Treatment Of Intractable Epilepsy In Children Research Articles

Intravenous immune globulin in the treatment of intractable childhood epilepsy

Many clinical and experimental data strongly support the role of immune mechanisms in the pathogenesis of childhood epilepsy. Following Pechadre's first observations with intramuscular immune globulin (IMIG), intravenous immune globulin (IVIG) has been employed in some forms of intractable childhood epilepsy (ICE), mainly in West syndrome (WS) and Lennox Gastaut syndrome (LGS), with good results. So far, 373 children suffering from ICE have been treated in 29 studies and 174 have responded favourably. Although these studies are heterogeneous and controls are lacking, most authors report similar responsiveness ranging from 30% to 50%. Several mechanisms have been suggested to account for the efficacy of IVIG in ICE including antiviral effect, substitutive therapy in patients with concomitant humoral immunodeficiency, idiotype-anti-idiotype interaction or a neuromodulant effect. To better define the real efficacy of IVIG in ICE in paediatric patients, a randomized, multicenter, double-blind clinical trial was started in 1993, including only patients suffering from WS and LGS. To date, only one double-blind trial had been carried out (with both adult and paediatric patients); it showed a clear trend in favour of IVIG treatment but lacked statistical significance, perhaps because of the small and heterogeneous sample. Controlled multicentre studies on well-defined populations are needed and patients with WS and LGS are probably the best candidates.

Advanced Treatment of Intractable Childhood Epilepsy

Objectives: Up to one third of epilepsy patients have an unsatisfactory treatment with antiepileptic drugs (AEDs), but advance in neuroimaging, neurophysiologic investigation and treatment modalities have substantially improved the approaches and understanding of intractable childhood epilepsy. Methods: Journal papers, reports, books and government publications on epilepsy treatment were collected and reviewed in chronological order. Results: There are approximately more than 15 newer AEDs developed since 1990, highlighted by the novel mechanism of action with minimal adverse effect, thus they have been frequently used for those who are unresponsive to conventional AEDs. Non-pharmacologic therapies including diet therapy, epilepsy surgery, and neuromodulatory treatment are also effective and should be considered early in the disease course. Diet therapy began to reemerge in mid 1990s, and studies with large data collection allowed to overcome major concerns; its side effects, difficult compliance and doubts on efficacy. And more liberal forms of the diet therapy were introduced to benefit adults and patients in developing counties, where strict supervision is unavailable. The surgical treatment has become increasingly more valuable and it is now accepted for the management of drug resistant focal epilepsy due to major advances in presurgical investigation methods, and surgical techniques. Conclusions: The timely assessment of children with drug-resistant epilepsy and active application of advanced treatment modalities were necessary to prevent the effect of uncontrolled seizures on cognitive and behavioral development.

Efficacy of the classic ketogenic and the modified Atkins diets in refractory childhood epilepsy.

We aimed to compare the efficacy, safety, and tolerability of a modified Atkins diet (MAD) with the classic ketogenic diet (KD) for the treatment of intractable childhood epilepsy. From March 2011 to March 2014, 104 patients aged 1-18 years who had refractory epilepsy were randomly assigned to each diet group (ClinicalTrials.gov, number NCT2100501). A seizure diary record was used to compare seizure frequencies with the baseline prediet seizure frequency at the third and sixth months after diet therapy initiation. Fifty-one patients were assigned to the KD and 53 patients to the MAD. The KD group had a lower mean percentage of baseline seizures compared with the MAD group at 3 months (38.6% for KD, 47.9% for MAD) and 6 months (33.8% for KD, 44.6% for MAD), but the differences were not statistically significant (95% confidence interval [CI] 24.1-50.8, p = 0.291 for 3 months; 95% CI 17.8-46.1, p = 0.255 for 6 months). Instead, for patients aged 1-2 years, seizure outcomes were consistently much more favorable in patients consuming the KD compared with those consuming the MAD. The rate of seizure freedom at 3 months after diet therapy initiation was significantly higher (53% for KD, 20% for MAD, p = 0.047) in these patients. The MAD had advantages with respect to better tolerability and fewer serious side effects. The MAD might be considered as the primary choice for the treatment of intractable epilepsy in children, but the classic KD is more suitable as the first line of diet therapy in patients <2 years of age.

