Atraumatic intraneural heterotopic ossification of the common peroneal nerve: illustrative case

Abstract

BACKGROUND

Intraneural heterotopic ossification, or neuritis ossificans (NO), is characterized by nonneoplastic calcifications of extra-skeletal soft tissue within a peripheral nerve. This report presents an atypical case of atraumatic NO with a chronic, progressive course that led to a unilateral foot drop. In our review of the published data, there are limited reports describing NO affecting the common peroneal nerve with such profound clinical manifestation.

OBSERVATIONS

A 70-year-old female presented with an 8-year history of progressive right lower extremity weakness and foot drop. Initial electrodiagnostic studies localized a peroneal neuropathy at the fibular head, with transient symptom improvement. Years later, worsening symptoms led to further evaluation. Imaging revealed an extensive, calcified lesion encasing the distal sciatic and common peroneal nerves. Intraoperatively, a rigid, 9-cm segment of ossified nerve was identified, decompressed, and biopsied. Histopathological analysis confirmed NO. Postoperative outcomes included improved motor function with ongoing rehabilitation.

LESSONS

This case highlights the atypical presentation of NO, diagnostic workup, and surgical interventions. It emphasizes the need for a high index of suspicion in patients with unexplained, progressive mononeuropathies. When conventional imaging and electrodiagnostic studies are inconclusive, early referral for advanced imaging and specialist evaluation may be critical. Delayed recognition can result in significant neurological impairment.

https://thejns.org/doi/10.3171/CASE25623

Intraneural heterotopic ossification, or neuritis ossificans (NO), is an abnormal formation of nonneoplastic calcifications of extra-skeletal soft tissue within a peripheral nerve, most commonly arising from the epineurium with progressive encasement or displacement of nerve fascicles.^1,2 This entity is distinct from the more common extraneural heterotopic ossification, in which ectopic bone forms in periarticular soft tissues and secondarily compresses adjacent neurovascular structures.¹ Clarifying this distinction is important, as the etiology, operative findings, and pathological interpretation differ between the two processes.

Regarding the differences in etiology itself, extraneural heterotopic ossification is more commonly an acquired manifestation of posttraumatic musculoskeletal or spinal cord injury, such as blast injuries, burns, and surgical procedures,^3–6 whereas NO is more commonly cited to be atraumatic,⁷ although it does also have reports following trauma as well.⁸ Furthermore, the histological presentation of these differ, as classic NO lesions demonstrate an organized, zonal architecture with a central fibroblastic or fibrovascular component that transitions through osteoid formation to mature peripheral lamellar bone, features that may be subtle or missed on limited biopsy specimens and would be best appreciated in larger samples or complete resections.^2,8–11

Beyond the distinction of diagnoses, however, the presentation of these lesions ultimately follows similar clinical courses,⁸ and can both range from incidental discoveries to symptomatic weaknesses that interfere with daily function. Clinically significant cases occur in approximately 10%–20% of cases, with detection typically noted at 2 months following the inciting event. Of these, roughly 10% progress to extensive lesions that markedly limit joint mobility or lead to ankylosis.¹² Although such ossification can occur nearly anywhere in the body, it is more commonly found surrounding joints, muscles, and tendons near the elbow, thigh, pelvis, shoulder, and fingers, given their susceptibility to trauma.^6,12,13 Direct involvement of a nerve, however, is less common,¹⁴ with most documented cases being secondary to compression or entrapment by ectopic bone formation encasing or exerting pressure on adjacent peripheral nerves. When mononeuropathies are involved, some that are frequently reported include the ulnar nerve at the elbow, the sciatic nerve following hip procedures, and the tibial or peroneal nerves in cases involving lower extremity trauma or surgery.

The typical clinical presentation depends on the temporal stage as the NO develops. During the early inflammatory phase, patients often experience localized pain, tenderness, and swelling of the affected tissue. As the calcifications gradually mature, the swelling becomes more localized and firm, leading to restrictive movement and eventually interfering with daily activities. Ultimately, however, the clinical presentation is largely site-specific, with different anatomical sites producing varying effects on mobility, strength, range of motion, and sensation. In cases in which NO causes impingement or encases a peripheral nerve, patients may develop neuropathic symptoms, including paresthesia, muscle weakness, and sensory deficits along the affected nerve distribution.^1,15

The clinical relevance of NO extends beyond its physical manifestations, as it presents significant challenges in overall diagnosis and management. While the pathogenesis is known to be related to a triggering nociception-induced inflammation,^16–18 there remain challenges for diagnosing atypical cases, particularly in cases in which no preceding trauma is identified. These gaps in understanding complicate diagnosis and treatment, emphasizing the need for further study.

