- Email: [email protected]
La Crosse Encephalitis: An Adult Case Series
Accepted Manuscript La Crosse Encephalitis: An Adult Case Series Amy Lynn A. Teleron, M.D., Brandon K. Rose, D.O., David M. Williams, M.D., Suzanne E. Kemper, M.P.H., James E. McJunkin, M.D. PII:
S0002-9343(16)30349-7
DOI:
10.1016/j.amjmed.2016.03.021
Reference:
AJM 13466
To appear in:
The American Journal of Medicine
Received Date: 19 November 2015 Revised Date:
4 March 2016
Accepted Date: 4 March 2016
Please cite this article as: Teleron ALA, Rose BK, Williams DM, Kemper SE, McJunkin JE, La Crosse Encephalitis: An Adult Case Series, The American Journal of Medicine (2016), doi: 10.1016/ j.amjmed.2016.03.021. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Adult La Crosse Encephalitis
LA CROSSE ENCEPHALITIS: AN ADULT CASE SERIES Manuscript Type: Brief Observation Author Names Amy Lynn A. Teleron, M.D.a1 – Corresponding and First Author [email protected] Phone: 802-847-7911
SC
Brandon K. Rose, D.O.a, [email protected]
James E. McJunkin, M.D.a [email protected]
M AN U
David M. Williams, M.D.a [email protected] Suzanne E. Kemper, M.P.H.a [email protected]
RI PT
Ref.: Ms. No. 15-1793
EP
TE D
Affiliation Address West Virginia University, Charleston Division Department of Internal Medicine 3110 MacCorkle Avenue SE Charleston, WV 25304 United States
a
Present Address of Corresponding Author University of Vermont Medical Center 111 Colchester Avenue Shephardson 567 Burlington, VT 05401
AC C
1
Conflicts of Interest: None Funding: None Authorship: All authors had access to the data and played a role in writing this manuscript Keywords: La Crosse virus, LACVE, meningoencephalitis, arboviral encephalitis, mosquito
ACCEPTED MANUSCRIPT Adult La Crosse Encephalitis
RI PT
ABSTRACT Background: La Crosse viral encephalitis is well described in children, but to date, there are only two adult cases described in the literature. Despite the fact that pediatric infection can be life-threatening and typically presents as a febrile meningoencephalitis often complicated by seizures and mental status changes, little is known about the presentation and course of adult infection. We report the largest case series of adult La Crosse encephalitis. Methods: Inpatient data was reviewed between 2001- 2012 to identify adults (≥ 18yrs) with possible La Crosse encephalitis. Subsequent review of serologic testing was followed by a comprehensive chart review.
M AN U
SC
Results: Ten cases were identified with ages ranging 20 to 80 years. Fever, headache, and hyponatremia were seen in the majority, while mental status changes occurred in five patients and seizures in two patients. The mean length of stay was 8.4 days (± 8.4), three patients required intensive care unit (ICU) admission, two of whom were intubated, and four patients required discharge to a rehabilitation facility.
BACKGROUND
TE D
Conclusions: La Crosse Virus produces a clinically significant encephalitis in adults, and a high index of suspicion should be maintained, particularly in endemic areas. There were no deaths, but La Crosse encephalitis in adults remained a morbid illness often associated with mental status changes, prolonged length of stay and/or ICU admission, and frequent need for postdischarge rehabilitation.
