Acute encephalitis with refractory, repetitive partial seizures (AERRPS): a peculiar form of childhood encephalitis.

OBJECTIVE: We conducted a nationwide multicenter study in Japan to elucidate the clinical and laboratory characteristics of acute encephalitis with refractory, repetitive partial seizures (AERRPS). MATERIALS AND METHODS: Clinical and laboratory features, treatment, and outcome were assessed using a structured questionnaire. RESULTS: Twenty-nine children were enrolled in the study. Refractory and repetitive partial seizures accompanied by fever were the cardinal clinical features. Partial seizures consisted principally of eye deviation or facial twitching, being periodically repeated during the acute phase. These seizures were refractory to conventional anticonvulsants and were only suppressed by high-dose intravenous barbiturate administration. Rhythmic activities on electroencephalography and non-specific cerebral atrophy on neuroimaging were common. Serum or cerebrospinal antibodies against GluRepsilon2 were positive in six patients. General prognosis was unfavorable due to intractable epilepsy and cognitive deficits. CONCLUSION: Based on the peculiar and homogenous features, AERRPS can be regarded as a distinct clinical entity.

Exercise-induced acute renal failure with renal hypouricemia: a case report and a review of the literature.

A previously healthy 16-year-old boy developed acute renal failure following a track race at a local athletic meeting. Several hours after the run, he expressed pain in the loins with nausea and vomiting. After 3 sessions of hemodialysis, he was referred to our hospital. On admission, serum creatinine was elevated to 2.3 mg/dl without an increase in serum uric acid level. After recovery from acute renal failure (ARF), hypouricemia (0.7 mg/dl) became evident in the patient. One year later, he suffered from ARF after a track race with the highest creatinine levels of 1.1 mg/dl. In order to clarify the cause and prognosis of ARF with renal hypouricemia, we summarized the clinical features in 18 patients previously described and our patient. Serum uric acid levels after recovery from ARF were below 1.0 mg/dl in all patients. Renal biopsy in 9 patients showed acute tubular necrosis in 8 patients and uric acid nephropathy in 1. The short-term prognosis of these patients seemed good, although 5 patients needed to undergo hemodialysis in their ARF courses. However, the recurrence of ARF episodes occurred in 6 patients (31.6%) including our patient, indicating that prevention of ARF might be necessary in these patients. More information is required to establish guidance for prevention of ARF.

KL-6 as an indicator for lymphocytic interstitial pneumonia (LIP) in a human T-lymphotrophic virus type 1 (HTLV-1) carrier.

A 59-year-old woman was admitted to our hospital complaining of a productive cough, dyspnea on effort, and low-grade fever. Although chest X-rays showed no marked abnormalities, her level of serum KL-6 was extremely high. We therefore suspected the presence of interstitial pneumonia. High-resolution computed tomography (CT) scan revealed infiltrative shadows in S6 of the right lung, and her serum was positive for antihuman T-lymphotropic virus type 1 (HTLV-1) antibodies. From the clinical symptoms, radiographic findings, and histological findings, the diagnosis was probable lymphocytic interstitial pneumonia (LIP). After high-dose corticosteroid therapy, the level of serum KL-6 decreased rapidly. We conclude that KL-6 is a convenient and reliable marker for evaluating the activity of pulmonary manifestations in HTLV-1 carriers and that it is especially useful in monitoring the effectiveness of treatments.

Phenytoin-induced choreoathetosis in patients with severe myoclonic epilepsy in infancy.

We describe three patients with severe myoclonic epilepsy in infancy (SME) who suffer from choreoathetosis due to the adverse effect of phenytoin. Choreoathetosis appeared when these patients were 8, 19, and 21 years old, 2 days to 6 months after increasing the phenytoin dosage. Choreoathetosis disappeared when the phenytoin dosage was decreased. The two elder patients experienced episodic and rather paroxysmal onset of long-lasting choreoathetosis, requiring the differential diagnosis from degenerative disease. In one of the patients, an ictal SPECT revealed decreased perfusion in the basal ganglia contralateral to the unilateral choreoathetosis. Polypharmacy, including carbamazepine and zonisamide, may have facilitated the onset of choreoathetosis. Phenytoin-induced choreoathetosis in the patients with SME is an important differential diagnosis among degenerative disorders involving involuntary movements. The episodic and paroxysmal nature of this movement disorder can delay its diagnosis and effective treatment. Patients with SME appear to be particularly vulnerable to this side effect of phenytoin, indicating the possible involvement of basal ganglia in the pathophysiology of this type of epilepsy.

