Aseptic Meningitis and Viral Meningitis

CHAPTER 35 Aseptic Meningitis and Viral Meningitis 355
Aseptic Meningitis and Viral Meningitis

35
David E. Bronstein • Carol A. Glaser
Aseptic meningitis is an inflammatory process of the meninges. It is alteration of CSF typical of meningitis, which may show a small or
relatively common and is caused by many different entities. The large number of cells; (3) absence of bacteria in the CSF, as shown by
cerebrospinal fluid (CSF) is characterized by pleocytosis, normal or appropriate culture; (4) a relatively short, benign course of illness; (5)
increased protein, and the absence of microorganisms on Gram stain absence of local parameningeal infection (e.g., otitis, sinusitis, or trauma)
and on routine culture. Usually the illnesses are self-limited; however, or a general disease that might have meningitis as a secondary manifesta-
with some etiologies, the resulting diseases may be severe, protracted, tion; and (6) absence from the community of epidemic disease, of
recurrent, or progressive, and lead to disability and death. Viral meningitis, which meningitis is a feature. In 1951, Wallgren379 redefined aseptic
an inflammation of the leptomeninges, is the most common type of meningitis as a syndrome likely to be encountered in many different
aseptic meningitis. Serous meningitis, lymphocytic meningitis, and infectious diseases.
nonparalytic poliomyelitis are terms that were used in the past to denote The clinical occurrence of aseptic meningitis first was recognized
aseptic meningitis. in epidemic poliomyelitis and in mumps at the beginning of the 20th
century.116,386 Rivers and Scott304 reported the recovery of lymphocytic
choriomeningitis virus from the CSF of several patients with aseptic
HISTORY meningitis in 1935, and, in 1934, Johnson and Goodpasture189 proved
Aseptic meningitis is a syndrome that first was described by Wallgren that mumps was caused by a virus. The discovery of coxsackieviruses
in 1925.378 Wallgren’s criteria for this diagnosis included (1) an acute in 1948 by Dalldorf and Sickles93 and the introduction of tissue culture
onset with obvious signs and symptoms of meningeal involvement; (2) in 1949 by Enders and colleagues,117 which resulted in the discovery of
Descargado para Laura bibiana Gomez Cortes (laurab.gomez@urosario.edu.co) en University of the Rosary de ClinicalKey.es por Elsevier en febrero 26, 2020.
Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2020. Elsevier Inc. Todos los derechos reservados.
356 SECTION 4 Central Nervous System Infections
echoviruses, paved the way for the widespread investigation into the Enterovirus 71 caused a major epidemic in Taiwan from 1998
etiology of aseptic meningitis. to 1999, with multiple cases of hand, foot, and mouth syndrome
Rasmussen297 reported on 374 cases evaluated at the Walter Reed associated with aseptic meningitis and other neurologic manifesta-
Army Institute of Research laboratory between 1941 and 1946 and tions.179,228,227,233,328,381,381,395,393 Similar outbreaks of aseptic meningitis
found the probable or definite etiology in 26% of “viral” disease of the caused by enterovirus 71 were reported in Malaysia, Japan, Hong Kong,
central nervous system (CNS). Mumps and lymphocytic choriomeningitis and Australia.72,131,172,237,247,327–329 Other enteroviruses involved in more
viruses were the two etiologic agents identified in his study. recent outbreaks include echovirus 4 in Italy, Greece, Israel, Palestine,
In 1953, Adair and associates7 reviewed 480 additional cases of aseptic and Australia160,235,241,289; echovirus 6 in China239; echovirus 9 in Japan
meningitis occurring in military personnel and their dependents from and regions of the United States10,67; echovirus 11 among institutionalized
1947 through 1952 and were able to confirm the etiology in 25% of children in Israel339; echovirus 16 in Cuba320; echovirus 18 in Taiwan
those patients. Herpes simplex virus (HSV) and Leptospira spp. were and Missouri363,367,380; echovirus 33 in New Zealand177; coxsackievirus
added to the previously identified mumps and lymphocytic chorio- A9 in Latvia and China91,281; and coxsackievirus B3 in China.354 In the
meningitis viruses as causes of aseptic meningitis. Meyer and associates248 United States, the most common serotypes are coxsackievirus A6, human
extended these studies to include 713 more children and adults with parechovirus 3, echovirus 11 and 18, coxsackieviruses A9 and B4, and
acute CNS syndromes of “viral” etiology admitted to military and echoviruses 30 and 6, with echoviruses 9 and 30 being the most frequently
Veterans Administration hospitals between 1953 and 1958. Of these identified etiologies of aseptic meningitis since 2003.1,68,69,66,305,355
713 patients, 430 had the clinical syndrome of aseptic meningitis. Sharing seasonality with the enteroviruses, several arboviruses cause
Approximately 80% of these patients were hospitalized in the United CNS disease in North America. Although encephalitis is the most
States. An etiologic diagnosis was determined in 71% of patients with recognizable manifestation of many of these infections, some arboviruses
aseptic meningitis. In addition to the agents identified earlier, poliovirus, commonly are associated with aseptic meningitis as well.70,144,305,309 Since
coxsackieviruses of groups A and B, echoviruses, and arthropod-borne the mid-1990s, outbreaks of West Nile virus (WNV) meningitis and
viruses were identified as causes of aseptic meningitis. encephalitis have occurred in Romania, Russia, and Israel.80,286,364 First
Lepow and colleagues220,221 reported the probable viral etiology in detected in the Western Hemisphere in 1999 in New York City, WNV
54% of the 407 patients they studied in Cleveland between 1955 and subsequently spread across North America from the Atlantic to the
1958. In 1958, Lennette and associates219 determined a viral etiology in Pacific coasts and into Canada and Mexico.47,120,181,266,283 Between 1999
65% of 511 children and adults with presumed viral CNS system disease and 2008, almost 29,000 cases were reported in the United States, with
in Los Angeles; 368 of these patients were diagnosed as having aseptic more than 1100 deaths.165,231 An estimated 1/150 infections results in
meningitis. Sköldenberg333 analyzed 3117 patients admitted to the severe neurologic illness, with meningitis as the primary manifestation
Hospital for Infectious Diseases in Stockholm between 1955 and 1964 in 16% to 40% of hospitalized patients.191 Although the incidence of
with the diagnosis of aseptic meningitis, with or without encephalitis neuroinvasive disease increases with age, WNV is more likely to manifest
or myelitis, and a virologic or clinical diagnosis (or both) of an associ- as meningitis in children than in older adults and occurred in at least
ated viral infection was established in 72.6%. Berlin and associates32 one-quarter of the 150 pediatric cases diagnosed in the United States
performed a surveillance study of aseptic meningitis in pediatric in 2002.82,128,164,185,230 Even in regions with increased incidence of WNV,
ambulatory clinics and emergency departments of three Baltimore episodes of meningitis caused by enterovirus greatly outnumber those
hospitals between July 1986 and December 1990. They identified a caused by WNV.191
single viral agent in 169 (62%) of the 274 cases with laboratory study; Before the introduction of WNV, arboviruses accounted for approxi-
168 enteroviruses and 1 adenovirus were identified. Today, with the use mately 5% of cases of aseptic meningitis in North America, with St.
of polymerase chain reaction (PCR) and culture and appropriate Louis encephalitis virus being the most common.48,58,60 Infection with
serologic study, the etiology of most cases of aseptic meningitis can be La Crosse encephalitis virus (a California encephalitis virus subtype)
determined. often resembles herpes encephalitis, but it may manifest as aseptic
meningitis in children.246 Unlike WNV, the majority of severe La Crosse
encephalitis virus cases occur in children 15 years of age and younger,
ETIOLOGY and in a study of 282 patients with La Crosse encephalitis virus infections
Box 35.1 lists infectious agents and other causes of aseptic meningitis. in the Eastern United States from 2003 to 2007, 17% had aseptic
At present, the diagnostic workup of aseptic meningitis usually is not meningitis.70,157 Other California serogroup viruses, such as Jamestown
undertaken vigorously, and the etiologic agent is identified in only Canyon virus and snowshoe hare virus, and other arboviruses, such as
approximately 10% of all cases. Epidemiologic study and intensive Colorado tick fever, result in aseptic meningitis more frequently than
investigations at some centers indicate, however, that most cases result encephalitis.144,305,344 Tick-borne encephalitis can manifest as aseptic
from viral infections. Enteroviruses account for approximately 85% of meningitis in endemic areas. Tick-borne encephalitis virus cases were
all cases of aseptic meningitis.55,99-101,258 The following enteroviruses have reported more recently in studies conducted in Poland, Slovenia, and
been associated with aseptic meningitis: polioviruses 1 to 3; coxsackie Sweden, and, in mild cases, the clinical presentation was that of aseptic
viruses A 1 to 14, 16 to 18, 21, 22, and 24; coxsackieviruses B 1 to 6; meningitis.154,222,234,402 Toscana virus, a sandfly-transmitted phlebovirus,
echoviruses 1 to 9, 11 to 21, 24 to 27, and 29 to 33; and enterovirus 71. is an emerging pathogen and cause of CNS infection, including aseptic
Recently described parechoviruses are closely related to enteroviruses meningitis, during the warm season in Mediterranean countries.13,113
and have also been associated with aseptic meningitis. Although 16 Aseptic meningitis is an occasional manifestation of acute and
genotypes of parechoviruses have been characterized,76 CNS infections recurrent genital infections with herpes simplex virus type 2
in young infants, including meningitis, are most frequently the result (HSV-2).22,31,88,109,334,359 In contrast to HSV-1 CNS infections, which
of human parechovirus 3 infections.119,302 without treatment usually are fatal, HSV-2 aseptic meningitis in otherwise
In recent years, multiple outbreaks of aseptic meningitis caused by immunocompetent patients is a benign, self-limited illness. Herpes
enteroviruses have been described, including outbreaks caused by family viruses other than HSV-1 and HSV-2 also are potential causes
echovirus 30 in several countries throughout Eastern and Western Europe, of aseptic meningitis. Although neurologic involvement in primary
China, Japan, Korea, Australia, the Arabian Gulf, the United States, and varicella-zoster virus (VZV) infections usually is encephalitis rather
Brazil.* Echovirus 13 was responsible for reported outbreaks of aseptic than benign meningitis, herpes zoster infection occasionally does present
meningitis in the United States, England, Wales, Germany, Belgium, with concurrent meningitis.99,159,182,183,278,290,300,384 VZV has been identified
Spain, France, Lithuania, Israel, Japan, Korea, and Australia.† by PCR in the CSF of patients who had acute aseptic meningitis without
cutaneous lesions, and meningitis associated with the VZV vaccine
*References 12, 25, 33, 44, 52, 66, 63, 71, 78, 90, 110, 123, 146, 163, 193, 203, strain has been described.* One report detected VZV vaccine strain in
223, 236, 238, 243, 250, 254, 268, 270, 272, 281, 285, 301, 324, 360, 370, 372, a young patient with viral meningitis 11 years after vaccination.273 A
382, 396, 401.
†
References 65, 75, 79, 107, 192, 200, 204, 263, 265, 338, 360, 362. *References 2, 74, 115, 133, 135, 138, 183, 188, 206, 216, 224, 225, 273, 342.
BOX 35.1 Etiologic Agents, Factors, and Diseases Associated With Aseptic Meningitis
Viruses Ureaplasma
Adenoviruses (1, 2, 3, 5, 6, 7, 12, 14, 32) Ureaplasma urealyticum
Arboviruses (in the United States: West Nile, St. Louis, California, Colorado
tick fever, eastern equine, western equine, Venezuelan equine, and Fungi
Powassan)a Blastomyces dermatitidis
Coronaviruses Candida spp.
Cytomegalovirus Coccidioides immitis
Encephalomyocarditis Cryptococcus neoformans
Enteroviruses (echoviruses, coxsackieviruses A and B, polioviruses, Histoplasma capsulatum
enteroviruses) Other: Acremonium spp., Alternaria spp., Aspergillus spp., Blastoschizomyces
Epstein-Barr capitus, Cephalosporium spp., Cladosporium trichoides, Drechslera
Hendra and Nipah hawaiiensis, Fusarium spp., Paecilomyces spp., Paracoccidioides
Herpes simplex type 1 brasiliensis, Penicillium marneffei, Phaeohyphomycosis, Pseudallescheria
Herpes simplex type 2 boydii, Sporothrix schenckii, Trichosporon beigelii, Ustilago spp.,
Human herpesvirus–6 Zygomycetes spp.
Human herpesvirus–7
Human immunodeficiency virus (HIV-1) Parasites (Eosinophilic Meningitis)
Human parechoviruses Flukes: Paragonimus westermani, schistosomiasis, fascioliasis
Human T-cell lymphotrophic virus (HTLV-1) Roundworms: Angiostrongylus cantonensis, Gnathostoma spinigerum,
Influenza A and B Baylisascaris procyonis, Strongyloides stercoralis, Trichinella spiralis,
Lymphocytic choriomeningitis Toxocara canis
Measles Tapeworms: Cysticercosis
Mumps Protozoa and free-living amoeba (noneosinophilic meningitis)
Parechoviruses Acanthamoeba
Parainfluenza Naegleria fowleri
Parvovirus B19 Toxoplasma gondii (toxoplasmosis)
Rhinoviruses
Vaccine Associated
Rotaviruses
Measles
Rubella
Mumps
Varicella zoster
Polio
Variola
Rabies
Bacteria Vaccinia
Atypical Mycobacteria
Parameningeal Infection
Bartonella henselae
Malignancy
Borrelia spp. (relapsing fever)
Central nervous system tumor
Borrelia burgdorferi (Lyme disease)
Leukemia
Brucella spp.
Leptospira spp. (leptospirosis) Immune Diseases
Mycobacterium tuberculosis Behçet syndrome
Nocardia spp. (nocardiosis) Lupus erythematosus
Sarcoidosis
Pyogenic: Partially Treated
Treponema pallidum (syphilis) Medications
Antimicrobial agents (e.g., trimethoprim-sulfamethoxazole)
Rickettsia
Intrathecal injections (e.g., contrast media, antibiotics)
Anaplasma phagocytophila
Nonsteroidal antiinflammatory drugs
Coxiella burnetii
Other drugs
Ehrlichia chaffeensis
Rickettsia rickettsii (Rocky Mountain spotted fever) Miscellaneous
Rickettsia prowazekii (typhus) Epidermoid, dermoid, other cysts
Foreign bodies (shunt, reservoir)
Mycoplasma
Heavy metal poisoning
Mycoplasma hominis
Kawasaki disease
Mycoplasma pneumoniae
Chlamydia
Chlamydia pneumoniae
Chlamydia psittaci
a
In other areas of the world, many other arboviruses are important.
variety of neurologic disorders, including aseptic meningitis, are rare Early treatment of this illness nearly always results in complete cure,
complications of Epstein-Barr virus infection.121,130,150,348,366 Most non- whereas diagnostic delay or inadequate treatment frequently results in
congenital infections with cytomegalovirus in nonimmunocompromised permanent neurologic sequelae. Lyme disease, relapsing fever, brucellosis,
