Neurologic Clinical, Electrophysiologic, and Pathologic Characteristics of Primary vs Secondary Neurolymphomatosis.

BACKGROUND AND OBJECTIVES: Neurolymphomatosis (NL) is characterized by lymphomatous infiltration of the peripheral nervous system presenting as the initial manifestation of a lymphoma (primary NL [PNL]) or in relapse of a known lymphoma (secondary NL [SNL]). This report details and compares the neurologic clinicopathologic characteristics of these 2 groups. METHODS: This retrospective study was performed on patients diagnosed with pathologically confirmed NL in nerve between January 1, 1992, and June 31, 2020. Patient clinical characteristics, neurologic examination, imaging studies, EMG, and nerve biopsy data were collected, analyzed, and compared between PNL and SNL. RESULTS: A total of 58 patients were identified (34 PNL and 24 SNL). Time from neurologic symptom onset to diagnosis was longer in PNL at 18.5 months compared with 5.5 months in SNL (p = 0.01). Neurologic symptoms were similar in both patient groups and included primarily sensory loss (98%), severe pain (76%), and asymmetric weakness (76%). A wide spectrum of EMG-confirmed different neuropathy patterns were observed, but patients with SNL had increased numbers of mononeuropathies (n = 8) compared with PNL (n = 1, p = 0.01). MRI studies detected NL more frequently (86%) compared with fluorodeoxyglucose (FDG)-PET CT imaging studies (60%) (p = 0.007). Nerve biopsies revealed B-cell lymphoma (PNL n = 32, SNL n = 22), followed by T-cell lymphoma (PNL n = 2, SNL n = 2), with increased demyelination in both groups and increased axonal degeneration (p = 0.01) and multifocal myelinated fiber loss (p = 0.04) significant in SNL vs PNL. Identifying SNL resulted in patient treatment modifications but a worse prognosis compared with PNL (p = 0.025). DISCUSSION: While PNL and SNL are both primarily painful and asymmetric neuropathies with axonal and demyelinating features on EMG and nerve biopsy, SNL presents somewhat differently than PNL with fulminant, asymmetric often mononeuropathies better detected on MRI than FDG-PET/CT. The focal pattern of SNL is likely a result of residual cancer cells that evaded initial chemotherapy, which does not cross the blood-nerve barrier, and these cells can later recur and result in fulminant disease. Although still resulting in a poorer prognosis, identifying SNL is important because this changed treatment and management in every SNL case.

Core outcomes in nerve surgery: development of a core outcome set for common peroneal (fibular) neuropathy.

OBJECTIVE: Common peroneal (fibular) neuropathy is the most common mononeuropathy of the lower extremity. Despite this, there are surprisingly few studies on the topic, and a knowledge gap remains in the literature. As one attempts to address this knowledge gap, a core outcome set (COS) is needed to guide the planning phases of future studies to allow synthesis and comparability of these studies. The objective of this study was to develop the COS-common peroneal neuropathy (CoPe) using a modified Delphi approach. METHODS: A 5-stage approach was used to develop the COS-CoPe: 1) stage 1, consortium development; 2) stage 2, a literature review to identify potential outcome measures; 3) stage 3, a Delphi survey to develop consensus on outcomes for inclusion; 4) stage 4, a Delphi survey to develop definitions; and 5) stage 5, a consensus meeting to finalize COS and definitions. The study followed the COS-STAndards for Development (COS-STAD) recommendations. RESULTS: The Core Outcomes in Nerve Surgery (COINS) Consortium comprised 23 participants, all neurological surgeons, representing 13 countries. The final COS-CoPe consisted of 31 data points/outcomes covering domains of demographics, diagnostics, patient-reported outcomes, motor/sensory outcomes, and complications. Appropriate instruments, methods of testing, and definitions were set. The consensus minimum duration of follow-up was 12 months. The consensus optimal time points for assessment were preoperatively and 3, 6, 12, and 24 months postoperatively. CONCLUSIONS: The COINS Consortium developed a consensus COS and provided definitions, methods of implementation, and time points for assessment. The COS-CoPe should serve as a minimum set of data that should be collected in all future neurosurgical studies on common peroneal neuropathy. Incorporation of this COS should help improve consistency in reporting, data synthesis, and comparability, and should minimize outcome reporting bias.