Severe myoclonic epilepsy in infants--a review based on the Tokyo Women's Medical University series of 84 cases.

Severe myoclonic epilepsy in infants (SME) is one of the most malignant epileptic syndromes recognized in the latest classification of epileptic syndromes. The clinical details and electroencephalographic (EEG) characteristics have been elucidated by Dravet et al. The diagnosis of SME depends largely on the combination of clinical and EEG manifestations at different ages, of which the presence of myoclonic seizures appears to be the most important. However, because of the inclusion of different types of myoclonic attack and the lack of strict criteria for diagnosing SME, there has been some confusion as to whether patients without myoclonic seizures or myoclonus should be classified as SME, despite other identical clinical symptoms (SME borderlands (SMEB) group). Among the various clinical manifestations characterizing SME, special attention has been paid to seizures easily precipitated by fever and hot baths in Japan. We have demonstrated that the onset of myoclonic attack in these patients is very sensitive to the elevation of body temperature itself rather than its etiology. Using simultaneous EEG and rectal temperature monitoring during hot water immersion, we showed that epileptic discharges increased in frequency, and eventually developed into seizures at temperatures over 38 degrees C. We believe that the unique fever sensitivity observed in SME is similar to, but more intense than that of febrile convulsions. We have also identified a group of cases who have had innumerous myoclonic and atypical absence seizures daily which were sensitive to the constant bright light illumination. In these cases, spike discharges increased or decreased depending on the intensity of constant light illumination. Although these cases form the most resistant SME group, they lost the constant light sensitivity with increasing age, leaving only relatively common types of fever-sensitive grand mal seizures (FSGM) at the age of around 5 years. In the long run, only convulsive seizures continue, while myoclonic or absence seizures and photosensitivity disappear with advancing age, thus it is conceivable that SMEB constitutes a basic epileptic condition underlying SME. There is a clinical continuum that extends from the mildest end of SMEB to the severest end of SME with constant light sensitivity, with intermediates of frequent or infrequent myoclonic and absence seizures in-between. This spectrum concept appropriately explains the clinical variabilities between SME and SMEB during early childhood.

Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene.

Friedreich ataxia (FRDA), the most common autosomal recessive neurodegenerative disease among Europeans and people of European descent, is characterized by an early onset (usually before the age of 25), progressive ataxia, sensory loss, absence of tendon reflexes and pyramidal weakness of the legs. We have recently identified a unique group of patients whose clinical presentations are characterized by autosomal recessive inheritance, early age of onset, FRDA-like clinical presentations and hypoalbuminemia. Linkage to the FRDA locus, however, was excluded. Given the similarities of the clinical presentations to those of the recently described ataxia with oculomotor apraxia (AOA) linked to chromosome 9p13, we confirmed that the disorder of our patients is also linked to the same locus. We narrowed the candidate region and have identified a new gene encoding a member of the histidine triad (HIT) superfamily as the 'causative' gene. We have called its product aprataxin; the gene symbol is APTX. Although many HIT proteins have been identified, aprataxin is the first to be linked to a distinct phenotype.

[Clinical study on epileptic aura in children with temporal lobe epilepsy].

