2. Scheme of presentation
Introduction
History
Definition
Epidemiology
Etiology
Clinical characteristics
EEG features
Treatment
Evolution and Outcome
Conclusion
3. Introduction
Lennox Gastaut Syndrome (LGS) is one of the most
severe childhood epilepsies.
It has precise well-defined clinical and
neurophysiological characteristics and is a fairly
homogenous, but uncommon entity.
However, its pathophysiological mechanisms remain
poorly understood.
Its definition has varied over time resulting in
misclassification and over-diagnosis in the past.
5. Historical perspective
Gibbs (1938) described the characteristic diffuse
2-2.5 Hz slow spike and wave discharges in EEG.
He called this ‘petit mal variant’.
Lennox (1945), and Lennox and Davis (1950)
described the triad of mental deficiency,
polymorphic seizures and diffuse slow spike and
wave discharges in EEG.
Margaret Buchtal-Lennox proposed the name LGS
in tribute to the work of Lennox and the Marseille
School headed by Gastaut.
6. ILAE Definition, 2001
Onset during childhood
Coexistence of multiple seizure types:
Common- atypical absence, axial tonic and atonic
seizures. Presence of tonic seizures in sleep is a
constant feature.
Infrequent- are myoclonic, GTCS, focal.
EEG: Diffuse slow spikes and waves and bursts of
fast rhythms at 10-12 Hz during sleep.
Permanent psychological disturbances with
psychomotor delay, personality disorders, or both.
7. Definitions of LGS
Group Onset in MR Multiple Tonic Sz Diffuse GPFA in
childhood Sz types in sleep SSW sleep
ILAE Yes Yes Yes Yes Yes Yes
2001
Genton Yes Yes Yes - Yes Yes
et al, 2000
Goldsmith Yes - Yes Yes Yes -
et al, 1999
Lennox - Yes Yes - Yes -
et al, 1950
Trevathan Yes - Yes - Yes -
et al, 1997
French - Yes Yes - Yes -
et al, 2004
Not all patients have all of the core seizure types, especially at onset.
Arzimanoglou et al., 2009.
When the complete criteria is applied, LGS is a rare disorder.
8. Classification
LGS is classified among the symptomatic or
cryptogenic generalized epilepsies.
In the 2001 proposal of ILAE, it is classified as an
epileptic encephalopathy, a concept formally
endorsed in 2006 by ILAE and further emphasized in
2010 (Berg et al., 2010).
International Classification of Epilepsies and Epileptic Syndromes
9. Classification
1. Cryptogenic (25%): onset between 1-8 years of age,
in a previously normal child, due to an undetected
but suspected cause.
(Abandoning this term has been suggested).
Engel 2001
2. Symptomatic (75%): onset between 1-15 years of
age, in a child with prior signs of brain damage.
Hancock and Cross, 2009; Borggraefe and Noachtar, 2010
11. Epidemiology
Accounts for 1- 5% of all epilepsies and 3- 10% of
childhood epilepsies.
Trevathan et al., 1997; Hancock & Cross, 2009.
No ethnic or geographic predilection.
Boys are slightly more affected than girls.
Markand O, 1977
In the Nova Scotia study, only 4 patients had LGS at
the time of epilepsy diagnosis; 20 years later the
number was 17, with most of the new cases evolving
from West syndrome.
Camfield & Camfield, 2007.
12. Incidence of LGS
Author Area N Definition Incidence
Heiskala H Finland 1-14 yrs of age Gastaut 1.9-2.1 /100,000
et al, 1997 children/yr
Rantala H et Finland < 15 yrs of age Gastaut 1.93/100,000 children/
al, 1999 yr
Camfield Nova Scotia 1m- 16yrs of age ? 0.6% of all new onset
1996 epilepsies
(46/100,000/yr).
Prevalence of LGS
Camfield Nova scotia 1m- 16 yrs of age ? 4% of symptomatic
1996 generalised epilepsy
Trevathan Atlanta < 10 yrs of age Gastaut Lifetime prevalence at
et al, 1997 10 yrs of age was
0.26/1000.
