***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: In an earlier study , we demonstrated efficacy of single oral doses of 4-aminopyridine ( 4-AP ) in improving motor and visual signs in multiple sclerosis ( MS ) patients for a mean of 4.97 hours . We attempted to determine whether efficacy could safely be prolonged using multiple daily doses over several days by administering 7.5 to 52.5 mg 4-AP to 17 temperature-sensitive MS patients in one to three daily doses at 3- to 4-hour intervals over 1 to 5 days in a double-blind study . Nine of these patients were also tested with identically appearing placebo .  Thirteen of the 17 patients ( 76 % ) given 4-AP showed clinical ly important motor and visual improvements compared with three of nine in the placebo group . Average peak improvement scores were 0.40 for 4-AP and 0.12 for placebo . Seventy percent of the daily 4-AP  improvements lasted 7 to 10 hours . The improvements for two consecutive doses of 4-AP lasted a mean of 7.07 hours ( 83 % of the average 8.53-hour treatment-observation period ) compared with 2.36 hours for placebo ( 26 % of the average 9.06-hour treatment-observation period ) . No serious side effects occurred . 4-AP is a promising drug for the symptomatic treatment of MS We performed magnetic resonance imaging and magnetic resonance spectroscopic imaging on 28 patients with multiple sclerosis stratified for disability and clinical course ( relapsing with at least partial remissions or secondary progressive disease ) . Lesions were segmented on the conventional proton density and T2‐weighted magnetic resonance images , and lesion distribution images were generated for each patient . The conventional magnetic resonance and spectroscopic images were transformed into a st and ard brain‐based stereotaxic coordinate space , allowing comparison of images from different patients on a voxel‐by‐voxel basis . The spatial distribution of lesions in the transformed magnetic resonance images did not differ significantly between the relapsing and the progressive disease groups . We then generated from the individual data sets , group lesion probability distribution images for the relapsing and the progressive disease groups . The spatial distribution of metabolites was characterized with respect to lesion distribution using the magnetic resonance spectroscopic images transformed into stereotaxic space and averaged . The neuronal marker N‐acetylaspartate was diffusely lower in the multiple sclerosis patients than in normal control subjects . Comparison of the averaged metabolite and T2‐weighted lesion probability images confirmed loss of N‐acetylaspartate in regions of both high and low lesion probability . This suggests that diffuse axonal volume loss or dysfunction extends beyond the inflammatory lesions of multiple sclerosis , perhaps due to microscopic disease or wallerian degeneration along projection pathways of axons traversing the lesions Objective To evaluate the efficacy of 4-aminopyridine sustained release ( 4AP SR ) ( fampridine , EL-970 ) using quantitative measures of motor function in multiple sclerosis ( MS ) patients . Background In vitro , 4AP improves conduction through demyelinated axons . A previous multicenter trial of 4AP SR using the Exp and ed Disability Status Scale ( EDSS ) as the primary outcome was unable to establish clinical efficacy . Design / Methods Ten MS patients with stable motor deficits ( EDSS 6.0–7.5 ) were given 4AP SR 17.5 mg bid and placebo for 1 week each in a double-blind , placebo-controlled , crossover trial . Time to walk 8 meters , time to climb four stairs , maximum voluntary isometric contraction measured quantitatively ( MVICT ) , manual muscle testing ( MMT ) , grip strength , EDSS , and the patient 's global impression were measured . Results Timed gait was improved on 4AP SR compared with placebo in 9 of 10 subjects ( p = 0.02 ) . Timed stair climbing , MVICT , MMT , grip strength , and EDSS showed nonsignificant improvements on 4AP SR . Based on their global impressions , seven subjects preferred 4AP SR over placebo ; only one preferred placebo . There were no serious side effects .  