Neurosurgery Department, University General Hospital of Alicante, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Alicante, Spain
Heinrich Quincke in 1897 reported the first cases of IIH shortly after he introduced the lumbar puncture into medicine. It was named pseudotumor cerebri in 1904 but was not well delineated clinically until the 1940's when cerebral angiography was added to pneumoencephalography to identify cases of cerebral mass lesions. Foley coined the term benign intracranial hypertension in 1955 but reports from the 1980's demonstrated a high incidence of visual loss 1) 2) and the term “benign” is no longer appropriate.
The syndrome of increased intracranial pressure without hydrocephalus or mass lesion and with normal CSF composition, is a diagnosis of exclusion now termed idiopathic intracranial hypertension (IIH). Diagnostic criteria of this disorder have not been updated since the Modified Dandy Criteria were articulated in 1985. Since then, new developments, including advances in neuroimaging technology and recognition of additional secondary causes of intracranial hypertension, have further enhanced the ability to diagnose conditions that may mimic IIH. These factors are not addressed in the Modified Dandy Criteria 3).
Patients in whom a syndrome of increased ICP secondary to certain medications develops or who are found to have cerebral lateral sinus thrombosis are nonetheless still classified as having idiopathic intracranial hypertension (IIH).
IIH is the preferred term for this condition, replacing pseudotumor cerebri, which often includes cerebral venous sinus thrombosis and other etiologies of increased ICP, and benign intracranial hypertension, which does not take into account that some IIH patients do not have a “benign” course and go on to irreversibly lose vision 4).
IIH usually occurs in obese women in the childbearing years.
The incidence of IIH in several Middle East countries has been estimated at 2.02-2.2/100,000 in the general population, which is higher than the Western rate. Obesity is a major risk factor globally and it is associated with an increased risk of severe vision loss due to IIH. There has been an increase in obesity prevalence in the Middle East countries mainly affecting the Gulf Council Countries (GCC), which parallels increased industrial development. This rise may be contributing to the increasing incidence of IIH in these countries. Other risk factors may also be contributing to IIH in Middle East countries and the differences and similarities to Western IIH merit further study 9).
Medical records of patients diagnosed with IIH between 2007 and 2014 in a general hospital in Northern Ireland were reviewed.
There were 45 patients with IIH, 44 women: 1 man. The mean age at presentation was 29.4 (SD 9.8) years and mean body mass index (BMI) 39.8 (SD 9.5) kg/ m2. All patients had neuroimaging, 44 (98%) had CT/MR venogram and 41 (91%) had visual perimetry. The crude incidence of IIH was 2.36 per 100,000 (95% CI 1.65-3.37). For women, the incidence was 4.65 per 100,000/year (95% CI 3.25-6.66). The prevalence was 14.3 per 100,000 overall (95% CI 9.72-20.9) but 28.1 per 100,000 in women (95% CI 19.2-41.2). Visual field defects were identified in 25 of 41 (61%); 4 patients (9%) required shunting procedures. At follow-up, the mean BMI decreased by 1.6 kg/m2 (p = 0.024).
The incidence of IIH in the northwest of Northern Ireland is among the highest ever reported and probably reflects the known increase in obesity 10).
Idiopathic intracranial hypertension (IIH) is still a grey area in the knowledge of the aetiology, diagnosis and management of neurosurgical diseases.
Although there are multiple hypotheses for the etiology of Idiopathic intracranial hypertension (IIH) mainly focused on obesity and metabolic dysfunction, there is no known cause of the development of IIH. IIH occurs most frequently among obese women of childbearing age 11).
The association of idiopathic intracranial hypertension (IIH) with stenosis or narrowing of the transverse sinuses (TSs) is well known. However, there is debate as to whether the stenosis is a cause or consequence.
Young women are more frequently involved with in half of cases a diffuse proliferative glomerulonephritis. Predisposing factors, like anaemia, must be associated. IH allows SLE diagnose in more than the third of the cases. Then, SLE has to be searched as an etiology of IH, in particular in non-obese patients and when nephritis is associated 14).
Raggi et al reported for the first time the presence of Binge eating disorder (BED) among patients with idiopathic intracranial hypertension (IIH) and showed that BED is associated to IIH, ICP and history of abuse or neglect 15).
Ahmed et al report a case of a young female who presented with signs and symptoms of IIH and was subsequently diagnosed with IgA nephropathy and end-stage renal disease. This is the first report of IgA nephropathy presenting as end-stage renal disease in a patient who presented with IIH 16).
The signs and symptoms of intracranial hypertension are that the patient maintains an alert and oriented mental state, but has no localizing neurologic findings.
