Managing Complications Related to Peripheral Nerve Surgery: Selected Illustrative Cases.

Peripheral nerve surgery mostly involves elective procedures; thus, the associated complications are of great clinical, social, and medicolegal importance. Apart from the general perioperative morbidity, complications during interventions on peripheral nerves are extremely rare. However, iatrogenic peripheral nerve injuries during unrelated surgical procedures performed by those not specialised in peripheral nerve surgery remain the most significant group of complications, accounting for up to approximately 17% of all cases. The aims of this review are to provide better insight into the multifaceted nature of complications related to peripheral nerve surgery-from the perspective of their causes, treatment, and outcome-and to raise surgeons' awareness of the risks of such morbidity. It should be emphasized that intraoperative complications in peripheral nerve surgery are largely "surgeon-related" rather than "surgery-related"; therefore, they have great potential to be avoided.

Distal nerve transfer (PT-AIN, SUP-PIN) for regaining hand function in C8, T1 root injury following extirpation of the right C8, T1 schwannoma.

A 48-year-old female was admitted to the authors' department due to hand weakness as a consequence of C8, T1 root injury. Eight months earlier, the patient had been treated by a pulmonary surgeon due to an expansive lesion near the apex of the right lung, which resulted in right lower brachial plexus palsy. Postoperative pathohistological findings indicated that the lesion was nerve schwannoma. The diagnostic process included physical examination, electromyoneurography, and MRI. A distal nerve transfer (pronator teres-anterior interosseus nerve [PT-AIN], supinator-posterior interosseus nerve [SUP-PIN]) was performed in order to restore hand function. The video can be found here: https://stream.cadmore.media/r10.3171/2022.10.FOCVID22110.

Quality of life and satisfaction in patients surgically treated for cubital tunnel syndrome.

OBJECTIVE: Cubital tunnel syndrome (CuTS) results from compression of the ulnar nerve at the elbow, resulting in pain, weakness, and numbness of the hand and forearm. This work describes the Quality of Life (QoL) and satisfaction after CuTS surgery and identifies the factors associated with those outcomes. METHODS: This cross-sectional study included patients surgically treated for CuTS from January 2011 to September 2021 at the Neurosurgery Clinic of the Clinic Center in Serbia. The questionnaires applied were the Short Form 36 (SF-36), EuroQol instrument (EQ-5D-5 L), Bishop's score and Patient-Rated Ulnar Nerve Evaluation (PRUNE). RESULTS: Sixty-two patients met the inclusion criteria. Bishop's score: The median score was 10 (7.75-11), 54.8% of the cases presented excellent results. PRUNE: The median score for symptoms was 19 (6-38.5); for functional, was 14 (0.75-38); and the total was 18.25 (5.87-34.12). SF-36: The subscale with the best result was social functioning (84.68 ± 22.79). The scale with the worst value was emotional well-being (49.35 ± 7.87). EQ-5D-5L: Over 50% patients did not present problems with mobility, self-care, activity, and anxiety. The average EQ-VAS was 72.77 ± 18.70; and 0.72 ± 0.21 of the EQ-index, revealing a good QoL. Models for QoL and satisfaction: Ten models showed statistical significance. The variables with major involvement were body mass index and time evolution of the symptoms. CONCLUSION: Surgical decompression has proved to diminish the symptoms, improving QoL and satisfaction. Many fixed and changeable factors can affect the satisfaction levels after surgery.

Useful functional recovery and quality of life after surgical treatment of peroneal nerve injuries.

Closed injuries to the peroneal nerve recover spontaneously in about a third of patients, but surgery may be needed in the remaining 2/3. The recovery after surgery is not always satisfactory and the patients may need an orthosis or a walking aid to cope with regular daily activities. This study aimed to evaluate the useful functional recovery and quality of life (QoL) in surgically treated patients with peroneal nerve (PN) injuries. The study involved 51 patients who have undergone surgical treatment due to PN injury in our department, within a 15-year period (2006-2020). Thirty patients (59%) were treated with neurolysis, 12 (23%) with nerve repair techniques, and 9 (18%) with tendon transfer (TT). Neurolysis is employed in the least extensive nerve injuries when nerve continuity is preserved and yields a motor recovery ratio of almost 80%. Nerve repairs were followed by 58.33% of patients achieving M3+ recovery, while 41.66% recovered to the useful functional state (M4 or M5) With the use of TTs, all patients recovered to the M3+, while 66.7% recovered to M4. All our results correspond to the results of previous studies. No statistically significant differences were found regarding the QoL of the groups. There is an apparent advantage of neurolysis, over nerve repair, over TT procedure, both in terms of useful functional recovery, and foot-drop-related QoL. However, when involving all aspects of QoL, these advantages diminish. The individual approach leads to optimal results in all groups of patients.

