Tuesday, April 17, 2012

Steroids & Epilepsy

The following compilation of documents was shared in a yahoohealthgroup for Rare Epilepsy Syndromes:

Pediatr Neurol. 2003 Mar;28(3):194-8.
Prednisone therapy in pediatric epilepsy.
Sinclair DB.


Comprehensive Epilepsy Program, University of Alberta, Edmonton, Alberta, Canada.


Steroids are often an effective treatment for the West's syndrome. There have been few reports of steroid use in children with epilepsy outside the first year of life. I report my experience with prednisone for the treatment of older children with intractable epilepsy. Twenty-eight children (17 boys, 11 girls) aged 18 months to 10 years with intractable epilepsy were studied. Prednisone 1 mg/kg/day for 12 weeks (6 weeks daily and 6 weeks alternate therapy) was prescribed in addition to their regular antiepileptic medications. The parents kept seizure diaries, and the patients were regularly assessed for seizure frequency and side effects. The follow-up period was for 1 to 5 years. Thirteen patients (46%) became seizure free on prednisone and another 18 (40%) had a significant decrease in seizure frequency. Five patients (19%) had no change in seizure frequency. The best outcomes were seen in the absence group in which six out of seven patients became seizure free and in the Lennox-Gastaut syndrome group in which seven out of 10 became seizure free. Side effects were uncommon and included weight gain in five patients and aggression in four patients. Prednisone therapy is a safe and effective adjunctive treatment for epilepsy. It should be considered as an alternative treatment for older children with intractable generalized epilepsy who have failed conventional antiepileptic therapy.

Epilepsia. 1990 Nov-Dec;31(6):768-77.

Landau-Kleffner syndrome: a pharmacologic study of five cases.

Service de Neurologie I, C.H.U. Strasbourg, France.


Five children with Landau-Kleffner syndrome (epilepsy, acquired aphasia, and continuous spike-wave discharges during sleep), were treated with antiepileptic drugs (AEDs), sleep-modifying drugs, and corticosteroids. The pharmacologic profiles differed from those observed in focal epilepsies, resembling instead those of certain generalized epilepsies, such as West or Lennox-Gastaut syndromes. Phenobarbital (PB), carbamazepine (CBZ), and phenytoin (PHT) were ineffective or worsened the EEG and neuropsychological symptoms, whereas valproate (VPA), ethosuximide (ESM), and benzodiazepines were partially or transiently efficacious. Dextroamphetamine produced a dramatic but transient improvement in waking and sleep EEG in one of two children; aphasia did not change. Corticosteroid treatment resulted in improved speech, suppression of seizures, and normalization of the EEG in three of three children. Our own experience and data from the literature suggest that corticosteroids should be given in high doses as soon as the diagnosis is firmly established and should be continued in maintenance dose for several months or years to avoid escape. Early diagnosis, before mutism or global deterioration develops, appears to be essential for effective therapy with minimal neuropsychological sequelae.

Dev Med Child Neurol. 1991 Mar;33(3):257-60.

Effect of early corticosteroid therapy for Landau-Kleffner syndrome.

Lerman P, Lerman-Sagie T, Kivity S.

Department of Pediatrics B, Beilinson Medical Centre, Petah Tikva, Israel.


Four children treated for seizures between 1980 and 1986 were diagnosed as having Landau-Kleffner syndrome (acquired aphasia with convulsive disorder), following the onset of aphasia. They received early and prolonged ACTH or corticosteroid therapy, with high initial doses. In all four cases the EEG promptly became normal, with subsequent long-lasting remission of the aphasia and improvement of seizure control. Three to six years after discontinuation of hormone therapy the children are off medication and free from seizures and language disability.

Pediatr Neurol. 2000 Feb;22(2):145-7.

Effects of high-dose intravenous corticosteroid therapy in Landau-Kleffner syndrome.

Tsuru T, Mori M, Mizuguchi M, Momoi MY.

Department of Pediatrics, Jichi Medical School, Tochigi, Japan.


Two children with Landau-Kleffner syndrome were successfully treated with antiepileptic drugs and a high-dose intravenous corticosteroid. A combination of valproate and a benzodiazepine (clonazepam or diazepam) ameliorated epileptic seizures and electroencephalographic spikes and waves, but speech disturbances persisted. Both patients were treated with an intravenous infusion of high-dose methylprednisolone sodium succinate (20 mg/kg daily) for 3 consecutive days. This infusion was repeated three times with a 4-day interval between treatments, which resulted in a rapid improvement in speech ability. After intravenous therapy, prednisolone was given orally (2 mg/kg daily for 1 month, then gradually withdrawn), which maintained the clinical improvement in speech.

Dev Med Child Neurol. 2006 Sep;48(9):766-9.

Efficacy of very high dose steroid treatment in a case of Landau-Kleffner syndrome.
Gallagher S, Weiss S, Oram Cardy J, Humphries T, Harman KE, Menascu S.

Division of Neurology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Canada. sgallagher@ireland.com


Landau-Kleffner syndrome (LKS) is an acquired childhood aphasia associated with paroxysmal bitemporal electroencephalogram (EEG) abnormalities and, sometimes, clinical seizures. We report the case of a female aged 5 years 6 months who presented clinically with apparent hearing loss, deterioration in speech, and seizure activity over 12 days. The female had previous detailed speech/language assessments at 3 to 4 years of age due to articulation delay. LKS was diagnosed on EEG with bitemporal spike and wave activity during sleep. The patient was treated with high dose prednisolone 3mg/kg/day, intensive speech/language therapy, and followed a modified educational program. We recorded a marked regression in receptive and expressive language skills, as well as her speech, language, and cognitive profiles before and during treatment with prednisolone, during an 18-month follow-up period. The patient demonstrated an excellent clinical response highlighting the importance of a multidisciplinary approach to management of LKS

Rev Neurol. 2010 Mar 3;50 Suppl 3:S37-47.

[Neurocognitive dysfunction in electrical status epilepticus during slow-wave sleep syndrome: Can the natural course of the syndrome be modified with early pharmacological treatment?].


