PRESURGICAL EVALUATION Patients with seizure disorders Gregory D. Cascino, MD Mayo Clinic Disclosure Research-Educational Grants Mayo Foundation Neuro Pace, Inc. American Epilepsy Society American Academy of Neurology National Institutes of Health R01NS053998 Educational Grant: UCB (lecture) ISLAND OF COS Hippocrates: On the Sacred Disease 1
HIPPOCRATES (400 BC) But this disease seems to me to be no more divine than others Its origin is hereditary the brain is the cause of this affection EPILEPSY history Supernatural disease Patron saint: St. Valentine Pilgrimages to certain sites: Rome, Terni (Italy), Ruffach (France), Poppel (Belgium) and Passau (Germany) 2
EPILEPSY J Hughlings Jackson (1835-1911) Basic tenets of partial epilepsy Cerebral cortex disease Cortical area and semiology Lesion location and seizure onset Rationale for epilepsy surgery Partial Epilepsy Mechanisms Partial seizures excessively excitable cortex Interictal spike is a marker for area of focal abnormality Hughlings Jackson: epileptic focus EPILEPSY epidemiology in U.S. Recurrent, unprovoked events Two or more seizures > 2,300,000 PWE Prevalence: 4% (80 years of age) Incidence: 180,000 per year Early and late onset 12.5 billion USD 3
EPILEPSY improvement in quality of life Related to seizure-free outcome DRIVING Education, Employment No need for caregiver Living independently 4
EPILEPSY partial seizure disorder 90% adult incident cases 45% medically refractory seizures Prognosis related to etiology 80% temporal lobe epilepsy amygdalohippocampal 5
EPILEPSY co-morbidity Cognitive disorder: memory loss Depression and anxiety Psychosocial debilitation Increased risk of morbidity and mortality EPILEPSY adverse effects 25,000-50,000 die of seizures or related causes each year SUDEP (sudden unexplained death in epilepsy) Risk of sudden death is 24 times controls PARTIAL EPILEPSY diagnostic evaluation Initial evaluation: routine EEG and MRI head seizure protocol Appropriate monotherapy trials with 2 or more AEDs (use response rather than AED levels) Scalp-recorded video-eeg monitoring for possible surgical localization Neuropsychological studies F7-LF7 T7-LT7 P7-LP7 F8-LF8 T8-LT8 P8-LP8 6
EPILEPSY diagnostic yield of EEG Epileptiform abnormalities Initial EEG recording: 29%-55% 3 or more EEG studies: 59%-90% Non-epilepsy population: 0.5-2.6% IS IT EPILEPSY? persistently normal EEG Non-epileptic disorder Infrequent seizures Generalized epilepsy tonic-clonic seizures Partial epilepsy extratemporal origin INPATIENT advantages Decreasing AED therapy Patient observation Electroclinical correlation Ictal SPECT scans LIMITATIONS ictal scalp-recorded Simple partial seizure Extratemporal origin Brief seizure duration Muscle artifact Aura 7
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MRI HEAD seizure protocol 1.5 or 3.0 Tesla Oblique-coronal 1.5 mm temporal lobe sections FLAIR imaging sequence Contrast if lesional pathology PARTIAL EPILEPSY lesional epileptic syndrome Primary brain tumor ganglioglioma, DNET, glioma Vascular anomaly cavernous hemangioma Malformation of cortical development focal cortical dysplasia 10
PARTIAL EPILEPSY malformations Etiology of 25% of partial epilepsies (Kuzniecky et al, 1993) 76% of patients with focal cortical dysplasia have intractable epilepsy (Semah et al, 1998) 11
MALFORMATIONS focal cortical dysplasia Type I: dyslamination with or without giant neurons but without balloon cells or dysmorphic neurons Type II: with dysmorphic neurons with or without balloon cells (Taylor-type dysplasia) Giant pyramidal neuron Dysmorphic neurons Balloon cells 12
