Neurocysticercosis

pharmacotherapy

1. Pharmacotherapy of neurocysticercosis Dr. Prerna Singh Junior Resident (3rd year) Department of Pharmacology JNMC, AMU

2. INTRODUCTION Most common parasitic disease of the CNS worldwide Most common cause of acquired epileptic seizure In developing countries Causative agent: larval stage T. solium /pork tapeworm Ingestion of food contaminated with the eggs of the parasite T. solium

3. Introduction Cysticerci : most commonly detected in the brain, CSF, skeletal muscle, subcutaneous tissue, or eye. Clinical presentation: Depends on the number and location of cysticerci Extent of associated inflammatory responses or scarring

4. Life cycle Human: definitive host Pigs: intermediate host

5. Clinical features Neurologic manifestations are the most common Seizures: generalized/focal Hydrocephalus may result from CSF flow obstruction by cysticerci and accompanying inflammation or by CSF outflow obstruction from arachnoiditis.

6. Clinical features Symptoms of increased intracranial pressure Headache Nausea Vomiting Changes in vision Dizziness Ataxia

7. CLINICAL FEATURES Patients with hydrocephalus may develop papilledema or display altered mental status. When cysticerci develop at the base of the brain or in the sub-arachnoid space, they may cause chronic meningitis or arachnoiditis, communicating hydrocephalus, haemorrhages, or strokes

8. Diagnosis MRI or CT scans - appear as cystic lesions/scolex can often be visualized Lesions may appear as contrast- enhancing lesions surrounded by edema . Parenchymal brain calcifications are the most common finding and evidence that the parasite is no longer viable. CSF- to rule out other causes

9. Stages Stage Vesicular Cyst & scolex Colloidal Ring enhancement and edema Granular Decreased enhancement and edema Involution Calcification

10. Stages

11. MANAGEMENT Anti epileptic drugs Anti parasitic drugs Steroids Surgery

12. Antiepileptics Initiated when the patient presents with a seizure Stopped once the follow-up CT scan shows resolution of the lesion Long-term antiepileptic therapy is recommended when seizures occur after resolution of edema and resorption or calcification of the degenerating cyst.

13. Anthelmintic Cysticidal drugs accelerate the destruction of the parasites, resulting in a faster resolution of the infection For lesions that are in the “ granulo -nodular” stage (surrounded by a contrast-enhancing ring) Calcified lesions do not need to be treated with anticysticidal therapy. Albendazole Praziquantel

14. Albendazole Mechanism of action: Binds to free β- tubulin in nematodes, inhibiting the polymerization of tubulin and the microtubule-dependent uptake of glucose. Irreversible damage occurs in gastrointestinal (GI) cells of the nematodes, resulting in starvation, death, and expulsion by the host. Dose: 15 mg/kg per day in two doses for 8 – 28 days Maximum 800 mg/day

15. Albendazole Poorly absorbed from the GI tract Metabolized in the liver Administration with a high-fat meal (~40 g) increases the drug’s absorption Albendazole sulfoxide (metabolite) crosses the blood–brain barrier

16. Albendazole Prolonged courses- associated with liver function abnormalities and bone marrow toxicity. Drug should be administered in treatment cycles of 28 days interrupted by 14-day intervals off therapy

17. Praziquantel Mechanism of action: increases the permeability of the membranes of schistosome cells towards calcium ions. Induces contraction of the parasites muscle, resulting in paralysis Dose: 50–100 mg/kg daily in three divided doses for 15–30 days A combination of albendazole and praziquantel is more effective in patients with more than two cystic lesions.

18. Praziquantel Rapid absorption orally Excreted in urine Side effects: headache, anorexia, drowsiness, allergic reactions

19. Steroids Prednisone- 1-2 mg/kg/day Dexamethasone – 0.1mg/kg/day IV starting one day before anthelmintic To reduce the host inflammatory response to degenerating parasites Glucocorticoids induce first-pass metabolism of praziquantel and may decrease its antiparasitic effect, cimetidine should be co-administered to inhibit praziquantel metabolism Serum levels of phenytoin and Carbamazepine may also be altered

20. FOR HYDROCEPHALUS In the case of obstructive hydrocephalus, the preferred approach is removal of the cysticercus via endoscopic surgery. Alternative approach - diverting procedure- ventriculoperitoneal shunting Prolonged courses of antiparasitic drugs Methotrexate should be used as a steroid-sparing agent in patients requiring prolonged therapy

21. Multiple lesions Glucocorticoids are the mainstay of therapy Antiparasitic drugs should be avoided

22. CALCIFIED LESIONS No anthelmintic needed – cyst dead Edema around calcification- anti inflammatory

23. Prevention Good personal hygiene Treatment and prevention of human intestinal infections. Adequate cooking of pork viscera Exposure to temperatures as low as 56°C for 5 min will destroy cysticerci

24. PREVENTION Refrigeration/salting for long periods or freezing at –10°C for 9 days also kills cysticerci Inspection of beef and proper disposal of human feces Mass chemotherapy - in efforts at disease eradication Vaccines are under development.

25. Thank you