eMedicine Specialties > Neurology > Pediatric Neurology

Epileptic and Epileptiform Encephalopathies: Treatment & Medication

Author: Dean Patrick Sarco, MD, Instructor, Department of Neurology, Harvard Medical School; Assistant Physician, Department of Neurology, Division of Epilepsy and Clinical Neurophysiology, Children's Hospital Boston
Coauthor(s): Masanori Takeoka, MD, Assistant Professor, Department of Neurology, Harvard Medical School; Consulting Staff, Department of Neurology, Division of Epilepsy and Clinical Neurophysiology, Children's Hospital Boston
Contributor Information and Disclosures

Updated: Jul 29, 2009

Treatment

Medical Care

This discussion includes all of the epileptic and epileptiform encephalopathies since the treatment approaches share some similarity. Early diagnosis and initiation of treatment appear to be important in achieving better long-term prognosis. Notably, for most of these disorders, there are no controlled clinical trials investigating the therapeutic options, and only open-label data are available. In general, antiepileptic drugs (AEDs) that are considered "spike suppressors" such as valproic acid, benzodiazepines, ethosuximide, levetiracetam, and lamotrigine may be preferable with regards to improving the EEG, in an effort to see if cognitive function improves. Additionally, adrenocorticotropic hormone (ACTH) or corticosteroids may be used, usually after standard AEDs have failed. A ketogenic diet and IVIG may also be helpful.

Regarding Landau-Kleffner syndrome (LKS) and epilepsy with continuous spike-waves during slow wave sleep (CSWS):

  • In the original paper, Landau and Kleffner discerned a relationship between treatment with antiepileptic drugs (AEDs) and improvement in the aphasia.49 In 1967, Deuel and Lenn reported a case with a clear relationship between AED treatment and language improvement, and subsequent reports have been published of improvement with various anticonvulsants.50 No data exist that support the use of any one AED, and whether any one anticonvulsant is better than others is unclear. Treatment is similar for the syndrome of continuous spikes and waves during sleep.
  • Aeby et al treated 12 children with behavioral and/or cognitive deterioration associated with CSWS with levetiracetam 50 mg/kg/day as add-on treatment.51 They found that levetiracetam had a positive effect on the EEG, behavior, and cognition.
  • High-dose pulse diazepam therapy also has been effective, according to De Negri et al, especially in cryptogenic cases.52
  • Rectal diazepam dosing up to 1 mg/kg qhs, followed by a gradual taper over months, has been reported to help in some children.53
  • Marescaux et al, in a pharmacologic study of 5 cases of LKS, gave VPA to all 5.54 In the first patient, comprehension and oral expression improved slightly during the first 2 months of treatment, concomitant with disappearance of spike and wave discharges for 3 months, but then the spike and wave discharges recurred. In their third patient, the spike and wave duration in sleep decreased from 80% to 45%. Treatment had no effect on behavior abnormalities, speech, or intellect in 4 of the children.
  • Both adrenocorticotropic hormone (ACTH) and prednisone have been used.
    • In 1974, McKinney and McGreal reported that 3 children with LKS treated with steroids had improvement, whereas only 1 of 6 in those who were not treated had improvement.55
    • Subsequently, it was reported that the rapidity of the response and the resultant neurological sequelae depend on the duration and severity of the symptoms before treatment, that initial high steroid doses were more effective, and that brief periods of steroid treatment appeared ineffective or led to a high rate of relapse.54,56
    • Current treatment protocols vary. Options include either a short or long course of steroids as well as low or higher dosages. It has been proposed that a longer course may prevent relapse.
    • Chez et al have advocated the use of pulse prednisone therapy, which achieves the therapeutic benefits while markedly reducing the adverse corticosteroid effects.57 The daily dose is calculated and then converted to a weekly dose.
    • Tsuru et al successfully treated 2 children with LKS with antiepileptic drugs and a high-dose intravenous corticosteroid.58 Epileptic seizures and EEG abnormalities were improved on a combination of valproate and a benzodiazepine, but speech disturbances persisted. Both patients were treated with an intravenous infusion of high-dose methylprednisolone (20 mg/kg daily) for 3 consecutive days. The infusion was repeated 3 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 mo, then gradually withdrawn), which maintained the clinical improvement in speech.
    • Sinclair and Snyder reported their experience with prednisone (1 mg/kg/d for 6 mo) in 8 patients with LKS and in 2 patients with CSWS.59 Mean yearly follow-up was 4 years. All but one patient manifested significant improvement in language, cognition, and behavior, which continued after the corticosteroid trial. Side effects were few and reversible, and benefits appeared to be long lasting.

Related practice parameters, treatment guidelines, and diagnostic criteria are available from the American Academy of Neurology, American Epilepsy Society, and American College of Radiology.60,61,62

Surgical Care

Some children who do not respond to medical therapy may be candidates for surgical treatment of their epilepsy. The most common procedure is focal cortical resection, where an epileptic focus is identified and resected. The goal of this type of surgery is complete removal or disconnection of the epileptogenic network, while preserving eloquent cortical areas so that a neurological deficit does not occur. Areas of eloquent cortex include those vital to motor, sensory, language, memory, or visual function.

Morrell devised the multiple subpial transection (MST) procedure, in which vertical incisions are made in the cortex, disconnecting the horizontal cortical layers while preserving vertical connections and thus eloquent cortical function. Cortical and subcortical connections remain intact, whereas, in a typical epilepsy surgery resection, the area of seizure origin is removed, eliminating the cortical and subcortical connections.

Morrell reported their results with MST for Landau-Kleffner syndrome (LKS) in 14 children, 11 of whom have improved. The indication for MST include focal origination of epileptiform discharges; normal development of language, up to speaking in sentences for a nonautistic child; and muteness for at least 2 years, since spontaneous improvement may occur.63,64

Grote et al reported their experience with 14 children who underwent MST for treatment of LKS. Eleven children demonstrated significant postoperative improvement on measures of receptive or expressive vocabulary. They concluded that MST may allow for a restoration of speech and language abilities and that early diagnosis and treatment optimize outcome. Additionally, they pointed out that gains in language function are most likely to be seen years, rather than months, after surgery.65

Favorable outcome after MST was also described in 5 children with LKS by Irwin et al who reported that behavior and seizure frequency improved dramatically after surgery in all children. Improvement in language also occurred in all children, although none improved to an age-appropriate level.66 The experience with MST at other centers has been variable.

Consultations

Management of epileptic and epileptiform encephalopathies may require a multispecialty team.

  • Neurologist, child neurologist, epileptologist
  • Pediatrician or developmental pediatrician
  • Psychologist, neuropsychologist
  • Psychiatrist, child psychiatrist, psychopharmacologist
  • Speech pathologist, audiologist
  • Physical therapist, occupational therapist
  • Ophthalmologist, when a metabolic disorder with ophthalmologic findings is in the differential diagnosis
  • Audiological testing to exclude hearing loss

Diet

The ketogenic diet is often helpful in the treatment of medically intractable epilepsy and in the epileptic encephalopathy disorders. 

Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Adrenocorticotropic hormones

These agents stimulate the adrenal cortex to release of corticosteroids.


Corticotropin (ACTH, Acthar)

Efficacy in this syndrome is variable. However, ACTH is associated with serious, potentially life-threatening side effects. Only anticonvulsant medication that must be administered by IM injection. ACTH gel preparation used in epilepsy.
No consensus on ACTH dosing for infants. In infantile spasms, prospective single-blind study showed no difference in effectiveness of high-dose, long-duration corticotropin (150 U/m2/d for 3 wk then taper over 9 wk) versus low-dose, short-duration corticotropin (20-30 U/d for 2-6 wk then taper over 1 wk) with respect to spasm cessation and improvement in patient's EEG; hypertension was more common with larger doses.