Peripheral nerve surgery in Serbia: "Think global, act local" and the privilege of service.

Introduction: The phrase "think globally, act locally", which has often been used to refer to conservation of the environment, highlights the importance of maintaining a holistic perspective and stipulates that each individual has a role to play in their community and larger world. Although peripheral nerve surgery has been largely unemphasized in global neurosurgical efforts, a wide disparity in peripheral nerve surgery is presumed to exist between high-income and low- and middle-income countries. Serbia is an upper middle-income country with a long history of peripheral nerve surgery. Research question: How can understanding the development of peripheral nerve surgery in Serbia advance global education and improve peripheral nerve surgery worldwide? Material and methods: An anecdotal and narrative review of recent advances in peripheral nerve surgery in Serbia was conducted. The World Federation of Neurosurgical Society (WFNS) Peripheral Nerve Surgery Committee discussions on improving peripheral nerve surgery education were summarized. Results: In this manuscript, we describe the application of "think globally, act locally" to peripheral nerve surgery by providing an account of the development of peripheral nerve surgery in Serbia. Then, we report measures taken by the WFNS Peripheral Nerve Surgery Committee to improve education on peripheral nerve surgery in LMICs. Discussion and conclusion: Viewing the development of peripheral nerve surgery in Serbia through the lens of "think globally, act locally" may guide the development of peripheral nerve surgery in LMICs.

Etiological and epidemiological characteristics of surgically treated radial nerve lesions: A 20-year single-center experience.

Introduction: Radial nerve lesions present a clinical entity that may lead to disability, psychological distress, and job loss, and thus requires great attention. Knowledge of the etiology and exact mechanism of the nerve impairment is of great importance for appropriate management of these patients, and there are only a few papers that focused on these features in patients with surgically treated radial nerve lesions. The lack of studies presenting the etiology and injury mechanisms of surgically treated radial nerve lesions may be due to a relatively small number of specialized referral centers, dispersion to low-flow centers, and a greater focus on the surgical treatment outcomes. Aim: The aim of this study was to describe the etiological and epidemiological characteristics of patients with surgically treated radial nerve lesions of various origins. Methods: This retrospective study evaluated 147 consecutive patients with radial nerve lesion, treated in the department during the last 20 years, from January 1, 2001, until December 31, 2020. Results: The majority of patients belonged to the working population, and 70.1% of them were male. Most commonly, the etiology of nerve lesion was trauma (63.3%) or iatrogenic injury (28.6%), while the less common origin was idiopathic (4.1%) or neoplastic (4.1%). The most frequent location of the lesion was in the upper arm, followed by the elbow and forearm. Fracture-related contusion was the most common mechanism (29.9%), followed by postoperative fibrosis (17.7%), lacerations (17.7%), and compression (15.6%). Conclusion: Based on the fact that traumatic or iatrogenic injuries constitute the majority of cases, with their relevant mechanisms and upper arm predomination, it is crucial to raise awareness and understanding of the radial nerve injuries among orthopedic surgeons to decrease the numbers of these patients and properly preserve or treat them within the initial surgery.

Phenotypic and Genetic Heterogeneity of Adult Patients with Hereditary Spastic Paraplegia from Serbia.

