OBJECTIVE:To determine if there is evidence for a causal relationship between acute encephalopathy followed by permanent brain injury or death associated with the administration of further attenuated measles vaccines (Attenuvax or Lirugen, Hoechst Marion Roussel, Kansas City, MO), mumps vaccine (Mumpsvax, Merck and Co, Inc, West Point, PA), or rubella vaccines (Meruvax or Meruvax II, Merck and Co, Inc, West Point, PA), combined measles and rubella vaccine (M-R-Vax or M-R-Vax II, Merck and Co, Inc, West Point, PA), or combined measles, mumps, and rubella vaccine (M-M-R or M-M-R II, Merck and Co, Inc, West Point, PA), the lead author reviewed claims submitted to the National Vaccine Injury Compensation Program.

METHODS:The medical records of children who met the inclusion criteria of receiving the first dose of these vaccines between 1970 and 1993 and who developed such an encephalopathy with no determined cause within 15 days were identified and analyzed.

RESULTS:A total of 48 children, ages 10 to 49 months, met the inclusion criteria after receiving measles vaccine, alone or in combination. Eight children died, and the remainder had mental regression and retardation, chronic seizures, motor and sensory deficits, and movement disorders. The onset of neurologic signs or symptoms occurred with a nonrandom, statistically significant distribution of cases on days 8 and 9. No cases were identified after the administration of monovalent mumps or rubella vaccine.

CONCLUSIONS:This clustering suggests that a causal relationship between measles vaccine and encephalopathy may exist as a rare complication of measles immunization.

We retrospectively collected three patients with clinically mild encephalitis with a reversible splenial lesion (MERS) after mumps vaccination, and reviewed five patients, including two patients previously reported. The five patients (all males, aged 1 to 9) presented with fever, vomiting, or headache as the initial symptoms (day 0), suggesting meningitis, at 13 to 21 days after mumps vaccination. Consciousness disturbance, delirious behavior, seizures, or dysarthria was observed on days 1 to 3, which had completely resolved before day 11. Hyponatremia was observed in all patients. A cerebrospinal fluid study showed pleocytosis, and confirmed the vaccine strain genome. MRI revealed reduced diffusion in the splenium of the corpus callosum on days 2 to 4, which had completely disappeared on the follow-up studies performed on days 7-15. EEG showed high voltage slow wave in three patients, which later normalized. These findings led to a diagnosis of MERS after mumps vaccination. MERS after mumps vaccination may be more common than previously considered. MERS is suspected when a male patient after mumps vaccination presents with neurological symptoms with hyponatremia, following symptoms of aseptic meningitis, and MRI would be performed to examine the splenium of the corpus callosum.

Routine childhood vaccination against measles, mumps and rubella has virtually abolished virus-related morbidity and mortality. Notwithstanding this, we describe here devastating neurological complications associated with the detection of live-attenuated mumps virus Jeryl Lynn (MuV) in the brain of a child who had undergone successful allogeneic transplantation for severe combined immunodeficiency (SCID). This is the first confirmed report of MuVassociated with chronic encephalitis and highlights the need to exclude immunodeficient individuals from immunisation with live-attenuated vaccines. The diagnosis was only possible by deep sequencing of the brain biopsy. Sequence comparison of the vaccine batch to the MuVisolated from brain identified biased hypermutation, particularly in the matrix gene, similar to those found in measles from cases of SSPE. The findings provide unique insights into the pathogenesis of paramyxovirus brain infections.

Encephalitis associated with varicella-zoster virus, rare among children in the varicella vaccine era, has generally been associated with a rash. We report fatal wild-type varicella-zoster virus encephalitis without a rash in a child who had received 1 dose of varicella vaccine. Varicella-zoster virus encephalitis should be considered in the differential diagnosis for children presenting with acute neurologic symptoms, even vaccine recipients.

