The spectrum of brachial plexopathy from perineural spread of breast cancer.

OBJECTIVE: Perineural spread of breast cancer to the brachial plexus can lead to pain, sensory alterations, and upper-extremity weakness. Although rare, perineural spread is an often-misdiagnosed long-term complication following breast cancer diagnosis. The objective of this study was to critically review the clinical, radiological, and pathological findings of biopsy-proven perineural spread of breast cancer to the brachial plexus. METHODS: This is a retrospective study from a single institution in which a total of 19 patients with brachial plexus involvement from perineural spread of breast cancer who underwent fascicular biopsy between 1999 and 2021 were identified. Clinical, radiographic, and pathological data were retrospectively collected. Descriptive statistics were calculated for the cohort. RESULTS: The mean age of patients at the time of diagnosis of breast cancer perineural spread was 60.6 ± 11.5 years. The diagnosis of brachial plexopathy due to perineural spread was on average 12 years after the primary diagnosis of breast cancer. There was also a delay in diagnosis due to the rarity of this disease, with a mean time from initial symptom onset to diagnosis of perineural spread of 25 ± 30 months. All patients at the time of presentation had upper-extremity weakness and pain. Nearly all patients demonstrated T2 signal change and nodular so-called sugar-coating contrast enhancement on brachial plexus MRI. Similarly, all patients who underwent PET/MRI or PET/CT had increased FDG uptake in the involved brachial plexus. Breast cancer perineural spread has an overall poor prognosis, with 16 of 19 patients dying within 5.9 ± 3.0 years after diagnosis of perineural spread. CONCLUSIONS: Perineural spread should be considered in patients with a history of breast cancer, even 10 years after primary diagnosis, especially in patients who present with arm pain, weakness, and/or sensory changes. Further diagnostic workup with electrodiagnostic studies; brachial plexus MRI, PET/CT, or PET/MRI; and possibly nerve biopsy is warranted to ensure accurate diagnosis.

Compressive epidural collection as an unusual complication of FESS for a pediatric mycetoma.

Functional endoscopic sinus surgery (FESS) is a treatment of choice for fungal sinus ball (mycetoma), which is considered safe with a very low major complication rate. We present an unusual case of a 12-year-old female, who underwent FESS for a sphenoid sinus mycetoma and which was complicated by an acute, compressive epidural fluid collection. This presumably resulted from sinus irrigation in the setting of an under-appreciated skull base and mucosal defects causing a ball-valve effect. Our patient had a temporary neurologic deficit with complete recovery, however, similar complications can have fatal consequences.

Tele-robotics and artificial-intelligence in stroke care.

In the last forty years, the field of medicine has experienced dramatic shifts in technology-enhanced surgical procedures - from its initial use in 1985 for neurosurgical biopsies to current implementation of systems such as magnetic-guided catheters for endovascular procedures. Systems such as the Niobe Magnetic Navigation system and CorPath GRX have allowed for utilization of a fully integrated surgical robotic systems for perioperative manipulation, as well as tele-controlled manipulation systems for telemedicine. These robotic systems hold tremendous potential for future implementation in cerebrovascular procedures, but lack of relevant clinical experience and uncharted ethical and legal territory for real-life tele-robotics have stalled their adoption for neurovascular surgery, and might present significant challenges for future development and widespread implementation. Yet, the promise that these technologies hold for dramatically improving the quality and accessibility of cerebrovascular procedures such as thrombectomy for acute stroke, drives the research and development of surgical robotics. These technologies, coupled with artificial intelligence (AI) capabilities such as machine learning, deep-learning, and outcome-based analyses and modifications, have the capability to uncover new dimensions within the realm of cerebrovascular surgery.

Understanding the Pathognomonic Tumefactive Appearance of Neurolymphomatosis: A Unifying Theory of Neurolymphoma.

