BACKGROUND: Gait imbalance is one of the frequent complications in subjects with multiple sclerosis (MS). Fampridine (4-aminopyridine) is a potassium-channel blocker that is administered for gait imbalance in MS. Different studies showed the effects of fampridine on gait status based on various tests in subjects with MS. Some showed significant improvement after treatment, and others did not. So, we designed this systematic review, and meta-analysis to estimate the pooled effects of fampridine on gait status in patients with MS.
METHODS: The main goal is the evaluation of times of different gait test pre and post fampridine treatment. Two independent expert researchers conducted a systematic and comprehensive search in PubMed, Scopus, EMBASE, Web of Science, and Google Scholar and also gray literature, including references of the references and conference abstracts. The search was done on September 16, 2022. Before-after studies trials reporting scores of the walking tests. We extracted data regarding the total number of participants, first author, publication year, country of origin, mean age, Expanded Disability Status Scale (EDSS), and the results of walking tests.
RESULTS: The literature search revealed 1963 studies; after deleting duplicates, 1098 studies remained. Seventy-seven full texts were evaluated. Finally, 18 studies were included for meta-analysis, while most of them were not placebo-controlled trials. The most frequent country of origin was Germany, and the mean age and EDSS ranged between 44 and 56 years and 4 and 6, respectively. The studies were published between 2013 and 2019. The pooled standardized mean difference (SMD) (after-before) of the MS Walking Scale (MSWS-12) was - 1.97 (95%CI: - 1.7, - 1.03) (I2 = 93.1%, P < 0.001). The pooled SMD (after-before) of the six-minute walk test (6MWT) was 0.49 (95%CI: 0.22, - 0.76) (I2 = 0%, P = 0.7). The pooled SMD (after-before) of T Timed 25-Foot Walk (T25FW) was - 0.99(95%CI: - 1.52, - 0.47) (I2 = 97.5%, P < 0.001).
CONCLUSIONS: This systematic review and meta-analysis show that fampridine improves gait imbalance in patients with MS.

UNASSIGNED: Systematic review.
UNASSIGNED: To provide current evidence on the efficacy of 4-aminopyridine (4-AP) to bring about functional improvement in individuals with chronic traumatic spinal cord injury (SCI).
UNASSIGNED: The Medline (PubMed), Web of Science and SCOPUS databases were systematically searched for relevant articles on the efficacy of 4-AP to treat SCI, from the dates such articles were first published until May 2022. Full-text versions of all the articles selected were examined independently by two reviewers. Methodological quality was rated using the Modified Jadad Scale, and risk of bias was assessed with the RoB-2 test. Data extracted included human models/types, PRISMA assessment protocols, and the results of each study. Descriptive syntheses are provided.
UNASSIGNED: In total, 28 articles were initially identified, 10 of which were included after screening. Most of the studies reviewed reported some degree of patient improvement in one or more of the following parameters: motor, sensitivity and sexual function, sphincter control, spasticity, ability to function independently, quality of life, central motor conduction, pain, and pulmonary function.
UNASSIGNED: This review confirms the efficacy of 4-AP in improving several conditions resulting from SCI but further research on this topic is warranted. Additional randomized clinical trials with 4-AP involving larger sample sizes are needed, as are consistent outcome measures in order to obtain adequate data for analysis with a view to enhance treatment benefits.
UNASSIGNED: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=334835, PROSPERO CRD42022334835.

OBJECTIVE: Dalfampridine (DFP) is used to improve motor functions in patients with multiple sclerosis (MS). Overdose of DFP can occur for a variety of reasons and can lead to a state of epilepsy.
METHODS: A 24-year-old woman with MS was admitted to hospital with severe sweating and delirium after attempting suicide by overdosing on DFP. At the time of hospitalization, she developed a tonic-clonic seizure that did not respond to immediate intravenous (IV) diazepam injection, followed by intravenous sodium valproate. Therefore, according to the hospital protocol of the neurology department, the patient was intubated and IV infusion of midazolam was started, Due to the persistence of seizures, sodium thiopental began and the patient was admitted to the intensive care unit (ICU). In the ICU, she received an infusion of sodium thiopental and intravenous sodium valproate, monitored by a daily electroencephalogram (EEG). The patient was discharged after four days due to her stable medical condition.
CONCLUSIONS: Epilepsy in case of overuse of DFP should be considered as a life-threatening side effect and timely treatment should be done to prevent damage to the nervous system.