Usefulness of liquid ketogenic milk for intractable childhood epilepsy

Summary Background & aims To evaluate the usefulness of a liquid ketogenic milk in the treatment of intractable childhood epilepsy. Methods We used liquid ketogenic milk, which is comprised of mainly olive oil and soybeans, and has a lipid to non-lipid ratio of 4:1. Prospective study evaluated outcomes in 28 children with intractable epilepsy who were supplemented with liquid ketogenic milk for at least three months during conventional ketogenic diet. The calories of the milk occupied over 50% of the total calories. Primary outcome measures included usefulness of the milk, tolerability, caretakers’ convenience and complications. Secondarily, seizure outcomes after diet therapy were evaluated. Results All patients obtained normal weight and height gain and natural increase of bone densitometry index according to increasing ages. There were no serious complications. It was well tolerated in most 85.7% (24/28) of the patients and especially, convenience of its preparation was reported in all caretakers. 57.1% (16/28) of the patients showed a ≥90% reduction in seizure frequency. Most of the patients (85.7%) wanted to continue to use liquid ketogenic milk. Conclusion We believe that the liquid ketogenic milk is useful formula to increase tolerability and widen application of the diet therapy in children with intractable epilepsy.

Prospective Study of the Modified Atkins Diet in Combination With a Ketogenic Liquid Supplement During the Initial Month

The modified Atkins diet is a high-fat, low-carbohydrate treatment for intractable childhood epilepsy. As data suggest that a stricter diet onset can be more effective, we added a ketogenic supplement to the modified Atkins diet during its initial month. Thirty children with intractable epilepsy were prospectively started on the modified Atkins diet in combination with a daily 400-calorie KetoCal shake. At 1 month, 24 (80%) children had >50% seizure reduction, of which 11 (37%) had >90% seizure reduction. There was no significant loss of efficacy during the second month after KetoCal was discontinued. The use of this ketogenic supplement increased daily fat intake and thus the ketogenic ratio (1.8:1 versus 1.0:1 in the modified Atkins diet alone, P = .0002), but did not change urinary or serum ketosis. The addition of a ketogenic supplement to the modified Atkins diet during its initial month appears to be beneficial.

Improvement of intractable childhood epilepsy following acute viral infection

In this study, we report 11 patients with intractable childhood epilepsy that improved following acute viral infection. The patients were 8 boys and 3 girls. Six of the 11 children were diagnosed as West syndrome (5 of the symptomatic type and 1 of the cryptogenic type). The remaining 5 children were myoclonic seizures. The patients became seizure free within 6 days following acute viral infections without an exchange or addition of antiepileptic drugs (AEDs). The types of acute viral infections were Exanthema subitum (Roseola infantum) in 5 patients, Rotavirus gastroenteritis in 2 patients, Measles infection in 2 patients, Herpetic stomatitis in 1 patient and Common cold in the remaining patient. Salaam seizures and/or tonic spasms disappeared within 6 days after the onset of viral infections, and hypsarrhythmia evolved to localized spikes on electroencephalography (EEG) in the patients with West syndrome. Epileptic seizures disappeared rapidly and EEG gradually normalized or improved in patients with myoclonic seizures. Four patients became seizure free for 5 years to 20 years. In 6 patients, seizures relapsed within 14 days to 1 month after the disappearance of seizures. One child remained seizure free for 12 months after viral infection. Common factors in 4 children who were continuously seizure free include (1) normal or almost normal findings of brain CT/MRI, (2) normal development prior to the onset of epileptic seizures, and (3) a short time interval between the onset of seizures and the acute viral infection. We propose several hypotheses including an immunological effect for the improvement of intractable childhood epilepsy following acute viral infection. Further study may provide important information concerning the mechanism of seizure control and the applicable to treatment for intractable childhood epilepsy.

