Pediatric Drugs

, Volume 7, Issue 6, pp 377–389 | Cite as

Management of Landau-Kleffner Syndrome

Therapy In Practice


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.



Dr Mikati has received within the past 10 years research grant support and honoraria from GlaxoSmithKline, Sanofi-Synthelabo, UCB, Janssen-Cilag, Octapharma, and Pfizer. Mrs A. Shamseddine has received grant support from GlaxoSmithKline. The authors have no conflicts of interest that are directly relevant to the content of this review.


  1. 1.
    Landau WM, Kleffner FR. Syndrome of acquired aphasia with convulsive disorder in children. Neurology 1957; 7(8): 523–30PubMedCrossRefGoogle Scholar
  2. 2.
    Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989; 30(4): 389–99CrossRefGoogle Scholar
  3. 3.
    Mantovani JF, Landau WM. Acquired aphasia with convulsive disorder: course and prognosis. Neurology 1980; 30: 524–9PubMedCrossRefGoogle Scholar
  4. 4.
    Gordon N. The Landau-Kleffner syndrome: increased understanding. Brain Dev 1997; 19: 311–6PubMedCrossRefGoogle Scholar
  5. 5.
    Bishop DVM. Age of onset and outcome in ‘acquired aphasia with convulsive disorder’ (Landau-Kleffner syndrome). Dev Med Child Neurol 1985; 27(6): 705–12PubMedCrossRefGoogle Scholar
  6. 6.
    Tsuru T, Mori M, Mizuguchi M, et al. Effects of high-dose intravenous corticosteroid therapy in Landau-Kleffner syndrome. Pediatr Neurol 2000; 22: 145–7PubMedCrossRefGoogle Scholar
  7. 7.
    Lagae LG, Silberstein J, Gillis PL, et al. Successful use of intravenous immunoglobulins in Landau-Kleffner syndrome. Pediatr Neurol 1998; 18: 165–8PubMedCrossRefGoogle Scholar
  8. 8.
    Tassinari CA, Terzano G, Capocchi G, et al. Epileptic seizures during sleep in children. In: Penry JK, editor. The 8th International Symposium. New York: Raven Press, 1977: 345–54Google Scholar
  9. 9.
    Li M, Hao XY, Qing J, et al. Correlation between CSWS and aphasia in Landau-Kleffner syndrome: a study of three cases. Brain Dev 1996 May–Jun; 18(3): 197–200PubMedCrossRefGoogle Scholar
  10. 10.
    Hirsch E, Marescaux C, Maquet P, et al. Landau-Kleffner syndrome: a clinical and EEG study of five cases. Epilepsia 1990; 31(6): 756–67PubMedCrossRefGoogle Scholar
  11. 11.
    Kossoff EH, Boatman D, Freeman JM. Landau-Kleffner syndrome responsive to levetiracetam. Epilepsy Behav 2003; 4: 571–5PubMedCrossRefGoogle Scholar
  12. 12.
    Parline J, Hommet C, Barthez MA, et al. Outcome at adulthood of the continuous spike-waves during slow sleep and Landau-Kleffner syndromes. Epilepsia 2003; 44(11): 1434–40CrossRefGoogle Scholar
  13. 13.
    Mantovani JF. Autistic regression and Landau-Kleffner syndrome: progress or confusion? Dev Med Child Neurol 2000; 42: 349–53PubMedCrossRefGoogle Scholar
  14. 14.
    Lerman P, Lerman-Sagie T, Kivity S. Effects of early corticosteroid therapy for Landau-Kleffner syndrome. Dev Med Child Neurol 1991; 33(3): 257–60PubMedCrossRefGoogle Scholar
  15. 15.
    Paquier PF, Van Dongen HR, Loonen CB. The Landau-Kleffner syndrome or ‘acquired aphasia with convulsive disorder’ long-term follow-up of six children and a review of the recent literature. Arch Neurol 1992; 49: 354–9PubMedCrossRefGoogle Scholar
  16. 16.
    Beaumanoir A. The Landau-Kleffner syndrome. In: Roger J, Dravet C, Bureau M, et al., editors. Epileptic syndromes in infancy, childhood and adolescence. London: John Libbey, 1985: 181–91Google Scholar
  17. 17.
    Appleton R. The Landau-Kleffner syndrome. Arch Dis Child 1995; 72: 386–7PubMedCrossRefGoogle Scholar
  18. 18.
    Stefanatos GA, Kinsbourne M, Wasserstein J. Acquired epileptiform aphasia: a dimensional view of Landau-Kleffner syndrome and the relation to regressive autistic spectrum disorders. Neuropsychol Dev Cogn C Child Neuropsychol 2002 Sep; 8(3): 195–228Google Scholar
