Background and aims: Normative values are lacking regarding intraepidermal nerve fiber density (IENFD) in thin sections of 5 µm. Thus, we aimed to assess IENFD in thin sections in a healthy adult population as well as to investigate whether IENFD is related to age, sex, and site of excision. Methods: Archival skin biopsies or excisions at the Department of Pathology, Lund, Sweden, from arm and leg were collected, re-sectioned, and immunohistochemically stained for Protein Gene Product 9.5 during 2020– 2023. Nerve fibers were manually quantified in the 5 µm thin sections, and IENFD was compared between age groups, sex, and excision sites. Results: IENFDs were evaluated in 602 samples from 591 healthy adults aged 18 to 97 years (295 women, 296 men). Median IENFD values are presented, stratified by age groups, sex, and excision sites. Higher IENFD was observed in the arm compared to the leg, as well as in the proximal compared to the distal leg, however not across all age groups. Levels of IENFD were lower among older adults, compared to all younger groups. Conclusion: We have presented data on IENFD in thin 5 µm sections from a healthy adult population. Despite differences in IENFD observed across age groups, sexes, and excision sites, no strong conclusions regarding affecting factors could be drawn except that individuals > 65 years present with lower IENFD. Additional research and development of the method are warranted. © 2024 The author(s).

Background: Adjunctive pharmacological treatment may improve nerve regeneration. We investigated nerve regeneration processes of PXL01 - a lactoferrin-derived peptide - after repair of the sciatic nerve in healthy Wistar rats. Materials & methods: PXL01, sodium hyaluronate (carrier) or sodium chloride was administered around the repair. After 6 days axonal outgrowth, Schwann cell response, pan- (CD68) and pro-healing (CD206) macrophages in sciatic nerve, sensory neuronal response in dorsal root ganglia (DRG) and expression of heat shock protein 27 (HSP27) in sciatic nerves and DRGs were analyzed. Results: Despite a lower number of pan-macrophages, other investigated variables in sciatic nerves or DRGs did not differ between the treatment groups. Conclusion: PLX01 applied locally inhibits inflammation through pan-macrophages in repaired sciatic nerves without any impact on nerve regeneration or pro-healing macrophages.

Idiopathic cubital tunnel syndrome is the second most common neuropathy in the upper limb. Best evidence regarding the surgical management of this condition has evolved from anterior or submuscular transposition as the former reference standard, to in situ simple release. Differences of opinion remain regarding the timing of surgery, type of surgery and adjunctive surgery. Four surgeons with Level 5 expertise were asked to answer specific questions regarding this condition.

AIMS: To investigate self-reported cold sensitivity and functional disability after a repaired major nerve trunk injury in the upper extremity.

METHODS: We identified 735 individuals with a major nerve trunk injury in the upper extremity, surgically treated with direct nerve repair or reconstructed with nerve autografts, in the Swedish national quality registry for hand surgery (HAKIR). Patient-reported symptoms, including cold sensitivity, and perceived disability were collected using two questionnaires (HQ-8 and QuickDASH) preoperatively, and at three and 12 months postoperatively.

RESULTS: We included 281 individuals, who had responded the questionnaires, where 197 (70%) were men (median age 34 [interquartile range 25-52] years) and 84 (30%) were women (median age 41 [25-55]). Cold sensitivity (scored 0-100) was the most prominent symptom 12 months postoperatively after an injured and repaired/reconstructed median (p<0.001) or ulnar (p<0.001) nerve, while individuals with a radial nerve injury showed milder symptoms. Concomitant injuries did not affect cold sensitivity scores. Individuals with ulnar nerve injuries scored higher in stiffness (p = 0.019), weakness (p<0.001) and ability to perform daily activities (p = 0.003) at 12 months postoperatively than median nerve injuries. Individuals with a median, ulnar or radial nerve injury with severe (>70) cold sensitivity had 25, 37 and 30 points higher QuickDASH scores, respectively (p<0.001), at 12 months postoperatively than individuals with mild (<30) cold sensitivity. There were no differences in QuickDASH score or cold sensitivity score at 12 months postoperatively between direct nerve repair or nerve reconstruction with nerve autografts. Neither age, nor sex, affected QuickDASH score at 12 months postoperatively.

CONCLUSION: Cold sensitivity after surgery for a major nerve trunk injury in the upper extremity can be substantial with impaired ability to perform daily activities, where an ulnar nerve injury may have a worse outcome.

Ulnar nerve compression at the elbow (UNE) frequently affects people of working age. Surgically treated patients may not immediately return to work (RTW) postoperatively. In 2008, the Swedish Social Insurance Agency reformed the national insurance policy. We aimed to examine RTW postoperatively for UNE, variations among surgical methods, and potential risk factors for prolonged RTW (sick leave > 6 weeks). Surgically treated cases of UNE (n = 635) from two time periods (2004-2008 and 2009-2014) and two healthcare regions (Southern and South-eastern) were studied retrospectively regarding age, sex, comorbidities, occupation, type of surgery and time to RTW. A sub-analysis of the exact number of weeks before RTW (n = 201) revealed longer RTW for unemployed cases compared to employed cases. Prolonged RTW was seen among younger, manual workers and after transposition or revision surgery. Prolonged RTW was approximately four times more likely after transposition than after simple decompression. Comparisons before and after 2008 showed occupational differences and differences in RTW, where cases operated before 2008 more often had permanent sickness benefit, but the reform of the social insurance system did not seem to influence RTW. In conclusion, unemployment, younger age at surgery, manual labour, transposition, and revision surgery were related to prolonged RTW.

The impact of preoperative electrophysiology on outcome of surgical treatment in ulnar nerve entrapment at the elbow (UNE) is not clarified. Our aim was to evaluate influence of preoperative electrophysiologic grading on outcome and analyse how age, sex, and in particular diabetes affect such grading. Electrophysiologic protocols for 406 UNE cases, surgically treated at two hand surgery units reporting to the Swedish National Quality Register for Hand Surgery (HAKIR; 2010-2016), were retrospectively assessed, and graded as normal, reduced conduction velocity, conduction block or axonal degeneration. Outcome of surgery after primary and revision surgery was evaluated using QuickDASH and a doctor reported outcome measure (DROM) grading. No differences in QuickDASH or DROM were found between the four groups with different electrophysiologic grading preoperatively, or at three and 12 months or at follow up, respectively. When dichotomizing the electrophysiologic grading into normal and pathologic electrophysiology, cases with normal electrophysiology had worse QuickDASH than cases with pathologic electrophysiology preoperatively (p=0.046). Presence of a conduction block or axonal degeneration indicated a worse outcome by DROM grading (p=0.011). Primary surgeries had electrophysiologic more pronounced nerve pathology compared to revision surgeries (p=0.017). Cases of older age, men, and those with diabetes had more severe electrophysiologic nerve affection (p<0.0001). In the linear regression analysis, increasing age (unstandardized B=0.03, 95% CI 0.02-0.04; p<0.0001) and presence of diabetes (unstandardized B=0.60, 95% CI 0.25-0.95; p=0.001) were associated with a higher risk of a worse electrophysiologic classification. Female sex was associated with a better electrophysiologic grading (unstandardized B=-0.51, 95% CI -0.75- -0.27; p<0.0001). We conclude that older age, male sex, and concomitant diabetes are associated with more severe preoperative electrophysiologic nerve affection. Preoperative electrophysiologic grade of ulnar nerve affection may influence surgical outcome.