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Infectious Disease Clinical Case Presentation

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Infectious Disease Clinical Case Presentation Samina Syed, MS IV Kees Van Dam, MD September 12, 2007 CC: Acute mental status changes I feel like I m going crazy ... – PowerPoint PPT presentation

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Title: 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 Im 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 patients 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)
CBC WBC 12.7 Gran 10.7 (84.3) Lymph 1.5 (11.7) Mono 0.5 (3.8) Eos 0.0 Baso 0.0 RBC 4.74 Hemoglobin 13.6 Hematocrit 41 Platelets 215 Chem panel Na 138 K 4.2 Cl 102 BUN 27 Creatinine 11 Anion gap 9
LFTs normal range UA trace protein, ketones 15, rare WBCs EKG NSR, biatrial enlargement
12
ADMISSION DIAGNOSTIC STUDIES
Toxicology Screen Negative Amphetamines Barbiturates Benzodiazepines Cocaine Opiates Phencycidine Cannaboids TCAs Methamphetamine Methadone Toxicology screen positive Acetaminophen
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
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MRI BRAIN FLAIR Images
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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. IMPRES
SION 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.

51
CDC Conference Call Later that evening the serum
and CSF IgM returned positive. Despite lack of
evidence for disseminated vaccinia, decided
patient might benefit from vaccinia
immunoglobulin and CDC shipped VIG overnight to
RDU. VIG started on Friday afternoon, IVIG
resumed afterwards until pt completed 2g/kg over
4 days. High dose steroids continued.
52
Course
  • Vancomycin, ceftriaxone, doxcycline dcd after
    gt48 hrs negative cultures, low susp for RMSF.
  • Ampicillin continued until final CSF cultures
    negative 9/10.
  • Acyclovir continued until CSF HSV, VZV PCR
    negative 9/11

53
Course
  • West Nile CSF negative
  • Lyme antibody CSF negative
  • RMSF serum IFA 180
  • CDC labs CSF negative for Adenovirus,
    Enterovirus, HSV, VZV
  • CDC testing of serum now positive for IgG on pre
    IVIG, pre VIG, post VIG serum

54
Vaccinia virus is a live DNA virus used as the
vaccine against smallpox, which is caused by the
Variola virus. Genus Orthopoxvirus.
Day 3-5 Papule Day 5-8 Vesicular Day 8-10
Pustular Day 14-21 Scab separation
55
Adverse events after smallpox vaccination
recommended for report Superinfection of the
vaccination site or regional lymph
nodes Inadvertent inoculation Contact
transmission Ocular vaccinia Generalized
vaccinia Eczema vaccinatum Progressive
vaccinia Erythema multiforme major or SJS Fetal
vaccinia Postvaccinial CNS disease Myo/pericarditi
s Dilated cardiomyopathy
56
Adverse Events
  • Inadvertent Inoculation
  • Results in a normal vaccinial lesion in an
    inappropriate site (most common complication in
    1968 study).

57
Adverse Events
  • Generalized Vaccinia
  • Generalized vaccinia is the result of the
    systemic spread of virus from the vaccination
    site. Despite the appearance of the lesions, it
    is usually a benign complication of primary
    vaccination that is self-limited except in some
    individuals with underlying immunosuppression
    (medications or illnesses).

58
Adverse Events
  • Eczema Vaccinatum
  • A local or disseminated vaccinia that occurs in
    patients with a hx of eczema or other types of
    atopic dermatitis
  • Erythema Multiforme
  • Pathogenesis thought to be allergic, toxic, or
    both.

59
Adverse Events
  • Progressive Vaccinia (Vaccinia Necrosum)
  • Universally fatal prior to VIG
  • Occurs in immunodeficient vaccinees
  • Progressive destruction of local areas of skin,
    subcutaneous tissue, and metastatic lesions can
    lead to death

60
Adverse Events
  • Myocarditis and Pericarditis
  • Effects range from asx T wave changes to fatal
    myocarditis.
  • During 2003 civilian first responders vaccination
    program, 6 out of 10,000 vaccinees developed
    myocarditis.

61
Post-Vaccinial Encephalitis
  • Neurological illness is a rare but severe Vaccine
    Adverse Event (VAER)
  • Post-vaccine Encephalitis (PVE)
  • Historically occurred with greater frequency in
    first time vaccinees.

