
Relevant answer
Answer
Try this pubmed search "Epilepsy"[Majr] AND ("Quality of Life"[Majr] or "Cost of Illness"[Majr] or burden)and "Caregivers"[mesh] (or follow the link below) http://www.ncbi.nlm.nih.gov/pubmed/?term=%22Epilepsy%22[Majr]+AND+%28%22Quality+of+Life%22[Majr]+or+%22Cost+of+Illness%22[Majr]+or+burden%29and+%22Caregivers%22[mesh]
Question
12 answers
We are conducting a review study on a relationship between chromosomal aberrations and childhood epilepsy. Has anyone had registered cases with chromosomal abnormalities and epilepsy?
Relevant answer
Answer
It depends on what you include in "chromosomal aberrations". If you consider the broadest of definitions, in other words any kind of genetic change, for example, intronic or exonic single-base substitutions leading to altered gene regulation, an amino acid exchange, or a premature stop codon)... certainly. Genetic epilepsy is obviously well documented in the literature and there are various locus-specific databases that inform you of the clinical consequences. Just check PubMed using, for example, "channel" (for ion channel) and "epilepsy".
There is also evidence of larger-scale rearrangements in the literature, where traditional direct sequencing had previously failed to detect abnormalities, but multiplex ligation-dependent probe amplification (MLPA) uncovered the issues (see PubMed - e.g., http://www.ncbi.nlm.nih.gov/pubmed/17000989). These days, MLPA and DNA microarray are becoming more and more common in genetic analyses of epilepsies where the genetic basis has been established (e.g., Dravet syndrome, ADNFLE, etc.) or is still unknown.
Question
5 answers
Currently am going to work on epilepsy so am interested to induce epilepsy physically.
Relevant answer
Answer
"Structural and Dynamic Insights into S100B Protein Activity Inhibition by Melittin for the Treatment of Epilepsy".
Question
2 answers
AM251, a specific CB1 receptor antagonist, has dose dependently intermittent weak and strong pro-convulsive effects in seizures following administration of pentylene tetrazole as a convulsant in animal studies. In my opinion the mechanisms that mediate this effects would be interesting.
Relevant answer
Answer
Would this ref be helpful?
by R Abalo - ‎2011 
Jan 10, 2011 - CB1 receptor antagonist/inverse agonist AM251 ... interest under certain circumstances. ... As the central effects of intermittent administration.
Question
40 answers
I am looking to record seizure activity during sleep in a patient with JME. It will be over a course of 2 months; therefore, I would like to minimize combinatory video/EEG footage (approximately 8 hours a night of sleep x 7 days a week equates to 56 hours a week for 2 months, adds up to be quite lengthy number of hours!). Is there a more streamlined approach to measuring seizure activity under lengthy sleeping conditions? I would have preferred to randomly select 3 days a week to video/EEG activity; however, I am afraid of compromising validity because the patient's seizure frequency and timing is not fully clear. Any feedback would be greatly appreciated.
Relevant answer
Answer
Dear Sarah,
Do you want to record clinical seizures ( you need video/EEG) or just inter-ictal epileptic discharges ? Because, in general JME tonic-clonic seizures occurs early in the morning,more than nocturnal hours. If you only wants to record epileptic discharges you can use ambulatory EEG recorder, that is more easy to use conventional sleep laboratory. More, using Electro-cap in appropiate way, is easier than standard colodión electrodes.
Question
2 answers
reduction of latency by a few seconds may not affect drug delivery system until it is automatic
Relevant answer
Answer
thanks for valuable informationAli Abdil Razzaq Muhammed Noori Aldallal  sir 
Question
3 answers
Hello,
Our group is interested to see the bdnf level in real time in epileptic rats since there are studies showing bdnf can increase seizure level.
We are interested in detecting bdnf level for epileptic rats over a long term. Is there any method for doing that? Such as Electrochemical sensor inserted inside the brain?
Relevant answer
Answer
It's not outside the realms of possibility but I imagine a lot of work would need to go into developing a suitable sensor. A number of challenges need to be overcome which can take years and from the literature, I can find no suitable background information on BDNF to even give an educated guess (I don't know how it is normally metabolised or whether it shows any electrochemical activity).
There are two basic ways of detecting an analyte with electrochemical techniques. The first and most straightforward is to find a potential where your target analyte (in this case BDNF) is oxidised or reduced and measure the current. This should be proportional to your concentration but is dependent on a number of factors such as whether your analyte is easily oxidised/reduced electrochemically and, if it is, are other analytes also being oxidised/reduced at the same potential; if there are a lot of substances with a similar electrochemical profile in the ECF in vivo it would be very hard to pick out BDNF directly. This is the case for dopamine and serotonin along with their analytes, there are ways of adjusting the electrochemical techniques (such as fast scan cyclic voltammetry) but I can find no publications applying any electrochemical technique to BDNF or other neurotrophins.
The other main way to detect an analyte electrochemically is to make a biosensor by using an enzyme as a recognition unit and measure a current generated by the 2 or 3 step reactions (measuring something like hydrogen peroxide which might be produced as part of the enzymatic reaction). This requires a suitable enzyme/antibody to act as a recognition unit - it will need to be specific for BDNF and it will need to produce something that is easily measured electrochemically. Oxidase enzymes are ideal but I am not aware of any for BDNF. Perhaps an antibody could work but I've no experience with using antibodies as recognition units personally.
Your best bet might be microdialysis but unfortunately that may be too slow to get precise measurements to match the timelines of the observed seizures. There are ways of increasing the temporal resolution with microdialysis but these methods tend to incorporate an electrochemical sensor off-line. The other thing to bear in mind is that a microdialysis probe causes more gliosis and metabolic disruption than a microsensor.
Question
5 answers
Anticonvulsants can alter some neurotransmitters in the CSF of epilepsy patients, but it is of difficulties to get this kind of specimen. Can the changes of neurotransmitters in plasma from patients after the treatment of anticonvulsants be a reflection about those in the brain and CSF? And can the changes of neurotransmitters in plasma from drug-treated patients be a biomarker of therapeutic effectiveness?
Relevant answer
Answer
I suspect that you will have difficulties in assessing the effectiveness of any antiepileptic drug by measuring neurotransmitters in plasma. The concentrations, and changes thereof as evoked by antiepileptic drugs, will be way too small. Also, many neurotransmitters are produced outside the brain, so how to distinguish the peripherical ones from the central ones? In other words, the concentration in plasma (if you could measure it) does not say anything about the concentration at the epileptic focus in the brain. Last, the ultimate marker for effectiveness is reduction in seizure frequency which is pretty easy to assess (and non-invasive, too). So why use a biomarker in plasma to measure effectiveness? Maybe I did not understand your question, but I do not think that this is a good idea.
Question
9 answers
Changes in NKCC1 expression are seen in in vivo models of epilepsy and brain tissue from patients with drug-resistant seizures. Is it possible to study such changes using acute hippocampal slice preparations (using western blotting)?  
More precisely, if I incubate hippocampal slices in zero Mg2+ or high K+  conditions for 1-3 hours, will that trigger changes in NKCC1 expression already?  
I am interested to know how long it would take to regulate NKCC1 expression.
Relevant answer
Answer
If you are trying to find conformation change use immuno precipitation and mass spec and phosphorylation specific antibodies in immunoblot
Question
9 answers
I'm looking for chemical or physiological parameters (which can be measured) that change minutes or seconds before an epilepsy crisis. In other terms, what are the chemical, biological and physiological changes that occur just before an epilepsy crisis ?
Relevant answer
Answer
On EEG, focal rhythmic delta-theta may predict an oncoming seizure as may an increase in the density of interictal spikes.
Question
18 answers
I am looking for some scalp-EEG based epilepsy seizure detection software/code that is implemented in MATLAB. I would appreciate any help regarding this issue. Thank you in advance :)
Relevant answer
Answer
You can find the complete code for implementation of Lan-Lan Chena, JianZhanga, Jun-ZhongZoua, Chen-JieZhaob, Gui-SongWang, A framework on wavelet-based non linear features and extreme learning machine for epileptic seizure detection, Elsevier, Biomedical signal procesisng and control doi : http://dx.doi.org/10.1016/j.bspc.2013.11.010) in the same
Question
14 answers
EEG done within 24h of the seizure was found to have more yields of epileptiform discharges as compared to an EEG done later.
