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Overview of Lennox-GastautSyndrome
John M. Pellock, MDInterim Senior Associate Dean
Continuing Medical Education
Professor of Neurology and Pediatrics
Virginia Commonwealth University
Richmond, Virginia
Introduction
• Lennox-Gastaut syndrome (LGS) is a severe
difficult-to-treat epilepsy of childhood onset1,2
– Frequently persists into adulthood
• Well-defined clinical and neurophysiologic features3
• Definition has varied over time resulting in
misclassification and overdiagnosis3
• Management in adulthood is problematic due to2
– Intractable seizures
– Complexity of intellectual development issues
– Social effects of intellectual disability/behavioral difficulties
1. Arzimanaglou A, et al. Lancet Neurol. 2009;8:82-93.
2. Kerr M, et al. Epileptic Disord. 2011;13:S15-26.
3. Van Rijkevorsel K. Neuropsych Dis Treat. 2008;4:1001-19.
LGS Defined by ILAE (2001)
• Childhood onset
• Multiple seizure types
– Common: tonic, atonic, atypical absence
– Rare: focal, myoclonic
• Specific EEG pattern
– Diffuse SSW complexes and bursts of fast rhythms (≥10 Hz)
during sleep
• Psychologic abnormalities with psychomotor delay,
behavioral disorder, or both
Abbreviations: EEG, electroencephalography; ILAE, International League Against Epilepsy; LGS, Lennox-Gastaut syndrome;
SSW, slow spike-wave.
Engel J. Epilepsia. 2001;42:796-803.
Varied Definitions of LGS
Abbreviations: IDD, intellectual developmental disorder; ILAE, International League Against Epilepsy; LGS, Lennox-Gastaut syndrome;
SSW, slow spike-wave.
1. Lennox WG, Davis JP. Pediatrics. 1950;5:626-44.
2. Trevathan E, Murphy CC. Epilepsia. 1997;38:1283-8.
3. Genton P, et al. Handbook of Clinical Neurology. 2000;73(29) (reviewed in Van Rijkevorsel K. Neuropsych Dis Treat.
2008;4:1001-19).
4. Engel J. Epilepsia. 2001;42:796-803.
5. French J, et al. Neurology. 2004;62:1261-73.
AuthorChildhood
OnsetIDD
Multiple
Seizure
Types
Tonic
Seizure in
Sleep
Diffuse
Slow SSW
Fast
Rhythms in
Sleep
Lennox
19501
Trevathan
19972
Genton
20003
ILAE
20014
French
20045
Complexities of LGS Definition
• Core seizure types (tonic, atonic, atypical absence)
not always present at onset1
• Interictal SSW EEG pattern not always
pathognomonic1
• Other seizure types (eg, focal or myoclonic) and
other EEG features can occur1
• Many patients do not fit the classic definition
– Elderly patient, started with focal pathology of frontal lobe,
evolved into LGS-like disorder (treated as LGS)
Abbreviations: EEG, electroencephalography; LGS, Lennox-Gastaut syndrome; SSW, slow spike-wave.
1. Arzimanaglou A, et al. Lancet Neurol. 2009;8:82-93.
Epidemiology of LGS
• Accounts for 1%-10% of all childhood epilepsies1
• May evolve from IS and encephalopathic epilepsy
– IS preceded LGS in 39% of cases2
• Annual incidence of LGS: 2 per 100,000 individuals2
• Prevalence ranges from 0.1-0.3 per 1000 individuals2
• Onset <8 years of age (peak 3-5 years)3,4
• More common in males than females4
• Seizures persist throughout life in >80% of cases4
Abbreviation: IS, infantile spasms; LGS, Lennox-Gastaut syndrome.
1. Crumrine P. Paediatr Drugs. 2011;13:107-18; 2. Trevethan E, Murphy CC. Epilepsia. 1997;38:1283-8.
3. Arzimanaglou A, et al. Lancet Neurol. 2009;8:82-93; 4. Van Rijkevorsel K. Neuropsych Dis Treat. 2008;4:1001-19.
LGS Classification
• Symptomatic (~75% of cases)1-3
– Clear underlying cause; significant abnormalities on
neuroimaging studies
– Various etiologies: pre- or perinatal insult, infection, various malformations (including dysplasia), brain tumor
– LGS often preceded by other epilepsy syndrome
(eg, infantile spasms, focal seizures)
• Cryptogenic/idiopathic (~25% of cases)1,4
– No identifiable etiology; normal neuroimaging studies
Abbreviation: LGS, Lennox-Gastaut syndrome.
