Incidence of Guillain-Barré syndrome in Alberta, Canada: an administrative data study.

BACKGROUND: To examine the epidemiology of Guillain-Barré syndrome (GBS) in Alberta between 1994 and 2004 with data derived from hospital administration procedures. METHODS: Data from 3,959,857 individuals (1,956,841 females and 2,003,016 males) aged 1-110 years and residing in Alberta, Canada, were included in the analysis. A Poisson regression analysis was performed to determine the predictors of GBS events. RESULTS: After age and sex standardisation to the 2001 Canadian census population, incidence rates ranged from 0.97 to 2.32 per 100,000 over the course of the 11-year period, with a mean incidence of 1.6 per 100,000. Significant effects of gender, age group and year were found. Males were found to be 1.5 times more likely to acquire GBS than females. Relative to those in their first decade, the risk of acquiring GBS increased with advancing age, whereby the incidence in males peaked in the 7th decade of life and in females in the 8th decade of life. The incidence fluctuated over the 11-year period, with a minimum in 1998 and a maximum in 2004. CONCLUSIONS: The incidence of GBS in Alberta between 1994 and 2004 fluctuated within a narrow range, was similar to that previously reported worldwide, demonstrated a male preponderance and increased in elderly patients.

Simultaneous carotid endarterectomy and coronary artery bypass surgery in Canada.

Stroke neurologists are commonly asked to review patients who require coronary artery bypass grafting (CABG) but who also have comorbid severe carotid stenosis; such patients may be offered simultaneous carotid endarterectomy (CEA). In Canada, 0.51% of CABG procedures were combined CEA-CABG. The adjusted stroke and death rate was 2.67-fold greater in the combined CEA-CABG group compared to CABG alone. Randomized trials of the combined procedure are needed.

Geographic variation in the rate of carotid endarterectomy in Canada.

UNLABELLED: Background and Purpose-- Carotid endarterectomy (CEA) is an important method of stroke prevention, but its usage in Canada is not well known. The indications for CEA have been well informed by the recent clinical trials, but the impact of this information on the rate and regional variation in the rate of CEA is unknown. This study sought to determine the rate and the regional variation in the rate of CEA in Canada, its provinces, and census divisions for 1994-1997. METHODS: Discharge data from all hospitals in Canada except Quebec were obtained from the Canadian Institute for Health Information for 1994-1997 and were searched for CEA by residential site. Rates and variations in rates were calculated. RESULTS: The national age- and sex-adjusted rate per 100 000 people of CEA for those aged >/=40 years rose from 31.7 in 1994 to 40.5 in 1997. Provincial rates in 1997 varied from a low of 25.7 in Saskatchewan to high of 82.8 in Prince Edward Island. The census division rates varied even more, from a low of 0 in several divisions to a high of 179. CONCLUSIONS: The recent slight increase in CEA rates may reflect the release of new efficacy results for CEA, especially for asymptomatic carotid stenosis, but the rates are still far below US levels. The marked regional variation in rates may reflect differing views on the appropriateness of indications such as asymptomatic carotid stenosis for CEA and the inconsistency of published clinical practice guidelines.

Multifocal motor neuropathy improved by IVIg: randomized, double-blind, placebo-controlled study.

OBJECTIVE: To determine the effect of IV immunoglobulin (IVIg) on neurologic function and electrophysiologic studies in multifocal motor neuropathy with conduction block (MMN). BACKGROUND: MMN is characterized by progressive, asymmetric, lower motor neuron weakness and is probably immune-mediated. IVIg treatment has been shown to have beneficial effects in several open-label studies and in one small controlled trial. However, larger randomized controlled studies are lacking. METHODS: The authors recruited 16 patients with MMN. All subjects were given each of two treatments (IVIg [0.4 g/kg/d for 5 consecutive days] or placebo [dextrose or saline]) that were assigned according to a randomized, crossover design under double-blind conditions. Patients were evaluated before and about 28 days after trial treatment for subjective functional improvement, neurologic disability score, grip strength, distal and proximal compound muscle action potential amplitude, and conduction block. RESULTS: Subjective functional improvement with IVIg treatment was rated as dramatic or very good in nine patients, moderate in one, mild in one, and absent in five patients. This improvement was absent after placebo. The neurologic disability score improved by 6.7+/-3.3 points with IVIg treatment, whereas it decreased by 2.1+/-3.0 with placebo (p = 0.038). Grip strength on the weaker side was increased by 6.4+/-1.9 kg with IVIg treatment; it decreased by 1.0+/-0.8 kg with placebo (p = 0.0021). Conduction block worsened by 12.98+/-6.52 % with placebo, but improved by 12.68+/-5.62 % with IVIg treatment (p = 0.037). Conduction block was reversed in five patients with IVIg but not placebo. CONCLUSION: IVIg improved conduction block as well as subjective and objective clinical measures of function in patients with MMN.

