Clinical characteristics, management, and prognosis of non-neoplastic central neurogenic hyperventilation: a retrospective analysis based on case reports

Background Central neurogenic hyperventilation (CNH) has conventionally been regarded as being associated predominantly with brainstem tumors, and its non-neoplastic etiologies have not been systematically summarized. Methods PubMed, EMBASE, and Web of Science were searched to identify case reports of non-neoplastic CNH fulfilling the diagnostic criteria. Data were extracted using a standardized form, and study quality was appraised using the Joanna Briggs Institute (JBI) critical appraisal checklist for case reports. Results A total of 22 articles were included, of which 14 were Grade A studies (22 patients) were assigned to the core analysis and 8 were Grade B studies (8 patients) served as a supplementary observation group. In the core analysis group, the median age was 54.5 years (range, 3–82 years) and 13 of 22 patients (59.1%) were male. The etiological spectrum included cerebrovascular disease (11/22, 50.0%), autoimmune/inflammatory disease (5/22, 22.7%), metabolic disease involving the central nervous system (3/22, 13.6%), iatrogenic factors (2/22, 9.1%), and toxic etiologies affecting the central nervous system (1/22, 4.5%). Eleven of the 22 patients (50.0%) died. Among them, 6/11 (54.5%) had diffuse brainstem lesions (4 cerebrovascular and 2 immune/inflammatory); 2/11 (18.2%) had secondary brainstem compression, including 1 case of right cerebral hemorrhage causing brainstem compression and 1 case of acute disseminated encephalomyelitis (ADEM) with brainstem compression due to extensive white matter edema; Another two (18.2%) had clinically presumed brainstem infarction and 1/11 (9.1%) had central pontine infarction. Among the deaths, 3/11 (27.3%) were immune/inflammatory-related (2 with failed immunotherapy and 1 who received no immunotherapy). Eleven of the 22 patients (50.0%) survived: among them, 2/11 (18.2%) had localized brainstem lesions, 3/11 (27.3%) had thalamic involvement without brainstem involvement, 4/11 (36.4%) had no definite structural lesion on imaging, and 2/11 (18.2%) had presumed brain injury in the absence of imaging data (1 carbon monoxide poisoning and 1 porphyria). Treatment was mainly etiology-directed and supportive. Among the 5 patients with autoimmune/inflammatory disease, 2/5 (40.0%) achieved complete remission (1 multiple sclerosis and 1 anti-NMDA receptor encephalitis). An additional 8 patients (from 8 Grade B studies) formed a supplementary observation group, with etiologies involving intracerebral hemorrhage, immune-mediated disease, histiocytosis, biopsy-confirmed cerebral inflammation, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS), and mitochondrial encephalopathy. Conclusion Non-neoplastic CNH has a broad etiological spectrum encompassing cerebrovascular, autoimmune/inflammatory, metabolic, iatrogenic, and toxic etiologies. Management is based on etiology-directed and supportive treatment; immunotherapy is effective in some patients with autoimmune/inflammatory disease, and centrally acting sedatives and anesthetics (e.g., benzodiazepines, propofol, ketamine, and opioids) may be considered for symptomatic control. The thalamus may participate in respiratory control. Diffuse brainstem lesions or secondary brainstem compression may be associated with poor prognosis. Early identification of treatable etiologies and timely treatment are key to improving outcomes.