What is Neurofibromatosis?

According to their clinical manifestations and genetic loci, in 1988 the National Institute of Health (NIH) classified them into Neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (Neurofibromatosis type 2, NF2).

Wu Fengzeng	(Chief physician)	Department of Neurosurgery, Xuanwu Hospital, Capital Medical University
Hu Peng	(Resident)	Department of Neurosurgery, Xuanwu Hospital, Capital Medical University

Neurofibromatosis (NF) is a benign peripheral nerve disease, which is an autosomal dominant genetic disease. Its histology originates from the connective tissue of the inner nerve membrane of the peripheral nerve sheath. It often involves organs that originate from the ectoderm, such as the nervous system, eyes, and skin, and is one of the common neurodermal syndromes.

Western Medicine Name: Neurofibromatosis
English name: Neurofibromatosis, NF

Affiliated Department: Surgery-Neurosurgery
Contagious: Non-contagious

Neurofibromatosis disease classification

Causes of neurofibromatosis

Neurofibromatosis is an autosomal dominant genetic disease. The pathogenic gene of NF1 is located on autosome 17q11.2. In patients with this disease, this chromosomal site is missing, preventing the patient from producing the corresponding protein-neurofibroma protein. Neurofibromatin is a tumor suppressor that slows cell proliferation by accelerating the reduction of the activity of the proto-oncogene p21-ras, which plays a major role in the intracellular mitotic signal transduction system. The NF2 pathogenic gene is located on the autosome 22q11.2. Patients with this gene locus have lost the ability to produce Schwann cell tumor proteins in patients. It is unclear whether the protein is a tumor suppressor gene and its mechanism of action. However, it may play a role in the functioning of the cell cycle, intracellular and extracellular signal transfer systems.

Pathogenesis of neurofibromatosis

Neurofibromas are composed of Schwann cells and fibroblasts. Its extracellular mechanisms are embedded in nerve bundle membrane cells, axons and mast cells. The cell composition of plexiform neurofibromatosis and cutaneous neurofibromatosis is the same. However, plexiform neurofibromatosis has a more extensive extracellular matrix and is often rich in vascular networks. Neurofibromatosis and the accumulation of multiple nerves or nerve bundles, which extend to the surrounding structure and cause corresponding dysfunction and hyperplasia of soft tissue and bone structure. Plexiform neurofibromatosis occasionally turns into a spindle cell tumor (malignant tumor of the peripheral nerve sheath). The role of each cell type in the occurrence and development of neurofibromatosis remains unclear.

Neurofibromatosis Pathophysiology

The main pathogenic mechanism of neurofibromatosis is that tumor growth causes damage to surrounding tissues, such as gastrointestinal bleeding; tumor growth itself causes compression of the corresponding peripheral nerves and corresponding neurological dysfunction such as numbness, muscle weakness, etc. In the cranial space, a space-occupying effect results in increased intracranial pressure and headaches and vomiting; or tumors stimulate brain tissue to produce abnormal discharges and form epilepsy.

Clinical manifestations of neurofibromatosis

1 Clinical manifestations of neurofibromatosis type 1

1) Milk coffee spots: Almost all patients have skin pigmentation spots, which are pale brown, dark brown or brown. Freckle-like pigmentation appears in the armpit, and physiological changes such as development, pregnancy, menopause, and mental stimulation can aggravate it. Sometimes the rash appears later, and it begins to develop and develop slowly during development.

2) Multiple neurofibromas: Patients often complain of painless subcutaneous masses throughout the body, which gradually increase and expand. Significant progression during puberty and pregnancy. More asymptomatic. A few manifestations are radiation-like or burning pain, and tumors compress the optic nerve and cause vision loss.

3) Neurological symptoms: Most patients have no complaints. Only a few patients have decreased intelligence, memory impairment, seizures, limb weakness, numbness, etc.

4) Bone damage: A small number of patients have abnormal bone development at birth, or they can cause abnormalities by compressing bones during tumor growth.

