Neurotherapeutic Briefs
April 1, 2000 3 minutes read
Neurotherapeutic Briefs
3,4 DAP for LEMS
Source: Sanders DB, et al. A randomized trial of 3,4-diaminopyridine in Lambert-Eaton myasthenic syndrome. Neurology 2000;54:603-607.
Though yet to be fda approved, 3,4-dia-minopyridine (DAP) appears to be safe and effective for Lambert-Eaton myasthenic syndrome (LEMS). Twenty-six LEMS patients were enrolled in this prospective, randomized, two-arm, parallel-treatment trial comparing DAP 20 mg tid (n = 12) vs. placebo (n = 14) for six days, followed by open-label DAP for as long as there was symptomatic improvement. Diagnosis was established by demonstrating proximal muscle weakness associated with characteristic electromyographic abnormalities (i.e., small-amplitude compound muscle action potentials [CMAP] that drop still further on low-frequency repetitive stimulation but increase at least twofold after maximal voluntary contraction). Exclusionary criteria included cardiac arrhythmia; seizures; renal, hepatic, or hematologic disease; and all female patients practiced contraception while on the drug. Quantitative myasthenia gravis (QMG) score, a functional assessment of involved muscle groups, was the primary end point, with the average summated CMAP amplitude of three intrinsic hand and foot muscles (abductor digiti minimi, abductor pollicis brevis, and extensor digitorum brevis) serving as secondary end points. Wilcoxon’s rank sum test provided statistical analysis.
Compared to baseline, at the end of the six-day blinded phase significant improvement in QMG scores and average summated CMAP amplitudes occurred in the DAP arm, with no significant change seen in the placebo group. On open label, 24 of 25 patients who continued on DAP improved, with the optimal response seen at 30 to 40 mg/day. One patient with recurrence of LEMS discontinued DAP, but without return of weakness. Side effects included mild perioral tingling and acral paresthesia, but no hematologic, renal, hepatic, or cardiac complications were seen.
Commentary
Until FDA approval, DAP may be obtained for compassionate use from Jacobus Pharmaceutical Company, Inc. (which provided the DAP for this study), in Princeton, NJ (fax: 609-799-1176). —mr
Avonex for ALS
Source: Beghi E, et al. A randomized controlled trial of recombinant interferon beta-1a in ALS. Neurology 2000; 54;469-474.
Hoping that interference with immune mechanisms would have an effect on amyotrophic lateral sclerosis (ALS), 61 patients were enrolled in this double-blind, randomized, placebo-controlled study of recombinant interferon beta-1a (Avonex), administered subcutaneously tid for six months. Multiple measures of disease progression and disability, including the ability to swallow, self-feed or walk unassisted, Medical Research Council scale of muscle strength, Norris scale, bulbar scores, spirometric forced vital capacity, and electrodiagnostic studies showed no difference between the two treatment groups. Sadly, treatment for ALS must look elsewhere, but why does it take five pages to say so? —mr
IVIG for Chronic Sensory Ataxic Neuropathy
Source: Takeuchi H, et al. Immunoglobulin therapy for idiopathic chronic sensory ataxic neuropathy. Neurology 2000; 54:1008-1010.
Chronic sensory ataxic (large-diameter fiber) neuropathy may occur as a consequence of toxic (pyridoxine, cisplatinum), nutritional (vitamin E deficiency), or infectious disorders (tabes, herpes zoster), malignancy (Ann Neurol 1977;2:7-19), Sjogren’s syndrome (Neurology 1989;39:390-394), monoclonal gammopathy (Ann Neurol 1985;18:655-659), or as a form of chronic inflammatory demyelinating polyneuropathy (J Neurol Neurosurg Psychiatry 1992;55:677-680). The last responds to immunosuppressive therapy, including plasma exchange and azathioprine, though not prednisone (Muscle Nerve 1992;15:255-256). It appears that intravenous immunoglobulin therapy (IVIG) may also be beneficial for the idiopathic form. Four women, ages 45 to 63 years, with idiopathic chronic sensory ataxic neuropathy of 1.5 to 15 years duration, with normal cerebrospinal fluid protein and cell count, and without evidence of malignancy or other cause of neuropathy, were treated in an open trial with IVIG, 2 gm/kg over five days. All improved remarkably after a single course, with three requiring additional courses to maintain improvement. Double-blind studies ought be next. —mr
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