Challenges in managing prolonged intensive care unit stay for Guillain–Barré syndrome–acute motor axonal neuropathy variant

Abstract

Guillain–Barré syndrome is a clinical syndrome manifesting as immune-mediated polyneuropathy. Approximately one-third of affected patients develop respiratory failure, necessitating intensive care unit admission and invasive mechanical ventilation. Multiple factors present at the onset and during intensive care unit stay are established predictors of the requirement for invasive mechanical ventilation. These include the rapid progression of motor weakness, concurrent involvement of peripheral limb and axial muscles, ineffective cough, bulbar muscle weakness, and the decline in rapid vital capacity. However, no reliable criteria currently exist to predict the duration of muscle weakness progression and plateau phases or the time to recovery. We herein report a case of a 55-year-old male admitted to the intensive care unit following a 5-day history of progressive ascending generalized weakness. His condition progressed to quadriplegia, diaphragmatic paralysis, and autonomic dysfunction. A diagnosis of Guillain–Barré syndrome–acute motor axonal neuropathy variant was confirmed via neurological examination, imaging, cerebrospinal fluid analysis, and nerve conduction studies. The patient exhibited no clinical improvement following two courses of five sessions each of plasma exchange and intravenous immunoglobulin. Owing to the refractory nature of his condition, he required more than 5 months of step-down intensive care unit care prior to transfer to a general medical ward and subsequent discharge home on hospital day 182.

Introduction

Polio has been almost eradicated globally, leaving Guillain–Barré syndrome (GBS) as the most common cause of acute flaccid paralysis, that is, triggered by a preceding respiratory or gastrointestinal infection. ¹ The annual incidence rate ranges from 0.8 to 1.9/100,000, with males being slightly more affected than females, and the incidence increases with age to 2.7/100,000 in older individuals above 80 years. ² Multiple clinical variants of GBS have been identified. Acute motor axonal neuropathy (AMAN) is one of these, which is distinguished by selective involvement of motor nerves and axonal involvement with sensory sparing in electrophysiological studies. In about 30% of cases, patients experience respiratory failure requiring intensive care and invasive mechanical ventilation (MV). ³ The weakness of the diaphragm is thought to be caused by phrenic nerve demyelination. Currently, there are no criteria that reliably predict the duration of the progression and plateau phases of muscle weakness, the time to recovery, or whether and when MV may be required. In one study, rapid disease progression with quadriplegia within 2–5 days was identified as a risk factor for MV, with a mean duration of more than 49 days and a need for a tracheostomy in 32% of patients. ⁴

This case report aims to emphasize the understanding of the clinical progression of GBS–AMAN heterogeneity to promote early and correct diagnosis, as well as interprofessional team management. It emphasizes that patients with these conditions should not be disregarded, as complete recovery remains achievable.

Case presentation

A 55-year-old Saudi male, who is working as a school teacher with a history of a stable course of sickle cell disease and hepatitis C virus (HCV), received the flu and two doses of SARS–CoV-2 vaccine 2 months before admission. He presented to the emergency department at Qatif Central Hospital, Eastern Province, Saudi Arabia, with progressive bilateral upper and lower limb weakness for 5 days preceded by a history of flu-like symptoms. On examination, he was conscious and oriented with stable vital signs with no signs of respiratory distress. Cranial nerves examination revealed no extraocular muscle abnormality, normal pupils, no facial asymmetry, normal gag and cough reflex, no bulbar, or pseudo bulbar palsy. Muscle power shows 3/5 for both upper and lower limbs with diffuse hypotonia. Hyporeflexia was observed in ankle and knee jerks, while areflexia was observed in biceps, triceps brachioradialis, and downgoing plantar reflexes. Also, he had hyperesthesia in all four limbs without a sensory level defect. Laboratory tests showed WBC: 3.8 (leukopenia), Hgb: 7.5 (chronic anemia), platelets: 112, with normal LDH: 51, and a metabolic panel. Autoimmune profile: ANA +4 coarse speckled, while other antibodies (anti-Dsdna, anti-SM, anti-RO, anti-LA, ANCA, lupus anticoagulants) were all negative. Cerebrospinal fluid (CSF) examination showed an albuminocytologic dissociation pattern (CSF pressure was normal, CSF cell count nil, CSF protein 350 mg/dl, and CSF sugar normal). The initial electromyography (EMG) and nerve conduction studies (NCS) were interpreted as showing features of early axonal neuropathy. A repeated EMG/NCS performed 8 weeks later provided clear evidence consistent with AMAN, as summarized in Tables 1 and 2. A brain and spine MRI showed normal findings, with no involvement of cauda equina. Based on the aforementioned clinical, laboratory, radiological, and EMG findings, along with the progression of muscle weakness, a diagnosis of AMAN variant of GBS was confirmed.