The present case report describes an atypical presentation of a nontraumatic NO involving the common peroneal nerve. The common peroneal nerve, a branch of the sciatic nerve, innervates muscles responsible for dorsiflexion and eversion of the foot, as well as providing sensation to the anterolateral leg and dorsum of the foot. Damage to this nerve can result in weakness or paralysis of the anterior and lateral leg compartments, leading to foot drop, gait instability, and sensory deficits. Prior literature has reported NO of the common peroneal nerve, with various management approaches.^10,19,20

In this case, the patient presented with a progressive, unilateral foot drop accompanied by chronic leg pain and weakness that developed insidiously over the course of 8 years. What began as mild discomfort gradually evolved into persistent pain and marked motor deficits, ultimately impairing the patient’s ability to ambulate and perform daily tasks. To the best of our knowledge, few reports, if any, have described a nontraumatic NO resulting in such profound and prolonged peroneal nerve dysfunction. This case highlights the importance of considering NO in the differential diagnosis and management of slowly progressive mononeuropathies, even in the absence of prior trauma or surgery.

Illustrative Case

A 70-year-old female with a past medical history of hypertension and who was otherwise healthy presented with a progressive right foot drop. She first sought medical attention for noticeable right lower extremity weakness, primarily affecting dorsiflexion, which led to a mild steppage gait. No sensory abnormalities were reported at this time. She denied any recent trauma, with the only prior trauma to this extremity being a remote right ankle fracture sustained approximately 20 years prior. However, this injury was anatomically distal to the site of current pathology and was ultimately deemed unrelated to the peroneal nerve compression or development of heterotopic ossification. In April 2016, initial nerve conduction and electromyography (EMG) studies were ordered by the patient’s primary care physician and revealed a right-sided peroneal neuropathy across the fibular head. The patient was advised to avoid crossing her legs, and no further medical evaluation or therapies were pursued at this time.

Six years later, she sought further evaluation for progressive right lower extremity weakness, now with a noticeable foot drop during ambulation. Given the increasing functional limitations, she was referred to a neurologist. In May 2022, nerve conduction and EMG studies again confirmed a right peroneal neuropathy, although the findings were nonlocalizable in contrast to the prior study. The needle examination revealed large motor unit potentials with reduced recruitment in the tibialis anterior and peroneus longus muscles, along with fibrillation potentials and positive sharp waves in the tibialis anterior. Other examined muscles, including the gastrocnemius, vastus medialis, tensor fascia latae, and biceps femoris, were within normal limits.

In August 2023, MRI of her knee and pelvis revealed atrophic changes and fatty infiltration in the anterior compartment of her right leg, including the tibialis anterior and peroneus longus, consistent with chronic peroneal neuropathy. However, no discrete lesion of the peroneal nerve was identified (Fig. 1).

FIG. 1.

Sequential coronal T1-weighted MR images of the right knee as of August 2023. A and B: Sequential slices demonstrating the course of the common peroneal nerve (orange arrow) as the nerve courses posterior to the biceps femoris tendon, curving toward the fibular head. C and D:The nerve continues on to wrap around the fibular neck. E:Distally, it divides into the superficial and deep peroneal nerves with no evidence of focal lesion. The MR images showed no actual lesion of the peroneal nerve.

In April 2024, the patient was referred to an orthopedic specialist, whose physical examination revealed a right-sided 0/5 dorsiflexion and eversion, 3/5 inversion, and 4/5 toe flexion. Sensation was decreased in the right superficial peroneal nerve and deep peroneal nerve distributions. At this time, management with an ankle foot orthosis brace was was recommended.

