NEUROPSYCHIATRIC ASPECTS OF EPILEPSY

Presenter: Dr. Shravan KumarModerator: Prof. R. K. Gaur

INTRODUCTION

• Clinicians have recognized the association of epilepsy with psychiatric disorders since antiquity.

• At the turn of the 19th century, Emil Kraepelin emphasized that epileptic patients possessed personality changes and a predisposition to psychosis.

• The development of new antiepileptic and psychiatric therapies and novel neuroimaging techniques makes understanding the association of epileptic seizures and psychopathology increasingly important.

• Epidemiological data support an increased risk for psychiatric comorbidity among epileptics as compared to nonepileptic patients..

• The most established association is between epilepsy and depression or dysthymia, but a range of psychopathology occurs in one-fourth or more epileptics.

• Psychiatric comorbidity has also a serious impact on the quality of life and social well-being of patients with epilepsy.

DEFINITIONS

Seizure

• This term came from a Latin word which means ‘to take possession of’

• This is a paroxysmal event due to abnormal, excessive, hyper synchronous discharges from an aggregate of CNS neurons.

• The seizure itself is known as the ictus.

Epilepsy

• Epilepsy is the recurrent tendency to seize i.e to have seizures.

• This is a clinical phenomenon rather than a single identity.

• In epilepsy, abnormal electrical discharges occurs due to hyperexcitable neurons with sustained postsynaptic depolarization.

Convulsion

• This is a condition where body muscles contract and relax rapidly and repeatedly, resulting in an uncontrolled shaking of the body.

• Convulsion is often a symptom of an epileptic seizure.

• Not all epileptic seizures lead to convulsions, and not all convulsions are due to epileptic seizures, examples being non convulsive epileptic seizures and eclampsia respectively.

Fits

• This is the general term often used for sudden violent attack of convulsion and also for presyncope/syncope by non medical persons.

EPIDEMIOLOGY OF EPILEPSY

• Seizure disorders are common and usually have an early onset.

• Epilepsy affects 20 to 40 million people worldwide and has a prevalence of at least 0.63 percent and an annual incidence of approximately 0.05 percent.

• The overall incidence is high in the first year, drops to a minimum in the third and fourth decades of life, then increases again in later life (bimodal distribution).

• More than 75 percent of patients have their first seizure before 18 years of age, and 12 to 20 percent have a familial incidence of seizures.

• Among adults, the most common seizures are complex partial and generalized tonic-clonic seizures.

• Epidemiological studies from communities, psychiatric hospitals, and epilepsy clinics report a 20 to 60 percent prevalence of neuropsychiatric problems among epilepsy patients.

• Epilepsy patients are prone to psychosis, depression, personality disorders, hyposexuality, and other behavioral disorders.

• The percentage of epilepsy patients in psychiatric hospitals was also higher than the general prevalence of epilepsy.

• Among patients attending epilepsy clinics, approximately 30 percent had a prior psychiatric hospitalization, and 18 percent were on at least one psychotropic drug.

• Furthermore, epidemiological studies indicate an increased interictal psychopathology among head-injured patients with epilepsy compared to head-injured patients without epilepsy.

• Studies on the laterality of the seizure focus suggest an association of a left-sided focus with psychosis.

CLASSIFICATION OF EPILEPTIC SEIZURES

Primary generalized seizure

• Absence (petit mal)

• Tonic Clonic (grand mal)

• Tonic• Atonic• Myoclonic

Partial seizures

• Simple partial• Complex partial• Partial with secondary generalization

Unclassified seizures

• Neonatal seizures• Infantile spasms

EPILEPSY SYNDROMES AND OTHER SPECIAL FORMS

Epilepsy syndromes

• Juvenile Myoclonic epilepsy (absence, myoclonic and GTC seizures)

• Lennox Gastaut syndrome (seizure of multiple types, intellectual impairment and abnormal EEG)

• Mesial Temporal Lobe epilepsy (seizure with sensory changes)

continued

• Landau-Kleffner syndrome (infantile acquired aphasia with convulsion)

• West syndrome (infantile spasm, mental retardation, hypsarrhythmia on EEG)

• Ramsay Hunt syndrome (myoclonic seizure, progressive ataxia, tremor, dementia)

Other special forms

• Reflex epilepsy (trigger present eg photosensitivity)

• Gelastic epilepsy (sudden uncontrollable burst of laughing/crying)

• Diencephalic or autonomic (episodes of sudden autonomic dysfunction)

PSYCHIATRY AND EPILEPSY

• Epilepsy is associated with a range of psychiatric disorders.