Hospital Infantil Universitario Niño Jesús, Madrid, España. jgarciape.hnjs@salud.madrid.org



Epileptic syndromes with continuous spike wave in slow-wave sleep (CSWS), including electrical status epilepticus in sleep (ESES) and Landau-Kleffner syndrome, are true epileptic encephalopathies where sustained epileptic activity is related to cognitive and behavioural decline.


To review the natural course of ESES, to define the general principles of treatment of epileptic syndromes with CSWS, to delineate the different options that are currently available for treating these epileptic encephalopathies, and to analyze the prognostic factors linked to pharmacological treatment of ESES.


Epileptic syndromes with CSWS are initially treated with a pharmacologic intervention with polytherapy of antiepileptic drugs in most cases. However, due to the poor response that CSWS often have to antiepileptic drugs, non-pharmacologic treatment options are an important part of a comprehensive treatment plan for this group of children. This article discusses the use of corticosteroids, intravenous immunoglobulins, ketogenic diet, vagus nerve stimulation, and epilepsy surgery in the treatment of patients with epileptic syndromes with CSWS.


Treatment of ESES extends beyond just control of the seizures; amelioration of the continuous epileptiform discharge must occur to improve neuropsychological outcome. There is a significant correlation between the length of the ESES period and the extent of residual intellectual deficit at follow-up. According to this knowledge, there is a well defined therapeutic interval where our different strategies of treatment may be useful, and the upper limits of this time frame to a critical period of 12-18 months.

Pediatr Neurol. 2005 May;32(5):300-6.

Corticosteroids for the treatment of Landau-kleffner syndrome and continuous spike-wave discharge during sleep.

Source Comprehensive Epilepsy Program, University Of Alberta, Edmonton, Alberta, Canada.


Landau-Kleffner syndrome and its variants such as continuous Spike-Wave Discharge during Sleep (CSWS) are progressive epileptic encephalopathies of childhood. The treatment of this unusual group of patients is controversial. We describe our experience in treating patients with Landau-Kleffner syndrome and CSWS with corticosteroids. The patients received Prednisone 1 mg/kg/day for 6 months, 1 year, then yearly. Follow-up was for 1-10 years (mean 4 years). Ten patients, 3 females, 7 males were studied. Age of onset ranged from 2 to 11 years (mean 7.5 years). Eight patients manifested Landau-Kleffner syndrome, and two had CSWS. Most patients had seizures (8/10); however, two patients did not have clinical seizures. MRI was normal in all patients. SPECT scan was abnormal in four patients, normal in three, and not available in three. All but one patient manifested significant improvement in language, cognition, and behaviour, which continued after the corticosteroid trial. Side effects were few (4/10) and transient and consisted of weight gain (2), behavioral change (1), and hypertension (1). Corticosteroids are a safe and effective treatment for patients with Landau-Kleffner syndrome and CSWS. Most patients had improvement in language, cognition, and behaviour after treatment. Side effects are few and reversible, and benefits appear long lasting. Corticosteroids should be considered as a treatment option in children with Landau-Kleffner syndrome and CSWS.

 Corticosteroids as treatment of epileptic syndromes with continuous spike-waves during slow-wave sleep.


Department of Pediatric Neurology, ULB-Hôpital Erasme, 808 Route de Lennik, Brussels, Belgium.


To assess the efficacy and tolerability of steroids in epileptic syndromes with continuous spike-waves during slow-wave sleep (CSWS), charts of 44 children (25 boys) who received corticosteroids for cognitive and/or behavioral deterioration associated with CSWS were retrospectively reviewed. Awake and sleep electroencephalography (EEG) records, clinical and neuropsychological assessments were available before, during, and after corticosteroid therapy. Evaluation focused on effects on EEG, behavior, and cognition. All but two patients received hydrocortisone (initial dose of 5 mg/kg/day). The treatment was slowly tapered with a total duration of 21 months. There were 18 symptomatic and 26 cryptogenic cases. Mean age was 7 years and mean intelligence quotient/developmental quotient (IQ/DQ) was 65. Mean CSWS duration before corticosteroid treatment was 1.7 years. Twenty patients had tried more than two antiepileptic drugs (AEDs) before steroids. Positive response to steroids was found during the first 3 months of treatment in 34 of 44 patients (77.2%), with normalization of the EEG in 21 patients. Relapse occurred in 14 of them. Hence, 20 patients (45.4%) were long-term responders after a single but prolonged trial of steroids, including all four cases of Landau-Kleffner syndrome. Positive response to steroids was highly significantly associated with higher IQ/DQ. Shorter CSWS duration, but not age, etiology, or previous AED trials, was associated with positive response to steroids. Early discontinuation of the treatment for side effects was encountered in seven patients. We conclude that corticosteroids are safe and efficient for treatment of epilepsy with CSWS. Poor responders are patients with very low IQ and long duration of CSWS.

J Med Assoc Thai. 2005 Nov;88 Suppl 8:S259-63.

Epilepsy with continuous spikes and wave during slow sleep: A case report. Likasitwattanakul S.


Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. sisli@mahidol.ac.th


This report presents a 5.5-year-old girl who presented with multiple types of seizure disorder along with behavioral change, cognitive deterioration, and language impairment. Electroencephalography showed nearly continuous spike-wave during slow wave sleep. Both clinical and electrographic findings were consistent with epilepsy with continuous spikes and wave during slow sleep (CSWS). Although the seizures were well controlled with conventional antiepileptic drugs, improvement of behavioral, cognitive, and language functions was observed only after adding corticosteroid as an adjunctive treatment. Corticosteriod may have a role in treatment in children with CSWS.

Epilepsy Res. 2008 Sep;81(1):80-5. Epub 2008 Jun 3.

A comparative study of hydrocortisone versus deflazacort in drug-resistant epilepsy of childhood. Grosso S, Farnetani M, Mostardini R, Cordelli D, Berardi R, Balestri P.