Adult

Pediatric

Daily dosages expressed as U/d (most common), U/m2/d, or U/kg/d
Regimens include 5-40 U/d IM for 1-6 wk and larger dosages of 40-160 U/d IM for 3-12 mo; using alternative methods of expressing dosages, some authors recommend 150 U/m2/d IM for 6 wk or 5-8 U/kg/d IM in divided doses for 2-3 wk

May decrease effects of aspirin, indomethacin, and insulin; diuretics increase effects

Documented hypersensitivity; scleroderma; recent surgery; congestive heart failure; primary adrenal insufficiency; hypercortisolism; active herpes infection; active tuberculosis; herpes simplex ocular infection; thromboembolic disease; active serious bacterial, viral, or fungal infection
ACTH may interfere with effects of vaccines/immunizations (should be avoided)

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Avoid vaccines and immunizations during ACTH therapy; due to increased risk of infection, hypertension, hypertrophic cardiomyopathy, and electrolyte disturbances, careful and frequent clinical and laboratory monitoring of patient essential; caution in Cushing disease, hypertension, hypokalemia, hypernatremia, diverticulitis, ulcerative colitis or intestinal anastomosis, renal disease, diabetes mellitus, hypothyroidism, hepatic disease


Prednisone (Deltasone, Meticorten, Orasone)

Few comparative studies have been performed between ACTH and prednisone. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Adult

Pediatric

Not established; possible PO regimens include the following:
Month 1: 2 mg/kg qd
Month 2: 1.5 mg/kg qd
Month 3: 1 mg/kg qd
Month 4: 1 mg/kg qod
Month 5: 0.5 mg/kg qod
Month 6: 0.25 mg/kg qod

Estrogens may decrease clearance; may cause digoxin (ie, digitalis) toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Documented hypersensitivity; viral, fungal, tubercular skin, or connective tissue infections; peptic ulcer disease; hepatic dysfunction; GI disease

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Prolonged therapy can affect metabolic, GI, neurological/behavioral, dermatologic, and endocrine systems; adverse metabolic events can include (but are not limited to) fluid retention and electrolyte disturbances (eg, hypernatremia, hypokalemia, hypokalemic metabolic alkalosis, hypocalcemia), edema, hypertension, and hyperglycemia; adverse GI events can include nausea, vomiting, abdominal pain, anorexia, diarrhea, constipation, gastritis, esophageal ulceration, weight loss, and delayed growth; adverse neurological and behavioral events reported during prolonged administration can include headache, insomnia, restlessness, mood lability, anxiety, personality changes, and psychosis; adverse visual events may include exophthalmos, retinopathy, posterior subcapsular cataracts, and ocular hypertension; adverse dermatologic effects can include skin atrophy, diaphoresis, impaired wound healing, facial erythema, hirsutism, ecchymosis, and easy bruising; adverse endocrinologic effects from prolonged use include hypercorticism and physiological dependence
Caution in patients with congestive heart failure, hypertension, glaucoma, GI disease, diverticulitis, intestinal anastomosis, hepatic disease, hypoalbuminemia, peptic ulcer disease, renal disease, osteoporosis, diabetes mellitus, hypothyroidism, coagulopathy or thromboembolic disease, or potential impending GI perforation

Anticonvulsant agents

These agents prevent seizure recurrence and terminate clinical and electrical seizure activity. If absence seizures present, ethosuximide is the appropriate medication. This may be the case for patients with chronic absence epilepsy. These agents may be used in conjunction with an anticonvulsive AED, such as phenytoin (Dilantin), for patients at risk of tonic-clonic seizures in whom VPA is contraindicated.


Carbamazepine (Tegretol)

Appears to act by reducing polysynaptic responses and blocking posttetanic potentiation. Major mechanism of action is to reduce sustained high-frequency repetitive neural firing.

Adult

200 mg bid (100 mg qid of susp); increase at weekly intervals by no more than 200 mg/d using tid/qid regimen (2 times/d with extended release) until best response obtained; not to exceed 1600 mg/d

Pediatric

<6 years: 10-20 mg/kg/d bid/tid (qid with susp); increase weekly to achieve optimal clinical response administered tid/qid
6-12 years: 100 mg bid (50 mg qid of susp); increase gradually at weekly intervals by adding 100 mg/d using tid/qid regimen (bid with extended release) until best response obtained; not to exceed 1000 mg/d
>12 years: Administer as in adults; not to exceed 1000 mg/d in children aged 12-15 years or 1200 mg/d in patients >15 years

Do not coadminister with MAOIs
May increase serum danazol levels significantly within 30 d of danazol coadministration (avoid whenever possible); cimetidine may increase toxicity, especially if taken in first 4 wk of therapy; may decrease primidone and phenobarbital levels (their coadministration may increase carbamazepine levels)

Documented hypersensitivity; history of bone marrow depression; MAOIs within last 14 d

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Do not use to relieve minor aches or pains; caution with increased intraocular pressure; obtain CBC and serum iron prior to treatment, during first 2 months, and yearly or every other year thereafter; can cause drowsiness, dizziness, and blurred vision; caution while driving or performing other tasks requiring alertness


Diazepam (Valium)

Long-acting benzodiazepine. Anxiolytic and anticonvulsant properties; effective for multiple seizure types, although usually used for control of intermittent episodes of increased seizure activity in epilepsy patients on stable anticonvulsant regimens.
Mechanism of action based on inhibition of neuronal excitation through binding to gamma-aminobutyric acid (GABA) and more specifically to GABA-A receptors.
Available in oral solution (5 mg/5 mL or 5 mg/mL), tablets (Valium) 2 mg, 5 mg, 10 mg, rectal gel (Diastat or Diastat AcuDial delivery system and injection), solution (5 mg/mL).

Adult

Status epilepticus: 5-10 mg IV q10-15 min up to 30 mg in 8-h period; may repeat in 2-4 h

Pediatric

Febrile seizure prophylaxis (oral): 1 mg/kg/d PO divided q8h; initiate therapy at first sign of fever and continue for 24 h after fever is gone
Status epilepticus (IV): Neonates: (Not recommended as first-line agent; injection contains benzoic acid, benzyl alcohol, and sodium benzoate; see Warnings) 0.1-0.3 mg/kg/dose IV given over 3-5 min, q15-30min to maximum total dose of 2 mg
Infants >30 d and children <5 years: 0.05-0.3 mg/kg/dose IV given over 3-5min, q15-30min to maximum total dose of 5 mg or 0.2-0.5 mg/dose q2-5min to maximum total dose of 5 mg; repeat in 2-4 h prn
Children >5 years: 0.05-0.3 mg/kg/dose IV given over 3-5 min, q15-30min to maximum total dose of 10 mg or 1 mg/dose q2-5min to maximum of 10 mg; repeat in 2-4 h prn

CNS depressants (alcohol, barbiturates, opioids) may enhance sedation and respiratory depression of diazepam; enzyme inducers may increase hepatic metabolism of diazepam; cimetidine and erythromycin may decrease metabolism of diazepam; valproic acid may displace diazepam from binding sites, which may result in increase in sedative effects; concurrent use of diazepam with ritonavir not recommended
Grapefruit juice significantly increases oral bioavailability of diazepam