Hirayama Disease: Surgical Restoration of Hand Function.

PURPOSE: Hirayama disease (HD) is a rare, nonfamilial, self-limiting, progressive lower cervical myelopathy, resulting in debilitating distal upper-extremity motor deficits, mimicking high ulnar neuropathy, lower trunk brachial plexopathy, or C8-T1 radiculopathy. Although most literature focuses on pathophysiology and prevention of disease progression, there remains limited discussion regarding treatment to improve upper-extremity function in patients with stable disease. The upper-extremity manifestations of HD are reviewed along with surgical options for restoring hand function. METHODS: A retrospective review of patients with HD who underwent reconstruction to improve hand function was undertaken. Demographic data, preoperative electrodiagnostic and electromyographic, and physical examination findings were collected. Outcome data involved postoperative grip, pinch, and functional assessment documented on clinical visits. Qualitative descriptions of the surgical techniques are described. RESULTS: Among six patients identified, four met the inclusion criteria and underwent tendon transfers and selected joint arthrodeses. All patients were diagnosed as teenagers, were right hand-dominant, and three were male. Unilateral symptoms were present in one patient and were bilateral in the rest. All patients were treated with tendon transfers for thumb opposition, grasp, anticlaw, and thumb interphalangeal joint arthrodesis. All patients had postoperative grip strength improvement. The average follow-up was 3.2 years. CONCLUSIONS: Hirayama disease is a rare disease often managed by spine surgeons and neurologists who may be unaware of options for restoring hand function deficits. Technical strategies and outcomes of improving hand function in HD have not been adequately described. Surgical options to improve hand function are tailored to the deficits and include tendon transfers, select joint arthrodeses, and/or tenodeses. Risk of disease progression and expectations following hand reconstruction must be managed carefully. TYPE OF STUDY LEVEL OF EVIDENCE: Therapeutic V.

Survival after resection of malignant peripheral nerve sheath tumors: Introducing and validating a novel type-specific prognostic model.

Background: This study aimed to assess the performance of currently available risk calculators in a cohort of patients with malignant peripheral nerve sheath tumors (MPNST) and to create an MPNST-specific prognostic model including type-specific predictors for overall survival (OS). Methods: This is a retrospective multicenter cohort study of patients with MPNST from 11 secondary or tertiary centers in The Netherlands, Italy and the United States of America. All patients diagnosed with primary MPNST who underwent macroscopically complete surgical resection from 2000 to 2019 were included in this study. A multivariable Cox proportional hazard model for OS was estimated with prespecified predictors (age, grade, size, NF-1 status, triton status, depth, tumor location, and surgical margin). Model performance was assessed for the Sarculator and PERSARC calculators by examining discrimination (C-index) and calibration (calibration plots and observed-expected statistic; O/E-statistic). Internal-external cross-validation by different regions was performed to evaluate the generalizability of the model. Results: A total of 507 patients with primary MPNSTs were included from 11 centers in 7 regions. During follow-up (median 8.7 years), 211 patients died. The C-index was 0.60 (95% CI 0.53-0.67) for both Sarculator and PERSARC. The MPNST-specific model had a pooled C-index of 0.69 (95%CI 0.65-0.73) at validation, with adequate discrimination and calibration across regions. Conclusions: The MPNST-specific MONACO model can be used to predict 3-, 5-, and 10-year OS in patients with primary MPNST who underwent macroscopically complete surgical resection. Further validation may refine the model to inform patients and physicians on prognosis and support them in shared decision-making.

Complete encasement of the radial nerve by a giant lipoma: illustrative case.

BACKGROUND: Among the spectrum of adipose lesions associated with peripheral nerves, complete circumferential encasement of the nerve by the lesion is a very rare entity. The authors report the first case of a giant lipoma that completely and circumferentially encased the radial nerve. OBSERVATIONS: A 57-year-old woman presented with a large left-arm mass that she had noticed over a year following significant weight loss. She had hypersensitivity and dysesthesias in the left posterior arm but no weakness or other symptoms. Magnetic resonance imaging of the left upper limb demonstrated a large lipoma completely encasing the radial nerve, originating at the level of the spiral grove proximally and extending distally to the lateral epicondyle. The lesion was completely resected at surgery with total preservation of radial nerve function. LESSONS: Lipomas encasing peripheral nerves can be difficult to manage while preserving function. This case adds to the intriguing spectrum of adipose lesions associated with peripheral nerves. https://thejns.org/doi/10.3171/CASE24148.

