Citations

AbstractIntroduction/AimsIn the Diabetes Control and Complications Trial (DCCT), the minimal nerve conduction (NC) criterion for diabetic sensorimotor polyneuropathy (DSPN) was abnormality of NC in more than one peripheral nerve without specifying the attributes of NCs to be evaluated. In the present study, we assess individual and composite scores of NCs meeting the DCCT criterion and signs for improved diagnosis and assessment of DSPN severity.MethodsEvaluated were 13 attributes and 6 composite NC scores and signs and symptoms in 395 healthy subjects (HS) and 388 persons with diabetes (DM).ResultsPercent abnormality between subjects with DM and HS was remarkably different among individual attributes and the six composite NC scores. For diagnosis of DSPN using the DCCT criterion, assessment of conduction velocities (CVs) and distal latencies (DLs) provided sensitive diagnoses of DSPN. NC amplitudes provided stronger measures of severity. In studied cohorts, DSPN was staged: N0, no NC abnormality using NC score 2 (CVs and DLs), 60.0%; N1, NC abnormality only, 18.4%; N2, NC abnormality and signs of feet or legs, 16.3%; and N3, NC abnormality and signs of thighs, 5.3%.DiscussionFor sensitive and standard diagnosis of DSPN using the DCCT NC criterion, specifically defined composite scores of CVs and DLs, e.g., score 2, is recommended. A composite score of amplitudes, e.g., score 4, provides a stronger measure of neuropathy severity. Also, provided are HS reference values of evaluated attributes of NCs and estimates of staged severity of DSPN of mid North American DM cohorts.

Abstract Variable differences of nerve conduction amplitudes vs velocities and distal latencies (DLs) of healthy subjects assessed in ethnic cohorts. Introduction/Aims The variables affecting reference compound muscle (CMAP) and sensory nerve action potential (SNAP) amplitudes as compared to ones affecting conduction velocities and DLs have not been adequately evaluated in previous studies. In this report, this subject is studied in healthy subject cohorts mainly of Northern European extraction, Northern Plains Indians, and Latinos. Methods Nineteen variables and 18 attributes of nerve conductions (NCs) were assessed using highly standard testing conditions and techniques. Classification and Regression Tree analyses were used to assess variable differences among amplitudes, conduction velocities, and DLs. Results The most important variable affecting CMAP and SNAP amplitudes was age. For conduction velocities (CVs) and DLs, the variables were height, ethnic cohort, and age. Discussion The variables affecting attributes of NCs were similar for the three ethnic cohorts evaluated. The differences of variables affecting amplitudes compared to CVs and DLs need to be taken into account in interpretation of NC results and in setting reference limits for use in medical practice, epidemiology surveys, and therapeutic trials. Scores of CMAP and SNAP amplitudes are suitable measures of sensorimotor polyneuropathy severity, whereas conduction velocities and DLs reflect physiologic/pathologic abnormality of nerve fibers.

Abstract Objectives: The objective of the study is to distinguish the mechanisms of disease for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN), which we believe to be fundamentally different. However, distinguishing the mechanisms is more difficult when the presentation of CIDP is motor-predominant, focal, or asymmetric. Methods: We describe 3 focal, motor-predominant, representative cases that could be interpreted on clinical and/or electrophysiological grounds as either MMN or focal CIDP, and present pathological findings. Results: We highlight pathological differences in these cases, and provide an argument that CIDP and MMN are distinct entities with different pathophysiological mechanisms—chronic demyelination for CIDP, and an immune-mediated attack on paranodal motor axons for MMN. Conclusions: Based on clinical evaluation, electrophysiology, and nerve biopsy pathology, we can divide the conditions into inflammatory demyelinating neuropathy (focal CIDP) versus chronic axonal neuropathy (MMN). The divergent pathological findings provide further evidence that CIDP and MMN are fundamentally different disorders.

