This study will examine whether the tendency to have thrombosis, or the formation of blood
clots inside blood vessels, has a role in the development of pseudotumor cerebri (PTC). PTC
causes symptoms and signs of isolated elevated blood pressure in the cranium, or covering of
the brain. The disorder can lead to significant, negative effects on the visual system.
Increased pressure of the cerebrospinal fluid, that is, fluid around the brain, is a factor,
but the cause of the disorder is not clear. There has been documentation of clustering of
PTC within families. It suggests that potential genetic polymorphisms-abilities to take on
different forms-may become evident after exposure to conditions known to trigger PTC.
Thrombosis comes about by interactions between genetic and environmental or acquired
factors, or both, resulting in a blood clot at a specific time and location. Because the
disease occurs in episodes, the interaction of the genetic and nongenetic risk factors is
important. Cystinosis is a recessive disorder caused by deposits of cystine within the
lysosomes of cells-that is, sac-like cell parts that contain various enzymes. Involvement of
the kidneys remains the primary characteristic, eventually leading to renal failure. Of all
of the risk factors that make it easier for blood clotting, a high level of a substance
called homocysteine is of particular interest. Too much homocysteine in blood plasma is a
common finding in patients with kidney failure, and it has been recently identified as an
independent risk factor for diseases of the blood vessels.
Participants of all ages who meet the Dandy criteria for PTC may be eligible for this study.
Pregnant women will be excluded. There will also be a control group of nephropathic
cystinosis patients who do not have PTC.
Participants will be asked to undergo the following tests and procedures:
- Medical history.
- Physical examination, to evaluate the eye and nervous systems.
- Collection of blood for DNA and other tests.
- Collection of cerebrospinal fluid, through a procedure called lumbar puncture or spinal
The evaluation of patients will generally last 3 to 4 days. For the collection of
cerebrospinal fluid, the patient's skin on the back will be numbed with a local anesthetic.
A special needle will be inserted into the back, and a small amount of the fluid will be
drawn through the needle. There will be pain for a minute, although there can be a headache
lasting 24 hours. Also, there may be bruising, local pain, bleeding, or infection where the
needle enters. Patients may also have a magnetic resonance imaging scan of their head.
During the MRI scan, patients will lie still on a table that slides in and out of a metal
cylinder surrounded by a strong magnetic field. Patients will be able to communicate with
the MRI staff at all times and may ask to be moved out of the machine at any time.
During the follow-up of cystinosis patients under protocol #78-HG-0093 "Use of Cysteamine in
the Treatment of Cystinosis", we found that 6 of our NIH patients developed papilledema and
were diagnosed with pseudotumor cerebri (PTC), whose occurrence has not been previously
reported in cystinosis. The goal of this protocol is to identify the role of thrombosis
susceptibility in the development of PTC in nephropathic cystinosis patients in view of our
recent findings regarding genetic susceptibility to thrombosis in PTC in general. We propose
a case-control study. A total of 9 nephropathic cystinosis patients who developed PTC and 9
control nephropathic cystinosis patients without PTC will be screened based upon a
thrombosis susceptibility screening panel, including total homocysteine, protein C and S,
antithrombin III, fibrinogen, Factor VIII, Factor IX, Factor XI levels, testing for PT, PTT,
activated protein C resistance, antiphospholipid antibodies (ACA panel and Lupus AC) and
screening for FV Leiden mutation, FV G1628A polymorphism, FV R2 allele, Prothrombin 20210
mutation and 5,10-methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism in
patients with severe homocysteinemia (greater than or equal to 100 micro mol/l).
We will compare the prevalence of the factors that lead to thrombosis susceptibility in the
cases and controls.
- INCLUSION CRITERIA:
The inclusion criteria include only a confirmed diagnosis of pseudotumor cerebri (past or
present) in a patient with nephropathic cystinosis. Patients will be diagnosed as having
pseudotumor cerebri based upon modified Dandy criteria:
1. signs and symptoms related to increased intracranial pressure;
2. no localizing neurological signs with the exception of unilateral or bilateral sixth
3. neuroimaging study showing no mass lesion or hydrocephalus;
4. elevated opening pressure with normal cerebrospinal fluid contents on lumbar
Nephropathic cystinosis patients of all ages who meet the Dandy criteria for PTC will be
considered for the study.
Pregnant patients will be excluded from the study.