Asymmetric limb weakness in Guillain-Barré syndrome:Three case reports

lNTRODUCTlON

Guillain-Barré syndrome(GBS)is one of the most common causes of acute flaccid paresis with significant clinical heterogeneity[1].At disease onset,most patients present with typical features of GBS such as symmetric tetraparesis,while some patients only present with incomplete variants,such as paraparetic or pharyngeal-cervical-brachial forms[2,3].Recently,some atypical forms,such as asymmetric cranial nerve palsies,have been reported in patients with GBS[4].However,asymmetric limb weakness in GBS is uncommon and may be confused with other conditions such as stroke.We herein describe three patients diagnosed with GBS who suffered from asymmetric limb weakness,review the literature and hypothesize the possible underlying mechanisms.

CASE PRESENTATlON

Chief complaints

A 56-year-old male worker presented with distal weakness of right upper and lower limb for five days and distal weakness of left upper and lower limb for two days.

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A 59-year-old male farmer presented with right upper and lower limb weakness for five days and left upper and lower limb weakness for four days.

A 36-year-old male farmer presented with right upper and lower limb weakness for two days and left upper and lower limb weakness for one day.

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History of present illness

The patient had a history of pneumonia two weeks previously.At disease onset,he complained of right distal upper and lower limb weakness,loss of pain and temperature sensation in the right hand and foot,and could not walk independently.Three days later,the limb weakness and numbness extended to the left distal upper and lower limb,which continued to worsen until day 5.

Typical GBS is a mono-phasic polyneuropathy with acute onset symmetric cranial or limb weakness[5].Asymmetric deficits,especially asymmetric limb weakness is easily confused with other neurological conditions such as stroke,demyelinating myelopathy,acute-onset chronic inflammatory demyelinating polyneuropathy[6],and beriberi neuropathy[7].Although a study from Israel reported that asymmetric weakness accounted for 23% of atypical clinical findings of GBS in children[8],atypical GBS in adults with asymmetric limb weakness is rarely reported.Weakness or paresthesia in GBS may begin with symptoms in one limb,but most of the asymmetric symptoms at onset are transient and will progress to symmetric weakness at nadir[9,10].Chi[11]reported a patient with axonal GBS who presented with acute onset of left hemiplegia and left sublingual nerve palsy mimicking stroke,of which the hemiplegia further progressed to tetraparesis within a few days.A Dutch study reported four patients who had asymmetric GBS[12],and three of these patients progressed to symmetric GBS within one week.Being different,both the case presented by Logullo[13]and our patients showed persistent asymmetric limb weakness starting from the acute phase until the recovery phase.In this report,we review the literature and summarize the clinical presentation of asymmetric GBS,including a case reported previously[13]and our cases reported in this paper(Table 1).

The three patients had no particular past history.

History of past illness

The patient had a history of gastroenteritis 10 d before the onset of limb weakness.Two days ago,he complained of right upper and lower limb weakness and numbness,which was initially diagnosed with cerebral infarction at another hospital.The following day,his clinical symptoms progressed and the limb weakness and numbness extended to the left right upper and lower limb.

Personal and family history

The three patients had no particular individual or family history.

Physical examination

A NCS on day 3 showed that the amplitudes of the median,ulnar,tibial and peroneal nerves were significantly reduced.

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On admission,neurological examination revealed weakness of both proximal and distal limbs,3/5 MRC on bilateral proximal,2/5 MRC on distal upper limbs,2/5 MRC on the left distal lower limb and 1/5 on the right distal lower limb,deep tendon reflexes were decreased and he had loss of pain and temperature sensation in bilateral hands and feet.

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Laboratory examinations

Cerebrospinal fluid(CSF)analysis on day 10 showed normal cell counts(normal range,0 to 8/mL)and increased protein concentration of 1.421 g/L(normal range,0 to 0.45 g/L).Serological analysis of IgG antibodies against GM1,GM1b,GalNAc-GD1a,GD1a,GD1b,GQ1b,and GT1a were negative.Serological testing for IgM antibodies against influenza A virus andwere positive.

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CSF analysis on day 6 showed normal cell counts and increased protein levels(0.987g/L).IgG antibodies against GM1 were positive.Serological testing for IgM antibodies against influenza A virus was positive.

Informed written consent was obtained from the three patients for publication of this report.

Imaging examinations

A nerve conduction study(NCS)on day 10 showed that the distal latencies of the median,ulnar and peroneal nerves were significantly increased,conduction velocities of the median,ulnar and tibial nerves were reduced and there was temporal dispersion of the median and tibial nerves.NCS results suggested demyelination.Magnetic resonance imaging(MRI)of the brain was normal.The spinal MRI was not performed.

MRI of the spine was normal.He refused to undergo a NCS.

Neurological examination on admission revealed bilateral distal and proximal limb weakness(for the distal,1/5 MRC on the right and 2/5 MRC on the left;for the proximal,3/5 MRC on the right and 4/5 on the left).Sensory examinations showed significant loss of pain and temperature sensation in bilateral hands and feet.The tendon reflex of four limbs was absent.

The neurological examination revealed normal cranial nerves,5/5 Medical Research Council(MRC)grade on proximal four limbs,3/5 MRC on the right distal limb and 4/5 on the left distal limb.The tendon reflex of the four limbs was absent.

FlNAL DlAGNOSlS

The three cases were diagnosed with GBS.

TREATMENT

The patient received intravenous immunoglobulin which was initiated on day 10 at 2 g/kg/day for 5 d.

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The patient opted for supportive treatment due to cost.

He was treated with plasma exchange(PE)every two days.

