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CASE REPORT Table of Contents  
Ahead of print publication
Norethisterone-induced subacute on chronic cerebral venous sinus thrombosis with secondary intracranial hypertension in a young woman: A case report


 Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, Mangalagiri, Andhra Pradesh, India

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Date of Submission13-Jul-2022
Date of Decision14-Sep-2022
Date of Acceptance22-Sep-2022
Date of Web Publication18-Oct-2022
 

  Abstract 


Background: Cerebral venous sinus thrombosis is associated with several etiologies and may present with various symptoms. Oral contraceptives are one of the potential risk factors for cerebral venous sinus thrombosis (CVST) apart from infection and genetically acquired prothrombotic states. Abnormal uterine bleeding (AUB) is one of the common clinical conditions in gynecology practice, for which hormonal therapy is prescribed. Progestogens are relatively safe compared to combined estrogen and progesterone hormonal pills and hence a preferred therapy for AUB management. Case Report: We report a subacute on chronic CVST with secondary intracranial hypertension, probably induced by norethisterone intake in a young woman for AUB management. Diagnosis: CVST is diagnosed by contrast-enhanced computed tomography, magnetic resonance imaging, or MR venography. Treatment: CVST is treated with heparin and switched to warfarin anticoagulant therapy. Conclusion: Physicians need to have a high index of suspicion of CVST and treat the condition to prevent significant morbidity and mortality.

Keywords: Cerebral venous sinus thrombosis, headache, norethisterone acetate


How to cite this URL:
Kavitha G, Sharmila V. Norethisterone-induced subacute on chronic cerebral venous sinus thrombosis with secondary intracranial hypertension in a young woman: A case report. Apollo Med [Epub ahead of print] [cited 2022 Nov 28]. Available from: https://apollomedicine.org/preprintarticle.asp?id=358844





  Introduction Top


Cerebral venous sinus thrombosis (CVST) is a rare condition that mimics stroke and can present with various symptoms such as headache, neurological symptoms, seizures, and coma. Physicians need to have a high index of suspicion and treat the condition to prevent significant morbidity and mortality.[1],[2] Risk factors associated with CVST are pregnancy, puerperium, combined oral contraceptive (COC) pill usage, hormone replacement therapy, steroids, malignancy, infections, systemic inflammatory diseases, polycythemia, sickle cell disease, dehydration, hyperhomocysteinemia, congenital heart diseases, and trauma to the head.[1]

Hormonal therapy is the mainstay of treatment for abnormal uterine bleeding (AUB). COC pills and progestogens (oral, injectables, implants, and intrauterine devices) are commonly used as cyclical or continuous methods. Progestogens have a relatively safe side effect profile compared to COCs and are hence preferred in AUB treatment.[1] We report a case of CVST in a young female who has been prescribed norethisterone for AUB therapy.


  Case Report Top


A young woman, 22 years of age, married for 1 year, with a known case of Polycystic ovarian disease (PCOD), presented with complaints of continuous bleeding Per vaginum (p/v) for 10 days. She was started on tablet norethisterone acetate 10 mg OD. After 5 days of starting therapy, she developed progressively worsening headaches associated with several episodes of projectile vomiting. There was no history of joint pains, fever, trauma, altered sensorium, visual disturbances, photophobia, arthritis, sinusitis, and migraine. No family history of migraine or vasculitis disorder. On examination, the patient has an ill look, conscious, cooperative, with moderate pallor, no icterus, cyanosis, clubbing, or edema. Except for mild tachycardia, vitals are stable. The cardiovascular and respiratory systems were normal – no signs of meningeal irritation. Hemoglobin was 7.8 gm/dl and red cell indices and peripheral smear suggest microcytic hypochromic anemia. Electrocardiogram showed sinus tachycardia.

