Epilepsispesifikke psykiatriske syndromer.
Prinsipper for inndeling, diagnostikk og terapi.
Arne Vaaler
Innhold
•  Hvorfor er epilepsi viktig i psykiatrisk praksis?
•  Hvor er det utfordringer og kunnskapsmangel.
•  Prinsipper for behandling.
•  Hva med EEG?
•  Noen gode referanser til slutt.
The classification of neuropsychiatric disorders in epilepsy
Historikk
•  Hippokrates
•  Falret og Samt 1800-tallet. Ictale og inter-ictale tilstander.
•  Hovedfokus psykose.
•  1950-tallet EEG.
•  2000-tallet systematisk arbeid med klassifisering.
• 
2007 ILAE «Commission of psychobiology in epilepsy». Publ egne kriterier
•  2015
DSM-5.
People with epilepsy (PWE) and Affective Disorders (AD)..
clinical and experimental links.
•  Frequency figures of comorbidity in neurology and psychiatry.
•  Antimanic, antidepressant, anti-kindling and mood stabilizing
properties of AEDs.
•  ECT
•  Kindling – phenomenon.
•  Animal models, neuro-biology, -transmitters, - anatomy.
Complex relationship between AD and E, based on the sharing of
common pathogenic mechanisms.
Bidirectional relationship between psychiatric disorders and epilepsy.
Hippocrates …..
•  PWE increased prevalence of affective disorders.
•  Depression preciding the onset of epilepsy 7 times more common
among adults with newly diagnosed epilepsy compared to controls.
17 times more common among patients who went on to
develop complex partial seizures.
Forsgren & Nystrøm. Epilepsy Res 1999
•  PWE increased prevalence of schizophrenia.
•  Patients with schizophrenia have increased risks of developing
epilepsy (HR 5.88, 95% CI 4.71 – 7.36).
Chang et al. Epilepsia 2011
Epilepsi - en spektrum tilstand.
•  Epilepsi økende ansett som en tilstand med mye mer enn anfall.
•  Halvparten av pasientene psykiatriske lidelser og/eller affiserte
kognitive evner.
-  Psykiatriske / kognitive tilstander:
1)  direkte konsekvens av anfallsaktivitet
2)  skyldes separate mekanismer parallelle til de som utløser ictal
activitet.
Jensen. Epilepsia 52, 2011.
Epilepsy-specific psychiatric disorders.
PWE compared to the non-epileptic population
PWE most often present with psychiatric disorders with atypical
characteristics (according to ICD-10 and DSM-4 criteria).
•  PWE have epilepsy-specific psychiatric disorders with specific
phenomenology.
•  Most of these disorders are clinically distinct.
Do not find a place in the current classification systems (DMS-IV) or ICD-10.
DMS-V!
As these disorders are phenomenologically distinct, they may
respond to specific therapeutic measures.
Klassifikasjon av psykiatriske lidelser i epilepsi.
International league against epilepsy.
«Commission on psychobiology of epilepsy».
Aims: Developing a more comprehensive and acceptable
system of classification for psychiatric disorders in epilepsy.
Krishnamoorthy et al. Epilepsy&Behavior 2007
APA. DMS-V
Psychosis of epilepsy.
Section «Psychotic disorders due to another medical condition».
ILE: The classification of neuropsychiatric disorders in E.
Main aim: Separation of disorders in PWE
1: Disorders co-morbid with E.
2: Psychiatric symptoms reflecting ongoing epileptic activity.
3: Epilepsy-specific psychiatric disorders.
Classification of 2+3 largely follow their relationship to the ictus.
Relationship to AED coded as additional information.
The classification presents a clinical and descriptive system rather
than an etiological classification due to inadequate information for
the latter to be employed globally.
Krishnamoorthy et al. Epilepsy&Behavior 2007
Psychiatric symptoms reflecting ongoing epileptic activity
Pre-ictal psychiatric symptoms:
Pre-ictal affective disorders
Pre-ictal psychoses (aura)
Ictal psychiatric symptoms:
Anxiety / fear is the most frequent ictal affect.
Mood changes may represent the only expression of
simple partial seizures.
May be difficult to recognize as epileptic phenomena.
Peri-ictal psychoses.
Complex partial status epilepticus (non-convulsive status)
Postictal disorders.
Psykoser og affektive.
• 
After multiple seizures or complex partial seizure status.
• 
A “free” or lucid interval (hours – 1 week) between the seizure and the rapid
development of psychiatric symptoms.
