Yu-Zen Shen

Docosahexaenoic acid inhibits synaptic transmission and epileptiform activity in the rat hippocampus.

Docosahexaenoic acid (DHA) has been suggested to be required for neuronal development and synaptic plasticity. However, in view of the fact that DHA facilitates NMDA responses and blocks K+ channels, it might predispose the neurons to epileptiform bursting. By using extracellular recording of population spikes in the CA1 region of rat hippocampal slices, we tested this possibility by examining the effect of DHA on the epileptiform activity induced by bicuculline or in Mg2+‐free medium. When stimuli were delivered to the Schaffer collateral/commissural pathway every 20 or 30 sec, DHA had no significant effect on the epileptiform activity. However, when the frequency of stimulation was increased to 0.2 Hz, DHA attenuated the amplitude of the bursting activity induced by bicuculline to 57.5 ± 10.8% and those induced by Mg2+‐free ACSF to 65.8 ± 13.9% of control. DHA reduced the slope of field excitatory postsynaptic potential (fEPSP) to 77.1 ± 7.4% of baseline, without significant effect on the ratio of paired‐pulse facilitation (PPF). By intracellular recording of neurons in the stratum pyramidale of rat hippocampal slices, we found that DHA markedly inhibited the repetitive firing of action potentials elicited by depolarizing current pulses but did not affect the initial action potential. Thus, DHA may attenuate epileptic activity mainly through the frequency‐dependent blockade of Na+ channels. Synapse 37:90–94, 2000.

Neuroprotective effect of lamotrigine and MK-801 on rat brain lesions induced by 3-nitropropionic acid : Evaluation by magnetic resonance imaging and in vivo proton magnetic resonance spectroscopy

Magnetic resonance imaging and in vivo proton magnetic resonance spectroscopy were used to evaluate the therapeutic effect of lamotrigine and MK-801 on rat brain lesions induced by 3-nitropropionic acid. Systemic administration of 3-nitropropionic acid (15 mg/kg per day) to two-month-old Sprague-Dawley rats (n = 10 for each group) for five consecutive days induced selective striatal and hippocampal lesions and specific behavioral change. Pretreatment with lamotrigine (10 mg/kg or 20 mg/kg per day) or MK-801 (2 mg/kg per day) attenuated the lesions and behavioral change. There were no significant differences in T2 values of the striatum and hippocampus among rats pretreated with MK-801, lamotrigine (20 mg/kg) and sham controls. Significant elevations of succinate/creatine and lactate/creatine ratios and decreases of N-acetylaspartate/creatine and choline/creatine ratios were observed after 3-nitropropionic acid injections (P < 0.001). The changes were nearly prevented after pretreatment with lamotrigine (20 mg/kg). However, the N-acetylaspartate/creatine in rats pretreated with lamotrigine (10 mg/kg) (P < 0.01) and MK-801 (P < 0.05) still showed significant reduction as compared with sham controls. Thus we conclude that both lamotrigine and MK-801 are effective in attenuation of brain lesions induced by 3-nitropropionic acid. A higher dose of lamotrigine provides a better neuroprotective effect than MK-801. With a better therapeutic effect and fewer side effects, lamotrigine is more promising for potential clinical application.

The mechanisms of neuronal death produced by mitochondrial toxin 3-nitropropionic acid: the roles of N-methyl-D-aspartate glutamate receptors and mitochondrial calcium overload

Previous studies showed that 3-nitropropionic acid, an irreversible inhibitor of succinate dehydrogenase, produced neuronal death secondary to perturbed intracellular calcium homeostasis. However, the response of intramitochondrial calcium ([Ca(2+)](m)) to 3-nitropropionic acid remains unknown. In this study, we investigated the roles of and relationships among [Ca(2+)](m) overload, mitochondrial reactive oxygen species, and mitochondrial membrane depolarization in 3-nitropropionic acid-induced neuronal death. Following 1 mM 3-nitropropionic acid treatment on primary rat neuronal cultures, there was a gradual increase of [Ca(2+)](m) beginning at 2-4 h post 3-nitropropionic acid application, and a twofold increase of mitochondrial reactive oxygen species at 4 h. These were followed by mitochondrial membrane depolarization at 6-8 h post-treatment. By inhibiting [Ca(2+)](m) uptake, Ruthenium Red attenuated the production of reactive oxygen species, and prevented the 3-nitropropionic acid-induced mitochondrial membrane depolarization and 70% of apoptotic neuronal death (P<0.001). Inhibition of caspase activation attenuated the elevation of [Ca(2+)](m) (P<0.001), indicating that caspase activation plays a role in the elevation of [Ca(2+)](m). MK-801, an antagonist of N-methyl-D-aspartate (NMDA) glutamate receptors, prevented 3-nitropropionic acid-induced [Ca(2+)](m) elevation, caspase-3 activation, mitochondrial depolarization, and neuronal death. We conclude that the activation of NMDA glutamate receptor contributes to mitochondrial alterations induced by 3-nitropropionic acid. Inhibition of its activation and [Ca(2+)](m) overload with subsequent mitochondrial membrane depolarization can therefore attenuate the neuronal death induced by 3-nitropropionic acid.

