Spinner, Robert J.

ABSTRACT The paraneurium is a distinct connective tissue sheath that loosely envelopes the epineurium. The space between the para‐ and epineurium (the subparaneurial compartment) holds significant clinical relevance, serving as a target for deposition of regional anesthesia and a potential pathway for the pathological spread of cysts and tumors. However, visualization of the paraneurial layer, as a separate structure from the epineurium, remains challenging with conventional MRI, especially in the absence of pathology. This study evaluated the visualization of the paraneurium using ultra‐high‐field 7‐Tesla (7 T) MRI compared to conventional field strengths. We assessed normal nerve anatomy and a spectrum of pathological cases, including intraneural ganglion cysts, schwannomas, intraneural perineuriomas, and metastatic melanoma. The results demonstrated that 7 T MRI provides superior resolution and delineation of the paraneurium compared to 1.5 and 3 T systems. In normal anatomy, T1‐weighted and proton density (PD) sequences provided optimal contrast between the paraneurium and surrounding adipose tissue. In contrast, for pathological cases, T2‐weighted sequences with fat suppression were superior for depicting the paraneurium and identifying subparaneurial involvement. In conclusion, 7 T MRI offers a significant advantage in identifying the thin paraneurial layer. This capability provides valuable insights into the pathogenesis of tumor spread and holds promise for improving pre‐operative planning and clinical decision‐making in peripheral nerve pathology.

Since its introduction into medical terminology by Lord Henry Cohen in 1941, the term “neurapraxia” has become established in the neurological and neurosurgical lexicon, although it is often misused or misspelled. It denotes a transient dysfunction of a peripheral nerve, as distinct from axonotmesis and neurotmesis, which describe more significant structural injuries to a peripheral nerve. To expand our understanding of neurapraxia, it is necessary to examine the phenomenon in both temporal and spatial contexts. This study examines neurapraxia in: (A) Time—(1) the origins of the term neurapraxia and (2) the time-course of a neurapraxic injury and its recovery, and (B) Space—(3) the microstructure of a neurapraxic injury and (4) the locations of neurapraxic injuries within the peripheral nervous system. We demonstrate that the term neurapraxia encompasses both a temporal and a spatial definition. In time, it applies to transient peripheral nerve palsy, from which recovery occurs before there is sufficient time for axonal regeneration, typically within a few weeks. In space, there is a histopathological change limited to localized demyelination in nerves lined by epineurium and myelinated by Schwann cells. Nerves distal to the spine qualify as nerves to which the term neurapraxia can apply; however, cranial nerves and spinal nerve roots (including cauda equina) are inconsistent with this owing to the variability in myelinating cells along their course (oligodendroglia proximally, i.e., central glial segment), the absence of an epineurial covering, and exposure to cerebrospinal fluid.

OBJECTIVE Cervical dystonia (CD) is the most common focal dystonia, characterized by abnormal head postures and pain, often refractory to botulinum toxin therapy. Selective peripheral denervation (SPD) remains a key surgical option, but long-term outcomes in large cohorts are underreported. The purpose of this study was to evaluate the long-term outcomes of SPD in patients with botulinum toxin–refractory CD, focusing on symptom severity, pain, and head posture improvement. METHODS This retrospective study included 160 adults (mean ± SD age 54 ± 12.0 years, 46% male) with refractory CD who underwent SPD at a single center by a single surgeon from January 2005 to July 2023. Outcomes were assessed using subjective clinical measures and the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), which was calculated retrospectively from clinical records. The modified Bertrand technique involved selective denervation and myotomies tailored to each patient’s dystonic pattern. TWSTRS scores were analyzed at baseline, 3 months, 1 year, and final follow-up (mean ± SD 10.3 ± 9.0 months). Time to minimal clinically important difference (MCID) (≥ 12-point TWSTRS drop) was evaluated with covariate-adjusted Kaplan-Meier modeling (ever vs never revised, evaluated with the log-rank test) and a counting-process Cox model with revision as a time-dependent covariate. RESULTS Among 160 patients (mean follow-up duration 21.6 ± 35.6 months), TWSTRS improved by 73.5% at 3 months and 61.3% at last follow-up (p < 0.001). Median time to MCID was 3.0 months for never revised patients versus 22.0 months for ever revised patients (log-rank chi-square statistic = 19.09, p < 0.0001). In a time-dependent Cox model, revision surgery was significantly associated with higher likelihood of achieving MCID (HR 2.31, p < 0.005). Pain relief and improved head posture were reported in over 50% of patients. Complications were minimal, and recurrence was observed in 4.2% of cases. Outcomes were consistent with or exceeded those reported in the literature with either SPD or deep brain stimulation (DBS). CONCLUSIONS SPD is an effective and durable surgical option for refractory CD, significantly improving pain, posture, and quality of life. Although revision surgery delayed time to improvement, it significantly increased the likelihood of achieving meaningful clinical improvement. Overall efficacy aligns with the existing literature, reinforcing its role as a first-line surgical intervention. Further studies should explore strategies to enhance long-term outcomes and delineate the role of SPD relative to DBS.