Department of Pediatrics, Pediatric Neurology Section, University of Siena, Viale M. Bracci, Le Scotte, Siena, Italy. grosso@unisi.it


Steroids are commonly used for the treatment of intractable epilepsy. Deflazacort has shown similar effects to prednisone, but with a less worrying adverse-effect profile. In this study, we first compared the efficacy, safety, and seizure relapse rate of deflazacort versus hydrocortisone in children affected by drug-resistant epilepsies. This was an open, non-blinded, randomized clinical study of 35 children affected by drug-resistant epilepsies. The study lasted 12 months. Group 1 (16 patients) received hydrocortisone for 6 months; group 2 (19 patients) was treated with deflazacort for the entire study period. Drug efficacy and tolerability were evaluated after 6 months of therapy. Seizure relapse rates were evaluated 12 months after the start of the study. After 6 months of therapy, hydrocortisone was effective in 44% of patients (responders, with a decrease in seizure frequency of >50%). Deflazacort was effective in 47% of patients (P=0.9). Adverse events occurred in 37% of patients using hydrocortisone and in none of those using deflazacort (P=0.002). At the end of the study, seizure relapse rate resulted significantly higher in group 1 than in group 2 (P=0.04). Hydrocortisone may be useful in the treatment of severely drug-resistant childhood epilepsies. However, its effects may be transient. Deflazacort should be considered in the therapeutic armamentarium for epileptic encephalopathies. The drug is as effective as hydrocortisone and may be used in therapy for a long period, with a less worrying adverse-effect profile.

Seizure. 2005 Sep;14(6):412-21.

Steroids in intractable childhood epilepsy: clinical experience and review of the literature. Verhelst H, Boon P, Buyse G, Ceulemans B, D'Hooghe M, Meirleir LD, Hasaerts D, Jansen A, Lagae L, Meurs A, Coster RV, Vonck K.


Department of Pediatrics, Division of Pediatric Neurology, Ghent University Hospital, De Pintelaan 185, 9000 Gent, Belgium. helene.verhelst@ugent.be


Steroids and adrenocorticotrophic hormone (ACTH) have been used for the treatment of infantile spasms for several years. However, the use of steroids in the treatment of epilepsy beyond infantile spasms has been limited to only a few studies. We report the experience with steroids in 32 children with intractable epilepsy, not including West syndrome. In 47% there was a decrease in seizure frequency, 25% became seizure free, 11% had a seizure reduction of >50% and 11% had a seizure reduction of <50%. Our study confirms the conclusions of few previous reports of effective adjunctive steroid treatment for children with intractable epilepsy. The possible side effects, however, especially during prolonged therapy remain an important concern.

Epileptic Disord. 2012 Mar 16. [Epub ahead of print]

Therapy of encephalopathy with status epilepticus during sleep (ESES/CSWS syndrome): an update.


National Neurologic Institute "C. Mondino", Child Neuropsychiatry Unit, University of Pavia, Italy.


Electrical status epilepticus in sleep (ESES)/continuous spikes and waves during slow sleep (CSWS) is an age-related, self-limiting disorder characterised by epilepsy with different seizure types, global or selective neuropsychological regression, motor impairment, and a typical EEG pattern of continuous epileptiform activity for more than 85% of non-rapid eye movement (NREM) sleep. Although the first description of ESES/CSWS dates back to 1971, an agreement about the optimal treatment for this condition is still lacking. ESES/CSWS is rare (incidence is 0.2-0.5% of all childhood epilepsies) and no controlled clinical trials have been conducted to establish the efficacy of different antiepileptic drugs; only uncontrolled studies and case reports are reported in the literature. Treatment options for ESES/CSWS include some antiepileptic drugs (valproic acid, ethosuximide, levetiracetam, and benzodiazepines), steroids, immunoglobulins, the ketogenic diet, and surgery (multiple subpial transections). In this study, the comparative value of each of these treatments is reviewed and a personal therapeutic approach is proposed.

Epilepsia. 2009 Jun;50(6):1517-24. Epub 2008 Nov 19.

Clinical spectrum and medical treatment of children with electrical status epilepticus in sleep (ESES).


Pediatric Neurology Unit, Dana Children's Hospital, Tel Aviv Medical Center, Tel Aviv, Israel. umkramer@netvision.net.il



To describe the clinical spectrum and to evaluate the efficacy of different therapeutic agents in children with electrical status epilepticus in sleep (ESES).


Clinical data of all patients with ESES (not including patients with Landau-Kleffner syndrome) in four pediatric neurology outpatient clinics were analyzed. Thirty patients with ESES had been treated between 1994 and 2007.


Eleven (37%) children had benign partial epilepsies of childhood, five (17%) had cerebral palsy, five (17%) had hydrocephalus, one (3%) had schizencephaly, one (3%) had prenatal parenchymal bleeding, and the etiology was unclear in seven (23%). The duration of ESES ranged between 2 and 60 months. The antiepileptic drugs that were found to be efficacious were: levetiracetam (41%), clobazam (31%), and sulthiame (17%). Valproic acid, lamotrigine, topiramate, and ethosuximide showed no efficacy. Steroids were efficacious in 65%; immunoglobulins were efficacious in 33%. High-dose diazepam was efficacious in 37%, but all the children had temporary response. Seventeen patients (57%) had cognitive deterioration, whereas the rest presented with regression in attention, speech, communication, and behavior. Fourteen children had permanent cognitive deficit. There was a significant correlation (p = 0.029) between the duration of ESES and residual intellectual deficit at follow-up.


ESES reflects an evolution of benign partial epilepsy of childhood in more than one-third of the patients, whereas there is an underlying structural brain anomaly in another one-third. The most efficacious antiepileptic drugs (AEDs) are levetiracetam and clobazam. The duration of ESES correlated significantly with residual intellectual deficit at follow-up.

Pediatr Neurol. 2005 Jan;32(1):64-7.

Treatment of electrical status epilepticus during slow-wave sleep with high-dose corticosteroid.


