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Vera Bril

Publications and source records attributed to Vera Bril.

At least 19 recordsLinked to original sources
PubMed2006

Sensitivity of repetitive facial-nerve stimulation in patients with myasthenia gravis.

Repetitive stimulation of the facial nerve is commonly performed in cases of suspected myasthenia gravis (MG) because bulbar weakness is often present, but the most sensitive facial muscle is unknown. We compared the sensitivity of repetitive nerve stimulation (RNS) to the frontalis and nasalis muscles in 244 patients with suspected MG. We found no difference in sensitivity of RNS when recording from these muscles in both ocular and generalized MG. In addition, we confirmed the low sensitivity of RNS for ocular (18%) or generalized (47%) MG. The specificity of facial RNS for both muscles was 100% and, in certain circumstances, may obviate the need for further diagnostic testing.

Aged↗
PubMed2006

Validation of a novel point-of-care nerve conduction device for the detection of diabetic sensorimotor polyneuropathy.

OBJECTIVE: The diagnosis of diabetic sensorimotor polyneuropathy using objective electrophysiological tests is hindered by limited access to the specialized laboratories and technicians that perform and interpret them. We evaluated the performance characteristics of a novel portable and automated point-of-care nerve conduction study device, which can be operated by nontechnical personnel, and compared it with conventional nerve conduction studies performed in a specialist setting. RESEARCH DESIGN AND METHODS: Seventy-two consecutive patients with diabetes (8 type 1, 64 type 2) from a diabetes and a neuropathy outpatient clinic were evaluated concurrently with conventional nerve conduction studies (the reference standard) and the point-of-care device for sural nerve function (sural nerve amplitude potentials in microvolts [microV]). RESULTS: Sural nerve amplitude potentials measured by the point-of-care device shared very strong correlation with the reference standard (Spearman's correlation coefficient 0.95, P < 0.001). The Bland and Altman method yielded agreement despite a small systematic underestimation by the point-of-care device of 1.2 +/- 3.4 microV. Despite this small systematic bias, the sensitivity and specificity of normal and abnormal sural nerve amplitude potentials measured by the point-of-care device for the detection of diabetic sensorimotor polyneuropathy defined by standard clinical and electrophysiological criteria were 92 and 82%, respectively. CONCLUSIONS: A novel point-of-care device has excellent diagnostic accuracy for detecting electrophysiological abnormality in the sural nerve of patients who have diabetes. This automated device represents an alternative to conventional nerve conduction studies for the diagnosis of diabetic sensorimotor polyneuropathy.

Aged↗
PubMed2006

Long-term effects of ranirestat (AS-3201) on peripheral nerve function in patients with diabetic sensorimotor polyneuropathy.

OBJECTIVES: We aimed to determine whether ranirestat, an aldose reductase inhibitor, maintains the improved nerve function observed in patients with diabetic sensorimotor polyneuropathy (DSP) after completing a 12-week nerve biopsy study. RESEARCH DESIGN AND METHODS: Patients with mild to moderate DSP, as determined by the presence of sural nerve responses, were enrolled in a double-blind, placebo-controlled biopsy trial and randomized to placebo or 5 or 20 mg/day ranirestat for 12 weeks. Patients completing this biopsy study were offered a 48-week extension at the same ranirestat dose or at 5 mg/day ranirestat if they were originally treated with placebo. Electrophysiological tests, the Toronto Clinical Neuropathy Score, and vibration perception thresholds (VPTs) were performed at entry and at 12 (end of the biopsy study) and 60 (end of the 48-week extension) weeks. RESULTS: Peroneal motor nerve conduction velocity (NCV) improved in the 20-mg/day group following 60 weeks of treatment. Sural and median sensory NCV improved after both 12 and 60 weeks of treatment with 20 mg/day. VPT improved after 60 weeks of treatment with 20 mg/day. Ranirestat was well tolerated with no difference in adverse events between the 5- and 20-mg/day groups. CONCLUSIONS: Twenty milligrams ranirestat per day improves NCV and VPT following 60 weeks of administration. The improved sensory nerve function observed after 12 weeks of therapy was maintained at 60 weeks, and improved motor nerve function was observed at 60 weeks.

