Viral encephalitis in children: detection with technetium-99m HMPAO brain single-photon emission CT and its value in prediction of outcome.

PURPOSE: To assess the role of regional cerebral blood flow measured by technetium-99m hexamethyl propyleneamine oxime (HMPAO) brain single-photon emission CT (SPECT) in viral encephalitis of children. METHODS: Eighteen children diagnosed as having viral encephalitis (12 Epstein-Barr virus, 4 herpes simplex virus, and 2 Japanese B virus) underwent Tc-99m HMPAO brain SPECT and brain MR and/or CT. RESULTS: During the acute episode, 4 (22%) of the 18 patients had localized abnormality on brain MR and/or CT. Tc-99m HMPAO brain SPECT in the acute phase showed that 17 (94%) of the 18 patients had increased regional cerebral blood flow and 1 (6%) of the 18 children had a normal brain SPECT. Follow-up brain SPECT was performed at least 15 days after the acute episode. In 17 patients with abnormal first brain SPECT, 12 (71%) had normal second brain SPECT and 5 (29%) had decreased regional cerebral blood flow. The group of patients with normal regional cerebral blood flow on the follow-up brain SPECT had a better outcome than the group of patients with decreased regional cerebral blood flow. CONCLUSIONS: (a) The Tc-99m HMPAO brain SPECT was abnormal more often than CT or MR in children with acute viral encephalitis and provided better location. (b) In acute episodes of encephalitis, most patients showed locally increased regional cerebral blood flow. (c) After acute episodes, the regional cerebral blood flow returned to normal in most cases. (d) A normal Tc-99m HMPAO brain SPECT in the subacute phase usually indicates a good clinical outcome (no neurologic defect) 1 year after the acute illness in children with viral encephalitis.

Guillain-Barré syndrome in children: a cooperative study in Taiwan.

Seventy-two children with Guillain-Barré syndrome (GBS), diagnosed at 11 major teaching hospitals in Taiwan during the period 1986-1990, were studied retrospectively. There were 44 males and 28 females ranging in age from 7 months to 15 years. Preceding events could be traced in 61 patients (85%), including antecedent infection in 59 patients and previous vaccination in 2. As well as the consistent pictures of progressive weakness and generalized hyporeflexia, there were sensory complaints (26%), cranial nerve lesions (46%), respiratory failure (14%) and autonomic dysfunction (25%). Motor symptoms reached a maximum within 20 days in 88% of the patients, with the plateau lasting less than 2 weeks in 75%, and became stable within 3 months in 76%. Overall outcome showed complete recovery in 73% of the patients within 6 months after onset. Four (5.6%) had recurrence, and there was no mortality. The present study revealed that the annual incidence of GBS in Taiwan can be estimated roughly as 0.66 per 100,000 and that the course of childhood GBS is relatively benign.

Leigh syndrome with progressive ventriculomegaly.

A 6-month-old female infant was diagnosed with Leigh syndrome after an abnormal muscle specimen was obtained and after magnetic resonance imaging demonstrated characteristic cranial lesions. She presented with episodic hyperventilation, myoclonus, ophthalmoplegia, hypotonia, and elevation of lactate in the cerebrospinal fluid and blood. A series of cranial ultrasounds revealed progressive ventricular enlargement before the typical lesions were detected by magnetic resonance imaging. Myelin destruction is believed to play an important role in the early stage of Leigh syndrome. Ultrasonography may provide a convenient way to document changes in brain that provide early suspicion of Leigh syndrome.

Oral glucose lactate stimulation test in mitochondrial disease.

We selected 23 patients with neurologic diseases, including 15 boys and 8 girls from 1 month to 10 years of age, who were divided into mitochondrial and nonmitochondrial disease groups. All patients were required to fast and rest for at least 4-10 hours before the test. Glucose was administered orally using a 50% glucose:water solution at a dose of 1.75 mg/kg. Blood samples then were drawn from a retained heparinized venous line at 0, 30, 60, 120, and 180 min and tested for lactate and glucose levels. Of the mitochondrial disease group, 10 of 11 patients had an upward sloping curve of lactate metabolism; the one who had a flat line response was a patient who suffered from a free-fatty-acid metabolic defect presenting with a recurrent Reye-like syndrome. There was a relatively flat line response in the nonmitochondrial disease group except in a patient with alternating hemiplegia whose symptoms responded well to flunarizine therapy. A significant increase in blood lactate content at 60 min after glucose loading occurred in the mitochondrial disease group, in contrast to that of the nonmitochondrial group. Sensitivity and specificity of a 5 mg/dl increase in blood lactate concentration at 60 min was 72.7% vs. 91.7% Moreover, all 4 patients whose blood lactate increased by 13 mg/dl at 60 min were in the mitochondrial disease group.

