INTRODUCTION

Brown-Vialetto-Van Laere syndrome (BVVLS) is characterized by progressive pontobulbar palsy with sensorineural deafness. Most frequently, the lower cranial nerves VII to XII are involved.^1-5 Brown⁶ originally identified this syndrome in 1894, followed by Vialetto⁷ in 1936 and Van Laere⁸ in 1966. About half of all cases are sporadic, and its etiopathogenesis is still unknown.⁹ There have also been reports of X-linked or autosomal dominant inheritance.² The earliest symptoms might appear at any age, from infancy to the third decade.² Although it has been proposed that males may be more seriously impacted than females,¹ reported cases show that females are affected more frequently than males.

Initial presenting signs, in addition to sensorineural hearing loss, include slurred speech,⁴ facial weakness,¹⁰ and weakness in the neck and shoulders. This condition is frequently regarded as one of the numerous motor neuron diseases.¹¹

We present the clinical and electrophysiological findings of the first case of a late-onset sporadic BVVLS in North Cyprus.

CASE PRESENTATION

Clinical History

A 47-year-old male presented with slurred speech, numbness of the mouth, and difficulty with swallowing. He reported that his symptoms had arisen during the previous 6 months. His neurologic examination revealed bifacial weakness, an atrophic tongue with fasciculation, and a weak gag reflex. However, sensory tests and deep tendon reflexes were within normal ranges.

In the following months, difficulty in swallowing and choking progressed, which caused weight loss. Atrophy and the fasciculations in the tongue became apparent (Figure 1). After one year, he had developed hearing loss in the left ear. His hearing deteriorated within two years, leading to total hearing loss on the left side and sensorineural hearing loss on the right side. With medical and symptomatic treatment, it has been four years since the diagnosis.

Investigations

There were no abnormalities in the biochemical laboratory tests. Acetylcholine receptor antibody test was found negative. The results of the abdomino-pelvic sonography, chest computed tomography scan, and brain magnetic resonance imaging did not show any abnormalities.

Electromyography (EMG) and nerve conduction studies showed the electrophysiological findings of lower motor neuron damage affected tongue and upper limb muscles on both sides with normal sensory and motor conduction values and chronic neurogenic MUAP changes in tongue, hand and arm muscles together with severely decreased interference pattern and spontaneous denervation activity in the hand muscles, while needle EMG findings of all abdominal and leg muscles were normal, as can be seen in Table 1.

The audiometry test revealed mild sensorineural hearing loss on the right side at high frequencies. However, on the left side, there was severe sensorineural hearing loss with non-measurable speech reception thresholds.

Medication

After the BVVLS diagnosis, the patient received intravenous immunoglobulin (IVIG) treatment at a dose of 0.4 g/kg for 5 days, followed by monthly repeated doses of 0.4 g/kg IVIG for one day for 6 months. However, this treatment did not result in any improvement in his symptoms.

He was also treated with 1,000 mg methylprednisolone for 10 days and continued to receive monthly steroid treatment after IVIG therapy. Although he experienced some improvement in swallowing and speech, it was limited.

In addition, he was prescribed riboflavin (B2) tablets at a daily dose of 300 mg. Supportive care and symptomatic treatment, such as botulinum toxin type A treatment for excessive salivation and a swallowing rehabilitation program were also administered. As a result, the patient’s clinical condition stabilized.

DISCUSSION

The rare neurological condition known as BVVLS, a type of motor neuron disorder, is characterized by bilateral hearing loss along with a number of other, primarily motor and cranial nerve dysfunctions.¹⁰ No definitive biochemical or genetic defect has been described, and its diagnosis is primarily dependent on clinical characteristics and electrophysiological tests.⁴ The clinical course of BVVL, which varies considerably from case to case, is one of the condition’s most intriguing characteristics. It can be fatal^9,10 or it can take a very long time to progress, with some patients still alive 20 to 30 years after the onset of the initial symptoms.^5,12 Respiratory failure is the leading cause of death. The condition can appear at any age, from infancy⁵ to the third decade,¹³ but it tends to manifest more frequently in the first and second decades.¹⁴ Our patient, however, had a late-onset of symptoms and was 47 years old. The disease can last from 0 (death at presentation) to 45 years.¹⁴

Nearly all instances begin with sensorineural deafness, which is typically severe and progressive over time. In our case, facial paralysis, slurred speech, and mouth numbness were the most prominent symptoms rather than hearing loss. The patient gradually lost his hearing. Although this is unusual, there have been a few instances where it has been documented in the literature. All of the cases^4,5,10,15,16 eventually developed hearing loss.

