Echocardiographic Findings and Genotypes in Autosomal Dominant Polycystic Kidney Disease.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary cystic kidney disease and is well known to have extrarenal complications. Cardiovascular complications are of particular clinical relevance because of their morbidity and mortality; however, unclear is why they occur so frequently in patients with ADPKD and whether they are related to the genotypes. Methods: We extracted and retrospectively analyzed clinical data on patients with ADPKD who underwent echocardiography and whose genotype was confirmed by genetic testing between April 2016 and December 2020. We used next-generation sequencing to compare cardiac function, structural data, and the presence of cardiac valvular disease in patients with 1 of 3 genotypes: PKD1, PKD2, and non-PKD1, 2. Results: This retrospective study included 65 patients with ADPKD. Patients were divided into 3 groups: PKD1, n = 32; PKD2, n = 12; and non-PKD1, 2, n = 21. The prevalence of mitral regurgitation (MR) was significantly higher in the PKD1 group than in the PKD2 and non-PKD1, 2 group (46.9% vs. 8.3% vs. 19.0%, respectively; p = 0.02). In contrast, no significant difference was found for other cardiac valve complications. Conclusion: This study found a significantly higher prevalence of MR in patients with the PKD1 genotype than in those with the PKD2 or non-PKD1, 2 genotypes. Physicians may need to perform echocardiography earlier and more frequently in patients with ADPKD and the PKD1 genotype and to control fluid volume and blood pressure more strictly in these patients to prevent future cardiac events.

Treatment outcomes for infantile spasms in Japanese children with Down syndrome.

BACKGROUND: The aim of this study was to assess the treatment response to conventional antiepileptic drugs and low-dose adrenocorticotropic hormone therapy for infantile spasms in children with Down syndrome. METHODS: We retrospectively investigated the response and relapse rates, electroencephalography findings, patient characteristics during drug withdrawal, and developmental outcome in 10 children with Down syndrome treated for infantile spasms in our hospital. RESULTS: All patients showed cessation of infantile spasms and achieved electroencephalographic normalization. Spasm relapse occurred in one of 10 patients (10%). Antiepileptic drugs have been withdrawn for seven of 10 patients (70%), none of whom have experienced seizure relapse since drug withdrawal. The median developmental quotient (n = 8) was 20.5, which shows that the developmental outcome was unfavorable. Low-dose adrenocorticotropic hormone therapy achieved a low seizure remission rate of 28.6%. CONCLUSIONS: Elucidation of the optimal treatment for infantile spasms in children with Down syndrome is needed to reduce the duration of infantile spasms and improve the developmental outcome.

An infant with acute gastroenteritis caused by a secondary infection with a Rotarix-derived strain.

Rotavirus vaccines have been successful in controlling severe diarrhea and have decreased deaths of young children globally. Rotarix and RotaTeq are the two currently available live-attenuated rotavirus vaccines. The vaccine virus can grow in a recipient's gut and spread from the vaccinee to naïve individuals. The potential for the emergence of revertant viruses is a concern with live-attenuated vaccines. We identified a previously healthy infant with severe acute gastroenteritis that was positive for rotavirus in a non-endemic season. A whole genome sequencing revealed that all of the viral genome segments were highly similar to those of the Rotarix virus, with the exception of five amino acid mutations in viral genes that could be associated with virulence. The younger sibling of this patient was administered Rotarix before the onset of disease in this patient, although no gastrointestinal symptoms were reported. Epidemiological data, circumstantial evidence, and the genome analysis suggest that the vaccine virus was transmitted from the vaccinee to the patient. CONCLUSION: This is a severe acute gastroenteritis case most probably attributed to the secondary infection of Rotarix-related virus without underlying diseases. The importance of molecular surveillance of rotavirus infections is discussed. What is Known: • The live-attenuated rotavirus vaccines, Rotarix and RotaTeq, have been successful in controlling severe diarrhea and have decreased deaths of young children globally. • Attenuated vaccine virus can grow in a recipient's gut and spread to naïve individuals and may revert to cause secondary symptomatic infections. What is New: • This is the first report describing a Rotarix-associated secondary infection resulting in severe acute gastroenteritis in an infant without underlying diseases. • Amino acid mutations that might contribute to viral pathogenesis were identified by whole genome sequencing.

Serum N-Terminal Pro-B-Type Natriuretic Peptide (NTproBNP) Levels Are Elevated During the Acute Phase of Acute Encephalopathy-Associated Virus Infection.

Acute virus-associated encephalopathy induces seizures. Serum N-terminal pro-B-type natriuretic peptide (NTproBNP) levels are elevated following febrile and afebrile seizures. However, the role of NTproBNP in acute virus-associated encephalopathy pathology is unknown. We enrolled 10 patients with acute virus-associated encephalopathy and convulsions (E group: 7 boys, 3 girls; median age, 3.10 ± 1.92 years) and 130 patients with febrile seizure (FS group: 80 boys, 50 girls; median age, 3.23 ± 2.44 years). The E group had significantly higher NTproBNP levels (345 ± 141 pg/mL) compared with the FS group (166 ± 228 pg/mL) (P < .0005). Furthermore, subjects with prolonged seizure within the E group had significantly higher NTproBNP levels (303 ± 107 pg/mL) compared with subjects with prolonged seizure within the FS group (134 ± 100 pg/mL) (P < .005). Our findings suggest that serum NTproBNP levels are increased during the acute phase of acute virus-associated encephalopathy associated with convulsion.