Leigh syndrome associated with mitochondrial DNA 8993 T-->G mutation and ragged-red fibers.

We report a 6-month-old girl with episodic hyperventilation, myoclonus, disturbed consciousness, and lactic acidosis. Brain sonogram revealed progressive ventriculomegaly, and MRI showed symmetric low densities over the putamen bilaterally with diffuse cortical cystic lesions. Ragged-red fibers were noted in the muscle biopsy. Molecular analysis revealed a heteroplasmic T-->G mutation at nucleotide position (np) 8993 of mitochondrial DNA (mtDNA). The proportion of the mutant mtDNA in the muscle of the proband was estimated to be 86%. Her mother and maternal uncle also harbored the same mutant mtDNA (54 and 48% in their leukocytes, respectively). One of her sisters carried 64% mutant mtDNA in her leukocytes, but another sister did not. These results suggest that this mutant mtDNA is transmitted through the maternal lineage in this family in a randomly segregated manner. To our knowledge, this is the first report of a Chinese patient with Leigh syndrome associated with the T-->G substitution at np 8993 of mtDNA.

Clinical observations and virological study of aseptic meningitis in the Kaohsiung area.

During 1988, an endemic outbreak of aseptic meningitis was noted in the Kaohsiung area. Throughout the year, a total of 89 cases were identified by cerebrospinal fluid (CSF) examination at the Pediatric Department of Kaohsiung Medical College. The peak incidence was from June to October. Scattered cases still occurred during November and December. The male to female ratio was 1.7:1 and the age distribution ranged from 1 month to 15 years old. Two peaks of age distribution were observed; one in infancy and the other in the 4-7 year old age group. Most of them exhibited fever (94.4%), headache (68.9%), and vomiting (68.5%). Other associated symptoms and signs included neck stiffness, sore throat, cough, Brudzinski's sign, abdominal pain, seizure, dizziness, rhinorrhea, diarrhea, Kernig's sign, skin rash, hyperemic conjunctiva, apnea, and oral ulcers. Most of them had CSF white blood cell (WBC) counts less than 1000/mm3, normal or mild elevated protein, and normal CSF/plasma sugar ratio. Three patients were found to have a virus in their CSF without pleocytosis. Virus isolations from CSF throat swabs and/or rectal swabs were performed in 65 patients, half of them (35/65, 53.8%) had positive results including echovirus type 9 (sixteen), echovirus type 30 (eighteen), and adenovirus type 3 (one). Echovirus type 9 was predominant during July and August whereas echovirus type 30 became predominant after September. All patients recovered spontaneously without any sequelae.

Tc-99m HMPAO brain SPECT findings in pediatric viral encephalitis.

Two children were diagnosed with viral encephalitis, due to Epstein-Barr virus infection in one case and to herpes simplex virus infection in the other. Tc-99m HMPAO brain SPECT was arranged to detect changes in regional cerebral blood flow (rCBF) secondary to viral encephalitis. During the acute episode, Tc-99m HMPAO brain SPECT showed that the two cases had increased rCBF. After the acute episode, follow-up brain SPECT was arranged 6 months later. The rCBF in one case was restored to normal on the second brain SPECT, and that in the other case was decreased. The child with normal rCBF in the follow-up brain SPECT had better learning ability and intelligence than the other child with decreased rCBF.

Clinical experience of ketogenic diet on children with refractory epilepsy.