BACKGROUND: The diagnosis of peripheral neurolymphomatosis (NL) is difficult and often delayed, because patients can have isolated, nonspecific nerve symptoms. Magnetic resonance imaging will usually show nonspecific findings of enlarged, contrast-enhancing nerves. We aimed to elucidate the mechanism behind an imaging finding we believe is pathognomonic of NL and likely of other hematologic diseases with peripheral nerve involvement. METHODS: We reviewed the imaging studies of a previously reported cohort of patients, in addition to those from more recent patients, all with tumefactive NL, in which enlarged nerve bundles were surrounded by tumor. We reviewed the demographic data, clinical data (e.g., primary or secondary disease, biopsy-proven diagnosis), and imaging findings (e.g., tumefactive appearance, primary involved nerve, location of epicenter of tumefactive appearance, vascular involvement). RESULTS: All cases showed a maximum tumefactive appearance at branch or junction points, with a gradual decrease of this appearance moving proximally and distally from the epicenter in a "crescendo-decrescendo" pattern. We have described this as a phasic mechanism with 3 phases: malignant cells fill the intraneural space; extrude at a weak spot of the nerve, which often occurs at a branch or junction point; and then expand and fill the subparaneurial space, creating the grossly tumefactive appearance with proximal and distal spread. CONCLUSIONS: We have presented a novel, unifying theory explaining the pathognomonic tumefactive appearance of NL. Our theory offers the first rational explanation for the radiological appearance of NL with peripheral nerve involvement. We believe that with earlier recognition of NL on imaging studies, patients will be able to receive an earlier diagnosis and undergo earlier treatment.

Hemorrhage Risk of Untreated Isolated Cerebral Cavernous Malformations.

OBJECTIVE: Predicting future hemorrhage risk may allow better selection of patients with cerebral cavernous malformations (CCMs) who will likely benefit from treatment. In this study, we sought to identify predictors of CCM hemorrhage, and to compare subsequent symptomatic hemorrhage risks between patients with and without previous hemorrhage. METHODS: We performed a retrospective review of consecutive CCM patients at our institution between 1982 and 2017. Patients with diffuse or familial CCM syndromes, and those without follow-up data were excluded. The primary endpoint was acute symptomatic hemorrhage causing transient or permanent neurological symptoms. Primary endpoint incidences were compared between patients with and without previous hemorrhage. RESULTS: The study cohort comprised 84 patients with 90 CCMs. Previous hemorrhage was the only significant predictor for the primary endpoint (P = 0.003). CCMs with previous hemorrhage had a higher risk of symptomatic hemorrhage in follow-up than those without previous hemorrhage (26.9 vs. 1.5 symptomatic hemorrhages per 1000 CCM-months, P < 0.001). CCMs with and without previous hemorrhage had annual hemorrhage rates of 2.7% and 0.15%, respectively. Symptomatic hemorrhage-free survival rates were significantly lower in CCMs with previous hemorrhage (log-rank test, P < 0.001). Actuarial hemorrhage-free survival rates for CCMs with previous hemorrhage were 75%, 60%, 60%, and 60% at 1, 2, 3, and 4 years, respectively, compared with rates of 95%, 95%, 95%, and 84% for CCMs without previous hemorrhage. CONCLUSIONS: Previous hemorrhage is a predictor of subsequent symptomatic hemorrhage in CCMs. Compared with CCMs without previous hemorrhage, those with prior hemorrhage have a significantly higher risk of future symptomatic hemorrhage.

Mathematical model of perineural tumor spread: a pilot study.

BACKGROUND: Perineural spread (PNS) of pelvic cancer along the lumbosacral plexus is an emerging explanation for neoplastic lumbosacral plexopathy (nLSP) and an underestimated source of patient morbidity and mortality. Despite the increased incidence of PNS, these patients are often times a clinical conundrum-to diagnose and to treat. Building on previous results in modeling glioblastoma multiforme (GBM), we present a mathematical model for predicting the course and extent of the PNS of recurrent tumors. METHODS: We created three-dimensional models of perineurally spreading tumor along the lumbosacral plexus from consecutive magnetic resonance imaging scans of two patients (one each with prostate cancer and cervical cancer). We adapted and applied a previously reported mathematical model of GBM to progression of tumor growth along the nerves on an anatomical model obtained from a healthy subject. RESULTS: We were able to successfully model and visualize perineurally spreading pelvic cancer in two patients; average growth rates were 60.7 mm/year for subject 1 and 129 mm/year for subject 2. The model correlated well with extent of PNS on MRI scans at given time points. CONCLUSIONS: This is the first attempt to model perineural tumor spread and we believe that it provides a glimpse into the future of disease progression monitoring. Every tumor and every patient are different, and the possibility to report treatment response using a unified scale-as "days gained"-will be a necessity in the era of individualized medicine. We hope our work will serve as a springboard for future connections between mathematics and medicine.

