Cerebrospinal fluid (CSF) flows into the nasal cavity through the base of the anterior cranial fossa, the base of the middle cranial fossa, or other sites of congenital or traumatic bone defects, ruptures, or thinning, and is called cerebrospinal fluid rhinorrhea (CFR).
Classification of cerebrospinal fluid rhinorrhea
1.Classification according to etiology
Generally, CSF nasal leakage can be classified into traumatic and non-traumatic nasal leakage according to the etiology. The former is divided into traumatic and medical, while the latter is divided into congenital, spontaneous (also known as primary cerebrospinal fluid nasal leakage, also called idiopathic) and CSF leakage caused by tumor or septic inflammation.
1.1 Traumatic CSF nasal leak.
Among the various cerebrospinal fluid nasal leaks, closedheadinjury (CHI) is the most common. The septal plate and the posterior wall of the frontal sinus are very thin and closely connected to the dura mater, and if the plate and dura mater rupture simultaneously during trauma, cerebrospinal fluid nasal leakage occurs. Fracture of the base of the middle fossa of the skull can damage the upper wall of the larger pterygoid sinus and lead to cerebrospinal fluid nasal leakage. Cerebrospinal fluid leakage caused by fractures of the middle ear mastoid skull or the bony part of the eustachian tube may flow through the eustachian tube into the nasal cavity, which is called cerebrospinal fluid aural-nasal leakage. Medically induced cerebrospinal fluid nasal leaks are caused by surgery, such as septal plate damage from middle turbinate resection or septal sinus resection, and pituitary tumor resection via the pterygoid sinus. Typical medical CSF leaks occur only when surgical resection of bone and mucosa results in a large skull base bone-dural defect, and are common in transnasal endoscopic surgery, neurosurgery, and combined craniofacial surgery, with an incidence of 5% to 50%.
1.2 Non-traumatic CSF nasal leak.
Tumors at the skull base can cause CSF leakage directly or indirectly. Tumors located at the anterior/middle skull base can directly erode the bone leading to local bone defects and pathological changes in its surrounding bone. Treatment of the tumor itself, including surgery, radiotherapy or chemotherapy, can lead to ischemia (around the leak) or skull base erosion that is difficult to repair. Tumors can also cause hydrocephalus and indirectly lead to CSF leak. These patients often need to have the primary tumor removed to recirculate the cerebrospinal fluid or have a cerebrospinal fluid shunt to lower the intracranial pressure, and then the CSF leak can be cured successively. Repairing the leak alone without treating the obstructive hydrocephalus actually increases the intracranial pressure, leading to repair failure.
Congenital CSF leaks with brain bulge are relatively rare but difficult to treat and may be caused by congenital hydrocephalus and the corresponding high cranial pressure, but more commonly by developmental malformations of the skull base. As the skull base and brain tissue continue to develop, these malformations may lead to localized herniation of meninges/brain tissue into the paranasal sinuses or natural weaknesses of the skull base such as the sieve plate (sieve foramen), which may be surrounded by a funnel-like change in the skull. There are two different views on the formation of spontaneous CSF leaks. One is the “focalatrophy” theory, which suggests that the sieve plate or the saddle base atrophies due to ischemia and the new gap is filled with arachnoid sacs filled with CSF, and the CSF pulses against the skull base and erodes the local bone to form a defect, which eventually leads to meningeal/cerebral bulge and CSF leak formation. If these arachnoid granules do not extend into the adjacent venous sinuses, they lack endothelium and are only covered by dura, and the pulsating impact of CSF leads to the destruction of the surrounding skull base bone, resulting in cerebral bulge and CSF leak.
Septic otitis media, inflammation of septal sinus and pterygoid sinus can also cause CSF rhinorrhea, which is now rare.
