key: cord-0694434-lfub6y5m
authors: Nanda, Satyan; Handa, Rahul; Prasad, Atul; Anand, Rajiv; Zutshi, Dhruv; Dass, Sujata K.; Bedi, Prabhjeet Kaur; Pahuja, Aarti; Shah, Pankaj Kumar; Sharma, Bipan
title: Covid-19 associated Guillain-Barre Syndrome: Contrasting tale of four patients from a tertiary care centre in India
date: 2020-09-16
journal: Am J Emerg Med
DOI: 10.1016/j.ajem.2020.09.029
sha: 234617db0a9bb818292e97e58f49b5c825c56b21
doc_id: 694434
cord_uid: lfub6y5m

BACKGROUND: Globally, more than 12 million people have been infected with COVID −19 infection till date with more than 500,000 fatalities. Although, Covid-19 commonly presents with marked respiratory symptoms in the form of cough and dyspnoea, a neurotropic presentation has been described of late as well. OBJECTIVE: In this brief communication we report four cases of Covid-19 who presented to our hospital with features suggestive of Guillain-Barre Syndrome (GBS). DISCUSSION: The mechanisms by which SARS-CoV-2 causes neurologic damage are multifaceted, including direct damage to specific receptors, cytokine-related injury, secondary hypoxia, and retrograde travel along nerve fibres. The pathogenesis of GBS secondary to Covid-19 is not well understood. It is hypothesised that viral illnesses related GBS could be due to autoantibodies or direct neurotoxic effects of viruses. CONCLUSION: Nervous system involvement in Covid-19 may have been grossly underestimated. In this era of pandemic, it is very important for the physicians to be aware of association of GBS with Covid-19, as early diagnosis and treatment of this complication could have gratifying results. To the best of our knowledge, this is the first such case series of Guillain-Barre Syndrome associated with Covid-19 to be reported from India.

described of late as well [3] . Guillain Barre Syndrome (GBS) is best described as an acute inflammatory polyradiculoneuropathy clinically characterised by areflexia and progressive weakness of arms and legs. Though, many rare variants of GBS have been described, the commonly observed subtypes such as Acute Motor Axonal Neuropathy (AMAN), Acute Motor Sensory Axonal Neuropathy (AMSAN) and Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP) tend to fulfil the above-mentioned criteria [4] . In this brief communication we report four cases of Covid-19 who presented to our hospital with features suggestive of GBS.

A 55-year-old female with background history of Diabetes Mellitus, Hypertension and Cholelithiasis presented with chief complaints of fever 10 days back lasting for 3 days, pain abdomen for 5 days; acute onset rapidly progressive symmetric weakness of all four limbs for 3 days (lower limbs followed by upper limbs). There was no history suggestive of cranial nerve, bowel or bladder involvement. On examination, patient was hemodynamically stable with 98% oxygen saturation (SpO2) on room air. Cranial nerve examination was normal. Motor examination revealed generalised hypotonia, Grade Table 2 ]. After informed consent the patient was started on J o u r n a l P r e -p r o o f IV Immunoglobulin (IVIG): 0.4 g/kg body weight per day for five days. In view of a possibility of Covid-19 associated hypercoagulable state (elevated D Dimer) she was also given therapeutic anticoagulation. There was no further progression of her symptoms after starting IVIG and the patient was discharged after 10 days of hospital stay with Grade 4/5 power in both lower limbs and Grade 4+/5 power in both upper limbs.

A 72-year-old male, known case of hypertension for 5 years on treatment, presented to the emergency department of our hospital with chief complaints of fever 6 days back lasting for 2 days, cough since past 3 days associated with progressive weakness of all four limbs since past 2 days. He had lost the ability to walk independently since 1 day. There was no history suggestive of cranial nerve involvement, diarrhoea, bowel and bladder symptoms, or dog bite. On examination, patient was hemodynamically stable and afebrile. Neurological examination revealed no cranial nerve involvement. Motor examination showed generalised hypotonia, Grade 2/5 power in both lower limbs and grade 3/5 in both upper limbs as per MRC grading. Deep tendon reflexes were universally absent and plantar response was flexor bilaterally. The sensory examination was normal. His SBC was 12. His routine blood investigations including complete blood count, serum sodium and potassium, liver and kidney function tests were normal. Viral markers including Human Immunodeficiency Virus, Hepatitis B Surface antigen (HBsAg) and

Hepatitis C Virus (HCV) antibody were negative. Serum B12 levels and Thyroid function tests were normal. Covid-19 testing was positive by RT-PCR technique. Contrast MRI of whole spine was suggestive of degenerative changes in the spine [ Table 2 ]. CSF examination showed albumino-cytological dissociation and inflammatory markers were elevated [ Table 1 limbs. Contrast MRI of whole spine showed mild degenerative changes of the spine [ Table 2 ].

CSF examination showed albumino-cytological dissociation with mildly elevated inflammatory markers in the blood [ Table 1 and 2]. Chest X-ray showed evidence of bilateral lower and midzone infiltrates. IVIG was given at 0.4gm/kg body weight/day for 5 days with other supportive treatment. Good neurological improvement was observed over the next 5 days and patient was discharged after 7 days. At the time of discharge patient had 4+/5 power in both lower limbs with mild residual facial palsy.

A member of the beta-coronaviridae family, SARS-CoV-2 is an enveloped, non-segmented, single-stranded, positive-sense RNA virus. The mechanisms by which SARS-CoV-2 causes neurologic damage are multifaceted, including direct damage to specific receptors, cytokinerelated injury, secondary hypoxia, and retrograde travel along nerve fibres [5] . Three of the above cases presented with neurological complaints and had no respiratory features secondary to Covid-19, and these were the ones who did quite well with treatment. One patient who presented with respiratory complaints and X-ray changes along with neurological deficits continued to deteriorate even after starting treatment for both GBS and Covid-19, and eventually succumbed to the disease.

In the past GBS has been associated with a number of viral infections, most recently to Zika virus [6] . The pathogenesis of GBS secondary to Covid-19 is not well understood. It is well documented that the cross immunity which plays an important role in GBS secondary to bacterial infections such as C. jejuni may not be the main reason behind GBS associated with viral infections namely Dengue and Zika. It is hypothesised that viral illnesses related GBS could be due to autoantibodies or direct neurotoxic effects of viruses [7] . Although, our patients had symptoms. This was in contrast to typical GBS, wherein cranial nerve involvement is quite common. Less frequent involvement of cranial nerves in GBS secondary to Covid-19 is also in contrast to Zika virus associated GBS, where facial and third nerve involvement was quite common [7] . All the above patients had significantly raised pro-inflammatory markers that might suggest a causal link to pro-inflammatory state secondary to Covid-19. Similar rise in inflammatory markers were noted in other case reports as well, and it was hypothesised that these inflammatory mediators and cytokines may play a role in triggering an immune mediated neuropathy [8] .

All our patients developed features of GBS, 5-10 days after the onset of Covid-19 symptoms, which is similar to the interval seen with Guillain-Barré syndrome that occurs secondary to other infections [9] . Most of the previous case reports documented a similar interval duration between the onset of Covid-19 symptoms and GBS [2, 9] . Three of our patients had an excellent response to IVIG and were ambulatory without support within 10 days of starting treatment. Previous case reports show mixed treatment response with some reporting very good recovery, while others 

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