Neurofibromatosis

Neurofibromatosis is a broad term used for three different genetic disorders all of which result in tumors on the tissues of the nerves. These tumors can occur anywhere on the nervous system, or beneath the skin or on the bones. It may also form on the eye. Neurofibromatosis is normally diagnosed in early childhood. In most cases, children inherit the defective mutated genes from their parents. However in certain cases it occurs through spontaneous mutation.

Neurofibromatosis (NF1)

NF1, also known as Von Recklinghausen, is the most common type of Neurofibromatosis. NF1 can lead to symptoms ranging from mild to very severe. Some of the distinctive signs of Neurofibromatosis Type 1 include:

• Au-lait spots (brown spots)
  
• Freckles in the armpit, groin, other skin folds
  
• Neurofibromas on or under the skin throughout the body
  
• Deformation of bones
  
• Big sized head and short stature
  
• Scoliosis
  
• Learning disabilities
  
• High blood pressure
  
• Tumors on the iris of the so called Lisch nodules
  
• Tumors on the optic nerve.

Physical examination and family history of the patient form the basis of the diagnosis of Neurofibromatosis Type1. Imaging tests such as x-ray, CT scan and MRI may also be ordered along with skin biopsy to confirm the diagnosis.

There is no cure for NF1; patients have to be monitored carefully on a regular basis to check for any sort of complications. Surgery is advised if the tumors are causing malformed bones. In very rare cases, the tumors become cancerous. Like any other cancers, these tumors are surgically removed and treated with chemotherapy or radiation.

Neurofibromatosis Type 2

Neurofibromatosis Type 2 is rare compared to NF1 and is characterized by multiple tumors on the cranial nerve that controls hearing and balance. These tumors are known as Vestibular Schwannomas and give rise to deafness and balance problems. Tumors may also develop on the spinal nerve and other peripheral nerves that control swallowing, speech, eye movements and facial sensations and eventually hamper their effective functioning. Patient may also develop weakness, numbness, or tingling in an arm or leg.

The symptoms of NF2 typically start in the teens or early twenties. Hearing loss beginning during adolescence is the first and most distinctive feature of Neurofibromatosis Type 2. Cataract that starts at an early age is also a strong indicator of NF2. Similar to NF1, NF2 is also caused by defective gene mutation.

There is no cure for NF2; however patients will be treated symptomatically. Regular monitoring of ear and eye functions is carried out to understand any further deterioration. MRI is advised at frequent intervals to assess the size of the tumors. If the tumors are growing in size, they may be removed surgically or shrunk through radiation.

Schwannomatosis

Schwannomatosis is a rare form of Neurofibromatosis and it varies from NF1 and NF2 genetically and clinically. This condition causes tumors on nerves of the brain and spinal cord and nerves in the arms and legs. However Schwannomatosis never causes tumors on the vestibular nerve. Intense pain is a characteristic feature of Schwannomatosis. As tumors press on the nerves and tissues pain, numbness or tingling occurs in the affected parts of the body. There is no definite treatment for Schwannomatosis. Treatment plan includes pain management through medications and regular monitoring of the size of the tumors. Not all the tumors are ideal for surgical removal due to their delicate location. If it is feasible, surgical removal of tumors is the most effective method to manage pain.

Neurofibromatosis

Neurofibromatosis (NF) also known as Von Recklinghausen disease is a relatively rare genetic disorder where the patients develop multiple benign tumors (neurofibromas). These tumors occur under the skin and throughout the nervous system. Neurofibromatosis occurs in about one in 4000 births. There are 2 types of Neurofibromatosis: Neurofibromatosis Type I (NF-1) is the most common - 90% of all cases and Neurofibromatosis Type II (NF-2) takes the remaining 10% of cases.

Causes of Neurofibromatosis :
Neurofibromatosis is caused by a defective gene - in the case of NF1, the defective gene responsible is chromosome 17 and in the case of NF2 , it is the chromosome 22. The defective gene manifestation is for half the cases. The other half is because of spontaneous mutation.

Symptoms:

• Presence of cafe-au-lait (brown/white) spots, patches of tan or light brown skin, usually about 5-15 mm in diameter.
  
