Luca Padua

Neurophysiological classification and sensitivity in 500 carpal tunnel syndrome hands

Objectives‐ To evaluate the following points about carpal tunnel syndrome (CTS): 1) characterization of a wide population; 2) sensitivity of electrodiagnostic tests, and particularly the contribution of disto‐proximal ratio test; 3) validity of a neurophysiological classification developed by us. Material and methods ‐ Prospective study in 500 hands with CTS symptoms. Neurophysiological “standard” tests were always performed: sensory nerve conduction velocity (SNCV) first‐ and third digit‐wrist and distal motor latency (DML). In “standard negative” hands disto‐proximal ratio technique (R) was performed. Neurophysiological classification: Extreme CTS (absence of median motor, sensory responses), Severe (absence of sensory response, abnormal DML), Moderate (abnormal SNCV, abnormal DML), Mild (abnormal SNCV, normal DML), Minimal (abnormal R or other segmental/comparative test, normal standard tests). Results‐ Sensibility of standard tests: 77%. R increased the diagnostic yield by 20%. CTS classification appeared reliable with significant differences between groups. Conclusion ‐ R is a useful test, the classification may be useful in clinical/therapeutical decisions.

Multiperspective follow-up of untreated carpal tunnel syndrome A multicenter study

Objective: To assess the course of untreated carpal tunnel syndrome (CTS). Methods: The Italian CTS Study Group prospectively followed up (10 to 15 months) 196 untreated patients (274 hands) with idiopathic CTS with multiple measurements of CTS. Baseline factors were used to predict the evolution of untreated CTS in multiple regression analysis. Results: Comparison of baseline and follow-up data showed a significant spontaneous improvement of patient-oriented and neurophysiologic measurements. A significant correlation between evolution and initial severity of CTS was observed. CTS measurements improved in patients with more severe initial impairment whereas they worsened in patients with milder initial impairment. The main positive prognostic factor was short duration of symptoms. Similarly, spontaneous improvement was more frequently associated with young age. Conversely, baseline bilateral symptoms and positive Phalen predicted a poor prognosis. Conclusions: Some patients with CTS improve spontaneously without surgical treatment.

Ascorbic acid in Charcot-Marie-Tooth disease type 1A (CMT-TRIAAL and CMT-TRAUK): a double-blind randomised trial

Summary Background Ascorbic acid reduced the severity of neuropathy in transgenic mice overexpressing peripheral myelin protein 22 (PMP22), a model of Charcot–Marie–Tooth disease type 1A (CMT1A) associated with the PMP22 duplication. However, in three 1-year trials, ascorbic acid had no benefit in human beings. We did a multicentre 2-year trial to test the efficacy and tolerability of ascorbic acid in patients with CMT1A. Methods Adult patients (aged 18–70 years) with symptomatic CMT1A were enrolled from nine centres in Italy and the UK, and were randomly assigned (1:1 ratio) to receive 1·5 g/day oral ascorbic acid or matching placebo for 24 months. The randomisation sequence was computer generated by block randomisation, stratified by centre and disease severity, and patients were allocated to treatment by telephone. The primary outcome was change in the CMT neuropathy score (CMTNS) at 24 months. Secondary outcomes were timed 10 m walk test, nine-hole peg test, overall neuropathy limitations scale, distal maximal voluntary isometric contraction, visual analogue scales for pain and fatigue, 36-item short-form questionnaire, and electrophysiological measurements. Patients, treating physicians, and physicians assessing outcome measures were masked to treatment allocation. Analysis of the primary outcome was done on all randomised patients who received at least one dose of study drug. This study is registered, numbers ISRCTN61074476 (CMT-TRAUK) and EudraCT 2006-000032-27 (CMT-TRIAAL). Findings We enrolled and randomly assigned 277 patients, of whom six (four assigned to receive ascorbic acid) withdrew consent before receiving treatment; 138 receiving ascorbic acid and 133 receiving placebo were eligible for analysis. Treatment was well tolerated: 241 of 271 patients (89% in each group) completed the study; 20 patients (nine receiving ascorbic acid) dropped out because of adverse events. Mean CMTNS at baseline with missing data imputed was 14·7 (SD 4·8) in the ascorbic acid group and 13·9 (4·2) in the placebo group. Mean worsening of CMTNS was 0·2 (SD 2·8, 95% CI −0·3 to 0·7) in the ascorbic acid group and 0·2 (2·7, −0·2 to 0·7) in the placebo group (mean difference 0·0, 95% CI −0·6 to 0·7; p=0·93). We recorded no differences between the groups for the secondary outcomes at 24 months. 21 serious adverse events occurred in 20 patients, eight in the ascorbic acid group and 13 in the placebo group. Interpretation Ascorbic acid supplementation had no significant effect on neuropathy compared with placebo after 2 years, suggesting that no evidence is available to support treatment with ascorbic acid in adults with CMT1A. Funding Telethon-UILDM and AIFA (Italian Medicines Agency) for CMT-TRIAAL, and Muscular Dystrophy Campaign for CMT-TRAUK.

