Hideo Aiba

Predictive value of serum interleukin-6 level in influenza virus–associated encephalopathy

Objective: In Japan, >200 children with influenza virus–associated encephalopathy were reported in 1999 and the mortality rate was high. The levels of tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6) in both CSF and serum were significantly increased in severe cases. The authors found a correlation between elevated serum cytokine levels and mortality and neurologic morbidity. Methods: TNFα, IL-6, soluble tumor necrosis factor receptor 1 (sTNF-R1), interferon-γ (IFNγ), and IL-2 were measured by the ELISA method in sera from six children with encephalopathy before and during therapy, and in six age-matched controls with influenza type A virus infection. Results: The increases in the serum TNFα, IL-6, and sTNF-R1 levels were statistically significant at the onset of symptoms before therapy, but the IL-6 level was most useful for diagnosis. The serum IL-6 levels were >6,000 pg/mL in children with brain stem dysfunction, about 150 pg/mL in children without brain stem dysfunction, and <80 pg/mL in controls. The time course of the serum IL-6 level also reflected the clinical condition. Once the serum IL-6 level was increased to >15,000 pg/mL, none of the children survived. The lower the maximal serum IL-6 level, the milder the CNS sequelae. Conclusion: The serum IL-6 level may be the most useful indicator for the diagnosis and the clinical severity of influenza virus–associated encephalopathy.

Outcome of acute necrotizing encephalopathy in relation to treatment with corticosteroids and gammaglobulin

OBJECTIVE To examine the relation between outcome and treatment with steroids and gammaglobulin in children with acute necrotizing encephalopathy. METHODS We retrospectively evaluated the clinical course and outcome of 34 children with acute necrotizing encephalopathy. They were divided into two groups; 17 patients with brainstem lesion and 17 patients without brainstem lesion. Early steroid use was defined as when steroids were administered within 24h after the onset. The outcome was judged as good when a patient had no or mild cognitive impairment and poor when a patient had more severe sequelae, or died. RESULTS Among patients without brainstem lesions, the outcome was good in 7 of 12 with early steroid, whereas it was poor in all 5 patients without early steroid. There was no significant difference in sex, age, and laboratory data between patients with and without early steroid. The outcome was not correlated with gammaglobulin treatment. As to patients without brainstem lesions, the outcome was not correlated with early steroid or gammaglobulin treatment. CONCLUSIONS Steroid within 24 h after the onset was related to better outcome of children with acute necrotizing encephalopathy without brainstem lesions. Early steroid treatment will be an important option of the treatment for acute necrotizing encephalopathy.

Measles virus-specific T helper 1/T helper 2-cytokine production in subacute sclerosing panencephalitis.

Live measles virus-specific T helper 1/T helper 2-cytokine productions by peripheral blood mononuclear cells in response to live measles, mumps or varicella virus were measured in 15 patients with subacute sclerosing panencephalitis and 15 controls by enzyme-linked immunosorbent assays. Most patients with subacute sclerosing panencephalitis had a defect in measles virus-specific production of interferon-gamma, one of the T helper 1 type cytokines, despite persistent presence of measles virus, with preserved interleukin-10 (T helper 2 type cytokine) synthesis. Patients with subacute sclerosing panencephalitis were divided into two groups: responders (group A) with significant interferon-gamma production (>20 pg/mL) in response to live measles virus and non-responders (group B) with a little or no interferon-gamma production. Comparison of the clinical courses between groups A and B revealed that all the patients of group A retained receptive function for a long time, while most patients of group B lost the function rapidly (P<0.01). An inverse correlation between interferon-gamma production by peripheral blood mononuclear cells and disease progression suggested that interferon-gamma plays an antiviral role in subacute sclerosing panencephalitis.

Opsoclonus-myoclonus syndrome with abnormal single photon emission computed tomography imaging

The single photon emission computed tomography (SPECT) findings in 2 patients with opsoclonus-myoclonus syndrome (OMS) who had similar symptoms in the acute stage of the disease are described. In 1 patient with encephalitis, SPECT showed increased blood flow in most of the cerebellum; the highest accumulation of the radiotracer was found in the cerebellar vermis and neighboring structures. These changes disappeared with clinical improvement. In the other patient with chronic OMS, SPECT demonstrated hypoperfusion in most of the cerebellum. Our results suggest that the cerebellum, particularly its middle portion, is involved in the generation of OMS. SPECt is a useful method that enables us to detect in vivo functional impairment in patients with OMS.

Different responses to auditory and somaesthetic stimulation in patients with an excessive startle: a report of pediatric experience

OBJECTIVES Children with cerebral injury often exhibit brief muscle contraction to a variety of stimuli. However, it remains to be determined whether or not the pattern of the reaction is stereotypical irrespective of the site stimulated. To answer this question, we studied electromyographic (EMG) responses to three types of stimuli in children. METHODS The EMG responses of cranial and limb muscles were recorded after acoustic or somaesthetic stimulation in 6 patients and 23 control subjects. RESULTS Acoustic stimuli evoked patterned motor activity with a rostrocaudal progression. Nose-tapping stimuli elicited reflex EMG activity in the VIIth cranial muscles that was similar to the R1 component of the electrical blink reflex. Sternum-tap stimuli evoked motor activity in the sternocleidomastoid and arm muscles, and this reflex was probably mediated through the cervical cord (H-reflex). Moreover, late reflexes were evoked following these early reflexes in the patients. In particular, atypical forms of myoclonic jerks were evoked on sternum-tap stimuli. CONCLUSIONS Many types of primitive reflexes were evoked following three types of stimuli. These reflexes included startle reflex, trigeminomotor reflex, H-reflex and atypical forms of myoclonus, and they were enhanced in the patient group. There are many startle-mimicking reflexes.

