2/13/2020 Disclosures • I have no disclosures. NEUROINFECTIOUS DISEASES 201: BEYOND THE BASICS Felicia Chow, MD, MAS Assistant Professor University of California, San Francisco Department of Neurology and Division of Infectious Diseases February 13, 2020 Title slide photo credit, Teresa Zgoda, 4 th place in Nikon’s small world contest: https://www.nikonsmallworld.com/galleries/2017- photomicrography-competition/taenia-solium-everted-scolex 1 2 Learning objectives Case One • 40-year-old man with no PMH presents with confusion, found to have • Discuss atypical presentations of common neuroinfectious ”idiopathic communicating hydrocephalus” requiring VP shunt diseases and typical presentations of less common neuroinfectious diseases • Developed persistent headaches a few weeks post-operatively; presented several times to the ED and diagnosed with migraines • Identify pitfalls of diagnostic testing in the evaluation and • Six months after the shunt surgery, the headaches became acutely management of neuroinfectious diseases worse, often accompanied by neck stiffness, N/V, and fever • Be familiar with updates in treatment strategies for several • Brought into ED from work after a possible seizure LP w/ 2,000 neuroinfectious diseases WBC (98% neutrophils), 1392 RBC, glucose <5, protein 778; CSF gram stain and bacterial culture negative • Started empirically on vancomycin and ceftriaxone broadened to vancomycin and cefepime 3 4 1
2/13/2020 Case One Case One 5 6 Case One Case One • VP shunt removed improved but then encephalopathy • EXAM: Afebrile. Eyes open, abulic; briefly regards, does and ventriculomegaly worsen, requiring EVD not track, intermittently follows simple commands. No verbal output. Pupils equal and reactive to light. No blink to threat bilaterally. Sustains arms antigravity, withdraws • Serial CSF evaluations, most of which were from legs to tickle. ventricular fluid, demonstrated marked improvement in pleocytosis and other parameters over 1 week WBC 3, glucose 60, protein 23 • Broad spectrum antibiotics continued clinically improved at first…but then worsens again • Transferred to UCSF for further evaluation and management 7 8 2
2/13/2020 Case One Case One • Ventricular CSF with 0 WBC, 180 RBC, glucose 57, protein <10 • Lumbar CSF with 8 WBC (36% neutrophils), glucose 22, protein 240 • Negative studies from CSF • Gram stain and bacterial culture • Bacterial antigen testing for H influenzae, group B strep, Strep pneumo, N meningitidis, E. coli • Coccidioidomycosis complement fixation and immunodiffusion • M. tuberculosis PCR • Negative blood cultures, HIV and Quantiferon-TB Gold 9 10 Case One Case One • Social history/exposures 40-year-old man with a history of “idiopathic • Married, no children communicating hydrocephalus” s/p right VP • Lives in Monterrey with his wife shunt who presents with meningitis with • Works in construction, mostly on roads improvement in CSF pleocytosis on broad- • Infrequent alcohol use; never smoker, no other substance use. spectrum antibiotics but persistent, progressive • Born in rural part of Jalisco, Mexico • Moved to Monterrey, CA in early 1990s radiological changes concerning for ventriculitis • Has a dog at home, no other animal exposures • Does not consume unpasteurized dairy • No history of incarceration or homelessness • No known TB contacts 11 12 3
2/13/2020 Case One: Back to the beginning What do you think is the most likely diagnosis? A. Incompletely treated nosocomial bacterial ventriculitis B. Neurocysticercosis 31% 22% 20% C. Neurobrucellosis 16% 11% D. TB meningitis E. CNS Coccidioidomycosis s s s s i i i i . s s t s . o o g i o . n c l l n c r e i y d e n m c c e u e t i r m o a t b d s e y o i r c B o r T t o u d i y r e u i e l N c e c t o e N C p l S m N o C c n I 13 14 Case One Intraventricular neurocysticercosis • 4 th ventricle lesion concerning for intraventricular cysticercosis • Serum cysticercus ELISA positive 2.49 • CSF cysticercus ELISA from ventricular fluid negative, but positive from lumbar fluid • MRI brain with FIESTA sequences negative for visualized intraventricular cysts • Started on dexamethasone with albendazole 15 16 4
