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.

Health-related quality-of-life improvements in CIDP with immune globulin IV 10%: the ICE Study.

BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy trials have demonstrated the efficacy of IV immunoglobulin vs placebo. However, these trails have not addressed the long-term impact on health-related quality of life (HRQoL). METHODS: One hundred seventeen patients in a randomized, double-blind, response-conditional crossover trial received immune globulin IV, 10% caprylate/chromatography purified (IGIV-C [Gamunex(R)]), or placebo every 3 weeks for up to 24 weeks in the first period (FP). Participants whose inflammatory neuropathy cause and treatment disability score did not improve by >/=1 point received alternate treatment in a 24-week crossover period (CP). In either period, participants who improved and completed treatment were eligible to be randomly reassigned to a blinded 24-week extension phase (EP). HRQoL analyses were conducted using the Short Form-36(R) (SF-36) and the Rotterdam Handicap Scale (RHS). RESULTS: In the FP, greater improvements in both SF-36 physical and mental component scores were observed with IGIV-C vs placebo, with a significant improvement in the physical component score (difference 4.4 points; 95% confidence interval [CI] 0.7-8.0). Improvements in all SF-36 domains favored IGIV-C vs placebo, with physical functioning, role-physical, social functioning, and mental health reaching significance. Participants receiving IGIV-C experienced a larger improvement in RHS vs those receiving placebo (difference 3.4 points; 95% CI 1.4-5.5; p = 0.001). In the CP, similar general trends were observed. In the EP, mean SF-36 improvements were generally improved or maintained in participants who continued IGIV-C therapy; however, worsening was observed in participants re-randomized to placebo. CONCLUSIONS: Long-term therapy with immune globulin IV, 10% caprylate/chromatography purified, improves and maintains health-related quality of life in chronic inflammatory demyelinating polyradiculoneuropathy.

The US health care system: Part 1: Our current system.

The US health care crisis is of great concern to American neurologists. The United States has the world's most expensive health care system yet one-sixth of Americans are uninsured. The cost and volume of procedures is expanding, while reimbursement for office visits is declining. Pharmaceutical costs, durable goods, and home health care are growing disproportionately to other services. Carriers spend more for their own administration and profit than on payments to physicians. This first article on the US health care system identifies problems and proposes solutions, many of which are championed by the American Academy of Neurology through its legislative and regulatory committees.

Invited article: the US health care system: part 2: proposals for improvement and comparison to other systems.

In the search for a universal, high quality, affordable health care system, Americans seek to identify and correct a series of current problems. In part one of this two-part series, we presented problems along with some suggested actions. This second part presents other health care systems in Europe and Canada. These different systems provide universal care and at a lower cost than in the United States. Further domestic proposals are presented from the Massachusetts plan and positions from US presidential candidates. These systems and proposals raise ideas about possible changes in the US health care system. Knowledge of these issues and other health care systems will help foster a meaningful dialog about changes in the US health care system.

Acute sensory neuropathy associated with rabbit antithymocyte globulin.

Rabbit antithymocyte globulin (RATG) is indicated for the treatment of acute renal transplant rejection and has also been shown to be effective as an induction immunosuppressive agent after renal transplantation. We report a patient that developed a painful sensory neuropathy within an hour of receiving RATG. The neuropathic symptoms resolved within a month, and a careful review of his medications, exposures and comorbid conditions revealed no other causes of neuropathy. Since the administration of RATG and onset of symptoms were so closely related temporally and the symptoms resolved after the cessation of RATG, we believe it is likely this medication led to the development of neuropathy.

Tolerance of high-dose (3,000 mg/day) coenzyme Q10 in ALS.

An open-label dose-escalation trial was performed to assess the safety and tolerability of high doses of coenzyme Q10 (CoQ10) in ALS. CoQ10, a cofactor in mitochondrial electron transfer, may improve the mitochondrial dysfunction in ALS. In this study, CoQ10 was safe and well tolerated in 31 subjects treated with doses as high as 3,000 mg/day for 8 months.

A clinical trial of creatine in ALS.

