Botulinum toxin injections for the treatment of neurogenic thoracic outlet syndrome: A systematic review.

Botulinum toxin (BTX) injections into the musculature surrounding the brachial plexus have been examined as a potential treatment for neurogenic thoracic outlet syndrome (nTOS). This systematic review identified 15 publications, of which one was a randomized controlled trial. BTX injections performed with ultrasound or electromyographic guidance, and with the inclusion of the pectoralis minor muscle, in addition to the anterior and/or middle scalenes, tended to provide greater symptom improvement and may predict response to first rib resection. Importantly, most studies were of low quality; thus, the results should be interpreted with caution. Further high-quality studies are needed to confirm these findings.

Retrograde labeling correlates with motor unit number estimation in rapid-stretch nerve injury.

INTRODUCTION/AIMS: Rapid-stretch nerve injuries represent a substantial treatment challenge. No study has examined motor neuron connection after rapid-stretch injury. Our objective in this study was to characterize the electrophysiological properties of graded rapid-stretch nerve injury and assess motor neuron health using retrograde labeling and muscle adenosine triphosphatase (ATPase) histology. METHODS: Male C57BL/6 mice (n = 6 per group) were rapid-stretch injured at four levels of severity: sham injury, stretch within elastic modulus, inelastic deformation, and stretch rupture. Serial compound muscle action potential (CMAP) and motor unit number estimation (MUNE) measurements were made for 48 days, followed by retrograde labeling and muscle ATPase histology. RESULTS: Elastic injuries showed no durable abnormalities. Inelastic injury demonstrated profound initial reduction in CMAP and MUNE (P < .036) on day 2, with partial recovery by day 14 after injury (CMAP: 40% baseline, P = .003; MUNE: 55% baseline, P = .033). However, at the experimental endpoint, CMAP had recovered to baseline with only limited improvement in MUNE. Inelastic injury led to reduced retrograde-labeled neurons and grouped fiber type histology. Rupture injury had severe and nonrecovering electrophysiological impairment, dramatically reducing labeled neurons (P = .005), and atrophic or type 1 muscle fibers. There was an excellent correlation between MUNE and retrograde-labeled tibial motor neurons across injury severities (R2  = 0.96). DISCUSSION: There was no significant electrophysiological derangement in low-severity injuries but there was recoverable conduction block in inelastic injury with slow recovery, potentially due to collateral sprouting. Rupture injuries yielded permanent failure of injured axons to reinnervate. These results provide insight into the pathophysiology of clinical injuries and recovery.

What's known and what's new in adipose lesions of peripheral nerves?

BACKGROUND: Adipose lesions of nerve primarily include intra- and extraneural lipomas and lipomatosis of nerve (LN). This paper will summarize the advances that have been made in the past decade, particularly related to LN and nerve territory overgrowth that have improved our understanding of the natural history, genetic background, diagnosis, imaging features, and clinical management. METHODS AND MATERIALS: Articles about adipose lesions of nerve were reviewed from 2011, when the last comprehensive review on this topic was published. Papers reporting advances on natural history, genetic background, diagnosis, imaging features, and clinical management were screened using PubMed and Google Scholar databases and then analyzed. Case reports and small case series were included only if they reported model examples of discussed pathologies, as these types of articles were summarized in recent systematic reviews on intraneural lipomas and LN. All eligible papers were assessed by the authors, who are subject matter experts. RESULTS: The first screen revealed 404 articles. After careful evaluation, a total of 53 articles were analyzed which includes advances in diagnosis (especially imaging), classification of the lesions, the role of somatic mutations in PIK3CA in LN, and treatment approaches for all adipose lesions of the peripheral nerve. CONCLUSION: Many advances have been made in the understanding of adipose lesions of nerve in the past decade. These pathologic entities are more readily recognized as a spectrum of lesions that share common phenotypic features.

Bilateral Nerve Involvement in Lipomatosis of Nerve.

