Vigorimeter grip strength in CIDP: a responsive tool that rapidly measures the effect of IVIG--the ICE study.

BACKGROUND AND PURPOSE: In a recent trial in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), the ICE study, grip strength measurement captured significantly more improvement in patients receiving immune globulin (IGIV-C) intravenously than in those receiving placebo. METHODS: We conducted a systematic analysis to determine the sensitivity of grip strength as an indicator of meaningful clinical changes in CIDP. RESULTS: A randomized double-blind trial was undertaken in 117 CIDP patients who received IGIV-C or placebo every 3 weeks for up to 24 weeks. Grip strength and inflammatory neuropathy cause and treatment (INCAT) disability scores were assessed at each visit, and the responsiveness of each scale was compared. A minimum clinically important difference cut-off value for grip strength (>8 kPa) and INCAT score (>1 point) was applied to assess the proportion of responders to IGIV-C versus placebo. This analysis showed that grip strength demonstrated significant improvement earlier (as early as day 16) than the INCAT disability scale in patients receiving IGIV-C compared with placebo. A significantly higher proportion of improvers were seen in the IGIV-C group (37.5%-50.9%) than in the placebo group (21.1%-25.9%) for grip strength at day 16, week 3, week 6 and the end of the first period. Also, grip strength showed within the first 6 weeks in the placebo group significantly more patients with a clinically meaningful deterioration (>8 kPa), compared with the INCAT (>1-point deterioration) findings. CONCLUSIONS: Grip strength can be considered a sensitive tool for assessing clinically relevant changes in patients with CIDP. Its use in daily practice is suggested.

A preterm infant with benign neonatal hemangiomatosis and persistent patent ductus arteriosus: a curious comorbidity.

A female infant had been delivered prematurely at 33 weeks to a gravida 1, para 0, 32-year-old mother following normal spontaneous vaginal delivery. Because of persistent patent ductus arteriosus the new born underwent surgery after 30 days. Four months later, when the infant arrived at our observation, approximately 13 red, nodular hemangiomas ranging from 0.5 to 30 mm in diameter were scattered over the scalp, trunk, abdomen, and extremities. Laboratory and instrumental tests investigating visceral involvement were all negative. Our diagnosis was of benign neonatal hemangiomatosis. Benign neonatal hemangiomatosis is a condition with multiple congenital hemangiomas limited to the skin. The incidence in the newborn population is between 1.0% and 4% with females 4 times more affected than males. Solitary hemangiomas occur more frequently in premature neonates with a reported incidence, inversely proportional to birth weight. Although the exact mechanism for hemangioma development remains unknown, vascular growth factors seem to play a role in the pathogenesis. Proliferation most likely results from an imbalance between positive and negative angiogenic factors expressed by the hemangioma and adjacent normal tissue. Patency of the ductus arteriosus is a common complication of preterm birth. During the immediate postpartum period, a loss of vasodilatory stimuli and activation of intrinsic contractile mechanisms facilitates ductus lumen occlusion. The imbalance of these forces, linked to premature birth, interrupts the normal maturation process, leaving the immature ductus patent. Our case is the first one of benign neonatal hemangiomatosis and patency ductus arteriosus described.

Cardiac transplantation in a patient with muscular dystrophy and cardiomyopathy.

A 17-year-old boy with muscular dystrophy developed a cardiomyopathy. His brother died of a cardiomyopathy, and muscle enzyme levels were elevated in asymptomatic family members. Examination revealed cardiomegaly, hepatomegaly, proximal muscle atrophy and weakness, and calf hypertrophy. Skeletal muscle and endomyocardial biopsy specimens were consistent with Becker's muscular dystrophy. Because of intractable heart failure, orthotopic cardiac transplantation was performed. Two years after transplantation, the patient has returned to work and regained previous exercise tolerance. Heart transplantation can be an acceptable treatment of patients who have muscular dystrophy, with preserved ambulation and favorable life expectancy, and also life-threatening cardiomyopathy refractory to medical management.

A false-positive edrophonium test in a patient with a brainstem glioma.

We report a photographically documented false-positive edrophonium test in a patient with a histologically verified brainstem glioma. While a positive response to intravenous edrophonium should usually be regarded as confirmatory for myasthenia gravis, the possibility of a false-positive test must be considered in patients with atypical physical findings.

Gangliosides GM1 and GD1b are antigens for IgM M-protein in a patient with motor neuron disease.

We studied a patient with an IgM M-protein and lower motor neuron disease to identify the antigens to which the M-protein bound. Gangliosides from peripheral nerve and spinal cord were separated by high-performance thin-layer chromatography and immunostained with the patient's serum. The serum IgM immunostained two gangliosides identified as GM1 and GD1b, and immunostaining was specific for the M-protein light chain type. IgM-binding to the two gangliosides was detectable by ELISA at serum dilutions of greater than 1:10,000, and the M-protein was selectively immunoabsorbed by liposomes containing GM1 or GD1b. The IgM M-protein also bound to asialo-GM1, indicating reactivity to the galactosyl(beta 1-3)N-acetylgalactosaminyl moiety shared by GM1, GD1b, and asialo-GM1.