Documented hypersensitivity to diazepam or any component; possible cross-sensitivity with other benzodiazepines; not for use in comatose patients, with preexisting CNS depression, respiratory depression, narrow-angle glaucoma, or severe uncontrolled pain; abrupt discontinuation may cause withdrawal symptoms or seizures

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Diazepam has been associated with increasing the frequency of grand mal seizures and an increase in seizure frequency; caution with drugs that may decrease diazepam metabolism and elderly or debilitated patients, patients with hepatic disease (including alcoholics), or renal impairment; active metabolites with extended half-lives may lead to delayed accumulation and adverse effects; caution in patients with respiratory disease or impaired gag reflex
Acute hypotension, muscle weakness, apnea, and cardiac arrest have occurred with parenteral administration; acute effects may be more prevalent in patients receiving concurrent barbiturates, narcotics, or ethanol; appropriate resuscitative equipment and qualified personnel should be available during administration and monitoring; avoid use of injection in patients with shock, coma, or acute ethanol intoxication; intra-arterial injection or extravasation of parenteral formulation should be avoided; parenteral formulation contains propylene glycol, which has been associated with toxicity when administered in high dosages; administration of rectal gel should only be performed by individuals trained to recognize characteristic seizure activity for which product is indicated, and capable of monitoring response to determine need for additional medical intervention
Causes CNS depression (dose-related) resulting in sedation, dizziness, confusion, or ataxia, which may impair physical and mental capabilities; caution patients about performing tasks that require mental alertness (eg, operating machinery, driving); caution in patients receiving other CNS depressants or psychoactive agents; effects with other sedative drugs or ethanol may be potentiated dosage of narcotics should be reduced by approximately one third when diazepam added; benzodiazepines have been associated with falls and traumatic injury and should be used with extreme caution in patients who are at risk of these events (especially elderly persons); caution in patients with depression, particularly if suicidal risk may be present; caution in patients with a history of drug dependence (benzodiazepines have been associated with dependence and acute withdrawal symptoms on discontinuation or reduction in dose); acute withdrawal, including seizures, may be precipitated in patients after administration of flumazenil to patients receiving long-term benzodiazepine therapy
Diazepam has been associated with anterograde amnesia; paradoxical reactions, including hyperactive or aggressive behavior, have been reported with benzodiazepines, particularly in adolescent/pediatric or psychiatric patients; does not have analgesic, antidepressant, or antipsychotic properties; precipitates absence status


Valproic acid (Depakote, Depakene, Depacon)

Chemically unrelated to other drugs used to treat seizure disorders.
Although mechanism of action not established, activity may be related to increased brain levels of GABA or enhanced GABA action. Also may potentiate postsynaptic GABA responses, affect potassium channel, or have direct membrane-stabilizing effect. For conversion to monotherapy, concomitant AED dosage ordinarily can be reduced by approximately 25% every 2 wk. Reduction may be started at initiation of therapy or delayed by 1-2 wk if concern that seizures are likely to occur with reduction. Monitor patients closely during this period for increased seizure frequency. As adjunctive therapy, may be added to patient's regimen at dosage of 10-15 mg/kg/d. The dosage may be increased by 5-10 mg/kg/wk to achieve optimal clinical response.
Ordinarily, optimal clinical response is achieved at daily doses <60 mg/kg/d.

Adult

Monotherapy: 10-15 mg/kg/d PO in 1-3 divided doses, increase by 5-10 mg/kg/wk until seizures controlled or adverse effects prevent further increases; not to exceed 60 mg/kg/d; if total daily dose >250 mg, give in divided doses

Pediatric

Administer as in adults

Cimetidine, salicylates, felbamate, and erythromycin may increase toxicity; rifampin may reduce levels significantly; in children, aspirin causes decreased protein binding and metabolism of valproate; may result in variable changes of carbamazepine concentrations with possible loss of seizure control; may increase diazepam and ethosuximide toxicity (monitor closely); may increase phenobarbital and phenytoin levels, while either one may decrease valproate levels; may displace warfarin from protein-binding sites (monitor coagulation tests); may increase zidovudine levels in HIV-seropositive patients

Documented hypersensitivity; hepatic disease/dysfunction

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Thrombocytopenia and abnormal coagulation parameters have occurred; risk of thrombocytopenia increases significantly at total trough plasma concentrations >110 mcg/mL in females and >135 mcg/mL in males; before initiating therapy, at periodic intervals, and prior to surgery, determine platelet count and bleeding time; reduce dose or discontinue therapy if hemorrhage, bruising, or hemostasis/coagulation disorder occurs
Hyperammonemia, resulting in hepatotoxicity, may occur; monitor patients closely for appearance of malaise, weakness, facial edema, anorexia, jaundice, and vomiting; may cause drowsiness


Ethosuximide (Zarontin)

Succinimide AED. Effective only against absence seizures. Has no effect on generalized tonic-clonic, myoclonic, atonic, or partial seizures.
Mechanism of action based on reducing current in T-type calcium channels found on thalamic neurons. Spike-and-wave pattern during petit mal seizures thought to be initiated in thalamocortical relays by activation of these channels.
Available in large 250-mg capsules, which may be difficult for some children to swallow, and as syrup (250 mg/5 mL).

Adult

250 mg PO bid; use 250-mg increments q4-7d until seizures controlled or maximum daily dose of 1.5 g reached

Pediatric

<6 years: 15 mg/kg/d PO divided bid initially; not to exceed initial dose of 250 mg; may increase to effect q4-7d
Maintenance dose: 15-40 mg/kg/d divided bid
>6 years: Administer as in adults

Phenytoin, carbamazepine, primidone, or phenobarbital may decrease effects; isoniazid may inhibit hepatic metabolism, increasing toxicity

Documented hypersensitivity; blood dyscrasias; renal or hepatic disease

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Blood dyscrasias, which may be fatal, may occur (monitor CBC); caution in hepatic or renal disease; abrupt withdrawal of drug may precipitate absence status

More on Epileptic and Epileptiform Encephalopathies

Overview: Epileptic and Epileptiform Encephalopathies
Differential Diagnoses & Workup: Epileptic and Epileptiform Encephalopathies
Treatment & Medication: Epileptic and Epileptiform Encephalopathies
Follow-up: Epileptic and Epileptiform Encephalopathies
Multimedia: Epileptic and Epileptiform Encephalopathies
References
[ CLOSE WINDOW ]

References

  1. A glossary of terms most commonly used by clinical electroencephalographers. Electroencephalogr Clin Neurophysiol. Nov 1974;37(5):538-48. [Medline].

  2. Nabbout R, Dulac O. Epileptic encephalopathies: a brief overview. J Clin Neurophysiol. Nov-Dec 2003;20(6):393-7. [Medline].

  3. Engel J Jr. A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology. Epilepsia. Jun 2001;42(6):796-803. [Medline].

  4. Coppola G, Plouin P, Chiron C, Robain O, Dulac O. Migrating partial seizures in infancy: a malignant disorder with developmental arrest. Epilepsia. Oct 1995;36(10):1017-24. [Medline].

  5. Moruzzi G, Magoun HW. Brain stem reticular formation and activation of the EEG. 1949. J Neuropsychiatry Clin Neurosci. Spring 1995;7(2):251-67. [Medline].

  6. Holmes GL, Lenck-Santini PP. Role of interictal epileptiform abnormalities in cognitive impairment. Epilepsy Behav. May 2006;8(3):504-15. [Medline].