Lipomatosis of nerve (LN) is an intriguing pathological entity defined by the abundance of fibro-adipose tissue within the epineurium, a pathognomonic magnetic resonance imaging (MRI), and frequently associated nerve-territory overgrowth. A recent systematic review showed that the majority of cases are unilateral and predominately involve the median nerve. We reviewed bilateral cases of LN to further understand this pathology. We conducted a review of the literature and our institutional databases. The cases from the literature were sorted into three groups - bilaterally confirmed LN (n = 9), unilaterally confirmed, opposite side probable LN (n = 4), and probable bilateral LN (n = 10). Review of our institutional databases identified one case: a 47-year-old man. MRI revealed LN of the brachial plexus bilaterally. To our knowledge, this is the first reported case of brachial plexus LN occurring bilaterally. More research is necessary on this topic to further understand the genetic background of this entity, particularly in relationship to the overgrowth. (Journal of Surgical Orthopaedic Advances 30(1):044-049, 2021).

The Effectiveness of Spinal Cord Stimulation for the Treatment of Axial Low Back Pain: A Systematic Review with Narrative Synthesis.

OBJECTIVE: Determine the effectiveness of spinal cord stimulation (SCS) for the treatment of axial low back pain (LBP) with or without leg pain. DESIGN: Systematic review. SUBJECTS: Persons aged ≥18 with axial LBP with or without accompanying leg pain. INTERVENTION: Traditional low-frequency, burst, or high-frequency SCS. COMPARISON: Sham, active standard of care treatment, or none. OUTCOMES: The primary outcome was ≥50% pain improvement, and the secondary outcome was functional improvement measured six or more months after treatment intervention. METHODS: Publications in PubMed, MEDLINE, and Cochrane databases were reviewed through September 19, 2019. Randomized or nonrandomized comparative studies and nonrandomized studies without internal controls were included. The Cochrane Risk of Bias Tool and GRADE system were used to assess individual study characteristics and overall quality. RESULTS: Query identified 262 publications; 17 were suitable for inclusion. For high-frequency SCS, the only level 1 study showed that 79% (95% confidence interval = 70-87%) of patients reported ≥50% pain improvement. For low-frequency SCS, the only level 1 study reported no categorical data for axial LBP-specific outcomes; axial LBP improved by a mean 14 mm on the visual analog scale at six months. Meta-analysis was not performed due to study heterogeneity. CONCLUSIONS: According to GRADE, there is low-quality evidence that high-frequency SCS compared with low-frequency SCS is effective in patients with axial LBP with concomitant leg pain. There is very low-quality evidence for low-frequency SCS for the treatment of axial LBP in patients with concomitant leg pain. There is insufficient evidence addressing the effectiveness of burst SCS to apply a GRADE rating.

Distal nerve transfer for thenar palsy: A cadaveric study.

INTRODUCTION: Severe proximal median nerve palsies often result in irreversible thenar atrophy and thumb abduction function loss. Tendon transfer involves substantial limitations and challenges; but, distal nerve transfer may provide an alternative treatment. Our goal was to validate the anatomical suitability of two distal ulnar nerve branches for thenar muscle reanimation. MATERIALS AND METHODS: We assessed nerve transfer to the recurrent branch of median nerve (RMN) in 16 embalmed cadaveric hands. The ulnar motor branch to the flexor digiti minimi brevis (FDMBn) and the ulnar motor branch to the third lumbrical (3rdLn) were assessed for transfer. Coaptation success was measured by the overlap of the nerve donor with the RMN and correspondence of nerve diameters. RESULTS: The mean transferable length and width of the RMN were 20.7 ± 4.5 and 1.0 ± 0.3 mm, respectively. We identified an average of three branches in the branching anatomy from the ulnar nerve to the hypothenar muscles. The maximal transferable lengths and widths of the FDMBn and the 3rdLn were 13.8 ± 4.4 and 0.5 ± 0.1 mm and 24.1 ± 6.4 and 0.4 ± 0.1 mm, respectively. The overlap with the RMN of the FDMBn and 3rdLn was 9.0 ± 3.6 (2.0-15.3) and 17.8 ± 6.0 (4.7-27.5) mm, respectively. CONCLUSIONS: This anatomical study demonstrates the feasibility of distal nerve transfers between the ulnar and median nerves in the hand for reanimation of thenar muscles. Ulnar motor donors of the BrFDMBn and 3rdLn likely represent the least morbid donors with short distances for regeneration and a single coaptation repair.

