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Readings About Cerebral venous sinus thrombosis (CVST) (ER-RMPH)

Submitted by: Ma. Lenie F. Tamayo BSN-III

Submitted to: Aizza Grace Tolentino Clincal Instructor

Date of Submission: August 1, 2011 I. OVERVIEW OF THE ARTICLE

Cerebral venous sinus thrombosis (CVST) is a rare form of stroke that results from thrombosis. Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss (a blood clot) of the dural venous sinuses, which drain blood from the brain. Symptoms may include headache, abnormal vision, any of the symptoms of stroke such as weakness of the face and limbs on one side of the body, and seizures. Causes: Cerebral venous sinus thrombosis is more common in particular situations. 85% of patients have at least one of these risk factors: a. Thrombophilia, a tendency to develop blood clots due to abnormalities in coagulation, e.g. factor V Leiden, deficiency of protein C, protein S or antithrombin, or related problems b.Nephrotic syndrome, a kidney problem causing protein loss in the urine c.Chronic inflammatory diseases, such as inflammatory bowel disease, lupus and d.Behçet's disease e.Pregnancy and puerperium (the period after giving birth) f. Particular blood disorders, especially polycythemia vera and paroxysmal nocturnal hemoglobinuria g. Use of estrogen-containing forms of hormonal contraception h.Meningitis and infections of the ear, nose and throat area such as mastoiditis and sinusitis i. Direct injury to the venous sinuses j. Medical procedures in the head and neck area Signs and symptoms: Nine in ten people with sinus thrombosis have a headache; this tends to worsen over the period of several days, but may also develop suddenly (thunderclap headache). The headache may be the only symptom of cerebral venous sinus thrombosis. Many patients have symptoms of stroke: inability to move one or more limbs, weakness on one side of the face or difficulty speaking. This does not necessarily affect one side of the body as in the more common "arterial" stroke. 40% of all patients have seizures, although it is more common still in women who develop sinus thrombosis peripartum (in the period before and after giving birth). These are mostly seizures affecting only one part of the body and unilateral (occurring on one side), but occasionally the seizures are generalised and rarely they lead to status epilepticus (persistent or recurrent seizure activity for a long period of time). In the elderly, many of the aforementioned symptoms may not occur. Common symptoms in the elderly with this condition are otherwise unexplained changes in mental status and a depressed level of consciousness. The intracranial pressure (pressure around the brain) may rise, causing papilledema (swelling of the optic disc) which may be experienced as visual obscurations. In severely raised intracranial pressure, the level of consciousness is decreased, the blood pressure rises, the heart rate falls and the patient assumes an abnormal posture. Diagnosis Diagnostic tests: The diagnosis may be suspected on the basis of the symptoms, for example the combination of headache, signs of raised intercranial pressure and focal neurological abnormalities, or when

alternative causes of headache and neurological abnormalities, such as a subarachnoid hemorrhage, have been excluded. There are various neuroimaging investigations that may detect cerebral sinus thrombosis. Cerebral edema and venous infarction may be apparent on any modality, but for the detection of the thrombus itself, the most commonly used tests are computed tomography (CT) and magnetic resonance imaging (MRI), both using various types of radiocontrast to perform a venogram and visualise the veins around the brain. Computed tomography, with radiocontrast in the venous phase (CT venography or CTV), has a detection rate that in some regards exceeds that of MRI. The test involves injection into a vein (usually in the arm) of a radioopaque substance, and time is allowed for the bloodstream to carry it to the cerebral veins - at which point the scan is performed. It has a sensitivity of 75-100% (it detects 75-100% of all clots present), and a specificity of 81-100% (it would be incorrectly positive in 019%). In the first two weeks, the "empty delta sign" may be observed (in later stages, this sign may disappear). Magnetic resonance venography employs the same principles, but uses MRI as a scanning modality. MRI has the advantage of being better at detecting damage to the brain itself as a result of the increased pressure on the obstructed veins, but it is not readily available in many hospitals and the interpretation may be difficult. Cerebral angiography may demonstrate smaller clots than CT or MRI, and obstructed veins may give the "corkscrew appearance". This, however, requires puncture of the femoral artery with a sheath and advancing a thin tube through the blood vessels to the brain where radiocontrast is injected before X-ray images are obtained. It is therefore only performed if all other tests give unclear results or when other treatments may be administered during the same procedure. D-dimer A 2004 study suggested that the D-dimer blood test, already in use for the diagnosis of other forms of thrombosis, was abnormal (above 500 μg/l) in 34 out of 35 patients with cerebral sinus thrombosis, giving it a sensitivity of 97.1%, a negative predictive value of 99.6%, a specificity of 91.2%, and a positive predictive value of 55.7%. Furthermore, the level of the D-dimer correlated with the extent of the thrombosis. A subsequent study, however, showed that 10% of patients with confirmed thrombosis had a normal D-dimer, and in those who had presented with only a headache 26% had a normal D-dimer. The study concludes that D-dimer is not useful in the situations where it would make the most difference, namely in lower probability cases. Treatment Various studies have investigated the use of anticoagulation to suppress blood clot formation in cerebral venous sinus thrombosis. Before these trials had been conducted, there had been a concern that small areas of hemorrhage in the brain would bleed further as a result of treatment; the studies showed that this concern was unfounded. Clinical practice guidelines now recommend heparin or low molecular weight heparin in the initial treatment, followed by warfarin, provided there are no other bleeding risks that would make these treatments unsuitable. Some experts discourage the use of anticoagulation if there is extensive hemorrhage; in that case, they recommend repeating the imaging after 7–10 days. If the hemorrhage has decreased in size, anticoagants are commenced, while no anticoagulants are given if there is no reduction. The duration of warfarin treatment depends on the circumstances and underlying causes of the condition. If the thrombosis developed under temporary circumstances (e.g. pregnancy), three months are regarded as sufficient. If the condition was unprovoked but there are no clear causes or a "mild" form of thrombophilia, 6 to 12 months is advised. If there is a severe underlying thrombosis disorder, warfarin treatment may need to continue indefinitely. Thrombolysis (removal of the blood clot with "clot buster" medication) has been described, either systemically by injection into a vein or directly into the clot during angiography. The 2006 European

