The Developmental Disabilities Assistance & Bill of Rights Act(DD Act) ensures that individuals with developmental disabilities and their families have access to community-based services and supports to promote opportunities for independence, productivity and inclusion. Title I of the Act established four components, including the:State Councils on Developmental Disabilities to represent and advocate for people with developmental disabilities; Protection and Advocacy (P&A) Systems to protect the legal and human rights of individuals with developmental disabilities within each state and U.S. territory;University Centers for Excellence in Developmental Disabilities to provide training, technical assistance, service, research and information sharing, with a focus on sustainable living for people with disabilities; andProjects of National Significance to support the development of national and state policy which enhances the independence, productivity, inclusion and integration of individuals with developmental disabilities in the community. Title II authorizes the Family Support Program, which provides in-home supports for families caring for individuals with disabilities.For more information, refer to the Developmental Disabilities Assistance and Bill of Rights Act (D.D. Act) fact sheet, developed by several leading disability advocacy organizations.
Selected Slides from the LGSF National Conference
Selected Presenter Slides
COMORBITIESASSOCIATED WITHLENNOX-GASTAUTSYNDROMENATIONAL LGS MEETINGCerritos CA May 3,4 2013
Michael G. Chez MDDirector Pediatric Neurology andEpilepsy, Sutter NeuroscienceInstititueSacramento, CAProfessional Advisory Board LGS FoundationNo conflicts with today’s lecture
History William G. Lennox 1884–1960 Henri Gastaut 1915-1995 Defined EEG and Clinical Abnormalities ofthis disease LGS clinically described syndrome isactually spectrum of causes
• DEFINED BY CLINICAL FINDINGS• HETEROGENOUS/ THEREFORE VARIOUSCAUSES• NOT ONE CAUSE SO NOT ALL CASESRESPOND RESPOND THE SAMELENNOX GASTAUT SYNDROME
Defining LGS Incidence: estimate 2:100,000 0.002% Approximately 5% of Children withepilepsy 20 % prior Infantile Spasms of WestSyndrome
Clinical Definition Age of onset typically after age 2 Can be normal before onset May rarely start in adolscence oradult Mortality rate ranges from 3% to 7%
Clinical Manifestations Seizure Onset may be sudden andprogress rapidly if not prior seizurehistory (i.e. prior infantile spasms) Spectrum of Causes Idiopathic 30% Lesional 70% Syndrome Genetics
• INJURY TO BRAIN• GENETICS/ DRAVETS• OTHER GENETICS FOX,CDLK, KCNQ2VARIENT,TSC1,2• ANGELMANNS; AICARDI,TSC RETTS ETC• De Novo Mutations CNV• INFECTION• IDIOPATHICLGS ETIOLOGY
LGS defined byclinical seizure typeand EEG pattern Irregularbackground High amplitude slow Slow spike and wave Electrodecrementalresponse spike wave Fast “buzz”typedischarges in sleepLGS DEFINEDEEG FINDING
TREATMENT LGSTREATMENT LGSMEDICATIONSCOGNITIVE EFFECTSOLD VS. NEW MEDICATIONS
LGS SEIZURE and TREATMENT LGS Seizure Patterns Can Alter Outcome Early Intervention Drop Attacks/ Atonic Atypical AbsenceWorsen EtilogyDoose vs. Dravet Head Injuries/ Status Epilepsticus Atypical Absence
EEG Improvement ususally correlates withbetter seizure control and cognitiveoutcomeTREATMENT LGSEEG PATTERN CORRELATES WITHDEVELOPMENTALARREST EARLY IN COURSEIF EEG IMPROVES MAY SEEBETTER OUTCOME
EEG PATTERNS Generalized attention Focal MemoryAEDS IN LGSAEDS CAN CAUSE SIDE EFFECTSEEG PATTERNS CAN AFFECTATTENTION (GENERALIZED SPIKEWAVE)EEG PATTERNS CAN AFFECTMEMORY (FOCAL)ATYPICAL ABSENCE/ STUPOR
Often Polytherapy Often mixture mechanisms All AEDs inhibitory cortical excitationAEDS IN LGSAEDS CAN CAUSE SIDE EFFECTSEEG PATTERNS CAN AFFECTATTENTION (GENERALIZED SPIKEWAVE)EEG PATTERNS CAN AFFECTMEMORY (FOCAL)ATYPICAL ABSENCE/ STUPOR
If Cortex in LGS less excitablethen local synaptic modelingless likely to adopt and learnnew connectivity or learningmay be inhibited LGS Brain may be less excitable thannormal brain Cause vs underlying issue of diseasestate?
