B. Matthew Howe

Intraneural ganglion cysts: a systematic review and reinterpretation of the world's literature

OBJECTIVE The etiology of intraneural ganglion cysts has been controversial. In recent years, substantial evidence has been presented to support the articular (synovial) theory for their pathogenesis. The authors sought to 1) perform a systematic review of the worlds literature on intraneural cysts, and 2) reinterpret available published MR images in articles by other authors to identify unrecognized joint connections. METHODS In Part 1, all cases were analyzed for demographic data, duration of symptoms, the presence of a history of trauma, whether electromyography or nerve conduction studies were performed, the type of imaging, surgical treatment, presence of a joint connection, intraneural cyst recurrence, and postoperative imaging. Two univariate analyses were completed: 1) to compare the proportion of intraneural ganglion cyst publications per decade and 2) to assess the number of recurrences from 1914 to 2003 compared with the years 2004-2015. Three multivariate regression models were used to identify risk factors for intraneural cyst recurrence. In Part 2, the authors analyzed all available published MR images and obtained MR images from selected cases in which joint connections were not identified by the original authors, specifically looking for unrecognized joint connections. Two univariate analyses were done: 1) to determine a possible association between the identification of a joint connection and obtaining an MRI and 2) to assess the number of joint connections reported from 1914 to 2003 compared with 2004 to 2015. RESULTS In Part 1, 417 articles (645 patients) were selected for analysis. Joint connections were identified in 313 intraneural cysts (48%). Both intraneural ganglion cyst cases and cyst recurrences were more frequently reported since 2004 (statistically significant difference for both). There was a statistically significant association between cyst recurrence and percutaneous aspiration as well as failure to disconnect the articular branch or address the joint. In Part 2, the authors identified 43 examples of joint connections that initially went unrecognized: 27 based on their retrospective MR image reinterpretation of published cases and 16 of 16 cases from their sampling of original MR images from published cases. Overall, joint connections were more commonly found in patients who received an MRI examination and were more frequently reported during the years 2004 to 2015 (statistically significant difference for both). CONCLUSIONS This comprehensive review of the worlds literature and the MR images further supports the articular (synovial) theory and provides baseline data for future investigators.

Perineural spread of malignant melanoma from the mandible to the brachial plexus: case report

Perineural spread is a well-known mechanism of dissemination of head and neck malignancies. There are few reports of melanoma involving the brachial plexus in the literature. To their knowledge, the authors report the first known case of perineural spread of malignant melanoma to the brachial plexus. Clinicoradiological and anatomopathological correlation is presented, highlighting the importance of peripheral nerve communications in perineural spread.

Segmental thoracic lipomatosis of nerve with nerve territory overgrowth.

Lipomatosis of nerve (LN), or fibrolipomatous hamartoma, is a rare condition of fibrofatty enlargement of the peripheral nerves. It is associated with bony and soft tissue overgrowth in approximately one-third to two-thirds of cases. It most commonly affects the median nerve at the carpal tunnel or digital nerves in the hands and feet. The authors describe a patient with previously diagnosed hemihypertrophy of the trunk who had a history of large thoracic lipomas resected during infancy, a thoracic hump due to adipose proliferation within the thoracic paraspinal musculature, and scoliotic deformity. She had fatty infiltration in the thoracic spinal nerves on MRI, identical to findings pathognomonic of LN at better-known sites. Enlargement of the transverse processes at those levels and thickened ribs were also found. This case appears to be directly analogous to other instances of LN with overgrowth, except that this case involved axial nerves rather than the typical appendicular nerves.