Targeted fascicular biopsy of the brachial plexus: rationale and operative technique.

OBJECTIVE Nerve biopsy is useful in the management of neuromuscular disorders and is commonly performed in distal, noncritical cutaneous nerves. In general, these procedures are diagnostic in only 20%-50%. In selected cases in which preoperative evaluation points toward a more localized process, targeted biopsy would likely improve diagnostic yield. The authors report their experience with targeted fascicular biopsy of the brachial plexus and provide a description of the operative technique. METHODS All cases of targeted biopsy of the brachial plexus biopsy performed between 2003 and 2015 were reviewed. Targeted nerve biopsy was performed using a supraclavicular, infraclavicular, or proximal medial arm approach. Demographic data and clinical presentation as well as the details of the procedure, adverse events (temporary or permanent), and final pathological findings were recorded. RESULTS Brachial plexus biopsy was performed in 74 patients (47 women and 27 men). The patients' mean age was 57.7 years. All patients had abnormal findings on physical examination, electrodiagnostic studies, and MRI. The overall diagnostic yield of biopsy was 74.3% (n = 55). The most common diagnoses included inflammatory demyelination (19), breast carcinoma (17), neurolymphomatosis (8), and perineurioma (7). There was a 19% complication rate; most of the complications were minor or transient, but 4 patients (5.4%) had increased numbness and 3 (4.0%) had additional weakness following biopsy. CONCLUSIONS Targeted fascicular biopsy of the brachial plexus is an effective diagnostic procedure, and in highly selected cases should be considered as the initial procedure over nontargeted, distal cutaneous nerve biopsy. Using MRI to guide the location of a fascicular biopsy, the authors found this technique to produce a higher diagnostic yield than historical norms as well as providing justification for definitive treatment.

Perineural Spread of Renal Cell Carcinoma: A Case Illustration with a Proposed Anatomic Mechanism and a Review of the Literature.

INTRODUCTION: Perineural spread (PNS) is an unusual mechanism of tumor extension and has been typically reported in squamous cell carcinoma, adenocystic carcinoma, and desmoplastic melanoma. Our group has previously demonstrated PNS in rectal, prostate, bladder, and cervical cancer from the primary site along the autonomic nerves to the major somatic nerves and even intradurally. We believe similar principles apply to renal cell carcinoma (RCC) as well, despite the different anatomy. CASE DESCRIPTION: We performed a retrospective search to identify cases of intradural-extramedullary metastases of RCC caused by PNS. Strict anatomic and imaging inclusion criteria were defined: only lesions located between T6 and L3 were included, and PNS as a potential cause had to be supported by imaging evidence. Although 3 cases of spinal intradural metastases were identified, only one met our strict inclusion criteria. A 61-year-old woman developed a late intradural-extramedullary metastasis of RCC 16 years after the original diagnosis that we believe represents an example of visceral organ PNS. CONCLUSIONS: RCC can propagate via PNS from the primary tumor along the autonomic nerves to the aorticorenal, celiac, and mesenteric ganglia and then along the thoracic and lumbar splanchnic nerves to the corresponding spinal nerves and intradurally. We present radiologic evidence together with the review of the literature to support the premise that PNS of RCC not only occurs but goes unrecognized.

Sequential imaging of intraneural sciatic nerve endometriosis provides insight into symptoms of cyclical sciatica.