Pathologic remodeling in human neuromas: insights from clinical specimens.

BACKGROUND: Neuroma pathology is commonly described as lacking a clear internal structure, but we observed evidence that there are consistent architectural elements. Using human neuroma samples, we sought to identify molecular features that characterize neuroma pathophysiology. METHODS: Thirty specimens-12 neuromas-in-continuity (NICs), 11 stump neuromas, two brachial plexus avulsions, and five controls-were immunohistochemically analyzed with antibodies against various components of normal nerve substructures. RESULTS: There were no substantial histopathologic differences between stump neuromas and NICs, except that NICs had intact fascicle(s) in the specimen. These intact fascicles showed evidence of injury and fibrosis. On immunohistochemical analysis of the neuromas, laminin demonstrated a consistent double-lumen configuration. The outer lumen stained with GLUT1 antibodies, consistent with perineurium and microfascicle formation. Antibodies to NF200 revealed small clusters of small-diameter axons within the inner lumen, and the anti-S100 antibody showed a relatively regular pattern of non-myelinating Schwann cells. CD68+ cells were only seen in a limited temporal window after injury. T-cells were seen in neuroma specimens, with both a temporal evolution as well as persistence long after injury. Avulsion injury specimens had similar architecture to control nerves. Seven pediatric specimens were not qualitatively different from adult specimens. NICs demonstrated intact but abnormal fascicles that may account for the neurologically impoverished outcomes from untreated NICs. CONCLUSIONS: We propose that there is consistent pathophysiologic remodeling after fascicle disruption. Particular features, such as predominance of small caliber axons and persistence of numerous T-cells long after injury, suggest a potential role in chronic pain associated with neuromas.

Lipomatosis of nerve and overgrowth: is there a preference for motor (mixed) vs. sensory nerve involvement?

BACKGROUND: Lipomatosis of nerve (LN) is a peripheral nerve disorder characterized by fibroadipose proliferation within the epineurium. It has been associated with nerve-territory overgrowth affecting soft tissue and/or bony structures. We sought to understand if there is an anatomical relationship associated with nerve-territory overgrowth. METHODS: A review of the literature and our institutional LN cases was performed to determine the prevalence of nerve-territory overgrowth. Only cases with sufficient clinical and/or imaging data were selected. The cases were then subdivided into two groups and analyzed: (1) motor (mixed) nerve and (2) predominant sensory nerve, based on the anatomical location of the LN lesion. Subgroup analysis was performed on median nerves affected by LN, for a more homogenous population. RESULTS: We identified 329 LN cases with sufficient information for analysis. Motor (mixed) nerve group (M) consisted of 287 cases (155 with overgrowth and 132 without overgrowth). Sensory nerve group (S) revealed group of 42 cases (4 cases with overgrowth and 38 without overgrowth). Statistical analysis comparing overgrowth status in the M and S nerve groups showed a statistically significant difference in overgrowth, favoring the M group for overgrowth (p < 0.0001). The analysis of median nerve group consisted of 225 cases in the M group (106 with overgrowth and 119 without overgrowth) and 20 cases in the S group (3 with overgrowth and 17 cases without overgrowth). A statistically significant difference in nerve-territory overgrowth status was present in the M vs. the S group, again favoring the M group for overgrowth. (p = 0.0083). Cases from our institution included 44 cases for this analysis. Forty-two cases in the M group (28 with overgrowth and 14 without overgrowth) and 2 cases in the S group (all 2 without overgrowth). CONCLUSION: We believe the association of LN and nerve-territory overgrowth might be explained by involvement of mixed motor nerves; however, the exact underlying mechanism is not known.

Surgical repair of sciatic nerve traumatic rupture: technical considerations and approaches.

Traumatic proximal sciatic nerve rupture poses surgical repair dilemmas. Disruption often causes a large nerve gap after proximal neuroma and distal scar removal. Also, autologous graft material to bridge the segmental defect may be insufficient, given the sciatic nerve diameter. The authors utilized knee flexion to allow single neurorrhaphy repair of a large sciatic nerve defect, bringing healthy proximal stump to healthy distal segment. To avoid aberrant regeneration, the authors split the sciatic nerve into common peroneal and tibial divisions. After 3 months, the patient can fully extend the knee and has evidence of distal regeneration and nerve continuity without substantial injury. The video can be found here: https://youtu.be/lsezRT5I8MU .