2.Classification according to location
According to the location of the leak, CSF leak can be divided into septal sinus leak, which can be caused by fracture/defect of the sieve plate/sieve hole or olfactory groove, tearing the local dura; frontal sinus leak is often caused by fracture of the posterior wall of the frontal sinus; pterygoid sinus leak is mainly caused by fracture or erosion of the pterygoid plateau, pituitary fossa, temporal bone rock tip and other parts of the lesion, resulting in the subarachnoid space and pterygoid sinus, and sometimes slope fracture/defect (posterior pterygoid sinus pneumatization) can also be caused, It is rare. CSF leaks in the temporal bone are caused by fractures/defects of the tympanic cap, sinus wall, mastoid airspace, or posterior cranial fossa wall of the rock. If the injury is severe, multiple CSF leaks may result. In addition, it can be divided into high cranial pressure CSF leaks and normal cranial pressure CSF leaks depending on the presence or absence of increased intracranial pressure. The CSF leaks can be divided into simple CSF leaks and CSF leaks with meningeal/bulging brain, depending on whether they are accompanied by meningeal/bulging brain. The latter two classifications are rarely used clinically or combined with other classifications.
Diagnosis of cerebrospinal fluid nasal leakage
1, preliminary determination of whether it is cerebrospinal fluid nasal leak traumatic injury, bloody fluid from the nasal cavity, the center of the trace is red and the periphery is clear, or the nostril outflow of colorless liquid dry without crust, in the case of low head force, compression of the jugular vein and other cases with increased flow, should be considered possible cerebrospinal fluid nasal leak. Queckenstedt’s and Valsalva’s experiments are rarely used because they can induce recurrence of CSF leakage and aggravate the patient’s symptoms.
2, qualitative diagnosis of CSF contains high sugar content, so the “urine glucose test paper” can be used to determine the sugar, protein content and electrolyte analysis, quantitative analysis of glucose, the content of 1.7mmol / (30mg%) or more. If the leaking fluid is mixed with blood, it is difficult to confirm the diagnosis by conventional measurement, so the red blood cell count method can be used to compare the hematocrit or red/white blood cell ratio of the leaking fluid and blood to determine. Recently, the application of immunofixation electrophoresis technique to detect β-2 ferritin in leaking fluid is very effective for the diagnosis of CSF ear and nasal overflow. Since β-2 ferritin is only present in CSF and inner ear exolymphatic fluid, it cannot be detected in blood, nasal and external auditory secretions. It can be detected by taking 0.5 ml of specimen, and its sensitivity, specificity and accuracy can reach more than 90%. The newly discovered β2 tracer protein, like β-2 ferritin, exists only in CSF and exolymphatic fluid, and can be detected by rocket immunoelectrophoresis with only 5 μL (2 mg PL) of specimen, with higher accuracy and specificity (95.68% and 100%, respectively), simple operation and less time (results can be obtained in 3 h). However, it is difficult to collect specimens from patients with intermittent CSF leaks, and the diagnosis must be confirmed in conjunction with other clinical examinations.
3. Localization of the fistula is first based on clinical manifestations to determine the general location. If the fluid flowing from the nostril changes with the body and head position, it suggests that the fistula comes from the sinus, especially from the pterygoid sinus; unilateral loss of smell suggests that the fistula is at the sieve plate; unilateral visual impairment suggests that the fistula is in the saddle node, pterygoid sinus or posterior group of sieve sinus; loss of sensation in the distribution of the supraorbital nerve suggests that the fistula is in the posterior wall of the frontal sinus; loss of sensation in the distribution of the maxillary branch of the trigeminal nerve suggests that the fistula is in the middle cranial fossa. The localization of CSF nasal leaks still depends on special examination methods:
Cranial radiographs can reveal the presence of fractures across the paranasal sinuses or rock bones, but are less precise in their localization.
