Seizures and Epilepsy Paul Garcia, M.D. UCSF Epilepsy Epileptic seizure: the physical manifestation of aberrant firing of brain cells Epilepsy: the tendency to recurrent, unprovoked epileptic seizures Epilepsy and Seizures Very common Lifetime risk of a seizure is about 10% Lifetime risk of epilepsy is about 3% Serious medical consequences Risk of serious injury ~1-2%/year Increased mortality Accidents Sudden Death Status Epilepticus Serious psychosocial consequences Buccal Midazolam vs. Rectal Diazepam for Serial Seizures Midazolam Therapeutic success 56% 27% Diazepam Median time to effect 8 mins 15 mins McIntyre J, et al. Lancet 2005;366:205-210 1
Status Epilepticus in California, 1990 s New Medications Incidence / 100,000 9 8 7 6 5 4 3 2 1 0 Incidence of generalized convulsive status epilepticus (GCSE) hospitalizations in California 1991-1998 1991 1992 1993 1994 1995 1996 1997 1998 Year Felbamate Gabapentin Lamotrigine Topiramate Tiagabine Oxcarbazepine Zonisamide Levetiracetam Pregabalin Treatment Outcomes in Patients with Newly-Diagnosed Epilepsy Treatment Outcomes in Patients with Medically-Refractory Seizures Kwan P and Brodie M. NEJM 2000;342:314-319 Callaghan BC, et al. Ann Neurol 2007;62:382-389 2
Old new treatments for epilepsy Ketogenic diet Ketogenic diet Resection of the seizure focus Ketogenic Diet in Adults: Seizure Control Atkins Diet: Treatment Outcomes >90% >50% Some none # patients 3 3 1 4 Clinic visit 0% 1 50% 51 75% 76 99% Seizure-free 1 month 15 (50%) 1 (3%) 10 (33%) 4 (14%) 0 (0%) Sirven J, et al. Epilepsia 1999;40:1721-6 3 months 14 (47%) 2 (6%) 7 (24%) 6 (20%) 1 (3%) 6 months 15 (50%) 5 (17%) 6 (20%) 3 (10%) 1 (3%) Kossoff EH, et al. Epilepsia 2008;49:316-9 3
Seizure Surgery: A randomized, controlled Trial PM: A 51 year old, right-handed sales clerk with seizures Her mother had a normal pregnancy Uncomplicated birth Normal early development Convulsion during febrile illness at age 1 Not treated No further seizures until grade school Wiebe S, et al. NEJM 2001;345:311-8 PM: Seizure History PM: Seizure History 1st unprovoked seizure in third grade Aura consisted of seeing a pink elephant waving its trunk Progression to a behavioral arrest with chewing automatisms for 20-30 seconds 5 minutes of inability to speak coherently Attacks occurred every few months Epilepsy finally diagnosed at age 15 Treatment with phenytoin decreased her seizure frequency; Nevertheless, seizures sometimes occurred despite good compliance with medication Trials of phenobarbital, carbamazepine, sodium valproate, lamotrigine and gabapentin failed to control her seizures 4
PM: Seizure History PM: Social Considerations At age 20, the character of the seizures changed; She no longer saw pink elephants but instead felt a cold chill down her spine prior to the attacks that were otherwise similar The attacks became more frequent (4-5/month) Her husband died in the Vietnam war after which she worked for almost 30 years as a store clerk to support herself She hated having seizures in public and she felt like a prisoner in my own home Upon hearing of seizure surgery, she requested a referral for evaluation PM: Presurgical Evaluation Video/EEG monitoring PM: Presurgical Evaluation MRI During 5 days she had 3 CPS All began with her aura followed by lip smacking and a post-ictal aphasia During the attack her right hand was held in a fist EEG onsets consisted of a rapid build up of rhythmic theta frequency activity over the left temporal region (arrows) 5
Prognostic Value of MRI PM: Presurgical Evaluation Neuropsychological Testing Number of patients 30 25 20 15 10 5 Sz-Free Not Sz-Free Wada (Intracarotid amytal) test Language on left side only No memory difference with left and right injections Performance and verbal IQ normal 0 MTS No MTS Garcia et al. Epilepsia. 35:520 1994 PM: Presurgical Evaluation Conclusions PM: Surgery She has complex partial seizures refractory to anticonvulsant treatment Clinical and EEG features are compatible with seizure origin from the left temporal lobe MRI suggests mesial temporal sclerosis is the underlying pathology She has an excellent chance for a seizure-free outcome with a left anterior temporal lobe resection Surgery under local anesthesia Language map determined by electrical stimulation Language areas (yellow arrow) and epileptogenic tissue (gray arrow) noted 6
PM: Surgery PM: Follow-up Anterior temporal lobe resected (arrow) Amygdala and hippocampus also resected Immediately following surgery she had a mild problem with speech At three months post-op, cognitive testing confirmed no change from pre-op She has had no seizures for ~four years: she initially declined a trial off of anticonvulsants for fear of recurrent seizures but eventually came off medicines PM: Follow-up Brain Surgery for Epilepsy: What s New? Efficacy demonstrated in RCT Better risk stratification Better information on long-term outcomes 7
New New Treatments for Epilepsy Vagus Nerve Stimulation Vagus nerve stimulator Brain stimulation for epilepsy Gamma knife radiosurgery Vagus Nerve Stimulation: Cerebral Blood Flow Brain Stimulation for Epilepsy Henry T, et al. Neurology 1999;52:1166-73 8
Brain Stimulation Trials Gamma Knife Radiosurgery Stimulation of the Anterior Nucleus of the Thalamus (SANTE) Direct Cortical Stimulation (NeuroPace) Gamma-Knife Surgery: Plan Gamma-Knife Surgery: Seizure control 9
Gamma-Knife Surgery: Imaging Epilepsy Update: Conclusions Most patients will gain seizure control using standard medications A substantial minority will continue having seizures and should be referred to specialists Rescue medications should be considered for most patients 10