  7. Shewmon DA, Erwin RJ. Transient impairment of visual perception induced by single interictal occipital spikes. J Clin Exp Neuropsychol. Oct 1989;11(5):675-91. [Medline].

  8. Shewmon DA, Erwin RJ. The effect of focal interictal spikes on perception and reaction time. II. Neuroanatomic specificity. Electroencephalogr Clin Neurophysiol. Apr 1988;69(4):338-52. [Medline].

  9. Kasteleijn-Nolst Trenite DG. Transient cognitive impairment during subclinical epileptiform electroencephalographic discharges. Semin Pediatr Neurol. Dec 1995;2(4):246-53. [Medline].

  10. Aarts JH, Binnie CD, Smit AM, Wilkins AJ. Selective cognitive impairment during focal and generalized epileptiform EEG activity. Brain. Mar 1984;107 (Pt 1):293-308. [Medline].

  11. Binnie CD. Cognitive impairment during epileptiform discharges: is it ever justifiable to treat the EEG?. Lancet Neurol. Dec 2003;2(12):725-30. [Medline].

  12. Binnie CD. Significance and management of transitory cognitive impairment due to subclinical EEG discharges in children. Brain Dev. Jan-Feb 1993;15(1):23-30. [Medline].

  13. Binnie CD, Kasteleijn-Nolst Trenite DG, Smit AM, Wilkins AJ. Interactions of epileptiform EEG discharges and cognition. Epilepsy Res. Jul 1987;1(4):239-45. [Medline].

  14. Aldenkamp AP, Overweg J, Gutter T, Beun AM, Diepman L, Mulder OG. Effect of epilepsy, seizures and epileptiform EEG discharges on cognitive function. Acta Neurol Scand. Apr 1996;93(4):253-9. [Medline].

  15. Nicolai J, Aldenkamp AP, Arends J, Weber JW, Vles JS. Cognitive and behavioral effects of nocturnal epileptiform discharges in children with benign childhood epilepsy with centrotemporal spikes. Epilepsy Behav. Feb 2006;8(1):56-70. [Medline].

  16. Massa R, de Saint-Martin A, Carcangiu R, et al. EEG criteria predictive of complicated evolution in idiopathic rolandic epilepsy. Neurology. Sep 25 2001;57(6):1071-9. [Medline].

  17. Morrell F. Secondary epileptogenesis in man. Arch Neurol. Apr 1985;42(4):318-35. [Medline].

  18. Morrell F, Whisler WW, Smith MC, et al. Landau-Kleffner syndrome. Treatment with subpial intracortical transection. Brain. Dec 1995;118 (Pt 6):1529-46. [Medline].

  19. Kobayashi K, Murakami N, Yoshinaga H, Enoki H, Ohtsuka Y, Ohtahara S. Nonconvulsive status epilepticus with continuous diffuse spike-and-wave discharges during sleep in childhood. Jpn J Psychiatry Neurol. Sep 1988;42(3):509-14. [Medline].

  20. Guzzetta F, Battaglia D, Veredice C, et al. Early thalamic injury associated with epilepsy and continuous spike-wave during slow sleep. Epilepsia. Jun 2005;46(6):889-900. [Medline].

  21. Kramer U, Nevo Y, Neufeld MY, Fatal A, Leitner Y, Harel S. Epidemiology of epilepsy in childhood: a cohort of 440 consecutive patients. Pediatr Neurol. Jan 1998;18(1):46-50. [Medline].

  22. Aicardi J, Ohtahara S. Severe neonatal epilepsies with suppression-burst pattern. In: Roger J, Thomas P, Bureau M, Hirsch D, Dravet C, Genton P. Epileptic Syndromes in Infancy, Childhood and Adolescence. Fourth Edition. John Libbey Eurotext; 2005:Chapter 3.

  23. Ohtahara S, Yamatogi Y. Ohtahara syndrome: with special reference to its developmental aspects for differentiating from early myoclonic encephalopathy. Epilepsy Res. Aug 2006;70 Suppl 1:S58-67. [Medline].

  24. Hrachovy RA, Frost JD. Severe Encephalopathic Epilepsy in Infants: Infantile Spasms (West Syndrome). In: Pellock JM, Bourgeois BFD, Dodson WE. Pediatric Epilepsy. Third Edition. New York, NY: Demos Medical Publishing; 2008:16.

  25. Chiron C, Marchand MC, Tran A, et al. Stiripentol in severe myoclonic epilepsy in infancy: a randomised placebo-controlled syndrome-dedicated trial. STICLO study group. Lancet. Nov 11 2000;356(9242):1638-42. [Medline].

  26. Hurst DL. Epidemiology of severe myoclonic epilepsy of infancy. Epilepsia. Jul-Aug 1990;31(4):397-400. [Medline].

  27. Dalla Bernardina B, Fontana E, Darra F. Myoclonic status in non-progressive encephalopathies. International Leauge Against Epilepsy. Available at http://www.ilae.org/ctf/myoclon_stat_nonpro_enceph.html. Accessed July 8, 1999.

  28. Oguni H, Hayashi K, Imai K, et al. Idiopathic myoclonic-astatic epilepsy of early childhood--nosology based on electrophysiologic and long-term follow-up study of patients. Adv Neurol. 2005;95:157-74. [Medline].

  29. Sasagawa M, Kioi Y. [A successful treatment with intravenous high doses of gamma globulin for a minor status in a patient with Doose syndrome]. No To Hattatsu. May 1997;29(3):261-3. [Medline].

  30. Guerrini R, Parmeggiani L, Bonanni P, Kaminska A, Dulac O. Myoclonic astatic epilepsy. In: Roger J, Bureau M, Dravet C, Genton P, Tassinari CA, Wolf P. Epileptic Syndromes in Infancy, Childhood and Adolescence. Fourth Edition. Montrouge, France: John Libbey Eurotext; 2005:Chapter 8.

  31. Morita DA, Glauser TA. Lennox-Gastaut Syndrome. In: Pellock JM, Bourgeois BFD, Dodson E. Pediatric Epilepsy: Diagnosis and Therapy. Third. New York, NY: Demos Medical Publishing; 2008:Chapter 21.

  32. Oguni H, Hayashi K, Osawa M. Long-term prognosis of Lennox-Gastaut syndrome. Epilepsia. 1996;37 Suppl 3:44-7. [Medline].

  33. McKinney W, McGreal DA. An aphasic syndrome in children. Can Med Assoc J. Mar 16 1974;110(6):637-9. [Medline].

  34. Riviello JJ, Hadjiloizou S. The Landau-Kleffner Syndrome and Continuous Spike-Waves during Sleep. In: Pellock JM, Bourgeois BFD, Dodson WE. Pediatric Epilepsy: Diagnosis and Therapy. Third Edition. New York, NY: Demos Medical Publishing; 2008:Chapter 24.

  35. Patry G, Lyagoubi S, Tassinari CA. Subclinical "electrical status epilepticus" induced by sleep in children. A clinical and electroencephalographic study of six cases. Arch Neurol. Mar 1971;24(3):242-52. [Medline].

  36. Van Hirtum-Das M, Licht EA, Koh S, Wu JY, Shields WD, Sankar R. Children with ESES: variability in the syndrome. Epilepsy Res. Aug 2006;70 Suppl 1:S248-58. [Medline].

  37. Smith MC, Hoeppner TJ. Epileptic encephalopathy of late childhood: Landau-Kleffner syndrome and the syndrome of continuous spikes and waves during slow-wave sleep. J Clin Neurophysiol. Nov-Dec 2003;20(6):462-72. [Medline].

