Litchy, William J.

While anal sphincter neurogenic injury documented by needle electromyography (EMG) has been implicated to cause fecal incontinence (FI), most studies have been uncontrolled. Normal values and the effects of age on anal sphincter motor unit potentials (MUP) are ill defined. The functional significance of anal sphincter neurogenic injury in FI is unclear. Anal pressures and EMG were assessed in 20 asymptomatic nulliparous women (age, 38 ± 5 yr; mean ± SE) and 20 women with FI (54 ± 3 yr). A computerized program quantified MUP duration and phases. These parameters and MUP recruitment were also semiquantitatively assessed by experienced electromyographers in real time. Increasing age was associated with longer and more polyphasic MUP in nulliparous women by quantitative analysis. A higher proportion of FI patients had prolonged (1 control, 7 patients, P = 0.04) and polyphasic MUP (2 controls, 9 patients, P = 0.03) at rest but not during squeeze. Semiquantitative analyses identified neurogenic or muscle injury in the anal sphincter (11 patients) and other lumbosacral muscles (4 patients). There was substantial agreement between quantitative and semiquantitative analyses (κ statistic 0.63 ± 95% CI: 0.32–0.96). Anal resting and squeeze pressures were lower ( P ≤ 0.01) in FI than controls. Anal sphincter neurogenic or muscle injury assessed by needle EMG was associated ( P = 0.01) with weaker squeeze pressures (83 ± 10 mmHg vs. 154 ± 30 mmHg) and explained 19% ( P = 0.01) of the variation in squeeze pressure. Anal sphincter MUP are longer and more polyphasic in older than younger nulliparous women. Women with FI have more severe neurogenic or muscle anal sphincter injury, which is associated with lower squeeze pressures.

OBJECTIVE To test whether diabetic polyneuropathies (DPNs), retinopathy, or nephropathy is more prevalent in subjects with impaired glycemia (IG) (abnormality of impaired fasting glucose [IFG], impaired glucose tolerance [IGT], or impaired HbA1c [IA1C]) than in healthy subjects (non-IG). RESEARCH DESIGN AND METHODS Matched IG and non-IG volunteers were randomly identified from population-based diagnostic and laboratory registries, restudied, and reclassified as non-IG (n = 150), IG (n = 174), or new diabetes (n = 218). RESULTS Frequency (%) of DPN in non-IG, IG, and new diabetes was 3 (2.0%), 3 (1.7%), and 17 (7.8%) narrowly defined (no other cause for polyneuropathy) and 19 (12.7%), 22 (12.6%), and 38 (17.4%) broadly defined. Mean and frequency distribution of composite scores of nerve conduction and quantitative sensation tests were not significantly different between IG and non-IG but were worse in new diabetes. Frequency of retinopathy and nephropathy was significantly increased only in new diabetes. In secondary analysis, small but significant increases in retinopathy and nephropathy were found in IGT, IFG, and IGT combined groups. CONCLUSIONS In population studies of Olmsted County, Minnesota, inhabitants, prevalence of typical DPN, retinopathy, and nephropathy was significantly increased only in subjects with new diabetes—not in subjects with IG as defined by American Diabetes Association (ADA) criteria of abnormality of IFG, IGT, or IA1C. For atypical DPN, such an increase was not observed even in subjects with new diabetes. In medical practice, explanations other than IG should be sought for patients with atypical DPN (chronic idiopathic axonal polyneuropathy) who have IG.

OBJECTIVE To evaluate the efficacy and safety of α-lipoic acid (ALA) over 4 years in mild-to-moderate diabetic distal symmetric sensorimotor polyneuropathy (DSPN). RESEARCH DESIGN AND METHODS In a multicenter randomized double-blind parallel-group trial, 460 diabetic patients with mild-to-moderate DSPN were randomly assigned to oral treatment with 600 mg ALA once daily (n = 233) or placebo (n = 227) for 4 years. Primary end point was a composite score (Neuropathy Impairment Score [NIS]–Lower Limbs [NIS-LL] and seven neurophysiologic tests). Secondary outcome measures included NIS, NIS-LL, nerve conduction, and quantitative sensory tests (QSTs). RESULTS Change in primary end point from baseline to 4 years showed no significant difference between treatment groups (P = 0.105). Change from baseline was significantly better with ALA than placebo for NIS (P = 0.028), NIS-LL (P = 0.05), and NIS-LL muscular weakness subscore (P = 0.045). More patients showed a clinically meaningful improvement and fewer showed progression of NIS (P = 0.013) and NIS-LL (P = 0.025) with ALA than with placebo. Nerve conduction and QST results did not significantly worsen with placebo. Global assessment of treatment tolerability and discontinuations due to lack of tolerability did not differ between the groups. The rates of serious adverse events were higher on ALA (38.1%) than on placebo (28.0%). CONCLUSIONS Four-year treatment with ALA in mild-to-moderate DSPN did not influence the primary composite end point but resulted in a clinically meaningful improvement and prevention of progression of neuropathic impairments and was well tolerated. Because the primary composite end point did not deteriorate significantly in placebo-treated subjects, secondary prevention of its progression by ALA according to the trial design was not feasible.

