The IIH is a syndrome of elevated ICP with obscure etiology. An underlying prothrombotic state would explain at least a part of its pathogenesis [12]. The d-dimer is a by-product of fibrinolysis and has an already established role in the diagnosis of venous thromboembolism and disseminated intravascular coagulation [13].
Our results showed a statistically significant higher mean of d-dimer among the cases compared to the controls. This result agrees with Kesler A. et al. 2010 [4]
Headache is the most common presenting symptom in IIH [2]. The HIT6 score improved statistically in all the patients on follow up after 1 and 6 months which agrees with Friedman D. and his colleagues who used the acetazolamide as a treatment for IIH [14].
Statistically significant differences were found in HIT6 score after 1 and 6 months follow up with lower mean in group [2] indicating that the headache improved much more in patients who did not receive anticoagulant therapy. This discrepancy between both groups in headache improvement can be explained by the fact that the present headache could be associated with tension type headache, depression, or psychosomatic symptoms. Nevertheless, the HIT6 score is a subjective evaluating method and not objective.
Regarding the ophthalmological assessment, our results showed a statistically significant improvement in papilledema’s grade at 6 months follow up among both groups which agrees with Wall M [15] who explained that the acetazolamide works by inhibition of carbonic anhydrase leading to reduction in sodium ions transport across the choroid plexus epithelium. There was a statistically significant decrease in papilledema after 6 months among patients who received anticoagulant treatment with acetazolamide while no statistically significant difference between both treatment groups after 1 month may be because the papilledema takes time to resolve.
Concerning the visual acuity, there was a statistically significant improvement in log-MAR after 6 months among both groups of patients which agrees with Wall M 15]. The improvement was more noticed in patients who received anticoagulant therapy.
Visual field assessment was considered the main criterion to assess the clinical improvement in IIH patients [16]. There was a statistically significant improvement in visual field after 6 months among patients who received anticoagulant therapy and acetazolamide. On the other hand, there was no difference in visual field follow up among patients who did not receive anticoagulation which disagrees with Wall M. [15] who found an improvement in visual field after 6 months among IIH patients who received acetazolamide added to low sodium diet. Moreover, Celebisoy N. and co-authors [16] showed visual field improvement on either acetazolamide or topiramate considering that the two medications exert their effect through the carbonic anhydrase inhibition. Nevertheless, Koc F and his colleagues 2018 [17] showed in their recent study that the weight reduction combined with acetazolamide significantly improve the visual field in IIH patients. The discrepancy in the results could be attributed to different methodology applied in the studies.
Finally, the VEPs results showed a statistically significant decrease in latency and significant increase in amplitude after 6 months among both groups with more improvement among the group who received anticoagulant therapy. This result was in accordance with Hamurcu M. and co-authors [18] who reported that the papilledema initially does not disrupt the function of the optic nerve and retinal nerve fiber layer (RNFL), but it may lead to an elongation of the p100 latency in VEP test and an increase in RNFL. After elimination of the effect of edema, changes in the optic nerve and RNFL improve. When papilledema is not treated and becomes chronic, ischemic symptoms may occur with the effect of pressure on the nerve fibers and RNFL. Therefore, early diagnosis and treatment are extremely important.
Up to our knowledge, this study is the first to investigate the quantitative d-dimer serum level in IIH patients and to study the role of anticoagulant therapy in IIH cases. The results obtained prove the possibility of an unrecognized non-occlusive venous cerebral thrombus impeding the CSF drainage as described in previous studies [3, 4]. We can assume that the anticoagulant therapy disrupted these microthrombi and improved the CSF drainage which was manifested by the improvement of the papilledema, visual field, visual acuity, and the VEPs results.
The limitations of this study were the small sample size and the absence of objective instrumental findings demonstrating the presence of unrecognized non-occlusive venous cerebral thrombus impeding the CSF drainage.
To conclude, our study demonstrated the presence of high serum quantitative d-dimer levels among the IIH patients and showed an improvement in visual assessment after 6 months in both groups of patients; more apparent in the cohort who received anticoagulant therapy added to the acetazolamide. Routine screening of d-dimer level is recommended in patients with IIH. Further studies are warranted for objective instrumental findings able to detect this unrecognized non-occlusive venous cerebral thrombus. Also, larger studies are needed to establish guidelines for the use of anticoagulation in IIH patients.