Carpal tunnel syndrome modifies sensory hand cortical somatotopy: A MEG study

The adult somatosensory system has shown reorganizational abilities at cortical and subcortical levels after peripheral nerve lesions. In the present study the effects of carpal tunnel syndrome (CTS) are investigated as reflected on the somatotopy of the primary cortical hand representation. Position and intensity of cortical sources activated by the separate electrical stimulation of median nerve and Digits 1, 3, and 5 of both affected and non‐affected hands are evaluated by magnetoencephalographic (MEG) technique. Correlation of MEG results with patient‐, physician‐ and neurophysiological‐oriented evaluations of CTS was carried out. Patients showed changes in cortical hand somatotopy in strict relationship to self‐referred assessment of symptoms and hand disability in daily activities, including: 1) a more extended representation of the affected hand when paresthesias prevailed; and 2) a more restricted representation due to lateral shift of the little finger was observed when pain symptoms dominated the clinical picture. Contralateral to the side of CTS, the cortical sources activated by Digit 5‐stimulation appeared significantly enhanced with respect to contralateral ones from non‐affected hand. When comparing the amplitude of peripheral sensory nerve action potentials of median and ulnar nerves to that of cortical responses (i.e., ECD strengths of M20 and M30 components after stimulation of Digits 3 and 5), a significant selective amplification of M30 with respect to M20 and sensory nerve action potential (SNAP) appeared during Digit 3 stimulation compared to that observed for Digit 5. This has been interpreted as a central magnification mechanism in brain responsiveness, possibly revealing a safety factor enabling sensory perception despite the small peripheral signal due to nerve trunk dysfunction. Hum. Brain Mapping 17:28–36, 2002.

A systematic review of conservative treatment of carpal tunnel syndrome

Objective : To assess the effectiveness of conservative therapy in carpal tunnel syndrome. Data sources : A computer-aided search of MEDLINE and the Cochrane Collaboration was conducted for randomized controlled trials (RCTs) from January 1985 to May 2006. Review methods : RCTs were included if: (1) the patients, with clinically and electrophysiologically confirmed carpal tunnel syndrome, had not previously undergone surgical release, (2) the efficacy of one or more conservative treatment options was evaluated, (3) the study was designed as a randomized controlled trial. Two reviewers independently selected the studies and performed data extraction using a standardized form. In order to assess the methodological quality, the criteria list of the Cochrane Back Review Group for systematic reviews was applied. The different treatment methods were grouped (local injections, oral therapies, physical therapies, therapeutic exercises and splints). Results : Thirty-three RCTs were included in the review. The studies were analysed to determine the strength of the available evidence for the efficacy of the treatment. Our review shows that: (1) locally injected steroids produce a significant but temporary improvement, (2) vitamin B6 is ineffective, (3) steroids are better than non-steroidal anti-inflammatory drugs (NSAIDs) and diuretics, but they can produce side-effects, (4) ultrasound is effective while laser therapy shows variable results, (5) exercise therapy is not effective, (6) splints are effective, especially if used full-time. Conclusion : There is: (1) strong evidence (level 1) on efficacy of local and oral steroids; (2) moderate evidence (level 2) that vitamin B6 is ineffective and splints are effective and (3) limited or conflicting evidence (level 3) that NSAIDs, diuretics, yoga, laser and ultrasound are effective whereas exercise therapy and botulinum toxin B injection are ineffective.

