Patient Case:

History:

  • A 60-year-old male with history of schizophrenia and depression on multiple unknown antipsychotic medications presents with unresponsiveness x 1 day. One week prior to ED arrival, the patient was becoming progressively despondent, less interactive with peers, exhibiting slow speech and movements, and was not eating.

Physical exam:

  • Vital signs – febrile, tachycardic, hypertensive
  • General – posturing with arms stretched out in front, eyes open without blinking, akinetic, no signs of trauma
  • HEENT – dry mucous membranes, trismus with repetitive dystonic movements of the jaw, pupils mildly dilated bilaterally
  • Neuro: no verbal or motor response to noxious stimuli, diffuse hyperreflexia, bilateral ankle myoclonus, tremulous, hypertonia
  • GU: low urine output without retention despite 3 liters of IV fluids

Pertinent lab findings:

  • Mildly elevated CPK
  • Leukocytosis
  • Urinalysis concentrated with large ketones

Summary:

  • 60-year-old male with history of psychotic and mood disorders on antipsychotic medications presenting with 1 day of stupor, mutism, akinesia with posturing associated with autonomic excitation, upper motor neuron signs, and dehydration preceded by 1 week of retarded catatonia, consistent with malignant catatonia.

Course:

  • The patient’s vital signs and catatonic features began improving with IV fluids and benzodiazepines in the emergency room. The patient was admitted to the medicine step down unit, managed by the psychiatry inpatient team, and transitioned to standing IV lorazepam during preparation for electroconvulsive therapy (ECT).

Definition:

Catatonia:

  • A behavioral motor dysregulation syndrome marked by an inability to move normally despite full physical capacity, which can occur in the context of many underlying psychiatric and general medical disorders [4].
  • According to the DSM-5, catatonia is diagnosed (classified as associated with another mental disorder, due to another medical condition, or unspecified catatonia) when 3 or more of the following symptoms are present: mutism, stupor, catalepsy, waxy flexibility, negativism, posturing, mannerism, stereotypy, unresponsive agitation, grimacing, echolalia, and echopraxia [1].

Malignant Catatonia (AKA “lethal catatonia”):

  • An acute onset life-threatening subtype of catatonia that is characterized by fever, autonomic instability, delirium, and rigidity [4].

Epidemiology:

Who typically suffers from catatonia?

  • Severely ill patients with an underlying psychiatric or medical disorder.
  • An estimated 7% to 15% of acutely hospitalized psychiatric patients and psychiatric emergency department patients exhibit catatonia [4].

Who typically suffers from malignant catatonia?

  • This has not been widely studied and remains unknown.

What are risk factors for catatonia?

  • Underlying mood disorders such as unipolar depression and bipolar disorder, psychotic disorders such as schizophrenia, and autism spectrum disorder [8,2].
  • Antipsychotic drugs with high D2-blockade (i.e. first-generation antipsychotics) [5]. However, neuroleptic drug use is not required for diagnosis.
  • Sociodemographic risk factors are unknown.

How serious is malignant catatonia?

  • High morbidity and mortality, sometimes with permanent cognitive and behavioral deficits.
  • Death rates may be as high as 20% [3].

Pathophysiology:

  • Largely unknown, but data have revealed some possibilities.

Neuropathologic and neuroimaging studies:

  • suggest catatonia may involve alterations in the basal ganglia, thalamus, and prefrontal, orbitofrontal, and parietal cortices [7, 6]

Neurotransmitter studies:

  • have linked catatonia with decreased activity at GABA-A and dopamine D2 receptors, and increased activity at NMDA receptors [6]

Presentation:

Features of catatonia:

  • Immobility (hypokinesis or akinesis)
  • Mutism
  • Stupor
  • Negativism (resistance to instructions or attempts to be moved)
  • Waxy flexibility (as opposed to lead pipe rigidity seen in NMS)
  • Posturing
  • Excessive purposeless motor activity
  • Staring
  • Echophenomena (repeating another’s words or movements)

Malignant catatonia = catatonia PLUS:

  • Fever (less likely in older patients)
  • Autonomic instability (labile or elevated blood pressure, tachycardia, tachypnea)
  • Autonomic excitation (pupil dilation, hyperreflexia, diaphoresis, tremors, clonus)
  • Rigidity
  • Delirium

Course:

  • May be preceded by a catatonic prodrome (retarded or excited)
  • Fulminant and progresses rapidly within a few days

Differential:

  • CNS or systemic infections
  • Brain mass lesions
  • Stroke
  • Seizures/status epilepticus
  • Alcohol withdrawal/delirium tremens
  • Metabolic abnormalities
  • Toxidromes (i.e. neuroleptic malignant syndrome (NMS), malignant hyperthermia, serotonin syndrome, lithium toxicity, etc.)