Conclusion 4AP SR  improved motor function in MS patients . The quantitative outcomes used in this study permit more sensitive evaluation of the therapeutic effect and promise to be useful in future trials of symptomatic treatments for MS To examine the efficacy and toxicity of oral 3,4 diaminopyridine ( DAP ) in dosages up to 100 mg/day , 36 patients with multiple sclerosis ( MS ) enrolled in a r and omized , double-blind , placebo-controlled , crossover trial . The primary outcome measure was improvement of a prospect ively defined neurologic deficit , which was leg weakness in 34 patients . Secondary outcome measures included the patient 's subjective response , scored manual motor testing ( MMT ) of leg strength , scored leg strength from videotaped motor testing ( VMT ) , quadriceps and hamstrings strength ( QMT ) measured by isometric dynamometry , neuropsychological testing ( NPT ) , ambulation index ( AI ) , and Exp and ed Disability Status Scale ( EDSS ) score . Paresthesias and abdominal pain were common and were dose limiting in eight patients . Three patients had episodes of confusion , and one patient had a seizure while on DAP . Eight patients withdrew from the study , leaving 28 evaluable patients for the efficacy analysis . The prospect ively defined neurologic deficit improved in 24 patients -22 on DAP and 2 on placebo ( p = 0.0005 ) . All improvements were in leg weakness . Subjective response and measures of leg strength and function ( MMT , VMT , QMT , and AI ) improved on DAP compared with placebo . Neither NPT nor EDSS scores improved . DAP treatment can induce improvements in leg strength in MS patients , but toxicity is limiting in many patients . NEUROLOGY 1996;47 : 1457 - Because 4-aminopyridine ( AP ) improves residual deficits in some multiple sclerosis ( MS ) patients but has a narrow toxic-to-therapeutic margin , we compared the safety and efficacy of two target peak serum concentration ranges ( low : 30 to 59 ng/ml and high : 60 to 100 ng/ml ) . We enrolled eight MS patients with temperature-sensitive visual and motor deficits in a r and omized , placebo-controlled , double-blind , crossover trial of short-term oral AP treatment . We r and omized patients to a sequence of three treatments on three separate days : placebo , low serum concentration , and high serum concentration . We determined dosing to achieve the desired steady-state peak serum concentration ranges from a test dose and population pharmacokinetic parameters using bayesian estimation . Contrast sensitivity , st and ard neurologic examination , ratings of videotaped neurologic examinations , and quantitative strength assessment all improved with treatment , but flicker fusion frequency , visual evoked response latencies , and Exp and ed Disability Status Scale scores did not . All patients experienced side effects during the high-serum-concentration arm . A gr and mal seizure occurred at a serum AP level of 104 ng/ml , and an acute confusional episode occurred at 114 ng/ml . AP treatment produced improvements in residual deficits in MS patients , but the occurrence of significant toxicity suggests that AP serum levels should be monitored and peak levels above 100 ng/ml should be avoided . Concentration-control methodology may be useful in testing putative treatments for other neurologic diseases In a recent r and omized , double-blind , placebo-controlled crossover trial , we demonstrated efficacy of 4-aminopyridine ( 4-AP ) in improving disability of patients with multiple sclerosis ( MS ) . Here we describe the relationship between dosage , serum level , efficacy , and safety of intravenously and orally administered 4-AP in the same group of 70 MS patients . After both intravenous and oral administration there was a significant relationship between serum levels and 4-AP doses used ( p < 0.001 and p < 0.01 , respectively ) . The use of 4-AP in oral doses three times a day showed a large variation and fluctuation in serum levels . After 12 weeks of oral treatment ( maximum daily dosage 0.5 mg/kg body weight ) , a statistically significant improvement was found for the smooth pursuit gain of the eye movements ( estimated effect 0.14 , 95 % confidence interval 0.06 - 0.23 , p < 0.001 ) . The amount of improvement was significantly related to  4-AP serum levels ( p = 0.0013 ) . Side effects after intravenous 4-AP  occurred frequently and were very troublesome ( pain in infusion arm , dizziness ) . Side effects during oral treatment ( dizziness , paresthesias ) were very mild and occurred 30 - 45 min after intake of the medication and could be related to high serum levels 4‐Aminopyridine ( 4‐AP ) , a potassium channel blocker , restores conduction in blocked , demyelinated animal nerve . Its administration to multiple sclerosis ( MS ) patients produces transient neurological improvements . Vision improves after either oral or intravenous administration , whereas motor function improvement has been reported only with the latter . To assess further its potential as a practical