Guillain-Barré syndrome with overlap between the finger drop variant and acute bulbar palsy: a case report

doi:10.21203/rs.3.rs-4211221/v1

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Case Report

Guillain-Barré syndrome with overlap between the finger drop variant and acute bulbar palsy: a case report

https://doi.org/10.21203/rs.3.rs-4211221/v1

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published 23 Oct, 2024

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Background

Guillain-Barré syndrome (GBS) encompasses diverse variants, and the overlap between these variants often makes the diagnosis of GBS difficult. We report a case of GBS overlapping with both the finger drop variant and acute bulbar palsy.

Case presentation:

An 81-year-old man presented with dysarthria, dysphagia, and upper limb weakness. The patient exhibited impaired tongue protrusion and the finger drop sign, whereas other cranial nerve functions, leg strength, touch sensation, and proprioception were normal. Brachioradialis and triceps reflexes were diminished. Cerebrospinal fluid analysis revealed elevated protein levels with normal cell counts. Nerve conduction studies showed reduced amplitudes and decreased velocities in the median and ulnar nerves. As GBS was suspected, we initiated intravenous immunoglobulin treatment, resulting in gradual improvement within 3 weeks. Serum IgG antibodies to gangliosides tested positive for GM1, asialo-GM1, GT1a, GD1b, and GQ1b. On the basis of the monophasic disease course and anti-ganglioside antibodies, we confirmed the diagnosis of GBS.

Conclusion

This case is the first reported instance of an overlap between the finger drop variant and acute bulbar palsy in GBS, highlighting the importance of considering GBS when patients present with a combination of atypical symptoms. Anti-ganglioside antibodies may assist in distinguishing these complex symptoms.

Guillain-Barré syndrome

finger drop sign

bulbar palsy

anti-ganglioside antibody

Guillain-Barré syndrome (GBS) is an acute autoimmune disorder that predominantly affects the peripheral nervous system and is characterized by a rapidly progressing course. Classical GBS typically begins with weakness in the legs that progressively ascends to involve the upper limbs, and in more severe cases, the respiratory muscles and cranial nerves (1).

GBS is characterized by a variety of subtypes, each defined by specific clinical features, a wide variety of which have been highlighted over time. For instance, the ‘finger drop sign’ was recently identified as a variant of GBS, known as the finger drop variant (FDv) (2). It is defined by prominent distal weakness in the upper limbs, predominantly affecting the fingers or wrist extensors more than the flexors. This variant usually exhibits no weakness or only mild weakness in the lower limbs. Because of its focal weakness and low disease frequency, this variant poses diagnostic challenges.

Another important clinical symptom in patients with GBS is acute bulbar palsy. This symptom is typical of the pharyngeal-cervical-brachial (PCB) variant, which is typified by oropharyngeal and cervicobrachial weakness, without lower limb involvement (3). However, some patients with GBS primarily present with acute bulbar palsy without significant neck and brachial weakness, indicating another GBS variant (3). Such variable manifestation often complicates the diagnostic process, especially in the early stage. Furthermore, overlap between these variants sometimes occurs in patients with GBS, and this can make the diagnosis extremely complicated for clinicians. However, anti-ganglioside antibodies may help elucidate the clinical subtypes (1). It was reported that IgG anti-GM1 antibodies, as well as the ganglioside complex of anti-GM1 antibodies with phosphatidic acid, are linked to typical GBS and FDv (2). Similarly, anti-GD1b antibodies are commonly associated with sensory ataxic neuropathy, whereas anti-GT1a antibodies are related to PCB variants and acute bulbar palsy in patients with GBS (1, 4). Furthermore, anti-GQ1b antibodies are often associated with Miller Fisher syndrome (MFS) (1). While definitive associations between these variants and specific anti-ganglioside antibodies have not been firmly established, the presence of these antibodies is often informative for the diagnosis of GBS.

In this report, we present a case of a patient with GBS who exhibited a combination of quite atypical features, specifically, the finger drop sign and acute bulbar palsy due to tongue weakness. A precise neurological examination was important for the accurate diagnosis of this case in the early stage. Anti-ganglioside antibodies were useful to explain the phenotypes.

