Tim H. J. Nijhuis

Natural conduits for bridging a 15-mm nerve defect: Comparison of the vein supported by muscle and bone marrow stromal cells with a nerve autograft

OBJECT The gold standard for reconstructing large nerve defects, the nerve autograft, results in donor-site morbidity. This detrimental consequence drives the search for alternatives. We used a vein filled with a small piece of fresh muscle to prevent the vein from collapsing and with bone marrow stromal cells (BMSCs) to enhance regeneration. METHODS In 60 rats, a 15-mm sciatic nerve defect was bridged with a nerve autograft, a vein filled with muscle or a vein filled with muscle and BMSCs. Toe spread and pinprick were used to evaluate motor and sensory function. Compound muscle action potentials (CMAPs) and the gastrocnemius muscle index (GMI) were recorded to assess conduction properties and denervation atrophy. Extensive histology was performed to confirm presence of BMSCs and to evaluate regeneration by staining neural tissue for Schwann cells and neural growth factor. RESULTS After 12 weeks, all animals responded with toe spread and pinprick reaction; significant differences were found between groups. Six weeks post grafting no difference was found comparing the GMI between the groups. Group I had a significant increase in GMI at 12 weeks compared to group II and group III. The CMAP measurements showed comparable results at 6 weeks post grafting. Twelve weeks after reconstruction, group I had significantly better results compared to group II and group III. Group III showed a tendency to outperform group II at 12 weeks postoperatively. Immunofluorescence analysis showed an increased number of Schwann cells in group III compared to group II. The BMSCs were visible 6 and 12 weeks postoperatively. CONCLUSIONS This study is a step forward in the search for an alternative to the nerve autograft because it demonstrates the beneficial effect of BMSCs to a conduit. However, our data do not demonstrate sufficient benefit to warrant clinical implementation at this stage.

Prevalence and severity of cold intolerance in patients after hand fracture.

Cold intolerance is a well-known phenomenon that develops in the first months after hand injury and generally does not decrease over time. In this study, we evaluated the prevalence and severity of cold intolerance after hand fracture in 129 patients using the Cold Intolerance Symptom Severity (CISS) questionnaire. Patients with nerve and/or vascular injuries were excluded. The response rate was 59%. The mean CISS score was 23. Pathological cold intolerance, defined as a CISS score over 30, was experienced by 38% of the patients. Cold intolerance is common after hand fractures and can be severely disabling in some patients.

Isogenic venous graft supported with bone marrow stromal cells as a natural conduit for bridging a 20 mm nerve gap.

In this study, we introduce a technique for bridging large neural gaps, using an isogenic vein graft supported with isogenic bone marrow stromal cells (BMSC). In three groups a nerve defect of 20 mm was bridged with a vein graft. Our first experimental group comprized an empty venous graft, in group II the venous nerve graft was filled with saline where as in group III the venous nerve graft was filled with BMSC. The animals were tested for functional recovery up to 3 months post repair. Our results show that the BMSC filled venous graft resulted in significantly better regeneration of the nerve defect compared to controls, as confirmed by the functional recovery measured by somatosensory evoked potentials, toe spread, pin prick, and gastrocnemius muscle index. Conclusively, the results confirm that the vein graft supported with BMSC is associated with better functional nerve regeneration.

Rewarming patterns in hand fracture patients with and without cold intolerance.

PURPOSE It is often assumed that cold intolerance is associated with abnormalities in the skin temperature due to changes in the blood flow of the hands. In this study, we determined whether patients with and without cold intolerance after a hand fracture or healthy controls have a diminished rewarming after a cold stimulus. METHODS The severity of cold intolerance was evaluated using the Cold Intolerance Symptom Severity (CISS) questionnaire. To determine whether abnormal rewarming plays a major role in the underlying pathophysiology of cold intolerance, a cold-stress test was applied at a mean of 30 months (with a range of 11 mo) after the patients recovered from a hand fracture. A control group also underwent identical cold-stress testing for comparison. Temperature during the rewarming phase was measured using videothermography. RESULTS Thirteen control subjects and 18 patients participated. Control subjects did not report any symptoms of cold intolerance (CISS score, 0) and no loss of sensibility was measured. The mean CISS score of all patients was 27.8; 9 patients scored above the cut-off value for normal cold intolerance. No significant differences were found in the rewarming patterns between (1) the affected and non-affected hand of the postfracture patients, (2) the dominant and non-dominant hand of the control subjects, and (3) the patients and controls. CONCLUSIONS The results of this study revealed no relation between the severity of cold intolerance and rewarming patterns after cold stress testing. This might suggest that temperature regulation of the hands in post-fracture patients might not be responsible for the symptoms of cold intolerance, based on cold-stress test response.

