Clinical and Radiological Profile of 122 Cases of Idiopathic Intracranial Hypertension in a Tertiary Care Centre of India: An Observational Study
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.344644
Source of Support: None, Conflict of Interest: None
Keywords: CSF opening pressure, idiopathic intracranial hypertension, IIH, papilledema, radiological profile
Idiopathic intracranial hypertension (IIH) is a syndrome of elevated intracranial pressure (ICP) without any identifiable brain pathology and with normal cerebrospinal fluid (CSF) composition., The cause of this raised ICP is unknown and diagnosis requires the exclusion of other secondary causes of raised ICP, like mass lesions, meningitis, venous sinus thrombosis, or hydrocephalus. Pseudo tumor-like presentation has also been described in neuro Brucellosis More Details. Before the advent of CT or MRI scanners, the complaint of headache and the finding of papilledema raised the suspicion of hydrocephalus or tumor. When tests were negative for either of these conditions, confusing names for the syndrome were invented, which have led to the use of multiple inappropriate terms for this syndrome. The term pseudo tumor cerebri was invented to describe patients with papilledema who had neither hydrocephalous nor tumor. More recently, the syndrome has been called benign intracranial hypertension; however, in view of impending loss of vision it cannot be considered benign. None of these terms are satisfactory, thus the descriptive term IIHis preferred nowadays.
IIH is a common clinical entity; it is missed frequently by the general practitioner and leading to irreversible consequences like blindness. There are only a few large scale studies analyzing various clinical and radiological profile of the patients with IIH.
Aims and objectives
This study was planned to review all the cases admitted with diagnosis of IIH in the department of Neurology at tertiary care center of India with the objective of analyzing of the clinical symptoms and radiological profile of IIH cases and to determine the association of these with papilledema and CSF opening pressure.
It is a hospital-based observational descriptive analysis of clinical and radiological findings in cases of IIH. All eligible IIH cases reported in the previous 5 years period (from January 2014 to December 2018) were included in the study. There were total 122 eligible cases of IIH. Of those, 2 cases had pregnancy at the time of presentation (both in the second trimester). Cases fulfilling the modified Dandy criteria for IIH were included in the study. A detailed history and clinical examination including detailed fundus examination were done. Every patient underwent magnetic resonance imaging (MRI) of brain and magnetic resonance venogram/CT venogram, CSF manometry, and routine CSF analysis. Cases with reactive CSF with signs of inflammation were excluded from the study. Cases with secondary causes (CNS infections, intracranial space-occupying lesions, trauma, strokes, and cerebral venous thrombosis) of raised ICP, history of glaucoma, retinal disease, other disease involving optic nerve (multiple sclerosis, neuromyelitis optica spectrum disorders) were excluded from study.
Descriptive analysis was done for the mean and standard deviation of age and BMI. Contingency tables were prepared to analyze categorical data and the association of various study parameters. Categorical data were presented by percentage. Chi-square (χ2) test examined the statistical significance of each categorical variable. Statistical significance was defined as P value less than 0.05. GraphPad Prism (version 8.0.1) for windows program was used for statistical analysis.
The study was performed with prior approval from the ethical committee and written consent was taken from each of the patient participating in this study.
Among the 122 study subjects, 36 (29.51%) were males and 86 (70.49%) were females. Age range was 11 years to 73 years, the median age was 32 years and mean age was 33 years. Patients were grouped in various age ranges. Most cases fall in 21-40 years of age range [Table 1].
The patients were categorized into groups of normal BMI (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2), and obese (≥30 kg/m2) patients as per the World Health Organization criteria. Twenty-eight (22.95%) cases were having normal body weight, 32 (26.33%) were overweight and 62 (50.82%) were obese. The mean (±SD) BMI was 28.84 (±4.146) kg/m2 (range 19.33–37.78kg/m2).
Most common clinical symptom was headache followed by transient visual obscuration and visual impairment [Table 2].
The duration of headache ranged from 5 days to 8 years. Among the cases, 38 (33.33%) patients had acute presentation, 50 (43.86%) patients had subacute presentation, and 26 (22.81%) patients had chronic headache. Most common pattern of headache was holocranial, which was reported in 92 (80.70%) cases. The most common character of headache was throbbing, which was reported in44.74% cases followed by heaviness of head in 42.11%. Most of the cases (63.16%) reported the severity of headache as 5-6 on visual analog scale (VAS). The frequency of headache was daily in 78.95% cases and weekly in rest of the cases. In 52.63% cases headache was more after awakening in the morning.
The most common visual symptom was transient visual obscuration. Impairment of vision was seen in 64 cases. Of them, 47 cases had bilateral and 17 cases had unilateral visual impairment. Double vision (binocular) was due to abducens nerve palsy.
