Recent guidelines for management of neurocystcercosis

1. Current knowledge about neurocystcercosis (NCC) Dr. Parag Moon Senior Resident, Neurology GMC, Kota.

2. Three types of tapeworms infect humans. Taenia saginata - beef T. s. asiatica -pig organs T. solium primarily in pork

3. Cysticercosis and Taeniosis - foodborne zoonotic infections with larval or metacestode and adult tapeworms, respectively Larvae meat-borne (pork) Adult stage-small intestine of the human host (obligate).

4. Risk factors Poor sanitation Intimate contact between humans and their livestock Use of untreated or partially treated wastewater in agriculture Uncooked or partially cooked meat

5. 50 million people have cysticercosis worldwide. Underestimate since many infections are not diagnosed . Cestodes are cosmopolitan in distribution Highly endemic in Latin America, Africa and Asia NCC -most common cause of adult-onset seizures in developing countries EPIDEMIOLOGY

6. Adult form-flat, opaque white or yellowish, long segmented parasites, measuring 1 to 12 m. Head or scolex -attachment organ Has four suckers and a rostellum that may be armed with hooks(T. solium ), or unarmed and sunken (T. saginata ), or with rudimentary hooklets ( Taenia saginata asiatica ) Morphology

7. Scolex -size of a pin-head Followed by a short and undivided region, the neck Long chain of proglottids or segments (termed the strobila ) proliferate Strobila has the appearance of a ribbon and may consist of more than a thousand proglottids . Posterior end of the tapeworm has the broadest, longest and oldest proglottids

8. Eggs are spherical Size -20 to 50 μm Radial appearance on light microscopy Eggs of all taeniids are morphologically indistinguishable by light and electron microscopy.

9. Humans as the sole definitive host Pigs are intermediate host. Humans acquire taeniosis by eating undercooked or raw pork infected with cysticerci . Acquire cystecercosis by ingesting eggs (exogenous or endogenous autoinfection) Life cycle of T. solium

10. A pork tapeworm cycle

11. Cellulose -small, spherical or oval, white or yellow vesicle, 0.5 and 1.5 cm Translucent bladder wall, through which scolex can be seen as a small solid eccentric granule. Generally separated from host tissue by a thin collagenous capsule, within which it remains alive Racemose -large, round or lobulated bladder circumscribed by a delicate wall Resembles a cluster of grapes,10 to 20 cm More common in immmunosupressed Morphological cysticerci types

12. 1)Vesicular stage -cyst with a translucent vesicular wall, transparent fluid, and a viable invaginated scolex . Little host inflammatory reaction. 2)Colloidal stage -thick vesicular wall, fluid turbid, scolex degenerates Varying degrees of acute and chronic inflammation. Radiography- cystic lesions with edema and enhancement and seizures are common. 3)Granular stage - thick vesicular wall, degenerated scolex , gliosis , little inflammatory host response.; 4) Calcific stage Stages of cysticerci

13. Asymptomatic to life threatening Can affect parenchyma, subarachnoid space, or intraventricular system,ocular,spinal Dependant on the location, number, and stage of the cysts at presentation L eading cause of adult-onset epilepsy in endemic areas(Latin America, Asia, Africa) Clinical Manifestations of Neurocysticercosis (NCC)

14. Commonly generalized tonic- clonic or simple partial More frequent in patients with parenchymal disease, Can occur in patients with cysts in the cortical sulci Usually occur when dying cyst incites an inflammatory reaction Has been reported in cystic stage 50%–70% of patients experience recurrent seizures Seizures

15. Also occur secondary to vasculitis and infarction in setting of subarachnoid disease Calcified NCC -development and maintenance of seizures and epilepsy Positive correlation between endemic populations with increased proportions of calcification and seizure activity. Calcified granulomas have increased risk of ongoing seizure Seizures

16. Perilesional edema related to calcification occurs episodically associated with seizures Accompanied by enhancement around the calcified focus Appx . 23%–35% Out of 110 patients, those with recurrent seizures, perilesional edema was noted on MRI in 50% as opposed to 9% of asymptomatic matched controls Seizures The Lancet Neurology, vol. 7, no. 12, pp. 1099– 1105, 2008

17. Focal neurologic signs Related to the number, size, and location of the parasites in individuals parenchymal disease.