LGS less synaptic potentiationLess ability to learn or inhibitdefective inhibition/excitation Synaptic stability is new area ofneuroscience Many genes associated with comorbidpsychiatric conditions exhibit less synapticexcitation/ inhibition Protein scaffolding abnormal Shank Genesand Rett’s Fragile X etc
COMORBID LEARNINGISSUES IN LGS Attention Deficit May see with AED and frequentgeneralized seizures Absence/ atypical absence >40% children with epilepsy may haveADD/ ADHD
Atypical Absence Prolonged staring Slow spike andwave or polyspike–wave 1-3 hz Frequency May be refractiveto typicalmedications forabsence seizures Sometimes worsebenzodiazepines
LANGUAGE COMORBIDITYEARLY ONSET EPILEPSYFocal Epilepsy Language RegionsSleep DysruptionOral Motor DelayEtiologyPrior IS Genetics Brain InjuryAuditory Processing IssuesMemory
BEHAVIORAL ISSUES LGSDelayed speechDelayed impulsesFrontal Lobe Pseudobulbar AffectSleep IssuesAggressionSelf-InjuryAutism Features80% will have autism spectrum featuresWorse with poor seizure control
CASE EXAMPLE LGS GENETICdenovo mutation 7q21 deletionThis is a case of 3.5 yr old boy with history of autism behavior andatypical absence seizures who begins drop attacks while startingvalproic acid therapyPatient found genetic defect on microarray 7q21-Patient negative for channelopathy screenParents negative for mutationPatient had diagnosis autism pre-treatment and LGS on EEG andseizures clinically12 weeks after normal EEG no longer autistic no in regular 1st grademild ADHD
Variability in LGS ComorbityTREAT THE PATIENTEEG TREATMENT CRITICALCOMORBID MEDICATION ISSUES NEED TO BE CONSIDEREDAED choices should use rational polytherapy: complimentarymechanismsPatient comorbid ADHD mood or anxiety, sleep, or otherdisorders need to be managed per individualEarly aggressive EEG treatment/ seizure control probablymost effective effort to llimit cognitive outcome especially inidiopathic cases, but also some genetic subtypes
LGS Summary Treatment should be aggressive due torefractory nature of seizures Treatment should includepharmacological, dietary, immune, andsurgical options Treatment of comorbid neuropsychologicalaspects may improve quality of life Thorough Genetic evaluation needed allcases without clear brain injury like HIE orstroke /infection
NeuromodulationEric BJ Segal, MDPediatric EpileptologistNortheast Regional Epilepsy GroupHackensack, New Jersey
Goal of treatment of epilepsy Eliminate seizures without a significantimpact on behavior or cognition. Initial therapy – medications More than 50% of patients becomeseizure-free with initial therapy Less than 20% will become seizure-freewith further medications.
When to consider non-medication therapies? When medications do not preventseizures or side effects are intolerable.
What is neuromodulation? Seizures are caused by synchronized firing ofan inappropriate network of neurons. Electrical current can be used to suppressneuronal firing or interfere with synchronizedfiring of a population of neurons. Electrical stimulation of the central nervoussystem in order to prevent seizures.
Types of neuromodulationmodalities Vagal Nerve Stimulation Deep Brain Stimulation Trigeminal Nerve Stimulation* Responsive Neurostimlation Transmagnetic Stimulation*
Vagal nerve stimulation (VNS) Generator deliversintermittent electricalstimulus to wire coiledaround left vagus nerve inneck Vagal nerve then transmitssignal to the brainstem andthen to areas involved inepileptogensis.*
VNS practicalities Battery is replaceable/removable. Programmed by non-invasive paddle. Additional stimulation administeredthrough magnet
VNS efficacy (for LGS) At 6 months – 27-64% reduction. 50% seizure reduction rate at 6 months–50% 50% seizure reduction rate at 12 months –65% Drop seizures decreased by 88%. References: Arzimangolu 2009, Kotagal 2011,Rosenfeld 2009.