1. Borggraefe I, Noachtar S. Clin Med Insights Ther. 2010;2:15-24.
2. Hancock E, Cross H. Cochrane Database Syst Rev. 2009;CD003277.
3. Van Rijkevorsel K. Neuropsych Dis Treat. 2008;4:1001-19.
4. Markand ON. J Clin Neurophysiol. 2003;20:426-41.
Evolution of LGS Into Adulthood: Seizure Types and EEG
• 50%-75% of adults diagnosed with LGS during
childhood no longer display all clinical/EEG features
• Number and types of seizures decrease over time
– Tonic seizures tend to persist, mainly during sleep
– Partial seizures become more apparent
– Seizures are often intractable
• EEG features change in adults
– SSW complexes transitory in many patients
– Paroxysmal fast activity during sleep
Abbreviations: EEG, electroencephalography; LGS, Lennox-Gastaut syndrome; SSW, slow spike-wave.Kerr M, et al. Epileptic Disord. 2011;13:S15-26.
3T MRI of Frontal Neuronal Migration Abnormality
Abbreviations: 3T, 3 tesla; MRI, magnetic resonance imaging.
Image courtesy of Dr. Michael Stein, Alexius Medical Center (personal communication).
Cognitive Impairment
• Abnormal cognitive development before seizure onset occurs
in most LGS patients1
– 20%-60% (symptomatic) have delayed development at LGS onset2
• 30% of patients (cryptogenic) have seemingly normal
development before seizure onset2
• By 5 years from LGS onset, 75%-95% of patients have
cognitive impairment1,2
• 90% of patients will eventually become intellectually
handicapped3
• Psychiatric disorders and behavioral problems may also
occur in LGS2
Abbreviation: LGS, Lennox-Gastaut syndrome.
1. Borggraefe I, Noachtar S. Clin Med Insights Ther. 2010;2:15-24.
2. Arzimanaglou A, et al. Lancet Neurol. 2009;8:82-93.
3. Van Rijkevorsel K. Neuropsych Dis Treat. 2008;4:1001-19.
Diagnostic Workup
• Complete medical history
• Detailed physical/neurologic exam
• Family history
• Routine blood work, toxic screening, metabolic
monitoring,* serum levels
• EEG (often requires sedation in multiply handicapped)
• Neuroimaging (MRI preferred)
• Video-EEG monitoring
• Video recording of events
*Consider metabolic monitoring in multiply handicapped patients who may not be able to express symptoms.
Abbreviations: EEG, electroencephalography; MRI, magnetic resonance imaging.
Prognosis
• Poor long-term prognosis due to uncontrolled seizures1,2
• Refractory epilepsy with multiple seizure types persists in
many LGS patients from childhood through adulthood1,3
• Worse prognosis in patients with symptomatic LGS (mainly
with preexistent IS/West syndrome), frequent seizures, and
repeated status epilepticus episodes4
• High and variable mortality rate5-8
– SUDEP accounts for up to 50% of deaths6
– 3%-7% largely related to accidents7
– 25% due to underlying neurologic conditions8
– Frequent falls with fracture (hip) or closed head injury
Abbreviations: IS, infantile spasms; LGS, Lennox-Gastaut syndrome; SUDEP, sudden unexpected death in epilepsy.
1. Markand ON. J Clin Neurophysiol. 2003;20:426-41; 2. Ferrie CD, Patel A. Eur J Paediatr Neurol. 2009;13:493-504;
3. Crumrine PK. J Child Neurol. 2002;17:S70-5;
4. Campos-Castelló J. Orphanet Encyclopedia. 2004:1-5. www.orpha.net/data/patho/GB/uk-Lennox.pdf.
5. Van Rijkevorsel K. Neuropsych Dis Treat. 2008;4:1001-19; 6. Sperling MR. CNS Spectr. 2004;9:98-101, 106-9.
7. Glauser TA. Epilepsia. 2004;45(S5):23-6; 8. Camfield P, Camfield C. Epilepsia. 2007;48:1128-32.
Goals of Adult LGS Management
• Multidisciplinary care approach
– Control seizures
– Reduce polypharmacy
– Minimize AED-associated toxicities
– Manage behavioral and cognitive comorbidities
– Provide support for social and developmental needs
Abbreviations: AED, antiepileptic drug; LGS, Lennox-Gastaut syndrome.