Department of Pediatric Neurology, Mersin University Medical Faculty, Ankara, Turkey.


A 4-year-old female patient with epilepsy with continuous spike-and-waves during slow-wave sleep not classified as Landau-Klefner syndrome, refractory to antiepileptic drugs including valproate, benzodiazepines, and lamotrigine, was treated successfully with high-dose intravenous methylprednisolone therapy. Valproate, clobazam, and lamotrigine were continued at the same dose during and after high-dose intravenous corticosteroid therapy. During corticosteroid therapy, awake and sleep electroencephalogram was recorded every day. On day 7, a dramatic clinical and electroencephalographic response was observed. After high-dose intravenous methylprednisolone, prednisolone was administered orally (2 mg/kg daily) for 2 months, then gradually withdrawn. After the withdrawal of corticosteroid therapy, the patient maintained the clinical improvement in behavior, and no continuous spike-and-wave electrical status epilepticus during slow-wave sleep occurred on routine monthly sleep electroencephalogram performed for the last 6 months. In the present case, an add-on high-dose intravenous corticosteroid seems to be effective in the treatment of patients with electrical status epilepticus during slow-wave sleep syndrome, especially when antiepileptic drugs fail.

An aphasic syndrome in children.

Can Med Assoc J.  1974; 110(6):637-9 (ISSN: 0008-4409)

McKinney W; McGreal DA

The paper presents case reports of nine children, all of whom had severe disturbances of language function of abrupt or gradual onset. Seizures occurred in seven of the children and all nine had EEG abnormalities.There was no apparent correlation between the seizures, the EEG changes and the aphasia. One patient had a brain biopsy performed at another hospital and the tissue was said to be normal. The cause of the abnormal language function is unknown. Five of the children failed to acquire normal speech subsequently. Three of the four children who made a complete recovery were treated with steroids.
Paediatr Drugs. 2005;7(6):377-89.

Management of Landau-Kleffner syndrome.


Department of Pediatrics, and Adult and Pediatric Epilepsy Program, Faculty of Medicine, American University of Beirut, Beirut, Lebanon. mamikati@aub.edu.lb


Landau-Kleffner syndrome (LKS) is an acquired epileptic aphasia disorder in which children, usually 3-8 years of age who have developed age-appropriate speech, experience language regression with verbal auditory agnosia, abnormal epileptiform activity, behavioral disturbances, and sometimes overt seizures. There are no controlled clinical trials investigating the therapeutic options for LKS. Only open-label data are available. Early diagnosis and initiation of prompt medical treatment appear to be important to achieving better long-term prognosis.Several antiepileptic drugs have been reported to be beneficial in treating this syndrome. These include valproic acid (valproate sodium), diazepam, ethosuximide, clobazam, and clonazepam. Reports on the efficacy of lamotrigine, sultiame, felbamate, nicardipine, vigabatrin, levetiracetam, vagal nerve stimulation, and a ketogenic diet are few and more experience is needed. Carbamazepine and possibly phenobarbital and phenytoin have been reported to occasionally exacerbate the syndrome. As initial therapy, valproic acid or diazepam is often empirically chosen. Subsequently, other antiepileptic drugs, corticosteroids, or intravenous immunoglobulin (IVIG) therapy are often used. Corticosteroid therapy should probably not be delayed more than 1-2 months after the initial diagnosis. Various corticosteroid regimens including oral prednisone and, recently, high doses of intravenous pulse corticosteroids, as well as corticotropin (adrenocorticotropic hormone) have been reported to be effective in LKS. Oral corticosteroids are used more often and usually need to be maintained for a long period of time to prevent relapses. The use of IVIG has been associated with an initial dramatic response in only a few patients. In our experience, a long-term worthwhile improvement has been noted in only 2 of 11 patients. These two patients had an immediate response to IVIG initially and after relapses before eventually achieving a long-term sustained remission. Surgical treatment by multiple subpial transection, which is reserved for patients who have not responded to multiple medical therapies, has been followed in selected cases by a marked improvement in language skills and behavior. However, a widely accepted consensus about suitable candidates for this surgery and about its efficacy is still lacking. Speech therapy, including sign language, and a number of classroom and behavioral interventions are helpful in managing LKS, and should be used in all patients.

J Pediatr. 1999 May;134(5):607-13.

Serum autoantibodies to brain in Landau-Kleffner variant, autism, and other neurologic disorders.


Departments of Neurology and Pediatrics, Washington University, St. Louis Children's Hospital, St Louis, Missouri, USA.



Etiologically unexplained disorders of language and social development have often been reported to improve in patients treated with immune-modulating regimens. Here we determined the frequency of autoantibodies to brain among such children.


We collected sera from a cohort of children with (1) pure Landau-Kleffner syndrome (n = 2), (2) Landau-Kleffner syndrome variant (LKSV, n = 11), and (3) autistic spectrum disorder (ASD, n = 11). None had received immune-modulating treatment before the serum sample was obtained. Control sera (n = 71) were from 29 healthy children, 22 with non-neurologic illnesses (NNIs), and 20 children with other neurologic disorders (ONDs). We identified brain autoantibodies by immunostaining of human temporal cortex and antinuclear autoantibodies using commercially available kits.


IgG anti-brain autoantibodies were present in 45% of sera from children with LKSV, 27% with ASD, and 10% with ONDs compared with 2% from healthy children and control children with NNIs. IgM autoantibodies were present in 36% of sera from children with ASD, 9% with LKSV, and 15% with ONDs compared with 0% of control sera. Labeling studies identified one antigenic target to be endothelial cells. Antinuclear antibodies with titers >/=1:80 were more common in children with ASD and control children with ONDs.


Children with LKSV and ASD have a greater frequency of serum antibodies to brain endothelial cells and to nuclei than children with NNIs or healthy children. The presence of these antibodies raises the possibility that autoimmunity plays a role in the pathogenesis of language and social developmental abnormalities in a subset of children with these disorders.

J Child Neurol. 2010 Aug;25(8):948-53. Epub 2010 Feb 8.