VNS Complications Infection rate: 3% (1% require explant) Most common side effects:hoarseness/voice alteration (37%),throat pain (11%), cough (7%).*
Additional considerations Generator can be removed, wiregenerally not. MRI compatible only if MRI has asend/receive coil.
VNS vs. corpus callosotomy:which is better for seizures? Only 2 studies comparing both procedures – smallnumber of patients. VNS is less invasive, lower risk procedure. VNSefficacy can be improved over time. Can take up to6-12 months to see full effect. Callosotomy has higher risk of complications (butrelatively low vs. other surgeries). Immediateimprovement (does not continue to improve overtime). Better for tonic/atonic seizures compared togeneralized tonic-clonic seizures.
Deep brain stimulation Successfully used in movement disorders. Similar structures stimulated in movementdisorders are thought to be helpful inepilepsy.
Deep Brain Stimulation Chronic electrical stimulation applieddirectly into deep nuclei in the brain.
Why are these nuclei chosen? Generalized seizures are likelygenerated by deep structures of thebrain. Utilize relay stations that communicatewith the cortex. Utilize inhibitory neurons in the brain.
Anterior Nucleus of Thalamus Many animalepilepsy modelsinvolve the Circuit ofPapez. Interruption of thiscircuit preventsseizures. The anterior portionof the thalamus ispart of this circuit.
Stimulation of anterior nucleusof thalamusSANTE (double-blinded,placebo-controlled) –110patients with partialseizures. 3 months: 40.4% mediandecrease vs. 13.5%. 2 years (unblinded): 56%median reduction with 54%have a >50% seizurereduction. 5 years later, >50% seizurereduction rate 69% andmedian seizure reduction ratealso 69%.
Stimulation of anterior nucleusof thalamusSide effects:18.2% paresthesias,10.9% implant site pain,9.1% site infections,8.2% lead replacement.
CentroMedian (CM) nucleusthalamic stimulation CM is part of thereticulthalamocortical systemthat is related to themodulation of the sleep-wakecycle and general alertness. Neurons from brainstemcommunicates with thethalamus and then sendssignals throughout cerebralcortex. High frequency stimulationdemonstrates EEGdesynchronization in animalstudies.
Centromedian stimulationefficacy Open label trial with 13 LGS patients(Velasco 2005) demonstrated overallseizure reduction 80%. 30% decrease in generalized tonicclonic seizures compared to 8% indouble blind study (7 patients, Fischer1992).
Cerebellar stimulation Cerebellum uses inhibitoryneurons to affect other parts ofthe brain including thehippocampus. Hypothesis: inhibition ofhippocampus and cortex cansuppress seizures. Therefore useelectical stimulation to activatecerebellum to inhibit seizurepathways. CAVEAT: stimulation ofcerebellum can suppresscerebellar fibers.
Subthalamic nucleusStimulation Used in movementdisorders. 9 patients implanted, upto 80% seizurereduction. Side effects: mild facialtwitching, numbness inextremities duringadjustment.
Responsive neurostimulation Electrodes placedover brain andrecord activity. Brain is stimulatedwhen seizure isdetected. Only tested for focalseizures.
Responsive neurostimulation 191 patients implanted,randomized. 12 weeksstudy period blinded. 37.9% decrease in seizurefrequency vs. 17.3%(sham). Near 50% have >50%seizure reduction by 2 years. Side effects: headache,dysesthesia, increasedseizures.
Transcranial magneticstimulation Hand-held magnet iscurrently used tomap the motor strip. Non-surgicaltherapy. Stimulation can feellike a static shock. Studied for focalseizures.
Transcranial magneticstimulation efficacy Mixed results in controlled trials: Theodore (2002) – mild and short-livedseizure reduction (n=24). Fregni (2006) – significant seizurereduction and EEG improvement (n=21). Cantello (2007) – significant EEGimprovement; no change in seizures(n=43).
Why are TMS resultsinconsistent? Low number of patientsstudied. Anatomy of stimulation –suboptimal for mesialseizure-generators. Coil construction (roundvs. figure of 8).
Where do we stand now? None of these devices make patients 100%seizure-free. Only VNS is FDA-approved. Of the long-term studies, there continues to beimprovement in many patients. DBS is awaiting final decision by FDA. FDApanel approved DBS by close vote (7-5). DBS is currently being used off-label and in 31countries. RNS received unanimous approval by FDA panelin 2/13 and is awaiting final approval.
