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Lyme Complicated by Rapidly Progressive Acute Disseminated (ADEM) Harshal Shah DO Lehigh Valley Health Network, [email protected]

Hermann C. Schumacher MD Lehigh Valley Health Network

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Published In/Presented At Shah, H., Schumacher, H. (2015, October 24). Lyme Encephalitis Complicated by Rapidly Progressive Acute Disseminated Encephalomyelitis (ADEM). Poster presented at: ACP (Eastern PA) Associates’ and Medical Students’ Annual Competition, Hershey, PA.

This Poster is brought to you for free and open access by LVHN Scholarly Works. It has been accepted for inclusion in LVHN Scholarly Works by an authorized administrator. For more information, please contact [email protected]. Lyme Encephalitis Complicated by Rapidly Progressive Acute Disseminated Encephalomyelitis (ADEM) Harshal P Shah DO, and Hermann C Schumacher, MD Lehigh Valley Health Network, Allentown, Pennsylvania

CT-Head without Contrast MRI Brain w/wo Contrast Background DWI

•  is a multisystem illness caused by the spirochete burgdorferi • It is the most common vector born illness in the United States • It can present as early localized, early disseminated, or chronic disease T2/Flair • Early disseminated Lyme disease usually presents 3-10 weeks after inoculation with musculoskeletal and neurologic symptoms being the most common. • Lymphocytic , cranial neuropathy, and radiculoneuritis constitute the triad of early neurologic Lyme disease. • MRI of the brain demonstrates areas of restricted diffusion with associated mass effect in the posterior corpus callosum and •  involvement only occurs in the early disseminated phase. splenium, bilateral cortical spinal tracts including, bilateral occipital subcortical white matter, with probable involvement of the • ADEM is an autoimmune of the CNS commonly preceded by a viral infection or cortex on the right, bilateral mesial temporal lobes, periaqueductal gray matter, and superior and middle cerebellar peduncles. immunization No definite enhancement is identified. • The incidence of ADEM is rare, with 0.8 cases per 100,000 population • Elsewhere in the cerebral periventricular and subcortical white matter, there are additional foci of T2/FLAIR high signal. • Herein, we describe a rare case of Lyme encephalitis complicated by ADEM. Discussion Case Presentation • Acute disseminated encephalomyelitis (ADEM) is an autoimmune demyelinating disease of the CNS • It is commonly triggered by a preceding viral infection with acute onset and can be rapidly progressive. • A 55 year old immunocompetent Caucasian male presented with complaints of generalized head and neck • It is also thought to occur more commonly in children. pain, chills and photophobia for 4 days. • Two theories are believed for the pathogenesis of ADEM, one being antigenic mimicry with antiviral antibodies • He denied any recent travel or infectious exposure. cross reacting with myelin auto-antigens vs increased vascular permeability due to systemic • Physical exam showed meningimus with no neurological deficits or skin findings, and he was febrile, • Common infectious pathogens thought to be associated with ADEM are MMR, Varicella, Smallpox, EBV, HSV, tachycardic, and had a leukocytosis HHV-6, Influenza and HIV, although a cause is not always identified 25% of the time • CSF studies were consistent with bacterial meningitis, but CSF culture was negative. • Diagnosis of ADEM is a clinical diagnosis based on presentation, white matter lesions on MRI, and exclusion of • MRI displayed DWI in area of splenium and corpus callosum and FLAIR imaging revealed multiple lesions. alternative diagnosis • Within 24 hours, he developed new-onset aphasia and became obtunded and required intubation with new • Neuroimaging with MRI usually reveals bilateral lesions, asymmetric, with lesions in the deep and subcortical imaging showing progressive . white matter including corpus callosum, periventricular, and gray matter including the cortex, basal ganglia, and •  activity was ruled out with continuous EEG and patient was maintained on anti-epileptics thalamus • Vasculitis was also unlikely with nondiagnostic cerebral angiogram • In ADEM, MRI lesions are hyperintense on T2 weighted and FLAIR sequences • Endocarditis was also unlikely with a negative transthoracic echo • Lumbar Puncture in ADEM typically reveals a lymphocytic pleocytosis and a mildly elevated CSF protein, and • Further diagnostic studies revealed positive Lyme antibodies, with a positive confirmatory western blot elevations in myelin basic protein • Patient was continued on antibiotics and high dose steroids, however with minimal improvement and cerebral • Differential diagnosis for ADEM includes MS, HSV encephalitis, Sarcoidosis, Vasculitis, PML edema, a diagnosis of ADEM was made. • Lyme associated with ADEM has rarely been reported and is infrequent. • Subsequent MRI’s done throughout his hospital stay remained unchanged, with no further improvement or new • Treatment is immunosuppression with high dose steroids, with alternative therapy consisting of IV IG or enhancing lesions plasmapheresis, although evidence based clinical trials of the treatment regimen are lacking • Plasmapheresis was initiated with a total of 5 treatments, which showed clinical and laboratory improvement • Clinical course is more severe in adults with less favorable outcomes. • Due to persistent altered mental status and inability to protect airway, patient eventually required a • Complete recovery was reported in only approximately 33% of adult patients. tracheostomy and PEG tube placement prior to discharge for rehabilitation • Long term complications include a 35% chance of developing MS within 5 years • Repeat LP done prior to discharge showed no WBC’s in the CSF • ADEM should be considered in patients with coma, CSF with protein and lymphocytes, negative CSF culture, • Prior to discharge, the patient had completed 28 days of IV Rocephin, 7 days of 1 gram of Methylprednisolone, and white matter lesions on MRI and was continued on Prednisone