Prognostic factors for outcome after median, ulnar, and combined median–ulnar nerve injuries: A prospective study

BACKGROUND A major problem in the surgical treatment of peripheral nerve injuries of the upper extremities is the unpredictable final outcome. More insight and understanding of the prognostic factors is necessary to improve functional outcome after repair of the peripheral nerves. The objective of this study was to identify prognostic factors for the functional recovery of peripheral nerve injury of the forearm and their independent contribution in the outcome in the first year after reconstruction. METHODS A multicentered prospective study in the Netherlands resulted in the inclusion of 61 patients with a median, ulnar, or combined median-ulnar nerve injury. The age, level of injury, type of nerve injury, number of damaged structures, number of damaged arteries, education, smoking, and posttraumatic stress were analyzed as prognostic factors for functional outcome after repair of the peripheral nerves. The outcome parameters were sensory recovery (Semmes-Weinstein monofilament test) and motor recovery (Medical Research Council (MRC) score, power grip, and pinch grip) and the ability to perform daily activities. RESULTS Gender, age, level of education, number of injured arteries and structures, damaged nerve, location of the injury, type of the nerve injury, and posttraumatic stress at 1 and 3 months after repair of the peripheral nerve injury were found to be predictors of functional recovery. CONCLUSIONS Our prospective analysis of prognostic factors shows several factors to be predictive for the functional recovery after peripheral nerve injuries of the median and/or ulnar nerve of the forearm. Sensibility of the hand, power grip, and DASH score (DASH, Disabilities of Arm, Shoulder and Hand) have proven to be the three best prognostic factors in this study. Of these prognostic factors, only posttraumatic stress can be influenced to optimize functional outcome.

The effect of stem cells in bridging peripheral nerve defects: a meta-analysis

UNLABELLED OBJECT.: For decades the gold standard for reconstructing a large peripheral nerve defect has been, and remains, the nerve autograft. Alternatives to the nerve autograft include biological conduits and vessels. Adding stem cells in the lumen of a nerve conduit has been the subject of multiple studies. The purpose of the present meta-analysis was to summarize animal experimental studies on the effect of stem cells as a luminal additive when reconstructing a peripheral nerve defect with a nerve graft. METHODS A literature search of the MEDLINE and Embase databases was performed from inception to April 2012, searching for animal experiments on peripheral nerve reconstruction models in which a nerve conduit was used with and without the support of 3 different types of stem cells. Stem cells were analyzed according to their origin: bone marrow, adipose tissue, and other origins. Included studies had consistent outcome measurements: walking track analysis, muscle mass ratio, and electrophysiology. RESULTS Forty-four studies were included in the final analysis. Forest plots of the 3 outcome measurements (walking track analysis, muscle mass ratio, and electrophysiology) showed positive effects of stem cells on the regeneration of peripheral nerves at different time points. Almost all comparisons showed significant differences for all 3 stem cells groups compared with a control group in which stem cells were not used. CONCLUSIONS The present report systematically analyzed the different studies that used stem cells as a luminal additive when bridging a large peripheral nerve defect. All 3 different stem cell groups showed a beneficial effect when used in the reconstruction compared with control groups in which stem cells were not used.

Ultrasonographic quantification of intrinsic hand muscle cross-sectional area; Reliability and validity for predicting muscle strength

OBJECTIVE To investigate whether ultrasonographic measurement of the cross-sectional area (CSA) of the intrinsic hand muscles can be used to predict muscle strength in a valid and reliable manner, and to determine if this method can be used for follow-up of patients with peripheral nerve injury between the wrist and elbow. DESIGN Repeated-measures cross-sectional study. SETTING Clinical and academic hospital. PARTICIPANTS Healthy adults (n=31) and patients with ulnar and median nerve injuries (n=16) between the wrist and elbow who were visiting the Erasmus Medical Center or Maasstad Hospital were included in the study (N=47). INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Correlation between measured muscle CSA and strength and assessment of inter- and intrarater reliability. Ultrasound and strength measurements of the intrinsic hand muscles were conducted bilaterally. To establish validity, the CSA of 4 muscles (abductor digiti minimi, first dorsal interosseus, abductor pollicis brevis, opponens pollicis) was compared with strength measurements of the same muscles conducted with the Rotterdam Intrinsic Hand Myometer. Repeated measures were conducted to assess inter- and intrarater reliability. RESULTS The assessed CSA strongly correlated with strength measurements, with correlations ranging from 0.82 to 0.93 in healthy volunteers and from 0.63 to 0.94 in patients. Test-retest reliability showed excellent intrarater reliability (intraclass correlation coefficient range, 0.99-1.00) in patients and volunteers and good interrater reliability (intraclass correlation coefficient range, 0.88-0.95) in healthy volunteers. CONCLUSIONS We found that ultrasound is a valid and reliable method to assess the CSA of specific muscles in the hand. Therefore, this technique could be useful to monitor muscle reinnervation in patients suffering from peripheral nerve injury as a valuable addition to strength dynamometers.