OBJECTIVE Core outcome sets (COSs) are needed to promote data consistency across studies as well as data synthesis and comparability. The aim of the current study was to use a modified Delphi process to develop a COS for lateral femoral cutaneous neuropathy (LFCN), hereafter COS-LFCN. METHODS A 5-stage approach was used to develop the COS-LFCN: 1) consortium development, 2) literature review to identify potential outcome measures, 3) Delphi survey to develop consensus on outcomes for inclusion, 4) Delphi survey to develop definitions, and 5) consensus meeting to finalize the COS and definitions. This study followed the Core Outcome Set - STAndards for Development, (COS-STAD) recommendations. RESULTS The Core Outcomes in Nerve Surgery (COINS) Consortium comprised 25 participants, all neurological surgeons, representing 14 countries. The final COS-LFCN consisted of 41 factors and 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, with the consensus optimal time points for assessment being preoperatively and 3, 6, and 12 months postoperatively. CONCLUSIONS The COINS Consortium developed a consensus COS for LFCN and provided definitions, methods of implementation, and time points for assessment. The COS-LFCN should serve as the minimum data to be collected in all future neurosurgical studies on LFCN. Incorporation of this COS will help improve consistency in reporting, data synthesis and comparability, and minimize outcome reporting bias.

BACKGROUND Ulnar neuropathy at Guyon’s canal is rare, but when it occurs, it is frequently due to underlying masses, including extraneural and intraneural ganglion cysts, as well as adventitial cysts. The pathogenesis of these cysts, especially at a rare site, remains controversial. The articular theory, which is gaining popularity, posits that a joint connection via a nerve (or vascular) branch to a neighboring joint represents the pathway for their formation and propagation. OBSERVATIONS A recently published case of a patient with an ulnar intraneural ganglion at the wrist with a series of postoperative cystic recurrences was reevaluated, as it challenged the articular theory. No discrete articular branch had been identified on imaging or at surgery. Serial MR images were reinterpreted, which revealed that the original intraneural cyst was treated; new sequential cysts—an adventitial cyst and then a soft tissue ganglion—developed, all arising from the same wrist joint. LESSONS This case strengthens the principles of the articular theory for intraneural ganglion, adventitial, and soft tissue ganglion cysts. A small wrist connection from the ulnar intraneural ganglion was unrecognized and untreated. Scarring disrupted the original nerve pathway and pressure dynamics. New cysts developed through neighboring joint capsular rents along different pathways into other “compartments” (vessel or soft tissues). https://thejns.org/doi/10.3171/CASE25618

BACKGROUND Recently, the distribution of subparaneurial ganglion cysts involving the common peroneal and tibial nerves was described based on MRI analysis. Crossover in extreme cases was observed at the sciatic bifurcation through a mechanism comparable to a geyser, enabled by fenestrations in the epi- and paraneurium at the level of the bifurcation. The goal of this study was to investigate whether the geyser theory for crossover holds for other locations. OBSERVATIONS The authors’ prospectively maintained database of > 1100 cases of intraneural ganglion cysts in the world’s literature was queried for the existence of subparaneurial ganglion cysts at locations other than the knee. A previously unrecognized case involving the ulnar nerve originating from the elbow joint was found. Reinterpretation of the patient’s MRI studies showed circumferential subparaneurial distribution of a cyst over a long distance. Based on their previously reported geyser theory, the authors wondered if crossover had occurred at the level of the medial cord. A fenestration in the epi- and paraneurium at this level was confirmed on histological analysis of a normal cadaveric specimen. LESSONS This illustrative case shows that the geyser theory also holds in other locations. Surgical treatment of these subparaneurial cysts still follows the principles of the unified articular theory. https://thejns.org/doi/10.3171/CASE25671