An ultrasound at this time showed posterior acoustic shadowing of unclear etiology just distal to the bifurcation of the right tibial and peroneal nerves, obscuring the peroneal nerve. Distal to this, the peroneal nerve exhibited marked enlargement, disrupted fascicular architecture, and increased cross-sectional area, suggestive of focal pathology. The nerve normalized in size and echotexture at the fibular head. One month later (May 2024), nerve conduction studies showed reduced amplitude of right fibular compound muscle action potential and superficial peroneal sensory nerve action potential. Needle EMG showed fibrillation potentials and positive sharp waves in the right tibialis anterior. Motor units with increased amplitude, long duration, and reduced recruitment were also seen in the right tibialis anterior and fibularis longus. Taken together, these findings reflect electrodiagnostic evidence of a chronic axonal peroneal mononeuropathy with signs of active denervation.

In May 2024, the patient sought a neurosurgical consultation, during which physical examination revealed an absent Tinel’s sign, and proximal MR neurograms of the pelvis and thigh were obtained. The case was reviewed by an interdisciplinary team consisting of neurosurgery, plastic surgery, physical medicine and rehabilitation, and radiology members. MR neurography of the thigh showed hypointensity of the common peroneal nerve near the bifurcation into the common peroneal and tibial nerves. CT was recommended and performed in June 2024, which revealed calcification of the common peroneal nerve from its takeoff from the sciatic nerve extending over a course of 7.5 cm to the lateral femoral condyle (Fig. 2). A diagnostic ultrasound was performed that redemonstrated a severe, predominantly chronic right common peroneal neuropathy, with an increased fascicle cross-sectional area size distal to the bifurcation of the right tibial and peroneal nerve, with the nerve returning to normal size and echogenicity at the level of fibular head (Fig. 3). The interdisciplinary team determined that exploration of the abnormal region of the common peroneal nerve with potential biopsy and neurolysis along this segment was indicated; while unlikely to reverse muscle atrophy, it would potentially provide a definitive diagnosis and prevent further deterioration. Indomethacin was neither tried nor considered.

FIG. 2.

Sequential axial CT images of the distal thigh to proximal leg demonstrating cross-sectional anatomy of the knee region as of June 2024. Sciatic nerve bifurcation into the tibial and common peroneal nerve. Calcification of the common peroneal nerve component begins in panel B, proximal to bifurcation. A: Noncalcified sciatic nerve (yellow arrow) proximal to bifurcation. B: Sciatic nerve with calcified common peroneal nerve component (orange arrow) and noncalcified tibial nerve (blue arrow). C–E: Course of the sciatic nerve, with increasing calcification of the common peroneal component (orange arrows) and continued visualization of the normal tibial nerve component (blue arrows). F: Distinct bifurcation into fully calcified common peroneal nerve (orange arrow) and noncalcified tibial nerve (blue arrow). G–J: Continuation of both nerves distally, maintaining the pattern of calcification. K: The common peroneal nerve reverts to a noncalcified appearance (purple arrow), with the tibial nerve remaining unchanged (blue arrow).

FIG. 3.

Diagnostic nerve ultrasound, right side as of April 2024. A and B: The peroneal nerve (yellow arrow) shows posterior acoustic shadowing of unclear etiology just distal to its bifurcation, followed by focal enlargement, loss of fascicular architecture, and increased cross-sectional area, suggestive of localized pathology. C: The nerve returns to normal size and echogenicity at the level of the fibular head. The tibial nerve (white arrow) remains normal throughout.

The patient elected to undergo surgical exploration and decompression of the common peroneal nerve. Intraoperatively, a 10-cm linear incision was made along the lateral right thigh ending at the flexor crease of the right popliteal fossa, where blunt dissection was used, exposing a highly calcified and noncompliant 9-cm segment of the right common peroneal nerve extending from the origin of the sciatic nerve to the lateral femoral head. The adjacent tibial nerve appeared completely normal without any pathological changes (Fig. 4). Nerve stimulation at 2 mA produced no observable motor activation in the common peroneal distribution, whereas stimulation of the adjacent tibial nerve elicited normal motor responses, including intact foot dorsiflexion and toe flexion.

FIG. 4.

Intraoperative findings of ossified common peroneal nerve in the posterior right thigh. Just distal to the bifurcation of the sciatic nerve (yellow arrow) into the tibial (blue arrow) and common peroneal nerve (orange arrow) branches, obvious abnormalities to the common peroneal nerve were immediately noted on visual inspection, as well as a palpable firmness and lack of flexibility of the common peroneal nerve. The proximal sciatic nerve appeared to be normal (proximal to the dotted line).