Hereditary spastic paraplegia (HSP) is among the most genetically diverse of all monogenic diseases. The aim was to analyze the genetic causes of HSP among adult Serbian patients. The study comprised 74 patients from 65 families clinically diagnosed with HSP during a nine-year prospective period. A panel of thirteen genes was analyzed: L1CAM (SPG1), PLP1 (SPG2), ATL1 (SPG3A), SPAST (SPG4), CYP7B1 (SPG5A), SPG7 (SPG7), KIF5A (SPG10), SPG11 (SPG11), ZYFVE26 (SPG15), REEP1 (SPG31), ATP13A2 (SPG78), DYNC1H1, and BICD2 using a next generation sequencing-based technique. A copy number variation (CNV) test for SPAST, SPG7, and SPG11 was also performed. Twenty-three patients from 19 families (29.2%) had conclusive genetic findings, including 75.0% of families with autosomal dominant and 25.0% with autosomal recessive inheritance, and 15.7% of sporadic cases. Twelve families had mutations in the SPAST gene, usually with a pure HSP phenotype. Three sporadic patients had conclusive findings in the SPG11 gene. Two unrelated patients carried a homozygous pathogenic mutation c.233T>A (p.L78*) in SPG7 that is a founder Roma mutation. One patient had a heterozygous de novo variant in the KIF5A gene, and one had a compound heterozygous mutation in the ZYFVE26 gene. The combined genetic yield of our gene panel and CNV analysis for HSP was around 30%. Our findings broaden the knowledge on the genetic epidemiology of HSP, with implications for molecular diagnostics in this region.

Physical and Mental Aspects of Quality of Life in Patients With Charcot-Marie-Tooth Disease Type 1A.

Introduction: Charcot-Marie-Tooth type 1A (CMT1A) comprises ~50% of all CMT cases. CMT1A is a slowly progressive motor and sensory neuropathy that leads to significant disability. We aimed to investigate the quality of life (QoL) in Serbian patients with CMT1A and to assess sociodemographic and clinical features associated with their QoL. Material and Methods: Forty-five genetically confirmed patients with CMT1A were included -60% women [age 50.4 ± 12.6 years, disease duration 22 (12.5-31.5) years]. SF-36, Medical Research Council (MRC) Sum Score, CMT Examination Score (CMTES), Overall Neuropathy Limitation Scale (ONLS), Beck Depression Inventory (BDI), and Krupp's Fatigue Severity Scale (FSS) were used in the study. Results: Regarding SF-36, Mental Health and Social Functioning were the scales with the best achievements, whereas Role Physical was the worst domain. Worse QoL in patients with CMT1A was associated with elder age (rho = -0.34, p < 0.05), longer disease duration (rho = -0.31, p < 0.05), more pronounced muscle weakness measured by MRC-SS (rho = 0.43, p < 0.01), presence of tremor (p < 0.05), worse CMTES (rho = -0.68, p < 0.01), more severe disability in upper (rho = -0.70, p < 0.01) and lower limbs (rho = -0.61, p < 0.01) measured by ONLS scores, use of walking aids (p < 0.01), and with depression (p < 0.01) and fatigue (p < 0.01). Worse scores on CMTES (beta = -0.43, p < 0.01), BDI (beta = -0.39, p < 0.01), and FSS (beta = -0.36, p < 0.01) were significant independent predictors of worse QoL in patients with CMT1A (adjusted R 2 = 0.77, p < 0.001). Conclusion: Besides impairment made directly by CMT1A itself, QoL in these patients was also strongly affected by the presence of depression and fatigue. Since CMT1A is still not a curable disease, it is of interest to identify factors associated with QoL that are amenable to treatment.

Surgical Treatment of Radial Nerve Injuries Associated With Humeral Shaft Fracture-A Single Center Experience.

Radial nerve injuries are often associated with humeral shaft fractures. The results of treatment of these injuries, by contemporary surgical approaches, remain diverse. In this paper we presented the outcomes and analyzed the patient, clinical, and surgical procedure related characteristics and factors that may influence the outcome overall, in 77 patients treated at Clinic for Neurosurgery, Clinical Center of Serbia during a 20 years period. The nerve injuries were verified by US and EMNG. The majority of patients were treated by neurolysis or sural nerve grafting, while only few were treated by direct suture. The final recovery was evaluated by muscle strength assessment and classified using MRC. We analyzed extension of the wrist, extension of the fingers including the thumb, and abduction of the thumb. There was a significant statistical difference in MRC grade following the treatment. The total rate of useful functional recovery was achieved in 69 (89.61%) out of all studied patients, out of whom 20 (28.99%) achieved excellent recovery, 26 (37.68%) achieved good recovery and 23 (33.33%) achieved fair recovery. Only 8 (10.39%) out of all studied patients achieved poor recovery. The injured nerves, that were preserved in continuity, acquired by a low-energy trauma, and treated earlier than the 6 months were associated with better functional outcome following the surgery. In addition, there was a trend of better functional improvement with aging, keeping in mind that the old were subjected to lower energy trauma. The expectant management followed by surgery of radial nerve injury associated with humeral shaft fracture should be around 3 months, and the surgical nerve repair should not be performed later than the 6 months after injury. The energy of trauma may be a factor predicting patient's final recovery following the treatment.