CSF Results Test Results Reference Range Antibody Profile Autoimmune Workup

Follow-up Component Result Latest Reference Range Test Results Reference Range Culture Negative x2 TSH 1.81 0.35-4.00 CSF Bands 1 Complement, C3 154 90-180 mg/dL Lyme Index Negative Folic Acid 12.5 >5.4 ng/mL Serum Bands 1 Complement, C4 29.7 10-40 mg/dL Cytology T-cell Lymphocytes Vitamin B12 475 >211 (pg/mL • At 2 months follow up, the patient and his family report continued progress. His tracheostomy has been CSF Olig Bands INT 0 <4 bands Complement, CH50 103 51-150 % Lyme PCR Negative Vitamin B6 39.2 20-125 nmol/L reversed and he has been cleared for a diet IgG Index, CSF 0.62 <=0.85 TPO AutoAb <10 <35 IU/mL VDRL Negative Vitamin B1 6 8-30 nmol/L • He is able to ambulate short distances with assistance and uses a wheelchair for long distances IgG, CSF 6.3 <=8.1 mg/dL ANA Screen Negative Negative T. Whipplei Negative Blood Cultures Negtive x2 Album, CSF 36.0 (H) <=27.0 mg/dL dsDNA AutoAb Negative Negative • He denies any pain or bladder/bowel dysfunction CMV Negative Urine Culture Negative IgG/Album, CSF 0.18 <=0.21 SSA (Ro) AutoAb <20 <20 ELISA Unit • He continues to have difficulty with visual spatial skills and , and difficulty with sequencing, however EBV PCR Negative Cryptococcal Antigen Negative Synthesis Rate, CSF 7.46 <=12 mg/24 h SSB (La) AutoAb <20 <20 ELISA Unit HSV DNA 1/2 Negative West Nile Virus Ab Negative overall has improved IgG, S 965 767-1590 mg/dL SM/RNP AutoAb <20 <20 ELISA Unit Enterovirus PCR Negative Borrelia Microti Ab Negative Album, S 3370 3200-4800 mg/dL Sm (Smith) Auto Ab <20 <20 ELISA Unit WNV Negative HHV-6 + IgG, -IgM References: IgG/Album, S 0.29 <=0.40 SCL-70 AutoAb <20 <20 ELISA Unit ACE Negative HIV 1 /2 Negative 1. Hu, Linden. “Clinical Manifestations of Lyme Disease in Adults.” UptoDate. Waltham, 2015. Print. Proteinase 3 Ab 1.2 <20 U/mL Myelin Basic Protein 15.4 (H) Toxoplasma Antibody Negative 2. Mahdi, Nicole, Peter Abdelmalik, and Mark Curtis. “A Case of Acute Disseminated Encecephalomyelitis in a Middle-Aged Adult.” Case Reports in Neurological Myeloperosidase Ab 1.3 <20 u/mL Medicine 2015 (2015). Print. JC Virus PCR Negative Lyme Ab (IgG - IgM) 3.03 <0.91 Borrelia Miyamotoi Serology Lyme IgM Ab 2.77 <0.91 Test Method Indirect EIA 3. Rovers, Jorgen, Elisabeth Louwerse, and C. Peter C. De Jager. “Complete Recovery from an Unusual Cause of Coma.” Intensive Care Med 2007.33 (2007): 542-44. HHV-6A and 6B Negative Print. igM - p23, p39, p41 GlpQ IgM 3.3 VZV PCR Negative Lyme Ab Western Blot all 3 bands positive 2/3 bands is positive Autoimmune Encephalitis Panel GlpQ IgG 3.0 4. Ruben, Rocha, and Lisboa Lurdes. “Neuroborreliosis Presenting as Acute Disseminated Encephalomyelitis.” Pediatric Emergency Care 28.December 2012 (2012): Test Result 1374-376. Print. Normal Range <1 NMDAR CSF Negative CSF Results *Comments: Significant Levels of IgM and IgG antibody 5. Waldman, Amy, and Dina Jacobs. “Acute Disseminated Encephalomyelitis in Adults.” UptoDate. Waltham, 2015. Print. LGI1 Negative to B.miyamotoi detected by indirect EIa. © 2015 Lehigh Valley Health Network RBC 20 (H) Interpretation: These findings are compatible with an GAD65 CSF Negative WBC 616 (H) infection with B.Miyamotoi at an undertermin time. GABA-B-R Negative neutrophils 86 (H) Toxicology Screen Results CASPR2 Negative

Lymphocytes 4 (L) AMPAR (GluR1) Negative Urine Heavy Metals Negative Glucose 53 AMPAR (GluR2) Negative Total Protein 110 (H) Serum Copper Normal