Expanding the spectrum of indirect trauma and superior tibiofibular joint-related intraneural ganglion cysts

Over the past few years, our group has published a series of articles in Clinical Anatomy (Lalezari et al., 2012; Spinner et al., 2012a, b, c) describing direct and indirect mechanisms for trauma affecting the superior tibiofibular joint (STFJ) that give rise to common fibular (peroneal) or tibial intraneural ganglion cysts. Direct trauma such as from blunt injury to the knee region seems like an obvious source for disruption of the STFJ capsule, and in extreme cases, dislocation, of the joint itself (Ogden, 1972, 1974; Sekiya and Kuhn, 2003). Indirect trauma to the STFJ, such as from injury to the ankle region, is a less obvious etiology. We have shown that even with minor trauma to the ankle region from mild ligamentous or bony injury, subtle injury to the interosseous membrane (IOM) and even proximal leg, nerve injuries may ensue without an associated proximal fibular fracture. Based on our initial cases following acute trauma, we put forth a mechanism: namely torsion, directed at the ankle, can be translated up the IOM to the STFJ and also produce a traction injury to the nerves, especially where the nerves might be vulnerable to injury, such as the fibular neck. A recently treated patient expands the spectrum of indirect traumatic mechanisms. A 37-year old man presented with the acute onset of

Elaborating upon the descent phase of fibular and tibial intraneural ganglion cysts after cross-over in the sciatic nerve.

In several previous publications, our group has proposed a mechanistic, anatomic explanation for intraneural ganglion cysts (Spinner et al., 2007a, b, 2008). General principles have been put forth for these cysts including: formation from a synovial joint with joint (cyst) fluid egressing through a capsular rent; propagation along an articular branch into the parent nerve; and pressure and pressure fluxes determining shapes and sizes following the path of least resistance (Spinner et al., 2007b). In most cases of fibular (peroneal) or tibial intraneural ganglion cysts arising from the superior tibiofibular joint (STFJ), cyst extends into the common fibular nerve or tibial nerve to the level of the knee. However, in the unusual cases where “extreme” cysts extend to the sciatic nerve bifurcation in the distal thigh and higher (even to the buttock; Spinner et al., 2011), different phases of propagation occur: they ascend within the parent nerve toward the sciatic nerve (Phase I), cross-over within the common epineurial sheath of the sciatic nerve (Phase II) and then descend (Phase III) down the same (i.e., primary, parental, or ipsilateral) nerve (Phase IIIA) and/or the “other” (secondary, cruciate, or contralateral nerve; Phase IIIB). We present this expanded classification based on our new appreciation of the descent phase after cross-over as illustrated in two recent patients. A 34-year-old man (Case 1) presented with symptoms and signs of a deep fibular nerve paralysis. Magnetic resonance imaging (MRI) demonstrated a fibular intraneural ganglion cyst, which derived from the anterior aspect of the STFJ and ascended eccentrically (Figs. 1A–1C) to the level of the sciatic bifurcation. Only a small amount of circumferential cyst was seen in the proximal tibial nerve (Fig. 1C). However, circumferential cyst descended down the common fibular nerve to surround not only the lateral sural (Fig. 1B) but also the superficial and deep fibular nerves and the articular trunk as well (Figs. 1D–1F). A 46-year-old man (Case 2) presented with a tibial neuropathy and was found to have a tibial intraneural ganglion cyst extending from the STFJ to the sciatic nerve (Fig. 2A) in the buttock (Spinner et al., 2011). The tibial intraneural ganglion ascended from the posterior aspect of the STFJ eccentrically within the tibial nerve. Cyst crossed over at the sciatic nerve bifurcation. Ascent continued around both divisions of the sciatic nerve to the upper thigh nearly to the ischial tuberosity with subtle cyst within the tibial division (depicted in Spinner et al., 2011). There was evidence of extraneural rupture of the cyst (Shahid et al., 2011). The MR images of this patient were recently re-reviewed and showed previously unrecognized extreme descent. There was a moderate amount of circumferential cyst around both the tibial and common fibular nerves from the level of the sciatic bifurcation to at least the level of the knee (Fig. 2B). In these two cases, a focused approach was used: disconnection of the articular branch, decompression of the cyst, resection of the STFJ—without resection of the extensive, interrelated intraneural cysts. At long-term clinical and radiologic follow-up, excellent neurologic recovery was made in both patients and MRIs done years later showed resolution of the intraneural ganglion cysts. These two cases and the other rare examples of cyst extending to the sciatic nerve demonstrate radiologic features that correlate with the phases of intraneural cyst propagation: (1) the signet ring sign: cyst eccentrically located within a nerve displacing fascicles (seen in ascent); (2) the extreme wedding ring sign: cyst circumferentially located around the sciatic nerve’s peroneal and tibial divisions within its common epineurial sheath (seen in cross-over); (3) the wedding ring sign: cyst circumferentially around the primary and/or the secondary cyst (seen in descent): a “ring within a ring” appearance signifies both ascent and descent phases occurring in the parent nerve (Phase IIIA); concentric cyst without the eccentric cyst component signifies descent in the contralateral nerve (Phase IIIB). Serial MRIs in both patients revealed the dynamic nature of these cysts with dramatic redistributions of cyst within weeks. These are the first known examples demonstrating the mechanism for “extreme” descent. In Case 1, cyst descended from the sciatic nerve down the primary pathway down the parent nerve to the level of its terminal branches, including the articular branch (Phase IIIA). In the nearly 400 reported cases of fibular intraneural ganglion cysts from the STFJ, we have not previously seen: (1) cyst descending down the superficial fibular nerve (except for cyst at the level of its origin from the common fibular nerve); and (2) circumferential cyst in the terminal branches. This case provides further radiologic insight into a case operated on in 1971 (Jacobs et al., 1975) wherein a tibial cyst extended to the sciatic nerve 15 cm above the knee and descended 22 cm below the knee in the tibial nerve and an unspecified distance in the common fibular nerve. This patient was reanalyzed by our group (Spinner et al., 2007b) to prove the existence of an articular origin even in an apparent example of a clinical outlier and to describe the cross-over mechanism.