Thirteen children with refractory epilepsy received a ketogenic diet (medium chain triglyceride oil diet) as an alternative therapy since September 1997. Their seizure patterns included (1) generalized tonic-clonic seizures, (2) myoclonic seizures, (3) generalized tonic + atonic seizures, (4) complex partial seizures, (5) generalized clonic + atonic + myoclonic seizures, (6) head nodding + myoclonic + gelastic seizures, and (7) generalized tonic-clonic + myoclonic + atonic seizures. Major concerns emphasized on the efficacy and side effects of the diet. Clinical observation one month after the diet revealed that 53.8% of the patients had a > 75% reduction in seizure frequency and 76.9% of the patients had a > 50% reduction in seizure frequency. Six patients had some degrees of improvement in cognitive function and/ or school performances. The most common side effects were body weight loss (n = 6) and diarrhea (n = 5). Others included bad temper (n = 1), abdominal cramps (n = 2), nausea (n = 2), bad body smell (n = 1), and renal stones (n = 1). Even after discontinuation of the diet, 61.5% of patients still had a > 50% reduction in seizure frequency. We concluded that the ketogenic diet deserves a trial in children with refractory epilepsy.

Stiff-Baby--an unusual manifestation of cytoplasmic body myopathy: report of one case.

A 2-month-old male baby was admitted to our hospital with episodic cyanosis and respiratory failure which required mechanical ventilation. He was found to have upper limb flexion rigidity and poor weight gain since one month old. Progressive muscle stiffness over the abdomen, chest wall, back and four limbs were also noted. He could not be weaned from the ventilator smoothly due to recurrent CO2 retention. Laboratory tests revealed a high serum creatine kinase level. Cytoplasmic body myopathy was confirmed by muscle biopsy. The unusual initial presentations of generalized stiffness and early onset of respiratory failure were quite different from those of patients reported in the literature, who had floppiness, muscular atrophy and weakness. Prednisolone and Vigabatrin were given and the patient showed slight improvement in muscle stiffness and spontaneous movement.

Zellweger syndrome: report of one case.

Zellweger syndrome is a fatal autosomal-recessive hereditary disease characterized by the absence of peroxisomes in liver and kidneys. The absence of peroxisomes results in impairment of many metabolic pathways, especially beta-oxidation of very long chain fatty acids (VLCFAs). We report a case of a three-month-old male infant with facial dysmorphism, hypotonia, psychomotor retardation, and hepatomegaly. He had an elder brother with the same facial features and hypotonia who died of hepatic failure at four months of age. Biochemical studies revealed elevation of blood pipecolic acid and VLCFAs, compatible with peroxisomal disorder. Electron microscopy of liver biopsy revealed absence of peroxisomes. Zellweger syndrome was diagnosed. Because this syndrome is usually fatal in early life, genetic counseling and prenatal diagnosis are crucial.

Barrett's esophagus in a child with de Lange syndrome: report of one case.

Barrett's esophagus, a premalignant condition, is recognized as stratified squamous epithelium of the esophagus substituted by columnar epithelium. The risk factors for development of Barrett's esophagus include frequent gastroesophageal reflux, esophageal stricture, male sex and mental retardation, but there is no report of Barrett's esophagus in children with de Lange syndrome. We report a 7-year-old boy who was diagnosed as de Lange syndrome shortly after birth and had gastroesophageal reflux since early infancy. Upper gastrointestinal endoscopic examination revealed a cauliflower-like mass and a pink-red velvety mass over the lower third of the esophagus. Biopsy showed goblet cells metaplasia, confirming Barrett's esophagus. We suggest surveillance of Barrett's esophagus could be done ahead of schedule in children with long-standing gastroesophageal reflux or with de Lange syndrome.

Clinical characteristics of cough mixture abusers referred to three substance abuse clinics in Hong Kong: a retrospective study.

