Infectious Disease Clinical Case Presentation

1. Infectious DiseaseClinical Case Presentation Samina Syed, MS IV Kees Van Dam, MD September 12, 2007

2. CC: Acute mental status changes “I feel like I’m going crazy”

3. History of Present Illness R.S. is a 19 year old white male in the Armed Forces, who was preparing for deployment to Iraq during the week of 9/3. The patient’s family visited him over the weekend (9/1-9/2) and he was in a normal state of health aside from complaints of a headache.

4. On Monday, 9/3, his father called him around 1300 and was surprised to find him still in bed. His son sounded unusually sleepy. That evening the patient told his mother that he with felt like he was “going crazy.” On 9/4 he did not show up for work.

5. On 9/4 he did not show up for work. He was found on his bed nude, mumbling incomprehensible words. He was taken to AF base facility and then to Wayne Memorial. Upon admission, he could state his first name and the year. He began showing signs of frontal disinhibition and rapidly deteriorated.

6. He underwent lumbar puncture and was placed on ceftriaxone, vancomycin, and acyclovir. He was intubated for airway protection and transferred to MICU at UNC. Upon arrival patient was minimally responsive to noxious stimuli.

7. Past Medical History: Previously healthy SOCIAL HX: Active duty stationed at a nearby airforce base. Deployment week of 9/3/07. Per coworkers, patient does not drink, smoke, or do illicit drugs. Travel: Patient trained in Texas November-April and then moved to North Carolina. He visited family in NY state in July. FAMILY HX: No hx of early CAD HOME MEDICATIONS: mefloquine ALLERGIES: NKDA

8. Review of Systems • Other than HPI fairly unobtainable. • Mother had noticed a rash on his feet bilaterally on Tuesday, 9/5 at Wayne Memorial. She thought it might have been due to the boots he had been wearing.

9. Vitals Tmax = 39.4 on admission BP 115/59 RR 20 Physical Exam: General: Intubated, no response to voice. Lymphadenopathy: 1 mm left axillary node Skin: Two to three 1 mm areas with blanching papules bilaterally on the feet. Similar papules were on the dorsum of PIP on left hand and DIP of ring finger on left hand.

10. Physical Exam: Neurological Comatose, no response to voice Visual fields show no reaction to threat bilaterally, PERRLA Normal bulk and tone, bilateral upper extremity extensor posturing with nail pressure Slight withdrawal on left lower extremity with nail pressure, slight movement of right quadricep with right lower extremity naill pressure Reflexes symmetric and 3+ bilaterally at bicep, tricep, bracheoradialis, patellar, ankle.

11. ADMISSION DIAGNOSTIC STUDIES: (WM)

12. ADMISSION DIAGNOSTIC STUDIES

13. ADMISSION DIAGNOSTIC STUDIES LP: opening pressure 36 Appearance: colorless clear RBCs 3, WBCs 135 28% neutrophils 59% lymphocytes, 13% monocytes, Glucose 65, Protein 91. CSF Gram stain: No organisms, few WBCs

14. ADMISSION DIAGNOSTIC STUDIES CT with and without contrast: showed “no acute intracranial process and no enhancing lesions.” An MRI was performed at Wayne Memorial prior to transfer. MRI also performed at UNC on evening of arrival to MICU.

15. MRI BRAIN 9/5/07: T2 Images

29. MRI BRAIN: FLAIR Images

43. FINDINGS There are large areas of abnormal T2 and FLAIR signal abnormalities involving the subcortical and deep white matter in the bilateral frontal, parietal, and occipital lobes. There is abnormal signal involving the the corpus callosum and periventricular white matter. There is abnormal increased T2 and FLAIR signal involving the medial portions of the temporal lobes and right thalamus. There is similar abnormal signal involving the posterior pons. There is a somewhat linear area of restricted diffusion in the left frontal region just superomedial to the sylvian fissure. This correlates with an area of FLAIR and T2 signal abnormality. There is abnormal FLAIR signal in the subarachnoid spaces bilaterally superiorly. This is nonspecific but can be seen with proteinaceous fluid or subarachnoid hemorrhage but can also be related to ventilation. IMPRESSION 1.Multiple areas of abnormal signal involving predominantly white matter but also areas of gray matter. 2. Nonspecific increased FLAIR signal in the subarachnoid space as described above.

44. DISCUSSION

45. Additional History: Vaccine History • On 8/18 pt received anthrax vaccine #1, as well as typhoid vaccine IM • On 8/23 patient received a smallpox vaccination left deltoid. • On 8/30 he received anthrax vaccine #2

46. Course: • Upon arrival to UNC his smallpox vaccination site was examined by Dr. Weber and found to be a “8 mm well scabbed over black eschar on left upper arm.” • He had no evidence on exam for satellite lesions. • Patient was placed on contact precautions. • ICU team added Doxycycline. • ID and Neurology were consulted.

47. LABS HIV negative RPR NR Crypto ag serum neg B12 normal TSH normal --------------------------------------------------------------------------------------------------- WNV (CSF) VZV PCR (CSF) HSV PCR (CSF) Lyme titer (CSF) Crypto Ag CSF Fungal and AFB stain and culture (CSF) VDRL (CSF)

48. Course: • We recommended addition of high dose ampicillin to cover Listeria in addition to continuing vancomycin, ceftriaxone, acyclovir and doxycycline. • Asked MICU to check RMSF titers, arbovirus serologies. • We were most concerned for a post vaccinia encephalitis (PVE). • Neuro-radiology and Neurology: Imaging, clinical picture c/w Acute Disseminated Encephalomyelitis (ADEM). • Neurology recommended high dose steroids and IVIG.

49. Consultation with the CDC and DOD on 9/5/07: A second LP at WM had been done on 9/4 with CSF and serum sent to CDC labs. Poxvirology Lab: PCR negative CSF and Blood for poxvirus nucleic acid Serum and CSF IgG negative for poxvirus Serum and CSF IgM pending CDC strongly endorsed adding IVIG to the high dose steroids.

50. CDC Conference Call • CDC also recommended several additional tests: • Pre-IVIG Serum sent to CDC for Poxvirus antibody testing. • highly sensitive CRP • complement levels and circulating immune complexes • EBV, CMV DNA PCR, serologies in blood • Chlamydia antibodies • Streptoccoccal antibodies Conference calls with the CDC were continued to follow the course of the post vaccinia complication: post vaccinial encephalitis.