A digest of the Evidence-Based Clinical Practice Guideline for Nephrotic Syndrome 2020

Clinical and Experimental Nephrology -     

Treatment and outcome in patients with febrile convulsion associated with epileptiform discharges on electroencephalography

The aim of this study is to determine the efficacy of prophylactic treatment for patients with febrile convulsions (FCs) in whom electroencephalograms (EEGs) revealed epileptiform discharges. We retrospectively investigated 43 patients who met the following criteria: (a) at least one FC during the study period; (b) epileptiform discharges were first recognized; (c) no unevoked seizures before epileptiform discharges were first seen; (d) normal psychomotor development and no neurological abnormality; and (e) follow-up >3 years. The clinical characteristics, treatment, and a later occurrence of FCs or unevoked seizures were studied. EEGs revealed focal epileptiform discharges in 25 patients and generalized ones in 18. There was no significant difference in the rate of recurrence of FC or occurrence of unevoked seizures between those with focal and generalized epileptiform discharges. No prophylaxis was performed in ten patients, 14 patients being treated with intermittent diazepam and 19 with a daily anticonvulsant. The rate of recurrence of FC was not significantly different between patients with and without prophylaxis. Unevoked seizures were only observed in two patients undergoing daily treatment. Intermittent or daily anticonvulsant therapy will not reduce the risk of recurrence of FCs or later development of unevoked seizures in patients with FC with epileptiform discharges.     

Mutations of neuronal voltage-gated Na+ channel alpha 1 subunit gene SCN1A in core severe myoclonic epilepsy in infancy (SMEI) and in borderline SMEI (SMEB)

PURPOSE: Severe myoclonic epilepsy in infancy (SMEI) is a distinct epilepsy syndrome. Patients with borderline SMEI (SMEB) are a subgroup with clinical features similar to those of core SMEI but are not necessarily consistent with the accepted diagnostic criteria for core SMEI. The aim of this study was to delineate the genetic correlation between core SMEI and SMEB and to estimate the frequency of mutations in both phenotypes. METHODS: We examined 96 healthy volunteers and 58 unrelated individuals whose clinical features were consistent with either core SMEI (n = 31) or SMEB (n = 27). We screened for genetic abnormalities within exons and their flanking introns of the genes encoding major subunits of the Na+ channels (SCN1A, SCN2A, SCN1B, and SCN2B) by using a direct sequencing method. RESULTS: In both core SMEI and SMEB, various mutations of SCN1A including nonsense and missense mutations were identified, whereas no mutations of SCN2A, SCN1B, and SCN2B were found within the regions examined. All mutations were heterozygous and not found in 192 control chromosomes. Mutations were identified in 26 (44.8%) of the 58 individuals and were more frequent (p < 0.05) in core SMEI (19 of 31) than in SMEB (seven of 27), as assessed by the continuity-adjusted chi2 test. Mutations resulting in a molecular truncation were found only in core SMEI. Among the mutations, two missense mutations were found in both core SMEI and SMEB. CONCLUSIONS: Our findings confirm that SMEB is part of the SMEI spectrum and may expand the recognition of SMEI and suggest other responsible or modifying genes.     

Absence seizures in patients with localization-related epilepsy

We studied the clinical features of 12 patients with localization-related epilepsy (LRE) associated with absence seizures (AS). AS did not appear in any patients before partial seizures (PS) were first observed. The interval between the onset of PS and AS ranged from 1 month to 7.2 years (mean 2.11 years). The duration of AS (mean 5 months) was short compared with that of PS (mean 3.8 years). Carbamazepine (CBZ) was used in seven patients at the onset of AS. It was discontinued in five but continued in the other two. AS was initially treated with valproate in ten patients. Three of them needed additional antiepileptic drugs: clonazepam in two patients and ethosuximide in one. All patients became free from AS after treatment for AS was started, whereas PS was relatively intractable. Generalized spike-and-waves were often observed before the onset of AS. The interval between the first appearance of generalized spike-and-waves and the onset of AS ranged from 1 to 53 months (mean 20 months). AS in patients with LRE will be relatively benign and transient, and will respond well to antiepileptic drugs.     