Relevant answer
Answer
In case of suspicion of an absence seizure without the occurrence of a grand mal seizure, I would request an EEG as soon as possible, since it may be very informative, showing generalized spike-wave disharges, either ictal or interictal, mostly when medication with antiepileptic drugs has not been started yet. If a grand mal seizure has occurred, it is a common sense to wait for about 48 hours, considering the possible transient slowing of background activity after such type of seizure. After the suspicion of a simple focal seizure, without secondary generalization, or a temporal lobe seizure, I usually request EEG as soon as possible, because, for partial epileptic syndromes, the amount of EEGs obtained along the time can improve the accuracy of the method in showing localized paroxysmal discharges. Also, if a focal background abnormality is seen, this could also reinforce the impression of a focal origin for the recently occurred seizure, when the ictal semiology was not very clear in defining a focal as opposed to a generalized event. Even though it does not mean the presence of a focal lesion, an MRI should be carried out to clarify the situation. For operational reasons (facility, patients coming from others towns without EEG services, etc…), we often register an EEG within the first 24 hours in patients attending the emergency room in our institution. And, the impression is that it can be as helpful as an EEG carried out one month after this first single seizure. Most of the time, it is always helpful to get the EEG as an extension of the Neurological Examination, or a good method for evaluating cortex functionality, besides pointing out the possibility of an epileptic syndrome.
Question
11 answers
AEDs for benign childhood epilepsy with centrotemporal spikes.
Relevant answer
Answer
Nurse Jason
Question
6 answers
Epileptic patients have varying signs and symptoms. The majority of the pseudoseizures typically exhibit purposeful signs and can respond verbally.
Relevant answer
Answer
how a person behaves during a pseudoseizure depends on what his/ her perception of a seizure is.It is a willful act unlike a true seizure . 
Question
9 answers
These pathways were ranked as follows in a reputable journal publishing an article about epilepsy related-genes, with -log (p-value) in bold; followed by p values in parentheses:
1. (top rank) Molecular Mechanisms of Cancer 9.66 ( 2.188 x 10-10)
8. Type II Diabetes Mellitus Signaling 6.14 (7.244 x 10-7)
11. Pancreatic Adenocarcinoma  5.7 (1.995 x 10-6)
A plausible pathway related to the Central Nervous System (CNS) appeared lower down:
12. Axonal Guidance Signaling 5.67 ( 2.13 x 10-6)
Does anyone else see highly ranked false positives in pathway analysis in their field- is this a systemic problem? Do you think it is a significant problem? How do you get around it? (It is possible to run several different pathway analyses, but they are often contradictory, and it should not be necessary to cherry-pick).
Do you think the problem lies in the realm of biological classification and annotation, and/or the algorithms used, and/or the statistics?
If this is an important issue, what do you think are potential solutions
Relevant answer
Answer
It is a systemic problem in all research that depends upon p-values. There is no basis to use p-values as a criterion for a conclusion. There are no rules as to how to apply them. As Jochen asked, what is the basis for deciding these are false positives? A p-value cannot be classified as false or true unless you have other information.
A study must start with information. The information leads to a proposition that can be tested. The proposition must be tested in a logical context. The context must include the degree of evidence necessary to make a conclusion. A conclusion can be drawn when the evidence is sufficient. If you need p-values to prove your point then you must qualify the context and evidence that is supported by that p-value. I think you will find that a p-value does not suffice.
Question
14 answers
I know about the link between the cerebral cortex (which plays an important role in  memory, attention, perceptual awareness, thought, language) and I would like to find out how a person which suffers from epilepsy can improve their memory.
I think there has to be some neuropsychological tests (to have a clear vision about the affected areas/skills).
Any information about the link between epilepsy and memory could be useful.
Thanks.
Relevant answer
Answer
Hi Alexandra,
There are several epileptic syndromes, and not all of them affect in  the same way. For example, Temporal Lobe Epilepsy and Frontal Lobe Epilepsy have their focus on different areas and their neuropsychological profile won't be the same. Identifying and taking into consideration variables like the patient specific epilepsy syndrome, seizure type and localization, age (adult brain doesn't work like a child one), treatment effectiveness in preventing seizures, possible cognitive size-effects associated to anti epileptic drugs... is important for a proper evaluation and so it is for the rehabilitation programme.
Regarding these variables, you could perform a more focal memory assessment or more exhaustive: both verbal and spatial, immediate memory, learning and recall, sentences memory... But remind the human brain is highly interconnected and a cognitive function rarely can be isolated (less if you plan its rehabilitation, which relies in the preserved skills).
Question
4 answers
Please suggest some ways to recruit children in a data registry and clinical trial. The disease is newly discovered genetically associated epilepsy and its association with the gene is strong but diagnosis rate is very low due to rarity and novelty of the disorder. Affected population includes infants and children.
Relevant answer
Answer
I suggest involving the parents and informing them of the real advantages of data registries and clinical trials in making progress in rare diseases. Consider holding an "Open Day" for parents and clinicians to publicise the matter. Establish a network of those clinicians who are already involved with cases.
Question
16 answers
Ketogenic diet in neurological disorders.
Relevant answer
Answer
I hope this is useful. For discussion, let's separate the topic into different categories. One category would be low-CHO diets that are within the ketogenic ratio and so when consistently followed promote moderate ketosis. For a stimulating discussion of the ketogenic ratio and using this to evaluate studies of diet effects, see -  Zilberter T. "Carbohydrate-biased control of energy metabolism: the darker side of the selfish brain." Front Neuroenergetics. 2011 Dec 20 PMID: 22194720. And also note that a search under "ketogenic diet" in clinicaltrials.gov yields 63 hits, most concern epilepsy, but also cancer, stroke, obesity, metabolic syndrome, Parkinson disease, brain injury are mentioned.
Another category would be methods of inducing moderate ketosis while generally leaving diet unaltered. Moderate ketosis could be promoted by regular ingestion of various ketone precursors such as medium-chain triglycerides, or related medium-length fatty acids (octanoic acid has been under study, though I haven't seen ketones mentioned in that work), or ketone salts (there is a US commercial supplement manufacturer who sells the mixed Na/K salts of beta-hydroxybutyrate), or ketone esters such as the beta-hydroxybutyrate butanediol monoester developed by Dr Richard Veech and Dr Kieran Clarke.
An example on this side would be the work done by Dr S. T. Henderson with caprylic triglyceride, administered to patients with probable Alzheimer's disease. Henderson ST, Poirier J "Pharmacogenetic analysis of the effects ofpolymorphisms in APOE, IDE and IL1B on a ketone body based therapeutic oncognition in mild to moderate Alzheimer's disease; a randomized, double-blind,placebo-controlled study." BMC Med Genet. 2011 Oct 12;12:137. doi:10.1186/1471-2350-12-137. PubMed PMID: 21992747.
Question
12 answers
Dear colleagues, I need some advice in a difficult clinical case.
It's about a young man 34 year old man, diagnosed with Type I diabetes mellitus at the age of 32 years and autoimmune thyroiditis at age 33 years.
Currently, this patient shows complex partial seizures, for what he was induced into barbiturate coma.
After 72 hours, the patient recovered in satisfactory condition and left ICU.
After another 24 hours, the condition worsened again. This patient shows a status epilepticus, complex partial seizures, although persistent anticonvulsant therapy with sodium valproate, which was started at first day of admission in our hospital.
This complex pathologies: Type I Diabetes Mellitus , autoimmune thyroiditis and seizures, can be explained by a autoimmune disorders?
 What is your experience in this regard? What would be the tactic of diagnosis and treatment in case of autoimmune diseases?
Relevant answer
Answer
I wonder why do you define this epilepsy as drug-resistant? Are you sure you gave high enough doses? Did you measure the serum levels of valproate? Was it administered as bolus injections or as continuous infusion? Have you tried levetiracetam or (fos)fenytoin in high enough doses?
Question
13 answers
The best explanation I could find is that levetiracetam attaches to SV2A on the surface of the neuron vesicles, and that this attachment reduces the backlog of signals that cause a seizure.  How exactly does it reduce the overload of signals? 
Relevant answer
Answer
Agree, but evidence in the PNAS paper is indirect and does not rule out voltage-gated channels associated with SV2a as LEV targets. SV2a is expressed at both Glu and GABA synapses, which makes a purely SV2a-dependent LEV mechanism difficult to explain - e.g. see: PubMed-ID 22046416 or 22847229 ? Anyway, the most important finding probably is that it acts at the presynaptic level of synaptic communication :-) ... Cheers, Jochen
Question
6 answers
Which is the best available automated real-time epilepsy seizure detection algorithm that you have come across given that the algorithm takes care of different artifacts' effect on the detection performance? The performance metrics should include detection accuracy, false alarms, latency/delay from original seizure onset, robustness, computational complexity, etc. Would be more than glad if someone could kindly post your suggestions, opinions or any direct answer. Thank you in advance
Relevant answer
Answer
Refer : Lan-Lan Chena, JianZhanga, Jun-ZhongZoua, Chen-JieZhaob, Gui-SongWang, A framework on wavelet-based non linear features and extreme learning machine for epileptic seizure detection, Elsevier, Biomedical signal procesisng and control doi : http://dx.doi.org/10.1016/j.bspc.2013.11.010. The results obtained here are very promising
Question
3 answers
I need to test the reaction to Pilocarpine of some mutant mice and need to know the exact maximum dose of Pilocarpine to which wild type animals do not respond.