OUTCOME AND FOLLOW-UP

On day 16,his limb weakness and numbness started to improve.On day 17,he was discharged.A follow-up at six months after onset showed 5/5 MRC on proximal four limbs,residual mild weakness of distal upper limbs(5/5 MRC on the left,4/5 MRC on the right)and lower limbs(4/5 MRC bilateral).

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His clinical symptoms progressed and reached the nadir on day 9 after onset and he developed urinary retention.The MRC on four proximal limbs was 2/5,left distal limb muscle strength was 1/5 and right distal limb muscle strength was 0/5.The patient was discharged and returned to a local hospital on day 11.Six months later,a follow-up of this patient showed 2/5 MRC on four proximal limbs and 2/5 MRC on the left distal limb and 1/5 MRC on the right distal limb.

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His clinical signs showed no response to the first session of PE and symptoms progressed on day 4 after onset.The neurological examination showed 2/5 MRC on the left proximal limb and 3/5 on the right proximal limb,1/5 MRC on the left and 2/5 MRC on the right distal lower limbs,and 1/5 on distal bilateral lower limbs.His sensory deficits in bilateral feet rose to bilateral legs.PE treatment proceeded as planned.On day 10 after onset,his weakness and numbness started to improve.Following PE,he was transferred to the rehabilitation ward for a course of electrical stimulation and physical rehabilitation.He was discharged on day 28.A follow-up at six months after onset showed asymmetric weakness on upper(4/5 MRC on the right and 3/5 on the left)and lower limbs(3/5 MRC on the right and 2/5 on the left).

DlSCUSSlON

The patient denied antecedent infections.His clinical symptoms started five days ago with right upper and lower limb weakness,which had been extended to the left upper and lower limb on day 2 after onset.He complained of significant loss of pain and temperature sensation in bilateral hands and feet.

Although the exact mechanism of asymmetric deficits in GBS remains unclear,current evidence suggests a potential association between anti-ganglioside antibodies and asymmetric deficits in GBS.Stork[14]previously suggested that auto-antibodies against asialo-GM1 were associated with more pronounced motor deficits and asymmetry.Kim and Yuki[15]reported an unusual patient with hemiparetic GBS who had preceding gastroenteritis and anti-GD1a antibodies.In our patients,two out of three had autoantibodies against GM1.Anti-GM1 IgG antibodies binding to the nodal axolemma,which locates the GM1 and voltage-gated sodium channels,leads to the formation of membrane attack complex and disruption of sodium channels,which causes axonal impairment and nerve-conduction failure[16].Binding of circulating antibodies onto the peripheral nerve myelin or axolemma relies on a rich blood supply and discontinuity of the blood-nerve barrier(BNB).Generally,the BNB along the nerve fiber is inhomogeneous and the distal and proximal are selectively more vulnerable to injury[17].Manousakis[18]reported a patient with melanoma who developed multifocal and asymmetric polyradiculoneuropathy after ipilimumab treatment.The asymmetry of congenital development of BNB including the vascular endothelium permeability or asymmetric disruption of the BNB may be one of the underlying mechanisms leading to asymmetric limb weakness in GBS and antibodies-related peripheral neuropathy.Furthermore,the asymmetric distribution of the gangliosides may also cause the difference in limb involvement on both sides of patients with GBS.Finally,body position or limb use has also been suggested as a possible cause,which influences the initial distribution of weakness during crucial moments of influx of inflammatory factors into nerves[19].All of our three patients were righthanded and their first clinical presentation at onset was all right-sided weakness.At nadir,the first two patients had more serious limb weakness on the right while the third patient had more serious limb weakness on the left.Our cases suggest a possible correlation between limb use and asymmetric GBS,which deserves further investigation.

CONCLUSlON

To sum up,asymmetric GBS is challenging the diagnosis criteria of GBS.To differentiate asymmetric GBS,especially the hemiplegia at onset with other similar conditions such as stroke,is important for an early treatment of IVIg or PE,which can lead to a good patient outcome and early recovery.Additionally,further study is necessary to investigate whether asymmetric GBS can be taken as a variant of GBS.

FOOTNOTES

Zhang GR and Hu M reviewed the literature and contributed to manuscript drafting;Li X and Feng XG played a major role in the acquisition of clinical data and the literature search;Wang YZ and Wong HY were responsible for the revision of the manuscript for important intellectual content;all authors issued final approval for the version to be submitted.

Teacher Research Support Foundation of Jining Medical University,No.JYFC2018FKJ140;Natural Science Foundation Youth Project of Shandong Province,No.ZR2020QH110.

CSF analysis showed normal cell counts and increased protein concentration of 0.483 g/L on day 3 after onset.IgG antibodies against GM1 were positive.Serological testing for IgM antibodies againstwas positive.

The authors declare that they have no conflict of interest.

The authors have read the CARE Checklist(2016),and the manuscript was prepared and revised according to the CARE Checklist(2016).

This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers.It is distributed in accordance with the Creative Commons Attribution NonCommercial(CC BYNC 4.0)license,which permits others to distribute,remix,adapt,build upon this work non-commercially,and license their derivative works on different terms,provided the original work is properly cited and the use is noncommercial.See:http://creativecommons.org/Licenses/by-nc/4.0/

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Ming Hu 0000-0003-2901-4812;Xiang Li 0000-0001-8491-8836;Hiu Yi Wong 0000-0001-5505-2447;Xun-Gang Feng 0000-0003-1009-2802;Yu-Zhong Wang 0000-0002-3145-9362;Guo-Rong Zhang 0000-0003-2901-4812.

Liu JH

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Liu JH