62
Case Definition of PVE for use in Smallpox
VAER(Sejvar et al JAMA 2005)
  • Confirmed PVE
  • acute cerebral /- menningeal inflammation or
    demyelination on histopathology
  • Probable PVE
  • Encephalopathy (AMS, personality change) gt24 hrs
  • AND
  • Additional features suggestive of cerebral
    inflammation including 2 or more of following
  • Fever (gt38) or Hypothermia (lt35)
  • Meningismus
  • Pleiocytosis
  • Presence of focal neurologic defect
  • EEG c/w encephalitis
  • Neuroimaging (MRI) c/w inflammation or
    demyelination
  • Seizures

63
Post-Vaccinial Encephalitis
  • Clinicohistopathologic data from the 1920s and
    1960s identified 2 clinicopathological forms of
    PVE
  • Microglial encephalitis
  • Post-vaccinial encephalopathy

64
PVE Microglial encephalitis
  • More frequent in gt2 years of age
  • 10-20 days after vaccination
  • Fever, vomiting, headache malaise followed by
    decreased consciousness, seizures, coma
  • Widespread demyelination of subcortical white
    matter (prob corresponds to ADEM)
  • ie MRI etc were not available in 1920s, 1960s.

65
PVE Post-vaccinial encephalopathy
  • More frequent in lt2 years of age
  • 6-12 days after vaccination
  • Fulminant seizures and hemiplegia, elevated ICP.
  • Diffuse cerebral edema and perivascular
    hemorrhages
  • At times vaccinial viremia and even vaccinia
    virus isolation/detection from brain or CSF.
  • A neuroinvasive form of vaccinia virus?

66
POST VACCINIAL ENCEPHALITIS
European Countries (1964) Incidence
Britain 1.5
Finland 3.1
Sweden 3.5
Switzerland 5.0
Belgium 7.0
Holland 13.0
Germany 11.0
Austria 30.0
The overall incidence in the U.S. was 2.9/million
vaccinees in 1968. The case fatality rate in the
U.S. was 25 and 30-50 in Europe (1959-1966). In
2001, the CDC reported the rate as 1 case per
300,000 vaccinees.
67
Acute Demyelinating Encephalomyelitis (ADEM)
  • ADEM is an immune mediated inflammatory disorder
    of the CNS, primarily of the white matter, that
    is typically precipitated by viral infection or
    vaccination

68
ADEM
  • Diagnosis of exclusion
  • Differential Infection, MS, Transverse Myelitis
  • Based on clinical and radiologic features (MRI
    critical)
  • Usually monophasic , recurrent ADEM has been
    reported

69
Clinical FeaturesADEM
  • Rapid onset encephalopathy
  • Prodrome with fever, malaise, headache, nausea,
    vomiting
  • Meningeal signs and drowsiness
  • Rapidly progressive, developing over hours to
    maximum deficits within days
  • Neurologic signs include acute hemiplegia,
    ataxia, cranial nerve palsies, seizures,
    impairment of speech, mental status changes

70
MRI FeaturesADEM
  • Patchy, poorly marginated areas of increased
    signal intensity large, asymmetric, multiple
  • Four patterns
  • ADEM with less than 5 mm lesions
  • Large, confluent lesions with edema and mass
    effect
  • ADEM with additional symmetric bithalamic
    involvement
  • Acute hemorrhagic encephalomyelitis (worst
    prognosis)

71
Epidemiology of ADEM
  • More common in pediatric patients
  • Recent study of persons less than 20 years with
    ADEM showed 5 had a vaccination within 1 month,
    93 had signs of infection in preceding 21 days
  • Post-vaccinial encephalitis usually occur 7-14
    days after vaccination
  • Incidence varies by country

72
Pathophysiology of ADEM
  • Pathogenesis is not well understood
  • Immune pathogenesis supported by time course
    between vaccine and encephalitis
  • Similarity in the neuropathology of ADEM with
    animal models of experimental allergic-autoimmune
    encephalitis (EAE)

73
Pathophysiology of ADEM
  • EAE is an autoimmune disease mediated by T cells
    directed at myelin antigens
  • Postulated that phosphorylation of myelin basic
    protein, by vaccinias viral kinase, may change
    the immunogenicity of myelin basic protein
  • Viral epitopes may resemble myelin reactive T
    cell clones through molecular mimicry