A 5 × 1–mm biopsy was taken from the deep epineural calcified tissue (sized 0.6 × 0.4 × 0.1 cm in aggregate) and was submitted for histopathological evaluation (Fig. 5). Fragments of ectopic mature lamellar bone were seen in association with extra-skeletal tissue including nerve twigs (approximately 40 μm in diameter), adipose tissue, and fibrovascular tissue, consistent with NO. No peroneal nerve was present.

FIG. 5.

Histopathological evidence of NO. A–C: Lamellar bone seen in association with soft tissue including small nerve twigs (arrowheads) and adipose tissue on hematoxylin and eosin staining. D: A neurofilament immunohistochemical stain positively highlights nerve twigs in association with bone and fibrovascular tissue. No peroneal nerve is identified. The asterisks indicate the vessel. Original magnification ×40 (A), ×100 (B), ×200 (C and D). a = adipose tissue; b = bone.

Postoperatively, the patient’s neurological status has remained relatively stable. Compared with the preoperative evaluation in June 2024, motor testing at follow-up in November 2024 demonstrated improvement in right foot inversion (4/5 to 5/5) and dorsiflexion (3/5 to 4/5). Foot eversion remained the same at 4/5 strength, and all other right-sided lower extremity motor function maintained full strength (5/5). No postoperative EMG or nerve conduction study was completed, given that the patient’s clinical status has since remained stable without evidence of regression following surgery, and repeat testing was not felt to provide additional value. The patient continues to participate in physical therapy, with transient subjective improvement early in the postoperative period, which has since stabilized, and she currently describes her function as similar to her preoperative baseline.

Informed Consent

The necessary informed consent was obtained in this study.

Discussion

NO can arise following both traumatic and atraumatic etiologies, but it typically does so within weeks to months whenever an inciting incident is identified. In contrast, this case is notable for its unusually protracted course, with symptom onset and progression occurring over 8 years. Aside from a remote right ankle fracture sustained 2 decades earlier, which was anatomically distal to the lesion, no clear inciting factor could be identified. While it is plausible that inversion or torsional stresses from the index injury could have transmitted traction proximally to the peroneal division of the sciatic nerve and predisposed to intraneural pathology,²¹ this mechanism was considered to be less likely given the 20-year interval between the injury and symptom onset. Even more, it is the prolonged and indolent course of development that makes this case of NO particularly interesting.

Observations

The first key aspect of this case is the atypical, progressive, and slow-developing nature of this patient’s symptoms that advanced to the point of a disabling foot drop. A similar pattern of delayed diagnosis and advanced neurological compromise has been reported in prior cases, in which the chronicity and atraumatic nature of this presentation affected and led to advanced progression and presentation.²² However, such slow-developing patterns are rather atypical, and this slow progression may contribute to underrecognition early on, as the absence of acute findings does not prompt immediate concern or aggressive diagnostic evaluation, eventually allowing the ossification process to advance to functionally significant symptomatic levels.

Given the presentation of an isolated noticeable foot drop with associated sensory deficits, early evaluations were focused predominantly on the common peroneal nerve in the distal lower extremity, as the fibular head/neck is the most common site of compression. This approach, however, delayed the ultimate diagnosis. When initial studies failed to localize the lesion, more proximal sites along the sciatic and common peroneal nerve trajectory should have been more aggressively considered. This diagnostic delay allowed the ossification to progress, ultimately requiring more extensive surgical intervention. This reflects a diagnostic bias toward common compression sites and a missed opportunity to consider more proximal etiologies when distal studies were unrevealing, underscoring the need to broaden the differential diagnosis early.

Regarding the diagnostic workup, this case illustrates the critical role of flexibility in imaging strategies. While MRI is a mainstay for evaluating peripheral nerve conditions, the initial hypointense signal areas resembled cortical bone, which raised suspicion for calcified lesions. Therefore, although CT imaging is not routinely used for nerve evaluations, its use in this patient became necessary to characterize the extent of ossification and its relationship to neural structures. Even more, earlier consideration of a high-resolution nerve ultrasound examination might have identified the posterior acoustic shadowing and fascicular distortion sooner, potentially expediting the CT evaluation and thus shortening time to diagnosis. The combined use of all these modalities in this case illustrates the usefulness of more comprehensive preoperative imaging assessments. Even more, this highlights that rigid adherence to standard imaging protocols may overlook atypical presentations.