Federation of Neurological Societies guideline recommends that thrombolysis is only used in patients who deteriorate despite adequate treatment, and other causes of deterioration have been eliminated. It is unclear which drug and which mode of administration is the most effective. Bleeding into the brain and in other sites of the body is a major concern in the use of thrombolysis. American guidelines make no recommendation with regards to thrombolysis, stating that more research is needed. Raised intracranial pressure, if severe or threatening vision, may require therapeutic lumbar puncture (removal of excessive cerebrospinal fluid), medication (acetazolamide), or neurosurgical treatment (optic nerve sheath fenestration or shunting). In certain situations, anticonvulsants may be used to prevent seizures; these are focal neurological problems (e.g. inability to move a limb) and/or focal changes of the brain tissue on CT or MRI scan.

II. COPY OF THE ARTICLE
Nicole De Jong My Experience with Cerebral Venous Thrombosis I gave birth to a healthy baby girl on March 24, 2007, and recovered just fine from a difficult delivery. One week after going home, I felt pain above my left eye that I thought might related to the shift in hormone levels after pregnancy, or possibly from the epidural anesthesia, since headaches are a side effect. My OB/GYN gave me a prescription for Imitrex that treats migraines, but it did nothing. The headaches increased the following week, and my pain was unbearable. I also had nausea, vomiting, dizziness, extreme fatigue, and blurred vision. I couldn't sleep or get out of bed for several days due to the pain and all the other symptoms. I lost all 40 pounds of my pregnancy weight. I called my primary care doctor, who was booked, so my mother drove me to the Emergency Room (ER). The physician on call was curt and I did not think he took my symptoms seriously, although I did have a CT scan that came back normal. I was diagnosed with a sinus infection, and given a narcotic for pain and an antibiotic to clear the infection. The day after my visit to the ER in mid-April, I lost all hearing in my left ear, and the excruciating, unbearable headache persisted. I returned to the ER where another physician diagnosed my headache as a consequence of post-partum (after delivery) anxiety. He prescribed a medication for anxiety, and discontinued the antibiotic for the previously diagnosed sinus infection. I still had an intolerable headache two days later, and was still unable to get out of bed or eat. My symptoms were increasing in severity and I reached my breaking point. That afternoon I saw my primary care doctor who ordered an MRI, which I had two days later. I was contacted by the MRI technician, who told me to meet my primary doctor in the ER right away. When we arrived, my mother and I were ushered into an office where my doctor and the Director of the ER explained that the MRI revealed a life-threatening blood clot in my brain. The exact diagnosis was a cerebral venous sinus thrombosis (blood clot). It was in my brain and extended to my neck. I was admitted to the hospital immediately, and at that point, no one could estimate the length of my stay. I spent the next 4 days in the hospital in a direct observation unit, and was given heparin (a blood thinner) into my vein. I was monitored every 5-6 hours to make sure that the heparin was effective. I was completely drained physically, and felt devastated and severely depressed emotionally. It broke my heart to be away from my newborn daughter, Natalie, for her and for me. Fortunately for both of us, I had the help of some wonderful nurses who wheeled me to the hospital lobby - IVs and all, so

