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Citation Information : Journal of Epileptology. Volume 23, Issue 1, Pages 7-23, DOI: https://doi.org/10.1515/joepi-2015-0021
License : (CC BY 4.0)
Received Date : 27-October-2014 / Accepted: 16-December-2014 / Published Online: 02-January-2015
Introduction. Lennox-Gastaut syndrome (LGS) is a type of therapy-resistant epileptic syndrome. Since the establishment of our Epilepsy Center in 1975 we have performed many studies to assess the clinical symptoms, seizure manifestations, sleep and long-term follow-up of the clinical course and changes on electroencephalographs (EEGs) in patients with LGS.
Aim. To review the updated pathophysiology of LGS based on our own clinico-electrophysiological data referring to recent advances in brain research.
Methods. All of our previously published and unpublished data were reviewed in order to investigate the pathophysiology of LGS and using PubMed database for relevant literature.
Results and Discussion. While LGS usually occurs in infancy, it has become apparent that there is a form of late-onset LGS (L-LGS) that may occur at age eight or older. L-LGS often occurs when there is a history of encephalitis/encephalopathy or status epilepticus. The long-term progression of LGS includes mainly tonic seizures that persist and are the basis of LGS. In approximately 30% of cases, the basic symptoms of LGS remain 10 years or longer after long-term progression, while the rest lose their characteristics, although the condition is residual in 60% of cases and remission occurs in fewer than 10%. Among the characteristic seizures associated with LGS, atypical absence seizures occur in response to a diverse range of EEG features; wherein, while they are mostly short, they are accompanied by a state of enervation along with a tendency for it to be unclear when the seizure has ended. Drop attacks can in fact be categorized into those in which the subject falls over due to hypertonia in the muscles used to maintain body posture and those in which the subject falls over due to loss of tension in the posture-retaining muscles. Tonic seizures range from those manifesting in the form of extremely mild axial muscle tonicity, open eyes and respiratory changes, accompanied by high voltage, fast rhythm (averaging 14 ± 0.4 Hz), or tonicity from axorhyzomelic muscles to the peripheral muscles, accompanying global tonic seizures, and EEG features showing low voltage fast activity (averaging 22 ± 0.6 Hz) from desynchronization. A total of 1191 clinical seizures were recorded upon overnight polysomnography and videotape, and seizure symptoms and their ictal EEGs were analyzed. In LGS, seizure activity increases during slow wave sleep, inhibiting progression into the further sleep stages but falls significantly during rapid eye movement (REM) sleep.
Conclusions. From the research into seizure symptoms, clinical progression, sleep and seizures during sleep, it was believed that in LGS epileptic native lesions occur due to mesencephalic reticular formation, in the thalamic reticular system and, as a result of recent of brain physiology research, it is considered that LGS is an epileptic reticulo-thalamo-cortical system disorder. This has been supported by EEG-fMRI findings (Siniatchikin et al., 2011). Further research is therefore necessary to elucidate the role of the reticular formation in controlling the thalamo-cortical networks in humans.
Avoli M.: A brief history on the oscillating roles of thalamus and cortex in absence. Epilepsia, 2012, 53: 779–789.
Bremer F.: Neurophysiological mechanisms in cerebral arousal. In: E.W. Wostenholm, M. O’Connor (eds), The nature of sleep. J. & A. Churchill Ltd., 1961, 30–56.
Blume W.T., David R.B., Gomez R.: Generalized sharp and slow wave complexes associated clinical features and long-term follow-up. Brain, 1973, 96: 289–306.
Burnham W.M.: Electrical stimulation studies: Generalied convulsions triggered from the brain-stem. In: G.H. Fromm, C.L. Faingold, R.A. Browning, W.M. Burnham (eds)., Epilepsy and the reticular formation. Alan R. Liss Inc., New York 1987, 25–38.
Chevrie J.J., Aicardi J.: Childhood epileptic encephalopathy with slow spike-wave. A stastical study of 80 cases. Epilepsia, 1972, 13: 259–271.
Crespel A., Gelisse P., Nikanorova M., Ferlazzo E., Genton P.: Lennox-Gastaut syndrome. In: M. Bureau, P. Genton, C. Dravet, A. Delgado-Escueta, C.A. Tassinari, P. Thomas, P. Wolf (eds), Epileptic syndromes in infancy, childhood and adolescence (5th ed.). John Libbey Eurotext Ltd., 2012, 189–216.
Gastaut H., Roger S., Ouahchi S., Timsit M., Broughton R.: An electroclinical study of generalized epileptic seizures of tonic expression. Epilepsia, 1963, 4: 14–44.
Gastaut H., Roger J., Sovlayrol R., Tassinari C.A., Rogis H., Dravet C.: Childhood epileptic encephalopathy with diffuse slow spike-waves of Lennox syndrome. Epilepsia, 1966, 7: 139–179.
Gastaut H., Tassinari C.A.: Ictal discharges in different types of seizures. In: Handbook of electroencephalography and clinical neurophysiology, vol. 13, part A. Elsevier, Amsterdam, 1975, 20–45.
