Intraneural cyst of peripheral nerve: scientific literature review and clinical case analyze

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The etiopathogenesis of these formations remains undetermined even today, and in the scientific literature there are even different names for this pathology -for example -intraneural pseudocyst.
A ganglion is a cystic structure that has an inner lining formed by flat spindle cells and contains mucin [2,3].Most often, such formations occur in the perineurium of the peroneal nerves; however, they can also form in the peripheral nerves of the upper limbs (ulnar, radial nerve).Theories of the INGC pathogenesis are still remain controversial.At present the most proven and accepted is the theory of cyst formation as a result of development of communication channel between the nearest synovial joint and the epineurium of the corresponding peripheral nerve («articular theory») [4].
The capsular defect of the synovial joint or the formation of a pedunculus of the membrane, for example, as a result of an injury, leads to the move of synovial fluid into the articular branch of the nerve.Further, the pressure of the synovial fluid contributes to the flow of a certain amount of synovial content directly to the epinevrium, which can cause symptoms of the nerve bundles compression; at this time the fluid can be organized into a cyst-like formation [2,3].Thus, taking into account this etiopathogenetic mechanism, it is necessary to find and disconnect the channel of communication between cyst and synovium of the joint during surgical intervention for cyst relapses prevention.
The clinical appearance of INGC is associated with the displacement and compression of the nerve bundles, which leads to pain, paresthesia, and muscle problems in the innervation zones of the involved nerve.During the clinical evaluation of the involved nerve, it is possible to detect surface thickening and varying degrees of sensor-motor disturbances along its distribution.The clinical picture of intermittent motor paralysis and sensory disturbances at an acute onset may mimic other pathological conditions, such as radiculopathy, pathology of the pelvis and shoulder, and may complicate and delay proper diagnosis.
The diagnosis of INGC can be confirmed by imaging techniques such as magnetic resonance imaging (MRI) and high-resolution ultrasound.
Nerve paralysis is usually reversible if the nerve is surgically decompressed at an early stage.To prevent recurrence, the connection of the cyst with the joint should be identified and destroyed during surgery.In the world literature, clinical cases of intraneural ganglion cyst of the radial, ulnar, sciatic, peroneal and calf nerves are described.
At the same time, it should be noted that despite the evidence and confirmation of the articular theory in the pathogenesis of INGC of the sciatic and peroneal nerves, no connection of the cyst with the elbow joint was detected during surgical interventions for INGC of the ulnar nerve [4].
Taking into account rather rare character of this pathology, it is rational to describe and publish all clinical cases for their further systematization and analysis with the aim to achieve a progress in understanding of the pathogenetic mechanisms of the cyst formation and, accordingly, use of the most effective approaches to treatment.

MATERIALS AND METHODS
This article describes and analyzes a clinical case of an intraneural ganglion cyst of the sciatic and peroneal nerves, for the first time in Ukrainian scientific literature.

RESULTS AND DISCUSSION
No published case of intraneural ganglion cyst of the sciatic and peroneal nerves was found in the Ukrainian sources.Therefore, presenting this clinical case will help to enrich knowledge about various manifestations and course of intraneural ganglion cyst of sciatic and peroneal nerves, and early diagnosis will help to achieve success in surgical treatment and regression of neurological consequences.