Relevant answer
Answer
200mg/Kg body weight is lowest dose at which occasionally seizure  can be seen. Increasing dose from 300mg/kg induces seizure which can be clearly noticed...Here is supporting article for your reference ..
Question
5 answers
I want to simulate seizure and epilepsy in mouse, but I can't find a proper dose of pentylenetetrazole in saline in papers.
Relevant answer
Answer
Dear Fereshteh
The answer of Beate is almost complete. I just want to say that according to the age of animals you may need different dose. Thus, please check the age of animals used in the articles. Usually the PTZ dose needed in young animals is less than older animals. The other thing which is very important is the time of your experiments. If you can not completely control the temperature and humidity of the animal house of your lab, you can find a lot of differences in seizure parameters of animals. Please try to do all of your experiments in warm seasons (Spring and Summer) or cold seaons (Autumn and Winter).
Question
16 answers
As i will participate at a study on Epilepsy in Tanzanian children with epilepsy (3-18 years) and intend to perform neuropsychological assessment using standard test batteries. As i do not speak the native language (Kiswahili) i thought about using nonverbal IQ test that cover a wide age-range, wide cognitive range, are nonverbal, measure and discriminate different parameters of intelligence are short and well established.
Does anyone have an experience with cToni, UNIT, Raven, nonverbal Wechsler WNV or others in rural african children?
Relevant answer
Answer
MANY TESTS THAT PRESUMABLY MEASURE "NON-VERBAL" INTELLIGENCE HAVE POOR REFERENCE POINTS, AND DO NOT CORRELATE WELL WITH RECOGNIZED "GENERAL ABILITY" MEASURES SUCH AS THE WECHSLER SCALES. THEREFORE, IT IS VERY DIFFICULT TO BE CONFIDENT ABOUT WHAT YOU ARE MEASURING. THAT SAID, THE RAVEN'S PROGRESSIVE MATRICES ARE ARGUABLY THE BEST MEASURE OF "g." THEY ARE AVAILABLE IN CHILD, ADULT, AND ADVANCED VERSIONS, SOLD BY A PUBLISHER IN THE UK. IMHO, THIS IS YOUR BEST BET; IT IS ALSO PRESUMABLY "CULTURE FREE," BUT I'M NOT SURE HOW THAT IS ESTABLISHED IF "TEST TAKING" IN GENERAL IS NOT PART OF ONE'S CULTURE.
AGAIN IMHO, I'M NOT SURE THAT "IQ" IS "THE" VARIABLE OF INTEREST IN EPILEPSY. I'M ASSUMING THAT YOU ARE EQUATING "NON-VERBAL" WITH NOT ORALLY EXPRESSIVE - A TEST THAT DOES NOT REQUIRE AN ACTIVE VERBAL REPLY. HOWEVER, THIS CAN BE MISLEADING, SINCE PEOPLE OFTEN USE VERBAL THINKING TO SOLVE PROBLEMS, EVEN WHEN NOT VERBALIZING A REPLY; STUDIES HAVE SHOWN THAT IN THE ABSENCE OF AN ACTIVE VERBAL REPLY, LANGUAGE NETWORKS ARE ACTIVATED ANYWAY; SIMILARLY, IT HAS BEEN DEMONSTRATED THAT ON WORD LIST LEARNING TASKS, THE BEST LEARNERS ACTIVATE ANTERIOR RIGHT HEMISPHERE BRAIN REGIONS. . MOST IQ TESTS HAVE SEVERAL/MANY SUBTESTS, AND THESE SUBTESTS ALMOST ALWAYS REQUIRE MULTIPLE COMPONENT COGNITIVE PROCESSES AND ACTIVATE WHATEVER BRAIN NETWORKS ARE REQUIRED, DEPENDENT UPON TASK DEMANDS. I AM TEMPTED TO THINK THAT IN SEIZURE DISORDERS, WITH A SPECIFIC FOCUS OF IMPAIRMENT, SELECTIVE BRAIN NETWORKS WOULD BE AFFECTED, SO INTELLIGENCE TEST SUBTESTS WILL NOT NECESSARILY SOLVE THE PROBLEM OF IDENTIFYING SPECIFIC REGIONAL NETWORK INVOLVEMENT.  YOUR BEST MEASURES MIGHT BE THOSE TESTS THAT ARE RELATIVELY "PURE," THOSE MEASURES THAT ARE INTERPRETED AS PATHOGNOMONIC SIGNS, OR PERHAPS THOSE TESTS WITH A SKEWED DISTRIBUTION, THOSE THAT DO NOT FOLLOW THE PERFORMANCE DISTRIBUTION OF A "BELL-SHAPED CURVE."  SEE LEZAK, ALMOST ANY EDITION, FOR FURTHER EXPLANATION. THIS WILL BE FOUND IN THE "BASIC CONCEPTS" CHAPTERS OF THE BOOK. - LK
Question
36 answers
I have 5 groups of rats (each group n=6), Group 1- healthy control rats, Group 2- Diseased control rats, Group 3- Drug A treated rats, Group 4- Drug B treated rats, Group 5- Drug C treated rats. I have to compare anxiety behavior within the groups for each treatment. Which statistical test will be appropriate for this analysis?
Relevant answer
Answer
Depend of your response variable. Whether it's cuantitative or categorical. Before run a test, if it's cuantitative, check the assumptions for ANOVA models i.e. homogeneity of variances and normality of residuals. If it meet the assumptions you can run an ANOVA test and if is necessary run post hoc test. Also, if you have a priori hypotheses about the effects of the drugs, you can consider planned contrasts, these are powerful than post hoc test. On the other hand, if your response variable on´t meet the assumptions for ANOVA, consider run a GLM.
good luck!
Question
3 answers
If I would like to provide energy to a brain using dietary MCT's in humans, which MCT would be most efficient for doing that, the C8 or C10-containing MCT's? Are there any known biochemical or physiological differences at all between the two?
Relevant answer
Answer
C8 MCTs produce much more ketone bodies than C10 MCTs and show potential in Alzheimer's disease. Furthermore, C8 MCTs have a spectacular effect on gut health (see article as included) and strongly induce anti-oxidaitve enzymes in vivo. All in one molecule....Great stuff!
Question
3 answers
.
Relevant answer
While the presence of unresectable areas within the lesion or the epileptogenic zone limited the utility of surgical resection, the poor outcomes in some of our patients, particularly in the AD group, require comment. One possible explanation is that the anatomical or functional alteration extended beyond the lesion revealed by MRI or SEEG and was not removed. Another possibility is that, following surgical ablation of the leading or at least electroclinically evident epileptogenic zone, another zone that previously was silent or covered by the leading one could become evident or ‘switched on.’
Question
5 answers
Epilepsy impacts the performance of cognition, but nowadays there is no multicenter study about it.
Relevant answer
Answer
There are some projects going on. For instance, there are the NIH common data elements for epilepsy that were proposed a year or two ago. This is simply supposed to serve as a common core of tests that will allow for gathering data across studies.
There are also some larger collaborations. For example, in the US, we are about to start a multisite study looking at the affects of laser ablation that will be sponsored by Visualase, Inc.
I would also advocate for making sure that we don't get too fixed on a set battery of tests. A lot of my work is looking at functions that are not routinely assessed in epilepsy surgery settings, but are proving to be very detrimental when they occur. I think we are likely still missing a number of cognitive areas that could be important to cover and can learn a lot from examining the cognitive neuroscience literature on what targeted brain regions are supposed to be doing.
Daniel Drane, Ph.D.
Assistant Professor of Neurology and Pediatrics
Emory University School of Medicine
Affiliate Associate Professor of Neurology
University of Washington School of Medicine
Question
3 answers
Intractable epilepsy in children
Relevant answer
Answer
If epilepsy is not controlled with three anti epileptic drugs.
Question
16 answers
What are the chances of epilepsy being cured, and if not upto what context we can say that it cannot be transferrable to the future generation?