4% of childhood
epilepsies
17. LGS and Infantile spasm
Author N h/o Infantile spasm Comment
Rantala H 25 40% 10/37 patients with IS
et al, (27%) evolved to LGS
Lombrosos CT, - - 23% of children with IS
et al, 1983 evolved to LGS
Riikonen. 192 20- 36%
1982
Ohtahara S - 36% 54% of IS evolved to
et al, 1980 LGS
Goldsmith IL 107 13.1 % h/o IS more common
et al, 2000 in symptomatic LGS
Mean time from the beginning of IS to beginning of LGS was 2.8 years
(0.4-8.8 years).
Rantala H et al. Epilepsia 1999; 40: 286-89.
18. History of Infantile spasms (IS) and other seizures in LGS.
Goldsmith I.L. et al. Epilepsia 2000; 41: 395- 99.
19. LGS and Infantile spasms (IS)
LGS evolved from other seizure types in 54.2% cases.
In 29.0% there was no history of seizures or epilepsy.
IS was more in the symptomatic subgroup (p= 0.05).
Patients with cryptogenic/ indeterminate LGS were
more likely to develop LGS without a h/o seizures.
Late onset LGS rarely had a h/o IS (6.3%) or seizures
(12.5%) compared to early-onset LGS (p= 0.05).
Goldsmith I.L. et al. Epilepsia 2000; 41: 395- 99.
20. LGS and West syndrome
Author N h/o West syndrome
Heiskala H 75 (1-14 yrs of age) 28 %
et al, 1997
Weinmann 174 17.8 %
et al, 1988
Yagi 102 22 %
et al, 1996
Oguni H 72 33 %
Et al, 2010
Camfield 692 children with epilepsy 65 %
et al, 2007
40 % of children who developed LGS from West syndrome had h/o
anoxic episodes early in life.
Blume 2001
22. Cognitive dysfunction
LGS has profound deleterious effects on intellectual
and psychosocial function.
Camfield & Camfield, 2008; Arzimanoglou et al., 2009.
Cognitive impairments are clinically apparent in 20–
60% of patients at the time of diagnosis of LGS.
Arzimanoglou et al., 2009.
The cognitive impairment becomes more apparent
over time, and within 5 years of onset, serious
intellectual problems is noted in 75–95% of patients.
Beaumanoir & Blume, 2005; Hancock & Cross, 2009.
23. Behavioural problems
Many patients with LGS develop behavioral and
psychiatric disorders.
Glauser, 2004
Attentional problems, aggression, and autistic features
can be very prominent in LGS and represent
enormous challenges for the family.
24. Tonic seizures
Tonic seizures are the most important seizures
associated with LGS and is required for diagnosis.
May not always be present at onset of LGS.
Arzimanoglou et al, 2009
Presentation: brief tonic upgaze, change in
respiration, facial tightening, neck flexion, brief
vocalization, involve axial muscles, or entire body.
Dulac & N’Guyen, 1993.
The frequency is easily underestimated because they
occur most often during sleep and are often subtle.
25. Atypical absence
It is the second most common seizure type in LGS.
It is not easily defined, and often being subtle, they
are not easily recognized.
Manifests as a brief lapse in consciousness, although
some awareness may be preserved.
Arzimanoglou et al., 2009.
Onset and termination are not always apparent;
patients seem to fade in and out of consciousness.
EEG: slow and often irregular spike waves (2.5 Hz)
that may be indistinguishable from interictal bursts.
Dulac & N’Guyen, 1993.
26. Sudden tonic or atonic falls
At least 50% of LGS patients have ‘‘drop attacks.’’
Often preceded by a single generalized myoclonic jerk
followed by a tonic contraction of axial muscles or
axial atony or a combination that leads to falls.
Prevention of facial injuries requires use of a helmet
and full face mask, which is highly stigmatizing and
often impractical.
Camfield & Camfield, 2002; Arzimanoglou et al., 2009.
27. Nonconvulsive status epilepticus
Occurs in 2/3rd of LGS patients and consists of
continuous/nearly continuous atypical absences
lasting minutes to hours that cause varying levels of
diminished consciousness.
Hancock and Cross, 2009.
Major contributor to intellectual impairment
Superimposed brief tonic seizures may occur.