HighResolutionComputedTomography (HRCT) cross-sectional and coronal scans can provide important information on bone structure for traumatic, spontaneous skull base defects, and are not limited by the activity of CSF leaks. CT brain pool imaging after intrathecal injection of contrast is the only method to detect contrast leakage into specific paranasal sinuses or into the meninges/brain herniation sac. The disadvantage is that it is only representative of an active CSF leak at one point in time and may miss information on inactive CSF leaks at that time, with a sensitivity of only 33% to 48%. Since contrast can accumulate in the sinus, middle ear tympanic chamber or mastoid airspace, this method is often used for the local diagnosis of CSF leaks in these areas. When combined with HRCT, it is more helpful in the diagnosis of active CSF leaks.
Intrathecal injection of radiotracer is used to perform nuclear brain pool imaging, and a small swab is placed in the nasal cavity before the injection, and a few hours later, the swab is removed and the radioactive element content is measured. Because the nasal swab is placed for a long time, CSF can be collected continuously, and this method is very helpful for the diagnosis of cases with small amount of leakage or intermittent CSF leakage, and the sensitivity can reach 76%-88%, but the disadvantage is that sometimes the leak cannot be precisely located. Intrathecal injection of fluorescein followed by close endoscopic examination of CSF leaks is also helpful, but its precise localization of the leak is limited by the small exposure of the skull base bone defect. The diagnosis is more accurate if the intraoperative field of view is more exposed, but fluorescein can be diluted or excreted by CSF with prolonged surgery time, the latter depending on the leak rate and intrathecal fluorescein injection time, and the sensitivity of diluted fluorescein detection can be improved by using blue light filters.
Magnetic resonanceimage (MRI) and magnetic resonancecisternography (MRC) can be used for non-invasive imaging of CSF leakage and brain expansion without lumbar puncture injection. In the past, MRC was based on conventional MRI, and the diagnosis of CSF leak was confirmed mainly at T2WI due to CSF signal enhancement. Recently, it has been reported in the literature that the CSF signal is enhanced by fat signal reduction and image reversal using a fast spin-2 echo sequence. Because of its clear visualization of brain parenchyma and CSF, both methods are valuable for the diagnosis of brain/meningeal herniation and CSF leak with a sensitivity of 89%. MRI with T2 images has replaced computerized poolography, although some studies have shown that intermittent or low-flow CSF leaks can be diagnosed with this method, but its sensitivity is low.
The most accurate method is nasal endoscopy. The nasal endoscope is inserted in the anterior nostril and carefully observed in five areas: anterior parietal, posterior, septal fossa, middle nasal tract, and pharyngopharyngeal opening. When examining each site, the internal jugular vein can be compressed bilaterally to raise the cranial pressure and see where the cerebrospinal fluid is flowing into the nasal cavity. For example, if the cerebrospinal fluid comes from the roof of the nose, the fistula is in the septal plate; if it comes from the middle nasal tract, the fistula is in the frontal sinus; if it comes from the septal fossa, the fistula is in the pterygoid sinus; if it comes from the eustachian tube, the fistula is in the tympanic ventricle or mastoid process. wormald et al. reported that in 5 of 6 cases of cerebrospinal fluid nasal leak surgery, the cerebrospinal fluid leak was not found under endoscopy.
Complications of cerebrospinal fluid rhinorrhea
A bone defect at the base of the skull is one of the prerequisites for the formation of a cerebrospinal fluid nasal leak. External air can also enter the cranial cavity by this route to form intracranial pneumatosis. Serious complications such as skull base defect, improper or failed early skull base repair, dural exposure wound infection, and upward intracranial infection (meningitis, epidural abscess, brain abscess) have high morbidity and mortality, and meningitis can be complicated in 4% to 50% of patients with CSF leak. Late complications: cerebral displacement, diplopia, malocclusion, nasopharyngeal stenosis, odontoclastic disease, chronic sinusitis, nasal obstruction, and facial deformity, with an overall complication rate of 11.5-63% and most scholars report between 25-50%. The soft tissues in the cranial defect area are directly connected to the outside world, and there is no hard tissue barrier. Patients lack a sense of security and are afraid of external blows and collisions in the defect area, which may lead to mental depression and other symptoms in the long term; cranial defect in children may cause mental retardation.
