**3. The Psychosocial Impact of Peripheral Nerve Lesions**

Uvarov was among the first to publish his hypothesis that negative emotions are involved in the pathogenesis of peripheral nervous system disorders in Russian in the year 1971 [35]. However, the topic remained of little interest for the scientific community in the following years and decades. More than thirty years after Uvarov published his work, Jaquet et al. conducted a retrospective chart review of 107 patients with either median nerve injury, ulnar nerve injury, or combined injuries of both nerves. 94% of these patients experienced early psychological stress following nerve trauma. More than a third of the affected patients reported psychological symptoms of clinical depression. The authors found that combined nerve injuries had a significantly higher risk for early psychological stress following trauma when compared to isolated injuries of either the median or ulnar nerve. Severe psychological distress as assessed by means of the Impact of Event Scale (IES) was associated with more severe functional deficits, mean time off work and motor recovery. Additionally, patients with higher psychological stress had an Odds ratio of 3.32 for longterm incapacity for work. A higher education level was identified as a protective factor in regard to psychological distress following nerve injury [36]. Ultee's group reproduced these findings in a prospective study which evaluated early posttraumatic psychological stress in 61 patients with either isolated or combined injuries of the median and ulnar nerve. The aforementioned authors found that >90% of patients experienced psychological stress one month postoperatively and about a fourth required psychological treatment based on their IES scores. Three months postoperatively, psychological stress was still reported by more than 83% of the patients, and around 13% qualified for psychological treatment. The authors identified a correlation of female gender, adult age, and combined nerve injuries with the occurrence of psychological stress symptoms 1 month postoperatively [37]. In regard to the impact of single or combined nerve injuries on the affected patients' work lives, Bruyns and colleagues analyzed potential predictors for return to work in 81 patients with median and/or ulnar nerve injuries in a retrospective study. Within a year after injury 59% of the patients returned to work after a mean time of work of 31 weeks. While 8 out of 10 patients with median nerve lesions were able to resume their work, this applied to less than 6 out of 10 and less than 3 out of 10 patients in the groups with ulnar nerve and combined nerve lesions, respectively. The ability to return to work (RTW) was significantly associated with the educational status of the participants and high rates of RTW were found in patients with white-collar employment, in comparison to those with blue-collar employment. Compliance to hand therapy was also found to result in odds ratio of 3.5 for RTW following nerve injury and repair [34]. Novak's group studied 158 patients who suffered from peripheral nerve injuries in the upper extremity and evaluated potential biomedical and psychosocial factors which correlated with disability. They found that patients who received worker's compensation, were involved in litigation or who were unemployed had significantly more severe disabilities of the affected extremity than their counterparts. These disabilities which were assessed by the Disabilities of Arm, Shoulder and Hand Questionnaire (DASH) score showed a significant correlation with the level of pain in these patients. In regard to potential predictors for post-injury disabilities, pain intensity, cold sensitivity, pain catastrophizing score, depression, employment status, worker's compensation and potential ongoing litigation were identified [18]. To summarize all aforementioned authors' findings, patients with combined median and ulnar nerve injuries are at higher risk for psychological stress and also not return to work as compared to patients with single site nerve lesions. Additionally, patients who report high levels of injury-related neuropathic pain, suffer from depression, are unemployed or have an ongoing lawsuit are also at higher risk for post-injury disability.

