epilepsy

neuropsychiatric aspect of epilepsy 1

1. Neuropsychiatric Aspect of Epilepsy Dr. Subodh Sharma Resident Department of Psychiatry, NMCTH, Birgunj

2. Definitions Seizure /Ictus/ Fits From a Latin word that means ‘to take possession of ‘ Paroxysmal event due to abnormal excessive, hypersynchronous discharges from an aggregate of CNS neurons. Epilepsy Clinical phenomenon rather than a single identity. Recurrent seizures due to chronic underlying process.

3. Definitions

4. Epidemiology Epilepsy knows no geographical, racial, or social boundaries. About 50 million people in world have Epilepsy. It occurs in men and women and can begin at any age, but it is most frequently diagnosed in infancy, childhood, adolescence, and age. Prevalence: Developed countries- 0.5% (0.4% - 1%) Developing countries- five times higher Incidence: After infancy annual incidence- is 20-70/100000 in developed countries. Developing countries- Incidence is double. (100/100000) The lifetime risk of having a single seizure: About 5%.

5. Classification

6. Epilepsy Syndromes And Other Special Forms

7. Epilepsy Syndrome

8. Etiology In about 70% of people with epilepsy, the cause is not known In 30%, most common causes are: Inherited genetic Acquired : Trauma Neurosurgery Inflammatory Metabolic Infections Tumor Toxic disorders Drugs Congenital: inborn error of metabolism. Withdrawal of drugs Alcohol Benzodiazepine Barbiturates Other Anti-Epileptics

9. Psychotropics and Seizure highest risk of seizures(0.5%) clomipramine 0.5%(tertiary amine TCA ) bupropion (0.4%, up to 2.2% with doses higher than 450 mg per day) maprotiline (0.4%) (tetracyclic)     Other TCAs: imipramine Intermediate in risk SSRI:- fluoxetine, sertraline, fluvoxamine, citalopram, and paroxetine NSRI :- venlafaxine Least risk – monoamine oxidase inhibitors (MAOIs)  http://www.epilepsy.com/information/professionals/diagno sis-treatment/drugs-their-contribution- seizures/antidepressants

10. Psychotropics and Seizure Antipsychotics Highest risk: clozapine loxapine chlorpromazine Intermediate ( less than 1.0–1.2%) fluphenazine thioridazine perphenazine Trifluoperazine Least seizure-induction haloperidol molindone pimozide The antipsychotics of choice on the basis both of epileptogenesis and the side effect profiles are atypical agents: Risperidone, olanzapine, quetiapine

11. Triggers Missed medication (#1 reason) Stress, anxiety Hormonal changes, Menses Dehydration Lack of sleep, extreme fatigue Photosensitivity Illicit Drug, and alcohol use Certain Medications Fever in Some Children

12. Risks Groups at Increased Risk for Epilepsy About 1% of the general population develops epilepsy The risk is higher in people with certain medical conditions: Mental retardation Cerebral palsy Alzheimer’s disease Stroke Autism

13. Pathophysiology Glutamate and GABA (gamma-aminobutyric acid): the brain's major "workhorse" neurotransmitters that regulate action potential traffic. GABA is an inhibitory neurotransmitter that stops action potentials. Glutamate, an excitatory neurotransmitter, starts action potentials or keeps them going. Both work together to control many processes, including the brain's overall level of excitation.

14. What is Seizure?   An unpredictable, uncontrolled, abnormal, and excessive paroxysmal synchronization imbalance of the excitatory and inhibitory forces within the CNS network of cortical neurons in the cerebral cortex. Repeated sub-threshold of a neuron generates action potentials leading to seizures It has been suggested that chronic epileptic discharges may lead to secondary epileptogenesis.

15. Clinical Presentation Partial Seizures Simple Partial Seizures: Consciousness is fully preserved Motor symptoms Involves motor strip, Manifested by abnormal movement of an extremity, Jacksonian motor seizure: progression to adjacent muscle groups Todds palsy: transient paralysis Adversive seizure: Forced deviation of the eyes and turning head to the opposite side.

