Neurinoma

NEUROFIBROMATOSIS HISTORY

Researchers suggest that Neurofibromatosis (NF) was identified through a painting at the beginning of the second century and later revealed in numerous papers. The fact is that Neurofibromatosis was detailed for the first time by Friedrich Daniel von Recklinghausen in 1882. Since that date, NF was usually called "Disorder of Recklinghausen".
NF was essentially ignored by the public in general until the report of the "Disorder of the Elephant Man" through the publication of the book by Ashley Montagu: "The Elephant Man: a study of the human dignity", in 1971.
Montagu's Book was based on the work of the famous British surgeon of 19th century, Frederick Treves, "The Elephant Man and another reminiscences", published in 1923.

Montagu introduces 25 pages about Joseph Merrick, a poor English young so grossly disfigured that had a miserable life as circus attraction. In 1884, Treves carried Merrick to the London's Hospital where he lived the four remaining years before death, at age 26. His courage and dignity deeply touched people of the society that visited him in the hospital.
Merrick's Condition was diagnosed as NF at the beginning of this century, and this wrong diagnosis remained up to 1986, when his condition was diagnose again as a "Syndrome of Proteus", a much more rare and serious disorder than NF.
In 1986, Dr. Michael Cohen, of Halifax's University, Canada, identified the medical condition of Joseph Merrick as the "Syndrome of Proteus". Scientists of the Massachusetts General Hospital and National Center for Human Genome Research continue searching Proteus' Syndrome.
The history of Joseph Merrick promotes a positive message, even for the patients and families who face NF: it is the history of a man who overcame his problems, living with dignity and transforming the public ignorance in compassion and respect.

References:
ABLON, Joan. Living with genetic disorder: the impact of neurofibromatosis 1, Auburn House, Unites States, 1.999.
Neurofibromatosis Inc: www.nfinc.org - The Misconception

DEFINITION

Neurofibromatose is a common genetics disease, what means that many professionals of health will come across it in some cases during their professional lives but not enough to become specialists.
This illness is an actual challenge for several medical specialties because its manifestation and severity varies in each patient.
In more than 100 years in which neurofibromatose has been described by Von Recklinghausen little yet is known about several points of this genetics pathology. It is believed that the new researches in the field of the gene-therapy and of modern exams will bring exciting results and a great comfort for patients and their families.
Neurofibromatose (NF) is a definition for two clinical genetical disorders with a few related characteristics, however with many distinct clinical manifestations and genetic origins.

The most common is denominated neurofibromatose type 1 (NF1, neurofibromatose von Recklinghausen) and the rarest is denominated neurofibromatose type 2 (NF2, neurofibromatose bilateral acoustics).

NF2 affects the central nervous system and it is characterized by acoustics neuromas occurrence (also called vestibular schwannomas). They are benign tumors that are developed in the eighth nerve of the cranium. Back subcapsular juvenile opacity of the lens is another feature found in a great number of individuals who have such disorder.
Acoustics neurinoma treatment has proved to be more challenging in patients with NF2 than in those who don't have the disorder because the tumors have a faster growth. If only one cell is left during removal, there is a great potential of the tumor starting to grow again.

In NF2 the tumors tend to infiltrate the nerves and to be less uniform, thus making it more difficult for surgery removal without sacrificing the nerves.
The individuals who have NF2 can also have other tumors in the brain and in the spine such as: meningiomas, schwannomas, gliomas.
It is worth pointing out that the manifestations and symptoms can differ a lot from patient to patient.

Both disorders are very distinct in their clinical characteristics and are caused by gens mutation in two different chromosomes.
The gen for NF1 is located in the long arm of chromosome 17 and the gen for NF2 in the long arm of chromosome 22. There is not much correlation.
People with NF1 are not submitted to enough risk of acoustic neuromas as a prevention with routine acoustic tests.
People with NF2 are not submitted to a feocromocitoma risk (a tumor of the adrenal gland) .

Neurofibromatose has been observed in different parts of the world, in all races, with identical correlation between men and women.
It is worth stressing that NF2 is the rarest and, based on data from American associations that study the disorder, the proportion is from 1 to 40,000 .
American data show that approximately half of all the cases are of new mutations, that is, without family antecedents.