Neuromuscular choristoma of the sciatic nerve and lumbosacral plexus: an association with nerve-territory undergrowth in the pelvis affecting soft tissue and bone.

BackgroundNeuromuscular choristomas (NMC) are rare congenital lesions with differentiated muscle found within peripheral nerves. Patients often present with progressive neuropathy, undergrowth of the affected limb, and limb length discrepancy. In the sciatic nerve (the most common location of NMC), this may lead to specific manifestations in the distal limb, including progressive neuropathy, a shortened atrophic limb and a cavus foot. We hypothesized that the presence of NMC of the sciatic nerve (proximal to the sciatic notch) extending to the lumbosacral plexus could lead to abnormalities in proximal nerve territories (i.e., nerve, muscle and bone) within the hemipelvis.MethodsA retrospective review of all cases of sciatic nerve NMCs diagnosed at the Mayo Clinic was performed.ResultsSeven patients were identified with sciatic nerve NMCs extending proximal and distal to the sciatic notch. Four patients with NMCs had denervation of muscles within the pelvis and ipsilateral undergrowth of bone which resulted in three cases of hip dysplasia. To our knowledge, the finding of proximal nerve-territory soft tissue and bony undergrowth (including hip dysplasia) in patients with NMCs involving the sciatic nerve and lumbosacral plexus has not previously been recognized.ConclusionThis finding will aid in both the diagnosis of the disease and an understanding of associated conditions.

Subparaneurial ganglion cysts of the fibular and tibial nerves: A new variant of intraneural ganglion cysts

Over the last decade, the mechanism of formation of intraneural ganglion cysts has been established through a meticulous review of clinical findings and correlation with patterns produced on magnetic resonance imaging (MRI). Pathognomonic imaging patterns distinguish these rare lesions from the more common extraneural variants in almost all cases. In this report, we present a new pattern of cyst occurrence in the subparaneurial compartment of the nerve and provide potential anatomic explanations for its pathogenesis. Using an anatomic framework of connective tissue compartments of the nerve, we reviewed 63 (56 fibular and seven tibial) intraneural ganglion cysts in the knee region evaluated at our institution and all reports with MRI in the worlds literature for evidence of cyst occurrence in the subparaneurial compartment. We identified six cases (five in the common fibular nerve and one in the tibial nerve) at our institution that had MR evidence of cyst in the subparaneurial compartment with a new complex lobulated pattern. All cases had articular branch connections to the superior tibiofibular joint, which at operation were resected along with the joints. Follow‐up revealed complete recovery in all instances and no clinical or radiological signs of recurrence. Three cases out of 80 in the literature exhibited the new complex lobulated MRI pattern. We present a new pattern of intraneural ganglion cyst occurrence in a potential space that surrounds peripheral nerves‐ the subparaneurial compartment. We believe that the unifying articular theory applies to the pathogenesis and management of these rare variants. Clin. Anat. 29:530–537, 2016.