The role of arm volumes evaluation in the functional outcome and patient satisfaction following surgical repair of the brachial plexus traumatic injuries.

OBJECTIVE: Brachial plexus injuries are among the most complex injuries of the peripheral nervous system and among the most devastating injuries overall. In complete lesions, functional priorities include the reinnervation of the musculocutaneous and axillary nerves for proximal functions restoration. Three major nerves - radial, median, and ulnar - and the corresponding muscles remain denervated, which results in subsequent muscle atrophy. This study was aimed at the evaluation of arm volumes in surgically treated patients with brachial plexus injuries, in correlation with the type of palsy, recovery and associated factors. METHODS: The study included 36 patients with brachial plexus injuries who were surgically treated in our institution over a 15-year-long period. The evaluation of arm and arm segments volumes was carried out using water displacement testing, based on the Archimedes principle. RESULTS: Statistically significant differences were noted between the operated arm and the healthy arm in all of the measured segments (hands, forearms and upper arms), as well as between the patients with complete and upper palsy, and in correlation with the shoulder abduction recovery. CONCLUSIONS: Previous studies were mainly focused on the functional outcome and quality of life; although related to both, arm volumes in patients with brachial plexus injuries were not analyzed before. Significant differences between the operated arm and the healthy arm volumes, as well as between the various types of palsy, found in the present study should trigger further prospective research in relation to neurophysiology, useful functional recovery and quality of life.

GIANT CAVERNOUS MALFORMATION WITH UNUSUALLY AGGRESSIVE CLINICAL COURSE: A CASE REPORT.

Giant cavernomas (GC) are rare lesions, with less than 50 cases reported so far. Clinical presentation usually involves epileptic seizures and less typically focal neurological deficit, due to repeated hemorrhages and GC mass effect and consequentially increased intracranial pressure. Although individual cases have been reported, due to the rarity and variable imaging appearance, GCs are usually not considered in the differential diagnosis of large hemorrhagic lesions, especially when significant mass effect is present. A 17-year-old boy presented due to severe headache, right-sided weakness, and slurred speech. Symptoms started three days before with occasional headaches, which intensified gradually. Emergency computed tomography revealed a left frontal massive heterogeneous lesion. Soon after, right-sided hemiparesis and speech impairment progressed, and the patient became drowsy with the slightly dilated left pupil. Emergency surgery was performed, and the lobed grayish lesion was entirely removed. Based on the macroscopic appearance, the surgeon assumed it was a metastasis of melanoma. Histopathologic analysis result was cavernoma. GC should be considered as an option in hemorrhagic lesions, especially in the young age population. Emergency surgery for mass lesions is not uncommon in neurosurgery; however, bleeding cavernomas are usually planned for elective surgery due to the specific approach and complications.

Peripheral Nerve Tumors as an Ongoing Challenge in Neuro-oncology: An Overview of Their Biological and Technical Nuances.

This paper aims to provide an overview of recent advances in the diagnosis and treatment of peripheral nerve tumors (PNTs) with regard to biological and technological nuances, and to highlight some recommendations for achieving better outcomes in the treatment of patients suffering from PNT. PNTs are probably the most challenging entity in the field of peripheral nervous system surgery. The goal of removing a nerve tumor while also preserving nerve function at the same time is often complicated, regardless of the surgeon's experience. Still, in most cases, high-quality results can be achieved upon carefully planned surgery. Clinical presentation, diagnosis, and indications for a specific type of treatment of PNTs still remain a topic of debate. Recent technological advances have led to an exponential improvement in the field with utilization of intraoperative ultrasound, neurostimulation devices, and intraoperative electrophysiological monitoring, along with the development of modern surgical techniques, whereby a multidisciplinary and individually shaped approach is necessary. CONCLUSION: These advances, however, still remain limited, and recent research is focused on the development of biological therapy. Biologically targeted therapies will emerge when there is a better understanding of the genetic and molecular mechanisms driving the development and growth of PNTs.