AC C
EP
La Crosse encephalitis is a vector-borne illness caused by La Crosse Virus, the most pathogenic agent of the California encephalitis serogroup, family Bunyaviridae. Its vector and primary host, Ochlerotatus triseriatus, the Eastern Treehole Mosquito, transmits the virus to humans.1 Although cases have been reported in thirty states, the disease is most prevalent in the midwestern and mid-Atlantic United States, with West Virginia (WV) consistently reported as the most highly endemic state in the U.S.,1-3 Despite adult La Crosse encephalitis being reported to the CDC yearly (most recently, 13 and 9 cases were reported in 2012 and 2013, respectively2,3), there is little clinical description of the disease in adults. Upon our literature review, we found only two such case reports in which both patients presented with fever, headache, and confusion4,5. The first case of a 39 year old immunocompromised renal transplant male had a delayed diagnosis due to presumptive herpes simplex virus encephalitis, with symptoms improving over months.4 The second case was a 43 year old pregnant female, who improved without complications and delivered a healthy baby at term.5 The objective of our study was to retrospectively review adult patients diagnosed with La Crosse encephalitis in order to better describe the presenting signs and symptoms, laboratory and
ACCEPTED MANUSCRIPT Adult La Crosse Encephalitis imaging findings, and hospital course in adults. METHODS
SC
RI PT
Patients A retrospective chart review was conducted to include patients age ≥18 years diagnosed with La Crosse encephalitis at Charleston Area Medical Center (Charleston, WV) between January 1, 2001 and October 31, 2012. Other than age, criteria for inclusion in the study were similar to that used in our previous report of pediatric cases, which included clinical evidence of neuroinvasive disease and appropriate serologic diagnosis by immunofluorescent assay.2 The serologic inclusion criteria were a serum titer of La Crosse Virus IgM antibody via indirect immunofluorescence assay of at least 1:10, or IgG antibody titer of at least 1:160, or both; or an increase in the serum titer of IgM or IgG antibody to La Crosse Virus to at least four times its value at the time of admission.
M AN U
Patient medical records were examined to determine the clinical course of these adults diagnosed with La Crosse Virus. Data collection included signs, symptoms, laboratory values, and imaging at presentation and during hospital course.
RESULTS
TE D
Statistical Analysis We used frequency distributions to describe proportions of categorical variables and means and standard deviations to describe continuous variables. Fisher’s exact test was used for comparative analyses of proportions of symptoms seen in adult La Crosse encephalitis versus pediatric La Cross encephalitis.6
AC C
EP
Patients Ten patients met inclusion criteria. All cases occurred between June and October. The mean age was 52+23 years (mean +SD; range 20 - 80), and the majority of patients were Caucasian (9/10). Six patients had at least one comorbid illness, including hypertension (5/10), diabetes mellitus (3/10), rheumatoid arthritis (1/10), chronic obstructive pulmonary disease (1/10), chronic kidney disease (1/10), heart failure (1/10), and coal workers pneumoconiosis (1/10). Nine patients were current or previous smokers. Except for one patient with rheumatoid arthritis, no other patient had an autoimmune disease or identifiable immune deficiency. Presentation and Hospital Course The most common sign of La Crosse encephalitis infection was fever (9/10), with six patients having had a fever on admission or documented at home, and three developing fever after admission. Other common presentations included headache (7/10), generalized weakness (5/10), and confusion (5/10), while neck stiffness (3/10) and vomiting (2/10) occurred less frequently. Two patients had seizures, one upon presentation and one during admission. (Table 1) Most of the symptoms in adult La Crosse encephalitis were similar in occurrence to that seen in
ACCEPTED MANUSCRIPT Adult La Crosse Encephalitis childhood disease6, with the possible exception of seizure occurrence (20% (2/10) in adults versus 46% (58/127) in children6) and vomiting (20% (2/10) in adults versus 70% (89/127) in children6), but only the latter difference reached statistical significance (p < .05). Hyponatremia was as common in adults (80%) as in children (70%)6.
SC
RI PT
Three patients required ICU admission, two of which were intubated. Six patients received acyclovir as empiric coverage for HSV encephalitis. Seven patients received empiric antibiotics, two of which received empiric corticosteroids. Eight of ten patients underwent lumbar puncture (LP), with six occurring upon presentation in the Emergency Department (ED). Arbovirus panels were not sent initially on any patient, with the latest panel sent on hospital day 14.
