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February 12, 2013; 80 (7) Article

ALS dysphagia pathophysiology

Differential botulinum toxin response

Domenico A. Restivo, Antonino Casabona, Alessia Nicotra, Mario Zappia, Maurizio Elia, Marcello C. Romano, Enrico Alfonsi, Rosario Marchese-Ragona
First published January 23, 2013, DOI: https://doi.org/10.1212/WNL.0b013e318281cc1b
Domenico A. Restivo
From the Neurologic Unit (D.A.R.), “Nuovo Garibaldi” Hospital, Catania; Department of Bio-Medical Sciences, Section of Physiology (A.C.), and Department “G.F. Ingrassia” Area of Neurosciences (M.Z.), University of Catania, Catania, Italy; Department of Clinical Neurophysiology (A.N.), Imperial College Healthcare, London, UK; Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS) (M.E.), Troina; Neurological Division (M.C.R.), “Villa Sofia” Hospital, Palermo; Fondazione Istituto “C. Mondino” IRCCS (E.A.), Pavia; and ENT Department (R.M.-R.), University of Padova, Padova, Italy.
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Antonino Casabona
From the Neurologic Unit (D.A.R.), “Nuovo Garibaldi” Hospital, Catania; Department of Bio-Medical Sciences, Section of Physiology (A.C.), and Department “G.F. Ingrassia” Area of Neurosciences (M.Z.), University of Catania, Catania, Italy; Department of Clinical Neurophysiology (A.N.), Imperial College Healthcare, London, UK; Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS) (M.E.), Troina; Neurological Division (M.C.R.), “Villa Sofia” Hospital, Palermo; Fondazione Istituto “C. Mondino” IRCCS (E.A.), Pavia; and ENT Department (R.M.-R.), University of Padova, Padova, Italy.
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Alessia Nicotra
From the Neurologic Unit (D.A.R.), “Nuovo Garibaldi” Hospital, Catania; Department of Bio-Medical Sciences, Section of Physiology (A.C.), and Department “G.F. Ingrassia” Area of Neurosciences (M.Z.), University of Catania, Catania, Italy; Department of Clinical Neurophysiology (A.N.), Imperial College Healthcare, London, UK; Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS) (M.E.), Troina; Neurological Division (M.C.R.), “Villa Sofia” Hospital, Palermo; Fondazione Istituto “C. Mondino” IRCCS (E.A.), Pavia; and ENT Department (R.M.-R.), University of Padova, Padova, Italy.
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Mario Zappia
From the Neurologic Unit (D.A.R.), “Nuovo Garibaldi” Hospital, Catania; Department of Bio-Medical Sciences, Section of Physiology (A.C.), and Department “G.F. Ingrassia” Area of Neurosciences (M.Z.), University of Catania, Catania, Italy; Department of Clinical Neurophysiology (A.N.), Imperial College Healthcare, London, UK; Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS) (M.E.), Troina; Neurological Division (M.C.R.), “Villa Sofia” Hospital, Palermo; Fondazione Istituto “C. Mondino” IRCCS (E.A.), Pavia; and ENT Department (R.M.-R.), University of Padova, Padova, Italy.
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Maurizio Elia
From the Neurologic Unit (D.A.R.), “Nuovo Garibaldi” Hospital, Catania; Department of Bio-Medical Sciences, Section of Physiology (A.C.), and Department “G.F. Ingrassia” Area of Neurosciences (M.Z.), University of Catania, Catania, Italy; Department of Clinical Neurophysiology (A.N.), Imperial College Healthcare, London, UK; Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS) (M.E.), Troina; Neurological Division (M.C.R.), “Villa Sofia” Hospital, Palermo; Fondazione Istituto “C. Mondino” IRCCS (E.A.), Pavia; and ENT Department (R.M.-R.), University of Padova, Padova, Italy.
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Marcello C. Romano
From the Neurologic Unit (D.A.R.), “Nuovo Garibaldi” Hospital, Catania; Department of Bio-Medical Sciences, Section of Physiology (A.C.), and Department “G.F. Ingrassia” Area of Neurosciences (M.Z.), University of Catania, Catania, Italy; Department of Clinical Neurophysiology (A.N.), Imperial College Healthcare, London, UK; Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS) (M.E.), Troina; Neurological Division (M.C.R.), “Villa Sofia” Hospital, Palermo; Fondazione Istituto “C. Mondino” IRCCS (E.A.), Pavia; and ENT Department (R.M.-R.), University of Padova, Padova, Italy.
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Enrico Alfonsi
From the Neurologic Unit (D.A.R.), “Nuovo Garibaldi” Hospital, Catania; Department of Bio-Medical Sciences, Section of Physiology (A.C.), and Department “G.F. Ingrassia” Area of Neurosciences (M.Z.), University of Catania, Catania, Italy; Department of Clinical Neurophysiology (A.N.), Imperial College Healthcare, London, UK; Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS) (M.E.), Troina; Neurological Division (M.C.R.), “Villa Sofia” Hospital, Palermo; Fondazione Istituto “C. Mondino” IRCCS (E.A.), Pavia; and ENT Department (R.M.-R.), University of Padova, Padova, Italy.
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Rosario Marchese-Ragona
From the Neurologic Unit (D.A.R.), “Nuovo Garibaldi” Hospital, Catania; Department of Bio-Medical Sciences, Section of Physiology (A.C.), and Department “G.F. Ingrassia” Area of Neurosciences (M.Z.), University of Catania, Catania, Italy; Department of Clinical Neurophysiology (A.N.), Imperial College Healthcare, London, UK; Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS) (M.E.), Troina; Neurological Division (M.C.R.), “Villa Sofia” Hospital, Palermo; Fondazione Istituto “C. Mondino” IRCCS (E.A.), Pavia; and ENT Department (R.M.-R.), University of Padova, Padova, Italy.
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Citation
ALS dysphagia pathophysiology
Differential botulinum toxin response
Domenico A. Restivo, Antonino Casabona, Alessia Nicotra, Mario Zappia, Maurizio Elia, Marcello C. Romano, Enrico Alfonsi, Rosario Marchese-Ragona
Neurology Feb 2013, 80 (7) 616-620; DOI: 10.1212/WNL.0b013e318281cc1b

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Abstract

Objectives: 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.

Patients and 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.

Classification of evidence: 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).

GLOSSARY

ALS=
amyotrophic lateral sclerosis;
BoTox-A=
botulinum toxin type A;
CP=
cricopharyngeal;
IC=
inferior constrictor;
LMN=
lower motor neuron;
MS=
multiple sclerosis;
PAS=
Penetration/Aspiration Scale;
PD=
Parkinson disease;
PEG=
percutaneous endoscopic gastrostomy;
UES=
upper esophageal sphincter;
UMN=
upper motor neuron

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received March 10, 2012.
  • Accepted October 11, 2012.
  • © 2013 American Academy of Neurology
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