Original Article
Clinical and Neuroradiographic Manifestations of Eastern Equine Encephalitis
N Engl J Med 1997; 336:1867-1874June 26, 1997
- Abstract
Background
Eastern equine encephalitis occurs principally along the east and Gulf coasts of the United States. Recognition of the neuroradiographic manifestations of eastern equine encephalitis could hasten the diagnosis of the illness and speed the response to index cases.
Methods
We reviewed all cases of eastern equine encephalitis reported in the United States between 1988 and 1994. The records of 36 patients were studied, along with 57 computed tomographic (CT) scans and 23 magnetic resonance imaging (MRI) scans from 33 patients.
Results
The mortality rate was 36 percent, and 35 percent of the survivors were moderately or severely disabled. Neuroradiographic abnormalities were common and best visualized by MRI. Among the patients for whom MRI scans were available, the results were abnormal for all eight comatose patients as well as for all three noncomatose patients who subsequently became comatose. The CT results were abnormal in 21 of 32 patients with readable scans. The abnormal findings included focal lesions in the basal ganglia (found in 71 percent of patients on MRI and in 56 percent on CT), thalami (found in 71 percent on MRI and in 25 percent on CT), and brain stem (found in 43 percent on MRI and in 9 percent on CT). Cortical lesions, meningeal enhancement, and periventricular white-matter changes were less common. The presence of large radiographic lesions did not predict a poor outcome, but either high cerebrospinal fluid white-cell counts or severe hyponatremia did.
Conclusions
Eastern equine encephalitis produces focal radiographic signs. The characteristic early involvement of the basal ganglia and thalami distinguishes this illness from herpes simplex encephalitis. MRI is a sensitive technique to identify the characteristic early radiographic manifestations of this viral encephalitis.
Media in This Article
Figure 2
Periventricular White-Matter Lesions in a 33-Year-Old Woman Who Contracted Eastern Equine Encephalitis during Her Seventh Month of Pregnancy.Figure 1
Lesions of the Basal Ganglia and Cortex in a 14-Year-Old Boy Who Died of Eastern Equine Encephalitis.Article Activity
- Article
Eastern equine encephalitis is a life-threatening mosquito-borne arboviral infection found principally along the east and Gulf coasts of the United States.1 It was first recognized in humans in 1938.2-4 Cases have occurred sporadically and in small epidemics: 223 cases were reported to the Centers for Disease Control and Prevention (CDC) between 1955 and 1993,5,6 including a peak of 36 in 1959.7 About one third of those affected die of the infection.
Diagnosing eastern equine encephalitis is difficult because its symptoms are nonspecific and confirmation requires either specific serologic findings or the demonstration of the virus in cerebrospinal fluid or brain tissue.1 Since cranial computed tomographic (CT) scans or magnetic resonance imaging (MRI) scans are obtained for most patients with encephalitis, the identification of neuroradiographic findings suggestive of eastern equine encephalitis could hasten its recognition. Although no specific treatment is available, rapid diagnosis is important for the institution of public health controls.8
Little is known about the neuroradiographic manifestations of eastern equine encephalitis. Cranial CT findings have been reported in 16 patients.6,9-14 Most were studied with early-generation scanners, and the results were considered either normal or indicative of cerebral edema. Two of the 16 patients had frontal lesions; 2 others had abnormalities of the thalami and basal ganglia. In two of these four patients, MRI confirmed the CT findings.6,14
To define the neuroradiographic manifestations of eastern equine encephalitis more clearly, we collected clinical and radiographic data on all 38 cases reported in the United States between 1988 and 1994.
Methods
Identification of Cases
The CDC identified states reporting cases between 1988 and 1994. Reporting physicians or institutions either obtained informed consent for the release of records or provided confidential copies of records after removing any identifying information. The information available on each patient included a comprehensive clinical narrative, laboratory data at admission, specific documentation of the means by which eastern equine encephalitis was diagnosed, and if available, copies of the neuroradiographic studies.
Putative cases were assigned to one of three diagnostic categories according to the CDC criteria.15 A confirmed case was one in which the IgM capture enzyme immunoassay of cerebrospinal fluid was positive, there was a fourfold rise in the titer of serum antibody against eastern equine encephalitis virus, or eastern equine encephalitis virus was isolated from cerebrospinal fluid or brain tissue. A probable case was one in which serum IgM capture enzyme immunoassay was positive or there was a single serum hemagglutination–inhibition titer of at least 1:320, a complement-fixation titer of at least 1:128, an immunofluorescence titer of at least 1:256, or a neutralization titer of at least 1:160. All other cases were considered unconfirmed.
This study was approved by the human research committee of Brigham and Women's Hospital. When requested, approval was also obtained from state or local research committees.
Abstraction of Clinical Data
The charts of all patients were reviewed independently by two clinicians, who abstracted the data. The prodrome was defined as the period between the onset of symptoms that were reasonably attributable to eastern equine encephalitis and the first major neurologic manifestation (altered mental status, seizure, hemiparesis, or severe headache and a temperature of at least 103°F). The severity of clinical sequelae was classified according to the patient's functional status on discharge from an acute care facility: a designation of normal indicated that no deficits remained; a designation of mild sequelae indicated that self-care was possible outside an institutional setting; a designation of moderate sequelae indicated that institutional care was required to manage the activities of daily living; a designation of severe sequelae indicated that the patient was in a permanent vegetative state; and a designation of death indicated that the patient had died before discharge.
