Bilateral vocal cord paralysis in Miller Fisher syndrome/Guillain-Barre overlap syndrome and a review of previous case series

Abstract

Miller Fisher syndrome (MFS), an acute demyelinating neuropathy, is characterised by a triad of areflexia, ataxia and ophthalmoplegia. It is the most common variant of Guillain-Barre Syndrome (GBS). In about 5.6%–7.1% of MFS cases, patients also suffer from progressive motor weakness of the limbs. This condition is termed MFS/GBS overlap syndrome. Whether it is in MFS or GBS, bilateral vocal cord paralysis (BVCP) is a rare manifestation with limited cases reported in the literature. We report an extremely rare case where a 65-year-old man developed BVCP in an MFS/GBS overlap syndrome. We have also reviewed previous case reports in the literature for comparison.

Background

Miller Fisher syndrome (MFS), a rare demyelinating disease, is the most common variant of Guillain-Barre syndrome (GBS).¹ While GBS is characterised by progressive ascending motor weakness, primarily arising in the lower extremities, MFS typically involves the cranial nerves first.² Bilateral vocal cord paralysis (BVCP) in either MFS or GBS is rare with limited cases reported in the literature. We report an unusual non-acute presentation of BVCP in MFS/GBS overlap syndrome, triggered by varicella zoster virus.

Case presentation

A 65-year-old man presented to a district general hospital in West Sussex with a 3-day history of sudden onset diplopia and dizziness. He denied dysphagia or hoarseness. There was no obvious limb weakness or other peripheral neurological symptoms. The history was significant for chicken pox 1 month ago, treated with acyclovir. His medical history included two previous autologous bone marrow transplants for multiple myeloma. He was not taking any regular medications.

Physical examination demonstrated a broad-based ataxic gait, areflexia in all limbs and mild bilateral ptosis. Initial blood tests did not reveal any abnormality. Lumbar puncture result was also unremarkable (white cell count: 1/mm³, protein level: 1.7 mg/dL, cerebrospinal fluid glucose level: 66% of serum glucose, gram stain: negative). With a high suspicion of acute inflammatory demyelinating polyneuropathy, intravenous immunoglobulin therapy (IVIG) was commenced for 5 days.

On the third day of admission, the patient showed worsened respiratory status with reduced forced vital capacity and poor tidal volume. He was subsequently intubated and transferred to the intensive care unit (ICU). In the absence of chest infection or signs of upper airway obstruction, this was most likely due to neuromuscular diaphragmatic failure. Clinical deterioration continued with a new onset of muscle weakness in a descending pattern. On day 8, he was transferred to The National Hospital for Neurology and Neurosurgery, London. Neurological examination revealed bilateral ophthalmoplegia of third, fourth, sixth and seventh cranial nerve palsies, as well as almost complete body numbness and tetraplegia. Percutaneous tracheostomy was inserted to aid the weaning of ventilation. Otolaryngology review was requested due to persistent dysphagia and communication difficulties. Flexible nasendoscopy demonstrated BVCP in a paramedian position with limited abduction. Although the patient no longer required mechanical ventilation, decannulation of tracheostomy was not advised due to the compromised upper airway. Four weeks post the initial IVIG, the patient’s delta IgG incremented appropriately but there were no signs of clinical improvement. Second dose of IVIG was not given in accordance with the data from International Guillain-Barre Syndrome Outcome Study.³

Investigations

Whole body CT demonstrated sclerotic and lytic bony lesions, which was in keeping with myeloma. Sural nerve biopsy and myeloma blood screen ruled out the possibility of myeloma recurrence. Several nerve conduction studies, however, consistently confirmed severe generalised demyelinating polyneuropathy. A clinical diagnosis of MFS overlapping GBS was made based on the patient’s clinical presentation. Varicella zoster virus was assumed to be the infectious stimulus.

Further investigations for causes of BVCP were conducted. Cross-section images including CT of the neck and chest, and MRI of the brain did not show any structural causes. Diagnostic laryngoscopy demonstrated posterior commissure oedema. Laryngeal biopsies of this oedema revealed inflammation. Therefore, MFS/GBS overlap syndrome was considered the sole cause of the patient’s BVCP.

Outcome and follow-up

Following 4 months of conservative management, sensation and proximal motor function started to return. Seven months after the initial presentation, he was discharged from ICU to a neuro-rehabilitation unit. His vocal cord function, however, has not recovered. He remained tracheostomy dependent.