Outcomes in treatment of infantile spasms with pulse methylprednisolone.


Department of Neurology, University of Virginia Health System, Charlottesville, Virginia 22908, USA.


The authors report their experience with intravenous methylprednisolone for the treatment of infantile spasms. A pulse dose of 20 mg/kg intravenous methylprednisolone on each of 3 successive days, followed by a 2-month oral prednisolone taper, led to the rapid remission (range, 2-6 days) of infantile spasms in 5 of 10 (50%) infants. In the subgroup of infants treated within 1 month of onset, 5 of 6 (83%) experienced remission within 6 days. The authors estimate the medication cost of intravenous methylprednisolone with prednisolone taper to be less than $200. In comparison, the cost of a typical course of adrenocorticotropic hormone in the United States can exceed $70,000. Initial treatment with intravenous methylprednisolone and/or oral corticosteroids is a reasonable cost-effective approach to infantile spasms. The lack of serious side effects, low cost, availability, ease of administration, and comparable efficacy suggests that intravenous methylprednisolone merits consideration for study in randomized prospective trials.

Shoddy review

Cochrane Database Syst Rev. 2007 Jan 24;(1):CD005222.

Corticosteroids including ACTH for childhood epilepsy other than epileptic spasms.


Leeds General Infirmary, Clarendon Wing, Belmont Grove, Leeds, UK, LS2 9NS. Neti.Gayatri@leedsth.nhs.uk



Epilepsy is a disorder with recurrent epileptic seizures. Corticosteroids have been used in the treatment of children with epilepsy and have significant adverse effects. Their efficacy and tolerability have not been not clearly established.


To determine the efficacy of corticosteroids in terms of seizure control, improvements in cognition and in quality of life and tolerability of steroids compared to placebo or other antiepileptic drugs.


We searched the following databases: The Cochrane Epilepsy Group Specialized Register (September 2006); Cochrane Central Register of Controlled Trials (CENTRAL)(The Cochrane Library Issue 2, 2006); MEDLINE (1966 - April 2004); EMBASE (1966 - December 2004); Database of Abstracts of Reviews of Effectiveness (DARE) (December 2004). We checked the reference lists of retrieved studies for additional reports of relevant studies.


All randomized controlled trials of administration of corticosteroids to children (less than 16 years) with epilepsy.


Three review authors independently selected trials for inclusion and extracted data. Outcomes included cessation of seizures, reduction in seizure frequency, improvement in cognition, quality of life and adverse effects of steroids.


A single randomized controlled trial (RCT) was included that recruited five patients in double blind crossover trial. One was withdrawn prematurely from the study and another had infantile spasms and hence was excluded from further analysis. ACTH 4-9 was administered. The overall reduction in seizure frequency of more than 25% and less than 50% occurred in one child at low dose and in two children at higher dose. One child did not show any reduction in seizure frequency. No adverse effects were reported.


No evidence was found for the efficacy or safety of corticosteroids in treating childhood epilepsies. Clinicians using steroids in childhood epilepsies, other than for epileptic spasms, should take this into account before using these agents.

The one study used in the above review!

Neuropediatrics. 1982 May;13(2):59-62.

Trial of an ACTH4-9 Analogue (ORG 2766) in children with intractable seizures.


The ACTH4-9 Analogue (ORG 2766) is an orally administered neuropeptide which has been showed to have behavioral effects in human subjects, but does not have any steroidogenic effects, nor other significant side effects. This study was a double-blind, crossover trial of the ACTH4-9 analogue in four children with intractable seizures. There was some slight improvement in seizure frequency in two patients, with an equivocal improvement in a third child. A fourth child was unchanged, while the fifth dropped out of the study. There were no side effects from the therapy. This questionable improvement in seizure frequency in some of the most intractable patients with seizure disorders indicates the need to further assess this ACTH4-9 analogue in a larger study over a longer period of time.

Interictal Encephalography Can Influence Patient Selection for Methylprednisolone Therapy in Pediatric Refractory Epilepsy

1 Department of Pediatric Neurology, Assaf Harofeh Medical Center, Zerifin, Israel

2 Sackler School of Medicine, Tel Aviv University, Israel

3 Electroencephalography Laboratory, Assaf Harofeh Medical Center, Zerifin, Israel

Revital S. Gandelman-Marton, Department of Neurology, Assaf Harofeh Medical Center, Zerifin 70300, Israel Email: revitalgm@hotmail.com


We describe our experience with intravenous methylprednisolone pulse therapy in older children with refractory epilepsy. Patients with refractory epilepsy, who were treated with steroids between 2005 and 2010, were retrospectively selected from the database of the pediatric epilepsy clinic at Assaf Harofeh Medical Center. Eight patients (5 boys) aged 1.1 to 9 years (5.2 ± 2.6) were identified. Intravenous methylprednisolone 30 mg/kg/d was given to all patients for 5 days in addition to a stable dosage of the regular antiepileptic drugs. Transient side effects were reported in 4 of the patients during pulse therapy. Significant clinical improvement was noted in 4 patients, accompanied by a significant reduction of the amplitude of the spike–slow wave discharges on the electroencephalogram (EEG). Children with refractory epilepsy, abnormal EEG background, and high-amplitude spike–slow wave discharges appear to be the best candidates for intravenous methylprednisolone pulse therapy.


Efficacy and prognosis of a short course of prednisolone therapy for pediatric epilepsy.


Department of Pediatrics, Epilepsy Center, Sanggye Paik Hospital, Inje University College of Medicine, 761-1 Sang-gye 7 Dong, No-won Gu, Seoul 139-707, Republic of Korea.



To evaluate the efficacy and safety of adjunctive prednisolone therapy in children with cryptogenic epileptic encephalopathy, other than infantile spasms, and to determine its prognosis.