Bilateral papilledema was noted in 114 (93.44%) the cases (4 cases had modified Frisén grade I papilledema, 38 cases grade II, 40 cases grade III, 26 cases grade IV and 6 cases had grade V papilledema) and bilateral optic atrophy (secondary) in one (0.82%) case. Rest 7 (5.74%) cases were kept as IIH without papilledema (IIHWOP) based on clinical, radiological findings, and high CSF opening pressure.
Correlation of various clinical parameters with grades of papilledema was analyzed. Cases ofIIH without papilledema (IIHWOP) (grade 0) and low modified Frisén papilledema grades (grades I–III) were grouped together. Cases with high modified Frisén papilledema grades (grades IV–V) and secondary optic atrophy were grouped together [Table 3].
As depicted in [Table 3], TVO and double vision showed statistically significant correlation with higher grades of papilledema (P < 0.05). Visual impairment and tinnitus didn't show statistically significant difference between two categories of papilledema mentioned.
CSF manometry was performed in all the study subjects. Cut off values of CSF opening pressure for diagnosis of IIH were taken as >200 mm of H2O in non-obese cases and >250 mm of H2O in obese cases. CSF pressure was raised above cut off values in all the study subjects. CSF opening pressure was recorded <350 mm of H2O in 86 (70.49%) cases and ≥350 mm of H2O was recorded in 36 (29.51%) cases. Correlation of CSF opening pressure values with various clinical and radiological was analyzed [Table 4].
As depicted in [Table 4], visual impairment and double vision showed statistically significant correlation with high CSF opening pressure (i.e., ≥350 mm of H2O). TVO and tinnitus were also observed more in cases with high CSF opening pressure (i.e., ≥350 mm of H2O), but the difference was not significant statistically.
Higher grade of papilledema was also observed significantly more in cases with higher CSF opening pressure (i.e., ≥350 mm of H2O). Cases of IIHWOP had relatively low CSF opening pressure (mean = 261 mm of H2O) as compared to cases of IIH with papilledema (mean = 310 mm of H2O).
CSF biochemistry and cytology were within normal range in all cases. Cases with reactive CSF with signs of inflammation were excluded from the study.
In this study, empty sella was found to be the most common radiological sign (100/122; 81.97%). Other radiological signs were optic nerve sheath thickening (72/122; 59.0%), buckling of the optic nerve (60/122; 49.18%), flattening of the globe (57/122; 46.72%), bilateral stenosis of transverse sinuses (55/122; 45.08%) and optic nerve head protrusion (53/122; 43.44%). Correlation between radiological signs and CSF opening pressure was analyzed [Table 5].
As depicted in [Table 5], radiological signs like optic nerve sheath thickening, buckling of the optic nerve, flattening of the globe, bilateral stenosis of transverse sinuses and optic nerve head protrusion showed significant correlation with high CSF opening pressure (i.e., ≥350mm of H2O) (P < 0.05). Empty sella was the only radiological sign which did not show a significant correlation with high CSF opening pressure (P > 0.05).
IIH is a condition defined by elevated ICP in the absence of clinical, laboratory, or radiographic evidence of infection, vascular abnormality, space-occupying lesion or hydrocephalus.
IIH, or Pseudo tumor cerebri, was originally described as “meningitis serosa” by Quincke in 1897. He reported several cases of increased ICP without a brain tumor. Nonne described the syndrome later and coined the term “pseudotumor cerebri” in 1904. It was later referred to as “otitic hydrocephalus” by Symonds in 1931, “hypertensive meningeal hydrops” by David of and Dyke in 1937 and “toxic hydrocephalus” by McAlpine in 1987.,
This entity was first described over a century ago; still there is very little knowledge about its pathogenesis. Most popular hypothesis IIH is that it is a syndrome of reduced CSF absorption. Dysfunction of the absorptive mechanism of the arachnoid granulations or through the extracranial lymphatics may lead to decreased conductance to CSF outflow.
The annual incidence of IIH is 0.9/100,000 persons and 3.3/100,000 females between 15 and 44 years of age, most being obese. In this study, most common age group of presentation was 21 to 40 years (57.58%) with mean age of 33 years (range 11 years to 73 years). In many previous reports, mean age of presentation ranged between 29 to 32 years.,,, Females were affected more commonly then males (70.49% versus 29.51%). Various previous reports has shown more frequency of female cases as 89%, 92%, 93.83% and 97.57%. Proportion of female cases with IIH is found to be slightly less in this study as compared to various previous reports.
