Brain plasticity in neonatal brachial plexus palsies: quantification and comparison with adults' brachial plexus injuries.

PURPOSE: To compare two populations of brachial plexus palsies, one neonatal (NBPP) and the other traumatic (NNBPP) who underwent different nerve transfers, using the plasticity grading scale (PGS) for detecting differences in brain plasticity between both groups. METHODS: To be included, all patients had to have undergone a nerve transfer as the unique procedure to recover one lost function. The primary outcome was the PGS score. We also assessed patient compliance to rehabilitation using the rehabilitation quality scale (RQS). Statistical analysis of all variables was performed. A p ≤ 0.050 set as criterion for statistical significance. RESULTS: A total of 153 NNBPP patients and 35 NBPP babies (with 38 nerve transfers) met the inclusion criteria. The mean age at surgery of the NBPP group was 9 months (SD 5.42, range 4 to 23 months). The mean age of NNBPP patients was 22 years (SD 12 years, range 3 to 69). They were operated around sixth months after the trauma. All transfers performed in NBPP patients had a maximum PGS score of 4. This was not the case for the NNBPP population that reached a PGS score of 4 in approximately 20% of the cases. This difference was statistically significant (p < 0.001). The RQS was not significantly different between groups. CONCLUSION: We found that babies with NBPP have a significantly greater capacity for plastic rewiring than adults with NNBPP. The brain in the very young patient can process the changes induced by the peripheral nerve transfer better than in adults.

When biopsy goes wrong: a case series of misdiagnoses and complications from biopsies of masses of unknown origin potentially originating from a peripheral nerve.

OBJECTIVE: Biopsies of peripheral nerve tumors (PNTs) are often used to plan an efficient treatment strategy. However, performing a biopsy is controversial when the mass is likely to be a benign PNT (BPNT). The aim of this study was to evaluate the side effects of biopsies in patients with potential PNTs. METHODS: A retrospective and cross-sectional study was conducted on 24 patients who underwent biopsy of a mass of unknown origin potentially originating from a peripheral nerve (MUOPON), performed in nonspecialty services, and who were later referred to the authors' service for resection of their lesion between January 2005 and December 2022. The patients were evaluated for pain score, presence of a motor or sensory deficit, biopsy diagnosis, and definitive histopathological postsurgical diagnosis. RESULTS: The location of the tumor was supraclavicular in 7 (29.2%) patients, in the axillary region in 3 (12.5%), in the upper limb in 7 (29.2%), and in the lower limb in 7 (29.2%). Twenty-one (87.5%) patients were evaluated by MRI before biopsy, and 3 (12.5%) underwent ultrasound. One patient did not have an examination before the procedure. Based on the biopsy findings, 12 (50%) analyses had an inconclusive histopathological result. The preexisting pain worsened, as measured 1 week after biopsy, in all patients and had remained unchanged at the first evaluation by the authors (median 3 months, range 2-4 months). In 1 case, the open biopsy had to be interrupted because the patient experienced excruciating pain. Four (16.7%) patients developed motor deficits. Subsequent surgery was hampered by scar formation and intratumoral hemorrhage in 5 (20.8%) patients. The initial diagnosis obtained by biopsy differed from the final histopathological diagnosis in all patients, of whom 21 (87.5%) had BPNTs, 2 (8.3%) malignant peripheral nerve sheath tumors, and 1 (4.2%) an ancient schwannoma. CONCLUSIONS: Biopsies of PNTs are controversial and may result in misdiagnosis, neuropathic pain, or neurological deficit due to axonal damage, and they may also hinder microsurgical resection when if performed when not indicated. Indications for biopsy of an MUOPON must be carefully considered, especially if BPNT is a possible diagnosis.

Brain plasticity and age after restoring elbow flexion with distal nerve transfers in neonatal brachial plexus palsy and nonneonatal traumatic brachial plexus injury using the plasticity grading scale.

