A comparison of two versus five epineural sutures to achieve successful polyethylene glycol (PEG) nerve fusion in a rat sciatic nerve repair model.

Background: We compared rates of successful polyethylene glycol (PEG) nerve fusion between two epineural suture repairs (2SR) and five epineural suture repairs (5SR) in a rat sciatic nerve transection neurorrhaphy model. We hypothesise that the two and five epineural neural suture repair groups will achieve a similar rate of PEG fusion. Methods: Twenty-five Lewis rats underwent bilateral sciatic nerve transection. Primary neurorrhaphy (PN) consisting of 2SR in one hind limb and 5SR in the contralateral hind limb was performed utilizing PEG fusion. Successful PEG fusion was confirmed by a distal muscle twitch after nerve stimulation proximal to the nerve fusion site. Sciatic nerve conduction velocity (SNCV) across the repair site and the force generated by tibialis anterior muscle (TAM) contraction were also compared between the 2SR and 5SR groups. Results: Success rates were 100% for the 2SR and the 5SR groups. No statistically significant differences in SNCV (P = 0.444) or isometric tetanic TAM contractile force (P = 0.820) were observed between 2SR and 5SR in the setting of PEG fusion. Conclusion: These findings demonstrate no significant difference in successful PEG fusion between the 2SR and 5SR groups. In addition, the findings demonstrate no statistically significant differences in SNCV or isometric tetanic TAM contractile force following sciatic nerve transection when performing a 2SR or 5SR PN in the setting of PEG fusion. Successful PEG fusion can be achieved acutely with either a two or five-epineural suture repair in a rat model.

Fibrin Glue Acutely Blocks Distal Muscle Contraction after Confirmed Polyethylene Glycol Nerve Fusion: An Animal Study.

Background: Polyethylene glycol (PEG) is a synthetic, biodegradable, and hyperosmotic material promising in the treatment of acute peripheral nerve injuries. Our team set out to investigate the impact of fibrin glue upon PEG fusion in a rat model. Methods: Eighteen rats underwent sciatic nerve transection and PEG fusion. Electrophysiologic testing was performed to measure nerve function and distal muscle twitch. Fibrin glue was applied and testing repeated. Due to preliminary findings, fibrin glue was applied to an uncut nerve in five rodents and testing was conducted before and after glue application. Mann-Whitney U tests were used to compare median values between outcome measures. A Shapiro-Wilk test was used to determine normality of data for each comparison, significance set at a P value less than 0.05. Results: PEG fusion was confirmed in 13 nerves with no significant change in amplitude (P = 0.054), latency (P = 0.114), or conduction velocity (P = 0.114). Stimulation of nerves following PEG fusion produced distal muscle contraction in 100% of nerves. Following application of fibrin glue, there was a significant reduction in latency (P = 0.023), amplitude (P < 0.001), and conduction velocity (P = 0.023). Stimulation of the nerve after application of fibrin glue did not produce distal muscle twitch. Five uncut nerves with fibrin glue application blocked distal muscle contraction following stimulation. Conclusions: Our data suggest that fibrin glue alters the nerve's function. The immediate confirmation of PEG fusion via distal muscle twitch is blocked with application fibrin glue in this experimental model. Survival and functional outcome studies are necessary to understand if this has implications on the long-term functional outcomes.

Postmortem toxicology findings from the Camden Opioid Research Initiative.

The United States continues to be impacted by decades of an opioid misuse epidemic, worsened by the COVID-19 pandemic and by the growing prevalence of highly potent synthetic opioids (HPSO) such as fentanyl. In instances of a toxicity event, first-response administration of reversal medications such as naloxone can be insufficient to fully counteract the effects of HPSO, particularly when there is co-occurring substance use. In an effort to characterize and study this multi-faceted problem, the Camden Opioid Research Initiative (CORI) has been formed. The CORI study has collected and analyzed post-mortem toxicology data from 42 cases of decedents who expired from opioid-related toxicity in the South New Jersey region to characterize substance use profiles. Co-occurring substance use, whether by intent or through possible contamination of the illicit opioid supply, is pervasive among deaths due to opioid toxicity, and evidence of medication-assisted treatment is scarce. Nearly all (98%) of the toxicology cases show the presence of the HPSO, fentanyl, and very few (7%) results detected evidence of medication-assisted treatment for opioid use disorder, such as buprenorphine or methadone, at the time of death. The opioid toxicity reversal drug, naloxone, was detected in 19% of cases, but 100% of cases expressed one or more stimulants, and sedatives including xylazine were detected in 48% of cases. These results showing complex substance use profiles indicate that efforts at mitigating the opioid misuse epidemic must address the complications presented by co-occurring stimulant and other substance use, and reduce barriers to and stigmas of seeking effective medication-assisted treatments.