The most common symptom of IIH is headache, which occurs in almost all (92–94%) cases. It is characteristically worse in the morning, generalized in character and throbbing in nature. It may be associated with nausea and vomiting. The headache can be made worse by any activity that further increases the intracranial pressure, such as coughing and sneezing. The pain may also be experienced in the neck and shoulders.
Many have pulsatile tinnitus, a whooshing sensation in one or both ears (64–87%); this sound is synchronous with the pulse.
The increased pressure can lead to papilledema.
Those who do experience symptoms typically report “transient visual obscurations”, episodes of difficulty seeing that occur in both eyes but not necessarily at the same time. Long-term untreated papilledema leads to visual loss, initially in the periphery but progressively towards the center of vision.
Visual acuity loss in IIH can be caused by both outer retinal changes and optic neuropathy. Vision loss from outer retinal changes is mostly reversible. The outcome of patients with coexisting outer retinal changes and optic neuropathy or optic neuropathy alone depends on the degree of optic neuropathy, which can be predicted by the retinal ganglion cell-inner plexiform layer complex (GCL-IPL) thickness 18).
Various other symptoms, such as numbness of the extremities, generalized weakness, loss of smell, and loss of coordination, are reported more rarely; none are specific for IIH.
More rarely, the oculomotor nerve and trochlear nerve (third and fourth nerve palsy, respectively) are affected; both play a role in eye movements.
The facial nerve (seventh cranial nerve) is affected occasionally –- the result is total or partial weakness of the muscles of facial expression on one or both sides of the face.
Skull base spontaneous cerebrospinal fluid fistulas have been recognized as secondary to pseudotumor cerebri. In most cases, they occur in the ethmoid region and the sphenoid bone which is much less affected. Regardless of their etiology, the clinical manifestation of skull base fistulas is usually the same and includes a rhinorrhea and less frequently an otorrhea 19).
In children, numerous nonspecific signs and symptoms may be present.
The differences are the absence of differences in the sex distribution at the onset and the absence of a significant correlation with obesity. In addition, adult IIH patients often complain of headaches, have transient low vision, and tinnitus, while pediatric IIH patients often complain of restlessness, dizziness, and neck pain. However, adolescent IIH patients have clinical features similar to that of adult IIH. Currently, there is ongoing prospective study of the treatment of IIH in adults, but no data exist in children 22).
Most children respond to typical medical treatment such as intravenous carbonic anhydrase or steroids. Indication for surgical treatment include initial severe visual dysfunction or a worsening of the results of a visual test 23).
At the moment, because the etiology of IIH in children remains unclear, a specific treatment has not yet developed 24)
Idiopathic intracranial hypertension (IIH) is still a grey area in the knowledge of the aetiology, diagnosis and management of neurosurgical diseases.
The diagnosis require a multidisciplinary approach.
The diagnosis may be suspected on the basis of the history and examination. To confirm the diagnosis, as well as excluding alternative causes, several investigations are required; more investigations may be performed if the history is not typical or the patient is more likely to have an alternative problem: children, men, the elderly, or women who are not overweight.
Idiopathic intracranial hypertension (IIH) is characterized by increased cerebrospinal fluid (CSF) pressure and normal or slit ventricles.
Physical examination of the nervous system is typically normal apart from the presence of papilledema, with ophthalmoscope or in more detail with a fundus camera. If there are cranial nerve abnormalities, these may be noticed on eye examination in the form of a squint (third, fourth, or sixth nerve palsy) or as facial nerve palsy.
If the papilledema has been longstanding, visual fields may be constricted and visual acuity may be decreased. Visual field testing by automated (Humphrey) perimetry is recommended as other methods of testing may be less accurate.
Neuroimaging, usually with computed tomography (CT/CAT) or magnetic resonance imaging (MRI), is used to exclude any mass lesions. In IIH these scans typically appear to be normal, although small or slit-like ventricles, dilatation and buckling of the optic nerve sheaths and “empty sella sign” (flattening of the pituitary gland due to increased pressure) and enlargement of Meckel's caves may be seen.
The protocol consists of a brain MRI and head magnetic resonance venography (MRV), both performed without and with intravenous gadolinium contrast material (Table 1) to minimize potential pitfalls of noncontrast MRV techniques and obviate ionizing radiation from CT/CT venography. Although low-field-strength MRI scanners may be sufficient to exclude large intracranial pathology, higher field strength (1.5 or 3.0 T) superconducting units are generally preferred to appreciate the imaging findings associated with chronically elevated ICP 26).