Optimal clinical management of children receiving the ketogenic diet: Recommendations of the International Ketogenic Diet Study Group

The ketogenic diet (KD) is an established, effective nonpharmacologic treatment for intractable childhood epilepsy. The KD is provided differently throughout the world, with occasionally significant variations in its administration. There exists a need for more standardized protocols and management recommendations for clinical and research use. In December 2006, The Charlie Foundation commissioned a panel comprised of 26 pediatric epileptologists and dietitians from nine countries with particular expertise using the KD. This group was created in order to create a consensus statement regarding the clinical management of the KD. Subsequently endorsed by the Practice Committee of the Child Neurology Society, this resultant manuscript addresses issues such as patient selection, pre-KD counseling and evaluation, specific dietary therapy selection, implementation, supplementation, follow-up management, adverse event monitoring, and eventual KD discontinuation. This paper highlights recommendations based on best evidence, including areas of agreement and controversy, unanswered questions, and future research.

Commentary on “Optimal clinical management of children receiving the ketogenic diet: Recommendations of the international ketogenic diet study group”

The ketogenic diet (KD) is an established, effective nonpharmacologic treatment for intractable childhood epilepsy. The KD is provided differently throughout the world, with occasionally significant variations in its administration. There exists a need for more standardized protocols and management recommendations for clinical and research use. In December 2006, The Charlie Foundation commissioned a panel comprised of 26 pediatric epileptologists and dietitians from nine countries with particular expertise using the KD. This group was created in order to create a consensus statement regarding the clinical management of the KD. Subsequently endorsed by the Practice Committee of the Child Neurology Society, this resultant manuscript addresses issues such as patient selection, pre-KD counseling and evaluation, specific dietary therapy selection, implementation, supplementation, follow-up management, adverse event monitoring, and eventual KD discontinuation. This paper highlights recommendations based on best evidence, including areas of agreement and controversy, unanswered questions, and future research.

International consensus statement on clinical implementation of the ketogenic diet: Agreement, flexibility, and controversy

The ketogenic diet (KD) is an established, effective nonpharmacologic treatment for intractable childhood epilepsy. The KD is provided differently throughout the world, with occasionally significant variations in its administration. There exists a need for more standardized protocols and management recommendations for clinical and research use. In December 2006, the Charlie Foundation commissioned a panel comprised of 26 pediatric epileptologists and dietitians with particular expertise in using the KD. This group was convened to create a consensus statement regarding the clinical management of the KD; the consensus statement has also been endorsed by the Child Neurology Society. Members were asked to write sections based on clinical interests and the full document was subsequently reviewed and approved by the entire group. Recommendations were made regarding evaluation of children before starting the diet, specifically in regards to ideal patient selection, pre-KD counseling and testing, and choice of specific dietary therapy (ketogenic or less restrictive alternative diets). In addition, there was information provided regarding diet implementation (need for fasting and admission), supplementation, follow-up management (frequency of visits as well as diet and laboratory evaluations while receiving the diet), adverse event monitoring, and timing and method of eventual KD discontinuation. This group effort highlights recommendations based on best evidence, including areas of agreement and controversy, unanswered questions, and future research.

Advanced Treatment of Intractable Childhood Epilepsy

Twenty to thirty percent of children with epilepsy continue to have seizures despite anti-epileptic drugs (AEDs) treatment and are defined as medically intractable epilepsy. Intractable epilepsy frequently has developmental impact, causing permanent neurodevelopmental deficits in children. Recently developed neurodiagnostic studies and treatment modalities have substantially altered the management of patients with intractable epilepsy. The newly developed AEDs are frequently used for the treatment of patients unresponsive to conventional AEDs. Nonpharmacologic options for intractable epilepsy include dietary therapy such as ketogenic diet and modified Atkins diet, epilepsy surgery, and neuromodulatory treatments such as vagus nerve stimulation. Ketogenic diet is an effective and safe treatment for epilepsy in children; increasing use has led to modification of protocol for higher efficacy and better tolerability. When epilepsy is intractable to medical treatment, epilepsy surgery including surgical resection of epileptogenic area, or palliative surgery can be considered. Vagal Nerve Stimulation is recommended for patients who are not candidates for resective surgery. These nonpharmcologic treatments could result in resumption of developmental progress in patients with childhood intractable epilepsy.Active application of newly developed medical and surgical treatments could provide better outcome in seizure control and developmental progress in patients with intractable epilepsy.

