June 7, 2007

Tuberculous Meningitis in Pregnancy Presenting As Hyperemesis Gravidarum

By Kutlu, Tayfun; Tugrul, Semih; Aydin, Arzu; Oral, zay

Hyperemesis gravidarum is a severe and intractable form of nausea and vomiting in pregnancy. The peak incidence is at 8-12 weeks of pregnancy, and symptoms usually resolve by week 16. The diagnosis of hyperemesis is easily made from clinical data; however, it is sometimes hard to diagnose because of accompanying symptoms and because other complex diseases may present with hyperemesis.

An 18-year-old woman presented with complaints of nausea, vomiting and headache at the emergency department of our hospital on 19 February 2006. She was 14 weeks pregnant according to her last menstrual period (LMP), had lost 6 kg since the beginning of pregnancy and weighed 47 kg. This was her first pregnancy; no special features were noted in her obstetrical and gynecological history. She was exhausted but conscious, and cooperating well. Her blood pressure was 90/60 mmHg, pulse rate 86/ minute, body temperature 36.2 C, and a systemic physical examination was normal. Laboratory findings were as follows: blood type A Rh(+), hemoglobin 12.9 g/dL, hematocrit 40.2%, white blood cells 7300/mm3, and platelets 254 000/mm3. Thyroid and liver function tests and other biochemical values were normal except for electrolyte values: Na+ 133 mEq/L, K' 3.4 mEq/L, Cr 87 mEq/L. Urine analysis showed ketonuria (+++) and proteinuria (++). Srologie screening was negative (HIV, hepatitis B and C). Ultrasonography of the upper abdomen was normal and obstetric ultrasonography revealed an intrauterine live singleton 14+l weeks pregnancy. Hence, the patient was diagnosed with hyperemesis gravidarum and hospitalized.

Following hospitalization, oral nutrition was ceased and balanced electrolyte and dextrose solutions were infused; anti-emetic treatment with meclizine was commenced. After some clinical improvement, on the third day of hospitalization symptoms worsened and her temperature became raised at 38 C. After consultation with Internal Medicine, she was re-diagnosed as having an upper respiratory tract infection and treatment with acetylcysteine and cefazolin was started. Despite this medication and the resolution of ketonuria, oral nutrition was inadequate, and nausea and headache persisted. Her body temperature was between 37 C and 38 C. On 22 February the patient had an apathie appearance; she rapidly became disoriented, was semi-conscious and was left hemiparetic. Physical examination was repeated and neck stiffness was observed. She was immediately transferred to the emergency department of neurology and on cranial magnetic resonance imaging (MRI), radiological indications of hypertensive encephalopathy were observed. Meanwhile the patient's blood pressure was within the normal range. Ceftriaxone + metronidazole + mannitol medication was commenced, and on 23 February a lumbar puncture was performed. The cerebrospinal fluid pressure was high, its appearance xanthochromic and findings were: protein 300 mg/dL, white blood cells 118/mm3 (high lymphocytes), and glucose 25 mg/dL (blood glucose 123 mg/dL). As a result of these findings the patient was transferred to the Infectious Diseases Department with a diagnosis of tuberculous meningitis. Antituberculosis treatment with isoniazid, rifampicin, ethambutol, and pyrazinamide was started. On 26 February she responded to these drugs, began to regain consciousness and she was mobilized. Treatment continued at the hospital until 21 April, and she was then discharged for 1-week control periods.

Hyperemesis gravidarum is seen in different diseases and can be due to different etiological factors. In differential diagnosis, gastroenteritis, biliary tract diseases, peptic ulcer, appendicitis, pancreatitis, hepatitis, diabetic ketoacidosis, Addison's disease, pyelonephritis, uremia, uterine myomas, intoxication, and vestibular lesions should be considered. In the literature, a patient with a cranial aneurysm presenting as hyperemesis has been reported [I].

In our patient, the persistence of nausea and vomiting, elevated body temperature and headache during treatment led us to re- evaluate the clinical diagnosis and determine the etiological factors, and hence we reached the diagnosis of tuberculous meningitis.

Tuberculous meningitis is a disease with great neurological morbidity and mortality in the event of late diagnosis and treatment; success is almost always achieved with early diagnosis and appropriate treatment [2]. It is a chronic disease spreading throughout the body via blood and lymph, but is basically localized in the lungs. Although the main transmission route of the Mycobacterium tuberculosis bacillus is the respiratory system, it can also spread from the skin, mucosa, birth canal and breast milk. Apart from the lungs, the bones and joints, urinary and reproductive system, brain membrane, pleura and peritoneum, skin, and lymphoid glands are the areas where the disease is most located. Non- specific symptoms can be seen for every system. In the largest recent series of pregnant women with tuberculosis in the UK, a high incidence of extrapulmonary tuberculosis was seen. The most common causes for a delay in diagnosis were late presentation and non- specific symptoms [3].