• There is increased prevalence of psychiatric problems among epileptic patients.

• There may have auras with psychic content.

• One-fourth or more have schizophreniform psychoses, depression, personality changes, or hyposexuality.

• Psychiatric phenomena can be associated with the seizure itself, as well as the peri ictal and interictal phases of epilepsy.

• Peri ictal disturbances include pre ictal dysphorias , ictal and post ictal syndromes.

PSYCHOPATHOLOGY ASSOCIATED WITH EPILEPSY

• The psychiatric manifestations of epilepsy are heterogeneous disorders with potentially different causes.

• The neuro-pathology itself could be the source of seizures and behavioral changes.

• Left hemisphere and temporal lobe lesions may be associated with a schizophreniform psychosis, and psychosis in epilepsy may be particularly frequent if there is specific underlying pathology or ventricular enlargement.

• Ictal or subictal epileptiform activity may promote behavioral changes by facilitating distributed neuronal connections, increasing limbic–sensory associations, or changing the overall balance between excitation and inhibition.

• The absence of function, such as the interictal hypometabolism observed on PET scans may lead to depression or other interictal behavioral changes.

• Seizures may result in neuroendocrine or neurotransmitter changes, such as increased dopaminergic or decreased inhibitory transmitters, decreased prolactin, increased testosterone, or increased endogenous opioids, all of which can affect behavior.

• Neurobiological factors may be potentiated by psychodynamic factors, such as feelings of helplessness, learned helplessness, dependency, low self esteem, and the disruption of reality testing.

PSYCHIATRIC FEATURES IN EPILEPSY

• Different psychiatric phenomena are associated with epilepsy and they are particularly associated with any phase.

Ictal Features• Psychic auras• Ictal fearPeri-ictal Features• irritability, • depression, • headache, • confusion, • twilight states

Interictal Features

• Schizophreniform Psychosis.

• Gastaut-Geschwind Syndrome temporal lobe epilepsy hypergraphia, hyperreligiosity, reduced sexuality, circustantiality,

intensified mental life

• Personality Disorders

AURAS OF EPILEPSY

• Occurs in the portion of the seizure just before consciousness is lost.

• Range from simple discrete sensation to complex abnormalities of emotion and ideation.

• Appear abruptly, rarely occupy more than a few seconds.

• Specially important in Temporal Lobe Epilepsy

EPILEPTIC AUTOMATISM

• Defined as state of clouding of consciousness

• Occurs during or immediately after seizure

• Individual retains control of posture and performs simple or complex movements

• Commonly preceded by aura

• Frequently terminates with a Grand Mal convulsions• Lasts for a few seconds to hours.

(continued)

Chiefly in the form of:

• epigastric sensation• confusion , difficulty with memory, diziness• feeling of strangeness• masticatory movements, • dazed expressions, • pulling out clothes and passing hand over face • walking around , searching or moving objects, removing clothes etc.

EPILEPTIC FUGUES

• Consists of longer lasting disturbances of behavior with tendency to wander away.

• Actions are usually erratic, may appear to be drowsy or intoxicated.

• Consciousness is said to be less severely impaired

• Abnormal behavior more complex, extended and integrated.• Lasts for many hours to days.• Upon recovery amnesia is typically complete.

TWILIGHT STATES

• Range from automatisms and fugues to schizophrenia like disorders.

• It lasts from one to several hours.

• May appear as: dream like absent minded behavior muddling of comprehension complete unawareness of environment

• Psychomotor retardation is common

(continued)

• Marked perseveration in speech and action can be present.

