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Neuropsychology of Epilepsy

Neuropsychology of Epilepsy. John Langfitt, Ph.D. Associate Professor Neurology & Psychiatry Strong Epilepsy Center University of Rochester. Overview. Definitions & Epidemiology Seizure Types & Cerebral localization

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Neuropsychology of Epilepsy

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  1. Neuropsychology of Epilepsy John Langfitt, Ph.D. Associate Professor Neurology & Psychiatry Strong Epilepsy Center University of Rochester

  2. Overview • Definitions & Epidemiology • Seizure Types & Cerebral localization • Neuropsychological Effects of Medial Temporal Lobe Epilepsy and its Surgical Treatment

  3. What is Epilepsy? • Seizure • when neural networks fire together in abnormal synchrony • Epilepsy • recurrent, unprovoked seizures • does not include single seizures provoked by metabolic disturbance or trauma

  4. Normal Neural Activity low-voltage mixed frequency pseudorandom (chaotic?) Seizure extreme voltage rhythmic paroxysmal

  5. Propagation of Neuronal Signal Pre- Synaptic Neuron Post- Synaptic Neuron Cell Body Axon Flow of Action Potential Synapse

  6. + + + + + + + + + + + + + + + + + - - - - - - - - - - - - - - - - - - Synaptic Cleft At Rest Post- Synaptic Neuron Pre- Synaptic Neuron

  7. + + + + + + + + + + + + + + + + + - - - - - - - - - - - - - - - - - - Synaptic Cleft Excitatory Post-Synaptic Potential Post- Synaptic Neuron Pre- Synaptic Neuron

  8. Bipolar EEG 1st 2nd -40 - (-100) = +60 -40 -100 - (-40) = -60 -100 -40 - (-20) = -20 -40 -20 - (-20) = 0 -20 -20

  9. Interictal Discharges

  10. Seizure (Ictal) Discharge

  11. Frequency of Epilepsy • Stroke >1/100 • Epilepsy 6/1000 • Parkinson’s 2/1000 • Mult. Sclerosis 2/10,000 • Huntington’s 4/1,000,000

  12. Causes of EpilepsyRochester, Minnesota 1935-1984 Infectious (3%) Degenerative (4%) Tumors (4%) Trauma (6%) Congenital (8%) Vascular (10%) Idiopathic (65 %) Hauser, 1997

  13. Peak Incidence in Childhood and Senescene

  14. Prognosis Silanpaa et al., 2000

  15. Living/Marital Situation p <.0001 Shackelton, 2003

  16. Employment p <.05 N Shackelton, 2003

  17. Living Situation/Healthby Seizure Control at Follow-up p =.05 p <.01 p <.01 p <.05 % Shackelton, 2003

  18. Educational/Occupational Statusby Age at Onset p <.01 p <.05 % Shackelton, 2003

  19. Percent Never Married Age > 35 (n=161) Onset < 22 Onset >= 22 100 80 3/3 60 40 20 0 Yes No Yes No USPop Special Education Male Female Langfitt & Janzen, 2002

  20. Percent Currently Unemployed (n=237) ‘Grand-mal’ No ‘Grand-mal’ Psychiatric History Langfitt & Janzen, 2002

  21. Summary • Definitions & Epidemiology • Seizures are rhythmic, paroxysmal neuronal discharges • Epilepsy is defined as 2 or more unprovoked seizures • Epilepsy • is common in the general population • is a symptom, not a disease • reflects a broad range of underlying neuropathology • can be successfully treated with medicine in most patients • and associated problems can lead to activity restrictions and significant psychosocial burden

  22. Partial Simple (no loss of awareness) sensory motor Complex (loss of awareness) involves spread to both hemispheres Seizure Types

  23. T4-T6 C6-T4 T4-S2 S2-S1

  24. Generalized- Primary absence (‘petit mal’) atonic (‘drop’) tonic-clonic (‘grand-mal’) myoclonic (‘jerks’) Secondary start as partial, but discharge spreads throughout brain Partial Simple (no loss of awareness) sensory motor Complex (loss of awareness) involves spread to both hemispheres Seizure Types