Aldehyde Reductase↗
PubMed2005

Sural sensory action potential identifies diabetic peripheral neuropathy responders to therapy.

Identifying patients with diabetic peripheral neuropathy (DPN) amenable to therapy is a challenge. To determine whether the amplitude of the sural sensory nerve action potential (sural SNAP) reflects the severity of DPN, an analysis was performed on 205 patients with DPN, identified by an abnormal vibration detection threshold (VDT), who were enrolled in a multinational clinical trial investigating ruboxistaurin (RBX) mesylate. Nerve conduction velocity and response amplitude and latency were measured and compared. VDT was significantly lower in those with preserved sural SNAPs (n = 128) than in those in whom they were absent (n = 77; 21.5 vs. 22.7 JND units, P = 0.002). Thus, preserved sural SNAP denoted less severe DPN. Logistic regression analyses evaluating baseline characteristics, HbA(1c), and baseline symptom scores identified only DPN duration as a factor that might contribute to the presence of sural SNAP (P = 0.004; OR = 0.896). For patients with abnormal VDT, preserved sural SNAP identifies a patient population with less severe DPN who may respond to therapeutic intervention in clinical trials.

Action Potentials↗
PubMed2005

Treatment of symptomatic diabetic peripheral neuropathy with the protein kinase C beta-inhibitor ruboxistaurin mesylate during a 1-year, randomized, placebo-controlled, double-blind clinical trial.

OBJECTIVE: The aim of this study was to assess the effects of ruboxistaurin (RBX) mesylate on nerve function and sensory symptoms in patients with diabetes mellitus (DM) and diabetic peripheral neuropathy (DPN). METHODS: Patients were enrolled in a multinational, randomized, Phase II, double-blind, placebo-controlled parallel-group trial comparing 32 mg/d or 64 mg/d RBX with placebo for 1 year. DPN was identified by abnormal measurable vibration detection threshold (VDT) and verified by abnormal neurologic examination and nerve electrophysiology measures. Baseline patient characteristics (eg, sex, type of DM, age, body mass index, glycosylated hemoglobin, and duration of DM and DPN) were measured. The primary end point was the change in VDT. Secondary end point measures included effects of RBX versus placebo on Neuropathy Total Symptom Score-6 (NTSS-6), neurologic examination, electrophysiologic nerve conduction studies, Neuropathy Impairment Score, Clinical Global Impressions, and safety. A post-hoc analysis was performed on patients with less severe DPN (sural sensory nerve action potential > or =0.5 microV and NTSS-6 total score >6). RESULTS: Two hundred five patients were assessed: 66 were assigned to the RBX 32 mg/d group, 71 to the RBX 64 mg/d group, and 68 to the placebo group. The demographic and baseline characteristics of the treatment groups were well matched between the RBX 32 mg/d, RBX 64 mg/d, and placebo groups: mean (SD) age, 45.6 (8.41) years; 122 (60%) men, 83 (40%) women; 110 (54%) with type 1 DM, 95 (46%) with type 2 DM; mean (SD) duration of DPN, 3.4 (4.21) years. The RBX 32 mg/d group had slightly more patients with type 1 DM (P = 0.05). Eighty-three patients had clinically significant symptoms at baseline (defined as NTSS-6 total score >6: RBX 32 mg/d, n = 22; RBX 64 mg/d, n = 26; placebo, n = 35); 122 patients had NTSS-6 total scores < or =6. No treatment differences were observed for change in VDT. Among the 83 patients with significant symptoms at baseline, there was a reduction from baseline at 12 months in the NTSS-6 total score in the RBX 32 mg/d (P = NS) and RBX 64 mg/d (P = 0.015) groups compared with placebo. In a subgroup of patients with clinically significant symptoms and less severe DPN (n = 50), there was a significantly greater reduction in the NTSS-6 total score with RBX 64 mg/d (P = 0.006 vs placebo). Furthermore, in these patients, there was a statistically significant improvement in VDT for both RBX 32 mg/d (P = 0.012) and RBX 64 mg/d (P = 0.026) compared with placebo. CONCLUSIONS: RBX appeared to be well tolerated in the patients with DPN who participated in this study. Overall, changes in VDT and NTSS-6 total scores did not differ among treatment groups at end point. However, RBX treatment appeared to be of benefit for the subgroup of patients with less severe symptomatic DPN by relieving sensory symptoms and improving nerve fiber function, as indicated by reductions in VDT and NTSS-6 total score.