Prednisolone, 2mg/kg per day for 6 weeks, tapered for a further 2 weeks, was given in combination with previously prescribed antiepileptic drugs. A retrospective assessment of 41 children thus treated included measurements of seizure frequency, electroencephalographic findings, global assessments of cognitive function, and adverse drug events. Long-term patient prognoses over a mean follow-up period of 3 years and 5 months (range, 14-90 months) were also examined.


Of 41 patients, 32 had Lennox-Gastaut syndrome, 4 had Doose syndrome, 1 had Otahara syndrome, 2 had Landau-Kleffner syndrome, and 2 had other unspecified generalized epilepsies. After prednisolone therapy, 73% (30/41) of patients showed a reduction in seizure frequency of >50%, and 59% (24/41) became seizure free. However, only seven patients (four with Lennox-Gastaut syndrome, two with Doose syndrome, and one with unspecified generalized epilepsy) who became seizure free remained free of seizures at the time of the final follow-up. Electroencephalographic findings and global assessments of cognitive function correlated well with seizure outcomes. No significant demographic factors influenced the efficacy of prednisolone or patient prognoses after prednisolone tapering. Most adverse events were transient, or were tolerated well with conservative management, with maintenance of the medication.


Prednisolone therapy may be a safe and effective adjunct in patients with cryptogenic epileptic encephalopathies, but the high relapse rate is of concern.


[Clinical characteristics and long-term prognosis of Landau-Kleffner syndrome].

[Article in Chinese]


Department of Pediatrics, First Hospital, Peking University, Beijing 100034, China.



To investigate the clinical and electroencephalographic (EEG) characteristics, therapeutic response and long-term prognosis of Landau Kleffner syndrome (LKS).


The clinical and EEG data of 10 children with LKS were analyzed, and therapeutic response and long-term outcome were followed up.


The age of onset was from 2 to 10.5 years of age. All patients had acquired aphasia, characterized by verbal auditory agnosia. All patients had epileptic seizures. Partial motor seizures during sleep occurred in 8 patients, and other seizure type including atypical absence seizure and generalized tonic-clonic seizure were also observed. Psychological and behavioral abnormalities occurred in 9 patients. There were no abnormalities of hearing and neuro-imaging tests in all patients, and family histories were negative. All the patients had EEG abnormalities. Focal spike and waves of temporal lobe were recorded in 9 patients. Electrical status epilepticus during sleep (ESES) was observed on Video-EEG (VEEG) monitoring in 4 patients. Anti-epileptic drugs (AEDs) showed favorable effects on epileptic seizures, but no effects on aphasia. All patients responded to corticosteroid, and got language improved. Eight patients were followed up for long-term outcome. All patients were seizure free, while the level of language development was abnormal in 5 patients. The VEEG follow-up was conducted in 6 patients. Continuous epileptic discharges in slow sleep recurred in 2 patients after the discontinuation of steroid therapy.


LKS is one of the childhood epileptic encephalopathy, and acquired aphasia and epileptic seizures are two main clinical characteristics. Aphasia is characterized by verbal auditory agnosia. Psychological and behavioral abnormalities are very common in children with LKS. Focal epileptic discharges were often located in temporal area, and usually generalized, and could be continuous during sleep. AEDs could control seizure but had no effects on aphasia. Early use of full dose corticosteroids could improve the language significantly. Long-term follow up showed that language impairments often remained, but the outcome in terms of EEG and epileptic seizure was good.

Epilepsia. 2010 Oct;51(10):2023-32. doi: 10.1111/j.1528-1167.2010.02578.x.

Long-term outcome of 32 children with encephalopathy with status epilepticus during sleep, or ESES syndrome.


Epilepsy Unit, Department of Pediatric Neurology, Helsinki University Central Hospital, HUS, Finland. elina.liukkonen@hus.fi



To prospectively evaluate the efficacy of drug treatment and long-term cognitive outcome in children with encephalopathy with status epilepticus during sleep (ESESS).


Thirty-two children were diagnosed and prospectively followed up for at least 3 years at our unit between 1991 and 2007. Twenty-seven children were included in the prospective treatment study with valproate (VPA) and 17 with VPA combined with ethosuximide (ESM). Treatment response of disappearance of electrical status epilepticus during sleep (SES) was documented with overnight EEG recordings. Neuropsychological follow up for at least 5 years was available in 18 patients.


Six children had atypical rolandic (AR) epilepsy, nine Landau-Kleffner syndrome (LKS), and 17 symptomatic epilepsy. Before ESESS, 20 children were cognitively normal. Prospective treatment with VPA and ESM was effective in 3 of the 17 children (18%) treated. Abolition of SES with drug treatment was observed in 16 patients. In all, 10 children (31%), 4 with AR (67%), 3 with LKS (33%), and 3 with symptomatic etiology (19%), including 9 with treatment response regained the pre-ESESS cognitive level. Unfavorable cognitive outcome was predicted by younger age at ESESS diagnosis, lower IQ at the time of the diagnosis, and no response to drug treatment when compared with those with favorable cognitive outcome. Eight of the 16 nonresponders underwent epilepsy surgery.


Treatment response with VPA combined with ESM was observed more often than with other drug combinations. Most children with ESESS experienced permanent cognitive impairment. Cognitive outcome depends on treatment response on electroencephalography (EEG) and seizures, and on underlying etiology.

NEW 120412

Title: NINDS Landau-Kleffner syndrome information page

Source: Pamphlet by: National Institute of Neurological Disorders and Stroke. National Institute of Neurological Disorders and Stroke, 2011.

What is Landau-Kleffner Syndrome?

Landau-Kleffner syndrome (LKS) is a rare, childhood neurological disorder characterized by the sudden or gradual development of aphasia (the inability to understand or express language) and an abnormal electro-encephalogram (EEG). LKS affects the parts of the brain that control comprehension and speech. The disorder usually occurs in children between the ages of 5 and 7 years. Typically, children with LKS develop normally but then lose their language skills for no apparent reason. While many of the affected individuals have seizures, some do not. The disorder is difficult to diagnose and may be misdiagnosed as autism, pervasive developmental disorder, hearing impairment, learning disability, auditory/verbal processing disorder, attention deficit disorder, mental retardation, childhood schizophrenia, or emotional/behavioral problems.

