Dysphagia in patients with spinal muscular atrophy

Spinal muscular atrophy (SMA, or 5q SMA) is a severe hereditary (autosomal recessive) neuromuscular disease characterized by progressive muscle weakness, loss of muscle tissue and abnormal fatigability. Four types of SMA are distinguished, based on age at the appearance of the first symptoms and the highest achieved motor milestone (sitting independently and walking independently). SMA type 1 is the most severe and common form (an estimated 50% of new patients) and SMA type 4, is the least severe and least common form of SMA. It is possible that the mastication and swallowing muscles are also weakened in patients with SMA. This can lead to dysphagia. Dysphagia refers to a disturbance in the swallowing process (sucking, chewing and swallowing) and this affects efficiency and safety of swallowing. As of 2016, the introduction of medications for SMA has led to an improvement in survival and some recovery of motor development in young children with SMA. The studies in this thesis address the swallowing function of untreated children, adolescents and adults with SMA, and feeding problems in the first infants treated with nusinersen (Spinraza). We described self-reported bulbar problems experienced by patients with SMA type 1-4. The most common reported complaints were difficulty biting off a larger piece of food (34%), fatigability during mastication (44%), choking (56%) and a weak voice (27%). Patients with the milder forms of SMA reported increasing swallowing problems after the age of 30. We studied the mastication and swallowing function in adolescent and adult patients with SMA types 2 and 3, who experienced mastication and/or swallowing problems. The study was conducted with clinical mastication and swallowing tests, a video fluoroscopic swallowing study, and muscle ultrasound of the bulbar muscles. Non-ambulant patients masticated inefficiently. This was caused by muscle weakness and a limited maximum mouth opening, which reduced the ability of vertical and horizontal jaw movements to thoroughly grind the food. Another characteristic was abnormal fatigability of the masticatory muscles. Ambulant patients had a mastication function comparable to healthy subjects. However, there was abnormal fatigability of the mastication muscles. Non-ambulant patients swallowed inefficiently. They had a limited swallowing volume. During the video fluoroscopic swallowing study, we observed inefficient swallowing with residue in the hypopharynx and an increased number of swallows when swallowing a standardized bolus. We found a striking phenomenon during the video fluoroscopic swallowing study, described as pharyngo-oral regurgitation. The bolus was transported back to the mouth after reaching the pharynx. It is probably caused by muscle weakness in the pharyngeal phase of swallowing, resulting in an insufficient propulsion of the tongue and pharynx during swallowing. Some patients swallowed unsafely (in other words, food ended up in the airway). Remarkably, this was not accompanied by coughing. This means that unsafe swallowing in these patients can go unnoticed in daily practice. Ambulant patients had a swallowing volume and swallowing speed for water comparable to normal subjects. However, on the video fluoroscopic swallowing study, residue remained in the hypopharynx. Muscle ultrasound of the masticatory, submental and tongue muscles showed an abnormal muscle structure in almost all patients, both in non-ambulant and ambulant patients. Infants with the most severe form of SMA became easily exhausted from drinking and there was an increased risk of choking. Infants with SMA who were treated with the new SMA drug nusinersen demonstrated an improvement of the motor function, but the treatment did not permanently improve the swallowing function. The thesis ends with recommendations for the care and treatment of dysphagia in infants, adolescents and adults with SMA.