Neurocysticercosis

Clinical presentation, diagnosis, stages, types and current treatment guidelines for Neurocysticercosis.

1. Neurocyscticercosis Dr. Yusuf Imran M.D Pediatrics J.N Medical College, Aligarh, India

2. Introduction Neurocysticercosis (NCC) is the infection of the CNS by the larval stage of the pork tapeworm Taenia solium . I nfection may develop in any organ- CNS (parenchyma , subarachnoid spaces, ventricles and spinal cord), eyes and muscles are the most commonly involved . Most common manifestation is epilepsy but can have several other neurological manifestations.

3. Epidemiology NCC is endemic in most Latin American countries, sub-Saharan Africa, and large regions of Asia (including Indian subcontinent and China ). Rare in developed countries, can occur in travelers/immigrants. A study from North India found point prevalence of NCC - 4.5/1000. In pig farming community it is upto 15 %. Proportion of NCC among patient with epilepsy is estimated @ 29 %. In those with partial seizures it was >50 %.

4. Life cycle of Taenia solium Taenia solium requires two hosts to complete its life cycle. Pigs (intermediate host) contain the cystecerci , primarily in muscle. Humans (definitive host) infected by consuming undercooked pork containing live T.solium cysticerci . Cysticerci develop into adult tapeworm which releases eggs in human feces. Eggs contaminate soil/vegetation, when ingested by pigs/humans eggs develop into larvae which pass through intestinal mucosa and reach various tissues.

5. Life cycle of Taenia solium

6. Growth stages of Taenia solium : A -Infective T.solium eggs, B -Larva or cysticercus , C - Evaginating cysticercus , D -Tapeworm scolex , E -Tapeworm strobila Life cycle of Taenia solium

7. Modes of infection Sources of infection- persons with Taeniasis (acquired from pork). Transmission ways- not spread from person to person directly persons with Taeniasis will shed tapeworm eggs in their bowel movements

8. Modes of infection Infection can happen by accidentally swallowing pork tapeworm eggs Through- drinking contaminated water or food by putting contaminated fingers to mouth (external autoinfection) by internal autoinfection

9. Disease spectrum of T.solium Taeniasis = adult tapeworm in small intestine Usually asymptomatic (eggs or proglottids in feces) Vague abdominal symptoms Cysticercosis = T. solium larvae in human tissues ( eg , muscle) Usually asymptomatic Painless subcutaneous nodules in arms and chest Neurocysticercosis (NCC) = cysts in the central nervous system Most severe manifestation

10. Etiopathogenesis Clinical expression, management and prognosis of NCC varies depending on the number of CNS lesions, their stage, size, location and host inflammatory response. Studies have identified a number of mechanisms used by the cycticercus to modulate host’s immune response. Protease inhibitor- Taeniaestatin Sulfated polysaccharides Parasite paramyosin Prostaglandins Stimulate antibody production

11. Etiopathogenesis Although, cysticerci reach mature size within a few weeks, there a period of several years between exposure and onset of symptoms. When parasite degenerates there is a brisk inflammatory response. The seizures are thought to result not from the parasitic infection per se, but from the host response.

12. Types of Neurocysticercosis Intraparenchymal NCC Most common form, seen at grey white matter junction. Single or Multiple. Range in size from a few mm to 1 to 2 cm. Commonly seen in children >5 years but can occur in toddlers and infants.

13. Types of Neurocysticercosis Intraparenchymal NCC cont … Seizures are most common manifestation of intraparenchymal NCC. 1/3 rd may have associated headache and vomiting. Papilloedema occurs in 2 to 7 %. Neurological deficits seen in 4 to 6 %. Seizures respond well to monotherapy . Cysticercal Encephalitis- results from large number of cysticeci in brain parenchyma with diffuse inflammation and edema.

14. Types of Neurocysticercosis The parenchymal cysts evolve through 4 stages- The vesicular cyst Colloidal stage Granular nodular stage Nodular calcified stage

15. Stages of Intraparenchymal NCC

16. Types of Neurocysticercosis Extraparenchymal NCC Ventricular NCC- can obstruct CSF flow causing hydrocephalus. CT may reveal only hydrocephalus and no cysticerci . Subarachnoid NCC- can occur in the gyri , fissures, basilar cisterns.

17. Types of Neurocysticercosis

18. Types of Neurocysticercosis Other forms of Cysticercosis Spinal Cysticercosis (intramedullary/ extramedullary ) Ocular Cysticercosis In Muscles In Subcutaneous tissue Other organs A single patient may have multiple types and locations of cysticercus .

19. Types of Cysticercosis

20. Clinical Manifestations A symptomatic. Most common manifestation is Seizure (focal, secondary generalized or generalized). (80%) Headache is common (unilateral/bilateral)- may reflect raised ICT or vasculitis . Focal neurological deficits (16%) Symptoms/signs of raised ICT-nausea, vomiting, altered mental status, visual changes, dizziness, cerebral edema. (12%) Neurocognitive defects- leaning disability, psychosis, depression. (5%)

21. Imaging CT Parenchymal cysts- usually appear as single, small (<20mm) with ring/disk enhancement and eccentric hyper dense scolex . Multiple lesions give ‘starry sky’ appearance. (colloidal stage). Enhancement indicates inflammation. Live vesicular cysts are non-enhancing. Extra-parenchymal cysts- may show hydrocephalus, enhancement of tenctorium and basal cisterns and occasionally infarcts.

22. Imaging MRI Superior to CT in detecting cysts in ventricles, posterior fossa, brainstem, small cysts. Small calcified lesions may be missed. Magnetization transfer images (MT) and magnetization transfer ratio (MTR), recovery (FLAIR) and fast imaging employing steady-state acquisition (FIESTA) sequences for lesions not visible on routine MRI.