• Abnormal affective states prominently panic , terror , anger , ecstasy

• Hallucinations may form a large part

• Usually ends spontaneously

• May also terminate in Grand Mal Convulsions

• Memory for the content is usually incomplete

ABSENCE STATUS (PETIT MAL STATUS)

• Longer lasting form of automatism.

• Periods of abnormality are too brief for resumption of awareness.

• Episodes starts and stops abruptly.

• There is marked disorientation, impaired grasp and automatic behavior.

• Patient may be virtually stupurous , motionless and apathetic.

• There may be paranoid delusional ideation , thought blocking and hallucinations.

TEMPORAL LOBE STATUS(PSYCHOMOTOR STATUS)

• Episodes can lasts for hours or days

• Patient is confused , withdrawn and retarded

• Sometimes continuous movements of hands , lip smacking and picking up of clothes

• Presence of confusion and disorientation

• Hallucinations and paranoid delusions may be present

POST-ICTAL DISORDERS

• Post ictal confusion may last hours to days

• Manifestations are very complex.

• Very confused and movements are clumsy and in coordinated .

• Usually followed by a period of sleep , malaise , headache and nausea

• Agitation and irritability are sometimes prominent

(CONTINUED)

• May be dangerously aggressive epileptic furore

• Post ictal twilight states last longer,and characterize by psychomotor retardation, vivid hallucinations affective abnormalities.

NEUROPSYCHIATRIC DISORDERS IN PATIENTS

WITH EPILEPSY

DEPRESSION AND EPILEPSY

• The prevalence of depression in different studies varies and may range from 7.5 to 34 percent of patients with epilepsy.

• Those with complex partial seizures and poor seizure control are more likely to have mood disorders.

• Psychological studies also suggest a greater incidence of ideational orientation, self-criticism, and depression among epilepsy patients with a left hemisphere focus.

(CONTINUED)

• More common in patients with CPS,TLE

• Tebartz van et al found a positive correlation between left amygdala volumes and depression

• They suggested that increased processing of negative emotional information might increase blood flow to left amygdala.

CAUSES OF DEPRESSION IN EPILEPTICS

[1] LOCATION OF THE SEIZURE FOCUS

• Studies report a higher prevalence of mood disorders in TLE, supporting a specific role for temporal–limbic disorder.

• Left-sided foci and with an increased risk of depression

• Right-sided foci and with an increased risk of mania.

[2] SEIZURE FREQUENCY

• Better seizure control and a reduction in interictal epileptiform abnormalities are associated with emergence of depressive symptoms or other psychiatric complaints (psychosis, mania or anxiety).

[3] IATROGENIC

• Poly pharmacy in epilepsy has been shown to be associated with depression.

• The anticonvulsants most associated with depression are barbiturates(phenobarbital, primidone, phenytoin and vigabatrin).

• Anticonvulsants least associated are Valproate, Gabapentin, Lamotrigine.

• Decrease in folate levels associated with mainly depression.

CHOICE OF ANTI DEPRESSANTS IN EPILEPSY

It depends on various factors

Efficacy• No significant difference in newer ADs and TCAsInteractions• Fluoxetine or Fluvoxamine can cause toxic anticonvulsants levels• Sertraline, Paroxetine, and Citalopram have little effectSafety• Incidence of seizures with therapeutic doses of ADs varies from 0.1

to 4%• This is not higher than incidence in general population.

SUICIDE AND EPILEPSY

• Rates higher among epileptics

• 20% deaths were due to suicides in mentally abnormal epileptics

• Suicide risks is 5 fold among epileptics

• Suicides attempts also appear to be especially common

BMD AND EPILEPSY

• Manic episodes described in range of 1.5 to 4.8%.

• Reported in patients with orbitofrontal and basotemporal cortical lesions of the right side.

• Mania is mostly related to peri-ictal state, and improves with seizure control.

• Hypomania has been described as occuring de novo after temporal lobe surgery with right sided emphasis.

