Otolaryngologist’s role in the diagnosis of amyotrophic lateral sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive and late-onset fatal neurodegenerative disease characterised by selective death of motor neurons. The aetiology of ALS is still unknown and it is extremely heterogeneous in genetics and clinical presentation, being the respiratory failure the usual cause of death. We describe a case of a 61-year-old male patient referred to the otolaryngology consultation for a 6-month history of progressive solid dysphagia and dysphonia. The patient presented several voice alterations such as a dysarthric speech with hypernasal voice which evoked the hypothesis of a neuromuscular disease. That patient was observed by a neurologist and was submitted to an electromyography that confirmed the ALS diagnosis. This case highlights the key role of otolaryngologists in the diagnosis of ALS, in a way that many patients with a bulbar ALS form are initially studied by an otolaryngologist.

Background

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by a progressive loss of the upper and lower motor neurons at the cortex, brainstem and spinal cord.¹ ALS is the most common adult motor neuron disorder with an incidence of 1–2/100.000 and prevalence of 5.4/100.000 individuals.² Onset typically occurs in late middle life between the ages of 50 and 65 years and there is a predominance of the male gender, with a ratio of 1.4:1.^{2 3} The definitive aetiology of ALS is still unknown but there are two types of ALS: in 90%–95% of patients, the form of the disease is sporadic, with no clear genetically inherited component; the remaining 5%–10% of the cases are familiar due to their associated genetic dominant inheritance factor.⁴

The clinical presentation of the disease is significantly heterogeneous but usually the disease manifests itself as a progressive muscular atrophy, lateral sclerosis, pseudobulbar and bulbar palsy in various combinations.⁵

The different ALS phenotypical expressions are usually classified as: limb-onset ALS with a combination of upper motor neuron (UMN) and lower motor neuron (LMN) signs in the limbs; bulbar-onset ALS with speech and swallowing difficulties followed by limb weakening in later stages of the disease.⁶ However, ALS may also present as a pseudobulbar syndrome that differs from bulbar palsy by the UMN involvement with a lack of facial expression, difficulty chewing, emotional lability, spastic tongue, exaggerated gag reflex and jaw jerk reflexes.⁷

The most common onset symptoms are muscular atrophy in the extremities, weakness, fasciculations and cramping and, typically in end-stage disease, a cranial nerve or bulbar involvement and symptoms such as dysarthria, dysphonia and dysphagia will show up.⁸ However, up to 28% of patients will initially report bulbar symptoms⁵ and at least 35% of patients with bulbar-onset ALS see an otolaryngologist at presentation.⁹

Despite examination findings which may include weakness and fasciculations of the facial muscles, palate or tongue, dysarthric features and voice changes as hypernasal, breathy, strained or harsh,^{5 10} ALS is infrequently diagnosed in an otolaryngology practice because recognising its manifestations presents a significant challenge.³

Usually the respiratory failure is the cause of death of patients with ALS and occurs approximately 2–4 years after disease onset in most cases.² Of the patients, 20% will survive beyond 5 years and 10% will survive beyond 10 years.¹¹

Current treatment options are based on symptom management and respiratory support, which provides a modest benefit for some patients.¹²

The present case report brings awareness of the necessity of a high index of suspicion in the otolaryngology consultation to consider the diagnosis of ALS in patients with minimal bulbar symptoms.

Case presentation

A 61-year-old man, with a personal antecedent of pulmonary tuberculosis and chronic smoking and alcohol habits, was referred to an otolaryngology consultation with 6 months of progressive dysphonia, solid dysphagia and weight loss of 15 kg. The patient also described a loss of lower limb muscle strength with frequent falls. The otolaryngological physical examination, complemented with flexible nasofibroscopy, has shown some tongue atrophy and fasciculations and a global hypomobility of pharyngo-laryngeal structures; there was no evidence of tumorous or infectious lesions. The patient underwent an upper digestive endoscopy, which showed a hypomobility of the oesophageal muscles and decreased gastric peristalsis, having excluded the presence of mechanical obstruction as the cause of dysphagia. The basic analytical study that was also carried out did not identify anaemia, elevated inflammatory parameters, changes in renal function or liver function.