EEG: nearly continuous slow spike-and-wave pattern
occasionally interrupted by brief bursts of generalized
polyspikes.
Dulac & N’Guyen, 1993.
28. Other seizure types
Most patients have myoclonic seizures that may be
subtle or severe enough to cause falls.
Myoclonia are not required for the diagnosis of LGS.
Camfield & Camfield, 2002; Arzimanoglou et al., 2009.
Other seizure types: GTCS, unilateral clonic, focal
clonic with or without secondary generalization.
These occur mostly in the later stages of LGS.
If very frequent, the diagnosis may be obscured.
Arzimanoglou et al., 2009.
30. EEG features
Slow (2.5 Hz) spike-and-wave bursts with abnormal
background activity is the hallmark.
Bursts may be irregular without a clear onset/ offset.
The average age of onset of slow spike wave is 8.2
years, with a mean duration of 8.6 years.
The distinction between ictal and interictal discharges
is often challenging.
Clinically apparent atypical absence seizures always
have an associated slow spike-wave burst.
Arzimanoglou et al., 2009.
33. Bursts of generalized fast polyspikes (10–20 Hz), especially in sleep,
also define the EEG of LGS.
Donat, 1992; Blume, 2001; Arzimanoglou et al., 2009.
34. EEG features
The slow spike-and-wave EEG pattern is transient,
and focal discharges are frequently seen with time.
Average age of onset of the classic, slow spike-wave
EEG patterns was 8.2 yrs (1– 35 yrs).
Average duration of the pattern was 8.6 yrs (1– 36 yrs).
After the slow spike-wave pattern disappeared, 95% of
patients had focal discharges and 95% had diffuse
slowing.
Hughes JR et al. Clin Electroencephalogr 2002;33:1–7.
35. EEG in tonic seizures
Sudden onset of generalized, rapid (10–13 Hz), low-
amplitude spikes predominantly in the vertex and
anterior head regions, and may increase progressively
in amplitude and decrease in frequency.
Duration: few seconds to minutes (typically 5–10 s).
Post-ictal: abrupt return to background rhythms or a
short epoch of generalized, high-amplitude delta.
EEG does not show generalized suppression that is
more typical of other tonic seizures.
Dulac & N’Guyen, 1993.
38. Differential diagnosis
Focal epilepsies with secondary bilateral synchrony,
Doose syndrome, Dravet syndrome, West syndrome.
Oguni, 2010.
Tonic seizures occur prominently in West syndrome,
frontal lobe epilepsies.
Dulac& N’Guyen, 1993.
Drop attacks, may occur in many other syndromes.
One study reported misdiagnosis in 38/103 patients
referred with a diagnosis of LGS.
Beaumanoir, 1982.
39. Pseudo-Lennox/atypical benign
partial epilepsy (ABPE)
Clusters of seizures are typical and there may be
striking periods with few or no seizures.
Arzimanoglou et al., 2009.
It may represent BECTS that is modified by
medication toxicity or illness.
Donat, 1992.
Unlike LGS, EEG does not show bursts of generalized
paroxysmal fast activity, and there are no tonic
seizures.
Arzimanoglou et al., 2009.
41. Evolution of LGS and Outcome
The long-term outcome for LGS patients is very poor,
and complete seizure freedom is unusual.
Dulac & N’Guyen, 1993; Goldsmith et al., 2000; Beaumanoir & Blume, 2005;
Arzimanoglou et al., 2009; Hancock & Cross, 2009.
In a recent study on the outcome of severe epileptic
encephalopathies, a new syndrome, the “severe
epilepsy with multiple independent spike foci” has
been suggested as the final evolution of LGS.
Yamatogi et al, 2006.
43. Evolution and outcome
The Nova Scotia population-based study investigated
long-term outcomes in 17 cases of LGS
Length of follow-up: 20 ± 6.5 years.
59% of patients had their first seizures in infancy.
At the end of follow-up, 94% of LGS cases had
intractable epilepsy, significantly more than other
SGE syndromes (p < 0.001).
Camfield & Camfield, 2007.
Of 9 patients with LGS included in the final analysis:
6 had poor and 3 had moderate social outcome.
Camfield and Camfield, 2008.
