Fibular (peroneal) neuropathy.

Fibular neuropathy has variable presenting features depending on the site of the lesion. Anatomical features make it susceptible to injury from extrinsic factors, particularly the superficial location of the nerve at the head of the fibula. There are many mechanisms of compression or other traumatic injury of the fibular nerve, as well as entrapment and intrinsic nerve lesions. Intraneural ganglion cysts are increasingly recognized when the mechanism of neuropathy is not clear from the medical history. Electrodiagnostic testing can contribute to the localization as well as the characterization of the pathologic process affecting the nerve. When the mechanism of injury is unclear from the analysis of the presentation, imaging with MRI and ultrasound may identify nerve lesions that warrant surgical intervention. The differential diagnosis of foot drop includes fibular neuropathy and other neurologic conditions, which can be distinguished through clinical and electrodiagnostic assessment. Rehabilitation measures, including ankle splinting, are important to improve function and safety when foot drop is present. Fibular neuropathy is less frequently painful than many other nerve lesions, but when it is painful, neuropathic medication may be required. Failure to spontaneously recover or the detection of a mass lesion may require surgical management.

Ultrahigh-frequency ultrasound of fascicles in the common fibular, superficial fibular, and sural nerves.

INTRODUCTION/AIMS: While ultrasound assessment of cross-sectional area and echogenicity has gained popularity as a biomarker for various neuropathies, there is a scarcity of data regarding fascicle count and density in neuropathies or even healthy controls. The aim of this study was to determine whether fascicles within select lower limb nerves (common fibular, superficial fibular, and sural nerves) can be counted in healthy individuals using ultrahigh-frequency ultrasound (UHFUS). METHODS: Twenty healthy volunteers underwent sonographic examination of the common fibular, superficial fibular, and sural nerves on each lower limb using UHFUS with a 48 MHz linear transducer. Fascicle counts and density in each examined nerve were determined by a single rater. RESULTS: The mean fascicle number for each of the measured nerves included the following: common fibular nerve 9.85 (SD 2.29), superficial fibular nerve 5.35 (SD 1.59), and sural nerve 6.73 (SD 1.91). Multivariate linear regression analysis revealed a significant association between cross-sectional area and fascicle count for all three nerves. In addition, there was a significant association seen in the common fibular nerve between fascicle density and height, weight, and body mass index. Age and sex did not predict fascicle count or density (all p > .13). DISCUSSION: UHFUS enabled the identification and counting of fascicles and fascicle density in the common fibular, superficial fibular, and sural nerves. Knowledge about normal values and normal peripheral nerve architecture is needed in order to further understand and identify pathological changes that may occur within each nerve in different disease states.

Acute-Onset Footdrop Caused by Intraneural Ganglion Cyst of the Common Peroneal Nerve: The Effects of Extraneural Pressure Gradients on Cyst Propagation.

Ganglion cysts are relatively common entities, but intraneural ganglia within peripheral nerves are rare and poorly understood. We present a case of a 51-year-old man who presented with acute left dropfoot. Initial magnetic resonance imaging (MRI) was misinterpreted as common peroneal neuritis consistent with a traction injury corroborated by the patient's history. However, after surgical decompression and external neurolysis were performed, the patient's symptoms worsened. Repeated MRI revealed an intraneural ganglion cyst of the common peroneal nerve with connection to the superior tibiofibular joint by means of its anterior recurrent branch that was evident retrospectively on preoperative MRI. It is crucial to carefully inspect atypical cases to further recognize and appreciate the dynamic aspect of this disease or "roller-coaster" phenomenon. Intraneural ganglion cysts rely heavily on intraneural and extraneural pressure gradients for propagation, which can be drawn from the expanded work of the unifying articular theory. This report emphasizes the importance of understanding the pathoanatomical and hydraulic factors to appropriately identify and treat intraneural ganglion cysts. Increased recognition of this pathologic entity as a differential diagnosis for acute onset dropfoot is also highlighted.