Kerr M, et al. Epileptic Disord. 2011;13:S15-26.
Treatment Approaches
• Pharmacotherapy
– Antiepileptic drugs (AEDs)
• Nonpharmacotherapy
– Surgery
Vagus nerve stimulation (VNS)
Corpus callosotomy
– Diet
Ketogenic
Modified Atkins
Arzimanaglou A, et al. Lancet Neurol. 2009;8:82-93.
Borggraefe I, Noachtar S. Clin Med Insights Ther. 2010;2:15-24.
Kerr M, et al. Epileptic Disord. 2011;13:S15-26.
Lemmon ME, Kossoff EH. Curr Treat Options Neurol. 2013;6:189-98.
Current AED Management Guidelines
*May worsen seizures in LGS patients.
Abbreviations: AAN, American Academy of Neurology; AED, antiepileptic drug; AES, American Epilepsy Society;
EU, European Union; NA+, sodium; NICE, National Institute for Health and Care Excellence; US, United States.
Figure adapted from Carmant L, Whiting S. Can J Neurol Sci. 2012;39:702-11.
1. French J, et al. Epilepsia. 2004;45:410-23; 2. Wheless J, et al. J Child Neurol. 2005;20:S1-56;
3. Wheless JW, et al. Epileptic Disord. 2007;9:353-412; 4. National Institute for Health and Care Excellence
(NICE) clinical guideline. 2012. Available at: http://www.nice.org.uk/nicemedia/live/13635/57779/57779.pdf.
Lamotrigine
Topiramate
Valproic acid
Topiramate
Lamotrigine
Valproic acid
Topiramate
LamotrigineValproic acid
Ethosuximide
Clobazam
Clonazepam
Levetiracetam
Zonisamide
Levetiracetam
Felbamate
Lamotrigine
Topiramate
Rufinamide
AVOID*Carbamazepine
Gabapentin
Oxcarbazepine
Pregabalin
Tiagabine
Vigabatrin
Expert opinion studies recommend
2 monotherapies prior to polytherapy
AAN/AES
20041
US Expert Opinion
20052
EU Expert Opinion
20073
NICE
20124
1st Line
2nd Line
3rd Line
• AEDs that excitability of neurons (eg, levetiracetam, gabapentin) may
exacerbate behavioral problems
• NA+ channel blockers (eg, carbamazepine, lamotrigine) can exacerbate
gait/balance and produce falls
Median Reduction in Drop Attacks With AEDs in LGS*
*Results are from individual studies. AEDs are listed from left to right by FDA approval date.
Abbreviations: AED, antiepileptic drug; FDA, Food and Drug Administration; LGS, Lennox-Gastaut syndrome.
1. The Felbamate Study Group. N Engl J Med. 1993;328:29-33; 2. Motte J, et al. N Engl J Med. 1997;337:1807-12;
3. Sachdeo RC, et al. Neurology. 1999;52:1882-7; 4. Glauser T, et al. Neurology. 2008;70:1950-8;
5. Ng YT, et al. Neurology. 2011;77:1473-81.
Felbamate1 Lamotrigine2 Topiramate3 Rufinamide4 Clobazam5
high dose
(1.0 mg/kg/day)
P = .041
P = .002P < .0001
P < .0001
-10
0
10
20
30
40
50
60
70
80
Pe
rce
nt re
du
ctio
n
P = .01
80
70
60
50
40
30
20
10
0
-10
Active Placebo
Median Reduction in Total Seizure Frequency With AEDs in LGS*
*Results are from individual studies. AEDs are listed from left to right by FDA approval date.
Abbreviations: AED, antiepileptic drug; FDA, Food and Drug Administration; LGS, Lennox-Gastaut syndrome.