  25. Absence (‘petit mal’) Seizure

  26. Somato-sensory tingling/numbness in contralateral extremity Focal motor hand>face>arm progression (‘jacksonian march’) Visual flashing lights (calcarine) formed visual hallucinations (secondary assn. cortex) Auditory formed auditory hallucinations (secondary assn. cortex) Frontal often nocturnal thrashing, vocal outbursts, genital rubbing Limbic olfactory/gustatory hallucinations, déjà vu, post-ictal amnesia Brainstem/Thalamus motor arrest, loss of consciousness, abrupt change in muscle tone Seizure Semiology & Cerebral Localization

  27. Summary • Seizure Types & Cerebral Localization • Seizures types • vary greatly in behavior across individuals • are highly consistent within an individual • are determined by origin and pattern of spread through CNS • vary greatly in severity & functional significance

  28. Mental Retardation Cerebral Palsy Stroke Lupus Traumatic Brain Injury Encephalitis Meningitis Tumor Migrational anomalies Mesial temporal sclerosis Conditions Associated with Epilepsy

  29. Causes of Cognitive & Behavioral Dysfunction • Underlying disease • Seizures • Psychosocial Factors • Treatments • Medical • Surgical

  30. Medial Temporal Lobe Epilepsy(MTLE) • Onset 1st 2 decades • ‘Cryptogenic’ etiology • Progressive course • Refractory to medical treatment • Significant psychosocial burden • Highly responsive to surgical removal of epileptogenic tissue • Quality of life improves with seizure-freedom • Pre-exisiting memory deficits worsen in some

  31. Normal Hippocampus Sclerotic Hippocampus Selective hippocampal cell loss(Bratz, 1898)

  32. Seizure frequency and HC volume over time r=.60 p< .007 34 TLE patients newly diagnosed 1st scan ‘normal’ Clinically apparent MTS on 2nd scan Briellmann et al., 2002

  33. Memory and the Medial Temporal Lobe • Scoville & Milner, 1957 • Bilateral medial temporal lesions produce anterograde amnesia • Penfield & Milner, 1958 • Unilateral medial temporal resections produce amnesia when there is damage contralaterally before surgery • Milner, 1972 • Unilateral lesions are associated with material-specific learning and memory deficits

  34. Dominant TL Verbal semantic retrieval deficits prominent Episodic memory deficits common, verbal > non-verbal Retrieval impaired, recognition typically preserved Co-morbid verbal learning disability may be present Non-Dominant TL Verbal semantic retrieval deficits less prominent Episodic memory deficits common, non-verbal > verbal Retrieval impaired, recognition typically preserved Co-morbid non-verbal learning disability may be present Mesial Temporal Sclerosis Neuropsychological Characteristics

  35. Anterior Temporal Lobectomy

  36. Canadian Randomized TrialSeizure Control P< .001 Wiebe et al., 2001

  37. Case Series OutcomeAnterior Temporal Lobectomy Langfitt & Bronstein, 1999

  38. Canadian Randomized TrialQuality of Life P< .001 Wiebe et al., 2001

  39. EESTLEEmployment P=.11 Wiebe et al., 2001

  40. Cognitive Effects of ATLIQ Chelune et al. 1993

  41. Cognitive Effects of ATLEpisodicRetrieval Chelune et al. 1993

  42. Cognitive Effects of ATLSemanticRetrieval Langfitt & Rausch, 1995

  43. Who is at Risk?(Functional Reserve/Adequacy Hypotheses) • Contralateral dysfunction associated with severe post-operative declines • Functional integrity of the ipsilateral tissue associated with milder levels of decline • MRI and neuropsychological variables reflect functional adequacy of the to-be-resected temporal lobe • Chelune & Najm (2000) found combination of side of surgery, MRI and baseline memory to predict risk of milder memory decline post-op

  44. Percent with Reliable Decline on One or Both Verbal Memory Tests # Baseline Tests Intact Stroup et al., 2003

  45. Summary • Neuropsychological Effects of MTLE and Surgery • MTLE often arises from dysfunctional re-organization of hippocampal neurons in response to injury • Re-organization leads to abnormal • propagation of excitatory inputs, leading to uncontrolled seizures • disruption of normal mnemonic function of MTL structures • Seizures can be controlled by removing abnormal circuitry • Effects on memory • are more measurable for verbal vs. non-verbal material • depend on functional integrity of both the remaining (contralateral) MTL structures and the removed (ipsilateral) MTL structures • Effects on function • seizure control leads to significant improvements in quality of life, even when memory decline occurs

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