Interpretation of Radiographic Films
The radiographic films were assessed independently by two neuroradiologists. One was unaware of the study's objectives, and both were unaware of the patients' histories. Differences in interpretation were resolved by consensus. The quality of the films was assessed subjectively. Poor-quality films were not analyzed. Radiographically evident lesions were scored as follows: 1+, less than 1 cm in diameter; 2+, 1 to 2.5 cm in diameter; and 3+, more than 2.5 cm in diameter.
Statistical Analysis
Univariate analyses were performed to correlate specific clinical or laboratory findings with the outcome. For contingency tables, Fisher's exact test was used. For unpaired nonparametric data, the Mann–Whitney rank-sum test was used. Two-tailed P values were calculated, and all values below 0.05 were considered to indicate statistical significance.
Results
Identification of Cases
Records were obtained for 38 patients with putative cases of eastern equine encephalitis, including all 36 reported to the CDC during the study years. Two cases did not meet diagnostic criteria and were eliminated. Of the remainder, 26 were defined as confirmed and 10 as probable. Three have been described in detail previously,6,14,16 and nine others briefly.17
Demographic and Epidemiologic Characteristics
Cases were recognized in 11 states. Twenty-five of the 36 patients were male, and 29 were white. The median age was 59 years (range, 6 months to 85 years). Seven patients were under 20 years of age. None were seriously impaired before their illness.
Clinical and Laboratory Characteristics
Thirteen of the 36 patients died (36 percent). Of the survivors, 1 recovered fully, 14 had mild impairments, 3 had moderate impairments, and 5 had severe impairments. The median duration of acute care hospitalization was 18 days (range, <1 to 89). Among the patients who died, the median duration of hospitalization was 16 days. Only three patients died during the first week of hospitalization.
For most patients, the illness began with a short prodrome (median, 5.0 days; range, 0 to 28), typically mimicking a benign viral illness; fever, headache, and abdominal distress were common (Table 1Table 1
Prevalence of Clinical Signs, Symptoms, and Laboratory Abnormalities on Hospitalization among 36 Patients with Eastern Equine Encephalitis.). Two patients were admitted during the prodromal period for presumptive abdominal emergencies. Neurologic symptoms (confusion, somnolence, focal weakness, seizures, and meningeal signs) prompted evaluation in all others. Once the neurologic symptoms began, the condition of the patients deteriorated rapidly. Four were stuporous or comatose when first evaluated; 21 others (for a total of 69 percent) became stuporous within two days after admission. In all, 32 of the 36 patients (89 percent) eventually became stuporous or comatose. The median (±SD) duration of coma in patients with a favorable outcome (no, mild, or moderate sequelae) was 5±4.7 days. One patient recovered with mild sequelae after nine days of coma.Seizures occurred in 18 patients: 15 had generalized seizures (tonic–clonic in most, and twitching in 2), 3 had focal events (1 of whom also had a generalized seizure), and 1 had partial complex seizures. Focal weakness, ranging from subtle to severe, occurred in 16 patients. Paresthesias accompanied paresis in one patient. Cranial-nerve palsies developed in nine patients (cranial nerve VII was affected in five, cranial nerve XII was affected in one, and five had oculomotor phenomena). The course in one patient was indistinguishable from that of aseptic meningitis.
Leukocytosis and hyponatremia were common (Table 1). At the time of admission, the median white-cell count was 14,500 cells per cubic millimeter (range, 3800 to 23,900), and the median serum sodium concentration was 134 mmol per liter (range, 123 to 146). Thirty-four patients (94 percent) had at least one lumbar puncture. The median initial cerebrospinal fluid white-cell count was 370 cells per cubic millimeter (range, 0 to 2400; median of 70 percent neutrophils), and the median protein concentration was 97 mg per deciliter (range, 31 to 297). Hypoglycorrhachia was typically absent.
Electroencephalographic results were available for 24 patients. All showed generalized slowing and disorganization of the background initially. Epileptiform discharges were noted in six patients, including four who had periodic lateralizing epileptiform discharges. No correlations could be drawn between specific clinical events and electroencephalographic patterns.
Neuroradiologic Findings
Thirty-five of the 36 patients underwent CT scanning at least once. We obtained 57 of the 76 scans that were performed and at least 1 study from 33 of the 35 patients who underwent CT (94 percent). Sixteen patients underwent MRI at least once. We obtained 23 of the 25 MRIs that were performed and at least 1 set from 15 of the 16 patients who had MRI (94 percent). One CT scan and one MRI were of poor quality and were not analyzed. Overall, we reviewed at least one CT scan from 89 percent of the patients and at least one MRI from 39 percent (Table 2Table 2
Results of Neuroradiographic Studies in 32 Patients with Eastern Equine Encephalitis.).The interval between the onset of neurologic symptoms and the initial radiographic study that we reviewed ranged from 1 to 14 days (median, 2). In all but one patient, CT was the initial study performed. In general, the CT and MRI findings were similar, but MRI was more sensitive.
MRI Findings
For 13 of the 14 patients included in this analysis, every MRI (21 studies altogether) revealed abnormalities. Five patients first underwent MRI within three days after the onset of neurologic symptoms; the results of all five scans were abnormal. In three of the five, the abnormal results preceded the onset of coma. Lesions were best seen on T2-weighted images, appearing as areas of increased signal intensity. Larger lesions were also visible on unenhanced T1-weighted images. The basal ganglia and thalami were most commonly involved. Noncontiguous abnormalities were also seen in the brain stem, cortex, and periventricular white matter. With the exception of white-matter changes, all abnormalities were evident early in the course of illness and diminished with clinical improvement.