Preoperative Imaging of Intraneural Ganglion Cysts: A Critical Systematic Analysis of the World Literature.

BACKGROUND: Advancements in imaging and an understanding of the pathomechanism for intraneural ganglion cyst formation have led to increased awareness and recognition of this lesion. However, the precise role of imaging has been advocated for but not formally evaluated. METHODS: We performed a systematic review of the world literature to study the frequency of imaging used to diagnose intraneural ganglion cysts at different sites and compared trends in identifying joint connections. RESULTS: We identified 941 cases of intraneural ganglion cysts, of which 673 had published imaging. Magnetic resonance imaging (MRI, n = 527) and ultrasonography (US, n = 123) were the most commonly reported. They occurred most frequently in the common peroneal nerve (n = 570), followed by the ulnar nerve at the elbow (n = 88), and the tibial nerve at the ankle (n = 58). A joint connection was identified in 375 cases (48%), with 62% of MRIs showing a joint connection, followed by 16% on US, and 6% on computed tomography (CT). MRI was statistically more likely to identify a joint connection than was US (P < 0.01). In the last decade, joint connections have been identified with increasing frequency using preoperative imaging, with up to 75% of cases reporting joint connections. CONCLUSIONS: Preoperative imaging plays an important role in establishing the diagnosis of intraneural ganglion cyst as well as treatment planning. Imaging has proved superior to the sole reliance of operative exposure to identify a joint connection, which is necessary to treat the underlying disease. Failure to identify cyst connections on imaging can result in an inability to truly address the underlying pathoanatomy at the time of definitive surgery, leading to a risk for clinical recurrence. Therefore, management should be guided by an intersection between new knowledge presented in the literature, clinical expertise, and surgeon experience.

Schwannomas of the peroneal nerves: Clinical and functional results of surgical treatment.

OBJECTIVES: Peroneal nerves Schwannomas are rare benign tumors. Literature is still poor of studies about clinical and functional outcomes after surgical treatment. We evaluated the pre-operative presentation of the disease and assessed clinical and functional outcomes after surgery. METHODS: We collected all the cases of peroneal nerves' neurinoma treated surgically between June 2016 and June 2020. We analyzed each patients' personal data and carried out accurate clinical examinations before and after surgery. MRI was performed both pre-operatively and post-operatively. RESULTS: We reported 9 cases of peroneal nerves schwannomas: five arising from the common peroneal nerve and four arising from the deep or superficial branches alone. Their mean size was 22.6 mm. Each patient showed sensation deficits before surgery; pre-operative MRC score was 4.2. Pre-Operative MSTS and LEFS scores were 23.6 and 64.4. Surgery was successful in each case. No local recurrence nor major complication occurred. Tumor size was significantly associated with both diagnostic delay and development of pre-operative deficits. Surgery was proven to be globally successful: post-operative evaluations highlighted a marked reduction of neurological signs and overall functional limitations. CONCLUSIONS: Surgical treatment at early stages of the disease represents a reliable and relatively safe therapeutic option.

Intracapsular Micro-Enucleation of a Painful Superficial Peroneal Nerve Schwannoma in a 60-Year Old Man: A Rare Encounter.