An 81-year-old man with a history of appendix cancer that recurred following treatment with cetuximab and encorafenib was admitted to a neurology department because of dysarthria, dysphagia, and weakness of the upper limbs lasting for 3 days. The patient had received no recent vaccinations, and had no prior infection, diarrhea, or upper respiratory symptoms. Neurological examination of the cranial nerves revealed dysarthria and dysphagia with an inability to protrude the tongue beyond the dental arch. There were no abnormalities in ocular movements and facial strength. The gait was normal, and no ataxia was observed; additionally, touch sensation and proprioception were also normal. Manual muscle testing conducted using the Medical Research Council scale revealed muscle weakness in the distal upper limbs. Bilateral wrist extensors and flexors scored two on the right and three on the left. Finger extensors were notably weak, with a uniform rating of two bilaterally, and the finger drop sign being shown (Fig. 1a). By contrast, the finger flexors exhibited only mild weakness, rated at three on the right and four on the left. The iliopsoas and hamstring muscles showed mild weakness, each scoring four. Muscles in other areas of the lower limbs were found to be at full strength. Tendon reflexes were diminished in the brachioradialis and triceps, but were normal in other sites. The blood test results were normal with no anti-SSA antibody, anti-SSB antibody, myeloperoxidase and proteinase 3 anti-neutrophil cytoplasmic antibodies, anti-acetylcholine receptor antibody, or anti-muscle-specific tyrosine kinase antibody. Nerve conduction studies revealed low amplitudes and deteriorated velocities with proximal stimulation in the median and ulnar motor nerves, with the results otherwise being within normal limits (Table 1 and Fig. 2). Respiratory function tests demonstrated a vital capacity of 71%. A cerebral spinal fluid test showed elevated protein levels of 48 mg/dL and normal cell counts, with five cells per mm³. Brain MRI and cervical contrast-enhanced MRI were normal. Tongue pressure quantified with a balloon-type tongue pressure measurement device (TPM-02; JMS Co. Ltd, Hiroshima, Japan) was low, at an average of 10.44 kPa over ten trials, with this being only 33% of the average of 32 kPa for a 70-year-old population (5). Videoendoscopic evaluation of swallowing revealed reduced pharyngeal contractility and normal laryngeal function.

Table 1

The results of nerve conduction studies on day 1 and 21 after admission
			day 1			day 21
Nerve	Stimulation	Latency(ms)	CMAP amp(mV)	Velocity(m/s)	Latency(ms)	CMAP amp(mV)	Velocity(m/s)
Rt. median	Wrist	3.1	6.7		3.1	6.1
	Elbow	7.9	2.2	47.0	8.1	3.4	47.0
Rt. ulnar	Wrist	2.7	7.7		2.5	7.1
	Below elbow	7.0	4.8	53.0	7.2	6.1	48.0
	Above elbow	10.3	4.6	42.0	9.7	6.0	47.0
Rt. peroneal	Ankle	6.1	1.9		5.8	3.1
	Fibular head	15.2	1.1	40.0	14.4	1.8	39.0
Rt. tibial	Ankle	4.5	8.3		3.8	9.8
	Pop fossa	14.4	4.0	41.0	14.4	5.0	41.0
On the first day, the study revealed low amplitude and reduced conduction velocities in the proximal segments of the median and ulnar motor nerves. By the 21st day, there was a slight improvement in the amplitude of these nerves.

As a result, we strongly suspected GBS because of the acute onset of the mostly symmetric pattern of limb and cranial nerve weakness with areflexia and albuminocytologic dissociation. Consequently, intravenous immunoglobulin therapy (0.4 g/day for 5 consecutive days), rehabilitation, and fluid administration were initiated on the day following admission. After the treatment, the patient’s symptoms gradually improved. By the 17th day of admission, there was a gradual improvement in the finger drop sign (Fig. 1b), and the patient was able to resume normal oral intake. The improvement in finger extension was slower than that of flexion, in line with the severity at onset. The patient’s tongue pressure had improved to 23.56 kPa, 74% relative to the normal value for a 70-year-old population (Fig. 3). On the 21st day of admission, we again conducted nerve conduction studies (Table 1 and Fig. 2), which showed a slight recovery in amplitude and a mild decrease in velocities, in line with acute motor axonal neuropathy (AMAN) (6–8). An enzyme-linked immunosorbent assay (ELISA) of serum IgG antibodies to gangliosides revealed positive results for GM1, asialo-GM1, GD1b, GT1a, and GQ1b, with titers of 0.422, 0.230, 0.404, and 0.452, respectively. On the 31st day after admission, the patient was discharged from the hospital. Given the monophasic disease course and the results of the nerve conduction studies, a diagnosis of AMAN, a subtype of GBS, was established.