Treatment of cerebrospinal fluid rhinorrhea
Non-surgical treatment is usually done by lying with the head 30° high to the affected side, so that the brain tissue settles at the leaky hole to facilitate adhesion and healing. At the same time, keep the nasal cavity or ear canal clean, avoid blowing the nose, coughing and holding the breath, keep the bowels open, limit the amount of fluid intake, and apply appropriate drugs to reduce CSF secretion, such as vincristine or mannitol for diuretic dehydration. If necessary, lumbar puncture can also be performed to drain CSF (5-10 ml Ph) to avoid the rise of intracranial pressure (ICP) and to reduce or stop the leakage, so that the leakage hole can be healed. Approximately 85% of patients with CSF nasal and ear leaks are cured after 1-4 weeks of palliative care. However, the long-term outcome is poor, and the recurrence rate is high, with a 30% to 40% chance of meningitis. Non-surgical treatment should also be implemented throughout the treatment of cerebrospinal fluid rhinorrhea.
Patients with acute skull base injury should be repaired immediately after admission; medical origin injury should be repaired immediately; tumor-induced defect should be repaired at the same time of surgery; congenital lesion should be repaired at the same time when fully prepared for surgery.
Indications for surgery
1.Cerebrospinal fluid nasal leakage with pneumocephalus (intracranial pneumatosis), brain tissue prolapse, intracranial foreign body.
2.Cerebrospinal fluid nasal leakage caused by tumor.
3, combined with repeated episodes of septic meningitis.
The surgical method is divided into intracranial method and extracranial method. Some scholars believe that the long-term efficacy of cerebrospinal fluid shunt method is poor, and there is a risk of inducing infection and pneumocephalus; it is rarely used alone, but it can be used as one of the adjuvant treatments.
Although the success rate of traditional neurosurgical transcranial repair of leaks is only 70% to 80%, the success rate of nasal endoscopic extracranial approach is only 80%. However, the extracranial approach via nasal endoscopy still has many limitations, especially for some patients requiring craniotomy, including multiple fractures, extensive craniocerebral injury or severe skull base deformities, intracranial diplomatous tumors and high cranial pressure CSF leaks requiring CSF shunt surgery.
The extracranial approach can be divided into intranasal and extracranial approaches.
The extra-nasal approach has the advantage of a large surgical field and can be combined with the intranasal approach to repair fistulas.
(1) Frontal sinus cerebrospinal fluid nasal leak repair method: make a brow arch incision or coronal incision, expose the posterior wall of the frontal sinus, locate the fistula, remove the mucosa around the fistula, enlarge the bone of the posterior wall of the frontal sinus at the fistula, expose the dura mater, and suture the dural fissure. Proper fixation is required in the frontal sinus.
(2) Septal sinus cerebrospinal fluid nasal leak repair method: make a nasal orbital incision, complete the extra-nasal septal sinus opening, expose the septal roof, turn the mucosa of the middle turbinate or nasal septum over the fistula and fix it with pressure.
(3) Pterygoid sinus cerebrospinal fluid nasal leak repair method: enter the pterygoid sinus through the nasal septal route, fill the fistula hole with muscle and reinforce it with broad fascia.
The intranasal method of fistula repair is applicable to fistula repair at the apex of the pterygoid sieve.
(1) Nasal septal mucosal flap method: the fistula is covered with an ipsilateral nasal septal mucosal flap turned over and fixed with antibiotic oil gauze compression.
(2) Free broad fascial repair method: for tumors in the pterygoid saddle that occur after pterygoid sinus resection, broad fascia and muscle are placed directly on the fistula at the base of the saddle, and local compression is applied for 2 weeks. It is more effective when combined with nasal endoscopy.
(3) Nasal endoscopic cerebrospinal fluid nasal leak repair method: It is the most successful and mature procedure of transnasal endoscopic skull base surgery, with a success rate of more than 80% for one operation and almost 100% for traumatic and medical cerebrospinal fluid nasal leak.
