Journal of Translational Neurosciences

Keywords

AIDP; GBS; Sars-Cov-2; IVIG

This research did not receive any specific grant from funding agencies in the public, commercial, or non-profit sectors.

Introduction

Novel coronavirus (Covid-19) that emerged in Wuhan, China's Hubei province in 2019 is a single-stranded RNA virus, causing acute respiratory distress which enters the cell by fusion through the Angiotensin-converting enzyme 2 (ACE2) receptors.[2]

The common symptoms of the disease are fever, shortness of breath, cough and diarrhea, however the disease includes neurological symptoms such as headache, dizziness, myalgia or taste and smell disorders. Moreover, Covid-19-associated acute cerebrovascular disease, transverse myelitis, movement disorders, encephalitis, and seizures have also been reported [3,4]

Guillain–Barré syndrome (GBS) is an immune-mediated polyradiculoneuropathy with demyelination which is post-infectious., and affects peripheral nerves and roots occuring within 1-3 weeks. GBS is most frequently associated with campylobacter jejuni and other viral infections such as cytomegalovirus and Ebstein Barr virus and Zika Virus [5].

It shows a symmetrical involvement from distal to proximal in which the most important cause of death is respiratory failure and serious arrhythmias due to autonomic nerve involvement [6]. Acute inflammatory demyelinating polyneuropathy (AIDP) is a sub-form of GBS.

Covid-related GBS cases reported in the literature are observed to be on the patients age of 50 and above. In this study, a 35-year-old AIDP case with Covid-19 is reported.

Case Presentation

A 35-year-old male patient was admitted to the neurology clinic with complaints of weakness and numbness in the legs and arms. Two weeks before the initial symptoms the patient has appealed to

the healthcare facility due to fever, cough and diarrhea where the real-time polymerase chain reaction (PCR) test of oropharyngeal swab samples has resulted positive in favor of Covid-19.

At the same time, mild lung involvement was observed in the pulmonary computed tomography (CT) scan and 200 mg hydroxychloroquine treatment was applied to the patient, twice a day, Remission of symptoms is observed at the end of second week of the treatment and the repeated PCR test was resulted negative for Covid-19. Following these, at the beginning of the third week, the patient has appealed to the neurology clinic due to loss of strength and numbness in the legs, consequently the patient was admitted to the neurology service for the further examination and treatment.

Physical examination resulted with; 36.6 °C body temperature, 125/80 mmhg blood pressure, 80/minute pulse, 18/minute respiration and 92 oxygen saturation.

The patient was conscious, oriented and cooperative in the neurological examination. Pupils were isochoric, light reflex was detected in both eyes and eye movements wereconsiderednormal.

The speech of the patient was slightly dysarthric and facial asymmetry was not observed.

According to the Medical Research Council (MRC) scale, on motor examination, the upper extremity proximals were 4/5, distally 3/5; lower extremity proximals were 4/5 and distally 3/5. Hypoesthesia was observed in all four extremities in which it was more prominent in the lower extremities.

Deep tendon reflexes (DTR) could not be obtained in bilateral lower extrimities and the plantar response was flexor. The patient was able to take only a few steps with help. There were no signs of meningeal irritation.

Routine blood, biochemistry, full blood and vitamin B12 tests have resulted normal, Elisa tests were negative and complete urinalysis has resulted within normal limits. Pathology was not detected in the pulmonary CT scan, and patient had a negative serology result for brucellosis.

As a result of lumbar puncture (LP), elevated levels of protein (700 g/l) and immunoglobin G (IgG) (101 mg / dl) were observed in the cerebrospinal fluid examination, and the cell count has resulted

normal. Furthermore, albuminocytological dissociation was observed and oligoclonal band, aquaporin-4 Ig M/IgG antibodies were reported as negative.

Leukocytes and microorganisms were not observed in the direct cerebrospinal fluid (CSF) microscopy, no growth was observed in the cultures. The positivity was not detected in antigangliosid antibodies GM1, GD1b and GQ1b; and in the antinuclear and antineutrophil cytoplasmic antibody titers.

Serological tests from cerebrospinal fluid (CSF) were negative for Camphylobacter jejuni, Toxoplasmosis, Herpes simplex virus types 1 and 2, Rubella, Varicella zoster virus, Lyme, Syphilis, Cytomegalovirus and Ebstein–Barr virüs.