Multiphase CT Angiography versus Single-Phase CT Angiography: Comparison of Image Quality and Radiation Dose

BACKGROUND AND PURPOSE: Conventional CT angiography (CTA) is acquired during only a short interval in the arterial phase, which limits its ability to evaluate the cerebral circulation. Our aim was to compare the image quality and radiation dose of conventional single-phase CTA (SP-CTA) with a multiphase CTA (MP-CTA) algorithm reconstructed from a perfusion CT (PCT) dataset. MATERIALS AND METHODS: Fifty consecutive patients undergoing head CTA and PCT in 1 examination were enrolled. The PCT dataset was obtained with 40.0-mm-detector coverage, 5.0-mm axial thickness, 80 kilovolt peak (kVp), 180 mA, and 30 mL of contrast medium. MP-CTA was reconstructed from the same PCT dataset with an axial thickness of 0.625 mm by using a new axial reconstruction algorithm. A conventional SP-CTA dataset was obtained with 0.625-mm axial thickness, 120 kVp, 350 mA, and 60 mL of contrast medium. We compared image quality, vascular enhancement, and radiation dose. RESULTS: SP-CTA and MP-CTA of 50 patients (male/female ratio, 31/19; mean age, 59.25 years) were analyzed. MP-CTA was significantly better than SP-CTA in vascular enhancement (P = .002), in the absence of venous contamination (P = .006), and was significantly higher in image noise (P < .001). MP-CTA used less contrast medium than SP-CTA and could demonstrate hemodynamic information. The effective dose of MP-CTA was 5.73 mSv, which was equal to that in conventional PCT, and it was 3.57 mSv in SP-CTA. CONCLUSION: It is feasible that MP-CTA may provide both CTA and PCT results. Compared with SP-CTA, MP-CTA provides comparable image quality, better vascular enhancement, hemodynamic information, and more noise with less detail visibility with a lower tube voltage. The radiation dose of MP-CTA is higher than that of SP-CTA, but the dose can be reduced by altering the sampling interval.

Cancellation of low-frequency stimulation-induced long-term depression by docosahexaenoic acid in the rat hippocampus

The effects of docosahexaenoic acid (DHA) on low-frequency stimulation (LFS)-induced long-term depression (LTD) were investigated in the CA 1 subfield of rat hippocampal slices. LTD was routinely produced by LFS of 900 pulses at 1 Hz. The field excitatory postsynaptic potential (fEPSP) 40 min after LFS was 59 +/- 4% (n = 18) of baseline response. However, in experiments from 18 neurons pretreated with DHA (50 microM), fEPSP returned to baseline levels within 20 min after LFS in eight cells and was slightly potentiated in three cells. Only in seven cells was LTD induced. The effect of DHA on LTD was concentration dependent. The slopes of fEPSP 40 min after LFS were 67 +/- 4% (n = 6), 72 +/- 7% (n = 7) and 80 +/- 5% (n = 18) of baseline response, with pretreatment of 1, 10 and 50 microM DHA, respectively. The blockade of LTD induction suggests that DHA may play a role in learning and memory.

Intracranial arachnoid cysts in children: related signs and associated anomalies

Intracranial arachnoid cysts are benign development anomalies that may be clinically asymptomatic. The authors describe 30 children with intracranial arachnoid cysts in terms of clinical manifestations and relations to the associated brain anomalies or lesions. The mean age at onset of clinical manifestations was 4 years, 7 months (range 1 day to 14 years). The mean age at diagnosis was 6 years, 2 months (range 10 days to 16 years). Most patients with nonprogressive symptoms, such as seizures and headache, had focal epileptiform discharges on electroencephalogram, and they benefited from antiepileptic drugs. Surgery resulted in only partial reduction in both cyst size and seizure frequency in patients with intractable seizures, and it also failed to improve some neurologic signs, such as sexual precocity or cranial neuropathy resulting from long-term compression of arachnoid cysts. We conclude that the only absolute indication for surgery is the presence of progressive hydrocephalus or intracranial hypertension. The associated anomalies or lesions include brain tumors, giant nevocellular nevi, achondroplasia, microphthalmia, intracystic hemorrhage, dysgenesis of the corpus callosum, and heterotopia.

Rotavirus Gastroenteritis Associated with Afebrile Seizure in Childhood

From September 1994 to April 1995, we encountered eight children, two boys and six girls, (aged 1 year 6 months to 9 years), presented with acute diarrhea followed by afebrile, generalized tonic-clonic seizures, or transient loss of consciousness with urine incontinence. Their biochemical data, including serum electrolyte levels, were within normal limits. The infective agent causing diarrhea was later proved by stool examination to be rotavirus, judged to be serotype G1 by reverse transcription - polymerase chain reaction (RT-PCR) typing. Cerebrospinal fluid (CSF) examinations performed in seven of the eight patients were within normal limits, and cultures for bacteria and virus were negative. The electroencephalograms (EEGs) performed from 1 to 13 days after seizure showed abnormal in six, and normal in two, patients. Follow-up EEGs, performed from 4 to 11 months after onset of seizure, were all normal. None had seizure recurrence despite the fact that no long-term anticonvulsant had been given. From observation here, the authors emphasize that there is a close relationship between rotavirus and afebrile seizure, and the course of afebrile seizure following rotavirus gastroenteritis is usually benign. Further studies are needed to elucidate the underlying pathogenesis.