Involvement of the central nervous system is common in measles, but rare in rubella. However, rubella virus (RV) can cause a variety of central nervous system syndromes, including meningitis, encephalitis, Guillain-Barré syndrome and sub acute sclerosing panencephalitis. We report the occurrence of one fatal case of the encephalitis associated with measles-rubella (MR) vaccine during an immunization campaign in São Paulo, Brazil. A 31 year-old-man, previously in good health, was admitted at emergency room, withconfusion, agitation, inability to stand and hold his head up. Ten days prior to admission, he was vaccinated with combined MR vaccine (Serum Institute of India) and three days later he developed 'flu-like' illness with fever, myalgia and headache. Results of clinical and laboratory exams were consistent with a pattern of viral encephalitis. During hospitalization, his condition deteriorated rapidly with tetraplegia and progression to coma. On the 3rd day of hospitalization he died. Histopathology confirmed encephalitis and immunohistochemistry was positive for RV on brain tissue. RV was alsodetected by qPCR and virus isolation in cerebrospinal fluid, brain and other clinical samples. The sequence obtained from the isolated virus was identical to that of the RA 27/3 vaccine strain.

Venezuelan equine encephalitis (VEE) virus causes an acute central nervous system infection in human and animals. Melatonin (MLT), minocycline (MIN) and ascorbic acid (AA) have been shown to have antiviral activities in experimental infections; however, the mechanisms involved are poorly studied. Therefore, the aim of this study was to determine the effects of those compounds on the viral titers, NO production and lipid peroxidation in the brain of mice and neuroblastoma cultures infected by VEE virus. Infected mouse (10 LD50) were treated with MLT (500μg /kg bw), MIN (50mg /kg bw) or AA (50mg /kg bwl). Infected neuroblastoma cultures (MOI: 1); MLT: 0.5, 1, 5mM, MIN: 0.1, 0.2, 2μM or AA: 25, 50, 75μM. Brains were obtained at days 1, 3 and 5. In addition, survival rate of infected treated mice was also analyzed. Viral replication was determinedby the plaque formation technique. NO and lipid peroxidation were measured by Griess' reaction and thiobarbituric acid assay respectively. Increased viral replication, NO production and lipid peroxidation were observed in both, infected brain and neuroblastoma cell cultures compared with uninfectedcontrols. Those effects were diminished by the studied treatments. In addition, increased survival rate (50%) in treated infected animals compared with untreated infected mice (0%) was found. MLT, MIN and AA have an antiviral effect involving their anti-oxidant properties, and suggesting a potentialuse of these compounds for human VEE virus infection.

We describe a case of a 15-month-old female child admitted to our hospital because of fever, rash, neurological signs (oscillation between states of irritability and drowsiness), palpebral edema and drooping eyelid, appeared 10 days after the vaccination for measles, mumps and rubella. Brain MRI images showed multiple bilateral hyperintense lesions in the white matter typical of acute disseminated encephalomyelitis (ADEM), an autoimmune demyelinating disorder with inflammatory lesions of the central nervous system, due to viral antigens or vaccines. In the mean time, because of patient's vague phenotypic manifestations, suggestive of a genetic defect, array comparative genomic hybridization was carried out which showed the presence of a microdeletion 22q11.21, linked to the DiGeorge syndrome. Our case suggests that pediatric cases of post-vaccination ADEM, in which neurological signs persist, should be investigated for genetic phenotypical features, in order to exclude the presence of a genetic syndrome or disease.

Influenza vaccine is rarely associated with neurological adverse effects such as Guillain Barré syndrome, encephalitis or aseptic meningitis. We report the case of a male patient that presented two episodes of acute encephalitis in consecutive years, 16 and 20 days after his annual influenza vaccine shot, respectively. In both instances, patient required ICU admission and evolved with fastrecovery and no sequels. The first episode was managed empirically as herpetic encephalitis but an extensive study was performed in the second episode without identifying any microorganism. Neuroimaging studies also discarded acute disseminated encephalomyelitis. Mild pleocytosis of mononuclear predominance was detected in both cases in CSF. Naranjo score punctuated 8 points indicating a probable causal relationship. Acute encephalitis is a rare adverse effect of influenza vaccine and occurs several days after immunization. It has a broad differential diagnosis, and appears to be of self-limited duration and associated with good prognosis.

Varicella-zoster virus vaccine has diminished the consequences of chicken pox in terms of health and economical burden. The increasing number of doses administered worldwide has revealed rare but important adverse effects that had not occurred during clinical trials. We report here the case of an immunocompetent 3(1/2)-year-old girl who developed encephalitis and herpes zoster opthalmicus 20 months after her immunization with varicella-zoster virus vaccine. Molecular analysis confirmed the vaccine strain as the causative agent. After an intravenous course with acyclovir, the child made a full recovery with no neurologic sequelae.