PET imaging characteristics of neuromuscular choristoma and associated desmoid-type fibromatosis.

BACKGROUND: Neuromuscular choristoma (NMC) is a rare peripheral nerve lesion characterized by abnormal presence of muscle within nerve. Associated desmoid-type fibromatosis (NMC-DTF) often develops. We report 18F-fluorodeoxyglucose positron emission tomography (FDG PET) characteristics of NMC and NMC-DTF and propose that increased FDG activity within NMCs may be associated with subclinical NMC-DTF or NMC-DTF "precursor" tissue. METHODS: Our institutional database was searched for all NMC cases. Inclusion criteria were 1) confirmed diagnosis of NMC with or without biopsy, and 2) available PET and MRI studies. PET data included SUVmax and SUVmean of NMCs, contralateral limb normal skeletal muscle and unaffected nerves, and SUVmax of NMC-DTF if present. SUV values were compared using paired t-test. A p value of < 0.05 was considered statistically significant. RESULTS: Our cohort consisted of 9 patients with NMC, 8 cases involving sciatic nerve and 1 of brachial plexus. On PET imaging, all NMC-affected nerve segments showed significantly higher FDG uptake (SUVmax/mean) compared to both contralateral normal nerve and normal skeletal muscle (all P < 0.05). Similar to sporadic DTF, NMC-DTF was highly FDG-avid (average SUVmax of 4.2). SUVmax in NMC with or without concurrent NMC-DTF did not differ (p = 0.76). Within NMC-affected nerve segment, FDG activity was relatively higher in areas with low T1/T2 MR signal. CONCLUSION: All NMCs were more FDG avid compared to both normal skeletal muscle and contralateral unaffected nerve, arguing against the presence of heterotopic muscle in NMC as the source of FDG avidity. FDG avidity within NMC may reflect subclinical NMC-DTF or a precursor lesion, as NMC-DTF are highly FDG-avid, and the highest regions of FDG avidity in NMC occurred in regions with MR characteristics associated with NMC-DTF (i.e., lower T1/T2 signal). We believe that the integration of FDG PET with serial MR imaging in patient follow up will clarify its utility in both detection and surveillance of NMC-DTF.

7T for clinical imaging of benign peripheral nerve tumors: preliminary results.

PURPOSE: MRI has become an essential diagnostic imaging modality for peripheral nerve pathology. Early MR imaging for peripheral nerve depended on inferred nerve involvement by visualizing downstream effects such as denervation muscular atrophy; improvements in MRI technology have made possible direct visualization of the nerves. In this paper, we share our early clinical experience with 7T for benign neurogenic tumors. MATERIALS: Patients with benign neurogenic tumors and 7T MRI examinations available were reviewed. Cases of individual benign peripheral nerve tumors were included to demonstrate 7T MRI imaging characteristics. All exams were performed on a 7T MRI MAGNETOM Terra using a 28-channel receive, single-channel transmit knee coil. RESULTS: Five cases of four pathologies were selected from 38 patients to depict characteristic imaging features in different benign nerve tumors and lesions using 7T MRI. CONCLUSION: The primary advantage of 7T over 3T is an increase in signal-to-noise ratio which allows higher in plane resolution so that the smallest neural structures can be seen and characterized. This improvement in MR imaging provides the opportunity for more accurate diagnosis and surgical planning in selected cases. As this technology continues to evolve for clinical purposes, we anticipate increasing applications and improved patient care using 7T MRI for the diagnosis of peripheral nerve masses.

Rescue version of a carotid micro-endarterectomy: an ACE-ICA anastomosis with proximal Ica and distal ACE hemoclip obliteration.

Aim of the study: To present our rescue approach of carotid artery occlusion as well as to discuss other possible techniques that can be applied in similar situations.Materials and methods: Two cases from our institution with acute complications during carotid micro-endarterectomy (CEA).Results: Two cases from our institution with acute postoperative complications during CEA that were successfully addressed are presented with imaging and detailed description of the surgical techniques used.Conclusion: CEA are common surgical procedures pursued to achieve revascularization of carotid arteries when occluded partially or fully by an atherosclerotic plaque. As with any surgical procedure, associated complications exist in small percentage of the cases. These can include blood flow limitation due to an insufficient artery wall after atherosclerotic plaque extraction as well as distal kinking of the internal carotid artery. A direct end-to-end ACE-ACI bypass with occlusion of the proximal ACI and distal ACE stump preserves distal flow to the ACI, however the original arteriotomy of ACC must be completely sutured up to the arterial stumps.