BACKGROUND Schwannomas are the most common benign peripheral nerve sheath tumors, localized mainly to the cranial and upper extremity nerves. Their occurrence in the lower limbs is uncommon, and specific involvement of the superficial peroneal nerve is exceedingly rare. We report a case of a painful right superficial peroneal nerve schwannoma that was excised via the intracapsular micro-enucleation technique. CASE REPORT A 60-year-old South Asian man presented with a 2-year history of a painful lump on the lateral aspect of the right upper leg. Clinical examination revealed a firm mass located at the proximal lateral aspect of the right leg, measuring approximately 3×2.5 cm. Severe tenderness over the mass was present. The Tinel test was positive. There were no sensory or motor deficits or history of neurofibromatosis. Imaging showed features suggestive of a schwannoma. Surgery was indicated; intracapsular micro-enucleation was performed. Histopathological assessment of the tumor demonstrated Antoni A and B patterns with nuclear palisading and Verocay bodies, hallmarks of a schwannoma. The postoperative period was uneventful; no neurological deficits were noted. CONCLUSIONS The case described is considered rare, with no data on disease epidemiology in the literature. We provide a brief review and add pivotal data to the literature. Despite its rarity, one should remain cognizant of the condition and consider it in the differential diagnosis of nontraumatic leg pain. Based on our experience, corroboration from previous case reports, and the satisfactory outcome of our case, we advocate the intracapsular micro-enucleation technique when possible for schwannomas.

Neurolymphomatosis related to direct epineural invasion of the superficial peroneal nerve from subcutaneous B-cell lymphoma.

Neurolymphomatosis is a rare complication of systemic lymphomas, and is classically related to hematogenous spread or intraneural spread of tumor cells from the leptomeninges. Here we report a case of neurolymphomatosis related to direct epineural invasion of the superficial peroneal nerve from subcutaneous localization of B-cell lymphoma. Nerve biopsy revealed striking histological features suggestive of contiguous infiltration of the superficial peroneal nerve by subcutaneous lymphoma. We think this case report sheds new light on neurolymphomatosis pathophysiology with an unreported mechanism in B-cell lymphoma. It also points out that the clinical spectrum in neurolymphomatosis is really variable, pure sensory mononeuritis being a rare presentation. Finally, our case is also strongly illustrative of the contribution of early nerve ultrasonography in the patient diagnosis and in guidance of the nerve biopsy.

Characterization of mononeuropathy of the lateral cutaneous nerve of the calf.

INTRODUCTION/AIMS: Isolated injuries to the lateral cutaneous nerve of the calf (LCNC) branch of the common peroneal nerve can cause obscure chronic posterolateral knee and upper calf pain and sensory symptoms. Routine examination and electrodiagnostic testing do not detect them because the LCNC has no motor distribution and it is not interrogated by the typical peroneal nerve conduction study. There are only about 10 prior cases, thus scant physician awareness, so most LCNC injuries remain misdiagnosed or undiagnosed, hindering care. METHODS: We extracted pertinent records from seven patients with unexplained posterolateral knee/calf pain, six labeled as complex regional pain syndrome, to investigate for mononeuropathies. Patients were asked to outline their skin area with abnormal responses to pin self-examination independently. Three underwent an LCNC-specific electrodiagnostic study, and two had skin-biopsy epidermal innervation measured. Cadaver dissection of the posterior knee nerves helped identify potential entrapment sites. RESULTS: Initiating events included knee surgery (three), bracing (one), extensive kneeling (one), and other knee trauma. All pin-outlines included the published LCNC neurotome. One oftwo LCNC-specific electrodiagnostic studies revealed unilaterally absent potentials. Longitudinal, controlled skin biopsies documented profound LCNC-neurotome denervation then re-innervation contemporaneous with symptom recovery. Cadaver dissection identified the LCNC traversing through the dense fascia of the proximolateral gastrocnemius muscle insertion. DISCUSSION: Isolated LCNC mononeuropathy can cause unexplained posterolateral knee/calf pain syndromes. This series characterizes presentations and supports patient pin-mappings as a sensitive, globally available, low-cost diagnostic aid. Improved recognition may facilitate more rapid, accurate diagnosis and, thus, optimize management and improve outcomes.

The relationship of the Phantom® Lapidus Intramedullary Nail System to neurologic and tendinous structures in the foot: An anatomic study.