Lesions of the basal ganglia ranged in size from 2+ to 3+, were either unilateral or asymmetric, and sometimes involved the adjacent internal capsule (Figure 1AFigure 1
Lesions of the Basal Ganglia and Cortex in a 14-Year-Old Boy Who Died of Eastern Equine Encephalitis.). Large lesions were associated with a mass effect. Thalamic and brain-stem lesions were smaller and either unilateral or asymmetric. The midbrain was the portion of the brain stem most often involved. Cortical lesions varied in location: in three cases they were in the temporal lobe, in two cases they were in the insula, and in one case each they were in the frontal lobe and cingulum (Figure 1C).Two young, previously healthy women had periventricular white-matter changes. In each, MRI revealing these abnormalities was performed well after the onset of neurologic disease (12 and 19 days later). The first woman had patchy abnormalities of the posterior periventricular white matter; the second had punctate lesions adjacent to the lateral ventricles that were reminiscent of those seen in multiple sclerosis (Figure 2Figure 2
Periventricular White-Matter Lesions in a 33-Year-Old Woman Who Contracted Eastern Equine Encephalitis during Her Seventh Month of Pregnancy.).Imaging with contrast medium was attempted in nine patients with abnormal imaging results. Definite enhancement was seen in five patients, and equivocal enhancement in one. When present, enhancement was confined to areas of abnormal T2-weighted signal.
A single patient in this series had no abnormalities on MRI scanning. His examination was performed 12 days after the onset of neurologic symptoms and 4 days after the resolution of coma.
CT Findings
Of the 32 patients whose scans were analyzed, 21 (66 percent) had abnormal findings at some point in their illness. Abnormalities were detected in 2 of 8 patients who underwent scanning after the onset of neurologic symptoms but before the onset of coma and in 9 of 15 others who underwent scanning at the onset of coma. Two of four patients who never became comatose also had abnormal results. Only 3 of 15 patients studied after the first day of the coma, but while still comatose, had normal results. In 11 patients, no specific abnormalities were seen.
As with MRI, lesions of the basal ganglia were the most common finding on CT scanning (Table 2). The putamen and the caudate head were particularly likely to be involved (Figure 1B). The lesions ranged from subtle to obvious. Intermediate or large lesions were common, the latter associated with a mass effect. In patients with subtle findings, serial studies often showed evolution of the lesions (Figure 3AFigure 3
The Evolution of Subtle Changes on CT and MRI Scanning in a 14-Year-Old Boy Who Survived Eastern Equine Encephalitis with Mild Sequelae. and Figure 3B). Thalamic and midbrain lesions were 1+ to 2+ in size. In all patients for whom both CT and MRI results were available, MRI was more sensitive, revealing more abnormalities and better detail (Figure 3C).Meningeal enhancement was unequivocally detected in two patients. In one, the appearance of the suprasellar cistern and the intensity of enhancement after the administration of contrast medium suggested the presence of subarachnoid hemorrhage or meningitis.
Characterization of Prognostic Factors
To identify prognostically important variables, we correlated the presence or absence of certain features with the outcome. Information on all features was not available for every patient. Sequelae were categorized in each of two ways: survival as opposed to death, and a favorable outcome (no, mild, or moderate sequelae) as opposed to an unfavorable outcome (severe sequelae or death). The prognostically important variables that were identified by the two categorization schemes were concordant.
Neither the age of the patient nor the duration of the prodrome was a statistically significant predictor of outcome, although patients with favorable outcomes tended to be younger and to have longer prodromes. No clinical variables correlated with outcome, including the temperature at admission or the presence of neck stiffness, seizures, focal weakness, or a plantar reflex.
Two laboratory variables did predict outcome: the initial white-cell count in cerebrospinal fluid and the severity of hyponatremia during hospitalization. Ten of 13 patients with initial cerebrospinal fluid white-cell counts of at least 500 cells per cubic millimeter had unfavorable outcomes, as compared with 6 of 21 with counts below 500 cells per cubic millimeter (P = 0.01; relative risk, 2.7; 95 percent confidence interval, 1.3 to 5.6). Similarly, 12 of 14 patients whose lowest serum sodium concentration was <130 mmol per liter had an unfavorable outcome, as compared with 4 of 16 whose lowest value exceeded 130 mmol per liter (P<0.01; relative risk, 3.4; 95 percent confidence interval, 1.4 to 8.2).
We could not correlate the severity of neuroradiographic lesions with outcome, although our attempt was undoubtedly confounded by uneven film quality and the disparate times of the radiographic studies during each patient's course. All three patients whose CT scans showed no abnormalities on day 2 of coma or beyond had favorable outcomes. We could not correlate the severity of lesions with any clinical variables. Patients with larger lesions tended to be older and to have higher cerebrospinal fluid white-cell counts than those with smaller lesions, but the differences were not significant.
Eight of 21 patients treated with anticonvulsants did well, as compared with 9 of 13 who were not treated with anticonvulsants (P = 0.16). Three of 12 patients who were given corticosteroids for cerebral edema did well, as compared with 13 of 20 who were not given corticosteroids (P = 0.07).
Discussion
We studied all cases of eastern equine encephalitis that were reported in the United States from 1988 through 1994, making this the largest case series since 1957.19 Radiographically, eastern equine encephalitis is a focal disease, with a predilection for early involvement of the basal ganglia, thalami, and brain stem. The prevailing view of the radiographic manifestations of the disease was shaped by just 14 cases studied with older-generation CT scanners.1,13 Accordingly, the prevalence of focal neuroradiographic abnormalities in eastern equine encephalitis has not been recognized. Focal clinical signs are well described in the illness,4,13,19 and occurred at some point in 59 percent of the patients in our series.