Gloor P., Avoli M., Kostopoulos G.: Thalamocortical relationships in generalized epilepsy with bilaterally synchronous spikeand- wave discharge. In: M. Avoli, P. Gloor, G. Kostopoulos, R. Naquet (eds), Generalized epilepsy. Birkhaeser, Boston–Basel– Berlin 1990, 190–212.
Habaguchi T., Takakusaki K., Saitoh J., Sugimoto J., Sakamoto T.: Medullary reticulospinal tract mediating the generalized motor inhibition in cats: II. Functional organization within the medullary reticular formation with respect to postsynaptic inhibition of forelimb and hindlimb motorneurons. Neuroscience, 2002, 113: 65–77.
Halasz P.: Is there a final common pathway for malignisation in different kind of epilepsies? Electrographic features and clinical correlations of generalized repetitive fast discharge (GRFD). Epilepsi, 1996, 2: 9–22.
Ikeno T., Shigematsu H., Miyakoshi M., Ohba A., Yagi K., Seino M.: An analytic study of epileptic falls. Epilepsia, 1985, 26: 612–621.
Jackson J.H., Singer H.D.: Observations of a case of convulsions. (Trunk fit or lowest level fit?). Brain, 1902, 25: 122–132.
Jackson J.H., Barnes S.: Further observations on a case of convulsions (Trunk fit or lowest level fit?). Brain, 1902, 25: 286–292.
Kreindler A., Zuckermann F., Steriade M., Chimion D.: Electroclinical features of convulsions induced by stimulation of brain stem. J. Neurophysiol. 1958, 21: 430–436.
Kostopoulos G., Gloor P., Pellegrini A., Gotman J.: A study of the transition from spindles to spike and wave discharges in feline generalized penicillin epilepsy. Exp. Neurol., 1981, 73: 55–77.
Kruse R.: Das myoklonisch-astatische petit mal. Springer, Berlin– Heidelberg 1968.
Lipinski C.G.: Epilepsies with astatic seizures of late onset. Epilepsia, 1977, 18: 13–20.
Min Byoung-Kyong.: A thalamic reticular networking model of consciousness. Theoretical biology and medical modeling. 2010; 7 10 doi: 10 1186/1742–4682-7.
Miyakoshi M., Yagi K., Osawa T., Seino M., Wada T.: Correlative study on symptomatology of epileptic seizures-behavioral manifestation and electro-encephalographic modalities. Folia Psychiat. Neurol. Jpn., 1977, 31: 451–461.
Moruzzi G., Magoun H.W.: Brain stem reticular formation and activation of the electroencephalogram. Electroencephalogr. Clin. Neurophysiol., 1949, 1: 455–473.
Morison R.S., Dempsy E.W.: A study of thalamocortical relations. Am. J. Physiol., 1942, 135: 281–292.
Morison R.S., Dempsy E.W.: Mechanism of thalamocortical augmentation and repetition. Am. J. Physiol., 1943, 138: 297–308.
Moruzzi G., Magoun H.W.: Brain stem reticular formation and activation of the EEG. EEG Clin. Neurophysiol., 1949, 1: 455–473.
Neckelmann D., Amzica F., Steriade M.: Spike-wave complexes and fast components of cortically generated seizures. III. Synchronization mechanisms. J. Neurophysiol., 1998, 80: 1480–1494.
Ohtahara S., Oka E., Ban K., Yamatogi Y., Inoue E.: An electro- encephalographic study in patients with Lennox-Gastaut syndrome. Clin. Neurol., 1970, 10: 617–627 (in Japanese).
Ohtahara S., Yamatogi Y., Ohtsuka Y.: Prognosis of the Lennox syndrome-long-term clinical and electroencephalographic followup study, especially with special reference to relationship with the West syndrome. Folia psychiatr. Neurol. Jap., 1976, 30: 275–287.
Ohtsuka Y., Yoshida H., Miyake S., Ichiba N., Inoue H., Yamatogi Y. et al.: Induced microseizures: a clinical and electro-encepharographic study. In: H. Akimoto, H. Kazamaturi, M. Seino, A. Ward (eds), Advance in Epileptology. XIIIth Epilepsy International Symposium. Raven Press, New York 1982, 33–35.
Petersen B.W., Pitts N.G., Fukushima K., Mackel R.G.: Reticulospinal excitation and inhibition of neck motoneurons. Expl. Brain Res., 1978, 32: 471–489.
Petersen B.W., Pitts N.G., Fukushima K.: Reticulospinal connection with limb and axial motoneurons. Expl. Brain Res., 1979, 36: 1–20.
Prior P.F., Macline G.N., Scott D.F., Laurance B.M.: Tonic status epilepticus precipitated by intravenous diazepam in a child with petit mal status. Epilepsia, 1972, 13: 467–472.
Ranson S.W., Clark S.L.: The diencephalon, upon the thalaMus. In: The anatomy of the nervous system, its development and function. 10th ed. W.B. Saunders company, Philadelphia, London, 1959, 292–300.
Schneider H., Vassella F., Karbowski K.: The Lennox syndrome. A clinical study of 40 children. Europ. Neurol., 1970, 4: 289–300.