Prolonged-release (PR) fampridine is a potassium channel blocker used as a symptomatic treatment for walking disability in patients with multiple sclerosis (MS). Its clinical effects in such patients have not been systematically reviewed, and may be more wide-ranging than expected.
To summarize the evidence on the effects of PR fampridine in patients with MS.
A systematic search of Pubmed, Scopus (including EMBASE), and PsycINFO (completed in 01/2019) was carried out to identify randomized controlled trials (RCT) that compared PR fampridine to placebo. When appropriate, data were pooled using a random-effects model, and standardized mean differences (SMD) were computed. Study quality was assessed using the Downs and Black checklist. PRISMA guidelines were followed. All retrieved functional outcomes were categorized according to the International Classification of Functioning, Disability and Health (ICF).
A total of 706 articles were screened for inclusion. Twenty RCTs involving 2616 patients met the eligibility criteria. Most studies were of good-to-excellent quality. PR fampridine administration resulted in significant benefits in relation to walking short distances (SMD: 1.23 (95% IC 0.65-1.81)) and perceived walking capacity (0.64 (0.27-1.02)). Its effects on muscle strength and middle-distance walking were not significant (0.53 (- 0.04 to 1.10) and 0.31 (- 0.18 to 0.80), respectively). No effect on higher-level cognitive functions (- 0.07 (- 0.58 to 0.45)) or hand and arm use (0.16 (- 0.33 to 0.64)) was observed. Individual studies reported effects on other outcomes across the ICF domains.
There is strong evidence that PR fampridine exerts strong effects on the ability to walk short distances and on perceived walking capacity. Other effects of PR fampridine according to the ICF are possible but still unclear.

Background: Spasticity is a common secondary complication of spinal cord injury (SCI), which can severely impact functional independence and quality of life. 4-Aminopyridine (4-AP) is a potassium channel blocker that has been studied as an intervention for spasticity in individuals with SCI. Objective: To conduct a systematic review of the available evidence regarding the effectiveness of 4-AP for the management of spasticity in individuals with SCI. Methods: A comprehensive literature search was conducted on five electronic databases for articles published in English up to January 2017. Studies were included if (1) the sample size was three or more subjects, (2) the population was ≥50% SCI, (3) the subjects were ≥18 years old, (4) the treatment was 4-AP via any route, and (5) spasticity was assessed before and after the intervention. Subject characteristics, study design, intervention protocol, assessment methods, side effects, adverse events, and outcomes were extracted from selected studies. Randomized controlled trials (RCTs) were evaluated for methodological quality using the Physiotherapy Evidence Database (PEDro) tool. Levels of evidence were assigned using a modified Sackett scale. Results: Nine studies met inclusion criteria with a pooled sample size of 591 subjects. Six studies were RCTs (PEDro = 6-10, Level 1 evidence) and three studies were pre-post tests (Level 4 evidence). There was a wide range in duration, severity, and level of SCI across subjects. Oral 4-AP was investigated in five studies; one study reported significant improvements on the Ashworth Scale (AS), while the remaining four studies found no improvement. Three studies found no significant improvements on the Spasm Frequency Scale. Intravenous 4-AP was investigated in three studies; no significant improvements were found on the AS or in the Reflex Score. Intrathecal 4-AP was investigated in one study, which did not find significant improvements on the AS. Conclusion: There is weak evidence supporting the effectiveness of 4-AP in reducing spasticity post SCI. Future research should utilize contemporary measures of spasticity and address methodological limitations such as small sample sizes.

Gait impairment is one of the most disabling symptoms in people with multiple sclerosis (PwMS). Fampridine, has demonstrated a positive effect on gait speed in PwMS after 14 days of treatment but the long-term effects have not yet been demonstrated. This study reviews the long-term effects of fampridine on gait in PwMS.
This systematic review was conducted according to the PRISMA statement. Studies were considered long term if treatment exceeded 28 days. From the 498 studies identified, 18 (2,200 patients) fulfilled all eligibility criteria. Only 3 studies followed-up patients for >1 year and one of these showed a non-significant improvement in the gait speed. Key Messages: Fampridine seems to be beneficial at improving gait speed in PwMS in the long term. Further long-term studies are needed on related gait and functional parameters.

BACKGROUND: Multiple sclerosis (MS) is a chronic immune-mediated inflammatory disease. Fatigue is the most common symptom of MS patients, affecting >80% subjects. Medical treatment is an important method for managing fatigue. Currently, although many drugs have been tested in treatment of MS fatigue, the efficacy of these drugs remain largely unclear.
METHODS: We researched available literatures in PubMed, Embase, Medline, Google Scholar, Cochrane Library (August 31, 2016). Search terms included multiple sclerosis, fatigue, medication treatments, amantadine, modafinil, aspirin, acetyl-l-carnitine, pemoline, 4-aminopyridine and randomized controlled trial (RCT). Two researchers were required to independently assess the quality of literatures, and finish data extraction. Meta-analysis was conducted using RevMan 5.3 software.
RESULTS: A total of 11 RCTs involving 723 patients were included. The therapeutic effects were quantified by different scales, such as Modified Fatigue Impact Scale (MFIS) or Fatigue Severity Scale (FSS). Here, meta-analysis suggested that amantadine, not modafinil, was effective for treating the fatigue in MS. Moreover, two studies implied that l-carnitine might have similar therapeutic effect with amantadine. However, the reliability of this finding was greatly weakened by the limited sample sizes. Additionally, current data could not answer whether treatment of MS fatigue using aspirin or 4-aminopyridine was beneficial. Finally, we found that all drugs except pemoline were relatively safe for treating MS fatigue.
CONCLUSIONS: Current limited data suggest that amantadine may be the only drug that has relatively sufficient evidences in treatment of fatigue symptoms in MS. Further RCT studies recruiting larger samples sizes are required to validate the therapeutic effect of these candidate drugs.

