An epileptic syndrome in which the primary clinical manifestation is
LANGUAGE REGRESSION
ACQUIRED AUDITORY AGNOSIA
- ONSET, subacute, steady or stuttering & initially consists of loss of understanding of spoken language
- EVENTUALLY, speech output is disrupted & paraphasias & phonologic errors appear
- SEVERE, child becomes entirely mute & doesn’t respond to nonverbal sounds (acknowledge phone ringing-knocking on the door)
- 200 cases described between 1968 & 1992
- Review of 1,497 overnight video EEG performed over 5-yr interval, Van Hirtum-Das et al found 102 records showed significant sleep activation defined as a spike-wave index of 25% or higher
- 20% --> LKS & 32% --> autistic
- Unknown
- Structural abnormalities
- Preceding neurologic condition (meningitis-neonatal encephalopathy)
- Immune disorder (45% IgG, 9% IgM anti-brain autoantibodies)
- Genetic disorder
AGE OF ONSET
3 – 8 yrs
Peak 4 – 5 yrs
- The apparently “generalized” epileptiform discharges --> caused by single primary focus with secondary bilateral synchrony
- Activation of reticulo-thalamic-cortical system with secondary bilateral synchronization through corpus callosum
OTHER SYMPTOMS
Before onset, language & development --> unremarkable
Irritability
Hyperactivity
Poor reasoning
Aggressiveness
Attention-deficit disorder
Autistic-like behavior
Sz 70-80%
Typically infrequent
Easily treated
Types (generalized tonic-partial clonic-atypical absence+atonic)
Most common sz, eye blinking or ocular deviation, head drops, minor automatisms + 2ry generalization
AWAKE:
- Variable
- Focal (posterior temporal)
- Multifocal
- Generalized epileptic abnormalities
- Normal
SLEEP:
- Marked activation
- Occupied 40-90% of the first slow-wave cycle
- Long clusters of spike-wave activity, maximal over centrotemporal head regions but spread diffusely
- Massa et al
- Less activation of epileptiform discharges in stages 1 & 2
The intrasylvian cortex is the likely pacemaker of epileptic discharges (4 children)
Perisylvian spikes (13/19 pts)
- 10 bilateral & 3 unilateral
- 4 --> spikes outside perisylvian region
- 2 --> no spikes
STRUCTURAL NEUROIMAGING
FUNCTIONAL NEUROIMAGING
Gaggero et al (10 children):
- 6 --> Reduced blood flow during drowsiness
- 4 --> Correlated with the site of most prevalent EEG discharges
- Longer duration of CSWS --> more likely abnormal study
De Tiege et al (18 children):
- 10 --> hypermetabolism, maximally in parietotemporal junction
- Furthermore, significant association existed between absence of hypermetabolic cerebral region & corticosteroid treatment before study
Focal hypermetabolism --> active phase
Evolution to focal hypometabolism or normal --> recovery
All children with regional hypermetabolism --> hypometabolism in frontal regions --> attention deficit
- No polysomnographic studies
- However, Beaumanoir, notes 10% --> absence of sleep spindles
Goal:
- Control sz
- Improve neuropsychological function
- Contraindicated --> phenytoin, CBZ & barbiturates --> worsen neuropsychological outcome & EEG discharges
- Avoid polypharmacy
- Valproic acid
- Ethosuximide
- Benzodiazepines
- Keppra
- Sulthiame
Diazepam:
3-4 weeks
0.5-0.75 mg/kg/d
Side effects: hypotonia, hyperexcitability, problematic behavioral disinhibition
- Prednisone 2-5 mg/kg/d
- Methylprednisolone 20 mg/kg/d X 3 days
- ACTH 80 IU/d with 3-month taper
- Earlier steroids --> shorter duration --> better outcome
- ?dose vs ?duration
- Tapering --> relapse
- 2 g/kg over 4 days
- ?more studies
- Multiple subpial transections
- Placing parallel slices through the cortex to disrupt horizontal cortical synchronizing networks yet leaving subcortical-cortical input intact
- More studies
Sz --> resolve or markedly decrease by puberty
EEG --> resolve by puberty
Neuropsychological --> problematic (10-44% normal language & intelligence)
- Uncommon (underrecognized)
- If clinically suspected, must obtian adequate sleep EEG + slow-wave sleep
- Treatment must extend beyond just controlling sz
- Early treatment with effective therapy is essential for improvement in neuropsyhological outcome
- Not good evidence to guide treatment decisions at this time
- AED have minimal role
- Multicenter studies to compare therapeutic efficacy & tolerability of the various regimens should be considered
THANK YOU
SUMMARY
PROGNOSIS
OTHER THERAPIES
IN THE NAME OF ALLAH,
MOST GRACIOUS, MOST MERCIFUL
Journal of clinical neurophysiology, 2003
LANDAU-KLEFFNER SYNDROME
SURGERY
INCIDENCE
IVIG
Mikati et al, Nickels et al
STEROIDS & ADRENOCORTICOTROPIC HORMONE
ETIOLOGY
HIGH-DOSE BENZODIAZEPINES
AED
TREATMENT
PATHOPHYSIOLOGY
EFFECT ON SLEEP PATTERNS
EEG
Journal of clinical neurophysiology, 2003
EEG
MAGNETOENCEPHALOGRAPHY
Paetau et al, Nickels et al, 2008
Sobel et al, Nickels et al, 2008