Acute repair of traumatic pan-brachial plexus injury: technical considerations and approaches.

Particularly challenging after complete brachial plexus avulsion is reestablishing effective hand function, due to limited neurological donors to reanimate the arm. Acute repair of avulsion injuries may enable reinnervation strategies for achieving hand function. This patient presented with pan-brachial plexus injury. Given its irreparable nature, the authors recommended multistage reconstruction, including contralateral C-7 transfer for hand function, multiple intercostal nerves for shoulder/triceps function, shoulder fusion, and spinal accessory nerve-to-musculocutaneous nerve transfer for elbow flexion. The video demonstrates distal contraction from electrical stimulation of the avulsed roots. Single neurorrhaphy of the contralateral C-7 transfer was performed along with a retrosternocleidomastoid approach. The video can be found here: https://youtu.be/GMPfno8sK0U .

Intraneural lipomas: institutional and literature review.

BACKGROUND: Adipose lesions of nerve can be envisioned as a spectrum ranging from intraneural/extraneural lipomas to lipomatosis of nerve (LN). We have noticed that intraneural lipomas are not as a homogenous group as previously thought and demonstrate differences which have clinical implications. To better understand intraneural lipomas, we conducted a search of cases at our institution and published cases in the world's literature. MATERIALS AND METHODS: Mayo Clinic's database was searched between years 1994-2018. Published cases were identified using PubMed and Google Scholar databases. Following terms were used: intraneural lipoma, lipoma and nerve, lipoma and neuropathy, lipofibroma and nerve, fibrolipoma and nerve and neural lipoma as well as lipofibroma and fibrolipoma alone. Cases that could be clearly identified as intraneural lipomas by the location of the lipoma within the epineurium were included for analysis. These cases were then sub-classified as encapsulated intraneural lipomas or hybrid intraneural lipomas (demonstrating features of both intraneural/extraneural lipomas and LN) based on their characteristics. RESULTS: We identified 12 cases at our institution (8 encapsulated, 4 hybrid) and 24 published cases (21 encapsulated, 3 hybrid). The most commonly affected nerve was median both at our institution and in the published cases. Encapsulated cases were found to be relatively easy to resect. Hybrid cases demonstrated variable degree of interdigitating fat between the fascicles and were relatively difficult to resect. CONCLUSION: Intraneural lipomas exist as two separate entities with distinct clinical implications. Although rare, this should be taken in account when planning surgery. Terminology should be clarified to prevent ambiguity and confusion.

Impact of removed tumor volume and location on patient outcome in glioblastoma.