Gross inspection of the brains of patients who died early in the course of eastern equine encephalitis reveals edema, leptomeningeal vascular congestion, hemorrhage, and encephalomalacia. Pyogenic meningeal exudate is rare.4 On cut sections, small necrotic foci are widely distributed.4,20,21 Histopathological manifestations include vascular, neuronal, and glial components. Vascular findings include arteriolar and venular inflammation, endothelial proliferation, small-vessel thrombosis, and perivascular cuffing. An inflammatory meningeal infiltrate is variably present.4,12,20-22 Focal parenchymal infiltration by neutrophils and macrophages causes neuronal destruction, neuronophagia, focal necrosis, and spotty demyelination. Glial proliferation results in glial nodules. In the brains of patients who died later in the course of illness, cortical atrophy predominates.3,4,11,20-22
The results of autopsy series differ on whether certain areas of the brain are particularly vulnerable to eastern equine encephalitis virus. Farber et al. suggested that the basal ganglia and brain stem are the most severely affected4; Hauser suggested the midbrain.21 Dent studied Hauser's patients but found no predilection for any particular areas.20 Our findings, like those of Farber et al., suggest that although focal lesions are variably distributed, involvement of the basal ganglia and thalami is prominent. These changes are evident early in the course of eastern equine encephalitis and often resolve with recovery. Accordingly, we suspect that they represent ischemia, inflammation, or edema, at least initially, rather than necrosis.
We cannot explain the predilection for this anatomical pattern, but it has also been described in other viral encephalitides. Basal ganglionic and thalamic lesions were identified radiographically in 7 of 13 patients with Japanese encephalitis.23 At autopsy, one had focal necrosis of the basal ganglia. Changes in the basal ganglia are also seen radiographically in measles,24 mumps,25,26 and echovirus 25 encephalitides27; in Creutzfeldt–Jakob disease28,29; and in noninfectious conditions, including cyanide and carbon monoxide poisoning.30 Influenza A encephalitis is associated with cortical, subcortical, thalamic, and pontine abnormalities.31,32 As was true in our series, MRI is a more sensitive method of identifying these changes than CT.
A minority of the patients in our series had cortical or subcortical lesions, predominantly involving the frontal lobes and anterior and medial portions of the temporal lobes. Herpes simplex encephalitis, which resembles eastern equine encephalitis clinically, typically also produces abnormalities of the frontal and temporal lobes.33,34 Unlike eastern equine encephalitis, however, herpes simplex encephalitis rarely involves the basal ganglia. When it does, the involvement is usually lateral and late34; in eastern equine encephalitis, the involvement is usually medial and early. The two diseases can be remarkably similar electroencephalographically. A minority of patients with eastern equine encephalitis have changes that are characteristic of herpes simplex encephalitis.35,36 Thus, a diagnosis based on isolation of the herpes simplex virus is imperative, even in apparently classic cases of herpetic encephalitis.
CT showed meningeal enhancement in two patients, presumably reflecting the meningeal component of infection.4,19-22 In two young patients, MRI showed late white-matter changes. Neither patient was studied early, so the changes cannot be definitively attributed to eastern equine encephalitis. Nevertheless, demyelination is a known sequel of the illness.4,20-22
MRI was exceedingly sensitive to the central nervous system manifestations of eastern equine encephalitis. The results of every MRI obtained from a comatose patient or a patient who subsequently became comatose were abnormal. Thus, the diagnosis of eastern equine encephalitis should be questioned in comatose patients with normal findings on MRI. Because CT remains the initial radiologic tool in suspected cases of encephalitis, physicians must be familiar with the subtle early CT changes of eastern equine encephalitis (Figure 3A, Figure 3B, and Figure 3C) that mimic early infarction or nonspecific findings common in elderly patients. Clinicians who encounter such findings should consider a diagnosis of eastern equine encephalitis in the appropriate setting, especially during mosquito season in areas in which the disease is endemic.
Our patients' courses closely matched those in earlier clinical descriptions. The median age in our series was older than in previous reports,13,19,21,37 possibly reflecting regional or temporal differences in demographics and human habitat. In contrast to an earlier series,13 neither the age of the patient nor the duration of the prodrome significantly predicted outcome.
High initial white-cell counts in cerebrospinal fluid and the development of severe hyponatremia during hospitalization each predicted a poor outcome. Both are probably markers of intense cerebral inflammation. Surprisingly, patients who were treated with either anticonvulsants or corticosteroids had poorer outcomes than those not so treated, associations that bordered on statistical significance. These results are probably confounded by unidentified variables, such as the severity of illness. We would not withhold corticosteroids or anticonvulsants from patients with eastern equine encephalitis solely on the basis of our findings.
