This retrospective study of nine cases of THS based on ICHD-3 beta criteria showed that the clinical manifestations were variable. The sixth CN (72.73%) was most commonly involved, followed by the third (45.45%), and fourth CN (45.45%). Previous studies reported a high rate of third CN (78–91%) involvement[6, 7], however, Curone et al. reported a low rate of third CN (39%) involvement.[8] As such, CN involvement has been variably reported in each study. THS is usually treated with steroid, but there are no rules regarding drugs, formulations, routes of administration, or therapeutic doses. Steroid treatment generally includes prednisone, MPD, and dexamethasone given orally or by IV injection. In this study, five patients were treated with IV MPD at 1 g/day for three days, and six patients received oral MPD at 50 mg/day for seven days, then the dosage was tapered. The difference in treatment dose was determined in consideration of the patient’s age, the severity of their symptoms, and underlying diseases. After the initiation of MPD treatment, pain resolved within two days in all patients, and ocular motor limitation gradually improved. Other studies reported that most patients achieved pain relief within 72 hours and that CN palsy resolved over two to eight weeks.[6, 7] In the patients in this study, the recovery period varied from one to eight weeks, similar to the previous report. Steroid treatment relieves the pain quickly, but the signs do not resolve immediately after treatment. As in this study and previous studies, because steroid administration had dramatic effects, when THS is diagnosed, it is important to start steroid therapy immediately.
An accurate diagnosis is important for quick and appropriate treatment, but many diseases must be considered in the differential diagnosis of painful ophthalmoplegia. The role of MRI in the criteria has been included as "granulomatous inflammation demonstrated by MRI or biopsy” in the ICHD 3 beta criteria. In most studies and our study, no patient had a biopsy or pathological examination.[3, 4, 6, 7] Also, the lesion location is an important factor in the differential diagnosis, especially an orbital pseudotumor with characteristics and steroid response similar to THS.[9] Therefore, MRI plays a key role in the diagnosis of THS. Since THS can be diagnosed by anatomical location, MRI should be performed if THS is suspected in a case of painful ophthalmoplegia. The recurrence rate in our study (18.18%) was similar to that of Rui et al. (23%)[6] and Colnaghi et al. (21%)[3] but was lower than that reported by Zhang et al. (37%).[7] Two patients in this study experienced recurrences, one recurred after five weeks and the other had a history of THS diagnosis five years earlier. THS patients have a good prognosis but recurrences occur in about 21–50% of the cases over an interval of months to years.[3, 7, 10] Thus, because THS often recurs after a full recovery, it is important to consider follow-up and the possibility of a recurrence. In this study, the laboratory test results showed elevated ESR values in three patients, which were the patients with third, fourth, and sixth CN involvement. It is thought that blood test results can be considered a factor predicting the severity of inflammation.
Meanwhile, ON dysfunction has been reported, indicating that the pathological process may involve the orbital apex.[10] Two patients in this study had ON involvement and enhanced apex lesions were confirmed by orbit MRI. One patient had fourth CN palsy and ON involvement and recovered completely after steroid treatment. In contrast, in other patients with third, fourth, and sixth CN palsy, relapsed five weeks later with ON dysfunction and third, fourth, and sixth CN palsy. After high-dose steroid treatment, the ocular motor limitation was completely recovered, but the vision loss (recognition of hand motion) did not improve and a pale optic disc was observed at follow-up. Kline and Hoyt[10] reported that the optic disc may be normal, swollen, or pale in appearance, with visual decline ranging from minimal to blindness, and variable final visual acuity. In the two cases in this study, the opposite results were found. In one case, the visual acuity was completely recovered and in the other case, it was not recovered despite the same treatment. Although ON involvement is not common in THS, the occurrence of ON dysfunction should be confirmed through a visual acuity examination during the follow-up period and immediate treatment should be initiated. In addition, even if the ocular motor limitation have improved, it is necessary to check for recurrence or ON function through sufficient follow-up.
Our study had several limitations. First, it was a retrospective, single-hospital-based study, suggesting possible selection bias. Second, the sample size was small due to the relatively uncommon occurrence of the disease. Third, the follow-up intervals were not standardized and were not long-term. Nevertheless, this study showed the strength of analyzing nine cases and reporting various THS clinical symptoms. In conclusion, considering that THS may cause ON involvement, immediate treatment should be performed at the time of diagnosis. In addition, since there is a possibility of recurrence, long-term follow-up is necessary.