Hiroatsu Hojo

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.

Age related incidence of cavum septi pellucidi and cavum vergae on CT scans of pediatric patients.

The computed tomography scans of 1.050 infants and children with various degrees of neurological involvement were reviewed to determine the incidence of cavum septi pellucidi (CSP) and cavum Vergae (CV). The incidence was 10% in patients under 1 year, gradually decreasing to 5 to 6% at 2 to 5 years, 2.7% at 6 to 9 years, and 2.3% at 10 to 14 years, with an average rate of 5.59%. An attempt was made to assess possible relationships between clinical syndromes (convulsive disorders, developmental delays, and others) and the presence of CSP-CV. No solid statistical evidence of such relationships could be established.

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.

18p− syndrome associated with hemivertebrae, fused ribs and micropenis

SummaryAn 11-month-old boy was found to have deletion of the short arm of chromosome 18. He was a short hypotonic infant with thoracic hemivertebrae, fused ribs and micropenis in addition to developmental delay, ptosis of the eyelids, epicanthal folds, hypertelorism, large prominent and low-set ears, micrognathia and short neck.Banding analysis showed the patients karyotype to be 46, XY,del(18) (p1103).

Tuberous sclerosis: Early neurologic manifestations and CT features in 18 patients

Early clinical manifestations and radiologic features of tuberous sclerosis were studied in 18 consecutive patients encountered in the past two years, including two patients harboring an associated intraventricular tumor (giant-cell astrocytoma). Depigmented naevi rather than adenoma sebaceum, infantile spasms and intracranial calcifications were the cardinal early features in this present series, and CT scanning proved to be the single most useful diagnostic technique in the early detection of intracranial calcifications and therefore for the early diagnosis of this disorder. CT scanning was also useful in detecting the intraventricular tumors in the early stage before they became clinically manifest.

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.

Computed tomography of cerebral palsy: evaluation of brain damage by volume index of CSF space.

Between 1976 and 1978, we examined 110 Japanese children with cerebral palsy using a CT 1000 and a CT 1010 (EMI). In 92% of all patients, there were abnormal findings. Cortical atrophy was seen in 51%, ventricular dilatation in 86%, localized low density areas in 22%, brain anomalies in 10% and asymmetry of cerebral hemisphere in 31%. In spastic hemiplegia, the characteristic CT revealed asymmetrical ventricular dilatation without cortical atrophy and localized low density areas in the cerebral hemisphere contralateral to the palsy. In spastic tetraplegia, CT revealed moderate to marked diffuse cerebral atrophy or brain anomalies. In athetosis, CT revealed normal or slight cerebral atrophy. In 60 cases where a CT 1010 was used, we calculated the volume index of CSF space by computer, Eclipse S/200, and analyzed the relationship between the clinical features of cerebral palsy and the volume index of CSF space.

Epileptiform EEG abnromalities in children with epilepsies after febrile seizures

A long-term follow-up study after the first episode of idiopathic status convulsivus in childhood. III. Its relation to the syndrome of m,edsial temporal lobe eplepsy Yutaka Awaya , Hiroko Iwamoto , Yukio Fukuyama ‘, Makiko Osawa d (” Department of Pediatrics, Seibo International Catholic Hospital, Tokyo; b Dept. of Pediatric Neurology, ’ Kanagawa Children’s Medical Center, Kanagawa, Child Neurology Institute, Tokyo; d Dept. of Pediatics, Tokyo Women’s Medical College, Tokyo, Japan.) The syndrome of mesial temporal lobe epilepsy (MTLE) was recently defined by Engel et al. (1992) as a characteristic symptom complex, indicating the presence of hippocampal sclerosis, which is a surgically remediable epileptic syndrome. MTLE usually begins in the latter part of the first decade of life, the seizures typically respond to medication initially, but after a ‘silent period’, intractable complex partial seizures (CPS) recur during adolescence. A high incidence of prolonged febrile convulsions has been recognized in the past histories of subjects with this syndrome. We have conducted a long-term follow-up study on children with idiopathic status convulsivus (ISC), placing a focus on the prognosis of childhood SC in relation to MTLE. Subjects. ISC was defined as a convulsion lasting for at least 1 h which occurred in a previously healthy child with no known underlying disorders. During the period from 1970-1984 at Tokyo Women’s Medical College, and 1972-1977 at Kanagawa Children’s Medical Center, 65 children with ISC were admitted. Of these cases, 54 could be followed for 5 years or more. We assessed the seizure prognosis in 1986 and 1991. In 1991, we found that 6 (15%) out of 40 fever-associated ISC cases and eight (57%) out of 14 afebrile ISC cases had developed epilepsy. We also found the mean onset age of ISC to be 1.5 + 1.4 years in the febrile group and 3.8 k 1.5 years in the afebrile group. As for those who developed epilepsy (6 + 8 = 14) four cases with afebrile ISC had dropped out; thus, in the present investigation, the seizure prognosis was evaluated in ten patients. Results and Conclusion. Ten epileptic patients were followed prospectively for a mean period of 16 years. Habitual seizures (CPS with/without generalized tonic seizures) developed 4.3 f 3.5 years after febrile ISC (n = 6) and 7.6 If: 6.7 years after afebrile ISC (n = 4). The ‘silent period’ characteristic of MTLE. was recognized in 7. As for seizure-frequencies, in the febrile group all cases were monthly-level, i.e., intractable, while in the non-febrile group the frequencies were monthly in one, yearly in two, and none in one. MRI (including coronal sections) was performed in six cases and hippocampal atrophy was detected in 3. As for the epilepsy diagnosis, all febrile ISC cases were thought oo be MTLE while two out of 4 non-febrile ISC cases were considered to be MTLE. In conclusion, six (15%) out of 40 children who experienced ISC in association with fever later developed epilepsy, all of which took the form of MTLE. Similar consequence was found in 2 out of 4 afebrile ISC children. These findings suggest that the episode of ISC in childhood indicates a high risk for later development of MTLE.