Patient Perceptions and Potential Utility of Pharmacogenetic Testing in Chronic Pain Management and Opioid Use Disorder in the Camden Opioid Research Initiative.

Pharmacogenetics (PGx) has the potential to improve opioid medication management. Here, we present patient perception data, pharmacogenetic data and medication management trends in patients with chronic pain (arm 1) and opioid use disorder (arm 2) treated at Cooper University Health Care in Camden City, NJ. Our results demonstrate that the majority of patients in both arms of the study (55% and 65%, respectively) are open to pharmacogenetic testing, and most (66% and 69%, respectively) believe that genetic testing has the potential to improve their medical care. Our results further support the potential for CYP2D6 PGx testing to inform chronic pain medication management for poor metabolizers (PMs) and ultrarapid metabolizers (UMs). Future efforts to implement PGx testing in chronic pain management, however, must address patient concerns about genetic test result access and genetic discrimination.

The Genomics of Opioid Addiction Longitudinal Study (GOALS): study design for a prospective evaluation of genetic and non-genetic factors for development of and recovery from opioid use disorder.

BACKGROUND: The opioid use disorder and overdose crisis in the United States affects public health as well as social and economic welfare. While several genetic and non-genetic risk factors for opioid use disorder have been identified, many of the genetic associations have not been independently replicated, and it is not well understood how these factors interact. This study is designed to evaluate relationships among these factors prospectively to develop future interventions to help prevent or treat opioid use disorder. METHODS: The Genomics of Opioid Addiction Longitudinal Study (GOALS) is a prospective observational study assessing the interplay of genetic and non-genetic by collecting comprehensive genetic and non-genetic information on 400 participants receiving medication for opioid use disorder. Participants will be assessed at four time points over 1 year. A saliva sample will be collected for large-scale genetic data analyses. Non-genetic assessments include validated surveys measuring addiction severity, depression, anxiety, and adverse childhood experiences, as well as treatment outcomes such as urine toxicology results, visit frequency, and number of pre and post-treatment overdoses extracted from electronic medical records. DISCUSSION: We will use these complex data to investigate the relative contributions of genetic and non-genetic risk factors to opioid use disorder and related treatment outcomes.

Comparison of Interpolation Methods in the Diagnosis of Carpal Tunnel Syndrome

Background: Diagnosis of carpal tunnel syndrome is based on clinical symptoms, examination findings, and electrodiagnostic studies. For carpal tunnel syndrome, the most useful of these are nerve conduction studies. However, nerve conduction studie can result in ambiguous or false-negative results, particularly for mild carpal tunnel syndrome. Increasing the number of nerve conduction studie tests improves accuracy but also increases time, cost, and discomfort. To improve accuracy without additional testing, the terminal latency index and residual latency are additional calculations that can be performed using the minimum number of tests. Recently, the median sensory-ulnar motor latency difference was devised as another way to improve diagnostic accuracy for mild carpal tunnel syndrome. Aims: The median sensory-ulnar motor latency difference, terminal latency index, and residual latency were compared for diagnostic accuracy according to severity of carpal tunnel syndrome. Study Design: Diagnostic accuracy study. Methods: A total of 657 subjects were retrospectively enrolled. The carpal tunnel syndrome group consisted of 546 subjects with carpal tunnel syndrome according to nerve conduction studie (all severities). The control group consisted of 121 subjects with no hand symptoms and normal nerve conduction studie. All statistical analyses were performed using SAS v9.4. Means were compared using one-way ANOVA with the Bonferroni adjustment. Sensitivity, specificity, positive predictive value, and negative predictive value were compared, including receiver operating characteristic curve analysis. Results: For mild carpal tunnel syndrome, the median sensory-ulnar motor latency difference showed higher specificity and positive predictive value rates (0.967 and 0.957, respectively) than terminal latency index (0.603 and 0.769, respectively) and residual latency (0.818 and 0.858, respectively). The area under the receiver operating characteristic was highest for the median sensory-ulnar motor latency difference (0.889), followed by the residual latency (0.829), and lastly the terminal latency index (0.762). Differences were statistically significant (median sensory-ulnar motor latency difference being the most accurate). For moderate carpal tunnel syndrome, sensitivity and specificity rates of residual latency (0.989 and 1.000) and terminal latency index (0.983 and 0.975) were higher than those for median sensory-ulnar motor latency difference (0.866 and 0.958). Differences in area under the receiver operating characteristic curve were not significantly significant, but median sensory-ulnar motor latency difference sensitivity was lower. For severe carpal tunnel syndrome, residual latency yielded 1.000 sensitivity, specificity, positive predictive value, negative predictive value and area beneath the receiver operating characteristic curve. Differences in area under the receiver operating characteristic curve were not significantly different. Conclusion: The median sensory-ulnar motor latency difference is the best calculated parameter for diagnosing mild carpal tunnel syndrome. It requires only a simple calculation and no additional testing. Residual latency and the terminal latency index are also useful in diagnosing mild to moderate carpal tunnel syndrome.

