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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.

We present a Chinese female infant with an intermittent form of MSUD whose early development was relatively well. A total of three episodes of stupor and metabolic acidosis developed with a concurrent illness after the age of 13 months. The initial analyses of plasma amino acid and urinary organic acid were normal. Initially, an abnormal oral glucose lactate stimulation test and high signal in the bilateral globus pallidus over T2-weighted brain MRI led us to suspect a mitochondrial disorder. The final diagnosis was made after the patient died at 31 months of age.

A 13 year-old girl with scoliosis and central core disease is reported. She was noted to have mild psychomotor developmental delay since early infancy. Scoliosis with minimal muscle weakness was noted at about five years old. The neurological examination disclosed absent knee jerk. The spine MRI showed no significant finding. The serum CK revealed 518 U/L. The muscle biopsy obtained from the quadriceps femoris muscle showed Type 1 fiber atrophy and predominance, as is commonly seen in congenital myopathies. Under nicotinamide adenine dinucleotide dehydrogenase (NADH) and succinate dehydrogenase (SDH) stains, core structures were identified and the diagnosis of central core disease (CCD) was made. Since kyphoscoliosis usually becomes prominent as muscle weakness progresses to loss of ambulation in other myopathies, the disproportionate spinal involvement in central core disease appears to be a striking feature. We suggest that all patients with idiopathic scoliosis deserve a thorough neurological evaluation if congenital myopathies are suspected. Muscle biopsy should also be recommended for a confirmatory diagnosis even if only minimal muscle weakness present. Besides, early detection of CCD helps us to identify the population who are at a higher risk for malignant hyperthermia.

A 2 5/12-year-old Chinese boy was investigated for refractory seizures and psychomotor regression. His birth history was unremarkable. Generalized seizures occurred at 2 weeks of age with hypocalcemia. They recurred at 7 months of age and have become aggravated since. During hospitalization, in addition to hypocalcemia and hypomagnesemia, he was found to have hypoparathyroidism, cardiomyopathy, and brain atrophy. Excessive renal loss of magnesium, general intestinal malabsorption, or inadequate dietary intake of magnesium were excluded. He was successfully treated with oral supplements of 19-25 mmole/day of magnesium. Over a few months, he made a dramatic progress in development. His hypoparathyroidism and cardiomyopathy gradually resolved. However, intermittent seizures and psychomotor retardation persisted up to his present age of 6 3/12 years. At 4 months of age his younger sister also developed seizures and was found to have isolated hypomagnesemia. This was corrected by oral magnesium and followed by resolution of the seizure. She has developed normally up to her present age of 1 10/12 years. Both patients are currently maintained on oral magnesium oxide.

The inclusion criteria for afebrile cluster seizures in infancy are defined as follows: (1) frequency of afebrile seizures at least 2 episodes within 72 hours; (2) seizure onset between 2 months and 3 years of age; (3) excluding febrile convulsion, central nervous system infections, status epilepticus, well-known epileptic syndromes in infancy (e.g. early myoclonic encephalopathy, early infantile epileptic encephalopathy, benign myoclonic epilepsy, infantile spasms. Lennox-Gastaut syndrome), electrolyte imbalance, watery diarrhea, head injury and intoxication. From 1986 to 1996, retrospectively and prospectively 22 patients were collected who fulfilled the above criteria. Based on whether or not a strong family history was present and a history of mild diarrhea was associated with seizure onset, they were divided into three groups: Group I, benign infantile familial convulsions (4 patients); Group II, cluster seizures with mild diarrhea in infancy (5 patients); Group III, cluster seizures without diarrhea in infancy (13 patients). Before seizure onset and during follow-up, all of the patients had normal development. The seizure pattern in all was generalized, most tonic type with duration of seizure less than five minutes in the majority. Recurrence rate was 100% in Group I and no recurrence in Group II. In 16 patients who were seizure-free over 12 months, the duration of persistence varied from 1 day to 8 months, and was shortest in Group II (range, 1 to 3 days). It was concluded that the vast majority of afebrile cluster seizures in infancy are benign in nature. Whether anticonvulsant therapy is justified must be individualized.

There were a total of 22 cases of cerebellar dysgenesis documented by brain sonogram, and/or brain computer-tomography scan, and/or brain magnetic resonance imaging (MRI) in our department over the past 10 years. There were ten males and twelve females. The mean age at diagnosis was 5.79 months. The follow-up period ranged from 2 days to 132 months. Seven cases were suspected upon prenatal examination. Three cases presented with isolated cerebellar hypoplasia, one with Dandy- Walker malformation and three with Joubert syndrome. Seven cases presented with cerebellar dysgenesis complicated with supratentorial brain dysgenesis. Among them, three had vermis hypoplasia with hypoplasia of the corpus callosum, 1 had vermis hypoplasia with holoprosencephaly, 1 had cerebellar hypoplasia with lissencephaly and hypoplasia of corpus callosum, 1 had vermis hypoplasia, agenesis of the corpus callosum and pachygyria, and 1 had cerebellar hypoplasia, hypoplasia of corpus callosum and midline cystic malformation. They all showed severe psychomotor retardation. Six cases showed chromosome anomalies. The neurological outcome for cases with isolated cerebellar hypoplasia was better than the outcome of the complicated cases. MRI is recommended for patients with microcephaly to check for the possibility of combined supratentorial brain dysgenesis. When performing MRI, a median sagittal view should be included. A classification for clinical approach was presented at the same time. In this retrospective study, this classification seemed to have benefits in prediction of clinical outcomes.