74
Treatment of ADEM
  • No standard therapy
  • Based on case reports and small series
  • Most therapies use a form of immunosuppressant
    therapy
  • Steroids
  • IV immunoglobulin
  • Plasmapheresis

75
Treatment of ADEM
  • IVIG
  • Interaction with Fc receptors on effector cells
  • Anti-idiotypic antibodies against circulating
    antibodies
  • May alter the number of T cells and subsets
  • Promote clearance of immune deposits
  • May contain neutralizing antibodies
  • May increase clearance of pathogenic IgG
  • May neutralize the inflammatory actions of
    complement

76
Treatment of ADEM
  • High dose steroids
  • Gastric perforation, hyperglycemia, hypokalemia,
    hypertension, facial flushing
  • Plasmapheresis
  • Hypotension, bleeding, allergic rxn,
    immunosuppresion
  • Vaccinia immunoglobulin

77
VIG and ADEM due to PVE?
  • Vaccinia Immunoglobulin (VIG) not thought to be
    useful because PVE thought to be immune mediated,
    and not due to vaccinial infection.
  • Nanning et al, 1962 Randomized trial of
    prophylactic VIG in gt106,000 Dutch troops
    vaccinated with smallpox vaccine reduced
    incidence of PVE from 13 to 3

78
Prognosis
  • Case reports
  • recovery
  • Mild to severe impairment
  • Fatalities
  • ADEM with 15 cases had a 50 recovery rate
  • Pooled summary of case fatality rates (CFR)
  • For every million primary vaccinations
  • 60 cases accidental infection
  • 40 cases of generalized vaccinia
  • 13 cases eczema vaccinatum
  • 3 cases of post-vaccinial encephalitis (CFR
    28.9)
  • 1 case of vaccinia necrosum (CFR 15.4)

79
Current clinical course
  • Patient has no spontaneous extremity movements
  • Patient has opened his eyes, and is moving his
    eyes in response to voice and movement
  • Continue tapering dose of steroids and watch for
    improvement

80
References
  • Aragon et al. Risks of serious complications and
    death from smallpox vaccination A systematic
    review of the United States experience,
    1963-1968. BMC Public Health. Vol.326. 2003
  • Casey et al. Adverse Events Associated with
    Smallpox Vaccination in the United States,
    January-October 2003. JAMA. Vol. 294 (21).
    December 7, 2005.
  • Isascs, S. and Harvey Friedman.Vaccinia Virus as
    the smallpox vaccine. March 16, 2007. UpToDate
    On-Campus Access Only
  • Kretzschmar et al. Frequency of Adverse Events
    after Vaccination with Different Vaccinia
    Strains. PLOS Medicine. Vol 3 8. August 2006.
  • Lofquist et al. Smallpox A review of clinical
    disease and vaccination. American Journal of
    Health-System Pharmacists. Vol. 60. April 15,
    2003.

81
References (contd.)
  • Menge et al. Acute disseminated
    encephalomyelitis an acute hit against the
    brain. Current Opinion in Neurology. Vol. 20 (3),
    247-254. June 2007.
  • Miravalle, A. and Karen Ross. Encephalitis
    Complicating Smallpox Vaccination. Arch Neurol.
    Vol. 60 925-928. July 2003.
  • Sejvar et al. Neurologic Adverse Events
    Associated with Smallpox Vaccination in the
    United States, 2002-2004. JAMA. Vol. 294 21.
    December 7, 2004.
  • Silvergleid, A. General Principles of the use of
    IVIG. January 4, 2007 UpToDate (On-Campus Only
    7/1/2007)
  • Temembaum et al. Acute Disseminated
    Encephalomyeltis. Neurology. Vol. 68 (2). April
    17, 2007

82
References (contd.)
  • CDC Surveillance Guidelines for Smallpox vaccine
    adverse reactions. Vol. 55 (RR01) 1-16. Feb. 3,
    2006.
  • CDC Update Adverse Events Following Civilian
    Smallpox Vaccination--U.S. 2003. Vol. 52 (20)
    475-477. May 23, 2003.
  • CDC Update Smallpox vaccination and adverse
    reactions. Vol, 52 (RR04) 1-28. Feb. 21, 2003.

83
Search PubMed
  • Post-vaccinial encephalitis
  • Case Reports
  • Reviews
  • Differential Diagnosis
  • Drug Therapy
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