We studied the clinical characteristics of epileptic aura with temporal lobe epilepsy (TLE) in children, by retrospectively reviewing medical records of 33 patients whose first seizures developed under 15 years of age. The diagnosis of TLE was made by interictal EEG and head MRI/SPECT, both of which demonstrated a temporal lesion. The patients were classified into 24 with mesial TLE syndrome, 3 with a temporal lobe tumor, 3 with temporal lobe dysplasia and 3 with other causes. The epileptic aura was not recognized in 5 patients (15%). The age at onset of aura ranged from 4 to 10 years with a median age at 7. In patients older than 10, it was always followed by impairment of consciousness. It was manifested with nausea in 14 patients (42%), vertigo, a sense of fear, palpitation and heating sensation on the back in three patients (9%) each. Thus, clinical manifestations of epileptic aura in children with TLE were largely identical to those of adult patients. Detailed history taking about the aura may provide a clue to the diagnosis of TLE even in children.

Two cases of severe bronchopneumonia due to influenza A (H3N2) virus: detection of influenza virus gene using reverse transcription polymerase chain reaction.

We report two cases of severe bronchopneumonia due to influenza A (H3N2) virus. The severity of the disease necessitated initiation of empiric therapy based on the present illness and clinical data on admission. Both patients were improved by artificial ventilation with positive end-expiratory pressures and administration of broad spectrum antibiotics and corticosteroids before confirming the diagnosis of viral bronchopneumonia using viral culture and serological tests. Within 24 hours, influenza A (H3N2) virus was identified by amplification of the pathogen genes by reverse transcription polymerase chain reaction (RT-PCR) using the stored bronchoalveolar lavage (BAL) fluids of both cases. This suggests that a combination of detection methods of pathogens using RT-PCR and BAL fluid will facilitate determination of rational treatment aimed at influenza A virus.

[A case report of pulmonary blastoma--biphasic pulmonary blastoma].

We report a biphasic pulmonary blastoma in a 77-year-old man. In a routine chest radiographic examination, in the left upper lung field, a massive shadow that had been entirely absent one year before was detected. The preoperative imaging films showed a 10 x 8 cm, well-circumscribed solid tumor in the upper lobe of the left lung. A preoperative clinical diagnosis of primary lung cancer was considered. The intraoperative findings were that the tumor had invaded the visceral pleura with adhesion to the parietal pleura. Left upper lobectomy with lymph node sampling was performed, and since invasion of the pulmonary artery wall was confirmed, complete removal of tumor was not possible. The postoperative diagnosis was biphasic pulmonary blastoma. The patient was treated with radiotherapy up to a limit of 50 Gy, covering the area around of the left hilum. At the latest follow-up, 1 year postoperatively, the patient was clinically and radiologically free of the disease.

Mutation and polymorphism analysis of the TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth factor in congenital insensitivity to pain with anhidrosis (CIPA) families.

The human TRKA gene encodes a high-affinity tyrosine kinase receptor for nerve growth factor. Congenital insensitivity to pain with anhidrosis (CIPA) is an autosomal recessive genetic disorder reported from various countries and characterized by anhidrosis (inability to sweat), the absence of reaction to noxious stimuli, and mental retardation. We have found that TRKA is the gene responsible for CIPA. We have studied TRKA in 46 CIPA chromosomes derived from 23 unrelated Japanese CIPA families. including three that have been previously reported, and identified 11 novel mutations. Four (L93P, G516R, R648 C, and D668Y) are missense mutations that result in amino acid substitutions at positions conserved in the TRK family, including TRKA, TRKB, and TRKC. Three (S131 fs, L579 fs, and D770 fs) are frameshift mutations. Three (E164X, Y359X, and R596X) are nonsense mutations. The other is an intronic branch-site (IVS7-33T-->A) mutation, causing aberrant splicing in vitro. We also report the characterization of eight intragenic polymorphic sites, including a variable dinucleotide repeat and seven single nucleotide polymorphisms, and describe the haplotypic associations of alleles at these sites in 106 normal chromosomes and 46 CIPA chromosomes. More than 50% of CIPA chromosomes share the frameshift mutation (R548 fs) that we described earlier. This mutation apparently shows linkage disequilibrium with a rare haplotype in normal chromosomes, strongly suggesting that it is a common founder mutation. These findings represent the first extensive analysis of CIPA mutations and associated intragenic polymorphisms; they should facilitate the detection of CIPA mutations and aid in the diagnosis and genetic counseling of this painless but severe genetic disorder with devastating complications.