OBJECTIVE: Ulnar and/or median nerve fascicle to musculocutaneous nerve (MCN) transfers are used to restore elbow flexion following severe neonatal and nonneonatal brachial plexus injuries (BPIs). Restoring volitional control requires plastic changes in the brain. To date, whether the potential for plasticity is influenced by a patient's age remains unknown. METHODS: Patients who had presented with a traumatic upper (C5-6 or C5-7) BPI were divided into two groups: neonatal brachial plexus palsies (NBPPs) and nonneonatal traumatic BPIs (NNBPIs). Both groups underwent ulnar or median nerve transfers to the MCN for elbow flexion restoration between January 2002 and July 2020. Only those who attained a British Medical Research Council strength rating of 4 were reviewed. The primary comparison between the two groups was the plasticity grading scale (PGS) score to determine the level of independence of elbow flexion (target) from forearm motor muscle movement (donors). The authors also assessed patient compliance with rehabilitation using a 4-point Rehabilitation Quality Scale. Bivariable and multivariable analyses were used to identify intergroup differences. RESULTS: In total, 66 patients were analyzed: 22 with NBPP (mean age at surgery 10 months) and 44 with NNBPI (age range at surgery 3-67 years, mean 30.2 years; mean time to surgery 7 months, p < 0.001). All NBPP patients obtained a PGS grade of 4 at the final follow-up versus just 47.7% of NNBPI patients (mean 3.27, p < 0.001). On ordinal regression analysis, after nature of the injury was excluded because of excessive collinearity with age, age was the only significant predictor of plasticity (ß = -0.063, p = 0.003). Median rehabilitation compliance scores were not statistically different between the two groups. CONCLUSIONS: The extent of plastic changes that occur for patients to regain volitional control over elbow flexion after upper arm distal nerve transfers following BPI is influenced by patient age, with complete plastic rewiring more likely in younger patients and virtually ubiquitous in infants. Older patients should be informed that elbow flexion after an ulnar or median nerve fascicle transfer to the MCN might require simultaneous wrist flexion.

The Combined TL-RS Approach: Advantages and Disadvantages of Working 360 Degrees around the Sigmoid Sinus.

Objective To highlight the advantages and disadvantages of the combined translabyrinthine (TL) and classic retrosigmoid (RS) approaches. Design Retrospective chart review. Setting National tertiary referral center for skull base pathology. Participants Twenty-two patients with very large cerebellopontine angle tumors were resected using the combined TL-RS approach. Main Outcome Measures Preoperative patient characteristics including age, sex, and hearing loss. Tumor characteristics, pathology, and size. Intraoperative outcome: tumor removal. Postoperative outcomes included facial nerve function, residual tumor growth, and neurological deficits. Results Thirteen patients had schwannoma, eight had meningioma, and one had both. The mean age was 47 years, mean tumor size was 39 × 32 × 35 mm (anterior-posterior, medial-lateral, craniocaudal), and mean follow-up period was 80 months. Tumor control was achieved in 13 patients (59%), and 9 (41%) had residual tumor growth that required additional treatment. Seventeen patients (77%) had postoperative House-Brackmann (H-B) facial nerve function grades I to II, one had H-B grade III, one H-B grade V, and three H-B grade VI. Conclusion Combining TL and RS approaches may be helpful in safely removing large meningiomas and schwannomas in selected cases. This valuable technique should be considered when sufficient exposure cannot be achieved with the TL or RS approach alone.

Early grafting in severe adult traumatic brachial plexus injury.

Nerve surgical treatment for severe adult traumatic brachial plexus injury is traditionally delayed for months to await spontaneous recovery. Since 2009, the authors have strived to operate on patients with severe brachial plexus lesions within 2 weeks after trauma. This video shows the workup, surgical strategy, and benefits of early supraclavicular nerve grafting, including intraoperative nerve stimulation. The video can be found here: https://stream.cadmore.media/r10.3171/2022.10.FOCVID2288.

Optimal timing of needle electromyography to diagnose lesion severity in traumatic radial nerve injury.