BACKGROUND: Increasing interest in neurosurgery residency has led to a growing number of unmatched applicants, who often struggle to find appropriate guidance for their next steps. The authors examined trends, opinions, and options available to unmatched neurosurgery residency reapplicants. STUDY DESIGN: Demographic data of US applicants from MD programs obtained from the National Resident Matching Program (2009 to 2024) were analyzed using 1-way ANOVA analysis of time-interval averages. Opinions about reapplicants were assessed via an online survey of national neurosurgery leaders, including residency program directors and chairpersons (N = 356). RESULTS: All application trends showed greater change over time; however, the rate of accepted reapplicants showed no significant change among early (2009 to 2013: 4.8 ± 1.8), mid (2014 to 2018: 7.6 ± 4.8), and recent periods (2019 to 2024: 9.8 ± 2.5; p = 0.068). The survey had a 23.0% response rate (82 of 356). Commonly indicated reasons for failure to match included poor interview skills, weak recommendation letters, and personality issues. Although most survey respondents supported candidates reapplying, dual applications (applying to more than 1 specialty) were not widely encouraged. For those reapplying, pursuing a preliminary general surgery or research fellowship, obtaining new letters of recommendation from new subinternships, and publishing higher-quality research were the most endorsed uses of time before reapplying. However, most programs reported interviewing reapplicants sometimes to rarely and matching a reapplicant rarely to never. CONCLUSIONS: The number of reapplicants successfully matching into neurosurgery has not changed significantly during the past 15 years. Surveys indicate that leaders view reapplicants unfavorably, despite reapplicants’ efforts to improve their applications. These results suggest that neurosurgery mentors may do a disservice to potential reapplicants based on how residency program leadership considers reapplications. Candid guidance is needed for reapplicants in the residency matching process.

Abstract Background Neurolymphomatosis (NL) is a rare and frequently underrecognized manifestation of lymphoma, characterized by infiltration of peripheral or cranial nerves by malignant lymphocytes. Limited data exist to guide optimal management. We present the largest single-enterprise (included the 3 Mayo Clinic sites) cohort to date, evaluating disease characteristics, treatment patterns, and outcomes in patients (pts) with NL. Methods We conducted a retrospective analysis of pts ≥18 years (yrs) diagnosed with clinical, radiographic, or biopsy-confirmed NL at Mayo Clinic between January 2002 and December 2024. Baseline characteristics were compared using independent t-tests for continuous variables and Fisher's exact or Pearson's chi-square tests for categorical variables. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Objective response rate (ORR) was a secondary endpoint. Kaplan–Meier methods, log-rank tests, and Cox proportional hazards regression were used to assess survival outcomes and associated factors. Results We included 149 pts. Median age at diagnosis was 64 yrs (range 22–83), and 23% were female. Most presented with stage IV disease (89%), and NL was part of the initial lymphoma presentation in 42% (primary NL). Diagnostic confirmation was based on histopathology and imaging in 55%, imaging alone in 26%, histopathology alone in 16%, and clinical features in 4%. Diffuse large B-cell lymphoma was the most common histology (61%), followed by marginal zone lymphoma (7%), and T-cell lymphoma (7%). Clinical presentation included painful neuropathy (65%), concurrent CNS involvement (37%), systemic disease (43%), elevated LDH (46.9%), and ECOG ≥2 (38%). Pattern of involvement included cranial nerves (29%), peripheral nerves (28%), and spinal nerve roots (27%). Median follow-up was 92 months (95% CI, 63–119). Among 137 treatment-evaluable pts, first-line regimens included methotrexate-based (MTX) (62%), bendamustine-based (B) (11%), cytarabine-based (Ara-C) (4%), and rituximab-based (R) (excluding MTX, B, or Ara-C) (15%) therapies. Radiation was used in 18%, and 21% underwent autologous stem cell transplant (ASCT). Among 103 response-evaluable pts, the ORR was 67% (52% complete response [CR], 16% partial response [PR]). ORRs by regimen were 78% (MTX), 92% (B), and 86% (R). On univariate analysis, primary NL (OR 4.3) and frontline ASCT (OR 8.47) were associated with higher odds of response (p&lt;0.05), while ECOG ≥2 (OR 0.24) and localized disease (OR 0.33) were associated with lower odds. On multivariable analysis (MVA), primary NL (OR 5.0 [1.5–12.1], p=0.02) and ECOG &gt;1 (OR 0.2 [0.06–0.79], p=0.018) remained significant predictors of response. Median PFS was 13 months (95% CI, 9–36), with a 2-yr PFS of 43% (95% CI, 35–53). On MVA, concurrent CNS involvement (HR 2.4, p=0.05), systemic disease (HR 2.7, p=0.02), and ECOG &gt;1 (HR 2.4, p=0.02) were associated with inferior PFS, while primary NL was associated with improved PFS (HR 0.3, p=0.002). Patients undergoing frontline ASCT had a median PFS of 108 months (95% CI, 58–not reached) with a 7-yr PFS of 62% (95% CI, 46–84). Among those receiving second line and beyond (2+) therapy, 24 received MTX-based regimens, 10 received CAR-T, and 8 received tyrosine kinase inhibitors. Post-ASCT median PFS was 30 months (95% CI, 15–NR). Among CAR-T recipients, evaluable responses (n=8) included 4 CR, 1 PR, and 3 PD. Median OS was 56 months (95% CI, 29–133), with a 5-yr OS of 50% (95% CI, 41–60). On MVA, ECOG ≥2 (HR 2.5, p=0.02) predicted worse OS, while receipt of ASCT (HR 0.4, p=0.04) and primary NL (HR 0.5, p=0.04) were associated with improved OS. Conclusion This study represents the largest single-enterprise cohort of pts with NL, providing comprehensive insight into its clinical presentation, treatment patterns, and outcomes. Primary NL and preserved PS were independently associated with improved response rates and survival, while CNS and systemic involvement at diagnosis portended poorer PFS. MTX and bendamustine-based regimens achieved high ORR, and frontline ASCT was associated with significantly prolonged remission duration and OS. These findings highlight the prognostic importance of baseline disease burden and functional status, support the early incorporation of high-intensity regimens in eligible patients, and underscore the urgent need for prospective studies to guide evidence-based management in this rare and understudied population.