In response to “Lipomatosis of the sciatic nerve secondary to compression by a desmoid tumor”

Dear Editor, We read with great interest the case report entitled “Lipomatosis of the sciatic nerve secondary to compression by a desmoid tumor.”We respectfully disagree with the authors’ interpretation of the imaging and their conclusions. Our group has had a particular interest in the clinical and radiological features of patients with lipomatosis of nerve (LN) and neuromuscular choristoma (NMC).The images provided in this report are strikingly similar to those published in our recent publication “Neuromuscular choristoma: characteristic magnetic resonance imaging findings and association with postbiopsy fibromatosis” [1], which included only biopsy-proven examples of NMC and fibromatosis (desmoid tumor). While the authors believe that the radiological features in their case are pathognomonic for LN, including the “coaxial cable sign” [2, 3], we feel that the imaging characteristics of the abnormal sciatic nerve in this report, namely, the non-enhancing fusiform enlargement of a large proximal peripheral nerve, and a <50 % fatty component, are more diagnostic of NMC than LN. Indeed, the sciatic nerve is the most common site for NMC, a rare one for LN, and this case overall is an excellent appearance of NMC complicated by aggressive fibromatosis. The postulated new association of LN and a desmoid tumor described in this case report is presumptive. While excellent radiological–pathological correlation between the enhancing mass component and the desmoid tumor is noted on biopsy, there is no tissue diagnosis of the sciatic nerve lesion itself. Nor would we have recommended a biopsy of it, owing to the potential exacerbation of the desmoid following surgery or biopsy of NMC [1, 4, 5]. Instead, we would try to support the diagnosis of the different clinical phenotypes of NMC and LN (NMC is associated with nerve territory undergrowth and LN with nerve territory overgrowth) [1]. We believe that the presented case offers additional evidence for the curious and unexplained association of NMC with desmoid development.

“Isolated long thoracic nerve palsy”: More than meets the eye

INTRODUCTION Two main hypotheses have been proposed for the pathophysiology of long thoracic nerve (LTN) palsy: nerve compression and nerve inflammation. We hypothesized that critical reinterpretation of electrodiagnostic (EDX) studies and MRIs of patients with a diagnosis of non-traumatic isolated LTN palsy could provide insight into the pathophysiology and, potentially, the treatment. MATERIAL AND METHODS A retrospective review was performed of all patients with a diagnosis of non-traumatic isolated LTN palsy and an EDX and brachial plexus or shoulder MRI studies performed at our institution. The original EDX studies and MR examinations were reinterpreted by a neuromuscular neurologist and musculoskeletal radiologist, respectively, both blinded to our hypothesis. RESULTS Seven patients met the inclusion criteria as having a non-traumatic isolated LTN palsy. Upon reinterpretation, all of them were found to have findings not consistent with an isolated LTN. On physical examination, three of them (43%) presented with weakness in muscles not innervated by the LTN. Four of them (57%) had additional EDX abnormalities beyond the distribution of the LTN. Five of them (71%) had MRI evidence of enlargement of nerves or denervation atrophy of muscles outside the innervation of the LNT, without evidence of compression of the LTN in the middle scalene muscle. CONCLUSION In our series, all 7 patients, originally diagnosed as having an isolated LTN, on reinterpretation, were found to have a more diffuse muscle/nerve involvement pattern, without MR findings to suggest nerve compression. These data strongly support an inflammatory pathophysiology.