Relevant answer
Answer
Epilepsy is usually manifested by seizures but akinetic periods of unconsciousness are also common. The mechanism was thought to be abnormal electrical discharges from an epileptic focus but recent studies in Mouse models of chronic seizures(chronic epilepsy) suggest a role for proteins and receptors involved in Sepsis and Inflammation viz High Mobility Group Box 1(HMGB1) protein released from Neurons and Glial Cells and its interaction with Toll Like Receptors which are key receptors of innate immunity( Incidentally the 2011 Nobel Prize for Medicine or Physiology were given to J Hoffmann B Beutler and R Steinman, the discoveres of these Toll like receptors and Dendritic Cells which are key players of our Innate and adaptive immunity. HMGB1 can come from our Macrophage cells too and play a definitive role in the propagation and fatal termination of Sepsis induced by bacteria, viruses, fungi and traumatic injuries. The HMGB1- TLR4 signaling in which the brain tissue receptors called NMDA(N-methyl D aspartate) receptors are also involved may initiate and perpetuate seizures in Epilepsy and agents which help to antagonize these proteins or receptors can retard seizures or even prevent their recurrence. I don't know whethe the oil from Madagascar in question has any such actions but is worthwhile checking by scientific experimental proof.
Convulsions seen in otherwise healthy volunteers following the infusion of a CD28 agonist antibody a few years back in Northwick Park Hospital London was from ' Cytokine Storm' and was possibly from a similar mechanism of induced inflammation of the normal brain tissue. ( Ref: NEJM 2006 and Nature Medicine 28th March 2010)
Professor K. A. Salim.
Question
8 answers
C121W mutation is relate to GEFS+. It's screening can be done by amplifying exon 3 of SCN1B gene.
Exon 3 of SCN1B gene is amplified by following primers:
5'-CCTTCCCCTCCCTGGCTAC-3' (Forward)
5'-AAGAGCAGGCGGTAGACGCG-3' (Reverse)
with 30 cycles and an annealing temperature of 59C (degree celcius). The concentration of various other components of the PCR master mix has not been mentioned anywhere.
In such a case, how should the master mix be prepared?
Relevant answer
Answer
Hi.Dear Shrestha
There are several kinds of ready to use Master Mix that you can use them readily such as Amplicon Master Mix which is also benefited from Hot-start PCR
in situation that you cannot optimize PCR reaction simply, in my opinion, you can use these master mixes. However, some of them are no cheap.
before using, please pay attention to the concentration of master mix for example 2X or 5X. Due to the concentration the amount of master mix will be changed.
I always use 5X master mix because in a 25 micoliter reaction I need 5 microliter of master mix where all PCR materials already have been provided.
Good Luck
Question
5 answers
I had one fifty-year-old male patient who had h/o low grade fever and three episodes of vomiting for three days. He had h/o GTCS two hours before arriving in ED. The patient was hypotensive but responding to fluid therapy, he had jerky movements and dysarthria but concious oriented. CT brain was normal. Blood investigation shows 45000 platelets and P.vivax schizontes, otherwise normal all reports.
Relevant answer
Answer
Hypovolemia and hypoperfusion could be a potential etiology for the GTCS, it it was a GTCS.
Question
1 answer
I want to use AED CBZ for my experiments and treat cells with this drug. I want to know what is the best solvent for it. I face some problems determining the right conc. of the drug.
Relevant answer
dichloromethane works good, from your two solvents I think DMSO will be better.
Question
8 answers
Lesionectomy can influence positively disturbed neurological functions by influencing neural neworks.
Relevant answer
Answer
Let me point you to an article recently published by the neurosurgery department of Geneva University Hospitals, Switzerland, that focused on neuropsychological outcomes following extra-temporal lobe resections. An interesting finding is that neuropsychological improvement did not depend strictly on seizure freedom.
El Hassani Y, Fournet M, Momjian S, Pollo C, Seeck M, Pegna A, Schaller K.
Neuropsychological outcome after extra-temporal epilepsy surgery.
Acta Neurochir (Wien). 2012 Aug;154(8):1337-42.
Of note, neuropsychological improvement following surgery in children with severe epilepsy of early onset is not systematic and depends on multiple factors. Cf. Roulet-Perez E, Davidoff V, Mayor-Dubois C, Maeder-Ingvar M, Seeck M, Ruffieux C, Villemure JG, Deonna T. Impact of severe epilepsy on development: recovery potential after successful early epilepsy surgery. Epilepsia. 2010 Jul;51(7):1266-76. http://dx.doi.org/10.1111/j.1528-1167.2009.02487.x.
Question
1 answer
They are oncologic preventive drugs, but are they also an antiepileptic/antipileptogenic drug?
Relevant answer
Answer
mTOR inhibitors are already used in a variety of clinical settings including as immunosuppressants, anticancer agents and antiproliferative agents in drug-eluting coronary artery stents. They also represent candidate therapies directed to the underlying molecular pathology in tuberous sclerosis and LAM. Phase I/II clinical trials of the mTORC1 inhibitor rapamycin have demonstrated reduction in size of tuberous-sclerosis- and LAM-associated renal tumours (angiomyolipomas) and some evidence for reversible improvement in lung function in patients with LAM. A case series of tuberous-sclerosis-associated brain tumours were also reported to shrink during rapamycin therapy. An important, although variable, feature of the tuberous sclerosis phenotype is learning difficulty. Recent studies in mouse models carrying heterozygous Tsc2 mutations demonstrated improvement in memory and learning deficits following treatment with rapamycin. These promising pre-clinical and early human trials are being followed by larger-scale randomized control trials of mTOR inhibitors for treatment of renal, lung and brain manifestations of TSC1- and TSC2-associated disease.
Question
1 answer
How often does epilepsy cause co-morbidity with autism ?
Relevant answer
Answer
In Western countries the latest estimate that I know is 17% of children who have autism develop epilepsy. I woudn't know why this would be different in the Middle-East.
Bertrand a.o. 2001; Fombonne 2002.
Question
1 answer
I am trying to develop a EMG (ElectroMyoGrphy) signals for my research - Have anybody an idea how I should emulate muscle contractions during seizure how often they occur? I have our own surface EMG wireless sensor but what I am looking for is a kind of recommendation on how a real seizure looks like (in terms of EMG signals). Now I can only guess.
Relevant answer
Answer
Take a look at the paper by Beniczky, Conradson et al. In Epilepsia (epub before print)
Question
9 answers
Solubility of drugs, EC50 determination, etc? What parameters or specifications should I consider, while working with signalling mechanisms involving AEDs?
Relevant answer
Answer
So one of the issues is a difference between ethanol and buffer soluble drugs. Often EtOH soluble drugs will fall out of solution when placed into the buffer or medium in the cell culture dish. While you haven't mentioned experimental design, I will assume you are doing these experiments without serum in the medium. If you are, then you need to take into account that the albumin may bind your drug of interest, thereby lowering the true free concentration.
Either way, just remember if you are comparing the impact of these two drugs, make sure EtOH is added to both groups to make the comparison valid.
Good luck with your experiments.
Question
2 answers
Could anyone suggest literature or provide information on frequency of spikes during an epileptic discharge. To be more specific, if one has only neuronal spikes recorded from few hundreds of neurons, how can one determine whether the network behaved epileptic-like from those spiking activity? What are the parameters or measures (in terms of spike analysis) are most important to determine the epileptic behavior?
Relevant answer
Answer
I don't think somebody has spikes recorded from a few hundreds of neurons in a time (I'm not sure about the state of the art number though), for sure nobody has this data from human epileptic seizure. The epileptic behavior in humans can be seen in extracellular fields generated by neural population, measured by EEG, ECoG, deep electrodes. The relationship between those signals to actual spiking activity is a big question in neuroscience.
How and when we have to tell epilepsy patients or their relatives about the risk of Sudep?
Question
6 answers
Debates about truth-telling on the prognosis, or even on the probability of a sudden death related to the main diagnosis (epilepsy) are old and controversial. Risk factors for SUDEP have been formulated and strategies to confront them have been put in place; however medical (pharmacological) compliance seems by large the most important protective factor. In our opinion, disclosing the risk of a sudden death to the family of a child suffering from epilepsy is a necessary act; timing and ways of disclosure are details that need to be refined case-by-case, in a situation where a general consensus or guidelines are lacking. A step-by-step approach and gradual informing are helpful and psychologically acceptable from the parents or other relatives.
Relevant answer
Answer
Thank you Sallieann! May I know the mean social and education level of the interviewed people?
Question
10 answers
Frequency, spread, morphology, other findings, all of them?
Relevant answer
Answer
The very occurrence of PLEDs (periodic lateralized epileptiform discharges) especially in Frontal region is suggestive of an epileptic state.
However, epilepsy is a clinical diagnosis; hence, clinical history is important in labeling the EEG findings as epileptogenic, otherwise in absence of clinical history of epileptic attacks, epileptiform discharges is a better term in my opinion.
Question
4 answers
Can anyone with epilepsy be advised to go on a ketogenic diet? Or is there any particular type of epilepsy on which this diet best works?
Relevant answer
Answer
Yes, all refractory epilepsy in infancy and childhood, specially Infantile spasms well respond to KD. There is special formula KETOCAL (Nutricia) 3:1, 4:1, for that purpose.