Glioblastoma is an aggressive primary brain tumor with devastatingly poor prognosis. Multiple studies have shown the benefit of wider extent of resection (EOR) on patient overall survival (OS) and worsened survival with larger preoperative tumor volumes. However, the concomitant impact of postoperative tumor volume and eloquent location on OS has yet to be fully evaluated. We performed a retrospective chart review of adult patients treated for glioblastoma from January 2006 through December 2011. Adherence to standardized postoperative chemoradiation protocols was used as an inclusion criterion. Detailed volumetric and location analysis was performed on immediate preoperative and immediate postoperative magnetic resonance imaging. Cox proportional hazard modeling approach was employed to explore the modifying effects of EOR and eloquent location after adjusting for various confounders and associated characteristics, such as preoperative tumor volume and demographics. Of the 471 screened patients, 141 were excluded because they did not meet all inclusion criteria. The mean (±SD) age of the remaining 330 patients (60.6% male) was 58.9 ± 12.9 years; the mean preoperative and postoperative Karnofsky performance scores (KPSs) were 76.2 ± 10.3 and 80.0 ± 16.6, respectively. Preoperative tumor volume averaged 33.2 ± 29.0 ml, postoperative residual was 4.0 ± 8.1 ml, and average EOR was 88.6 ± 17.6%. The observed average follow-up was 17.6 ± 15.7 months, and mean OS was 16.7 ± 14.4 months. Survival analysis showed significantly shorter survival for patients with lesions in periventricular (16.8 ± 1.7 vs. 21.5 ± 1.4 mo, p = 0.03), deep nuclei/basal ganglia (11.6 ± 1.7 vs. 20.6 ± 1.2, p = 0.002), and multifocal (12.0 ± 1.4 vs. 21.3 ± 1.3 months, p = 0.0001) locations, but no significant influence on survival was seen for eloquent cortex sites (p = 0.14, range 0.07-0.9 for all individual locations). OS significantly improved with EOR in univariate analysis, averaging 22.3, 19.7, and 13.2 months for >90, 80-90, and 70-80% resection, respectively. Survival was 22.8, 19.0, and 12.7 months for 0, 0-5, and 5-10 ml postoperative residual, respectively. A hazard model showed that larger preoperative tumor volume [hazard ratio (HR) 1.05, 95% CI 1.02-1.07], greater age (HR 1.02, 95% CI 1.01-1.03), multifocality (HR 1.44, 95% CI 1.01-2.04), and deep nuclei/basal ganglia (HR 2.05, CI 1.27-3.3) were the most predictive of poor survival after adjusting for KPS and tumor location. There was a negligible but significant interaction between EOR and preoperative tumor volume (HR 0.9995, 95% CI 0.9993-0.9998), but EOR alone did not correlate with OS after adjusting for other factors. The interaction between EOR and preoperative tumor volume represented tumor volume removed during surgery. In conclusion, EOR alone was not an important predictor of outcome during GBM treatment once preoperative tumor volume, age, and deep nuclei/basal ganglia location were factored. Instead, the interaction between EOR and preoperative volume, representing reduced disease burden, was an important predictor of reducing OS. Removal of tumor from eloquent cortex did not impact postoperative KPS. These results suggest aggressive surgical treatment to reduce postoperative residual while maintaining postoperative KPS may aid patient survival outcomes for a given tumor size and location.

Establishing reconstructive neurosurgery as a subspecialty.

Neurosurgery is experiencing the emergence of a new subspecialty focused on function restoration. New, evolving, and reappraised surgical procedures have provided an opportunity to restore function to many patients with previously undertreated disorders. Candidates for reconstruction were previously limited to those with peripheral nerve and brachial plexus injuries, but this has been expanded to include stroke, spinal cord injury, and a host of other paralyzing disorders affecting both upper and lower motor neurons. Similar to the recent evolution of the well-established subdisciplines of spinal and vascular neurosurgery, reconstructive neurosurgery requires the adaptation of techniques and skills that were not traditionally a part of neurosurgical training. Neurosurgeons-as the specialists who already manage this patient population and possess the requisite surgical skills to master the required techniques-have a unique opportunity to lead the development of this field. The full development of this subspecialty will lay the foundation for the subsequent addition of emerging treatments, such as neuroprosthetics and stem cell-based interventions. As such, reconstructive neurosurgery represents an important aspect of neurosurgical training that can ameliorate many of the deficits encountered in the traditional practice of neurosurgery.

An update on addressing important peripheral nerve problems: challenges and potential solutions.

From time to time it is thoughtful and productive to review a medical field and reflect upon what are the major issues that need to be addressed and what is being done to do so. This review article is not meant to be all-inclusive but rather focuses on four evolving areas in the field of peripheral nerve disorders and treatments: (1) nerve surgery under ultrasound guidance using a new ultra-minimally invasive thread technique; (2) evolving magnetic resonance imaging (MRI) and ultrasound imaging techniques that are helping to both diagnose and treat a variety of peripheral nerve problems including entrapment neuropathies, traumatic nerve injuries, and masses arising from nerves; (3) promoting recovery after nerve injury using electrical stimulation; and (4) developing animal models to reproduce a severe nerve injury (neurotmetic grade in continuity) that requires a surgical intervention and repair. In each area we first describe the current challenges and then discuss new and emerging techniques and approaches. It is our hope that this article will bring added attention and resources to help better address peripheral nerve problems that remain a challenge for both patients and physicians.

Anatomy of psoas muscle innervation: Cadaveric study.

