Histopathological effects of radiosurgery on a human trigeminal nerve
A 43-year-old female not known to have any concomitant medical problems was diagnosed to have classical trigeminal neuralgia 4 years ago when she presented with paroxysmal electric-shock-type pain involving the dermatomes of the left maxillary and mandibular trigeminal branches. Her symptoms were aggravated by eating, brushing her teeth, and drinking cold water. The maximal intensity of pain was at the left cheek and left side of the upper lip and radiating to the side of the nose. There was no history of any associated sustained background pain or sensory symptoms. Her pain responded well to carbamazepine initially; however, the dose was escalated after few months without complete control of her symptoms. Subsequently, she was treated with carbamazepine, pregabalin, and baclofen without complete resolution of her severe pain. The pain remained intractable to medical therapy with a visual analogue score (VAS) for pain of 10 points prior to medical therapy and 8 points after.\nOn clinical examination, there were no sensory deficits or dermatological changes at trigeminal nerve distribution and no abnormal neurological signs. Magnetic resonance imaging (MRI) of the brain did not reveal any signs of demyelinating disease, tumor, vascular malformation, or any other structural lesion. A small vessel was seen above the trigeminal nerve juxtpontine segment by MRI constructive interference in steady state (CISS) sequence []. Management options were offered for the patient, which included percutaneous procedures, radiosurgery, and MVD. After discussing the pros and cons of each procedure, the patient decided to go for radiosurgery.\nSubsequently, she underwent stereotactic image-guided radiosurgery using CyberKnife® (Accuray, Inc., Sunnyvale, CA, USA). A total dose of 60 Gy prescribed to 76% Isodose line covering 100% of the target, which consisted of a 6-mm length of the left trigeminal nerve cisternal segment []. Maximum dose to the target was 7894.74 cGy. This was delivered by a single fixed 5-mm cone with a total of 100 beams. The conformality index was 1.61, and the homogeneity index was 1.32. The stereotactic planning was carried out with fusing 1 mm cuts computed tomography (CT) scan with T1 3D MRI and 3D CISS sequence. Of note, the identified length of trigeminal nerve by MRI CISS sequence was 11.5 mm. The pain relief benefit started approximately 10 days after the procedure, and the patient continued to have 80% reduction of the lancinating trigeminal neuralgia pain (Barrow Neurological Institute (BNI) grade III).[] However, 2 months later, she started complaining of dull background pain with an intensity of 3 VAS and intermittent mild facial numbness at V2 distribution (BNI grade II for facial numbness). There was no change in the lancinating shooting pain pattern. The medications remained unchanged. The patient had a recurrence of the pain 8 months later with more frequent attacks than before the procedure and remained intractable to medical therapy. At that time, clinical examination showed reduced sensation at V2 and V3 and relative reduction in the corneal reflex on the left eye. No corneal ulceration was noted, and the patient had with normal visual acuity. MRI of the brain did not demonstrate any enhancement or signal changes at the trigeminal nerve and brainstem.\nWe elected to perform MVD to explore the nerve with possible partial sensory sectioning. The procedure was done under neurophysiology monitoring of the facial, vestibulocochlear, and trigeminal nerves on the left side in addition to motor evoked potential (MEP) and somatosensory evoked potential (SSEP). Electromyography (EMG) was used for trigeminal nerve monitoring. Intraoperatively, the trigeminal nerve appeared atrophied and flattened with grayish discoloration of the nerve rootlets []. An arterial loop was identified at the superior surface of the juxtpontine trigeminal nerve segment; however, the artery was not causing obvious compression []. This vessel was separated from the nerve by a Teflon patch. Partial sensory sectioning was done and a small nerve rootlets biopsy from the midcisternal nerve segment was taken and submitted for histopathological examination []. The interval between histological examination and radiosurgery was 13 months.\nThe submitted specimen was too small to be utilized for full staining methods. Therefore, the biopsy was completely processed for electron microscopy (EM). The toluidine blue-stained, epoxy-embedded section revealed fibrous tissue (fibrosis) and a few haphazardly arranged and distorted myelinated nerve fibers []. Some were thinly myelinated and many had empty or dense axoplasm. A regenerative axonal cluster was noted as well. Transmission EM revealed variably sized myelinated axons in a marked collagenous background []. Most axons had empty axoplasm with markedly degraded myelin sheaths. Few had filamentous axoplasmic inclusions. There were many degenerated myelin/myelinoid profiles in the background. No active cellular component was noted. The changes were suggestive of advanced traumatic/destructive process.