Michael Rubin

Neurogenic orthostatic hypotension: a double-blind, placebo-controlled study with midodrine

PURPOSE To investigate the efficacy and safety of midodrine for treatment of patients with orthostatic hypotension due to autonomic failure. PATIENTS Ninety-seven patients with orthostatic hypotension were randomized in a 4-week, double-blinded, placebo-controlled study with a 1-week placebo run-in period. Patients ranged in age from 22 to 86 years (mean: 61 years). METHODS After a 1-week run-in phase, either placebo or midodrine at a dose of 2.5 mg, 5 mg, or 10 mg was administered three times a day for 4 weeks. Both the placebo group and the 2.5-mg midodrine group received constant doses throughout the double-blind phase. The patients receiving 5 mg or 10 mg of midodrine were given doses that were increased at weekly intervals by 2.5-mg increments until the designated dose was reached. Efficacy evaluations were based on an improvement at 1-hour postdose in standing systolic blood pressure and in symptoms of orthostatic hypotension (syncope, dizziness/lightheadedness, weakness/fatigue, and low energy level). RESULTS Midodrine (10 mg) increased standing systolic blood pressure by 22 mm Hg (28%, p < 0.001 versus placebo). Midodrine improved (p < 0.05) the following symptoms of orthostatic hypotension compared to placebo: dizziness/lightheadedness, weakness/fatigue, syncope, low energy level, impaired ability to stand, and feelings of depression. The overall side effects were mainly mild to moderate. One or more side effects were reported by 22% of the placebo group compared with 27% of the midodrine-treated group. Scalp pruritus/tingling, which was reported by 10 of 74 (13.5%) of the midodrine-treated patients, was most frequent. Other reported side effects included supine hypertension (8%) and feelings of urinary urgency (4%). CONCLUSION We conclude that midodrine is an effective and well-tolerated treatment for moderate-to-severe orthostatic hypotension associated with autonomic failure.

Clinical utility of surface EMG: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology

This report reviews the clinical uses of surface electromyography (SEMG) as a diagnostic tool for neurologic disorders. SEMG is assessed with regard to the evaluation of patients with neuromuscular diseases, low back pain, and disorders of motor control. This broadens the scope of a previous assessment of SEMG in neurologic practice by the American Association of Electrodiagnostic Medicine1 in which its utility was examined with regard to neuromuscular diseases only. Needle electromyographic evaluation (NEMG), in combination with nerve conduction studies, is the gold standard methodology for assessing the neurophysiologic characteristics of neuromuscular diseases. Moreover, fine-wire EMG (FWEMG) often has been used in the evaluation of gait disorders, kinesiologic studies, and research and is also considered a standard. Nevertheless, NEMG and FWEMG are both invasive and painful, and this limits their use when activity from several muscles needs to be monitored simultaneously. SEMG is a technique to measure muscle activity noninvasively using surface electrodes placed on the skin overlying the muscle. SEMG differs from NEMG and FWEMG with respect to technical requirements and electrical properties. Unlike NEMG, SEMG electrodes record from a wide area of muscle territory, have a relatively narrow frequency band (range, 20 to 500 Hz), have low-signal resolution, and are highly susceptible to movement artifact. SEMG electrodes typically are approximately 10 mm in diameter and usually are passive (i.e., they are simple conductive surfaces requiring low skin resistance). They can, however, be active, incorporating preamplifier electronics that lessen the need for low skin resistance and improve the signal-to-noise ratio. SEMG can record both voluntary and involuntary muscle activity in addition to externally stimulated muscle action potentials such as motor evoked potentials after central or peripheral nerve stimulation.2 SEMG has also been used in several non-neurologic settings such as obstetric monitoring and animal research, but these potential …

NGX-4010, a capsaicin 8% dermal patch, for the treatment of painful HIV-associated distal sensory polyneuropathy: Results of a 52-week open-label study