INTRODUCTION/AIMS: In patients with traumatic radial nerve injury (RNI), the chance of spontaneous recovery must be balanced against the benefits of early surgical reconstruction. We aimed to explore the time-specific value of needle electromyography (NEMG) to diagnose nerve lesion severity. METHODS: In this retrospective diagnostic accuracy study at Leiden Nerve Center, patients at least 12 years of age with RNI caused by fractures or fracture treatment were included. The sensitivity and specificity of the patients' first NEMG examination were assessed, stratified by the timing after the nerve injury. The absence of motor unit potentials (MUPs) in muscles distal to the nerve lesion was considered a positive test result. Lesion severity was dichotomized to moderate injury (spontaneous Medical Research Council grade ≥3 recovery) or severe injury (poor spontaneous recovery or surgical confirmation of a mainly neurotmetic lesion). RESULTS: Ninety-five patients were included in our study. The sensitivity of NEMG to detect severe RNI was 75.0% (3 of 4) in the fourth, 66.7% (2 of 3) in the fifth, and 66.7% (2 of 3) in the sixth month after the nerve injury. The specificity in the first to the sixth month was 0.0% (0 of 1), 50.0% (2 of 4), 77.3% (17 of 22), 95.5% (21 of 22), 95.8% (23 of 24), and 100.0% (12 of 12), respectively. DISCUSSION: The specificity of NEMG is higher than 95% and therefore clinically relevant from the fourth month after the nerve injury onward. Absence of MUPs at this time can be considered an indication to plan nerve exploration. Moreover, the presence of MUPs on NEMG does not completely exclude the necessity for surgical reconstruction.

Differences in the perspectives of functioning and health in the ICF model between patients with brachial plexus birth injury and their parents versus healthcare professionals.

PURPOSE: To explore and compare the perspectives of patients and their parents (PPs) with a brachial plexus birth injury (BPBI) with those of health care professionals (HCPs). MATERIALS AND METHODS: We conducted a study using a questionnaire among PPs and HCPs. Importance of different outcome categories was scored on a Likert scale. Items were linked to corresponding categories of the International Classification of Functioning, Disability and Health. Means were compared using analysis of variance (ANOVA). RESULTS: Data were collected from 184 patients and 65 HCPs. We found a difference in 7/14 outcome categories between joint PP groups and HCPs. Parents scored outcome evaluation categories as more important than patients, categories filled out together by patient and parent scored in between (p < 0.05). The majority of PPs and HCPs rated outcome assessment as important in more domains than "Body functions" and "Body structures". The biggest difference was found in the importance of evaluation of pain. CONCLUSIONS: Outcome assessment in the domains "Activities and participation" and "Environmental factors" was rated as important by both PPs and HCPs. Evaluation of pain was more often scored as important by PPs. Different domains seem to be underestimated by HCPs and need more attention during consultation. Implications for rehabilitationThe importance of outcome evaluation concerning "Pain", "Interaction with peers", and "Interaction with medical and paramedical specialists" should be taken into account in the rehabilitation for this specific group of patients and their parents (PPs).Comparison of perspectives on functioning between brachial plexus birth injury (BPBI) PPs and health care professionals.Outcome assessment in domains "Activities and participation" and "Environmental factors" is important.Health care professionals undervalue the importance of pain evaluation in BPBI as compared with PPs.

Nerve transfers for brachial plexus injuries: grading of volitional control.

OBJECTIVE: After brachial plexus injuries (BPIs), nerve transfers are used to restore lost muscle function. Brain plasticity underlies the process of regaining volitional control, which encompasses disconnection of the original donor nerve-related programs and reconnection to acceptor nerve programs. To the authors' knowledge, the levels of disconnection and reconnection have never been studied systematically. In this study, the authors developed a novel 4-point plasticity grading scale (PGS) and assessed the degree of volitional control achieved, identifying clinical correlations with this score. METHODS: Patients with BPI who underwent a phrenic, spinal accessory, median, and/or ulnar fascicle nerve transfer to restore biceps and deltoid function were asked to maximally contract their target muscle as follows: 1) by using only the donor nerve program, and 2) by activating the target muscle while consciously trying to avoid using the donor nerve, with assessment each time of the Medical Research Council (MRC) scale grade for muscle strength. The authors' PGS was used to rate the level of volitional control achieved. PGS grade 1 represented the lowest independent volitional control, with MRC grade 4 obtained in response to the donor command and MRC grade 0 in response to the acceptor command (minimum brain plasticity), whereas PGS grade 4 was no noticeable contraction in response to the donor command and MRC grade 4 in response to the acceptor command (maximum brain plasticity). RESULTS: In total, 153 patients were studied. For biceps restoration, the phrenic nerve was used as a donor in 44 patients, the spinal accessory nerve in 40 patients, and the median and/or ulnar fascicles in 44 patients. A triceps branch was used to restore deltoid function in 25 patients. The level of volitional control achieved was PGS grade 1 in 1 patient (0.6%), grade 2 in 21 patients (13.7%), grade 3 in 103 patients (67.3%), and grade 4 in 28 patients (18.3%). The median PGS grade did not differ significantly between the four donor nerves. No correlations were observed between age, time from BPI to surgery, duration of follow-up, or compliance with rehabilitation and PGS grade. CONCLUSIONS: Just around 20% of the authors' patients developed a complete disconnection of the donor program along with complete independent control over the reinnervated muscle. Incomplete disconnection was present in the vast majority of the patients, and the level of disconnection and control was poor in approximately 15% of patients. Brain plasticity underlies patient ability to regain volitional control after a nerve transfer, but this capacity is limited.