Sequential MR imaging demonstrates evolution of a fibular intraneural ganglion cyst after knee dislocation

To the Editor, Clinical Anatomy:The basis for the articular (unified) theory for the for-mation of intraneural ganglion cysts is a capsular disrup-tion through which joint (cyst) fluid egresses into thearticular branch and then a parent nerve (Spinner et al.,2003). Trauma has been associated with intraneural gan-glion cysts. A recent meta-analysis revealed trauma beingassociated with intraneural ganglion cysts in our group (Figs. 2A–2E) showed both a neuroma in conti-12% ofcases (Desy and Spinner, 2014). Our group has describedthe pathoanatomy by which direct and indirect traumamay give rise to the most common form, fibular (pero-neal), and its rarer corollary, tibial intraneural ganglioncysts, both derived from the superior tibiofibularjoint (STFJ) (Lalezari et al., 2012; Spinner et al.,2012a,b; Cesmebasi et al., 2014). In direct trauma, therewould be a force generated near the proximal leg/kneeregion that would affect the STFJ (Ogden, 1972, 1974;Sekiya and Kuhn, 2003); in indirect trauma, forces wouldbe translated from the ankle region (such as in anklesprains or fracture) via the interosseous membrane to theproximal leg (Cesmebasi et al., 2014). A direct cause–effect relationship between traumatic injury and intraneu-ral ganglion cyst formation has yet to be definitivelyestablished.A 20-year-old man tripped off a curb and fell on his leftknee. He sustained a multi-ligamentous knee injury as aresult from a knee dislocation. He presented to an emer-gency room with exquisite pain and foot drop from a com-mon fibular nerve (CFN) palsy and was discharged afternegative plain radiographs were obtained. Several days later,he noted increasing pain and was found to have elevated legcompartment pressures for which he underwent four com-partment fasciotomies. MRI performed 7 days after the initialinjury revealed a posterolateral corner injury involving dis-ruption of the fibular collateral and posterior cruciate liga-ments, posterolateral capsule, and the musculotendinousjunction of the popliteus, lateral meniscus, and medial patel-lofemoral ligament. There was edema and thickening of theCFN extending from the fibular neck to a point just distal tothe sciatic nerve bifurcation (Figs. 1A–1C). He was referredto colleagues at our institution for definitive care of themulti-ligament injury and the CFN injury. Repeat MRI 3months after the injury confirmed the previous findingsreferable to the ligamentous injury. The CFN was markedlyenlarged in the popliteal fossa. There was anterior and lat-eral compartment musculature atrophy consistent withdenervation. Electromyography (EMG) confirmed a com-plete common fibular neuropathy. He underwent stagedreconstruction over the course of 9 months: (1) explora-tion and nerve grafting of the left CFN with 2 cable grafts(9 cm in length) using the superficial fibular nerve; (2)high tibial wedge osteotomy with allograft bone graft; and(3) multi-ligament knee reconstruction. At last follow-up,15 months post nerve grafting, he had no return of neuro-logic function but had regained a stable knee. It was rec-ommended he undergo tendon transfer for persistent footdrop. Retrospective reinterpretation of the second MRI bynuity involving the CFN as well as an unrecognized com-plex fibular intraneural cyst, which could be traced alongits articular branch to the anterior portion of the STFJ. Afracture line was noted at the STFJ extending to the originof the intraneural cyst from the joint. The cyst was notpresent on the initial MRI.Direct blunt force trauma to the knee has long beenknown to result in severe injuries to the knee causing pos-terolateral corner, multi-ligamentous knee, and CFN inju-ries. They have also been associated with instability of theSTFJ (Fallon et al., 1994; Kapur et al., 2009; Jabara et al.,2014). The resultant stretch tends to affect a long seg-ment of the CFN. Stretch injuries associated with kneedislocations are known to have poor recovery after nervesurgery (Fallon et al., 1994; Seidel et al., 2008). In ourpatient, we believe that the knee dislocation caused theimmediate clinical appearance of the foot drop involvingthe CFN. This stretch injury resulted in a lengthy neuromain continuity of the CFN. The effect of the stretch injury onthe articular branch and/or the bony injury to the STFJresulted in a capsular injury (without instability) and theegress of joint fluid (Fallon et al., 1994; Spinner et al.,2003, 2012a,b; Lalezari et al., 2012). Unfortunately, the2nd MRI was done of the knee rather than the CFN andSTFJ and did not provide full visualization of the proximalleg. In this case, despite the limitations, serial MR imagingdemonstrates a temporal relationship following kneetrauma and documents the evolution of an intraneuralganglion cyst.