Difficult Diagnosis E. ALEXANDRA BROWN, MD ASSISTANT PROFESSOR OF - - PowerPoint PPT Presentation

SLIDE 1

2/16/2018 1

Difficult Diagnosis

• E. ALEXANDRA BROWN, MD

ASSISTANT PROFESSOR OF NEUROLOGY, UCSF DIRECTOR, ZUCKERBERG SAN FRANCISCO GENERAL NEUROLOGY CLINIC

Disclosures

 I have nothing to disclose.

54F with 6 month history of headache

• Out of medical care x 7 years
• Headaches are 2-3 days per month
• Pulsating, severe, bitemporal location
• Nausea, photophobia, phonophobia
• Previously relieved by rest and OTCs
• OTCs no longer help
• Neuro exam reportedly normal per PCP

54F with 6 month history of headache

• Out of medical care x 7 years
• Headaches are 2-3 days per month
• Pulsating, severe, bitemporal location
• Nausea, photophobia, phonophobia
• Previously relieved by rest and OTCs
• OTCs no longer help
• Neuro exam reportedly normal per PCP

Cephalalgia 2013;33:629-808.

ICHD-3 Criteria: Migraine without Aura

SLIDE 2

2/16/2018 2 54F with 6 month history of headache

• Out of medical care x 7 years
• Headaches are 2-3 days per month
• Pulsating, severe, bitemporal location
• Nausea, photophobia, phonophobia
• Previously relieved by rest and OTCs
• OTCs no longer help
• Neuro exam reportedly normal per PCP

ICHD-3 Criteria: Migraine without Aura

Cephalalgia 2013;33:629-808.

54F with 6 month history of headache

• Out of medical care x 7 years
• Headaches are 2-3 days per month
• Pulsating, severe, bitemporal location
• Nausea, photophobia, phonophobia
• Previously relieved by rest and OTCs
• OTCs no longer help
• Neuro exam reportedly normal per PCP

Red flags

 What features should worry you about secondary headache? -Systemic symptoms (fevers, chills, weight loss, HIV, cancer) -New headache in an older patient >50 y.o. -Abrupt onset reaching maximum intensity in < 1 minute -Exacerbated by positioning or Valsalva -Abnormal neurological/fundoscopic exam

Nye BL, Ward TN. Headache 2015 Oct: 1301-1308.

Neurology consultation further details

∙ Awakens from sleep with occipital headache x 1 year ∙ No previous headache history ∙ Born in Mexico ∙ Has not been taking any medications for HA ∙ Neurological exam reveals right dysmetria MRI brain with and without Gad was performed

SLIDE 3

2/16/2018 3 T1 T2 FLAIR Post Gad T1 Neurocysticercosis

 CNS infection by larval form of pork tapeworm Taenia solium  Most common helminthic CNS infection  A leading cause of acquired epilepsy worldwide  Clinical presentation depends on:  Location of cysts  Stage of parasite  Host immune response

Garcia HH, et al. Lancet Neurol. 2014;13: 1202-15.

Endemic regions

Garcia HH, et al. Lancet Neurol. 2014;13: 1202-15.

Q1: How do humans become

infected with neurocysticercosis?

• A. Eating undercooked pork containing viable

cysticerci

• B. Ingesting food or water contaminated with

human feces containing T. solium eggs

• C. Ingesting food or water contaminated with

porcine feces containing T. solium eggs

• D. Transmission through blood from an infected

person

• E. None of the above

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SLIDE 4

2/16/2018 4 Life cycle of Taenia solium

Kraft R. Am Fam Physician. 2008 Mar 15;77(6):748.

1 parasite, 2 infections Taeniasis and Cysticercosis

Life cycle of Taenia solium

Taeniasis:

∙ Adult tapeworm infection ∙ Human eats undercooked pork containing viable cysticerci

Kraft R. Am Fam Physician. 2008 Mar 15;77(6):748.

Life cycle of Taenia solium

Kraft R. Am Fam Physician. 2008 Mar 15;77(6):748.

Cysticercosis:

∙ Infection caused by larval stage of tapeworm T. solium

• T. Solium Cyst Stages of Development

Colloidal

∙ Begins Degeneration ∙ Ring enhances ∙ +/- Scolex ∙ Edema

Granular nodular

∙ Degenerates further ∙ Ring enhances ∙ No Scolex ∙ Less edema

Calcified

∙ Dead ∙ Punctate Ca2+ ∙ No Scolex ∙ Minimal/No Edema

• Garcia. Lancet Neurol. 2014;13: 1202-15.

Sinha S, et al. Journal of Clinical Neuroscience 2009;16: 867-76. Zhao JL, et al. Radiology of Infectious Disease 2015;1:94-102. Del Brutto OH. Scientific World Journal 2012;2012:159821.