TREATMENT OF BMD

• Most of the antipsychotics possess proconvulsant effect.Hence they should be used very cautiously.

• Lithium at therapeutic levels has very low proconvulsant effect.

• At toxic levels Lithium causes neuronal hyperexcitability and thus acts as proconvulsant.

• The use of anticonvulsants as Carbamazepine and Valproic acid are

known to be effective in treatment of BMD in epilepsy.

ANXIETY DISORDERS AND EPILEPSY

• Generalized anxiety , phobic and panic disorders are common.

• The lifetime prevalence is 21% in epileptics, much higher than 1% prevalence rate in the general population.

• Interictal panic disorder represents a paroxysmal condition that can be misdiagnosed as an epileptic seizure. Conversely, anxiety symptoms during seizures need to be distinguished from interictal

anxiety.

(CONTINUED)

• Ictal anxiety or fear is usually stereotyped, with rapid onset and shorter duration than panic attacks.

• Anxiety can be reaction to acquiring the diagnosis of epilepsy.

• Treatment of anxiety in epilepsy consists of relaxation techniques, counselling, and behavior therapy mainly.

OCD AND EPILEPSY

• Abnormal EEG is recorded in some patients of OCD consisting of temporal sharp waves activity.

• One case report described inverse relationship between seiures and OCD.

• Higher obsessionality scores is associated with hyperperfusion in ipsilateral temporal, thalamic and basal ganglia.

Treatment

• Serotonergics may be given.

• Carbamazepine may be an effective and safer alternative.

• Behavioral therapy and psychosurgery are effective.

PSYCHOSES AND EPILEPSY

• Range from transient self limiting episodes to chronic illnesses.

• Various population based studies found a prevalence of 2 to 7 % .

Divided into:

[1] Psychoses in which confusion and impairment of consciousness are outstanding features while affective or schizophreniform elements are absent.

(conti nued)

[2] Psychoses with admixture of ‘organic’ and ‘functional’ manifestations.

[3] Psychoses which occur in setting of clear consciousness and take a form characteristic of schizophrenia or affective disorder.

CLINICAL CHARACTERISTICS OF PSYCHOSIS IN RELATION TO

SEIZURE ACTIVITYIctal psychosis Post ictal

psychosisPeri ictal psychosis

Inter ictal psychosis

Consciousness impaired Impaired or normal

Impaired normal

Duration Hours to days Days to weeks Days to weeks months

EEG Status epilepticus

Increased epileptic and Slow activity

Increased epileptic and Slow activity

unchanged

Treatment Anticonvulsants (i/v)

Spontaneous recovery in many cases

Improved seizure control

Neuroleptic drugs

POST ICTAL PSYCHOSIS (PIP)

Risk factors

• Bilateral cerebral dysfunction• Ictal fear• Clusters of seizures • H/O febrile convulsions or mesial temporal sclerosis• Less hippocampal sclerosis, anterior preservation of hippocampus• Preexisting psychiatric disorder• Family H/O psychotic disorder

CLINICAL FEATURES AND PHENOMENOLOGY OF POST ICTAL

PSYCHOSIS

• PIP develops in patients with Complex Partial Seizure mostly.

• Duration of PIP ranges from 1 to 90 days

• There can be Delirium Delusions, Hallucinations Mood disorders Aggressive behavior Sexual disorders (hypersexuality)

OPERATIONAL CRITERIA FOR POST ICTAL PSYCHOSIS

1. Onset of confusional psychosis within a week of the return of apparently normal mental function

2. Duration of between one day to three months

3. A mental state characterized by a) clouding of consciousness, disorientation or delirium b) delusions, hallucinations in clear consciousness c) a mixture of a and b

4. No evidence of factors which may have contributed to the abnormal mental state:

a) anticonvulsant toxicity b) previous history of interictal psychosis c) EEG evidence of status epilepticus d) recent head injury or alcohol or drugs

PERI ICTAL PSYCHOSIS

• A wide range of phenomena including affective, behavioral , and perceptual experiences may occur

• Often accompanied by automatisms

• Consciousness is usually impaired

• Amnesia will often follow

• Diagnosis is made by EEG

INTER ICTAL PSYCHOSIS

• It tends to last days to weeks.