The patient presented with the finger drop sign and acute bulbar palsy, which are both relatively rare manifestations of GBS. First, the finger drop sign is a distinctive feature observed in this case. Recent research defined the FDv as corresponding to the AMAN type in nerve conduction studies (2). Initially, our patient’s nerve conduction studies demonstrated low amplitude, suggesting a conduction block. However, early reversible conduction failure is a known phenomenon in GBS (9), with this abnormality often being observed in the early stage of AMAN type. In subsequent nerve conduction studies, the conduction velocities returned to normal, confirming the AMAN classification of our case according to the Ho criteria, Hadden criteria, and Uncini criteria (6–8). While our case fulfills the definition of FDv, including positive anti-GM1 antibodies and AMAN type, it is important to note that the presence of a combination of positive anti-GT1a antibodies in FDv has not been previously reported.

The occurrence of acute bulbar palsy in GBS is frequently associated with anti-GT1a antibodies (10). Interestingly, there are no specific studies that have conclusively identified which cranial nerves are predominantly involved in acute bulbar palsy in patients with GBS with positive anti-GT1a antibodies (10, 11). Our patient exhibited pronounced tongue weakness at the onset of GBS, which improved rapidly following IVIg treatment. The improvement in tongue pressure was associated with amelioration of the dysarthria and dysphasia, suggesting that tongue pressure may reflect the overall severity of GBS. Tongue weakness is reported to be correlated with respiratory function in GBS (12). As GT1a is reported to be expressed in the glossopharyngeal nerve, vagal nerve, human cerebrum, and hypoglossal nerve, the presence of anti-GT1a antibodies raises the possibility that the effect of these antibodies on the hypoglossal nerve could cause the unique tongue weakness (4, 13). Measuring tongue strength can be a valuable tool to not only assess the severity and progression of bulbar palsy, but to also determine the targets of intervention in rehabilitation.

In our case, anti-GD1b and anti-GQ1b antibodies were also positive. While anti-GD1b antibodies indicate sensory ataxic neuropathy and anti-GQ1b antibodies are typically indicative of MFS, the clinical presentation of our patient did not exhibit ataxia and did not align with MFS (1, 14). Despite the occurrence of anti-GD1b and GQ1b antibodies in MFS and sensory ataxic neuropathy cases, it is important to consider the possibility of cross reactivity (4, 15, 16). The absence of typical MFS symptoms and reduced deep sensation indicated that the presence of anti-GD1b and anti-GQ1b antibodies in this case may have been due to cross reactivity to anti-GM1 and anti-GT1a antibodies, respectively. In addition, while the patient had appendix cancer, there was low probability of paraneoplastic syndrome because of his monophasic disease course and marked response to IVIg treatments.

Our case exhibited a rare combination of clinical features, namely, acute bulbar palsy and the finger drop sign. The simultaneous presence of these symptoms, coupled with the detection of both anti-GT1a and anti-GM1 antibodies, highlights the intricacies and diagnostic challenges associated with overlapping subtypes of GBS, underscoring the need for clinicians to consider the possibility of such overlapping syndromes. Our case particularly suggests an association between anti-GT1a antibody and its impact on the hypoglossal nerve. This finding suggests that measuring tongue strength could be a valuable method for assessing clinical progression and determining appropriate rehabilitation strategies. To disentangle the complexities of these overlapping subtypes, further research is essential to elucidate the distinct clinical subtypes of GBS, their specific associations with anti-ganglioside antibodies, and the mechanisms underlying these associations.

GBS: Guillain-Barré syndrome

FDv: finger drop variant

PCB: Pharyngeal-cervical-brachial

MFS: Miller Fisher syndrome

MRI: Magnetic resonance imaging

IVIg: Intravenous immunoglobulin

ELISA: Enzyme-linked immunosorbent assay

AMAN: Acute motor axonal neuropathy

Acknowledgments:

Not applicable.

Funding:

None.

Availability of data and materials:

All data analyzed are included in the published article.

Author’s contributions:

Shota Ito, Satoshi Yokoi, and Yuki Fukami drafted the manuscript. Ayumi Uchibori measured serum IgG antibodies against gangliosides. Masahisa Katsuno reviewed and revised the manuscript. All authors read and approved the final manuscript.

Ethics approval and consent to participate:

Written informed consent was obtained from the patient.

Consent for publication:

The authors have obtained written informed consent from the patient for the publication of this paper.

Competing interests:

None.

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No competing interests reported.

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You are reading this latest preprint version

Guillain-Barré syndrome with overlap between the finger drop variant and acute bulbar palsy: a case report

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Abstract

Background

Case presentation:

Conclusion

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Background

Case Presentation

Discussion and Conclusion

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Journal Publication

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