• 
Condition with affective symptoms together with anxiety, extensive panic,
psychosis, aggression, suicid attempts 1
• 
Pleomorphism and rapid changes are core symptoms.
• 
Suicidal ideations, violence to oneself or others. 2
1
2
Kanner et al. Neurology 2004;62:708-13.
Kanemoto et al. Epilepsia 1999;40:107-9.
Clinical characteristics –
acute epilepsy-specific psychiatric syndromes (peri-ictal).
•  Pleomorphic with rapidly changing psychiatric
symptoms.
•  Symptoms of mania, panic, delirium, depression, and
delusions can be changing in short time intervals.
•  Acting out towards one-self or others have to be taken
into consideration (post-ictal phase).
Inter-ictal psychiatric disorders.
Clinical characteristics - chronic epilepsy-related affective syndromes.
Affective-somatoform disorders of epilepsy.
- Irritability, depression, anergia, insomnia, atypical pains,
anxiety,phobic fears, euphoric moods.
- Symptoms fluctuate lasting from hours to 2-3 days.
- In women the disorder is manifest (or accentuated) in
the premenstrual phase.
Kanner et al. Neurology 2004;62:708-13.
Blumer. Harv Rev Psychiatry 2000;8:8-17.
Interictal psychoses (”schizophrenia-like”).
Psychoses of complex partial seizure disorder (CPSD).
Haver B. ”From a sick physician to a difficult patient”.
Tidsskr Nor Laegefor. 2004;124(3):373-5
Interictal psychoses (”schizophrenia-like”).
Psychoses of complex partial seizure disorder (CPSD).
•  Organic mental disorder misdiagnosed as a variety of functional
disorders; schizophrenia, schizoaffective, bipolar disorders,
psychotic depression, ”atypical” psychosis.
•  The phenomenology of psychoses in CPSD permits it to be
distinguished from other forms of psychosis.
•  CPSD-psychoses can be successfully treated with
anticonvulsants, with or without neuroleptics.
•  It is generally refractory to neuroleptic medication
alone.
Brewerton 1997.
Interictal psychoses of epilepsy.
•  Characterized by strong affective components without affective
flattening.
•  May include command hallusinations, third-person auditory
hallusinations, and other first-rank symptoms.
•  There is a preoccupation with religious themes.
•  Personality and affect tend to be well preserved unlike in other forms
of schizophrenia.
•  Usually lack of family history.
Treatment of epilepsy specific psychiatric disorders.
Psychotherapy!!!
•  Information, information, information… (psykiatrisk behandlingsapparat….)
•  Automatisms, complex partial seizures, post-ictal affective
conditions and psycoses… the effects on emotions and behaviour.
•  About how epileptic seizures induce affective phenomenae and
syndromes….
•  Accordingly prophylaxis against seizures most important…
alcohol, sleep, regular life etc.
Motivational Interviewing ?
•  Be an optimistic phycisian regarding stabilization of affective
phenomenae.
•  YouTube….
Pharmacological treatment of psychiatric disorders in PWE.
Core questions:
A: What kind of psychiatric condition?
1: Disorder co-morbid with E.
2: Psychiatric symptoms reflecting ongoing epileptic
activity.
3: Epilepsy-specific interictal disorders.
B: Seizure threshold, proconvulsants, anticonvulsants and
mood-stabilizers.
C: Trial derived evidence? If not evidence from nonepileptic population?
Principles of treatment affective disorders in PWE.
1: Disorder comorbid with E.
Similar to the non-epileptic population.
+ cautious regarding medications with proconvulsive
properties or potential interactions with AEDs.
2: Psychiatric symptoms reflecting ongoing epileptic
activity.
Part of the ictus. Optimizing AEDs! Benzo / atypical
antipsychotics short time for behavioural disturbances
only.
Epilepsy-specific inter-ictal disorders.
Interictal Dysphoric Disorder (IDD) + en rekke
andre.
- Traditionally treatments based on AEDs and
antidepressants (ADs).
- No trial derived evidence.
Treatment with antidepressants in PWE.
•  Recommended in present guidelines.
•  Present evidens rely on studies from non-epileptic populations.
•  Effects on seizure threshold.
Anti- or proconvulsive (?). Therapeutic window?
Agitation, affective switch and cycle accelration?
Suicidal ideations? Suicide risk?
• 
ADs favourably affect the course of the depressive illness?
Dyremodell viser at SSRI øker tendens til kindling.
• 
Some ADs increase hyperactivity (bupropion). MAOI’s are epileptogenic.
•  SSRIs dose-dependant pro- or anticonvulsive properties.