44. 102 patients of LGS > 15 yrs of age.
Mean age at time of survey: 28.6 yrs (15- 60 yrs).
Mean age at epilepsy onset: 4.3 yrs (2m to 18 yrs).
Average length of follow-up: 16.3 yrs (10- 20 yrs)
82/102 required multiple hospitalisations.
The typical clinical and EEG features of LGS
continued in 1/3rd of cases during the study period.
No patient evolved to any LRE during the study.
Yagi K et al. Epilepsia 1996; 37:48- 51
45. Evolution of LGS: etiology and outcome
In the 22 patients who evolved from West syndrome, 15 evolved
imperceptibly into LGS, while 7 had a mean interval of > 6 months
between end of West syndrome and beginning of LGS.
Yagi K et al. Epilepsia 1996; 37:48- 51
46. Seizure type at study end in 102 patients
Generalized tonic seizures were the most resistant to therapy
and persisted for years in nearly all patients.
Eight patients were seizure free for > 1 year.
Yagi K et al. Epilepsia 1996; 37:48- 51
47. 72 patients (M:F= 46:26)
Prenatal, perinatal, and postnatal factors were
considered to have been etiologic factors in 30, 14, and
seven patients, respectively.
Motor deficits were noted prior to epilepsy onset in 21
patients.
Mean age at epilepsy onset: 2 years 4 months.
Oguni H et al. Epilepsia 1996; 37: 44-47
48. Comparison of types of LGS
Cryptogenic LGS Symptomatic LGS
Number 21 51
Mean age (in yrs) 21± 5 23± 5
Follow-up period (in yrs) 17± 4 17± 5
Mean age at 1st visit (in yrs) 6± 3 3± 3
Average age at LGS 6± 3 (2- 10) 6± 3 (2- 15)
diagnosis
Oguni H et al. Epilepsia 1996; 37: 44-47
49. Age at diagnosis of LGS: Sympt West(+), Symptomatic LGS with a h/o
West syndrome; Sympt West(-), symptomatic LGS without a h/o West
syndrome; Crypt, cryptogenic LGS.
Oguni H et al. Epilepsia 1996; 37: 44-47
50. Age at appearance of drop attacks: Sympt West(+), Symptomatic LGS
with a h/o West syndrome; Sympt West(-), symptomatic LGS without
a h/o West syndrome; Crypt, cryptogenic LGS.
61% had onset at older than 10 years.
Oguni H et al. Epilepsia 1996; 37: 44-47
51. Seizure types during the clinical course
Seizure type Number
Tonic seizures 100 %
Myoclonic seizures 51 %
Atypical absence seizures 50 %
Atonic seizures 46 %
Astatic seizures 32 %
GTCS 28 %
Periodic spasms 15 %
Status epilepticus/ tonic status 15 %
Complex partial seizures 14 %
Focal motor seizures 3%
Oguni H et al. Epilepsia 1996; 37: 44-47
52. Epilepsy outcome at final examination
LGS MISF SGE LRE N
Crypto (n= 21) 14 (67%) 0 5 1 1
Sympto (n= 51) 23 (45%) 8 14 4 2
West (-) 11 4 7 4 1
West (+) 12 4 7 0 1
Total 37 8 19 5 3
More than two thirds of the patients had daily/ weekly seizures, of
which tonic seizures were the most frequent.
No difference in seizure outcome between the cryptogenic and
symptomatic groups.
Six (8%) patients were either seizure free (3), or had only a few
attacks annually (3).
Oguni H et al. Epilepsia 1996; 37: 44-47
53. Retrospective chart review of 107 patients.
Median age of LGS onset: 4 yrs (6m- 29 yrs).
M:F= 1.49: 1.0
Late-onset LGS (age > 8 yrs) in 17/107 patients.
74 had follow-up of > 3 yrs: Cryptogenic (12),
indeterminate (29) and symptomatic (33) groups.
Mean duration of follow up: 12.8 yrs
Goldsmith I.L. et al. Epilepsia 2000; 41: 395- 99.
54. Seizure outcome
No significant difference in outcome between the 3
subgroups with regard to seizures and cognition.