23. Serological Tests Seropositivity depends on parasite load and endemicity . False positive and false negative results can occur. False-negative result: Single lesions Calcification False-positive: Other parasitic infections High percentage of false positive for patients from endemic area

24. Serological Tests EITB assay- uses lentil lectin purified glycoprotein antigens (LLGP) to detect antibodies to T soliumin in serum. Sensitivity 98% (multiple parasites), 50-70 % (solitary cysticercus ). Detection of anticysticercal antibodies in the CSF by ELISA. Detection of circulating parasitic antigens in serum by ELISA with monoclonal antibodies is experimental. In patients with reliable diagnosis of NCC by imaging studies, immunological test is not required, since a negative test will not discard a NCC.

25. Other lab tests… Eosinophilia may occur. CSF- Usually done to rule out other causes. Can be normal in inactive disease. M oderate pleocytosis (mostly mononuclear cells; upto 300/mm 3 ), increased protein (50-300 mg/dl). Correlate with disease activity and whether or not the parasites are located in sub-arachnoid space.

26. Other lab tests… Biopsy of subcutaneous nodules. Radiographs of skeletal muscles. Specific coproantigen detection by ELISA for screening for T solium carriers. Stool examination for T.solium eggs has poor sensitivity.

27. Diagnostic criteria Definitive diagnosis- one absolute criterion or two major plus one minor and one epidemiologic criteria P robable diagnosis - one major plus two minor criteria , one major plus one minor and one epidemiologic criteria, three minor plus one epidemiologic criteria.

28. Differential diagnosis Tuberculoma (presence of raised ICT, progressive focal neurodeficit , size >20mm, lobulated irregular shape, midline shift & marked edema, lesions at base of brain) Special MRI sequences – diffusion weighted MRI and proton magnetic resonance spectroscopy (MRS) are being tried. Case discussion-   A two month old child was referred for evaluation of fever associated with fits. Plain CT brain showed a 1.1.x 1.0 cms . round hypodense lesion in the right  frontal lobe . There was dilatation of all the ventricles , basal cisterns . The anterior fontanalle was bulging. On contrast study there was dense enhancement of basal meninges, dense ring enhancement  ( 4 mm thick ) of the the right frontal lobe lesion.

29. Differential diagnosis Microabscesses Toxoplasmosis Fungal lesions Low grade astrocytoma Cystic cerebral metastasis CNS lymphoma

30. Management Emergency care Manage seizure activity Supportive care (A-B-C) Monitor , and correct metabolic abnormalities Anticonvulsants are effective. Evidence of increased ICP- Steroids , osmotic agents, and/or diuretics Initiate proper diagnostic procedures B lood work and imaging

31. Management Intraparenchymal NCC- Symptomatic treatment, anti-parasite treatment or surgery ? Calcified cysts only- antiepileptic , analgesic, and anti-inflammatory drugs; for seizures relapses, repeat imaging looking for peri -calcification oedema . AED for at least 2yrs since last seizure. No anti-parasite drugs. * One or more cystic or degenerating lesions- antiepileptic , analgesic, and anti-inflammatory drugs; antiparasitic treatment under hospital conditions with steroid treatment. Discontinue AED in single lesions after they resolve (without calcification). *Level 1 evidence Cysticercal encephalitis- Manage intracranial hypertension; do not use antiparasitic drugs.

32. Management Asymptomatic parenchymal lesions Prophylactic AED not justified in calcified lesions without seizures. Viable cysts- Give prophylactic AED when antiparasite treatment is also planned. Repeat neuroimaging after 3-6 m to document lesion resolution. Repeat course of cysticidal therapy if persistent lesion.

33. Management Drugs: Albendazole - 15mg/kg/day in 2-3 divided doses for 2-4 weeks. Shorter courses of 3 to 14 days tried in single lesions. Praziquintal - 50mg/kg/day, less effective than albendazole . Combinations of two antiparasitic drugs- increased cyst clearance in multiple lesions. Steroids- Dexamethasone- 0.1 mg/kg/day i.v starting one day before antiparasite drugs, give for 1 to 2 weeks then taper. Prednisolone- 1 to 2 mg/kg/day.

34. M anagement

35. Management Extraparenchymal NCC

36. Management Other forms of NCC Spinal- Intramedullary cysts are treated with surgery, albendazole with steroids is being tried. Subarachnoid cysts can migrate so imaging is done just before surgery. Ocular- Surgical management is the standard of care.

37. Prognosis Single lesions- good prognosis, disappears in >60% at 6m. Seizure recurrence is 10-20% with single lesions, multiple lesions have more frequent seizures. Prognosis is poorer in cysticercal encephalitis and extraparenchymal NCC.

38. Prevention T solium infection is one of a few diseases targeted for focal elimination and eventual eradication by the International Task Force for Disease Eradication . Public education, proper hygiene, provision for toilets. Safe handling of meat, strict animal husbandry and meet inspections procedures.

39. Prevention Mass deworming of population with Niclosamide or Praziquintal . Mass vaccination of pigs and treatment of pigs with Oxfendazole . Community interventions reduce rate of epilepsy in hyper-endemic areas.

40. Conclusion NCC is a common cause of seizures and other neurological manifestations and needs to be considered in D/D of many neurological conditions. Treatment with cycticidal therapy leads to reduction in seizure frequency and faster resolution of lesions. Children with a single or few lesions have a good outcome. Prevention of NCC is important and feasible.

41. Thank you