Efficacy and Tolerability of the Ketogenic Diet According to Lipid:Nonlipid Ratios—Comparison of 3:1 with 4:1 Diet

The ketogenic diet (KD) has been considered a highly potent antiepileptic treatment for intractable childhood epilepsy. In this study, we compared the antiepileptic efficacy and diet tolerability of two different diets with lipid:nonlipid ratios of 3:1 and 4:1. Seventy-six patients with refractory childhood epilepsy were randomly placed into two groups and were started on KD diets with nonlipid:lipid ratios of either 3:1 or 4:1. Antiepileptic efficacy and diet tolerability were evaluated 3 months after initiating the diet. Patients showing seizure-free outcome with the 4:1 diet were changed to the 3:1 diet, and those without a seizure-free outcome on the 3:1 diet were changed to the 4:1 diet, for three more months, after which time their progress was monitored. (1) Antiepileptic efficacy was higher for the 4:1 than the 3:1 diet (p < 0.05). Twenty-two (55.0%) of 40 patients on the 4:1 diet and 11 (30.5%) of 36 patients on the 3:1 diet became seizure free. Seizure reduction of over 90% was observed in 2 (5.0%) patients on the 4:1 diet, and 2 (5.6%) on the 3:1 diet. (2) Dietary tolerability was better for the 3:1 than the 4:1 diet. Gastrointestinal symptoms were observed in 5 (13.9%) patients with the 3:1 diet and 14 (35.0%) patients with the 4:1 diet (p < 0.05). (3) For seizure-free patients who started on the 4:1 diet, antiepileptic efficacy was maintained after changing to the 3:1 diet, while 10 (83.3%) of 12 patients who were not seizure free with the 3:1 diet showed increased seizure reduction after changing to the 4:1 diet. (4) Complications from the KD and laboratory data were not significantly different between the two groups. The 4:1 KD showed greater antiepileptic efficacy than the 3:1 diet with higher seizure-free outcome. In most cases, seizure free outcome was maintained even after changing the ratio to 3:1. Dietary tolerability was better in the 3:1 diet than the 4:1 with less frequent gastrointestinal symptoms.

Pyridoxal phosphate is better than pyridoxine for controlling idiopathic intractable epilepsy

Aim: To study the difference between pyridoxine (PN) and its active form, pyridoxal phosphate, (PLP) in control of idiopathic intractable epilepsy in children. Methods: Among 574 children with active epilepsy,...

The ketogenic diet in intractable childhood epilepsy

The ketogenic diet is a high-fat, adequate protein, low carbohydrate diet that has been used for decades in the treatment of intractable childhood epilepsy. The mechanism of action of the diet remains unknown, but the diet has been proven an effective alternative epilepsy treatment in children that have been carefully selected, monitored, and followed. The diet requires a comprehensive medical team approach in concert with intensive parental involvement.

Evaluation of SPECT in the assessment and treatment of intractable childhood epilepsy.

The authors retrospectively examined the role of SPECT in 65 children undergoing video-EEG telemetry. SPECT was concordant in most children whose lesions were already localized by MRI and epilepsy syndrome and provided localizing data in more than half not localized by these modalities. Ictal SPECT provided no additional prognostic benefit in patients undergoing epilepsy surgery (n = 23) who have a localized MRI lesion. In patients without lesions, however, ictal SPECT provides useful additional localization that may be used as a guide to intracranial implantation.

Study on surgical treatment of intractable childhood epilepsy

We studied the clinical details of 14 children with intractable epilepsies, all of whom underwent epilepsy surgery before age 18 years. All 14 suffered catastrophic seizures, which were resistant to the full range of available medical treatments. The ages at operation ranged from 4 years 7 months to 17 years 2 months, with a mean of 9 years 11 months. In nine patients, the age at onset of epilepsy was less than 2 years. The seizure disorders were classified as temporal lobe epilepsy in two patients, extratemporal lobe epilepsy in 10, and symptomatic generalized epilepsy in two. Eight patients had a hemicorporeal deficit (hemiparesis or hemiplegia) preoperatively. All 14 patients showed localized magnetic resonance imaging (MRI), single photon emission computer tomography (SPECT) and/or positron emission tomography (PET) abnormalities, providing crucial information regarding the epileptic focus. As to the surgical outcomes, four patients became seizure-free and the other 10 showed significant improvement during a mean follow-up period of 2 years 5 months. As to etiology, cortical dysplasia was identified in seven patients. Epilepsy surgery should be considered for intractable childhood epilepsy based on individual clinical characteristics, including seizure status, cognitive development, and evidence indicating location of the seizure focus, rather than age.