1. The Felbamate Study Group. N Engl J Med. 1993;328:29-33; 2. Motte J, et al. N Engl J Med. 1997;337:1807-12;
3. Sachdeo RC, et al. Neurology. 1999;52:1882-7; 4. Glauser T, et al. Neurology. 2008;70:1950-8;
5. Ng YT, et al. Neurology. 2011;77:1473-81.
Perc
en
t re
duction
Felbamate1 Lamotrigine2 Topiramate3 Rufinamide4 Clobazam5
high dose
(1.0 mg/kg/day)
70
60
50
40
30
20
10
0
-10
P = NS
P < .001
P = .002 P = .0015
P < .0001Active Placebo
Median Reduction in Drop Seizures and Total Seizures With Clobazam
Abbreviation: CLB, clobazam.
Ng YT, et al. Neurology. 2011;77:1473-81.
Drop Seizures Total Seizures
Perc
en
t re
duction
P < .0001
P = .0015
P = .0120
P < .0001
P = .0044
P = .0414
80
70
60
50
40
30
20
10
0
70
60
50
40
30
20
10
0
Placebo
Low-dose (0.25 mg/kg/d) CLB
Medium-dose (0.5 mg/kg/d) CLB
High-dose (1.0 mg/kg/d) CLB
Potential for Drug-Drug Interactions With AEDs
Cytochrome P450
Negligible or
no effect
Lamotrigine
Levetiracetam
Zonisamide
Abbreviations: AED, antiepileptic drug; EH, epoxide hydrolase; UGT, UDP-glucuronosyltransferase.
Asconape JJ, et al. Neurol Clin. 2010;28:843-52.
Mild inducers (3A4) or
inhibitors (2C19)
Oxcarbazepine
Topiramate
Rufinamide
Inhibitors
(2C9, UGT, EH)
Valproate
Felbamate
Strong or moderate
inhibitors (2C19)
Clobazam
Drug Level Monitoring
• Establish “baseline” effective concentrations
• Evaluate potential causes for lack of efficacy
– Monitor free AED levels for all highly protein-bound AEDs (VPA, CLB)
– “Fast metabolizers”
– Noncompliance
• Evaluate potential causes for toxicity
– Altered drug utilization as a result of physiologic (eg, puberty) and/or
pathologic (eg, renal/liver failure) conditions
– “Slow metabolizers”
– Drug-drug interactions
• Evaluate potential causes for loss of efficacy
– Altered drug utilization as a result of physiologic conditions (eg, neonates)
– Change in formulation
– Drug-drug interaction
Abbreviations: AED, antiepileptic drug; CLB, clobazam; VPA, valproate.
Treatment Approaches
• Pharmacotherapy
– Antiepileptic drugs (AEDs)
• Nonpharmacotherapy
– Surgery
Vagus nerve stimulation (VNS)
Corpus callosotomy
– Diet
Ketogenic
Modified Atkins
Arzimanaglou A, et al. Lancet Neurol. 2009;8:82-93.
Borggraefe I, Noachtar S. Clin Med Insights Ther. 2010;2:15-24.
Kerr M, et al. Epileptic Disord. 2011;13:S15-26.
Lemmon ME, Kossoff EH. Curr Treat Options Neurol. 2013;6:189-98.
Medical Marijuana and Epilepsy
• Anecdotal reports – few negative
• Overall efficacy, safety, dosing not defined
• “Charlotte’s Web” – cannabidiol (CBD) – Weed (CNN)
• Legal in 15 states
• AES: support well designed clinical research
• EF: Change from Schedule I (DEA) to allow research
• FDA: Granted orphan status for Epidiolex (GW) –Dravet, LGS, Phase 1, CBD, 5 sites
• No trial has yet demonstrated efficacy (Willner, Medscape, 2014)
Vagus Nerve Stimulation (VNS)
• Pulse generator implanted
subcutaneously and
connected to left vagus nerve1
– Stimulation parameters can
be programmed
• Approved as adjunctive
therapy for patients aged
≥12 years with refractory
partial-onset seizures
• Evidence-based guidelines
recommend VNS for LGS-
associated seizures2
Figure from http://epilepsy.med.nyu.edu/diagnosis-treatment/vagus-nerve-stimulation-vns#sthash.QxsV6OfH.dpbs.
Abbreviation: LGS, Lennox-Gastaut syndrome.