It is often manifested at a later time, specifically at puberty or in young adults with chronic progression along years. There are some difficulties in the treatment of patients afflicted with NF. It is too difficult to foresee the location and the severity of the next lesions. Some medical specialties are more acting in the follow-up of patients with NF, like the pediatrician, the geneticist, the otorhinolaryngologist, the ophthalmologist, the neurosurgeon, the radiologist and the dermatologist.
Many patients do not fit properly in NF1 and NF2 criteria, even though they're afflicted with NF.

Blood tests can prove the presence of NF2; through them it's possible to identify an individual genetic change. After this identification (in case the person wants to have a child), it'll be possible to do pre-birth tests at about 10 gestation weeks to identify if the baby is afflicted with NF2.
NF2's first symptoms are usually indications of hearing deficiency and off-balance, which result from problems in the acoustic nerve that carries the audition to the brain and also from lesions in the vestibular nerve that carries information of the balance to the brain. Such 'problems or lesions in the nerves' consist of a compression of the tumor against the nerves, thus resulting in the symptoms abovementioned.

Other NF2's less common indications are:
Problems in the facial nerve (facial paralysis) , headaches , sight problems and skin problems caused by neurofibromas.
There are two important characteristics to diagnose if an individual is afflicted with NF2:
Schwannomas Bilateral Acoustic (Neurinoma/Neuroma)
Or
First relatives afflicted with NF2

FAQs (frequently asked questions) and their corresponding answers:

1-Do people with NF2 develop NF1 ?
Answer: No. Both diseases are genetically and functionally distinct.
2-What is the commonest treatment form for a person afflicted with NF2 who has developed tumors in the brain?
Answer: The surgery is still the commonest treatment form; however, there are other alternatives of treatment as the radiotherapy and the Gamma Knife (radiosurgery).
It's important to notice that not all the tumors that are developed in a patient afflicted with NF2 should be treated as soon as detected because they usually have a slow growth and can remain for years without causing any problems.
3-What is the difference between NF2 tumors and cancer tumors?
Answer: NF2 tumors growth is slow and they do not cause metastase, i. e., are not spread in the body. That's why they're called benign tumors.
4-Does NF2 have a cure?
Answer: No. At the moment, there isn't yet a cure for NF2.
Various institutions make researches and work in the pursuit of developing a medical or genetic treatment for NF2 and the related tumors. Based on data from the Neurofibromatosis Association, researches are being held in a good pace. It's believed that in approximately 10 years an effective treatment will be available for this disorder.
5-Which are the important exams for people with NF2?
Answer: The most important exams are brain magnetic resonances and audition tests such as audiometria.
Other important exams are spine magnetic resonances and ophthalmologic exams.

Questions not answered yet:

1-Do expositions to the X-ray affect NF2 progression?
Although individual experiences suggest that the exposition to x-ray exams can increase the number of tumors in people afflicted with NF2, this issue hasn't yet been proved by any study.
2-Do people afflicted with NF2 have a larger incidence of cancer than those without the disorder?
In most NF2 cases, tumors are benign. There are some researches in progress to verify if malignant tumors are being developed (cancer).
So far, there isn't any study that demonstrates some connection.
3-What is the probability of a person afflicted with NF2 needing a surgery?
There is a great variation in the development of the disease among individuals and even at different ages along life. It's very difficult to determine the probability of an individual needing a surgery along life. Nevertheless, the great majority of individuals afflicted with NF2 need at least a surgery in a certain stage of their lives.
4-Does the person afflicted with NF2 die younger than one without the disorder?
In past studies, life average time of people afflicted with NF2 was smaller than life of people without it, but due to technological advances, enhancement in the diagnosis, monitoring and modern surgical techniques, such data cannot be applied any more.

Typical problems and tumors in NF2:

As described above, here you can find a list of some tumors and other possible problems that can be found in people afflicted with NF2, followed by a brief description.
Vestibular Schwannomas bilateral (Neurinoma/Neuroma):
These tumors are developed in the eighth nerve of the cranium that has two portions:
Acoustic nerve that carries information about the sound to the brain and the vestibular nerve that carries balance information to the brain.
This kind of tumor is the one that usually shows the first indications of the disease, causing audition loss, humming and balance loss.

Schwannomas on the skin and in the spine:

Schawannomas symptoms are closely related to their location. In case they're developed in the spine, they can cause drowsiness of the legs or of some part of the body.
When they appear on the skin, they tend not to show neurological symptoms, whereas in tiny nerves they can even be detected.