Table 1.

Motor nerve conduction studies at week 1.

Nerve	Lat (ms)	Amp (mV)	Area (ms × mV)	CV (m/s)	F-M Lat (ms)	F Lat (ms)
Medianus motor right
Wrist—APB	3.87	5.2	15.2		30.1	33.7
Elbow–wrist	8.80	4.7	12.1	48.7
Ulnaris motor right
Wrist—ADM	2.93	4.1	15.2		32.3	35.2
BI. elbow–wrist	8.10	2.7	8.7	42.6
Elbow–Bl. elbow	9.58	2.8	9.7	50.7
Peroneus motor left
Ankle—EDB	3.95	1.11	3.3		56.1	60.0
BI. knee–ankle	13.3	0.67	1.28	35.3
Ab. knee–Bl. knee	14.6	0.70	1.36	46.2
Peroneus motor right
Ankle—EDB	4.46	1.35	2.9		50.6	55.2
BI. knee–ankle	13.2	1.09	2.4	35.5
Ab. knee–Bl. knee	14.8	1.01	2.1	50.0
Tibialis motor left
Med. mal—Abd hal	5.27	4.2	8.9		55.5	57.1
Pop fossa–Med. mal	13.6	3.8	8.1	42.0
Tibialis motor right
Med. mal—Abd hal	5.09	1.89	5.1		50.0	55.3
Pop fossa–Med. mal	14.4	1.11	3.2	36.5
Sensory nerve conduction studies
Nerve	Peak Lat (ms)	Amp (µV)	CV (m/s)
Medianus sensory right
Wrist—Dig II	–	–
Ulnaris sensory right
Wrist—Dig V	3.10	8.0	45.9
Suralis sensory left
Mid. lower leg—Ext saph	–	–
Suralis sensory right
Mid. lower leg—Ext saph	–	–

Abd hal: abductor hallucis muscle; Ab: above; ADM: abductor digiti minimi muscle; APB: abductor pollicis brevis muscle; BI: bilateral; CV: conduction velocity; Dig: digit; EDB: extensor digitorum brevis muscle; Ext saph: external saphenous (sural) nerve; Med. mal: medial malleolus; ms: milliseconds; mV: milli volt; Pop fossa: popliteal fossa.

Mixed axonal–demyelinating polyneuropathy with severe involvement (both motor and sensory).

Table 2.

Motor nerve conduction studies at week 8.

Nerve	Lat (ms)	Amp (mV)	Area (ms × mV)	CV (m/s)	F-M Lat (ms)	F Lat (ms)
Medianus motor right
Wrist—APB	5.03	0.91	2.7		36.7	41.7
Elbow—wrist	12.0	0.52	1.58	38.7
Ulnaris motor right
Wrist—ADM	3.11	0.58	2.6		39.5	42.6
BI. elbow—wrist	11.0	0.53	1.31	34.2
Ab. elbow—Bl. elbow	12.9	0.50	1.28	52.6
Peroneus motor left
Ankle—EDB	3.53	0.89	2.3		52.6	56.1
BI. knee—ankle	11.4	0.59	1.35	40.0
Ab. knee—Bl. knee	12.8	0.52	1.16	46.4
Peroneus motor right
Ankle—EDB	3.59	0.79	1.82		57.4	61.0
BI. knee—ankle	11.6	0.69	1.85	40.0
Ab. knee—Bl. knee	13.4	0.77	2.3	50.0
Tibialis motor left
Med. mal—Abd hal	5.57	1.65	11.0		54.4	60.0
Pop fossa—Med. mal	15.0	0.83	2.7	41.4
Tibialis motor right
Med. mal—Abd hal	5.33	1.72	5.8		55.7	61.0
Pop fossa—Med. mal	14.4	0.90	2.0	41.9
Sensory nerve conduction studies
Nerve	Peak Lat (ms)	Amp (µV)	CV (m/s)
Medianus sensory right
Wrist—Dig II	3.63	28.8	51.3
Ulnaris sensory right
Wrist—Dig V	3.02	21.1	54.5
Suralis sensory left
Mid. lower leg—Ext saph	3.42	6.4	48.8
Suralis sensory right
Mid. lower leg—Ext saph	3.62	8.0	49.3
Superficial peroneal sensory left
Lateral malleolous—ankle	3.27	6.5	40.7
Superficial peroneal sensory right
Lateral malleolous—ankle	3.05	6.6	44.8

