Aseptic Meningitis Syndrome Research Articles

Virological studies of summer exanthems.

Each summer many patients, predominantly in the pediatric age group, presenting benign exanthems, clearly not rubeola, varicella, or herpes simplex, are seen in the outpatient department, accident floor, and wards of this hospital. These illnesses are usually ascribed to household chemicals, parasites, heat, or medications. We were stimulated to study these eruptions because multiple cases seemed to occur over relatively short periods in families and in the community, suggesting a possible infectious origin. Several years before the initiation of this study Neva and Enders 1 isolated a virus from the feces of patients with so-called Boston exanthem; this virus was later classified as ECHO 16, 2 but most of the other enteroviruses associated with rashes were reported in patients with the aseptic meningitis syndrome. 3 The present study represents an attempt to relate some of these summer rashes to various viral infections * known to be prevalent during the summer months

AN EPIDEMIC OF ASEPTIC MENINGITIS SYNDROME DUE TO ECHO VIRUS TYPE 6

The clinical features of 130 cases of aseptic meningitis syndrome associated with ECHO virus type 6 infection were studied. Characteristically, the onset was acute with the development of fever, headache, muscle pains, and vomiting. A biphasic course was present in 8% of the cases. The physical findings included mild to moderate stiffness or spasm of the neck, back, and posterior thigh muscles. Disturbance in sensorium, cranial nerve involvement, and bulbar signs were conspicuously absent. Absence of deep tendon and superficial reflexes occurred in 16% of the cases. Evidence of mild muscle weakness occurred in 39% of cases, more commonly in the axial rather than peripheral muscles. Most of these patients had bilateral weakness of the anterior neck muscles, but included in the group were five with bilateral weakness of the back or abdominal muscles and six with some involvement of the extremities. Neuromuscular changes were mild and frequently questionable. Where follow-up was available, the changes were usually found to be transient. The effect of age upon the clinical picture was analyzed. Only 3 of 130 patients were less than 4 years of age. Young children had a more acute onset and were admitted to the hospital more promptly than older children and adults. The incidence of pleurodynia was 38% in adults and only 5% in patients less than 20 years of age. The cerebrospinal fluid revealed pleocytosis, with lymphocyte counts ranging from a few cells to 930/mm3. The protein values exceeded 40 mg/100 ml in 48% of the cases, the highest value being 102 mg/100 ml. An undifferentiated febrile illness in household associates of patients with aseptic meningitis, characterized by headache, vomiting and muscle pain, was associated with a high recovery rate of ECHO 6 virus. This is presumably the forme fruste of the fully developed aseptic meningitis syndrome. ECHO 6 virus was recovered from four patients in whom there was evidence of neurologic involvement beyond that seen in the aseptic meningitis syndrome. ECHO 6 virus was the probable etiologic agent in two of these cases. A 15-year-old girl with mild encephalitis marked by disorientation, hallucinations, and weakness of the legs yielded ECHO 6 from her alimentary tract. ECHO 6 was recovered from the cerebrospinal fluid and alimentary tract of a 15-year-old boy with features of the Guillain-Barré syndrome.

AN EPIDEMIC OF ASEPTIC MENINGITIS SYNDROME DUE TO ECHO VIRUS TYPE 6

Ninety-three patients with aseptic meningitis syndrome due to ECHO virus type 6 were evaluated 3 years following their acute infection to determine the extent of neuromuscular residua. In addition, 9 patients with aseptic meningitis due to other enteroviruses and 19 patients with paralytic poliomyelitis were similarly evaluated. Forty-four individuals with no history of central nervous system disease were studied for comparison. Residua following aseptic meningitis were minimal and fell into two categories: 1. Approximately 20% gave a history of minor changes in behavior, easy fatigability, headaches or pain, stiffness or subjective weakness of the back or legs, the onsets of which were associated with the acute illness. 2. On examination approximately 25% revealed subtle neuromuscular changes such as altered reflexes, minor weaknesses in anterior neck or trunk muscles, or slight skeletal abnormalities, particularly scoliosis. The group with no history of central nervous system disease demonstrated an appreciable, but somewhat lesser, incidence of minor neuromuscular changes, further tending to minimize the specific significance of the findings in the study group.

