Researchers at Cleveland Clinic Weston Hospital are hoping to avoid the potential for unnecessary reoperations and potential morbidities in cases of delayed pain relief following treatment for trigeminal neuralgia (TN), one of the most prevalent facial pain syndromes.
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Led by Hamid Borghei-Razavi, MD, a board-certified neurosurgeon with the Headache & Facial Pain Center at Weston Hospital and Director of Cleveland Clinic’s Minimally Invasive Cranial and Pituitary Surgery Program in Florida, the team conducted a systematic review of available literature to investigate the occurrence of delayed response following microvascular decompression (MVD), the most common surgical treatment for drug-resistant TN.
Though rare, an estimated 15,000 people each year in the United States are diagnosed with TN, a chronic condition characterized by recurrent, unilateral, transient electric shock-like facial pains that usually start and stop abruptly.
“There are many nuances to the clinical diagnosis and treatment of trigeminal neuralgia, including how to manage a patient with a delayed response to treatment,” says Dr. Borghei-Razavi, who recently served as course director for TN at this year’s annual meeting of the Congress of Neurological Surgeons. “If we can identify the optimal duration for observation after treatment and factors that contribute to delayed relief, we can provide patients with better counsel and care.”
Of the three types of TN – classical, atypical and idiopathic – classical TN (type 1) is the most common, accounting for about 80% of cases. It is primarily caused by vascular compression of the nerve root near the brainstem.
Atypical TN (type 2) is associated with an underlying condition, such as multiple sclerosis or compression from a tumor, and usually presents with a different pain pattern that is less intense but more widespread. The least common form, idiopathic TN, has no specific identifiable cause.
“Pharmacologic therapy is usually the first-line treatment for trigeminal neuralgia, including anticonvulsant medications, skeletal muscle relaxants, and antidepressants,” says Anam Baig, DO, a board-certified neurologist who specializes in headache and facial pain. “While this approach can be initially effective for many patients, some will have a tapered response to medication that diminishes with time.”
Dr. Baig is part of Cleveland Clinic Weston Hospital’s Trigeminal Neuralgia program, which includes a multidisciplinary team of specialists in neurology, neurosurgery, pain management, and neurointerventional radiology. Established approximately four years ago, the Florida program is patterned after its counterpart in Cleveland, Ohio, and is one of the highest-volume centers in the region.
“For drug-resistant TN, our team can offer other treatment modalities including microvascular decompression and neuroablative procedures, such as stereotactic radiosurgery and percutaneous balloon compression,” says Dr. Baig.
According to Dr. Borghei-Razavi, MVD is the most successful surgical approach for type 1 TN with about 90% of patients achieving pain relief and some for as long as 10 years. It is a microsurgical technique used to relocate the vascular compression and relieve the pressure on the nerve.
“While many of our patients achieve immediate pain relief with microvascular decompression surgery, a small portion experience a delayed response that can take weeks or even months to manifest,” he says.
To investigate the occurrence of delayed response following MVD and to identify potential contributing factors, the Cleveland Clinic team conducted a systematic review of available literature from 1975 to 2022. The study was published this year in Neurological Sciences.
The team identified 28 eligible studies out of 2543 screened reports. Their analysis included 2869 patients who underwent MVD for TN, with 322 cases of delayed pain relief. Based on their review, the team determined an average incidence rate of 10.5% for delayed response, with a range of 0.95 to 57.14% across the different studies.
“The reported time to pain relief in the studies ranged from 4 days post-surgery to 74 months, with a median duration of 1 month,” says Dr. Borghei-Razavi. “But the majority of delayed cases experienced pain relief within 3 months.”
Further analysis of 11 studies that included detailed data from the cases of delayed response identified a “significant female predominance, surpassing the observed ratio in the general TN population.” The researchers also found that venous involvement was a significant contributing factor.
Along with the systematic review, the recent Cleveland Clinic study included two cases from Weston Hospital demonstrating the delayed response phenomenon.
The first was a 72-year-old male who presented with type 1 TN affecting the maxillary (V2) and mandibular (V3) nerve branches on the right side of his face. He experienced medically refractory pain for 2 years prior to being referred to Weston Hospital. Imaging revealed compression of the trigeminal nerve by the right superior cerebral artery in the cisternal segment.
“The patient’s pain was unchanged immediately following the decompression procedure, but eventually resolved after a period of 2.5 months,” describes Dr. Borghei-Razavi. “At his 12-month follow-up, he remained pain-free and required no medication.”
The second case was a 41-year-old female whose pain persisted for 3 years prior to referral. She also presented with right-sided facial pain in the V2 and V3 distribution resulting from compression of the trigeminal nerve by the right superior cerebral artery within its cisternal segment.
“In this case the patient had a brief period without pain following the surgery before it gradually returned, raising the prospect of retreatment,” says Dr. Borghei-Razavi. “But at 3 months post-op, the patient’s pain again began to improve, allowing us to reduce her medication dosage. By 6 months she was pain-free with no medication.”
Right now there is a lack of consensus on the appropriate timing for retreatment in patients who do not have an initial favorable response after MVD, notes Dr. Borghei-Razavi.
“Based on our review, we propose a minimum observation period of 3 months before contemplating reoperation, though individual patient-specific factors require flexibility in this timeframe,” he says.
Specifically, the literature review suggests that “female patients with typical right-sided TN and venous compression” are more likely to experience delayed pain relief and may merit a longer observation period.
“Our hope is to one day develop post-operative guidance and decision-making support tools to help avoid unnecessary reoperations and potential morbidities,” says Dr. Borghei-Razavi, who also serves as Research Director of the Neurosciences Institute for Cleveland Clinic in Florida. “This study brings us one step closer, but more research is needed to determine the quantitative value of each contributing factor.”
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