• More common when seizures are infrequent or fully controlled.

• Premonitory symptoms as anxiety and insomnia may be present.

• EEG normalizes during such episodes generating the terms ‘ forced normalization’.

SCHIZOPHRENIA LIKE PSYCHOSIS OF EPILEPSY

(SLPE)• Develops in 7 -9 % cases of epilepsy.

• TLE is the most common form of epilepsy.

• Most patients have delusions without any changes in level of consciousness.

• Delusions are mainly paranoid.

• Vivid hallucinations of all kinds may occur.

RISK FACTORS FOR SLPE

• Age of onset before or around puberty.• TLE• Seizure frequency is diminished• Gender F>M• No family history• EEG- mesio basal focus L> R , or B/L• SPECT- left temporal hyper perfusion• Pathology- Ganglioglioma/ Hamartoma

CLINICAL FEATURES OF SLPE

• Paranoid psychosis

• Religious delusions

• Preservation of affect and lack of negative symptoms

• Rarely catatonic symptoms

• Patients with frontal lobe epilepsy show marked emotional withdrawal and blunted affect

PRINCIPLES OF TREATMENT OF PSYCHOSIS

• First line management of patients who only have episodes of psychosis after seizures should be attaining seizure control.

• All neuroleptics reduce seizure threshold so they should be uesd very cautiously.

• Rates of seizure range from 0.5 to 1.2 with neuroleptic use in cases of previously controlled epilepsy.

• Avoid Clozapine , Loxapine, Chlorpromazine

• Of conventional neuroleptics Haloperidol is relatively safe

• Sulpiride , Quetiapine, Olanzapine and Risperidone are safe in long term treatment

• When possible, give only one drug

• Monitor seizure frequency strictly.

PERSONALITY DISORDER AND EPILEPSY

• Most commonly associated with TLE

• Dependent and avoidant personality disorders were the most common diagnoses

• Epileptic aura was positively correlated

• It has been associated with poorer response to treatment, lower compliance, and increased risk of suicide attempts.

PERSONALITY TRAITS A/W EPILEPSY

• Aggression , Anger• Circumstantiality • Dependence • Passivity • Depression, sadness, elation• Emotionality• Increased philosophical

interest• hyposexuality

• Guilt• Humourlessness• Hyper graphia• Hyper moralism• Hyper religiosity• Obsessionalism• Paranoia• viscosity

PD IN ASSOCIATION WITH TYPE OF EPILEPSY

• TLE > Grand mal > Petit mal

• In Petit mal patients are generally passive and ‘nice mannered’

• They are referred for neurotic symptoms mainly

• In TLE children are more aggressive and less neurotic

• Brain injured epileptic patients are often aggressive, explosive and unpredictable.

(continued)

• Other characteristics seen in TLE are: impulsiveness, antisocial conduct, paranoid attitude moodiness hysterical symptoms, perseveration and viscosity of thoughts

• ‘Ixophrenic Syndrome’ of slowness, perseveration and viscosity is common in TLE.

ETIOLOGY OF PD IN EPILEPSY

[1] Psychosocial Effects

• Behavioral disturbances closely related to adverse factors in family

• Patient is liable to be object of anxious concern and overprotection

• Attitude of dependency, egocentricity or hypochondriasis in personality.

(continued)

[2] Effects of brain damage

• Many problems seen are similar to those in brain damage

• Nothing specific to epilepsy about mental slowing, perseveration, stickiness or viscosity of thoughts and emotions.