Endometriosis of the nerve often remains an elusive diagnosis. We report the first case of intraneural lumbosacral plexus endometriosis with sequential imaging at different phases of the menstrual cycle: during the luteal phase and menstruation. Compared to the first examination, the examination performed during the patient's period revealed the lumbosacral plexus larger and hyperintense on T2-weighted imaging. The intraneural endometriosis cyst was also larger and showed recent hemorrhage. Additionally, this case represents another example of perineural spread of endometriosis from the uterus to the lumbosacral plexus along the autonomic nerves and then distally to the sciatic nerve and proximally to the spinal nerves.

Targeted fascicular biopsy of the sciatic nerve and its major branches: rationale and operative technique.

OBJECT Nerve biopsy is typically performed in distal, noncritical sensory nerves without using imaging to target the more involved regions. The yield of these procedures rarely achieves more than 50%. In selected cases where preoperative evaluation points toward a more localized (usually a more proximal) process, targeted biopsy would likely capture the disease. Synthesis of data obtained from clinical examination, electrophysiological testing, and MRI allows biopsy of a portion of the major mixed nerves safely and efficiently. Herein, experiences with the sciatic nerve are reported and a description of the operative technique is provided. METHODS All cases of sciatic nerve biopsy performed between 2000 and 2014 were reviewed. Only cases of fascicular nerve biopsy approached from the buttock or the posterior aspect of the thigh were included. Demographic data, clinical presentation, and the presence of percussion tenderness for each patient were recorded. Reviewed studies included electrodiagnostic tests and imaging. Previous nerve and muscle biopsies were noted. All details of the procedure, final pathology, and its treatment implications were recorded. The complication rate was carefully assessed for temporary as well as permanent complications. RESULTS One hundred twelve cases (63 men and 49 women) of sciatic nerve biopsy were performed. Mean patient age was 46.4 years. Seventy-seven (68.8%) patients presented with single lower-extremity symptoms, 16 (14.3%) with bilateral lower-extremity symptoms, and 19 (17%) with generalized symptoms. No patient had normal findings on physical examination. All patients underwent electrodiagnostic studies, the findings of which were abnormal in 110 (98.2%) patients. MRI was available for all patients and was read as pathological in 111 (99.1%). The overall diagnostic yield of biopsy was 84.8% (n = 95). The pathological diagnoses included inflammatory demyelination, perineurioma, nonspecific inflammatory changes, neurolymphomatosis, amyloidosis, prostate cancer, injury neuroma, neuromuscular choristoma, sarcoidosis, vasculitis, hemangiomatosis, arteriovenous malformation, fibrolipomatous hamartoma (lipomatosis of nerve), and cervical adenocarcinoma. The series included 11 (9.9%) temporary and 5 (4.5%) permanent complications: 3 patients (2.7%) reported permanent numbness in the peroneal division distribution, and 2 patients (1.8%) were diagnosed with neuromuscular choristoma that developed desmoid tumor at the biopsy site 3 and 8 years later. CONCLUSIONS Targeted fascicular biopsy of the sciatic nerve is a safe and efficient diagnostic procedure, and in highly selected cases can be offered as the initial procedure over distal cutaneous nerve biopsy. Diagnoses were very diverse and included entities considered very rare. Even for the more prevalent diagnoses, the biopsy technique allowed a more targeted approach with a higher diagnostic yield and justification for more aggressive treatment. In this series, new radiological patterns of some entities were identified, which could be biopsied less frequently.

Perineural spread of pelvic malignancies to the lumbosacral plexus and beyond: clinical and imaging patterns.