patients are unrecognized; however, occasional instances of aseptic leptospirosis, and rickettsial infections are illnesses acquired either
meningitis have been noted.99–101,292,293 directly or indirectly from animals, in which aseptic meningitis may
The role of human herpesvirus–6 (HHV-6) in causing meningitis be a part of the disease process.* Mycoplasma pneumoniae has been
is unclear; although HHV-6 has been found in CSF samples from infants implicated as a causative agent of neurologic illness.52,115,158,293,372 Pönkä288
with meningitis, the virus also is detectable in the CSF of asymptomatic noted that 8/560 hospitalized patients with M. pneumoniae infections
individuals.15,50,394,399 Similarly PCR identified HHV-7 in the CSF of six had aseptic meningitis and 18 had encephalitis or meningoencephalitis.
children with neurologic diseases, including aseptic meningitis, menin- Despite numerous case reports and case series, the role of M. pneumoniae
goencephalitis, facial palsy, vestibular neuritis, and febrile seizures.287 is thought by some experts to be unknown.37 Mycoplasma hominis and
The role of HHV-7 as a causative agent in aseptic meningitis remains Ureaplasma urealyticum are rare causes of neonatal meningitis.134,240,375,376
to be determined. Meningitis and meningoencephalitis have been associated with Chlamydia
Occasionally meningitis or meningoencephalitis occurs as a manifesta- pneumoniae infections.17,152,335,349 Partially treated common bacterial
tion of acute illness with HIV-1 infection.23,158 Neurologic manifestations meningitides are a common cause of meningitis in which cultures of
develop 3 to 6 weeks after primary infection at the same time as an CSF fail to grow organisms. Antigen detection systems, such as latex
infectious mononucleosis–like illness. agglutination, can be useful in identifying the causative agents in some
Lymphocytic choriomeningitis virus was an important historical of these cases.
cause of aseptic meningitis. In 1974, eight cases of aseptic meningitis Numerous fungi and yeasts cause meningitis.317 Although many
caused by lymphocytic choriomeningitis virus were found in New York fungal meningitides occur almost exclusively in immunocompromised
state.102 Today it is rarely recognized as a cause of meningitis, which is patients, children and adults with normal immune status may experience
likely a result of both decreasing incidence of disease and decreased meningitis caused by Blastomyces dermatitidis, Coccidioides immitis,
detection.11,21,24,28,35,39,102,248,340 Seroprevalence studies conducted more Cryptococcus neoformans, Cladosporium spp., Histoplasma capsulatum,
than 2 decades ago found seroprevalence of 4.7%, whereas more recent Paracoccidioides brasiliensis, and Aspergillus spp.16,27,127,244 In infants who
studies show a much lower seroprevalence of 0.4%.77,208 Nevertheless are premature or younger than 1 month of age, Candida albicans is an
physicians should be alert to the possibility in all situations of rodent important cause of meningitis and is associated with significant morbidity
(pet or wild) exposure and test appropriately. Encephalomyocarditis and mortality.29,148,259
virus is another rodent virus that rarely is recognized in humans.383 It Parasites occasionally cause aseptic meningitis. Eosinophilic meningitis
is associated with a variety of neurologic manifestations, including is caused by Angiostrongylus cantonensis, a rat lungworm.73,158,173,174,226,295,307,385
aseptic meningitis.132 Aseptic meningitis caused by A. cantonensis has been observed on several
Adenoviral types 1, 2, 3, 4, 5, 6, 7, 11, 12, 14, and 32 have been islands in the Pacific, and the infection may be acquired by the consump-
associated with meningitis and meningoencephalitis.* Although they tion of freshwater shrimp.
occur infrequently, adenoviral CNS infections tend to be more severe A sterile CSF pleocytosis occurs in 12% to 13% of young infants
than enteroviral infections. Rarely aseptic meningitis has been noted with bacterial urinary tract infections8,124,351 and in approximately one-
during illnesses caused by influenza A viruses, including 2009 pandemic third of patients with Kawasaki disease who undergo lumbar punc-
influenza (H1N1), influenza B, rhinoviruses, parainfluenza viruses, ture.103,143 Numerous drugs and biologics have been implicated in aseptic
parvovirus B19 virus, rotaviruses, and coronaviruses.† Most infections meningitis.† Of most importance in pediatrics are trimethoprim-
with measles, rubella, and variola viruses that involve the CNS are sulfamethoxazole and intravenous immunoglobulin. Other causes of
encephalitic.57,53,251 aseptic meningitis are listed in Box 35.1.‡
In the prevaccine era, mumps virus was the agent responsible for
the greatest number of cases of aseptic meningitis; today, in the United
States, use of vaccine has rendered mumps rare, although mumps EPIDEMIOLOGY
outbreaks with associated cases of aseptic meningitis occur occasion- No unified epidemiologic pattern exists because so many different types
ally.67,59 Aseptic meningitis and encephalitis resulting from administration of organisms cause aseptic meningitis. The epidemiology of the specific
of mumps vaccine have been noted in Canada, Brazil, Japan, and Europe.‡ individual infectious agents or diseases is presented in detail in the
The Leningrad 3, Urabe Am 9, and three Japanese strains of vaccine various chapters of this book, and only a brief overview is presented
viruses have been implicated. In the United States, where the Jeryl Lynn here.
vaccine strain has been used exclusively, the rate of encephalitis in Because approximately 85% of all cases of aseptic meningitis are
vaccinees has been no higher than that of the observed background caused by enteroviral infections, the basic epidemiologic pattern of
incidence of similar illness in the population.54 A preliminary analysis aseptic meningitis reflects these agents. In temperate climates, most
of the Vaccine Safety Datalink project showed a possible increased risk cases occur in the summer and fall; infection with enteroviruses is
for developing aseptic meningitis 8 to 14 days after receiving immuniza- spread directly from person to person, and the incubation period usually
tion with Jeryl Lynn mumps vaccine strain. A follow-up case-control is 4 to 6 days. Epidemiologic considerations in aseptic meningitis caused
evaluation of hospitalized cases failed to show an increased risk, however.38 by agents other than enteroviruses depend markedly on season, geography,
Neurologic illness is a rare complication of measles, smallpox, polio, climatic conditions, animal exposures, and many other factors related
and rabies viral vaccines. In most instances, the illnesses are complex to the specific pathogens.
and severe, but occasionally aseptic meningitis is the only manifesta-
tion.32,64,57,53,253,325,343 A case of aseptic meningitis caused by vaccine-derived
poliovirus was reported in the Philippines in 2001.64 It was in association CLINICAL MANIFESTATIONS
with two pediatric cases of acute flaccid paralysis that occurred during Aseptic meningitis has many causes (see Box 35.1), and clinical
the same time period. Viral isolates from all three patients revealed type manifestations vary with the different diseases. In some instances,
1 poliovirus derived from the Sabin vaccine strain. the signs and symptoms resulting from meningeal inflammation
Certain bacteria are important to recognize as etiologic agents in dominate the clinical illness, whereas in other instances the main signs
aseptic meningitis because the illnesses are treatable and early initiation and symptoms reflect other organ system involvement. Clinical
of therapy is crucial. Of greatest importance is tuberculous meningitis.
*References 3, 34, 36, 40, 41, 43, 118, 142, 176, 186, 187, 190, 195, 209, 217,
*References 32, 86, 99–101, 122, 178, 201, 280, 281, 330, 337. 275, 282, 341, 356, 358, 374, 377, 389, 391, 400.
† †
References 19, 51, 89, 99-101, 106, 147, 175, 199, 257, 269, 271, 274, 279, 303, References 24, 45, 49, 104, 125, 145, 156, 184, 196, 242, 247, 249, 261, 262,
373, 392, 398. 296, 331, 390.
‡ ‡
References 14, 20, 83, 84, 92, 94, 111, 245, 252, 264. References 61, 108, 129, 141, 167, 171, 205, 209, 211, 218, 242, 326, 350.
manifestations in aseptic meningitis, regardless of etiology, also vary nerve palsies, inequality of the pupils, vomiting, and seizures. Finally,
markedly by patient age. coma, irregular pulse and respirations, and high fever occur. In fungal
diseases, the course of meningitis is similar to the course of tuberculosis.
Enteroviruses In tuberculosis and several fungal meningitides, such as those caused
Enteroviruses are the most common cause of aseptic meningitis, and by C. immitis, H. capsulatum, and C. neoformans, historical and radio-
they can be considered the prototype for a description of general clinical graphic evidence of pulmonary disease may be present.
manifestations of aseptic meningitis.* Even among the enteroviruses, Aseptic meningitis associated with M. pneumoniae is unique in
however, significant differences in clinical manifestations exist among that it frequently occurs a few days to 3 weeks after a respiratory
the different viral types. Some general aspects of epidemic enteroviral illness (i.e., pharyngitis, bronchitis, or pneumonia).153,229,336,365 Generally
aseptic meningitis are presented by viral type in Chapter 165. the likelihood of a predominance of neutrophils is less in other
The onset of illness generally is acute, although it may be insidious aseptic meningitides, and low glucose levels are likely in parameningeal
over the course of a week or so or may be preceded by a nonspecific bacterial infections, partially treated bacterial meningitides, brain tumors,
acute febrile illness of a few days’ duration. Almost all children have leukemic infiltration, M. pneumoniae infections, fungal infections, and
fever, and most older children have headache, which most often is tuberculosis.
retro-orbital or frontal in location. Photophobia is common. Temperature
elevation varies, ranging from 38°C to 40.5°C (100.4°F to 105°F), and Recurrent Aseptic Meningitis (Mollaret Meningitis)
usually lasts approximately 5 days. Occasionally, fever is biphasic, with In 1944, Mollaret256 described three patients with recurrent aseptic
the initial elevation occurring before the onset of neurologic signs and meningitis whom he had observed over the course of 15 years. Subse-
symptoms. Anorexia, nausea, and vomiting are common, and abdominal quently many other cases have been reported, and some cases have
pain and diarrhea also are reported frequently. been noted in children.46,84,85,170,284,345,357 The illness is characterized by
Meningeal signs (i.e., stiff neck and back, tightness of the hamstring recurrent attacks of fever with meningeal signs and symptoms. The
muscles, and Brudzinski and Kernig signs) usually are present, but deep attacks last several days and are separated by symptom-free periods
tendon reflexes usually are normal or hyperactive. Seizures occur lasting weeks or months. In addition to a lymphocyte-predominant
occasionally, usually when concomitant high fever is present. Muscle pleocytosis, CSF samples obtained from certain patients contain large
weakness rarely is reported, but myalgia occasionally is noted. In young mononuclear cells (Mollaret cells). The disease remits spontaneously.
children, fever, irritability, and lethargy are the most common findings. HSV-2 has been identified by PCR or DNA probes in the CSF of most
Infants may be irritable and show resentment to handling, and the patients with recurrent meningitis.25,84,114,213,284,321,353,357,368 Other viruses,
fontanelle may be tense. such as HSV-1 and Epstein-Barr virus, and noninfectious causes, such
Other manifestations of enteroviral infections also occur in children as systemic lupus erythematosus, intracranial cysts, antibiotics such as
with aseptic meningitis. The most common is pharyngitis, which may amoxicillin, and environmental exposures, also have been identified as
occur during infection with all of the neurotropic enteroviral types. less frequent etiologies of recurrent meningitis.150,205,291,315,319,345
Rash occurs commonly but varies by viral type. With echovirus 9
meningitis, 30% to 50% of children have rashes, whereas with echovirus
6, exanthem is rare. Cases of meningitis caused by enterovirus 71 and DIFFERENTIAL DIAGNOSIS
coxsackie virus A16 frequently are accompanied by hand, foot, and Careful analysis of the history and epidemiologic circumstances may
mouth syndrome. Enanthem, pleurodynia, pericarditis, myocarditis, point toward one of the specific causes listed in Box 35.1. During the
and conjunctivitis are other findings noted in children with enteroviral summer and autumn, the presence of pleurodynia, herpangina, or
aseptic meningitis. Illness often is biphasic, with fever, an interlude, unexplained febrile eruptions in the community suggests the possibility
then return of fever and neurologic manifestations. of enteroviral infections. Acute paralytic disorders in other patients
CSF leukocyte counts vary from a few cells to a few thousand cells; suggests poliomyelitis, enterovirus 71, or WNV. Exposure to mosquitoes
the median is in the range of 100 to 500 cells/mm3. The percentage of and encephalitis in horses implicates certain arboviruses, and exposure
neutrophils also varies greatly. Initially a predominance of neutrophils to ticks may be suggestive of Lyme disease, relapsing fever, or rickettsial
commonly occurs; later, CSF examinations show a decline in the percent- disease, depending on the geographic location and other symptoms of
age of neutrophils. The CSF protein usually is elevated mildly, and the the illness. A history of swimming in waters contaminated by urine
glucose concentration usually is normal; rarely hypoglycorrhachia is from infected animals and exposure to rats in urban slums suggest
noted. leptospiral infection. Knowledge of clear-cut exposure to or concurrent
The duration of illness varies. Usually disability because of neurologic evidence of mumps or of one of the common exanthems is helpful in
involvement lasts 1 to 2 weeks. delineating the differential diagnosis. The association of pneumonia or
other respiratory illness preceding aseptic meningitis strongly suggests
Aseptic Meningitis Caused by Other Agents the possibility of M. pneumoniae as the etiologic agent.
Of 1478 pediatric WNV cases reported from 1999 through 2007, 30% Most difficult from the diagnostic, therapeutic, and prognostic points
were classified as West Nile neuroinvasive disease (WNND).230 Unlike of view are instances of incipient or partially treated bacterial (especially
in older adults who often have encephalitis, most WNND in pediatric when caused by Haemophilus influenzae) or mycobacterial meningitis.