BACKGROUND: The purpose of our cadaveric study was to determine the proximity of nail insertion and interlocking mechanisms in the Phantom® Lapidus Intramedullary Nail System to neurologic and tendinous structures in the foot. METHODS: We used 10 fresh-frozen human lower-extremity specimen cadavers. For each specimen, the Nail System was inserted as described in the published technique guide. We then performed dissection on the tibialis anterior tendon, extensor hallucis longus tendon, and medial dorsal cutaneous branch of the superficial peroneal nerve and we measured and averaged the distances from each of these structures from the nail. RESULTS: The tibialis anterior tendon was in closest proximity to the insertion of the proximal medial interlock K-wire with an average distance of 0.4mm from the tendon. The extensor hallucis longus tendon was in closest proximity to nail insertion with an average distance of 1.2mm. The medial dorsal cutaneous branch of the superficial peroneal nerve was in closest proximity to the distal interlock K-wire with an average distance of 7.5mm. CONCLUSIONS: The tibialis anterior tendon, extensor hallucis longus tendon, and the medial dorsal cutaneous branch of the superficial peroneal nerve are at risk with the insertion of the nail system. Blunt dissection should be performed using this system with a path to bone before instrumentation to reduce the risk of nerve and tendon injury in the foot.

A CNTNAP1 Missense Variant Is Associated with Canine Laryngeal Paralysis and Polyneuropathy.

Laryngeal paralysis associated with a generalized polyneuropathy (LPPN) most commonly exists in geriatric dogs from a variety of large and giant breeds. The purpose of this study was to discover the underlying genetic and molecular mechanisms in a younger-onset form of this neurodegenerative disease seen in two closely related giant dog breeds, the Leonberger and Saint Bernard. Neuropathology of an affected dog from each breed showed variable nerve fiber loss and scattered inappropriately thin myelinated fibers. Using across-breed genome-wide association, haplotype analysis, and whole-genome sequencing, we identified a missense variant in the CNTNAP1 gene (c.2810G>A; p.Gly937Glu) in which homozygotes in both studied breeds are affected. CNTNAP1 encodes a contactin-associated protein important for organization of myelinated axons. The herein described likely pathogenic CNTNAP1 variant occurs in unrelated breeds at variable frequencies. Individual homozygous mutant LPPN-affected Labrador retrievers that were on average four years younger than dogs affected by geriatric onset laryngeal paralysis polyneuropathy could be explained by this variant. Pathologic changes in a Labrador retriever nerve biopsy from a homozygous mutant dog were similar to those of the Leonberger and Saint Bernard. The impact of this variant on health in English bulldogs and Irish terriers, two breeds with higher CNTNAP1 variant allele frequencies, remains unclear. Pathogenic variants in CNTNAP1 have previously been reported in human patients with lethal congenital contracture syndrome and hypomyelinating neuropathy, including vocal cord palsy and severe respiratory distress. This is the first report of contactin-associated LPPN in dogs characterized by a deleterious variant that most likely predates modern breed establishment.

A Cadaveric Study of the Distal Biceps Femoris Muscle in relation to the Normal and Variant Course of the Common Peroneal Nerve: A Possible Cause of Common Peroneal Entrapment Neuropathy.

The most frequent mononeuropathy in the lower extremity has been reported as the common peroneal nerve entrapment neuropathy (CPNe) around the head and neck of the fibula, although the mechanism of the neuropathy in this area cannot be fully explained. Therefore, the aim of this cadaveric study was to evaluate the relationship between morphologic variations of the distal biceps femoris muscle (BFM) and the course of the common peroneal nerve (CPN) and to investigate the incidence and morphological characteristics of anatomical variations in the BFM associated with CPNe. The popliteal region and the thigh were dissected in 115 formalin-fixed lower limbs. We evaluated consensus for (1) normal anatomy of the distal BFM, (2) anatomic variations of this muscle, and (3) the relationship of the muscle to the CPN. Measurements of the distal extents of the short and long heads of the BFM from insertion (fibular head) were performed. Two anatomic patterns were seen. First, in 93 knees (80.8%), the CPN ran obliquely along the lateral side of the BFM and then superficial to the lateral head of the gastrocnemius muscle. Second, in 22 cases (19.2%), the CPN coursed within a tunnel between the biceps femoris and lateral head of the gastrocnemius muscle (LGCM). There was a positive correlation between the distal extents of the short heads of the biceps femoris muscle (SHBFM) and the presence of the tunnel. The "popliteal intermuscular tunnel" in which the CPN travels can be produced between the more distal extension variant of the SHBFM and the LGCM. This anatomical variation of BFM may have a clinical significance as an entrapment area of the CPN in the patients in which the mechanism of CPNe around the fibula head and neck is not understood.