Anatomical basis for transnasal endoscopic cerebrospinal fluid nasal leak repair
The anterior cranial base refers to the skull located in the anterior cranial fossa, below which are the frontal sinus, sieve sinus, pterygoid sinus, nasal cavity and orbit, and above which is the anterior cranial fossa, which is composed of the frontal orbit, sieve plate of the sieve, pterygoid winglet and anterior part of the pterygoid body, and the posterior boundary is the posterior edge of the pterygoid winglet, posterior edge of the anterior bed process, cranial opening of the optic nerve canal and anterior edge of the optic cross groove. The sieve plate is in the middle, and the olfactory nerve leads to the nasal cavity through the sieve foramen. The bone of the sieve roof and the inner plate of the frontal sinus are also thin and easily injured by trauma or surgery. The middle cranial base is the cranial bone located in the middle cranial fossa, below which is mainly the pterygoid sinus. The middle cranial fossa is composed of the pterygoid and temporal bones, and in the middle is the pterygoid saddle, in front of which is the optic nerve cross sulcus. On both sides of the slope area are forward, outward, and downward into the cavernous sinus, internal auditory meatus, and jugular foramen, respectively. The anatomical relationship of this region is complex and deep, and the surgical treatment of this region has been a problem for clinicians.
Clinical rationale for transnasal endoscopic cerebrospinal fluid nasal leak repair
The dura mater at the base of the skull is relatively weak and tightly adherent to the skull, making tight suturing almost impossible once the defect is present. They are often the source of postoperative cerebrospinal fluid leaks. The basic principle of skull base reconstruction is to tightly repair the dura and place various free or tipped grafts outside the dura to strengthen it and repair the skull base bone defect if necessary. Usually, as long as the dura is intact at the base of the skull, even large bone defects are not affected. The transendoscopic nasocranial or frontal, septal and pterygoid sinus surgery provides a short and easy access and is less traumatic (no life-threatening trauma) than traditional surgery (craniotomy). At present, we limit our transnasal endoscopic repair of skull base defects to repair of the anterior middle skull base in the midline region.
Transnasal endoscopic cerebrospinal fluid nasal leak repair methods
If there is no cerebrospinal fluid leak, only fibrin glue or gelatin sponge can be used to fill in the surgical cavity, the mucosa of the middle turbinate can be closed or the incised dura can be repaired, the mucosa can be fixed along the edge of the graft with otocerebral glue, the posterior wall of the pterygoid sinus can be covered with gelatin sponge, and the pterygoid sinus cavity can be filled with iodoform gauze. If there is cerebrospinal fluid leakage, muscle and fascia are taken for repair.
(2) For repair of septoparietal defect with cerebrospinal fluid nasal leak, the tumor of the nasal septal sinus or the affected hook and sieve vesicles were removed, the posterior group of septum was opened, and the sinus cavity was thoroughly cleaned; the septoparietal was fully exposed, the affected bone and dura were removed or the fistula hole was found, the meatus was scraped, and the bone wound was enlarged; the transverse muscle was taken, pounded into muscle pulp, and accurately filled into the fistula; the fascia closed the wound or was accurately lined between the dura and the bone surface of the cranial fossa; the gelatin sponge and iodine-like gauze strips were filled nasal cavity. If the bony defect is large, the sieve plate defect may be filled with bone with a tipped middle turbinate; the sieve roof defect may be filled with nasal septal cartilage, bone or titanium mesh, but it should be trimmed flat and covered with another piece of fascia outside, rather than exposed to the surgical cavity for epithelialization of the surgical cavity.
