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

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

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 1999 14/3; 404-416]

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; 160:1233-41

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)

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

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

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.

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

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

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…

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

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

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

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

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

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%)

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

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

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

Treatment of catatonia Benzodiazepines, most studied are lorazepam and clonazepam at high doses: 70% response within 4 days ECT bilateral usually 8- 15 sessions 3x/week Benzodiazepines suspend the symptoms; ECT treats underlying disease Antipsychotics ineffective, often detrimental

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

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