  19. 19.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington (DC): American Psychiatric Association, 1994: 66–71Google Scholar
  20. 20.
    Rossi PG, Parmeggiani A, Bach V, et al. EEG features and epilepsy in patients with autism. Brain Dev 1995; 17: 169–74PubMedCrossRefGoogle Scholar
  21. 21.
    Morrell F, Whisler WW, Smith MC, et al. Landau-Kleffner syndrome: treatment with subpial intracortical transection. Brain 1995 Dec; 118(6): 1529–46PubMedCrossRefGoogle Scholar
  22. 22.
    Guillioto LMFF, Morrell F. Electropsychological differences between Landau-Kleffner syndrome and other conditions showing the CSWS electrical pattern [abstract]. Epilepsia 1994; 35Suppl. 8: 126Google Scholar
  23. 23.
    Nass R, Gross A, Wisoff J, et al. Outcome of multiple subpial transections for autistic epileptiform regression. Pediatr Neurol 1999; 21: 464–70PubMedCrossRefGoogle Scholar
  24. 24.
    Mikati MA, Saab R. Successful use of intravenous immunoglobulin as initial monotherapy in Landau-Kleffner syndrome. Epilepsia 2000; 41(7): 880–6PubMedCrossRefGoogle Scholar
  25. 25.
    Park YD. The effects of vagus nerve stimulation therapy on patients with intractable seizures and either Landau-Kleffner syndrome or autism. Epilepsy Behav 2003; 4: 286–90PubMedCrossRefGoogle Scholar
  26. 26.
    Soprano AM, Gracia EF, Caraballo R, et al. Acquired epileptic aphasia: neuropsychologic follow-up of 12 patients. Pediatr Neurol 1994; 11: 230–5PubMedCrossRefGoogle Scholar
  27. 27.
    Rossi PG, Parmeggiani A, Posar A, et al. Landau-Kleffner syndrome (LKS): longterm follow-up and links with electrical status epilepticus during sleep (ESES). Brain Dev 1999; 21: 90–8PubMedCrossRefGoogle Scholar
  28. 28.
    Smith MC, Spitz MC. Treatment strategies in Landau-Kleffner syndrome and paraictal psychiatric and cognitive disturbances. Epilepsy Behav 2002; 3: S24–9CrossRefGoogle Scholar
  29. 29.
    Holmes GL, Riviello Jr JJ. Treatment of childhood idiopathic language deterioration with valproate. Epilepsy Behav 2001 Jun; 2(3): 272–6PubMedCrossRefGoogle Scholar
  30. 30.
    Marescaux C, Hirsch E, Finck S, et al. Landau-Kleffner syndrome: a pharmacologic study of five cases. Epilepsia 1990; 31(6): 768–77PubMedCrossRefGoogle Scholar
  31. 31.
    Ravnik I. A case of Landau-Kleffner syndrome: effect of intravenous diazepam. In: Roger J, Dravet C, Bureau M, et al., editors. Epileptic syndromes in infancy, childhood and adolescence. London: John Libbey Eurotext, 1985: 192–3Google Scholar
  32. 32.
    De Negri M, Baglietto MG, Battaglia FM, et al. Treatment of electrical status epilepticus by short diazepam (DZP) cycles after DZP rectal bolus test. Brain Dev 1995; 17(5): 330–3PubMedCrossRefGoogle Scholar
  33. 33.
    Glauser TA, Olberding LS, Titanic MK, et al. Felbamate in the treatment of acquired epileptic aphasia. Epilepsy Res 1995 Jan; 20(1): 85–9PubMedCrossRefGoogle Scholar
  34. 34.
    Pascual-Castroviejo I. Nicardipine in the treatment of acquired aphasia and epilepsy [letter]. Dev Med Child Neurol 1990; 32: 930PubMedCrossRefGoogle Scholar
  35. 35.
    Bharani S, Trivedi C, Shendurnikar N, et al. Landau Kleffner syndrome. Indian J Pediatr 2001; 68(6): 567–9PubMedCrossRefGoogle Scholar
  36. 36.
    Appleton R, Hughes A, Beirne M, et al. Vigabatrin in the Landau-Kleffner syndrome. Dev Med Child Neurol 1993; 35(5): 457–9PubMedGoogle Scholar
  37. 37.
    Hankey GJ, Gubbay SS. Acquired aphasia of childhood with epilepsy: the Landau-Kleffner syndrome. Clin Exp Neurol 1987; 24: 187–94PubMedGoogle Scholar
  38. 38.
    Wakai S, Ito N, Ueda D, et al. Landau-Kleffner syndrome and sulthiame. Neuropediatrics 1997; 28: 135–6PubMedCrossRefGoogle Scholar
  39. 39.
    Bergqvist AG, Chee CM, Lutchka LM, et al. Treatment of acquired epileptic aphasia with the ketogenic diet. J Child Neurol 1999; 14: 696–701PubMedCrossRefGoogle Scholar