The chemotherapy-induced peripheral neuropathy outcome measures standardization study: from consensus to the first validity and reliability findings

BACKGROUND Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting complication of cancer treatment. Thus far, the impact of CIPN has not been studied in a systematic clinimetric manner. The objective of the study was to select outcome measures for CIPN evaluation and to establish their validity and reproducibility in a cross-sectional multicenter study. PATIENTS AND METHODS After literature review and a consensus meeting among experts, face/content validity were obtained for the following selected scales: the National Cancer Institute-Common Toxicity Criteria (NCI-CTC), the Total Neuropathy Score clinical version (TNSc), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) group sensory sumscore (mISS), the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, and CIPN20 quality-of-life measures. A total of 281 patients with stable CIPN were examined. Validity (correlation) and reliability studies were carried out. RESULTS Good inter-/intra-observer scores were obtained for the TNSc, mISS, and NCI-CTC sensory/motor subscales. Test-retest values were also good for the EORTC QLQ-C30 and CIPN20. Acceptable validity scores were obtained through the correlation among the measures. CONCLUSION Good validity and reliability scores were demonstrated for the set of selected impairment and quality-of-life outcome measures in CIPN. Future studies are planned to investigate the responsiveness aspects of these measures.BACKGROUND Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting complication of cancer treatment. Thus far, the impact of CIPN has not been studied in a systematic clinimetric manner. The objective of the study was to select outcome measures for CIPN evaluation and to establish their validity and reproducibility in a cross-sectional multicenter study. PATIENTS AND METHODS After literature review and a consensus meeting among experts, face/content validity were obtained for the following selected scales: the National Cancer Institute-Common Toxicity Criteria (NCI-CTC), the Total Neuropathy Score clinical version (TNSc), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) group sensory sumscore (mISS), the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, and CIPN20 quality-of-life measures. A total of 281 patients with stable CIPN were examined. Validity (correlation) and reliability studies were carried out. RESULTS Good inter-/intra-observer scores were obtained for the TNSc, mISS, and NCI-CTC sensory/motor subscales. Test-retest values were also good for the EORTC QLQ-C30 and CIPN20. Acceptable validity scores were obtained through the correlation among the measures. CONCLUSION Good validity and reliability scores were demonstrated for the set of selected impairment and quality-of-life outcome measures in CIPN. Future studies are planned to investigate the responsiveness aspects of these measures.

Multiperspective assessment of carpal tunnel syndrome A multicenter study

Objective: To assess the clinical and neurophysiologic dissociation often observed in clinical practice, and to improve patient evaluation for diagnosis of carpal tunnel syndrome (CTS). Methods: The Italian CTS Study Group studied 1,123 idiopathic CTS hands with multiple measurements—clinical, neurophysiologic, and patient-oriented—of CTS. Results: Clinical and neurophysiologic relationships were very strong when the clinical picture was evaluated by the hand functional measurements, with an exponential increase in functional impairment as the classification of neurophysiologic severity progressed. Conversely, symptoms and pain did not increase as the classification of neurophysiologic severity progressed: 1) A large part of the CTS population complained of severe symptoms, although minimal functional impairment and minimal or no electrophysiologic abnormalities were observed; and 2) symptoms improved in the patients with more severe neurophysiologic and clinical examination scenarios. Conclusions: Multiperspective and multimeasurement assessment, even when using a validated patient-oriented tool, provided interesting information that confirmed and clarified the clinical neurophysiologic dissociation often observed in carpal tunnel syndrome (CTS) patients. Furthermore, CTS appeared to be an ideal model for evaluating the importance of patient-oriented measurement.

