01 friday morning 10-24-14

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.


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.


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


1. Borggraefe I, Noachtar S. Clin Med Insights Ther. 2010;2:15-24.



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.

http://www.orpha.net/data/patho/GB/uk-Lennox.pdf

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.


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

http://www.nice.org.uk/nicemedia/live/13635/57779/57779.pdf

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.


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.


1. Sethi NK, et al. The Internet J Neurol. 2008;9.

2. Morris GL, et al. Neurology. 2013;81:1-7.

http://epilepsy.med.nyu.edu/diagnosis-treatment/vagus-nerve-stimulation-vns#sthash.QxsV6OfH.dpbs

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.

http://www.gru.edu/mcg/neurosurgery/clinicalprograms/esphoto_gallery.php

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


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

………………..……………………………………………………………………………………………………………………………………..

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)

………………..……………………………………………………………………………………………………………………………………..

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!

Health & Medicine

01 friday morning 10-24-14