that I could see and hold Natalie, if only for a short time. These visits were bittersweet, because although I was delighted to see her, I had to leave her to go back to my hospital bed. On my fourth day in hospital, my headache became tolerable. My hearing was returning, my vision was clearing, and I was tolerating food. My INR was within normal range, so I was discharged from the hospital. I was placed on an anti-seizure medication and another antibiotic in addition to Coumadin®. My INR was monitored every Monday at the hospital's out-patient lab and followed-up every Thursday to determine any need for an adjustment in dose. My mother took time off in anticipation of Natalie’s birth and cared for her during my hospital stay, and was there to help me recover. My parents, Dennis and Janice, were there to help in so many ways, for which I am so grateful. In June 2007, I had my first appointment with a neurologist at the University of Southern California (USC), who informed me that the clot was permanent, and that I need to be monitored for the rest of my life. She recommended that I stay on oral blood thinners for another 6 months, followed by aspirin therapy indefinitely, and to take anti-seizure medication for another 3-4 months. She told me that any future pregnancy would be extremely high risk with need for careful medical oversight. I was told about the risk of bleeding with blood thinners, and to avoid any undue risk, most especially head injury. The neurologist ran every genetic test possible in August 2007, and everything showed up completely normal, which was a huge relief. My neurologist said that my cerebral venous sinus thrombosis (CVST) was likely due to a bout of sinusitis and mastoiditis. I was told that my clot was permanent, would not get smaller or larger, and was more than likely a one-time occurrence. In October of that year, my anti-seizure medication caused me to lose my appetite, and I had to discontinue it, and I’ve been fortunate not to have had any more seizures. My blood thinner was also stopped, because my blood was getting “too thin.” I had sudden bleeding from my nose, rectum, and gums, so my neurologist stopped the warfarin one week earlier than originally planned, and advised me to take aspirin (325mg) daily for the rest of my life. My doctors believed that I could live a completely normal life, and I was free of lab visits and “sticks” to draw blood to keep an eye on my INR. I was told by both my neurologist and OB/GYN that I could consider another pregnancy if I continued daily aspirin during my pregnancy. I could not put into words how blessed I felt that it was not genetic, for my daughter’s sake, and how relieved I felt to return to a more normal life. Little did I know at the time that this was incorrect advice. Another upsetting life event is that my daughter's biological father couldn’t handle the responsibility of a new daughter and a sick girlfriend and chose to leave our lives right after her birth and my blood clot. However, a friend, Jeremy De Jong, whom I knew for 4 years due to a friendship between our parents, became my biggest support, best friend, father to my daughter, and now husband. We were married a year and a half later in September 2008. He is a miracle in our lives. As I was thinking about my upcoming one year survival anniversary, I was taken back to something at the forefront of my mind during my hospitalization for the clot. I was adopted at birth, and had no medical or personal family history about my biological parents. In April 2008, I contacted the California Department of Public Social Services to find my biological parents. I wanted to learn as much as I could about their health history for the benefit of both me and my daughter. I received a package that included medical histories from my biological parents, as well as contact information for my mother, who sent me a letter in May 2008. I replied immediately and told her about my blood clot and need for her medical information. I called her a few nights later, and it was an extremely emotional phone call for the both of us. She found out she was a grandmother, and we agreed to meet. I did not meet my biological father.