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.

A 22-month-old female presented with developmental delay and dystonia. The T2 weighted image of the brain MRI showed bilateral symmetrical high signal lesions over the putamen. An increased serum lactate pyruvate ratio (29.25) and a positive oral glucose lactate stimulation test were noted. Electron microscopic examination showed abnormal mitochondrial aggregation with band cristae in the subsarcolemmal area. These findings were indicative of clinical Leigh's syndrome. However, unusually the mt DNA analysis showed a point mutation at the nucleotide position 8344.

Lesch-Nyhan syndrome is a rare X-linked disease characterized by over-production of uric acid and a central nervous system (CNS) disorder consisting of mental retardation, spasticity, choreoathetosis, and a compulsive form of self-mutilation. A deficiency in hypoxanthine-guanine phosphoribosyl transferase (HPRT) provides the underlying metabolic basis for this disease. A 12 month-old male baby who had orange crystals over the diapers since he was 3 months old was brought to our hospital due to developmental delay. Mental retardation and athetosis were also noted. Chemical analysis revealed hyperuricemia (uric acid 8.6 mg/dl). Urine routine showed microscopic hematuria and uric acid crystals. The activity of HPRT in erythrocyte lysates of parents were both within normal limits, but that of the patient was very low (0.0547 nm/min/mg protein, < 0.05% of control). His younger brother was born 2 months after this disorder diagnosed in this patient. The younger brother was noted to have uric acid crystals over the diapers when he was 40 days old and hyperuricemia (10.6 mg/dl) showed up later. He was also a case of Lesch-Nyhan syndrome since the activity of HPRT in erythrocyte lysates was also low (0.0327 nmol/min/mg protein, < 0.05% of control). Further studies, including carrier detection and deoxyribonucleic acid (DNA) analysis, could be helpful for genetic counseling. This syndrome is rare among Chinese, and this may be due to underdiagnosis.

Hallervorden-Spatz syndrome is generally considered to be an autosomal recessively hereditary disorder of unknown etiology. Some reported cases have been known to be sporadic. We present a boy who suffered from regressive developmental milestones since he was 2 years and 6 months old. He began to manifest tremors of the upper extremities, followed by unsteady gait, choreoathetosis, dystonia, dysarthria, and dysphagia at 4 years old, and subsequently became completely bedridden at 6 years old. Neurologically, opisthotonus, rigidity of extremities, dystonia, hyperreflexia, profound emaciation, and bilaterally positive Babinski signs were present. The brain magnetic resonance imaging (MRI) done at the age of 8 years revealed symmetrical low signal intensity over the bilateral globus pallidi in the T2-weighted images coexistent with an area of high signal intensity over the anteromedial portion, known as "eye of the tiger" sign. Another MRI, followed up two years later, did not show marked difference in signal abnormalities over the globus pallidi in the T2-weighted images as compared with that of the previous one. However, progressive neurological deterioration existed.

From October 1982 to June 1992, 94 neurologically normal Chinese Children (50 males & 44 females) with benign partial epilepsy of childhood with centrotemporal spikes were studied among 1847 epileptic infants and children. Their ages at onset were between 3.6 and 12 years (a mean of 7.3 years). All of them had normal birth and developmental histories. Seven patients (7.5%) had past history of febrile convulsion and 12 cases (12.8%) had family history of epilepsy. The depicted seizure patterns were protean, but most attacks (83%) occurred during sleep (nocturnal & diurnal). The duration of active period and seizure frequency had no significant difference in terms of sex and treatment, but early-onset patients (< 7.3 years) had statistically significant longer duration of active period than that of late-onset group (p < 0.01). We recommend that antiepileptic drug treatment is not essential for this disease. Even if antiepileptic drug is used, the low-dosed carbamazepine is suggested.

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.

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.

Fourteen patients (10 boys, 4 girls) aged from 4 months to 14 years old were diagnosed with mitochondrial disease based on the clinical manifestations together with abnormal muscle mitochondrial morphologies. Their clinical diagnoses included Leigh syndrome, three; Menkes' syndrome, three; Kearns-Sayre syndrome, two; myoclonic epilepsy with ragged fibres, one; and infant-onset progressive myoclonic epilepsy, one; fatal infantile mitochondrial myopathy, one; fatty acid oxidation defect, two; and myopathy with cardiopathy, one. Organs involved other than muscles included central nervous system, ten; heart, six; eye, two; liver, two; and kidney, two. Clinical manifestations varied to include hypotonia, seizures, myoclonus, mental retardation, nystagmus, ataxia, ptosis, ophthalmoplegia, retinal degeneration, muscle atrophy, spasticity etc. Nine had an abnormal rise in lactate after glucose loading. Ragged-red fibres were found in four patients. Abnormal mitochondrial morphology included abnormal accumulation, abnormal cristae pattern of tubular, concentric, or parallel form, some contained osmiophilic inclusion bodies. One patient of Leigh syndrome had had brain necropsy which showed intramyelin splitting of myelinated axons.