We are indebted to the following persons for facilitating access to the clinical material that is the basis of this work: CDC, Division of Vector-Borne Diseases: Dr. D. Bruce Francy; Florida cases: Dr. Richard Hopkins (state epidemiologist, Florida Department of Health and Rehabilitation Services), Dr. Lisa Bailey, Ms. Trudy Bentley, Dr. James Clemmons, Ms. Robin Goetsman, Ms. Kathy J. Hurt, Dr. Donald Jackson, Dr. Eacharangad Jacob, Dr. Leena Jadeja, Dr. Clifford Spohr, Dr. Thomas A. Tomlin, and Dr. Robert W. Yancey, Jr.; Georgia cases: Dr. Kathleen Toomey (state epidemiologist, Epidemiology and Prevention Branch), Dr. Patricia C. Davis, and Dr. P. Maramareddy; Louisiana cases: Dr. Louise McFarland (state epidemiologist, Department of Health and Hospitals), Dr. Sol Courtman, Dr. Daniel McNeill, and Ms. Susan A. Wilson; Massachusetts cases: Dr. Alfred DeMaria, Jr. (director, Massachusetts Bureau of Communicable Disease Control), Dr. Michael Bennish, Dr. Martin Gaynor, Dr. Stefan Schatzki, Dr. Beth Weinstein-Nash, and Dr. Samuel Wolpert; Michigan cases: Dr. Mary Grace Stobierski (infectious disease epidemiologist, Michigan Department of Public Health), Dr. David D. Baumgartner, Dr. Michael Bergquist, Dr. David Davenport, Dr. Mark J. Harrison, Dr. Samuel D. Hirsch, Dr. David Janssen, Dr. David B. Martin, Dr. Douglas J. Quint, and Dr. Steve Ross; Mississippi cases: Dr. Mary Currier (state epidemiologist, Mississippi State Department of Health), Dr. Susan Ashbee, Dr. Russell Belenchia, Dr. Mary Ann Cowart, Dr. David K. Dunigan, Dr. Rodrigo M. Galvez, Dr. David Morgan, Dr. Allen Oaks, and Dr. Ethel Rose; North Carolina cases: Dr. Jean-Marie Maillard (state epidemiologist, North Carolina Department of Environment, Health and Natural Resources), Dr. G. Tillman Bailey, Dr. William Bobzien, Dr. Kevin Good, Dr. Jean Kenny, Dr. Henry Liverman, Dr. William Richey, Dr. Robert J. Schiess, and Dr. David J. Weber; Rhode Island cases: Ms. Marilyn Rittmann (Rhode Island Department of Health, Disease Prevention and Control), Dr. John Boyce, Dr. Frederick Crisafulli, Dr. Keivan Ettefagh, and Dr. Sanford Schatz; South Carolina cases: Dr. Eric Brenner and Dr. Jerry Gibson (state epidemiologists, South Carolina Department of Health and Environmental Control), Ms. Mary Brown, Ms. Julie Corbett, Dr. Sidney Griffin, Dr. George Hazleton, Dr. R. Joseph Healy, Dr. John Manos, Dr. Monnieque Singleton, and Dr. Braxton Wannamaker; and Virginia cases: Dr. Grayson Miller, Jr. (director, Office of Epidemiology, Commonwealth of Virginia Department of Health), and Dr. Suzanne Lavoie; to the patients involved in this study and to their family members, several of whom graciously spoke with us at length in the hope that the information gained by this study might aid future victims of eastern equine encephalitis; to Dr. Richard Platt and Dr. James Maguire for their many helpful suggestions during the preparation of the manuscript; and to Ms. Jaylyn Olivo for her expert editorial assistance.
Source Information
From the Infectious Disease Division (R.L.D., S.J.T.) and the Channing Laboratory (R.L.D.), Department of Medicine, and the Department of Radiology (L.H., A.A.Z.), Brigham and Women's Hospital and Harvard Medical School, Boston.
Address reprint requests to Dr. Deresiewicz at the Channing Laboratory, 181 Longwood Ave., Boston, MA 02115.
- References
References
1
Tsai TF . Arboviral infections in the United States. Infect Dis Clin North Am 1991;5:73-102
Medline2
Fothergill LD ,Dingle JH ,Farber S ,Connerley ML . Human encephalitis caused by the virus of the Eastern variety of equine encephalomyelitis. N Engl J Med 1938;219:411-411
Full Text | Web of Science3
Feemster RF . Outbreak of encephalitis in man due to the Eastern virus of equine encephalomyelitis. Am J Public Health 1938;28:1403-1410
CrossRef4
Farber S ,Hill A ,Connerly ML ,Dingle JH . Encephalitis in infants and children caused by the virus of the eastern variety of equine encephalitis. JAMA 1940;114:1725-1731
Web of Science5
McGowan JE Jr ,Bryan JA ,Gregg MB . Surveillance of arboviral encephalitis in the United States, 1955-1971. Am J Epidemiol 1973;97:199-207
Web of Science | Medline6
Piliero PJ ,Brody J ,Zamani A ,Deresiewicz RL . Eastern equine encephalitis presenting as focal neuroradiographic abnormalities: case report and review. Clin Infect Dis 1994;18:985-988
CrossRef | Web of Science | Medline7
Monath TP . Arthropod-borne encephalitides in the Americas. Bull World Health Organ 1979;57:513-533
Web of Science | Medline8
Arboviral disease -- United States, 1994
Medline9
Davenport DS ,Batts DH ,Carter JW . Eastern equine encephalitis in Michigan. Arch Neurol 1982;39:322-323
Web of Science | Medline10
Fernandez RJ ,Dooling EC . Eastern equine encephalitis mimicking herpes simplex encephalitis. Neurology 1982;32:Suppl:A178-A178 abstract.
