Couple of more abstracts at the ECTRIMS.
Thursday, September 10, 2009, 15:15 - 15:30
Fampridine-SR for cognitive improvement in multiple sclerosis
K. Edwards, W. Goodman, A. Button (Latham, US)
Background: Fampridine has been shown to improve walking in large controlled studies in multiple sclerosis (MS) patients. The mechanism of action is proposed to be via closure of potassium channels through demyelinated axons. In studies of cognitive dysfunction in MS patients with impaired neuropsychological function, fMRI studies have shown that there is a delay of conduction through demyelinated segments. It is reasonable to postulate that if Fampridine-SR can improve motor function in some MS patients by improving conduction velocity through demyelinated central nervous system neurons to leg muscles, then Fampridine-SR might be able to improve cognitive function by improving conduction velocity in interconnecting neurons involved in cognitive function in cortical and subcortical regions of the brain.
Goals: To determine whether Fampridine-SR can be shown to improve cognitive function in MS patients with cognitive impairment.
Methods: MS patients with cognitive impairment who participated in the Fampridine-SR studies at our site (MS-F203 and MS-F204), and who also had taken a comprehensive neuropsychological battery before beginning the blinded part of the study and who had taken a repeat neuropsychological battery at least 3 months after being enrolled in the open-label extension studies, were indentified. An impairment rating was assigned to each patient based on the results of each of 10 neuropsychological tests specific for the cognitive deficits typical in MS.
Results: Ten patients were identified who had reliable neuropsychological testing before entering either the MS-F203 or MS-F204 study and who had repeated neuropsychological testing more than 3 months on open-label Fampridine-SR 10 mg twice daily. Of these 10 patients, 6 showed significant improvement in cognition, 2 were unchanged and 2 showed mild decline. Overall, the impairment ratings of the 10 patients showed improvement favorable to Fampridine-SR compared to their pre-treatment status (p=0.05).
Conclusions: Fampridine-SR may be useful in the management of MS patients with cognitive impairment. Prospective, controlled studies are needed.
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And they provided info on the QTc study. Nothing new as far as I can see.
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Plus...
Friday, September 11, 2009, 15:30 - 17:00
Electroencephalogram epileptiform activity in multiple sclerosis patients without a history of seizures
C. Riley, A.D. Goodman, A. Warsi, J. Smrtka, L. Marinucci, M. Tullman (New York, Rochester, Hawthorne, Fort Lauderdale, US)
Objective: To determine the prevalence of epileptiform activity in multiple sclerosis (MS) patients.
Background: Most studies have found that the prevalence of epilepsy in MS patients is about 3–8 times greater than the general population. However, a recent study concluded that MS is not a significant risk factor for seizures. Electroencephalogram (EEG) epileptiform activity occurs in about 0.5% of healthy individuals. There is a paucity of EEG data in MS patients.
A phase 2 and two phase 3 trials recently examined the effects of a sustained-release formulation of fampridine (4-aminopyridine) on strength and ambulation in patients with all forms of MS. Because 4-aminopyridine has been associated with a risk of seizures, especially at doses higher than 10 mg bid, patients with epileptiform activity on a screening EEG or prior seizures were excluded from these trials. This provided an opportunity to determine the prevalence of epileptiform activity in a large MS cohort.
Methods and results: Case report forms for all patients screened in the fampridine phase 2 (n=271) and phase 3 (n=763) MS trials were reviewed. The prevalence of epileptiform activity was determined.
255/1034 patients did not fulfill other inclusion criteria and were excluded from the trials before having an EEG. The remaining 779 patients underwent a standard EEG. Epileptiform activity was present in 33/779 patients (4.2%). In a preliminary analysis with data from the phase 2 and first phase 3 studies, age, disease duration, Expanded Disability Status Scale (EDSS) score, and MS type were not associated with an increased risk of epileptiform activity. However, women were significantly more likely than men to have epileptiform activity.
Conclusions: In this large cohort of MS patients without a history of seizures, EEG epileptiform activity occurred in 4.2% of individuals, which is about eight times greater than what is reported in healthy individuals. These data provide evidence supporting an increased risk of seizures in MS. Additional analyses that will include baseline demographic and clinical characteristics of patients from the second phase 3 trial will be presented. |