symptomatic treatment , we studied the efficacy of single , oral doses of 4‐AP on both visual and motor signs in MS . Twenty temperature‐sensitive male MS patients were given either 10 to 25 mg of 4‐AP or identically appearing lactose placebo capsules . Static quantitative perimetry , critical flicker‐fusion , visual acuity , visual evoked potentials , and videotaped neurological examinations were monitored . All of 15 MS patients given 4‐AP mildly to markedly improved . Motor functions ( power , coordination , gait ) improved in 9 of 13 involved , vision in 11 of 13 , and oculomotor functions in 1 of 2 . Improvements developed gradually at doses as low as 10 mg , usually beginning within 60 minutes after drug administration , and reversed gradually over 4 to 7 hours . No serious adverse effects occurred . No significant changes were observed in 5 MS patients given placebo . We conclude that orally administered 4‐AP produces clinical ly important improvements in multiple , chronic deficits in MS . Further studies are warranted to assess efficacy and safety of prolonged administration To find out whether treatment with 4‐aminopyridine is beneficial in multiple sclerosis ( MS ) , 70 patients with definite MS entered into a r and omized , double‐blind , placebo‐controlled , cross‐over trial in which they were treated with 4‐aminopyridine and placebo for 12 weeks each ( maximum dose , 0.5 mg/kg of body weight ) . The estimated effect of the treatment as measured with the Kurtzke exp and ed disability status scale , which was the main evaluation parameter , was 0.28 point ( p = 0.001 ) . A significant decrease in the scale score ( 1.0 point or more ) was encountered in 10 patients ( 16.4 % ) during oral treatment with 4‐aminopyridine whereas it was not seen during placebo treatment ( p < 0.05 ) . A significant subjective improvement ( defined as an improvement that significantly affected the activities of normal daily life ) was indicated by 18 patients ( 29.5 % ) during 4‐aminopyridine treatment and by 1 patient ( 1.6 % ) during placebo treatment ( p < 0.05 ) . Significant improvements related to 4‐aminopyridine occurred in a number of neurophysiological parameters . No serious side effects were encountered . However , subjective side effects such as paresthesias , dizziness , and light‐headedness were frequently reported during 4‐aminopyridine treatment . Analysis of subgroups revealed that there was no difference in efficacy between those patients r and omized to receive 4‐aminopyridine and then placebo and those r and omized to receive placebo and then 4‐aminopyridine or between patients with and those without subjective side effects . Especially patients with temperature‐sensitive symptoms and patients characterized by having a longer duration of the disease and being in a progressive phase of the disease were likely to show clear clinical benefit Lambert-Eaton myasthenic syndrome is characterized by muscle weakness , hyporeflexia , and autonomic dysfunction , which result from impaired release of acetylcholine from cholinergic nerve terminals . It is frequently associated with cancer , it is autoimmune-mediated , and treatment has been unsatisfactory . 3,4-Diaminopyridine enhances the release of acetylcholine . In this prospect i ve , double-blind , placebo-controlled crossover study of 12 patients with Lambert-Eaton myasthenic syndrome ( 7 of whom had cancer ) , 3,4-diaminopyridine in doses up to 100 mg per day was effective in treating both the motor and the autonomic deficits of the syndrome . Muscle strength increased from an average of 70 percent of normal to 81 percent of normal in the upper extremities , and from 45 to 65 percent of normal in the lower extremities . The amplitudes of compound-muscle-action potentials nearly doubled , increasing from an average of 2.9 mV to 5.0 mV in the arm and from 1.6 mV to 3.1 mV in the leg . Autonomic symptoms were relieved . One patient had a seizure after 10 months of treatment , but other side effects from the drug were minimal and dose-related . We conclude that 3,4-diaminopyridine , either alone or in conjunction with other therapies , may be useful in the treatment of Lambert-Eaton myasthenic syndrome Previous studies suggest that aminopyridine may play a role in the symptomatic treatment of fatigue in multiple sclerosis . Although the mechanism underlying the beneficial effect on fatigue remains unclear , 
    Output:
    
REVIEW ER 'S CONCLUSIONS Currently available information allows no unbiased statement about safety or efficacy of aminopyridines for treating MS symptoms .