Arthrogryposis multiplex congenita is a congenital syndrome characterized by multiple congenital joint contractures; and refers to a large heterogeneous group of disorders. We present a 40 days old male baby who has had multiple fixed contractures of joints since birth. Midline capillary hemangioma, internal rotation of bilateral shoulders, extension contracture of elbows, flexed wrists with pronation deformity, flexion and internal rotation of hips, equinovarus of feet were noted. A series of examinations for differential diagnosis including brain sonogram, echocardiogram, muscle echogram, muscle biopsy, chromosome study were performed and all showed normal findings. Amyoplasia was impressed. Early rehabilitation was arranged. Normal intelligence and a normal life span are expected.

Exophthalmos occurs in more than half of the patients with childhood Graves' disease, while severe Graves' ophthalmopathy is uncommon in children. Myasthenia gravis is even more rare in association with Graves' disease. A 7-year-old girl is reported; she had ptosis for two years; this was treated irregularly, and she then developed exophthalmos, ophthalmoplegia and thyroid goiter. Her laboratory tests showed T3 496 ng/dl, T4 17.05 ug/dl, TSH < 0.1 uU/ml, fT4 > 4.2 ng/dl. Antithyroglobulin antibody was 1:25600 and antimicrosomal antibody was 1:102400. Myasthenia gravis was confirmed by a positive neostigmine test. Due to allergic reaction to propylthiouracil, she was treated with carbimazole and propranolol. Thereafter the thyrotoxicosis was was well controlled. The ocular-type myasthenia gravis remained stable with minimum medical treatment.

Metachromatic leukodystrophy (MLD) is a neurodegenerative disorder with autosomal recessive inheritance, in which cerebroside sulphate (sulphatide) accumulates in the central and peripheral nervous systems due to a deficiency of arylsulphatase A. This article presents a 2-year-old boy who had occasional shortness of breath, horizontal nystagmus and unstable gait for 3 months prior to the entry. He was admitted to our hospital due to shortness of breath, frequent apnea, generalized hypotonia and conscious disturbance. The lumbar puncture, brain CT scan, serum amino acid analysis, urine organic acid assay and nerve conduction velocity of lower extremities all showed negative findings. The electron microscopic finding of muscle elicited lipid deposition. The auditory brainstem response showed bilateral impairment. The routine EEG revealed diffuse slow waves. The brain MRI showed widespread low signals over the white matter of bilateral frontal and parietotemporal areas of the cerebral hemispheres, as well as the white matter of the bilateral cerebellar hemispheres, and the brain stem in the T1-weighted image corresponding the high signals in T2-weighted image. The blood leukocyte lysosomal enzyme activity test revealed arylsulphatase A deficiency. Rapid progressive neurological deterioration was noted since admission. Unfortunately, the patient expired due to respiratory failure in the final.

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.

Myoclonic epilepsy with ragged-red fibers (MERRF) is one of the mitochondrial encephalomyopathies. This article presents a nine-year-old boy who had been noted to have psychomotor retardation since infancy, and had progressive myoclonic epilepsy since he was four. The myoclonic epileptic seizures were refractory to the conventional anticonvulsants. The brain MRI, echocardiography and brainstem auditory-evoked-potential showed negative findings, but electroencephalography showed episodic generalized spike wave complexes. Oral glucose lactate stimulation test revealed abnormal elevation of lactic acid, and muscle biopsy showed ragged-red fibers. Subsarcolemmal accumulations of mitochondria with abnormal cristae in the muscle cells were noted under electronmicroscopic study. The patient was administered coenzyme Q 90 mg per day orally, with dramatic improvement in myoclonic seizures. The patient is still being followed up as an outpatient.

Congenital fiber type disproportion (CFTD) is described clinically as muscle weakness and hypotonia with delayed motor development, usually from infancy. Muscle biopsy reveals that type 1 fibers predominate and smaller than type 2 fibers by a margin greater than 12% of the diameter of the type 2 fibers. There are no other subcellular abnormalities, and generally prognosis is good. The CFTD case is a six-month-old girl who manifested clinically as a floppy infant. A biopsied specimen from the left biceps brachii muscle revealed type 1 fiber predominance and hypoplasia with an increased number of undifferentiated type 2C fibers. Electromyogram, nerve conduction velocity and serum creatine kinase level were normal. The child learned to walk without assistance at 1 year 7 month old. Now 2-years and 10-months old, she can climb stairs without difficulty, although she cannot run fast.