Osteoradionecrosis of the Jaws: A Review of Conservative and Surgical Treatment Options

Although surgery still is the most important treatment modality in the management of head and neck cancer, radiotherapy is increasingly being used. Consequently, the majority of head and neck cancer patients are at risk of developing osteoradionecrosis of the jaws, which is the most serious and important complication of radiotherapy. This review presents the etiology, pathophysiology, diagnosis, classification, and prevention of osteoradionecrosis. In addition, the body of evidence regarding conservative as well as surgical treatment of osteoradionecrosis is reviewed, and studies on complications, tumor recurrence and patient survival, dental rehabilitation, and functional and aesthetic outcome after surgical treatment for osteoradionecrosis are discussed.

A New Approach to Assess the Gastrocnemius Muscle Volume in Rodents Using Ultrasound; Comparison with the Gastrocnemius Muscle Index

Introduction The purpose of this study was to determine the reliability and validity of a new non-invasive ultrasound technique to measure gastrocnemius muscle atrophy after nerve denervation in an animal model. Methods In sixteen rodents an eight mm sciatic nerve gap was created. In the following 8 weeks, each week, two rodents were euthanized and the gastrocnemius muscle was examined using two different ultrasound systems and two investigators. The standardized ultrasound measurement protocol consisted of identifying pre-defined anatomical landmarks: 1) the fibula, 2) the fibular nerve, and 3) the junction between the most distal point of the semitendinosus muscle and gastrocnemius muscle. Consequently, we measured the muscle thickness as the length of the line between the fibula and the junction between the two muscles, perpendicular to the fibular nerve. After the ultrasound recording, the muscle mass was determined. Results A steep decline of muscle weight of 24% was observed after one week. In the following weeks, the weight further decreased and then remained stable from 6 weeks onwards, resulting in a maximal muscle weight decrease of 82%. The correlation coefficient was >0.96 between muscle diameter and weight using both ultrasound systems. The inter-rater reliability was excellent for both devices on the operated side (ICC of 0.99 for both ultrasound systems) and good for the non-operated site (ICC’s: 0.84 & 0.89). The difference between the muscle mass ratio and the muscle thickness ratio was not more than 5% with two outliers of approximately 13%. Discussion We have developed an innovative, highly reliable technique for quantifying muscle atrophy after nerve injury. This technique allows serial measurements in the same animal over time. This is a significant advantage compared to the conventional technique for quantifying muscle atrophy, which requires sacrificing the animal.

Early posttraumatic psychological stress following peripheral nerve injury : A prospective study

BACKGROUND Psychological symptoms frequently accompany severe injuries of the upper extremities and are described to influence functional outcome. As yet, little knowledge is available about the occurrence of posttraumatic psychological stress and the predictive characteristics of peripheral nerve injuries of the upper extremity for such psychological symptoms. In this prospective study, the incidence of different aspects of early posttraumatic stress in patients with peripheral nerve injury of the forearm is studied as well as the risk factors for the occurrence of early psychological stress. METHODS In a prospective study design, patients with a median, ulnar or combined median-ulnar nerve injury were monitored for posttraumatic psychological stress symptoms with the Impact of Event Scale (IES) questionnaire up to 3 months postoperatively. RESULTS Psychological stress within the first month after surgery occurred in 91.8% of the population (IES mean=22.0, standard deviation (SD)=17.3). Three months postoperatively, 83.3% (IES mean=13.3, SD=14.1) experienced psychological stress. One month postoperatively 24.6% and 3 months postoperatively 13.3% of the patients had IES scores indicating for the need for psychological treatment. Female gender, adult age and combined nerve injuries were related to the occurrence of psychological stress symptoms 1 month postoperatively. CONCLUSIONS In the majority of these patients, peripheral nerve injury of the forearm is accompanied by early posttraumatic psychological stress, especially in female adults who suffered from combined nerve injuries.