OBJECT Perineural spread along pelvic autonomie nerves has emerged as a logical, anatomical explanation for selected cases of neoplastic lumbosacral plexopathy (LSP) in patients with prostate, bladder, rectal, and cervical cancer. The authors wondered whether common radiological and clinical patterns shared by various types of pelvic cancer exist. METHODS The authors retrospectively reviewed their institutional series of 17 cases concluded as perineural tumor spread. All available history, physical examination, electrodiagnostic studies, biopsy data and imaging studies, evidence of other metastatic disease, and follow-up were recorded in detail. The series was divided into 2 groups: cases with neoplastic lumbosacral plexopathy confirmed by biopsy (Group A) and cases included based on imaging characteristics despite the lack of biopsy or negative biopsy results (Group B). RESULTS Group A comprised 10 patients (mean age 69 years); 9 patients were symptomatic and 1 was asymptomatic. The L5-S1 spinal nerves and sciatic nerve were most frequently involved. Three patients had intradural extension. Seven patients were alive at last follow-up. Group B consisted of 7 patients (mean age 64 years); 4 patients were symptomatic, 2 were asymptomatic, and 1 had only imaging available. The L5-S1 spinal nerves and the sciatic nerve were most frequently involved. No patients had intradural extension. Four patients were alive at last follow-up. CONCLUSIONS The authors provide a unifying theory to explain lumbosacral plexopathy in select cases of various pelvic neoplasms. The tumor cells can use splanchnic nerves as conduits and spread from the end organ to the lumbosacral plexus. Tumor can continue to spread along osseous and muscle nerve branches, resulting in muscle and bone "metastases." Radiological studies show a reproducible, although nonspecific pattern, and the same applies to clinical presentation.

Neural involvement in endometriosis: Review of anatomic distribution and mechanisms.

Endometriosis (EM) is an infrequent cause of peripheral neuropathy, most commonly sciatic. Perineural spread has recently been introduced as an alternate explanation for cases of lumbosacral or sciatic nerve EM. We performed a literature review to collect all reported cases of peripheral and central nervous system EM in search of anatomic patterns of involvement; potentially to support the perineural spread theory. If available, intraneural invasion and presence of peritoneal EM were recorded. The search revealed 83 articles describing 365 cases of somatic peripheral nervous EM and 13 cases of central nervous EM. The most frequently involved site was the sacral plexus (57%, n = 211), followed by the sciatic nerve (39%, n = 140). Other nerves were reported in significantly smaller numbers. Ninety seven percent (97%, n = 355) of peripheral nerve cases presented with pain, 20% (n = 72) reported weakness and 31% (n = 114), numbness. Thirty four percent (34%, n = 38) had solely intraneural EM of which 89% (n = 33) had no peritoneal EM (percentage based on available information). In the central nervous system, the conus medullaris and/or cauda equina constituted the majority of cases with 54% (n = 7). Apart from perineural spread, other discussed mechanisms include retrograde menstruation with peritoneal seeding, hematogenous and lymphogenous spread, stem cell implantation either hematogenously or via retrograde menstruation with subsequent EM differentiation, and coelomic or Müllerian duct metaplasia. We believe this literature review supports perineural spread as an alternate mechanism for EM of nerve, particularly the subgroup with intraneural EM and without peritoneal disease.

The subparaneurial compartment: A new concept in the clinicoanatomic classification of peripheral nerve lesions.

Based on our experience in treating peripheral non-neural sheath derived pathology, we have identified a novel pattern of lesion progression along the anatomic course of nerves. This report highlights the existence of a subparaneurial compartment around peripheral nerves. We first applied an anatomic framework to review MR images and intraoperative photographs of patients treated by the senior author in the last 10 years. After identifying a pattern that was consistent with subparaneurial lesion progression, we searched for other examples of cases that might exhibit this pattern. Four examples of subparaneurial pathology were identified, a hemangioma of the ulnar nerve, a ganglion cyst of the common fibular nerve, a lymphoma of the sciatic nerve and a lipoma of the ulnar nerve. All four patients were operated on and had intraoperative photographs; three had high resolution MR imaging. This report highlights the existence of pathology contained within a subparaneurial compartment, outside of the epineurium, that follows the course of the nerve and surrounds it circumferentially. The subparaneurial localization of peripheral nerve lesions has hitherto received little attention. Identification of this new pattern on preoperative MRI may have implications for surgical management.

Perineural spread in pelvic malignancies can be an alternate explanation for pelvic bony metastases rather than hematogenous spread. A report of two cases.

We propose that pelvic malignancies can spread to bone and cause bony metastases using nerves as conduits. We reviewed two cases of pelvic malignancy with perineural spread of bladder cancer and prostate cancer. In a patient with prostate cancer, we identified six lesions that were positive on the (11)C-choline PET/CT scan and MRI; in a patient with bladder cancer, we identified two lesions positive on the (18)F-deoxy-glucose PET/CT scan and MRI. We carefully reviewed the imaging studies, and using established sclerotome maps we identified spinal nerves supplying each of eight pelvic bony lesions. All these spinal nerves showed evidence of tumor infiltration with extension toward the affected bones. We theorize that perineural tumor spread may serve as an additional mechanism of pelvic osseous metastases in pelvic malignancies.