Health promotion programs may target a variety of behaviors including weight loss, exercise, stress, nutrition, or other risk factors. Comparing the outcomes of diverse programs is hampered by the absence of a common metric. Overall self-rated health has been used as a health outcome measure in population studies and in some primary care studies, but its potential use to monitor the outcomes of health programs is unexplored. The purpose of this study was to compare the outcomes of 4 health promotion programs using change in overall self-rated health as a common metric. Program-specific metrics used were weight change, change in minutes of exercise, change in stress management activities, and change in healthy nutrition practices. We found that, although all of our lifestyle interventions positively affected the program-specific metrics, only the weight loss and exercise programs showed improvement in specific metrics correlated with improvements in overall self-rated health. ( Population Health Management 2010;13:91–95)

OBJECTIVE—Assessing clinimetric performance of diabetic sensorimotor polyneuropathy (DSPN) end points in single and multicenter trials. RESEARCH DESIGN AND METHODS—Assessed were placebo-treated patients with DSPN in the Viatris and Eli Lilly trials and an epidemiologic cohort. RESULTS—Test reproducibility in clinical trial cohorts (rI ∼ 0.7–0.85) approached that in the epidemiologic cohort (rI ∼ 0.85–0.95). Associations between pairs of end points explained <10% of the variability of data (sometimes 15–35%), being higher in the epidemiologic cohort and the Viatris trial than in the Lilly trial. Most end points did not show monotonic worsening over 4 years. However, sural nerve amplitude and peroneal motor conduction velocity did. A nerve conduction score (Σ 5 NC nds [5 attributes of nerve conduction expressed as normal deviates]) did not show monotonic worsening in established DSPN. In the epidemiologic cohort followed for 9.5 years, monotonic worsening of small magnitude occurred for sural amplitude, vibration detection threshold, and especially for composite quantitative sensation. CONCLUSIONS—The main reason why it is difficult to demonstrate monotonic worsening of neuropathic end points appears to be a very slow worsening of DSPN, a placebo effect for symptoms and signs, and measurement noise. Demonstrating disease progression in controlled trials of DSPN is more likely when 1) patients with developing rather than established DSPN are selected, 2) type 1 diabetic patients are preferentially recruited, 3) patients are selected who cannot or will not achieve ideal glycemic control, 4) end points chosen are known to show monotonic worsening, and 5) a restricted number of centers and expert examiners (trained, certified, using standard approaches, and reference values and interactive surveillance of tests) are used.

This study analyzed forces in the tibiofemoral and pa tellofemoral joints during isokinetic exercise using an analytical biomechanical model. The results show that isokinetic exercise can produce large loads on these joints, especially during extension exercises. The tibio femoral compressive force (4.0 body weight) is approx imately equal to that obtained during walking but it occurs at 55° of knee flexion. Anterior shear forces (resisting force to anterior drawer) exist during exten sion exercise at less than 40° of knee flexion, with a maximum of 0.3 body weight. Posterior shear forces (resisting force to posterior drawer) exist during exten sion exercise at knee joint angles greater than 40° and during the flexion portion of isokinetic exercise. The maximum posterior shear force is 1.7 body weight. The patellofemoral joint can encounter loads as high as 5.1 body weight which are 10 times higher than during straight leg raises. These results suggest that isokinetic exercise should be used cautiously in patients with knee lesions.

OBJECTIVE—The objective of this study was to test whether monotone worsening of nerve function, attributable to diabetes, can be demonstrated before criteria for diabetic sensorimotor polyneuropathy (DSPN) have been met. Which nerve tests are best? RESEARCH DESIGN AND METHODS—From a prevalence cohort of 504 individuals in the Rochester Diabetic Neuropathy study (RDNS), we identified 238 individuals (group 1) who at first examination were without polyneuropathy (DSPN) by a sum score of the normal deviates (from percentiles) of five attributes of nerve conduction of the legs (i.e., their five nerve conduction normal deviate values were <97.5th percentile) and were followed longitudinally two or more times. Of these 238, 90 (group 2) were followed six or more times at yearly or biyearly intervals. We compared different nerve tests for the ones most sensitive and reliable in showing latent nerve dysfunction and monotone (the extent to which a variable measured repeatedly over time reveals a significant trend of worsening or improvement). RESULTS—In group 1 patients, the mean sum score of five attributes of nerve conduction (Σ 5 NC nds) at baseline was 1.08 and at the last examination (only patients with Σ 5 NC nds <97.5th percentile) was 3.63, markedly higher than that in healthy subjects (only of individuals with Σ 5 NC nds <97.5th percentile) (−0.12), indicating a subtle latent shift of nerve conduction tests toward abnormality. Serial evaluations of many individual and especially sum scores of nerve conduction tests in group 2 patients showed statistically significant worsening with time, even when nerve conduction tests were still well within normal limits. Neurologic signs also worsened but barely to significant levels; however, symptoms and quantitative sensation tests did not. Considering the composite score Σ 5 NC nds, 42 (of 90 group 2 patients) showed significant worsening, 22 were still without DSPN by nerve conduction test criteria, and some were even below the 50th percentile at the last evaluation. CONCLUSIONS—Subtle and latent functional worsening of nerve conduction can be demonstrated even before nerve conduction test criteria for DSPN have been met. For demonstrating monotone worsening, the order (from best to worst) of tests was: some composite scores of nerve conduction and individual attributes of nerve conduction. We did not show monotone worsening of symptoms or of quantitative sensation test results. In multivariate analysis of risk factors and their association with worsening Σ 5 NC nds, 24-h microalbuminuria (a marker of microvessel disease) was found to be a significant covariate, an indication that the asymptomatic alterations of nerve conduction are meaningful.