• Multiple freckles in the armpit or groin area
  
• 90 % of cases of NF1 have tiny tumors called Lisch nodules in the iris (colored area) of the eye
  
• soft tumors are the hallmark of NF-1. They occur under the skin (plexiform neurofibromas) located along nerves or within the gastrointestinal tract
  
• Neurofibromas are small and rubbery and the skin overlying them may be somewhat purple in color
  
• Skeletal deformities - twisted spine (scoliosis), curved spine (humpback) or bowed legs
  
• Tumors along the optic nerve, which result in vision disturbance in about 20% of patients
  
• The presence of NF-1 in a patient’s parent, child or sibling
  
• speech impairment, learning disabilities and attention deficit disorder
  
• seizure disorder
  
• abnormal accumulation of fluid within the brain (hydrocephalus)
  

Apart from the above mentioned symptoms, the NF1 patients are susceptible to malignant brain tumors, as well as leukemia and cancerous tumors of certain muscles (rhabdomyosarcoma), the adrenal glands (pheochromocytoma) or the kidneys (Wilms’ tumor).

NF-2 symptoms: Tumors along the acoustic nerve resulting in the loss of hearing. If the tumor spreads to the neighboring nervous system it will cause weakness of the muscles of the face, headache, dizziness, poor balance and uncoordinated walking. Cataracts may form at an early age. Chances of developing brain tumors are high.

Diagnosis: If the presence of 2 or more symptoms mentioned above is there, it calls for additional steps in diagnosis. Diagnosis of NF-2 requires the presence of either a mass on the acoustic nerve or another distinctive nervous system tumor. The most diagnostic factor is the presence of the disorder in a patient’s parent, child or sibling. Careful testing of vision and hearing is mandatory to know about the progression of Neurofibromatosis. In addition X-rays of the bones will help to track the development of deformities. CT/MRI scans also help to check for the progression of tumors.
The electric response evoked in the cerebral cortex by stimulation of the acoustic nerve will be quite useful to determine the involvement of the acoustic nerve, while EEG (electroencephalogram) may be useful for suspected seizures.

Treatment: As of now, there are no treatment options available. The symptoms of NF1 /NF2 are treated individually. Tumors are removed surgically wherever possible. Some cases may require Chemotherapy or radiation therapy. Curving of spine or bowed legs (tibial dysplasia) may be corrected by special braces.

Prognosis varies depending upon the individual cases. If the tumors continue to grow, they may destroy the surrounding nerves. Blindness, loss of hearing and poor balance may be the outcome.

Meningioangiomatosis

This is a rare malformation of the central nervous system, so rare that not many cases of cystic Meningioangiomatosis (MA) have been reported. First described by Bassoe and Nuzum in 1915, Meningioangiomatosis was found incidentally in an autopsy of a 15-year old boy. It is characterized by a plaque-like or nodular mass overlapping leptomeninges in patients.

Though the pathogens are unknown, there are three possible theories – first, these lesions probably represent a hamartoma - a benign malformation made up of an abnormal mixture of cells and tissues. Second, they could result from direct invasion of the brain tissue by a leptomeningeal meningioma. Third, they represent a vascular malformation.

A rare disease characterized by the brain, benign lesion of the leptomeninges, MA usually involves the cerebral cortex. Seizures are often noticed in these patients. Though extremely rare multifocal cases have been reported both in adults and children, the lesion is normally found in one place. Biopsy is necessary for diagnosis and conventional treatment is to surgically remove the lesion.

Meningioangiomatosis may either be sporadic or associated with Neurofibromatosis type 2. In sporadic Meningioangiomatosis, seizures and headaches are present. Whereas, NF2 is asymptomatic and diagnosed only at autopsy. Meningioangiomatosis is benign and the seizures can be surgically corrected.

Analysis

When medical records of ten histopathologically confirmed MA patients were treated between 2010 and 2011, all the patients presented with symptomatic seizure attacks before surgery. MRI and CT were the radiological examinations done for pre-operative diagnosis of all cases. Accurate diagnosis of Meningioangiomatosis is important because it is a benign surgically correctable cause of seizures.

Results

All patients underwent craniotomy surgeries with total gross resections of MA lesions.

Post operative follow-ups range from 8 to 108 months. No radiological recurrence was found in any case. While eight patients achieved total symptomatic remission after surgeries, two were found to suffer from attacks infrequently under severe anti-epileptic drugs.

Although MA is rare and usually misdiagnosed, it is possible for correct preoperative diagnosis with differential diagnosis taking into consideration patient's ages, symptomatic seizure attacks, and radiological findings. MA is curable and the prognosis is excellent since patients become free of seizure after surgical treatments.