Question
2 answers
Most of the literature is about adults
Relevant answer
Answer
Thank you.
Question
2 answers
A genome-wide screen of a large GEFS+ family demonstrated linkage to a single region on chromosome 19q13.1, and subsequently identified a mutation (c.387C>G) of the voltage-gated sodium channel 1 subunit gene (SCN1B). The mutation changes a conserved cysteine residue (C121W) disrupting a putative disulfide bridge, which maintains an extracellular immunoglobulin-like fold.
Relevant answer
Answer
I'm a little confused, because your description is essentially identical to the original report by Robin Wallace and colleagues (http://www.ncbi.nlm.nih.gov/pubmed/9697698), who mapped the GEFS+ genetic defect to exactly the chromosomal boundaries you mention, which is unlikely in two different kindreds... I guess, I'm not clear on what *you* specifically did in your laboratory as opposed to what *others* did. This is critical if I want to address you question properly...
Assuming that you did all that you describe personally, here's what I understand: you have a GEFS+ kindred in which you established linkage to 19q13.1. Based on this finding, you then screened the subjects' SCN1B gene and you found c.387C>G, which is predicted to give rise to the famous p.Cys121Try exchange.
Given that you did the linkage analysis, and it pointed you to the SCN1B gene, odds are that you indeed identified the correct genetic alteration. There are several lines of evidence that confirm the functional importance of this residue and you can readily search PubMed for these reports. In terms of penetrance: skimming through Robin's report, if I'm not mistaking, she also had two asymptomatic subjects who were positive for the c.387C>G exchange (Fig. 2, Subjects #35 and 105). So, it seems, penetrance is not 100%.
In terms of therapy: I know from personal communication that the outcome in related but more severe phenotypes (Dravet syndrome) can be improved with early therapy (cannot say more, sorry).
Question
6 answers
Do different subregions of the hippocampus (EC, DG, CA1, CA3) have different roles in the induction and maintenance of temporal lobe epilepsy?
Relevant answer
Answer
There is no real answer to your question. All we know for sure from patients is that EC and hippo can be involved in seizure genesis in TLE. If you remove these regions, you can cure some patients.
To show causality between these subregions and epilepsy, one would need to specifically repair (or prevent degradation) of one or several subfields and demonstrate that epilepsy does not appear or evolve. So far, no one has been able to do that.
I have been focusing for 15 years onto CA1, and I am pretty confident ... about nothing!
Again, 50 years of research on patients, demonstrate that TLE involves networks of networks; hence other structures are also likely involved like perirhinal, amygdala, septum, locus coeruleus etc.
We can carry on forever describing circuit reorganization, but I am not sure it will tell us something valuable. It could be physiological homeostasis.
Question
11 answers
What is the role of synaptic plasticity in epilepsy?
Relevant answer
Answer
This is an interesting article and citations to it provide more recent insight into this interesting field:
Question
25 answers
A tool for automatic critical area detection? A tool for reliable autotomatic EEG artifact rejection (with minimal information loss)? A tool for automatic critical events detection? Or what else? Thank you very much for your kind attention.
Relevant answer
Answer
Dear Dr. Mammone,
after everybody has mentioned seizures, epilepsy, interictal epileptiform changes, I would like to mention another important EEG element: Background activity and background reactivity to exteroceptive stimulation and changes of background activity in arousals. EEG background activity has been underestimated for years, although it holds great promises especially for the diagnosis of encephalopathy. Loss of background reactivity to noxious stimulation was shown to have a high predictive value for poor outcome in patients with hypoxic-ischemic encephalopathy after cardiac arrest and resuscitation (Rossetti et al. Neurology 2009, Rossetti et al. Critical Care 2010, Rossetti et al. Annals of Neurology 2011...). However, continuous tracing and quantification of frequency of background activity and quantification or even semi quantification of background reactivity would be of great use for monitoring critically ill patients with different kinds and stages of encephalopathy.
Best regards and thank you for posting this interesting topic
R.C. Sutter
Question
4 answers
There are differences in duration and severity of polymorphic delta slowing depending on the type of syndrome or crisis? If a dog (or a man) experienced a long lasting seizure (Status epilepticus) or different number of clusters, or daily repeated crises that lead to background slowing the neuronal alteration can be demonstrated even with low field MRI (0.2 tesla)?
Relevant answer
Answer
The EEG might be of value to reflect the presence of pathology but the findings are not going to be specific to the type of the pathology.
Question
6 answers
I've done several using Curry (inverse problem) with good results on grid data, but I don't trust the spherical model on these data. Also results with grid and depth data or grid plus scalp are poor. Anyone have a better model or experience with application?
Relevant answer
Answer
Hi Daniel? Hows it going? They have used Curry here for about 5 years or so. I know what you're talking about. I know they have a way to manipulate it somehow to account for that , because it does throw off data. I agree it is very good for just grid data. We do depths rarely here, but have done many grids. Often the scalp along with is less useful, and they tend to use the localization mostly for the subdural grid and strips alone. I have had one case with extensive grid and depths, but I do not remember how the model affected the data.
Question
9 answers
I'm curious if there is any consensus in the field regarding where research should be focused. Epilepsy is a broad category of diseases. Is there one that is closer to being "solved" mechanistically, and thus closer to bringing new treatments/prevention strategies to the clinic? Thank you for any thoughts your can contribute!
Relevant answer
Answer
I think that dravet syndrome is the prototype.
We know the natural course of the syndrome, the genetic background, and we can use propertly aed in these patients.
Maybe in 2-3 years we can use genetic therapy in patients with dravet syndrome and scn1a truncating mutations in order to minimaze the effect of mutation.
Question
2 answers
I am planning a prospective study in the use of ketogenic diet in refractory epilepsy. I plan to look at effect on development milestones, behaviour and quality of life in children. Unfourtunately all tools to measure above need payment. I would be glad if anyone can tell me a way to get these tools ( i.e. deleopment profile, Child behavoir check list) for free or for discout
Relevant answer
Answer
Thanks for your suggestions
Question
19 answers
Truncal myoclunus one form of spinal myoclunus
Relevant answer
Answer
Dear gabriela. You can try high doses of levetiracetam. Recently, some authors reported good results using lacosamide.
Question
2 answers
Ideally the software would adjust the PET signal by tissue type and provide some normative values from healthy individuals.
Relevant answer
Answer
Just an add-on software from the previous answer could be the Analyze by the Biomedical Imaging Resource (BIR) at Mayo Clinic.
The only disadvantage is that it accepts images where the format has to be in Analize (.img and the respective .hdr).
Plus you have to create an object map of the brain for GM and WM in order to get concentration values.
Question
14 answers
Status epilepticus is a severe neurologic emergency. In 10-40% of status epilepticus patients, seizure activity cannot be controlled with antiepileptic drugs and mortality in this context is ~40%. The definition of treatment refractory status epilepticus as a state where first- and second-line antiepileptic drugs fail has been questioned (Bleck TP. Curr Opin Crit Care 2005). Many opinion leaders require failure of two antiepileptic drugs before deeming status epilepticus "refractory", but this may produce delays in treatment escalation and in using definitive therapies. In the veterans affair trial, the likelihood that a second conventional agent would succeed after the first one had failed was unacceptably small (Treiman DM, et al. N Engl J Med. 1998). Therefore it has been proposed that failure of any one of the first administered regimens should constitute treatment refractory status epilepticus (Bleck TP. Curr Opin Crit Care 2005). However, this ongoing debate and these conflicting definitions are critical as they may hamper future studies in this field. Therefore, I would like to open the discussion and invite you to reveal your individual opinion.
Relevant answer
Answer
Thank you all - especially Raoul - for the exciting questions and discussion. Hoping that my answer is not too late, I will add some lines. Refractory status epilepticus (RSE) and refractory epilepsy - in my opinion - are rather worthless terms. Epileptologists prefer to speak about best treatment of epilepsies and the treatment of all variants of status epiletipcus (SE), not only to mention epileptic seizures control.
The incidence of grand-mal-status ranges from 18 – 28/100 000 inhabitants/year. I agree with Francois: The US-statistic number of mortality (40 %) is probably a bit too high. In Europe “mortality” of SE ranges from 3 (!) -33 % (Holtkamp et al. 2003; Meierkord et al. 2010). However, we prefer the term "lethality" to discribe the fatality of SE regarding clinical statistics and no definite numbers concerning the prevalence of SE in a certain European population. I think this could help to avoid the term “refractory”:
Important for any treatment of SE is the time factor, not wasting the time (I agree with Raoul and Anthony), not beginning with thinking over some known and sometimes unexplained fatal results - regardless of any interesting pospective or restrospective discussion - but to describe the very beginning of SE (convulsive or non-convulsive) and Video-EEG-Monitoring of each single epileptic seizure (focal, partial or generalized). That ist not new, but always important, I suppose.
