|Year : 2020 | Volume
| Issue : 2 | Page : 158-162
Nightmares with a starry sky – Treating neurocysticercal encephalitis, how far to go
Anirban Ghosal1, Kajari Bhattacharya2, A Shobhana3, Rashmi Saraff4
1 Department of Neurology, Institute of Neurosciences, Kolkata, West Bengal, India
2 Department of Neuroradiology, Institute of Neurosciences, Kolkata, West Bengal, India
3 Department of Neurocritical Care, Institute of Neurosciences, Kolkata, West Bengal, India
4 Department of Neuro-Ophthalmology, Institute of Neurosciences, Kolkata, West Bengal, India
|Date of Submission||06-Jun-2020|
|Date of Decision||12-Aug-2020|
|Date of Acceptance||07-Oct-2020|
|Date of Web Publication||23-Jan-2021|
185/1, A.J.C. Bose Road, Kolkata - 700 017, West Bengal
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Cysticercosis, an infection caused by the larval stage of tapeworm Taenia solium, is the most common parasitic disease of the human nervous system and the single most common cause of acquired epileptic seizures in the developing world. Here, we describe the stormy course of a 67-year-old female with neurocysticercosis (NCC) having a recurrent encephalitic presentation. She went through the most severe spectrum of this disease, namely NCC encephalitis and disseminated cysticercosis and had a classical starry sky brain in neuroimaging. In contrary to the popular practice of avoiding antihelminthic drugs in such extreme presentation, as a desperate measure, we had to use albendazole in this case, which showed clinical and radiological improvement.
Keywords: Albendazole, disseminated neurocysticercosis, neurocysticercosis encephalitis, starry sky pattern
|How to cite this article:|
Ghosal A, Bhattacharya K, Shobhana A, Saraff R. Nightmares with a starry sky – Treating neurocysticercal encephalitis, how far to go. Trop Parasitol 2020;10:158-62
| Introduction|| |
Neurocysticercosis is an infection of the central nervous system by the larval stages of Taenia solium. Patients with multiple ring enhancing brain lesions surrounded by perilesional edema and features of raised intracranial pressure like headache, vomiting, papilloedema, altered sensorium etc are considered to have neurocysticercal encephalitis. Randomized controlled trials have proven that cysticidal agents like albendazole and praziquantel are effective in treating neurocysticercosis. However in neurocysticercal encephalitis cysticidal therapy is conventionally avoided in fear of worsening cerebral edema. Here we report a case of NCC encephalitis showing clinico-radiological improvement after being treated with antihelminthic agent.
| Study|| |
A 67-year-old Indian woman without any known comorbidity developed new-onset moderate daily headache, imbalance while walking, difficulty remembering usual household works, and irritable mood for 10 days. Later, she had two episodes of generalized tonic-clonic seizure and was admitted to a general hospital. Laboratory tests showed leukocytosis with eosinophilia. X-ray chest, blood glucose, electrolytes, liver, renal function tests, and blood ammonia levels were normal. Computed tomography of the brain showed hypodensity in the bilateral fronto-temporo-occipital cortical-subcortical region consistent with diffuse cerebral edema. She was drowsy, had neck rigidity but was afebrile. She was started with intravenous levetiracetam, acyclovir and mannitol as antiedema measure. Ceftriaxone was added in view of possible meningoencephalitis of bacterial etiology. A guarded lumbar puncture and cerebrospinal fluid analysis revealed 170 cells, all lymphocytes (normal range : 0–10 cells), mild elevated protein of 53 mg/dl (normal range : 15–45 mg/dl), glucose 110 mg/dl (normal, simultaneous plasma glucose 160 mg/dl). Cerebrospinal fluid Mycobacterium tuberculosis GeneXpert test was negative. A provisional diagnosis of viral meningoencephalitis was made. After initial seizure control, she was referred to our tertiary neurological care setup in 3 days.
A contrast magnetic resonance imaging (MRI) of the brain showed multiple ring-enhancing lesions suggestive of cysts in different stages in brain parenchyma with diffuse cerebral edema [Figure 1]a, [Figure 1]b, [Figure 1]c. Neuroimaging and clinical features were consistent with neurocysticercosis (NCC) encephalitis. Serum IgG anticysticercal antibody by enzyme immunoassay test came positive. She had no visible or palpable subcutaneous nodules and fundoscopy did not reveal any retinal or optic nerve head NCC. She was from an urban area, had no history of pork consumption, and used to maintain an apparently hygienic lifestyle. She lived with her husband who was asymptomatic and his MRI brain, stool examination for tapeworm, and serum anticysticercal antibody screened were normal.
