Diagnose, Pathophysiologie und Behandlung der Katatonie - Prof. Dr. med. Sebastian Walther
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Diagnose, Pathophysiologie
und Behandlung der Katatonie
Prof. Dr. med. Sebastian Walther
PUK Zürich
Universitätsklinik für Psychiatrie und Psychotherapie, Bern
15.03.2019
Catatonia – a challenge for psychiatry
Disease entity Subtype of Frequent only in
(presentation, schizophrenia affective disorders
course, ?aetiology?) (presentation, course) (not psychoses)
1874 1902 1976 +
Autoimmune Syndrome
reaction dimension
(not genuine psychiatric)
2001 + 2010 + 2013 +
2
§ Entwicklung des Katatonie-Konzeptes
§ Klinisches Bild
§ Diagnose der Katatonie
§ Pathophysiologie
§ Behandlung
3
Classification changes over time
subtype of min. 3 subtypes of
endogeneous schizophrenias
distinct disease entity psychosis
affective non-affective
4
Change in diagnostic criteria of
Schizophrenia
«…modern criteria
underemphasize
signs vs. symptoms.
The very commonly
described sign of odd
movements or
posture is absent from
all diagnostic criteria.»
5
Kendler 2016 JAMA Psychiatry
Catatonia in DSM-5
Disease entity Schizophrenia subtype Psychosis subtypes
6
Motor abnormalities – biomarker for
psychosis
§ Screening in risk states
Torticollis
§ Staging in schizophrenia
§ Outcome prediction in
schizophrenia
Gesture-
Speech-
Mismatch
Balance Parkinsonism
Clumsiness
Parakinesia
van Harten, Walther et al. 2017 Neuroscience Biobehavioral Reviews 7
Motorikdomäne im RDoC
cortico-cortical
Basalganglien cerebello-thalamo-cortical
Cuthbert & Insel 2015, Mittal et al.2017, Walther et al. 2019 Psychol Med, Sanislow et al. 2019 Neuron 8
Catatonia - concepts § Motor syndrome § Paralysis of will § Fear syndrome § Immune dysregulation § Medical condition Walther et al. in press Lancet Psychiatry 9
KLINISCHES BILD
10Weygandt 1902
Weygandt 1902
Catatonia symptoms
§ Pure motor signs
— posturing § Movement control
— Manierisms — Rituals Internal
— Immobility — Stereotypies
— Rigor External
— Echophenomena
— Stereotypies
— Catalepsy
§ Other
— Grimacing — Stupor
— excitement
— Flexibilitas Cerea
— Verbigeration
§ Volitional issues — Nudism
— Automatic obedience — Perseveration
— Negativism — Staring
— Refused food intake — Autonomic instability
— withdrawal
— Ambitendency
— echophenomena
Walther & Strik 2012 Neuropsychobiology 13Motor signs in drug-naive first episode
psychosis
20 18.5
18
Prevalence
Percentage of patients
16
14 12.5
11.5
12
9.5
10
8 7
6 4.5
3.5
4
2
0
AIMS Hypokinesia Retarded Echo-Phenomena Excited Catatonia Catalepsy Parkinsonism
Catatonia
Retarded Echo‐ Excited
AIMS Mean Hypokinesia Catalepsy Parkinson.
catatonia phenomena catatonia
(SD) Mean (SD) Mean (SD) Mean (SD)
Mean (SD) Mean (SD) Mean (SD)
F (df = 1) 20.1 9.1 12.2 14.0 10.7 1.76 9.18
Time effect
P 0.0001 0.003 0.001 0.0009 0.001 0.186 0.003
F (df = 3) 0.59 1.25 1.69 0.68 0.51 0.19 3.41
Treatment
effect
P 0.620 0.294 0.172 0.563 0.679 0.904 0.019
Peralta & Cuesta 2010 Movement Disorders 14Associated symptoms
15Motorik und nonverbale Kommunikation
bei Psychosen
§ 50-67% benutzen Gesten falsch
§ Generalisiertes nonverbales Defizit
§ Verlaufsvorhersage
§ Reduziertes soziales Funktionsniveau
§ Stabile Negativsymptomatik
§ Stört Interaktion mit anderen
§ Neuronale Veränderungen im Gestennetzwerk
Patienten < Kontrollen
p(FWE) < .05
Walther et al. 2013 Cortex, 2015 & 2016 Schizophr Bull, Stegmayer...Walther 2018 Schizophr Bull 16Is Catatonia vanishing? No!