Is there any treatment?

Treatment for LKS usually consists of medications, such as anticonvulsants and corticosteroids, and speech therapy, which should be started early. A controversial treatment option involves a surgical technique called multiple subpial transection in which the pathways of abnormal electrical brain activity are severed

What is the prognosis?

The prognosis for children with LKS varies. Some affected children may have a permanent severe language disorder, while others may regain much of their language abilities (although it may take months or years). In some cases, remission and relapse may occur. The prognosis is improved when the onset of the disorder is after age 6 and when speech therapy is started early. Seizures generally disappear by adulthood.

What research is being done?

The NINDS supports broad and varied programs of research on epilepsy and developmental disorders. This research is aimed at discovering new ways to prevent, diagnose, and treat epilepsy and developmental disorders and, ultimately, to find cures for them.
Semin Pediatr Neurol. 2008 Jun;15(2):50-60.

Electrical status epilepticus in sleep.


Department of Neurology, Mayo Clinic, Rochester, MN 55902, USA.


Electrical status epilepticus in sleep (ESES) describes an electroencephalographic pattern showing significant activation of epileptiform discharges in sleep. The terms continuous spike wave in slow-wave sleep (CSWS) and Landau-Kleffner syndrome (LKS) describe the clinical epileptic syndromes seen with ESES. Although there is an overlap between these 2 syndromes, children with CSWS present with a more global regression have more problematic epilepsy and have EEG foci located predominantly in frontotemporal or frontocentral regions. In contrast, children with LKS present with an acquired auditory agnosia, fewer seizures, and EEG foci in the posterotemporal regions. ESES requires a high degree of clinical suspicion because slow-wave sleep must be recorded to confirm this diagnosis. Treatment of ESES extends beyond just control of the seizures; amelioration of the continuous epileptiform discharge must occur to improve neuropsychological outcome. Although there is little evidence to guide treatment, conventional antiepileptic drugs play only a minimal role. Steroid therapy and high-dose benzodiazepines are most commonly used, but other therapies including intravenous gamma-globulin, the ketogenic diet, and surgical therapy with multiple subpial transaction have shown efficacy in small case series. Although epilepsy resolves with time in most cases, many children are left with significant cognitive or language impairment. Longer duration of ESES appears to be the major predictor of poor outcome; markedly abnormal neuronal activity during a critical period for synaptogenesis may result in aberrant synapse formation, explaining the poorer neuropsychological outcome. Early recognition and effective therapy are necessary to improve long-term prognosis in this condition.

Dev Med Child Neurol. 2001 Apr;43(4):243-7.

Landau-Kleffner syndrome: course and correlates with outcome.


Newcomen Centre, Guy's Hospital, London, UK. richard.robinson@gstt.sthames.nhs.uk


The presenting characteristics of 18 (11 female, seven male) children with Landau-Kleffner syndrome (LKS) were studied with respect to course and outcome of their condition at a mean length of 67 (SD 46) months' follow-up. All had regression of receptive language (mean age of onset 4 years 9 months) and electrical status epilepticus in sleep (ESES). Length of ESES correlated strongly with length of period between onset of illness and onset of recovery (p<0.006) and also with eventual receptive (p<0.001) and expressive (p<0.007) language. Behaviour during the acute phase was severely affected in nine children and associated with frontal lobe discharges in awake EEGs (p<0.004). Age at onset was not correlated with outcome. All children had impaired short-term memory at follow-up. Three children had language outcome within the normal range. No child with ESES lasting longer than 36 months had normal language outcome. These data lend support for intervention in ending ESES by 36 months using multiple subpial transection (MST) if steroids are ineffective or cause unacceptable side effects.

Pediatr Neurol. 2010 Dec;43(6):411-9.

Atypical benign partial epilepsy: recognition can prevent pseudocatastrophe.


Department of Pediatrics, Tokyo Women's Medical University, Shinjuku-Ku, Tokyo, Japan.


To characterize and distinguish atypical benign partial epilepsy of childhood among various epileptic syndromes, we conducted a clinical and electroencephalogram study. Seventeen children with atypical benign partial epilepsy of childhood were followed at our hospital. They all underwent a video/polygraphic study of characteristic daily seizures, facilitating a diagnosis of atypical benign partial epilepsy of childhood. Their clinical and electroencephalogram features were retrospectively analyzed. A video/polygraphic study indicated negative motor seizures including epileptic negative myoclonus, atonic absence seizures, or atonic seizures corresponding to spike-and-wave complexes arising from centro-parieto-temporal regions. Early in the clinical course, these seizures appeared every 4 ± 2 months, and lasted 1-3 months. Interictal sleep electroencephalograms, initially localizing in the centro-parieto-temporal regions, became widespread and displayed continuous, diffuse, spike-and-wave complexes, although the spike-wave index did not exceed 85%. Negative motor seizures responded to ethosuximide, corticotropin, and high-dose steroid, whereas other antiepileptic drugs were much less effective. All patients ultimately entered remission before age 12 years. Patients with atypical benign partial epilepsy of childhood exhibited a characteristic clinical course, and responded favorably to anti-absence treatment. Atypical benign partial epilepsy of childhood should be recognized as a discrete epileptic syndrome. Its early diagnosis leads to the prevention of pseudocatastrophe.

Pediatr Neurol. 2006 Sep;35(3):204-8.

Sulthiame therapy for continuous spike and wave in slow-wave sleep.


Department of Pediatrics, University of Calgary, Calgary, Canada. elaine.wirrell@calgaryhealthregion.ca


Corticosteroids are often considered as the first therapeutic choice in children with continuous spike and wave in slow-wave sleep on electroencephalogram; however, they are associated with significant adverse effects. "Idiopathic" forms of continuous spike and wave in slow-wave sleep may represent the severe end of the spectrum of benign rolandic epilepsy of childhood. This report describes a 5-year-old male with language delay who presented with a single focal-onset, nocturnal seizure and had continuous spike and wave in slow-wave sleep on electroencephalography. After 1 month of sulthiame therapy, his electroencephalographic abnormality had resolved, and his language development improved.