Clinical case
Patient T., DOB 01.04.1975, male, had pain in the knee joint, periodical weakness and numbness in calf and foot of the right leg for more than a year.Before the appearance of these symptoms, he was healthy, did not have any medical history in the past.The pain had a burning character, occurred periodically, sometimes reaching an unbearable level, when patient could not walk more than 200 m.
Decrease in physical activity and rest of the limb brought relief, the pain went away on its own without taking any remedies.The patient underwent an outpatient ultrasound examination (US) of the extremities and received the result: deep vein thrombosis (DVT) and rupture of the Baker's cyst of the right leg.Appropriate treatment was prescribed, which brought some relief to the patient, probably due to prescribed restful regimen.Subsequently, the clinical signs progressed in a wave-like manner, and after some time the patient began to notice the increase in weakness of dorsiflexion and abduction of the right foot.
In the conditions of martial law, the patient was conscripted into the military, and was referred for the medical evaluation.Having a history of DVT, he had been sent for consultation to vascular surgeon, who in turn recommended an ultrasound of the veins of the lower extremities to clarify the diagnosis.
Prior to instrumental examinations, the patient underwent a comprehensive laboratory examination.Below are the results of the lab tests.19.04.2023.Ultrasound of the veins of the lower limbs: Superficial and deep veins of the right lower limb are passable.Thrombosis was not detected.Blood reflux is not recorded.On the back surface of the limb, extending from the middle third of the thigh to the middle third of the calf, at a depth of up to 30 mm from the surface of the skin on the thigh and 15 mm on the calf, along the way of the sciatic nerve on the thigh and the vascular-nerve bundle in the popliteal fossa, and along the peroneal nerve on the cruris, -an avascular, anechoic tubular structure is visualized, 16-17 mm thick, with a clear uneven contour, with linear hyperechoic layers present, that create the appearance of «cells» (Fig. 1a, b).
Visual connection with the main vessels, the knee joint was not detected.Conclusion: ultrasound signs of impaired blood flow in the veins of the right lower limb were not detected.Bulky formation of the soft tissues of the thigh of the right leg (Disease of the sciatic nerve?Differential diagnosis: lymphoma, neuroma, neurofibroma, perineurinoma?).
The next stage of examination was MRI, as this method is the method of choice for the nerves surrounding soft tissues visualization 18.04.2023.MRI of the soft tissues of the right leg (Fig. 2, 3).A series of MR tomograms of the right lower extremity revealed uneven expansion of the anterior and posterior tibial, popliteal, and deep femoral veins As we can see both MRI evaluations (made on 18.04.2023and 20.04.2023 -as a second opinion by another radiologist) were focused on venous pathology, but at the same time had significant differences between them, as they described the state of DVT in the acute stage in the first case, and the residual phenomena of past thrombosis in the second.Taking into account the conflicting results of the two evaluations, a decision was made to get an additional independent consultation of MRI images at an alternative medical institution.To compare the conclusions, we present the third MRI description.20.04.2023.In the projection of the sciatic nerve of the right leg with extension to the level of the bifurcation and proximal parts of the common peroneal nerve, a tubular-shaped, uneven diameter (≈ 9-16 mm), cyst-like formation (high signal in T2-weighted image, reduced signal in T1-weighted images), with fairly clear contours is present.Surrounding adipose tissue with minimal MR signal enhancement on STIR images due to edema.On the presented DWI images, the formation shows no signs of diffusion restriction (measurable diffusion coefficient ≈ 2.1-2.7×10-3mm 2 /s).
The superficial femoral artery and vein as well as popliteal artery and vein were found in a typical places with unchanged appearance (uniform width with clear and even contours, hypointense signal in T2, STIR images).At the same time, moderately pronounced diffuse edema of the popliteal muscle was visualized.In the area of the medial process of the tibia of the right knee joint, a diffuse uneven trabecular edema is visualized, a significant amount of effusion is noted in the joint and adjacent bags.
Conclusion: MR signs of a cyst-like formation in the projection of the sciatic and common peroneal nerves, which may be caused by an intraneural ganglion cyst.
Taking into account the complaints, the clinical course of the disease, its duration, the diagnostic search was directed to determine the nature of the cyst, which was detected by ultrasound and MRI.In order to rule out the nerve damage, in addition to the clinical neurologic examination and imaging methods, it was recommended to perform electrophysiological studies, including electromyography and nerve conduction studies.On the same day, April 28, 2023, an MRI of the right knee joint was performed.
As we can see on Fig. 4, at the MRI of the knee, presence of the intraneural ganglion cyst of the peroneal nerve was diagnosed and confirmed.MRI conclusion: MR signs of peripheral subcapsular damage of the posterior horn of the medial meniscus, degenerative changes in the lateral meniscus, anterior horn and body of the medial meniscus (grade 2 by Stoller), third-degree chondromalacia. of the medial facet of the kneecap, ligamentopathy of the anterior cruciate ligament, osteoarthritis of the I-II stage, quadriceps tendinopathy, swelling of prepatellar soft tissues.
The detected multicystic fluid collector along the course of the vascular-nerve bundle, according to MR characteristics, corresponds to peroneal intraneural ganglion cysts.Detected changes in the MR signal from the belly of the popliteal muscle require differential diagnosis between neurotrophic and edematous changes.
Soon 8.06.2023, after pre-operative examinations, surgical removal of the cyst with excision of its walls and preserving the integrity of the sciatic and fibular nerves was performed (Fig. 5).
During the surgery, neurolysis of the fibular nerve was performed at the level of the fibula shin (Fig. 5).Also denervation of the branch of the peroneal nerve to the capsule of the medial compartment of the knee was performed.Neurolysis of the sciatic nerve was performed, the epineurium was dissected and the intraneural ganglion was resected.
The medial compartment of the knee was mobilized, resection of the articular surfaces was performed, and the connection of the joint with the INCG was disconnected.The early postoperative period was uneventful, the postoperative wound healed with primary intention.
Monitoring of the physical condition of the right lower limb in dynamics was recommended.
On 20.07.2023, the patient came for ENMG monitoring of the right lower limb.
The conclusion of the control ENMG: compared to 21.04.2023, a negative dynamic is observed: the muscle response to stimulation of the right fibular and tibial nerves decreased (the strength of the flexor muscles of the right foot remained up to 22%, the extensor muscles of the right foot -up to 60%, the left -up to 68% of the normal).The conduction speed by motor and sensory fibers of nerves on the right is reduced.Reflex excitability of spinal motoneurons of the lumbar thickening on the right -4%, on the left -44.8% (normal 17-27%).Conclusion: ENMG signs of the pronounced axonal-demyelinating motor-sensory lesion of the tibia and fibula nerves (at the level of the knee joint).
During the examination 1.5 months after the operation, the patient noted a slight recovery of sensitivity in the area of the lower leg and foot, the burning pain no longer bothered him.The feeling of numbness still remained, but it no longer prevented him from physical activities and work.
The concept and pathogenesis of intraneural ganglia has been the subject of research, debate, and controversy for 200 years [4,5].Intraneural ganglion cyst of the sciatic and peroneal nerve is a rare pathology in the adult population, mostly occurring in young men with an average age of 34 years.The articular (synovial) theory of pathogenesis describes a common origin of intraneural cysts, even if they arise in unusual locations [6].In this clinical case, the connection of the intraneural ganglion with the proximal intertibial joint was found and resected intraoperatively.
The «gold standard» of INCG diagnostics is MRI.Magnetic resonance imaging provides a better assessment of the regional anatomic relationships, including the connection to the joint through the pedicle and the extra-or intraneural location of the cyst [7][8][9].Ultrasound is another method for detection of the soft tissue masses and can be useful in unclear cases, but this method has certain limitations, such as difficulty in differentiating between benign and malignant tumors and detecting of the cyst-to-joint connections [10][11][12][13].
The treatment strategy is complete surgical removal and excision of the intraneural cyst.Targeted and precise dissection with the help of an surgery microscope often allows complete removal of the cyst without damaging the nerve bundles, thus creating conditions for good functional recovery.Literature data indicate recovery of limb function within 45 days to 1 year after surgical removal of the cyst [14][15][16][17].But another article reported that despite surgical removal, sometimes neurological symptoms (foot drop) persist without recurrence of the cyst [18,19].
The degree of recovery depends mostly, unfortunately, not on the skill of the surgeon, but on the early diagnosis of the cyst.According to the literature data, late diagnosis or late referral to the hospital is considered to be 7 and more months after the onset of nerve palsy [20][21][22][23][24][25].In this clinical case, the delay in surgical treatment arose as a result of erroneous conclusions regarding the ultrasound picture of the pathological condition at the beginning of the disease.The combination of thorough knowledge of anatomy and ultrasound semiotics, the clinical experience of the operator with the capabilities of modern equipment is decisive in the verification of pathological changes and selection of the optimal treatment tactics.