Anaphylactoid reactions and angioedema during alteplase treatment of acute ischemic stroke.

Among 105 patients given recombinant tissue plasminogen activator (rt-PA, alteplase) intravenously for acute stroke, 2 (1.9%) had lingual angioedema, which progressed to a fatal anaphylactoid reaction in 1. The authors review the 2 cases and possible mechanisms responsible. They warn that patients who are taking an angiotensin-converting-enzyme inhibitor may be at increased risk for angioedema with concomitant alteplase therapy.

Autoantibodies from patients with idiopathic ataxia bind to M-phase phosphoprotein-1 (MPP1).

In an attempt to identify unique disease-related autoantibodies, the serum from an ataxia and sensory neuropathy patient was used as a probe to isolate a 2.5-kd cDNA from a HeLa expression library. The nucleotide sequence was 99% identical to MPP1, a cell-cycle-related nuclear protein phosphorylated during mitosis. Expression of the cDNA in an in vitro translation system yielded a recombinant protein that migrated in SDS-PAGE at approximately 97 kd. This protein was immunoprecipitated by the prototype human serum, by an immune guinea pig anti-MPP1 serum, but not by normal human serum or preimmune guinea pig serum. Western blot analysis of HeLa cell proteins showed that the prototype human serum and immune guinea pig antiserum recognized an approximately 225-kd protein, suggesting that the isolated clone contained a partial cDNA. By indirect immunofluorescence, the affinity-purified antibody and a guinea pig antiserum reacted with nuclei of interphase HEp-2 cells and the cytoplasm of certain neuronal cells. Sera from 10 of 25 unselected patients with ataxia, 1 of 30 patients with peripheral neuropathy, 1 of 50 multiple sclerosis patients, 0 of 20 amyotrophic lateral sclerosis, 0 of 10 children with postviral ataxia, 0 of 10 systemic lupus erythematosus patients, 0 of 3 patients with hereditary cerebellar ataxia, 0 of 8 with ataxia telangiectasia, and 0 of 30 age- and gender-matched controls immunoprecipitated the recombinant MPP1 protein. None of the patients with anti-MPP1 antibodies had evidence of malignancy. This is the first report of MPP1 as a target autoantigen in patients with idiopathic ataxia.

Effectiveness of t-PA in acute ischemic stroke: outcome relates to appropriateness.

OBJECTIVE: To examine whether the demonstrated efficacy of tissue-type plasminogen activator (t-PA) for acute ischemic stroke can be effective in a community setting. METHODS: Sixty-eight consecutive patients with acute ischemic stroke treated with IV t-PA within 3 hours of symptom onset by attending general neurologists in a busy teaching hospital. Outcome measures at 3 months were the National Institute of Health Stroke Scale (NIHSS), functional outcome (independence [modified Rankin score 0-2], dependence [modified Rankin score 3-5], and death), and symptomatic hemorrhage. Appropriately treated patients were defined by adherence to the National Institute of Neurological Disorders and Stroke (NINDS) guidelines. Effectiveness is expressed as the absolute risk reduction in which the baseline risk is assumed to be similar to that of the NINDS control group. RESULTS: Of 68 consecutively treated patients (with a mean baseline NIHSS score of 15 +/- 6), 26 (38%) made a full recovery and 39 (57%) made an independent recovery. The 11 patients who violated protocol had a lower probability of independence (p < 0.02) and full neurologic recovery (p < 0.02) and a higher probability of symptomatic hemorrhage (p < 0.05) and death (p < 0.01) compared with those of 57 patients treated according to NINDS guidelines. CONCLUSIONS: The use of t-PA for stroke in this community is effective with a number needed to treat of six. The risk of symptomatic hemorrhage is similar to that noted in randomized trials. Treating patients who violate protocol results in excess risk with no observable benefit.

Impact of plasma exchange on indices of demyelination in chronic inflammatory demyelinating polyradiculoneuropathy.