  38. Takeoka M, Riviello JJ Jr, Duffy FH, et al. Bilateral volume reduction of the superior temporal areas in Landau-Kleffner syndrome. Neurology. Oct 12 2004;63(7):1289-92. [Medline].

  39. Strug LJ, Clarke T, Chiang T, et al. Centrotemporal sharp wave EEG trait in rolandic epilepsy maps to Elongator Protein Complex 4 (ELP4). Eur J Hum Genet. Jan 28 2009;[Medline].

  40. Weglage J, Demsky A, Pietsch M, Kurlemann G. Neuropsychological, intellectual, and behavioral findings in patients with centrotemporal spikes with and without seizures. Dev Med Child Neurol. Oct 1997;39(10):646-51. [Medline].

  41. Staden U, Isaacs E, Boyd SG, Brandl U, Neville BG. Language dysfunction in children with Rolandic epilepsy. Neuropediatrics. Oct 1998;29(5):242-8. [Medline].

  42. Massa R, de Saint-Martin A, Carcangiu R, et al. EEG criteria predictive of complicated evolution in idiopathic rolandic epilepsy. Neurology. Sep 25 2001;57(6):1071-9. [Medline].

  43. Nicolai J, van der Linden I, Arends JB, et al. EEG characteristics related to educational impairments in children with benign childhood epilepsy with centrotemporal spikes. Epilepsia. Nov 2007;48(11):2093-100. [Medline].

  44. Saint-Martin AD, Seegmuller C, Carcangiu R, et al. [Cognitive consequences of Rolandic Epilepsy]. Epileptic Disord. 2001;3 Spec No 2:SI59-65. [Medline].

  45. Metz-Lutz MN, Filippini M. Neuropsychological findings in Rolandic epilepsy and Landau-Kleffner syndrome. Epilepsia. 2006;47 Suppl 2:71-5. [Medline].

  46. Tuchman R, Rapin I. Epilepsy in autism. Lancet Neurol. Oct 2002;1(6):352-8. [Medline].

  47. Levisohn PM. The autism-epilepsy connection. Epilepsia. 2007;48 Suppl 9:33-5. [Medline].

  48. Deonna T, Roulet E. Autistic spectrum disorder: evaluating a possible contributing or causal role of epilepsy. Epilepsia. 2006;47 Suppl 2:79-82. [Medline].

  49. Landau W, Kleffner FR. Syndrome of acquired aphasia with convulsive disorder in children. Neurology. 1957;7:523-530.

  50. Deuel RK, Lenn NJ. Treatment of acquired epileptic aphasia. J Pediatr. Jun 1977;90(6):959-61. [Medline].

  51. Aeby A, Poznanski N, Verheulpen D, Wetzburger C, Van Bogaert P. Levetiracetam efficacy in epileptic syndromes with continuous spikes and waves during slow sleep: experience in 12 cases. Epilepsia. Dec 2005;46(12):1937-42. [Medline].

  52. De Negri M, Baglietto MG, Battaglia FM, Gaggero R, Pessagno A, Recanati L. Treatment of electrical status epilepticus by short diazepam (DZP) cycles after DZP rectal bolus test. Brain Dev. Sep-Oct 1995;17(5):330-3. [Medline].

  53. Hadjiloizou SM, Bourgeois BFD, Duffy FH, et al. Childhood-onset epileptic encephalopathies with sleep activated EEG (EESA_EEG) and high dose diazepam treatment (HDDT): Review of a 5-year experience at Children's Hospital Boston. Epilepsia. Suppl. 8; 2005;46:150-151.

  54. Marescaux C, Hirsch E, Finck S, et al. Landau-Kleffner syndrome: a pharmacologic study of five cases. Epilepsia. Nov-Dec 1990;31(6):768-77. [Medline].

  55. McKinney W, McGreal DA. An aphasic syndrome in children. Can Med Assoc J. Mar 16 1974;110(6):637-9. [Medline].

  56. Lerman P, Lerman-Sagie T, Kivity S. Effect of early corticosteroid therapy for Landau-Kleffner syndrome. Dev Med Child Neurol. Mar 1991;33(3):257-60. [Medline].

  57. Chez MG, Loeffel M, Buchanan CP, et al. Pulse high-dose steroids as combination therapy with valproic acid in epileptic aphasia patients with pervasive developmental delay or autism. Ann Neurol. 1998;44(3):539.

  58. Tsuru T, Mori M, Mizuguchi M, Momoi MY. Effects of high-dose intravenous corticosteroid therapy in Landau-Kleffner syndrome. Pediatr Neurol. Feb 2000;22(2):145-7. [Medline].

  59. Sinclair DB, Snyder TJ. Corticosteroids for the treatment of Landau-kleffner syndrome and continuous spike-wave discharge during sleep. Pediatr Neurol. May 2005;32(5):300-6. [Medline].

  60. [Guideline] Karis JP, Seidenwurm DJ, Davis PC, Brunberg JA, De La Paz RL, Dormont PD, et al. ACR Appropriateness Criteria epilepsy. Epilepsy. [online publication]. 2006;8. [Full Text].

  61. [Guideline] Krumholz A, Wiebe S, Gronseth G, Shinnar S, Levisohn P, Ting T, et al. Practice Parameter: evaluating an apparent unprovoked first seizure in adults (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. Nov 20 2007;69(21):1996-2007. [Medline]. [Full Text].

  62. [Guideline] Hirtz D, Ashwal S, Berg A, Bettis D, Camfield C, Camfield P, et al. Practice parameter: evaluating a first nonfebrile seizure in children: report of the quality standards subcommittee of the American Academy of Neurology, The Child Neurology Society, and The American Epilepsy Society. Neurology. Sep 12 2000;55(5):616-23. [Medline]. [Full Text].

  63. Morrell F, Whisler WW, Bleck TP. Multiple subpial transection: a new approach to the surgical treatment of focal epilepsy. J Neurosurg. Feb 1989;70(2):231-9. [Medline].

  64. Morrell F, Whisler WW, Smith MC, et al. Landau-Kleffner syndrome. Treatment with subpial intracortical transection. Brain. Dec 1995;118 (Pt 6):1529-46. [Medline].

  65. Grote CL, Van Slyke P, Hoeppner JA. Language outcome following multiple subpial transection for Landau-Kleffner syndrome. Brain. Mar 1999;122 (Pt 3):561-6. [Medline].

  66. Irwin K, Birch V, Lees J, et al. Multiple subpial transection in Landau-Kleffner syndrome. Dev Med Child Neurol. Apr 2001;43(4):248-52. [Medline].

  67. Aicardi J. Epilepsies with Predominantly Myoclonic Seizures. In: Epilepsy in Children.

  68. Aicardi J, Chevrie JJ. Atypical benign partial epilepsy of childhood. Dev Med Child Neurol. Jun 1982;24(3):281-92. [Medline].

  69. Aldenkamp AP. Effect of seizures and epileptiform discharges on cognitive function. Epilepsia. 1997;38 Suppl 1:S52-5. [Medline].

  70. Barton M, Volkmar F. How commonly are known medical conditions associated with autism?. J Autism Dev Disord. Aug 1998;28(4):273-8. [Medline].

  71. Beaumanoir A. The Landau-Kleffner Syndrome. In: Roger J, Bureau, Dravet C, eds. Epileptic Syndromes in Infancy, Childhood, and Adolescence. 2nd ed. London: John Libbey and Company Ltd; 1992:231-43.