Web of Science11
Case records of the Massachusetts General Hospital (Case 50-1984)
Full Text | Web of Science | Medline12
Kim JH ,Booss J ,Manuelidis EE ,Duncan CC . Human eastern equine encephalitis: electron microscopic study of a brain biopsy. Am J Clin Pathol 1985;84:223-227
Web of Science | Medline13
Przelomski MM ,O'Rourke E ,Grady GF ,Berardi VP ,Markley HG . Eastern equine encephalitis in Massachusetts: a report of 16 cases, 1970-1984. Neurology 1988;38:736-739
Web of Science | Medline14
Morse RP ,Bennish ML ,Darras BT . Eastern equine encephalitis presenting with a focal brain lesion. Pediatr Neurol 1992;8:473-475
CrossRef | Web of Science | Medline15
Case definitions for public health surveillanceMMWR Morb Mortal Wkly Rep 1990;39:11-12
Medline16
Lavoie SR ,Markowitz S ,Kapadia SJ . Eastern equine encephalomyelitis with hematuria and bladder dysfunction. South Med J 1993;86:812-814
CrossRef | Web of Science | Medline17
Letson GW ,Bailey RE ,Pearson J ,Tsai TF . Eastern equine encephalitis (EEE): a description of the 1989 outbreak, recent epidemiologic trends, and the association of rainfall with EEE occurrence. Am J Trop Med Hyg 1993;49:677-685
Web of Science | Medline18
Isselbacher KJ, Martin JB, Braunwald E, Fauci AS, Wilson JD, Kasper DL, eds. Harrison's principles of internal medicine. 13th ed. New York: McGraw-Hill, 1994.
19
Feemster RF . Equine encephalitis in Massachusetts. N Engl J Med 1957;257:701-704
Full Text | Web of Science | Medline20
Dent JH . Pathological changes in the brains of children infected with the virus of eastern equine encephalomyelitis. Bull Tul Med Fac 1955;14:85-96
Medline21
Hauser GH . Human equine encephalomyelitis, eastern type, in Louisiana. New Orleans Med Surg J 1948;100:551-558
Medline22
Jordan RA ,Wagner JA ,McCrumb FR . Eastern equine encephalitis: report of a case with autopsy. Am J Trop Med Hyg 1965;14:470-474
Web of Science | Medline23
Shoji H ,Hiraki Y ,Kuwasaki N ,Toyomasu T ,Kaji M ,Okudera T . Japanese encephalitis in the Kurume region of Japan: CT and MRI findings. J Neurol 1989;236:255-259
CrossRef | Web of Science | Medline24
Ochi J ,Okuno T ,Uenoyama Y ,Narita H ,Mikawa H . Symmetrical low density areas in bilateral thalami in an infant with measles encephalitis. Comput Radiol 1986;10:137-139
CrossRef | Medline25
Leheup BP ,Feillet F ,Roland J ,Andre JL ,Pierson M . Lésions des noyaux gris centraux au cours des oreillons évolution clinique et neuroradiologique d'un cas. Rev Neurol (Paris) 1987;143:301-303
Web of Science | Medline26
Tarr RW ,Edwards KM ,Kessler RM ,Kulkarni MV . MRI of mumps encephalitis: comparison with CT evaluation. Pediatr Radiol 1987;17:59-62
CrossRef | Medline27
Peters ACB ,Vielvoye GJ ,Versteeg J ,Bots GTAM ,Lindeman J . ECHO 25 focal encephalitis and subacute hemichorea. Neurology 1979;29:676-681
Web of Science | Medline28
Gertz H-J ,Henkes H ,Cervos-Navarro J . Creutzfeldt-Jakob disease: correlation of MRI and neuropathologic findings. Neurology 1988;38:1481-1482
Web of Science | Medline29
Di Rocco A ,Molinari S ,Stollman AL ,Decker A ,Yahr MD . MRI abnormalities in Creutzfeldt-Jakob disease. Neuroradiology 1993;35:584-585
CrossRef | Web of Science | Medline30
Aicardi J ,Gordon N ,Hagberg B . Holes in the brain. Dev Med Child Neurol 1985;27:249-252
CrossRef | Web of Science | Medline31
Protheroe SM ,Mellor DH . Imaging in influenza A encephalitis. Arch Dis Child 1991;66:702-705
CrossRef | Web of Science | Medline32
Fujii Y ,Kuriyama M ,Konishi Y ,Sudo M . MRI and SPECT in influenzal encephalitis. Pediatr Neurol 1992;8:133-136
CrossRef | Web of Science | Medline33
Hindmarsh T ,Lindqvist M ,Olding-Stenkvist E ,Skoldenberg B ,Forsgren M . Accuracy of computed tomography in the diagnosis of herpes simplex encephalitis. Acta Radiol Suppl 1986;369:192-196
Medline34
Demaerel P ,Wilms G ,Robberecht W , et al. MRI of herpes simplex encephalitis. Neuroradiology 1992;34:490-493
CrossRef | Web of Science | Medline35
Griffith JF ,Ch'ien LT . Herpes simplex virus encephalitis: diagnostic and treatment considerations. Med Clin North Am 1983;67:991-1008
Web of Science | Medline36
Gasecki AP ,Steg RE . Correlation of early MRI with CT scan, EEG, and CSF: analyses in a case of biopsy-proven herpes simplex encephalitis. Eur Neurol 1991;31:372-375
CrossRef | Web of Science | Medline37
Goldfield M ,Sussman O . The 1959 outbreak of Eastern encephalitis in New Jersey. I. Introduction and description of outbreak. Am J Epidemiol 1968;87:1-10
Web of Science | Medline
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J. David Beckham, Kenneth L. Tyler. (2011) Neuro-Intensive Care of Patients with Acute CNS Infections. Neurotherapeutics
CrossRef5
John-Paul Mutebi, Charles Lubelczyk, Rebecca Eisen, Nicholas Panella, Katherine MacMillan, Marvin Godsey, Bethany Swope, Ginger Young, Robert P. Smith, Lee Kantar, Sara Robinson, Stephen Sears. (2011) Using Wild White-Tailed Deer to Detect Eastern Equine Encephalitis Virus Activity in Maine. Vector-Borne and Zoonotic Diseases 11:10, 1403-1409
CrossRef6
C. L. Gardner, G. D. Ebel, K. D. Ryman, W. B. Klimstra. (2011) Heparan sulfate binding by natural eastern equine encephalitis viruses promotes neurovirulence. Proceedings of the National Academy of Sciences 108:38, 16026-16031
CrossRef7
Katherine B. Gibney, Sara Robinson, John-Paul Mutebi, Donald E. Hoenig, Brian J. Bernier, Lori Webber, Charles Lubelczyk, Randall J. Nett, Marc Fischer. (2011) Eastern Equine Encephalitis: An Emerging Arboviral Disease Threat, Maine, 2009. Vector-Borne and Zoonotic Diseases 11:6, 637-639
CrossRef8
Mark E. Rowin, Erin P. Reade, John C. Christenson. 2011. Central Nervous System Infections Presenting to the Pediatric Intensive Care Unit. , 918-932.