1. Sethi NK, et al. The Internet J Neurol. 2008;9.
2. Morris GL, et al. Neurology. 2013;81:1-7.
Corpus Callosotomy (CC)
• CC entails sectioning of either
anterior two-thirds only or entire
corpus callosum1,2
– Partial: better speech preservation
– Complete: better seizure control
• CC effective for treating drop
attacks, absence, GTCS2-4
– 61%-85% of patients achieve >80%
reduction in drop attacks2,3
• VNS often considered first due to
invasive nature and risk of AEs
with CC1
Abbreviations: AE, adverse event; GTCS, generalized tonic-clonic seizure; VNS, vagus nerve stimulation.
Figure from http://www.gru.edu/mcg/neurosurgery/clinicalprograms/esphoto_gallery.php.
1. VanStraten AF, Ng Y-T. Pediatr Neurol. 2012;47:153-61. 2. Maehara T, et al. Epilepsia. 2001;42:67-71.
3. Nei M, et al. Epilepsia. 2006;47:115-22. 4. Asadi-Pooya AA, et al. Epilepsy Behav. 2013;29:285-8.
Efficacy of Ketogenic Diet in LGS
– Results were similar after 12 months
• Limitations
– Treatment noncompliance may be worse with ketogenic diet due to its
restrictive and complicated nature
• Efficacy
– Ketogenic diet is efficacious in the treatment of LGS
Author NAge
(yrs)
>50% Reduction in
Seizure Frequency
>90% Reduction in
Seizure Frequency
Freeman et al, 20091 20 1-7.4 65 --
Lemmon et al, 20122 71 4-52 51 23
Abbreviation: LGS, Lennox-Gastaut syndrome.
1. Freeman JM, et al. Epilepsia. 2009;50:322-5.
2. Lemmon ME, et al. Dev Med Child Neurol. 2012;54:464-8.
Management of LGS
• Long-term treatment is deceptive
– Danger of excessive therapy
• AED combinations may facilitate episodes of nonconvulsive/
tonic status epilepticus
– Risk for adverse events
• AED interactions
• Transitory efficacy of benzodiazepines
– Utilize alternately/intermittently
• Avoid AEDs such as carbamazepine, oxcarbazepine, and
phenytoin that may exacerbate seizures
– Many AEDs (such as gabapentin, levetiracetam, phenobarbital,
benzodiazepines) exacerbate behavioral problems
Abbreviations: AED, antiepileptic drug; LGS, Lennox-Gastaut syndrome.Arzimanaglou A, et al. Lancet Neurol. 2009;8:82-93.
Management of LGS (cont.)
• Choice of drug to be added may depend on prominent
seizure at that time
– Felbamate, lamotrigine, rufinamide, topiramate, clobazam indicated for
drop attacks
• Given the evolving nature of LGS, identify seizure pattern
changes
• Management of LGS requires multidisciplinary medical and
psychosocial team
• Issues to consider beyond seizures
– Sleep, cognition, behavior, physical impact
• Be aware of potential side effects of multiple AEDs and
medications for comorbid disorders
Abbreviations: AED, antiepileptic drug; LGS, Lennox-Gastaut syndrome.Arzimanaglou A, et al. Lancet Neurol. 2009;8:82-93.
Conclusions
• LGS remains one of the most challenging epileptic
encephalopathies despite availability of several new AEDs1
• Long-term outcome regarding seizure control and intellectual
development is disappointing and can be taxing for families2
• Management of LGS into adulthood requires global care
approach3
– Offers unique challenges regarding recognition and diagnosis
• Total seizure control not necessarily the main concern as
management of comorbidities is often a higher priority3
− Coordinate educational and psychosocial needs with medical care
Abbreviations: AED, antiepileptic drug; LGS, Lennox-Gastaut syndrome.1. Arzimanaglou A, et al. Lancet Neurol. 2009;8:82-93. 2. Camfield PR. Epilepsia. 2011;52:3-9.3. Kerr M, et al. Epileptic Disord. 2011;13:S15-26.
………………..……………………………………………………………………………………………………………………………………..
Non-pharmacological
therapies for LGS
………………..……………………………………………………………………………………………………………………………………..
33
Anup Patel, M.D.
Director of Complex Epilepsy Clinic
Associate Medical Director Partners for Kids
Associate Director Child Neurology Residency Program
Assistant Professor of Neurology and Pediatrics
Nationwide Children’s Hospital & The Ohio State University College of Medicine
………………..……………………………………………………………………………………………………………………………………..