Ophthalmoscopy revealed bilateral papilledema. Magnetic resonance imaging (MRI) brain showed thrombosis of superior sagittal sinus and right transverse sinus [Figure 1] and [Figure 2] Mild sulcal space effacement and tortuous bilateral optic nerves with prominent optic cerebrospinal fluid space and flattening of the sclera was present suggestive of possible intracranial hypertension. Angiography of common bilateral carotid, internal, and external carotid arteries was normal. Fasting lipid profile and serum electrolytes were normal. Antiphospholipid antibody screen for Ig G and IgM was negative, serum homocysteine – 12.31 μmol/L (normal). Thyroid profile, liver, and renal function tests were normal with a negative urine pregnancy test. Based on the above clinical profile and MRI findings, a diagnosis of subacute on chronic CVST with secondary intracranial hypertension, probably induced by norethisterone intake with superimposed anemia, was made.
Figure 1: MRI brain showing thrombosis of the superior sagittal sinus. MRI: Magnetic resonance imaging

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Figure 2: MRI brain showing mild sulcal space effacement and tortuous bilateral optic nerves with prominent optic cerebrospinal fluid space and flattening of the sclera. MRI: Magnetic resonance imaging

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The patient was treated with heparin therapy for 5 days, then switched to warfarin therapy with regular monitoring of prothrombin time and activated partial thromboplastin time. The patient improved symptomatically and was discharged on day 7 with the advice not to take oral hormonal preparations (prothrombotic). She was on regular follow-up, and a repeat brain MRI 3 months later revealed no obvious abnormality.


  Discussion Top


CVST is a rare syndrome mimicking stroke that may pose a diagnostic dilemma in view of various signs and symptoms. The incidence of thrombosis in superior sagittal, transverse, and sigmoid sinuses has been reported to be 62%, 45%, and 10%, respectively.[3] Thrombosis causes local effects by venous obstruction leading to cerebral edema, venous infarction, impaired cerebrospinal fluid absorption, and raised intracranial hypertension.[4] It has a variable presentation such as severe headaches (90%) due to Intracranial hypertension (ICH), focal neurological symptoms (40%), seizures (30%–40%), encephalopathy (22%), ocular complaints, cranial nerve palsies, aphasia, transient ischemic attacks, or coma. The most common symptom is headache, typically presenting as localized, dull aching, slow-onset headache, which is worsened by recumbent posture.[1] Our case had progressively worsening headaches associated with vomiting episodes.

There are diverse risk factors for CVST; in more than 85%, at least one risk factor has been identified.[4] Risk factors associated are pregnancy, puerperium, COC pills, steroids, hormone replacement therapy, malignancy, systemic inflammatory diseases, infections, coagulation disorders, polycythemia, sickle cell disease, dehydration, hyperhomocysteinemia, trauma to the head, and congenital heart diseases.[1] With oral COCs, a 2–6 fold risk of venous thrombosis is noted.[5] A case of CVST with norethisterone in a case of menorrhagia secondary to Polycystic ovarian disease (PCOD) has been reported.[6] CVST in a case of severe iron-deficiency anemia (IDA) caused by fibroid uterus with menorrhagia has also been reported.[7] CVST in isolation without focal neurological deficit or papilledema occurs in only 15% of cases.[6] Our patient took norethisterone pills for less than a week before being diagnosed with CVST. She also had moderate IDA, which might be a precipitating factor. The proposed mechanisms of IDA causing CVST include IDA-induced reactive thrombocytosis, alteration in blood flow pattern within vessels, and metabolic stress precipitated by hypoxia in basal ganglia and thalamus.[7]

First-generation progestogens like norethisterone have a lower venous thrombosis risk profile as they partly metabolize to ethinylestradiol compared to the second and third generations.[6] CVST is diagnosed by contrast-enhanced computed tomography (CECT), MRI, or MR venography (MRV). CECT may show a classic “empty delta” sign in which a central hypodensity within the sinus surrounded by contrast enhancement in the triangular shape is visualized. With MRI, early signs are the absence of flow void with alteration of signal intensity in the dural sinuses. The combination of abnormal signals in a sinus and the corresponding absence of flow on MRV confirm the diagnosis of CVST. MRI/MRV is the imaging test of choice for suspected CVST according to the American Heart Association/American Stroke Association 2011 scientific statement. In cases, wherein MRI/computed tomography is inconclusive brain angiography is reserved.[8]

Our patient was treated with heparin for anticoagulation, a safe and effective therapy in CVST.[1],[2] Following the acute phase, treatment is often switched to warfarin which is continued for 3 months, as recanalization is expected after 3 months. CVST has a favorable prognosis, with more than 80% of patients having good neurological outcomes.[9] Our patient showed full recovery 3 months after oral warfarin therapy. Her hemoglobin improved with oral hematinics, and she was advised not to take any hormone preparations.