Adult↗
PubMed2005

Development and validity testing of the neuropathy total symptom score-6: questionnaire for the study of sensory symptoms of diabetic peripheral neuropathy.

OBJECTIVE: The aim of this study was to develop and validate a neuropathy sensory symptom scale, the Neuropathy Total Symptom Score-6 (NTSS-6), which evaluates individual neuropathy sensory symptoms in patients with diabetes mellitus (DM) and diabetic peripheral neuropathy (DPN) in clinical trials, with the intent of distinguishing a response to therapy. METHODS: The NTSS-6 questionnaire was developed to evaluate the frequency and intensity of individual neuropathy sensory symptoms identified frequently by patients with DPN (ie, numbness and/or insensitivity; prickling and/or tingling sensation; burning sensation; aching pain and/or tightness; sharp, shooting, lancinating pain; and allodynia and/or hyperalgesia). The NTSS-6 was administered 8 times over a 1-year period to DPN patients. The NTSS-6's reliability (determined by internal consistency and test-retest reproducibility), construct validity, convergent validity, and minimally clinically important differences (MCIDs) were determined. RESULTS: The NTSS-6 was administered to a total of 205 patients at 10 centers in the United States, Canada, Belgium, Germany, Hungary, Croatia, Slovenia, and the United Kingdom. Internal consistency was demonstrated at all 8 visits (Cronbach's alpha > 0.7). Test-retest reproducibility (intraclass correlation coefficient >0.9) was observed during the baseline period and at end point. Construct validity was demonstrated by statistically significant correlations between the NTSS-6 total score and the Neuropathy Symptoms and Change (NSC) score (r = 0.773-0.885, P < 0.001). Convergent validity was demonstrated by statistically significant correlations between the change in NTSS-6 total scores and the following: change in NSC scores (r = 0.519-0.708, P < 0.001); change in Neuropathy Impairment Score of the Lower Limbs and composite nerve function scores (r = 0.188-0.202, P < 0.007), and categories of the Clinical Global Impressions (r = 0.402, P < 0.001). The within- and between-groups MCIDs for the total NTSS-6 total scores were -1.26 and 0.97 points, respectively. The mean (SD) within-group MCID for all patients who improved on the Clinical Global Impression was -2.29 (3.4) points. CONCLUSIONS: The NTSS-6 provided a valid assessment of neuropathy sensory symptoms in this sample of patients with DM and DPN, which suggests that it may be useful for symptom evaluation in clinical trials and practice. The NTSS-6 showed internal consistency, test-retest reliability, and construct validity. There was also convergent validity of the scores, indicating that the NTSS-6 may be a suitable questionnaire for clinical trials that evaluate symptoms of DPN in this well-defined patient population.

Adult↗
PubMed2005

Hyaline body myopathy: adulthood manifestations.

