Nerve Function Tests Research Articles

Screening for the High-risk Foot of Ulceration: Tests of Somatic and Autonomic Nerve Function

Diabetic foot ulcers affect almost 5% of the patients with diabetes and carry a huge physical, emotional, and financial burden. Almost 80% of amputations in patients with diabetes are preceded by a foot ulcer. The need for simple screening methods for prevention of foot ulcers and amputations is indisputable. Simple tests such as monofilament, tuning fork, vibration perception threshold determination, ankle reflexes, and pinprick sensation alone or in combination have been studied prospectively and can be used for identification of patients at risk. Newer tests examining sudomotor dysfunction and skin dryness have been introduced in recent years. In cross-sectional studies sudomotor dysfunction assessed by either sympathetic skin response or NEUROPAD™ (Miro Verbandstoffe GmbH, Wiehl-Drabenderhöhe, Germany) testing has been consistently associated with foot ulceration. In addition, NEUROPAD™ testing is simple, reproducible, and widely available and has a high sensitivity for the diagnosis of clinical or subclinical diabetic polyneuropathy. Prospective studies are required to establish whether sudomotor dysfunction can predict foot ulcers and if simple methods assessing sudomotor dysfunction (eg, NEUROPAD™ testing) can be included in the screening tests for the prevention of this complication.

Preliminary Data on Vibratip®, A New Source of Standardised Vibration for Bedside Assessment of Peripheral Neuropathy

Testing vibration sense is a recognised component of neuropathy assessment. One hundred consecutive patients attending diabetic annual review and podiatry clinics were enrolled in a study to compare a 10 g Semmes-Weinstein monofilament and a 128Hz tuning fork with VibraTip®, a novel, key-fob-sized source of fixed amplitude vibration for the identification of peripheral neuropathy. Patients were tested sequentially with the three devices in random order on either the left or right foot. Of the 100 patients 55 felt both the vibrating tuning fork and VibraTip, the remaining 45 patients felt neither. Pressure from the 10 g monofilament was perceived by 53 patients of whom 51 also felt VibraTip®. VibraTip® proved a practical, hygienic, simple, rapid and very specific test of the integrity of vibration sense, easily controlled with a null stimulus, that appeared highly engaging for patients. As the utility of testing for neuropathy is no more or less than a strategy to persuade patients to change their behaviour, VibraTip® may be a useful addition to sensory nerve function testing at the clinical interface.

Multimodality Imaging of Peripheral Neuropathies of the Upper Limb and Brachial Plexus

The peripheral nerves of the upper limb are affected by a number of entrapment and compression neuropathies. These discrete syndromes involve the brachial plexus as well as the musculocutaneous, axillary, suprascapular, ulnar, radial, and median nerves. Clinical examination and electrophysiologic studies are the traditional mainstay of diagnostic work-up; however, ultrasonography and magnetic resonance imaging provide spatial information regarding the affected nerve and its surroundings, often assisting in narrowing the differential diagnosis and guiding treatment. Imaging is particularly valuable in complex cases with discrepant nerve function test results. Familiarity with the clinical features of various peripheral neuropathies of the upper extremity, the relevant anatomy, and the most common sites and causes of nerve entrapment assists in diagnosis and treatment.

Evaluation of a Novel, Noninvasive, Objective Test of Auditory Nerve Function in Paediatric Cochlear Implant Candidates

(2010). Evaluation of a Novel, Noninvasive, Objective Test of Auditory Nerve Function in Paediatric Cochlear Implant Candidates. Cochlear Implants International: Vol. 11, Proceedings of the 9th European Symposium on Paediatric Cochlear Implantation, Warsaw, 2009, pp. 421-425.

Long‐term neurologic and peripheral vascular toxicity after chemotherapy treatment of testicular cancer