Neuropathologic findings in cortical resections (including hemispherectomies) performed for the treatment of intractable childhood epilepsy.

Despite the use of hemispherectomy in the treatment of medically refractory seizures since the early 1950's, few studies published have documented neuropathologic findings in the resected specimens. This report describes the neuropathologic findings in 38 children who underwent either hemispherectomy or multilobar cortical resection as treatment for medically intractable epilepsy between 1986 and 1990. Examination of the resected specimens revealed a variety of abnormalities which fell into four broad categories. Malformations or hamartomatous lesions were the dominant finding in 15 patients, whereas encephalomalacic lesions were the most prominent abnormality in 16; chronic pathogen-free encephalitits (Rasmussen's encephalitis) was present in 3 and an additional 3 children had Sturge-Weber-Dimitri syndrome. There were no gross or microscopic abnormalities in 1 patient. This report provides the first comprehensive description of the pathologic findings in a series of children with refractory epilepsy of varying types treated by hemispherectomy-multilobar resection.

Treatment of Intractable Childhood Epilepsy with High‐Dose Valproate

Forty-six children with refractory epilepsy (12 with symptomatic generalized epilepsy, 14 with symptomatic partial epilepsy, and 20 with undetermined epilepsy) were treated by high-dose (serum level above 100 micrograms/ml) valproate (VPA) therapy. Monotherapy was used with 34 patients and two drugs with 12. Serum VPA concentrations ranged from 105.1 to 198.4 micrograms/ml. Assessment of initial response to treatment, after the serum level had reached the appropriate level, showed seizures to be completely controlled in 15 (32.6%) of 46 patients and improved in 12 (26.1%) (50% or more). Follow-up of more than 6 months after the time of initial response showed control of seizures in 14 (30.4%) and improvement in 11 (23.9%). The initial effect on EEG was the disappearance of epileptic discharges in 3 (6.5%) of 46 patients and marked improvement in 15 (32.6%). Follow-up revealed the disappearance of epileptic discharges in 7 (15.2%) and marked improvement in 9 patients (19.6%). High-dose VPA therapy was especially effective for West syndrome and for epilepsy with continuous spike-waves during slow-wave sleep. Control of atypical absences and myoclonic seizures was relatively good. Hypofibrinogenemia and thrombocytopenia were sometimes encountered but these side effects were reversible with reduction of dosage.

Medium‐chain Triglyceride Diet in the Treatment of Intractable Childhood Epilepsy

Developmental Medicine & Child NeurologyVolume 20, Issue 2 p. 249-250 Medium-chain Triglyceride Diet in the Treatment of Intractable Childhood Epilepsy Wulfred Berman M.D., Wulfred Berman M.D. Assistant Professor of Pediatrics, University of Maryland, Rosewood Center, Owings Mills, Maryland 21117Search for more papers by this author Wulfred Berman M.D., Wulfred Berman M.D. Assistant Professor of Pediatrics, University of Maryland, Rosewood Center, Owings Mills, Maryland 21117Search for more papers by this author First published: April 1978 https://doi.org/10.1111/j.1469-8749.1978.tb15211.xCitations: 14AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume20, Issue2April 1978Pages 249-250 RelatedInformation

Letter: Sodium valproate in the treatment of intractable childhood epilepsy.

Letter: Sodium valproate in the treatment of intractable childhood epilepsy.

Sodium valproate in the treatment of intractable childhood epilepsy.

Sodium valproate has been used, in combination with a variety of standard anticonvulsant drugs, to treat 24 children with intractable epilepsy. A reduction of fit frequency greater than 90 percent was obtained in six patients, and a reduction of over 50 per cent in another six, with an improvement in alertness and school performance in the majority of cases. Grand mal, myoclonic and petit mal epilepsy gave the best response, while infantile spasms responded least well. No serious side-effects were encountered.