Classification on the basis of the presence or absence
of partial seizures at LGS onset did not result in a
significant difference in seizure or cognitive outcome.
Symptomatic patients had more atonic and atypical
absences at the end of study versus frequent tonic and
myoclonic seizures in the cryptogenic group.
Goldsmith I.L. et al. Epilepsia 2000; 41: 395- 99.
55. Long-term follow-up (> 3 yrs) of patients with LGS.
Goldsmith I.L. et al. Epilepsia 2000; 41: 395- 99.
56. Seizure outcome
No significant difference in seizure frequency
between the cryptogenic (54%) and symptomatic
(63%) subgroups, although patients in the
symptomatic subgroup had more types of seizures.
Tonic, atypical absence, and GTCS were the most
common seizure types seen at end of follow-up.
Only 3 (4.6%) patients were seizure free, and all were
part of the indeterminate subgroup.
Goldsmith I.L. et al. Epilepsia 2000; 41: 395- 99.
57. Seizure types in patients with LGS.
Goldsmith I.L. et al. Epilepsia 2000; 41: 395- 99.
58. 25 children with LGS (M:F= 14:11).
Mean age at onset: 4 yrs (1.2- 9.0)
Mean follow-up: 10.2 yrs (5.3- 15.6)
Mean age at last F/U: 13 yrs (6.6- 17.9)
1/16 (6%) children with symptomatic LGS and 2/8
(25%) children with cryptogenic LGS recovered from
their epilepsy.
Rantala H et al. Epilepsia 1999; 40: 286- 89.
61. Evolution of epileptiform discharges
in sleep
Slow spike-and-wave complexes during waking
disappeared first.
Multiple spike-and-wave complexes in repetition or
burst or fast rhythms or both during ‘sleep’ remained
for several years.
Finally, solitary spike-and-wave complex during sleep
were seen before epileptic discharges disappeared.
This evolution was characteristic of patients whose
seizures improved.
Yagi K et al. Epilepsia 1996; 37:48- 51
63. Mental retardation in LGS subtypes
Goldsmith I.L. et al. Epilepsia 2000; 41: 395- 99.
64. Mental retardation in LGS patients with normal cognition
at LGS diagnosis
Goldsmith I.L. et al. Epilepsia 2000; 41: 395- 99.
65. Intellectual outcome
33% of cryptogenic cases were normal, compared to
indeterminate (3%) and symptomatic cases (3%) (p≤
0.01).
When patients with MR at onset were excluded, 33%
of the cryptogenic patients were normal, compared to
indeterminate (17%) and symptomatic (20%) groups.
No significant difference was seen in terms of seizure
frequency or types, EEG findings, or antiepileptic
medications.
Goldsmith I.L. et al. Epilepsia 2000; 41: 395- 99.
66. Intellectual outcome
At end of study 8.1% of the patients were cognitively
normal.
The 6 patients with a good cognitive outcome had a
median age of LGS onset of 9.5 years compared with
4.5 years for those who were initially normal but
eventually had a poor cognitive outcome (p≤ 0.01).
It is likely the brain of such patients has already gone
through certain critical developmental stages such as
apoptosis and synaptogenesis.
Goldsmith I.L. et al. Epilepsia 2000; 41: 395- 99.
67. Intellectual Outcome in LGS
IQ Cryptogenic Symptomatic Total LGS
First/Last visit First/Last visit First/last visit
Normal (> 70) 7/1 17/0 24/1
Mild MR (55- 70) 5/2 7/2 12/4
Moderate MR (35- 55) 5/9 11/10 16/19
Severe MR (20- 35) 4/4 21/13 25/17
Profound MR (< 20) 0/5 0/26 0/31
Oguni H et al. Epilepsia 1996; 37: 44-47
68. Intellectual outcome in LGS
Severe or profound MR was diagnosed in 9 (43%)
patients in the cryptogenic and 39 (76%) patients in
the symptomatic group.
IQ scores below the moderate levels composed 86% of
the cryptogenic and 96% of the symptomatic group.
IQ score decrease of ≥15 points was seen in 9/11
(82%) patients with cryptogenic LGS and in 7/9 (78%)
patients with symptomatic LGS.