Doubtless there is a rare “malignant variant” of SE (Holtkamp et al. 2005). In such subtle SE i.v. anaesthesia is required. On the other hand many types of generalized and some types of nonconvulsive SE cause little permanent neurologic sequelae (Kaplan, 2000). Anaesthesia is not required in the most cases.
SE as result of intoxication, encephalitis, brain tumor, stroke - or the beginning with early focal postraumatic fits - is not very difficult to treat (with benzodiazepine and phenytoine), if there is not (yet) a big progress of brain edema. The lethality, due mainly to the causing illness and comorbidity is 20 % (higher in the elderly, especially in some cases of nonconvulsive SE). RSE is not the leading cause of death. In this point I agree with Francois, too.
According to literature and our experience SE in chonical epilepsies has an overall lethality of only 4 % !
In most cases of noncompliance, drug - or alcohol and sleep withdrawal and in all cases of status pseudo-epilepticus we have not to use the questionable term “refractory”. Why in the rest of it? What is the sense and purpose? Even when the end will be fatal in 3 - 33 % of severe SE, who will think of RSE, when seizures, epilepsies and status begin?
Kaplan PW. No, some types of nonconvulsive status epilepticus
cause little permanent neurologic sequelae (or:
‘‘the cure may be worse than the disease’’). Clin Neurophysiol
2000; 30: 377–382.
Holtkamp M, Masuhr F, Harms L, Einhaupl KM, Meierkord
H, Buchheim K. The management of refractory
generalised convulsive and complex partial status epilepticus
in three European countries: a survey among epileptologists
and critical care neurologists. J Neurol
Neurosurg Psychiatry 2003; 74: 1095–1099.
Holtkamp M, Othman J, Buchheim K, Masuhr F, Schielke
E, Meierkord H. A ‘‘malignant’’ variant of status
epilepticus. Arch Neurol 2005; 62: 1428–1431.
Meierkord H, Boon P, Engelsen, B, K. Gocke,
S. Shorvonf, S Tinuper P, Holtkamp M:
EFNS guideline on the management
of status epilepticus in adults. Eur J Neurol 17(2010) 348-355.
Question
2 answers
We are conducting a study on a relationship between Mg and epilepsy. Had anyone registered cases with Mg deficit and epilepsy?
Relevant answer
Answer
I have seen 4 - 5 cases of epilepsy due to hypomagnesemia. all of them were responded to magnesium.
Question
4 answers
Seizure is thought to be caused by increased extracellular glutamate. Do we have a final answer to what causes this neuroexitotoxity?
Relevant answer
Answer
Would recommend starting here: http://www.ncbi.nlm.nih.gov/pubmed/23298414
Question
2 answers
In the past there has been research indicating REM sleep activity may be inversely related to epileptic activity. I am interested in an updated exploration of the relationship between REM sleep, schizophrenic hallucinations and epileptic activity, in terms of neuroanatomy and neurophysiology (including related neuromodulators).
Relevant answer
Answer
We have published a few years ago a paper on Clinical Neurophysiology ( Clin Neurophysiol 2005; 116: 1520-1532) where we have analyzed the relationship between sleep state and ictal seizures in neonates. We have observed a predominance of seizures in REM sleep in this population and we have hypothesized that in the developing brain the expression of ictal activity may have an age dependent mechanism.
Question
1 answer
Otherwise normal SNP array.
Relevant answer
Answer
Hi,
Is this copy number neutral LOH or is it LOH associated with a loss Xq material?
In any case, in combination with skewed inactivation you can have a good lead to find mutations.
Are there similar cases in Decipher?
kind regards,
Karoly
Question
2 answers
In a recent paper by Leventer et al. (2010) it is noted that "further studies focussing on patients without seizures or with delayed onset seizures may provide insight into mechanisms protective of seizure generation in individuals otherwise predisposed to epilepsy by the presence of polymicrogyria." Is anyone aware of any advances in this research area?
Relevant answer
Answer
Prevention of epileptic seizures:
Perhaps somewhat surprisingly, there has been little research and little discussion within the literature about this potentially important aspect of epilepsy. In view of the fact that a significant proportion of epilepsy in childhood (up to 30–40%, possibly higher) has a genetic basis and given that for most of these patients genetic ‘modification’ will never be practicable or clinically justified (irrespective of the ethical dimension), it is unlikely that many of these epilepsies will ever be ‘preventable’. For over a decade it has been claimed that with a greater understanding of the molecular (pathophysiological and genetic) basis of epilepsy, including the relatively newly discovered channelopathies, there would be novel and targeted treatments for the epilepsies, including possible prevention.
Unfortunately and not unexpectedly, this has not—and is unlikely—to become a reality within even the next decade.
Obviously, where epilepsy is a common and disabling manifestation of a genetic and neurodegenerative disorder, such as the neuronal ceroid lipofuscinoses, genetic modification and/or therapy may be justifiable, although still not necessarily feasible.
Nevertheless there are many situations where the prevention of epilepsy or consequences of epilepsy will be both desirable and achievable; this is particularly applicable, but certainly not exclusive, to the developing world:
• Reduced incidence of high-risk, including teenage, pregnancies.
• Improved monitoring and ante-natal care of women with high-risk pregnancies.
• Improved perinatal care and prevention of any secondary brain damage particularly in extremely premature and very low birth-weight infants
• Identification of any neuroprotective therapies that may reduce or prevent any secondary brain damage following an initial primary insult in early life.
• Earlier recognition and appropriate treatment of meningitis, encephalitis and intracranial abscesses, particularly in infants and young children
• Improved uptake of childhood immunizations to reduce both the acute encephalopathies and the delayed complications associated with these illnesses (e.g. mumps and measles encephalitis and subacute sclerosing panencephalitis [SSPE]).
• Improved road safety and traffic-exclusion measures to reduce the incidence
of traumatic brain injury and post-traumatic epilepsy
• Improved resuscitation of children with acquired traumatic and non-traumatic
brain injury and the prevention of secondary brain damage
• Correct identification and aggressive management of the relatively rare but
important epileptic encephalopathies (e.g. West’s syndrome, Landau-Kleffner
syndrome, pyridoxine dependency) and non-convulsive status epilepticus,
that if unrecognized may potentially cause irreversible cognitive impairment
Avoidance of using inappropriate antiepileptic drugs, and specifically drugs
that may exacerbate seizures
• Avoidance of the use of multiple antiepileptic drugs and in high doses that
may have an adverse effect on concentration and short-term memory that,
even if transient, may still irreversibly reduce educational potential (e.g. poor
examination results)
• Early rather than late surgery for medically intractable epilepsy, particularly
in mesial temporal lobe epilepsy where it may prevent irreversible
psychosocial and cognitive (memory) impairment
• Improved pre-, intra-, and post-operative neurosurgical access (availability)
and care for children requiring a surgical treatment for their epilepsy
• Identification of the child’s (and the family’s, including siblings’)
understanding and perceptions of epilepsy to prevent any additional
psychopathology within the family
• Improved awareness, knowledge and understanding of epilepsy—what it is
and what it is not—amongst all health-care and education professionals and
the public to reduce, if not eliminate, the stigmatization of and not infrequent
prejudice against all people with epilepsy
Question
10 answers
If mothers smoke and subsequently go on to develop lung cancer, their children are more at risk of schizophrenia and other psychiatric disorders?
Relevant answer
It could mean so although parental cancer in general does not increase the risk of psychiatric disorders, As regards tobacco use conflicting findings are at hand:
Zammit S, Allebeck P, Dalman C, Lundberg I, Hemmingsson T, Lewis G (December 2003). "Investigating the association between cigarette smoking and schizophrenia in a cohort study". Am J Psychiatry 160 (12): 2216–21. doi:10.1176/appi.ajp.160.12.2216. PMID 14638593.
Question
19 answers
My work involves transportation of biological samples from the hospital to the lab. I was wondering about the best liquid nitrogen container to do that, my samples are small so a 1-2 L containers are enough for me.
Relevant answer
Answer
Dear Narumi, you hit the nail on the head…
knowing my post here to be a little bit late, but nevertheless: unfortunately this thread contains some inaccuracies which have to be credited to our life as “lab-workers”…
Dry Ice filled boxes MUST NOT be closed tightly unless you would like to create a <bomb> with <biological impact(= the cooled specimens)>. Dry ice evaporates permanently to a reasonable amount and therefore is capable to blast the wrapping box easily.
