Amifampridine Phosphate (Firdapse) Is Effective in a Confirmatory Phase 3 Clinical Trial in LEMS.

OBJECTIVE: To assess tolerability and efficacy of amifampridine phosphate versus placebo for symptomatic treatment of Lambert-Eaton Myasthenic Syndrome (LEMS). METHODS: This phase 3 randomized, double-blind, placebo-controlled withdrawal trial in 26 adults with LEMS compared efficacy of amifampridine phosphate versus placebo over a 4-day period. The primary endpoints were quantitative myasthenia gravis score (QMG) and subject global impression, and the secondary endpoint was Clinical Global Impression-Improvement. The exploratory endpoints were 3TUG (timed up and go) test and QMG limb domain score. All participants had been receiving amifampridine phosphate (30-80 mg/d divided into 3 or 4 doses daily) in an expanded access protocol and had been titrated to the optimal dose and frequency for at least 1 week before randomization into the current study. After completion of assessments after 4 days of double-blind treatment, patients had the option to return to open-label amifampridine phosphate. The efficacy endpoints were mean changes from baseline in the various evaluation parameters. RESULTS: Amifampridine phosphate (n = 13) demonstrated significant benefit in QMG and subject global impression compared with placebo (n = 13) at 4 days. Other measures of efficacy, including Clinical Global Impression-Improvement, 3TUG, and QMG limb domain score also improved. The most common "adverse events" in the placebo group were muscle weakness (n = 5) and fatigue (n = 4), as expected from withdrawal of amifampridine phosphate, whereas only back pain (n = 1), pain in extremity (n = 1), and headache (n = 1) were reported in amifampridine phosphate group. CONCLUSIONS: This phase 3 randomized, double-blind, placebo-controlled withdrawal trial in adults with LEMS provided class I evidence of efficacy of amifampridine phosphate as symptomatic treatment in LEMS.

Diffuse large B-cell lymphoma presenting as Miller Fisher syndrome.

We report a patient with diffuse large B-cell lymphoma (DLBCL) who initially presented as Miller Fisher syndrome (MFS) responsive to high-dose immunoglobulin treatment. Detailed investigations for the recurrence of neurological symptoms revealed DLBCL that was responsive to chemotherapy. DLBCL should be considered in the differential diagnosis of patients with MFS who have worsening of their neurological condition after initial improvement with conventional therapy.

Chronic inflammatory demyelinating polyneuropathy responsive to mycophenolate mofetil therapy.

OBJECTIVE: To evaluate the efficacy of mycophenolate mofetil (MMF) in chronic inflammatory demyelinating polyneuropathy (CIDP). BACKGROUND: Evidence is growing that MMF is effective as an immunomodulatory drug in neuromuscular diseases. METHODS: A database of 184 patients with CIDP was analysed to obtain clinical, laboratory and electrophysiological information for patients with CIDP treated with MMF. RESULTS: Eight patients, who met the inclusion criteria, received MMF (mean dose 2 g/day; median duration 15.2 months). The average Neuropathy Impairment Score of the eight patients improved from baseline (72.3+/-35) after initiation of MMF therapy (37.8+/-37; p<0.001). Six of these eight patients were either able to stop concomitant medications (corticosteroid, intravenous immunoglobulin) or reduce their doses and frequency by > or = 50%. CONCLUSIONS: Our pilot data suggest that MMF appears to be an effective therapy for patients with naive or refractory CIDP, and further controlled studies are warranted for their confirmation.

Incidence of acute femoral neuropathy following renal transplantation.

BACKGROUND: Case reports exist of femoral neuropathy following renal transplantation (RTSP) with possible pathophysiology, including direct compression and nerve ischemia. However, the occurrence of acute femoral neuropathy (AFN) following RTSP has not been studied prospectively. OBJECTIVE: To determine the occurrence of AFN following RTSP. METHODS: We prospectively studied the occurrence of AFN following RTSP from June 1, 1998, to October 31, 1999. A total of 184 RTSPs were performed during this period. All the patients had end-stage renal failure and had effective hemodialysis before RTSP. All patients with AFN underwent neurologic examination, nerve conduction and electromyographic studies (5 to 7 days after the onset of symptoms), and magnetic resonance imaging or computed tomography of pelvis and lumbosacral spine within 24 hours of onset of symptoms. RESULTS: Four (2.2%) of 184 patients developed AFN (ipsilateral to the RTSP surgery) postoperatively between 24 (3 patients) and 48 hours. All the patients achieved good renal function after RTSP. All the patients had excellent recovery of motor function in 4 to 9 months. CONCLUSION: We believe that AFN following RTSP is an uncommon (2.2%) complication from which patients have an excellent chance of recovery.