BACKGROUND: Mitochondrial dysfunction occurs early in the course of ALS, and the mitochondria may be an important site for therapeutic intervention. Creatine stabilizes the mitochondrial transition pore, and is important in mitochondrial ATP production. In a transgenic mouse model of ALS, administration of creatine prolongs survival and preserves motor function and motor neurons. METHODS: The authors conducted a randomized double-blind, placebo controlled trial on 104 patients with ALS from 14 sites to evaluate the efficacy of creatine supplementation in ALS. The primary outcome measure was maximum voluntary isometric contraction of eight upper extremity muscles, with secondary outcomes including grip strength, ALS Functional Rating Scale-Revised, and motor unit number estimates. Patients were treated for 6 months, and evaluated monthly. RESULTS: Creatine was tolerated well, but no benefit of creatine could be demonstrated in any outcome measure. CI analysis showed that the study, although powered to detect a 50% or greater change in rate of decline of muscle strength, actually made an effect size of greater than 23% unlikely. It was also demonstrated that motor unit number estimation was performed with acceptable reproducibility and tolerability, and may be a useful outcome measure in future clinical trials. CONCLUSION: Any beneficial effect of creatine at 5 g per day in ALS must be small. Other agents should be considered in future studies of therapeutic agents to address mitochondrial dysfunction in ALS. In addition, motor unit number estimation may be a useful outcome measure for future clinical trials in ALS.

Topiramate vs placebo in painful diabetic neuropathy: analgesic and metabolic effects.

BACKGROUND: Using identical methods, three simultaneous placebo-controlled trials of topiramate for painful diabetic neuropathy (PDN) did not reach significance. This independent yet concurrent placebo-controlled trial used different methods to assess topiramate efficacy and tolerability in PDN. METHODS: This 12-week, multicenter, randomized, double-blind trial included 323 subjects with PDN and pain visual analog (PVA) score of at least 40 on a scale from 0 (no pain) to 100 (worst possible pain). Topiramate (n = 214) or placebo (n = 109) was titrated to 400 mg daily or maximum tolerated dose. Short-acting rescue analgesics were permitted only during the first 6 weeks. RESULTS: Baseline characteristics were comparable between groups except for mean body weight (topiramate, 101.4 kg; placebo, 95.7 kg; p = 0.028). Twelve weeks of topiramate treatment reduced PVA scale score (from 68.0 to 46.2 mm) more effectively than placebo (from 69.1 to 54.0 mm; p = 0.038). Fifty percent of topiramate-treated subjects and 34% of placebo-treated subjects responded to treatment, defined as >30% reduction in PVA scale score (p = 0.004). Topiramate monotherapy also reduced worst pain intensity (p = 0.003 vs placebo) and sleep disruption (p = 0.020 vs placebo). Diarrhea, loss of appetite, and somnolence were the most commonly reported adverse events in the topiramate group. Topiramate reduced body weight (-2.6 vs +0.2 kg for placebo; p < 0.001) without disrupting glycemic control. CONCLUSIONS: Topiramate monotherapy reduced pain and body weight more effectively than placebo in patients with painful diabetic neuropathy.

Spontaneously remitting dermatomyositis.

Dermatomyositis (DM) is an inflammatory myopathy of skeletal muscle with characteristic cutaneous findings. It is a rare disorder with a bimodal age distribution that affects almost twice as many women as men. One category of DM, normal-enzyme DM, is characterized by cutaneous changes only at baseline, normal serum muscle enzyme levels and myositis demonstrated by electromyography (EMG) and/or muscle biopsy specimens. Typically, patients with normal-enzyme DM progress to severe muscle involvement and require systemic corticosteroid therapy. The patient we report has normal-enzyme DM confirmed by serial serum enzymes, EMG, and skin and muscle biopsies but is unique in that she never experienced progression of muscle weakness although muscle involvement was documented histologically and by EMG. Follow-up examination after 1 year revealed near-complete resolution of cutaneous involvement after topical therapy and no evidence of muscle weakness.

A randomized, placebo-controlled trial of topiramate in amyotrophic lateral sclerosis.