CONCLUSIONS
An intraneural ganglion cyst of the sciatic and peroneal nerves is a rare cause of peripheral neuropathy, which is completely curable with timely surgical intervention, but requires the awareness of doctors of various specialties regarding this pathology to avoid errors in differential diagnosis and treatment approaches.Knowledge of the articular theory of the pathogenesis of INCG can improve the results of surgical treatment to avoid recurrence.Early diagnosis and surgical treatment play a crucial role in the full recovery of motor and sensory functions.
up to 13 mm, up to 300 mm long, with heterogeneous hyperintense on T2 and weakly hyperintense on T1 W1 with signs of diffusion restriction, which is more likely due to thrombosis.Moderate swelling of the interfascial fatty tissue is determined by the course of these vessels.Posterior tibialis muscle with signs of interstitial edema.Pathological changes in MR signal intensity from thigh muscles are not detected.The femur is intact.Lymph nodes are unchanged in size and structure.Conclusion: DVT of the right lower extremity without signs of recanalization.20.04.2023.MRI of the right leg consultation (middle lower third of the thigh, upper third of the lower leg from 18.04.2023).An MR tomogram shows uneven expansion of the veins of the lower limb, namely the anterior and posterior tibial, popliteal, and deep veins of the thigh, up to 15 mm in diameter, with a total length of up to 300 mm.Slight swelling of the surrounding fatty tissue.Muscles of the thigh and lower leg without visible changes.The MR signal from the bone marrow of the femur, tibia and fibula is unchanged.Conclusion: at the time of examination, there were signs of varicose changes of the anterior and posterior tibial veins, the popliteal and deep veins of the thigh with signs of slight edema of the surrounding fatty tissue, which may correspond to the residual changes of the previous acute thrombosis.Additionally: a stress fracture of the medial meniscus, synovitis of the left knee joint is determined.

Fig. 1a .
Fig. 1a.Ultrasound examination of the soft tissues of the thigh of the lower extremities, transverse image.Comparative images of the right and left sciatic nerves.Bulky formation of the soft tissues of the thigh of the right lower limb Fig. 2. Magnetic resonance imaging of the lower extremity (middle and lower thirds of the thigh, upper third of the calf), sagittal images in the STIR mode (a) and in the THRIVE (3D T1) mode (b).Cyst-like changes along the course of the sciatic and common peroneal nerves

Fig. 3 .
Fig. 3. Magnetic resonance imaging of the lower extremity at the level of the knee joint, axial images in T2 mode.Cyst-like changes in the area of the vascularnerve bundle of the popliteal region

Fig. 4 .
Fig. 4. Magnetic resonance imaging of the right knee joint, sagittal images in the PD-fsat mode.Intraneural ganglion