BACKGROUND: Hyaline body myopathy (HBM) is a rare chronic nonprogressive congenital myopathy, with variable patterns of inheritance. METHODS: We describe a patient with congenital HBM with progression of weakness and increasing muscle pain in adulthood. Three muscle biopsies, done at various times in her life, are reported. RESULTS: Symptoms started during childhood; however, as an adult, following a period of stability with no progression of the disease, the patient became symptomatic with worsening proximal limb weakness, severe aching pain and hypertrophy of calves. Moderate elevations of serum creatine kinase and myopathic features were noted on electrophysiologic testing. Muscle pathology showed significant fatty infiltration of skeletal muscle and increased number of fibers with internal nuclei. Histology demonstrated the presence of subsarcolemmal, well-delineated hyaline areas, which on histochemical studies was shown to be limited to typel fibers. The hyaline bodies were dark with pH 4.2 ATPase and with immunohistochemical studies reacted only with myosin heavy chain slow. Electron microscopy showed the hyaline bodies to be composed of nonmembrane bound, fairly even sized granular material, which merged with the adjacent myofibrils. Earlier muscle biopsies, done during childhood, also revealed presence of similar subsarcolemmal hyaline deposits. CONCLUSION: There appears to be a pattern of presentation with adulthood progression in HBM, which has not been described before. Further case studies are required to understand the clinical progression in HBM.

Age Factors↗
PubMed2004

Carpal tunnel syndrome: cross-sectional and outcome study in Ontario workers.

PURPOSE: To carry out an analytic cross-sectional study of Ontario workers with carpal tunnel syndrome (CTS) and to assess workers' symptoms, functional disabilities, recreational difficulties, and work capability 4 years after treatment of their CTS. METHODS: Data were obtained by review of Ontario Workers Safety and Insurance Board (WSIB) files and by completion of self-assessment questionnaires. Inclusion criteria included all workers registered with the Ontario WSIB who were off work with newly diagnosed carpal tunnel syndrome in 1996. RESULTS: There are 3 million workers covered by the WSIB in the province of Ontario. In 1996, 964 of them developed work-related CTS that required time off for treatment. Of these patients 53% were women and 75% had bilateral CTS. Eighty-one percent of the unilateral cases involved the dominant extremity. The average age at the time of claim was 41 years and workers were at the same job type for an average of 7.4 years (unilateral) and 8.5 years (bilateral), respectively. Thirty-nine percent of workers had a history of another tendonitis or epicondylitis. Seventy-five percent of workers had surgery and on average returned to work 3 months later. Four years after treatment, outcome was assessed by self-administered questionnaires, for which there was a 73% response rate. Forty-six percent of workers experienced moderate to severe pain, 47% had moderate to severe numbness, and 40% had difficulty grasping and using small objects. Only 14% were symptom free. Successful return to work was considered to be a return to the same job with or without modifications, and it occurred in 64% of cases. Better clinical outcome scores were found to occur with surgery and abnormal nerve conduction study results. Worse clinical outcome scores were present with repeat surgery and surgical complications. Concurrent diagnoses of either tendonitis or epicondylitis also resulted in worse clinical outcome scores and worse return-to-work outcomes. The average total cost in Canadian dollars to the WSIB exceeded $13,700 per worker for a total cost in excess of $13,200,000 per year. (In 1996, $1 Canadian = $1.365 US.) CONCLUSIONS: These outcomes indicate that Canadian workers have a large amount of permanent pain and suffering, a large loss of work productivity, and incur a considerable financial cost as a result of work-related CTS.

Adult↗
PubMed2004

Aldose reductase inhibition by AS-3201 in sural nerve from patients with diabetic sensorimotor polyneuropathy.