Meningiomas, ependymomas and astrocytomas:

Besides schwannomas, people with NF2 can have other kinds of tumors in the brain and in the spine; meningioma is the commonest.
Older patients afflicted with NF2 can have tumors growing along the brain. Since the removal of the tumors is delicate, one should have caution.
If a tumor is not causing severe symptoms, we should observe it because the removal could be more harmful than the tumor itself.
Ependymomas and astrocytomas are rarer, they are generally developed in the spine next to the neck. Notice that in patients without NF2 these tumors are removed as soon as discovered; however, in NF2 cases it can be more prudent to observe and only intervene when the neurological indications start to appear.

Cataracts

Finally, some patients can develop a special kind of cataract, known as posterior juvenile cataract, sublenticular opacity or have other problems in the eyes.
As NF2 patients have great chances of losing audition, follow-up ophthalmologic exams are of extreme importance.

NF2 Treatments (Acoustic Neurinomas) *

1-Observe and wait:

The habitual progression of the disorder usually results in total deafness.
The House Ear Institute, a neurinomas treatment center of the acoustic, developed a solution that allows the patient with audition loss to recover hearing.
The name of the device is ABI(Auditory Brainstem Implant) and it is being tested in several centers in the world.
In order to preserve the audition, one should not intervene unless the tumors take great proportions.
So, it's important to detect which tumor is growing faster so that we can follow its evolution.
However, the larger the tumor the more difficult will it be to preserve the audition and other functions of the nerve with the surgery. Thus, it's very difficult for the person afflicted with NF2 to decide when to intervene and which treatment option is the most appropriate.

2-Surgical removal

It's crucial for the surgeon to have experience in NF2, what enables the patient to have more chances of success in the surgery.
We should emphasize that the smallest the tumors the greatest the chances of preserving the nerves' functions. But this does not mean a guarantee of the nerves preservation.

3-Gamma Knife

It's a high, necessary, and very concentrated form of radiation that produces excellent results in those who are not afflicted with NF2.
In NF2 cases, the tumor involves more the nerve and it becomes difficult to preserve it.
There's less preservation of the hearing and facial nerve in NF2 than in individuals who don't have this disorder.
According to physicians, FSR has proved to be better in the audition preservation attempt, even though there are no long-term studies yet.

4-Fractionated stereotactic radiosurgery (FSR)

FSR is another alternative of radiosurgery that differs from Gamma Knife.
The main difference is that Gamma Knife sends a great quantity of rays at once while FSR sends smaller doses of rays during some sessions. The time of treatment is defined by the medical team.
In both treatments the chances of having rays reaching another part of the brain that is not the tumor are very small.

* The treatments described above are better clarified in the section

Controlling the Manifestations

1-Magnetic Resonance (MRI)

It's the most accurate form of lesions' control. It should be performed at a regular basis because it is through this that the doctors follow the progress of the disorder or any re-growth after a treatment.
After discovering a first lesion, in case it's not advisable the intervention , the exam should be repeated annually.
It's very important that an individual who is afflicted with NF2 is submitted to a MRI of the spine.
During a MRI exam the patient needs to remain still for about 45 minutes.
The patient is laid down in a small bed that slips in a machine with a capsule form (tube).
The magnets are activated around the patient and produce a high sound inside the tube.
At a certain point of the exam, the patient may receive a contrast (injected in the vein of the arm) which highlights the tumors. This is done only when the physician recommends it or in case the radiologist finds it necessary.

2-Audiogram

Simple audition test, not evasive, that lasts around 30 minutes and should be performed at intervals similar to MRI.
Even with the presence of neurinoma of the acoustic, the tests can be normal. Generally small tumors do not jeopardize the audition, but that's not a rule.
Some tumors can have a reasonable growth without affecting the audition; that's why these exams complement each other.

3-ABR

Hearing answer of the brain (ABR), also known as (BAER), is one of the oldest available tests.
It's highly accurate in finding problems and takes the same time of audigram, though it does not show the cause of the problems.
This exam assists the doctors to follow the disorder.

4-Exam of the Eye

An experienced ophthalmologist can discover ocular abnormalities before the manifestation of the symptoms.
It's important for the doctor to be familiarized with NF2.

Author notes:
I'd like to thank Dr.Leide de Almeida Praxedes (Human Genetics Lab - IBUSP) for collaborating in the review of this section content and for the dedication in the study of this disorder.

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