Diagnostic and management considerations in incidental common peroneal intraneural haemangioma.

Intraneural haemangiomas are rare tumours that can affect peripheral nerves. We describe a case of a 10-year-old female with an incidental finding of a common peroneal nerve lesion following knee injury. MRI demonstrated avid heterogeneous enhancement and peri-lesional oedema, and an open biopsy was performed revealing haemangioma on histopathological analysis. The patient was managed with observation and remains intact at 24-month follow-up.

Skin and Nerve Neovascularization in POEMS Syndrome: Insights From a Small Cohort.

Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS) syndrome is a rare systemic disorder linked to plasma cell dyscrasia and is related to elevation of vascular endothelial growth factor (VEGF). Diagnosis is still challenging and pathophysiology unclear. Because VEGF drives neovascularization, we investigated skin and nerve vascularization in 6 patients with POEMS syndrome compared with 5 control groups of polyneuropathies and healthy subjects (n = 104) from the University Hospital of Limoges between 2009 and 2018. We evaluated loss of small and large fibers in these patients. Skin and nerve vascularization were quantified manually on immunofluorescence using vessel staining (anti-α-SMA antibody). Dermal vascularization was significantly higher in POEMS syndrome than in other groups, but unrelated to loss of small fibers and VEGF. Perineurial vascularization was higher in POEMS syndrome than in healthy controls, and was related to loss of large fibers and VEGF level. Our study highlights the existence of neovascularization in skin of patients with this rare disorder. These data suggest that skin neovascularization could be an additional biomarker to help in the diagnosis and understanding of POEMS syndrome. Moreover, nerve neovascularization, driven by VEGF overexpression, may play a role in the pathophysiology of large fiber loss in this condition.

Intraneural Peroneal Ganglion Cyst Excision in a Pediatric Patient: A Case Report.

CASE: A 14-year-old female presented with a profound foot drop after trauma to the right leg. Clinical examination and electrodiagnostic studies demonstrated a dense palsy of the common peroneal nerve. Magnetic resonance imaging revealed an intraneural peroneal ganglion cyst at the fibular neck. Surgical treatment included decompression and transection of the articular branch to the proximal tibiofibular joint. At the 1-year follow-up, the patient demonstrated complete recovery of peroneal nerve function. CONCLUSIONS: This case demonstrates a rare finding of a pediatric intraneural peroneal ganglion cyst. The presentation and treatment is well-documented and adds depth to the literature on a sparsely reported condition.

Nerve size correlates with clinical severity in Charcot-Marie-Tooth disease 1A.

INTRODUCTION: Nerve cross-sectional area (CSA) is larger than normal in Charcot-Marie-Tooth disease 1A (CMT1A), although to a variable extent. We explored whether CSA is correlated with CMT clinical severity measured with neuropathy score version 2 (CMTNS2) and its examination subscore (CMTES2) in CMT1A. METHODS: We assessed 56 patients with CMT1A (42 families). They underwent nerve conduction study (NCS) and nerve high-resolution ultrasound (HRUS) of the left median, ulnar, and fibular nerves. RESULTS: Univariate analysis showed NCS and HRUS variables to be significantly correlated with CMTNS2 and CMTES2 and with each other. Multivariate analysis showed that ulnar motor nerve conduction velocity (ß: -0.19) and fibular compound muscle action potential amplitude (-1.50) significantly influenced CMTNS2 and that median forearm CSA significantly influenced CMTNS2 (ß: 5.29) and CMTES2 (4.28). DISCUSSION: Nerve size is significantly associated with clinical scores in CMT1A, which suggests that it might represent a potential biomarker of CMT damage and progression.