Tactile Perception of the Hand in Children With an Upper Neonatal Brachial Plexus Palsy.

OBJECTIVE: To investigate factors that cause impairment of hand function in children with an upper Neonatal Brachial Plexus Palsy (NBPP), we performed an in-depth analysis of tactile hand sensibility, especially the ability to correctly localize a sensory stimulus on their fingers. DESIGN: A cross-sectional investigation of children with NBPP, compared with healthy controls. The thickest Semmes-Weinstein (SW) monofilament was pressed on the radial or ulnar part of each fingertip (10 regions), while a screen prevented seeing the hand. SETTING: Tertiary referral center for nerve lesions in an academic hospital in The Netherlands. The control group was recruited at their school. PARTICIPANTS: Forty-one children with NBPP (mean age 10.0 y) and 25 controls (mean age 9.5 y; N=41). INTERVENTIONS: Not applicable. MAIN OUTCOMES MEASURES: Correct localization of the applied stimuli was evaluated, per region, per finger, and per dermatome with a test score. The affected side of the NBPP group was compared with the non-dominant hand of the controls. RESULTS: The ability to localize stimuli on the tips of the fingers in children with an upper NBPP was significantly diminished in all fingers, except for the little finger, as compared with healthy controls. Mean localization scores were 6.6 (thumb) and 6.3 (index finger) in the NBPP group and 7.6 in both fingers for controls (maximum score possible is 8.0). Localization scores were significant lower in regions attributed to dermatomes C6 (P<.001) and C7 (P=.001), but not to C8 (P=.115). CONCLUSION: Children with an upper NBPP showed a diminished and incorrect ability to localize sensory stimuli to their fingers. This finding is likely 1 of the factors underlying the impairment of hand function and should be addressed with sensory focused therapy.

Shoulder Internal Rotation Contracture Formation in Surgically Managed C5, C6 Brachial Plexus Birth Injuries: Neurotmetic Lesions Fare Worse Than Avulsions.

BACKGROUND: A typical feature in infants with severe C5-C6 brachial plexus birth injury (BPBI) requiring nerve repair is the formation of shoulder internal rotation contracture (IRC). The underlying pathophysiological mechanism is unknown, and the sequelae can be difficult to treat. The severity of the IRC differs among children. C5-C6 lesions are heterogeneous at the root level. Our null hypothesis was that the type of root-level lesion (axonotmesis or neurotmesis versus avulsion) was not associated with the extent of IRC formation over time in children with upper-trunk BPBI. METHODS: We performed a retrospective analysis of all patients with upper-trunk BPBI who underwent primary surgery of the C5 and/or C6 spinal nerves between 1990 and 2020 and had follow-up of at least 2 years. The primary outcome was passive shoulder external rotation (ER) in adduction at 1, 3, 5, 7, and 15 years of age. The secondary outcome was whether additional shoulder surgery was performed. The relationship between the nature of the C5-C6 lesion and IRC formation was analyzed using linear mixed models. The Kaplan-Meier method was used to estimate the cumulative risk of secondary shoulder procedures. RESULTS: In total, 322 patients were analyzed; mean follow-up was 7.2 ± 4.6 years. The C5-C6 root lesion type was significantly related to the passive range of ER (overall test in linear mixed model, p = 0.007). Children with avulsion of C5 and C6 (n = 21) had, on average, 18° (95% confidence interval [CI], 6.3° to 30°) less IRC formation than those with neurotmesis of C5 and C6 (n = 175) and 17° (2.9° to 31°) less than those with neurotmesis of C5 and avulsion of C6 (n = 34). IRC formation did not differ between the neurotmesis C5-C6 and neurotmesis C5-avulsion C6 groups. Secondary shoulder procedures were performed in 77 patients (10-year risk, 28% [95%CI, 23% to 34%]). CONCLUSIONS: Shoulder IRC formation in infants with BPBI with surgically treated C5-C6 lesions occurs to a lesser degree if the C5 root is avulsed than when C5 is neurotmetic. This finding provides insight into the possible causative pathoanatomy and may ultimately lead to strategies to mitigate IRC. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