Abd hal: abductor hallucis muscle; Ab: above; ADM: abductor digiti minimi muscle; AMAN: axonal motor neuropathy; APB: abductor pollicis brevis muscle; BI: bilateral; CV: conduction velocity; Dig: digit; EDB: extensor digitorum brevis muscle; Ext saph: external saphenous (sural) nerve; Med. mal: medial malleolus; ms: milliseconds; mV: milli volt; Pop fossa: popliteal fossa.

Sensory responses recovered, motor nerves still show axonal loss, which is consistent with AMAN in the recovery phase.

Intensive care unit course/therapeutic intervention/procedure/follow-up and outcome

The patient was admitted to the medical ward with a diagnosis of GBS–AMAN, and then transferred to the intensive care unit (ICU) for further monitoring. Initially, he was commenced on five sessions of plasmapheresis followed by intravenous immunoglobulin (IVIG), but with no improvement. His weakness progressed to quadriplegia, and he started to show signs of respiratory failure and aspiration. He was intubated and placed on a mechanical ventilator on day 23. He was tracheostomized on day 44.

A daily spontaneous breathing trial (SBT) was attempted, but failed because the patient’s diaphragm was paralyzed and unable to trigger spontaneous breathing. Thus, a decision was made to start a second course of plasmapheresis, and IVIG therapy was started. Despite this intervention, no significant neurological improvement was observed. Consequently, the patient was shifted to the step-down ICU and subjected to intensive limb physiotherapy sessions. He was put on synchronized intermittent mandatory ventilation mode, minimal settings, with daily SBT until he demonstrated the ability to take his first spontaneous breath on day 95. He was shifted to pressure support mode on day 129. Upon being placed on theromovent room air on day 146, he showed improvement in his upper and lower limb weakness, bulbar function, and swallowing capabilities.

The rehabilitation program was divided into two phases according to the patient’s clinical status and prolonged hospitalization. Phase I: during the 5-month ICU stay, therapy focused on maintaining joint mobility and preventing complications. Initially, the patient required active-assisted limb exercises (twice daily, 30 repetitions divided into three sets). Following a clinical setback, passive physiotherapy was provided, with all movements performed by the physiotherapist until muscle strength gradually returned. Phase II: during the subsequent 1-month inpatient stay, rehabilitation progressed to active exercises and resistance training using therapeutic elastic bands, starting with low resistance and gradually increasing as tolerated. Functional training was introduced, including bed mobility (rolling), sitting tolerance (from 1 to 15 min), standing, and ambulation. At discharge, the patient advanced from walking with a Zimmer walker to ambulating with a single cane. The patient was followed for 6 months after discharge in our outpatient neurology and physiotherapy clinics. At the 3-month visit, he showed substantial improvement in motor strength, ambulating independently with a single cane and exhibiting full resolution of autonomic instability. At 6 months, he was able to walk without assistive devices for short distances and had regained independence in performing daily activities.

During his extended stay on step-down ICU, he had multiple episodes of autonomic dysfunction (frequently managed with atropine, dopamine, noradrenaline, beta blockers, and antihypertensive medications), depression (managed with aripiprazole, amitriptyline, prolonged family visiting time), and lower limb hyperesthesia (managed with carbamazepine).

He was transferred to the medical ward on day 158. After his tracheostomy was closed on day 179, he was discharged on day 182, walking with assistance, and he was advised to continue physical rehabilitation in outpatient clinics.

Discussion and literature review

Several studies indicated that GBS patients requiring MV during the acute phase exhibit poor clinical outcomes. About 27% of GBS patients required MV for a median of 28 days, ⁵ and the mortality rate for those required MV was reported to be up to 13%.^6–8 ICU complications are frequently associated with prolonged ventilation, concomitant medical conditions, or advanced age. GBS patients are more likely to survive the acute phase of the disease in comparison to other neurological ICU patients with, for example, cerebral ischemia, subarachnoid hemorrhage, or intracerebral hemorrhage. ⁹ The implementation of neuro-ICUs and new promising treatment options during the past decades would lead to a reduction in ventilated GBS mortality. ⁸