CrossRef9
Sanjay P. Prabhu, Tina Young-Poussaint. (2010) Pediatric Central Nervous System Emergencies. Neuroimaging Clinics of North America 20:4, 663-683
CrossRef10
Sandra Camelo-Piragua, E. Tessa Hedley-Whyte. 2010. Infections of the Nervous System. , 483-518.
CrossRef11
Michele A. Zacks, Slobodan Paessler. (2010) Encephalitic alphaviruses. Veterinary Microbiology 140:3-4, 281-286
CrossRef12
Erin Reichert, Amanda Clase, Ada Bacetty, Joseph Larsen. (2009) Alphavirus Antiviral Drug Development: Scientific Gap Analysis and Prospective Research Areas. Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science 7:4, 413-427
CrossRef13
N. M. Dung, Lance Turtle, W. K. Chong, N. T. Mai, T. T. Thao, T. T. Thuy, R. Kneen, N. H. Phu, B. Wills, J. Farrar, K. Das, Tom Solomon. (2009) An evaluation of the usefulness of neuroimaging for the diagnosis of Japanese encephalitis. Journal of Neurology 256:12, 2052-2060
CrossRef14
A.B. Allison, D.E. Stallknecht. (2009) Genomic sequencing of Highlands J virus: A comparison to western and eastern equine encephalitis viruses. Virus Research 145:2, 334-340
CrossRef15
U.K. Misra, J. Kalita. (2009) Seizures in encephalitis: Predictors and outcome. Seizure 18:8, 583-587
CrossRef16
Gyanendra Kumar, Jayantee Kalita, Usha Kant Misra. (2009) Raised intracranial pressure in acute viral encephalitis. Clinical Neurology and Neurosurgery 111:5, 399-406
CrossRef17
Mary Y. Mancao, Hamayun Imran, Sharat Chandra, Benjamin Estrada, Maria Figarola, Jeffrey Sosnowski, Rosa Vidal. (2009) EASTERN EQUINE ENCEPHALITIS VIRUS INFECTION AND HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS IN A 5-MONTH-OLD INFANT. The Pediatric Infectious Disease Journal 28:6, 543-545
CrossRef18
Benjamin J. Espinosa, Scott C. Weaver, Slobodan Paessler, Douglas Brining, Milagros Salazar, Tadeusz Kochel. (2009) Susceptibility of the Aotus nancymaae owl monkey to eastern equine encephalitis. Vaccine 27:11, 1729-1734
CrossRef19
Heli Harvala, John Bremner, Susan Kealey, Belinda Weller, Stuart McLellan, Graham Lloyd, Erin Staples, Federica Faggian, Tom Solomon. (2009) Case report: Eastern equine encephalitis virus imported to the UK. Journal of Medical Virology 81:2, 305-308
CrossRef20
Rene Hull, Seela Nattanmai, Laura D. Kramer, Kristen A. Bernard, Norma P. Tavakoli. (2008) A duplex real-time reverse transcriptase polymerase chain reaction assay for the detection of St. Louis encephalitis and eastern equine encephalitis viruses. Diagnostic Microbiology and Infectious Disease 62:3, 272-279
CrossRef21
Larry E. Davis, J. David Beckham, Kenneth L. Tyler. (2008) North American Encephalitic Arboviruses. Neurologic Clinics 26:3, 727-757
CrossRef22
Anita J. Reddy, Christopher W. Woods, Karen E. Welty-Wolf. (2008) Eastern equine encephalitis leading to multi-organ failure and sepsis. Journal of Clinical Virology 42:4, 418-421
CrossRef23
Usha Kant Misra, Chong Tin Tan, Jayantee Kalita. (2008) Viral encephalitis and epilepsy. Epilepsia 49, 13-18
CrossRef24
Cabot, Richard C.Harris, Nancy Lee, Shepard, Jo-Anne O., Rosenberg, Eric S., Cort, Alice M., Ebeling, Sally H.Peters, Christine C., Hirsch, Martin S., DeMaria, Alfred Jr., Schaefer, Pamela W., Branda, John A., . (2008) Case 22-2008. New England Journal of Medicine 359:3, 294-303
Full Text25
Diana Hans, Erin Kelly, Krista Wilhelmson, Eric D. Katz. (2008) Rapidly Fatal Infections. Emergency Medicine Clinics of North America 26:2, 259-279
CrossRef26
Gregory J. Moran, David A. Talan, Fredrick M. Abrahamian. (2008) Biological Terrorism. Infectious Disease Clinics of North America 22:1, 145-187
CrossRef27
Rakesh K. Gupta, Krishan K. Jain, Sunil Kumar. (2008) Imaging of Nonspecific (Nonherpetic) Acute Viral Infections. Neuroimaging Clinics of North America 18:1, 41-52
CrossRef28
Karen C. Bloch, Carol Glaser. (2007) Diagnostic approaches for patients with suspected encephalitis. Current Infectious Disease Reports 9:4, 315-322
CrossRef29
Loren Ketai, C.C. Tchoyoson Lim. (2007) Radiology of Biological Weapons—Old and the New?. Seminars in Roentgenology 42:1, 49-59