5) Visceral damage: Neurofibromas growing in the chest, mediastinum, abdomen, or pelvis can cause visceral symptoms. Involvement of the digestive tract can cause gastrointestinal bleeding or obstruction, as well as endocrine abnormalities.

2 Clinical manifestations of neurofibromatosis type 2

The first symptom is the most common bilateral progressive hearing loss, and some patients present with unilateral severe hearing impairment or fluctuating hearing loss or sudden hearing loss. The most common clinical manifestations are tinnitus, hearing loss, dizziness, and dizziness, which are rare, followed by ataxia such as hand tremor, walking sway, and abnormal tone, and skewness of the mouth and facial numbness. These symptoms are mostly unilateral. A few patients complain of persistent headache with increased intracranial pressure such as nausea, vomiting, and blurred vision.

Diagnosis and differential diagnosis of neurofibromatosis

Neurofibromatosis auxiliary examination

1) Ultrasound examination: multiple substantial masses can be seen, which can be located subcutaneously, abdominal cavity, pelvic cavity, etc.

2) Ophthalmological examination: The iris miliary, brownish yellow round nodules can be seen through the slit lamp, and they also become Lisch nodules or iris hamartomas. Ophthalmoscope may reveal optic nipple edema or optic nerve atrophy due to increased intracranial pressure.

3) CT and MRI: For spinal or intracranial tumors can be detected by CT or MRI. Tumor density in CT is usually slightly higher than that in spinal cord and brain tissue, and is round or round. On MRI, neurofibromas show low or equal signals on T1 and high signals on T2. Some tumors are accompanied by cystic changes. The tumors were significantly enhanced after the enhanced scan.

4) Nerve electrophysiological examination: manifested as neurogenic damage, slower electrical signal transmission, etc.

Diagnosis of neurofibromatosis

In 1987, the United States NIH formulated diagnostic standards:

NF1:

1) 6 or more milk coffee spots with a maximum diameter of 5 mm or more before puberty and 15 mm or more after puberty;

2) 2 or more neurofibromas or 1 plexiform neurofibromas;

3) brown freckles on the armpit or groin;

4) optic glioma;

5) 2 or more Lisch nodules, namely iris hamartoma;

6) Obvious skeletal lesions: such as dysplasia of sphenoid bone, thin long cortical bone, and pseudoarticular formation;

7) Patients with confirmed NF1 among first-degree relatives.

NF1 can be diagnosed if the above criteria meet 2 or more.

NF2

1) bilateral acoustic neuroma;

2) Family history of NF2 (patients with NF2 in first-degree relatives) and unilateral auditory neuroma;

3) A family history of NF2 (with NF2 in first-degree relatives). The patient had 2 of the following lesions: neurofibromas, meningiomas, gliomas, Schwann cell tumors, and posterior lens opaque plaques.

NF2 can be diagnosed by meeting the above criteria.

Differential diagnosis of neurofibromatosis

NF1 needs to be identified from:

1) Nodular sclerosis is also an autosomal antecedent inheritance of neurocutaneous syndrome, which accumulates skin and nervous system. Skin This table includes symmetrical butterfly-shaped sebaceous adenomas, lobular leukoplakia, and shark skin plaques, as well as milk coffee plaques; the neurological damage is characterized by intracranial nodular calcifications, which are common in clinical Intractable epilepsy and decreased intelligence; ophthalmological examination can show worm-like calcified nodules near the visual nipples or yellow circular damage around the retina.

2) A rare congenital disease of McCune-Abright syndrome, which is characterized by abnormal bone fiber development, thinning of the cortex, prone to pathological fractures, and increased alkaline phosphatase; coffee-like pigmentation with large patches of skin, and endocrine Diseases, such as hyperthyroidism, parathyroidism, precocious puberty, and Cushing syndrome. Generally does not involve the nervous system, normal intelligence.

