Landau-Kleffner syndrome (LKS) is a rare neurological condition with no known cause. It is an acquired epileptic aphasia that was first described by William Landau and Frank Kleffner in 1957. The prevalence of LKS remains unclear, but several hundred cases have been reported worldwide (Tassinari et al., 2012). LKS is twice as common in males and the peak age of onset is between the ages of 5 and 7 (Caraballo et al., 2014).
The syndrome manifests as a regression in language along with paroxysmal epileptiform activity, particularly during slow-wave sleep. The abnormal electrical activity in LKS is found in both cerebral hemispheres, predominantly in temporal or parieto-occipital regions (Loddenkemper, Wyllie, & Hirsch, 2012; Pearl, Carrazana, & Holmes, 2001). The aphasia in LKS is characterized by a loss of receptive language followed by expressive deficits; a marked decline in spontaneous speech often ensues (Caraballo et al., 2014). Complete loss of the ability to speak (mutism) can occur (Ardila, 2014).
Overnight or extended electroencephalogram (EEG) is typically used to detect abnormal epileptic activity during sleep in order to confirm the diagnosis of LKS. Surgical outcomes for LKS are poor, but the combination of antiepileptic drugs with corticosteroids has been shown to be efficacious (Sinclair & Snyder, 2005). While seizure activity typically resolves in adolescence, LKS can have lasting effects on language functioning, sometimes resulting in a chronic and severe aphasia. In general, earlier onset of the disease is associated with poorer language recovery (Duran, Guimarães, Medeiros, & Guerreiro, 2009).
Evidence for normal letter-sound integration, but altered language pathways in a case of recovered Landau–Kleffner syndrome (2015)
Landau–Kleffner Syndrome (LKS) is a rare form of acquired aphasia in children, characterized by epileptic discharges, which occur mostly during sleep. After normal speech and language development, aphasia develops between the ages of 3–7 years in a period ranging from days to months. The epileptic discharges usually disappear after reaching adulthood, but language outcomes are usually poor if no treatment focused on restoration of (non-) verbal communication is given. Patients often appear deaf–mute, but sign language, as part of the treatment, may lead to recovery of communication. The neural mechanisms underlying poor language outcomes in LKS are not yet understood. In this detailed functional MRI study of a recovered LKS patient – that is, a patient no longer suffering from epileptic discharges, audiovisual multi-sensory processing was investigated, since LKS patients are often proficient in reading, but not in speech perception. In the recovered LKS patient a large difference in the neural activation to auditory stimuli was found in the left versus the right auditory cortex, which cannot be attributed to hearing loss. Compared to healthy proficient readers investigated earlier with the same fMRI experiment, the patient demonstrated normal letter-sound integration in the superior temporal gyrus as demonstrated by the multi-sensory interaction index, indicating intact STG function. Diffusion Tensor Imaging (DTI) based fiber tracking in the LKS patient showed fibers originating from Heschl’s gyrus that seem to be left-right inverted with respect to HG fiber pattern described in the literature for healthy controls. In the patient, in both hemispheres we found arcuate fibers projecting from (homologues of) Broca’s to Wernicke’s areas, and a lack of fibers from arcuate left inferior parietal and sylvian areas reported in healthy subjects. We observed short arcuate segments in the right hemisphere. Although speculative, our results suggest intact temporal lobe processing but an altered temporal to frontal connectivity. The altered connectivity might explain observed short-term verbal memory problems, disturbed (speech) sound-motor interaction and online feedback of speech and might be one of the neuronal factors underlying LKS.
Pullens, P., Pullens, W., Blau, V., Sorger, B., Jansma, B. M., & Goebel, R. (2015). Evidence for normal letter-sound integration, but altered language pathways in a case of recovered Landau–Kleffner syndrome. Brain and cognition, 99, 32-45. doi:10.1016/j.bandc.2015.07.003 http://www.sciencedirect.com/science/article/pii/S0278262615300051
Other Media and Resources
Website: Landau-Kleffner Syndrome Overview, National Organization for Rare Disorders
Podcast: Landau Kleffner Syndrome
Epilepsy Foundation’s Epilepsy Talk Radio program featuring Hallway Conversations with Dr. Joseph Sirven, Professor of Neurology at Mayo Clinic Arizona and Editor-in-Chief of Epilepsy.com. In this segment he interviews Katherine Nickels, MD, Assistant Professor of Neurology and Pediatrics at Mayo Clinic, Rochester, Minnesota, about Landau Kleffner Syndrome (LKS).
[Tip: Go to the 12:50 mark for the segment on LKS, the first 12 minutes are on a related condition, Continuous Spikes and Waves during Slow-Wave Sleep (CSWS).]
Podcast: Lesson of the Week, Landau-Kleffner Syndrome [23:50 - 36:26]
Dr. Chris Boes interviews Dr. William Landau about his contributions to the discovery of Landau-Kleffner syndrome for the Lesson of the Week segment of Neurology® Podcast sponsored by the American Academy of Neurology.
[Tip: Scroll down and click on the last segment titled “LOTW: Landau-Kleffner Syndrome. Then click “Play Segment”]
Blog: Living with Landau-Kleffner Syndrome
A personal account from a mother whose son was diagnosed with Landau-Kleffner syndrome.
Devinsky, O., Goldberg, R., Miles, D., Bojko, A., & Riviello, J. (2014). Episodic epileptic verbal auditory agnosia in Landau Kleffner syndrome treated with combination diazepam and corticosteroids.Journal of child neurology, 0883073813516381.http://jcn.sagepub.com/content/early/2014/01/20/0883073813516381.abstract
Downes, M., Greenaway, R., Clark, M., Helen Cross, J., Jolleff, N., Harkness, W., ... & Neville, B. G. (2015). Outcome following multiple subpial transection in Landau‐Kleffner syndrome and related regression. Epilepsia, 56(11), 1760-1766. http://onlinelibrary.wiley.com/doi/10.1111/epi.13132/full
Korkman, M., Granström, M. L., Appelqvist, K., & Liukkonen, E. (1998). Neuropsychological characteristics of five children with the Landau-Kleffner syndrome: Dissociation of auditory and phonological discrimination. Journal of the International Neuropsychological Society, 4(6), 566-575. http://www.ncbi.nlm.nih.gov/pubmed/10050361
Landau, W. M., & Kleffner, F. R. (1957). Syndrome of acquired aphasia with convulsive disorder in children. Neurology, 7(8), 523-530.http://www.neurology.org/content/51/5/1241.2.short
Metz-Lutz, M., & Filippini, M. (2006). Neuropsychological findings in rolandic epilepsy and Landau-Kleffner syndrome. Epilepsia 47(s2), 71-75. doi:10.1111/j.1528-1167.2006.00695.x. http://onlinelibrary.wiley.com/doi/10.1111/j.1528-1167.2006.00695.x/full
Ragsdale, K. A., Bunnell, B. E., & Beidel, D. C. (2015). Social skills training for a young adult with Landau–Kleffner syndrome. Clinical Case Studies, 14(2), 129-140. doi:10.1177/1534650114543642.http://ccs.sagepub.com/content/early/2014/07/17/1534650114543642.abstract
Titus, J. B. (2016). Neuropsychological Assessment of Children with Landau-Kleffner Syndrome. Journal of Pediatric Epilepsy. doi:10.1055/s-0036-1585061
Turner, S. J., Morgan, A. T., Perez, E. R., & Scheffer, I. E. (2015). New genes for focal epilepsies with speech and language disorders.Current neurology and neuroscience reports, 15(6), 1-13.http://link.springer.com/article/10.1007/s11910-015-0554-0