M AN U
Average length of hospital stay was 8.4 days (range 2 – 25). Four patients required rehabilitation services after hospitalization. (Table 2)
Laboratory and Imaging Findings Seven patients presented with hyponatremia on admission while one developed it on hospital day two. Seven patients had mild hyponatremia (130-135 mg/dl), and one patient had moderate hyponatremia (nadir 124 mg/dl). (Figure 1) Peripheral leukocytosis of >12,000 wbc/mm3 was present in two patients upon presentation (Table 3).
TE D
Of the eight patients who underwent LP, seven had cerebrospinal fluid white blood cells >10 per mm3 (mean 141, range 9-492) with a lymphocytic predominance. Cerebrospinal fluid protein was elevated in all eight patients, while glucose was not decreased in any (Table 3).
AC C
EP
Six patients had electroencephalography (EEG) with four revealing generalized slowing. Of the patients without generalized slowing, one showed bitemporal slowing, and one was normal. Epileptiform discharges were absent on all EEGs. Brain imaging with computed tomography only revealed chronic findings, ie. atrophy, and magnetic resonance imaging did not show any acute changes. Focal cortical inflammation or cerebral edema was not seen.
DISCUSSION
This is the first reported series of adults diagnosed with La Crosse encephalitis. Our results suggest that La Crosse encephalitis in adults is not a benign disease. In order to recognize patients with this infection, we must consider the diagnosis in the early summer to fall months in patients presenting with a febrile meningoencephalitis picture, particularly in endemic regions or following travel to those regions. It is also possible that milder forms of the disease are occurring but are not being recognized. Hyponatremia notably occurred in the majority (80%) of infected adults just as it does in children, and mental status changes were common (50%) in adults as well, whereas vomiting
ACCEPTED MANUSCRIPT Adult La Crosse Encephalitis and seizures were rarely seen in adults as opposed to children. On brain imaging, there was no focal cortical inflammation, cerebral edema, or epileptiform discharges as described in the pediatric population.2
SC
RI PT
The diagnosis remains challenging because cerebrospinal fluid viral culture is usually negative, and diagnostic capabilities via La Crosse viral RNA detection in cerebrospinal fluid remain experimental.1 In endemic areas where rapid diagnostic testing can be justified, serologic testing with attention to acute rise in La Crosse virus IgM can provide an early presumptive diagnosis. Convalescent titers are recommended at 1-2 weeks with detection of a four-fold rise as the gold standard of diagnosis. In non-endemic areas where rapid serologic testing is not available, serum and cerebrospinal fluid can be sent to the CDC for diagnostic testing. Whatever the diagnostic test used, the physician must consider alternative diagnoses during the acute illness, particlularly HSV encephalitis, which would call for empiric acyclovir until it is ruled out.
TE D
M AN U
Given the absence of specific antiviral therapy for La Crosse encephalitis, supportive management remains the mainstay of therapy. Intravenous ribavirin has been examined as a potential antiviral therapy in a small study in pediatric disease, but it failed to reach effective levels in cerebrospinal fluid before adverse events occurred. 7 In the hospitalized pediatric population, risk factors for clinical deterioration included mental status changes and vomiting.6 Of these factors, mental status changes occurred frequently in adult disease (50%), and therefore may prove to also be a reasonable marker for ICU admission in adults. The current study also indicates that hyponatremia, which appears to be associated with in-hospital deterioration in children6, occurs in the majority of adults (80%) with La Crosse encephalitis.
EP
Increased consideration of La Crosse encephalitis in adults may lead to a more timely diagnosis, which is worthwhile because the disease requires careful attention to supportive management during hospitalization and because it is associated with considerable morbidity as judged by the severity of illness and the need for long-term services after discharge.
AC C
Acknowledgements We are indebted to Linda Minnich, S.M. for her La Crosse viral encephalitis diagnostic proficiency and consultation and Douglas Haden, M.D. for his clinical expertise and project support.
