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 Kanner et al. Neurology 2004;62:708-13. 2 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 non-

epileptic 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?

•  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