Viable C5 and C6 Proximal Stump Use in Reconstructive Surgery of the Adult Brachial Plexus Traction Injuries.

BACKGROUND: In patients with only upper (C5, C6) brachial plexus palsy (BPP), the pooled international data strongly favor nerve transfers over nerve grafts. In patients with complete BPP, some authors favor nerve grafts for the restoration of priority functions whenever there is a viable proximal stump. OBJECTIVE: To evaluate functional recovery in cases of upper and complete BPP where only direct graft repair from viable proximal stumps was performed. METHODS: The study included 36 patients (24 with complete BPP and 12 with only upper BPP) operated on over a 15-yr period. In all cases, direct graft repair from C5 to the musculocutaneous and the axillary nerve was performed. In cases with complete BPP, additional procedures included either direct graft repair from C6 to the radial nerve and the medial pectoral nerve or the dorsal scapular nerve transfer to the branch for the long head of the triceps. RESULTS: The use of C5 proximal stump grafts (in both complete and upper BPP) resulted in satisfactory elbow flexion in 26 patients (72.2%) and satisfactory shoulder abduction in 22 patients (61.1%). The use of C6 proximal stump grafts in patients with complete BPP resulted in satisfactory elbow extension in 5 (50%) and satisfactory shoulder adduction in another 5 (50%) patients. CONCLUSION: Although nerve transfers generally enable better restoration of priority functions, in cases of infraganglionary injuries, especially in shorter defects, it is also necessary to consider direct graft repair, or at least its combination with nerve transfers, as a potentially beneficial treatment modality.

Nerve Grafting versus Common Infraclavicular Intraplexal Nerve Transfer in Elbow Flexion Restoration.

AIM: To compare the results of nerve grafting versus common infraclavicular intraplexal nerve transfer in elbow flexion restoration. MATERIAL AND METHODS: The study included 39 patients with upper brachial plexus palsy who were operated using common intraplexal nerve transfer (Oberlin procedure) and the thoracodorsal and medial pectoral nerve transfer to the musculocutaneous nerve or grafting of C5 to the musculocutaneous nerve, for elbow flexion restoration. All patients underwent detailed preoperative evaluation, which included clinical and neurological examinations, electrophysiological investigation and neuroradiological studies. The final evaluation of achieved recovery of elbow flexion was done two years after surgery, using the British Medical Council scale. RESULTS: We achieved functional satisfactory recovery (M3, M4, M5) in 29 of 30 patients (96.7%) in the common intraplexal nerve transfer group, and in 4 of 9 patients in the nerve grafting group (44.4.%). There was a significant statistical difference between these two groups in favor of common intraplexal nerve transfers over C5 grafting to the musculocutaneous nerve regarding functional recovery. CONCLUSION: The results of our study concur with the findings of previous studies favoring intraplexal nerve transfers over nerve grafting in the restoration of elbow flexion in upper brachial plexus palsy. They reveal that intraplexal nerve transfers are clearly the primary treatment modality in cases of upper brachial plexus palsy without any sign of viable proximal C5 stump presence, while in cases of upper brachial plexus palsy with signs of viable proximal C5 stump the choice of the best treatment modality is still controversial.

Simultaneous bone remodeling and surgical decompression of large Sylvian arachnoid cyst.

The most common location for intracranial arachnoid cysts is the region of the Sylvian fissure, where they can be found in 49% of cases. Management of these cysts is still quite controversial. We present our surgical technique for the treatment of large Sylvian fissure arachnoid cysts which involves cyst decompression and simultaneous calvarial remodeling. After decreasing cyst size, remodeling of the frontal, temporal, and parietal bones follows. The cyst itself is treated with a cystoperitoneal shunt. In immediate postoperative period, correction of the deformity is observed. The cyst volume is reduced immediately after surgery, and adequate adaptation of the bone is achieved. Our surgical procedure for simultaneous bone remodeling and cyst decompression is a fast, simple, and effective treatment option for patients with large Sylvian fissure arachnoid cysts associated with significant cranial disfigurement. We consider cranial remodeling in case of large arachnoid cyst important not just because of the cosmetic result but also for reducing remaining intracranial space filled with cerebrospinal fluid. It may be an important factor to reduce the risk of intracystic and subdural hemorrhage. It is a widely applicable procedure that does not require special tools and expensive equipment, and yet it can help avoid multiple surgeries and complications tied to them.