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PARTIAL EPILEPSY medial temporal lobe epilepsy Early life insult (acquired or genetic) usually associated with GTCs variable lateralized deficit Ripening period of several years Emergence of auras and CPS 14
PARTIAL EPILEPSY mesial temporal sclerosis Jack et al. (Mayo) Radiology 1996;199:367-373 3 blinded reviewers FLAIR: 97%, double spin-echo 91% FLAIR superior contrast to noise FLAIR preferred by radiologists EPILEPSY goals of therapy Render patient seizure-free No seizures Avoid neurological morbidity No side effects Participating and productive member of society No lifestyle limitations EPILEPSY goals of therapy Educate and counsel Discuss issues of daily living : e.g., safety in the home, driving, employment, birth control, alcohol, AED compliance Map a strategy of care (routine and urgent) 15
EPILEPSY efficacy of treatment Neurology 2003;60(Suppl 4):S2-12 About 30-40% will have a difficult to control seizure disorder The 1st and 2nd AEDs are highly predictive of medical outcome INTRACTABLE EPILEPSY efficacy of treatment INTRACTABLE EPILEPSY efficacy of treatment Epilepsia 2007;62:375-381 PENN Epilepsy Center Refractory epilepsy Randomized add-on trials Seizure-free rates LEV: LTG: OXC: PBG: ZNS: 3.9-7.1% 0.8% 2.6% 1.3% 0% 16
INTRACTABLE EPILEPSY treatment strategies Curative surgical therapy focal cortical resection, reoperation Palliative surgery VNS, corpus callosotomy Antiepileptic drug medication Ketogenic or Atkins diet Investigational studies PARTIAL EPILEPSY treatment strategies II MRI: Lesional pathology or MTS consider surgical evaluation depends on pathology, anatomy, seizure-types), etc. MRI: Indeterminate continued AED trials EPILEPSY SURGERY surgical candidates Medically refractory seizures Physically, socially disabled Localization-related epilepsy Low risk for morbidity Potential for rehabilitation 17
EPILEPSY SURGERY long-term outcome Unfavorable predictors of outcome: Extratemporal localization Normal histopathology Indeterminate MRI NON-LESIONAL EPILEPSY neocortical onset MRI is normal Limitations of ictal EEG May have focal cortical dysplasia May be surgical candidates Usually require chronic intracranial EEG studies Intraoperative digital photography Intraoperative digital photography 18
Digital photographic grid map NON-LESIONAL EPILEPSY SPECT Ictal functional imaging SISCOM subtraction ictal SPECT co-registered with MRI Reliable indicator of ictal onset zone Select operative candidates SISCOM Elson So (Mayo) Subtraction peri-ictal SPECT Ictal and interictal SPECT Co-registration MRI head seizure protocol 19
SISCOM Mayo protocol I Admitted to EMU MRI head (Jack protocol) Ictal video-eeg recordings Injections: 7 AM to 11 PM EMU technicians Neurolite (R) SISCOM Mayo protocol II Children and adults Presurgical evaluation Surgical epilepsy conference Target for intracranial electrodes Convergence of studies 20
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SISCOM Extratemporal I Neurology 2000;55:1668-1677 Operative outcome Predictive value Co-registered with postop MRI SISCOM Extratemporal III LOCALIZING SISCOM SISCOM (+): 24 of 36 (67%) Concordant: 19 of 24 (79%) MRI (-): 13 of 17 (76%) SISCOM Extratemporal V Complete SISCOM resection: 100% excellent outcome Partial SISCOM resection: 60% excellent outcome No SISCOM resection: 20% excellent outcome 23
IMAGING IN EPILEPSY partial epileptic syndromes Substrate-directed epilepsy MRI Medial temporal lobe epilepsy MRI, PET Neocortical (non-lesional) epilepsy Ictal SPECT "The function of a physician is to cure a few, help many and comfort all" Percival Bailey 1892-1973 neurosurgeon, physiologist, professor, University of Chicago 24