Quadriplegia after ECMO therapy with sluggish recovery in a COVID‐19 patient: A case report with a 14‐month follow‐up

Abstract

COVID‐19 patients often develop neuromuscular complications, and critically ill patients often develop ICU‐acquired weakness. We report a COVID‐19 patient who developed flaccid quadriplegia after ECMO therapy and achieved a slow but consistent recovery during a 14‐month period of sustained holistic rehabilitation including early mobilization to an outdoor environment.

A severe case of COVID‐19 developed serious ICU‐acquired weakness manifesting as flaccid quadriplegia. Holistic intervention including early out‐of‐door mobilization contributed to his and his caretakers' motivation for undergoing the long‐term physical therapy required for rehabilitation.

1. INTRODUCTION

Patients with coronavirus disease 2019 (COVID‐19) are at risk of developing neuromuscular complications involving the central and peripheral nervous systems as well as the muscles themselves. Manifestations in the central nervous system include headache, dizziness, anosmia, ageusia/hypogeusia, stroke, epilepsy, and encephalopathy. ¹ , ² , ³ Peripheral nervous system and/or muscular involvements include Guillain–Barre syndrome (GBS), ⁴ , ⁵ , ⁶ polyneuropathy, ⁷ mononeuritis multiplex, ⁸ myopathy, and opthalmoparesis. ¹ , ² , ³

Also, critically ill patients who require mechanical ventilation or other intensive treatments often develop ICU‐acquired weakness (ICU‐AW) due to critical illness polyneuropathy and/or myopathy. ⁹ , ¹⁰ Therefore, COVID‐19 patients in critical conditions treated in ICUs are likely to suffer gravely from the debilitating impacts of both neuromuscular damages from SARS‐CoV‐2 infection and ICU‐AW. ¹¹ , ¹² , ¹³ , ¹⁴

We herein present a case in which the patient developed flaccid quadriplegia persisting for more than 2 months after treatment by extracorporeal membrane oxygenation (ECMO) due to severe acute respiratory distress syndrome (ARDS) caused by COVID‐19, and who was discharged home after vigorous and sustained holistic rehabilitation.

2. CASE REPORT

A previously healthy 46‐year‐old man (174 cm, 111 kg, BMI 36.7) was admitted to our hospital with a high fever that lasted for 3 days. He had shortness of breath with an SpO₂ of 95% on room air. His body temperature was 38.5 degrees Celsius. He tested positive for the SARS‐CoV‐2. The patient's chest CT revealed small ground‐glass shadows beneath the pleura. Administration of supplemental oxygen and dexamethasone was started. His condition remained unchanged until Day 7, when his respiratory condition deteriorated rapidly with an SpO₂ level of 90 on 10 L of oxygen. A chest X‐ray showed significant bilateral shadows, indicating severe ARDS. The patient was transferred to a tertiary hospital for possible ECMO implementation. In the tertiary hospital, the patient's CT images showed extensive bilateral ground‐glass opacity with some infiltration shadows. He was intubated, and mechanical ventilation was commenced. High‐dose corticosteroid pulse therapy (1 g methylprednisolone per day for 3 consecutive days) was administered twice, followed by 80 mg of methylprednisolone tapered to 2 mg of prednisolone iv administration for 80 days in total. The patient underwent ECMO for 15 days and continuous renal replacement therapy due to acute kidney injury (AKI) for 21 days. He also suffered from complications of Candida sepsis and cytomegalovirus enteritis.

On Day 71, he was transferred back to our hospital. He was fully alert. However, he presented with flaccid quadriplegia, a Medical Research Council (MRC) score of 18 out of 60, and significantly decreased rectal sphincter tone, as though he was completely paralyzed below the neck. He was being mechanically ventilated through a tracheostomy tube and was hemodynamically stable but had severe diarrhea due to the cytomegalovirus enteritis. His AKI remained (blood urea nitrogen level of 94 mg/dL, serum creatinine level of 2.4 mg/dL), but renal replacement therapy was no longer required. Vigorous and holistic rehabilitation interventions were implemented, including passive range‐of‐motion exercises, occupational therapy, and speech and swallowing exercises. We took him to the outdoor garden in a wheelchair with a ventilator accompanied by his family members and gave him baths, as mobilization activities with the intent to provide not only physical exercise but also cognitive stimulation and mental (motivational) care. Tilting training was added once he became able to support his torso. Psychological interventions were also applied by a clinical psychologist. His spinal magnetic resonance imaging (MRI) showed no abnormalities. Nerve conduction studies revealed profoundly reduced compound motor action potentials in the tibial nerve and the peroneal nerve, reduced sensory nerve action potentials in the sural nerve, and almost normal nerve conduction velocity (Figure 1), indicating severe axonopathy. Anti‐ganglioside antibodies (anti‐GQ1b IgG antibody and anti‐GM1 IgG antibody) were all negative. He was weaned from the ventilator, and the tracheostomy tube was removed.