Ultrasound in the diagnosis and management of fibular mononeuropathy.

INTRODUCTION: Ultrasound (US) evaluation of peripheral nerves is a noninvasive, cost-effective approach to diagnosing focal mononeuropathies and guiding surgical management. We used the intranerve ratio to evaluate for possible cut-off values in diagnosis of fibular mononeuropathies (FNs). METHODS: A retrospective analysis of FN confirmed by electrodiagnosis (EDx) was performed to identify intranerve ratio values between affected and unaffected limbs at the fibular head and popliteal fossa. RESULTS: The optimal fibular head/popliteal fossa intranerve ratio to discriminate between limbs with and without disease was 1.25 (sensitivity, 51%; specificity, 71%). There was no statistically significant difference between affected vs unaffected limbs (ratio, 1.13; P = .15) nor in subgroup analyses. However, 25% of patients had structural lesions amenable to surgery. DISCUSSION: The utility of US in diagnosis of FN is limited using intranerve ratio data, but US has a distinct advantage over EDx for identifying treatable structural lesions.

Association of Serum Cholesterol Levels With Peripheral Nerve Damage in Patients With Type 2 Diabetes.

Importance: Lowering serum cholesterol levels is a well-established treatment for dyslipidemia in patients with type 2 diabetes (T2D). However, nerve lesions in patients with T2D increase with lower serum cholesterol levels, suggesting that lowering serum cholesterol levels is associated with diabetic polyneuropathy (DPN) in patients with T2D. Objective: To investigate whether there is an association between serum cholesterol levels and peripheral nerve lesions in patients with T2D with and without DPN. Design, Setting, and Participants: This single-center, cross-sectional, prospective cohort study was performed from June 1, 2015, to March 31, 2018. Observers were blinded to clinical data. A total of 256 participants were approached, of whom 156 were excluded. A total of 100 participants consented to undergo magnetic resonance neurography of the right leg at the Department of Neuroradiology and clinical, serologic, and electrophysiologic assessment at the Department of Endocrinology, Heidelberg University Hospital, Heidelberg, Germany. Exposures: Quantification of the nerve's diameter and lipid equivalent lesion (LEL) load with a subsequent analysis of all acquired clinical and serologic data with use of 3.0-T magnetic resonance neurography of the right leg with 3-dimensional reconstruction of the sciatic nerve. Main Outcomes and Measures: The primary outcome was lesion load and extension. Secondary outcomes were clinical, serologic, and electrophysiologic findings. Results: A total of 100 participants with T2D (mean [SD] age, 64.6 [0.9] years; 68 [68.0%] male) participated in the study. The LEL load correlated positively with the nerve's mean cross-sectional area (r = 0.44; P < .001) and the maximum length of a lesion (r = 0.71; P < .001). The LEL load was negatively associated with total serum cholesterol level (r = -0.41; P < .001), high-density lipoprotein cholesterol level (r = -0.30; P = .006), low-density lipoprotein cholesterol level (r = -0.33; P = .003), nerve conduction velocities of the tibial (r = -0.33; P = .01) and peroneal (r = -0.51; P < .001) nerves, and nerve conduction amplitudes of the tibial (r = -0.31; P = .02) and peroneal (r = -0.28; P = .03) nerves. Conclusions and Relevance: The findings suggest that lowering serum cholesterol levels in patients with T2D and DPN is associated with a higher amount of nerve lesions and declining nerve conduction velocities and amplitudes. These findings may be relevant to emerging therapies that promote an aggressive lowering of serum cholesterol levels in patients with T2D.