She was started on intravenous dexamethasone. Ceftriaxone and acyclovir were omitted. Due to her fluctuating sensorium, a prolonged electroencephalogram (EEG) was done which was consistent with nonconvulsive status epilepticus. Phenytoin and clobazam were added to the regimen and repeat EEG after 24 h showed bi-hemispheric slow waves without any epileptiform activity. After 3 days she started accepting oral feed and was obeying commands. She could utter a few meaningful words on day 7 after admission. On day 12, she became restless, agitated. Repeat EEG was normal and oral quetiapine was initiated keeping steroid psychosis a possibility. Later, olanzapine was also added. A repeat MRI of the brain on day 14 showed a marked decrease in cerebral edema [Figure 1]d and [Figure 1]e, plan of gradually tapering off steroid was done, and she was discharged home on levetiracetam, phenytoin, clobazam, quetiapine, olanzapine, and dexamethasone.
|Figure 1: Magnetic resonance imaging brain axial sections (a) T2- weighted image showing classical “starry sky” appearance of the brain studded with numerous cysticercal cysts. (b) Fluid-attenuated inversion recovery shows the inversion of the cysts with extensive vasogenic edema of white matter (arrows). (c) Postcontrast imaging of the brain shows thin rim enhancement of the lesions. Repeat magnetic resonance imaging performed after 2 weeks shows (d and e) reduction in the edema along the lesions|
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As she was improving, dexamethasone dose was gradually lowered over 6 weeks and olanzapine and quetiapine could be stopped. After 2 weeks, she was readmitted with neurological deterioration; increasing confusion, unsteady gait, drowsiness, and global aphasia. There were no meningeal signs. EEG ruled out any nonconvulsive seizure. A contrast MRI of the brain (at 10th week from initial admission) showed diffuse parenchymal edema and the cyst burden had increased from before [Figure 2]a, [Figure 2]b, [Figure 2]c. Dexamethasone dose was again increased and continued for the next 1 month. Repeat MRI of the brain with contrast after 1 month revealed the persistence of perilesional edema surrounding the increasing number of cysts. A decision to administer a course of intravenous methylprednisolone (1 g/day) for 5 days was taken. MRI done after 7 days showed a decrease in edema. After discussion with family members, it was decided to start albendazole as she had recurrent encephalopathy and the cyst burden was increasing in neuroimaging. There was no lesion in the eye and so far, brain imaging had been negative for any orbital lesions. She was discharged home on albendazole (400 mg twice daily) for 4 weeks along with oral steroids and anti-seizure drugs. The repeat MRI of the brain (at 20th week from initial admission) showed a significant decline in the radiological burden of NCC [Figure 2]d and [Figure 2]e.
|Figure 2: Magnetic resonance imaging brain axial section: at 10th week from initial admission (a) T2-weighted image, (b) Fluidattenuated inversion recovery image, (c) Contrast-enhanced image showing an increase in the lesion burden and edema since the last magnetic resonance imaging. At second readmission (20th week from 1st admission), there was a significant reduction in lesion burden and parenchymal edema as seen in (d) T2-weighted image and (e) Fluidattenuated inversion recovery|
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Her sensorium and gait improved at home but after 3 weeks developed red eye on the right side, drowsiness, and decreased speech output. On ophthalmological examination, the right eye had ciliary congestion with fibrinous exudates in the anterior chamber obscuring the pupillary area. Digital intraocular pressure (IOP) was high. A provisional diagnosis of right eye fibrinous anterior uveitis was made. She was started on topical steroid, cycloplegic, antibiotic, and antiglaucoma eye drops. The next day, anterior chamber reaction had reduced, but a typical cysticercus larva was visible on inspection in the right eye [Figure 3]a. Ultrasound of the posterior segment of the right eye revealed another cyst in the vitreous cavity close to the macula. At this point, she fulfilled the definition for disseminated cysticercosis as she had cysts in both brain parenchyma and eye.
|Figure 3: Clinical image (a) anterior chamber larvae with fibrinous exudates and conjunctival inflammation. (b) First postoperative day showing reduced inflammation. (c) Fifth post-operative day, inflammation almost subsided|
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The guarded visual prognosis was discussed with relatives and high-dose intravenous dexamethasone was restarted. The anterior chamber cyst was removed through a limbal incision. On the 1st postoperative day, the anterior chamber reaction had reduced significantly, the pupillary area was reasonably clear, and the posterior segment was hazily visible [Figure 3]b. There was mild vitritis with a cyst visible in the vitreous cavity. On the 5th postoperative day, the eye had become considerably white and the posterior segment inflammation had not increased [Figure 3]c. Albendazole was restarted as her sensorium started improving. On follow-up, after 1 month the right eye anterior segment was clear with normal digital IOP and in ocular ultrasound, the lesion in the posterior chamber was not seen.
