Acute vision loss in post-partum period as presenting symptom of HIV-associated cryptococcal meningitis–an unusual case report

Background Acute vision loss in the post-partum period can occur due to many reasons. Eclampsia, posterior reversible encephalopathy syndrome (PRES), pituitary apoplexy, and central serous retinopathy are some of the important causes. Cryptococcal meningitis as a cause of acute vision loss in the post-partum period has not been mentioned in literature. Case presentation A 25-year-old female presented to us with acute bilateral complete vision loss in the post-partum period. Her serum was tested positive for HIV antibodies. Cerebrospinal fluid (CSF) examination revealed cryptococcal meningitis. She was started on amphotericin B, antiretroviral drugs, and steroids. Though symptoms of meningitis resolved after treatment no significant improvement in vision was observed at 3 months. Conclusions Cryptococcal meningitis may be considered as one of the causes of acute vision loss in pregnant/post-partum females with human immunodeficiency virus (HIV) positivity.


Background
Approximately, 36.7 million people globally were suffering from HIV infection at end of 2015 [1]. About 17.4 million women were suffering from HIV infection worldwide in 2014 [2]. HIV infection in pregnancy has become the most common complication of pregnancy in some developing countries. In pregnancy immune function is suppressed in HIV infected as well as non-infected subjects [3]. There is a reduction in immunoglobulin, reduced complement levels and a significant decrease in cell-mediated immunity during pregnancy [3]. This leads to increased susceptibility of pregnant females to opportunistic infections like tuberculosis and cryptococcal meningitis. Cryptococcal disease is very uncommonly seen in HIV infected pregnant females and to date only three cases of HIV infection with cryptococcal meningitis have been reported during the peripartum period [4]. Symptoms of cryptococcal meningitis include fever, headache, nausea/vomiting, altered sensorium, and multiple cranial nerve palsies. Vision loss is seen in 33-47 % of patients [5]. Seven percent of HIV infected individuals suffer from cryptococcal meningitis in the course of their illness out of which only 1.9 % have cryptococcal meningitis as the presenting symptom [5,6]. Complete bilateral vision loss as presenting symptom of HIV related cryptococcal meningitis is extremely rare [7]. Similar presentations in post-partum female, as it was in our case, are unique and high index of suspicion is necessary for accurate diagnosis.

Case presentation
A 25-year-old previously healthy pregnant female in 36th week of her gestation presented in labour to the department of Obstetrics & Gynecology of our hospital. Before admission she was having mild to moderate headache of 10 days duration which was associated with mild fever with intermittent high grade spikes which used to subside on administration of antipyretic medications.
Her serum tested positive, by ELISA, for antibodies towards HIV. She delivered a still-born baby vaginally. She was apparently asymptomatic for 2 days, besides fever and headache which were relieved by antipyretics and analgesics. On the 3rd day post-partum day, she woke up in the morning realizing that she was not able to see from both eyes; the loss of vision was painless and symmetrical. She was transferred to the department of Neurology unit of our hospital for further evaluation. On clinical examination, her vitals and level of consciousness were normal. Her visual acuity was significantly reduced and she could only perceive light in both eyes. Her pupils were completely dilated and not reacting to light. Fundus examination revealed bilateral edematous optic discs suggestive of papillitis. Other cranial nerves were normal on examination. Motor and sensory system examination were normal. Plantar reflex was bilaterally flexor. She had neck stiffness and Kerning's sign was positive. Urgently a CT scan of her head was done which showed no significant abnormality and then her CSF examination was done based on her clinical signs. Her CSF opening pressure was mildly elevated (200cms of H 2 O). CSF examination showed mild pleocytosis (35 cells/mm 3 ) with lymphocytic predominance, mildly elevated proteins (76.5 mg%) and low sugars (32.7 mg% with corresponding blood glucose of 117 mg%). Her CSF was tested positive for Cryptococcus by India ink staining (Fig. 1). The CSF showed a titre of 1:100 for cryptococcal antigen by latex agglutination method. Since she was diagnosed with cryptococcal meningitis she was categorized as having stage 4 disease according to WHO clinical staging for HIV/AIDS. All other hematological and biochemical parameters were within normal limits. Her CD4 counts were done which turned out to be 166 cells/mm 3 . The plasma HIV-RNA levels were not performed in this case. As per National AIDS Control Guidelines of India prior HIV-RNA levels assessment, before starting antiretroviral drugs, is not mandatory. Her MRI was planned to evaluate the cause of her blindness which showed signal intensity changes in bilateral optic nerve and (cryptococcoma/cryptococcal) infiltration in bilateral ganglio-capsular region (soap-bubble appearance) (Fig. 2). She was initiated on amphotericin-B 0.7 mg/kg/day IV once daily (slow infusion) and intravenous methylprednisolone 1 gm IV once daily (for 5 days), and an antiretroviral regimen consisting of zidovudine (300 mg once daily), lamivudine (150 mg once daily), and nevirapine (200 mg once daily) was planned. She received amphotericin B for 21 days after which she was started on tablet fluconazole 400 mg per day which was continued for 8 weeks. Antiretroviral medications were started after completion of intravenous antifungal medications. Her headache improved with treatment and she became afebrile. Repeat CSF examination was negative for Cryptococci by India ink staining. Though she showed significant improvement in meningitic symptoms, her vision did not show any significant improvement even at end of 3 months of her illness.