Besides the number of injured nerves, another point to consider in regard to the psychosocial impact is the severity of the respective lesion. In 2009, Bailey et al. aimed to evaluate the relationship between the degree of nerve damage in the upper extremity and psychosocial parameters such as activity participation, perceived quality of life (QoL), pain, and depression. Two individual groups were analyzed, one with compression neuropathies (*n* = 25), the other suffering from traumatic PNI of the upper extremity (*n* = 24). The authors observed that their study cohort of 49 individuals have given up about a fifth of their daily activities prior to their initial surgeon consultation and a significantly greater activity loss was observable in the group with traumatic PNI. Especially high-demand leisure activity such as physical exercise was reduced by almost 50% in the nerve injury group while social activities were reduced to 82%. In the group with compression neuropathies, leisure activities decreased by 30% and social activities were reduced to 87%, respectively. Pain intensity was reported as moderate among the studied patient sample with no significant differences between groups. The overall ratings for physical and psychological qualities of life were under average and almost 40% of the studied patients suffered from signs of depression secondary to the nerve damage. Interestingly, the cut-off for clinical depression was transgressed in the group with traumatic nerve injury only, but this difference was not statistically significant. Correlation analysis revealed a strong association between activity loss on the one hand and higher levels of depression as well lower perceived QoL on the other hand. Higher level of depression did also strongly correlate with lower perceived QoL. More severe pain was moderately associated with higher depression scores but only a weak correlation was found between the former and QoL. Interestingly, no correlation was observable between pain severity and physical QoL following peripheral

nerve damage. In summary, more than 60% of the observed variance could be predicted by means of the two factors depression and activity participation, indicating that these two factors could be addressed as potential targets to improve the QoL in patients with upper extremity nerve damage, regardless of its genesis. However, it must be noted that the authors did not assess the manifestation of depression or other psychosocial factors prior to nerve damage, a potential confounder for the observed results [38]. Aiming to further differentiate the psychosocial impact of different types of nerve injuries, e.g., single site compression neuropathies from more complex pathologies like brachial plexus injuries and neuromas, Mackinnon's group performed a retrospective chart review of 490 patients presenting to their department between 2010 and 2012. The divided their patient sample into seven groups in accordance with their respective diagnosis: 1. Brachial plexus injuries; 2. Thoracic outlet syndrome (TOS); 3. single compression neuropathy; 4. dual compression neuropathy; 5. ulnar nerve lesions other than cubital tunnel syndrome; 6. compression mononeuropathy in the lower extremity and 7. neuroma. To distinguish between motor deficits due to compression of the common peroneal nerve and sensory disturbances caused by compressions of the cutaneus branches or the superficial or deep peroneal nerve, the sixth group was further subdivided. The authors reported a statistically significant difference regarding the pain-related decrease of QoL which was more severe in patients suffering from TOS, neuroma, or compression neuropathies of the superficial and deep branch of the peroneal nerve when compared to patients suffering from compression mononeuropathy in the upper extremity. Patients in the neuroma subgroup also reported significantly more stress at home as well as at work when compared to the patients with single compression mononeuropathies. Patients with dual compression neuropathies had reported higher stress levels and a decreased ability to cope with stress at work. Other factors which were identified as negative predictors for a significant decrease in QoL were female sex, smoking and anti-alcoholism. Female sex and anti-alcoholism were also associated with higher pain intensities. In regard to the reported stress-at-home, significantly higher levels were reported by female patients. Non-alcoholics had an increased risk for reduced coping abilities and higher stress-at-work levels [17]. Stonner, Mackinnon and Kaskutas conducted a retrospective cross-sectional study, including 627 patients with nerve disorders of the upper extremity. In the style of the aforementioned study conducted by Wojtkiewicz [17] patients were grouped based on the nerve disorder they were diagnosed with. The seven groups were categorized as follows: 1. lesions of the median nerve; 2. lesions of the ulnar nerve; 3. lesions of the radial nerve; 4. proximal lesions of either the axillary, long thoracic, suprascapular, or musculocutaneous nerve; 5. compression neuropathies of at least two different nerves; 6. TOS; 7. brachial plexus injuries. The authors found little difference in regard to post-injury work status when comparing the seven different groups with the exception of patients suffering from brachial plexus injuries. In this group only a fourth of the patients continued to work in their respective jobs on a daily basis and almost half of all patients did not work at all. More than ten percent of the entire study population of 627 received worker's compensation and more than half of these patients did not return to work. These participants reported significantly higher levels of depression and higher stress at home when compared to patients which did not receive worker's compensation and were not working. The latter group's proportion was also markedly smaller, comprising only 14% of the patients which did not receive worker's compensation. In regard to the overall disability following peripheral nerve lesions as assessed by the DASH score, the studied patients reported a significantly higher degree of disability in comparison to the general population. A quarter of all patients were unable to work as they wanted to. Both general disability as well as work-related disability were more severe in patient who were unemployed, received worker's compensation or reported depression ratings which were significantly higher than the general population's mean. While patients with brachial plexus lesions scored highest in the DASH, median nerve lesions were associated with lowest disability ratings. Both the mean mental and physical QoL were significantly lower in the participants when compared to the general population