OBJECTIVES. Cough mixture is the third most commonly abused substance in patients attending the Prince of Wales Hospital Substance Abuse Clinic. The content of the local cough mixture is not well researched. Paranoid psychosis manifesting as persecutory delusions and derogatory hallucination, as well as mood symptoms, is common in these patients. The natural history and outcome of such psychoses associated with cough mixture abuse are not well known. This study aimed to address these questions. METHODS. This was a retrospective study of cough mixture abuse in Hong Kong. Case records of cough mixture abusers currently receiving treatment at the 3 substance abuse clinics at the Prince of Wales Hospital, Alice Ho Miu Ling Nethersole Hospital, and the North District Hospital were retrieved for data collection. The patients' demographic data, duration and intake pattern of cough mixture, and use of any other drugs were documented. The presenting psychopathology, first urine toxicology results, diagnosis, treatment, number of hospitalizations, and course of the illness were also recorded. RESULTS. A total of 63 patients with the diagnosis of cough mixture abuse were identified in the database; 89% were male. The mean +/- SD age of the patients was 34.4 +/- 6.2 years; 67% were single and 83% were unemployed. The mean +/- SD age of onset of cough mixture abuse was 20 +/- 5 years. Psychiatric symptoms developed a mean +/- SD of 7.6 +/- 6.0 years after onset of abuse. According to the ICD-10 Mental and Behavioural Disorders criteria, the top psychiatric diagnoses were substance-induced psychotic disorder (67%), schizophrenia (19%), depressive disorder (11%), and dysthymia (10%). The most common ingredients in the urine sample at first presentation were promethazine (75%), pseudoephedrine (67%), codeine (60%), ephedrine (57%), zopiclone (17%), and hydrocodone (16%). Additionally, 16% of patients were in the priority follow-up group. The mean +/- SD follow-up period was 6.2 +/- 7.1 years during which there were 3.2 +/- 3.7 episodes of hospitalizations, with a mean +/- SD length of stay in each admission of 25.0 +/- 40.9 days. CONCLUSIONS. Promethazine, ephedrine, pseudoephedrine, codeine, and hydrocodone are the most common ingredients of cough mixture abused in this locality. Psychotic disorders are the most frequent psychiatric diagnosis associated with cough mixture abuse.

[Infantile bilateral necrosis of the striatum of corpus: report of four cases].

The designation of "Infantile Bilateral Striatal Necrosis" (IBSN) was first given by Friede in 1975. However, this unusual condition was first described by Paterson and Carmichael in 1924. The disease is rare with uncertain etiology. The clinical picture includes choreoathetosis, abnormal eye movements, seizures and mental dullness. These circumstances often follow symptoms such as fever, vomiting and impaired consciousness. The final diagnosis is confirmed by pathological examination, which reveals symmetrical degeneration of bilateral basal ganglia. With present technology IBSN can be well demonstrated in the brain Ct scans or MRI scans nowadays. This article reports four cases with clinical manifestations which had appeared before the age of one year. Three cases had prodromal upper respiratory tract infection symptoms with vomiting, while seizure and impaired consciousness ensued. One case had several bouts of pneumonitis followed by seizures, impaired consciousness and abnormal eye movement. Brain sonogram of one of these cases showed hyper-echoic basal ganglia, while CT scans or MRI scans revealed symmetrical hypodensity or signal change over bilateral basal ganglia, respectively. All of these led to a bedridden life. These four cases are reported based on their clinical presentations and brain imaging findings, in spite of the absence of pathological confirmation. Some of the literature are also reviewed. To sum up, IBSN should be kept in mind in the differential diagnosis of symmetrical bilateral basal ganglia lesion after the exclusion of other disorders such as neurometabolic disorders, central nervous system infection, carbon monoxide intoxication, hypoxic-ischemic encephalopathy, tumors and cerebrovascular disorders etc.

Intramyelin splitting in the spongiform lesions of Leigh syndrome.

A 5-month-old male infant, diagnosed as Leigh syndrome, presented with developmental delay, episodic apnea, metabolic acidosis, and myoclonic seizures. The magnetic resonance image of brain showed multiple symmetric low signals over the putamen in the T1-weighted axial view and linear high signal over the brainstem in the T2-weighted sagittal view. On electron microscopy, subsarcolemmal aggregation of abnormal mitochondria in muscle cells were found via biopsy. Small samples of myocardium, liver and brainstem, obtained via necropsy, were subjected to pathological examinations. On light microscopy, vacuoles were found in the myocardium and hepatocytes, while spongiform lesions in the neuropils, round cell infiltration, and vascular proliferation were observed in the brainstem. On electron microscopy, intramyelin splittings were observed in the spongiform lesions. We believe that intramyelin splitting must play an important role in the pathogenesis of spongiform lesions in Leigh syndrome.

Hemorrhagic shock and encephalopathy-like syndrome: report of a case with emphasis on the pathological findings.

The case of a 5-month-old boy with sudden onset of shock, encephalopathy, watery diarrhea, bleeding tendency, and impaired hepatic and renal functions was reported. The different pathological findings as compared with the previous reports made the term "hemorrhagic shock encephalopathy-like syndrome" (HSE-like syndrome) more suitable for this case. Marked fatty metamorphosis with hemorrhage was found with a light microscope. Electron microscopy revealed flocculent densities in the mitochondria which might be a poor prognostic indicator in this syndrome. Diffuse electron-dense deposits in the peroxisomes were also seen and the significance of this finding was discussed. The patient died on the third day after admission due to multiorgan failures in spite of our aggressive management.