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).

PIK3CA mutations in lipomatosis of nerve with or without nerve territory overgrowth.

Lipomatosis of nerve is a rare malformation characterized by a fibrolipomatous proliferation within peripheral nerve. Lipomatosis of nerve most frequently involves the median nerve, and manifests clinically as a compressive neuropathy. However, 30-60% of cases are associated with tissue overgrowth within the affected nerve's territory (e.g., macrodactyly for lipomatosis of nerve in the distal median nerve). Somatic activating PIK3CA mutations have been identified in peripheral nerve from patients with lipomatosis of nerve with type I macrodactyly, which is now classified as a PIK3CA-related overgrowth spectrum disorder. However, the PIK3CA mutation status of histologically confirmed lipomatosis of nerve, including cases involving proximal nerves, and cases without territory overgrowth, has not been determined. Fourteen histologically confirmed cases of lipomatosis of nerve involving the median (N = 6), brachial plexus (N = 1), ulnar (N = 3), plantar (N = 2), sciatic and superficial peroneal nerves (N = 1 each) were included. Ten cases had nerve territory overgrowth, ranging from macrodactyly to hemihypertrophy; and four cases had no territory overgrowth. Exome sequencing revealed "hotspot" activating PIK3CA missense mutations in 6/7 cases. Droplet digital polymerase chain reaction for the five most common PIK3CA mutations (p.H1047R, p.H1047L, p.E545K, p.E542K, and p.C420R) confirmed the exome results and identified an additional six cases with mutations (12/14 total). PIK3CA mutations were found in 8/10 cases with territory overgrowth (N = 7 p.H1047R and N = 1 p.E545K), including two proximal nerve cases with extremity overgrowth, and 4/4 cases without territory overgrowth (p.H1047R and p.H1047L, N = 2 each). The variant allele frequency of PIK3CA mutations (6-32%) did not correlate with the overgrowth phenotype. Three intraneural lipomas had no detected PIK3CA mutations. As PIK3CA mutations are frequent events in lipomatosis of nerve, irrespective of anatomic site or territory overgrowth, we propose that all phenotypic variants of this entity be classified within the PIK3CA-related overgrowth spectrum and termed "PIK3CA-related lipomatosis of nerve".

Combined treatment of a medulla oblongata hemangioblastoma via permanent cysto-cisternal drainage and (postponed) gamma knife radiosurgery: a case report and review of the literature.

BACKGROUND: Hemangioblastomas are histologically benign tumors with a variable degree of morbidity and mortality based on various factors, including their anatomical location. The following paper illustrates a unique approach of combined therapy of a brainstem hemangioblastoma (HB) not associated with von Hippel-Lindau disease (vHLd) located in the medulla oblongata. CASE DESCRIPTION: A 21-year-old preschool teacher presented with vertigo, followed by dysphagia, trouble coughing, tongue paresis and headache and vomiting. Magnetic resonance imaging (MRI) revealed a large cystic lesion with a small intramural nodule located in the left anterolateral medulla oblongata directly behind the vertebral artery. The diagnosis of hemangioblastoma was supported by digital subtraction angiography. CONCLUSION: Combined therapy consisted primarily of acute surgical fenestration and permanent drainage of the cystic portion of the tumor, due to symptomatic expansion. Follow-up stereotactic gamma knife radiosurgery was performed after 2 years for minor progression of the tumor nodule. To the best of our knowledge, this is the first time such approach has been described in the literature for this pathology.

H3K27 trimethylation loss in malignant peripheral nerve sheath tumor: a systematic review and meta-analysis with diagnostic implications.