patients manifests as meningitis. Seizures occur more commonly in The clinical findings; the dosage of antibiotic previously used; the spinal
arboviral meningitides than in enteroviral illnesses of otherwise com- fluid smear, latex agglutination, or other rapid antigen identification
parable severity.162 The CSF findings generally are similar to those in test; the culture; and the glucose level may be helpful in diagnosing
enteroviral disease, although some reports suggest that neutrophils are bacterial meningitis. The quantitative determination of C-reactive protein
more commonly seen with WNV than with other viral entities.96,298 in the CSF also may be useful in differentiating bacterial from viral
Examination of the CSF in mild cases of mumps often reveals pleocytosis, meningitis.4,87,97,276,277 Lindquist and associates232 found that the determina-
and mumps is one of the few viral infections that can cause hypoglycor- tion of CSF concentrations of lactate was the most useful test in dif-
rhachia. When neurologic disease caused by mumps is recognized, usually ferentiating bacterial from nonbacterial causes of meningitis. Studies
evidence of brain involvement is present. suggest that the presence of tumor necrosis factor-α in the CSF is rare
Tuberculous meningitis usually has a gradual onset over the course in viral infections but common in bacterial disease.9,112,140 When tuber-
of 2 to 3 weeks.202,255,306 Initially, personality changes, irritability, anorexia, culous meningitis is suspected, a careful evaluation of contacts, a careful
listlessness, and low-grade fever may be present, followed by signs of examination of an appropriately stained smear from the pellicle of the
increased intracranial pressure, such as drowsiness, stiff neck, cranial CSF that was allowed to settle, and a positive tuberculin reaction or
positive interferon-γ release assay may confirm the diagnosis. Because
*References 5, 8, 12, 42, 64, 65, 62, 63, 71, 95, 107, 126, 137, 151, 155, 161, combined bacterial and viral infection has occurred, examinations of
166, 168, 160, 179, 193, 197, 198, 214, 228, 299, 308, 313, 314, 316, 318, 332, CSF should be repeated if any doubt exists. The possibility that the
347, 352, 387. observed meningeal reaction is of neither viral nor bacterial origin
must be considered. Finally, CNS tumor must be considered in the Several weeks after the patient has apparently recovered, a careful
differential diagnosis, particularly if hypoglycorrhachia and prominent neuromuscular assessment should be conducted to ensure that muscular
signs of increased intracranial pressure are present.211 weakness is not a sequela. Bilateral audiometry is recommended, especially
when mumps virus was involved.
SPECIFIC DIAGNOSIS
Obtaining a meticulous history is essential. The clinician must evaluate PROGNOSIS
exposure of the patient in the past 2 to 3 weeks to illness in contacts; The prognosis in aseptic meningitis depends on the etiology. Some
exposure to mosquitoes, ticks, and animals during recent vacations, illnesses have an ominous prognosis (i.e., tuberculous meningitis,
picnics, and so on; awareness of illness in animals, especially horses parameningeal infections, rickettsial infections), but patients usually
and other Equidae, in the patient’s environment; recent travel from the do well if appropriate specific therapy is instituted early in the course
home area; recent injections or medications of any kind; and the pos- of the illness. In C. immitis meningitis, the prognosis for cure is guarded
sibility of accidental exposure to heavy metals. even with early optimal therapy.
The CSF must be examined carefully to exclude disorders that respond In enteroviral and other viral meningitides, children usually recover
to specific therapy. Smears for bacteria, appropriate rapid antigen completely. Some patients complain of fatigue, irritability, decreased
identification tests, and cultures of the CSF are mandatory; the history ability to concentrate, muscle pain, muscle weakness and spasm, and
and clinical findings may indicate the need for performing acid-fast incoordination for several weeks after an acute illness. Although the
stain and culture of the sediment for mycobacteria. Other circumstances outcome of enteroviral meningitis most often is without residual, some
may indicate the need for excluding fungal or protozoal infection; atypical infants who have enteroviral meningitis in the first few months of life
cells may require cytopathologic study to exclude neural neoplasms, have an increased risk for altered language development.30,388 Formally
which may manifest acutely. evaluating such children at age 3 to 6 years is important.
The introduction of PCR has facilitated the etiologic diagnosis of
CNS viral infections, particularly infections caused by enteroviruses
and herpesviruses.6,139,149,180,194,212,322,361,397 PCR detects enterovirus in the PREVENTION
CSF more rapidly than does cell culture and has been shown to shorten The universal use of polio and mumps vaccines in children clearly is
the duration of hospitalization for children with meningitis, thus reducing effective in controlling these two diseases. Control of insect vectors by
costs.18,207,267,323,346 Enterovirus PCR tests do not detect human parecho- suitable spraying methods and eradication of insect breeding sites is
viruses; specific PCR testing for human parechoviruses should be ordered important in the control of many arboviruses. The control of animal
in the appropriate population (especially children younger than 3 years). vectors such as mice and rats alters the incidence of infections with
The absence of pleocytosis occurs rarely in patients with enteroviral lymphocytic choriomeningitis and encephalomyocarditis viruses.
meningitis but is relatively common in infants with meningitis resulting
from human parechovirus.98,119,136,169,260,294,302,371
PCR is the test of choice for detecting CNS infections caused by NEW REFERENCES SINCE THE SEVENTH EDITION
HSV, and molecular techniques also have been used to identify in CSF 1. Abedi GR, Watson JT, Pham H, et al. Enterovirus and human parechovirus
such causes of meningitis and meningoencephalitis as VZV, HHV-6, surveillance – United States, 2009–2013. MMWR Morb Mortal Wkly Rep.
parvovirus B19, and rotavirus.26,188,210,369 2015;64:940-943.
For many arboviruses, serologic examination is more sensitive than 3. Abhilash KP, Gunasekaran K, Mitra S, et al. Scrub typhus meningitis: an under-
recognized cause of aseptic meningitis in India. Neurol India. 2015;63:209-214.
molecular methods, especially for arboviruses that have a short period
13. Anagnostou V, Papa A. Seroprevalence of Toscana virus among residens of Aegean
of viremia and presence in the CSF, such as WNV. Molecular methods Sea islands, Greece. Travel Med Infect Dis. 2013;11:98-102.
may have a complementary role, as in one study in which WNV PCR 16. Antinori S, Corbellino M, Meroni L, et al. Aspergillus meningitis: a rare clinical
analysis had a 57% sensitivity and 100% specificity.81,215 manifestation of central nervous system aspergillosis. Case report and review
In any patient suspected to have viral meningitis, spinal fluid, serum, of 92 cases. J Infect. 2013;66:218-238.
feces, and throat swabs should be collected and either held in the hospital 18. Archimbaud C, Ouchchane L, Mirand A, et al. Improvement of the management of
laboratory or sent to a public health laboratory with viral diagnostic infants, children and adults with a molecular diagnosis of enterovirus meningitis
services. An additional serum specimen should be collected 10 to 21 during two observational study periods. PLoS ONE. 2013;8:1-8.
days later so that paired sera can be examined for antibody titer increases. 39. Bonthius DJ. Lymphocytic choriomeningitis virus: an underrecognized cause
of neurologic disease in the fetus, child, and adult. Semin Pediatr Neurol.
This pairing is particularly useful in arboviral, lymphocytic chorio-
2012;19:89-95.
meningitis, encephalomyocarditis, leptospiral, borrelial, rickettsial, 40. Boorugu H, Chrispal A, Gopinath KG, et al. Central nervous system involvement
mycoplasmal, and toxoplasmal infections. Although these studies may in scrub typhus. Trop Doct. 2014;44:36-37.
not provide an immediate diagnosis, they may give early warning of a 45. Bruner KE, Coop CA, White KM. Trimethoprim-sulfamethoxazole-induced
specific epidemic, and they are useful for prognostication, particularly aseptic meningitis – not just another sulfa allergy. Ann Allergy Asthma Immunol.
in very young infants. 2014;113:520-526.
90. Croker C, Civen R, Keough K, et al. Aseptic meningitis outbreak associated
with echovirus 30 among high school football players – Los Angeles County,
TREATMENT California, 2014. MMWR Morb Mortal Wkly Rep. 2015;63:1228.
98. de Crom SCM, van Furth AM, Peeters MF, et al. Characteristics of pediatric
Hospitalization usually is necessary because of the possibility of treatable
patients with enterovirus meningitis and no cerebral fluid pleocytosis. Eur J
bacterial disease, the frequent need for fluid therapy for dehydration, Pediatr. 2012;171:795-800.
and sometimes for analgesics. Headache and hyperesthesia are treated 113. Dupouey J, Bichaud L, Ninove L, et al. Toscana virus infections: a case series
with rest; analgesics; and a reduction in room light, noise, and visitors. from France. J Infect. 2014;68:290-295.
Antipyretics are recommended for fever. Using acetaminophen rather 119. Esposito S, Rahamat-Langendoen J, Ascolese B, et al. Pediatric parechovirus
than aspirin is prudent because of the risk for developing Reye syndrome infections. J Clin Virol. 2014;60:84-89.
associated with the latter antipyretic. Codeine, morphine, and the 136. Ghanem-Zoubi N, Shiner M, Shulman LM, et al. Human parechovirus type 3
phenothiazine derivatives often are used for pain and vomiting but are central nervous system infections in Israeli infants. J Clin Virol. 2013;58:205-210.
rarely necessary in children and should be avoided because they may 149. Graham AK, Murdoch DR. Association between cerebrospinal fluid pleocytosis
and enteroviral meningitis. J Clin Microbiol. 2005;43:1491.
induce misleading signs and symptoms. The investigational antiviral
169. Henquell C, Chambon M, Bailly JL, et al. Prospective analysis of 61 cases
drug pleconaril has been shown effective in the treatment of enteroviral of enteroviral meningitis: interest of systematic genome detection in cerebro-
meningitis; however, this drug presently is unavailable.105,310–312 Treatment spinal fluid irrespective of cytologic examination results. J Clin Virol. 2001;21:
for illnesses such as tuberculous meningitis, fungal meningitides, and 29-53.
other illnesses for which specific therapies are available is covered in 178. Huang YC, Huang SL, Chen SP, et al. Adenovirus infection associated with central
specific chapters of this book. nervous system dysfunction in children. J Clin Virol. 2013;57:300-304.
182. Ibrahim W, Elzouki AN, Husain A, et al. Varicella zoster aseptic meningitis: 257. Moon JH, Na JY, Kim JH, et al. Neurological and muscular manifestations
report of an atypical case and literature review. Am J Case Rep. 2015;16:594-597. associated with influenza B infection in children. Pediatr Neurol. 2013;49:97-101.
184. Jain RS, Kumar S, Aggarwal R, et al. Acute aseptic meningitis due to intravenous 260. Mulford WS, Buller RS, Arens MQ, et al. Correlation of cerebrospinal (CSF) cell
immunoglobulin therapy in Guillain-Barré syndrome. Oxf Med Case Reports. counts and elevated CSF protein levels with enterovirus reverse transcription-PCR
2014;2014(7):132-134. results in pediatric and adult patients. J Clin Microbiol. 2004;42:4199-4203.
196. Karmacharya P, Mainali NR, Aryal MR, et al. Recurrent case of ibuprofen-induced 261. Mullane D, Williams L, Merwick A, et al. Drug induced aseptic meningitis caused
aseptic meningitis in mixed connective tissue disease. BMJ Case Rep. 2013; by intravenous immunoglobulin therapy. Ir Med J. 2012;105:182-183.
10:1-3. 268. Nougairede A, Bessaud M, Thiberville SD, et al. Widespread circulation of a new
207. Kleines M, Scheithauer S, Schiefer J, et al. Clinical application of viral cerebrospinal echovirus 30 variant causing aseptic meningitis and non-specific viral illness,
fluid PCR testing for diagnosis of central nervous system disorders: a retrospective South-East France, 2013. J Clin Virol. 2014;61:118-124.
11-year experience. Diagn Microbiol Infect Dis. 2014;80:207-215. 294. Ramers C, Billman G, Hartin M, et al. Impact of a diagnostic cerebrospinal
212. Kumar A, Shukla D, Kumar R, et al. Molecular identification of enteroviruses associ- fluid enterovirus polymerase chain reaction test on patient management. JAMA.
ated with aseptic meningitis in children from India. Arch Virol. 2013;158:211-215. 2000;283:2680-2685.
236. Lu J, Zheng H, Guo X, et al. Elucidation of echovirus 30’s origin and transmission 302. Renaud C, Harrison CJ. Human parechovirus 3: the most common cause of
during the 2012 aseptic meningitis outbreak in Guangdong, China, through meningoencephalitis in young infants. Infect Dis Clin North Am. 2015;29:415-428.
continuing environmental surveillance. Appl Environ Microbiol. 2015;81:2311-2319. 331. Simms KM, Kortepeter C, Avigan M. Lamotrigine and aseptic meningitis.
238. Mantadakis E, Pogka V, Voulgari-Kokota A, et al. Echovirus 30 outbreak associ- Neurology. 2012;78:921-927.
ated with a high meningitis attack rate in Thrace, Greece. Pediatr Infect Dis J. 354. Tao Z, Song Y, Li Y, et al. Coxsackievirus B3, Shandong Province, China 1990–2010.
2013;32:914-916. Emerging Infect Dis. 2012;18:1865-1867.
243. Martinez AA, Castillo J, Sanchez MC, et al. Molecular diagnosis of echovirus 371. Vergnano S, Kadambari S, Whalley K, et al. Characteristics and outcomes of human
30 as the etiological agent in an outbreak of aseptic meningitis in Panama: parechovirus infection in infants (2008–2012). Eur J Pediatr. 2015;174:919-924.
May–June 2008. J Infect Dev Ctries. 2012;6:836-841. 396. Yang XH, Yan YS, Weng YW, et al. Molecular epidemiology of echovirus 30 in
250. Milia MG, Cerutti F, Gregori G, et al. Recent outbreak of aseptic meningitis in Fujian, China between 2001–2011. J Med Virol. 2013;85:696-702.
Italy due to echovirus 30 and phylogenetic relationship with other European 402. Zielicka-Hardy A, Rosinska M, Kondrusik M, et al. Predictors for diagnosis
circulating strains. J Clin Virol. 2013;58:579-583. of tick-borne encephalitis infection in Poland, 2009–2010. Infect Dis (Lond).
254. Mladenova Z, Buttinelli G, Dikova A, et al. Aseptic meningitis outbreak caused 2015;47:604-610.
by echovirus 30 in two regions in Bulgaria, May–August 2012. Epidemiol Infect.
2014;142:2159-2165. The full reference list for this chapter is available at ExpertConsult.com.
CHAPTER 35 Aseptic Meningitis and Viral Meningitis 361.e1
33. Bernit E, de Lamballerie X, Zandotti C, et al. Prospective investigation of a large