18%
Code%Cat%
Code%Cat%
Code%Cat%
DSM+IV%Cat%
DSM+IV%Cat%
No%Cat%
BFCRS%Cat%
No%Cat%
No%Cat%
Sporadic catatonias reduced
Familial catatonias are stable Acute admissions 17%
Untreated first episode cases 12%
Stompe et al. 2002, van der Heijden et al. 2005, Peralta & Cuesta 2001, Peralta et al. 2010Schwerste Fälle
§ Maligne Katatonie:
§ Hyperthermie, Tachykardie,
§ Massive Katatoniesymptome
§ Malignes neuroleptisches Syndrom
§ Nach Exposition zu Antipsychotika (seit 1952)
§ Hyperthermie, Verwirrtheit, Rhabdomyolyse
§ Schwerster Rigor, massive Katatoniesymptome
18DIAGNOSE
19Catatonia checklist
Observa)on Interview Physical exam
Agita'on/Excitement
Impulsivity
Increased
Comba'veness
Grimacing Echolalia * Waxy Flexibility
Stereotypy Echopraxia * Catalepsy *
Psychomotor
Mannerism Verbigera'on Rigidity
ac)vity Abnormal
Posturing * Automa'c Gegenhalten
Persevera'on obedience Mitgehen
Grasp reflex
Stupor Nega'vism
Decreased Ambitendency Mu'sm
Staring Withdrawal
Autonomic abnormality
Walther et al. in press Lancet Psychiatry 20Diagnosekriterien Katatonie
DSM-5 ICD-10
3 oder mehr von Katatone Schizophrenie
1. Katalepsie Schizophreniekriterien erfüllt.
2. Flexibilitas cerea >2 Wochen lang 1 oder mehr von
3. Stupor 1. Stupor
4. Agitation 2. Erregung
5. Mutismus 3. Haltungsverharren
6. Negativismus 4. Negativismus
7. Haltungsverharren 5. Rigidität
8. Manierismen 6. Flexibilitas cerea
9. Stereotypien 7. Befehlsautomatismen
10. Grimassieren
11. Echolalie Organische Katatonie
12. Echopraxie 1. Stupor bei normalem Tonus
2. Negativismus
Walther & Strik 2016 CNS Spectrums 21Prevalence rates of catatonia
22
Walther & Strik 2016 CNS SpectrumsKatatonie Prävalenz und Stabilität
N = 1094
Peralta & Cuesta 2017 Schizophrenia Bulletin 23Zusammenfassung Diagnose
§ Klinische Katatonie-Skalen
§ Bush Francis Catatonia Rating Scale
§ Modified Rogers Scale
§ Northoff Catatonia Rating Scale
§ DSM-5 - Katatonie bei verschiedenen Erkrankungen
§ Schizophrenie
§ Affektive Störungen
§ Entwicklungsstörungen
§ Neurodegenerative Erkrankungen
§ 10-20% der Akutpsychiatrischen Patienten
24PATHOPHYSIOLOGIE
25Catatonia brain imaging:
a mission impossible?
§ 3105 hits in PubMed
§ 345 reviews
§ 51 studies on psychometrics or treatment
§ 10 studies on brain imaging
§ A rare condition?
§ A matter of consent?
26Catatonia brain imaging:
planning the impossible
Who? When? How?
§ Diagnoses § Acute episode § Functional MRI
§ Presentations § During treatment § Structural MRI
§ Courses § After remission § Perfusion MRI
27Schaltkreise der RDoC Motorik-Domäne
cortico-cortical circuit
cerebello-
thalamo-cortical circuit
basal ganglia circuit
Walther et al. 2019 Psychol Med; Mittal et al. 2017 Schiz Bull; Garvey & Cuthbert 2017 Schiz Bull 28Ruheperfusion bei Katatonie
15 Sz-Cat
27 SZ-Noncat
41 HControls
Walther 2017a Schizophrenia Bulletin 29Ruheperfusion bei Katatonie –
Strasbourger Kohorte
20 Sz-Catatonia
9 SZ-Cataphasia
27 HControls
Foucher et al. 2018 Prog Neuropsychopharmacol Biol Psychiatry 30Decreased GABAA-receptor density in
catatonia
healthy control Catatonia patient psychiatric control
Northoff et al. 1999 JNNP 31Pathophysiologie Katatonie Walther et al. in press Lancet Psychiatry 32
Katatonie bei Maus und Mensch
Inflammation und Hypomyelinierung
CNP rs2070106
Hagemeyer et al. 2012, Poggi et al. 2016, Janova et al. 2018 33Katatonie Phänotyp – reversibel? Präventionsmodell Behandlungsmodell Janova et al. 2018 J Clin Invest 34
Pathophysiologie
§ Prämotorischer Kortex
§ Frontale weisse Substanz
§ Inflammation?
