A 23-year-old woman presented to our center with long-standing history of spontaneous right median nerve mononeuropathy. Prior to presentation, her initial symptoms included difficulty keying with her thumb and index finger of her right hand. She gradually developed numbness in the right first and second fingers and associated weakness in the anterior interosseous nerve distribution. This weakness progressed until she was unable to flex the thumb at the interphalangeal joint or the index finger at its distal interphalangeal joint.
Initial management was undertaken at an outside institution. She had an electrodiagnostic study, the findings of which were felt to be consistent with anterior interosseous nerve (AIN) palsy with a superimposed mild to moderate carpal tunnel syndrome. At that time, approximately 1 year after the initial development of symptoms, she underwent a standard carpal tunnel release and median nerve release within the forearm. Despite this procedure, she did not regain function within the AIN distribution or sensation within the index finger. As a result, she then underwent cervical spine imaging which was non-diagnostic.
In the interval prior to her referral to our institution, her numbness progressed to involve the long finger with additional development of thenar eminence atrophy. She had a diffusely positive Tinel-like sign within the upper arm, which could not be well localized.
The patient was then referred to the senior author for further evaluation and management of a possible brachial plexus lesion. Based on the above findings she was presumed to be suffering from brachial neuritis (Parsonage–Turner Syndrome) with a superimposed carpal tunnel syndrome and she was taken for a re-release of the carpal tunnel with appropriate tendon transfers. This was performed 19 months after her first procedure.
Ten months after her second surgery, there was no improvement of sensation from her pre-operative status. Electrodiagnostic studies were repeated at this juncture and demonstrated a median mononeuropathy at or proximal to the branch to the pronator teres. An ultrasound of the median nerve, performed at time of the electodiagnostic studies, demonstrated a fusiform dilatation of the median nerve at the mid-humeral level (Fig. ). This investigation prompted further evaluation of the median nerve by MRI of the arm and proximal forearm. This study demonstrated a lobulated, hyperintense dilatation of the brachial median nerve measuring 2.8 cm in length and 1.1
0.7 mm in the axial dimension (Fig. ). The image was initially interpreted as consistent with a traumatic neuroma or perineurial scarring.
Figure 1 Ultrasound image depicting a the enlarged portion of the right median nerve with a cross-sectional area 46.7 mm2 and b normal left median nerve with a cross-sectional area of 8.1 mm2. Bar=1 cm, a = brachial artery. (more ...)
MRI image of the right arm depicting the enlarged lobulated enhancing region of the median nerve. a Pre-contrast, b enhancing, and c subtraction image of pre and post contrast images.
Given our concern for malignancy, exploration was undertaken. The median nerve in the upper arm was found to be dilated with palpable firmness for a length of approximately 5 cm. Above and below this region the nerve was normal in appearance, texture, and consistency. Internal neurolysis revealed that each of the fascicles in this region was uniformly dilated in a fusiform fashion, without a single predominant fascicle. Individual fascicles were stimulated and only limited pronation was found in a single fascicle. This fascicle was therefore preserved as were the lateral presumably sensory fascicles due to the preserved sensation in her thumb. The remainder of the nerve at this level was then excised and sent for pathologic evaluation. Neither nerve grafting nor nerve transfer was performed at the time of biopsy since her deficits had now been long standing.
On pathologic examination, epithelial membrane antigen (EMA) staining of involved fascicles was positive (Fig. ) while the S-100 stain was negative (Fig. ), demonstrating that the whorls of cells seen were indeed composed of perineurial cells and not Schwann cells, thereby forming pseudo-onion bulbs. Electron microscopy showed perineurial cells circumferentially enwrapping collagen and nerve fibers (Fig. ). S-100 did highlight scattered Schwann cells within the fascicles (Fig. ) as would be expected, but note that these are not the predominant cell as would be in a Schwannoma. Neurofilament staining showed some residual axons in the involved fascicles (Fig. ) corresponding to the degree of functional loss in this nerve.
Figure 3 This set of images shows our pathologic specimen of intraneural perineurioma with appropriate staining methods. a Epithelial membrane antigen. Original magnification ×1,000. Epithelial membrane antigen (EMA) positive staining shows pseudo-onion (more ...)
As the disease progresses, the amount of myelin and axons seen in the fascicles diminish and the collagen content increases (as seen in Fig. ). Conspicuous pinocytotic vesicles were seen within thin cell processes, an ultrastructural finding typical for cells of perinuerial origin. The latter figures (Fig. ) show progressive magnification of the lesion with the hematoxylin and eosin stain with involved fascicles appearing hyperchromatic in their periphery due to the hypercellularity of the perineurium (Fig. ), and pseudo-onion bulbs seen in the perineurial lesions(Fig. ). Based on the features discussed, the diagnosis of intraneural perineurioma was made.
One month following this biopsy her pronation strength persisted and has not subsequently undergone any further decline in function.