  72. Besag FM. The therapeutic dilemma: treating subtle seizures or indulging in electroencephalogram cosmetics?. Semin Pediatr Neurol. Dec 1995;2(4):261-8. [Medline].

  73. Bishop DV. Age of onset and outcome in 'acquired aphasia with convulsive disorder' (Landau-Kleffner syndrome). Dev Med Child Neurol. Dec 1985;27(6):705-12. [Medline].

  74. Bolanos A, Mikati M, Holmes G. Landau-Kleffner Syndrome: Clinical and EEG Features. Neurology. 1995;45(Supp14):A180.

  75. Bolanos A, Urion DK, Helmers SL. Serial electroencephalographic changes in children with Landau-Kleffner Syndrome. Epilepsia. 1997;38(Suppl.3):27.

  76. Boyer JP, Deschatrette A. [Convulsive autism or Lennox-Gastaut syndrome? Apropos of 9 cases of primary autism associated with Lennox-Gastaut syndrome]. Neuropsychiatr Enfance Adolesc. Mar 1980;28(3):93-100. [Medline].

  77. Childs JA, Blair JL. Valproic acid treatment of epilepsy in autistic twins. J Neurosci Nurs. Aug 1997;29(4):244-8. [Medline].

  78. Chudley AE, Gutierrez E, Jocelyn LJ, Chodirker BN. Outcomes of genetic evaluation in children with pervasive developmental disorder. J Dev Behav Pediatr. Oct 1998;19(5):321-5. [Medline].

  79. Chugani HT, Da Silva E, Chugani DC. Infantile spasms: III. Prognostic implications of bitemporal hypometabolism on positron emission tomography. Ann Neurol. May 1996;39(5):643-9. [Medline].

  80. Commission on Classification and Terminology of the International League Against. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia. Jul-Aug 1989;30(4):389-99. [Medline].

  81. Connolly AM, Chez M, Streif EM, et al. Brain-derived neurotrophic factor and autoantibodies to neural antigens in sera of children with autistic spectrum disorders, Landau-Kleffner syndrome, and epilepsy. Biol Psychiatry. Feb 15 2006;59(4):354-63. [Medline].

  82. Connolly AM, Chez MG, Pestronk A, Arnold ST, Mehta S, Deuel RK. Serum autoantibodies to brain in Landau-Kleffner variant, autism, and other neurologic disorders. J Pediatr. May 1999;134(5):607-13. [Medline].

  83. Deonna T. Cognitive and behavioral disturbances as epileptic manifestations in children: an overview. Semin Pediatr Neurol. Dec 1995;2(4):254-60. [Medline].

  84. Deonna TW, Roulet E, Fontan D, Marcoz JP. Speech and oromotor deficits of epileptic origin in benign partial epilepsy of childhood with rolandic spikes (BPERS). Relationship to the acquired aphasia-epilepsy syndrome. Neuropediatrics. Apr 1993;24(2):83-7. [Medline].

  85. Deykin EY, MacMahon B. The incidence of seizures among children with autistic symptoms. Am J Psychiatry. Oct 1979;136(10):1310-2. [Medline].

  86. Diagnostic and Statistic Manual of Mental Disorders,. (DSM IV). 4th ed. Washington, DC: American Psychiatric Association; 1994:65-78.

  87. Duffy FH, Riviello JJ. Changes in Frequency-Modulated steady state auditory evoked response (FM-AER) after treatment in Landau-Kleffner Syndrome (LKS) and LKS variants (LKSV). Epilepsia. 1999;40(Suppl. 7):84-85.

  88. Echenne B, Cheminal R, Rivier F, Negre C, Touchon J, Billiard M. Epileptic electroencephalographic abnormalities and developmental dysphasias: a study of 32 patients. Brain Dev. Jul 1992;14(4):216-25. [Medline].

  89. Eriksson K, Kylliainen A, Hirvonen K, Nieminen P, Koivikko M. Visual agnosia in a child with non-lesional occipito-temporal CSWS. Brain Dev. Jun 2003;25(4):262-7. [Medline].

  90. Fayad MN, Choueiri R, Mikati M. Landau-Kleffner syndrome: consistent response to repeated intravenous gamma-globulin doses: a case report. Epilepsia. Apr 1997;38(4):489-94. [Medline].

  91. Fitzgerald LF, Stone JL, Hughes JR, Melyn MA, Lansky LL. The Lennox-Gastaut syndrome: electroencephalographic characteristics, clinical correlates, and follow-up studies. Clin Electroencephalogr. Oct 1992;23(4):180-9. [Medline].

  92. Fombonne E. The epidemiology of autism: a review. Psychol Med. Jul 1999;29(4):769-86. [Medline].

  93. Galanopoulou AS, Bojko A, Lado F, Moshé SL. The spectrum of neuropsychiatric abnormalities associated with electrical status epilepticus in sleep. Brain Dev. Aug 2000;22(5):279-95. [Medline].

  94. Giannakodimos S, Ferrie CD, Panayiotopoulos CP. Qualitative and quantitative abnormalities of breath counting during brief generalized 3 Hz spike and slow wave 'subclinical' discharges. Clin Electroencephalogr. Oct 1995;26(4):200-3. [Medline].

  95. Gillberg C, Schaumann H. Epilepsy presenting as infantile autism? Two case studies. Neuropediatrics. Nov 1983;14(4):206-12. [Medline].

  96. Gillberg C, Wahlstrom J. Chromosome abnormalities in infantile autism and other childhood psychoses: a population study of 66 cases. Dev Med Child Neurol. Jun 1985;27(3):293-304. [Medline].

  97. Gordon K, Bawden H, Camfield P, Mann S, Orlik P. Valproic acid treatment of learning disorder and severely epileptiform EEG without clinical seizures. J Child Neurol. Jan 1996;11(1):41-3. [Medline].

  98. Guilhoto LMFF, Morrell F. Electrophysiological differences bewteen Landau-Kleffner Syndrome and other conditions showing the CSWS electrical pattern. Epilepsia 1994;35(Suppl. 8):126. Epilepsia. 1994;35(Suppl. 8):126.

  99. Gurrieri F, Battaglia A, Torrisi L, et al. Pervasive developmental disorder and epilepsy due to maternally derived duplication of 15q11-q13. Neurology. May 12 1999;52(8):1694-7. [Medline].

  100. Hall NE. Developmental language disorders. Semin Pediatr Neurol. Jun 1997;4(2):77-85. [Medline].

  101. Hirsch E, Maquet P, Metz-Lutz N-M, et al. The eponym 'Landau-Kleffner Syndrome' should not be restricted to childhood-acquired aphasia with epilepsy. In: Beaumanoir A, Bureau M, Deonna T, et al, eds. Continuous Spikes and Waves During Slow Sleep. London: John Libbey & Co; 1995:57-62.

  102. Hirsch E, Marescaux C, Maquet P, et al. Landau-Kleffner syndrome: a clinical and EEG study of five cases. Epilepsia. Nov-Dec 1990;31(6):756-67. [Medline].

  103. Hirsch E, Marescaux C, Maquet P, et al. Landau-Kleffner syndrome: a clinical and EEG study of five cases. Epilepsia. Nov-Dec 1990;31(6):756-67. [Medline].

  104. Holmes GL, McKeever M, Saunders Z. Epileptiform activity in aphasia of childhood: an epiphenomenon?. Epilepsia. Dec 1981;22(6):631-9. [Medline].

