Abstract
Idiopathic intracranial hypertension is an enigmatic disorder of elevated cerebrospinal fluid pressure. In adulthood, patients are typically obese women of childbearing age; however, in young children the clinical picture is strikingly different, indicating age-related differences in the aetiology of idiopathic intracranial hypertension. To investigate this phenomenon, we analysed the clinical details of 15 pre-pubertal children with the diagnosis of idiopathic intracranial hypertension. Evaluating the date of initial presentation, we discovered a distinct seasonal variation. Ten patients presented between November and March, thus coinciding with the typical season of paediatric viral and bacterial infections in Germany. Therefore, we suggest an association between intracranial hypertension and possibly concurrent infections in these children. Moreover, eight children presented only with ophthalmologic findings without any other obvious symptoms, raising questions regarding the incidence of undetected cases, particularly in this age group.
Keywords
Introduction
Idiopathic intracranial hypertension (IIH) is a puzzling disorder of raised cerebrospinal fluid (CSF) pressure for which no causative factor can be identified (1). It may be complicated by severe headaches and the feared consequence is permanent visual loss. Recognized primarily in adults, there is a strong female preponderance and an association with obesity. However, in young children the characteristics of this disease differ. In the pre-pubertal age group IIH affects boys and girls equally and obesity is not a common association (2,3). In contrast, the condition in post-pubertal children has similar characteristics to the disease in adults. This obvious discrepancy in the clinical presentation indicates age-related differences in the aetiology of IIH. So far, there exists no plausible theory explaining this phenomenon.
Methods
We reviewed records of 19 pre-pubertal children with suspected IIH, seen at our hospital between 1997 and 2006. Diagnosis was established according to Dandy's Modified Criteria (1): raised CSF pressure above 25 cm H2O, normal CSF contents, no neurological abnormality other than papilledema or abducens palsy, normal brain MRI, and exclusion of underlying conditions. The existence of an associated factor was determined on the basis of patient's history, results of physical examination, findings on neuroimaging, and results of laboratory work-up (including screening for anaemia, infections, and endocrine abnormalities). A simplified classification of headache was used as available data were not detailed enough to apply the International Classification of Headache Disorders in all patients. We defined five types of headache according to the temporal pattern (4): acute headache, acute-recurrent headache, chronic-progressive headache, chronic-daily headache, and mixed headache.
Furthermore, we investigated the date of initial clinical presentation. Pubertal development was determined according to the Tanner staging system. Body mass index (BMI) was expressed as kg/m2. All subjects were defined as obese on the basis of a BMI >97th percentile for age and sex, using the local growth charts. As a control group we analysed charts of eight adolescents, diagnosed with IIH at our hospital.
Statistical analysis of seasonal variation was performed using the chi-square test for categorical data. To allow for statistical analysis of this small cohort of patients, the time point of presentation was categorized into two groups, defined as winter (November–March) and summer (April–October) season.
Results
Fifteen patients fulfilled the criteria for the diagnosis of IIH. Four children were excluded because an associated factor could be identified (sinus thrombosis following otitis media, cortisone therapy, and anaemia). Nine boys and six girls were between the ages of 8 months and 11 years at their initial consultation. Obesity was present in three patients. The most common clinical symptom was headache (seven patients). Patient 7 suffered from acute-recurrent headache; patients 8, 11 and 15 had acute headache accompanied by nausea and vomiting; patients 6, 10 and 12 had chronic daily headache.
Eight children, including the five youngest ones, presented only with ophthalmologic findings without any other obvious symptoms (for clinical details see Table 1). The reasons for the eye examination in the asymptomatic patients were variable: Patient 2 was seen by an ophthalmologist because of a relatively large head circumference (97 percentile); patients 3 and 9 had an eye exam because of a mild head trauma; patients 4 and 5 had an eye examination to fit glasses because of convergent strabismus; patient 3 lost her glasses and was therefore seen by an ophthalmologist; patient 14 had an afebrile seizure and was therefore examined.