Monoclonal IgM with unique specificity to gangliosides GM1 and GD1b and to lacto-N-tetraose associated with human motor neuron disease.

IgM lambda monoclonal antibodies in two patients with motor neuron disease showed the same unique antigenic specificity. They bound to gangliosides GM1 and GD1b and to lacto-N-tetraose-BSA. By immunofluorescence microscopy they bound to central and peripheral nerve tissue and to motor end-plates at the neuromuscular junction. Sera from control subjects did not contain antibodies of similar specificity. Monoclonal IgMs with the same unique specificity could be responsible for motor neuron disease in some patients with monoclonal gammopathies.

Double-blind randomized trial of tramadol for the treatment of the pain of diabetic neuropathy.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of tramadol in treating the pain of diabetic neuropathy. BACKGROUND: The pain of diabetic neuropathy is a major cause of morbidity among these patients and treatment, as with other small-fiber neuropathies, is often unsatisfactory. Tramadol is a centrally acting analgesic for use in treating moderate to moderately severe pain. METHODS: This multicenter, outpatient, randomized, double-blind, placebo-controlled, parallel-group study consisted of a washout/screening phase, during which all analgesics were discontinued, and a 42-day double-blind treatment phase. A total of 131 patients with painful diabetic neuropathy were treated with tramadol (n=65) or placebo (n=66) tramadol, which were administered as identical capsules in divided doses four times daily. The primary efficacy analysis compared the mean pain intensity scores in the tramadol and placebo groups obtained at day 42 of the study or at the time of discontinuation. Secondary efficacy assessments were the pain relief rating scores and a quality of life evaluation based on daily activities and sleep characteristics. RESULTS: Tramadol, at an average dosage of 210 mg/day, was significantly (p < 0.001) more effective than placebo for treating the pain of diabetic neuropathy. Patients in the tramadol group scored significantly better in physical (p=0.02) and social functioning (p=0.04) ratings than patients in the placebo group. No statistically significant treatment effects on sleep were identified. The most frequently occurring adverse events with tramadol were nausea, constipation, headache, and somnolence. CONCLUSIONS: The results of this placebo-controlled trial showed that tramadol was effective and safe in treating the pain of diabetic neuropathy.

Pilot study of fluzinamide (N-methyl-3-[3-(trifluoromethyl)phenoxy]-1-azetidinecarboxamide) in refractory partial seizures.

We conducted a pilot study of fluzinamide in 15 adults with refractory partial seizures. After a baseline period, fluzinamide was added to the existing regimen of phenytoin and carbamazepine and increased to maximum tolerated dose. Common side effects included dizziness, diplopia, ataxia, headache, nausea, and rash, resulting in patient withdrawal in six cases. Seizures became less frequent in four of the nine patients who completed the 8-week trial.

Randomized controlled trial of IVIg in untreated chronic inflammatory demyelinating polyradiculoneuropathy.

OBJECTIVE: To determine the efficacy of IV immunoglobulin (IVIg) given patients with untreated chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: A randomized, double-blind, multicenter, investigator-initiated study compared IVIg (Aventis Behring LLC, King of Prussia, PA) with placebo (5% albumin). On days 1, 2, and 21, IVIg (1 g/kg) or placebo was given. The primary outcome measure was the change in muscle strength from baseline to day 42, using the average muscle score (AMS). Secondary outcome measures included change from baseline AMS at days 10 and 21, the Hughes' functional disability scale, forced vital capacity (FVC), and nerve conduction studies (NCS) of four motor nerves (median, ulnar, peroneal, and tibial). RESULTS: The patients (n = 33) were randomized. Of these, 30 (14 women, 16 men, aged 54 +/- 20 years, range 13 to 82) received IVIg and 23 were given placebo (12 women, 11 men, aged 50 +/- 18 years, range 23 to 73). Baseline AMS values of the groups were similar (IVIg 7.06 +/- 1.31 versus placebo 7.28 +/- 1.18, p = 0.53). There were two dropouts in placebo group and one in the IVIg group. Mean AMS improved at day 42 comparing IVIg with placebo (0.63 versus -0.1, p = 0.006). Improved strength was seen by day 10. The placebo group lost strength over this same interval. In the IVIg, 11 subjects improved by the functional disability scale; none worsened. This differed (p = 0.019) from those in the placebo-treated group (two improved, two got worse, remainder unchanged). Forced vital capacity did not improve with IVIg treatment. IVIg improved ulnar motor distal latency (p = 0.005), tibial distal compound muscle amplitude (p = 0.003), and peroneal nerve conduction velocity (p = 0.03). CONCLUSIONS: IVIg improves strength in patients with untreated CIDP by day 10 with continued benefit through day 42; more than one third improve by at least a functional grade on a disability scale. This study provides data supporting IVIg as the initial treatment for CIDP.