For repair of pterygoid sinus and peripterygoid sinus defect with cerebrospinal fluid nasal leak, Messerklinger approach is used to remove the septal sinus lesion; simple pterygoid sinus tumor or fracture is taken in Wigand’s style, and the pterygoid sinus cavity is entered directly; the tumor or mucosa in the pterygoid sinus that can be removed is excised and explored for bone destruction or fistula; the meatus is scraped and the wound margin is enlarged appropriately; the fistula hole is closed according to the above method, and the entire pterygoid sinus cavity is filled with muscle if necessary If necessary, the entire pterygoid sinus cavity should be filled with muscle. If the fistula is too large, the fistula can be repaired with a bathtub plug, and if the optic nerve is involved, the optic canal should be decompressed at the same time.
(4) Repair of posterior frontal sinus plate defect with cerebrospinal fluid nasal leak is more difficult, and the tumor in principle needs to be combined with an external approach in order to be removed. The repair steps are: resection of the hooked process, opening of the frontal crypt or resection of the tumor, enlargement of the frontal sinus opening; 70-degree microscopic scraping of the mucosa in the sinus and the granulation around the fistula and removal of the broken bone fragments; filling of the fistula hole and the frontal sinus cavity according to the above method. If the fistula is located in the higher or lateral posterior plate, the defect is large or there is brain tissue herniation, the fistula should be repaired by a combined approach if the simple intranasal approach fails.
Selection and application of grafts
The ideal dural replacement material should have the following characteristics: 1. be able to protect the brain and neural tissue from infection and not interfere with their normal physiological function or cause abnormal electrical activity. 2. have good histocompatibility and non-toxicity; have a certain degree of flexibility, elasticity and strength; be of moderate thickness and easy to close tightly. 3. be easily available and moderately priced. Commonly used grafts include repair/reconstruction materials, tissue adhesives, and other filler materials. Different repair materials and repair techniques have been reported in the literature, most with satisfactory outcomes. Since each skull base fracture/defect, brain/meningeal bulge, or CSF leak has its own characteristics, it is not possible to have a universal rule of thumb for repair. In general, for patients with skull base fracture sutures or small bone defects with normal CSF pressure, simple nasal mucosal repair is sufficient to plug the leaks, and fibrin glue can also be used to repair these small leaks with normal CSF pressure. For patients with large skull base defects or small leaks with elevated CSF pressure (e.g., spontaneous brain expansion), epidural placement of autologous bone, cartilage, fascia, fat, or other alternative materials such as stainless steel, titanium plates, Al2O3 ceramic sheets, silicone polyketide, polylactic acid polymer, hydroxyapatite, and artificial dura mater is required. The advantage is that it can stop CSF leakage in the short term, repair skull base defects, and prevent meningitis. In addition, many studies have applied free mucosa to repair leaks, and the mucosa of the pterygoid sinus is thicker than that of the middle turbinate and is potentially a good repair material. The mucosa of the inferior turbinate is relatively thick and is also a good mucosal graft material. The turbinate and its mucosa can be removed at the same time for double-layer repair, and the mucosa can be placed over the defect area, but this is not a commonly used epidural repair material.
Commonly used medical adhesives include isobutyl cyanoacrylate, methyl cyanoacrylate, cyanoacrylate and fibrin glue, the use of which is controversial in the literature. Other biodegradable filler materials such as gelatin sponge, Avitene, and cellulose oxide (surgicel) are also used clinically, but the efficacy of these materials has not yet been proven.
The efficacy of these materials has not yet been proven to be better. Gelatin sponges can be placed between other grafts to prevent displacement and dislodgement of the repair material in the early postoperative period. In conclusion, a proper evaluation of the characteristics of the leak and the surrounding skull base bone defect is the basis for selecting the appropriate repair material, while maintaining normal intracranial pressure and carefully repairing the skull base defect, especially the dural/arachnoid fissure, are crucial to the success of the procedure.
There is no uniform evaluation standard for the efficacy evaluation. We believe that the healing of skull base defect repair must be: 1) continuous skull base with flat and smooth trauma; 2) no cerebrospinal fluid leakage; 3) no intracranial pneumatization (except spontaneous intracranial pneumatization); 4) no intracranial infection; 5) no meningeal brain bulge.