We studied the impact of plasma exchange (PE) on indices of primary demyelination in patients of the Canadian multicenter trial of PE in chronic inflammatory demyelinating polyneuropathy (CIDP). Individual motor nerves (median, ulnar, peroneal, tibial) were studied: distal motor latencies (DMLs), proximal and distal compound muscle action potential (M-wave) amplitudes, negative peak areas and durations, and motor conduction velocities (CVs). Proximal M-wave amplitudes in individual motor territories, particularly in the ulnar nerve (from below elbow, above elbow, and axillary stimulating sites) demonstrated significant improvement with PE, but not sham exchange. Proximal ulnar M-wave areas also had significant improvement with PE. Trends toward improvement of individual nerve motor CVs, M-wave durations, and DMLs did not achieve statistical significance. Proximal M-wave amplitudes, particularly in the ulnar motor territory, and proximal M-wave areas (providing a measure of conduction block) were the most sensitive indices of improvement conferred by PE in CIDP. In individual patients, these indices may help judge the efficacy of therapy.

Medical and neurological complications of ischemic stroke: experience from the RANTTAS trial. RANTTAS Investigators.

BACKGROUND AND PURPOSE: Medical and neurological complications after acute ischemic stroke may adversely impact outcome and in some cases may be preventable. Limited data exist regarding the frequency of such complications occurring in the first days after the ictus and the relationship of these complications to outcome. Our objective was to identify the types, severity, and frequency of medical and neurological complications following acute ischemic stroke and to determine their role in mortality and functional outcome. METHODS: Rates of serious (life-threatening) and nonserious medical and neurological complications and mortality were derived from the placebo limb of the Randomized Trial of Tirilazad Mesylate in Acute Stroke (RANTTAS) database (n=279). Complications were correlated with clinical outcome using logistic regression techniques. RESULTS: Of all patients, 95% had at least one complication. The most common serious medical complication was pneumonia (5%), and the most common serious neurological complication was new cerebral infarction or extension of the admission infarction (5%). The 3-month mortality was 14%; 51% of these deaths were attributed primarily to medical complications. Outcome was significantly worse in patients with serious medical complications, after adjustment for baseline imbalances, as measured by the Barthel Index (odds ratio [OR], 6.1; 95% confidence interval [CI], 2.5 to 15.1) and by the Glasgow Outcome Scale (OR, 11.6; 95% CI, 4.3 to 30.9). After death was discounted, serious medical complications were associated with severe disability at 3 months as determined by the Glasgow Outcome Scale (OR, 4.4; 95% CI, 1.3 to 14.8). CONCLUSIONS: Medical complications that follow ischemic stroke not only influence mortality but may influence functional outcome.

Pain in Guillain-Barré syndrome.

OBJECTIVES: To determine the character, intensity and frequency of pain in Guillain-Barré syndrome (GBS) and to evaluate the response to treatment. DESIGN: A prospective longitudinal study. SETTING: Academic hospital-based practices. PATIENTS: Fifty-five consecutive patients with GBS. INTERVENTIONS: Patients were evaluated on admission and at 2, 4, 8, 16, and 24 weeks. MAIN OUTCOME MEASURES: Character of pain, pain intensity using Visual Analogue Scale ([VAS] 0 to 10 cm) and Present Pain Intensity of McGill Pain Questionnaire, pain relief (VAS 0 to 10 cm), Disability Grading Scale for GBS. RESULTS: Forty-nine patients (89.1%) described pain during the course of their illness. On admission, mean pain intensity (VAS) was 4.7 +/- 3.3. However, 26 patients (47.3%) described pain that was either distressing, horrible, or excruciating (mean VAS, 7.0 +/- 2.0). The most common pain syndromes observed were deep aching back and leg pain and dysesthetic extremity pain. Pain intensity on admission correlated poorly with neurologic disability on admission (r = 0.26, p = 0.06) and throughout the period of study (r < 0.20, p > 0.10). Forty-one patients (74.5%) required opioid analgesics, with 16 (29.0%) receiving parenteral morphine to provide adequate pain relief. CONCLUSIONS: Moderate to severe pain is a common and early symptom of GBS and requires aggressive treatment. Pain intensity on admission is not a predictor of poor prognosis. Back and leg pain usually resolves over the first 8 weeks, but dysesthetic extremity pain may persist longer in 5 to 10% of patients despite motor recovery and the use of adjuvant analgesics.

Plasma-exchange therapy in chronic inflammatory demyelinating polyneuropathy. A double-blind, sham-controlled, cross-over study.