16. SPS Somatosensory symptoms Involves sensory strip, temporal(hearing and smell) or occipital(visual) lobe Autonomic symptoms involve the temporal lobe (tachycardia, pallor, flushing, sweating, and Piloerection. Psychic manifestation Dysphasic- when cortical speech area is affected (left perisylvian ) Dysmnestic- disturbance of memory (mesobasal temporal right) Cognitive symptoms- dreamy state (mesobasal temporal and temporal neocortex) Affective symptoms- fear, depression, anger, irritability, elation, erotic thoughts (mesobasal temporal and temporal neocortex) Illusion of size, structured hallucination (mesobasal temporal and temporal neocortex)

17. Complex Partial Seizure Complex partial seizures (= psychomotor seizures) Initial subjective feeling (aura) loss of consciousness abnormal behavior (perioral and hand automatisms) Majority originate in the Temporal lobe (60%) but also originate another lobe – particularly the Frontal(30%).   Discriminating features Consciousness is altered Stereotyped Focal spikes in interictal EEG

18. CPS Consistent Features Approximately 60-180 seconds duration Paroxysmal Post-ictal confusion Variable Features Presence of aura Automatisms May secondarily generalize to a tonic- clonic seizure Associated with a focal structural lesion May elevate prolactin level May be confused with Drunkenness or drug use willful belligerence aggressiveness

19. Generalised Seizure Gtcs Absences Myoclonic seizures Clonic seizures Tonic seizures Atonic seizures Discriminating features Initial tonic phase followed by clonic activity involving all extremities Consistent Features Loss of consciousness Typically 60-second duration Post-ictal period associated with confusion and drowsiness Variable Features Tongue biting or injury Urinary incontinence Nonspecific prodrome post-ictal paralysis

20. Absence Seizure Discriminating features Very brief duration (5-15 seconds) and 100 – 200 time/day mat Family H/O of typical absence seizures Response to ethosuximide and valproate Consistent Features EEG-3 cycles/ sec of generalized spike and wave(typical) No aura Impaired consciousness No post-ictal state Variable Features Automatisms Change in body tone Precipitation hyperventilation Atypical absence seizures Longer duration of loss of consciousness Less abrupt onset and cessation More obvious focal signs Less responsive to drugs

21. Atypical Seizures Reflex epilepsy Hot water epilepsy: a person gets a seizure whenever he/she pours hot water on the head. Initially it is reported more from South India, especially from Bangalore. Eating epilepsy: Seizures are usually precipitated while a person starts eating food. The masticatory and oro - mandibular movements might trigger the seizure. Watching TV can precipitate seizures in a vulnerable individual. This is akin to the photostimulation procedure seen in EEG recording. Hyperventilation can also precipitate seizures

22. Differential Diagnosis Syncope Vasovagal syncope Cardiac arrhythmia Valvular heart disease Cardiac failure Orthostatic hypotension Psychological disorders Psychogenic seizure Hyperventilation Panic attack Metabolic disturbances Alcoholic blackouts Delirium tremens Hypoglycemia Hypoxia Psychoactive drugs (e.g., hallucinogens) Migraine Confusional migraine Basilar migraine Transient ischemic attack (TIA) Basilar artery TIA Sleep disorders Narcolepsy/cataplexy Benign sleep myoclonus Movement disorders Tics Nonepileptic myoclonus Paroxysmal choreoathetosis Special considerations in children Breath-holding spells Migraine with recurrent abdominal pain and cyclic vomiting Benign paroxysmal vertigo – Apnea – Night terrors – Sleepwalking

23. Investigations

24. EEG in epilepsy A normal single EEG does not exclude the diagnosis of epilepsy. If a normal awake EEG is obtained in an individual with the clinical suspicion of seizures, one should repeat the EEG capturing sleep because many epileptic abnormalities appear only in sleep Interictal findings in the EEG are invaluable aids for classifying seizures and epilepsy syndromes

25. Management

26. Types of Treatment

27. Single Unprovoked Seizures Common affecting 4% of the population by age 80 30%-40% of patients with a first seizure will have a second unprovoked seizure ( epilepsy) Risk factors for seizure recurrence include a history of neurologic insult, focal lesions on MRI, epileptiform EEG, and family history of epilepsy Adult patients with these risk factors have a 60%-70% of recurrence

28. First Aid Stay calm and track time Protect head, remove glasses, loosen tight neckwear Move anything hard or sharp out of the way Turn person on one side, position mouth to ground Check for epilepsy or seizure disorder ID Understand that verbal instructions may not be obeyed Stay until person is fully aware and help reorient them Call ambulance if seizure lasts more than 5 minutes or if it is unknown whether the person has had prior seizures