BACKGROUND: Multiple studies have reported the loss of trimethylation at lysine (K) 27 on histone 3 (H3K27me3) in high-grade malignant peripheral nerve sheath tumors (MPNSTs). However, the diagnostic potential of this finding in MPNSTs remains yet to be fully substantiated. Correspondingly, our aim was to pool systematically-identified metadata in the literature and substantiate the incidence of H3K27me3 loss in this setting. METHODS: Searches of 7 electronic databases from inception to May 2019 were conducted following PRISMA guidelines. Articles were screened against pre-specified criteria. The incidence of loss was then pooled by random-effects meta-analysis of proportions. RESULTS: Nine pertinent studies described a total of 823 high-grade MPNST samples. When pooled, incidence (sensitivity) of complete H3K27me3 loss was estimated to be 53% (95% CI 42-64%). For MPNST subtypes, estimated incidences of complete loss in NF1 subtype was 52% (95% CI 41-62), in sporadic subtype was 53% (95% CI 36-70%), in the epithelioid subtype was 0% (95% CI 0-7%), and radiation-associated subtype was 98% (95% CI 86-100%). Finally, incidence of incomplete loss (specificity) in 1231 MPNST-mimic samples was estimated to be 96% (95% CI 90-99%). Certainty of these outcomes ranged from very low to high. CONCLUSIONS: The incidence of complete H3K27me3 loss is substantial in high-grade MPNSTs and is low in MPNST-mimics. Greater cohort study and biological investigation will validate the certainty of these findings as well as elucidate their true molecular and clinical significances.

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.

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.

Extensive perineural spread of an intrapelvic sciatic malignant peripheral nerve sheath tumor: a case report.

Perineural spread has been described in multiple neoplasms of neural and non-neural origin. The peripheral nervous system may represent a highway by which tumors can spread throughout the body. Malignant peripheral nerve sheath tumor (MPNST) is a neoplasm arising from peripheral nerves with high rates of local recurrence and distant metastases, leading to a poor 5-year overall survival. In many cases, the optimal treatment involves wide en bloc excision with negative margins as well as chemotherapy and radiation. Even in cases of negative surgical margins, recurrence rates are high, suggesting possible skip lesions or very distant infiltration along the involved nerve. We report a case of high-grade MPNST of the sciatic nerve with post-mortem dissection and histopathologic characterization of perineural spread of microscopic disease to sites significantly proximal and distal to areas with evidence of gross disease, which may help to explain the high rates of local and distal recurrence in MPNST.

Unrecognized sciatic lipomatosis of the nerve diagnosed by telehealth: illustrative case.

BACKGROUND: Lipomatosis of the nerve (LN) is a rare congenital hamartoma in which abundant fibroadipose tissue is found within the epineurium of peripheral nerves. It is frequently associated with nerve territory overgrowth affecting bones or soft tissues. The clinicoradiological features are well known and pathognomonic. OBSERVATIONS: A 38-year-old female was evaluated via telehealth for worsened sciatica after the resection of a sciatic notch lipoma, after having been evaluated over a decade for symptoms. Virtual physical examination revealed previously unrecognized subtle limb discrepancy (i.e., overgrowth). Although preoperative radiographs were unavailable during the initial evaluation, postoperative magnetic resonance imaging studies showed evidence of sciatic nerve LN. A diagnosis of LN and nerve territory overgrowth was established. LESSONS: Despite its limitations, telehealth can be an effective alternative or adjunct to in-person evaluations in making complex diagnoses. Dedicated examination without clinical suspicion can miss subtle findings. An iterative process prompted by a focused history, knowledge of clinical associations, and pattern recognition can facilitate an accurate diagnosis without obvious face-to-face visual clues. In patients with rare disorders, asynchronous evaluation allows in-person visits to be supplemented by subsequent telehealth virtual physical exam findings. This case illustrates how examination via telehealth can be used to effectively diagnose a rare syndrome.

Neuromuscular choristoma and circumferential nerve territory desmoid-type fibromatosis: imaging findings supporting a nerve-driven mechanism.

OBJECTIVE: Neuromuscular choristoma (NMC) is a rare developmental malformation of peripheral nerve that is frequently associated with the development of a desmoid-type fibromatosis (DTF). Both NMC and NMC-DTF typically contain pathogenic CTNNB1 mutations and NMC-DTF develop only within the NMC-affected nerve territory. The authors aimed to determine if there is a nerve-driven mechanism involved in the formation of NMC-DTF from the underlying NMC-affected nerve. METHODS: Retrospective review was performed for patients evaluated in the authors' institution with a diagnosis of NMC-DTF in the sciatic nerve (or lumbosacral plexus). MRI and FDG PET/CT studies were reviewed to determine the specific relationship and configuration of NMC and DTF lesions along the sciatic nerve. RESULTS: Ten patients were identified with sciatic nerve NMC and NMC-DTF involving the lumbosacral plexus, sciatic nerve, or sciatic nerve branches. All primary NMC-DTF lesions were located in the sciatic nerve territory. Eight cases of NMC-DTF demonstrated circumferential encasement of the sciatic nerve, and one abutted the sciatic nerve. One patient had a primary DTF remote from the sciatic nerve, but subsequently developed multifocal DTF within the NMC nerve territory, including 2 satellite DTFs that circumferentially encased the parent nerve. Five patients had a total of 8 satellite DTFs, 4 of which abutted the parent nerve and 3 that circumferentially involved the parent nerve. CONCLUSIONS: Based on clinical and radiological data, a novel mechanism of NMC-DTF development from soft tissues innervated by NMC-affected nerve segments is proposed, reflecting their shared molecular genetic alteration. The authors believe the DTF develops outward from the NMC in a radial fashion or it arises in the NMC and wraps around it as it grows. In either scenario, NMC-DTF develops directly from the nerve, likely arising from (myo)fibroblasts within the stromal microenvironment of the NMC and grows outward into the surrounding soft tissues. Clinical implications for patient diagnosis and treatment are presented based on the proposed pathogenetic mechanism.