J Clin Neurophysiol. 2003 Nov-Dec;20(6):462-72.

Epileptic encephalopathy of late childhood: Landau-Kleffner syndrome and the syndrome of continuous spikes and waves during slow-wave sleep.


Departmernt of Neurosciences, Rush University Medical Center, Chicago, IL 60612-3833, USA.


Landau-Kleffner syndrome (LKS) and the syndrome of continuous spikes and waves during slow wave sleep (CSWS) are two points on the spectrum of functional childhood epileptic encephalopathies. They are characterized by a severe paroxysmal EEG disturbance that may permanently alter the critical synaptogenesis by strengthening synaptic contacts that should have been naturally "pruned." The much more common benign epilepsy with centrotemporal spikes is also related to LKS and CSWS by a common pathophysiology. Although prognosis in LKS and CSWS for seizure control is good, cognitive function declines and permanent neuropsychologic dysfunction is seen in many cases. This permanent damage is most evident in those patients who had early-onset EEG abnormality and a prolonged active phase of continuous spike-and-wave discharges during sleep. If the active phase of paroxysmal activity persists for over 2 to 3 years, even successful treatment does not resolve neuropsychologic sequelae. In LKS, the paroxysmal activity permanently affects the posterior temporal area and results in auditory agnosia and language deficits; in CSWS, the frontal lobes are more involved and other cognitive disturbances predominate. Aggressive treatment should include high-dose antiepileptic drugs, corticosteroids, and surgery in specific cases.

Brain Dev. 2000 Aug;22(5):279-95.

The spectrum of neuropsychiatric abnormalities associated with electrical status epilepticus in sleep.


Department of Neurology, Albert Einstein College of Medicine, 1410 Pelham Parkway South, NY 10461, Bronx, USA. aris3@aol.com


Electrical status epilepticus in sleep (ESES) is an electrographic pattern consisting of an almost continuous presence of spike-wave discharges in slow wave sleep. ESES is frequently encountered in pediatric syndromes associated with epilepsy or cognitive and language dysfunction. It can be present in various evolutionary stages of a spectrum of diseases, the prototypes of which are the 'continuous spikes and waves during slow wave sleep' syndrome (CSWS), the Landau-Kleffner syndrome (LKS), as well as in patients initially presenting as benign childhood epilepsy with centrotemporal spikes (BECTS). The purpose of this article is to review the literature data on the semiology, electrographic findings, prognosis, therapeutic options, as well as the current theories on the pathophysiology of these disorders. The frequent overlap of CSWS, LKS, and BECTS urges an increased level of awareness for the occasional transition from benign conditions such as BECTS to more devastating syndromes such as LKS and CSWS. Identification of atypical signs and symptoms, such as high discharge rates, prolonged duration of ESES, neuropsychiatric and cognitive dysfunction, lack of responsiveness to medications, and pre-existing neurologic conditions is of paramount importance in order to initiate the appropriate diagnostic measures. Prolonged and if needed repetitive sleep electroencephalographs (EEGs) are warranted for proper diagnosis.

Eur J Paediatr Neurol. 2000;4(2):81-6.

Landau-Kleffner syndrome with onset at 18 months and an initial diagnosis of pervasive developmental disorder.


Danish Epilepsy Hospital, Dianalund. pu@rh.dk


We report one of the youngest and most intensively studied cases of Landau-Kleffner syndrome, with a follow-up of 5 years. The boy developed normally until the age of 18 months when he had two attacks, possibly epileptic. Electroencephalogram (EEG) was normal. Over the next 5 months he lost his six to ten words, did not engage with other children and became mute. When he was 34 months old a child-psychiatrist suggested a diagnosis of pervasive developmental disorder or developmental dysphasia. An EEG 3 months later showed abnormalities typical of Landau-Kleffner syndrome. His non-verbal abilities were normal as well as his neurological examination and brain magnetic resonance imaging (MRI). A trial of clobazam and vigabatrin was unsuccessful. When he was 4 years and 9 months old he was treated with corticosteroids and within 3 months his vocabulary increased from the standard for 1 1/2 years of age to that for 2 1/2 years of age. His language abilities continued to improve slowly until a stagnation period at the age of 6 years and 9 months. A second course of corticosteroids improved his comprehension and vocabulary to an almost normal level, and his EEG normalized. A total of 11 EEGs were obtained; all included sleep, but continuous spike and wave during slow sleep was never documented. This report illustrates that Landau-Kleffner syndrome should be considered as an alternative diagnosis in children diagnosed with developmental dysphasia. An EEG including sleep should be considered, and in the presence of abnormalities a trial of anti-epileptic drugs or corticosteroids should be undertaken.

Brain Dev. 1996 May-Jun;18(3):197-200.

Correlation between CSWS and aphasia in Landau-Kleffner syndrome: a study of three cases.


Department of Pediatrics, First Hospital, Beijing Medical University, China.

We report three typical cases of Landau-Kleffner syndrome with varied courses. The very frequent discharges in sleep EEGs, often showing the patterns of CSWS (continuous spike-waves during slow-wave sleep), either typical (spike-wave complex occupying over 85% of slow-wave sleep duration) or atypical (spike-waves occupying less than 85% of slow-wave sleep), were presented in all our cases. The CSWS seems correlated with aphasia in our cases. Since the disappearance of CSWS might be indicative of a lagged improvement in aphasia, we suggest that sufficiently long-term treatment with anticonvulsants and/or corticosteroids is worthwhile, if the EEG is improved significantly by this treatment.


Cristina said...

Thanks for sharing these! Bertrand's EEG completely normalized on steroids (ACTH and prednisone taper). He developed amazingly during that time! Unfortunately, the effects were temporary for him, but for many kids the effects are permanent! We're big fans, even if the side-effects were brutal. Best wishes!

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