Involvement of inflammatory mechanisms and changes in cytokine levels has been proposed recently as a theory for IIH pathophysiology especially as it is sometimes associated with immunologic disorders such as systemic lupus erythematosus (SLE) and antiphospholipid syndrome and it may also show a fluctuating course with “remission and relapses” like that seen in autoimmune disorders. However, the exact pathophysiology of it is still not clear [8, 9].
Interleukin-4, IL-10, and TNF-α are involved in the pathogenesis of autoimmune disorders such as SLE [10] which is commonly associated with IIH. There is growing evidence showing that cytokines play crucial roles in the pathology of various neurological disorders and therefore are potential targets for the development of novel and effective therapeutics for central nervous system diseases [11]. Accordingly, guided by the theory of involvement inflammatory mechanisms in IIH pathogenesis, this study aimed to detect the serum levels of IL-4, IL-10, and TNF-α and the presence of OCB in CSF in IIH patients and their relation to the severity of the condition.
In this study, a statistical highly significant difference was found between IIH patients group (n = 27) and control group (n = 21) as regards to the levels of IL-4, IL-10, and TNF-α being higher in IIH patients than controls (p < 0.001); our results agreed with Altıokka-Uzun and colleagues [6] and with Dhungana and colleagues [12]. While it disagreed with Edwards and colleagues [4] who found no significant difference in serum levels of these cytokines between IIH patients and healthy controls while they were higher in the CSF of IIH patients than healthy controls. It may be explained by intrathecal synthesis of these cytokines that may diffuse to the serum [4].
Samanci and colleagues [13] disagreed with our results as they found that levels of TNF-α were significantly lower in IIH patients than in normal controls (p = 0.008); this difference can be explained by using different methods in detection of TNF-α, as they used multiplex immunoassay while this study used the ELISA method, also their study included IIH patients with other comorbidities including hypertension, hypothyroidism, diabetes mellitus, psoriasis, and juvenile myoclonic epilepsy while our IIH patients had no comorbidities.
In the present study, it was found that 6 patients out of 27 IIH patients had positive CSF oligoclonal bands which conformed to the results of Samanci and colleagues [13] and Altıokka-Uzun and colleagues [6]. In a study conducted by McLean and colleagues [14] on isoelectric focusing of CSF in patients with different neurological disorders including IIH patients, they found that CSF of IIH patients was negative for local synthesis of IgG by oligoclonal banding.
Results of the current study showed that there was a statistically significant difference between OCB +ve and –ve patients as regards to the duration of illness (p = 0.033) being longer in OCB +ve patients with a mean of (27.5 + 15.92 months) than in OCB –ve with a mean of (11.76 + 11.25) while there were no statistically significant difference between both groups regarding age (p = 0.887) or age of onset (p = 0.842). These results agreed with Haertle and colleagues [15].
In this study, TNF-α level was significantly higher in OCB +ve than in OCB −ve patients (p < 0.001) while there was no significant difference between both groups as regards to the levels of IL-4 and IL-10 which agreed with Altıokka-Uzun and colleagues [6]. Samanci and colleagues [13] found that there was no significant difference between OCB +ve and OCB –ve IIH patients regarding TNF-α serum level but they did not mention demographics (age, duration of illness, and BMI) or compare comorbidities of both subgroups.
In the current study, it was found that there is statistically significant positive correlation between opening pressure and serum level of TNF-α (p = 0.047, r = 0.386) which confirms the inflammatory hypothesis in IIH, and insignificant positive correlation between it and IL-4 (p = 0.071, r = 0.353) or IL-10 (p = 0.632, r = 0.097). TNF-α by its proinflammatory role may be related to severity of IIH [6] while it did not conform to Edwards and colleagues [4], this difference can be explained by statistical methods used in each study as they used simple linear regression while we used Pearson’s correlation test.
In this study, a statistically significant correlation between BMI and opening pressure (p = 0.002) and significant difference in BMI in patients with or without history of TVOs (p ≤ 0.001), tinnitus (p = 0.031), phonophobia (P = 0.01), and visual field deterioration (p = 0.009) were found. This result agreed with Rowe and Sarkies [16] and Bruce and colleagues [15]. This relation to obesity can be explained by that increased intra-abdominal pressure produces raised intracranial pressure by elevating the diaphragm and increasing the intrathoracic pressure, leading to reduced cerebral venous return by the jugular system. This in turn would obstruct cerebral venous outflow, raise cerebral blood volume, and increase intracranial pressure by preventing normal cerebrospinal fluid absorption [16].
This study showed no statistically significant correlation between BMI and levels of IL-4, IL-10, and TNF-α (p ≥ 0.05); this result conformed with Altıokka-Uzun and colleagues [6] and Charles and colleagues [17] while it disagreed with Esposito and colleagues [18] who found significant negative correlation between level of IL-10 and BMI.