Hip flexion weakness is relatively common after lateral transpsoas surgery. Persistent weakness may result from injury to the innervation of the psoas major muscles (PMMs); however, anatomical texts have conflicting descriptions of this innervation, and the branching pattern of the nerves within the psoas major, particularly relative to vertebral anatomy, has not been described. The authors dissected human cadavers to describe the branching pattern of nerves supplying the PMMs. Sixteen embalmed cadavers were dissected, and the fine branching pattern of the innervation to the PMM was studied in 24 specimens. The number of branches and width and length of each branch of nerves to the PMMs were quantified. Nerve branches innervating the PMMs arose from spinal nerve levels L1-L4, with an average of 6.3 ± 1.1 branches per muscle. The L1 nerve branch was the least consistently present, whereas L2 and L3 branches were the most robust, the most numerous, and always present. The nerve branches to the psoas major commonly crossed the intervertebral (IV) disc obliquely prior to ramification within the muscle; 76%, 80%, and 40% of specimens had a branch to the PMM cross the midportion of the L2-3, L3-4, and L4-5 IV discs, respectively. The PMMs are segmentally innervated from the L2-L4 ventral rami branches, where these branches course obliquely across the L2-3, L3-4, and L4-5 IV discs. Knowledge of the mapping of nerve branches to the PMMs may reduce injury and the incidence of persistent weak hip flexion during lateral transpsoas surgery. Clin. Anat. 30:479-486, 2017. © 2017 Wiley Periodicals, Inc.

The genetic basis of intradural spinal tumors and its impact on clinical treatment.

Genetic alterations in the cells of intradural spinal tumors can have a significant impact on the treatment options, counseling, and prognosis for patients. Although surgery is the primary therapy for most intradural tumors, radiochemothera-peutic modalities and targeted interventions play an ever-evolving role in treating aggressive cancers and in addressing cancer recurrence in long-term survivors. Recent studies have helped delineate specific genetic and molecular differences between intradural spinal tumors and their intracranial counterparts and have also identified significant variation in therapeutic effects on these tumors. This review discusses the genetic and molecular alterations in the most common intradural spinal tumors in both adult and pediatrie patients, including nerve sheath tumors (that is, neurofibroma and schwannoma), meningioma, ependymoma, astrocytoma (that is, low-grade glioma, anaplastic astrocytoma, and glioblastoma), hemangioblastoma, and medulloblastoma. It also examines the genetics of metastatic tumors to the spinal cord, arising either from the CNS or from systemic sources. Importantly, the impact of this knowledge on therapeutic options and its application to clinical practice are discussed.

A practical review of prognostic correlations of molecular biomarkers in glioblastoma.

Despite extensive efforts in research and therapeutics, achieving longer survival for patients with glioblastoma (GBM) remains a formidable challenge. Furthermore, because of rapid advances in the scientific understanding of GBM, communication with patients regarding the explanations and implications of genetic and molecular markers can be difficult. Understanding the important biomarkers that play a role in GBM pathogenesis may also help clinicians in educating patients about prognosis, potential clinical trials, and monitoring response to treatments. This article aims to provide an up-to-date review that can be discussed with patients regarding common molecular markers, namely O-6-methylguanine-DNA methyltransferase (MGMT), isocitrate dehydrogenase 1 and 2 (IDH1/2), p53, epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), phosphatase and tensin homolog (PTEN), phosphoinositide 3-kinase (PI3K), and 1p/19q. The importance of the distinction between a prognostic and a predictive biomarker as well as clinical trials regarding these markers and their relevance to clinical practice are discussed.

The first radiographic image of a peripheral nerve disorder? Lipomatous macrodactyly (unrecognized lipomatosis of nerve).

Lipomatosis of nerves (LN) involves benign fibro-fatty infiltration and is often associated with territorial overgrowth of soft tissue and bone; this distinctive disease pattern can be visualized on plain radiographs. We recently discovered a case (presented by Sir Robert Jones in 1898 to the Pathological Society of London) that indirectly represents a historical landmark in the imaging of peripheral nerves. The clinical findings and image, with obvious soft tissue and bone overgrowth, are pathognomonic for LN, making this one of the earliest radiological observations of a peripheral nerve lesion.