Bilateral tibial and peroneal and right median and ulnar nerve combined muscle action potential (CMAP) amplitudes were low in nerve conduction studies in electromyography (EMG). Bilateral tibial and peroneal and right median nerve motor distal latencies were very long Bilateral sural and right median ulnar nerve sensory nerve action potential (DSAP) could not be obtained. Bilateral tibial nerve motor conduction velocity was very slow.AIDP was diagnosed because of abnormalities meeting the electrodiagnostic criteria for demyelination in EMG.(Table 1)

Intravenous immunoglobin (IVIG) was given at the dosage of 400 mg/kg/day for 5 days.

He was referred to physical therapy outpatient clinic after discharge and received physical therapy for two weeks. Fifteen days later, the patient, who was examined by us, started to walk without an assistance and his upper and lower extremities’ motor strength were evaluated as -5/5 in the motor examination.

Discussion

GBS is one of the rare neurological complications of Covid-19; which is an acute-onset, post-infectious, immune-mediated flaccid paralysis with symmetrical involvement from distal to proximal. It is known that Camphylobacter jejuni, EBV, influenza virus and cytomegalovirus are responsible for two-thirds of GBS cases [ 7].

There have been cases of GBS in the Middle East Respiratory Syndrome (MERS) and the Far East Respiratory Syndrome (SARS). GBS incidence has increased after the Zika virus outbreak in South America. GBS cases in Sars-COV-2 (Covid19), a new strand of the coronavirus family, are also have been reported.

Covid-19 stimulates inflammatory cells that causes the release of various cytokines and creates immune processes. GBS is an immune-mediated disease, it is suggested that cross-reactivity between viral protein-associated gangliosides and peripheral nerve gangliosides may result in molecular mimicry as the mechanism of autoimmune disorder. [8]

Alternatively, T cell activation and the release of inflammatory mediators by macrophages can facilitate nerve and myelin damage.[7] It has been concluded that the pathophysiological mechanism of GBS in COVID-19 may be para-infectious. The presented case is clinically and electrophysiologically compatible with AIDP; the age of the patient is younger contrary to the cases reported in the literature which are age of 50 and above. The case presented in this study is one of the youngest patient case reported in the literature.Additionally, while most of the cases in the literature has an underlying chronic disease, in this paper the patient was completely healthy before case.

Conclusions

In conclusion, the possibility of having Covid-19 should be considered in patients with GBS without any respiratory symptoms and Covid-19 may trigger GBS.

The Covid19-GBS relationship may be seen in the patients at earlier ages and may have affect people without underlying chronic diseases.

Positive response was observed by IVIG treatment in our patient as in many cases in the literature.

Table 1: Nerve conduction study parameters in patient with GBS Sensory nerve conduction study (NCS)

Motor NCS

F Wave

References

1. Schield E,Conseco DD, Aleksandar HN, Bereznai B.Guillain Barre syndrome during SARS-COV-2 pandemic:A case report and review of recent literature.J Pheriper nerv syst. 2020; 25: 204-207.
2. Lu H,Strattan CW,Tang YW.Outbreak of pneumonia pf unknown etiology in Wuhan, China:The mystery and the miracle.J Med Virol 2020.
3. Mao L,Jin H, Wang M,Hu Y,Chen S et al.Neurologic manifestations of hospitalized patients with Coronavirus disease 2019 in Wuhan,China retrospective case series study (February 24,2020)Available at ssrn.
4. Romero-Sanchez CM, Díaz-Maroto I, Fernández-Díaz E, Sánchez-Larsen A, Layos Romero A, García-García J, et al. Neurologic manifestations in hospitalized patients with COVID-19: the ALBACOVID registry. Neurology. 2020. 37
5. Zito A, Alfonsi E, Franciotta D, Todisco M, Gastaldi M, Ramusino MC, Ceroni M, Costa A. COVID-19 and Guillain–Barré Syndrome: A Case Report and Review of Literature. Front Neurol. 2020; 11: 909
6. Varkal MA,Yildiz E,Yildiz I,Aydinli N et al. Çocukluk çaginda Guillain Barre sendromu. J child 2015. Carress JB,Castoro RJ, Zachary S et al. Covid-19-associated-Guillain-Barre syndrome:The early pandemic experience.Muscle Nerve 2020 oct.
7. Sedaghat Z,Karimi N.Guillain Barre syndrome asociated with Covid-19 infection:A case report.J Clin Neurosci.