Rosenfeld, Eldar MD; Dotan, Gad MD; Kimchi, Tali J. MD; Kesler, Anat MD
Cerebrospinal fluid (CSF) leakage is a rare complication of idiopathic intracranial hypertension (IIH). We describe four patients with this disorder. Although rhinorrhea previously has been reported in patients with this disorder, we describe three additional patients with IIH & CSF rhinorrhea, one as the initial chief complaint, and the others later in the clinical course. We also describe one patient with IIH who developed CSF otorrhea, and we are unaware of other reports of this association.
MATERIALS AND METHODS
Medical records, including patient history, examination findings, and neuroimaging results of four IIH patients who developed CSF leaks were reviewed. All patients were treated at the same medical institution and examined by the same neuro-ophthalmologist (AK). This study was performed in accordance with the principles set out in the Declaration of Helsinki.
A 48-year-old Caucasian woman with a body mass index (BMI) of 42 presented with headaches and transient visual obscurations of 2-month duration. Computed tomography (CT) of the brain was normal. For approximately 4 months, she noted a clear fluid discharge from the left nostril and occasionally, after an overnight sleep, her pillow was wet. Evaluation by an otolaryngologist was unremarkable.
Because of persistent headaches, she was sent to a neuro-ophthalmologist, who found bilateral papilledema on examination. Lumbar puncture (LP) revealed an opening pressure of 280 mm of water, with normal CSF composition. The patient was diagnosed with IIH and was treated with acetazolamide.
Fluid collected from her nostril was found to be positive for beta-2 transferrin. Magnetic resonance imaging (MRI) of the brain revealed an encephalocele descending from the cribriform plate (Fig. 1). The patient underwent an endonasal reconstruction of the bony defect with a nasoseptal flap.
Within 1 week, her symptoms and CSF rhinorrhea resolved. With weight loss (12 kg) and acetazolamide, there was gradual resolution of papilledema.
A 35-year-old Caucasian woman with a BMI of 39 had been diagnosed 9 years earlier with IIH. Since then, she had been poorly compliant with treatment. She had a history of recurrent sinusitis, and 3 years previously, she experienced 2 episodes of tonic-clonic seizures. At that time, brain CT and computed tomographic venography (CTV) were unremarkable. She had normal visual function but bilateral papilledema.
During routine follow-up, the patient complained of exacerbation of headaches and the appearance of a watery discharge from her nose. CT revealed an eroded cribriform plate, with an encephalocele and CSF in the left nasal cavity. The nasal fluid was positive for beta-2 transferrin.
The patient underwent an endonasal closure of the eroded cribriform plate and was maintained on acetazolamide. CSF rhinorrhea and headache promptly resolved.
A 42-year-old Caucasian woman with a BMI of 25 had been diagnosed 4 years earlier with IIH. At that time, she had normal neuroimaging, and on LP, the opening pressure was 270 mm of water. Because of allergic reactions to acetazolamide and topiramate, she was treated with furosemide.
On a follow-up visit, the patient reported a clear fluid discharge from her nose for the past 3 weeks. She had been examined by an otolaryngologist, who found no abnormality and recommended a decongestant nasal spray. However, her neuro-ophthalmologist had the nasal fluid tested for beta-2 transferrin, and it was found to be present.
While brain CT was unremarkable, MRI revealed CSF leakage in the region of the left cribriform plate. The patient underwent lumboperitoneal shunt surgery, with prompt resolution of CSF rhinorrhea and headaches.
A 44-year-old Caucasian woman with a BMI of 33 had undergone gastric bypass surgery 13 years previously. Two years later, she was diagnosed with IIH, following presentation with headaches and bilateral papilledema. At that time, MRI of the brain was normal, and opening pressure on LP was 370 mm of water, with normal CSF constituents. Treatment with acetazolamide was begun.
During follow-up, the patient was noncompliant, often discontinuing her medication and gaining weight. She occasionally complained of tinnitus and transient visual obscurations, but her visual function remained stable. Repeat LPs revealed opening pressures as high as 410 mm of water.
Eleven years after being diagnosed with IIH, the patient began complaining of fullness, pain, and autophonia in the left ear. MRI and magnetic resonance venography did not show any interval changes.