Testicular cancer is curable in the majority of men, and persisting treatment toxicity is a concern. The authors report a cross-sectional study of the long-term effects of chemotherapy (C) on neurologic function and development of Raynaud phenomenon. Seven hundred thirty-nine patients who were treated between 1982 and 1992 gave consent to enter the study. Patients were classified according to the receipt of C (n = 384) or no C (n = 355). Patients completed a general health questionnaire and a quality-of-life form (the European Organization for Research and Treatment of Cancer Quality-of-Life C30 questionnaire with testicular module). Symptom scores of 3 or 4 were considered clinically significant. Patients were assessed in the clinic, and clinical history was used to diagnose Raynaud phenomenon (RP) and tinnitus. Examinations included peripheral nerve function testing for light touch and vibration sense. Five hundred seventy-seven patients underwent audiometry. On physician assessment, peripheral neuropathy and RP were more common after C (21.7% vs 9.1% [P<.001] and 20.3% vs 1.7% [P<.001], respectively). Similar results were obtained for symptom scores (12.5% vs 5.5% [P = .002] and 9.7% vs 3.7% [P<.001], respectively). On multivariate analysis, for peripheral neuropathy, the significant predictors were cisplatin dose, carboplatin dose, and age. For RP, the significant predictor was bleomycin. Significant differences in hearing thresholds were noted at 8000 hertz only and, on multivariate analysis, were related to age, cisplatin dose, and vincristine dose. Auditory symptom scores did not differ between groups. With long-term follow-up, peripheral neuropathy and RP remained detectable in approximately 20% of patients and caused significant symptoms in 10% of patients. Detectable effects on high frequency remained but caused little symptomatic problem. These effects persisted and were related to the cumulative chemotherapy dose.

Comments on Van Veen et al.’s simplified nerve function tests

Comments on Van Veen et al.’s simplified nerve function tests

Evaluation of a Novel, Noninvasive, Objective Test of Auditory Nerve Function in Cochlear Implant Candidates

To investigate whether the objective noninvasive recording of the electrically evoked amplitude modulation following response (EAMFR) can be applied for the assessment of auditory nerve function before cochlear implant surgery. Prospective clinical study from January 2005 to August 2008. Cochlear Implant Program at the Charité University Hospital (Berlin, Germany). One hundred twenty-one patients with severe to total bilateral sensorineural hearing impairment. Diagnostic. All EAMFR thresholds were correlated with the mean intraoperative electrically evoked compound action potential (ECAP) thresholds. In a subgroup of 16 patients, the objective thresholds of the EAMFR were compared with the subjective auditory thresholds for the electrical stimuli applied. The intraindividual left-right concordance of the EAMFR and ECAP thresholds was investigated in 22 patients with bilateral implants. The EAMFR-auditory nerve function test produced clear responses in all patients examined. The threshold of auditory perception for the applied stimuli correlated highly significantly with the EAMFR threshold (r = 0.89, p < 0.01). The correlation between the EAMFR and mean ECAP thresholds was again highly significant (r = 0.49, p < 0.01). In all patients with bilateral implants, the ear with the lower preoperative EAMFR threshold was also the one with the lower intraoperative mean ECAP threshold. These results indicate that the objective noninvasive recording of EAMFR seems to be a useful diagnostic tool for the evaluation of the auditory nerve function in cochlear implant candidates, especially in children or in adult patients who require objective examination.

Microvascular and macrovascular complications associated with diabetes in children and adolescents

Department of Pediatrics, Ulleval University˚Hospital, and Faculty of Medicine, University of Oslo, NorwayCorresponding author:Assoc. Prof. Kim DonaghueThe Children’s Hospital at Westmead, Locked Bag 4001,Westmead, NSW 2145, Australia.Tel: C61 2 9845 3172;fax: C61 2 9845 3170;e-mail: kimd@chw.edu.auAcknowledgments: Esko Wiltshire, Gisela Dahlquist, KennethLee Jones, Edna Roche, Amina Balafrej and Riccardo Bonfanti.Conflicts of interest: The authors have declared no conflictsof interest.Editors of the ISPAD Clinical Practice Consensus Guide-lines 2009 Compendium: Ragnar Hanas, Kim Donaghue,Georgeanna Klingensmith, and Peter Swift.This article is a chapter in the

Predicting Neuropathy and Reactions in Leprosy at Diagnosis and Before Incident Events—Results from the INFIR Cohort Study