29. Safety Issues for Patients with Epilepsy Cant Drive for about a year after the last seizure Climbing altitudes Swimming/ Bathing alone Operating heavy machinery or weapons that can be dangerous Cooking, hot water Taking care of babies Bone Health

30. Antiepileptic Drug Therapy

31. Guidelines for Anticonvulsant Therapy Start with one of the first line drugs Start with low dose: Gradually increase to effective dose or until side effects. Check compliance If first drug fails due to side effects or continue seizures, start second line drugs whilst gradually withdrawing first. Try Three AED singly before using combinations Beware about drug interactions Do not use more than two drugs in combination at any one time If above fails consider occult structural or metabolic lesion and whether seizures are truly epileptic.

32. Second Generation AED’S Topiramate ( Topomax – 1996) Oxcarbazepine (Trileptal – 2000) Lamotrigine (Lamictal – 1994) Gabapentin ( Neurotin – 1993) Levetiracetam (Keppra – 1999) Tiagabine (Gabitril – 1997) Zonisamide (Zonegran – 2000) Pregabalin (Lyrica - 2005) Felbamate (Felbatol-1993) Vigabatrin (Sabril 2005-2006 Available in Canada and Europe)

33. Second Generation AEDs With the exception of Felbamate second generation AED’S have advantages over first generation agents. Generally lower side effect rates Little or no need for serum monitoring Once or twice daily dosing Fewer drug interactions There is no significant difference in efficacy with the second generation agents Higher cost associated with the new agents Monotherapy is well established for Lamotrigine and Oxcarbazepine The other agents are undergoing and many have completed monotherapy trials

34. AED In General The most important factor in determining the success of drug therapy is the duration of the epilepsy The patient needs to know that AED treatment is a commitment and non-compliance can be dangerous Pregnancy Considerations Consider withdrawing of AED’S if the patient is a good candidate Use monotherapy where appropriate Folate 1-4 mg per day in all women on AED The risk of fetal malformations is increased in pregnant women on AED Seizures during pregnancy can induce miscarriage Seizures during pregnancy can be deleterious to the mother or fetus The possibility of prenatal diagnosis of malformations can be considered with AFP levels and ultrasonography

35. Withdrawal of AED After complete control of seizures for 3-5 years withdrawal of Anti Epileptic drugs may be considered But in the case of a special professional group (car driver, machine man, etc ) withdraw the AED after keen follow-up. 20% of pts will suffer a further sz within 2 yrs. AED should be tapered during the stopping of medications. Slow reduction by increments over at least 6 months. If the patient is taking two AEDs one drug should be slowly withdrawn before the second is tapered. The risk of teratogenicity is well known (~5%), especially with valproates, but withdrawing drug therapy in pregnancy is riskier than continuation. Epileptic females must be aware of this problem and thorough family planning should be recommended. Over 90% of pregnant women with epilepsy will deliver a normal child.

36. Epilepsy Surgery Factors influencing decision Likelihood seizures are due to epilepsy Likelihood surgery will help Ability to identify focus of seizures Other treatments attempted, and seizures couldn’t be treated with 2-3 medications Benefits vs risks Surgical treatment: Removal of epileptic focus ( eg:mesial temporal sclerosis) Anterior Temporal Lobectomy Corpus callostomy Subpial transection

37. Vagus Nerve Stimulation Device is implanted to control seizures by delivering electrical stimulation to the vagus nerve in the neck, which relays impulses to widespread areas of the brain Used to treat partial seizures when medication does not work 

38. Ketogenic Diet Based on finding that starvation -- which burns fat for energy -- has an antiepileptic effect Used primarily to treat severe childhood epilepsy, has been effective in some adults & adolescents High fat, low carbohydrate and protein intake Usually started in hospital Requires strong family commitment

39. Other Treatment Approaches Behavioral therapy Biofeedback Relaxation Positive reinforcement Cognitive therapy Aromatherapy

40. References Harrison’s principles of internal medicine , 17th edition Organic psychiatry William Alwyn Lishman, 3rd edition. Ictal and postictalpsychiatric disturbances, Michael R. Trimble Institute of Neurology, University College, London. CTP 10TH EDITION

41. Thank You!