Increasingly more tests are being used to detect and characterize diabetic polyneuropathy, but their value in setting minimal criteria for the diagnosis of neuropathy and for staging severity remains inadequately studied. In 180 diabetics, we compared the percentage of patients with test abnormalities and associations among test results, evaluating neuropathic symptoms [neuropathy symptom score (NSS) and neuropathy scale of neuropathy symptom profile (NNSP)], deficits [neurologic disability score (NDS) and vibratory (VDT) and cooling (CDT) detection thresholds], or nerve dysfunction [nerve conduction (NC)]. The percentage of patients that were abnormal varied considerably depending on criteria for abnormality and the tests used. Abnormality (≥ 3 SD of 1 or more parameters) of NC of one or more of four nerves occurred in 80%, of two or more in 69%, of three or more in 46%, and of four in 21%. Similarly, for other tests, the rate of abnormality decreased with use of increasingly stringent criteria. Setting the criteria for abnormal NC at abnormality of two or more nerves, NSS at ≥ 1, NDS at > 6, NNSP at ≥ 97.5th percentile, and at ≥ 95th percentile for the other tests, NC was abnormal in 69%, NSS in 54%, NDS in 48%, NNSP in 47%, VDT in 44%, and CDT in 35%. Abnormality of any two or more of the six tests evaluated occurred in 64% of patients. We estimated that at least 16% of patients without abnormal NC (<2 abnormal nerves) had other findings indicative of neuropathy. By regression analysis, results of one test were in almost all cases associated with those of another test, but the association was not close enough to be predictive. Therefore, although NC provides objective and repeatable results, symptoms and deficits must be measured independently. Assuming no differences between groups of patients, the standardized and validated test (NNSP, VDT, or CDT) should provide the same results at different medical centers. By contrast, the results of NSS or NDS tests, with less standardized approaches and based on the judgment of physicians, might not provide the same results at different medical centers. Tests such as the ones described here may be used to define minimal criteria for the diagnosis of polyneuropathy and for staging its severity.

OBJECTIVE— Because α-lipoic acid (ALA), a potent antioxidant, prevents or improves nerve conduction attributes, endoneurial blood flow, and nerve (Na(+) K(+) ATPase activity in experimental diabetes and in humans and may improve positive neuropathic sensory symptoms, in this report we further assess the safety and efficacy of ALA on the Total Symptom Score (TSS), a measure of positive neuropathic sensory symptoms. RESEARCH DESIGN AND METHODS— Metabolically stable diabetic patients with symptomatic (stage 2) diabetic sensorimotor polyneuropathy (DSPN) were randomized to a parallel, double-blind study of ALA (600 mg) (n = 60) or placebo (n = 60) infused daily intravenously for 5 days/week for 14 treatments. The primary end point was change of the sum score of daily assessments of severity and duration of TSS. Secondary end points were sum scores of neuropathy signs (NIS), symptoms (NSC), attributes of nerve conduction, quantitative sensation tests (QSTs), and an autonomic test. RESULTS— At randomization, the groups were not significantly different by the criteria of metabolic control or neuropathic end points. After 14 treatments, the TSS of the ALA group had improved from baseline by an average of 5.7 points and the placebo group by an average of 1.8 points (P < 0.001). Statistically significant improvement from baseline of the ALA, as compared with the placebo group, was also found for each item of the TSS (lancinating and burning pain, asleep numbness and prickling), NIS, one attribute of nerve conduction, and global assessment of efficacy. CONCLUSIONS— Intravenous racemic ALA, a potent antioxidant, rapidly and to a significant and meaningful degree, improved such positive neuropathic sensory symptoms as pain and several other neuropathic end points. This improvement of symptoms was attributed to improved nerve pathophysiology, not to increased nerve fiber degeneration. Because of its safety profile and its effect on positive neuropathic sensory symptoms and other neuropathic end points, this drug appears to be a useful ancillary treatment for the symptoms of diabetic polyneuropathy.