and lowest scores were observed in the patients with brachial plexus injuries. Poorer QoL ratings were associated with female sex, unemployment, worker's compensation status and above-mean depression ratings. Final stepwise linear regression analysis yielded ten variables which accounted for more than 60% of the observed variability in reported disability ratings. Among them were 7 psychosocial factors: 1. depression; 2. the level of pain; 3. momentary unemployment; 4. difficulties in sleeping; 5. affection of intimate relationships; 6. modified job demands and 7. stress at work. 46% of variance regarding work disability could be predicted by five variables: 1. affection of intimate relationships; 2. performance of household chores by others; 3. performance of a reduced amount of household chores; 4. difficulties with sleeping and 5. performance of the same level of household chores but with pain. Around 50% of physical QoL scores were predictable by: 1. DASH score; 2. the level of pain; 3. number of medications and 4. Work DASH scores. Slightly less than 50% of variability in mental QoL scores could be explained by: 1. the ability to cope with stress at home; 2. DASH score; 3. stress at home and 4. sleeping difficulties [39]. In accordance with the aforementioned authors' findings, Yannascoli et al. found significantly increased rates of coded depression and coded anxiety in their study sample of >1800 patients suffering from brachial plexus injury as compared to >18,000 healthy subjects. While 46% of the control patients had coded depression and/or anxiety, this rate was 54% in the group of patients suffering from brachial plexus injuries. Additionally, there were significantly increased incidences of new-onset postoperative depression (20%) and anxiety (12%) in the latter group when compared to the healthy controls [40]. Landers et al. reported that about one fifth of their study population of 21 patients with brachial plexus injuries met criteria for posttraumatic stress disorder (PTSD) and exhibited clinical depression, respectively. Most concerningly, about a third of the studied patients reported suicidal ideation [41]. In regard to the impact of injury severity in case of isolated hand injuries, Tezel's group found no correlation between psychological morbidities and injury severity and hand function, respectively in patients suffering from traumatic hand injury with major nerve involvement. The hand injury severity as assessed by the modified Hand Injury Severity Score (MHISS) correlated significantly with the patients' ability to return to work following hand trauma [42]. In conclusion, the reviewed studies indicate, that traumatic nerve injuries are more likely to have a strong psychosocial impact as compared to compression mononeuropathies. Notably, severe nerve lesions, especially brachial plexus injuries, have devastating consequences for the affected patients both in regard to employment status and work life as well as mental health [43].

In addition to upper extremity nerve lesions, the impact of PNI has also been studied in patients with lower extremity nerve damage, e.g., peroneal mononeuropathy. Aprile assessed QoL by means of the SF-36 in 69 patients with peroneal mononeuropathy and found significantly lower scores for the aspects of vitality, social function and is emotional role in their study sample as compared to healthy subjects. However, when stratification was performed to exclude patients with peroneal mononeuropathy which reported predisposing factors which were likely to affects QoL, no significant differences between the healthy sample and the sample with peroneal mononeuropathy were found [44].

### **4. Psychosocial Factors as Predictors of Functional Outcome Following Treatment of Peripheral Nerve Lesions**

#### *4.1. Surgical Repair of Traumatic Nerve Injuries*

Hundepool et al. conducted a prospective multicenter study in 61 patients, aiming to identify prognostic factors for functional recovery in the first postoperative year following injuries of the median nerve (*n* = 28), ulnar nerve (*n* = 27) or combined lesions (*n* = 6) at forearm level. The majority of patients (85%) were blue-collar workers and the median educational score equaled a high-school degree. One year after injury, 84.6% of patients had returned to work. Besides the identification of the DASH score, power grip and sensibility of the hand as best prognostic factors, the aforementioned authors found gender, level of education as well as posttraumatic levels of stress at one- and three months post-injury as highly predictive in regard to functional recovery [45]. Building on the aforementioned