FIGURE 1.

Motor nerve conduction study and sensory nerve conduction study. (A) Tibial nerve: The CMAP amplitude was 0.60 mV on ankle stimulation and 0.64 mV on popliteal stimulation, both of which were extremely reduced. (NR >5 mV) The motor nerve conduction velocity was 39.0 m/s. (NR > 40 m/s) (B) Sural nerve: The SNAP amplitude was 2.7 μV. (NR > 10 μV) The sensory nerve conduction velocity was 45.8 m/s. (NR > 40 m/s) CMAP, compound motor action potential; SNAP, sensory nerve action potential; NR, normal range at our institution

He was discharged from the ICU on Day 85 with an MRC score of 27 and transferred to a rehab hospital on Day 130 with a Barthel index (BI) of 20 and an MRC score of 33, indicating persistent severe ICU‐AW. On Day 195, he returned to our hospital with an MRC score of 41 due to unrelated issue. Holistic rehabilitation was continued. Despite persisting bilateral foot drop, he became able to walk with the aid of an ankle orthotic device, and was discharged home on Day 229 with a BI of 85 and an MRC score of 44. He has returned to his job, starting from PC‐work at home to complete recovery of his previous workload within 6 months. Outpatient rehabilitation has been ongoing. His BI and MRC score have improved very slowly to 100 and 55, respectively, over 14 months. (Table 1) He can now walk steadily on his own without the ankle device, although foot dorsiflexion is still weak.

TABLE 1.

Slow improvements in muscle strength and Barthel index

Event			Previous hospital	Transfer to our hospital	ICU discharge	Transfer to a rehab hospital	Return to our hospital	Discharge home	Follow‐up	Follow‐up
Day of illness			28	71	85	130	195	229	275	433
MRC score			6	18	27	33	41	44	49	55
MMT	Deltoid	r	1	2	3	4	4	5	5	5
		l	1	1	2	3	3	4	4	5
	Biceps	r	1	2	3	4	4	4	5	5
		l	1	1	2	4	4	4	4	5
	FCR	r	1	2	4	4	5	5	5	5
		l	1	2	3	4	5	5	5	5
	Psoas	r	0	2	2	2	3	3	4	5
		l	0	1	2	2	3	3	4	4
	Quad	r	0	2	2	2	4	4	5	5
		l	0	1	2	2	4	4	5	5
	TA	r	0	1	1	1	1	1	1	2
		l	0	1	1	1	1	2	2	4
Grip Strength (kg)		r	0	0	5.6	9.5	14.3	15.5	17.2	25.2
		l	0	0	0	7.5	10.3	9.5	12	20.6
Barthel Index			0	0	5	20	35	85	85	100

Abbreviations: Biceps, biceps brachii; FCR, flexor carpi radialis; l, left; MMT, manual muscle testing; MRC, medical research counsel; Quad, quadriceps femoris; r, right; TA, tibialis anterior.

3. DISCUSSION

Patients with COVID‐19 have been shown to develop a wide range of neuromuscular manifestations involving the central and peripheral nervous systems and the muscles themselves. Neurological manifestations in the central nervous system include headache, dizziness, anosmia, ageusia/hypogeusia, stroke, epilepsy, encephalopathy, and altered mental status. ¹ , ² , ³ Peripheral nervous system manifestations include GBS, ⁴ , ⁵ , ⁶ polyneuropathy, ⁷ mononeuritis multiplex, ⁸ opthalmoparesis, ¹ and positioning nerve injury. ¹⁴ Muscular manifestations include myopathy, rhabdomyolysis, and myositis. ¹ , ² , ³ Meanwhile, critically ill patients who require mechanical ventilation or other intensive treatments often develop ICU‐AW caused by critical illness polyneuropathy (CIP), critical illness myopathy (CIM), or critical illness neuromyopathy (CINM). ⁹ , ¹⁰ This puts critically ill COVID‐19 patients at grave risk of developing neuromuscular complications.

To the best of our knowledge, this is the first report to describe a 14‐month recovery from flaccid quadriplegia due to COVID‐19 characterized by slow but consistent progress. Madia et al. reported acute flaccid quadriplegia in COVID‐19 patients. They considered that the etiology was myopathy, that is, CIM, based on the results of electrophysiological studies as well as the reversible nature of the muscle weakness. ¹⁵ Bagnato et al. reported a patient with an acute motor axonal neuropathy variant of GBS causing quadriplegia, who presented with persisting severe weakness in the lower limbs and only limited recovery in the upper limbs after 242 days of rehab hospital stay. ¹⁴