BackgroundLeprosy is a disease of skin and peripheral nerves. The process of nerve injury occurs gradually through the course of the disease as well as acutely in association with reactions. The INFIR (ILEP Nerve Function Impairment and Reactions) Cohort was established to identify clinically relevant neurological and immunological predictors for nerve injury and reactions.Methodology/Principal FindingsThe study, in two centres in India, recruited 188 new, previously untreated patients with multi-bacillary leprosy who had no recent nerve damage. These patients underwent a series of novel blood tests and nerve function testing including motor and sensory nerve conduction, warm and cold detection thresholds, vibrometry, dynamometry, monofilament sensory testing and voluntary muscle testing at diagnosis and at monthly follow up for the first year and every second month for the second year. During the 2 year follow up a total of 74 incident events were detected. Sub-clinical changes to nerve function at diagnosis and during follow-up predicted these new nerve events. Serological assays at baseline and immediately before an event were not predictive; however, change in TNF alpha before an event was a statistically significant predictor of that event.Conclusions/SignificanceThese findings increase our understanding of the processes of nerve damage in leprosy showing that nerve function impairment is more widespread than previously appreciated. Any nerve involvement, including sub-clinical changes, is predictive of further nerve function impairment. These new factors could be used to identify patients at high risk of developing impairment and disability.

Small fiber neuropathy: A burning problem

Small fiber neuropathy is increasingly being recognized as a major cause of painful burning sensations in the feet, especially in the elderly. Although strength remains preserved throughout the course of the disease, the pain and paresthesias are often disabling. Diabetes mellitus is the most common identifiable cause of small fiber neuropathy, and impaired oral glucose tolerance and individual components of the metabolic syndrome are often associated with it. Some cases, however, are idiopathic. Skin biopsy (with an evaluation of the density of intraepidermal nerve fibers) and tests of autonomic nerve function are useful for the diagnosis. Management involves controlling pain and identifying and aggressively treating the underlying cause.

Using botulinum toxin to treat diabetic foot pain

Botulinum toxin type A (BoNT/A) is made naturally by certain bacteria. BoNT/A works by paralyzing specific kinds of nerve cells. BoNT/A can be used to treat many illnesses that affect either nerves or the muscles with which they communicate. In the article “Botulinum Toxin for Diabetic Neuropathic Pain: A Randomized Double-Blind Crossover Trial,” Dr. Yuan and associates describe how BoNT/A might be used to treat the kind of nerve pain that develops in some people who have diabetes.1 The study compares whether injecting BoNT/A into the skin is better at reducing neuropathic pain than injecting a placebo (saline, salt water) into the skin. Dr. Yuan and colleagues looked carefully at 20 people who had neuropathic pain due to type 2 diabetes. Each person had been diagnosed with diabetes for at least 3 years. Patients with neuropathy experienced either paresthesias (prickling, tingling, or numbness) or a specific kind of pain (burning, itchy, shooting, etc.) in both of their feet up to the ankle or mid-shin. Doctors assessed the pain by 1) physical examination, 2) a specific questionnaire for pain, and 3) a specific test of nerve function. The nerve test is called a nerve conduction velocity test. It is designed to see how well patients’ nerves can transmit electrical signals. If the nerve is damaged, as happens in diabetes, the signals carried by the nerves are either slower or weaker than normal. As in all studies, there are reasons to include specific participants. This makes sure that the group is alike and that the results are solid. For instance, only people with proven polyneuropathy due to diabetes were included. Since a specific treatment was being studied, only people who had not changed …

Management of Adult Vocal Fold Nerve Injury

AbstractDiagnosis and management of nerve impairment in adults can be difficult due to the myriad of other diagnoses that must be considered. Accurate diagnosis of severity of a nerve impairment and determination of prognostic indicators for return of adequate function are paramount to best management. The strongest prognostic test of nerve function is electromyography. Team management by an otolaryngologist and speech-language pathologist of vocal fold paralysis needs to be sensitive to the patient's needs, both short-term and long-term. This article summarizes the current diagnostic tests and options. Case studies are included to guide the reader through team management and surgical options.

Reliability of clinical tests to evaluate nerve function and mechanosensitivity of the upper limb peripheral nervous system