REFERENCES
1. Hunt, WG, McJunkin, JE. La Crosse Encephalitis and Other California Serogroup Viruses. In: Feigin and Cherry Textbook of Pediatric Infectious Diseases. 7th ed. Philadelphia: Elsevier; 2014: 2513-2537. 2. Centers for Disease Control and Prevention. West Nile virus and other arboviral diseases-United States, 2012. MMWR 2013;62:513-7. 3. Lindsey, NP, Lehman JA, Staples JE et al. West nile virus and other arboviral diseases - United States, 2013. MMWR 2014;63:521-6.
ACCEPTED MANUSCRIPT Adult La Crosse Encephalitis
AC C
EP
TE D
M AN U
SC
RI PT
4. Wurtz R, Paleologos N. La Crosse encephalitis presenting like herpes simplex encephalitis in an immunocompromised adult. Clin Infect Dis. 2000; 4:1113-4. 5. Centers for Disease Control and Prevention. Possible congenital infection with La Crosse encephalitis virus--West Virginia, 2006-2007. MMWR 2009;58:4-7. 6. McJunkin, JE, De Los Reyes EC, Irazuzta, JE et al. La Crosse Encephalitis in Children. NEJM 2001; 344:801-80. 7. McJunkin JE, Nahata MC, De Los Reyes EC, et al. Safety and pharmacokinetics of ribavirin for the treatment of la crosse encephalitis. Pediatr Infect Dis J 2011; Oct 30: 860-5.
ACCEPTED MANUSCRIPT
Table 1: Characteristics of Adult Patients with La Crosse Encephalitis (n=10)
4 (40)
RI PT
Male Female
6 (60)
Age (years + SD)
52 + 23
Prior visits to ED within 30 days
5 (50)
SC
Month of Presentation June August September October Symptoms on presentation Fever at home or on admission Headache
Diarrhea Weakness Photophobia
TE D
Nausea/Vomiting
M AN U
July
Neck Stiffness
EP
Confusion/Disorientation Seizures
n (%) Mean + SD
AC C
SD = standard deviation, ED = Emergency Department
1 (10) 3 (30) 3 (30) 2 (20) 1 (10) 6 (60) 7 (70) 3 (30) 3 (30) 0 (0) 5 (50) 3 (30) 5 (50) 1 (10)
ACCEPTED MANUSCRIPT
Table 2: Outcomes of Adult Patients with La Crosse Encephalitis (n=10)
n (%) Mean + SD
Hospital length of stay (days)
8.4 + 8.4
Rehabilitation*
4(40) 2 (20)
RI PT
Home Health Physical Therapy
1 (10)
Skilled Nursing Facility
2 (20)
AC C
EP
TE D
M AN U
SC
SD = standard deviation
ACCEPTED MANUSCRIPT
Table 3: Laboratory Values at Admission of Adults with La Crosse Encephalitis (n=10) 3
Leukocytosis (>12,000 wbc/mm )
N/total (%)
Mean Value ± SD
2/10 (40)
9.9 ± 3.1
Cerebrospinal fluid Elevated leukocytes (≥10 wbc/mm3)
7/8 (87.5)
3
Elevated red cells (≥25 rbc/mm )
1/8 (12.5)
Decreased glucose (≤40 mg/dl)
8/8 (100)
19.1 ± 43.7
64.5 ± 26.4
AC C
EP
TE D
M AN U
SC
SD = standard deviation
140.6 ± 209.5 63.6 ± 12.0
0/8 (0)
Elevated protein (≥45 mg/dl)
RI PT
Peripheral blood
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT
LA CROSSE ENCEPHALITIS: AN ADULT CASE SERIES Teleron AA, Rose BK, Williams DM, Kemper SE, McJunkin JE Manuscript Type: Brief Observation
RI PT
Ref.: Ms. No. 15-1793 HIGHLIGHTS
Like children, adults can suffer a clinically significant encephalitis caused by La Crosse virus
-
Adults most commonly present with fever, headache, and hyponatremia and can have resultant considerable morbidity
-
La Crosse encephalitis may be responsible for idiopathic cases of encephalitis during summer and fall months and must be considered, especially in or upon return from endemic areas