ECHO 9 VIRUS INFECTION AND CONGENITAL ABNORMALITIES: A NEGATIVE REPORT

Approximately 200,000 residents of Hennepin and Ramsey counties in Minnesota developed an aseptic meningitis syndrome during the summer and fall of 1957. One fourth of the patients had a maculopapular rash very similar to that of rubella. The etiologic agent was found to be ECHO virus type 9. This epidemic provided an opportunity to determine whether infection with this virus during the first trimester of pregnancy could be related to the appearance of congenital defects such as occurs in rubella. From March 3 through June 13, 1958, 10,109 liveborn infants and 105 stillborn infants were delivered in the 12 Minneapolis and 10 St. Paul hospitals serving these two counties. All mothers had been exposed to the 1957 epidemic. Public health nurses interviewed 9,990 mothers in the hospitals within a few days after birth for detailed histories of infection during pregnancy. On the basis of these interviews it was judged that 6.5% of the mothers had historic evidence of an ECHO 9 infection during pregnancy. Serologic evidence of ECHO 9 infection in the recent past was present in 19% of 853 antibody titrations carried out on cord blood specimens from abnormals and normals (controls). To discover anomalies not recognized at birth, a follow-up was carried out 11 to 12 months later by the public health nurses by telephone interviews of some 9,600 mothers. There were 356 major and minor congenital anomalies recognized during the first year of life. An additional 63 hernias were diagnosed during the first year for a total of 419 anomalies found in 10,109 live births in the study. This rate of 41.4 total anomalies per 1,000 live births, or 4.1%, is well within the rates reported by other authors. A total of 39.6% of the anomalies were diagnosed at birth and 60.4% during the first year of life. Of the anomalies, 61% occurred in males and 39% in females; 1.5% of the infants had major abnormalities and 0.74% died as a result of these anomalies during their first year of life. There were 105 stillbirths recorded, or 10.4 per 1,000 live births. This compares with a rate of 13.6 for Hennepin and Ramsey counties for the year. Among the stillbirths, 11.4% died from congenital anomalies, in comparison with 10.95% statewide for the year. A statistical analysis of the findings which compares the ECHO 9 antibody titer distributions in the cord blood of the normal and the abnormal infants does not justify the conclusion that ECHO 9 infection in the mother increases the incidence of congenital anomalies in the offspring. The only exception to this generalization is in the case of skin abnormalities, where there is a statistical suggestion of association.

An etiologic study of seasonal aseptic meningitis and encephalitis in the Central Valley of California.