REFERENCES outbreak of meningitis due to echovirus 30 during summer 2000 in Marseilles,
1. Abedi GR, Watson JT, Pham H, et al. Enterovirus and human parechovirus France. Medicine (Baltimore). 2004;83:245-253.
surveillance – United States, 2009–2013. MMWR Morb Mortal Wkly Rep. 34. Bharti AR, Nally JE, Ricaldi JN, et al. Leptospirosis: a zoonotic disease of global
2015;64:940-943. importance. Lancet Infect Dis. 2003;3:757-771.
2. Aberle SW, Aberle JH, Steininger C, et al. Quantitative real time PCR detection 35. Biggar RJ, Woodall JP, Walter PD, et al. Lymphocytic choriomeningitis outbreak
of varicella-zoster virus DNA in cerebrospinal fluid in patients with neurological associated with pet hamsters: fifty-seven cases from New York State. JAMA.
disease. Med Microbiol Immunol. 2005;194:7-12. 1975;232:494-500.
3. Abhilash KP, Gunasekaran K, Mitra S, et al. Scrub typhus meningitis: an under- 36. Bingham PM, Galetta SL, Athreya B, et al. Neurologic manifestations in children
recognized cause of aseptic meningitis in India. Neurol India. 2015;63:209-214. with Lyme disease. Pediatrics. 1995;96:1053-1056.
4. Abramson JS, Hampton KD, Babu S, et al. The use of C-reactive protein from 37. Bitnun A, Richardson SE. Mycoplasma pneumoniae: innocent bystander or a
cerebrospinal fluid for differentiating meningitis from other central nervous true cause of central nervous system disease? Curr Infect Dis Rep. 2010;12:
system diseases. J Infect Dis. 1985;151:854-858. 282-290.
5. Abzug MJ, Levin MJ, Rotbart HA. Profile of enterovirus disease in the first two 38. Black S, Shinefield H, Ray P, et al. Risk of hospitalization because of aseptic
weeks of life. Pediatr Infect Dis J. 1993;12:820-824. meningitis after measles-mumps-rubella vaccination in one- to two-year-old
6. Abzug MJ, Loeffelholz M, Rotbart HA. Diagnosis of neonatal enterovirus infection children: an analysis of the Vaccine Safety Datalink (VSD) Project. Pediatr Infect
by polymerase chain reaction. J Pediatr. 1995;126:447-450. Dis J. 1997;16:500-503.
7. Adair CV, Gauld RL, Smadel JE. Aseptic meningitis, a disease of diverse etiology: 39. Bonthius DJ. Lymphocytic choriomeningitis virus: an underrecognized cause
clinical and etiologic studies on 854 cases. Ann Intern Med. 1953;39:675-704. of neurologic disease in the fetus, child, and adult. Semin Pediatr Neurol.
8. Adler-Shohet FC, Cheung MM, Hill M, et al. Aseptic meningitis in infants younger 2012;19:89-95.
than six months of age hospitalized with urinary tract infections. Pediatr Infect 40. Boorugu H, Chrispal A, Gopinath KG, et al. Central nervous system involvement
Dis J. 2003;22:1039-1042. in scrub typhus. Trop Doct. 2014;44:36-37.
9. Akalin H, Akdis AC, Mistik R, et al. Cerebrospinal fluid interleukin-1 beta/ 41. Bowen AP. A cluster of children with lyme meningitis presenting to one emergency
interleukin-1 receptor antagonist balance and tumor necrosis factor-alpha department in a Boston suburb. J Emerg Nurs. 2002;28:355-357.
concentrations in tuberculous, viral and acute bacterial meningitis. Scand J 42. Bowen GS, Fisher MC, DeForest A, et al. Epidemic of meningitis and febrile
Infect Dis. 1994;26:667-674. illness in neonates caused by ECHO type 11 virus in Philadelphia. Pediatr Infect
10. Akasu Y. Outbreak of aseptic meningitis due to ECHO-9 in northern Kyushu Dis. 1983;2:359-363.
island in the summer of 1997. Kurume Med J. 1999;46:97-104. 43. Bruhn FW. Lyme disease. Am J Dis Child. 1984;138:467-470.
11. Al-Zein N, Boyce TG, Correa AG, et al. Meningitis caused by lymphocytic 44. Brunel D, Leveque N, Jacques J, et al. Clinical and virological features of an
choriomeningitis virus in a patient with leukemia. J Pediatr Hematol Oncol. aseptic meningitis outbreak in North-Eastern France, 2005. J Clin Virol. 2008;42:
2008;30:781-784. 225-228.
12. Amvrosieva TV, Titov LP, Mulders M, et al. Viral water contamination as the cause 45. Bruner KE, Coop CA, White KM. Trimethoprim-sulfamethoxazole-induced
of aseptic meningitis outbreak in Belarus. Cent Eur J Public Health. 2001;9:154-157. aseptic meningitis – not just another sulfa allergy. Ann Allergy Asthma Immunol.
13. Anagnostou V, Papa A. Seroprevalence of Toscana virus among residens of Aegean 2014;113:520-526.
Sea islands, Greece. Travel Med Infect Dis. 2013;11:98-102. 46. Bruyn GW, Straathof LJ, Raymakers GM. Mollaret’s meningitis: differential
14. Anonymous. Mumps meningitis and MMR vaccination. Lancet. 1989;2:1015-1016. diagnosis and diagnostic pitfalls. Neurology. 1962;12:745-753.
15. Ansari A, Li S, Abzug MJ, et al. Human herpesviruses 6 and 7 and central nervous 47. Buck PA, Sockett P, Barker IK, et al. West Nile virus: surveillance activities in
system infection in children. Emerg Infect Dis. 2004;10:1450-1454. Canada. Ann Epidemiol. 2003;13:582.
16. Antinori S, Corbellino M, Meroni L, et al. Aspergillus meningitis: a rare clinical 48. Calisher CH. Medically important arboviruses of the United States and Canada.
manifestation of central nervous system aspergillosis. Case report and review Clin Microbiol Rev. 1994;7:89-116.
of 92 cases. J Infect. 2013;66:218-238. 49. Carlson J, Wiholm BE. Trimethoprim associated aseptic meningitis. Scand J
17. Anton E, Otegui A, Alonso A. Meningoencephalitis and Chlamydia pneumoniae Infect Dis. 1987;19:687-691.
infection. Eur J Neurol. 2000;7:586. 50. Caserta MT, Hall CB, Schnabel K, et al. Neuroinvasion and persistence of human
18. Archimbaud C, Ouchchane L, Mirand A, et al. Improvement of the management of herpesvirus 6 in children. J Infect Dis. 1994;170:1586-1589.
infants, children and adults with a molecular diagnosis of enterovirus meningitis 51. Cassinotti P, Schultze D, Schlageter P, et al. Persistent human parvovirus B19
during two observational study periods. PLoS ONE. 2013;8:1-8. infection following an acute infection with meningitis in an immunocompetent
19. Arisoy ES, Demmler GJ, Thakar S, et al. Meningitis due to parainfluenza virus patient. Eur J Clin Microbiol Infect Dis. 1993;12:701-704.
type 3: report of two cases and review. Clin Infect Dis. 1993;17:995-997. 52. Castro CM, Oliveira DS, Macedo O, et al. Echovirus 30 associated with cases
20. Arruda WO, Kondageski C. Aseptic meningitis in a large MMR vaccine campaign of aseptic meningitis in state of Para, Northern Brazil. Mem Inst Oswaldo Cruz.
(590,609 people) in Curitiba, Parana, Brazil, 1998. Rev Inst Med Trop Sao Paulo. 2009;104:444-450.
2001;43:301-302. 53. Centers for Disease Control. Neurotropic diseases surveillance: summary 1974–1976.
21. Asnis DS, Muana O, Kim DG, et al. Lymphocytic choriomeningitis virus meningitis, Available at https://stacks.cdc.gov/view/cdc/43830.
New York, NY, USA, 2009. Emerg Infect Dis. 2010;16:328-330. 54. Deleted in review.
22. Atia WA, Ratnatunga CS, Greenfield C, et al. Aseptic meningitis and herpes 55. Centers for Disease Control. Enterovirus surveillance, summary 1970–9. Available
simplex proctitis: a case report. Br J Vener Dis. 1982;58:53-58. at https://stacks.cdc.gov/view/cdc/6759.
23. Atwood WJ, Berger JR, Kaderman R, et al. Human immunodeficiency virus type 56. Deleted in review.
1 infection of the brain. Clin Microbiol Rev. 1993;6:339-366. 57. Centers for Disease Control. Measles surveillance report no. 11, 1977–1981. Atlanta,
24. Auxier GG. Aseptic meningitis associated with administration of trimethoprim GA: US Department of Health and Human Services, Public Health Service; 1982.
and sulfamethoxazole. Am J Dis Child. 1990;144:144-145. 58. Centers for Disease Control. Arboviral infections of the central nervous system:
25. Bailly JL, Brosson D, Archimbaud C, et al. Genetic diversity of echovirus 30 United States, 1985. MMWR Morb Mortal Wkly Rep. 1986;35:341-350.
during a meningitis outbreak, demonstrated by direct molecular typing from 59. Centers for Disease Control. ACIP: mumps prevention. MMWR Morb Mortal
cerebrospinal fluid. J Med Virol. 2002;68:558-567. Wkly Rep. 1989;38:388-400.
26. Barah F, Vallely PJ, Chiswick ML, et al. Association of human parvovirus B19 60. Centers for Disease Control. Arboviral surveillance: United States, 1990. MMWR
infection with acute meningoencephalitis. Lancet. 2001;358:729-730. Morb Mortal Wkly Rep. 1990;39:593-598.
27. Bariola JR, Perry P, Pappas PG, et al. Blastomycosis of the central nervous system: 61. Centers for Disease Control. Outbreak of Hendra-like virus: Malaysia and
a multicenter review of diagnosis and treatment in the modern era. Clin Infect Singapore—1998–1999. MMWR Morb Mortal Wkly Rep. 1999;48:265-269.
Dis. 2010;50:797-804. 62. Centers for Disease Control. Enterovirus surveillance: United States, 1997–1999.
28. Barton LL, Hyndman NJ. Lymphocytic choriomeningitis virus: reemerging central MMWR Morb Mortal Wkly Rep. 2000;49:913-916.
nervous system pathogen. Pediatrics. 2000;105:835. 63. Centers for Disease Control. Outbreak of aseptic meningitis associated with
29. Benjamin DK Jr, Stoll BJ, Fanaroff AA, et al. Neonatal candidiasis among extremely multiple enterovirus serotypes: Romania, 1999. MMWR Morb Mortal Wkly Rep.
low birth weight infants: risk factors, mortality rates, and neurodevelopmental 2000;49:669-671.
outcomes at 18 to 22 months. Pediatrics. 2006;117:84-92. 64. Centers for Disease Control. Acute flaccid paralysis associated with circulating
30. Bergman I, Painter MJ, Wald ER, et al. Outcome in children with enteroviral vaccine-derived poliovirus: Philippines, 2001. MMWR Morb Mortal Wkly Rep.
meningitis during the first year of life. J Pediatr. 1987;110:705-709. 2001;50:874-875.
31. Bergstrom T, Vahlne A, Alestig K, et al. Primary and recurrent herpes simplex 65. Centers for Disease Control. Echovirus type 13: United States, 2001. MMWR
virus type 2-induced meningitis. J Infect Dis. 1990;162:322-330. Morb Mortal Wkly Rep. 2001;50:777-780.
32. Berlin LE, Rorabaugh ML, Heldrich F, et al. Aseptic meningitis in infants < 2 66. Centers for Disease Control and Prevention. Outbreaks of aseptic meningitis
years of age: diagnosis and etiology. J Infect Dis. 1993;168:888-892. associated with echoviruses 9 and 30 and preliminary surveillance reports
361.e2 SECTION 4 Central Nervous System Infections
on enterovirus activity: United States, 2003. MMWR Morb Mortal Wkly Rep. 95. Davies JW, McDermott A, Severs D. Epidemic virus meningitis due to ECHO
2003;52:761-764. 9 virus in Newfoundland. Can Med Assoc J. 1958;79:162-167.
67. Centers for Disease Control and Prevention. Update: multistate outbreak of 96. Davis LE, DeBiasi R, Goade DE, et al. West Nile virus neuroinvasive disease.
mumps—United States, January 1–May 2, 2006. MMWR Morb Mortal Wkly Ann Neurol. 2006;60:286-300.
Rep. 2006;55:559-563. 97. de Beer FC, Kirsten GF, Gie RP, et al. Value of C reactive protein measurement
68. Centers for Disease Control and Prevention. Increased detections and severe in tuberculous, bacterial, and viral meningitis. Arch Dis Child. 1984;59:653-656.
neonatal disease associated with coxsackievirus B1 infection: United States, 2007. 98. de Crom SCM, van Furth AM, Peeters MF, et al. Characteristics of pediatric
MMWR Morb Mortal Wkly Rep. 2008;57:553-556. patients with enterovirus meningitis and no cerebral fluid pleocytosis. Eur J
69. Centers for Disease Control and Prevention. Nonpolio enterovirus and human Pediatr. 2012;171:795-800.
parechovirus surveillance: United States, 2006–2008. MMWR Morb Mortal Wkly 99. Deibel R, Flanagan TD. Central nervous system infections: etiologic and
Rep. 2010;59:1577-1580. epidemiologic observations in New York State, 1976–1977. N Y State J Med.
70. Centers for Disease Control and Prevention. West Nile virus disease and 1979;79:689-695.
other arboviral diseases: United States, 2010. MMWR Morb Mortal Wkly Rep. 100. Deibel R, Flanagan TD, Smith V. Central nervous system infections in New
2011;60:1009-1013. York State: etiologic and epidemiologic observations, 1974. N Y State J Med.
71. Cernescu C, Tardei G, Ruta S, et al. An outbreak of aseptic meningitis due to 1975;75:2337-2342.
ECHO 30 virus in Romania during the 1999 summer. Rom J Virol. 1999;50: 101. Deibel R, Flanagan TD, Smith V. Central nervous system infections: etiologic
99-106. and epidemiologic observations in New York State, 1975. N Y State J Med.
72. Chan LG, Parashar UD, Lye MS, et al. Deaths of children during an outbreak 1977;77:1398-1404.
of hand, foot, and mouth disease in Sarawak, Malaysia: clinical and patho- 102. Deibel R, Woodall JP, Decher WJ, et al. Lymphocytic choriomeningitis virus in
logical characteristics of the disease. Outbreak Study Group. Clin Infect Dis. man: serologic evidence of association with pet hamsters. JAMA. 1975;232:501-504.
2000;31:678-683. 103. Dengler LD, Capparelli EV, Bastian JF, et al. Cerebrospinal fluid profile in patients
73. Char DF, Rosen L. Eosinophilic meningitis among children in Hawaii. J Pediatr. with acute Kawasaki disease. Pediatr Infect Dis J. 1998;17:478-481.
1967;70:28-35. 104. Derbes SJ. Trimethoprim-induced aseptic meningitis. JAMA. 1984;252:2865-2866.