  105. Jayakar PB, Seshia SS. Electrical status epilepticus during slow-wave sleep: a review. J Clin Neurophysiol. Jul 1991;8(3):299-311. [Medline].

  106. Kasteleijn-Nolst Trenite DG, Bakker DJ, Binnie CD, Buerman A, Van Raaij M. Psychological effects of subclinical epileptiform EEG discharges. I. Scholastic skills. Epilepsy Res. Mar-Apr 1988;2(2):111-6. [Medline].

  107. Kasteleijn-Nolst Trenite DG, Smit AM, Velis DN, Willemse J, van Emde Boas W. On-line detection of transient neuropsychological disturbances during EEG discharges in children with epilepsy. Dev Med Child Neurol. Jan 1990;32(1):46-50. [Medline].

  108. Kawasaki Y, Yokota K, Shinomiya M, Shimizu Y, Niwa S. Brief report: electroencephalographic paroxysmal activities in the frontal area emerged in middle childhood and during adolescence in a follow-up study of autism. J Autism Dev Disord. Oct 1997;27(5):605-20. [Medline].

  109. Kurita H. Infantile autism with speech loss before the age of thirty months. J Am Acad Child Psychiatry. Mar 1985;24(2):191-6. [Medline].

  110. Lagae LG, Silberstein J, Gillis PL, Casaer PJ. Successful use of intravenous immunoglobulins in Landau-Kleffner syndrome. Pediatr Neurol. Feb 1998;18(2):165-8. [Medline].

  111. Lewine JD, Andrews R, Chez M, et al. Magnetoencephalographic patterns of epileptiform activity in children with regressive autism spectrum disorders. Pediatrics. Sep 1999;104(3 Pt 1):405-18. [Medline].

  112. Lockyer L, Rutter M. A five- to fifteen-year follow-up study of infantile psychosis. Br J Psychiatry. Aug 1969;115(525):865-82. [Medline].

  113. Lockyer L, Rutter M. A five- to fifteen-year follow-up study of infantile psychosis. IV. Patterns of cognitive ability. Br J Soc Clin Psychol. Jun 1970;9(2):152-63. [Medline].

  114. Maccario M, Hefferen SJ, Keblusek SJ, Lipinski KA. Development dysphasia and electroencephalographic abnormalities. Dev Med Child Neurol. Apr 1982;24(2):141-55. [Medline].

  115. Mantovani JF, Landau WM. Acquired aphasia with convulsive disorder: course and prognosis. Neurology. May 1980;30(5):524-9. [Medline].

  116. Marston D, Besag F, Binnie CD, Fowler M. Effects of transitory cognitive impairment on psychosocial functioning of children with epilepsy: a therapeutic trial. Dev Med Child Neurol. Jul 1993;35(7):574-81. [Medline].

  117. McLaren J, Bryson SE. Review of recent epidemiological studies of mental retardation: prevalence, associated disorders, and etiology. Am J Ment Retard. 1987;92:243-254.

  118. Mikati M, Fayad M, Choueri R. IVIG in Landau-Kleffner syndrome. Pediatr Neurol. Nov 1998;19(5):399-400. [Medline].

  119. Mikati MA, Lee WL, DeLong GR. Protracted epileptiform encephalopathy: an unusual form of partial complex status epilepticus. Epilepsia. Nov-Dec 1985;26(6):563-71. [Medline].

  120. Minshew NJ. Indices of neural function in autism: clinical and biologic implications. Pediatrics. May 1991;87(5 Pt 2):774-80. [Medline].

  121. Mouridsen SE, Rich B, Isager T. Epilepsy in disintegrative psychosis and infantile autism: a long-term validation study. Dev Med Child Neurol. Feb 1999;41(2):110-4. [Medline].

  122. Nass R, Devinsky O. Autistic regression with rolandic spikes. Neuropsychiatry Neuropsychol Behav Neurol. Jul 1999;12(3):193-7. [Medline].

  123. Nass R, Gross A, Devinsky O. Autism and autistic epileptiform regression with occipital spikes. Dev Med Child Neurol. Jul 1998;40(7):453-8. [Medline].

  124. Nass R, Petrucha D. Acquired aphasia with convulsive disorder: a pervasive developmental disorder variant. J Child Neurol. Oct 1990;5(4):327-8. [Medline].

  125. Nordin V, Gillberg C. The long-term course of autistic disorders: update on follow-up studies. Acta Psychiatr Scand. Feb 1998;97(2):99-108. [Medline].

  126. O'Tuama LA, Urion DK, Janicek MJ, Treves ST, Bjornson B, Moriarty JM. Regional cerebral perfusion in Landau-Kleffner syndrome and related childhood aphasias. J Nucl Med. Oct 1992;33(10):1758-65. [Medline].

  127. oguni. 122.

  128. Oguni H, Tanaka T, Hayashi K, et al. Treatment and long-term prognosis of myoclonic-astatic epilepsy of early childhood. Neuropediatrics. Jun 2002;33(3):122-32. [Medline].

  129. Olsson I, Steffenburg S, Gillberg C. Epilepsy in autism and autisticlike conditions. A population-based study. Arch Neurol. Jun 1988;45(6):666-8. [Medline].

  130. Papini M, Pasquinelli A, Armellini M, Orlandi D. Alertness and incidence of seizures in patients with Lennox-Gastaut syndrome. Epilepsia. Apr 1984;25(2):161-7. [Medline].

  131. Plioplys AV. Autism: electroencephalogram abnormalities and clinical improvement with valproic acid. Arch Pediatr Adolesc Med. Feb 1994;148(2):220-2. [Medline].

  132. Praline J, Hommet C, Barthez MA, et al. Outcome at adulthood of the continuous spike-waves during slow sleep and Landau-Kleffner syndromes. Epilepsia. Nov 2003;44(11):1434-40. [Medline].

  133. Rapin I. Autism. N Engl J Med. Jul 10 1997;337(2):97-104. [Medline].

  134. Rapin I. Autistic regression and disintegrative disorder: how important the role of epilepsy?. Semin Pediatr Neurol. Dec 1995;2(4):278-85. [Medline].

  135. Rescorla L, Mirak J. Normal language acquisition. Semin Pediatr Neurol. Jun 1997;4(2):70-6. [Medline].

  136. Riikonen R, Amnell G. Psychiatric disorders in children with earlier infantile spasms. Dev Med Child Neurol. Dec 1981;23(6):747-60. [Medline].

  137. Rossi PG, Parmeggiani A, Bach V, Santucci M, Visconti P. EEG features and epilepsy in patients with autism. Brain Dev. May-Jun 1995;17(3):169-74. [Medline].

  138. Rossi PG, Parmeggiani A, Posar A, Scaduto MC, Chiodo S, Vatti G. Landau-Kleffner syndrome (LKS): long-term follow-up and links with electrical status epilepticus during sleep (ESES). Brain Dev. Mar 1999;21(2):90-8. [Medline].

  139. Roulet Perez E. Syndromes of acquired epileptic aphasia and epilepsy with continuous spike-waves during sleep: models for prolonged cognitive impairment of epileptic origin. Semin Pediatr Neurol. Dec 1995;2(4):269-77. [Medline].

  140. Sato S, Dreifuss FE. Electroencephalographic findings in a patient with developmental expressive aphasia. Neurology. Feb 1973;23(2):181-5. [Medline].