Tumefactive appearance of peripheral nerve involvement in hematologic malignancies: a new imaging association.

OBJECTIVE: In neurolymphomatosis (NL), the affected nerves are typically described to be enlarged and hyperintense on T2W MR sequences and to avidly enhance on gadolinium-enhanced T1WI. This pattern is highly non-specific. We recently became aware of a "tumefactive pattern" of NL, neuroleukemiosis (NLK) and neuroplasmacytoma (NPLC), which we believe is exclusive to hematologic diseases affecting peripheral nerves. MATERIALS AND METHODS: We defined a "tumefactive" appearance as complex, fusiform, hyperintense on T2WI, circumferential tumor masses encasing the involved peripheral nerves. The nerves appear to be infiltrated by the tumor. Both structures show varying levels of homogenous enhancement. We reviewed our series of 52 cases of NL in search of this pattern; two extra outside cases of NL, three cases of NLK, and one case of NPLC were added to the series. RESULTS: We identified 20 tumefactive lesions in 18 patients (14 NL, three NLK, one NPLC). The brachial plexus (n = 7) was most commonly affected, followed by the sciatic nerve (n = 6) and lumbosacral plexus (n = 3). Four patients had involvement of other nerves. All were proven by biopsy: the diagnosis was high-grade lymphoma (n = 12), low-grade lymphoma (n = 3), acute leukemia (n = 2), and plasmacytoma (n = 1). CONCLUSIONS: We present a new imaging pattern of "tumefactive" neurolymphomatosis, neuroleukemiosis, or neuroplasmacytoma in a series of 18 cases. We believe this pattern is associated with hematologic diseases directly involving the peripheral nerves. Knowledge of this association can provide a clue to clinicians in establishing the correct diagnosis. Bearing in mind that tumefactive NL, NLK, and NPLC is a newly introduced imaging pattern, we still recommend to biopsy patients with suspicion of a malignancy.

An inferior alveolar intraneural cyst: a case example and an anatomical explanation to support the articular theory within cranial nerves.

The authors describe the case of an intraneural ganglion cyst involving a cranial nerve (V3), which was found to have a joint connection in support of an articular origin within the cranial nerves. An inferior alveolar intraneural cyst was incidentally discovered on a plain radiograph prior to edentulation. It was resected from within the mandibular canal with no joint connection perceived at surgery. Histologically, the cyst was confirmed to be an intraneural ganglion cyst. Reinterpretation of the preoperative CT scan showed the cyst arising from the temporomandibular joint. This case is consistent with the articular (synovial) theory of intraneural ganglion cysts. An anatomical explanation and potential joint connection are provided for this case as well as several other cases of intraneural cysts in the literature, and thus unifying cranial nerve involvement with accepted concepts of intraneural ganglion cyst formation and propagation.

Prostate cancer with perineural spread and dural extension causing bilateral lumbosacral plexopathy: case report.

Perineural tumor spread in prostate cancer is emerging as a mechanism to explain select cases of neurological dysfunction and as a cause of morbidity and tumor recurrence. Perineural spread has been shown to extend from the prostate bed to the lumbosacral plexus and then distally to the sciatic nerve or proximally to the sacral and lumbar nerves and even intradurally. The authors present a case of a bilateral neoplastic lumbosacral plexopathy that can be explained anatomically as an extension of the same process: from one lumbosacral plexus to the contralateral one utilizing the dural sac as a bridge between the opposite sacral nerve roots. Their theory is supported by sequential progression of symptoms and findings on clinical examinations as well as high-resolution imaging (MRI and PET/CT scans). The neoplastic nature of the process was confirmed by a sciatic nerve fascicular biopsy. The authors believe that transmedian dural spread allows continuity of a neoplastic process from one side of the body to the other.