1. Catatonia Kristen Shirey, M.D. Duke University Hospital
Internal Medicine and Psychiatry

3. Catatonia Common Signs are easily identifiable Many faces
NMS is a form of malignant catatonia
Differential diagnosis
Syndrome of motor dysregulation
Good-prognosis condition
Easy to treat

4. Catatonia is common
Prevalence is estimated at 6-15% of adult psychiatric inpatients
Approximating incidence at 10%, catatonia may be 2-3 times more common than suicide in the United States
Immobility & mutism often recognized while whispered/robotic voice, pacing, or other purposeless movement missed
Rating scale has inter-rater reliability >0.90 [Norhoff et al. Movement Disorders /3; ]

5. Definition of catatonia
First described by Kahlbaum in 1874 as a specific motor dysfunction, phase of progressive illness including stages of mania, depression, psychosis ending in dementia
Includes 3 distinct categories of symptoms: hypo/hyperkinetic, affective & behavioral
Excellent review by Taylor & Fink AMJP 2003; 160:

6. Classic signs of catatonia
Stupor Extreme hypoactivity, immobility, minimally responsive to stimuli (including pain)
Mutism Verbally minimally responsive
Negativism Involuntary/amotivational resistance, oppositional behavior (Gegenhalten)

8. Additional signs
Automatic obedience Exaggerated cooperation with examiner’s request; mitgehen
Stereotypy Repetitive, non-goal-directed motor acitivity, echopraxia, echolalia, verbigeration
Catalepsy/Posturing Maintains postures ie. pillow-sign, waxy flexibility

9. Other sx Excitement Staring Grimacing
Mannerisms: odd, purposeful movements
Rigidity
Impulsivity
Ambitendency (alternating cooperation and opposition)
Combativeness

10. ProcedureBush
Examines
Observe patient while trying to engage in a conversation
Activity level Abnormal movements Abnormal speech
Examiner scratches head in exaggerated manner
Echopraxia
Examine arm for cogwheeling. Attempt to reposture, instructing patient to "keep your arm loose" - move arm with alternating lighter and heavier force.
Negativism Waxy flexibility Gegenhalten
Ask patient to extend arm. Place one finger beneath hand and try to raise slowly after stating, "Do NOT let me raise your arm".
Mitgehen
Extend hand stating "Do NOT shake my hand".
Ambitendency
Reach into pocket and state,"Stick out your tongue, I want to stick a pin in it".
Automatic obedience
Check for grasp reflex.
Grasp reflex
Check chart for reports of previous 24-hour period. In particular check for oral intake, vital signs, and any incidents.
Attempt to observe patient indirectly, at least for a brief period, each day.

11. 2 out of following 5 criteria:
DSM IV => specifier of schizophrenia, mood disorder or general medical condition
2 out of following 5 criteria:
Motoric immobility ( catalepsy, waxy flexibility, stupor)
Excessive motor activity (purposeless, not influenced by external stimuli)
Extreme negativism (rigid posture, resistance to instructions, gegenhalten, mutism)
Peculiarities of voluntary movement (grimacing, bizarre postures, stereotyped movements)
Echolalia or echopraxia

12. Fink’s proposed catatonia classification
Diagnostic criteria:
Immobility, mutism or stupor for at least 1 hour + one of the following: Catalepsy, automatic obedience, posturing, observed or elicited at least twice
In the absence of immobility, mutism or stupor, need to observe or elicit at least twice at least two of the following: stereotypy, echophenomena, catalepsy, automatic obedience, posturing, negativism, ambitendency
Catatonia:
Non-malignant catatonia: criteria A
Delirious mania (excited catatonia): criteria B + severe mania or excitement
Malignant catatonia A or B + fever and autonomic instability
Modifiers:
2/2 Mood disorder
2/2 General medical condition or toxic state
2/2 a Brain disorder
2/2 Psychotic disorder

13. Malignant Catatonia
Dopamine loss, sympathetic overdrive lead to hyperadrenergic state.
Tachycardia, fever (hotness of body), hypertension, diaphoresis ensue
Increased vagal tone in the heart stimulates mechanoreceptors, which in turn modulate sympathetic tone -> hypotension, bradycardia, and even asystole…