I cannot put into words the anticipation, fear, and years of emotion involved in our meeting. I learned that my biological great-grandmother and great aunt died of heart disease at very young ages, and that my great uncle and my grandmother underwent triple bypass heart surgeries. A year after my grandmother's triple bypass she redeveloped 100% heart blockage in those arteries. My grandmother takes both aspirin (81 mg) and Plavix® daily to prevent clotting. None of them have been diagnosed with any blood clotting disorders. They were told they had “sticky” blood, but it was in the arteries rather than the veins like mine. We have continued building a relationship, and are now a part of each other's lives. I have met all my maternal biological family. My adoptive family was a constant support through the whole process because they understood my need to connect. Both adoptive and biological families attended my wedding in September 2008. It was the best gift I could ever want! In April 2009, I changed doctors because I was under a new health insurance plan. I discussed my history with my new OB/GYN. While reviewing my history, she was especially thorough and chose to run extensive blood testing for genetic blood clotting disorders. When the results came back, I was speechless. I was heterozygous for both the C677T and A1298C MTHFR gene mutations. My first reaction was anger. Why hadn’t any of my previous doctors tested for this mutation? My biggest concern was whether I was properly caring for myself in the 2 years since my blood clot. This new OB/GYN was truly wonderful, and took time with me to go over all my original test records, and stated simply that MTHFR mutations are not tested by all doctors. She referred me to a hematologist who advised me that the MTHFR gene mutation would not change my treatment. I became pregnant in July 2009. My husband and I were overjoyed and very afraid at the same time, knowing that this was a high risk pregnancy for me and the baby. I self-injected blood thinners twice daily during my pregnancy. My OB/GYN arranged a team of doctors for me that were in constant communication about my progress. Besides her, I saw a perinatologist, a maternal and fetal specialist, a hematologist, and a neurologist. I began having episodes of an extremely rapid heartbeat three months later, and a cardiologist was added to my team of doctors. The cardiologist found that the strain of the pregnancy on my heart was causing a heart murmur and irregular heartbeat. 22 weeks into my pregnancy, a partial placental abruption was found. It caused a blood clot to form in the space between my placenta and uterus. I was put on full bed rest immediately for the duration of my pregnancy, and prescribed with medication to slow my daily premature contractions. I was also seen twice weekly by my OB/GYN. Despite all the medical oversight, I had another severe bleeding episode at 28 weeks, and was hospitalized for a week because the placental abruption was persisting. I was given 2 steroid injections to limit or prevent complications of a premature delivery, and was sent home. At 36 weeks into my pregnancy, in preparation for the upcoming delivery, my blood thinner was changed to one that had short-acting effects. Ultimately, I was scheduled me for an emergency Csection, where I delivered a baby boy, Wyatt. After 5 days in the hospital, my son and I went home with a good bill of health. I was restarted on self-injections of blood thinners twice daily for 7 weeks. I began having horrible headaches, and within two days lost the hearing in my left ear again. I was terrified that the blood clot I had after my daughter’s birth was recurring. I went to see my neurologist immediately on the advice of my OB/GYN, and had an MRI, which was surprisingly normal. The neurologist found extensive scar tissue in the place of my original clot, and that was what was causing my headaches, with some additional stress from my fluctuating hormones postdelivery. My neurologist thought that this scar tissue could possibly continue to cause headaches of varying intensity. My heart symptoms resolved after I delivered my son.

I have been lucky to survive two high risk pregnancies, and deliver two beautiful and healthy children. I decided to have a tubal ligation to avoid any future risk attached to another pregnancy. I enrolled in a research study on rare blood clots at the University of Miami’s genetic research department. My daughter tested positive for heterozygous A1298C, and I plan to take her to a pediatric hematologist. I still have headaches, some worse than others, but they are usually relieved with Extra Strength Tylenol, or a narcotic when they are excruciating. I also found out that I lost some vision permanently in my left eye due to the clot. I have run the gauntlet emotionally, but I am so grateful to have a strong support network. The amazing support of my family and loved ones and the lifesaving treatment from my doctors helped me survive. I see every day as a miracle, especially since I was first told that I would not live to see my daughter’s first birthday, and now I can watch two children grow up. My experience taught me how absolutely precious life is and I cherish every moment I have. My four year survival anniversary is in April 2011, and I look back on my blood clot as my true second chance at life! "You gain strength, courage, and confidence by every experience by which you really stop to look fear in the face. You are able to say to yourself, 'I lived through this horror. I can take the next thing that comes along." - Eleanor Roosevelt

V. REFERENCES 1.Towbin A. The syndrome of latent cerebral venous thrombosis: its frequency and relation to age and congestive heart failure. Stroke. May-Jun 1973;4(3):419-30. [Medline]. 2.Daif A, Awada A, al-Rajeh S, et al. Cerebral venous thrombosis in adults. A study of 40 cases from Saudi Arabia. Stroke. Jul 1995;26(7):1193-5. [Medline]. 3.Ferro JM, Lopes MG, Rosas MJ, et al. Long-Term Prognosis of Cerebral Vein and Dural Sinus Thrombosis. results of the venoport study. Cerebrovasc Dis. 2002;13(4):272-8. [Medline]. 4.Buccino G, Scoditti U, Patteri I, et al. Neurological and cognitive long-term outcome in patients with cerebral venous sinus thrombosis. Acta Neurol Scand. May 2003;107(5):330-5. [Medline].

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