Natural history of liver imaging reporting and data system category 4 nodules in MRI

Purpose: The purpose of this study was to characterize the MR imaging features and outcomes of liver imaging reporting and data system (LI-RADS) category 4 (LR4) nodules, with an emphasis on upgrade to category 5 (LR5) and development of contraindications to curative therapy. Methods: Institutional review board approval was obtained for this retrospective, dual-institutional Health Insurance Portability and Accountability Act-compliant study. The requirement for informed consent was waived. Contrast-enhanced MRI studies performed on patients with cirrhosis were retrospectively assessed using LI-RADS 2014 by at least two readers. All nodules were individually evaluated to determine their major imaging features at diagnosis, and follow-up data were used to determine the associated imaging outcomes. Results: One hundred eighty-one untreated LR4 nodules in 139 patients had adequate imaging and follow-up for inclusion in the study. Most (61% [111/181]) of these demonstrated arterial phase hyperenhancement, washout, and diameter less than 20 mm. During the follow-up period (median 163 days), 31% (56/181) of the nodules upgraded to LR5, 40% (73/181) remained stable, and 29% (52/181) downgraded. Of the nodules that upgraded, 61% (34/56) increased their size category and 54% (30/56) developed newly visualized capsules. No LR4 nodules developed venous invasion, satellites nodules, or new intrahepatic or extrahepatic metastatic disease. 75% (42/56) of the nodules that upgraded to LR5 did so within 6 months. Conclusions: Approximately one-third of LR4 nodules upgrade to LR5, and the short-term risk of developing venous invasion or metastasis is very low.     

Insulin-like effect of vanadyl ion on streptozotocin-induced diabetic rats

Recent studies have indicated that the blood glucose level of rats with streptozotocin (STZ)-induced diabetes (type 1) is normalized without an increase in the plasma insulin level by administration of sodium orthovanadate in the drinking water. The mechanism of this insulin-like effect of vanadate is unknown. In this study, we investigated whether vanadyl ion, which is less toxic than vanadate to rats, also has an insulin-like effect in rats with STZ-induced diabetes. When rats with STZ-induced diabetes were given a daily i.p. injection of vanadyl sulphate (9.3 and 4.6 mg vanadium/kg body weight), their blood glucose level decreased from about 22.2 to about 7.2 mmol glucose/l within 2 days and remained low for at least 12 weeks. This treatment did not affect their low plasma insulin level. Quantitative electron spin resonance (ESR) spectrometry showed that most of the vanadium (about 90%) in their tissues was present as a vanadyl form (VO2+). ESR analysis also showed that the vanadyl ion in tissues was bound endogenously with four oxygen ligands from either water or oxyamino acid residues in proteins. Vanadyl sulphate accelerated glucose incorporation into adipocytes of rats, suggesting that the action of vanadyl ion is peripheral. Interestingly, vanadyl sulphate at a high concentration (about 10 mmol/l) was more effective than insulin in enhancing glucose uptake. This study demonstrated that: (1) vanadyl sulphate (+4 oxidation state), like vanadate ion, normalizes the blood glucose levels of rats with STZ-induced diabetes; (2) the action of vanadyl ion is peripheral; and (3) the active form of vanadium for an insulin-like effect may be a vanadyl form, not vanadate.     

Uptake of nicotinamide by rat pancreatic beta cells with regard to streptozotocin action.