OBJECTIVE Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas predominantly associated with neurofibromatosis type 1 (NF1). However, their occurrence within NF type 2 (NF2)–related and SMARCB1-related schwannomatosis remains rare and poorly characterized. Accurate and timely diagnosis is challenging due to clinical and radiological similarities with benign schwannomas, potentially delaying appropriate management and impacting outcomes. This study presents an institutional case series aiming to better characterize the clinical presentations specifically for MPNSTs arising in patients with NF2- and SMARCB1-related schwannomatosis. METHODS This retrospective case series included patients diagnosed with schwannomatosis who subsequently developed histopathologically confirmed MPNSTs. Conducted at Mayo Clinic (Rochester, Minnesota) and University Health Network (Toronto, Canada), the study spanned January 1, 2003, to November 1, 2024. Patients were selected based on clinical or genetic diagnoses of schwannomatosis using International Consensus Group on Neurofibromatosis Diagnostic Criteria. Comprehensive clinical, radiological, and pathological data, including demographics, presenting symptoms, tumor features (size, location, immunohistochemistry, genetics), treatments (resection, chemotherapy, radiotherapy), and follow-up outcomes were extracted from electronic medical records. RESULTS The authors identified 8 patients with a mean age of 36 years, half of whom had NF2-related schwannomatosis. The most common presenting symptom was pain (71%). The mean tumor size was 8.2 ± 7.0 cm, with gross-total resection being the most common surgical treatment (67%), typically supplemented with radiation therapy (78%). More than half of the patients (56%) exhibited metastatic disease, and all tumors with reported grading were Fédération Nationale des Centres de Lutte Contre le Cancer grade 3. No tumors were associated with LZTR1 mutations. One notable case involved a 39-year-old male with SMARCB1-related schwannomatosis who had a femoral MPNST resected 13 years prior and subsequently developed a sciatic nerve MPNST that was managed successfully with neoadjuvant chemotherapy, radiation therapy, and negative margin resection. Of note, the second lesion arose from a hybrid neurofibroma/schwannoma. Another case, a 33-year-old male with SMARCB1-related schwannomatosis, had an incidental finding of epithelioid MPNST in a minimally symptomatic small palmar lesion. CONCLUSIONS This case series highlights that MPNSTs, although uncommon, can arise in NF2- and SMARCB1-related schwannomatosis without prior radiation exposure, presenting significant diagnostic challenges due to their similarity to benign schwannomas. The findings underscore the importance of maintaining clinical vigilance and employing individualized management strategies, balancing thorough resection with the preservation of function and patient quality of life.