Comment and Summary The results of this inquiry indicated that illnesses reported as encephalitis to health departments in the Central Valley of California covered a broad spectrum of syndromes ranging from frank severe encephalitis to mild meningitic illness with no definite signs of cerebral involvement. Of 153 illnesses observed during three consecutive summers and recorded as cases of encephalitis in official morbidity records, unequivocal encephalitic manifestations were noted in approximately 30%, and borderline encephalitic signs in an additional 22%. In the entire group of reported encephalitis cases, group B Coxsackie virus and WEE virus infections were encountered with equal frequency, although each virus was associated with only 14% of the cases. Mumps, ECHO, SLE, and herpes simplex viruses, in declining order of frequency, were each associated with a lesser number of illnesses, but in 40% of the cases no viral infection was established. When only the illnesses classified unequivocally as encephalitis were considered, however, the proportion attributed to WEE virus increased to 35%; Coxsackie virus infection was associated with 13%, and other virus infections were encountered in less than 10% of the cases. In the cases of doubtful encephalitis, the mumps virus was implicated most frequently (25%) followed by Coxsackie B virus (11%), WEE virus (8%), and SLE virus (3%). In illnesses classified as aseptic meningitis with no signs of encephalitic involvement, group B Coxsackie and polioviruses were the agents most frequently encountered (each in 16%) followed by ECHO (10%), mumps (7%) and WEE (4%). In each clinical category, no viral infection was established in 35 to 45% of the cases. There was appreciable variation in these proportions from year to year, but in each year the arthropod-borne viruses, WEE and SLE together, were implicated most often in cases classified as frank encephalitis, and Coxsackie group B viruses equaled or exceeded the mumps virus in such illnesses. Of the other enteroviruses, an ECHO virus (type undetermined) was associated in only one instance, and poliovirus not at all, with frank encephalitis. Inasmuch as the role of group B Coxsackie viruses as causal agents of aseptic meningitis is well established,7,9 the association of these viruses with 12 to 19% of such illnesses each year is believed to be a reasonable approximation of their relative etiologic importance in the endemic occurrence of this syndrome in the particular localities and seasons represented in this study. While the frank encephalitic illness observed in association with group B Coxsackie viruses in this study could reflect the occurrence of coincidental infections in persons whose illness was due to other unrecognized causes, the probability of an etiologic association may be supported on several grounds: (1) the frequency of association of group B Coxsackie viruses with encephalitic illness equaled or exceeded that of other commonly recognized encephalitogenic viruses including mumps and herpes simplex, and was exceeded only by WEE virus; (2) the consistency of such association over three consecutive summer periods; (3) the lack of a similar association of poliovirus or ECHO viruses with encephalitis, although both of the latter were associated with other illnesses in the areas under study and could have been present in coincidental alimentary infections; (4) the occurrence of rises in titer of neutralising antibody to Coxsackie virus, indicating a temporal relationship of the infection to the encephalitic illness; and (5) the concentration in infants and young children of encephalitic illness associated with Coxsackie viruses. It appears reasonable to conclude that perhaps 10 to 15% or more of the incidence of summer illnesses reported as encephalitis from the California Central Valley in recent years may have been attributable to Coxsackie group B viruses. Although the majority of the reported cases of encephalitis found to be associated with a Coxsackie virus infection could more appropriately be classified as an aseptic meningitis syndrome, group B Coxsackie viruses may also have accounted for possibly 10 to 15% of the frank encephalitic illnesses. Poliovirus and ECHO viruses were also implicated in about 15% of the cases reported as encephalitis, but on review these cases were almost uniformly classified clinically as aseptic meningitis or doubtful encephalitis. Despite the implication of enteroviruses in over one-fourth of the cases of reported encephalitis, there still remained roughly one-fourth of the cases in which both virus isolation attempts and serologic tests failed to establish a possible viral etiology.

Effectiveness of Salk vaccine in reducing nonparalytic poliomyelitis in a large urban epidemic.

IN the 1954 field trial with poliomyelitis vaccine1 and in subsequent outbreaks of poliomyelitis2 3 4 5 6 the Salk vaccine was shown to be highly effective in reducing the incidence of paralytic poliomyelitis. Although it might be expected theoretically, evidence for a comparable effectiveness against nonparalytic poliomyelitis was not described. Kansas City, Missouri, had a severe poliomyelitis epidemic in 1959 that was carefully investigated. Etiologic studies were performed in four fifths of the cases. The majority of the reported paralytic and nonparalytic cases were proved to be due to poliovirus Type 1 infection. Other enterovirus infections were associated with the aseptic-meningitis syndrome in . . .

Aseptic meningitis and nonparalytic poliomyelitis.

The association of enteroviruses with the aseptic meningitis syndrome has been not only of academic interest, but has also offered the clinician an additional buffer against hysteria in his practice. The wide-spread publicity given poliomyelitis in the past 2 decades has raised the sensitivity of both the lay public and physicians to a hyperactive state when the diagnosis of poliomyelitis is considered. Certainly everyone appreciates and respects the seriousness of this disease in the paralytic form. However, when there is no evidence of weakness, but a tentative diagnosis of poliomyelitis is made, a chain reaction is frequently encountered similar to that when the patient does have paralytic disease. The hospital and physicians are then bombarded with questions from various persons or groups who were even in the remote vicinity of the patient. Obviously many patients in the past who had been reported as nonparalytic poliomyelitis in reality had other