  Conclusion Top


We report a rare case of CVST following minimal dosing of norethisterone intake for a short duration and IDA as a predisposing risk factor, who completely recovered following anticoagulant therapy. Predisposing risk factors must be thoroughly checked by detailed history and evaluation before prescribing hormonal therapy. With early detection and treatment, CVST can be managed easily with full recovery in the majority of cases.

Conflicts of interest

There are no conflicts of interest.

Consent for publication

The case report is in accordance with the ethical principles that have their origin in the Declaration of Helsinki. The authors certify that the patient has given verbal and analytical approval, and written informed consent has been obtained for publishing the case details in a journal.

Declaration of patient consent

The authors certify that he has obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published, and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.

Funding

Nil.



 
  References Top

1.
Ferro JM, Canhão P, Stam J, Bousser MG, Barinagarrementeria F, ISCVT Investigators. Prognosis of cerebral vein and Dural sinus thrombosis: Results of the international study on cerebral vein and Dural sinus thrombosis (ISCVT). Stroke 2004;35:664-70.  Back to cited text no. 1
    
2.
Devasagayam S, Wyatt B, Leyden J, Kleinig T. Cerebral venous sinus thrombosis incidence is higher than previously thought: A retrospective population-based study. Stroke 2016;47:2180-2.  Back to cited text no. 2
    
3.
Saposnik G, Barinagarrementeria F, Brown RD Jr., Bushnell CD, Cucchiara B, Cushman M, et al. Diagnosis and management of cerebral venous thrombosis: A statement for healthcare professionals from the American heart association/American stroke association. Stroke 2011;42:1158-92.  Back to cited text no. 3
    
4.
Rajput R, Dhuan J, Agarwal S, Gahlaut PS. Central venous sinus thrombosis in a young woman taking norethindrone acetate for dysfunctional uterine bleeding: Case report and review of literature. J Obstet Gynaecol Can 2008;30:680-3.  Back to cited text no. 4
    
5.
Stegeman BH, de Bastos M, Rosendaal FR, van Hylckama Vlieg A, Helmerhorst FM, Stijnen T, et al. Different combined oral contraceptives and the risk of venous thrombosis: Systematic review and network meta-analysis. BMJ 2013;347:f5298.  Back to cited text no. 5
    
6.
Ramya T, Prakash B, Devi B. Norethisterone induced cerebral venous sinus thrombosis (CVST): A rare case report and literature review. Int J Reprod Contracept Obstet Gynecol 2014;3:231-5.  Back to cited text no. 6
    
7.
Busani S, Scott S, Neely JA, Calvo AR. Cerebral venous thrombosis secondary to severe iron deficiency anemia: A case study. Cancer Clin Oncol 2012;1:91-8.  Back to cited text no. 7
    
8.
Alvis-Miranda HR, Milena Castellar-Leones S, Alcala-Cerra G, Rafael Moscote-Salazar L. Cerebral sinus venous thrombosis. J Neurosci Rural Pract 2013;4:427-38.  Back to cited text no. 8
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9.
Girot M, Ferro JM, Canhão P, Stam J, Bousser MG, Barinagarrementeria F, et al. Predictors of outcome in patients with cerebral venous thrombosis and intracerebral hemorrhage. Stroke 2007;38:337-42.  Back to cited text no. 9
    

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Correspondence Address:
Vijayan Sharmila,
Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, Mangalagiri - 522 503, Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/am.am_105_22



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