Vesicular

∙ Viable ∙ Non-enhancing ∙ Scolex=“hole-with-dot” ∙ No edema

SLIDE 5

2/16/2018 5 NCC brain locations

Parenchymal Extraparenchymal Usually gray-white junction Intraventricular (usually 4th ventricle) Subarachnoid (basal cisterns, sylvian fissure) Can manifest as seizures Can manifest as hydrocephalus, focal neurological deficits, complications of ↑ ICP

Sinha S, Sharma BS. Journal of Clinical Neuroscience 2009;16: 867-76.

Subarachnoid NCC

 Excessive T. solium larval growth

enlarged multiloculated cysts (racemose=“bunch of grapes”)

 MRI spine should be performed in basal

subarachnoid NCC

 High risk asymptomatic spinal cord

• involvement. If present  treat surgically

(consensus)

Garcia HH, et al. Clin Microbiol Rev 2002;15:747-56. Callacondo et al. Neurology 2012;78(18):1394-1400.

Immunological Diagnosis

EITB assay (Western Blot): TEST OF CHOICE ELISA based assay

• Gripper. Acta Tropica 2017;166:218-224.

Diagnostic Criteria for NCC

Clinical Presentation Imaging (MAINSTAY) Exposure Hx Serologic Testing

Dx

SLIDE 6

2/16/2018 6 Q2: What is the next step in this

patient’s care?

• A. Start antihelminthic therapy with Albendazole 15

mg/kg/day for a minimum of 10 days

• B. Start steroid therapy with Dexamethasone 0.1

mg/kg/day then administer Albendazole 15 mg/kg/day for a minimum of 10 days

• C. No indication for antihelminthic therapy given that the

appearance of these cysts does not warrant antihelminthic drugs

• D. Do not initiate antihelminthic therapy until further

workup is performed

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Subretinal cysts

Del Brutto OH, et al. Journal Neurol Sci 2017;372:202-10. Kori P, et al. Neurology 2013;81:135-6. Padhi TR, et al. Survey of Ophthalmology 2017;16:161-89.  Dilated eye exam is essential prior to initiating Albendazole or Praziquantel  Antihelminthic therapy provokes inflammatory response around dying cysticerci

can lead to blindness

 Surgical removal of cyst is treatment of choice for ocular cysts (consensus)

Q3: Which antihelminthic drug regimen is appropriate for a patient with NCC whose brain imaging is notable for >3 calcified cysts?

A.

Albendazole 15 mg/kg/day x 7-10 days

B.

Albendazole 22.5 mg/kg/day x 7-10 days

• C. Combination therapy Albendazole 15 mg/kg/day x 7-10

days + Praziquantel 50 mg/kg/day x 7-10 days

• D. Concurrent treatment of Dexamethasone 0.1 mg/kg/day

with Albendazole 15 mg/kg/day x 7-10 days to control intracranial inflammation

E.

None of the above

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Antihelminthic drugs

 Albendazole, Praziquantel - Used to treat viable cysts  Not used for calcified cysts which are already dead  Worsened inflammation during cyst destruction temporarily worsens symptoms  Must control symptoms first (if needed, undergo lesion resection, ventricular

shunt placement, steroids, etc) There is no rush to initiate antihelminthic drugs!

 Give steroids simultaneously to control inflammation

• Gripper. Acta Tropica 2017;166:218-224.

Garcia HH, et al. Clin Inf Dis 2016;62: 1375-79.

SLIDE 7

2/16/2018 7 Back to our case

 Steroids were initiated right away  Dexamethasone 4 mg TID x 3 days,

then 2 mg TID x 2 weeks, then Prednisone 0.4 mg/kg daily

 Clinic follow-up: headaches resolved, R dysmetria resolved  Ophthalmology: no intra-ocular cysticercosis  Spine MRI with and without Gad: no cysticerci  Cysticercosis IgG Ab: 3.77 H (>0.51 is positive)  Alongside Prednisone, administered Albendazole 15 mg/kg/day x 4 weeks  Ca+Vit D, Famotidine while receiving steroids  Return precautions given; patient closely monitored, remained asymptomatic

T2 FLAIR at 4 months T2 FLAIR at 15 months INITIAL T2 FLAIR

Take home points

 Antihelminthic drug treatment is NEVER the main priority, rather first

address patient’s symptoms (seizures, increased ICP). There is no rush to begin antihelminthic drugs.

 Pay attention to cyst stage: there is no role for antihelminthic drugs if

• nly calcified lesions are seen.

 Obtain dilated eye exam prior to initiating antihelminthic drugs; subretinal

cysticerci should be surgically resected.

 Administer steroids alongside antihelminthic drugs to limit inflammation

that occurs with dying cysts.

Garcia HH, et al. Clin Microbiol Rev 2002;15:747-56.

Thank you

Happy to answer questions