Analysis of measles virus binding sites of the CD46 gene in patients with subacute sclerosing panencephalitis

Measles virus (MV) binding sites of the CD46 gene were sequenced in patients with subacute sclerosing panencephalitis (SSPE) and in controls. There were 3 novel polymorphisms, including C/T at nucleotide position 38 (C/T38), G/A at position 176 (G/A176), and C/T at position 453 (C/T453), at allele frequencies of.97:.03, .99:.01, and.97:.03, respectively. The G/A176 polymorphism causes an Arg/Gln amino acid change within the essential binding sites of MV, whereas the C/A38 polymorphism causes a Ser/Phe change outside the MV binding sites. The C/T453 polymorphism does not produce an amino acid change. Two of the 40 SSPE patients and 2 of the 32 controls had both C/T38 and C/T453 polymorphisms in heterozygous patterns. One control subject, but no SSPE patients, had the G/A176 polymorphism in a heterozygous pattern. Thus, it is not likely that CD46 gene alteration has a role as a host susceptibility factor in the development of SSPE.

Delirious behavior in children with acute necrotizing encephalopathy

OBJECTIVE To clarify the features of delirious behavior in patients with acute necrotizing encephalopathy. METHODS We retrospectively evaluated the clinical course of 38 children with acute necrotizing encephalopathy diagnosed on the basis of neuroradiological findings. The patients were divided into two groups according to the presence or absence of delirious behavior. We compared clinical features, laboratory data, neuroimaging findings, and outcome between those with and without delirious behavior. In patients with delirious behavior, chronological sequence of neurological symptoms and the characteristics of delirious behavior were investigated. RESULTS Delirious behavior was observed in 8 patients. Patient characteristics or most laboratory data on admission were not significantly different between those with and without delirious behavior. Brainstem lesions were more frequent in patients with delirious behavior than in those without. In contrast, lesions in lentiform nuclei, cerebral hemisphere, or cerebellum were relatively more frequent in patients without delirious behavior. It was the initial neurological symptom in 7 of 8 patients. Stupor and seizures were observed after delirious behavior in most patients. CONCLUSIONS Delirious behavior was not uncommon in children with acute necrotizing encephalopathy. Brainstem lesions may be related to the development of delirious behavior of children with acute necrotizing encephalopathy.

Cortical myoclonus in children

Cortical myoclonus is a distinct clinical condition that can be defined electrophysiologically, and occurs in both children and adults. It is well known that patients sometimes exhibit stimulus-sensitive jerks and giant somatosensory-evoked potentials (SEPs). In contrast, imaging abnormalities are less prominent in many patients. Reports focusing on cortical myoclonus, except for epilepsia partialis continua, in childhood have been limited in Japan. One reason for this could be that Japanese pediatric neurologists are not familiar with the backaveraging technique. We describe the clinical and physiological features of cortical myoclonus in ten children. Routine EEG, EEG backaveraging, SEP measurement, CT/MRI (computed tomography/magnetic resonance imaging), and TMS (transcranial magnetic stimulation) were performed. All patients exhibited clear evidence of cortical myoclonus. In six patients, backaveraging was necessary since spikes were absent on routine EEG. A cortical source of the myoclonus was further supported by a TMS study performed on four patients. The etiologies of the myoclonus were diverse, cerebrovascular disease being the most common (three patients). Stimulus-sensitive or action-induced jerks were observed in three patients. Cortical SEPs were enlarged in one patient, and reduced or absent in six. Lesions were found on CT/MRI in nine patients, in five of whom the margin of the lesion was within, or adjacent to, the sensorimotor cortex. Complete destruction of the sensorimotor cortex was not observed. It was suggested that cortical neurons in the vicinity of a lesion, rather than in the lesion itself, play a role in the generation of focal myoclonus.

Trigeminally induced startle in children with hyperekplexia

To determine the physiological features of startle reactions in children with hereditary hyperekplexia, motor responses to auditory and trigeminal stimulation were investigated in 2 patients and 3 control subjects by means of multiple surface electromyographic recordings. The pattern of motor activation in auditory startle was similar in the two groups, although the responses in the patients were increased in terms of the extent of the responses. In the patients, nose taps elicited two separate responses in various muscles. The initial, short‐latency response was often elicited in all the muscles examined. This reflex was similar to the R1 component of the electrical blink reflex. In addition, the early reflex was immediately followed by the second response, which also appeared widely and was similar to R2 of the blink reflex. Taps on the supraorbital nerve elicited multiple startle patterns consisting of these two responses, although generalization was infrequent. In the control subjects, these responses were elicited in a few muscles. In the hyperekplectic children, both the early and second responses to trigeminal stimulation were increased, in addition to the audiogenic reflex. It was suggested that enhancement of these responses occurred due to hyperexcitability in the brainstem reticular formation in our patients.

Survey of Subacute Sclerosing Panencephalitis in Japan

Investigators conducted a retrospective epidemiological study of subacute sclerosing panencephalitis, a fatal disease caused by measles infection, over the past few years in Japan. Data on 118 cases obtained from a questionnaire sent to attending physicians were analyzed. The annual incidence of subacute sclerosing panencephalitis was approximately 0.03 cases per million from 2001 to 2005. Children infected with measles at a young age (<12 months) showed a high incidence of subacute sclerosing panencephalitis, and those infected before 6 months of age showed earlier onset. Because a positive correlation was found between the prevalence of measles and the onset of subacute sclerosing panencephalitis, particularly among children infected at an early age, it is vital to eradicate measles infection by vaccination.