This study finds obesity (BMI ≥30 kg/m2) in 62 (50.82%) cases. 32 (26.33%) cases were found overweight (BMI 25.00–29.99 kg/m2). The mean (±SD) BMI was 28.84 (±4.146) kg/m2 (range 19.33–37.78 kg/m2). Various other reports have mentioned very high frequency of obesity among IIH cases (71% to 95%).,,,In an Indian study of 50 cases of IIH study by Gafoor et al., 64% cases found to have BMI ≥25 kg/m2 (32% overweight and 32% obese) with mean BMI of 27.71 ± 6.12 kg/m2. In a recent Indian study of 33 cases by Pal A et al., only 24.24% (8/33) cases were shown to have BMI of ≥25kg/m2. Although many western literatures report significant proportion of obesity among IIH cases, this study and some other Indian studies, found IIH in many cases with normal BMI too. Even non-obese cases presenting with signs of raised ICP with normal neuro imaging should undergo evaluation for IIH. Despite the association between IIH and an obese phenotype, the pathological mechanisms tying the two together are still not very clear.Although a study by Sugarman et al. suggested raised intra-abdominal pressure due to central obesity, increases cardiac filling pressure and obstructs venous return from brain, leads to increased intracranial venous and raised ICP. Another study bu Y Lampl et al. proposed relation between high level of serum leptins in obese women and IIH.
Among endocrine abnormalities, steroid withdrawal and Addison's disease are clearly associated with IIH,, the role of other endocrine abnormalities as risk factors remain unproven.
The most common clinical symptom was headache (93.44% cases). Other symptoms include transient visual obscuration (54.91%), visual impairment (52.46%), double vision due to abducens nerve palsy (29.51%) and tinnitus (28.68%). In a prospective study of 50 IIH cases, symptoms included headache (92%), transient visual obscuration (72%), intracranial noises/tinnitus (60%), visual loss (26%), and diplopia (38%). Headache is the most frequently reported symptom in IIH,,,, ranging from 78% to 100% cases of IIH. It is usually severe and of throbbing type, generalized, continuous, and associated with neck pain. It worsens in the morning and is increased by Valsalva maneuver. However, it may conspicuously be absent in some cases.
In this study, visual complaints like TVO and double vision showed a significant correlation with high grades of papilledema. Symptoms of visual impairment and double vision showed a significant correlation with high CSF opening pressure (≥350 mm of H2O). In a study of 165 cases by Kattah et al., TVO and double vision were observed more commonly among cases with high CSF opening pressure, but statistically non-significant.
Bilateral papilledema was observed in 93.44% cases. One case had bilateral secondary optic atrophy. Seven (5.74%) cases had IIH without papilledema. In a study of 353 cases, Digre KB et al. also found 5.7% cases of IIH without papilledema (IIHWOP). Papilledema of higher modified Frisén grades (grade IV-V) showed statistically significant correlation with higher CSF opening pressure (i.e., ≥350 mm of H2O) [Table 4]. Kattah et al. also found the similar correlation of high grades of papilledema and high CSF opening pressure.
Among radiological signs, empty sella was the most common (81.97%) finding. Other signs like optic nerve sheath thickening (59%), buckling of the optic nerve (49.18%), flattening of the globe (46.72%), bilateral stenosis of transverse sinuses (45.08%) and optic nerve head protrusion (43.44%) were noted in various proportions. All the observed radiological signs except empty sella were found to have a significant correlation with high opening pressure [Table 5]. In a study by Brodsky MC et al., the MR imaging found empty sella in 70% of patients with IIH, flattening of the posterior sclera in 80%, enhancement of the prelaminar optic nerve in 50%, distension of the perioptic subarachnoid space in 45%, vertical tortuosity of the orbital optic nerve in 40%, and intraocular protrusion of the prelaminar optic nerve in 30%. They concluded that in patients with IIH, all neuroimaging signs except for intraocular protrusion of the optic disc are highly significant for the presence of elevated ICP. Hingwala et al. found perioptic nerve sheath distension in 95.2% and empty sella in 76.2% cases. Contrary to other studies, we found empty sella as the most common radiological sign and it did not have statistically significant correlation with CSF opening pressure.
This study highlights clinical and radiological profile of IIH and their correlation with CSF opening pressure. This is probably one of the largest studies on IIH from India to best of our knowledge. Obesity and female sex (especially childbearing age group) preponderance in IIH have already been described in a large number of western studies. However present study differs as male sex and nonobese contributed to 29.51% and 49.18% cases, respectively, which is a newer observation. Similarly western literatures emphasize more on flattening of globe and optic nerve sheath distension as radiological findings of IIH, whereas in present empty sella was the most noticeable radiological observation. Another interesting observation was correlation of higher CSF opening pressure with higher grades of papilledema and radiological abnormalities around optic nerve rather than empty sella. Interestingly IIHWOP patients had milder rise in CSF opening pressure in comparison to patients with IIH with papilledema. To conclude, cases with clinical features of raised ICP and normal neuroimaging even in non-obese and male sex should be evaluated for IIH. Similarly early diagnosis of IIH while keeping high index of suspicion in patients of refractory headache and empty sella may prevent serious consequences like loss of vision in this subgroup of the patients.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]