  40. 40.
    McKinney W, McGreal DA. An aphasic syndrome in children. CMAJ 1974; 110: 637–9Google Scholar
  41. 41.
    Perniola T, Margari L, Buttiglione M, et al. A case of Landau-Kleffner syndrome secondary to inflammatory demyelinating disease. Epilepsia 1993 May–Jun; 34(3): 551–6PubMedCrossRefGoogle Scholar
  42. 42.
    Raybarman C. Landau-Kleffner syndrome: a case report. Neurol India 2002 Jun; 50(2): 212–3PubMedGoogle Scholar
  43. 43.
    Tutuncuoglu S, Serdaroglu G, Kadioglu B. Landau-Kleffner syndrome beginning with stuttering: case report. J Child Neurol 2002; 17: 785–8PubMedCrossRefGoogle Scholar
  44. 44.
    Aykut-Bingol C, Arman A, Tokol O, et al. Pulse methylprednisolone therapy in Landau-Kleffner syndrome. J Epilepsy 1996; 9: 189–91CrossRefGoogle Scholar
  45. 45.
    Coutinho dos Santos LH, Antoniuk SA, Rodrigues M, et al. Landau-Kleffner syndrome: study of four cases. Arq Neuropsiquiatr 2002; 60(2A): 239–41CrossRefGoogle Scholar
  46. 46.
    Guerreiro MM, Camargo EE, Kato M, et al. Brain single photon emission computed tomography imaging in Landau-Kleffner syndrome. Epilepsia 1996 Jan; 37(1): 60–7PubMedCrossRefGoogle Scholar
  47. 47.
    Sinclair DB, Snyder TJ. Corticosteroids for the treatment of Landau-Kleffner syndrome and continuous spike-wave discharge during sleep. Pediatr Neurol 2005; 32(5): 300–6PubMedCrossRefGoogle Scholar
  48. 48.
    Uldall P, Sahlholdt L, Alving J. Landau-Kleffner syndrome with onset at 18 months and an initial diagnosis of pervasive developmental disorder. Eur J Pediatr Neurol 2000; 4: 81–6CrossRefGoogle Scholar
  49. 49.
    Kellerman K. Recurrent aphasia with subclinical bioelectric status epilepticus during sleep. Eur J Pediatr 1978; 128(3): 207–12CrossRefGoogle Scholar
  50. 50.
    Van de Sandt-Koenderman WM, Smit IA, Van Dongen HR, et al. A case of acquired aphasia and convulsive disorder: some linguistic aspects of recovery and breakdown. Brain Lang 1984; 21(1): 174–83PubMedCrossRefGoogle Scholar
  51. 51.
    Fayad MN, Choueiri R, Mikati M. Landau-Kleffner syndrome: consistent response to repeated intravenous γ-globulin doses: a case report. Epilepsia 1997; 38(4): 489–94PubMedCrossRefGoogle Scholar
  52. 52.
    Mikati MA, Saab R, Fayad MN, et al. Efficacy of intravenous immunoglobulin in Landau-Kleffner syndrome. Pediatr Neurol 2002 Apr; 26(4): 298–300PubMedCrossRefGoogle Scholar
  53. 53.
    Sawhney IM, Robertson IJ, Polkey CE, et al. Multiple subpial transection: a review of 21 cases. J Neurol Neurosurg Psychiatry 1995 Mar; 58(3): 344–9PubMedCrossRefGoogle Scholar
  54. 54.
    Rintahaka PJ, Chugani HT, Sankar R. Landau-Kleffner syndrome with continuous spikes and waves during slow-wave sleep. J Child Neurol 1995; 10: 127–33PubMedCrossRefGoogle Scholar
  55. 55.
    Grote CL, Van Slyke P, Hoeppner JA. Language outcome following multiple subpial transection for Landau-Kleffner syndrome. Brain 1999 Mar; 122 (Pt 3): 561–6PubMedCrossRefGoogle Scholar
  56. 56.
    Irwin K, Birch V, Lees J, et al. Multiple subpial transection in Landau-Kleffner syndrome. Dev Med Child Neurol 2001; 43: 248–52PubMedCrossRefGoogle Scholar
  57. 57.
    Rotenberg J, Pearl PL. Landau-Kleffner syndrome. Arch Neurol 2003 Jul; 60(7): 1019–21PubMedCrossRefGoogle Scholar
  58. 58.
    Van Slyke PA. Classroom instruction for children with Landau-Kleffner syndrome. Child Lang Teach Ther 2002 Feb; 18(1): 23–42CrossRefGoogle Scholar
  59. 59.
    Vance M. Educational and therapeutic approaches used with a child presenting with acquired aphasia with convulsive disorder (Landau-Kleffner syndrome). Child Lang Teach Ther 1991; 7: 41–60CrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  1. 1.Department of Pediatrics, and Adult and Pediatric Epilepsy Program, Faculty of MedicineAmerican University of BeirutBeirutLebanon

Personalised recommendations