Maintenance of the long-term effectiveness of tramadol in treatment of the pain of diabetic neuropathy.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of tramadol in a 6-month open extension following a 6-week double-blind randomized trial. RESEARCH DESIGN AND METHODS: Patients with painful diabetic neuropathy who completed the double-blind study were eligible for enrollment in an open extension of up to 6 months. All patients received tramadol 50-400 mg/day. Self-administered pain intensity scores (scale 0-4; none to extreme pain) and pain relief scores (scale -1-4; worse to complete relief) were recorded the first day of the open extension (last day of the double-blind phase) and at 30, 90, and 180 days. RESULTS: A total of 117 patients (56 former tramadol and 61 former placebo) entered the study. On the first day of the study, patients formerly treated with placebo had a significantly higher mean pain intensity score (2. 2+/-1.02 vs. 1.4+/-0.93, P<0.001) and a lower pain relief score (0. 9+/-1.43 vs. 2.2+/-1.27, P<0.001) than former tramadol patients. By Day 90, both groups had mean pain intensity scores of 1.4, which were maintained throughout the study. Mean pain relief scores (2. 4+/-1.09 vs. 2.2+/-1.14) were similar after 30 days in the former placebo and former tramadol groups, respectively and were maintained for the duration of the study. Four patients discontinued therapy due to ineffective pain relief; 13 patients discontinued due to adverse events. The most common adverse events were constipation, nausea, and headache. CONCLUSIONS: Tramadol provides long-term relief of the pain of diabetic neuropathy.

Electrophysiologic evaluations.

Electrophysiologic testing in concert with the neurologic history and physical examination can be useful for evaluating the patient with suspected neurotoxicity. Procedures are selected depending on whether the central or peripheral nervous system, or both, are considered to be affected. Extensive data is available on the use of nerve conduction studies to substantiate and serially follow patients with peripheral neuropathy, and the electrophysiologic findings can be used to predict the most likely focus of pathology in the peripheral nervous system. With this information in hand, the electrodiagnostician can guide the clinical neurotoxicologist towards a broad differential diagnosis of the most likely neurotoxins.

Electromyography monitoring for percutaneous placement of iliosacral screws.

OBJECTIVE: To report our experience with the use of continuous electromyography (EMG) for placement of iliosacral screws. DATA SOURCES: Concurrently acquired data as well as patient charts, intraoperative EMG records, x-rays, and pelvic computed tomography (CT) scans. DESIGN: The monitored group of twenty-nine patients was studied prospectively. The control group consisted of twenty-two patients studied retrospectively. SETTING: Level One trauma center. METHODS: Continuous electromyograms were recorded for twenty-nine patients and compared with those from a group of twenty-two antecedent patients who were not monitored. The primary parameter of interest of this study was the presence or absence of neurologic change after iliosacral screw placement. This information was obtained prospectively in the study group and by retrospective review in the historical control. RESULTS: Four patients in the control group had postoperative and/or sensory motor changes prompting a postoperative CT scan; in each of these patients, a misdirected screw was identified and subsequently removed in a second procedure. There were no neurologic changes subsequent to placement in the twenty-nine patients who were monitored (7.5 percent versus 0 percent; p = 0.029, Fisher's exact test). All monitored patients had postoperative CT scans and showed the screw in a safe position with no significant violations of the S1 tunnel. CONCLUSION: Continuous EMG monitoring during iliosacral screw placement may be a useful neuroprotective tool.

MRI findings of sciatic endometriosis.

Endometriosis is a rare cause of sciatic mononeuropathy. We report a woman with cyclic, menstruation-related hip pain associated with right leg weakness and sensory loss. Examination and electrodiagnostic studies suggested sciatic nerve dysfunction. Magnetic resonance imaging (MRI) revealed abnormal signal consistent with endometriotic tissue in the region of the right sciatic nerve. The abnormal signal partially regressed after treatment of the endometriosis. This case further illustrates the utility of MRI in the assessment of rare pelvic disorders.

[Condylomata acuminata: immunological evaluation and interferon therapy]. / Condilomi acuminati: valutazioni immunologiche e terapia con interferone.

The distribution of peripheral blood T lymphocytes in 35 patients aged 16 to 49 years with genital warts was studied. Patients with genital warts were found to be less responsive than a control group, and this deficiency was related to duration of genital wart infection. 11 patients affected with long lasting genital warts were treated with interferon. The results are reported and briefly discussed.

[Oral hairy leukoplakia]. / Oral hairy leukoplakia.

We report our experience of oral hairy leukoplakia in HIV seropositive patients. Etiopathogenesis and relationship between oral hairy leukoplakia and HIV infection are briefly discussed, as well as its prognostic value.