What is the Elbow Flexion Strength After Free Functional Gracilis Muscle Transfer for Adult Traumatic Complete Brachial Plexus Injuries?

BACKGROUND: Traumatic brachial plexus injuries (BPIs) in the nerve roots of C5 to T1 lead to the devastating loss of motor and sensory function in the upper extremity. Free functional gracilis muscle transfer (FFMT) is used to reconstruct elbow and shoulder function in adults with traumatic complete BPIs. The question is whether the gains in ROM and functionality for the patient outweigh the risks of such a large intervention to justify this surgery in these patients. QUESTIONS/PURPOSES: (1) After FFMT for adult traumatic complete BPI, what is the functional recovery in terms of elbow flexion, shoulder abduction, and wrist extension (ROM and muscle grade)? (2) Does the choice of distal insertion affect the functional recovery of the elbow, shoulder, and wrist? (3) Does the choice of nerve source affect elbow flexion and shoulder abduction recovery? (4) What factors are associated with less residual disability? (5) What proportion of flaps have necrosis and do not reinnervate? METHODS: We performed a retrospective observational study at Dr. Soetomo General Hospital in Surabaya, Indonesia. A total of 180 patients with traumatic BPIs were treated with FFMT between 2010 and 2020, performed by a senior orthopaedic hand surgeon with 14 years of experience in FFMT. We included patients with traumatic complete C5 to T1 BPIs who underwent a gracilis FFMT procedure. Indications were total avulsion injuries and delayed presentation (>6 months after trauma) or after failed primary nerve transfers (>12 months). Patients with less than 12 months of follow-up were excluded, leaving 130 patients eligible for this study. The median postoperative follow-up period was 47 months (interquartile range [IQR] 33 to 66 months). Most were men (86%; 112 of 130) who had motorcycle collisions (96%; 125 patients) and a median age of 23 years (IQR 19 to 34 years). Orthopaedic surgeons and residents measured joint function at the elbow (flexion), shoulder (abduction), and wrist (extension) in terms of British Medical Research Council (MRC) muscle strength scores and active ROM. A univariate analysis of variance test was used to evaluate these outcomes in terms of differences in distal attachment to the extensor carpi radialis brevis (ECRB), extensor digitorum communis and extensor pollicis longus (EDC/EPL), the flexor digitorum profundus and flexor pollicis longus (FDP/FPL), and the choice of a phrenic, accessory, or intercostal nerve source. We measured postoperative function with the DASH score and pain at rest with the VAS score. A multivariate linear regression analysis was performed to investigate what patient and injury factors were associated with less disability. Complications such as flap necrosis, innervation problems, infections, and reoperations were evaluated. RESULTS: The median elbow flexion muscle strength was 3 (IQR 3 to 4) and active ROM was 88° ± 46°. The median shoulder abduction grade was 3 (IQR 2 to 4) and active ROM was 62° ± 42°. However, the choice of distal insertion was not associated with differences in the median wrist extension strength (ECRB: 2 [IQR 0 to 3], EDC/EPL: 2 [IQR 0 to 3], FDP/FPL: 1 [IQR 0 to 2]; p = 0.44) or in ROM (ECRB: 21° ± 19°, EDC/EPL: 21° ± 14°, FDP/FPL: 13° ± 15°; p = 0.69). Furthermore, the choice of nerve source did not affect the mean ROM for elbow flexion (phrenic nerve: 87° ± 46°; accessory nerve: 106° ± 49°; intercostal nerves: 103° ± 50°; p = 0.55). No associations were found with less disability (lower DASH scores): young age (coefficient = 0.28; 95% CI -0.22 to 0.79; p = 0.27), being a woman (coefficient = -9.4; 95% CI -24 to 5.3; p = 0.20), and more postoperative months (coefficient = 0.02; 95% CI -0.01 to 0.05]; p = 0.13). The mean postoperative VAS score for pain at rest was 3 ± 2. Flap necrosis occurred in 5% (seven of 130) of all patients, and failed innervation of the gracilis muscle occurred in 4% (five patients). CONCLUSION: FFMT achieves ROM with fair-to-good muscle power of elbow flexion, shoulder abduction, and overall function for the patient, but does not achieve good wrist function. Meticulous microsurgical skills and extensive rehabilitation training are needed to maximize the result of FFMT. Further technical developments in distal attachment and additional nerve procedures will pave the way for reconstructing a functional limb in patients with a flail upper extremity. LEVEL OF EVIDENCE: Level III, therapeutic study.