The patient was referred to speech therapy and the therapist described a tense breathing pattern and a low inspired air volume, a dysarthric speech with hypernasal voice, little pitch variation, decreased loudness and average phonation time, changes in prosody as short sentences, decreased debit in prolonged phonation, decreased intonation and prolonged speech breaks. It was also noticeable the patient had difficulty in controlling saliva swallowing during speech.

Given the motor changes identified, the patient was referred to a neurology consultation. In addition to some minor asymmetries in the degrees of muscle strength, a significant bilateral periscapular amyotrophy, fasciculations in various muscle groups, hyper-reflexia and positive extensor plantar response have been described.

Investigations

Additionally, the patient had already undergone extensive investigations. A fibre-optic endoscopic evaluation of swallowing was performed and has shown weakness and fatigue of oropharyngeal and laryngeal muscles with laryngeal hyposensitivity and weakened cough reflex leading to an inability to prevent laryngeal penetration and consequent aspiration.

A cranial CT and an MRI were performed whose results were normal. The patient was also submitted to a cervical and limb electromyography that showed a pattern of extensive multifocal neurogenic atrophy, with active denervation criteria, affecting the lumbosacral, thoracic, cervical and bulbar segments with predominance of the left hemibody. A more extensive blood and urine analytical study did not show anaemia, vitamin deficiencies or thyroid function anomalies; the autoimmune study was normal and all the serologies came back negative.

The diagnosis of ALS was assumed, and the patient started a pharmacological treatment with riluzol, vitamin supplements and calcium. Counselling about dysphagia and safe swallowing techniques were performed and the patient was referred also to a nutrition and pneumology consultations.

Outcome and follow-up

Three months after the diagnosis, the disease progressed with a clinical worsening of dysphagia and dyspnoea, decline of left hemibody muscle strength and a progressive respiratory tiredness, which conditioned a type II respiratory failure without acidaemia. A respiratory infection and other decompensation causes were ruled out and a progression of the underlying ALS was assumed as the cause of clinical situation. The patient was hospitalised for 12 days in the intensive care unit and 3 days in medicine department for implementing a complete rehabilitation programme. From the respiratory point of view, the patient initiated an intensive respiratory rehabilitation programme with cough-assist, non-invasive ventilation (NIV) in the first 24 hours of hospitalisation with Philips Trilogy Ventilator, with a significative improvement of pulmonary function. It was decided to realise a percutaneous endoscopic gastrostomy to feed the patient; and after a urinary retention episode, the patient was numbed and treated with tamsulosin. Because it is a rapidly progressive, limiting disease with poor prognosis, the medical team agreed to signalise the patient to palliative care and to reference him to physiatry, psychology and ventilotherapy consultations.

Currently, the patient keeps the pharmacology treatment with riluzol, analgesia, tamsulosin and vitaminic supplements; he also maintains the cough assist, the airstacking and NIV.

So far, the patient is followed by different specialty doctors, is partially autonomous in self-care and has not had additional episodes of ALS decompensation.

Discussion

ALS was first described by Jean-Martin Charcot in 1869 as an association of progressive muscular atrophy and sclerosis of the lateral column.¹³ It became famous in 1939 when a North American baseball player was diagnosed with the disease,¹⁴ and then Charcot’s original concept of ALS has been broadened to include a spectrum of neuromuscular disease from progressive bulbar palsy, the wasting of the muscles innervated by cranial nerves to primary lateral sclerosis, spasticity and hyper-reflexia without muscle wasting.⁵

There is no single diagnostic test for ALS. ALS is largely a clinical diagnosis, defined via the El Escorial and subsequently revised El Escorial/Airlie House Criteria by the following three factors: (1) evidence of LMN degeneration (either on examination or through specialised testing), (2) evidence of UMN disease on examination and (3) the presence of either of the above in more than one region of the body.¹⁵ In addition, the course must be progressive with no evidence of a reasonable alternative diagnosis.