74. Chaves SS, Haber P, Walton K, et al. Safety of varicella vaccine after licensure in 105. Desmond RA, Accortt NA, Talley L, et al. Enteroviral meningitis: natural history and
the United States: experience from reports to the vaccine adverse event reporting outcome of pleconaril therapy. Antimicrob Agents Chemother. 2006;50:2409-2414.
system, 1995–2005. J Infect Dis. 2008;197(suppl 2):S170-S177. 106. Dickey M, Jamison L, Michaud L, et al. Rotavirus meningoencephalitis in a
75. Cheon DS, Lee J, Lee K, et al. Isolation and molecular identification of echovirus previously healthy child and a review of the literature. Pediatr Infect Dis J.
13 isolated from patients of aseptic meningitis in Korea, 2002. J Med Virol. 2009;28:318-321.
2004;73:439-442. 107. Diedrich S, Schreier E. Aseptic meningitis in Germany associated with echovirus
76. Chieochansin T, Vichiwattana P, Korkong S, et al. Molecular epidemiology, genome type 13. BMC Infect Dis. 2001;1:14.
characterization, and recombination event of human parechovirus. Virology. 108. Dimmitt DC, Fishbein DB, Dawson JE. Human ehrlichiosis associated with
2011;421:159-166. cerebrospinal fluid pleocytosis: a case report. Am J Med. 1989;87:677-678.
77. Childs JE, Glass GE, Ksiazek TG, et al. Human-rodent contact and infection with 109. Do AN, Green PA, Demmler GJ. Herpes simplex virus type 2 meningitis
lymphocytic choriomeningitis and Seoul viruses in an inner-city population. and associated genital lesions in a three-year-old child. Pediatr Infect Dis J.
Am J Trop Med Hyg. 1991;44:117-121. 1994;13:1014-1016.
78. Choi YJ, Park KS, Baek KA, et al. Molecular characterization of echovirus 30-associ- 110. Dos Santos GP, Skraba I, Oliveira D, et al. Enterovirus meningitis in Brazil,
ated outbreak of aseptic meningitis in Korea in 2008. J Microbiol Biotechnol. 1998–2003. J Med Virol. 2006;78:98-104.
2010;20:643-649. 111. Dourado I, Cunha S, Teixeira MG, et al. Outbreak of aseptic meningitis associated
79. Chomel JJ, Antona D, Thouvenot D, et al. Three ECHOvirus serotypes responsible with mass vaccination with a urabe-containing measles-mumps-rubella vaccine:
for outbreak of aseptic meningitis in Rhone-Alpes region, France. Eur J Clin implications for immunization programs. Am J Epidemiol. 2000;151:524-530.
Microbiol Infect Dis. 2003;22:191-193. 112. Dulkerian SJ, Kilpatrick L, Costarino AT Jr, et al. Cytokine elevations in infants
80. Chowers MY, Lang R, Nassar F, et al. Clinical characteristics of the West Nile with bacterial and aseptic meningitis. J Pediatr. 1995;126:872-876.
fever outbreak, Israel, 2000. Emerg Infect Dis. 2001;7:675-678. 113. Dupouey J, Bichaud L, Ninove L, et al. Toscana virus infections: a case series
81. Cinque P, Bossolasco S, Lundkvist A. Molecular analysis of cerebrospinal fluid from France. J Infect. 2014;68:290-295.
in viral diseases of the central nervous system. J Clin Virol. 2003;26:1-28. 114. Dylewski JS, Bekhor S. Mollaret’s meningitis caused by herpes simplex virus type 2:
82. Civen R, Villacorte F, Robles DT, et al. West Nile virus infection in the pediatric case report and literature review. Eur J Clin Microbiol Infect Dis. 2004;23:560-562.
population. Pediatr Infect Dis J. 2006;25:75-78. 115. Echevarria JM, Casas I, Tenorio A, et al. Detection of varicella-zoster virus-specific
83. Cizman M, Mozetic M, Radescek-Rakar R, et al. Aseptic meningitis after vac- DNA sequences in cerebrospinal fluid from patients with acute aseptic meningitis
cination against measles and mumps. Pediatr Infect Dis J. 1989;8:302-308. and no cutaneous lesions. J Med Virol. 1994;43:331-335.
84. Cohen BA, Rowley AH, Long CM. Herpes simplex type 2 in a patient with 116. Enders JF. Mumps. In: Rivers TM, Horsfall FL, eds. Viral and rickettsial infections
Mollaret’s meningitis: demonstration by polymerase chain reaction. Ann Neurol. of man. Philadelphia: J. B. Lippincott; 1959:780-789.
1994;35:112-116. 117. Enders JF, Weller TH, Robbins FC. Cultivation of the Lansing strain of poliomyelitis
85. Coleman WS, Lischner HW, Grover WD. Recurrent aseptic meningitis without virus in cultures of various human embryonic tissues. Science. 1949;109:85-87.
sequelae. J Pediatr. 1975;87:89-91. 118. Eppes SC, Nelson DK, Lewis LL, et al. Characterization of Lyme meningitis and
86. Connor JD, Buchta RM, DeGenaro F Jr, et al. Specialty conference: potpourri comparison with viral meningitis in children. Pediatrics. 1999;103:957-960.
of adenoviral infections. West J Med. 1974;120:55-61. 119. Esposito S, Rahamat-Langendoen J, Ascolese B, et al. Pediatric parechovirus
87. Corrall CJ, Pepple JM, Moxon ER, et al. C-reactive protein in spinal fluid of infections. J Clin Virol. 2014;60:84-89.
children with meningitis. J Pediatr. 1981;99:365-369. 120. Estrada-Franco JG, Navarro-Lopez R, Beasley DW, et al. West Nile virus in
88. Craig CP, Nahmias AJ. Different patterns of neurologic involvement with herpes Mexico: evidence of widespread circulation since July 2002. Emerg Infect Dis.
simplex virus types 1 and 2: isolation of herpes simplex virus type 2 from the 2003;9:1604-1607.
buffy coat of two adults with meningitis. J Infect Dis. 1973;127:365-372. 121. Evans AS, Niederman JC. Epstein-Barr virus. In: Evans AS, ed. Viral infections
89. Craver RD, Gohd RS, Sundin DR, et al. Isolation of parainfluenza virus type 3 of humans: epidemiology and control. 2nd ed. New York: Plenum Medical;
from cerebrospinal fluid associated with aseptic meningitis. Am J Clin Pathol. 1982:253-281.
1993;99:705-707. 122. Faulkner R, Van Rooyen CE. Adenoviruses types 3 and 5 isolated from the
90. Croker C, Civen R, Keough K, et al. Aseptic meningitis outbreak associated cerebrospinal fluid of children. Can Med Assoc J. 1962;87:1123-1125.
with echovirus 30 among high school football players – Los Angeles County, 123. Faustini A, Fano V, Muscillo M, et al. An outbreak of aseptic meningitis due
California, 2014. MMWR Morb Mortal Wkly Rep. 2015;63:1228. to echovirus 30 associated with attending school and swimming in pools. Int J
91. Cui A, Yu D, Zhu Z, et al. An outbreak of aseptic meningitis caused by coxsacki- Infect Dis. 2006;10:291-297.
evirus A9 in Gansu, the People’s Republic of China. Virol J. 2010;7:72. 124. Finkelstein Y, Mosseri R, Garty BZ. Concomitant aseptic meningitis and bacterial
92. da Cunha SS, Rodrigues LC, Barreto ML, et al. Outbreak of aseptic meningitis and urinary tract infection in young febrile infants. Pediatr Infect Dis J. 2001;20:630-632.
mumps after mass vaccination with MMR vaccine using the Leningrad-Zagreb 125. Fobelo MJ, Corzo Delgado JE, Romero Alonso A, et al. Aseptic meningitis related
mumps strain. Vaccine. 2002;20:1106-1112. to valacyclovir. Ann Pharmacother. 2001;35:128-129.
93. Dalldorf G, Sickles GM. An unidentified, filtrable agent isolated from the feces 126. Forbes JA. Meningitis in Melbourne due to E.C.H.O. virus. I. Clinical aspects.
of children with paralysis. Science. 1948;108:61-62. Med J Aust. 1958;45:246-248.
94. da Silveira CM, Kmetzsch CI, Mohrdieck R, et al. The risk of aseptic meningitis 127. Francesconi F, Francesconi do Valle AC, Silva MT, et al. International issues: menin-
associated with the Leningrad-Zagreb mumps vaccine strain following mass goencephalitis due to Paracoccidioides brasiliensis. Neurology. 2008;71:e65-e67.
vaccination with measles-mumps-rubella vaccine, Rio Grande do Sul, Brazil, 128. Francisco AM, Glaser C, Frykman E, et al. 2004 California pediatric West Nile
1997. Int J Epidemiol. 2002;31:978-982. virus case series. Pediatr Infect Dis J. 2006;25:81-84.
129. Fryden A, Kihlstrom E, Maller R, et al. A clinical and epidemiological study of 160. Handsher R, Shulman LM, Abramovitz B, et al. A new variant of echovirus 4
“rnithosis” caused by Chlamydia psittaci and Chlamydia pneumoniae (strain associated with a large outbreak of aseptic meningitis. J Clin Virol. 1999;13:29-36.
TWAR). Scand J Infect Dis. 1989;21:681-691. 161. Hanninen P, Pohjonen R. Echovirus type 6 meningitis: clinical and viro-
130. Fujimoto H, Asaoka K, Imaizumi T, et al. Epstein-Barr virus infections of the logical observations during an epidemic in Turku in 1968. Scand J Infect Dis.
central nervous system. Intern Med. 2003;42:33-40. 1971;3:121-125.
131. Fujimoto T, Chikahira M, Yoshida S, et al. Outbreak of central nervous system 162. Hardin SG, Erwin PC, Patterson L, et al. Clinical comparisons of La Crosse
disease associated with hand, foot, and mouth disease in Japan during the summer encephalitis and enteroviral central nervous system infections in a pediatric popula-
of 2000: detection and molecular epidemiology of enterovirus 71. Microbiol tion: 2001 surveillance in East Tennessee. Am J Infect Control. 2003;31:508-510.
Immunol. 2002;46:621-627. 163. Hauri AM, Schimmelpfennig M, Walter-Domes M, et al. An outbreak of
132. Gajdusek DC. Encephalomyocarditis virus infection in childhood. Pediatrics. viral meningitis associated with a public swimming pond. Epidemiol Infect.
1955;16:902-906. 2005;133:291-298.
133. Galea SA, Sweet A, Beninger P, et al. The safety profile of varicella vaccine: a 164. Hayes EB, O’Leary DR. West Nile virus infection: a pediatric perspective. Pediatrics.
10-year review. J Infect Dis. 2008;197(suppl 2):S165-S169. 2004;113:1375-1381.
134. Garland SM, Murton LJ. Neonatal meningitis caused by Ureaplasma urealyticum. 165. Hayes EB, Sejvar JJ, Zaki SR, et al. Virology, pathology, and clinical manifestations
Pediatr Infect Dis J. 1987;6:868-870. of West Nile virus disease. Emerg Infect Dis. 2005;11:1174-1179.
135. Garnier A, Frascari F, Decramer S. Varicella-zoster virus meningoencephalitis 166. Haynes RE, Cramblett HG, Kronfol HJ. Echovirus 9 meningoencephalitis in
without skin lesions in a paediatric kidney recipient. Nephrol Dial Transplant. infants and children. JAMA. 1969;208:1657-1660.
2011;26:378-379, author reply 379. 167. Haynes RE, Sanders DY, Cramblett HG. Rocky Mountain spotted fever in children.
136. Ghanem-Zoubi N, Shiner M, Shulman LM, et al. Human parechovirus type 3 J Pediatr. 1970;76:685-693.
central nervous system infections in Israeli infants. J Clin Virol. 2013;58:205-210. 168. Helin I, Widell A, Borulf S, et al. Outbreak of coxsackievirus A-14 meningitis
137. Gilbert GL, Dickson KE, Waters MJ, et al. Outbreak of enterovirus 71 infection among newborns in a maternity hospital ward. Acta Paediatr Scand. 1987;76:
in Victoria, Australia, with a high incidence of neurologic involvement. Pediatr 234-238.
Infect Dis J. 1988;7:484-488. 169. Henquell C, Chambon M, Bailly JL, et al. Prospective analysis of 61 cases of
138. Gilden D, Cohrs RJ, Mahalingam R, et al. Neurological disease produced by enteroviral meningitis: interest of systematic genome detection in cerebrospinal
varicella zoster virus reactivation without rash. Curr Top Microbiol Immunol. fluid irrespective of cytologic examination results. J Clin Virol. 2001;21:29-53.
2010;342:243-253. 170. Hermans PE, Goldstein NP, Wellman WE. Mollaret’s meningitis and differential
139. Glimaker M, Johansson B, Olcen P, et al. Detection of enteroviral RNA by diagnosis of recurrent meningitis: report of case, with review of the literature.
polymerase chain reaction in cerebrospinal fluid from patients with aseptic Am J Med. 1972;52:128-140.
meningitis. Scand J Infect Dis. 1993;25:547-557. 171. Heusner AP. Nontuberculous spinal epidural infections. N Engl J Med.
140. Glimaker M, Kragsbjerg P, Forsgren M, et al. Tumor necrosis factor-alpha 1948;239:845-854.
(TNF alpha) in cerebrospinal fluid from patients with meningitis of different 172. Ho M. Enterovirus 71: the virus, its infections and outbreaks. J Microbiol Immunol
etiologies: high levels of TNF alpha indicate bacterial meningitis. J Infect Dis. Infect. 2000;33:205-216.
1993;167:882-889. 173. Hochberg NS, Blackburn BG, Park SY, et al. Eosinophilic meningitis attributable
141. Golden SE. Aseptic meningitis associated with Ehrlichia canis infection. Pediatr to Angiostrongylus cantonensis infection in Hawaii: clinical characteristics and
Infect Dis J. 1989;8:335-337. potential exposures. Am J Trop Med Hyg. 2011;85:685-690.
142. Gonzalez Garcia H, Ernandez Alonso JF, de Paz Garcia M, et al. Meningitis 174. Hochberg NS, Park SY, Blackburn BG, et al. Distribution of eosinophilic men-
as the first and only manifestation of brucellosis. An Esp Pediatr. 2000;53: ingitis cases attributable to Angiostrongylus cantonensis: Hawaii. Emerg Infect
280-282. Dis. 2007;13:1675-1680.
143. Gonzalez Pascual E, Villanueva Lamas J, Ros Viladoms J, et al. [Kawasaki disease: 175. Holzel A, Smith PA, Tobin JO. A new type of meningo-encephalitis associated
a report of 50 cases]. An Esp Pediatr. 1999;50:39-43. with a rhinovirus. Acta Paediatr Scand. 1965;54:168-174.
144. Goodpasture HC, Poland JD, Francy DB, et al. Colorado tick fever: clinical, 176. Hoppa E, Bachur R. Lyme disease update. Curr Opin Pediatr. 2007;19:275-280.
epidemiologic, and laboratory aspects of 228 cases in Colorado in 1973–1974. 177. Huang QS, Carr JM, Nix WA, et al. An echovirus type 33 winter outbreak in