Objectives:To evaluate the efficacy, safety, and tolerability of repeated NGX-4010 treatments in the open-label extension phase of a 52-week study in patients with neuropathic pain due to HIV-associated distal sensory polyneuropathy (HIV-DSP). Methods:Patients completing the 12-week, randomized, double-blind phase of the study could enter a 40-week, open-label phase, and receive up to 3, 60-minute NGX-4010 treatments. Patients recorded their “average pain for the past 24 hours” daily using the Numeric Pain Rating Scale (NPRS). Efficacy assessment included the percentage NPRS score reduction from baseline to weeks 2 to 12 after the final treatment, and Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) questionnaires at study termination. Results:Of 307 patients randomized, 272 entered the open-label phase; 81, 90, 55, and 46 received 0, 1, 2, and 3 retreatments, respectively. The mean percentage decrease in NPRS score from baseline to weeks 2 to 12 after the final treatment was similar in patients receiving single or multiple NGX-4010 treatments (−25.8%, −27.1%, −24.6%, and −22.7% for 1, 2, 3, and 4 NGX-4010 treatments, respectively). PGIC and CGIC results demonstrated a benefit of NGX-4010 treatment through to the end of the study regardless of the number of treatments received. Transient local application site reactions were the most frequently reported adverse events, and were mainly mild to moderate, nonserious, and did not increase with repeated treatment. Discussion:Repeated NGX-4010 treatments were generally well tolerated and resulted in consistent reductions in HIV-DSP-associated pain and improvement in patient-reported outcomes.

Spontaneous temporary remission in primary CNS lymphoma.

We report a case of primary CNS lymphoma in which complete, though temporary, spontaneous clinical and radiologic remission occurred. This is the first such case report to our knowledge.

The utility of F wave chronodispersion in lumbosacral radiculopathy

The sensitivity of F wave chronodispersion (Fc) in evaluating nerve root pathology is unknown. We compared Fc in 91 patients with clinical and EMG evidence of L5 or S1 radiculopathy with Fc in 81 controls in order to evaluate its sensitivity in lumbosacral radiculopathy. F waves were obtained by stimulating the peroneal and tibial nerves behind the knee and recording from the extensor digitorum brevis (L5 predominant) and flexor hallucis brevis (S1 predominant) muscles, respectively. Fc was calculated by subtracting the shortest F wave latency from the longest and, in controls, ranged from 0.2 to 23.4 ms in the peroneal nerve, and from 1.2 to 13.4 ms in the tibial nerve (95th percentile = 13 ms for the peroneal nerve and 9.2 ms for the tibial nerve). In the patient group, Fc also ranged from 0.2 to 23.4 ms in the peroneal nerve, and from 0.4 to 18.2 ms in the tibial nerve. Only 5 (5.5%) and 8 (11.3%) patients for the peroneal and tibial nerves, respectively, had Fc values which fell beyond the 95th percentile, a percentage far below the sensitivity of F wave latency measurement and not substantially different from chance. Thus we conclude that Fc has no substantial additional value in evaluating lumbosacral radiculopathy over that of F wave latency.

Sensory Nerve Abnormalities in Brachial Plexopathy

Sensory nerve action potential (SNAP) amplitude should be abnormal in brachial plexopathies (BP) which cause axonal degeneration in distal segments. Fifty-six patients with BP were identified. In diffuse BP, 22/25 (88%) showed low amplitude or absent median or ulnar SNAP. Three of 5 patients with upper trunk BP had low amplitude or absent SNAP (1 median, 1 radial, 1 lateral antebrachial cutaneous). Seventy-five percent of patients with lower trunk/medial cord BP had low amplitude or absent SNAP (8/24 median, 18/24 ulnar). Overall, 82.5% of patients had low amplitude or absent SNAP when a sensory nerve in the distribution of signs was studied. Testing multiple sensory nerves to include symptomatic regions enhances the diagnostic yield of SNAP in BP.

Entrapment of an accessory superficial peroneal sensory nerve.

A 29 year old man had an accessory branch of the superficial peroneal nerve which entered the foot by rostro-caudally traversing the lateral malleolus laterally. The nerve was entrapped by a fascial band, resulting in pain over the lateral malleolus and dorsum of foot. Symptoms resolved when the nerve was surgically released.