Fava & Offidani. Progr Neuropsychopharmacol Biol Psychiatry 2011
Possible mechanisms.
Epilepsi og psykose.
•  Neurotoksisk effekt av epilepsi. Økt inhibisjon over tid?
•  «Kindling prosess» hvor aktivitet medfører endret funksjon
•  «Forced normalization process». Inverst forhold mellom
anfallskontroll og psykose.
•  «On-going subictal activity» i limbiske strukturer, ikke påvislig på
EEG.
•  Epilepsi og psykose kan representere «different outcomes of a
common aetiological process». Data fra nevropatologi, imaging og
genetikk.
Clancy et al. BMC Psych 2014.
«Kroniske», schizofreniforme epileptiske psykoser –
hvordan ter vi oss i praksis?
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• 
• 
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Ydmyke for det vi ikke forstår.
Hvis de skal brukes ikke høye doser «antipsykotika».
Funn på EEG, klinikk, sykehistorie gir indikasjoner på terapivalg.
Akutteffekt kontra langtidseffekt.
•  Vanligvis: Fokus på stemningsstabiliserende antiepileptika.
•  «Forced normalization» / «alternating psychoses» forkommer…
Klinisk vanskelig.
The scalp EEG…
Noen av hovedproblemene..
•  Forced normalization:
-  Pas med epilepsi ble psykotiske «associated with the
disappearances of the epileptiform discharges on the EEG».
Landolt 1958.
-  Introduksjon av et bestemt medikament (etosuxemide) cases↑
Trimble&Schmitz 1998.
-  Intensivering av psykiatriske symptomer i TLE når «seizures are
suppressed».
Gibbs. J Nerv Ment Dis 1951
-  Invers relasjon mellom frekvens av interictale spikes på EEG og
diagnose mood-disorders i TLE.
Bragatti et al. Clin Neurophysiol 2014.
EEG and psychiatric populations.
Please read!
1: Shelley & Trimble. ”All that spikes is not fits,”. Mistaking
the woods for the trees: The interictal spikes – an ”EEG
chameleon” in the interface disorders of mind and brain:
a critical review.
Clinical EEG and Neuroscience 2009; 40: 245-261.
2: Elliott et al. Delusions, illusions and hallucinations in
epilepsy: 2. Complex phenomena and psychosis.
Epilepsy Res. 2009 Aug;85(2-3):172-86.
(intracranial stereoelectroencephalography (SEEG))
EEG – funn/ikke-funn - konsekvenser.
•  EEG beskrevet som «negativt» betyr ikke at pas ikke har organisk
patologi.
•  Er det epileptiform aktivitet må det ha konsekvenser!!!
•  Er det annen mer diffus patologi…langsom aktivitet bør det ha
konsekvenser for terapivalg.
•  Hvis pas har klinikk som peker mot organisk patologi, men med
negativ EEG bør vi tenke oss nøye om.
Some excellent papers in the field.
•  Treatment:
Barry et al. ”Consensus statement: The evaluation and treatment of
people with epilepsy and affective disorders.” Epilepsy&Behavior
2008;13.
Elger & Scmidt. ”Modern management of epilepsy: A practical
approach.” Epilepsy&Behavior 2008;12.
Kaufman. ”Antiepileptic drugs in the treatment of psychiatric
disorders” . Epilepsy&Behavior 2011; 21.
•  Classification:
Krishnamoorthy et al. ”The classification of neuropsychiatric
disorders in epilepsy…” Epilepsy&Behavior 2007;10.
•  Neurobiology:
Kondziella et al. ”Which clinical and experimental data link temporal
lobe epilepsy with depression?” J Neurochem 2007.
Kanner. ”Mood disorders and epilepsy: A neurobiologic perspective
of their relationship.” Dialogues Clin Neurosci 2008;10.
Some excellent articles in the field.
•  For those of you most interested in schizofrenia
and schizofrenia-like psychotic disorders:
Brewerton. ”The phenomenology of psychosis
associated with complex partial seizures”.
Annals of Clinical Psychiatry 1997;9: 31-51.
•  Kanner. ”When did neurologists and
psychiatrists stop talking to each other?”
Epilepsy&Behavior 2003;4:597-601.
International league against epilepsy.
”Commission on the neuropsychiatric aspects of epilepsy”.
Aims: To address the major impact on quality of life and
epilepsy management caused by associated
neuropsychiatric conditions.
Lack of guidance.
Give consensus based practice statements.
Kerr et al. Epilepsia 2011 . doi:10.1111/j.1528-1167.2011.03276.x