Sudden death of both brothers with Menke's disease

Cockayne syndrome complicated by acute subdural hemorrhage Hide0 Shimoizumi “jb, Mika Matsui a, ‘, Shigeko Ito “24 Masutomo Miyao ‘jb and Shigeichi Kobayashi b (” Tochigi Prefectural Hospital and Welfare Center for the Crtppled. Tochigi; b Department of Pediatrics. Jichi Medical College, Tochigi, Japan) We describe a patient with Cockayne syndrome who developed an acute cerebral hemorrhage as a late complication with rapid clinical deterioration. Case report: A lZyear-old boy was the term product of an uncomplicated pregnancy and delivery. He was referred to an institution for handicapped children at 1 year 2 months of age because of his motor delay. He was diagnosed as having Cockayne syndrome on the basis of stunted growth, special facial features, rigid muscle tone and skin photosensitivity. He began to walk at 2 years of age, but became unable to walk after 3 years 6 months of age. He was referred to our hospital at 6 years of age. On examination he was found to be a cachectic dwarf (BH 86.5 cm, -6.5 SD) with microcephalus (HC 44.0 cm, 5.1 SD), multiple joint contractures, deafness and retinal pigmentary abnormalities. He could sit without aid but showed cerebellar ataxia, rigidity and hyperreflexia. Cranial CT showed atrophy of the cerebrum, cerebellum and brain stem, and calcification in the basal ganglia and paraventricular parenchyme. MRI showed changes compatible with leukodystrophy. NCVs were abnormally slow. At 12 years of age, he developed acute renal failure and hypertension after some febrile illness. CT demonstrated bilateral acute subdural hemorrhage. His neurological status deteriorated rapidly. After this episode he responded poorly to external stimuli. Conclusion: Subdural hemorrhage could be a serious complication in the late stage of Cockayne syndrome.

Hypothesis as to the age of onset of seizures provoked by fever

A clinical survey of febrile convulsions Toshihide Ishibashiavb and Yoshifumi Yamashitaa (aDepartment of Pediatrics, Kamigotoh Hospital, Nagasaki, Japan; bDepartment of Pediatrics, Shimabara Maternity Hospital, Nagasaki, Japan) In general, febrile convulsions have a good prognosis, but some cases of complex febrile convulsions and epilepsy developing from febrile convulsions require long-term treatment with anticonvulsants. Patients with febrile convulsions were investigated as to the correlations between the outcome and the cause of the seizures, the cause of the fever, and risk factors. Subjects and Methods. This study included 117 inpatients with febrile convulsions at Kamigotoh Hospital during the 15year period between January 1979 and December 1993. Information on age at initial onset, sex, cause of fever, duration, frequency of repetitive convulsions, and electroencephalographic findings was collected from charts and letters. Results. The male-to-female ratio of the febrile convulsion patients was 1.86. A viral disease was the cause of the fever in 63.9%, and a bacterial infection was involved in the etiology of the febrile convulsions in 19.6%. The outcome was simple febrile convulsions in 47%, no medication for complex febrile convulsions in 29.1%, medication for complex febrile convulsions in 14.6%, and epilepsy in 9.4% of the 117 patients 3-18 years after the initial onset. There were significant differences in terms of neurological symptoms at the time of onset, partial seizures, neurological symptoms after seizures, frequent seizures, abnormal EEG, and low grade fever ( < 37.9”C) in febrile convulsions with and without epilepsy. Conclusions. Viral diseases were the most frequent causes of fever in febrile convulsions. Bacterial infections were involved in the etiology in many patients, but this was difficult to demonstrate in most cases. Neurological symptoms at the time of onset, partial seizures, neurological symptoms after seizures, frequent seizures, and abnormal EEG findings are considered to be risk factors for transition to epilepsy even when such symptoms occur in isolation. Prophylactic administration of anticonvulsants is commonly performed in the treatment of complex febrile convulsions, but it is generally believed that treatment cannot prevent the onset of epilepsy. Such problems as hepatopathy and intellectual disturbance have also recently become issues. Intermittent administration of anticonvulsants during fever is therefore recommended.