35THERAPIE
36Treatment of acute catatonia
Effect?
continue Lorazepam,
consider
Antispychotic
T < 39°C?
Lorazepam up to 20
mg/d ECT
Antipsychotic
Start ECT
Antipsychotic
ECT
Effect?
Ungvari et al. 1994, Rosebush et al. 1990, Bush et al. 1996, Fink et al. 2009 37Treatment of chronic catatonia
18 chronic Catatonia patients
Placebo-controlled, randomised, 25"
Lorazepam 6mg/d
double-blind, crossover - Add-
on-trial of Lorazepam 6 mg/d 20"
12 weeks 15"
MRS$Score$
§ Antipsychotics 10"
§ Clozapin
§ Atypical 5"
§ Haloperidol
0"
Baseline" Week"3" Week"6" Baseline" Week"3" Week"6"
§ ECT Lorazepam" washout" Placebo"
No effect on catatonia
§ Activation therapy
§ Sport
Ungvari et al. 1999, Van der Een et al. 2005, Fink et al. 2009, Suzuki et al. 2005Antipsychotics and motor symptoms
Neuromotor Abnormalities in Psy
100 drug-naive first episode psychosis patients - 4 week antipsychotics
tment Response Pattern of Neuromotor Abnormalities in 100 Psychotic Patients
35
Drug-responsive
30 28 Drug-unchanged
Drug-emergent
25
Number of Patients
20
15 15
15 13
11
10 8
6
5 3
2 2 2 2
1 0 0
0
Parkinsonism Dyskinesia Akathisia Catatonia Dystonia
Peralta & Cuesta 2010Verlauf einer malignen Katatonie unter
EKT
12 sessions of ECT for severe malignant catatonia
30
25
BFCRS Score
20
15
10
5
0
ECT sessions
40Zusammenfassung
§ Diagnose Katatonie sichern – Skalen nutzen
§ Prophylaxe
§ Thrombembolien
§ Druckulzera
§ Muskelkontrakturen
§ Dehydratation / Malnutrition
§ Benzodiazepine bei akuter Katatonie (1. Wahl Lorazepam)
§ EKT bei fehlendem Ansprechen auf Benzos
§ Clozapin für chronische Katatonie bei Psychosen
41Ausblick
§ Overcoming psychomotor slowing in Psychosis
§ RCT über 3 Wochen rTMS mit SMA Stimulation
§ klinische und Imaging-Outcomes
§ SNF 182469
§ An examination of psychomotor disturbance in current and
remitted MDD – an RDoC Study
§ Longitudinale Studie
§ NIMH R01 MH118741
42Vielen Dank !
Universitätsklinik für Psychiatrie und Universiteit Antwerpen
Psychotherapie Bern Prof. Manuel Morrens
Prof. Bernard Sabbe
Arbeitsgruppe Prof. Sebastian Walther Prof. Didier Schrijvers
Dr. Linda van Diermen
Dr. Katharina Stegmayer
Dr. Tobias Bracht Maastricht University
Dr. Petra Viher Prof. Peter van Harten
Dr. Andrea Cantisani
Dr. Lea Schäppi
Danai Alexaki
Northwestern University
Prof. Vijay Mittal
Dr. Nadja Razavi
Prof. Andrea Federspiel Prof. Stewart Shankman
Texas A&M University
Prof. Jessica Bernard
Universitätsklinik für Neurologie
Prof. Roger Kalla
Prof. Andrew Chan
Dr. Robert Hoeppner
Dr. Anke Salmen Vanderbilt University
Prof. Stephan Heckers
Dr. Jo Ellen Wilson
Universitätsinstitut für Neuroradiologie
Prof. Roland Wiest
MPI Göttingen
Prof. Hannelore Ehrenreich
Bangerter- PD Martin Begemann
Rhyner Stiftung
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