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? • • • • 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
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