Final thoughts… Stimulation can be very effective, butnot a cure. These decisions require an epilepsycenter team approach.
Lennox-Gastaut Syndrome (LGS)Working Group MembersBlaise F. D. Bourgeois, MDProfessor of Neurology, Harvard Medical SchoolDirector, Division of Epilepsy & Clinical NeurophysiologyWilliam G. Lennox Chair in Pediatric EpilepsyChildrens HospitalBoston, MALaurie M. Douglass, MDDirector, Pediatric EpilepsyPediatric EEG Director, Pediatric Neurology Residency ProgramDivision of Pediatric NeurologyBoston Medical CenterSouth Boston, MAPatricia A. Gibson, MSSW, ACSWDirector, Epilepsy Information ServiceAssociate Director, Comprehensive Epilepsy ProgramWake Forest UniversityWinston-Salem, NCTracy A. Glauser, MDDirector, Comprehensive Epilepsy CenterCo-Director, Genetic Pharmacology ServiceProfessor, Department of Pediatrics, University of CincinnatiCincinnati Childrens Hospital Medical CenterCincinnati, OhioEric H. W. Kossoff, MDAssociate Professor, Neurology and PediatricsMedical Director, Ketogenic Diet CenterDirector, Pediatric Neurology Residency ProgramJohns Hopkins HospitalBaltimore, MDGeorgia D. Montouris, MDClinical Associate Professor of NeurologyBoston University School of MedicineDirector of Epilepsy ServicesComprehensive Epilepsy Care Program for Children and AdultsBoston Medical CenterBoston, MA
LGS Working Group Members (cont.)John M. Pellock, MDDivision Chairman, Vice Chairman, Department of NeurologyProfessor of Neurology, Pediatrics, and Pharmacy and PharmaceuticsVirginia Commonwealth University School of MedicineChildren’s PavilionRichmond, VAJay Salpekar, MDAssociate Professor of Psychiatry and PediatricsGeorge Washington University School of MedicineDirector, Outpatient Psychiatry ServicesChildrens National Medical CenterWashington, DCChristina SanInocencioPresident and Executive DirectorLennox-Gastaut Syndrome FoundationNew York, NYRaman Sankar, MD, PhDProfessor and Chief, Rubin Brown Distinguished ChairDivision of Pediatric Neurology, 22-474 MDCCDavid Geffen School of Medicine at UCLALos Angeles, CAW. Donald Shields, MDChief, Clinical Trials in Pediatric NeurologyDirector, Pediatric Epilepsy ProgramMember, The Ketogenic Diet ProgramProfessor Emeritus, PediatricsLos Angeles, CAJames W. Wheless, MDDirector, Neuroscience Institute and Le BonheurComprehensive Epilepsy ProgramLe Bonheur Chair in Pediatric NeurologyLe Bonheur Childrens HospitalProfessor and Chief, Department of Pediatric NeurologyUniversity of Tennessee Health Science CenterMemphis, TN
LGS Resources Registry• Resources for parents and caregivers to findsolutions to challenges they will face in caring for aperson with LGS• Services identified by location• Available on LGS Foundation website and separateportal
LGS Resources Survey• Information utilized to populate the LGS ResourcesRegistry• LGS Foundation members• Augmented with additional research• Survey to be initiated this month• Look for LGS Foundation email• http://www.lgshope.com/survey
LGS Hope Monthly Newsletter (cont.)• Introduction to recent research and literature• Updates on LGS Foundation activities• Interviews with caregivers and healthcareprofessionals• Updates on new policies and regulations that impactavailability of LGS care• Available via email, website, or mailing
LGS Fact Sheet or FAQ• Clinical overview of LGS• Diagnosis and prognosis• Transition into adulthood• Collaborative effort with medical societies andpatient advocacy organizations
LGS Physician Guide and Call SheetLGS Physician Guide• Increasing awareness among physicians of special needsof LGS patients• Defining best practices in LGS diagnosis, treatment, andmanagementLGS Call Sheet• Standardized communication to be adopted by multipleorganizations• Answering calls from caregivers and healthcare providers
Agenda:1. Transition into Adulthood andPerson-Centered Planning2. What’s Next? Resources for anIndependent and Productive Life inthe Community3. Volunteering and EmploymentPossibilities4. Q and A
• Every individual, regardless of ability, has the right to determine thecourse of their life. And it’s up to us; family, friends, providers tomake sure the voices of our loved ones are heard.• Four Basic Principles of Self-Determination:• Freedom: People must have the freedom to make basic lifechoices. This includes balancing the risks and possibleconsequences.• Authority: People must have control over their lives andmeaningful options if they are to exercise freedom of choice• Support: Supports must be available to help people connect withopportunities for increased personal and social inclusion.• Responsibility: As people gain control over their lives, they willalso be able to take on their obligations as citizens and give back tothe community.