Oguni H et al. Epilepsia 1996; 37: 44-47
69. Intellectual outcome in LGS at mean follow- up of 10 yrs
Cognitive status LGS (n= 14)
Normal 2
Subnormal 2
Mild retardation 2
Moderate retardation 5
Severe retardation 1
Profound retardation 2
No child with symptomatic LGS was mentally and neurologically
normal at follow-up compared with 2/8 children with cryptogenic
LGS, but the difference was not statistically significant.
Rantala H. Epilepsia 1999; 40: 286- 89.
70. Persistence of Seizures and MR in LGS patients
Study N Duration of Seizure MR
F/U (yrs) persistence persistence
(% of pts) (% of pts)
Kurokawa 123 >5 66 93
et al, 1980
Ohtsuka 89 >5 76 91
et al, 1990
Yagi 102 > 10 92 75
et al, 1996
Oguni 72 > 10 92 99
et al, 1996
Goldsmith IL 74 >3 95 92
et al, 2000
Glauser TA. Epilepsia 2004; 45: 23- 26.
72. Functional outcome of LGS patients
Normal occupational status 12
Working part time 7
Housewife 1
Vocational training at work/training centres 29
Students at special school for handicapped 5
Institutionalised for care 21
Custodial care at home 19
Hospitalised for care 6
Death (details not provided) 2
Total 102
Yagi K et al. Epilepsia 1996; 37:48- 51
73. Other outcome measures
Variable gait disturbances, preexisting and acquired,
developed in 22/74 patients by the end of follow-up.
Some became wheelchair bound, due to gait
disturbance and also due worsening of the violent
drop attacks in those who were ambulant.
Deficits at end of follow-up (but not at onset) and
developmental delay correlated significantly with
severity of epilepsy.
Oguni H et al. Epilepsia 1996; 37: 44-47
74. Neurologic findings in LGS after mean follow-up of 10.2 years
Deficit LGS (n= 14)
Normal 2
Clumsiness 4
Muscular hypotonia 0
Ataxia 4
Spastic hemiplegia 1
Spastic tetraplegia 1
Flaccid paraparesis due to meningomyelocele 0
Pure cognitive disability 2
Rantala H et al. Epilepsia 1999; 40: 286-89
75. Mortality in LGS
The mortality rate is high.
Varies from about 3%–7%, mostly related to accidents
(Glauser 2004), to 25% due to underlying neurological
conditions
Camfield and Camfield 2007.
The incidence of SUDEP is higher in these patients.
Markand ON, J Clin Neurol 2003.
2/102 patients with LGS were death by the end of the
follow-up period.
Yagi K et al. Epilepsia 1996; 37:48- 51
76. 80% of children with LGS continue to experience
seizures, severe cognitive, psychiatric, and behavioral
deficits.
Camfield & Camfield, 2008; van Rijckevorsel, 2008.
It has a devastating impact on patients’ quality of life
and inflicts a considerable burden on their caregivers.
Gallop et al., 2009.
A defined strategy for transitioning patients from
pediatric to adult care should be an essential
component of the long-term management plan.
Jurasek et al., 2010.
77. Outcome of LGS
Author N F/U Result
Ohtsuka 89 > 5 yrs 31 (34.8%) had features of LGS.
et al, 1990 28 (31%) of those who had lost the
features of LGS had progressed to severe
epilepsy with MISF.
Beaumanoir 103 10 yrs 48/103 (46.6%) had features of LGS.
et al, 1982
Oller- Daurella 235 > 5 yrs 50% retained features of LGS.
et al, 1987
Oguni H 72 17 yrs LGS features disappeared in 33% of
et al, 1996 cryptogenic and 55% of symptomatic
cases.
78. SCTIMST experience
56 patients with follow-up of > 2 yrs.
Idiopathic (11), symptomatic (33), indeterminate (6).
Median age at onset of LGS: 24 months.
No late onset (after 8 years) LGS.
First unprovoked seizures and LGS in the
symptomatic group was before 2 years of age, which
was statistically significant.
2 patients (1 each in symptomatic and indeterminate
group) were seizure free at the end of follow up.
Mini S et al. (unpublished)
79. SCTIMST experience
Cognitive decline was progressive and 96% patients
had intellectual disability at final follow-up.