A prediction model for recurrence after translabyrinthine surgery for vestibular schwannoma: toward personalized postoperative surveillance.

PURPOSE: The aim of this study is to compute and validate a statistical predictive model for the risk of recurrence, defined as regrowth of tumor necessitating salvage treatment, after translabyrinthine removal of vestibular schwannomas to individualize postoperative surveillance. METHODS: The multivariable predictive model for risk of recurrence was based on retrospectively collected patient data between 1995 and 2017 at a tertiary referral center. To assess for internal validity of the prediction model tenfold cross-validation was performed. A 'low' calculated risk of recurrence in this study was set at < 1%, based on clinical criteria and expert opinion. RESULTS: A total of 596 patients with 33 recurrences (5.5%) were included for analysis. The final prediction model consisted of the predictors 'age at time of surgery', 'preoperative tumor growth' and 'first postoperative MRI outcome'. The area under the receiver operating curve of the prediction model was 89%, with a C-index of 0.686 (95% CI 0.614-0.796) after cross-validation. The predicted probability for risk of recurrence was low (< 1%) in 373 patients (63%). The earliest recurrence in these low-risk patients was detected at 46 months after surgery. CONCLUSION: This study presents a well-performing prediction model for the risk of recurrence after translabyrinthine surgery for vestibular schwannoma. The prediction model can be used to tailor the postoperative surveillance to the estimated risk of recurrence of individual patients. It seems that especially in patients with an estimated low risk of recurrence, the interval between the first and second postoperative MRI can be safely prolonged.

Molecular Changes in the Dorsal Root Ganglion during the Late Phase of Peripheral Nerve Injury-induced Pain in Rodents: A Systematic Review.

The dorsal root ganglion is widely recognized as a potential target to treat chronic pain. A fundamental understanding of quantitative molecular and genomic changes during the late phase of pain is therefore indispensable. The authors performed a systematic literature review on injury-induced pain in rodent dorsal root ganglions at minimally 3 weeks after injury. So far, slightly more than 300 molecules were quantified on the protein or messenger RNA level, of which about 60 were in more than one study. Only nine individual sequencing studies were performed in which the most up- or downregulated genes varied due to heterogeneity in study design. Neuropeptide Y and galanin were found to be consistently upregulated on both the gene and protein levels. The current knowledge regarding molecular changes in the dorsal root ganglion during the late phase of pain is limited. General conclusions are difficult to draw, making it hard to select specific molecules as a focus for treatment.

Origin, branching pattern, foraminal and intraspinal distribution of the human lumbar sinuvertebral nerves.