With the advent of magnetic resonance (MR) venography and increased use of cerebral angiography, there has been recent emphasis on the significant number of patients with IIH found to have associated non-thrombotic dural venous sinus stenosis. This has led to a renewed interest in endovascular stenting and angioplasty as a treatment for IIH in patients non-responsive to medical treatment.
An Magnetic resonance venography is also performed in most cases to exclude the possibility of venous sinus stenosis/obstruction or cerebral venous sinus thrombosis.
A contrast-enhanced MRV (ATECO) scan has a high detection rate for abnormal transverse sinus stenoses.
These stenoses can be more adequately identified and assessed with catheter cerebral venography and manometry.
Buckling of the bilateral optic nerves with increased perineural fluid is also often noted on MRI imaging.
Lumbar puncture is performed to measure the opening pressure, as well as to obtain cerebrospinal fluid (CSF) to exclude alternative diagnoses. If the opening pressure is increased, CSF may be removed for transient relief.
Lumbar puncture is performed routinely for diagnostic and therapeutic purposes in idiopathic intracranial hypertension, despite lumbar puncture being classically contraindicated in the setting of raised intracranial pressure. 27).
A 30-year-old female with known idiopathic intracranial hypertension who had cerebellar tonsillar herniation following therapeutic lumbar puncture. Management followed guidelines regarding treatment of traumatic intracranial hypertension, including rescue decompressive craniectomy. Hoffman et al. hypothesize that the changes in brain compliance that are thought to occur in the setting of idiopathic intracranial hypertension are protective against further neuronal injury due to axonal stretch following decompressive craniectomy. 29)
A 30-year-old woman with coexisting renal tubular acidosis and idiopathic intracranial hypertension (IIH), treated with acetazolamide, experienced coning (cerebellar tonsillar herniation) after a lumbar puncture (LP). Brain magnetic resonance imaging at initial diagnosis of IIH showed minor tonsillar descent and computed tomographic venography revealed hypoplasia of the left transverse sinus. The patient previously had three uneventful LPs, all of which showed high opening pressures and normal cerebrospinal fluid composition. In retrospect, it was noted that her serum bicarbonate had fallen to 9 mmol/L (normal: 22-28 mm/L) 1 week before the LP. We hypothesize that the combination of cerebral edema (due to worsening metabolic acidosis), poor venous drainage, and preexisting minor tonsillar descent contributed to her post-LP coning 30).
The CSF is examined for abnormal cells, infections, antibody levels, the glucose level, and protein levels. In IIH, by definition all of these are within their normal limits.
The most frequent abnormal laboratory findings were elevated C reactive protein (CRP) (51 %), thrombophilia (31 %), increased plasma cortisol levels (29 %) and elevated lactate dehydrogenase (LDH) (20 %). Patients with elevated CRP and patients with thrombophilia had an unfavorable visual outcome. Increased cortisol levels and abnormal calcium correlated with a higher rate of recurrence. The visual outcome of patients with elevated LDH was better than those with normal LDH. It seems that certain metabolic, inflammatory and coagulation abnormalities may influence the course of IIH. If confirmed in further studies, these findings could contribute to elucidation of the etiology and prognosis of IIH. 31).
Vascular intracranial hypertension.
Idiopathic intracranial hypertension (IIH) or pseudotumor cerebri is a potentially blinding disease.
Few studies have directly compared headache and visual outcomes across treatment modalities.
A systematic analysis of case series was conducted to compare therapeutic efficacies among currently available interventions. The electronic databases from EMBASE (1980-17 September 2013), Medline (1980-17 September 2013), Cochrane databases, and references of review articles was searched. All publications reporting headache and visual outcomes following intervention for IIH were included. A total of 457 manuscripts were selected and full text analysis produced 30 studies with extractable data. All studies constituted Class III evidence. Overall, 332 patients treated by optic nerve sheath fenestration (ONSF), 287 by lumboperitoneal shunt (LPS), 61 by ventriculoperitoneal shunt (VPS), and 88 by dural venous sinus stenting, were identified.
Visual acuity improved in 49.3%, 56.6%, 67.2% and 84.6% of patients following VPS, LPS, ONSF, and stent placements, respectively. Resolution of papilledema was noted in 59.9% to 97.1%. Postoperative headache improved in 36.5%, 62.5%, 75.2%, and 82.9% of patients treated with ONSF, VPS, LPS, and stenting, respectively. Shunt revision was more frequent for LPS compared to VPS (46% versus 36%; p<0.2). Among the LPS revisions, 87.5% occurred within the first 12months following initial surgery. A pooled analysis indicated an overall similar improvement in visual outcomes across treatment modalities, and a modest improvement in headache following cerebrospinal fluid shunting and endovascular stent placement. Based on currently available literature, there is insufficient evidence to recommend or reject any treatments modalities for IIH 32).
