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.

Ganglioglioma

First described by CB Courville in 1930, Ganglioglioma comes from the Greek work 'ganglion' meaning know, and the Greek word glia meaning glue and the Greek word oma meaning tumor. Strung together, the words mean 'glue knot tumor'. Ganglioglioma is a rare type of tumor that originates from nerve cells and develops in the central nervous system. The growth of the tumor and its symptom may vary depending on its exact location and size.

Ganglioglioma accounts for 2% of all primary intracranial tumors and up to 10% of primary cerebral tumors in children. Ganglioglioma can occur anywhere in the brain and rarely in the spine as well. Most Gangliogliomas are located on the sides of the brain by the ears and in children about 70% are located above in a part in the brain known as the tentorium - a membrane that separates an area in the back, lower part of the brain known as cerebellum, from an area in the back, upper part of the brain known as occipital lobes. Ganglioglioma can also occur in the brain stem, located below the cerebellum that controls many important motor, sensory and reflex actions.

Symptoms

The signs and symptoms depend on the location of the tumor and how fast it can spread, depending upon the age of the patient. In those above ages 10-20, symptoms include:

• Seizures
  
• Involuntary muscle movements
  
• Decreased awareness of the environment.

If Gangliogliomas appear in the ear lobes, it can lead to seizures and symptoms such as:

• Loss of awareness
  
• Abnormal sensations
  
• Feeling of being detached from oneself
  
• Involuntary muscle movements

If Gangliogliomas are present in the cerebellum, signs and symptoms include:

• Impaired motor coordination
  
• Headache
  
• Buildup of cerebrospinal fluid in the brain

Causes

Gangliogliomas are caused by abnormal glial cells. Glial cells support and maintain other cells. Gangliogliomas are partly made of neurons or nerve cells in various degrees of abnormality. In Gangliogliomas are also found supportive tissue known as stroma, which contain fibers and blood vessels. Fibers are flexible, threadlike objects found outside the cells. In Gangliogliomas are neurons, glial cells and stroma in abnormal shape, size and appearance. The more the cells change in structure, size and appearance; the more harmful the tumor is.

Diagnosis

Initially the seizures associated with Ganglioglioma lead a patient to seek medical help. The doctor uses various techniques to diagnose the cause of the seizures. Pictures of the brain are taken and CT scans done to get clear and detailed pictures. MRI scans are sensitive and specific at detaching a tumor and when contrast is injected into the person's body during the scan. About 50% of Gangliogliomas are detected when contrast is used. MRI scans can also detect if there are any cysts in an abnormal lump, swelling or sac that contains fluid and is covered with a membrane.

But it is not until a sample of the tumor is removed during surgery that it can be tested in a laboratory and definitively stated that it is Ganglioglioma. In a laboratory abnormal neurons are stimulated and the irritation produces a protein called synaptophysin and glial fibrillary acidic protein. There are special stains applied to the neurons in the lab to detect the presence of these proteins. However regular x rays do not help in diagnosing Gangliogliomas as they are best at detecting bones and can only detect if calcium is near the Ganglioglioma.

Gangliogliomas are common before age 20 and about 60% of people who are diagnosed with Ganglioglioma are adolescents and adults younger than age 30. However, even those as young as 2 or as old as 70 have been known to develop Ganglioglioma. It affects equal numbers of males and females. In the US approximately 1 to 2% of brain tumors are Gangliogliomas. About 10% of all primary brain tumors in children are Gangliogliomas.

Treatment

Surgery is most often done to remove Ganglioglioma tumor. After the tumor is removed, radiation therapy is not needed unless the tumor shows signs of growing back, which is rare. Radiation is aimed at tumors to destroy or weaken them. Prognosis of people with Ganglioglioma is excellent as it is easy for surgeons to remove them as they are typically found in one place and can be separated from the brain tissue. Most get cured after surgery and chance of tumor coming back after it has been totally removed is rare.

PET scan

PET - Positron Emission Tomography scan is a non-invasive test that aids in imaging the cellular functions and body tissues. It helps in observing the blood flow, oxygen use, and glucose metabolism. A PET scan is of immense help in the diagnosis of cancer, heart disease and brain disorders. The PET scan has been of particular help in the diagnosis of brain tumors, head and neck cancer and esophageal cancer. Since the PET scan reveals metabolic changes in the cells, it aids in early detection of certain conditions such as epilepsy. A PET scan involves injection of a small amount of radioactive tracer drug such as FDG-18. After an hour when the radioactive tracer has spread to the body, the scan is taken. The tracer emits tiny positively charged particles (positrons) that produce signals. A PET scan produces three-dimensional color images from the images taken by a camera that records the tracer as it travels through the body. It is often combined with a CT scan to study a particular body area. Lactating mothers must not breast feed their babies for a few hours after the PET scan.