Fulminant acute motor-sensory axonal neuropathy, a severe subtype of Guillain-Barré syndrome (GBS), may produce clinical manifestations resembling brain death despite preserved cerebral function. The findings highlighted the importance of distinguishing severe peripheral nerve dysfunction from irreversible loss of brain function in patients presenting with complete paralysis, respiratory failure, and absent brainstem reflexes.
In the retrospective study, investigators evaluated 2 patients with acute motor-sensory axonal neuropathy (AMSAN) who developed brain death-like manifestations at Yichang Central People's Hospital in China between 2016 and 2024. They also conducted a literature review using CNKI, Wanfang Data, and PubMed through June 2025, identifying 25 publications describing 28 adult patients with fulminant GBS and similar clinical presentations. The 2 newly reported patients were men aged 52 and 69 years.
The investigators examined clinical progression, electrophysiological characteristics, cerebrospinal fluid findings, treatment, and neurological recovery. Key assessments included nerve conduction studies, electroencephalography (EEG), duration of mechanical ventilation, return of spontaneous breathing, and functional outcomes. The literature review additionally evaluated the frequency of axonal involvement, autonomic dysfunction, and persistent neurological impairment.
Both newly reported patients developed rapidly progressive quadriplegia, respiratory failure, fixed pupils, and absent brainstem reflexes, creating clinical presentations resembling brain death. However, peripheral nerve conduction studies demonstrated severe motor and sensory axonal neuropathy, while cerebrospinal fluid findings supported the diagnosis of AMSAN. Both patients subsequently regained spontaneous breathing and were weaned from mechanical ventilation following different courses of immunotherapy and prolonged supportive care, although substantial neurological deficits persisted.
The first patient, aged 52 years, presented with progressive limb weakness, numbness, and dysphagia lasting 4 days. Within 5 hours of admission, he developed respiratory distress requiring invasive mechanical ventilation. By hospital day 4, he exhibited complete quadriplegia, fixed and nonreactive pupils, absent brainstem reflexes, and no spontaneous respiration. His Glasgow Coma Scale score was 3.
Following treatment with intravenous immunoglobulin (IVIG), the patient began following simple commands on hospital day 10 and regained limited spontaneous breathing by day 15. Extraocular movements returned to normal by day 23, and he was completely weaned from mechanical ventilation on day 42. Despite these improvements, substantial limb weakness persisted, requiring continued rehabilitation following transfer on hospital day 60.
The second patient, aged 69 years, developed progressive weakness and impaired consciousness following traumatic brain injury and neurosurgical intervention. He presented with complete quadriplegia, fixed pupils, absent corneal and pupillary reflexes, and respiratory failure, initially raising concern for brain death associated with intracranial injury. However, bedside EEG performed on hospital day 4 demonstrated preserved wake–sleep cycling, an alpha rhythm of approximately 8 Hz during wakefulness, and suppression of alpha activity with passive eye opening, indicating preserved cortical function despite the absence of clinically detectable brainstem reflexes.
The patient initially received IVIG at 0.4 g/kg daily for 5 days without obvious improvement. Plasma exchange was subsequently initiated on hospital day 26, with 3 sessions performed on alternate days. Spontaneous breathing emerged following plasma exchange, and the patient was completely weaned from mechanical ventilation by day 55. At discharge on hospital day 72, muscle strength remained markedly reduced, with a grade of 3 in the left upper limb and 1 in the right upper limb and both lower limbs.
The literature review demonstrated that brain death-like manifestations in fulminant GBS were associated with rapid neurological deterioration and prolonged respiratory support. Among the 28 previously reported patients, 20 were male and 8 were female, with a mean age of approximately 50 years. The mean interval from symptom onset to brain death-like manifestations was 5.4 days, while the mean interval to tracheal intubation was approximately 3 days.
All 28 patients required invasive mechanical ventilation, with a reported mean duration of approximately 111 days. Most underwent tracheostomy, and autonomic dysfunction, including fluctuating blood pressure, tachycardia, and diaphoresis, was frequently reported. Two patients died, representing 7.1% of the reviewed cases.
Electrophysiological abnormalities were prominent among patients with this severe presentation. Of the 25 patients with available nerve conduction data, 17 demonstrated absent sensory and/or motor responses. The authors identified axonal involvement as a common feature and suggested that early absence of nerve conduction responses may be associated with prolonged recovery and persistent neurological impairment.
Among the 25 patients who underwent EEG following the loss of brainstem reflexes, 10 demonstrated alpha or theta activity reactive to external stimuli. These findings supported the presence of preserved cerebral activity in some patients despite profound peripheral paralysis and absent clinically detectable brainstem responses. The investigators emphasized the diagnostic value of EEG alongside peripheral nerve conduction studies and cerebrospinal fluid analysis.
Neurological recovery was frequently prolonged and incomplete. In 2 previously reported cases, mechanical ventilation continued for 300 days. One patient with a demyelinating electrophysiological pattern regained the ability to walk with a cane after 2 years, whereas another patient with absent early sensory and motor responses remained severely quadriparetic and unable to stand after 2.5 years. Early electrophysiological abnormalities may help identify patients at risk for prolonged disability, although further investigation is needed.
Treatment approaches varied across the published cases. IVIG and plasma exchange were commonly administered, sometimes alongside additional immunomodulatory therapies. The authors discussed reports of intensified treatment strategies, including corticosteroids and immunosuppressive agents, but emphasized that available evidence was insufficient to establish whether these approaches improved outcomes. They also noted preliminary reports involving efgartigimod in refractory GBS while underscoring the need for prospective studies.
The study had several limitations. The 2 newly reported cases were retrospectively evaluated at a single center, and EEG was unavailable during the acute presentation of the first patient. Serum antiganglioside antibody testing was not performed in either case, while comprehensive viral and autoimmune testing was unavailable in the second. Additionally, the literature review relied on heterogeneous case reports with variable diagnostic assessments, treatment approaches, and follow-up durations, limiting comparisons and conclusions about prognosis or treatment effectiveness.
The findings suggested that fulminant AMSAN should be considered in the differential diagnosis of patients with rapidly progressive paralysis and brain death-like manifestations. EEG, nerve conduction studies, and cerebrospinal fluid analysis may help distinguish severe peripheral neurological dysfunction from irreversible loss of brain function. Although neurological recovery was possible, prolonged mechanical ventilation and persistent motor deficits remained important features of the reported clinical courses.
"Early absent motor and sensory responses were frequently observed among patients with prolonged recovery and may represent a marker of severe disease," wrote lead study author Ling Zhong, of the Department of Neurology at the Affiliated Renhe Hospital of China Three Gorges University, and colleagues.
Disclosures: The authors declared no competing interests.
Source: BMC Neurology