The main problem in the diagnosis and treatment of tuberculous meningitis is the lack of suspicion. The most sensitive and economical diagnostic method is lumbar puncture; however, this method takes time and whenever it is suspected, antituberculosis drugs should be started immediately while the patient awaits the test results [4]. With good compliance, the response to therapy, and maternal and perinatal outcomes are favorable [3]. The teratogenic effects of twelve antituberculosis drugs in animal models and humans have been reviewed, and isoniazid (INH) and ethambutol (EB) are considered the safest for use in pregnancy. It has been noted that although rifampicin (RFP) appears to be more problematic, if the disease is severe or extensive, it may be added to the regimen, but preferably after the first trimester [5]. In a report by Toyota and Minoura, streptomycin (SM) is contraindicated because of the adverse effect of hearing loss in all periods of pregnancy [6]. It is known that most antituberculosis drugs are secreted in the breast milk but concentrations are sub-therapeutic, and pregnancy and breastfeeding are not contraindications for treatment with tuberculostatic drugs [7]. Tripathy and Tripathy reported that there were no statistical differences in duration of gestation, preterm labor and other complications of pregnancy, labor and the puerperium between pregnant women with pulmonary and glandular tuberculosis and healthy pregnant women. If proper and adequate treatment is given to pregnant women with tuberculosis, they are not at higher risk for complications than non-pregnant women. Neither the disease nor its treatment is threatening to the mother or newborn [8]. Perinatal morbidity and neonatal mortality have been found to be significantly higher in pregnant women with tuberculosis who started treatment late in pregnancy, but perinatal morbidity was similar in pregnant women receiving antituberculous drugs early in pregnancy to that in healthy women. Although there were no congenital anomalies reported in the babies born to pregnant women with or without tuberculosis [8], reports of some developmental anomalies of newborns in women with tuberculosis, such as spina bifida, inherited luxation of the hip joint and other abnormalities are growing; in order to come to general conclusions there is a need for additional data [9].

Cases of active tuberculosis are increasing among pregnant women in epidemic communities and are associated with HIV infection. The factors implicated in the resurgence of tuberculosis include immigration from countries with high prevalence, HIV infection, emergence of resistant strains, poverty, homelessness, drug abuse, and a decline in tuberculosisrelated health services [10]. However, once diagnosed, tuberculosis is treated as aggressively in pregnancy as it is in the non-pregnant patient.

Although the gynecologist can easily make the diagnosis of hyperemesis gravidarum, the reasons for its appearance are not always simple; the patient should be evaluated systematically so that a differential diagnosis can be made without any doubt. Although hyperemesis gravidarum is seen with or secondary to many other diseases, we should never forget that it can also be the presentation of a serious and insidious disease such as tuberculous meningitis, which can be successfully treated in pregnancy. The most important issue is to suspect the presence of the disease.


1. Georgantopoulou C, Jha R. Intracranial aneurysm in pregnancy presenting as hyperemesis gravidarum. J Obstet Gynecol 2003;23:74- 75.

2. Kingdom JC, Kennedy DH. Tuberculous meningitis in pregnancy. Br J Obstet Gynecol 1989;96:233-235.

3. Kothari A, Mahadevan N, Girling J. Tuberculosis and pregnancy- results of a study in a high prevalence area in London. Eur J Obstet Gynecol Reprod Biol 2006; 126:48-55.

4. Clark WC, Metcalf JC Jr, Muhlbauer MS. Mycobacterium tuberculosis meningitis: a report of twelve cases and a literature review. Neurosurgery 1986;18:604-610.

5. Holdincss MR. Teratology of the antituberculosis drugs. Early Hum Dev 1987; 15:61-74.

6. Toyota E, Minoura S. Management of tuberculosis during pregnan\cy and puerperium. Kekkaku 2002;77:703-708.

7. Khilnani GC. Tuberculosis and pregnancy. Indian J Chest Dis Allied Sci 2004;46:105-111.

8. Tripathy SN, Tripathy SN. Tuberculosis and pregnancy. Int J Gynaecol Obstet 2003;80:247-253.

9. Pranevicius A, Radzeviciute V. Course of pregnancy, delivery and newborn status in case of maternal tuberculosis. Medicina (Kaunas) 2003;39:399-402.

10. Laibl VR, Sheffield JS. Tuberculosis in pregnancy. Clin Perinatol 2005;32:739-747.


Zeynep Kamil Gynecologic and Pediatric Training and Research Hospital, Istanbul, Turkey

(Received 17 November 2006; revised 27 November 2006; accepted 8 December 2006)

Dr Semih Tugrul

Bagdat Cad. Bagdat ikmazi

Serap Apt. 89/3


Istanbul, Turkey

Tel: +90 216 347 95 00

Fax: +90 216 337 02 35

E-mail: [email protected]

Copyright Taylor & Francis Ltd. Apr 2007

(c) 2007 Journal of Maternal - Fetal & Neonatal Medicine. Provided by ProQuest Information and Learning. All rights Reserved.