BACKGROUND CONTEXT: The lumbar sinuvertebral nerve (SVN) innervates the outer posterior intervertebral disc (IVD); it is thought to mediate discogenic low-back pain (LBP). Controversy, however, exists on its origins at higher (L1-L2) versus lower (L3-L5) lumbar levels. Additionally, lack of knowledge regarding its foraminal and intraspinal branching patterns and extensions may lead to iatrogenic damage. PURPOSE: To systematically describe the origins of the L2 and L5 SVNs, their morphological variation in the intervertebral foramen (IVF) and intraspinal distribution. STUDY DESIGN: Dissection-based study of 20 SVNs with histological confirmation in five embalmed human cadavers. METHODS: The origin, branching pattern and distribution of the L2 and L5 SVNs was investigated bilaterally in five human cadavers using dorsal and anterolateral dissection approaches. Parameters studied included somatic and/or autonomic SVN root contributions, foraminal SVN morphology and course, diameter, branching point, intraspinal distribution and IVD innervation pattern. Nerve tissue was confirmed by immunostaining for neurofilament and S100 proteins. RESULTS: The SVN and its origins was identified in all except one IVF at L2 and in all foramina at L5. At L2, the SVN arose in nearly 90% of sides from both somatic and autonomic roots and at L5 in 40% of sides. The remaining SVNs were formed by purely autonomic roots. The SVN arose from significantly more roots at L2 than L5 (3.1 ± 0.3 vs. 1.9 ± 0.3, respectively; p=.022). Four different SVN morphologies could be discerned in the L2 IVF: single filament (22%), multiple (parallel or diverging) filament (33%), immediate splitting (22%) and plexiform (22%) types, whereas the L5 SVN consisted of single (90%) and multiple (10%) filament types. SVN filaments were significantly thicker at L2 than L5 (0.48 ± 0.06 mm vs. 0.33 ± 0.02 mm, respectively; p=.043). Ascending SVN filaments coursed roughly parallel to the exiting spinal nerve root trajectory at L2 and L5. Branching of the SVN into ascending and descending branches occurred mostly intraspinal both at L2 and L5. Spinal canal distribution was also similar for L2 and L5 SVNs. Lumbar posterior IVDs were innervated by the descending branch of the parent SVN and ascending branch of the subjacent SVN. CONCLUSIONS: The SVN at L2 originates from both somatic and autonomic roots in 90% of cases and at L5 in 40% of cases. The remaining SVNs are purely autonomic. In the IVF, the L2 SVN is morphologically heterogeneous, but generally consists of numerous filaments, whereas at L5 90% contains a single SVN filament. The L2 SVN is formed by more roots and is thicker than the L5 SVN. Intraspinal SVN distribution is confined to its level of origin; lumbar posterior IVDs are innervated by corresponding and subjacent SVNs (ie, two spinal levels). CLINICAL SIGNIFICANCE: Our findings indicate that L5 discogenic LBP may be mediated both segmentally and nonsegmentally in 40% of cases and nonsegmentally in 60% of cases. Failure of lower lumbar discogenic pain treatment may be the result of only interrupting the nonsegmental pathway, but not the segmental one as well. Relating SVN anatomy to microsurgical spinal approaches may prevent iatrogenic damage to the SVN and the formation of postsurgical back pain.

Smart Polymeric Micelles for Anticancer Hydrophobic Drugs.

Cancer has become one of the deadliest diseases in our society. Surgery accompanied by subsequent chemotherapy is the treatment most used to prolong or save the patient's life. Still, it carries secondary risks such as infections and thrombosis and causes cytotoxic effects in healthy tissues. Using nanocarriers such as smart polymer micelles is a promising alternative to avoid or minimize these problems. These nanostructured systems will be able to encapsulate hydrophilic and hydrophobic drugs through modified copolymers with various functional groups such as carboxyls, amines, hydroxyls, etc. The release of the drug occurs due to the structural degradation of these copolymers when they are subjected to endogenous (pH, redox reactions, and enzymatic activity) and exogenous (temperature, ultrasound, light, magnetic and electric field) stimuli. We did a systematic review of the efficacy of smart polymeric micelles as nanocarriers for anticancer drugs (doxorubicin, paclitaxel, docetaxel, lapatinib, cisplatin, adriamycin, and curcumin). For this reason, we evaluate the influence of the synthesis methods and the physicochemical properties of these systems that subsequently allow an effective encapsulation and release of the drug. On the other hand, we demonstrate how computational chemistry will enable us to guide and optimize the design of these micelles to carry out better experimental work.