Eighteen patients with definite, untreated chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) of chronic progressive (nine patients) or relapsing course (nine patients) were randomized prospectively to receive 10 plasma-exchange (PE) or sham plasma-exchange (SPE) treatments over 4 weeks in a double-blind trial. After a wash-out period of 5 weeks or when they returned to baseline scores, patients were crossed over to the alternate treatments. Neurological function was assessed serially using a quantitative neurological disability score (NDS), a functional clinical grade (CG) and grip strength (GS) measurements. Electrophysiological studies were done at the beginning and end of each treatment. A primary 'intention to treat' analysis showed significant improvement with PE in all clinical outcome measures: NDS by 38 points, P < 0.001; CG by 1.6 points, P < 0.001; GS by +13 kg, P < 0.003 and in selected electrophysiological measurements, sigma proximal CMAP, P < 0.01; sigma motor conduction velocities, P < 0.006; sigma distal motor latencies, P < 0.01. Fifteen patients completed the trial and of those, 12 patients (80%) improved substantially with PE; i.e. five out of seven patients with chronic progressive course and seven out of eight patients with relapsing CIDP improved. There were three drop-outs; one patient lost venous access; one patient suffered a stroke and one patient left the trial to receive open treatment elsewhere. The improvement in motor functions correlated with the electrophysiological data, i.e. with improved motor conduction velocities and reversal of conduction block. Eight of 12 PE responders (66%) relapsed within 7-14 days after stopping PE. All improved with subsequent open label PE; all but two patients required long-term immunosuppressive drug therapy for stabilization. The PE non-responders improved with prednisone. We conclude that PE is a very effective adjuvant therapy for CIDP of both chronic progressive and relapsing course; concurrent immunosuppressive drug treatment is required. Exchange treatments should be given two to three times per week until improvement is established; the treatment frequency should then be tapered over several months.

Intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyneuropathy. A double-blind, placebo-controlled, cross-over study.

Thirty patients with definite or probable chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) of chronic progressive (16 patients) or relapsing (14 patients) course were randomly assigned to receive intravenous immunoglobulin (IvIg) 0.4 g per kg body weight or a placebo treatment on 5 consecutive days in a double-blind, cross-over trial. Neurological function was monitored by serial quantitative assessments [neurological disability score (NDS); clinical grade (CG) and grip strength (GS) measurements] and by electrophysiological studies before and after each treatment period. Twenty-five patients completed both treatment periods. A comparison of the observed changes in clinical outcome measures revealed statistically significant differences in favour of IvIg, with (mean +/- SD) improvements in NDS by 24.4 +/- 5.4 points (P < 0.002) in CG by 1 +/- 0.3 points (P < 0.001) in GS by +6.3 +/- 1.7 kg (P < 0.005), whereas scores were unchanged or worse with placebo. A secondary two-groups analysis of the first trial period included all 30 patients; 16 patients had been randomly assigned to IvIg and 14 to placebo treatments. Again significant differences in favour of IvIg were observed in all the clinical end-points: improvement in NDS was 35.6 +/- 25 points (P < 0.0001), in CG it was 1.3 +/- 1.9 points (P < 0.002) and in GS +9.8 +/- 7.7 kg (P < 0.001), whereas all scores worsened with placebo. Of the 30 patients, 19 (63%) improved with IvIg treatments; nine out of 16 patients (56%) with chronic progressive CIDP, and 10 out of 14 patients (71%) with relapsing CIDP (differences were not statistically significant). A placebo response was seen in five patients. Comparison of paired electrophysiological measurements before and 4 weeks after IvIg treatments revealed statistically significant improvements in the summed motor conduction velocities (sigma MCV; P < -0.0001) and in the summed compound muscle action potentials (CMAP) evoked with proximal stimulation (sigma proximal CMAP, P < 0.03) of median, ulnar, peroneal and tibial nerves. Eight of nine IvIg responders with chronic progressive CIDP improved gradually to normal function with a single 5 day course of IvIg; in five of these, small doses of prednisone were prescribed during follow-up. In 10 IvIg responders with relapsing CIDP, improvements lasted a median 6 weeks (range 3-22 weeks) and was reproducible with open label treatments. All 10 patients have been maintained and stabilized with IvIg pulse therapy of 1 g per kg body weight or less, given as a single infusion prior to the expected relapse. A beneficial response to IvIg was found to be most likely in patients with acute relapse or with disease of one year or less. Patients with predominantly sensory signs did not improve.