MANAGEMENT OF BRACHIAL PLEXUS MISSILE INJURIES.

- Missile injuries are among the most devastating injuries in general traumatology. Traumatic brachial plexus injuries are the most difficult injuries in peripheral nerve surgery, and most complicated to be surgically treated. Nevertheless, missile wounding is the second most common mechanism of brachial plexus injury. The aim was to evaluate functional recovery after surgical treatment of these injuries. Our series included 68 patients with 202 nerve lesions treated with 207 surgical procedures. Decision on the treatment modality (exploration, neurolysis, graft repair, or combination) was made upon intraoperative finding. Results were analyzed in 60 (88.2%) patients with 173 (85.6%) nerve lesions followed-up for two years. Functional recovery was evaluated according to functional priorities. Satisfactory functional recovery was achieved in 90.4% of cases with neurolysis and 85.7% of cases with nerve grafting. Insufficient functional recovery was verified in ulnar and radial nerve lesions after neurolysis, and in median and radial nerve lesions when graft repair was done. We conclude that the best time for surgery is between two and four months after injury, except for the gunshot wound associated with injury to the surrounding structures, which requires immediate surgical treatment. The results of neurolysis and nerve grafting were similar.

Outcome after brachial plexus injury surgery and impact on quality of life.

BACKGROUND: The aim of this study was to investigate outcomes after surgery for brachial plexus injury (BPI), not only motor outcomes but also the quality of life of the patients. METHODS: We operated on 128 consecutive patients with BPI from 1992 to 2012. We documented the information on the injured nerve, level of injury, type of treatment used, timing of surgery, patient age, and preoperative and postoperative motor deficits. In 69 patients who agreed to participate in a quality of life study, additional assessments included functionality, pain, quality of life, patient satisfaction, and psychosocial health. RESULTS: Of patients who underwent only exploration and neurolysis, 35.3% showed a good quality of recovery. Patients who underwent nerve reconstruction using nerve grafting showed a better rate of good quality recovery (56.7%), and the results following nerve transfer depended on the type of transfer used. After surgery, 82.6% of patients showed significant improvement, 82.6% were satisfied, and 81.2% responded positively when asked if they would undergo surgery again if they knew the current result beforehand. Overall, 69.6% patients continued working after surgery. The mean DASH disability score was high (58.7) in the study group. Patients who had early surgery showed a consistently higher DASH score. About 76% of patients reported having pain regularly, and 18.8% reported depression or anxiety. CONCLUSIONS: We consider that it is important to report not only muscle recovery, but also other aspects of recovery.

Iatrogenic Peripheral Nerve Injuries-Surgical Treatment and Outcome: 10 Years' Experience.

BACKGROUND: Iatrogenic nerve injuries are nerve injuries caused by medical interventions or inflicted accidentally by a treating physician. METHODS: We describe and analyze iatrogenic nerve injuries in a total of 122 consecutive patients who received surgical treatment at our Institution during a period of 10 years, from January 1, 2003, to December 31, 2013. The final outcome evaluation was performed 2 years after surgical treatment. RESULTS: The most common causes of iatrogenic nerve injuries among patients in the study were the operations of bone fractures (23.9%), lymph node biopsy (19.7%), and carpal tunnel release (18%). The most affected nerves were median nerve (21.3%), accessory nerve (18%), radial nerve (15.6%), and peroneal nerve (11.5%). In 74 (60.7%) patients, surgery was performed 6 months after the injury, and in 48 (39.3%) surgery was performed within 6 months after the injury. In 80 (65.6%) patients, we found lesion in discontinuity, and in 42 (34.4%) patients lesion in continuity. The distribution of surgical procedures performed was as follows: autotransplantation (51.6%), neurolysis (23.8%), nerve transfer (13.9%), direct suture (8.2%), and resection of neuroma (2.5%). In total, we achieved satisfactory recovery in 91 (74.6%), whereas the result was dissatisfactory in 31 (25.4%) patients. CONCLUSIONS: Patients with iatrogenic nerve injuries should be examined as soon as possible by experts with experience in traumatic nerve injuries, so that the correct diagnosis can be reached and the appropriate therapy planned. The timing of reconstructive surgery and the technique used are the crucial factors for functional recovery.