Clinical findings at initial presentation and date of diagnosis in 15 pre-pubertal children with suspected idiopathic intracranial hypertension, sorted by age. ♀= female; ♂= male; ⊘= no clinical symptoms; HE = headache; VOM = vomiting; VO = visual obscuration; BP = bilateral papilledema; UP = unilateral papilledema; IAP = isolated abducens palsy; CST = convergent strabismus
Although the CSF opening pressure was variable in our cohort, there was no association between the CSF pressure level and the severity of clinical symptoms.
Evaluating the date of initial presentation, we discovered a distinct seasonal variation. Ten of 15 patients presented between November and March, thus coinciding with the typical season of paediatric viral and bacterial infections in Germany. However, only in two patients was a history of infection in the past obtained: patient 3 had an acute tonsillitis around 6 weeks before admission; patient 5 had a viral infection with headache and fever around 4 weeks before admission. Social problems of the families of patients 2 and 8 might have hampered a proper medical history and possibly important symptoms were not noticed. In all other patients the parents reported no severe infections; however, minor infections could not be ruled out with certainty.
In the control group of adolescents with IIH all patients presented with headache, some of them in combination with vomiting, visual obscuration or neck pain (see Table 2). Patients 1 and 2 suffered from acute-recurrent headache; patients 3, 4, 6 and 7 had acute headache accompanied by nausea and vomiting; patients 5 and 8 suffered from chronic daily headache. Comparing the two age groups, a clustering during wintertime was observed predominantly in children and less frequently in adolescents; however, only with borderline significance (chi-square test: P = 0.057). No pubertal patient had a history of infection in the last few weeks before diagnosis.
Clinical findings at initial presentation and date of diagnosis in 8 pubertal children with suspected idiopathic intracranial hypertension, sorted by age. ♀= female; ♂= male; HE = headache; VOM = vomiting; VO = visual obscuration; BP = bilateral papilledema; BAP = bilateral abducens palsy; NP = neck pain
Discussion
To highlight the possible importance of our observation, it is essential to draw attention to secondary causes of intracranial hypertension. Among various medical conditions and diverse medications, acute or chronic infections have been reported frequently to be associated with intracranial hypertension (5–8). Furthermore, the occurrence of transiently raised intracranial pressure after vaccination in young children is a known phenomenon, also suggesting an underlying immunopathological mechanism at least in some patients (9). In view of our findings, it is important to note that in young children recurrent infections are common during the cold season. Therefore, in children with suspected IIH a possible disease association cannot be ruled out with certainty during that time of the year (although our observation could still represent a statistical coincidence). For this reason, we strongly support the view of Friedman and Jacobson, who stated that a secondary cause for intracranial hypertension should be suspected in any ‘atypical’ patient, including any child (1).
Additional evidence is possibly provided by the study of Soriani et al., who reported clustering of migraine episodes in children during autumn–winter (10). This might be of particular interest because headache caused by IIH might have been misinterpreted as migraine in some of these children. Moreover, IIH has been described as a coexisting condition in patients with migraine (11).
Nevertheless, one might be under the impression that the considerable number of asymptomatic children may restrain possible interpretations of seasonal variation. Absence of symptoms in these patients probably refers to the problem that young children are not able to articulate possible symptoms. Moreover, parents may not have recognized IIH-related complaints; thus the time of diagnosis might not reflect the actual onset of intracranial hypertension. However, none of our patients had signs of chronic papillledema or suffered from severe visual defects. Apart from patients 2 and 3, all children had rapid resolution of papilledema after the start of treatment without permanent alterations of the optic disc documented on follow-up. Therefore, we conclude that the time of onset of intracranial hypertension did not considerably precede the date of diagnosis in those children.
Even though the number of patients in our retrospectively analysed cohort is relatively small, we hypothesize that IIH in many pre-pubertal children might not be idiopathic in nature but is potentially associated with prior or simultaneous infections. This hypothesis needs to be further assessed in controlled prospective epidemiological studies. As to the rarity of the disease in pre-pubertal children, this task can only be fulfilled with national and international clinical cooperation. Additionally, the high number of asymptomatic children in our cohort raises questions regarding the incidence of undetected cases, particularly in this age group.