Development of a tibial intraneural ganglion cyst after surgery on a peroneal intraneural ganglion in a pediatric patient: further support for the articular origin of intraneural ganglion cysts. Illustrative case.

BACKGROUND: The articular origin of intraneural cysts has been previously described and well supported. Intraneural ganglion cysts most commonly occur in adults and in the common peroneal nerve arising from the anterior aspect of the superior tibiofibular joint (STFJ). OBSERVATIONS: The authors report a pediatric patient who developed a tibial intraneural cyst arising from the posterior aspect of the STFJ within months after surgical treatment of a peroneal intraneural cyst from the anterior aspect of the same joint. Surgery consisted of disconnecting the articular branch of the peroneal nerve and decompression of the cyst. Three-month postoperative magnetic resonance imaging showed resolution of the peroneal intraneural cyst and anterior compartment denervation but demonstrated a clinically occult small tibial intraneural ganglion cyst arising from the STFJ with popliteus muscle atrophy. LESSONS: This case underscores the importance of addressing the underlying etiology (articular synovitis) or the communication pathways (articular branches) whenever feasible to mitigate intraneural cyst recurrence. Furthermore, this report reinforces the validity of the articular theory. https://thejns.org/doi/10.3171/CASE24277.

Superficial Branch of the Radial Nerve Versus Sural Nerve Grafting After Traumatic Adult Brachial Plexus Injury.

The purpose of this study was to compare two sources of nerve graft for brachial plexus reconstruction: the denervated superficial branch of the radial nerve (SBRN) and the sural nerve. Ninety-seven patients who underwent brachial plexus reconstruction with denervated SBRN nerve (24 patients with 24 grafts) or with sural nerve grafting (73 patients with 83 nerve grafts) were included. The two groups were compared with respect to postoperative muscle reinnervation, disabilities of the arm, shoulder, and hand (DASH) scores. In the SBRN group, only four (17%) of the nerve grafts provided grade III or higher muscle function. In the sural nerve group, 31 (37%) of the nerve grafts provided grade III or higher muscle function. Smoking had a negative impact on muscle recovery. Denervated SBRN grafts are associated with inferior outcomes when compared with sural nerve grafts in the treatment of traumatic adult brachial plexus injuries. (Journal of Surgical Orthopaedic Advances 33(2):080-083, 2024).

Triceps-to-Biceps Tendon Transfer Technique for Restoration of Elbow Flexion in Adult Brachial Plexus Injury.

Restoration of elbow flexion is a priority in treating adult traumatic brachial plexus injuries. A tendon transfer is an ideal option for patients not candidates for reconstructive nerve surgery or free-functioning muscle transfer. For patients with a partial brachial plexus injury or a pan plexus injury with adequate recovered triceps function and loss of elbow flexion, a triceps-to-biceps tendon transfer is a nonmicrosurgical option to restore elbow flexion. The technique of triceps-to-biceps transfer in which the complete triceps tendon is transferred laterally, secured lateral to the radial tuberosity, and reinforced with suture to the biceps tendon is described.

Motor Examination of the Brachial Plexus.

Serial physical examination is often required in the evaluation of brachial plexus injuries. (Noland, 2019) A comprehensive evaluation that includes a thorough history, electrodiagnostic evaluation, and imaging studies, in addition to physical examination, can provide valuable information about the location of the lesion, prognosis for recovery, and whether surgical intervention is necessary. After brachial plexus reconstruction, physical examinations are also performed to document clinical improvement and identify any residual issues. The videos included in this clinical examination techniques section demonstrate the muscle strength examination testing for the brachial plexus and offer best practices for documentation.

Precision oncology in neurofibromatosis type 1: quantification of differential sensitivity to selumetinib in plexiform neurofibromas using single-cell RNA sequencing.