IIH affects QOL at time of diagnosis even in patients with mild visual impairment. Vision-specific QOL in patients with newly diagnosed IIH may be as decreased as that for patients with other neuro-ophthalmic disorders. IIH treatment should target visual loss and other symptoms of increased intracranial pressure associated with reduced QOL. Reduced QOL does not simply reflect obesity, an underlying IIH risk factor 33).
Headache was the only clinical outcome that correlated with enhanced QOL. Effective headache management is required to improve QOL in IIH 34).
Patients with elevated CRP and patients with thrombophilia had an unfavorable visual outcome. Increased cortisol levels and abnormal calcium correlated with a higher rate of recurrence. The visual outcome of patients with elevated LDH was better than those with normal LDH. It seems that certain metabolic, inflammatory and coagulation abnormalities may influence the course of IIH. If confirmed in further studies, these findings could contribute to elucidation of the etiology and prognosis of IIH. 35).
A systematic review of the surgical treatment of IIH was carried out. Cochrane Library, MEDLINE and EMBASE databases were systematically searched from 1985 to 2014 to identify all relevant manuscripts written in English. Additional studies were identified by searching the references of retrieved papers and relative narrative reviews.
Forty-one (41) studies were included (36 case series and 5 case reports), totalling 728 patients. Three hundred forty-one patients were treated with optic nerve sheath fenestration (ONSF), 128 patients with lumboperitoneal shunting (LPS), 72 patients with ventriculoperitoneal shunting (VPS), 155 patients with venous sinus stenting and 32 patients with bariatric surgery. ONSF showed considerable efficacy in vision improvement, while CSF shunting had a superior headache response. Venous sinus stenting demonstrated satisfactory results in both vision and headache improvement along with the best complication profile and low relapse rate, but longer follow-up periods are needed. The complication rate of bariatric surgery was high when compared to other interventions and visual outcomes have not been reported adequately. ONSF had the lowest cost.
No surgical modality proved to be clearly superior to any other in IIH management. However, in certain contexts, a given approach appears more justified. Therefore, a treatment algorithm has been formulated, based on the extracted evidence of this review. The traditional treatment paradigm may need to be re-examined with sinus stenting as a first-line treatment modality 36).
The Idiopathic Intracranial Hypertension Treatment Trial represents the largest prospectively analyzed cohort of untreated patients with IIH. The data show that IIH is almost exclusively a disease of obese young women. Patients with IIH with mild visual loss have typical symptoms, may have mild acuity loss, and have visual field defects, with predominantly arcuate loss and enlarged blind spots that require formal perimetry for detection 37).
Levitt et al., reviewed all cerebral venograms with manometry performed for headache between January 2008 and May 2015. Patient demographics, headache etiology, intracranial pressure (ICP) measurements, and radiographic and manometric results were recorded. CVPG was defined as a difference ≥ 8 mm Hg by venographic manometry. RESULTS One hundred sixty-four venograms were performed in 155 patients. There were no procedural complications. Ninety-six procedures (58.5%) were for patients with IIH. The overall incidence of CVPG was 25.6% (42 of 164 procedures): 35.4% (34 of 96 procedures) in IIH patients and 11.8% (8 of 68 procedures) in non-IIH patients. Sixty procedures (36.6%) were performed in patients with preexisting shunts. Seventy-seven patients (49.7%) had procedures preceded by an ICP measurement within 4 weeks of venography, and in 66 (85.7%) of these patients, the ICP had been found to be elevated. CVPG was seen in 8.3% (n = 5) of the procedures in the 60 patients with a preexisting shunt and in 0% (n = 0) of the 11 procedures in the 77 patients with normal ICP (p < 0.001 for both). Noninvasive imaging (MR venography, CT venography) was assessed prior to venography in 112 (68.3%) of 164 cases, and dural venous sinus abnormalities were demonstrated in 73 (65.2%) of these cases; there was a trend toward CVPG (p = 0.07). Multivariate analysis demonstrated an increased likelihood of CVPG in patients with IIH (OR 4.97, 95% CI 1.71-14.47) and a decreased likelihood in patients with a preexisting shunt (OR 0.09, 95% CI 0.02-0.44).
CVPG is uncommon in IIH patients, rare in those with preexisting shunts, and absent in those with normal ICP 38).