Exuberant circumferential fibroproliferative neuromas in lipomatosis of nerve: a unifying theory. Illustrative case.

BACKGROUND: Lipomatosis of nerve (LN) is a rare disorder characterized by the massive enlargement of peripheral nerves, frequently accompanied by generalized fibroadipose proliferation and skeletal overgrowth. OBSERVATIONS: The authors have been routinely following a 20-year-old male for lipomatosis of median nerve at the wrist noted shortly after birth. He had undergone resection of the lesion accompanied by sural nerve grafting at another institution. Clinically, although his neurological loss of function has been stable, he has had continued soft tissue growth. Serial magnetic resonance imaging has revealed persistent LN proximal to the repair sites with evidence of fatty proliferation in the sural grafts and continued LN and fatty proliferation distally. There has been a progressive circumferential pattern of fibrosis around the proximal and distal suture lines, which has a similar radiological pattern to desmoid type fibromatosis (a pattern recently described in neuromuscular choristoma [NMC] desmoid-type fibromatosis). LESSONS: Considering the similar reaction of nerve in both LN and NMC despite differing genetic cascades, the authors believe a unifying process occurs in both lesions. The pattern of circumferential fibroproliferation would be most consistent with neuron-mediated growth from unspecified trophic factors, supporting a previously reported a nerve-derived "inside-out mechanism." The clinical consequences of this unifying process are presented.

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.

Neurohormonal response patterns to hunger, satiation, and postprandial fullness in normal weight, anorexia nervosa, and obesity.

BACKGROUND: Food intake is regulated by homeostatic and hedonic systems that interact in a complex neuro-hormonal network. Dysregulation in energy intake can lead to obesity (OB) or anorexia nervosa (AN). However, little is known about the neurohormonal response patterns to food intake in normal weight (NW), OB, and AN. MATERIAL & METHODS: During an ad libitum nutrient drink (Ensure®) test (NDT), participants underwent three pseudo-continuous arterial spin labeling (pCASL) MRI scans. The first scan was performed before starting the NDT after a > 12 h overnight fast (Hunger), the second after reaching maximal fullness (Satiation), and the third 30-min after satiation (postprandial fullness). We measured blood levels of ghrelin, cholecystokinin (CCK), glucagon-like peptide (GLP-1), and peptide YY (PYY) with every pCASL-MRI scan. Semiquantitative cerebral blood flow (CBF) maps in mL/100 gr brain/min were calculated and normalized (nCBF) with the CBF in the frontoparietal white matter. The hypothalamus (HT), nucleus accumbens [NAc] and dorsal striatum [DS] were selected as regions of interest (ROIs). RESULTS: A total of 53 participants, 7 with AN, 17 with NW (body-mass index [BMI] 18.5-24.9 kg/m2 ), and 29 with OB (BMI ≥30 kg/m2 ) completed the study. The NW group had a progressive decrease in all five ROIs during the three stages of food intake (hunger, satiation, and post-prandial fullness). In contrast, participants with OB showed a minimal change from hunger to postprandial fullness in all five ROIs. The AN group had a sustained nCBF in the HT and DS, from hunger to satiation, with a subsequent decrease in nCBF from satiation to postprandial fullness. All three groups had similar hormonal response patterns with a decrease in ghrelin, an increase in GLP-1 and PYY, and no change in CCK. CONCLUSION: Conditions of regulated (NW) and dysregulated (OB and AN) energy intake are associated with distinctive neurohormonal activity patterns in response to hunger, satiation, and postprandial fullness.