Epileptic seizures and electroencephalographic evolution in genetic leukodystrophies.

Summary The purpose of this study is to explore and compare epileptic seizures and EEG evolution in the various types of genetic leukodystrophy (GL). The authors reviewed the medical records and analyzed 69 serial EEGs in 27 patients with GLs: 13 with late infantile metachromatic leukodystrophy, one with juvenile metachromatic leukodystrophy, one with globoid cell leukodystrophy, six with X-linked childhood adrenoleukodystrophy, one with neonatal adrenoleukodystrophy, four with classic Pelizaeus–Merzbacher disease (PMD), and 1 with connatal Pelizaeus–Merzbacher disease. The diagnoses were made by biochemical and molecular studies. Two or more EEG studies with both awake and sleep traces were recorded during the varying clinical stages for each patient. At the beginning of the GLs, the EEGs were normal or showed mild slowing of background activity. Clinical seizures, mainly of focal origin, with progressive slowing and paroxysmal discharges on EEGs, usually appeared during the later stages of metachromatic leukodystrophy, X-linked childhood adrenoleukodystrophy, and classic Pelizaeus–Merzbacher disease. However, intractable seizures, mainly generalized in nature, and more severe slowing and abundant paroxysmal discharges on EEGs, with commensurate neurologic deterioration, were observed during the earlier course of globoid cell leukodystrophy, neonatal adrenoleukodystrophy, and connatal Pelizaeus–Merzbacher disease. These results indicate that GLs involve not only white matter, but gray matter as well. In all types of GL, there is good correlation between the severity of EEG changes, the severity of the diseases, and the clinical state of the patient.

Duplication of proteolipid protein gene: A possible major cause of Pelizaeus-Merzbacher disease

The classic form of Pelizaeus-Merzbacher disease is a rare X-linked dysmyelinating disorder of the central nervous system in which mutations of the proteolipid protein gene have been reported since 1989. However, mutations in the proteolipid protein gene have been identified in only 10 to 25% of all cases of Pelizaeus-Merzbacher disease, which suggests that other genetic aberrations may be present. Recently, proteolipid protein gene overdosage was discovered to cause Pelizaeus-Merzbacher disease. By using comparative multiplex polymerase chain reaction and restriction fragment length polymorphism analysis, we confirmed the proteolipid protein gene duplication as the cause of Pelizaeus-Merzbacher disease in 4 patients from 3 Chinese families with Pelizaeus-Merzbacher disease with no detectable exonic mutations. These results support the hypothesis that proteolipid protein gene duplication may be a major cause of Pelizaeus-Merzbacher disease in all ethnic groups and also suggest that the molecular diagnosis of Pelizaeus-Merzbacher disease should therefore include duplication analysis of proteolipid protein gene.

Early epileptic encephalopathy with suppression burst electroencephalographic pattern – an analysis of eight Taiwanese patients

Early epileptic encephalopathy with suppression burst (SB) comprises two distinct epileptic syndromes, early infantile epileptic encephalopathy (EIEE) and early myoclonic encephalopathy (EME). We reviewed etiologies, neurological outcome and clinico-electroencephalographic features of EIEE and EME. Chart records of early epileptic encephalopathy with SB from January 1997 to December 2000 were reviewed. These cases fulfilled the diagnostic criteria of EIEE and EME. Totally eight patients (four females, four males) were enrolled. They consisted of three cases of EIEE and five cases of EME. The follow-up periods ranged from 6 to 30 months. For EIEE, two cases had migrational disorders, and one was cryptogenic; for EME, three cases had non-ketotic hyperglycinemia (NKH), one was pyridoxine dependency and one was cryptogenic. The main initial seizure patterns were tonic spasms in EIEE, and were erratic myoclonus in EME. The age of seizure onset ranged from 26 h to 5 days after birth for EIEE, and 2 h to 7 days of life for EME. The SB pattern in the electroencephalography (EEG) was noted mainly during sleep state in EME, but in both awake and sleep states in EIEE. Asymmetric SB pattern and background activities in EEG were found in migrational disorders. The EEG in all cases of EIEE changed to hypsarrhythmia at 4-6 months of age. In EME, only the EEG in cases of NKH evolved to hypsarrhythmia. Response to anti-convulsants was generally poor. All had severe psychomotor retardation. Although EIEE and EME share several common features, differences in terms of seizure seminology and evolution, EEG patterns and etiologies still exist.