3-Methyl-1-phenyl-2-pyrazolin-5-one or N-acetylcysteine prevents hippocampal mossy fiber sprouting and rectifies subsequent convulsive susceptibility in a rat model of kainic acid-induced seizure ceased by pentobarbital.

There is accumulating evidence that reactive oxygen species are involved in the development of seizures under pathological conditions, and antioxidant treatments are a novel therapeutic approach for epilepsy. The kainic acid (KA) model of induced seizures has been widely used to study temporal lobe epilepsy. However, research on the use of free radical scavengers following KA-induced status epilepticus (SE) is limited. We examined whether antioxidants already used in humans could reduce hippocampal neuronal cell loss, mossy fiber sprouting and the acquisition of hyperexcitability when administered as a single dose after SE. The antioxidant 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone) (30mg/kg) or N-acetylcysteine (NAC) (30mg/kg) was administered after KA-induced SE ceased by pentobarbital. We evaluated neuronal cell viability 1 week after SE, determined the threshold for seizures induced by inhalation of flurothyl ether 12 weeks after SE, and examined the extent of mossy fiber sprouting 12 weeks after SE. We found that edaravone or NAC prevented neuronal cell loss and mossy fiber sprouting, and increased the threshold for seizures induced by flurothyl ether, even when administered after KA-induced SE. These results demonstrate that a single dose of edaravone or NAC can protect against neuronal cell loss and epileptogenesis when administered after SE ceased by pentobarbital.

Prolonged left homonymous hemianopsia associated with migraine-like attacks in a child with Sturge-Weber syndrome.

We report a patient with Sturge-Weber Syndrome (SWS) who developed migraine-like headaches followed by cerebral infarction. SWS without facial nevus was diagnosed based on calcification detected by CT and pial angioma detected by enhanced MRI. His migraine-like headaches were preceded by left homonymous hemianopsia, which persisted for more than 60 min. Although homonymous hemianopsia disappeared with cessation of the headache until 13 years of age, from age 14 years onward, this homonymous hemianopsia persisted after the headaches ended. Moreover, reduced cerebral blood flow was seen in the right occipital area on SPECT. At first, his left homonymous hemianopsia persisted for several months after the headache disappeared, but it had recovered completely. However, the durations of episodes of left homonymous hemianopsia, which persisted after headache disappearance, gradually became longer. At last one year after his first admission, the visual defect had become permanent. SWS is well known to be associated with migraine attacks and hemianopsia. However, the course of our present patient, i.e. recurrent homonymous hemianopsia, associated with migraine-like headaches becoming permanent, is rare. The pathophysiological mechanism underlying this clinical course is uncertain. The efficacy of valproate and propranolol as preventive therapy has been inadequate, to date.

Edaravone prevents kainic acid-induced neuronal death.

There is growing evidence that free radical generation may play a key role in the neuronal damage induced by prolonged convulsions. Free radical scavengers are known to inhibit neuronal death induced by exposure to excitotoxins. However, this neuroprotective effect has not been demonstrated with treatment after seizures had been stopped. We investigated whether 3-methyl-1-phenyl-2-pyrazolin-5-one, edaravone (Ed), a newly developed free radical scavenger that has been used clinically to treat cerebral infarction, could prevent neuronal loss when administered after the occurrence of seizures in a kainic acid (KA)-induced seizure model. Compared with KA alone, cell loss was significantly reduced when animals received Ed (10 mg/kg i.v.) just after seizures, and when Ed was administered both 60 min before (30 mg/kg i.p.) and after KA injection. Combined before-and-after treatment with Ed significantly ameliorated the KA-induced decrease of glutathione and blocked the KA-induced increase of 4-hydroxy-2-nonenal (HNE). Because before-and-after treatment with Ed significantly lessened the KA-induced increase of HNE, Ed may exert its neuroprotective effect by inhibiting lipid peroxidation. However, post-treatment with Ed prevented neuronal cell loss, while HNE and glutathione levels did not differ from those in animals without Ed, so a mechanism other than free radical scavenging must be involved in the prevention of cell loss. Patients who develop status epilepticus are unlikely to receive adequate antioxidant therapy before the onset, so it is an advantage that Ed can prevent neuronal death even when administered after seizures.

Neuropilin-2 is overexpressed in the rat brain after limbic seizures.

Structural rearrangement and synaptic reorganization are known to occur in the brain after seizures. If neuronal rearrangement after seizures always results in abnormal hyperexcitability, it would provide an accurate pathway to the appropriate target and as a result, it may be the mechanism of epileptogenesis. This study examined the mechanism of axon guidance in the mature rat brain after seizures by evaluating the expression of the axonal guidance molecule, neuropilin-2. We assessed the expression of neuropilin-2 by northern blotting and immunohistochemistry in rat with seizures created by kindling stimulation and kainate injection.The neuropilin-2 mRNA level was increased in the whole brain of the rats at 24 h after either type of seizure. Neuropilin-2 mRNA was not increased at 2 weeks after the last stimulation. Immunohistochemistry demonstrated that neuropilin-2 protein was increased in the dentate gyrus and the entorhinal cortex in the both seizure models. These findings suggested that there was overexpression of neuropilin-2 in the brains of mature rats with different types of seizure. Accordingly, neuropilin-2 might regulate remodeling after seizures as it does during the development of the hippocampal formation. Our findings suggest that axons may not project and outgrow 'aberrantly' after seizures, but may be regulated by the chemorepellent effect through neuropilin-2.