CrossRef30
E. Paul J. Gibbs, Maureen T. Long. 2007. Equine Alphaviruses. , 191-197.
CrossRef31
J. Kalita, U.K. Misra. (2006) EEG in dengue virus infection with neurological manifestations: A clinical and CT/MRI correlation. Clinical Neurophysiology 117:10, 2252-2256
CrossRef32
Jos?? R. Romero, Jason G. Newland. (2006) Diagnosis of Viral Encephalitides: Zoonotic-Associated Viruses. The Pediatric Infectious Disease Journal 25:8, 741-742
CrossRef33
James J Sejvar. (2006) The evolving epidemiology of viral encephalitis. Current Opinion in Neurology 19:4, 350-357
CrossRef34
U.K. Misra, J. Kalita, U.K. Syam, T.N. Dhole. (2006) Neurological manifestations of dengue virus infection. Journal of the Neurological Sciences 244:1-2, 117-122
CrossRef35
K. Li, D. Thomasson, L. Ketai, C. Contag, M. Pomper, M. Wright, M. Bray. (2005) Potential Applications of Conventional and Molecular Imaging to Biodefense Research. Clinical Infectious Diseases 40:10, 1471-1480
CrossRef36
Peter Vogel, Wayne M. Kell, David L. Fritz, Michael D. Parker, Randal J. Schoepp. (2005) Early Events in the Pathogenesis of Eastern Equine Encephalitis Virus in Mice. The American Journal of Pathology 166:1, 159-171
CrossRef37
Lindsey R. Baden, R. H. Rubin. (2004) Community-Acquired West Nile Virus Infection in Solid-Organ Transplant Recipients.. Transplantation 77:3, 356
CrossRef38
Tori L. McKlveen, Jeryl C. Jones, D. Phillip Sponenberg, Kent Scarratt, Daniel L. Ward, Charles H. Aardema. (2003) Assessment of the accuracy of computed tomography for measurement of normal equine pituitary glands. American Journal of Veterinary Research 64:11, 1387-1394
CrossRef39
K. L. Roos. (2003) Fever and Asymmetrical Weakness in the Summer: Evidence of a West Nile Virus-Associated Poliomyelitis-Like Illness. Mayo Clinic Proceedings 78:10, 1205-1206
CrossRef40
Nick Karabatsos, John Booss. 2003. Arthropod-Borne Virus Encephalitis. .
CrossRef41
Cabot, Richard C.Harris, Nancy Lee, McNeely, William F., Shepard, Jo-Anne O., Ebeling, Sally H.Ellender, Stacey M.Peters, Christine C., Hirsch, Martin S., Werner, Barbara, . (2003) Case 17-2003. New England Journal of Medicine 348:22, 2239-2247
Full Text42
Charulata Sankhla Savant, B.S. Singhal, Joseph Jankovic, Mak Khan, Amin Virani. (2003) Substantia nigra lesions in viral encephalitis. Movement Disorders 18:2, 213-216
CrossRef43
A. M. Sardesai, N. M. Brown, D. K. Menon. (2002) Deliberate release of biological agents. Anaesthesia 57:11, 1067-1082
CrossRef44
Thiravat Hemachudha, Jiraporn Laothamatas, Charles E Rupprecht. (2002) Human rabies: a disease of complex neuropathogenetic mechanisms and diagnostic challenges. The Lancet Neurology 1:2, 101-109
CrossRef45
Richard J Whitley, John W Gnann. (2002) Viral encephalitis: familiar infections and emerging pathogens. The Lancet 359:9305, 507-513
CrossRef46
Kristen A. Bernard, Laura D. Kramer. (2001) West Nile Virus Activity in the United States, 2001. Viral Immunology 14:4, 319-338
CrossRef47
Richard C Butler, Elizabeth Buetow. (2000) Clinicopathological Conference: A Previously Healthy Man with Fever and Pancytopenia. Academic Emergency Medicine 7:7, 792-796
CrossRef48
J Kalita, U.K Misra. (2000) Comparison of CT scan and MRI findings in the diagnosis of Japanese encephalitis. Journal of the Neurological Sciences 174:1, 3-8
CrossRef49
Karen L. Roos. (1999) ENCEPHALITIS. Neurologic Clinics 17:4, 813-833
CrossRef50
J. Kalita, U.K. Misra. (1999) Brainstem auditory evoked potential in Japanese encephalitis. Journal of the Neurological Sciences 165:1, 24-27
CrossRef51
U.K Misra, J Kalita, M Srivastava. (1998) Prognosis of Japanese encephalitis: a multivariate analysis. Journal of the Neurological Sciences 161:2, 143-147
CrossRef52
James W. Lance, Ian Hickie, Denis Wakefield, James G. Colebatch, Francisco Cardoso, Marie Vidailhet. (1998) An akinetic-rigid syndrome, depression, and stereotypies in a young man. Movement Disorders 13:5, 835-844
CrossRef53
Amy A. Pruitt. (1998) INFECTIONS OF THE NERVOUS SYSTEM. Neurologic Clinics 16:2, 419-447
CrossRef54
Gilman, Sid, . (1998) Imaging the Brain. New England Journal of Medicine 338:13, 889-896
Full Text55
(1997) Neuroradiographic Manifestations of Encephalitis. New England Journal of Medicine 337:19, 1393-1394
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