AC C
EP
TE D
M AN U
SC
-
S0002-9343(16)30349-7
DOI:
10.1016/j.amjmed.2016.03.021
Reference:
AJM 13466
To appear in:
The American Journal of Medicine
Received Date: 19 November 2015 Revised Date:
4 March 2016
Accepted Date: 4 March 2016
Please cite this article as: Teleron ALA, Rose BK, Williams DM, Kemper SE, McJunkin JE, La Crosse Encephalitis: An Adult Case Series, The American Journal of Medicine (2016), doi: 10.1016/ j.amjmed.2016.03.021. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Adult La Crosse Encephalitis
LA CROSSE ENCEPHALITIS: AN ADULT CASE SERIES Manuscript Type: Brief Observation Author Names Amy Lynn A. Teleron, M.D.a1 – Corresponding and First Author [email protected] Phone: 802-847-7911
SC
Brandon K. Rose, D.O.a, [email protected]
James E. McJunkin, M.D.a [email protected]
M AN U
David M. Williams, M.D.a [email protected] Suzanne E. Kemper, M.P.H.a [email protected]
RI PT
Ref.: Ms. No. 15-1793
EP
TE D
Affiliation Address West Virginia University, Charleston Division Department of Internal Medicine 3110 MacCorkle Avenue SE Charleston, WV 25304 United States
a
Present Address of Corresponding Author University of Vermont Medical Center 111 Colchester Avenue Shephardson 567 Burlington, VT 05401
AC C
1
Conflicts of Interest: None Funding: None Authorship: All authors had access to the data and played a role in writing this manuscript Keywords: La Crosse virus, LACVE, meningoencephalitis, arboviral encephalitis, mosquito
ACCEPTED MANUSCRIPT Adult La Crosse Encephalitis
RI PT
ABSTRACT Background: La Crosse viral encephalitis is well described in children, but to date, there are only two adult cases described in the literature. Despite the fact that pediatric infection can be life-threatening and typically presents as a febrile meningoencephalitis often complicated by seizures and mental status changes, little is known about the presentation and course of adult infection. We report the largest case series of adult La Crosse encephalitis. Methods: Inpatient data was reviewed between 2001- 2012 to identify adults (≥ 18yrs) with possible La Crosse encephalitis. Subsequent review of serologic testing was followed by a comprehensive chart review.
M AN U
SC
Results: Ten cases were identified with ages ranging 20 to 80 years. Fever, headache, and hyponatremia were seen in the majority, while mental status changes occurred in five patients and seizures in two patients. The mean length of stay was 8.4 days (± 8.4), three patients required intensive care unit (ICU) admission, two of whom were intubated, and four patients required discharge to a rehabilitation facility.
BACKGROUND
TE D
Conclusions: La Crosse Virus produces a clinically significant encephalitis in adults, and a high index of suspicion should be maintained, particularly in endemic areas. There were no deaths, but La Crosse encephalitis in adults remained a morbid illness often associated with mental status changes, prolonged length of stay and/or ICU admission, and frequent need for postdischarge rehabilitation.