Autonomic dysfunction with variable manifestations affects nearly 65% of patients with GBS, including brady- or tachy-arrhythmias, orthostatic hypotension, episodic hypertension, abnormal hemodynamic responses to vasoactive drugs, gastrointestinal dysfunction, and sweating abnormalities. In the same patient, over- and undersigns of autonomic activity may concur or alternate. Death in GBS patients or the necessity for pacemaker placement were attributed to episodic bradycardia, sinus arrest, and asystole. These arrhythmias could occur spontaneously and could also be triggered by tracheal suction or other vagotonic stimulation. ¹⁰ Caution should be used in tracheal suctioning, with ready access to atropine and external pacing devices. Atropine and external pacing devices should be ready to use while undergoing tracheal suctioning, which should be performed with caution. Paroxysmal hypertension, when it happens, rarely requires treatment and is generally short-lived. Rapidly titratable, short-acting medications should be used to avoid hypotension when fluctuations are severe enough to cause end-organ damage. It should be kept in consideration that emergency intubation may trigger cardiovascular dysautonomia, which may precipitate death.^11,12 Constipation, gastric immobility, and ileus result from gastrointestinal autonomic dysfunction. Studies have shown ileus in up to 15% of patients with GBS requiring ICU care, and medical management was successful in all patients. ¹³

Pain is a common but often overlooked feature of GBS, occurring in 55% of patients. ¹⁴ It precedes the development of weakness and persists long after recovery. The proposed mechanisms include inflammation of proximal nerve roots, sensory nerve fiber dysfunction during degeneration or regeneration, and musculoskeletal pain due to immobility. Opiates have a reliable analgesic effect, but sedation and potential ileus may limit their use. Data on non-opiate pharmacological interventions are limited, but one study suggested that gabapentin or carbamazepine may reduce pain and lower narcotic requirements in some patients. ¹⁵

As most of these types of patients experience the dramatic loss of independence, prolonged hospitalization, and may even lose communication, they will produce several psychiatric complications. For example, anxiety occurs in 82% of patients, with moderate to severe depression occurring in 67%. Healthcare providers should precisely inquire about symptoms of anxiety or depression for early detection and treatment. Selective serotonin reuptake inhibitors, anxiolytics, and continuous psychosocial support are often beneficial.^16,17

There is a lack of sufficient comparisons between IVIG and placebo in adults. A meta-analysis study found no difference between IVIG and plasma exchange in terms of mortality, improvement at 4 weeks, residual disability, or time on MV. ¹⁸ Another study found that IVIG added after plasma exchange offered a small, insignificant benefit over IVIG alone. ¹⁹ The mechanism by which IVIG exerts its beneficial effect in GBS is not firmly established, but it may result from neutralization of autoantibodies or cytokines, saturation of macrophage Fc receptors, or inhibition of complement activation. ²⁰

Respiratory failure is one of the most common and deadly complications of GBS. The mortality rate in GBS surpassed the level of 30% prior to MV, mostly due to respiratory failure. The percentage of patients with GBS eventually requiring MV ranges from 25% to 44%. ¹¹ Phrenic and intercostal nerve demyelination produce restrictive lung mechanics, while bulbar muscle weakness may prevent adequate airway protection and place patients at risk of aspiration. Respiratory failure can occur abruptly in patients with GBS and should be carefully and frequently monitored. Since hypoxemia and hypercarbia are late symptoms of respiratory failure, pulse oximetry and blood gases are often insufficient for early detection. Continual monitoring of vital capacity, maximal inspiratory pressure (MIP or PI_max), and maximal expiratory pressure (MEP or PE_max) should be performed at the bedside. Elective intubation should be performed when the vital capacity falls below 15 mL/kg or the MIP and MEP have reached −25 and 40 cm H₂O, respectively.^11,21

Recovery of independent breathing can be slow in GBS, as in the case for this patient, resulting in prolonged periods of MV, and the optimal time for performing a tracheostomy is not known. ²² Early tracheostomy may be unnecessary in patients who experience prompt improvement, allowing rapid successful extubation, and late tracheostomy may increase the rate of complications associated with the tracheal tube, such as tracheal stenosis or tracheomalacia. When prolonged ventilatory support is needed, a tracheostomy is often considered after 3 weeks. Tracheostomy is needed in patients with factors that predict prolonged ventilatory assistance or weaning problems, namely, older age or underlying pulmonary disease. ²³