Exposure of rat pancreatic beta cells in monolayer culture to 2 mmol streptozotocin (STZ)/l for 1 h followed by thorough washing inhibited their uptake of [14C]nicotinamide and [3H]2-deoxyglucose [( 3H]2-DG) to about 50% and also reduced the intracellular ATP concentration to 50% of that in control cells. These changes were not due to a lethal cytotoxic effect of STZ, because cell viability, as estimated by succinic dehydrogenase activity, was 90% of that of control cells. Oligomycin and carbonylcyanide-m-chlorophenylhydrazone (CCCP), an uncoupler of oxidative phosphorylation, caused a dose-dependent decrease in intracellular ATP concentration while maintaining high cell viability. These ATP-depleted cells showed a decrease in insulin release and an inhibition of the uptake of [14C]nicotinamide and [3H]2-DG in a dose-dependent manner. Therefore oligomycin and CCCP reproduced the same effects as those found in beta cells treated with STZ. These results suggest that the uptake of nicotinamide and 2-DG by beta cells might be regulated by their intracellular ATP concentration. The decreased uptake of nicotinamide in ATP-depleted beta cells caused by STZ might explain the lack of protective effect of nicotinamide against STZ cytotoxicity when administered after the latter. Furthermore, the radiotracer experiments demonstrated that the transport of nicotinamide by intact beta cells was inhibited in a dose-dependent manner by 2-DG and vice versa, i.e. the transport of 2-DG was inhibited by nicotinamide. These findings suggest the existence of a common transport mechanism in beta cells responsible for the uptake of nicotinamide and 2-DG, the transport of which is known to occur by facilitated diffusion.     

A dose-response study with dihydroergotoxine mesylate in cerebrovascular disturbances

Basic pharmacologic evidences have suggested the effects of dihydroergotoxine mesylate (DEM) on neurotransmitters. In its clinical use, however, various therapeutic effects and side effects are observed when the dose is changed, because of the complexity of this compound and the delicate mechanism of neurotransmitters in the brain, especially when modified by aging and vascular lesions. In order to investigate the optimal dose, a double-blind study in 550 patients with cerebrovascular disorders was carried out at 68 centers under observation by experienced specialists. Dihydroergotoxine mesylate in sublingual tablets, 3 mg daily, and in oral tablets, 6 mg daily, respectively, was given for 12 weeks, and therapeutic effects at those doses were compared by a double-blind method. In utility ratings for subjective and psychiatric symptoms, the effects in the oral tablet group at a daily dose of 6 mg were significantly superior to those in sublingual tablet group at a daily dose of 3 mg. There was no significant difference between those two groups in the comparison of side effects. These results show that the daily oral administration of 6 mg of DEM is more suitable for the improvement of subjective and psychiatric symptoms due to cerebrovascular disorders than is the daily sublingual administration of 3 mg. These results suggest that, despite much complexity in the neurohumoral transmitter mechanism in the brain, relatively simple dose-dependent efficacy of the drug in the range of the therapeutic doses was confirmed for many subjective and psychiatric symptoms of patients with cerebrovascular disorders.     

Comparison of regional brain volume and glucose metabolism between patients with mild dementia with lewy bodies and those with mild Alzheimer's disease.

The aim of this study was to investigate regional differences between morphologic and functional changes in patients with mild dementia with Lewy bodies (DLB) compared with those with Alzheimer's disease (AD). METHODS: Twenty patients with very mild DLB (mean age, 74.5 y; mean Mini-Mental State Examination [MMSE] score, 24.0), 20 patients with very mild AD (mean age, 74.1 y; mean MMSE score, 24.0), and 20 age- and sex-matched healthy volunteers (normal controls [NC]) underwent both (18)F-FDG PET and 3-dimensional spoiled gradient echo MRI. Fully automatic volumetry of the MRI data was used to obtain whole brain, hippocampal, occipital, and striatal volumes, which were compared with the results of a similar analysis of glucose metabolic data. RESULTS: In DLB patients, volumetric data indicated a significant volume decrease in the striatum, whereas (18)F-FDG PET showed significant glucose metabolic reductions in the temporal, parietal, and frontal areas--including in the occipital lobe--compared with those in the NC group. In contrast, in AD patients, both the hippocampal volume and glucose metabolism were significantly decreased, whereas the occipital volume and metabolism were preserved. CONCLUSION: Comparison of very mild DLB and AD revealed different morphologic and metabolic changes occurring in the medial temporal lobes and the occipital lobe, demonstrating characteristic pathophysiologic differences between these 2 diseases.