Seino M., Fujiwara T., Miyakoshi M., Yagi K.: A tautology in the classification of generalized non-convulsive epileptic seizures. Folia Psych. Neurol. Jpn., 1980, 34: 257–269.
Siniatchikin M., Coropceanu D., Moeller F., Boor R., Stephani U.: EEG-fMRI reveals activation of brainstem and thalamus in patients with Lennox-Gastaut syndrome. Epilepsia, 2011, 52: 766–774.
Steriade M., Contreras D.: Spike-wave complexes and fast components of cortically generated seizures. I. Role of neocortex and thalamus. J. Neurophysiol., 1998, 80: 1439–1455.
Steriade M., Amzica F., Neckelmann D., Timofeev I.: Spikewave complexes and fast components of cortically generated seizures. II. Extra- and Intracellular patterns. J. Neurophysiol., 1998, 80: 1456–1479.
Steriade M., Domich L., Oakson G., Deschenes M.: The deafferented reticular thalamic nucleus generates spindle rhythmicity. J. Neurophysiol., 1987, 57: 260–273.
Takakusaki K., Kohyama J., Matsuyama K., Mori S.: Medullary reticulospinal tract mediating the generalized motor inhibition in cats: parallel inhibitory mechanisms acting on motorneurons and on interneuronal transmission in reflex pathways. Neuroscience, 2001, 103: 511–527.
Takakusaki K., Kohyama J., Matsuyama.: Medullary reticulospinal tract mediating a generalized motor inhibition in cats: III. Fuctional organization of spinal interneurons in the lower lumbar segments. Neuroscience, 2003, 121: 731–746.
Takakusaki K., Okumura T.: Neurobiological basis of controlling posture and locomotion. Advanced Robotics, 2008, 22: 1629–1663.
Tassinari C.A., Dravet C., Roger J., Cano J.P., Gastaut H.: Tonic status epilepticus precipitated by intravenous benzodiazepine in five patients with Lennox-Gastaut syndrome. Epilepsia, 1972, 13: 421–435.
Timofeev I., Grenier F., Steriade M.: Spike-wave complexes and fast components of cortically generated seizures. IV. Paroxysmal fast runs in cortical and thalamic neurons. J. Neurophysiol., 1998, 80: 1495–1513.
Timofeev I., Steriade M.: Neocortcal seizures: initiation, development and cessation. Neuroscience, 2004, 123: 299–336.
Timofeev I., Steriade M.: Cellular mechanisms underlying intrathalamic augmenting responses of reticular and relay neurons. J. Neurophysiol., 1998, 79: 2716–2729.
Velasco M., Velasco F., Alcala H., Davila G., Djaz-de-Leon A.E.: Epileptiform EEG activity of the centromedian thalamic nuclei in children with intractable generalized seizures of the Lennox-Gastaut syndrome. Epilepsia, 1991, 32: 310–321.
Velasco F. Velasco M.: Mesencephalic structures and tonic-clonic generalized seizures. In: M. Avoli, P. Gloor, G. Kostopoulos, R. Naquet (eds), Generalized epilepsy. Birkhaeser, Boston–Basel –Berlin, 1990, 368–384.
Yagi K., Miyakoshi M., Morikawa T., Yamamoto K., Kakegawa N., Osawa T. et al.: A clinico-electroencephalographical analytic study on ictal phenomena of secondary generalized epilepsy. Electroenceph. Clin. Neurophysiol., 1977, 43: 897.
Yagi K., Miyakoshi M., Morikawa T., Osawa T., Seino M., Wada T.: An analytic study on clinic-electroencepharographical correlates of sleep seizures with tonic state in secondary generalized epilepsies. Clin. EEG., 1978, 20: 377–385 (in Japanese).
Yagi K., Morikawa T., Miyakoshi M., Kakegawa N., Osawa T., Seino M., Wada T.: Analytic study of epileptic absence seizures and effect of sodium valproate treatment. Monogr. Neurol. Sci., 1980, 5: 137–141.
Yagi K, Seino M., Fujiwara T.: Typical and atypical epileptic absence seizures. Advances in Epileptology, 1982, 13: 49–53.
Yagi K., Morikawa T., Fujiwara T., Osawa T., Seino M., Wada T.: A clinical study of seventy adult patients with the Lennox- Gastaut syndrome. J. Jpn. Epil. Soc., 1983, 1: 23–30.
Yagi K., Seino M.: Epileptic seizure manifestations analized by intensive monitoring methods. Advances in Neurological Sciences., 1983, 27: 657–668 (in Japanese).
Yagi K., Seino M.: The use of the proposed classification of epileptic syndromes – 1985. Advances in Epileptology, 1989, 17: 244–246.
Yagi K.: A long-term longitudinal study of Lennox-Gastuat syndrome – evolution of epileptic EEG abnormalities. Clin. EEG, 1990, 32: 155–160 (in Japanese).
Yagi K.: Evolution of Lennox-Gastaut syndrome: A long-term longitudinal study. Epilepsia, 1996, 37 (Suppl. 3): 48–51.