3) Proteus syndrome caused by asymmetric overgrowth of various tissues. The characteristic manifestation is tissue nevus, which is yellow-brown or black-brown, with clear borders, swelled with a cobblestone texture, and often has a striped appearance. It is located on the toes, palms, fingers, nose and trunk. Biopsy of the case showed hyperkeratosis, spines. Layer hypertrophy and papillomatous hyperplasia. Nervous system damage is mainly manifested as mental retardation. Ophthalmic manifestations include itchy cysts on the outer layer of the eyeballs and cysts above the eyeballs.

NF2 needs to be identified from:

1) Dizziness caused by other vestibular and central nervous system diseases manifests as rotation of the visual object, with autonomic symptoms such as nausea, vomiting, and sweating. NF2 tumors wrap and compress the vestibular nerves. Due to the slow growth of tumors, patients can gradually compensate, so patients rarely have true vertigo, which can only manifest as dizziness and instability in walking. NF2 is often accompanied by progressive decline in bilateral hearing.

2) Meningiomas, cholesteatoma, and trigeminal schwannoma are common tumors in the cerebellopontine angle region. Meningiomas have typical meningeal tail signs. Cholelipoma and trigeminal schwannomas can cause trigeminal neuralgia. symptom.

3) Multiple lesions in the brain of metastatic tumors should be distinguished from metastatic tumors. Most of the latter have primary lesions, which can be identified based on clinical and medical history. ^[1]

Neurofibromatosis Disease Treatment

NF1 Treatment of neurofibromatosis NF1

1) Generally does not require treatment;

2) Symptomatic treatment: if the patient suffers from radiation or burning-like pain that is intolerable, the pain medication can be reused; antiepileptic treatment can be given for secondary symptomatic epilepsy. Carbamazepine is the drug of choice, with a starting dose of 0.2 g, twice a day. The dose of the drug can be adjusted gradually according to the concentration of the drug and the therapeutic effect. Monitor the patient's blood and blood biochemical indicators during the medication;

3) Surgical treatment:

a) Pediatric localized neurofibromas can be removed at one time;

b) Large tumors can be completely or partially removed.

c) Plexiform neurofibromatosis lesions are often rich in vascular network. During the operation, attention should be paid to the incisions in the normal tissues surrounding the lesions. The tumor and surrounding tissues should be completely removed. Postoperative laser irradiation can be used to prevent recurrence.

d) Unilateral orbital plate deficiency can be repaired. ^[2]

NF2 Treatment of neurofibromatosis NF2

Surgical treatment is currently the effective treatment of choice. In most cases, the posterior sigmoid sinus approach is used for surgery. The position of the facial and auditory nerves is carefully identified under electrophysiological testing, and the above nerves are dissected and functionally preserved. Often the posterior wall of the internal auditory canal is removed during the operation in order to achieve a total tumor resection.

Neurofibromatosis disease prognosis

There are no effective measures to prevent or reverse the course of NF1. However, most of the NF1 disease itself only affects the face and does not affect normal lifespan, unless benign tumors affect the function of important organs.

The prognosis of NF2 is poor. Bilateral surgical deafness often leads to total deafness of the ears, and the recurrence rate after subtotal resection is high. The main outcomes were death, hearing loss and facial paralysis. However, with the help of modern microneurosurgery concepts and intraoperative electrophysiological monitoring, the opportunities for anatomical or functional preservation of the facial auditory nerve and total resection of tumors are increasing. ^[3]

Neurofibromatosis disease prevention

There is no effective preventive measure for this disease.

Neurofibromatosis disease care

Neurofibromatosis is rarely malignant and patients can maintain a good psychological state. Proper diet, enhanced nutrition, and proper exercise can help strengthen immunity. People with neurological disorders suggest orderly rehabilitation training under the guidance of a rehabilitation physician. Periodic follow-up, generally follow-up review 3-6 months, can be extended or shortened according to specific circumstances.