Is electrodiagnosic testing for polyneuropathy overutilized?

Distal symmetric polyneuropathy (DSP) is one of the most common problems seen in clinical practice and one of the most frequent reasons for electrodiagnostic (EDx) testing. Most studies have supported the use of EDx testing for patients with suspected DSP. Some recent articles assert that EDx testing has a low yield in suspected DSP and is only needed for atypical presentations (a minority). However, many peer-reviewed articles indicate that EDx frequently changes diagnosis and management, and leads to a better understanding of the underlying pathology, severity, and prognosis. Overall, EDx is appropriate for most patients with new signs and symptoms of DSP. Muscle Nerve 55: 301-304, 2017.

The relationship between sensory latency and amplitude.

PURPOSE: To prove that the relationship between sensory latencies and amplitudes is useful in determining the severity of neuropathies. This is achieved by deriving a mathematical relationship between sensory distal latency and amplitude. Determine whether sensory amplitudes below predicted correlate with a worse pathology. PROCEDURES: Patients seen for Nerve Conduction Studies by the Department of Physical Medicine and Rehabilitation at Cooper University Hospital between 12/1/12 and 12/31/14 were invited to participate in a prospective database. The median, ulnar and sural sensory latencies and amplitudes were analyzed with both linear and power regression. Patients with amplitudes above and below the regression curve were compared for latency, amplitude and velocity of other nerves. Carpal Tunnel Patients were analyzed to determine whether Median sensory amplitude below predicted correlated with more severe disease. RESULTS: For the Median nerve, Power Regression Analysis showed a stronger correlation (R2=0.54) than linear regression (R2=0.34). Patients with Median sensory amplitude below the power correlation curve showed significantly longer ulnar sensory latency, and lower sensory amplitude than those above. Carpal Tunnel Syndrome patients with Median sensory amplitude well below predicted by the power relationship showed more advanced disease. For the ulnar and sural sensory nerve, the difference between power and linear regression was not significant. CONCLUSIONS: A power regression curve correlates sensory latency and amplitude better than linear regression. The latency amplitude relationship correlates with other parameters of nerve function and severity of Carpal Tunnel Syndrome. This implies that below predicted sensory amplitude may indicate worse disease, and could be a useful diagnostic tool.

Contraction induced h reflexes in the diagnosis of cervical radiculopathy.

PURPOSE: To determine whether Contraction Induced H Reflexes (CIHR) can accurately detect cervical radiculopathy. METHODS: Comparison of CIHR results with Needle Electromyography at academic outpatient Electromyography/Nerve Conduction laboratories. Participants were all patients over 18 with a needle electromyography diagnosis of cervical radiculopathy. Patients were tested for CIHR in at least two upper extremity muscles in electromyographically proven myotomes bilaterally. Patients were requested to perform a moderate contraction while stimulus was applied proximally (elbow or Erb's point). Outcome measures included H Reflex onset latency and side-to-side latency differences. These were compared against previously established normal values. RESULTS: Overall, 10 of 15 patients who met criteria for cervical radiculopathy showed CIHR abnormalities (sensitivity = 67%; 95% confidence interval, 43-91). Counting each side and level separately, CIHR identified 16/27 radiculopathies (sensitivity = 59.2%; 95% confidence interval, 40.6-77.8). Contraction Induced H Reflexes identified 1 possible radiculopathy not seen on electromyography (specificity = 98%; 95% confidence interval, 95-100). CONCLUSIONS: Contraction induced H Reflexes have a sensitivity and specificity for cervical radiculopathy similar to the resting Gastroc-Soleus H Reflex.