50% of patients had physical disability or behavioural
problems (ADHD, autistic features).
Quality of life of the patient was rated as poor.
Idiopathic and symptomatic LGS were similar in
terms of final seizure and intellectual outcome.
Absence of preceding West syndrome did not predict
a better prognosis.
Mini S et al. (unpublished)
81. Treatment of LGS
Chronic medical treatment remains disappointing.
Only 6 randomized double-blind controlled trials.
Treatment: broad spectrum AEDs/ polypharmacy.
AEDs effective for one seizure type may worsen
another or provoke SE.
No specific experimental model for LGS.
Treatment of comorbidities may aggravate seizures.
Disease may fluctuate independent of treatment.
82. Comparison of double blind randomized placebo controlled trials in LGS
Van Rijckervorsel K. Neuropsychiatric disease and treatment 2008; 4: 1001-19
83. Treatment strategy for LGS
Van Rijckervorsel K. Neuropsychiatric disease and treatment 2008; 4: 1001-19
84. Drug Benefit Disadvantages/ worsening of seizures
VPA Drug of choice Risk of hepatotoxicity/ pancreatitis with polytherapy.
FBM All Sz types Aplastic anemia/ hepatic failure.
LTG All Sz types Drug interaction with VPA, skin rashes.
TPM All Sz types Interaction with VPA, cognitive side-effects.
RUF All Sz types Headache, sedation, tremor.
LEV Myoclonus Behavioural side effects
ZSN >50% seizure Cognitive slowing, ataxia, sedation.
reduction
CLB Drop attacks Tonic seizures, tonic status epilepticus, behavioural
problems, sedation, tolerance.
CZP Myoclonus Same as above. In addition, ataxia, significant drug
interactions.
CBZ/OXC Tonic- clonic, Atypical absences, myoclonus.
tonic, focal
PHT Tonic- clonic, Atypical absences, myoclonus.
tonic
PB/PRM Tonic- clonic, Sedation, cognitive and behavioural worsening.
86. Immunotherapy in LGS
Prednisolone Prednisone 1 mg/kg/day for 12 weeks (6 weeks daily and 6
Sinclair weeks alternate therapy) in addition to their regular AEDs.
et al, 2003 The follow-up period was for 1 to 5 years.
7/10 children with LGS became seizure free.
Side effects: were uncommon; weight gain, aggression.
Verhelst 32 children with intractable epilepsy (excluding West
et al, 2005 syndrome). In 47% there was a decrease in seizure frequency.
25% became seizure free.
11% had a seizure reduction of >50%
11% had a seizure reduction of <50%.
IVIG Anecdotal and case series suggest benefit in LGS.
87. ACTH in LGS
N= 45 23 (51.1%) became "seizure free" for over 10 days.
10/23 relapsed within 6 months.
13/23 cases were seizure free for > 6 months.
8/13 patients had relapse from 9 months to 7 years later.
5/13 cases did not have relapse.
Factors Age at ACTH treatment: up to 4 years old
affecting Early initiation of ACTH: (within 1 year, preferably within 3
response mth).
Idiopathic/ cryptogenic cases.
No cognitive defects at onset.
Absence of tonic seizures.
EEG findings: absence of asymmetry.
Note Continue ACTH as long as possible, till disappearance of
seizure discharges, or at least the disappearance of diffuse
seizure discharges.
Yamatogi Y, et al. Brain Dev 1979; 4: 267- 76
88. Prognostic factors
Normal neurologic examination.
Cryptogenic LGS.
Normal cognitive status at onset.
Older age of onset.
EEG changes, seizure frequency, seizure type, family
history of epilepsy does not affect outcome.
Furune S et al. Brain dysfunction 1988; 1: 146- 53.
Oguni H et al. Epilepsia 1996; 37: 44- 47.
89. Conclusion
Long-term outcome in terms of seizure control and
intellectual development are disappointing and can be
extraordinarily stressful for families.
Cognitive problems are greatest with earlier onset
suggesting a profound effect on brain maturation at a
critical stage of development.
Seizure control is only one of the important goals in
attempting to improve the lives of these patients.