Discussion
Acute vision loss in the post-partum period is reported due to severe preeclampsia/eclampsia (in which vision loss could be due to exudative retinal detachment, hypertensive retinopathy and cortical blindness) [8], PRES which can cause reversible acute vision loss [9], pituitary apoplexy [10], posterior ischemic optic neuropathy [11], anterior ischemic optic neuropathy [12], cortical venous sinus thrombosis [13], and central serous retinopathy [14]. Cryptococcal meningitis as a cause of acute vision loss in the post-partum period has not yet been reported in literature.
Vision loss in HIV infected individuals can be due to infectious and non-infectious causes [15][16][17]. HIV retinopathy is the most common non-infectious ocular complication. Amongst infectious causes cytomegalovirus retinitis is considered as the most common ocular infection. Neuro-ophthalmic lesions affected 6 % of individuals of acquired immunodeficiency states of which most common cause was cryptococcal meningitis. Approximately 25 to 50 % patients with cryptococcal meningitis demonstrate a neuro-ophthalmic complication. In a cross-sectional analysis looking at the ophthalmic complications in the pre-HAART (Highly Active Anti-Retroviral Therapy) and HAART period, it has been suggested that despite of an advancement in terms of treatment the difference between the two treatment protocols has not been significant (pre-HAART (41.67 %) versus HAART (38 %). Of significance was the fact that the odds of development of ophthalmic complications with a CD4 count of >200 cells/μL were significantly higher (4.87) during the HAART period [17]. Since most patients with ophthalmic complications have been noted to present in WHO stage 3 and 4, it has been recommended that regular ophthalmic assessments are done in patients with HIV positivity.
Vision loss in cryptococcal meningitis can be rapid (<3 days) occurring as rapidly as 12 h or can occur slowly (>3 days) over weeks to months [20]. Possible mechanisms of rapid visual loss include direct invasion of optic nerve by Cryptococcus, optic neuritis, and optochiasmatic arachnoiditis while a possible mechanism for slow vision loss has been attributed to raised intracranial pressure [20]. Factors predicting vision loss are presence of papilledema, high CSF opening pressure, and a positive India ink preparation. In cases with acute vision loss despite of giving antifungals and steroids no substantial improvement in vision is expected and these cases tend to have a poor prognosis for visual recovery. In cases with slow visual loss therapeutic measures to reduce intracranial pressure like shunting or optic nerve sheath fenestration have been shown to halt vision loss and shown improvement in some cases [20].
Vision loss in our patient was most probably due to infiltration of optic nerve by Cryptococcus causing optic neuritis and acute vision loss. This was supported by fact that her MRI showed enhancement of both optic nerves and presence of papillitis on ophthalmoscopy with cryptococcal infiltration in both ganglio-capsular regions. This also explains her poor recovery of vision despite of receiving steroids as noted in previous studies ( Table 1). The general belief that pregnancy is a state of immune suppression may not hold true in all patients. Pregnancy, indeed, is a state of an altered immune status which may respond to different stimuli variably. Thus, in the background of pregnancy and a HIV positive state, this rare manifestation of Cryptococcus appears to have evolved [21].

Conclusions
Cryptococcal meningitis may be considered as one of causes of acute vision loss in HIV-infected pregnant females with suggestive symptoms; needless to say that a high index of suspicion should be kept to diagnose the condition. Though prognosis of visual recovery is poor in cases of acute vision loss, early therapeutic measures to relieve intracranial pressure may potentially halt the progression while some recovery may be observed in cases with slowly progressive vision loss.