Ann Intern Med. 1978;88:303-310. New Zealand. Clin Infect Dis. 2003;37:650-657.
145. Gordon MF, Allon M, Coyle PK. Drug-induced meningitis. Neurology. 178. Huang YC, Huang SL, Chen SP, et al. Adenovirus infection associated with central
1990;40:163-164. nervous system dysfunction in children. J Clin Virol. 2013;57:300-304.
146. Gosbell I, Robinson D, Chant K, et al. Outbreak of echovirus 30 meningitis in 179. Huang CC, Liu CC, Chang YC, et al. Neurologic complications in children with
Wingecarribee Shire, New South Wales. Commun Dis Intell. 2000;24:121-124. enterovirus 71 infection. N Engl J Med. 1999;341:936-942.
147. Goto T, Kimura H, Numazaki K, et al. A case of meningoencephalitis associ- 180. Huang C, Morse D, Slater B, et al. Multiple-year experience in the diagnosis of
ated with G1P[8] rotavirus infection in a Japanese child. Scand J Infect Dis. viral central nervous system infections with a panel of polymerase chain reaction
2007;39:1067-1070. assays for detection of 11 viruses. Clin Infect Dis. 2004;39:630-635.
148. Gottfredsson M, Perfect JR. Fungal meningitis. Semin Neurol. 2000;20:307-322. 181. Huhn GD, Sejvar JJ, Montgomery SP, et al. West Nile virus in the United States:
149. Graham AK, Murdoch DR. Association between cerebrospinal fluid pleocytosis an update on an emerging infectious disease. Am Fam Physician. 2003;68:653-660.
and enteroviral meningitis. J Clin Microbiol. 2005;43:1491. 182. Ibrahim W, Elzouki AN, Husain A, et al. Varicella zoster aseptic meningitis:
150. Graman PS. Mollaret’s meningitis associated with acute Epstein-Barr virus report of an atypical case and literature review. Am J Case Rep. 2015;16:594-597.
mononucleosis. Arch Neurol. 1987;44:1204-1205. 183. Iyer S, Mittal MK, Hodinka RL. Herpes zoster and meningitis resulting from
151. Grist NR, Bell EJ, Assaad F. Enteroviruses in human disease. Prog Med Virol. reactivation of varicella vaccine virus in an immunocompetent child. Ann Emerg
1978;24:114-157. Med. 2009;53:792-795.
152. Guglielminotti J, Lellouche N, Maury E, et al. Severe meningoencephalitis: an 184. Jain RS, Kumar S, Aggarwal R, et al. Acute aseptic meningitis due to intravenous
unusual manifestation of Chlamydia pneumoniae infection. Clin Infect Dis. immunoglobulin therapy in Guillain-Barré syndrome. Oxf Med Case Reports.
2000;30:209-210. 2014;2014:132-134.
153. Guleria R, Nisar N, Chawla TC, et al. Mycoplasma pneumoniae and central nervous 185. Jean CM, Honarmand S, Louie JK, et al. Risk factors for West Nile virus neu-
system complications: a review. J Lab Clin Med. 2005;146:55-63. roinvasive disease, California, 2005. Emerg Infect Dis. 2007;13:1918-1920.
154. Gunther G, Haglund M, Lindquist L, et al. Tick-borne encephalitis in Sweden in 186. Jha S, Ansari MK. Leptospirosis presenting as acute meningoencephalitis. J Infect
relation to aseptic meningo-encephalitis of other etiology: a prospective study Dev Ctries. 2010;4:179-182.
of clinical course and outcome. J Neurol. 1997;244:230-238. 187. Jhaveri R, Cherry JD, Phillips S, et al. Erythema migrans after ceftriaxone treat-
155. Guthrie N. Coxsackie B5 meningitis: report of an outbreak in a high school ment of aseptic meningitis caused by Borrelia burgdorferi. Pediatr Infect Dis J.
football squad. J Tn State Med Assoc. 1962;55:355-356. 2001;20:1010-1012.
156. Haase KK, Lapointe M, Haines SJ. Aseptic meningitis after intraventricular 188. Jhaveri R, Sankar R, Yazdani S, et al. Varicella-zoster virus: an overlooked cause
administration of gentamicin. Pharmacotherapy. 2001;21:103-107. of aseptic meningitis. Pediatr Infect Dis J. 2003;22:96-97.
157. Haddow AD, Odoi A. The incidence risk, clustering, and clinical presentation of 189. Johnson CD, Goodpasture EW. An investigation of the etiology of mumps. J
La Crosse virus infections in the eastern United States, 2003–2007. PLoS ONE. Exp Med. 1934;59:1-20.
2009;4:e6145. 190. Jorbeck HJ, Gustafsson PM, Lind HC, et al. Tick-borne Borrelia-meningitis in
158. Hammer SM, Connolly KJ. Viral aseptic meningitis in the United States: clinical children; an outbreak in the Kalmar area during the summer of 1984. Acta
features, viral etiologies, and differential diagnosis. Curr Clin Top Infect Dis. Paediatr Scand. 1987;76:228-233.
1992;12:1-25. 191. Julian KG, Mullins JA, Olin A, et al. Aseptic meningitis epidemic during a West
159. Han JY, Hanson DC, Way SS. Herpes zoster and meningitis due to reactivation Nile virus avian epizootic. Emerg Infect Dis. 2003;9:1082-1088.
of varicella vaccine virus in an immunocompetent child. Pediatr Infect Dis J. 192. Kaida A, Kubo H, Iritani N, et al. Isolation of Echovirus type 13 in Osaka City
2011;30:266-268. during 2001–2002. Jpn J Infect Dis. 2004;57:127-128.
193. Kajiwara I, Kusaba T, Hayashida I, et al. [Clinical study of an outbreak of 224. Levin MJ, Dahl KM, Weinberg A, et al. Development of resistance to acyclovir
aseptic meningitis due to echovirus type 30 in Munakata City in 1997–1998]. during chronic infection with the Oka vaccine strain of varicella-zoster virus,
Kansenshogaku Zasshi. 2000;74:231-236. in an immunosuppressed child. J Infect Dis. 2003;188:954-959.
194. Kammerer U, Kunkel B, Korn K. Nested PCR for specific detection and rapid 225. Levin MJ, DeBiasi RL, Bostik V, et al. Herpes zoster with skin lesions and meningitis
identification of human picornaviruses. J Clin Microbiol. 1994;32:285-291. caused by 2 different genotypes of the Oka varicella-zoster virus vaccine. J Infect
195. Karande S, Patil S, Kulkarni M, et al. Acute aseptic meningitis as the only presenting Dis. 2008;198:1444-1447.
feature of leptospirosis. Pediatr Infect Dis J. 2005;24:390-391. 226. Li H, Xu F, Gu JB, et al. A severe eosinophilic meningoencephalitis caused by
196. Karmacharya P, Mainali NR, Aryal MR, et al. Recurrent case of ibuprofen- infection of Angiostrongylus cantonensis. Am J Trop Med Hyg. 2008;79:568-570.
induced aseptic meningitis in mixed connective tissue disease. BMJ Case Rep. 227. Li CC, Yang MY, Chen RF, et al. Clinical manifestations and laboratory assess-
2013;10:1-3. ment in an enterovirus 71 outbreak in southern Taiwan. Scand J Infect Dis.
197. Karzon DT, Barron AL. An epidemic of aseptic meningitis syndrome due to 2002;34:104-109.
echo virus type 6. I. Correlation of enterovirus isolation with illness. II. Clinical 228. Liao HT, Hung KL. Neurologic involvement in an outbreak of enterovirus 71
study. III. Sequelae. Pediatrics. 1962;29:409-417, 418–31, 432–7. infection: a hospital-based study. Acta Paediatr Taiwan. 2001;42:27-32.
198. Karzon DT, Eckert GL, Barron AL, et al. Aseptic meningitis epidemic due to 229. Lin WC, Lee PI, Lu CY, et al. Mycoplasma pneumoniae encephalitis in childhood.
ECHO 4 virus. Am J Dis Child. 1961;101:610-622. J Microbiol Immunol Infect. 2002;35:173-178.
199. Kehle J, Metzger-Boddien C, Tewald F, et al. First case of confirmed rotavirus 230. Lindsey NP, Hayes EB, Staples JE, et al. West Nile virus disease in children,
meningoencephalitis in Germany. Pediatr Infect Dis J. 2003;22:468-470. United States, 1999–2007. Pediatrics. 2009;123:e1084-e1089.
200. Keino M, Kanno M, Hirasawa K, et al. Isolation of echovirus type 13 from 231. Lindsey NP, Staples JE, Lehman JA, et al. Surveillance for human West Nile virus
patients of aseptic meningitis. Jpn J Infect Dis. 2001;54:249-250. disease: United States, 1999–2008. MMWR Surveill Summ. 2010;59:1-17.
201. Kelsey DS. Adenovirus meningoencephalitis. Pediatrics. 1978;61:291-293. 232. Lindquist L, Linne T, Hansson LO, et al. Value of cerebrospinal fluid analysis in
202. Kennedy DH, Fallon RJ. Tuberculous meningitis. JAMA. 1979;241:264-268. the differential diagnosis of meningitis: a study in 710 patients with suspected
203. Khalfan S, Aymard M, Lina B, et al. Epidemics of aseptic meningitis due to central nervous system infection. Eur J Clin Microbiol Infect Dis. 1988;7:374-380.
enteroviruses following national immunization days in Bahrain. Ann Trop Paediatr. 233. Liu CC, Tseng HW, Wang SM, et al. An outbreak of enterovirus 71 infection in
1998;18:101-109. Taiwan, 1998: epidemiologic and clinical manifestations. J Clin Virol. 2000;17:23-30.
204. Kirschke DL, Jones TF, Buckingham SC, et al. Outbreak of aseptic meningitis 234. Logar M, Arnez M, Kolbl J, et al. Comparison of the epidemiological and clinical
associated with echovirus 13. Pediatr Infect Dis J. 2002;21:1034-1038. features of tick-borne encephalitis in children and adults. Infection. 2000;28:74-77.
205. Kitai I, Navas L, Rohlicek C, et al. Recurrent aseptic meningitis secondary to 235. Logotheti M, Pogka V, Horefti E, et al. Laboratory investigation and phylogenetic
an intracranial cyst: a case report and review of clinical features and imaging analysis of enteroviruses involved in an aseptic meningitis outbreak in Greece
modalities. Pediatr Infect Dis J. 1992;11:671-675. during the summer of 2007. J Clin Virol. 2009;46:270-274.
206. Klein NC, McDermott B, Cunha BA. Varicella-zoster virus meningoencephalitis in 236. Lu J, Zheng H, Guo X, et al. Elucidation of echovirus 30’s origin and transmission
an immunocompetent patient without a rash. Scand J Infect Dis. 2010;42:631-633. during the 2012 aseptic meningitis outbreak in Guangdong, China, through
207. Kleines M, Scheithauer S, Schiefer J, et al. Clinical application of viral cerebrospinal continuing environmental surveillance. Appl Environ Microbiol. 2015;81:2311-2319.
fluid PCR testing for diagnosis of central nervous system disorders: a retrospective 237. Ma E, Chan KC, Cheng P, et al. The enterovirus 71 epidemic in 2008: public
11-year experience. Diagn Microbiol Infect Dis. 2014;80:207-215. health implications for Hong Kong. Int J Infect Dis. 2010;14:e775-e780.
208. Knust B, Macneil A, Wong SJ, et al. Exposure to lymphocytic choriomeningitis 238. Mantadakis E, Pogka V, Voulgari-Kokota A, et al. Echovirus 30 outbreak associ-
virus, New York, USA. Emerg Infect Dis. 2011;17:1324-1325. ated with a high meningitis attack rate in Thrace, Greece. Pediatr Infect Dis J.
209. Kochar DK, Agarwal N, Jain N, et al. Clinical profile of neurobrucellosis: a 2013;32:914-916.
report on 12 cases from Bikaner (north-west India). J Assoc Physicians India. 239. Mao N, Zhao L, Zhu Z, et al. An aseptic meningitis outbreak caused by echovirus
2000;48:376-380. 6 in Anhui province, China. J Med Virol. 2010;82:441-445.
210. Kondo K, Nagafuji H, Hata A, et al. Association of human herpesvirus 6 infection 240. Mardh PA. Mycoplasma hominis infection of the central nervous system in
of the central nervous system with recurrence of febrile convulsions. J Infect newborn infants. Sex Transm Dis. 1983;10:331-334.
Dis. 1993;167:1197-1200. 241. Markey PG, Davis JS, Harnett GB, et al. Meningitis and a febrile vomiting illness
211. Kriss TC, Kriss VM, Warf BC. Recurrent meningitis: the search for the dermoid caused by echovirus type 4, Northern Territory, Australia. Emerg Infect Dis.
or epidermoid tumor. Pediatr Infect Dis J. 1995;14:697-700. 2010;16:63-68.
212. Kumar A, Shukla D, Kumar R, et al. Molecular identification of enteroviruses associ- 242. Martin MA, Massanari RM, Nghiem DD, et al. Nosocomial aseptic meningitis
ated with aseptic meningitis in children from India. Arch Virol. 2013;158:211-215. associated with administration of OKT3. JAMA. 1988;259:2002-2005.
213. Kupila L, Vainionpaa R, Vuorinen T, et al. Recurrent lymphocytic meningitis: 243. Martinez AA, Castillo J, Sanchez MC, et al. Molecular diagnosis of echovirus
the role of herpesviruses. Arch Neurol. 2004;61:1553-1557. 30 as the etiological agent in an outbreak of aseptic meningitis in Panama:
214. Laforest RA, McNaughton GA, Beale AJ, et al. Outbreak of aseptic meningitis May–June 2008. J Infect Dev Ctries. 2012;6:836-841.
(meningoencephalitis) with rubelliform rash: Toronto, 1956. Can Med Assoc J. 244. Mathisen G, Shelub A, Truong J, et al. Coccidioidal meningitis: clinical presentation
1957;77:1-4. and management in the fluconazole era. Medicine (Baltimore). 2010;89:251-284.
215. Lanciotti RS, Kerst AJ, Nasci RS, et al. Rapid detection of West Nile virus 245. McDonald JC, Moore DL, Quennec P. Clinical and epidemiologic features of
from human clinical specimens, field-collected mosquitoes, and avian samples mumps meningoencephalitis and possible vaccine-related disease. Pediatr Infect
by a TaqMan reverse transcriptase-PCR assay. J Clin Microbiol. 2000;38: Dis J. 1989;8:751-755.
4066-4071. 246. McJunkin JE, de los Reyes EC, Irazuzta JE, et al. La Crosse encephalitis in children.
216. Leahy TR, Webb DW, Hoey H, et al. Varicella zoster virus associated acute aseptic N Engl J Med. 2001;345:148-149.
meningitis without exanthem in an immunocompetent 14-year-old boy. Pediatr 247. McMinn P, Stratov I, Nagarajan L, et al. Neurological manifestations of enterovirus
Infect Dis J. 2008;27:362-363. 71 infection in children during an outbreak of hand, foot, and mouth disease
217. Lecour H, Miranda M, Magro C, et al. Human leptospirosis: a review of 50 in Western Australia. Clin Infect Dis. 2001;32:236-242.