AC C
EP
La Crosse encephalitis is a vector-borne illness caused by La Crosse Virus, the most pathogenic agent of the California encephalitis serogroup, family Bunyaviridae. Its vector and primary host, Ochlerotatus triseriatus, the Eastern Treehole Mosquito, transmits the virus to humans.1 Although cases have been reported in thirty states, the disease is most prevalent in the midwestern and mid-Atlantic United States, with West Virginia (WV) consistently reported as the most highly endemic state in the U.S.,1-3 Despite adult La Crosse encephalitis being reported to the CDC yearly (most recently, 13 and 9 cases were reported in 2012 and 2013, respectively2,3), there is little clinical description of the disease in adults. Upon our literature review, we found only two such case reports in which both patients presented with fever, headache, and confusion4,5. The first case of a 39 year old immunocompromised renal transplant male had a delayed diagnosis due to presumptive herpes simplex virus encephalitis, with symptoms improving over months.4 The second case was a 43 year old pregnant female, who improved without complications and delivered a healthy baby at term.5 The objective of our study was to retrospectively review adult patients diagnosed with La Crosse encephalitis in order to better describe the presenting signs and symptoms, laboratory and
ACCEPTED MANUSCRIPT Adult La Crosse Encephalitis imaging findings, and hospital course in adults. METHODS
SC
RI PT
Patients A retrospective chart review was conducted to include patients age ≥18 years diagnosed with La Crosse encephalitis at Charleston Area Medical Center (Charleston, WV) between January 1, 2001 and October 31, 2012. Other than age, criteria for inclusion in the study were similar to that used in our previous report of pediatric cases, which included clinical evidence of neuroinvasive disease and appropriate serologic diagnosis by immunofluorescent assay.2 The serologic inclusion criteria were a serum titer of La Crosse Virus IgM antibody via indirect immunofluorescence assay of at least 1:10, or IgG antibody titer of at least 1:160, or both; or an increase in the serum titer of IgM or IgG antibody to La Crosse Virus to at least four times its value at the time of admission.
M AN U
Patient medical records were examined to determine the clinical course of these adults diagnosed with La Crosse Virus. Data collection included signs, symptoms, laboratory values, and imaging at presentation and during hospital course.
RESULTS
TE D
Statistical Analysis We used frequency distributions to describe proportions of categorical variables and means and standard deviations to describe continuous variables. Fisher’s exact test was used for comparative analyses of proportions of symptoms seen in adult La Crosse encephalitis versus pediatric La Cross encephalitis.6
AC C
EP
Patients Ten patients met inclusion criteria. All cases occurred between June and October. The mean age was 52+23 years (mean +SD; range 20 - 80), and the majority of patients were Caucasian (9/10). Six patients had at least one comorbid illness, including hypertension (5/10), diabetes mellitus (3/10), rheumatoid arthritis (1/10), chronic obstructive pulmonary disease (1/10), chronic kidney disease (1/10), heart failure (1/10), and coal workers pneumoconiosis (1/10). Nine patients were current or previous smokers. Except for one patient with rheumatoid arthritis, no other patient had an autoimmune disease or identifiable immune deficiency. Presentation and Hospital Course The most common sign of La Crosse encephalitis infection was fever (9/10), with six patients having had a fever on admission or documented at home, and three developing fever after admission. Other common presentations included headache (7/10), generalized weakness (5/10), and confusion (5/10), while neck stiffness (3/10) and vomiting (2/10) occurred less frequently. Two patients had seizures, one upon presentation and one during admission. (Table 1) Most of the symptoms in adult La Crosse encephalitis were similar in occurrence to that seen in
ACCEPTED MANUSCRIPT Adult La Crosse Encephalitis childhood disease6, with the possible exception of seizure occurrence (20% (2/10) in adults versus 46% (58/127) in children6) and vomiting (20% (2/10) in adults versus 70% (89/127) in children6), but only the latter difference reached statistical significance (p < .05). Hyponatremia was as common in adults (80%) as in children (70%)6.
SC
RI PT
Three patients required ICU admission, two of which were intubated. Six patients received acyclovir as empiric coverage for HSV encephalitis. Seven patients received empiric antibiotics, two of which received empiric corticosteroids. Eight of ten patients underwent lumbar puncture (LP), with six occurring upon presentation in the Emergency Department (ED). Arbovirus panels were not sent initially on any patient, with the latest panel sent on hospital day 14.
M AN U
Average length of hospital stay was 8.4 days (range 2 – 25). Four patients required rehabilitation services after hospitalization. (Table 2)
Laboratory and Imaging Findings Seven patients presented with hyponatremia on admission while one developed it on hospital day two. Seven patients had mild hyponatremia (130-135 mg/dl), and one patient had moderate hyponatremia (nadir 124 mg/dl). (Figure 1) Peripheral leukocytosis of >12,000 wbc/mm3 was present in two patients upon presentation (Table 3).