BackgroundClinical tests to assess peripheral nerve disorders can be classified into two categories: tests for afferent/efferent nerve function such as nerve conduction (bedside neurological examination) and tests for increased mechanosensitivity (e.g. upper limb neurodynamic tests (ULNTs) and nerve palpation). Reliability reports of nerve palpation and the interpretation of neurodynamic tests are scarce. This study therefore investigated the intertester reliability of nerve palpation and ULNTs. ULNTs were interpreted based on symptom reproduction and structural differentiation. To put the reliability of these tests in perspective, a comparison with the reliability of clinical tests for nerve function was made.MethodsTwo experienced clinicians examined 31 patients with unilateral arm and/or neck pain. The examination included clinical tests for nerve function (sensory testing, reflexes and manual muscle testing (MMT)) and mechanosensitivity (ULNTs and palpation of the median, radial and ulnar nerve). Kappa statistics were calculated to evaluate intertester reliability. A meta-analysis determined an overall kappa for the domains with multiple kappa values (MMT, ULNT, palpation). We then compared the difference in reliability between the tests of mechanosensitivity and nerve function using a one-sample t-test.ResultsWe observed moderate to substantial reliability for the tests for afferent/efferent nerve function (sensory testing: kappa = 0.53; MMT: kappa = 0.68; no kappa was calculated for reflexes due to a lack of variation). Tests to investigate mechanosensitivity demonstrated moderate reliability (ULNT: kappa = 0.45; palpation: kappa = 0.59). When compared statistically, there was no difference in reliability for tests for nerve function and mechanosensitivity (p = 0.06).ConclusionThis study demonstrates that clinical tests which evaluate increased nerve mechanosensitivity and afferent/efferent nerve function have comparable moderate to substantial reliability. To further investigate the clinometric properties of these tests, more studies are needed to evaluate their validity.

糖尿病性ニューロパチーの病態と治療

Diabetic neuropathy (DN) is the most frequent among peripheral neuropathies. Since its pathophysiology is so complicated, neither classification nor therapeutic management of DN has been established. Sensory/autonomic polyneuropathy (DP) is the main type of DN. Since diabetic patients occasionally have one or more subtypes of DN and/or other polyneuropathy including treatable neuropathy like CIDP, the treatment for DP has to be conducted after excluding the possibility of other conditions. Glycemic control is most essential to prevent the development of DP. However, it is practically difficult to keep HbA1c under 6.5% so that drinking and smoking better be restricted and blood pressure be properly maintained to retard the progression of DP. Aldose reductase inhibitor is only one commercially available drug for DP and its efficacy must be evaluated by nerve function tests along with subjective symptoms. More vigorous therapeutic procedure is expected by obtaining not only more potential drugs based on pathogenic mechanisms but also the technique targeting of DNA/siRNA of given peptides at dorsal root ganglion neurons.

The significance of second lumbrical-interosseous latency comparison in the diagnosis of carpal tunnel syndrome

To assess the significance of the second lumbrical-interosseous latency (2LI-DML) comparison in the diagnosis of carpal tunnel syndrome (CTS). We examined 150 consecutive hands of patients referred with suspected CTS, using the 2LI-DML test and other standard measures of median nerve function. Correlations of the 2LI-DML test with standard tests were computed. Hundred and four hands were electrophysiologically confirmed to have CTS. The 2LI-DML test was abnormal in 99/104 (95.2%) hands with CTS with a mean value of 1.54 +/- 1.12 ms. Among the other measures, the orthodromic median-ulnar palmar velocity comparison was the most frequently abnormal test (95/104 hands, 91.3%), followed by the double-peak morphology of orthodromic sensory action potential from digit 4 (94/104, 90.4%). The 2LI-DML test significantly correlated, either positively or negatively, with all other standard tests. The 2LI-DML comparison is highly sensitive in diagnosing CTS, even in mild cases in which standard tests fail to detect abnormalities.

Importance of extrasphincteric mechanisms in the pathophysiology of faecal incontinence in adults with a history of anorectal anomaly

Although surgery for congenital anorectal anomalies (ARAs) aims to preserve anorectal function, faecal incontinence and constipation often result. Apart from the anal sphincters, continence is dependent on multiple anatomical and physiological factors. The aim of this study was to evaluate adults with a history of ARA to determine the role of such factors in functional outcome. The study included 20 consecutive adult patients with faecal incontinence who had undergone anorectal surgery as infants. Comprehensive testing included anal manometry, endoanal ultrasonography, tests of pudendal nerve function and rectal sensory function, evacuation proctography and colonic transit studies. Anal resting tone and squeeze increments were both attenuated in 15 of 19 patients. Integrity of the internal and external anal sphincters was compromised in 16 and 15 of 18 patients respectively. Eleven of 13 had evidence of pudendal neuropathy. Rectal sensation was abnormal in 14 of 18 patients, of whom ten were hypersensitive and four hyposensitive. Rectal evacuation was abnormal in nine of 14. Colonic transit was delayed in five of eight patients with constipation. Faecal incontinence in adult patients with ARA is related to various pathophysiologies. Structural integrity of the anal sphincters is a major factor, but extrasphincteric mechanisms, notably rectal sensory function, may be as important.

