A nation-wide survey of Japanese pediatric MOG antibody-associated diseases.

OBJECTIVE: To elucidate the clinical characteristics of Japanese pediatric patients with acquired demyelinating diseases (ADS), positive for myelin oligodendrocyte glycoprotein antibody (MOG-IgG), we conducted a nation-wide survey. METHODS: Information about pediatric patients under 18 years old with ADS was solicited with surveys sent to 323 facilities. In an initial survey, we asked whether the center had any patients with ADS, and the MOG-IgG serostatus of the patients. In a follow-up survey, we requested more precise information on patients with ADS. RESULTS: Initial survey: 263 replies providing information on 175 patients were received. MOG-IgG were examined in 78 patients and 54 of those (69%) were positive for MOG-IgG. Follow-up survey: The characteristic involvement was optic neuritis, with visual disturbance and optic pain as characteristic symptoms. The relapse rate was 44% in patients positive for MOG-IgG, which was higher than that in seronegative patients (38%). For acute phase treatments, corticosteroid (CS), plasma exchange, and intravenous immunoglobulin (IVIG) were useful. To prevent relapse, CS, intermittent IVIG, immunosuppressants, and monoclonal antibodies were useful, but the efficacies of disease modifying drugs were uncertain. Sequelae such as visual disturbance, cognitive impairment, motor dysfunction, and epilepsy were observed in 11% of patients with MOG-IgG. CONCLUSIONS: MOG antibody-associated diseases were found to be common among pediatric ADS patients. Since a variety of sequelae were observed in these patients, it is important to identify the appropriate treatment to ensure the best outcome. The presence of the MOG autoantibody should be taken into consideration as part of the diagnostic criteria for pediatric ADS.

Post-vaccination MDEM associated with MOG antibody in a subclinical Chlamydia infected boy.

The mechanism of post-vaccination acute disseminated encephalomyelitis (ADEM) has been hypothesized as resulting from vaccination-injected antigens cross-reacting with myelin components, however, a precise etiology has been uncertain. In this report, we describe the case of a 6-year-old Japanese boy who had multiphasic disseminated encephalomyelitis (MDEM), and was positive for both anti-myelin oligodendrocyte glycoprotein (MOG) antibodies and Chlamydophila pneumoniae antibodies. After vaccinations that were the second one for measles and rubella, and the booster immunization for Japanese encephalitis, the patient presented with fever, headache, vomiting, and a change in personality. He was treated with a high-dose of intravenous methylprednisolone in the diagnosis of ADEM. However, these symptoms recurred with different magnetic resonance imaging lesion, and he was diagnosed as MDEM. Retrospective testing for pathogens revealed C. pneumoniae IgM and IgG antibodies, and it was considered that he was infected with C. pneumoniae subclinically. The patient's serum indicated a positive response for the anti-MOG antibody from the onset of the ADEM diagnosis and in all recurrent episodes. Chlamydia species infection has been known to play a role in demyelinating diseases. It is also known that the anti-MOG antibody may be present but not exhibit its pathogenesis in the absence of a cell-mediated inflammatory response; however, the precise mechanism of action of the anti-MOG antibodies is not yet determined. We propose the possibility that post-vaccination demyelinating disease may result from the synergistic effects of a preceding anti-MOG antibody, possibly produced in response to a subclinical Chlamydia species infection.

Dynamics of hydroxyoctadecadienoic acid in epilepsy patients treated with valproic acid.

BACKGROUND: The effects of valproic acid (VPA) on oxidative stress are controversial due to differences in experimental conditions. Recently, total hydroxyoctadecadienoic acid (tHODE), derived from linoleic acid, was proposed as a potent biomarker to evaluate oxidative stress. METHODS: The subjects consisted of 10 new-onset epilepsy patients treated with VPA. We measured plasma tHODE consecutively for 1 year to evaluate the degree of oxidative stress and then compared plasma tHODE at the beginning and the end of experiments with the peak level. Ten age-matched healthy subjects were recruited as a control group and their plasma tHODE was compared to the initial plasma tHODE of the epilepsy group. Measurements were done using liquid chromatography-tandem mass spectrometry. RESULTS: Mean initial plasma tHODE in the epilepsy group was 165.2 ± 76.8 nmol/L, which was not significantly different from that of the control group (199.3 ± 62.5 nmol/L). In five epilepsy patients, plasma tHODE increased above the pathological level in 6 months, but returned to normal within 1 year. In the whole group, the difference plasma tHODE between peak, at the beginning and 1 year later, was significant. CONCLUSION: Oxidative stress generated by VPA increased temporarily, but decreased to normal after 1 year. it is reasonable to be concerned about the effects of oxidative stress, especially at the start of VPA treatment.