Disclosures
• Research grant from Eisai
• Consulting for Health Logics, Cyberonics, and GW
Pharmaceuticals
• Webinar development for American Academy of Neurology
………………..……………………………………………………………………………………………………………………………………..
According to the Epilepsy Foundation, the goal of all epilepsy treatment is to:
•Prevent further seizures•Avoid side effects•Make it possible for people to lead active lives
Individual treatment goals may include:•Ability to regain/retain your driving privileges•Job stability•Academic success
Goals of Treatment
………………..……………………………………………………………………………………………………………………………………..
• Most people who have epilepsy are on medications
• Unfortunately, no “magic bullet”
• Biofeedback, chiropractic manipulation, antioxidants, chelation,
hypnosis, or exorcism not clinically proven to be effective
• Vitamin B6 and/or folinic (not folic) acid used for infants who
have a deficiency of this vitamin as a cause for their seizures
• Other vitamins not clinically proven to help
Treating Seizures
………………..……………………………………………………………………………………………………………………………………..
Use a single drug whenever possible
However, remember that only around 60% of patients are controlled on
one medication
Start low and go slow
Increase the dose of that medication to either seizure control or toxicity
(decreasing the dose if toxicity occurs)
If a medication does not control seizures without toxicity, switch to
another appropriate medication used alone, and again increase the
dose until seizure control occurs or toxicity intervenes
Medication Therapy
basic principles
………………..……………………………………………………………………………………………………………………………………..
The chance of seizure freedom after starting one medication is
about 60%
If you fail an adequate trial of one medication, the likelihood you
will be seizure free on the second medication is about 10%
If you fail the second medication, the likelihood you will be seizure
free on the third medication is about 1 to 3 %
Many children and adults with LGS are treatment resistant
Medications
………………..……………………………………………………………………………………………………………………………………..
Seizure Triggers
• In some people, seizures are triggered by specific events
Missing a dose of medication
Drugs and Alcohol
A small number of people may be sensitiveto flickering lights
Overly tired
Infection (fever)
• Avoid triggers if possible
• Seizures may be improved by treating sleep apnea
………………..……………………………………………………………………………………………………………………………………..
How Many Medications Are Available?
Older Medications
(1st Generation)
Generic Name Year IntroducedTrade
Name
Bromides 1857 —
Phenobarbital 1912 Luminal®
Phenytoin Sodium 1956 Dilantin®
Ethosuximide 1960 Zarontin®
Diazepam 1963 Valium®
Carbamazepine 1968 Tegretol®
Lorazepam 1977 Ativan®
Valproic acid 1978 Depakene®
Divalproex sodium 1983 Depakote®
Carbamazepine 1986 Epitol®
Diazepam 1997 Diastat®
Carbamazepine 1997 Carbatrol®
Phenytoin Sodium 1998 Phenytek®
Newer Medications
(2nd & 3rd Generation)
Generic Name FDA ApprovalTrade
Name
Felbamate 1993 Felbatol®
Gabapentin 1993 Neurontin®
Lamotrigine 1994 Lamictal®
Topiramate 1996 Topamax®
Tiagabine 1997 Gabitril®
Levetiracetam 1999 Keppra®
Oxcarbazepine 2000 Trileptal®
Zonisamide 2000 Zonegran®
Pregabalin 2005 Lyrica®
Rufinamide 2007 Banzel ®
Lacosamide 2008 Vimpat ®
Vigabatrin 2009 Sabril ®
Clobazam 2011 Onfi ®
Esogabine 2012 Potiga ®
Preampanel 2013 Fycompa®
Eslicarbazepine 2013 Aptiom®
………………..……………………………………………………………………………………………………………………………………..
Bromides
Dose for Potassium Bromide:
Pediatric: 45 mg/kg/day, titrate to 75 mg/kg/day (slow titration considering the long half-life)
Adults: 30-50 mg/kg/day
Dose for Triple Bromide:
10 to 30 mg/kg/day
Dosage forms:
850 mg capsule used in German study (COCP willing to make any size we want)
Oral solution may go as high as 600 mg/mL if needed (250-300 mg/mL may be more reasonable and aid with palatability)
Clinical Pearls:
Keep dietary sodium content consistent
Renally-cleared, contact clinical pharmacy for dosing in patients with comorbid renal disease
Half-life 6-8 days in children, 8-14 days in adults
Lasix may increase renal excretion in acute toxicity
………………..……………………………………………………………………………………………………………………………………..