Diagnosis:

  • Largely clinical and a diagnosis of exclusion.

Key history:

  • Psychiatric comorbidity
  • Neuroleptic or psychotropic medications (especially first-generation antipsychotics including Haloperidol, Prochlorperazine, and Droperidol)
  • Prior history of catatonia
  • Retarded or excited catatonic features preceding onset of autonomic changes
    • **this is especially helpful to differentiate malignant catatonia from NMS, serotonin syndrome, and other potential diagnoses**

Workup (to assess for alternative life-threatening diagnoses):

  • ED: EKG, CXR, urine studies, full set of labs (including CK, electrolytes, CBC, LFTs, serum iron), VBG, head CT, LP, cultures, consider Utox, Tylenol level, salicylate level, psychiatry consult
  • Floor: EEG, advanced neuroimaging (i.e. MRI)

Lab findings (common but nonspecific):

  • Elevated CK
  • Elevated lactate
  • Leukocytosis
  • Low serum iron

Lorazepam (Ativan) challenge:

  • 1 to 2 mg IV bolus of lorazepam
  • Can repeat dose after 5 to 10 minutes if no change in patient’s catatonic symptoms
  • Partial temporary relief of catatonic signs 5 to 10 minutes after IV administration of lorazepam is consistent with a diagnosis of catatonia
  • A negative response occurs commonly and does not rule out any subtype of catatonia

Management:

Supportive care:

  • Volume resuscitation with IV fluids
  • Benzodiazepines (lorazepam 1 to 2 mg q8 hours) are used to bridge patients to ECT
  • Cardiac monitor while hemodynamically unstable
  • 1:1 observation

Psychiatry consult:

  • Obtain collateral, assess for suicidality, prepare for ECT

Definitive management:

  • Treatment of underlying condition

Disposition:

  • Psychiatry floor: resolution of vital sign abnormalities in the emergency department
  • Step down unit: persistent but improved autonomic excitation (tachycardia and hypertension)
  • MICU: Autonomic instability (severe tachycardia, severe hypertension or hypotension, persistent fever)

Key Points:

  • Malignant catatonia is a life-threatening subtype of catatonia, marked by autonomic excitation and instability, rigidity, and delirium.
  • It is critical to quickly diagnose and treat malignant catatonia, as its course is fulminant and progresses rapidly, and morbidity and mortality is high.
  • The most common underlying psychopathology of malignant catatonia are psychotic disorders, mood disorders, and autism spectrum disorder, and first-generation anti-psychotic medications especially may precipitate or worsen disease.
  • Malignant catatonia is a clinical diagnosis guided largely by history, mental status exam, and physical exam.
  • Malignant catatonia closely resembles both NMS and serotonin syndrome; past medical history, medication history, and clinical history of a catatonic prodrome prior to the onset of delirium and autonomic excitation is helpful in differentiating malignant catatonia from related presentations.
  • An IV lorazepam challenge can help diagnose malignant catatonia and management should include standing IV lorazepam boluses and IV fluid resuscitation until the patient can undergo ECT.
  • Disposition to the psychiatry floor, medicine step down unit, or MICU should be guided by the degree of the patient’s vital sign abnormalities, the presence or absence of autonomic instability, and the patient’s response to therapy in the emergency room.

Further Reading:

References:

  1. American Psychiatric Association. (2013). In Diagnostic and statistical manual of mental disorders (5th ed.).
  2. Burrow JP, Spurling BC, Marwaha R. Catatonia. Treasure Island (FL): StatPearls Publishing; 2021 Jan. Available from: https://www.ncbi.nlm.nih.giv/books/NBK430842
  3. Fink M and Taylor MA. Catatonia: a clinician’s guide to diagnosis and treatment, Cambridge University Press, Cambridge, UK 2003.
  4. Fink M and Taylor MA. The catatonia syndrome: forgotten but not gone. JAMA Psychiatry. 2009;66(11):1173-1177. doi:10.1001/archgenpsychiatry.2009.141
  5. Lee JW. Neuroleptic-induced catatonia: clinical presentation, response to benzodiazepines, and relationship to neuroleptic malignant syndrome. J Clin Psychopharmacol 2010;30(1):3. doi:10.10.1097/JCP.0b013e3181c9bfe6
  6. Northoff G. Brain imaging in catatonia: current findings and a pathophysiologic model. CNS Spectr 2000; 5:34.
  7. Northoff G. What catatonia can tell us about “top-down modulation”: a neuropsychiatric hypothesis. Behav Brain Sci 2002; 25:555.
  8. Taylor MA and Fink M. Catatonia in psychiatric classification: a home of its own. AM J Psychiatry. 2003;160(7):1223.