Although the initial NCS demonstrated findings that could be interpreted as demyelination or early axonal neuropathy, subsequent clinical correlation and electrophysiological features were more compatible with the AMAN subtype. It is important to emphasize that AMAN may present with reversible conduction block, which can mimic demyelinating features in early studies. Repeated electrophysiological assessments are therefore recommended to avoid misclassification and to confirm axonal involvement. This diagnostic complexity highlights the challenges clinicians face when distinguishing AMAN from acute inflammatory demyelinating polyradiculoneuropathy (AIDP), especially in the acute phase.^24,25

The patient showed no neurological improvement after receiving standard first-line therapies, including plasma exchange followed by IVIG. Several factors might have contributed to this poor response. First, the AMAN variant itself has been associated with slow and sometimes incomplete recovery compared to AIDP. Second, the coexistence of chronic conditions such as sickle cell disease and HCV infection may have negatively influenced immune-mediated repair mechanisms or exacerbated systemic complications. Finally, individual heterogeneity in treatment response is well documented, and in some cases, no clear predisposing factor can be identified. ²⁶

Despite limited evidence supporting the benefit of repeated immunotherapy in non-responders, the decision to initiate a second course was made due to the patient’s ongoing critical deterioration and prolonged respiratory failure. This highlights a real-world clinical dilemma, where physicians must weigh the risks of additional therapy against the potential for recovery in a severely disabled but potentially reversible condition. Such decisions should ideally be individualized and made within a multidisciplinary team.

Critical illness polyneuropathy (CIP) was considered an important differential diagnosis given the patient’s prolonged ICU stay and need for MV. However, several clinical and paraclinical features argue strongly against CIP as the primary cause of weakness in this case. First, the patient developed progressive ascending limb weakness 5 days prior to ICU admission, with neurological deficits clearly established before exposure to prolonged critical illness or MV. This temporal pattern is characteristic of GBS and contrasts with CIP, which typically develops after days to weeks of severe critical illness. Second, serial electrophysiological studies supported the diagnosis of AMAN. While early NCS showed axonal features, repeat studies at week 8 demonstrated recovery of sensory nerve action potentials with persistent motor axonal involvement, a pattern consistent with AMAN in the recovery phase. By contrast, CIP usually presents with diffuse and persistent axonal involvement of both the motor and sensory nerves. Third, CSF analysis revealed marked albuminocytologic dissociation (elevated protein with normal cell count), a hallmark of GBS. CIP is not associated with CSF abnormalities, further arguing against this diagnosis. Finally, the distinction between CIP and AMAN has important prognostic and therapeutic implications. Weakness related to CIP often improves with resolution of the underlying critical illness and supportive care alone, whereas AMAN represents an immune-mediated neuropathy that may require immunotherapy and prolonged rehabilitation. Taken together, the clinical timeline, CSF findings, and serial electrophysiological evolution support AMAN as the primary cause of this patient’s prolonged neuromuscular weakness rather than ICU-acquired polyneuropathy.^27,28

Additional diagnostic considerations such as muscle ultrasound or inflammatory markers (e.g., CRP, IL-6) can support differentiation between CIP and AMAN. However, these were not pursued in this case, as the clinical timeline, CSF profile, and serial electrophysiological findings were considered diagnostic.

This case further illustrates that patients with severe AMAN may require exceptionally long periods of ventilatory support and rehabilitation before achieving functional recovery. While the prolonged ICU stay is often associated with complications, careful multidisciplinary management, including intense monitoring of autonomic instability, early psychiatric and physiotherapy interventions, and family involvement, may ultimately contribute to favorable long-term outcomes.

Conclusion

As there are multiple clinical variants of GBS, including AMAN, timely diagnosis is critical. This case highlights the clinical challenges of diagnosing and managing the AMAN variant of GBS. The physician should consider early ICU admission and intubation based on neurological and respiratory deterioration. Early electrophysiological findings may mimic demyelination, underscoring the importance of repeated NCS and careful clinical correlation to establish the correct subtype. The patient’s lack of response to first-line therapy with plasma exchange and IVIG illustrates the variability in treatment outcomes and the need for individualized decision-making. Although repeated courses of immunotherapy remain controversial, in this case, they were pursued due to persistent deterioration and the potential for meaningful recovery.

Prolonged ICU stay in patients with severe AMAN requires meticulous multidisciplinary care, including vigilant management of autonomic dysfunction, early psychiatric and physiotherapy support, and family involvement. Despite the extended critical illness, recovery is possible, and this case demonstrates that even patients requiring months of ventilatory support may achieve functional independence. Physicians should therefore maintain an active and sustained approach to supportive management, with the recognition that long-term outcomes can still be favorable.