Relationship between the Self-Administered Boston Questionnaire and Electrophysiological Findings in Follow-Up of Surgically-Treated Carpal Tunnel Syndrome:

A prospective study of electrophysiological examination and the Boston self-administered questionnaire (BQ) was carried out in patients with surgically-treated carpal tunnel syndrome. There were 104 hands in 93 patients (13 men and 80 women, mean age 56 years). The BQ was used to assess the severity of symptoms and function, and nerve conduction studies were done before surgical release by short incision at the palm, and at follow-ups 1 and 6 months after surgery. The BQ severity score improved or became normal in 98% of hands. The mean BQ scores and distal sensory and motor conduction velocities in the median nerve showed significant improvement at the 1 month follow-up. Further significant improvement was found at 6 months. There was no relationship between the improvements in BQ scores and the distal conduction in the median nerve. The degree of improvement in sensory and motor distal conduction velocities could be forecast from presurgical values, whereas the degree of improvement in the symptoms and the functional status after release could not be predicted from the presurgical BQ scores.

A useful electrophysiologic parameter for diagnosis of carpal tunnel syndrome

In 43 patients (50 hands) with clinical manifestations of mild‐moderate carpal tunnel syndrome (CTS) and 36 healthy volunteers (40 hands), orthodromic sensory nerve conduction velocity (SNCV) was measured with surface electrodes in the median nerve between the third digit and palm and between the palm and wrist. These figures were used to calculate the ratio of distal to proximal conduction (distoproximal ratio). All 90 hands were also subjected to other nerve conduction studies used for diagnosis of CTS. All control hands presented distoproximal ratios <1.0, reflecting higher conduction rates in the proximal segment. In contrast, 49 of 50 CTS hands (98%) presented reversed ratios (>1.0) indicating compromised proximal conduction. The sensitivity of this test was significantly greater than that of other methods evaluated, including comparative studies and segmental study of the palm‐wrist portion of the median nerve. Segmental study of median SNCV with calculation of the distoproximal ratio is a sensitive technique for diagnosis of CTS in patients with normal findings in standard nerve conduction studies.

Multi‐center assessment of the Total Neuropathy Score for chemotherapy‐induced peripheral neurotoxicity

Abstract  The aim of this multi‐center study was to assess with reduced versions of the Total Neuropathy Score (TNS), the severity of chemotherapy‐induced peripheral neurotoxicity (CIPN), and to compare the results with those obtained with common toxicity scales. An unselected population of 428 cancer patients was evaluated at 11 different centers using a composite (clinical + neurophysiological, TNSr) or clinical (TNSc) examination and with the National Cancer Institute – Common Toxicity Criteria (NCI‐CTC) 2.0 and Eastern Cooperative Oncology Group (ECOG) scores. A highly significant correlation was demonstrated between the TNSr and the NCI‐CTC 2.0 and ECOG scores; but the TNSr evaluation was more accurate in view of the more extended score range. Also, the simpler and faster TNSc (based only on the clinical neurological examination) allowed to grade accurately CIPN and correlated with the common toxicity scores. The correlation tended to be closer when the sensory items were considered, but also the TNSr motor items, which were not specifically investigated in any other previous study, significantly correlated with the results of the common toxicity scales. In conclusion, this study suggests that the TNSr is a reliable tool for accurately grading and reporting CIPN, with the additional and so far unique support of a formal comparison with known and widely used common toxicity scales. The TNSc is a valid alternative if neurophysiological examination is not feasible. The longer time needed to calculate the TNSr and TNSc in comparison to the ECOG or the NCI‐CTC 2.0 scales is offset by the more detailed knowledge of the CIPN characteristics.