Oral fampridine prolonged release (PR) [Fampyra®] is a lipid-soluble selective potassium channel blocker that is approved in the EU for the improvement of walking in adult multiple sclerosis (MS) patients with walking disability (expanded disability status scale score of 4-7). In clinical trials (MS-F203 and MS-F204) using an objective measure of walking improvement [the timed 25-foot walk (T25FW)], more than one-third of patients receiving fampridine PR achieved a consistent on-treatment improvement in walking speed (i.e. became TW responders) over 9-14 weeks of treatment. Fampridine PR recipients who fulfilled the definition of TW responder had mean improvements of ≈25% from baseline in T25FW walking speed. In a clinical trial (ENHANCE) that used a patient-rated measure of walking improvement [12-item MS walking scale (MSWS-12)], a significantly greater proportion of fampridine PR recipients than placebo recipients achieved a ≥8-point improvement on the MSWS-12 with 24 weeks of treatment. Where reported, adverse events were mostly mild or moderate in severity, and generally consistent with the underlying disease or mechanism of action of fampridine PR. Fampridine PR is a useful treatment option to consider in adult MS patients with walking disability.

OBJECTIVE: To synthesise and critically appraise randomised controlled trials examining the effect of symptom-controlling medication on gait outcomes in people with multiple sclerosis (MS).
METHODS: The literature search examined five databases (Medline, Embase, AMED, Cochrane (CENTRAL), and CINAHL until the end of November 2016. Eligible studies included medication to address symptoms associated with MS and an objective gait outcome measure. Two reviewers independently extracted data and assessed study quality using structured data extraction forms and the PEDro scale.
RESULTS: From 249 papers identified, 13 papers met inclusion criteria, examining three medications. Fampridine was found to significantly increase gait speed, but only in those people who responded to medication, which was less than half (pooled mean: 39%). Ten milligrams of fampridine twice daily significantly improves gait endurance. No definitive conclusions can be made about the efficacy of cannabinoid medication due to conflicting results across three studies. A single study of baclofen did not provide evidence to support the use of this medication to improve gait.
CONCLUSIONS: Limited evidence is available to guide gait symptom control for people with MS. Further research that includes three-dimensional gait analysis, patient perceived measures of gait dysfunction and explores combined efficacy of other modalities on gait is needed. Implications for Rehabilitation Gait disturbance is a common and disabling symptom of multiple sclerosis. Fampridine and cannabis medication may increase gait speed, baclofen does not. Fampridine can be used to improve gait endurance. Future research should include both quantitative and qualitative outcome measures of gait and investigate the combined efficacy of pharmacological and non-pharmacological interventions to assist clinicians to maximise gait improvements.

METHODS: Review study.
OBJECTIVE: Alternative treatments to oral phosphodiesterase type 5 inhibitors (PDE5Is) in individuals with spinal cord lesions (SCLs) and erectile dysfunction (ED).
METHODS: Italy.
METHODS: Research clinical trials (1999-2014).
RESULTS: Twelve studies were selected. One article documented that 76% of subjects reached satisfactory sexual intercourse (SI) using intracavernosal injection of vasoactive medications (papaverine and prostaglandin E1). One study regarding perineal training showed a significant increase (P<0.05) in penile tumescence in 10 individuals with preserved sacral segment. Two studies reported contrasting results on erectile function (EF) using various dosages of oral fampridine (25-40 mg). Furthermore, 95.1% of patients on fampridine 25 mg experienced drawbacks. Disappointing findings were found with intraurethral alprostadil (125-1000 μg) and sublingual apomorphine 3 mg. Two studies concerning penile prosthesis reported valid SI more than 75% of the time with a mean follow-up of 11 years, although around 15% of individuals showed side effects. As for surgical treatments, 88% of males submitted to Brindley sacral anterior root stimulator after sacral dorsal rhizotomy achieved valid erection up to 8 years following the procedure. Three studies documented the impact of definitive sacral neuromodulation implant (Medtronic, Minneapolis, MN, USA) also on EF. After surgery, 20-37.5% of patients with ED recovered normal EF.
CONCLUSIONS: Data are scant on the efficacy of ED treatments for SCL subjects who did not respond to PDE5Is. Further research should investigate the effects of any SCL treatments even when they are not strictly used for neurogenic sexual dysfunction.