Up to 25% of patients with ALS present with oropharyngeal symptoms and, because of that, a significant number of undiagnosed patients with ALS are referred at presentation to otolaryngologists. The problem is that the average time taken from symptom onset to diagnosis in motor neuron disease is many months and has shown no sign of improving despite the introduction of riluzole therapy.¹⁶

Studies from the 1990s to 2020 have mostly reported ALS diagnostic delays of 10–16 months,^{17 18} although establishment of clinical criteria and growing public awareness of ALS do not appear to be associated with a reduction in the time required for diagnosis.⁹ The reasons that may justify the late diagnosis are delays from referrals to specialists, in a way that only about 60% of initial specialist referrals are to neurologists and the remaining were referred to other specialties such as Ear, Nose and Throat doctors, orthopaedists and rheumatologists.¹⁹ The misdiagnosis is also an important factor for diagnostic delay, as there is an incorrect diagnosis rate of 13%–68%.²⁰ Clinical presentation also plays a role in ALS diagnostic delay because patients with bulbar disease form appear to be diagnosed 4 months earlier than patients with the spinal onset.^{20 21} Age may be relevant too, in a way that patients older than 60 years were more likely to be misdiagnosed initially compared with younger ones (48% vs 16%, respectively).¹⁷ Finally, patients with neurological comorbidities are associated with a delay in ALS diagnosis of nearly 20 months, compared with 11 months for patients without known neurological pathology.¹⁹

A complete differential diagnosis must be considered since the non-specific symptoms such as dysphagia and dysphonia can be the form of presenting of totally different pathologies with completely different approaches. Often, it is common that otolaryngologist hypothesises a malignant aetiology for the patient’s reports, due to the frequency of this type of pathology in clinical practice and the fact that often patients with ALS are smokers, as in the presented case report. A vascular disease rather than a neurodegenerative one is also frequently equated, given the age of the patient (epidemiologically, patients with bulbar-onset ALS are older than those with spinal onset ALS). However, the absence of structural abnormalities in the objective examination, the absence of changes in upper digestive endoscopy and the description of the patient’s breathing pattern and prosody by speech therapist are important for the otolaryngologist to raise alternative diagnostic hypothesis as neuromuscular pathology, which favours the referral to the neurology consultation, highlighting the role that the otolaryngologist plays in shortening the diagnostic process.

The support of the speech therapist is essential since the therapist can use recordings, manometrics, cinefluoroscopy pharyngeal studies and voice prints to identify, document and objectively grade articulation errors, velopharyngeal incompetence and breathiness. Carrow et al published a review of 69 patients with ALS, of which 99% had speech abnormalities, being the harshness (80%), hypernasality (75%) and breathiness (65%) the most common problems.^{13 22}

In the case reported, there was not personal or familiar history of neurological disease but the patient had heavy smoking habits and cigarette smoke has been found to increase the probability of developing ALS through inflammation, oxidative stress and neurotoxicity by heavy metals contained in cigarettes.¹⁴ Relatively recent reports of solid dysphagia, dysphonia and weight loss in a smoker always make clinicals think about a tumour; however, given that in this patient the physical examination did not identify any neoformation, the reference to the speech therapist was fundamental to ALS diagnosis suspicion, which was confirmed after neurological evaluation and electromyography. In the literature, about 42% of patients with bulbar ALS primarily evaluated by otolaryngologists have an incorrect diagnosis.³ That can be explained by the low incidence, non-specificity and indolent course of symptoms.³ Thus, in the observation of the patient, it is essential to evaluate not only the characteristics that correspond to the otorhinolaryngological symptoms, but also the aforementioned physical signs that may help to define the diagnostic suspicion. In the case presented, the patient has already reported about loss of lower limb muscle strength and frequent falls, which should have raised the hypothesis of a neuromuscular disease.

Although treatment and prognosis are unfavourable, precocious diagnosis allows the patient and his family dealing with the morbidities of the disease. Thus, multidisciplinary follow-up is imperative, not only for early diagnosis, but also for symptomatic control that slows down the progression of the disease.

Learning points.

• Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease that limits the patient quality of life.

• Although voice symptoms caused by ALS are rare in the otolaryngology practice, in the early insidious phase of ALS, a significant proportion of patients with ALS with primarily bulbar features will initially see an otolaryngologist (Ear, Nose and Throat/ENT).

• Dysarthria, tongue fasciculations, dysphonia and incomplete vocal fold closure are a constellation of findings which increase suspicion of neuromuscular disease.

• ENT plays a key role in the diagnosis of ALS and must keep a high index of suspicion for this disease.

• Vigilance for ALS in the differential diagnosis of voice disturbance may quicken the diagnosis of this motor neuron disease and expedite symptom management.