She was examined by an otolaryngologist and was treated with antibiotic drops for mild left otitis. Because of lack of improvement over the next 2 weeks, she was reexamined by the same otolaryngologist, who found fluid and air in her left middle ear, as well as pulsatile movement of the tympanic membrane. Additional neuroimaging studies confirmed a CSF leak into the left middle ear (Fig. 2). Fluid from the ear was collected and was found to contain beta-2 transferrin.
The patient underwent a lumboperitoneal shunt, with resolution of her headaches, autophonia, and the sensation of left ear fullness. During follow-up, she has remained stable.
Spontaneous CSF leakage occurs in patients without a history of head trauma, sinus surgery, or craniotomy (1). Such leaks occur with approximately equal frequency in the settings of normal and increased ICP (2). The most common causes of increased ICP are intracranial tumors, hydrocephalus, and IIH.
Table 1 summarizes previous reports of patients with IIH who developed a CSF leak. Many had received medical therapy, including weight loss, acetazolamide, diuretics, corticosteroids, multiple LPs, and some had undergone a CSF diversion procedure. Once identified, not all had resolution of their CSF leakage following initial surgery.
In addition, there are other reports of patients presenting with a CSF leak, yet the diagnosis of IIH had not been established. These patients had clinical features such as high BMI and neuroimaging abnormalities, including empty sella, making the diagnosis of IIH likely. Most patients experienced CSF rhinorrhea (11–14), a few experienced CSF otorrhea (15,16), some experienced both (17), and other studies did not mention the location of the leak (18,19).
The basic cause of CSF leak is disruption in the arachnoid and dura mater, coupled with an osseous defect, and a CSF pressure gradient that is continuously or intermittently greater than the tensile strength of the disrupted tissue (20). Disruption of the barrier between the sinonasal cavity and the anterior and middle cranial fossae can lead to the discharge of CSF into the nasal cavity. Otorrhea may be serous, serosanguineous, or purulent. Associated symptoms include ear pain, fever, vertigo, tinnitus, and hearing loss. The resulting communication within the central nervous system can lead to a multitude of infectious complications, with significant morbidity, potentially disastrous long-term neurologic deficits, and even death (21).
When serous discharge from the ear or nose is considered to be CSF, the initial diagnostic test is examination of the fluid for the presence of beta-2 transferrin. This is a carbohydrate-free isoform of transferrin produced by cerebral neuro-transaminase from beta-1 transferrin by desialization. This substance is present only in the CSF, perilymph, and vitreous of the eye (22,23).
Localization of the bony defect is the second diagnostic step. High-resolution CT is considered the method of choice for evaluating the bony integrity of the skull base (24). Arachnoid pits, secondary to bony impressions from the arachnoid villi at the base of the skull, are present in 63% of patients with spontaneous CSF leakage (25). The lateral recess of the sphenoid bone and the ethmoid roof are also common sites of skull base dehiscence (26,27).
The initial step in repairing a CSF leak is to lower the ICP, if possible before repair of the site of CSF leakage. Lumboperitoneal or ventriculoperitoneal shunt procedures are generally performed. In some patients, the fistula may not close completely after a shunt procedure, and the patient may be exposed to increased risk of infection because the pressure gradient across the fistula has been reversed. In cases of rhinorrhea where the fistula has not closed and the ICP is controlled by the shunt, surgical repair can be undertaken, either by intracranial and extracranial endoscopic approaches. Extracranial techniques carry reduced morbidity compared to intracranial repair (5,28).
In cases of CSF otorrhea, the tegmen mastoideum and tegmen tympani are the most common locations of middle fossa defects. A craniotomy gives maximum exposure to the entire floor of the middle cranial fossa, including defects adjacent to the zygomatic root and over the internal auditory canal. A transmastoid approach is appropriate for posterior fossa and tegmen mastoideum defects. Successful repair is achieved in most cases using autologous materials and alloplastic bone cement (17).
In conclusion, the clinician should be aware of CSF leak as a rare complication of IIH. Because most patients do not relate a clear fluid discharge from the nose or ear with their IIH, they usually do not provide this information. Initial patient evaluation includes analysis of the fluid discharge for the presence of beta-2 transferrin. Maxillofacial and brain neuroimaging with CT or MRI is essential, carefully searching for a defect of the skull base. Optimal therapy includes lowering of ICP and surgical repair of the bony defect.
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