As rapid development in radiological imaging, clinicians are able to make a more reliable diagnosis of IIH, combined with clinical and laboratory findings. Some imaging findings defined in the past decades can contribute to support or exclude the diagnosis of IIH in clinically suspicious cases. Several studies have reported significant correlations of imaging findings, such as empty sella, increased tortuosity of optic nerve, DPSS and flattened posterior globe/sclera with the diagnosis of IIH[2-4]. All these findings, together with intraocular protrusion of optic nerve head, bilateral transverse sinus stenosis or stenosis of a dominant transverse sinus, were adopted by the latest IIH guideline [5].
In this report, we found that ONS were Gd-enhanced confirmed by orbital MRI in 12 patients with IIH, which has never been reported in Chinese population before. Only a few studies in Caucasian mentioned the similar sign. A report from Brodsky MC[3] in twenty patients with IIH, discovered that enhancement of the prelaminar optic nerve has observed in 50% of these patients. Another two research observed also marked enhancement of optic nerve heads in patients with IIH[2,4]. But significantly different from the previous studies, Gd-enhanced ONS found in the present observation located in the retrobulbar segment of ON.
The median age of these 12 patients was 32.91±14.36 years, females account for the majority (83.3%), with common symptoms of IIH such as blurred vision (100%), headache (33.3%), and transient visual obscurations (41.67 %), pulsatile tinnitus (16.7%), and double vision1(7%). According to the IIH guideline of 2018[5], only 6/12 patients in this cohort (patient 1, patients 6, patient 7, patient 9, patient11 and patient 12) are “typical IIH” who satisfy the following criterion: female, childbearing age, obese BMI with typical symptoms. While four of the six patients with “atypical IIH” experienced misdiagnosis and mistreatment in local hospitals, especially those with longer clinical courses. These IIH sufferers had been misdiagnosed as “optic neuritis”, “ischemic optic neuropathy” or other optic neuropathies, and received treatment of intravenous/oral methylprednisolone in different dosage after misdiagnosis. But no obvious alleviation has made on these symptoms, inversely, they aggravated gradually. Then, all the patients received complete examinations together with lumbar puncture after receiving admission from our department. A rare imaging sign of IIH, enhancement in optic nerves/ ONS on MRI scan, surprisingly appeared in front of radiological and neuro-ophthalmological clinicians. The first possible diagnosis was a certain kind of optic neuropathy according to the medical records. However, the markedly elevated CSF-OP and chronic courses of the patients are confusing. Moreover, imaging findings, such as empty sella, DPSS, unilateral or bilateral TVSS, indicated the possibility of increased ICP. Series of in-depth tests were arranged to clarify underlying causes for secondary intracranial hypertension and optic nerves injury, including infectious/immunological diseases, medications, systemic disorders, obstruction to venous drainage, and so on. Finally, the diagnosis of IIH was confirmed. The lumbar puncture OP was one debatable area. It was reported that there seemed to be a “grey zone” of lumbar puncture OP between 25 cm and 30 cm H2O, people in “grey zone” might be normal for some individuals[6]. In this report, there are no such “grey zone” concerns, for CSF OPs of all patients were all above 30 cmH2O.
The etiology of IIH is still unknown, however, there has a strong connection between IIH and obesity. The pattern of fat distribution in patients with IIH may be relevant. The mechanical effects of excessive abdominal fat elevate intra-abdominal pressure, which increases intrathoracic pressure and, thereby, increases cerebral venous pressure, and, eventually leads to the intracranial hypertension[7]. Moreover, obesity is a chronic inflammatory condition, consequently, pathogenic inflammation may cause IIH [8-10]. But the hypothesis would not explain why only a proportion of all individuals with obesity develop IIH. Some researchers have shown a significantly increased level of the chemokine CCL2, IL-2 and IL-17 in CSF of patients with IIH , compared with controls[11, 12]. These investigations indicate that inflammatory factors are involved in the occurrence of IIH, although lack of compelling evidence. Immunomodulatory therapy therefore has not been listed as one of the main treatment strategies for the disease until now.
The principal pathogenic mechanisms of IIH has been in dispute, which makes it difficult to illuminate the abnormal singles of ONS detected in this report. Some scientists assumed that enhancement of the optic nerves is reflective of the same pathology leading to papilledema: increased pressure referred from the cranial fossa generates venous congestion, capillary leakage, and possible breakdown of the blood-retinal barrier[13]. It remains unclear that in which way and to what extent the CSF space is affected in response to increasing intracranial pressure. It has been assumed that what leads to increased transmission of CSF into the sheaths of optic nerves shall be ICP, which also impedes axoplasmic transport of synaptic vesicles, organelles, and molecules followed by optic nerve fiber swelling[14]. However, scientists have not found any correlation between increased ICP and the degree of hypophysis compression or the DPSS supporting this hypothesis. [15].
In this group, only 6 of 12 patients are obese, and methylprednisolone treatments were proved ineffective in patients received glucocorticoid therapy. Combined with negative laboratory tests, neither of obesity nor inflammatory factors could be used to clarify the causes of IIH and abnormal signals of optic nerves. Significantly elevated ICP (>30cmH2O) is one of the characteristics of these patients. Moreover, after receiving the treatments of lowering intracranial pressure, the visual functions and other symptoms of the patients has ameliorated., This suggests that intracranial hypertension plays a key role in the course of the disease. We tend to agree that increased pressure generates venous congestion and capillary leakage[13]. Possible Destruction of blood-brain barrier (BBB) around optic nerve aroused by elevated ICP, attributes to the abnormal signals of ONS. Regrettably, we failed to rearrange MRI scans for the patients in time when the symptoms became relieved, hence failed to observe whether the optic nerve signal disappears. In addition, whether inflammatory factors are involved in or not, still need to be further clarified through subsequent experiments.