PURPOSE: Selumetinib is an FDA-approved targeted therapy for plexiform neurofibromas in neurofibromatosis type 1(NF1) with durable response rates seen in most, but not all patients. In this proof-of-concept study, we demonstrate single-cell RNA sequencing(scRNAseq) as a technique for quantifying drug response to selumetinib at the single cell level. METHODS: scRNAseq data from neurofibroma biopsies was obtained from a public genomics repository. Schwann cell populations were identified through standard clustering techniques and single-cell selumetinib sensitivity was quantified on a scale of 0(resistant) to 1(sensitive) based on the expression pattern of a 500 gene selumetinib sensitivity signature from the BeyondCell sensitivity library. RESULTS: A total of seven plexiform neurofibromas were included in our final analysis. The median absolute number of Schwann cells across samples was 658 cells (IQR: 1,029 cells, Q1-Q3: 135 cells to 1,163 cells). There was a statistically significant difference in selumetinib sensitivity profiles across samples (p < 0.001). The tumor with the highest median selumetinib sensitivity score had a median selumetinib sensitivity score of 0.64(IQR: 0.14, Q1-Q3: 0.59-0.70, n = 112 cells) and the tumor with the lowest median selumetinib sensitivity score had a median score of 0.37 (IQR: 0.21, Q1-Q3: 0.27-0.48, n = 1,034 cells). CONCLUSIONS: scRNAseq of plexiform neurofibroma biopsies reveals differential susceptibilities to selumetinib on a single cell level. These findings may explain the partial responses seen in clinical trials of selumetinib for NF1 and demonstrate the value of collecting scRNAseq data for future NF1 trials.

Evaluating the Ability of Brachial Plexus-Injured Patients to Control an Externally Powered (Myoelectric) Hand Prosthesis.

BACKGROUND: Restoration of hand function after traumatic brachial plexus injury (BPI) remains a formidable challenge. Traditional methods such as nerve or free muscle transfers yield suboptimal results. Advancements in myoelectric prostheses, characterized by novel signal acquisition and improved material technology, show promise in restoring functional grasp. This study evaluated the ability of adults with a BPI injury to control an externally powered prosthetic hand using nonintuitive signals, simulating the restoration of grasp with a myoelectric prosthesis. It also assessed the effectiveness of a comprehensive multidisciplinary evaluation in guiding treatment decisions. METHODS: A multidisciplinary brachial plexus team assessed adults with compromised hand function due to BPI. The feasibility of amputation coupled with fitting of a myoelectric prosthesis for grasp reconstruction was evaluated. Participants' ability to control a virtual or model prosthetic hand using surface electromyography (EMG) as well as with contralateral shoulder motion-activated linear transducer signals was tested. The patient's input and injury type, along with the information from the prosthetic evaluation, were used to determine the reconstructive plan. The study also reviewed the number of participants opting for amputation and a myoelectric prosthetic hand for grasp restoration, and a follow-up survey was conducted to assess the impact of the initial evaluation on decision-making. RESULTS: Of 58 subjects evaluated, 47 (81%) had pan-plexus BPI and 42 (72%) received their initial assessment within 1 year post-injury. Forty-seven patients (81%) could control the virtual or model prosthetic hand using nonintuitive surface EMG signals, and all 58 could control it with contralateral uniscapular motion via a linear transducer and harness. Thirty patients (52%) chose and pursued amputation, and 20 (34%) actively used a myoelectric prosthesis for grasp. The initial evaluation was informative and beneficial for the majority of the patients, especially in demonstrating the functionality of the myoelectric prosthesis. CONCLUSIONS: The study indicates that adults with traumatic BPI can effectively operate a virtual or model myoelectric prosthesis using nonintuitive control signals. The simulation and multidisciplinary evaluation influenced informed treatment choices, with a high percentage of patients continuing to use the myoelectric prostheses post-amputation, highlighting its long-term acceptance and viability. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

High Resolution MRI Confirms Torsional Injury as Mechanism for Combined Ankle and Common Fibular (Peroneal) Nerve Injuries.