• Many well-intentioned parents will make choices for theiradult sons and daughters, believing that as parents, they knowwhat’s best.• If we want to promote independence and encourageproductive involvement in the community, it is ourresponsibility to ask our adult sons and daughters what theywant from life. It is our responsibility to listen to theiranswers. And it is up to us to learn about the services availableand maximize those community resources that support the lifegoals of the people we love.
• An individual’s Circle of Support come together to assist inhelping that individual define his or her abilities, interests anddreams for the future.• Focus on independence, possibilities, dreams, desires,meaningful experiences and quality of life.• Emphasis is on:• Promoting Choice: How can we help people have morecontrol and choice in life?• Community Presence: How can we increase anindividual’s presence in the community, through an engagingand productive life?• Supporting Contribution: How can we assist people todevelop skills and competencies, How can we help themshare their unique gifts with the world?
Using Your Budget – Creating Your PlanDevelopmental Disabilities Assistance Act andBill of Rights (2000)• Federal Law creating funding for adults with developmental disabilities, promotes:• Self-Determination• Independence• Productivity• Integration and Inclusion• Created:• State Councils on Developmental Disabilities• Protection and Advocacy Systems for each state• National Network of University Centers forExcellence in Developmental Disabilities
Federal FundingState FundingCounty ResourcesSocial Security Disability, MedicaidState Health Care, State Funds (to match Federal Funds), and more…Registration is at the county level, funds disbursed through county-run agencies,non-profit organizations and brokerages. You have a choice!
Services Current FutureAdaptive AidsTransportationSocial/RecreationalLearning/EducationalHealth/NutritionExerciseEmployment/VolunteerOther
Healthy Living• Opportunities to learn about nutrition• Planning and cooking healthy meals• Gym Memberships and Personal Trainers• Community Classes•Offered at non-profit organizations•YMCA•Community centers•College campuses
Transportation•Public Transportation –Learning to ride independently•Public Transportation – PrivateShuttle•Driving with a Mentor•Family Involvement•Thinking outside of the Box!
Living Arrangements• Residential Facilities (for adults with specialhealthcare needs)• Community Care Facilities• Developmental Centers• Family Home Agency• Independent Living• Intermediate Care Facilities• Supported Living Services• Affordable Housing
Emergency Preparedness•Brochure – Emergency Preparednessfor People with Disabilities•Let’s Get Prepared: Tools forEmergency Preparedness
Social Activities andCommunity Inclusion• Large, national Non-Profit Organizations:- YMCA - Special Olympics• Small, local Non-Profit Organizations that provide:- Art Programs - Athletic Training/Classes - Music Lessons- Outdoor Events/Camps - Social Events - Mentor Programs• State- and County-Funded Programs:- Day Habilitation• Trip and Vacation Planning for adults with Disabilities• Political Action and Self-Advocacy Groups
Mentorship and Skills Training• Mentors can be funded with Plan dollars• Mentors can provide transportation• Mentors can provide companionship for activities in thecommunity• Mentors can provide guidance with regards to living skills• Mentors can serve as coaches for volunteer work and paidemployment• Mentors may be knowledgeable about other activities inthe community• Non-Profit Organizations and local colleges often offer avariety of skills classes for adults with developmentaldisabilities.
Legal Issues• Disability Rights __________ (your state)• Non-profit legal groups found in most majorcities• Free Legal Advice for anybody with a disability:• Accommodations• Discrimination• Policy Question• Access to Services• Social Security Offsets after attaining paidEmployment
Volunteering and Employment• Video: Working for a Living – Andy Owens• Volunteering in the Community• Vocational Rehabilitation Services• Vocational Assessments• Job Coaches• Natural Supports• Video: Jennifer’s Story (time permitting)
Questions???• “Pose your questions to people and you will get countlessuseless answers.”― Dejan Stojanovic, The Sun Watches the Sun