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R G Miller,
D H Moore,
V Dronsky,
W Bradley,
R Barohn, W Bryan,
T W Prior,
D F Gelinas,
S Iannaccone,
J Kissel,
R Leshner,
J Mendell,
M Mendoza,
B Russman,
F Samaha,
S Smith
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ABSTRACT: To evaluate the efficacy of gabapentin in increasing muscle strength of patients with spinal muscular atrophy (SMA).
Preclinical data in experimental models of motor neuron disease suggest a neuroprotective effect of gabapentin.
Gabapentin (1200 mg), or placebo, was administered three times daily in a randomized, double-blind trial for 12 months. The primary outcome measure was the average percent change from baseline, based on the measurement of strength in four muscles (elbow flexion and hand grip bilaterally) for each patient. Drug efficacy was examined by comparing the percent change in strength for patients on drug vs. placebo. Secondary efficacy variables included: forced vital capacity (FVC), SMA functional rating scale (SMAFRS), and mini-Sickness Impact Profile (SIP).
Eighty-four patients, with type II or III SMA, were enrolled at eight sites across the United States. There were no differences in baseline features. There was no difference between the placebo and drug groups in any outcome measure.
This study demonstrates the feasibility of this trial design and provides data for the design of future clinical trials in SMA.
Journal of the Neurological Sciences 11/2001; 191(1-2):127-31. · 2.35 Impact Factor
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R G Miller,
D H Moore,
D F Gelinas,
V Dronsky,
M Mendoza,
R J Barohn, W Bryan,
J Ravits,
E Yuen,
H Neville, [......],
W Johnson,
R Mandler,
P Bosch,
B Smith,
M Graves,
M Ross,
E J Sorenson,
P Kelkar,
G Parry,
R Olney
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ABSTRACT: Preclinical and clinical studies of gabapentin in patients with ALS led the authors to undertake a phase III randomized clinical trial.
Patients were randomly assigned, in a double-blinded fashion, to receive oral gabapentin 3,600 mg or placebo daily for 9 months. The primary outcome measure was the average rate of decline in isometric arm muscle strength for those with two or more evaluations.
Two hundred four patients enrolled, 196 had two or more evaluations, and 128 patients completed the study. The mean rate of decline of the arm muscle strength was not significantly different between the groups. Moreover, there was no beneficial effect upon the rate of decline of other secondary measures (vital capacity, survival, ALS functional rating scale, timed walking) nor was there any symptomatic benefit. In fact, analysis of the combined data from the phase II and III trials revealed a significantly more rapid decline of forced vital capacity in patients treated with gabapentin.
These data provide no evidence of a beneficial effect of gabapentin on disease progression or symptoms in patients with ALS.
Neurology 05/2001; 56(7):843-8. · 8.31 Impact Factor
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V Sansone,
R C Griggs,
G Meola,
L J Ptácek,
R Barohn,
S Iannaccone, W Bryan,
N Baker,
S J Janas,
W Scott,
D Ririe,
R Tawil
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ABSTRACT: A previous study of 4 patients defined Andersen's syndrome (AS) as a triad of potassium-sensitive periodic paralysis, ventricular dysrhythmias, and dysmorphic features. AS appears to be distinct in terms of its genetic defect from the alpha-subunit of skeletal muscle sodium channel and the cardiac potassium channel responsible for most long QT syndromes (LQT1). We studied 11 additional patients with AS from 5 kindreds. Spontaneous attacks of paralysis were associated with hypokalemia, normokalemia, or hyperkalemia. All 11 patients had similar dysmorphic features. The QT interval was prolonged in all patients although only 4 were symptomatic. Genetic linkage studies excluded linkage to the alpha-subunit of the skeletal muscle sodium channel and to four distinct LQT loci. In addition, none of the common dihydropyridine receptor mutations responsible for hypokalemic periodic paralysis were present. We conclude that (1) AS is a genetically unique channelopathy affecting both cardiac and skeletal membrane excitability, (2) attacks of paralysis may be either hypokalemic or hyperkalemic, (3) a prolonged QT interval is an integral feature of this syndrome, and (4) a prolonged QT interval may be the only sign in an individual from an otherwise typical AS kindred. This may be confused with more common, potentially lethal LQT syndromes.
Annals of Neurology 10/1997; 42(3):305-12. · 11.09 Impact Factor
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ABSTRACT: The Tufts Quantitative Neuromuscular Exam (TQNE) is a standardized tool for measuring muscle strength and pulmonary function in patients with amyotrophic lateral sclerosis (ALS). We describe the relationship of TQNE scores to functional disability and health-related quality of life as measured by the Sickness Impact Profile (SIP) in 524 ALS patients. There was a significant relationship (p < 0.0001) between TQNE and SIP scores, both in cross section and over time. TQNE scores strongly relate to ALS patients' quality of life and ability to perform activities of daily living.
Neurology 05/1996; 46(5):1442-4. · 8.31 Impact Factor
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ABSTRACT: Using 42 strength and functional assessments recorded monthly, the natural history of amyotrophic lateral sclerosis (ALS) is described in 167 patients (98 men, 67 women) followed in five medical centers in the western United States. The mean age at onset was 57.4 years, and symptoms were present for 2.64 years before study entry. Although there was a highly variable rate of decline within the group of patients, there were no differences in rate of decline by age or gender. Older patients and women were weaker on entry. Forty-eight patients died during the study. The median survival was 4.0 years for the study cohort but 2.1 years for newly diagnosed cases. Decline in pulmonary function most closely correlated with death. Our results emphasize the importance of considering clinical variability in planning clinical trials. One possible strategy is to identify and stratify patients by rate of decline in pulmonary function since prospectively identifying homogeneous subgroups allows investigators to substantially reduce sample size in therapeutic trials.
Neurology 08/1993; 43(7):1316-22. · 8.31 Impact Factor