• Association claimed b/w TLE and PD is likely d/t brain damage in limbic system

(continued)

[3] Effect of seizures and abnormal electrical activity

• Disorganization of cerebral functioning by epileptic discharge also contribute

• Shown by : Increase disturbance in some prior to fit Traits may improve when fit frequency is low Effect of temporal lobectomy postoperatively

SEXUAL DISORDERS

• Especially reported with TLE, resolves with cessation of attacks• Prevalence varies from 22-67%• Most common sexual dysfunction is inter ictal disorder of

hyposexuality• Self mutilation, transvestism , masochism, exhibitionism and

fetishism have been reported• More vaginismus in women, more ED in men with physiologic

origin• Endocrine changes have been reported on t/t with liver enzyme

inducing antiepileptics

EPILEPTIC DEMENTIA

• Many epileptics undergo a decline in intellectual ability.

• Progressive impairment of memory, concentration and judgment.

• Usually coupled with severe personality deterioration and behavioral disorders.

• Neuro imaging may demonstrate cerebral atrophy.

• Common when epilepsy is secondary to a known brain lesion.

(continued)

In children a/w• prolonged febrile status• West syndrome• Lennox – Gastaut syndrome

In adults • Etiology differs from case to case• Epileptic with brain lesion dement earlier• It may represent chronic end state of SLPE

PSYCHOSOCIAL ISSUES

ASSOCIATED WITH EPILEPSY

Common problems reported in epileptics:

• Anxiety• Poor self-esteem• Social isolation• Depression• Stigma• Marriage issues• Employment• Poor quality of life

WAYS TO COPE WITH EPILEPSYCounselling – to educate regarding epilepsy, assist in adaption of life with epilepsy and

treat any comorbid psychiatric conditions

Recreation therapy – to approach social isolation problem and relationship with peers

Social skills and cognitive rehabilitation – to assist patient with brain dysfunction complicated by epilepsy

Self-help and support group

Vocational rehabilitation

EPILEPSY IN

THE INDIAN LAW

Marriage

• The Hindu Marriage Act of 1955 and the Special Marriage Act of 1954 stated that a marriage under these acts can be solemnized “if at the time of marriage neither party suffers from recurrent attacks of insanity or epilepsy”.

• After 12 years of struggle by the Indian Epilepsy Association the word ‘epilepsy’ deleted from this law in December 1999.

• The religion Hindu includes followers of Sikh, Jain and Buddhism also.

• Marriages in muslims and christians are governed by personal laws based on their religious books.

Employment paradoxical laws

• Barring employment to any person on the grounds he/she has epilepsy would amount to violation of the Indian constitution.

• However the law also says that a State can prohibit employment of persons who are medically unfit if the nature of the job requires a “fit” person!

• And the paradox is still present in law.

Insurance

• The Life Insurance Company of India issue life insurance policies to epilepsy patient at a slightly increased premium rate of 10-15%.

• However personal, accident, health and travel insurances are available with a provision that the insurance does not cover illness/ accident related to epilepsy.

• Motor insurance and home insurance are issued without any restrictions.

• There are also private companies who provide life insurance with or without extra premium depending on recommendations of a medical board.

Driving

• All driving license applicants have to fill in a form which specifically asks ‘Do you have epilepsy?’.

• If a person answers in the affirmative, he or she is denied a license.

Disability status

• In India, epilepsy does not fall under the ‘disability’ category.

• We also do not have a disability discrimination act applying for epilepsy.

REFERENCES

• Harrison’s principles of Internal medicine , 19th ed.• Kaplan and Sadock’s CTP 9th ed. • CMDT 2016.• Organic psychiatry William Alwyn Lishman, 3rd ed.• The Psychiatric Perspectives of Epilepsy Joseph M.

Schwartz, and Laura Marsh, Psychosomatics 41:31-38, February 2000

• Neuropsychiatry BY Randolph B. Schiffer, Stephen M. Rao, Barry S. Fogel

REFERENCES (continued)

• www.indianlaw.gov.in

• Personality Disorders Among Medically Refractory Epileptic Patients ,Faustino Lopez-Rodriguez, Lori Altshuler Joanne Kay, Mario Mendez, and Jerome Engel, J Neuropsychiatry Clin Neuroscience 11:464-469, November 1999.

• Ictal and postictal psychiatric disturbances, Michael R. Trimble Institute of Neurology, University College, London.

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