@ Nadine: came up with the LN2-dewar-matter which might be a good solution especially for storage of LN2 in the Lab. The problem for you, dear RANA, is to overcome and follow legal regulations (at least in the European Community – and I guess “Ireland” is in the EC), i. e. ADR-regulations (transport of hazardous material on roads: “Accord européen relatif autransport international des marchandises Dangereuses par Route”, cf.: http://en.wikipedia.org/wiki/ADR_(treaty) ) as you told us of nearly 1 hr by car from Hospital to your Lab. If I (in Salzburg or Austria or Germany) get caught in a police action on the road carrying with me a filled liquid nitrogen dewar (perhaps additionally NOT secured properly) I think I would not be allowed to drive the car further (independing of the fact I am transporting valid medical tissue specimens for diagnosis or not), and would face a police charge…
So the proposal of Narumi seems (in my opinion/experience) to be the best way to overcome the issue transport as well as of ADR regulations too (since the <disposable DryShipper> is also IATA = flights approved certified ).
@ Dear Rana, you haven’t specified in more detail which purpose the frozen specimens after coming to the lab will serve: is it e.g. cryosectioning (muscle, skin, or tissue in general etc.) for histology / (I)HC or mainly storing for e.g. DNA-RNA testing. Some posters in other threads on ResearchGate mentioned that – at least tissue (when freezing) for further use in histology and histochemistry should be “snap frozen” by use of LN2-precooled isopentane (2-methylbutane) for several reasons (dipping and dropping tissues into almost viscous cooled isopentane gives the most increased cooling rate without “Leidenfrost’s phenomenon”). After rapid freezing the frozen specimens CAN be stored in Liquid nitrogen. Long-time storage usually is done in a ultra-low-temperature freezer achieving at least – 80 degr.C (this T to be a so called “recrystallization”-point for tissues, where tissues thawed beyond that temperature will be destroyed by big ice crystal formation). Remember: Temp. of LN2 = -196 degr.C, Dry Ice = - 76 degr.C, so called CryoCans (usually with fluorinated hydrocarbons) will allow freezing only at – 40 to – 45 degr.C, as measured at the inverted can’s outlet nozzle, too high the temperature for a really “ultrastructural” preservation of tissue morphology, so this only usable as an exceptional method.
Best Regards and wishes
Question
10 answers
I would like to ask your valuable suggestion on which seizure analysis software I can use for analysing different parameters. I have already recorded EEG files for several days. This I have done by EEG telemetry method, and for the same I used the software provided by the company who provided us the electrode transmitters. But I find the software limited for analysis purpose. My target is to separate seizures and analyze different parameters like frequency distribution, inter-spike intervals, number of spikes. I am seeking any good software that I can analyze seizures and would achieve my purpose. I would be grateful to have your suggestions in this case.
Thank you,
Relevant answer
Answer
EpiScan is a seizure detection software developed by the Austrian Institute of Technology. The detection performance of EpiScan will be much higher than Persyst, a publication including a large prospective study (228 patients) will be published soon. The software will be available from this side: www.eeg-vienna.com
Question
5 answers
I am interested in the accuracy of an MRI conducted on a seven month old infant. There was some evidence of mild cortical dysplasia, but the epilepsy is now well-controlled with Keppra and there are no EEG abnormalities. Is there any evidence for changes in diagnosis when MRIs are repeated at a later age, especially taking into account what we now know about neural plasticity? Any information on neuronal migration disorders would be appreciated. As research area still in its relative infancy, it is difficult to find appropriate information.
Relevant answer
Answer
Thanks Simone, I wish I could make it your lecture - if you are in Sydney any time soon I will definitely come along. I have been following some of the great work you guys are doing in Melbourne on cortical malformations and epilepsy, although I had no idea it was so comprehensive. Thanks for the info.
Question
44 answers
I am a RMN by profession and personally am interested in this subject as my baby son developed epilepsy 8 days after having mmr vaccination. He was perfectly healthy before this for 13 months.
Relevant answer
Answer
The chance that he got it from MMR are slim to none. There are lots of reasons for epilepsy; my son's epilepsy is the result of a mitochondrial disorder. He was born "perfectly healthy" but obviously there was a genetic component that led to it.
As someone who went through an infant diagnosed with epilepsy, I know it's hurting you a lot. I, too, went nuts casting around for a reason I could pin his condition on. But knowing really didn't make it any easier. And sometimes you never find a reason; brain science still has a long, long way to go. I wish you luck, and while you search for a reason, remember that loving him and just being "mom" is the single best thing you can do.
Question
2 answers
Non
Relevant answer
Answer
is it diet (Ketogenic) you mean?
Question
1 answer
At what point in neurogenesis in the dorsal telencephalon is the neurotransmitter (glutamatergic) fate decided? Which molecules are involved apart from neurogenin? Also, are antibodies available for immunohistochemistry of Ngn1?
Relevant answer
Answer
Presence (expression) of GAD (the GABA-synthetic enzyme) is a key criterion for determining that the neuron will become a GABA neuron rather than a glutamate neuron. You can see in the attached screenshot several sources for Ngn1 antibodies. I've had good experiences with Abcam antibodies & theirs is listed as "improved", for what it's worth. Good luck!
Question
2 answers
In order to make a comprehensive review of this matter.
Relevant answer
Answer
You can read these articles:
1. Perucca P, Gilliam FG. Adverse effects of antiepileptic drugs. Lancet Neurol. 2012 Sep;11(9):792-802
2. Oh-Young Kwon,Adverse Effects of Antiepileptic DrugsJ Korean Med Assoc. 2005 Jun;48(6):571-578. Korean.
3. Rafael Toledano , Antonio Gil-Nagel. Adverse Effects of Antiepileptic Drugs.Semin Neurol 2008; 28(3): 317-327
Question
21 answers
I do low-magnesium seizure experiments on 400 um cortical slices obtained from mouse brain. I have seen many people do low-magnesium seizure experiments on hippocampal slices obtained from rat. Has anybody done low-Mg seizure experiments on hippocampal slices obtained from mouse? What are the probable difficulties? Are these difficulties exclusively related to the small size of the mouse brain compared to the rats one?
Relevant answer
Answer
I have been creating brain slices from both rats and mice for many many years. In addition, I have created slices from avian brain and human brain. Overall, it is just as easy to create slices from mouse brain. The only down side is that the slices are smaller from mice and so the experimenter has to have "good hands" and practice with the smaller brain. There are several considerations. One important aspect to all this is what type of instrument is used for slicing. We use both the McIlwain slicer and a vibratome. Both have advantages and disadvantages. In addition, the region (s) of interest will make a difference. So if one is looking at the mouse hippocampus, then the area of the hippocampus is proportionately smaller than a rat's hippocampus. If one is working with just cortex, then it doesnt matter so much. Also, another consideration involves whether or not the animal is receiving some sort of stroke or trauma. This will have an effect on the slice, which might make smaller brains more difficult to work with. However, in this case, I would recommend using the vibratome and slicing the entire brain.
Question
1 answer
TP53 seems to have vital roles in a wide range of activities in a cell. What sort of influence might it have on seizure initiation, progression or maybe recurrence of seizures? Are there any attractive hypotheses that people are working on regarding the role of TP53 in seizure? Can you suggest any important paper on this topic?
Relevant answer
Answer
The Mdm2-p53 complex is involved in seizure-induced damage and seizure recurrence. Check this recent paper in Brain: http://brain.oxfordjournals.org/content/136/2/577.long
and also this one, quite interesting: http://www.ncbi.nlm.nih.gov/pubmed/22612817
it is an area of interest, considering how many tools are available to manipulate p53. My advice is, if you like the subject, go into it....
Question
2 answers
All anti epileptic drugs reduce seizure or convulsion in epileptic patients. But their use to reduce convulsion in non epileptic patient are rare. but why?
Relevant answer
Answer
It is not surprising to hear that convulsions/seizures will also occur in non-epileptic patients. While the agencies like epilepsy society UK are classifying even syncopal episode as a seizure attack, it can be implied that many of us will have seizures at least once in a life time. Non-epileptic seizures are usually paroxysmal and has a myriad of causes. They may appear either due to physiological factors like hypoglycemia or due to psychological factors. I believe that the physician's approach to treat this condition would be by manipulating the cause and not by treating the symptom. Also, the research indicates that Non-epileptic seizures (NES) seems to be refractory to treatment with AEDs, which might be due to difference in pathophysiology of NES. Hence, AEDs will have limited application in treating NES.
Question
7 answers
Until today, EEG has been widely used in research into activity of the human brain. However, attempts to use EEG techniques in clinical diagnostic conditions have proved to be unsuccessful; as far as I'm aware, no specific patterns have been discovered relating to any specific nosology, including in particular epilepsy.