BVVL is frequently categorized among the vast array of motor neuron disorders. However, its erratic course and neurophysiological improvement contrast with the prevalent heredodegenerative disease of motor neurons’ more stable advance (slow or rapid).¹⁵

When making a differential diagnosis for BVVL, numerous alternative diseases should always be taken into consideration because they closely resemble BVVL. Another potential diagnosis is amyotrophic lateral sclerosis (ALS). However, sensorineural deafness is not a symptom of ALS, and ALS typically does not present at young ages.¹⁷

BVVL and the madras motor neuron disease (MMND) are also closely connected medical conditions. Sensorineural deafness, multiple cranial nerve palsies mainly affecting cranial nerves VII, IX, and XII, and muscular atrophy and weakness are all symptoms of MMND. The cranial nerves III and VI have not been observed in MMND. Compared to 50% of BVVL cases, only 15% of MMND patients are familial.¹⁶

Neurophysiological studies have shown alterations of chronic^{1,2,12,15,18-20} or active^1,13,17,21 denervation in muscles, but normal conduction velocities of the motor nerves. In our case, motor nerve conduction investigations were normal, but EMG showed persistent neurogenic alterations in the tongue, arm, and hand muscles along with active denervation.

A specific treatment for BVVL does not exist. In a few instances, steroids and immunoglobulins have been used. Two patients experienced brief stabilization. In the first, steroid treatment temporarily stabilized the situation for at least eight months.¹ Another patient who had IVIG had their illness stabilized for a year.²⁰ Two further patients who received IVIG did not, however, make any progress.¹⁸ In our situation, steroids stabilized the patient’s condition, while IVIG had no effect on the disease. The cornerstones of BVVL management are symptomatic and supportive care. However, the efficacy of the interventions can still be considered anecdotal when treating an uncommon ailment such as BVVL, since it is impossible to conduct randomized controlled trials with the insufficient number of patients available. Regardless, it is possible to generalize for BVVL from the experience of utilizing these treatments in other disorders which are similar, particularly ALS. For instance, in ALS, maintenance of nutrition and assisted ventilation have been shown to increase survival.¹⁷

It is critical that as BVVL instances are identified, these cases continue to be documented in the literature so that we can better understand this uncommon progressive neurological condition. Due to its rarity and similarities to other neurological illnesses, BVVLS is thought to be underdiagnosed and frequently misdiagnosed. We probably still do not fully understand the clinical range of BVVL. If more cases are reported in the literature, this will make it possible to give affected people and their families a better understanding of the clinical course, prognosis, and treatment of this crippling ailment. In order to contribute to the understanding of this disease, we described the clinical and neurophysiological characteristics of a patient with late-onset sporadic BVVLS in this case report. This is the first instance of BVVLS from Northern Cyprus to be reported.

MAIN POINTS

• The prevalence of BVVLS is estimated to be less than 1 in 1,000,000.

• Due to its rarity and similarities to other neurological illnesses, BVVLS is thought to be underdiagnosed and frequently misdiagnosed.

• The cornerstones of BVVL management are symptomatic and supportive care.

• This is the first instance of BVVLS from North Cyprus to be reported.

ETHICS

Informed Consent: It was obtained.

Peer-review: Externally peer-reviewed.

Authorship Contributions

Surgical and Medical Practices: F.S., M.E., Concept: F.S., M.E., Design: F.S., M.E., Data Collection and/or Processing: F.S., M.E., Analysis and/or Interpretation: F.S., M.E., Literature Search: F.S., M.E., Writing: F.S., M.E.

DISCLOSURES

Conflict of Interest: The authors have no conflicts of interest to declare.

Financial Disclosure: The authors declared that this study has received no financial support.