Surgical intervention is the usual treatment of choice in cases in which NO causes functional impairment, and ultimately was indicated in this case given the patient’s significant functional decline and EMG/ultrasound evidence of advanced nerve compromise. While excision of NO carries known risks, including recurrence and wound complications, it has been shown to produce favorable outcomes.²³ In this case, the severity of the patient's symptoms warranted decompression, with the goals of preventing further worsening of neurological symptoms, obtaining diagnostic biopsy, and potentially improving neurological status through decompression. While the first two objectives were achieved, the extent of postoperative neurological improvement still remains uncertain.

Regarding the choice and timing of surgical intervention, this remains a matter of debate. Historically, surgical intervention has involved excision and has been delayed until the traumatic NO has fully matured, typically around 6–18 months postinjury.²⁴ However, when atraumatic NO phenomena occur, there remains no clear consensus on optimal timing. Some literature suggests that early excision may be justified in cases of progressive neurological impairment, although this remains controversial,²⁵ as other studies report lack of association.²⁶ Ultimately, the conclusion was to undergo surgical decompression once symptomatic, rather than to focus on timing itself. Additionally, recurrence rates may be influenced not only by timing but also by surgical technique. The extent of the excision, whether partial versus complete removal of the NO lesions is achieved, has been reported to significantly influence recurrence rates, with incomplete excision associated with a higher risk of regrowth and persistent symptoms.²⁷ While the decision here was decompression, rather than excision, it is important to consider that recurrence may still be possible.

Furthermore, beyond surgical timing and technique, there have been attempts to determine other preventative methods. This seems controversial, as some studies report that radiotherapy combined with excision can help prevent recurrence, yet other studies report that radiotherapy does not prevent recurrence and, in fact, is associated with an increased risk of postoperative sepsis.²⁸ Other studies support the use of prophylactic nonsteroidal anti-inflammatory drugs (NSAIDs). The variability in reported outcomes may be due to heterogeneity in NO etiology, radiation therapy protocols, and patient-specific risk factors, suggesting that individualized risk assessment may be more effective than blanket prophylactic strategies.^29–32 In the present case, indomethacin was not considered; rather, surgical decompression was prioritized given the symptomatic severity and the goals of the patient.

Postoperatively, the patient experienced transient partial recovery of motor function and reduction in neuropathic symptoms, although full reversal of foot drop was not achieved and then returned to preoperative baseline. Persistent deficits were likely attributable to chronic axonal degeneration that had occurred prior to surgical decompression. This outcome highlights the importance of early detection and intervention. Had the diagnosis been made earlier, prophylactic therapies such as NSAIDs or radiation therapy might have limited the extent of ossification and associated nerve injury, potentially resulting in more complete functional recovery.

As a single patient case, the findings may not be generalizable, and causative conclusions cannot be drawn. Additionally, given that this is an atypical presentation, the applicability may also be limited. However, the strength of this report lies in its detailed documentation of the timeline of the diagnostic approach and surgical decision-making process that may guide clinicians facing similar scenarios. It also highlights the importance of considering such atypical presentations in the differential diagnosis to avoid delays in recognition and management.

Lessons

Overall, this case emphasizes several important clinical lessons. First, clinicians should maintain a high index of suspicion for atypical presentations, particularly when symptoms are chronic, progressive, and inconclusive to standard evaluations. Second, diagnostic workups for peripheral neuropathies may benefit from early use of multimodal imaging. Lastly, timely recognition of compressive NO, regardless of a known traumatic etiology or not, can potentially prevent irreversible nerve damage and improve surgical outcomes.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: Grannan, Vu, El-Ghazali, Liu. Acquisition of data: Grannan, Vu, Evans, Scherpelz. Analysis and interpretation of data: Grannan, Vu, Evans, Liu. Drafting the article: Vu, El-Ghazali, Liu, Smith. Critically revising the article: all authors. Reviewed submitted version of manuscript: Grannan, Vu, Scherpelz, Liu. Approved the final version of the manuscript on behalf of all authors: Grannan. Administrative/technical/material support: Vu. Study supervision: Grannan, Vu. Histology: Evans.

Correspondence

Benjamin Grannan: University of Washington, Seattle, WA. bgrannan@uw.edu.