Epidiolex®
98% CBD
1-2% CBDv and/or THC
On 11/15/2013, GW Pharmaceuticals (based in England) granted orphan drug status by FDA for cannabidiol in Dravet Syndrome
Likely will attempt same status for LGS
Dosage forms 25 mg/ml and 100 mg/ml concentrations
Adverse effects appear mild with sedation, and nausea.
Dosing 25 to 50 mg/kg/day
Phase II/III studies in LGS likely late 2014 or early 2015
………………..……………………………………………………………………………………………………………………………………..
Charlotte’s Web
Strain of marijuana also high in CBD and lower in THC
Concentrated cannabis oil
Pediatric Dosing 200 to 300 mg per day
No good studies supporting its use
Adverse effects not fully known
Featured on CNN with Sanjay Gupta, MD
Available from Realm of Caring Foundation
Legal issues remain
………………..……………………………………………………………………………………………………………………………………..
What is The Ketogenic Diet?
High-fat, adequate-protein, low-carbohydrate diet
90% of the calories are from fat
The diet forces the body to burn fats rather than carbohydrates
Unsure how it works exactly
Been used to treat epilepsy for over 90 years
………………..……………………………………………………………………………………………………………………………………..
Ketogenic Diet
Approximately 50% of patients with LGS respond to the KD with a >50% reduction in seizures and some patients (23%) may achieve a >90% reduction
Patients usually admitted to start diet
Starts with a 48 hour fast followed by diet introduction to get to ketosis
Should give it 3 months
Re-evaluate after 1-2 years on treatment
Must have strong Dietitian support
………………..……………………………………………………………………………………………………………………………………..
Ketogenic Diet – Side Effects
Constipation
Vomiting
Abdominal pain
Decreased energy
High cholesterol
Kidney stones
Slower growth potential (?)
………………..……………………………………………………………………………………………………………………………………..
Other Forms of Dietary Therapy
Modified Adkins diet
Low-Glycemic index diet
Less restriction
Not been well studied in LGS patients
Could be good options for some to consider
What is VNS Therapy?
The VNS Therapy System
consists of an implanted
pacemaker-like generator and
nerve stimulation electrodes,
which deliver intermittent
stimulation to the patient’s left
vagus nerve that sends signals to
the brain
………………..……………………………………………………………………………………………………………………………………..
Vagus nerve stimulation
It is used as add on treatment for drug-resistant epilepsy (including
patients with LGS) who are not suitable candidates for resective
surgery
50% of LGS patients respond to VNS therapy, with at least
a >50% reduction in seizures
Response may improve over time
Appeared best for drop attack (atonic) seizures
Recent American Academy of Neurology (AAN) guideline
recommends that VNS be considered for patients with LGS
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VNS may be considered for seizures in children, for LGS-associated
seizures
Currently developing wireless wand to handheld (tablet)
communication
Seizure detection recognition for activation (Aspire SD)
Longer battery life (now available)
Telephone adjustments ?
Vagal Nerve Stimulator (VNS)
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105 Generator and Beyond
Longer battery life
May have ability for seizure detection (being tested)
Wireless programming via bluetooth
Trying to develop telephone programming changes
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VNS – Side Effects
Site infection
During stimulation:
•Hoarseness
•Drooling
•Cough
•Voice alteration
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New Devices
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CNS implanted device that would recognize seizure activity and activate signal to stop it
Potentially more benefit for patients with bilateral mesial temporal sclerosis
Brain surgery
Recently FDA approved
Will not be considered for children less than 12 due to skull growth
Neuropace
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Deep Brain Stimulation
Stimulation rods inserted directly into portion of the brain
Originally developed for Parkinson’s Disease
Used in severe Tourette’s and other movement disorders
Currently being evaluated in adults with epilepsy
Preliminary results not promising
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Epilepsy
Epilepsy is a treatable condition and epileptic patients can live a
normal and healthy life. Epilepsy should not be a social taboo.
Questions?
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Thank You!