18. Cysticercotic encephalitis -Intracranial hypertension in patients with parenchymal NCC Seen in children and young woman Acute inflammatory response to massive cysticercal infection resulting in brain edema Presents with clouding of consciousness, seizures, decreased visual acuity, headache, vomiting, and papilledema - subacute or acute in onset

19. Treated with mannitol and corticosteroids May require decompressive temporal craniotomy Not candidate for antiparasitic agents Other causes of intracranial hypertension -large cyst displacing midline structures or obstructs the flow of CSF at aqueduct

20. Psychiatric manifestations -depression, psychosis Study showed chronic inpatient psychiatric pts were more likely to have a positive serology for T. solium than healthy controls Increased risk with pts with mental retardation American Journal of TropicalMedicine and Hygiene, vol. 73, no. 3, pp. 504–509, 2005

21. Subarachnoid NCC Seen in Sylvian fissure or basilar cisterns Normal evolution not occur in the intraventricular or subarachnoid form Racemose type- aberrant proliferating cestode larvae Local mass effect Arachnoiditis resulting in communicating hydrocephalus secondary to chronic inflammation or fibrosis of arachnoid villi

22. Cysticercotic arachnoiditis can lead entrapment of cranial nerves in the inflammatory exudates . Extraocular muscle paralysis, diplopia and papillary abnormalities Decreased visual acuity,visual field defects Acute aseptic meningitis- signs of meningeal irritation rare

23. Cerebral infarction, transient ischemic attacks, brain hemorrhage Mechanism-Cerebral arteritis , particularly with subarachnoid cysticercosis Middle-size vessel involvement common Cerebrovascular complications

24. Vary according to size of parasites, their location inside ventricular system, and the coexistence of granular ependymitis Lateral ventricles -syndrome of increased intracranial pressure, may be associated with focal neurological signs due to compression. Third ventricle cysticerci -progressively worsening headaches and vomiting due to developing obstruction May present with sudden loss of conscious from acute hydrocephalus Ventricular NCC

25. Paroxysmal headache and vomiting secondary to intermittent obstruction at the level of the cerebral aqueduct Fourth ventricle - subacute hydrocephalus that may be associated with signs of brainstem dysfunction secondary to compression of fourth ventricle

26. Bruns ’ syndrome -Fourth ventricle cyst Characterized by episodic headache, papilledema , neck stiffness, sudden positional vertigo induced by rotatory movements of the head, nausea and vomiting, drop attacks and loss of consciousness Rapid recovery and long asymptomatic periods Cysts in the third and fourth-cause of sudden death due acute obstructive hydrocephalus

27. Granular ependymitis Degenerating cyst in the ventricles can result in inflammatory reaction throughout the ventricular system Cyst fixed to the ventricular wall with strong adhesions and fibrosis leading to hydrocephalus Tend to have a more chronic course

28. 1%–5% of all cases Extramedullary more common Intramedullary cysts are most common in thoracic spine Extramedullary cysts or leptomeningeal NCC-extension of subarachnoid disease,migrated from basilar cisterns Single or may form clumps Combination of radicular pain and motor deficits of subacute onset and progressive course Spinal cord involvement

29. Subretinal space -progressive decrease in visual acuity Vitreous cysts -worsening vision with perception of something moving within the eye Anterior chamber cyst -may induce a severe iridocyclitis Retro-ocular intraorbital cyst -decreased visual acuity due to pressure on the optic nerve Intraocular cysticerci

30. In the vesicular stagem cysticerci appear as cystic lesions within the brain parenchyma CT and MRI –thin walled cyst well demarcated from parenchyma,lack perilesional edema and do not enhance after administration of contrast medium. May be a bright nodule in their interior giving the lesion a “hole with dot” appearance that represents the scolex Radiological Manifestations

31. Colloidal stage so-called “acute encephalitic phase” of NCC has intense host reaction Appear as ill-defined lesions surrounded by edema which enhance after contrast medium administration MRI reveals a thick and hypointense wall with marked perilesional edema

32. Granular cysticerci appear as nodular hyperdense lesions surrounded by edema or a rim of gliosis after contrast medium administration Calcified (dead) cysticerci appear on CT as small hyperdense nodules without perilesional edema

33. Cysticerci within the basilar cisterns missed by CT scan, require MRI Subarachnoid cysts located in the Sylvian fissure may reach 50mm or more in size;have a mulitlobulated appearance, behave as mass occupying lesions. Hydrocephalus is most common CT finding in subarachnoid NCc . Leptomeningeal enhancement at the base of the brain observed on MRI Subarchanoid cysts