Abstract Patients with Type 2 Diabetes (T2D) are at higher fracture risk despite having relatively normal or even increased BMD by DXA. Increased cortical porosity has emerged as a potential factor contributing to fragility fractures in T2D. However, there is conflicting evidence whether T2D patients have increased cortical porosity. We hypothesized that microvascular complications have an important role in cortical porosity. Thus, we performed high-resolution peripheral quantitative computed tomography imaging at the distal radius and tibia to evaluate bone microarchitecture in men with T2DM age ≥ 50 yrs or postmenopausal women with T2DM and nondiabetic controls. Comprehensive diabetic complications were assessed in all patients including urine microalbuminuria, retinopathy, neuropathy (touch, temperature, and vibration sensation), ankle brachial index (ABI) and transcutaneous oxygen tension (TcPO2). Percent differences between groups were obtained from linear regression models adjusting for age, BMI, and sex. Relationships between variables were assessed using adjusted Spearman correlations. A total of 164 T2D patients (mean age 68.9 ±7.8 yrs.; 56.7% men; HbA1C=7.7 ±0.9%; mean diabetes duration 15.2 yrs.) and 107 nondiabetic controls (mean age 67.3±8.8 yrs.; 42.1% men; HbA1C =5.4 ±0.3%) were recruited to the study. Overall, there was a trend for increased cortical porosity at the distal tibia in the T2D group (+12.2%; p=0.063) compared with nondiabetic controls. Of note, TcPO2 was negatively correlated with cortical porosity at the distal radius (r= -0.17; p= 0.039) and distal tibia (r= -0.15; p= 0.073). In particular, the Low TcPO2 (≤40 mmHg) group (n=29) had greater cortical porosity at the distal tibia (+19.6 %; p=0.037) compared with the High TcPO2 (>40 mmHg) group (n=133). In addition, the low TcPO2 group had a significant increase in cortical porosity in the distal tibia (+24.8% p=0.020) compared with nondiabetic controls. In conclusion, this is the first evidence in humans indicating that TcPO2, a measure of microvascular blood flow, is linked to cortical porosity in the distal radius and tibia in T2D patients. Our findings may explain the conflicting findings regarding cortical porosity in T2D because only T2D patients with impaired microvascular blood flow have increased cortical porosity. Collectively, our data indicate that cortical porosity is a microvascular complication of longstanding T2D.

19613 Background: Paclitaxel therapy often results in a unique sub-acute pain syndrome, whose pathophysiology is unknown. While this syndrome is often termed as a ‘myalgia’ or ‘arthralgia’, it has not been demonstrated to be associated with any structural injury of muscles or joints. Identifying the pathophysiology mechanisms that result in the paclitaxel-acute pain syndrome might be a positive step in the development of effective prevention and/or treatment strategies. With the hypothesis that the paclitaxel-acute pain syndrome occurs as a result of nerve injury, an observational study to clarify the clinical characteristics of this syndrome was initiated. Methods: Oncology patients who were treated with at least one dose of paclitaxel and reported developing sub-acute pain were questioned using a detailed structured interview. Various aspects of the pain, including the time of onset, duration, location, severity, and exacerbating factors were evaluated. Data were tabulated descriptively. Results: Eighteen patients were interviewed. The onset of pain typically occurred 1–2 days after therapy and lasted for a median of 4–5 days. Pain was most commonly located in the back, hips, shoulders, thighs, legs and feet, with the most common descriptors used being ‘aching’ or ‘deep pain’. Commonly used adjectives to describe the pain were: ‘radiating’, ‘shooting’, ‘aching’, ‘stabbing’ and ‘pulsating’. Some patients described increased pain with weight bearing or walking. Fifteen of 18 patients specifically denied localization of pain to either joints or muscles. Conclusions: The nature of the pain, i.e. , generalized, deep aching pain, the notation of increased sensitivity with weight bearing (mechanical hyperalgesia) and the lack of localization to joints or muscles, support the hypothesis that the paclitaxel-acute pain syndrome results from a hyperalgesic dysfunction of nociceptive receptors, their fibers, or the spinothalamic system. These clinical conclusions are supported by the recent findings that markers of cellular injury can be identified in peripheral nerve tissues shortly following paclitaxel administration in an animal model (Peters CM, et al., Exp Neurol. 2007 Jan;203(1):42- 54). No significant financial relationships to disclose.

See article on pages 141–146 in this issue.