The Periodical Case

Stroke in a young woman 

History: 

• 24 year old woman, married with 2 children and no medical illnesses

• Presented with an acute speech difficulties, visual disturbance and right side weakness

• This occurred following paracentesis for an abdominal ascites which occurred 8 days following start of recombinant follicular stimulating hormone to stimulate ovaries for artificial insemination.

• No history of trauma, cardiac disease, joint pain, month ulcers, skin rashes, or drug abuse.

• No history of leg swelling.

Physical Examination: 

• A young thin woman with normal vitals.

• CVS: Normal

• Chest: Normal

• Abdomen: soft and lax, with mild ascitis.

• CNS: conscious, alert, oriented but has dysartheria, right homonomous hemianopia, right hemihyposthesia and right hemiplegia.

• No evidence of DVT.

Summary of Investigation: 

• Hemogram: raised hemeatocrit, hemoglobin and leucocytes.

• Albumin: low

• CT-Scan brain: images no. 1and 2

• MRI brain: images no. 3-6

• MR Angio: image no. 7

• Autoimmune screen: negative

• Homocystiene screen: normal

• Hypercoaguble screen: normal

• ECG: normal

• TT Echo normal + TEE: normal

Conclusion: 

• Young woman with sever ovarian hyperstimulation syndrome, complicated with an acute ischemic stroke, involving the basal ganglia and internal capsule of the left hemisphere. 

• Patient admitted into the intensive care unit, received IV hydration, IV heparin, IV albumen and intensive physiotherapy. 

• Particular care for body fluid collection in interstitial spaces, hydration state and viability of her pregnancy.

Ovarian hyperstimulation syndrome and stroke 

Ovarian hyperstimulation syndrome: 

Ovarian hyperstimulation syndrome (OHSS) occurs in 1–10% of women undergoing ovarian hyperstimulation with exogenous gonadotrophin administration, and is a recognized and potentially life-threatening complication (Brinsden et al., 1995).  

Severe cases of OHSS, enough to require hospitalization, occur in about 1 out of 200 ovulation induction cases. For those undergoing IVF, the risk factors include the number of eggs retrieved and the peak estradiol level. As retrieving a large number of eggs is one of the goals in IVF, this is a risk associated with this procedure (Mark Perloe, 2003) 

OHSS presents with a wide clinical spectrum ranging from mild abdominal discomfort to potentially lethal complications such as adult respiratory distress, renal failure and thromboembolism (Brinsden et al., 1995).  

Recent advent of ovulation induction and assisted reproductive techniques is a newly recognized cause of OHSS and the devastating squeal of cerebral infarction in otherwise healthy women (Hou NT. et al, 1998), and it is by far the most serious side-effects of this syndrome (Fahmy M., 1998) 

Pathogenesis: 

A hypercoagulable state with secondary supraphysiological hyperestrogenaemia and haemoconcentration after ovarian hyperstimulation have been proposed to induce attack of thromboembolism. In addition, some inherited deficiencies referred to as thrombophilias, such as antithrombin III, protein C and protein S deficiency, factor V Leiden mutation, and antiphospholipid antibody syndrome that can lead to hypercoagulability are thought to be predisposing factors. It has been reported (Kim et al., 1981) that hyperestrogenaemia might cause an increase in platelet count, fibrinogen and von Willebrand factor, and a decrease in antithrombin III level. Hence, those patients with a peak serum estradiol level 3000 pg/ml should be managed with care. A combination of iatrogenic hyperestrogenism and established pregnancy may have a synergistic effect on the risk of thromboembolism.  

Haemoconcentration has been thought to be a contributing factor to thromboembolism in patients with OHSS. It was reported that 62% of OHSS cases would have haemoconcentration with a haematocrit >42%. Interestingly, this was more prevalent in the neck and intracranial thrombosis groups (81 and 67% respectively). Either haemoconcentration itself or in association with OHSS is able to increase both the viscosity of blood and the concentration of coagulation factors. It has been reported that ovarian stimulation in IVF is associated with an increase in both fibrinogen level and clot lysis time, as well as a decrease in antithrombin III level (Aune et al., 1991). A significant differences was demonstrated in serum fibrinogen, thrombin–anti thrombin III complex, plasmin-2 antiplasmin complex, D-dimers and prekallikrein between the OHSS and control groups (Kodaman et al., 1996). These authors also found that activation of the coagulation cascade system occurred within 2 days after hCG administration, while activation of the fibrinolytic system occurred a few days later in OHSS patients. Early activation of the fibrinolytic system may indicate the occurrence of subclinical thrombus formation. The onset was seen to be earlier in the intracranial group because the diameter of intracranial vessels is much smaller than that of other vessels in other groups.  

Manifestation: 

Ovarian hyperstimulation syndrome can be mild, moderate, or severe: 

• Mild hyperstimulation causes enlargement of the ovaries and discomfort and fluid buildup in the abdomen.

• Moderate hyperstimulation causes additional symptoms including nausea, vomiting, and shortness of breath. This condition may require bed rest.

• Severe hyperstimulation can cause life-threatening fluid buildup around the heart and lungs and in the abdomen, and a drop in blood fluid content. This condition requires urgent medical care and hospitalization to prevent liver failure, stroke, or heart damage. (Katy Magee, MA, 2003)

Management: 

With severe hyperstimulation, the ovaries enlarge and result in abdominal pain, and fluid leaks into the abdomen and the chest cavity. This can result in bloating, pressure, nausea and shortness of breath, as well as blood chemistry abnormalities and a thickening of the blood. The important thing to remember is that if a patient undergone an ovulation induction treatment and experience any of these symptoms, she must check with her reproductive endocrine physician. Ovarian hyperstimulation syndrome can be a life-threatening condition if not recognized and treated in a timely fashion. Some women assume that as the symptoms do not appear to be related to their ovaries, they should go to an emergency room or see an internist or family physician. This can be a grave mistake.  

Despite the severity of this situation, there is often a silver lining to the cloud. First, removal of the fluid often provides rapid and dramatic relief. Rarely, a repeat 'fluid tap" is necessary to remove a reaccumulation of fluid. More important, hyperstimulation is frequently associated with pregnancy, and resolution of the symptoms will usually proceed without adverse effects on the pregnancy (Mark Perloe, 2003). 

Doctors should monitor closely for signs of ovarian hyperstimulation during superovulation. When this condition develops, the medication is stopped. Any procedure, such as collecting eggs, planned for that particular cycle is postponed until all symptoms are gone, usually in 2 to 4 weeks. 

Dose-adjusted heparinization is recommended as the first-line treatment of choice, while intravascular thrombolysis or operative thrombectomy is an aggressive but effective treatment. Continuation of pregnancy is considered safe, without any increased risk of fetal congenital anomalies (Yu-Che OU, et al, 2003). 

Some physicians believe that the use of intravenous albumin at the time of retrieval may reduce the risk, but research data have provided conflicting results. 

Intra-arterial thrombolysis can be used with relative safety even in very early pregnancy. (Stys PK., 2002)

Dr Waleed Khoja, Neurologist, Armed Forces Hospital-Riyadh