She had improved to an awake, alert but mute state [Figure 4]. She was continued on oral anthelminthic therapy and steroids. As both clinical and radiological improvements were seen, it was decided to add another cysticidal drug praziquantel under supervision. She was waiting for admission when she developed respiratory distress and died due to acute myocardial infarction.
|Figure 4: Flow chart depicting the clinical course of events in the patient|
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NCC is a major cause of neurological morbidity in the developing world. Disseminated cysticercosis is diagnosed if there are multiple cystic/enhancing lesions in the brain, along with evidence of involvement of at least one extra site, like subcutaneous tissues, skeletal muscles, eyes, and any visceral organ (like liver, lung, spleen, and heart). Patients with prominent headache, vomiting, papilloedema, altered sensorium, and neuroimaging showing multiple enhancing lesions with perilesional edema, are considered to have cysticercal encephalitis.,
NCC management can be challenging as current treatment options are limited to symptomatic agents, antiparasitic drugs, steroids, or surgery. Although antiparasitic treatment reduces the number of active lesions and long-term seizure frequency, its efficacy is limited, and treatment decisions should be individualized according to the type of NCC. Initial measures should focus on symptomatic management, and antiparasitic therapy only should be considered later on, for active disease depending on the number, size, location, and developmental stage of the cysts; as well as potential risks of treatment. Symptomatic treatment should focus on epilepsy, headache, cognitive, and psychological issues.
Recurrent encephalopathy following neurocysticercosis is an uncommon entity. However, such a possibility exists in the developing world where it is endemic, even in the apparently hygienic urban lifestyle, as was noted in the index case. Corticosteroids are solely used in the management of this condition and cysticidal therapy is conventionally avoided in fear of worsening cerebral edema by the inflammatory response from degenerating cysts leading to elevated intracranial pressure. Qavi et al. reported 60 cases with disseminated cysticercosis and 8 of them had encephalitic presentation where cysticidal therapy was avoided. Six patients improved with steroids while one became corticosteroid-dependent. Another inference in their study was that patients with a heavy parasitic load enter into a cycle of recurrent cystic degeneration and release of toxins leading to recurrent corticosteroid use and dependence. Thus, antiparasitic drugs may help in the prevention of such dependence.
However, it is not clear what should be the treatment direction if in an encephalopathic background the cyst burden progressively increases, as happened in our case. Especially it seems in this case the increase in cyst burden and concomitant cyst degeneration led to a cycle of recurrent encephalopathy. It also appears the encephalopathy became steroid dependent needing recurrent steroid courses. Despite the steroid course, she acquired ocular cysticercosis, hence entering into the spectrum of disseminated cysticercosis.
The goal of antiparasitic therapy when used for the active disease is the destruction of cysts with simultaneous control of the host immune reaction by corticosteroids. This strategy prevents the inflammation related to cyst degeneration and improves clinical outcomes. The existing two main antiparasitic agents, albendazole and praziquantel, however, have a partial efficacy. One course of antiparasitic treatment yields a 60%–70% cyst resolution versus 40% in untreated patients. Unfortunately, only 30%–40% of patients are free of viable brain cysts. Hence repeated antiparasitic courses are also used in selected cases.
Pandey et al. in a recent publication, discussed the effect of 3 cycles of albendazole in Twenty-nine patients with disseminated cysticercosis (21 with > 20 lesions), they noted a significant reduction in the occurrence of seizures, headache, and significant reduction in lesion load. No patient developed serious side-effects. We also considered high dose steroid to reduce intracerebral edema, and then used albendazole to reduce cyst burden. Prolonged and multiple courses of albendazole helped. Explaining every pros and cons of such unusual, but inevitable therapeutic intervention and discussing the possible outcome and adverse situations with relatives is of utmost importance with similar attempts. Combination therapy using albendazole and praziquantel is reported to have an increased cysticidal effect in multiple cerebral cysts without increased side effects and we also decided a similar approach after initial response to albendazole.
Bhalla et al. used both albendazole and praziquantel in a case of disseminated cysticercosis with simultaneous brain, subcutaneous tissues, skeletal muscles, orbit, and thyroid involvement and got an excellent response. The Infectious Diseases Society of America and the American Society of Tropical Medicine and Hygiene guideline also recommends the use of both antihelminth drugs concurrently in more than 2 viable cysts and emphasizes on monitoring for hepatotoxicity and leucopenia when prolonged therapy is used.
Treating the complications of ocular cysticercosis was another challenge. As per consensus, surgical removal of ophthalmic cysticercus from the anterior chamber was done., Among ocular cysticercosis, while anterior segment cysticercosis is rarely seen, posterior segment involvement is common. The occurrence of a floating cyst in the anterior chamber is rare which was noted in our case. The degenerating parasite releases a large amount of toxins causing a significant fibrinous reaction locally. There may be pain and redness with associated iridocyclitis or glaucoma. As anthelminthic therapy can lead to severe inflammation from live cyst degeneration, surgical removal of the intact parasite is the treatment of choice. To prevent such inflammation, Albendazole in our case was started after removal of the anterior chamber cyst.
| Conclusion|| |
Treatment of NCC needs to be individualized and needs awareness and anticipation of the emergence of active larvae in previously unaffected areas. NCC can have recurrent encephalitic presentation requiring multiple courses of steroid, ultimately leading to steroid dependence and related complications. Antihelminthics may be judiciously used in such cases carefully judging the risks and benefits.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]