TE D
Of the eight patients who underwent LP, seven had cerebrospinal fluid white blood cells >10 per mm3 (mean 141, range 9-492) with a lymphocytic predominance. Cerebrospinal fluid protein was elevated in all eight patients, while glucose was not decreased in any (Table 3).
AC C
EP
Six patients had electroencephalography (EEG) with four revealing generalized slowing. Of the patients without generalized slowing, one showed bitemporal slowing, and one was normal. Epileptiform discharges were absent on all EEGs. Brain imaging with computed tomography only revealed chronic findings, ie. atrophy, and magnetic resonance imaging did not show any acute changes. Focal cortical inflammation or cerebral edema was not seen.
DISCUSSION
This is the first reported series of adults diagnosed with La Crosse encephalitis. Our results suggest that La Crosse encephalitis in adults is not a benign disease. In order to recognize patients with this infection, we must consider the diagnosis in the early summer to fall months in patients presenting with a febrile meningoencephalitis picture, particularly in endemic regions or following travel to those regions. It is also possible that milder forms of the disease are occurring but are not being recognized. Hyponatremia notably occurred in the majority (80%) of infected adults just as it does in children, and mental status changes were common (50%) in adults as well, whereas vomiting
ACCEPTED MANUSCRIPT Adult La Crosse Encephalitis and seizures were rarely seen in adults as opposed to children. On brain imaging, there was no focal cortical inflammation, cerebral edema, or epileptiform discharges as described in the pediatric population.2
SC
RI PT
The diagnosis remains challenging because cerebrospinal fluid viral culture is usually negative, and diagnostic capabilities via La Crosse viral RNA detection in cerebrospinal fluid remain experimental.1 In endemic areas where rapid diagnostic testing can be justified, serologic testing with attention to acute rise in La Crosse virus IgM can provide an early presumptive diagnosis. Convalescent titers are recommended at 1-2 weeks with detection of a four-fold rise as the gold standard of diagnosis. In non-endemic areas where rapid serologic testing is not available, serum and cerebrospinal fluid can be sent to the CDC for diagnostic testing. Whatever the diagnostic test used, the physician must consider alternative diagnoses during the acute illness, particlularly HSV encephalitis, which would call for empiric acyclovir until it is ruled out.
TE D
M AN U
Given the absence of specific antiviral therapy for La Crosse encephalitis, supportive management remains the mainstay of therapy. Intravenous ribavirin has been examined as a potential antiviral therapy in a small study in pediatric disease, but it failed to reach effective levels in cerebrospinal fluid before adverse events occurred. 7 In the hospitalized pediatric population, risk factors for clinical deterioration included mental status changes and vomiting.6 Of these factors, mental status changes occurred frequently in adult disease (50%), and therefore may prove to also be a reasonable marker for ICU admission in adults. The current study also indicates that hyponatremia, which appears to be associated with in-hospital deterioration in children6, occurs in the majority of adults (80%) with La Crosse encephalitis.
EP
Increased consideration of La Crosse encephalitis in adults may lead to a more timely diagnosis, which is worthwhile because the disease requires careful attention to supportive management during hospitalization and because it is associated with considerable morbidity as judged by the severity of illness and the need for long-term services after discharge.
AC C
Acknowledgements We are indebted to Linda Minnich, S.M. for her La Crosse viral encephalitis diagnostic proficiency and consultation and Douglas Haden, M.D. for his clinical expertise and project support.
REFERENCES
1. Hunt, WG, McJunkin, JE. La Crosse Encephalitis and Other California Serogroup Viruses. In: Feigin and Cherry Textbook of Pediatric Infectious Diseases. 7th ed. Philadelphia: Elsevier; 2014: 2513-2537. 2. Centers for Disease Control and Prevention. West Nile virus and other arboviral diseases-United States, 2012. MMWR 2013;62:513-7. 3. Lindsey, NP, Lehman JA, Staples JE et al. West nile virus and other arboviral diseases - United States, 2013. MMWR 2014;63:521-6.