Discussion

MFS is the most common variant of GBS. Its incidence is 0.09 per 100 000, accounting for only 5% in Western countries.⁴ While GBS presents as a rapid onset of symmetrical motor weakness and areflexia, arising in the lower extremities, symptoms and signs of MFS typically begin proximally with diplopia being the most common initial symptom. Clinically, MFS is characterised by a triad of areflexia, ataxia and ophthalmoplegia.

Our patient who initially presented with typical MFS symptoms later developed progressive bilateral weakness in arms and legs in a descending fashion. The constellation of symptoms and signs was consistent with MFS/GBS overlap syndrome, which has been reported in 5.6%–7.1% of MFS cases.⁴ Whereas descending tetraparesis is rare in GBS, it is more common in MFS/GBS overlap syndrome. In two-thirds of all cases, GBS is thought to be triggered by a preceding upper respiratory tract or gastrointestinal viral infection such as Campylobacter, Epstein-Barr virus and cytomegalovirus.⁵ Varicella zoster virus is considered as a rare stimulus.

BVCP is a rare manifestation of GBS or MFS. A review in the literature identified six accessible case reports describing either GBS or MFS-induced BVCP (see table 1).^6–11

Table 1.

Case reports of BVCP in GBS or MFS and their clinical features

	Acute presentation of respiratory distress or hoarseness of voice	Other neurological function at initial presentation	Treatment for GBS/MFS	Use of tracheostomy	Recovery of BVCP
Rodrigues et al6	No	Abnormal	Supportive measures	Yes	No
Panosian and Quatela7	Yes	Abnormal	Plasmapheresis (day 2)	Yes	Yes
Yoskovitch et al8	Yes	Normal	Plasmapheresis (day 2)	Yes	No
Hsia et al9	Yes	Normal	Immunoglobulin (unclear)	No	Yes
Lee et al10	Yes	Normal	Immunoglobulin (unclear)	No	Yes
Ramakrishna et al11	Yes	Abnormal	Immunoglobulin	Yes	No

BVCP, bilateral vocal cord paralysis; GBS, Guillain-Barre syndrome; MFS, Miller Fisher syndrome.

Acute clinical features of BVCP such as respiratory distress or hoarseness of voice were the primary presenting symptoms in five of the reported cases.^7–11 Additionally, patients did not have any other neurological abnormalities at the initial presentation.^8–10 This in combination with negative laboratory test results, and cross-section images made it difficult to establish a diagnosis in the early stage. The remaining case, together with our case, demonstrated a delayed onset of BVCP. Once the diagnosis GBS or MSF was confirmed, standard treatment of plasmapheresis or IVIG was administered to accelerate the recovery.

A tracheostomy procedure was performed in four of the cases to maintain airway. In two cases, tracheostomy was not required.^{9 10} In the case reported by Lee et al,¹⁰ the vocal cords were fixed in lateral position, leaving the patient with adequate upper airway but poor voice. The other case reported by Hsia et al⁹ was of a girl aged 3 years and 2 months who presented with viral croup-like symptoms. The patient’s airway was not compromised clinically with symptoms resolving quickly within 5 days since the administration of immunoglobulin, not requiring a tracheostomy.

Although most patients (80%–90%) made full recovery, it varied from several weeks to 2 years.^6–11 Full recovery within 6 weeks was seen in three cases, while the patients of the other three cases were still tracheostomy dependent at 15 months, 6 months and 4 months.^{6 8 11} Our patient also had a prolonged recovery with sensation and motor function only returning after 4 months of treatment. He remained tracheostomy dependent at 7 months.

This case report describes an infrequent phenomenon of BVCP in an also rare MFS/GBS overlap syndrome. Although the BVCP was a non-acute presentation in our case, it can be the sole presenting symptom at the initial clinical presentation making the diagnosis of GBS or MFS difficult to establish at an early stage. In most cases, patients make a full recovery with tracheostomy required only as a temporary supportive measure. However, recovery phase may vary widely between individuals leaving some patients still tracheostomy dependent months after initial treatment.

Learning points.

• The term Miller Fisher syndrome/Guillain-Barre syndrome (MFS/GBS) overlap syndrome is used when patients with MFS also suffer from progressive motor weakness of the limbs.

• Bilateral vocal cord paralysis is an infrequent phenomenon of MFS/GBS overlap syndrome.

• Bilateral vocal cord paralysis may be the sole presenting symptom at the initial clinical presentation.

• Varying recovery phase of bilateral vocal cord paralysis has been reported with some patients making a full recovery, while others remaining tracheostomy dependent after initial treatment.