14. Clinical features of MC/NMS
Fever
Muscle rigidity
Dyskinesia
Posturing, waxy flexibility, catalepsy, mutism
Dysarthria, dysphagia, sialorrhea
Altered consciousness, may appear comatose
Autonomic instability: lability of blood pressure, tachycardia, vasoconstriction, diaphoresis

15. Early signs of MC/NMS Mania with fever
Any catatonic features within 24h of antipsychotic initiation
Autonomic instability or sialorrhea within 24 h of antipsychotic initiation
Rapidly developed EPS symptoms with administration of low dose of antipsychotic

16. Drugs associated with MC/NMS
All antipsychotics
Metoclopramide
ATD combined with AP
Lithium
MAOIs
CBZ
Valproic acid
Cyclobenzaprine
Alpha-methyltyrosine
Abrupt withdrawal from antipsychotic
dopamine agonists BZD antihistamines anticholinergics
Intoxication with: disulfiram corticosteroids PCP, cocaine antihistaminergics anticholinergics

17. Abnormal labs in MC/NMS
Proteinuria
Myoglobinuria
Very high CPK
High LDH
Leukocytosis (10-25k)
Thrombocytosis
Low serum iron
Diffuse EEG slowing
Abnormal electrolytes: Low calcium Low magnesium High potassium
Elevated LFTs: AST, ALT, rarely bilirubin

18. Clinical risk factors for MC/NMS
Dehydration
Exposure to high temperatures
Agitation
Thyrotoxicosis
Basal ganglia disorder: TD akathisia
EPS from Rx
Past hx catatonia
Past hx NMS
Receiving high potency AP or >1 AP
IM antipsychotic
AP + ATD or mood stabilizers
Recent alcohol abuse with liver dysfunction

19. Most commonly associated with psychiatric disorders
Bipolar and schizophrenia
Withdrawal from dopaminergic medications or cocaine (also implicated in NMS)
Withdrawal from BZD (must exclude nonconvulsive status epilepticus)
Medical causes (up to 16%)

20. Medical conditions associated with catatonia
Endocrinopathies: hypoparathyroidism, thyrotoxicosis, pheochromocytoma
Infections: viral, HIV, typhoid fever
Tumors: esp fronto-temporal lesions
Stroke: esp anterior brain regions
Traumatic brain injuries: subdural hematoma
Epilepsy: post-ictal immobility & NCSE
Autoimmune: SLE
Heat stroke
Toxins: tetanus, staph., fluoride, strychnine
Poisoning: salicylates, inhalational anesthesics

21. False positives
Mutism alone is not sufficient; need at least 1 or 2 other motor symptoms
Stupor alone is not sufficient (EEG)
Parkinson disease, in particular akinetic parkinsonism, OCD, tic disorder, Tourette syndrome
Malignant hyperthermia (rare AD genetic d/o)
Stiff-person syndrome and locked-in syndrome

23. Catatonia has a good prognosis
No RCTs of in Rx of catatonia
Management is well-defined
Important to treat emergently, as catatonia can evolve in life-threatening condition
“When properly treated almost all episodes of catatonia fully resolve” Fink & Taylor
“Most likely cause of failure is … prolonged inadequate treatment” Fink & Taylor

24. Treatment of catatonia
Benzodiazepines, most studied are lorazepam and clonazepam at high doses: 70% response within 4 days
ECT bilateral usually sessions 3x/week
Benzodiazepines suspend the symptoms; ECT treats underlying disease
Antipsychotics ineffective, often detrimental

25. Acute management Hospitalization BZD challenge BZD treatment trial
Maintain fluid and electrolyte balance
Avoid antipsychotic agents
Avoid prolonged immobility
Identify and correct underlying neuropsychiatric or medical cause
If not improved in 4 days => ECT
Tx may be augmented with NMDA antagonists amantadine or memantine

26. Conclusions Common Signs are easily identifiable Many faces
NMS is a form of malignant catatonia
Differential diagnosis
Syndrome of motor dysregulation
Good-prognosis condition
Easy to treat