OBJECTIVE: To determine if long-term topiramate therapy is safe and slows disease progression in patients with ALS. METHODS: A double-blind, placebo-controlled, multicenter randomized clinical trial was conducted. Participants with ALS (n = 296) were randomized (2:1) to receive topiramate (maximum tolerated dose up to 800 mg/day) or placebo for 12 months. The primary outcome measure was the rate of change in upper extremity motor function as measured by the maximum voluntary isometric contraction (MVIC) strength of eight arm muscle groups. Secondary endpoints included safety and the rate of decline of forced vital capacity (FVC), grip strength, ALS functional rating scale (ALSFRS), and survival. RESULTS: Patients treated with topiramate showed a faster decrease in arm strength (33.3%) during 12 months (0.0997 vs 0.0748 unit decline/month, p = 0.012). Topiramate did not significantly alter the decline in FVC and ALSFRS or affect survival. Topiramate was associated with an increased frequency of anorexia, depression, diarrhea, ecchymosis, nausea, kidney calculus, paresthesia, taste perversion, thinking abnormalities, weight loss, and abnormal blood clotting (pulmonary embolism and deep venous thrombosis). CONCLUSIONS: At the dose studied, topiramate did not have a beneficial effect for patients with ALS. High-dose topiramate treatment was associated with a faster rate of decline in muscle strength as measured by MVIC and with an increased risk for several adverse events in patients with ALS. Given the lack of efficacy and large number of adverse effects, further studies of topiramate at a dose of 800 mg or maximum tolerated dose up to 800 mg/day are not warranted.

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.

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.

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.

Iatrogenic superior gluteal mononeuropathy.

Injuries to the superior gluteal nerve (SGN) have been reported as a result of trauma, pyriformis muscle entrapment, injections, and lumbar lordosis and inadequate back stabilization. We report 3 patients who developed isolated SGN injuries, 1 after a partial nephrectomy and 2 following revision of a total hip arthroplasty. SGN should be suspected in anyone developing an abnormal gait after hip or pelvic surgery or after prolonged lateral decubitus positioning.

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.

Videofluoroscopic evaluation of patients with Guillain-Barré syndrome.

We reviewed 14 patients with clinically confirmed Guillain-Barré syndrome for swallowing dysfunction. All had swallowing dysfunction varying from mild to severe. Six patients (43%) had equivalent impairment during oral and pharyngeal phases. Seven patients (50%) had more severe functional abnormalities during the pharyngeal phase than during the oral phase. One patient (7%) had moderate disorder during the oral phase and mild disorder during the pharyngeal phase. Thirty-six percent of the patients had moderate-to-severe dysfunction during the oral phase, and 71% had moderate-to-severe dysfunction during the pharyngeal phase. In 5 patients who had multiple sequential examinations, moderate or severe swallowing disorders improved to mild-to-moderate disorders within 4-8 weeks after the onset of the symptoms. Residual swallowing disorders may be seen in those who had severe swallowing dysfunction during the later phases of their disease. Further investigations are needed to determine if swallowing abnormalities persist after complete recovery from Guillain-Barré syndrome.

AAEM case report #28: monomelic amyotrophy.

Monomelic amyotrophy is a rare form of motor neuron disease usually presenting as painless asymmetric weakness and atrophy in the distal upper extremities of young adults. Only rarely are the legs involved and pyramidal findings are uncommon. Monomelic amyotrophy is most often observed in people of Japanese and Indian heritage and affects men almost exclusively. Most cases are sporadic. Laboratory testing is frequently normal or nonspecific except for electrophysiologic studies which typically demonstrate reduced compound muscle action potential amplitudes, fasciculations, and features consistent with acute and chronic denervation in distal upper extremity muscles. Necropsy in 1 patient identified anterior horn cell shrinkage, necrosis, and gliosis in appropriate spinal cord segments. Symptoms and signs often progress for several years before spontaneously arresting. The differential diagnosis for monomelic amyotrophy is broad, including processes which affect the cervical cord, roots, brachial plexus, and individual or multiple nerves in the upper extremity.