Common fibular nerve (CFN) injury due to ankle fracture is an underreported complication. The authors have proposed that torsional injury to the ankle can be translated along the interosseous membrane (IOM), producing tension on the CFN at the fibular neck. A 23-year-old woman presented to our clinic for left foot drop. Three months prior, the patient sustained a fall with left ankle inversion injury while running. She was diagnosed with a minor ankle fracture and placed in an orthopaedic boot. Unfortunately, her swelling worsened and one week later the patient was diagnosed with foot drop, which was further corroborated with EMG studies showing severe CFN injury localizing to the fibular neck. Because of the lack of recovery, she underwent decompression of the CFN. She experienced immediate symptomatic relief. High resolution imaging in this case supports our previous mechanism for indirect trauma to the ankle resulting in CFN injury. (Journal of Surgical Orthopaedic Advances 33(1):053-055, 2024).

Neuromuscular choristoma-associated desmoid-type fibromatosis of the brachial plexus: Additional evidence to support a nerve-driven mechanism.

BACKGROUND: We have recently described circumferential nerve involvement of neuromuscular choristoma associated with desmoid-type fibromatosis (NMC-DTF) in cases involving the sciatic nerve, supporting a nerve-derived mechanism for the DTF. We wondered whether a similar growth pattern occurs in cases involving the brachial plexus (BP). METHODS: We reviewed all available magnetic resonance (MR) imaging in patients diagnosed at our institution with NMC or NMC-DTF of the BP. We also performed a literature search of patients with NMC or NMC-DTF of the BP. RESULTS: In our clinical records, four patients with NMC of the BP were identified, and three developed NMC-DTF. All three patients had MR imaging evidence of circumferential encasement of the BP. In the literature, we identified 15 cases of NMC of the BP, of which 12 had identified NMC-DTF. Four published cases included MR images, and only two were of sufficient quality for review. The single provided image in both cases demonstrated a similar pattern of circumferential encasement of the BP by the NMC-DTF. One additional case report was published without MR images but described circumferential involvement in the surgical findings. One unpublished case of NMC-DTF of the BP from an international radiology meeting also had this circumferential pattern pattern on MRI. CONCLUSIONS: The MRI findings of circumferential nerve involvement in patients with NMC-DTF of the BP are similar to our previously reported data in patients with NMC-DTF of the sciatic nerve, providing further imaging-based support of a nerve-driven mechanism. Clinical implications are presented based on the proposed pathogenetic mechanism.

Injury and Biological Factors Impact Shoulder Function following Autogenous Grafting of Spinal Nerves for Pan-Brachial Plexus Reconstruction.

BACKGROUND: Shoulder function following spinal nerve grafting in pan-brachial plexus injuries(Pan-BPI) is not well described. The purpose of this study was twofold: 1)to evaluate shoulder abduction(ABD) and external rotation(ER) after grafting of viable spinal nerves to the suprascapular nerve(SSN), axillary nerve(AxN), or posterior division of the upper trunk(PDUT); and 2)to determine patient characteristics, injury severity/characteristics, and nerve graft factors that influenced outcomes. METHODS: 362 Pan-BPI reconstruction patients from a single institution were reviewed for those who underwent spinal nerve grafting for shoulder reanimation between 2001 and 2018. Patient demographics, injury severity scores(ISS), graft characteristics, strength, range of motion for shoulder ABD and ER, and patient-reported outcomes were recorded. Patients were divided into three groups based on the recovery of shoulder function: no return, ABD only, and ABD and ER. RESULTS: 110 patients underwent spinal nerve grafting, with 41 meeting inclusion criteria. 17(41.5%) had no return of shoulder function, 14(34.1%) had ABD alone, and 10(24.4%) had ABD and ER. Patients with recovery of both ABD and ER were significantly younger(18.6±5.56), had lower BMI(22.4±4.0), and lower ISS(10.5±6.24, p=0.003). Multivariable analysis found that with increasing age(OR:0.786, 95%CI:0.576,0.941) and ISS(OR:0.820, 95%CI:0.606-0.979), odds for return of ABD and ER significantly decreased. CONCLUSIONS: In Pan-BPI, 24.4% of patients demonstrated return of both ABD and ER following spinal nerve grafting to SSN and either AxN or PDUT. Age, BMI, and ISS were associated with poorer recovery of shoulder function. Careful patient selection and consideration of age, BMI, and ISS may improve outcomes of spinal nerve grafting for shoulder reanimation. LEVEL OF EVIDENCE: III.

The paraneurium and the tumefactive appearance of peripheral nerve neurolymphomatosis: illustrative case.