In the present case, the electrophysiological examination showed axonal damage in both the motor and the sensory nerves, implying possible CIP causing ICU‐AW. However, concomitant myopathy or CINM cannot be ruled out, as a muscle biopsy was not conducted. CIP, CIM, and CINM frequently occur in critically ill patients. CIM is associated with a more favorable prognosis ¹¹ , ¹⁶ with most patients recovering completely within 3–6 months, ¹⁷ while muscle weakness in CIP lasts for months to years, or ends up in incomplete recovery and compromised quality of life (QOL). ¹⁰ , ¹⁷ CIP has been shown to occur more often in COVID‐19 patients than in non‐COVID‐19 patients, ¹² , ¹³ , ¹⁶ although in general CIM occurs more often in an ICU setting. ¹¹ , ¹⁶

Also, the axonal variants of GBS, namely acute motor sensory axonal neuropathy, cannot be ruled out, as a cerebrospinal fluid test was not conducted. This appears less likely to be the case, given the facts that anti‐ganglioside antibodies were negative in this case, that a demyelinating pattern is common in GBS with COVID‐19, ² , ⁴ , ⁵ and that GBS often occurs earlier and then consequently leads to ICU admission. ³ , ⁷

The risk factors of ICU‐AW are systemic inflammation, prolonged mechanical ventilation, organ failures, immobility, hyperglycemia, female sex, older age, and parenteral nutrition. ⁹ , ¹⁰ , ¹⁸ The roles of corticosteroids and neuromuscular blocking agents are controversial. ⁹ , ¹⁰ , ¹¹ , ¹⁸ , ¹⁹ , ²⁰ Simultaneous administration of large amounts of a corticosteroid and neuromuscular blocking agent, along with profound systemic inflammation, prolonged mechanical ventilation, AKI, and immobility, appeared to be the plausible causes of severe ICU‐AW manifesting as flaccid quadriplegia in this case. In addition, the potentially neurotropic properties of SARS‐CoV‐2 may have played a substantial role in the debilitating neurological injury. ¹ , ² , ³

Regarding the prevention and management of ICU‐AW, risk factors should be avoided. Glucose levels need to be well managed. Also, mobilizing the patient and providing holistic rehab programs are crucial. Bagnato et al. reported rehabilitation and neuromuscular improvement during the post‐acute phase in 21 COVID‐19 patients. ¹⁴ Human interactions especially with family members in a pleasurable outdoor activity, as in this case, appear to be beneficial for cognitive stimulation, reorientation, a sense of normalcy, and reassurance to patients during their ICU stay, since contact isolation has been associated with depression and anxiety. ²¹ We have reported the safety of out‐of‐the‐ICU mobilization ²² and show evidence suggesting that out‐of‐the‐ICU activities contributed to this critically ill patient's psychological orientation and his family's motivation to undertake a long course of rehabilitation. Numerous reports have shown that subsequent post‐acute rehabilitation programs need to be established in a holistic and seamless manner to support COVID‐19 survivors. ⁷ , ¹⁴ , ²¹ , ²³ Not only physical but also mental and social approaches with a multidisciplinary team are essential for the survivors to return to their homes, improve their long‐term QOL, and regain meaningful lives.

4. CONCLUSION

We experienced a patient who developed flaccid quadriplegia after treatment by ECMO due to severe ARDS from COVID‐19. Possible factors that contributed to the neuromuscular impairment include severe inflammation, prolonged mechanical ventilation, AKI, immobilization, and the administration of large amounts of corticosteroids and a neuromuscular blocking agent, in addition to the neurotropic properties inherent to SARS‐CoV‐2. Physicians should be aware of this serious potential complication of COVID‐19 and provide sustained holistic rehabilitation services when necessary.

Patient's comment

“I was very surprised that I was taken to the outdoor garden on the day of returning to this hospital. But it was really refreshing, and I was encouraged by the realization that I could come outside. Seeing my family in the garden was also great. And taking a bath was really superb!”

Question: If you were to be hospitalized in the ICU again, would you want to go outdoors?

“Yes, I would!”

Wife's comment

I was relieved to see him doing well, and very glad that our daughter was able to see him outdoors despite the visiting ban due to the pandemic.

AUTHOR CONTRIBUTIONS

Nobuko Sasano: Conceptualization; investigation; writing – original draft; writing – review and editing. Masami Yasuda: Data curation; visualization. Gohei Yamada: Formal analysis; validation.

Funding Information:

None.

CONFLICT OF INTEREST

The authors declare that they have no competing interests.

CONSENT

Written informed consent was obtained from the patient for the publication of this case report. A copy of the written consent is available for review by the editor in chief of this journal.

Sasano N, Yasuda M, Yamada G. Quadriplegia after ECMO therapy with sluggish recovery in a COVID‐19 patient: A case report with a 14‐month follow‐up. Clin Case Rep. 2022;10:e06735. doi: 10.1002/ccr3.6735

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.