OBJECTIVE: The primary purpose of this investigation was to determine whether AS-3201, a new aldose reductase inhibitor, penetrates the sural nerve and inhibits sorbitol and fructose accumulation in patients with diabetic sensorimotor polyneuropathy (DSP). An additional aim was to determine whether any changes in nerve function would manifest with AS-3201 therapy. RESEARCH DESIGN AND METHODS: Patients with mild to moderate DSP based on nerve conduction studies were randomized into one of three treatment groups in a double-blind fashion: placebo or AS-3201 at 5 or 20 mg/day. After 12 weeks of administration, the sural nerve was biopsied for measurement of sorbitol, fructose, and AS-3201. RESULTS: At baseline, no important clinical, electrophysiological, or laboratory differences were found between the three groups. The nerve sorbitol concentration of 3.14 x 10(-2) nmol/mg wet nerve in patients in the placebo group was inhibited by 65 and 84% in patients on AS-3201 at 5 and 20 mg/day, respectively (P < 0.001). Fructose levels were similarly inhibited. Sensory nerve conduction velocities improved by > or = 1 m/s (P < 0.05). CONCLUSIONS: AS-3201 penetrates the sural nerve and inhibits sorbitol accumulation in patients with DSP. Additional studies are needed to confirm the electrophysiological suggestion that AS-3201 delays progression or leads to regression of DSP.

Adolescent↗
PubMed2004

Low-intensity laser therapy for painful symptoms of diabetic sensorimotor polyneuropathy: a controlled trial.

OBJECTIVE: Low-intensity laser therapy (LILT) has been advocated for treatment of chronic pain disorders. Although the mechanism of pain relief is uncertain, this therapy has been suggested for relief of painful symptoms of diabetic sensorimotor polyneuropathy (DSP). The objective of this study was to determine whether LILT relieves the pain of DSP. RESEARCH DESIGN AND METHODS: We conducted a randomized, double-masked, sham therapy-controlled clinical trial in 50 patients with painful DSP diagnosed with the Toronto Clinical Neuropathy Score. All patients received sham therapy over a 2-week baseline period and were then randomized to receive biweekly sessions of either sham or LILT for 4 weeks. The primary efficacy parameter was the difference in the weekly mean pain scores on a visual analog scale (VAS). RESULTS: The patients had similar baseline characteristics for pain intensity, HbA(1c), and duration of DSP. Both groups noted a decrease in weekly mean pain scores during sham treatment. After the 4-week intervention, the LILT group had an additional reduction in weekly mean pain scores of -1.0 +/- 0.4 compared with -0.0 +/- 0.4 for the sham group (P = 0.07). LILT had no effect on the Toronto Clinical Neuropathy Score, nerve conduction studies, sympathetic skin response, or quantitative sensory testing. CONCLUSIONS: Although an encouraging trend was observed with LILT, the study results do not provide sufficient evidence to recommend this treatment for painful symptoms of DSP.

Adult↗
PubMed2004

Sural nerve sorbitol in patients with diabetic sensorimotor polyneuropathy.

OBJECTIVE: Nerve sorbitol levels have been measured in sural nerve biopsy samples from patients with diabetic sensorimotor polyneuropathy in several studies using different methods and measurement units. In this study, we compared the results of sorbitol assays to determine the required sensitivity of analytical methods for nerve sorbitol measurements. RESEARCH DESIGN AND METHODS: We performed a literature search using PaperChase for reports of nerve sorbitol in diabetic patients and selected those with nerve conduction studies to delineate the severity of nerve damage. RESULTS: In patients who had undergone a nerve conduction study, the standardized nerve sorbitol levels were 0.034-0.300 nmol/mg wet nerve. CONCLUSIONS: Our results showed the level of sensitivity required in laboratory methodology to perform this assay in the target population and aid in the planning of clinical research trials of aldose reductase inhibitor agents.

Adult↗
PubMed2004

Cooling detection thresholds in the assessment of diabetic sensory polyneuropathy: comparison of CASE IV and Medoc instruments.