Incidence of febrile seizure in patients with Down syndrome.

BACKGROUND: It is unclear whether the incidence of febrile seizure (FS) in children with Down syndrome (DS) is higher or lower than in the general population. In this study, we investigated the incidence of FS in DS patients using mailed questionnaires. METHODS: The questionnaires were distributed to parents or caregivers of DS patients attending Osaka Medical College Hospital and six other facilities. The questionnaires were returned by mail from February 2012 to September 2013 from 323 families of DS patients (176 male, 147 female; age range, 3 months-47 years; median age, 5.0 years). To assess the incidence of FS in DS, we performed the following two analyses: (i) we calculated the incidence of FS among DS patients between the ages of 4 and 20 years (n = 199; 113 male, 86 female), and (ii) we extracted families with both DS and healthy siblings between the ages of 4 and 20 years (n = 150; 77 male, 73 female) and compared the incidence of FS in these sibling groups. RESULTS: Five DS patients had a past history of FS. The incidence of FS in DS was 2.5%. The incidence of FS was significantly lower in DS patients compared with healthy siblings (P < 0.003; OR, 0.14). CONCLUSION: The incidence of FS is lower in DS patients than in the general population.

Serum N-Terminal Pro-B-Type Natriuretic Peptide (NTproBNP) Levels Are Elevated During the Acute Phase of Acute Encephalopathy-Associated Virus Infection.

Acute virus-associated encephalopathy induces seizures. Serum N-terminal pro-B-type natriuretic peptide (NTproBNP) levels are elevated following febrile and afebrile seizures. However, the role of NTproBNP in acute virus-associated encephalopathy pathology is unknown. We enrolled 10 patients with acute virus-associated encephalopathy and convulsions (E group: 7 boys, 3 girls; median age, 3.10 ± 1.92 years) and 130 patients with febrile seizure (FS group: 80 boys, 50 girls; median age, 3.23 ± 2.44 years). The E group had significantly higher NTproBNP levels (345 ± 141 pg/mL) compared with the FS group (166 ± 228 pg/mL) (P < .0005). Furthermore, subjects with prolonged seizure within the E group had significantly higher NTproBNP levels (303 ± 107 pg/mL) compared with subjects with prolonged seizure within the FS group (134 ± 100 pg/mL) (P < .005). Our findings suggest that serum NTproBNP levels are increased during the acute phase of acute virus-associated encephalopathy associated with convulsion.

Delirious behavior or mild reduction of consciousness mimicking influenza-associated encephalopathy.

BACKGROUND: During the A/H1N1 pandemic, patients suffered from impaired consciousness. They were suspected of or diagnosed as having influenza-associated encephalopathy (IAE) in an emergency situation. Their symptoms resembled those of a recently described 'unique clinical group', which were reported to have a favorable prognosis. METHODS: We retrospectively examined 46 patients and divided them into two groups. Group IC contained the 26 patients with persisting impaired consciousness. The remainder of the patients were categorized into group R, consisting of patients with only neurological symptoms without impaired consciousness. RESULTS: Male predominance (22 male/four female) was noted in group IC. Patient age ranged from 5 to 12 years old (mean ± SD, 7.7 ± 2.3 years). Impaired consciousness such as delirious behavior or mild reduction of consciousness lasted continuously or intermittently from 5 min to 2.5 days. On electroencephalogram, semi-rhythmic high-voltage slow waves in the parieto-occipital regions and diffuse high-voltage slow waves were observed in eight and in two patients, respectively. In group R, there was no gender predominance. Patient age ranged from 1 to 9 years old (mean ± SD, 4.1 ± 2.5 years). All group R patients were clinically diagnosed with febrile seizure. CONCLUSIONS: Some of the characteristics in group IC resembled those of the unique clinical group, and are part of a continuous clinical spectrum. Some patients may have favorable outcome without specific treatment.

Non-operative treated spontaneous spinal epidural hematoma in a 12-year-old boy.