BACKGROUND: Peripheral neurolymphomatosis (NL) is an often-misdiagnosed condition characterized by lymphomatous infiltration within the peripheral nerves. Its rarity and complexity frequently result in delayed diagnosis and suboptimal patient outcomes. This study aims to elucidate the role of the paraneurium (circumneurium) in NL, emphasizing its diagnostic and therapeutic significance. OBSERVATIONS: A 72-year-old man presented with lesions on his right lower eyelid. Initial diagnostics were inconclusive until an excisional biopsy confirmed extranodal marginal zone lymphoma. Following a complete metabolic response to rituximab treatment, the patient relapsed 14 months later with progressive lymphoma and bilateral sciatic nerve involvement, as confirmed by positron emission tomography-computed tomography and magnetic resonance imaging. LESSONS: This paper underscores the critical role of the paraneurium in NL, enhancing understanding of its pathophysiology. Integrating advanced imaging techniques have proved essential in accurately identifying neurolymphomatous involvement within the paraneurium. This study paves the way for more effective management strategies in NL and similar conditions, focusing on improving patient care and outcomes.

The 2-by-2 Inch "Key Window" in the Upper Extremity: An Anatomical Appraisal of the Accessibility and Proximity of the Major Nerves and Vessels.

BACKGROUND: The brachial plexus is a network of nerves located between the neck and axilla, which receives input from C5-T1. Distally, the nerves and blood vessels that supply the arm and forearm form a medial neurovascular bundle. The purpose of this study was to illustrate that a peripheral nerve dissection via a 2 × 2 inch window would allow for identification and isolation of the major nerves and blood vessels that supply the arm and forearm. METHODS: A right side formalin-fixed latex-injected cadaveric arm was transected at the proximal part of the axillary fold and included the scapular attachments. Step-by-step anatomical dissection was carried out and documented with three-dimensional digital imaging. RESULTS: A 2 × 2 inch window centered 2 inches distal to the axillary fold on the medial surface of the arm enabled access to the major neurovascular structures of the arm and forearm: the median nerve, ulnar nerve, medial antebrachial cutaneous nerve, radial nerve and triceps motor branches, musculocutaneous nerve and its biceps and brachialis branches and lateral antebrachial cutaneous nerve, basilic vein and brachial artery and vein, and profunda brachii artery. CONCLUSIONS: Our study demonstrates that the majority of the neurovascular supply in the arm and forearm can be accessed through a 2 × 2 inch area in the medial arm. Although this "key window" may not be entirely utilized in the operative setting, our comprehensive didactic description of peripheral nerve dissection in the cadaver laboratory can help in safer identification of complex anatomy encountered during surgical procedures.

Academic Promotions in Medicine: An Appraisal of Fairness.

OBJECTIVE: To investigate whether the process of conferring academic rank or components of the promotion packet contribute to the lack of parity in academic advancement for women and individuals underrepresented in medicine (URMs). PATIENTS AND METHODS: We retrospectively reviewed prospective promotion applications to the position of associate professor or professor at Mayo Clinic from January 2, 2015, through July 1, 2019. Individuals with doctorate degrees who applied for either rank were included in the study. Data collected included demographic characteristics, curriculum vitae at time of application, committee score sheets, and deferral and approval decisions. Deferral rates for women compared with men and for URMs compared with non-URMs was the primary outcome. RESULTS: Of 462 people who applied for associate professor, 10% (n=46) were deferred. Those promoted had worked longer at Mayo Clinic (median, 6 years vs 2 years; P=.01), had more mentees (median, 6 vs 4; P=.02), authored more publications (median [interquartile range (IQR)], 39 [32-52] vs 30 [24-35]; P<.001), and were more likely to be on a National Institutes of Health or institutional grant (P<.05). Of the 320 people who applied for professor, 8.8% (n=28) were deferred. Those promoted had authored more publications (median [IQR], 77 [60-99] vs 56 [44-66]; P<.001) and were less likely to hold an elected office to a professional society (22.6% vs 39.3%; P=.05). There was no significant association between deferral status and sex (P>.4) or race/ethnicity (P>.9) for either rank. CONCLUSION: The process for academic advancement for professorships does not contribute to the gap in promotion rates for women and URMs.