34. Appear on CT images as cystic lesions. Initially isodense with the CSF so not well visualized. Can be inferred from distortions of the ventricular system causing asymmetric or obstructive hydrocephalus Well visualized by MRI particularly using FLAIR techniques Ventricular migration sign move within ventricular cavities in response to movements of patients’ head a phenomenon best observed with MRI Ventricular cysts

35. CT -symmetrical enlargement of the cord ( intramedullary cysts ) Pseudoreticular formations within the spinal canal ( leptomeningal cysts ). MRI - intramedullary cysticerci to be ring enhancing lesions that have eccentric hyperintense nodule representing the scolex . Myelography in spinal leptomeningeal cysticercosis shows multiple filling defects in column of contrast material corresponding to each cyst Spinal NCC

36. Electroimmunotransfer blot (ETIB) using partially purified antigenic extracts Specificity 100% & sensitivity 94%–98% in two or more cystic or enhancing lesions False negative results in patients with single intracranial cysticerci Detection of circulating parasite antigen reflects presence of live parasites, ongoing viable infection, permit quantitative verification of successful treatment Serology

37. Monoclonal antibody-based ELISA to detect T. solium antigens in urine Sensitivity of urine antigen detection for viable parasites was 92%, which decreased to 62.5% in patients with a single cyst. Only calcified cysticercosis were urine antigen negative Indirect haemagglutination tests

38. Lymphocyte transformation test (LTT) has sensitivity of 93.7% and specificity of 96.2% Single cyst infection sensitivity of test was 87.5%

39. For Parenchymal Disease- Praziquantel and albendazole are antiparasitic agents Efficacy 60%-85% Greater cyst reduction with albendazole administration Praziquantel dose-50 mg/kg/d for 2 weeks Albendazole dose-15mg/kg for four weeks later reduced to 15 days then to one week Treatment

40. Between second and fifth day of treatment-exacerbation of neurologic symptoms attributed to inflammation secondary to killing of cysticerci Steroids used in conjunction to control resulting edema Steroids decrease the plasma level of praziquantel,but not albendazole

41. Oral prednisolone preferred Started 2-3 days before cysticidal therapy and continued for 7-10 days along with cysticidal therapy High dose corticosteroids in cysticercotic encephalitis

42. Whether provoked or acute symptomatic seizures and unprovoked seizures Acute symptomatic seizures patients may be treated only for duration of acute condition No guideline regarding duration Unprovoked seizures -2 years seizure free period SSECTG -monitor cyst activity with neuroimaging (6months) and to continue AED until resolution of the acute lesion. Resolved then AED may be tapered off over next 12 weeks Antiepileptic drugs

43. Ventricular, subarchanoid cysts- neuroendoscopic removal Giant cysticerci Hydrocephalus Cysticercoid enchephalitis with raised ICT may require temporal hemicraniotomy . Indications of surgery

44. Current consensus guidelines for treatment of neurocysticercosis . Clin Microbiol Rev 2002; 15: 747-756

45. Cochrane Database review on drugs for treating NCC concludes that there is insufficient evidence to assess whether cysticidal therapy in NCC is associated with beneficial effects

46. Depends on degree of infection and host response to parasite 85% with a SCCG have good seizure outcome following resolution of lesion With more than two seizures, breakthrough seizures, whose follow-up CT scan shows a calcific granuloma have a higher risk of recurrence Prognosis

47. Eradication of swine cysticercosis through improved animal husbandry and meat inspection procedures No vaccine developed Prevention and control

48. Thanks

49. Neurocysticercosis : Management Issues;Tarun Dua,S . Aneja Indian Pediatrics 227-236 Volume 43;march 17, 2006 Human Cysticercosis And Indian Scenario: A Review ;KASHI NATH PRASAD Et Al. J. Biosci. 33(4), November 2008, 571–582 Diagnostic criteria for neurocysticercosis : Some modifications are needed for Indian patients; Ravindra Kumar Garg : Neurology India June 2004 Vol 52 Issue 2 Neurocysticercosis – Indian Scenario; G. Singh, M. Sappal ; Medicine Update 2012  Vol. 22 Neurocysticercosis : Revisited; K.Kulkantrakorn ; J INFECT DIS ANTIMICROB AGENTS Jan.-Apr. 2005 References

50. Diagnosis and Treatment of Neurocysticercosis;C . Coyle, H. Tanowitz ; Interdisciplinary Perspectives on Infectious Diseases Volume 2009, 9 pages WHO/FAO/OIE Guidelines for the surveillance, prevention and control of taeniosis / cysticercosis 2005