Malignant catatonia with systemic inflammation: diagnostic and therapeutic challenges in differentiating NMS and neurosarcoidosis

Background

Malignant catatonia, neuroleptic malignant syndrome (NMS), and neurosarcoidosis may present with overlapping neuropsychiatric and autonomic features in systemic inflammatory diseases. This overlap may lead to diagnostic uncertainty and complicate clinical decision-making, requiring a structured multidisciplinary approach.

Case Presentation

A 57-year-old female with a 20-year history of pulmonary sarcoidosis and 30-year history of bipolar disorder was admitted with one month of progressive neuropsychiatric deterioration, including insomnia, reduced oral intake, functional decline, 10 kg weight loss, disorganized behavior, and paranoid ideation. Despite outpatient psychotropic adjustments, deterioration continued.

On admission, she exhibited stupor, mutism, negativism, posturing, waxy flexibility, and catalepsy, fulfilling six DSM-5 [1] catatonia criteria with a BFCRS [2] score of 27. Autonomic instability included hyperthermia (39°C), diaphoresis, bradycardia, and labile blood pressure. Early hospitalization was complicated by oxygen desaturation attributed to severe catatonia (GCS: E2V2M3) and also pulmonary sarcoidozis.

Due to ocular sarcoidosis with risk of vision loss in her only functional eye, electroconvulsive therapy (ECT) was initially deferred. After multidisciplinary evaluation, ECT was considered necessary due to life-threatening clinical deterioration.

Results

A structured stepwise diagnostic approach was applied.

Catatonia was confirmed based on DSM-5 criteria and BFCRS scoring.

NMS was evaluated in the context of recent antipsychotic exposure and autonomic instability. However, only mildly elevated creatine kinase levels (137–206 U/L), absence of sustained rigidity, and predominance of catatonic features argued against this diagnosis.

Neurosarcoidosis was considered given systemic sarcoidosis and persistent inflammatory markers. Brain and spinal MRI showed no granulomatous lesions or contrast enhancement, and cerebrospinal fluid analysis revealed isolated protein elevation without pleocytosis, making active CNS involvement unlikely.

Infectious etiologies were systematically excluded through repeated negative blood and urine cultures and cerebrospinal fluid analysis.

Following this stepwise exclusion, the clinical presentation was considered most consistent with malignant catatonia.

Despite this, persistent inflammatory activity and underlying systemic disease prevented complete exclusion of an immune-mediated contribution. Based on this residual uncertainty, history of sarcoidosis-related organ involvement, and emerging respiratory deterioration, azathioprine was initiated by the rheumatology team within a multidisciplinary framework.

A lorazepam trial showed no response. Given life-threatening deterioration, ECT was initiated [3] despite ophthalmologic risk, with four sessions completed without acute complications.

Azathioprine was continued alongside ECT as a parallel strategy. After one week of azathioprine and two ECT sessions, the patient developed pancytopenia, leading to discontinuation of azathioprine. Five days later, septic shock and subsequently disseminated intravascular coagulation occurred.

Conclusions

This case illustrates the diagnostic complexity of malignant catatonia in systemic inflammatory disease, where overlapping psychiatric and immunological features may obscure the primary pathology. A stepwise differential diagnostic approach, including systematic exclusion of NMS, neurosarcoidosis, and infectious causes, supported malignant catatonia as the primary diagnosis.

However, persistent inflammatory findings and systemic disease context necessitated consideration of parallel pathophysiological processes. Management therefore required continuous reassessment and multidisciplinary decision-making under conditions of diagnostic uncertainty.

This case underscores the importance of integrating psychiatric urgency with systemic disease considerations and demonstrates how therapeutic decisions made under uncertainty may carry significant and sometimes unforeseen risks, highlighting the need for careful risk–benefit evaluation in complex neuropsychiatric presentations.

Informed consent was obtained from patient’s relatives.

References

1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed, Text Revision (DSM-5-TR). Washington, DC: American Psychiatric Publishing; 2022.
2. Bush G, Fink M, Petrides G, Dowling F, Francis A. Catatonia I: Rating scale and standardized examination. Acta Psychiatr Scand. 1996;93(2):129–136.
3. Taylor D, Barnes TRE, Young AH. The Maudsley Prescribing Guidelines in Psychiatry. 15th ed. Wiley-Blackwell; 2023.