Hereditary spastic paraplegia: report of two siblings.

Hereditary spastic paraplegia (HSP) is a degenerative disorder of the central nervous system, characterized by progressive weakness and spasticity of the lower extremities. The first symptom is usually leg stiffness, unstable gait with difficulty in walking. According to the clinical features, hereditary spastic paraplegia can be divided into pure type and complicated type. The mode of hereditary spastic paraplegia can be autosomal dominant, autosomal recessive or X-linked. There have been many loci on chromosomes identified in recent years. We present two Chinese siblings with unstable gait, a 5-year-3-month-old brother and his 3-year-1-month-old sister, who belong to the pure type hereditary spastic paraplegia. Both of them had motor deficit on follow up.

Mitochondrial encephalomyopathy presenting with clinical Leigh's disease: report of a case.

Leigh's disease is one of the mitochondrial encephalomyopathies. This article presents a 7-month-old baby boy who had been well-being since birth until 6 months of age when episodic downward gaze of both eyes with limitation of horizontal eye movement were noted. This episode of cranial nerve palsies lasted about 4-5 days and subsided spontaneously. The second attack was noted one month later, to be associated with hypotonia and truncal ataxia. Episodic hyperventilation with resultant gasping and myoclonus was noted at the third attack but spontaneous respiration resumed soon with persistent ophthalmoplegia and truncal ataxia. Lumbar puncture, brain MRI, amino acid assay and cardiac echo all showed negative finding. The oral glucose lactate stimulation test revealed an elevation of lactic acid, brain stem evoked potential indicated bilateral obscure 4th and 5th waves, and muscle biopsy showed ragged red fibres with aggregation of structurally abnormal mitochondria noted under electron microscope. Coenzyme Q, thiamine and carnitine had been given before biochemical study; however, the neurological symptoms did not show any improvement. Biochemical study finally revealed normal respiratory chain enzymes including NADH-coenzyme Q reductase, succinate coenzyme Q reductase and cytochrome c oxidase while other enzymes were technically unavailable for study. Unfortunately the patient died at 18-month-old due to respiratory failure.

Neuroimage in infants and children with mitochondrial disorders.

Neuroimage studies of thirty-eight infants and children with mitochondrial disorders were reviewed: 24 ultrasound (US), 21 computed tomography (CT), and 27 magnetic resonance image (MRI) examinations were analyzed. Patients included seventeen with Leigh syndrome, two with Kearns-Sayre syndrome (KSS), one with myoclonus, epilepsy, and ragged red fibers (MERRF), one with Alpers disease, five with Menkes disease, two with fatty acid metabolic defect, two with Rett syndrome, and eight with unspecified mitochondrial disorders. KSS and MERRF tended to occur in older children, whereas Leigh syndrome, Menkes disease, and Alpers disease occurred in infants and young children. The deep cerebral nuclei and the cerebral white matter were commonly involved in Leigh syndrome and KSS. Subdural hematomas or effusions with profound cerebral atrophy was found in Alpers disease and Menkes disease. Tortuosities of basilar, Willis circle, and cerebral vessels were also noted in Menkes disease. MRI and CT examinations of Rett syndrome, fatty acid metabolic defect, and most of the unspecified mitochondrial disorders were normal. Our results indicate that neuroimage studies have characteristic findings for specific mitochondrial syndromes.

Epstein-Barr virus encephalitis: clinical observations in nine Chinese children.

Nine Chinese children (four males, five females) in whom serology showed Epstein-Barr virus infection were studied retrospectively. They were from 1.5 to 14 years of age. Various symptoms and signs, including disturbance of consciousness, visual hallucination, cranial neuropathies and sphincter dysfunction, led to initial clinical impressions of encephalitis, encephalomyelitis and neuro-degenerative disease. Electroencephalography showed focal spikes over the frontal, occipital, temporal and parietal areas. The patients underwent brain computed tomography and/or magnetic resonance imaging, and three of them underwent HMPAO SPECT. Eight patients appeared normal neurologically during follow-up, and the single patient who had spastic quadriparesis improved gradually. Though visual hallucination is not a specific presentation, it is a peculiar picture of Epstein-Barr virus encephalitis. Epstein-Barr virus encephalitis seemed to be self-limiting without specific treatment in this group.