  141. Scheffer IE, Jones L, Pozzebon M, Howell RA, Saling MM, Berkovic SF. Autosomal dominant rolandic epilepsy and speech dyspraxia: a new syndrome with anticipation. Ann Neurol. Oct 1995;38(4):633-42. [Medline].

  142. Scholtes FB, Hendriks MP, Renier WO. Cognitive deterioration and electrical status epilepticus during slow sleep. Epilepsy Behav. Mar 2005;6(2):167-73. [Medline].

  143. Shafrir Y, Prensky AL. Acquired epileptiform opercular syndrome: a second case report, review of the literature, and comparison to the Landau-Kleffner syndrome. Epilepsia. Oct 1995;36(10):1050-7. [Medline].

  144. Silver JM, Shin C, McNamara JO. Antiepileptogenic effects of conventional anticonvulsants in the kindling model of epilespy. Ann Neurol. Apr 1991;29(4):356-63. [Medline].

  145. Small JG. EEG and neurophysiological studies of early infantile autism. Biol Psychiatry. Aug 1975;10(4):385-97. [Medline].

  146. Smith MC, Pierre-Louis SJC, Kanner A, et al. Pathologic spectrum of acquired epileptic aphasia of childhood. Epilepsia. 1992;33(Suppl 3):115.

  147. Soprano AM, Garcia EF, Caraballo R, Fejerman N. Acquired epileptic aphasia: neuropsychologic follow-up of 12 patients. Pediatr Neurol. Oct 1994;11(3):230-5. [Medline].

  148. Stefanatos GA. Frequency modulation analysis in children with Landau-Kleffner syndrome. Ann N Y Acad Sci. Jun 14 1993;682:412-4. [Medline].

  149. Stefanatos GA, Foley C, Grover W, Doherty B. Steady-state auditory evoked responses to pulsed frequency modulations in children. Electroencephalogr Clin Neurophysiol. Jan 1997;104(1):31-42. [Medline].

  150. Stefanatos GA, Green GG, Ratcliff GG. Neurophysiological evidence of auditory channel anomalies in developmental dysphasia. Arch Neurol. Aug 1989;46(8):871-5. [Medline].

  151. Stefanatos GA, Grover W, Geller E. Case study: corticosteroid treatment of language regression in pervasive developmental disorder. J Am Acad Child Adolesc Psychiatry. Aug 1995;34(8):1107-11. [Medline].

  152. Tassinari CA, Bureau M, Dravet, et al. Epilepsy with continuous spikes and waves during slow sleep-otherwise described as ESES (Electrical status epilepticus of sleep). In: Roger J, Bureau M, Dravet C, eds. Epileptic Syndromes in Infancy, Childhood, and Adolescence. 2nd ed. London: John Libbey and Co Ltd; 1992:245-56.

  153. Taylor DC, Neville BG, Cross JH. Autistic spectrum disorders in childhood epilepsy surgery candidates. Eur Child Adolesc Psychiatry. Sep 1999;8(3):189-92. [Medline].

  154. Tuchman R, Rapin I. Epilepsy in autism. Lancet Neurol. Oct 2002;1(6):352-8. [Medline].

  155. Tuchman RF. Acquired epileptiform aphasia. Semin Pediatr Neurol. Jun 1997;4(2):93-101. [Medline].

  156. Tuchman RF, Rapin I. Regression in pervasive developmental disorders: seizures and epileptiform electroencephalogram correlates. Pediatrics. Apr 1997;99(4):560-6. [Medline].

  157. Tuchman RF, Rapin I, Shinnar S. Autistic and dysphasic children. I: Clinical characteristics. Pediatrics. Dec 1991;88(6):1211-8. [Medline].

  158. Tuchman RF, Rapin I, Shinnar S. Autistic and dysphasic children. II: Epilepsy. Pediatrics. Dec 1991;88(6):1219-25. [Medline].

  159. Veggiotti P, Beccaria F, Guerrini R, Capovilla G, Lanzi G. Continuous spike-and-wave activity during slow-wave sleep: syndrome or EEG pattern?. Epilepsia. Nov 1999;40(11):1593-601. [Medline].

  160. Vergnes M, Marescaux C, Depaulis A. Mapping of spontaneous spike and wave discharges in Wistar rats with genetic generalized non-convulsive epilepsy. Brain Res. Jul 16 1990;523(1):87-91. [Medline].

  161. Volkmar FR, Nelson DS. Seizure disorders in autism. J Am Acad Child Adolesc Psychiatry. Jan 1990;29(1):127-9. [Medline].

  162. Wilson S, Djukic A, Shinnar S, Dharmani C, Rapin I. Clinical characteristics of language regression in children. Dev Med Child Neurol. Aug 2003;45(8):508-14. [Medline].

  163. Wisniewski KE, Segan SM, Miezejeski CM, Sersen EA, Rudelli RD. The Fra(X) syndrome: neurological, electrophysiological, and neuropathological abnormalities. Am J Med Genet. Feb-Mar 1991;38(2-3):476-80. [Medline].

  164. Wong V. Epilepsy in children with autistic spectrum disorder. J Child Neurol. Oct 1993;8(4):316-22. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

epileptic encephalopathy, epileptic encephalopathies, epileptiform encephalopathy, epileptiform encephalopathies, catastrophic epilepsy, catastrophic epilepsies, epileptiform aphasia, malignant epilepsy, malignant epilepsies, early myoclonic encephalopathy, early infantile epileptic encephalopathy, Ohtahara syndrome, migrating partial epilepsy, migrating partial epilepsy in infancy, West syndrome, infantile spasms, severe myoclonic epilepsy in infancy, Dravet syndrome, myoclonic status, myoclonic status in non-progressive syndromes, myoclonic astatic epilepsy, Doose syndrome, Lennox-Gastaut syndrome, Landau-Kleffner syndrome, LKS, acquired epileptiform aphasia, verbal auditory agnosia, language regression, word deafness, continuous spikes and waves during slow wave sleep, electrical status epilepticus of sleep, autism, autistic spectrum disorders, pervasive development disorder, PDD, transient cognitive impairment, benign childhood epilepsy with centro-temporal spikes, BCECTS, benignrolandic epilepsy

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Dean Patrick Sarco, MD, Instructor, Department of Neurology, Harvard Medical School; Assistant Physician, Department of Neurology, Division of Epilepsy and Clinical Neurophysiology, Children's Hospital Boston
Dean Patrick Sarco, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

Coauthor(s)

Masanori Takeoka, MD, Assistant Professor, Department of Neurology, Harvard Medical School; Consulting Staff, Department of Neurology, Division of Epilepsy and Clinical Neurophysiology, Children's Hospital Boston
Masanori Takeoka, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, American Medical Association, Child Neurology Society, and Massachusetts Medical Society
Disclosure: Nothing to disclose.

Medical Editor

Robert Baumann, MD, Program Director, Professor, Departments of Neurology and Pediatrics, University of Kentucky
Robert Baumann, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American College of Epidemiology, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Jose E Cavazos, MD, PhD, FAAN, Associate Professor with Tenure, Departments of Neurology, Pharmacology, and Physiology, University of Texas Health Science Center at San Antonio; Co-Director, South Texas Comprehensive Epilepsy Center; Director of the Epilepsy Center, Audie L Murphy Veterans Affairs Medical Center
Jose E Cavazos, MD, PhD, FAAN is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society, and Society for Neuroscience
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD, Assistant Professor, Department of Pediatrics, Division of Pediatric Neurology, Department of Neurology, Oregon Health and Science University; Consulting Staff, Shriners Hospital for Children
Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.