ALS dysphagia pathophysiology: differential botulinum toxin response.
OBJECTIVE
This study looked at the effect of botulinum toxin type A (BoTox-A) in patients with amyotrophic lateral sclerosis (ALS) with dysphagia due to isolated upper motor neuron (UMN) involvement or combined UMN/lower motor neuron (LMN) impairment associated with oral phase or oropharyngeal muscles involvement. Establishing whether different pathophysiologic mechanisms underlie different responses to BoTox-A treatment may have important implications for patient management.


METHODS
We screened 35 patients with sporadic ALS with dysphagia and included in the study 20 out of 35 with upper esophageal sphincter (UES) hyperactivity. We divided these 20 patients into 2 groups, based on the presence or absence of LMN impairment. Irrespective of the groups, we treated all 20 patients with BoTox-A injected into the UES. The study outcome was dysphagia severity scored using the Penetration/Aspiration Scale (PAS), measured before and 2, 4, and 20 weeks after injection.


RESULTS
Significant mean PAS reduction was noted at weeks 2 and 4. The botulinum-dependent PAS reduction was entirely associated with the variability shown by the group of patients with no sign of LMN impairment (group 2) and was not observed in group 1.


CONCLUSIONS
The significant improvement observed in patients with isolated UES dysfunction suggests that a different pathophysiology of ALS dysphagia predisposes patients to a different response to treatment with BoTox-A. This treatment may represent an alternative treatment to percutaneous endoscopic gastrostomy (PEG) or prolong PEG-free time.


METHODS
This study provides Class III evidence that botulinum is more effective at 2 and 4 weeks in improving dysphagia in patients with ALS with UES hyperactivity without LMN involvement (vs those with LMN involvement).
Neurologic Unit, Nuovo Garibaldi Hospital, Catania, Italy. darestivo@libero.it
Domenico A
DA
Restivo
Antonino
A
Casabona
Alessia
A
Nicotra
Mario
M
Zappia
Maurizio
M
Elia
Marcello C
MC
Romano
Enrico
E
Alfonsi
Rosario
R
Marchese-Ragona
D000367:Age Factors; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications*; D019274:Botulinum Toxins, Type A / Q000627:therapeutic use*; D003680:Deglutition Disorders / Q000188:drug therapy* / Q000209:etiology*; D004576:Electromyography; D049631:Esophageal Sphincter, Upper / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D005471:Fluoroscopy; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009465:Neuromuscular Agents / Q000627:therapeutic use*; D010609:Pharyngeal Muscles / Q000187:drug effects / Q000503:physiopathology; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D014741:Video Recording
D009465:Neuromuscular Agents; D019274:Botulinum Toxins, Type A