2/13/2020 Neurocysticercosis (NCC) Stage of Number cysts Location • Infection of the nervous system of cysts of cysts with larval stage of the tapeworm, Taenia solium • 50+ million people affected Natural history, worldwide clinical presentation, • >2000 cases diagnosed annually in US diagnostic testing, and management of • One of the most common causes of acquired epilepsy in endemic NCC countries (Latin America, sub- Saharan Africa, parts of Asia) Ndimubanzi et al. PLOS Negl Trop Dis 2010 17 18 Intraventricular NCC Location, location, location • Presenting form of NCC in 10-20% of • Intraparenchymal (70%) cases • Cortical (>90%), deep gray matter (5%), brainstem/infratentorial (uncommon) • Acute hydrocephalus is the most • Most commonly present with common complication of ventricular NCC seizures • Viable/vesicular cysts: Transient • Extraparenchymal (30%) mechanical obstruction of CSF outflow • Sylvian fissure, basal cisterns, through “ball-valve” movement, including intraventricular, spinal (usually extramedullary) with change in head position (Bruns syndrome) • Most commonly present with hydrocephalus and increased intracranial pressure • Degenerating cysts: Can adhere to • Associated with more protracted ependymal lining and surrounding tissue, course and worse prognosis leading to ventriculitis, periventricular edema, and hydrocephalus • Mixed (10-30% of cases) Nash et al. Am J Trop Med Hyg 2018, Sierra et al. PLOS Neg Trop Dis 2017 19 20 5
2/13/2020 FIESTA/CISS Surgical intervention for intraventricular NCC and SWI to detect IV • Extraction of cysts is mainstay of treatment for viable, non- cysts inflamed intraventricular cysts a: T1 • Cyst rupture during surgical removal has NOT been b: T2 associated with adverse outcomes c: SWI • Pre-treat with steroids but not d: FIESTA antiparasitic therapy Neyaz et al. Neurol India 2012 Nash Am J Trop Med Hyg 2018, Campbell J Rare Dis Res Treat 2017, Khade World Neurosurg 2013, Ho Cureus 2015, Li World Neurosurg 2017 21 22 Intraoperative video of endoscopic Medical therapy for extraction of intraventricular cyst ventricular cysts As an alternative to surgery • High risk of complications (e.g., hemorrhage, neurologic deficits) associated with surgical removal of inflamed, adherent cysts treat with albendazole +/- praziquantel + steroids As an adjunct to surgery? • Consider albendazole + steroids for up to 4 weeks after surgical removal of viable, non-inflamed cysts, although many experts suggest this may be unnecessary if residual cysts are not seen on imaging Khade World Neurosurg 2013, Husain Acta Neurochir 2007, Goel J Clin Neurosci 2008, White Clin Infect Dis 2018 Rangel-Castilla et al. Am J Trop Med Hyg 2009 23 24 6
2/13/2020 Neuro-Infectious Diseases 201: Beyond the Basics Ventricular • Discordant profiles of CSF sampled from Key learning points different compartments is a common versus lumbar phenomenon in CNS infections, • Obtain serologies for neurocysticercosis in patients with epidemiological CSF: does it especially those that cause a basal risk factors presenting with unexplained ventriculomegaly/hydrocephalus meningitis (e.g., TB, coccidioidomycosis, matter? or culture-negative neutrophil or lymphocyte-predominant pleocytosis cryptococcosis, neurocysticercosis) • FIESTA sequences can help to identify difficult-to-visualize subarachnoid • Typically ventricular CSF profile more and intraventricular cysts in neurocysticercosis ‘normal’ compared with lumbar fluid • Surgical removal of viable intraventricular cysts is first-line therapy; cysts that have begun to degenerate, however, are typically not amenable to • In addition to discrepant CSF parameters, surgery microbiological testing can be positive from one compartment but not the other • Remember that ventricular and lumbar CSF profiles can look vastly different in patients with certain CNS infections (e.g., basal meningitis), • May not be able to compare CSF results and the diagnostic yield of microbiologic testing may depend on the CSF compartment tested from different compartments Khan OFID 2019 25 26 Case Two Case Two • 60-year-old man with essential thrombocytosis, • EXAM: T 39.5. Awake, alert, conversant. Neck supple, no polycythemia vera, and nephrotic syndrome 2/2 minimal meningismus. Binocular horizontal diplopia with impaired change disease on prednisone who presented with abduction of right eye and right INO. Dense right facial several days of double vision, gait imbalance, and right weakness involving upper and lower face. Moderate facial droop dysarthria. Normal tone. Strength in upper and lower extremities intact. Wide-based ataxic gait. • Endorsed fever, chills, drenching night sweats, and malaise for 1 month 27 28 7
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