Progression of Cardiovascular Autonomic Dysfunction in Patients With Type 2 Diabetes

OBJECTIVE—We investigated whether cardiovascular autonomic dysfunction was associated with glycemic control status over time in patients with type 2 diabetes.RESEARCH DESIGN AND METHODS—From 1999 to 2000, cardiovascular autonomic nerve function testing (AFT) was performed on patients with type 2 diabetes (n = 1,021) and was followed-up in 2006 and February 2008. Tests for cardiovascular autonomic functions measured heart rate variability parameters (expiration-to-inspiration [E/I] ratio, responses to the Valsalva maneuver, and standing). AFT scores were determined from the results of the each test as follows: 0 for normal and 1 for abnormal. We began with those who had a score of 0 and assessed the changes in total score along with biannual A1C levels.RESULTS—At follow-up, the development of cardiovascular autonomic dysfunction was 34.5% (E/I ratio 21.9%, Valsalva maneuver 77.8%, and posture 58.9%; n = 783). The development of cardiovascular autonomic dysfunction was higher in older patients (P < 0.001); in those with longer duration of diabetes (P < 0.001); of hypertension (P = 0.005), and of diabetic retinopathy (P < 0.001); and in those who had higher levels of microalbuminuria (P = 0.002). Logistic regression analysis revealed that the development of cardiovascular autonomic dysfunction was strongly associated with the mean A1C level during the follow-up period (mean A1C >9.0% vs. ≤7.0%, odds ratio 2.984, 95% CI 1.177–7.561; P = 0.021).CONCLUSIONS—The development of cardiovascular autonomic dysfunction was independently associated with microvascular complications and glycemic control status during this 7.5-year follow-up in patients with type 2 diabetes.

RETRACTED: Epalrestat, an aldose reductase inhibitor, in diabetic neuropathy: An Indian perspective

Background:A number of diabetic patients with diabetic neuropathy, in India, were treated with epalrestat, an aldose reductase inhibitor. In this study, more than 2000 patients with diabetic neuropathy, who were treated with epalrestat for 3-12 months, were analyzed to assess the efficacy and the adverse reactions of the drug.Method:We analyzed the subjective symptoms (spontaneous pain, numbness, coldness and hypoesthesia) and the nerve function tests (motor nerve conduction velocity, sensory nerve conduction velocity and vibration threshold).Result:The improvement rate of the subjective symptoms was 75% (slightly improved or better) and that of the nerve function tests 36%. Adverse drug reactions were encountered in 52 (2.5%) of the 2190 patients, none of which was severe.Conclusion:Although data are limited, it is strongly suggested that epalrestat is a highly effective and safe agent for the treatment of diabetic neuropathy.

Erythrocyte sorbitol level as a predictor of the efficacy of epalrestat treatment for diabetic peripheral polyneuropathy

The relationship between the effect of aldose reductase inhibitors (ARIs) on the activation of the polyol pathway and on diabetic neuropathy has not been fully established. To address this issue, we investigated the effect of epalrestat (150 mg/day), an ARI, on erythrocyte sorbitol levels as an index of polyol activation and on nerve function test results in 43 patients with diabetic peripheral polyneuropathy. After 6 months of epalrestat administration, erythrocyte sorbitol levels did not decrease in patients as a whole. However, a decrease in erythrocyte sorbitol levels during epalrestat administration was significantly correlated with baseline erythrocyte sorbitol levels ( ρ=−.47, P<.01): The higher the level at baseline, the greater the decrease after epalrestat treatment. Moreover, the mean sorbitol level during epalrestat treatment was associated with the beneficial effect of epalrestat on vibration sensitivity as measured with a C-128 tuning fork ( ρ=−.66, P<.01) and/or a pallesthesiometer TM-31A ( ρ=.53, P<.05). On the other hand, erythrocyte sorbitol levels did not reflect the prognosis of nerve conduction velocity. These findings at least partly suggest a causal relationship between polyol activation and the development of diabetic neuropathy. Aldose reductase inhibitor treatment may be clinically useful in the control of polyol activation, especially in patients with excessive accumulation of sorbitol.

FC17.2 Symptoms and peripheral nerve function tests in Fabry’s disease

FC17.2 Symptoms and peripheral nerve function tests in Fabry’s disease