cases. Infection. 1989;17:8-12. 248. Meyer HM Jr, Johnson RT, Crawford IP, et al. Central nervous system syndromes
218. Lee KE, Umapathi T, Tan CB, et al. The neurological manifestations of Nipah of “vital” etiology: a study of 713 cases. Am J Med. 1960;29:334-347.
virus encephalitis, a novel paramyxovirus. Ann Neurol. 1999;46:428-432. 249. Mifsud AJ. Drug-related recurrent meningitis. J Infect. 1988;17:151-153.
219. Lennette EH, Magoffin RL, Knouf EG. Viral central nervous system disease: an 250. Milia MG, Cerutti F, Gregori G, et al. Recent outbreak of aseptic meningitis in
etiologic study conducted at the Los Angeles County General Hospital. JAMA. Italy due to echovirus 30 and phylogenetic relationship with other European
1962;179:687-695. circulating strains. J Clin Virol. 2013;58:579-583.
220. Lepow ML, Carver DH, Wright HT Jr, et al. A clinical, epidemiologic and 251. Miller HG, Gibbons JL, Stanton JB. Para-infectious encephalomyelitis and related
laboratory investigation of aseptic meningitis during the four-year period, syndromes; a critical review of the neurological complications of certain specific
1955–1958. I. Observations concerning etiology and epidemiology. N Engl J fevers. Q J Med. 1956;25:427-505.
Med. 1962;266:1181-1187. 252. Miller E, Goldacre M, Pugh S, et al. Risk of aseptic meningitis after measles,
221. Lepow ML, Coyne N, Thompson LB, et al. A clinical, epidemiologic and laboratory mumps, and rubella vaccine in UK children. Lancet. 1993;341:979-982.
investigation of aseptic meningitis during the four-year period, 1955–1958. II. 253. Miller HG, Stanton JB. Neurological sequelae of prophylactic inoculation. Q J
The clinical disease and its sequelae. N Engl J Med. 1962;266:1188-1193. Med. 1954;23:1-27.
222. Lesnicar G, Poljak M, Seme K, et al. Pediatric tick-borne encephalitis in 371 254. Mladenova Z, Buttinelli G, Dikova A, et al. Aseptic meningitis outbreak caused
cases from an endemic region in Slovenia, 1959 to 2000. Pediatr Infect Dis J. by echovirus 30 in two regions in Bulgaria, May–August 2012. Epidemiol Infect.
2003;22:612-617. 2014;142:2159-2165.
223. Leveque N, Jacques J, Renois F, et al. Phylogenetic analysis of Echovirus 30 isolated 255. Molavi A, LeFrock JL. Tuberculous meningitis. Med Clin North Am. 1985;69:315-331.
during the 2005 outbreak in France reveals existence of multiple lineages and 256. Mollaret P. La meningite endothelio-leukocytaire multirecurrente benigne:
suggests frequent recombination events. J Clin Virol. 2010;48:137-141. syndrome nouveau ou maladie nouvelle? Rev Neurol. 1944;72:57-76.
257. Moon JH, Na JY, Kim JH, et al. Neurological and muscular manifestations 291. Prieto-Gonzalez S, Escoda R, Coloma E, et al. Amoxicillin-induced acute aseptic
associated with influenza B infection in children. Pediatr Neurol. 2013;49:97-101. meningitis. J Clin Neurosci. 2011;18:443-444.
258. Moore M. Centers for Disease Control. Enteroviral disease in the United States, 292. Rafailidis PI, Kapaskelis A, Falagas ME. Cytomegalovirus meningitis in an
1970–1979. J Infect Dis. 1982;146:103-108. immunocompetent patient. Med Sci Monit. 2007;13:CS107-CS109.
259. Moylett EH. Neonatal Candida meningitis. Semin Pediatr Infect Dis. 293. Rafailidis PI, Mourtzoukou EG, Varbobitis IC, et al. Severe cytomegalovirus
2003;14:115-122. infection in apparently immunocompetent patients: a systematic review. Virol
260. Mulford WS, Buller RS, Arens MQ, et al. Correlation of cerebrospinal (CSF) cell J. 2008;5:47.
counts and elevated CSF protein levels with enterovirus reverse transcription-PCR 294. Ramers C, Billman G, Hartin M, et al. Impact of a diagnostic cerebrospinal
results in pediatric and adult patients. J Clin Microbiol. 2004;42:4199-4203. fluid enterovirus polymerase chain reaction test on patient management. JAMA.
261. Mullane D, Williams L, Merwick A, et al. Drug induced aseptic meningitis caused 2000;283:2680-2685.
by intravenous immunoglobulin therapy. Ir Med J. 2012;105:182-183. 295. Ramirez-Avila L, Slome S, Schuster FL, et al. Eosinophilic meningitis due to
262. Muller MP, Richardson DC, Walmsley SL. Trimethoprim-sulfamethoxazole induced Angiostrongylus and Gnathostoma species. Clin Infect Dis. 2009;48:322-327.
aseptic meningitis in a renal transplant patient. Clin Nephrol. 2001;55:80-84. 296. Rao SP, Teitlebaum J, Miller ST. Intravenous immune globulin and aseptic
263. Mullins JA, Khetsuriani N, Nix WA, et al. Emergence of echovirus type 13 as a meningitis. Am J Dis Child. 1992;146:539-540.
prominent enterovirus. Clin Infect Dis. 2004;38:70-77. 297. Rasmussen AF. The laboratory diagnosis of lymphocytic choriomeningitis and
264. Nagai T, Okafuji T, Miyazaki C, et al. A comparative study of the incidence of mumps. In: Rocky Mountain Conference on Infantile Paralysis. Denver: University
aseptic meningitis in symptomatic natural mumps patients and monovalent of Colorado School of Medicine; 1946:45.
mumps vaccine recipients in Japan. Vaccine. 2007;25:2742-2747. 298. Rawal A, Gavin PJ, Sturgis CD. Cerebrospinal fluid cytology in seasonal
265. Narkeviciute I, Vaiciuniene D. Outbreak of echovirus 13 infection among Lithu- epidemic West Nile virus meningo-encephalitis. Diagn Cytopathol. 2006;34:
anian children. Clin Microbiol Infect. 2004;10:1023-1025. 127-129.
266. Nash D, Mostashari F, Fine A, et al. The outbreak of West Nile virus infection 299. Reeves WC, Quiroz E, Brenes MM, et al. Aseptic meningitis due to echovirus 4
in the New York City area in 1999. N Engl J Med. 2001;344:1807-1814. in Panama City, Republic of Panama. Am J Epidemiol. 1987;125:562-575.
267. Nigrovic LE, Chiang VW. Cost analysis of enteroviral polymerase chain reaction 300. Reimer LG, Beller LB. CSF in herpes zoster meningoencephalitis. Arch Neurol.
in infants with fever and cerebrospinal fluid pleocytosis. Arch Pediatr Adolesc 1981;38:668.
Med. 2000;154:817-821. 301. Reintjes R, Pohle M, Vieth U, et al. Community-wide outbreak of enteroviral
268. Nougairede A, Bessaud M, Thiberville SD, et al. Widespread circulation of a new illness caused by echovirus 30: a cross-sectional survey and a case-control study.
echovirus 30 variant causing aseptic meningitis and non-specific viral illness, Pediatr Infect Dis J. 1999;18:104-108.
South-East France, 2013. J Clin Virol. 2014;61:118-124. 302. Renaud C, Harrison CJ. Human parechovirus 3: the most common cause of
269. Okumura A, Ichikawa T. Aseptic meningitis caused by human parvovirus B19. meningoencephalitis in young infants. Infect Dis Clin North Am. 2015;29:415-428.
Arch Dis Child. 1993;68:784-785. 303. Riski H, Hovi T. Coronavirus infections of man associated with diseases other
270. Ortner B, Huang CW, Schmid D, et al. Epidemiology of enterovirus types causing than the common cold. J Med Virol. 1980;6:259-265.
neurological disease in Austria 1999–2007: detection of clusters of echovirus 30 and 304. Rivers TM, McNair Scott TF. Meningitis in man caused by a filterable virus.
enterovirus 71 and analysis of prevalent genotypes. J Med Virol. 2009;81:317-324. Science. 1935;81:439-440.
271. Ozdemir H, Karbuz A, Ciftci E, et al. Aseptic meningitis in a child due to 2009 305. Romero JR, Newland JG. Viral meningitis and encephalitis: traditional and
pandemic influenza A (H1N1) infection. Turk J Pediatr. 2011;53:91-93. emerging viral agents. Semin Pediatr Infect Dis. 2003;14:72-82.
272. Ozkaya E, Hizel K, Uysal G, et al. An outbreak of aseptic meningitis due to 306. Roos KL. Mycobacterium tuberculosis meningitis and other etiologies of the
echovirus type 30 in two cities of Turkey. Eur J Epidemiol. 2003;18:823-826. aseptic meningitis syndrome. Semin Neurol. 2000;20:329-335.
273. Pahud BA, Glaser CA, Dekker CL, et al. Varicella zoster disease of the central 307. Rosen L, Loison G, Laigret J, et al. Studies on eosinophilic meningitis. III.
nervous system: epidemiological, clinical, and laboratory features 10 years after Epidemiologic and clinical observations on Pacific islands and the possible
the introduction of the varicella vaccine. J Infect Dis. 2011;203:316-323. etiologic role of Angiostrongylus cantonensis. Am J Epidemiol. 1967;85:17-44.
274. Paisley JW, Bruhn FW, Lauer BA, et al. Type A2 influenza viral infections in 308. Rotbart HA. Enteroviral infections of the central nervous system. Clin Infect
children. Am J Dis Child. 1978;132:34-36. Dis. 1995;20:971-981.
275. Panicker JN, Mammachan R, Jayakumar RV. Primary neuroleptospirosis. Postgrad 309. Rotbart HA. Viral meningitis. Semin Neurol. 2000;20:277-292.
Med J. 2001;77:589-590. 310. Rotbart HA, O’Connell JF, McKinlay MA. Treatment of human enterovirus
276. Peltola HO. C-reactive protein for rapid monitoring of infections of the central infections. Antiviral Res. 1998;38:1-14.
nervous system. Lancet. 1982;1:980-982. 311. Rotbart HA, Sawyer MH, Fast S, et al. Diagnosis of enteroviral meningitis by
277. Peltola H, Valmari P, Serum C. reactive protein as detector of pretreated childhood using PCR with a colorimetric microwell detection assay. J Clin Microbiol.
bacterial meningitis. Neurology. 1985;35:251-253. 1994;32:2590-2592.
278. Pena JA, Pirics ML, DiCaprio HS, et al. Varicella reactivation presenting as shingles 312. Rotbart HA, Webster AD. Treatment of potentially life-threatening enterovirus
and aseptic meningitis in an immunocompetent 11-year-old boy. Clin Pediatr infections with pleconaril. Clin Infect Dis. 2001;32:228-235.
(Phila). 2009;48:435-437. 313. Rotem CE. Meningitis of virus origin. Lancet. 1957;272:502-504.
279. Pereira AC, Barros RA, do Nascimento JP, et al. Two family members with a 314. Rothenberg R, Murphy W, O’Brien CL, et al. Aseptic meningitis associated
syndrome of headache and rash caused by human parvovirus B19. Braz J Infect with ECHO virus, type 9: an outbreak in Norfolk, Virginia. South Med J.
Dis. 2001;5:37-39. 1970;63:280-285.
280. Pereira MS, Maccallum FO. Infection with adenovirus type 12. Lancet. 315. Rottach K, Scheglmann K, Pfadenhauer K. Mollaret’s meningitis: a new aetiologic
1964;1:198-199. feature. Eur Neurol. 1996;36:172-173.
281. Perevoscikovs J, Brila A, Firstova L, et al. Ongoing outbreak of aseptic meningitis 316. Sabin AB, Krumbiegel ER, Wigand R. ECHO type 9 virus disease. AMA J Dis
in South-Eastern Latvia, June–August 2010. Euro Surveill. 2010;15:pii:19639. Child. 1958;96:197-219.
282. Peter G. Leptospirosis: a zoonosis of protean manifestations. Pediatr Infect Dis. 317. Salaki JS, Louria DB, Chmel H. Fungal and yeast infections of the central nervous
1982;1:282-288. system: a clinical review. Medicine (Baltimore). 1984;63:108-132.
283. Petersen LR, Marfin AA. West Nile virus: a primer for the clinician. Ann Intern 318. Samuda GM, Chang WK, Yeung CY, et al. Monoplegia caused by enterovirus
Med. 2002;137:173-179. 71: an outbreak in Hong Kong. Pediatr Infect Dis J. 1987;6:206-208.
284. Picard FJ, Dekaban GA, Silva J, et al. Mollaret’s meningitis associated with herpes 319. Sands ML, Ryczak M, Brown RB. Recurrent aseptic meningitis followed by
simplex type 2 infection. Neurology. 1993;43:1722-1727. transverse myelitis as a presentation of systemic lupus erythematosus. J Rheumatol.
285. Pinto Junior VL, Rebelo MC, Costa EV, et al. Description of a widespread outbreak 1988;15:862-864.
of aseptic meningitis due to echovirus 30 in Rio de Janeiro state, Brazil. Braz J 320. Sarmiento L, Mas P, Goyenechea A, et al. First epidemic of echovirus 16 meningitis
Infect Dis. 2009;13:367-370. in Cuba. Emerg Infect Dis. 2001;7:887-889.
286. Platonov AE, Shipulin GA, Shipulina OY, et al. Outbreak of West Nile virus 321. Sato R, Ayabe M, Shoji H, et al. Herpes simplex virus type 2 recurrent meningitis
infection, Volgograd region, Russia, 1999. Emerg Infect Dis. 1999;7:128-132. (Mollaret’s meningitis): a consideration for the recurrent pathogenesis. J Infect.
287. Pohl-Koppe A, Blay M, Jager G, et al. Human herpes virus type 7 DNA in the 2005;51:e217-e220.
cerebrospinal fluid of children with central nervous system diseases. Eur J Pediatr. 322. Sawyer MH, Holland D, Aintablian N, et al. Diagnosis of enteroviral central
2001;160:351-358. nervous system infection by polymerase chain reaction during a large community
288. Pönkä A. Central nervous system manifestations associated with serologi- outbreak. Pediatr Infect Dis J. 1994;13:177-182.
cally verified Mycoplasma pneumoniae infection. Scand J Infect Dis. 1980;12: 323. Schlesinger Y, Sawyer MH, Storch GA. Enteroviral meningitis in infancy:
175-184. potential role for polymerase chain reaction in patient management. Pediatrics.
289. Portolani M, Pecorari M, Pietrosemoli P, et al. Outbreak of aseptic meningitis by 1994;94:157-162.
echo 4: prevalence of clinical cases among adults. New Microbiol. 2001;24:11-15. 324. Schumacher JD, Chuard C, Renevey F, et al. Outbreak of echovirus 30 meningitis
290. Preblud SR. Age-specific risks of varicella complications. Pediatrics. 1981;68:14-17. in Switzerland. Scand J Infect Dis. 1999;31:539-542.