Spontaneous spinal epidural hematoma (SSEH) has been reported as a rare condition especially in childhood. Because its symptoms are atypical, it is not easy to diagnose the onset of SSEH. However, with wider use of magnetic resonance imaging (MRI), several SSEH cases, especially not requiring surgical intervention, have been reported. We report on a 12-year-old boy who presented with a 5-day history of progressive pain in his back and extremities and numbness of his lower legs. An MRI of the spine demonstrated a dorsal epidural hematoma extending from C4 to T4, and the axial scan of the MRI revealed a posterior hematoma. Neurological deficit was estimated as not severe and not progressive, therefore surgery was postponed, and the patient was discharged without surgical intervention. Seven months later, MRI and myelography were performed, and we confirmed that the spinal epidural hematoma was absorbed. There have been some cases showing spontaneous regression of SSEH, and in younger than 18 years old, most of those cases that were treated with hematopathy such as hemophilia and spontaneous regression after SSEH correlated to larger size of hematoma. Because of bleeding tendencies in these cases the spinal cord was not pressed by the hematoma; this contributed conclusively to the prognosis. On the contrary, the 12-year-old boy, not having bleeding tendency, had the larger lesion of SSEH and recovered spontaneously without surgical intervention. Evaluation of MRI findings and neurological deficits in SSEH cases is important for deciding the indication of surgical intervention.

Four cases of arthritis associated with Mycoplasma pneumoniae infection.

BACKGROUND: Mycoplasma pneumoniae infection is diagnosed commonly by marked elevation of serum antibodies, but this requires several days and consequently M. pneumoniae infection might be overlooked in some cases. Recently an ImmunoCard Mycoplasma rapid diagnosis test (IC) has been developed and used clinically. One of the advantages of this diagnosis test is that clinicians can recognize the infection by a single administration at the beginning of treatment. METHODS: A total of 1033 children aged 1-15 years (average 2.0 years) were examined. The diagnosis of M. pneumoniae infection was made mainly on the basis of a positive reaction to the IC. Also where possible, particle agglutination (PA) was performed as a confirmatory test. Diagnosis was made on the basis of a fourfold or greater rise in the PA antibody titer by paired sera or an initial single PA titer >1:320. Arthritis was diagnosed mainly on clinical symptoms. Additionally, ultrasonography (US) was conducted to confirm arthritis. In using US, arthritis was defined as an enlargement of the low echoic section or fluid retention inside the articular capsule. RESULTS: IC was used in 1033 patients and results were positive in 348 (33.6%). Of these 348, there were 70 cases of pneumonia (20.1%) and four cases of arthritis (1.1%). IC was positive in all of the cases of arthritis, and in two of the four arthritis patients the PA titers were also useful for diagnoses. In three of four cases, US was performed and lesions were observed in two of three cases. Three of the four arthritis patients were infants and only one of these three had pneumonia. CONCLUSIONS: Using IC as a screening test, occult M. pneumoniae infections were discovered that would otherwise have been overlooked. These included two patients with US-proved arthritis. Arthritis in the absence of pneumonia may not be an unusual manifestation in infants infected by this organism.

Anorexia nervosa and refeeding syndrome. A case report.

This is a case story of a 14-year-old girl with severe anorexia nervosa (AN) (158 cm, 28 kg, -44.1% ideal body mass index), admitted with purpura, edema, and general fatigue. We treated her carefully and paid particular attention to prevent development of refeeding syndrome (RS), and her body weight increased satisfactorily. However, RS (edema, hypoalbuminemia, and heart failure) occurred despite careful treatment. We used albumin and diuretics for treatment of RS, but severe liver damage resulted. RS was aggravated by the medical treatment. More attention should have been paid to her weight gain and medical treatment should have been initiated more slowly to prevent dramatic changes in the patient's fluid and electrolyte status.

Neopterin, biopterin, and nitric oxide concentrations in the cerebrospinal fluid of children with central nervous system infections.

We measured neopterin, biopterin and nitric oxide (NO) concentrations in the cerebrospinal fluid of pediatric patients with central nervous system (CNS) infectious diseases. The nitric oxide and neopterin concentrations were significantly elevated in encephalitis patients, especially in two cases with serious neurological sequelae, while the biopterin levels were not elevated. The bacterial meningitis patients, on the contrary, had high cerebrospinal fluid concentrations of neopterin and biopterin, but not of NO. Although these findings are preliminary, it may suggest that cerebrospinal fluids nitric oxide would be a useful marker to prospect neurological prognoses in the CNS infections.