ACCEPTED MANUSCRIPT Adult La Crosse Encephalitis
AC C
EP
TE D
M AN U
SC
RI PT
4. Wurtz R, Paleologos N. La Crosse encephalitis presenting like herpes simplex encephalitis in an immunocompromised adult. Clin Infect Dis. 2000; 4:1113-4. 5. Centers for Disease Control and Prevention. Possible congenital infection with La Crosse encephalitis virus--West Virginia, 2006-2007. MMWR 2009;58:4-7. 6. McJunkin, JE, De Los Reyes EC, Irazuzta, JE et al. La Crosse Encephalitis in Children. NEJM 2001; 344:801-80. 7. McJunkin JE, Nahata MC, De Los Reyes EC, et al. Safety and pharmacokinetics of ribavirin for the treatment of la crosse encephalitis. Pediatr Infect Dis J 2011; Oct 30: 860-5.
ACCEPTED MANUSCRIPT
Table 1: Characteristics of Adult Patients with La Crosse Encephalitis (n=10)
4 (40)
RI PT
Male Female
6 (60)
Age (years + SD)
52 + 23
Prior visits to ED within 30 days
5 (50)
SC
Month of Presentation June August September October Symptoms on presentation Fever at home or on admission Headache
Diarrhea Weakness Photophobia
TE D
Nausea/Vomiting
M AN U
July
Neck Stiffness
EP
Confusion/Disorientation Seizures
n (%) Mean + SD
AC C
SD = standard deviation, ED = Emergency Department
1 (10) 3 (30) 3 (30) 2 (20) 1 (10) 6 (60) 7 (70) 3 (30) 3 (30) 0 (0) 5 (50) 3 (30) 5 (50) 1 (10)
ACCEPTED MANUSCRIPT
Table 2: Outcomes of Adult Patients with La Crosse Encephalitis (n=10)
n (%) Mean + SD
Hospital length of stay (days)
8.4 + 8.4
Rehabilitation*
4(40) 2 (20)
RI PT
Home Health Physical Therapy
1 (10)
Skilled Nursing Facility
2 (20)
AC C
EP
TE D
M AN U
SC
SD = standard deviation
ACCEPTED MANUSCRIPT
Table 3: Laboratory Values at Admission of Adults with La Crosse Encephalitis (n=10) 3
Leukocytosis (>12,000 wbc/mm )
N/total (%)
Mean Value ± SD
2/10 (40)
9.9 ± 3.1
Cerebrospinal fluid Elevated leukocytes (≥10 wbc/mm3)
7/8 (87.5)
3
Elevated red cells (≥25 rbc/mm )
1/8 (12.5)
Decreased glucose (≤40 mg/dl)
8/8 (100)
19.1 ± 43.7
64.5 ± 26.4
AC C
EP
TE D
M AN U
SC
SD = standard deviation
140.6 ± 209.5 63.6 ± 12.0
0/8 (0)
Elevated protein (≥45 mg/dl)
RI PT
Peripheral blood
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT
LA CROSSE ENCEPHALITIS: AN ADULT CASE SERIES Teleron AA, Rose BK, Williams DM, Kemper SE, McJunkin JE Manuscript Type: Brief Observation
RI PT
Ref.: Ms. No. 15-1793 HIGHLIGHTS
Like children, adults can suffer a clinically significant encephalitis caused by La Crosse virus
-
Adults most commonly present with fever, headache, and hyponatremia and can have resultant considerable morbidity
-
La Crosse encephalitis may be responsible for idiopathic cases of encephalitis during summer and fall months and must be considered, especially in or upon return from endemic areas
AC C
EP
TE D
M AN U
SC
-