325. Sejvar JJ, Labutta RJ, Chapman LE, et al. Neurologic adverse events associated with 357. Tedder DG, Ashley R, Tyler KL, et al. Herpes simplex virus infection as a cause
smallpox vaccination in the United States, 2002–2004. JAMA. 2003;294:2744-2750. of benign recurrent lymphocytic meningitis. Ann Intern Med. 1994;121:334-338.
326. Shaked Y, Samra Y. Q fever meningoencephalitis associated with bilateral abducens 358. Tena D, Gonzalez-Praetorius A, Lopez-Alonso A, et al. Acute meningitis due to
nerve paralysis, bilateral optic neuritis and abnormal cerebrospinal fluid findings. Brucella spp. Eur J Pediatr. 2006;165:726-727.
Infection. 1989;17:394-395. 359. Terni M, Caccialanza P, Cassai E, et al. Aseptic meningitis in association with
327. Shekhar K, Lye MS, Norlijah O, et al. Deaths in children during an outbreak of herpes progenitalis. N Engl J Med. 1971;285:503-504.
hand, foot and mouth disease in Peninsular Malaysia: clinical and pathological 360. Thoelen I, Lemey P, Van Der Donck I, et al. Molecular typing and epidemiology
characteristics. Med J Malaysia. 2005;60:297-304. of enteroviruses identified from an outbreak of aseptic meningitis in Belgium
328. Shimizu H, Utama A, Yoshii K, et al. Enterovirus 71 from fatal and nonfatal cases during the summer of 2000. J Med Virol. 2003;70:420-429.
of hand, foot and mouth disease epidemics in Malaysia, Japan and Taiwan in 361. Thoren A, Widell A. PCR for the diagnosis of enteroviral meningitis. Scand J
1997–1998. Jpn J Infect Dis. 1999;52:12-15. Infect Dis. 1994;26:249-254.
329. Shinohara M, Uchida K, Shimada S, et al. [Characterization of enterovirus type 71 362. Trallero G, Casas I, Avellon A, et al. First epidemic of aseptic meningitis due to
isolated in Saitama Prefecture in 2000]. Kansenshogaku Zasshi. 2001;75:490-494. echovirus type 13 among Spanish children. Epidemiol Infect. 2003;130:251-256.
330. Simila S, Jouppila R, Salmi A, et al. Encephaloningitis in children associated 363. Tsai HP, Huang SW, Wu FL, et al. An echovirus 18-associated outbreak of aseptic
with an adenovirus type 7 epidemic. Acta Paediatr Scand. 1970;59:310-316. meningitis in Taiwan: epidemiology and diagnostic and genetic aspects. J Med
331. Simms KM, Kortepeter C, Avigan M. Lamotrigine and aseptic meningitis. Microbiol. 2011;60:1360-1365.
Neurology. 2012;78:921-927. 364. Tsai TF, Popovici F, Cernescu C, et al. West Nile encephalitis epidemic in
332. Singer JI, Maur PR, Riley JP, et al. Management of central nervous system infections southeastern Romania. Lancet. 1998;352:767-771.
during an epidemic of enteroviral aseptic meningitis. J Pediatr. 1980;96:559-563. 365. Tsiodras S, Kelesidis I, Kelesidis T, et al. Central nervous system manifestations
333. Sköldenberg B. On the role of viruses in acute infectious diseases of the central of Mycoplasma pneumoniae infections. J Infect. 2005;51:343-354.
nervous system: clinical and laboratory studies on hospitalized patients. Scand 366. Tsutsumi H, Kamazaki H, Nakata S, et al. Sequential development of acute
J Infect Dis. 1975;3:5-95. meningoencephalitis and transverse myelitis caused by Epstein-Barr virus during
334. Sköldenberg B, Jeansson S, Wolontis S. Herpes simplex virus type 2 and acute infectious mononucleosis. Pediatr Infect Dis J. 1994;13:665-667.
aseptic meningitis: clinical features of cases with isolation of herpes simplex 367. Turabelidze G, Lin M, Butler C, et al. Outbreak of echovirus 18 meningitis in
virus from cerebrospinal fluids. Scand J Infect Dis. 1975;7:227-232. a rural Missouri community. Mo Med. 2009;106:420-424.
335. Socan M, Beovic B, Kese D. Chlamydia pneumonia and meningoencephalitis. 368. Tyler KL. Herpes simplex virus infections of the central nervous system: encephalitis
N Engl J Med. 1994;331:406. and meningitis, including Mollaret’s. Herpes. 2004;11(suppl 2):57A-64A.
336. Socan M, Ravnik I, Bencina D, et al. Neurological symptoms in patients whose 369. Ushijima H, Xin KQ, Nishimura S, et al. Detection and sequencing of rotavirus
cerebrospinal fluid is culture- and/or polymerase chain reaction-positive for VP7 gene from human materials (stools, sera, cerebrospinal fluids, and throat
Mycoplasma pneumoniae. Clin Infect Dis. 2001;32:E31-E35. swabs) by reverse transcription and PCR. J Clin Microbiol. 1994;32:2893-2897.
337. Sohier R, Chardonnet Y, Prunieras M. Adenoviruses. Status of current knowledge. 370. Uysal G, Ozkaya E, Guven A. Echovirus 30 outbreak of aseptic meningitis in
Prog Med Virol. 1965;7:253-325. Turkey. Pediatr Infect Dis J. 2000;19:490.
338. Somekh E, Cesar K, Handsher R, et al. An outbreak of echovirus 13 meningitis 371. Vergnano S, Kadambari S, Whalley K, et al. Characteristics and outcomes of
in central Israel. Epidemiol Infect. 2003;130:257-262. human parechovirus infection in infants (2008–2012). Eur J Pediatr. 2015;
339. Somekh E, Shohat T, Handsher R, et al. An outbreak of echovirus 11 in a children’s 174:919-924.
home. Epidemiol Infect. 2001;126:441-444. 372. Vieth UC, Kunzelmann M, Diedrich S, et al. An echovirus 30 outbreak with a
340. Sosa LE, Gupta S, Juthani-Mehta M, et al. Meningitis in a college student in high meningitis attack rate among children and household members at four
Connecticut, 2007. J Am Coll Health. 2009;58:12-14. day-care centers. Eur J Epidemiol. 1999;15:655-658.
341. Southern PM Jr. Relapsing fever. In: Tice F, ed. Practice of medicine. Vol. 3. 373. Vreede RW, Schellekens H, Zuijderwijk M. Isolation of parainfluenza virus type
Scranton, PA: Hoeber Medical Div., Harper & Row; 1969:1-19. 3 from cerebrospinal fluid. J Infect Dis. 1992;165:1166.
342. Spiegel R, Miron D, Lumelsky D, et al. Severe meningoencephalitis due to late 374. Waespe N, Steffen I, Heininger U. Etiology of aseptic meningitis, peripheral
reactivation of varicella-zoster virus in an immunocompetent child. J Child facial nerve palsy, and a combination of both in children. Pediatr Infect Dis J.
Neurol. 2010;25:87-90. 2010;29:453-456.
343. Spillane JD, Wells CE. The neurology of Jennerian vaccination. a clinical account 375. Waites KB, Duffy LB, Crouse DT, et al. Mycoplasmal infections of cerebrospinal
of the neurological complications which occurred during the smallpox epidemic fluid in newborn infants from a community hospital population. Pediatr Infect
in South Wales in 1962. Brain. 1964;87:1-44. Dis J. 1990;9:241-245.
344. Srihongse S, Grayson MA, Deibel R. California serogroup viruses in New York State: 376. Waites KB, Rudd PT, Crouse DT, et al. Chronic Ureaplasma urealyticum and
the role of subtypes in human infections. Am J Trop Med Hyg. 1984;33:1218-1227. Mycoplasma hominis infections of central nervous system in preterm infants.
345. Steel JG, Dix RD, Baringer JR. Isolation of herpes simplex virus type I in recurrent Lancet. 1988;1:17-21.
(Mollaret) meningitis. Ann Neurol. 1982;11:17-21. 377. Wallach JC, Baldi PC, Fossati CA. Clinical and diagnostic aspects of relaps-
346. Stellrecht KA, Harding I, Woron AM, et al. The impact of an enteroviral RT-PCR ing meningoencephalitis due to Brucella suis. Eur J Clin Microbiol Infect Dis.
assay on the diagnosis of aseptic meningitis and patient management. J Clin 2002;21:760-762.
Virol. 2002;25(suppl 1):S19-S26. 378. Wallgren A. Une nouvelle maladie infectieuse du système nerveux central? Acta
347. Sumaya CV, Corman LI. Enteroviral meningitis in early infancy: significance in Paediatr Scand. 1925;4:158-182.
community outbreaks. Pediatr Infect Dis. 1982;1:151-154. 379. Wallgren A. [Etiology of meningoencephalitis in children, especially the syndrome
348. Sumaya CV, Ench Y. Epstein-Barr virus infectious mononucleosis in children. of acute aseptic meningitis]. Acta Paediatr. 1951;40:541-565.
I. Clinical and general laboratory findings. Pediatrics. 1985;75:1003-1010. 380. Wang SM, Ho TS, Shen CF, et al. Echovirus 18 meningitis in southern Taiwan.
349. Sundelof B, Gnarpe H, Gnarpe J. An unusual manifestation of Chlamydia Pediatr Infect Dis J. 2011;30:259-260.
pneumoniae infection: meningitis, hepatitis, iritis and atypical erythema nodosum. 381. Wang JR, Tsai HP, Chen PF, et al. An outbreak of enterovirus 71 infection in Taiwan,
Scand J Infect Dis. 1993;25:259-261. 1998. II. Laboratory diagnosis and genetic analysis. J Clin Virol. 2000;17:91-99.
350. Suzuki N, Terada S, Inoue M. Neonatal meningitis with human parvovirus B19 382. Wang JR, Tsai HP, Huang SW, et al. Laboratory diagnosis and genetic analysis
infection. Arch Dis Child Fetal Neonatal Ed. 1995;73:F196-F197. of an echovirus 30-associated outbreak of aseptic meningitis in Taiwan in 2001.
351. Syrogiannopoulos GA, Grivea IN, Anastassiou ED, et al. Sterile cerebrospinal J Clin Microbiol. 2002;40:4439-4444.
fluid pleocytosis in young infants with urinary tract infection. Pediatr Infect Dis 383. Warren J. Encephalomyocarditis viruses. In: Horsfall FL, Tamm I, eds. Viral and
J. 2001;20:927-930. rickettsial infections of man. Philadelphia: J. B. Lippincott; 1965:562-568.
352. Syverton JT, McLean DM, Martins Da Silva M, et al. Outbreak of aseptic meningitis 384. Weller TH. Varicella-Herpes zoster virus. In: Evans AS, ed. Viral infections
caused by coxsackie B5 virus; laboratory, clinical, and epidemiologic study. JAMA. of humans: epidemiology and control. 2nd ed. New York: Plenum Medical;
1957;164:2015-2019. 1982:569-595.
353. Tang YW, Cleavinger PJ, Li H, et al. Analysis of candidate-host immunogenetic 385. Weller PF. Eosinophilic meningitis. Am J Med. 1993;95:250-253.
determinants in herpes simplex virus-associated Mollaret’s meningitis. Clin Infect 386. Wickman I. Studien über poliomyelitis acuta: Zugleich ein beitrag zur kenntnis
Dis. 2000;30:176-178. der myelitis acuta. Engl Trans Nev Ment Dis Monog. 1905;16:1913.
354. Tao Z, Song Y, Li Y, et al. Coxsackievirus B3, Shandong Province, China 1990–2010. 387. Wilfert CM, Lehrman SN, Katz SL. Enteroviruses and meningitis. Pediatr Infect
Emerg Infect Dis. 2012;18:1865-1867. Dis. 1983;2:333-341.
355. Tavakoli NP, Wang H, Nattanmai S, et al. Detection and typing of enteroviruses 388. Wilfert CM, Thompson RJ Jr, Sunder TR, et al. Longitudinal assessment of
from CSF specimens from patients diagnosed with meningitis/encephalitis. J children with enteroviral meningitis during the first three months of life. Pediatrics.
Clin Virol. 2008;43:207-211. 1981;67:811-815.
356. Tayal S, Chadwick D, Chawla G. Considering syphilis in aseptic meningitis. Clin 389. Williams CL, Strobino B, Lee A, et al. Lyme disease in childhood: clinical and
Med. 2009;9:626-627. epidemiologic features of ninety cases. Pediatr Infect Dis J. 1990;9:10-14.
390. Wong JG, Hathaway SC, Paat JJ, et al. Drug-induced meningitis: a case involving 396. Yang XH, Yan YS, Weng YW, et al. Molecular epidemiology of echovirus 30 in
trimethoprim-sulfamethoxazole. Postgrad Med. 1994;96:117-118, 121, 124. Fujian, China between 2001–2011. J Med Virol. 2013;85:696-702.
391. Wong ML, Kaplan S, Dunkle LM, et al. Leptospirosis: a childhood disease. J 397. Yerly S, Gervaix A, Simonet V, et al. Rapid and sensitive detection of enteroviruses in
Pediatr. 1977;90:532-537. specimens from patients with aseptic meningitis. J Clin Microbiol. 1996;34:199-201.
392. Wong CJ, Price Z, Bruckner DA. Aseptic meningitis in an infant with rotavirus 398. Yildizdas D, Kendirli T, Arslankoylu AE, et al. Neurological complications of
gastroenteritis. Pediatr Infect Dis. 1984;3:244-246. pandemic influenza (H1N1) in children. Eur J Pediatr. 2011;170:779-788.
393. Yan JJ, Wang JR, Liu CC, et al. An outbreak of enterovirus 71 infection in Taiwan 399. Yoshikawa T, Ihira M, Suzuki K, et al. Invasion by human herpesvirus 6 and
1998: a comprehensive pathological, virological, and molecular study on a case human herpesvirus 7 of the central nervous system in patients with neurological
of fulminant encephalitis. J Clin Virol. 2000;17:13-22. signs and symptoms. Arch Dis Child. 2000;83:170-171.
394. Yanagihara K, Tanaka-Taya K, Itagaki Y, et al. Human herpesvirus 6 meningo- 400. Young EJ. Human brucellosis. Rev Infect Dis. 1983;5:821-842.
encephalitis with sequelae. Pediatr Infect Dis J. 1995;14:240-242. 401. Zhao YN, Jiang QW, Jiang RJ, et al. Echovirus 30, Jiangsu Province, China. Emerg
395. Yang TT, Huang LM, Lu CY, et al. Clinical features and factors of Infect Dis. 2005;11:562-567.
unfavorable outcomes for non-polio enterovirus infection of the central 402. Zielicka-Hardy A, Rosinska M, Kondrusik M, et al. Predictors for diagnosis
nervous system in northern Taiwan, 1994–2003. J Microbiol Immunol Infect. of tick-borne encephalitis infection in Poland, 2009–2010. Infect Dis (Lond).
2005;38:417-424. 2015;47:604-610.

Aseptic Meningitis and Viral Meningitis

Hochgeladen von

Dokumentinformationen

Copyright

Verfügbare Formate

Dieses Dokument teilen

Dokument teilen oder einbetten

Freigabeoptionen

Stufen Sie dieses Dokument als nützlich ein?

Sind diese Inhalte unangemessen?

Copyright:

Verfügbare Formate

Aseptic Meningitis and Viral Meningitis

Hochgeladen von

Copyright:

Verfügbare Formate

CHAPTER 35 Aseptic Meningitis and Viral Meningitis 355