[Chlamydia pneumoniae infection in patients with acute bronchitis and bronchial asthma].

In this study, a total of 60 patients with acute bronchitis, 71 patients with bronchial asthma and 20 healthy volunteers were serologically and bacteriologically analyzed to investigate whether Chlamydia pneumoniae infection is associated with the onset and the exacerbation with acute bronchitis and bronchial asthma. Antibody titers to Chlamydia pneumoniae were also measured and compared by ELISA method. The antibody-positive rate in the patients with acute bronchitis (88.4%) was significantly higher than that in the patients with bronchial asthma (73.3%) or that in the healthy volunteers (60%). And the levels of the IgA antibody in the patients with acute bronchitis were significantly higher than those in the patients with bronchial asthma or those in the healthy volunteers. The rate of acute C. pneumoniae infection in the patients with acute bronchitis (20%) did not show significantly differences compared with that in the patients with bronchial asthma (15.5%) or that in the healthy volunteers (10%). The cases of acute C. pneumoniae infection had both as a single etiologic agent and as a mixed infection, most often with Streptococcus pneumoniae. Therefore, we demonstrated that the acute C. pneumoniae infection may be associated with the onset and the exacerbation in acute bronchitis and bronchial asthma.

[An autopsy case of catastrophic antiphospholipid syndrome presenting with recurrent multiple cerebral infarction associated with lung cancer].

We reported an autopsy case of cerebral infarction with primary lung cancer. The patient was a 50-year-old man. Despite having been treated with warfarin potassium and ticlopidine hydrochloride, he relapsed cerebral infarction. His laboratory data on admission showed that lupus anticoagulant was positive, together with a high value of beta-thromboglobulin, thrombin-antithrombin III complex, markers of platelet and coagulation activation, CEA and CA 19-9. The autopsy finding revealed a primary papillary adenocarcinoma in the right lower lung, multiple cerebral infarction, renal infarction, pulmonary infarction and splenic infarction. The atherosclerotic changes were mild in the whole tissues and findings of vasculitis were not observed. Recurrence of cerebral infarction was effectively suppressed with the addition of steroid therapy to antithrombotic therapy. This case was considered as catastrophic antiphospholipid syndrome. It is necessary to differentiate antiphospholipid syndrome in case of the abnormal coagulation and fibrinolytic factors with recurrent cerebral infarction. Moreover, systemic examinations are important, because malignant tumor may exist on the background of the case.

Surgical indication for refractory childhood epilepsy.

Recent progress in surgical intervention for medically refractory epilepsy has helped to shed light on more complex epileptogenic problems in children and infants. Surgical treatment increasingly is being used in pediatric patients, but the indications for surgery in this age group have not been well defined. The developing child with a seizure disorder has several problems that are different from adults, such as neural plasticity, deleterious effects of seizures on developmental status, and spontaneous resolution of epilepsy. The critical age for irreversible brain dysfunction and the timing of surgery are the main issues for the treatment of children. Thus, earlier surgical intervention is generally recommended to prevent further detrimental seizure effects, but we still do not know the optimal age. Until the establishment of guidelines for pediatric epilepsy surgery, surgical indications should be determined by the prognosis and the presence of a resectable epileptogenic focus, which in turn are based on the localization of the epileptic focus, seizure frequency, severity, and cognitive function of each case, rather than just the patient's age.

[Monozygotic twins with suspected hereditary sensory and autonomic neuropathy (HSAN) type V].

We report a pair of 1-year-5-month-old female monozygotic twins with generalized loss of pain sensation, but without impairment of other sensory modalities and the diaphoretic function. Routine electrophysiological investigations revealed no abnormalities. Morphometric analysis of biopsied sural nerve showed that the number of small myelinated fibers was reduced and that of unmyelinated fibers was normal or mildly reduced. On the basis of these findings, we suspected a diagnosis of a rare disorder, HSAN type V, which has not previously been reported in Japan.