authors' work, Goswami and colleagues evaluated ten patients with isolated or combined transection lesions of the median and ulnar nerve three weeks and approximately one year following surgical treatment of their injuries, aiming to identify potential predictors for the observed functional outcome. The patients completed the Brief Pain Inventory (BPI) Short Form, NEO Five Factor Inventory (NEO-FFI), and Pain Catastrophizing Scale (PCS) and the McGill Pain Questionnaire (MPQ) at both postoperative time points. Ten healthy individuals served as control group and were evaluated by means of the NEO and PCS. The authors found that pain-catastrophizing was correlated both with the reported pain intensity as well as the occurrence of neuropathic pain. The level of pain-catastrophizing at the first postoperative time-point served as predictor for cold pain thresholds twelve months postoperatively. The level of chronic pain reported at the second assessment time point was also related to the level of pain-catastrophizing as assessed by the PCS which in turn showed correlation with cold pain threshold at this time point [46]. Logically related to Goswami's research question, Mackinnon's group investigated the relationship between psychosocial factors and pain relief following peripheral nerve surgery. 331 patients who underwent surgery for peripheral nerve injuries or compression neuropathies and returned for at least two postoperative follow-ups were included. On the one hand, an increased impact of pain on QoL or reported anger, respectively were significant predictors of nextvisit pain. On the other hand, self-reported hopefulness, sadness, and depression were not found to be predictive of next-visit pain. Patients who suffered from upper extremity PNI and refused to comment on a possible history of childhood trauma had a significant association with both same-visit pain and next-visit pain. The level of pain served a significant predictor of the reported impact of pain on QoL, sadness, depression, anger, and hopefulness during the next visit. Lower extremity nerve injury was predictive of anger during the next visit, whereas upper extremity nerve injury had no predictive value. Female sex served as a significant predictor for next-visit sadness and anger. Next-visit sadness and depression could be predicted in case the patient reported a positive history of childhood trauma, which was the case in 7.9% of study sample. While 89.3% of the patients denied childhood trauma, 2.8% refused to comment on this question [47]. In conclusion, the listed studies' results suggest that surgeons should be aware of the fact that functional recovery following repair of peripheral nerve lesions can be significantly influenced by the prevalence of postoperative stress and pain-catastrophizing. In regard to the psychosocial Sadness and depression, although not predictive of functional outcome in the limited number of studies investigating this relationship, are more likely in patients suffering from PNI and have a positive or suspected positive history of childhood trauma.

#### *4.2. Surgical Treatment of Compression Neuropathies*

Besides cases of traumatic nerve injuries, patients suffering from compression neuropathies also frequently require surgical treatment. In consequence, predictors of functional outcomes following peripheral nerve decompression have been studies by several groups. A retrospective study aiming to identify outcomes of care and predictors of disability and health status in adults with peripheral nerve injuries included >360 patients with PNI which underwent surgical treatment. Included patients presented with 1. median nerve compression; 2. ulnar neuropathy; 3. mixed median and ulnar nerve compression; 4. radial nerve palsy; 5. thoracic outlet syndrome or 6. brachial plexus injury. About 80% of the patients were treated operatively and 70% of these underwent nerve release while the remaining 20% received conservative treatment. The authors found that while health status changed minimally, significant improvements in disability, work disability, pain, depression, and stress were observable following any treatment. At discharge, 57% of employed patients had resumed their work. No significant differences were observable between patients who were treated surgically or those who underwent conservative therapy. Disability was most significantly increased in patients with brachial plexus injuries. More favorable outcomes were observable in patients who pursued gainful employment and had reported symptoms less than six months prior to treatment. Post-treatment functional outcomes

could be predicted by psychosocial factors like work status, household management, pain, depression, stress, and difficulty sleeping [48]. In addition to Stonner's comprehensive analysis of patients with different compression neuropathies, other authors have evaluated cohorts of patients suffering from one distinctive nerve compression syndrome alone with the results summarized in the following paragraphs.