OBJECTIVE: Cooling detection threshold testing may be an important quantitative method for assessing polyneuropathy, in that it has traditionally been viewed as a measure of small-fiber involvement. The present study sought to determine the agreement between two common testing devices and to determine whether these are concordant in their association with predictor variables for diabetic sensory polyneuropathy. RESEARCH DESIGN AND METHODS: A total of 83 patients with diabetes (10 patients with type 1 diabetes and 73 patients with type 2 diabetes) and a wide spectrum of diabetic sensory polyneuropathy severity underwent concurrent cooling detection threshold testing using the Medoc and CASE IV instruments. Common predictor variables for diabetic sensory polyneuropathy were measured on the same day. RESULTS: Measurements of cooling detection thresholds by both instruments were highly correlated (Spearman's correlation coefficient 0.81, P < 0.001) and demonstrated a high degree of agreement by the method of Bland and Altman (95% distribution critical values for the difference in cooling detection thresholds, +7.5 and -5.6 degrees C). Cooling detection thresholds by both instruments were strongly correlated with clinical indicators of large-fiber neuropathy but not with the symptoms of small-fiber neuropathy (pain). CONCLUSIONS: These two instruments available for assessment of cooling detection thresholds are interchangeable for research in diabetic sensory polyneuropathy. However, this modality is equivalent to other modalities of quantitative sensory threshold testing in its association with indicators of large-fiber neuropathy and does not seem to provide an advantage for the prediction of small-fiber involvement.

Diabetic Neuropathies↗
PubMed2003

Impact of minimally invasive trans-cervical thymectomy on outcome in patients with myasthenia gravis.

OBJECTIVE: To study the impact of minimally invasive trans-cervical thymectomy on the incidence of remission of patients with myasthenia gravis (MG) in a single institution over a 10-year period. METHODS: A total of 120 consecutive patients referred for video-assisted trans-cervical thymectomy between 1991 and 2000 were included in the analysis. Complete remission was defined as no symptoms and no treatment for 6 months, and remission as minimal ocular symptoms (slight ptosis) or treatment with pyridostigmine only for 6 months. RESULTS: There were 86 females and 34 males with a median age of 33 (range 14-79) and 36 years (range 12-68), respectively. Symptoms of MG lasted between 2 months and 17 years before thymectomy (median 10 months). Surgery was converted to a partial upper sternotomy in 23 cases (19%). The median hospital stay decreased from 2 days (range 1-8) before 1994 to 1 day (range 1-8) thereafter (p<0.0001). Postoperative complications occurred in four patients (3.3%). After a median follow-up of 48 months (range 6-117 months), 50% of the patients were in complete remission (41%) or in remission (9%). Kaplan-Meier estimates rate of complete remission were 30% after 5 years of follow-up and 91% after 10 years. CONCLUSIONS: Minimally invasive trans-cervical thymectomy can be performed with short hospital stay and low morbidity, and achieve excellent durable results at 10 years.

Adult↗
PubMed2003

Diabetic neuropathy: a review emphasizing diagnostic methods.

Diabetic sensorimotor polyneuropathy (DSP) is the most common complication of diabetes. In order to manage DSP effectively, it is necessary to formulate an accurate diagnosis and monitor subjects regularly. This review of important aspects of the diagnosis of DSP starts with a conceptual framework that includes elements of DSP epidemiology, pathophysiology, and therapy. The emphasis of the review is to present our current understanding of diagnostic methods for DSP including their utility and limitations. Screening for DSP in the diabetes clinic can be achieved successfully using simple clinical tests. Clinical neurophysiological methods are necessary to exclude other diagnoses, stage severity, and monitor the course of DSP. Novel investigative techniques are highly promising, but their usefulness in the clinic setting remains limited at this time. This article presents an overview of diagnostic methods for DSP.

Diabetes Complications↗
PubMed2002

Comparison of sensory testing on different toe surfaces: implications for neuropathy screening.

Successful screening for neuropathy in patients with diabetes is available using the 10 g Semmes-Weinstein monofilament (Mid-Delta Health Systems, Inc., Belzoni, MS) (touch/pressure sensation) and the Neurothesiometer (Horwell Scientific, London, UK; vibration perception threshold). In healthy volunteers and patients with a broad range of diabetic sensorimotor neuropathy, we show that the predictive value of either test for diabetic sensorimotor neuropathy depends on the toe surface tested. These results establish the importance of standardized screening methods for diabetic sensorimotor neuropathy in the clinic and in clinical research trials.

Diabetes Complications↗