Relevant answer
Answer
Yes, you are totally right in this regard. It´s impossible to make any clinical diagnosis based merely on the EEG aspects of an individual patient. Indeed, I think that EEG is an auxiliary test, and as with other exams, it is absolutely necessary to include its features in a patient´s clinical setting to extract the its best performance.
On the other hand, it is practically impossible to manage some medical conditions without the use of an EEG. As a neurophysiological method, it has the peculiar property to identify normal and pathologic findings on brain electrical activity.
In this regard, EEG is undoubtedly the best assay to study and manage patients presenting with paroxysmal events, and it is central for the diagnosis of an epileptic disorder and its classification, and for the differential diagnosis of epilepsy with its imitators. It also provides valuable information for the clinical management of patients with epilepsy.
In another relevant set, individuals with acute decrease in level of consciousness, EEG is considered the gold standard test for the diagnosis of a potentially fatal disorder called nonconvulsive status epilepticus. It also assists diagnosing the severity and providing elements to establish a prognosis for comatose patients.
For neurological conditons like headache, dementia, movement disorders, autism, ADHD, and cognitive-behavioral disorders of children, the role of EEG remains rather limited. But still, it is the only one which can identify epileptiform discharges, often useful in neurological settings.
We cannot deny that Hans Berger´s original goal of distinguishing the different psychopathologies by their electrical expression was not achieved. However, 90 years after its invention, EEG still has a role in the management of patients with neuropsychiatric conditions, despite being just a drop in the Medicine´s ocean.
Best regards
Question
7 answers
I've been undertaking EEG recordings in the GAERS model of absence seizures which display typical spike-and-wave discharges @ ~6-9Hz interspike frequency. My recordings typically last 30-60 mins during which time there are on average 0.5-2 seizures per minute. The seizures vary in duration from ~1s to ~60s.
Since analyzing by hand (I've just been using Clampfit) is rather time consuming I'd like to run these data through some automated software to tell me (a) what time the seizures occur (b) how long the duration of the seizures and (c) what interspike frequency the spiking occurs at.
Can anyone provide any recommendations for software to perform this that is either free or commercially available?
Relevant answer
Answer
I can recommend two tools/algorithms which I both used very successfully in GAERS.
1.developped by the University of Ghent, contact person Prof. Boon (paul.boon@ugent.ac.be), see paper (Van Hese et al 2003) in attachment.
2. Another tool is commercially available from Radboud University (the Netherlands): The person involved in the development was "Jos Wittebrood" engineer at Donders Institute for Brain, Cognition and Behaviour, Dept. Cognitive Neuroscience (Radboud University, The Netherlands). The group is called Electronic Research Group, http://www.socsci.ru.nl/erg/index.html.
They have a paper on it: Westerhuis, M.F., Van Schaijk, W.J., & Van Luijtelaar, E.L.J.M. (1996). Automatic detection of spike-wave discharges in the cortical EEG of rats. In N.Beaujean (Ed.), Proceedings of Measuring Behavior 1996 (pp. 109-110).
Good luck!
Question
1 answer
After the FDA warning on Retigabine / Ezogabine I consider the attitude to go into a epileptic patient. This patient has presented for more than 20 years uncontrolled focal seizures with antiepileptic drugs. By introducing the Retigabine the patient was seizure-free. What attitude recommended in these patients? Regular checks?? Decrease dose? Antiepileptic drug change?
Relevant answer
Answer
In general, the attitude to adopt is to target the best balance "risk / benefit" individually. Patients, that were refractory for years, can not interrupt their treatment simply because they are seizure free.
If your patient has little or no side effects with retigabine, you should initially continue the treatment, but with more regular controls (mainly eyes exams).
If side effects become too severe, then you should reduce the dose of retigabine and gradually replace it with another treatment. This attitude could also be taken after about 3 years of treatment with retigabine, before appearance of most uncontrolled side effects, like depigmentation of the face, eyes, ...
Question
2 answers
Does anyone know a standard definition of cognitive impairment for refractory epilepsy?
Relevant answer
Answer
A battery of neuropsychological tests.
Question
1 answer
Does anyone has experience with pharamacological or other treatment for aggressive behavior in Dravet. I have a 4 year old girl with extreme disruptive episodes. We managed it with risperidone for a while with surprisingly positive outcome. But now the symptoms becomes worse and increasing risperidone dose doesn't help.
Relevant answer
Answer
I know the question is old but maybe someone can get the answer useful
From Luismi Aras MD and father of a 10 years old girl
 
Behavioral issues In Dravet  are part of the disease as a channelopathy  but  also can be caused or made worse by AEs
Risperidone  is the  most commonly used drug  not only  in aggressive also in other behavioral problems without risk of injury.
Some Dravet kids use as rescue behavior med in extreme agitation Ativan
In behavioral issues some of the new approaches are melatonin and fluoxetine maybe not in case of risk of damage
Melatonin widely used to improve the sleep pattern , can also improve behavior.
Fluoxetine  , especially after  Kalume`s papers  pointing to it as an option  to reduce the risk of sudden death.
Does the property of fatigue in synaptic transmission have an effect on Status Epilepticus?
Question
7 answers
If so, is the duration of fatigue modulated in these cases where the seizure takes longer time than usual? How does the modulation take place?
Relevant answer
This is not a simple question and you may benefit from this paper: The Neurobiology of Epilepsy
Question
15 answers
I am interested in extracellular field recording during seizure-like events (SLEs) simultaneously from neocortex and hippocampus of mice slices. Please note that I am not going to work on isolated hippocampal slices in this stage of my work.
Up to now I have been recording from coronal slices containing parts of hippocampus and cortex (please see attached image). I get interictal-like short events (length 0.5-2 sec), not long-lasting (~10 sec) ictal events, as is reported in many low-Mg hippocampal slices.
What should I do in order to get long-lasting ictal events? Should I use pharmacological modifiers on top of low-Mg (eg GABA blockers or NMDA/AMPA enhancers) or maybe another direction of slicing (like sagittal or transversal) may help me to preserve necessary parts of hippocampus which are responsible in producing those ictal events?
Relevant answer
Answer
There are many factors that can influence the production of SLEs
Age is critical: the older the animal the more difficult it is
Slice thickness, the thicker the better (you need the max of connectivity), with mice you can go up to 500-600 um in adult
Perfusion speed, the faster the better, up to 8-10 ml/min
Temperature, must be physiological, around 35 (can be tricky to maintain at high perfusion speed without degassing)
Slice orientation. If you cur sagittal, use slices from dorsal hippocampus (parasagittal may work, but I have not checked).
Increasing K, and bicu may work, but I have experienced that too epilepetogenic conditions kill epilepsy
If you want to benchmark your preparation, just use 0 Ca ACSF, which invariably triggers SLEs (check J. Jefferys' papers). That way you are sure that everything works (slice orientation, hippo-Cx propagation etc).
Question
1 answer
DNT and GG are the most frequent long-term epilepsy associated brain tumors. However, their definition by the WHO classification 2007 remain ambiguous with respect to tumor variants and atypical grading. As a consequence, the risk for malignant progression in GG and DNT is contradictory. I would like to discuss this issue with a broad audience and I'm interested to know which histopathology markers you are using to differentiate these tumors, i.e. CD34, MAP2, GFAP, p53, IDH1 or any other.
Relevant answer
Answer
This can be a difficult issue to address as occasionally, both lesions can be found together. I depend more on the H&E than any other stain. I reserve the diagnosis of DNET for those cases with clearly circumscribed mucinous lesions in the cortex or in the gray-white junction. Tumors with accumulations of ganglion cells or mixtures of dysplastic ganglion cells and neurocytic cells are "lumped" into gangliogliomas. There are, however, the rare lesions of DNET that are not circumscribed and are found in association with apparent infiltrating edges. these are found most commonly in children and in the temporal lobes. These tumors quite frequently have very good prognoses, but predicting which ones will do well is still problematic. (I use the NeuN stain to identify and better characterize dysmorphic ganglion cells.)
Question
2 answers
Gaussian white noise is used as the input for the neural mass model (NMM) in EEG/MEG simulation. In one of Dr. Fabrice Wendling's publications (Relevance of nonlinear lumped-parameter models in the analysis of depth-EEG epileptic signals. Biol Cybern 2000, 83, 367-378), there was one statement on the simulation of this input-"A Gaussian white noise was used as the model input. The mean and variance were adjusted ..." in order to obtain a rate of 30-150 pulses/s. My question is how do I compute this "pulse rate" given the mean and variance of the Gaussian white noise. For example, I usually use randn or normrnd to model the Gaussian white noise in MATLAB. So, what's the pulse rate for the noise "220+ 22.*randn(1, 1000)"?
Relevant answer
Dear Peng Li,
Just apply a 30 -150Hz bandpass filter to that white noise, such that its PDF keeps only this range of frequencies.
Best