Journal of the Neurological Sciences最新文献

Background

Proton pump inhibitors (PPIs), which inhibit gastric acid secretion, are frequently prescribed to patients with Parkinson's disease (PD). Levodopa, the gold-standard treatment for PD, demonstrates enhanced solubility in acidic environments. Although PPIs increase gastric pH and may affect levodopa absorption, the effect of concomitant PPI use on levodopa pharmacokinetics in patients with PD remains unknown. This study aimed to investigate the effect of the concomitant use of esomeprazole, a PPI, on the pharmacokinetics of levodopa and carbidopa and clinical symptoms in patients with PD.

Methods

We prospectively enrolled 40 patients with PD and compared the pharmacokinetics of levodopa and carbidopa and clinical symptoms before and two weeks after the concomitant use of esomeprazole.

Results

The plasma concentrations of levodopa 30 min after concomitant oral administration of levodopa and esomeprazole were significantly lower (4.92 ± 4.10 μmol/L) than those without concomitant esomeprazole use (6.26 ± 3.75 μmol/L; p = 0.027). The plasma concentrations of carbidopa showed no significant differences with respect to concomitant esomeprazole use. Significant elevation was recorded in all subscores of the Movement Disorder Society-sponsored revision of the Unified Parkinson's disease Rating Scale scores after concomitant use of esomeprazole. No significant differences were observed between Helicobacter pylori-negative and Helicobacter pylori-positive patients. Non-elderly patients (age ≤ 70 years) tended to be more susceptible to the effect of esomeprazole on levodopa pharmacokinetics and clinical symptoms.

Conclusions

The unnecessary use of PPIs should be avoided in patients with PD, especially in non-elderly patients, to improve absorption of levodopa.

We have read with a great deal of interest the article by Hwang et al. (1) and appreciate the authors’' commendable efforts. The article was intelligently written and provides a significant insight into the study carried out by the authors. We greatly acknowledge the brief concepts the authors have shared regarding Parkinson's disease and epilepsy, which are without doubt an asset to the field of neurology. The study has laid a good foundation for future related studies. The article mentions epilepsy as an uncommon comorbidity of Parkinson's disease and the transition of a non-epilepsy brain to an epilepsy brain. It is also mentioned that PD is a progressive neurodegenerative disorder of dopaminergic neurons in the substantia nigra, and the incidence of the two diseases. However, as we assess the article in depth, we have found some shortcomings that would have enhanced the sense and purpose of the study.

Congenital Zika syndrome (CZS) comprises a set of clinical manifestations that can be presented by neonates born to mothers infected by the Zika virus (ZIKV). CZS-associated phenotypes include neurological, skeletal, and systemic alterations and long-term developmental sequelae. One of the most frequently reported clinical conditions is microcephaly characterized by a reduction in head circumference and cognitive complications. Nevertheless, the associations among the diverse signaling pathways underlying CZS phenotypes remain to be elucidated. To shed light on CZS, we have extensively reviewed the morphological anomalies resulting from ZIKV infection, as well as genes and proteins of interest obtained from the published literature. With this list of genes or proteins, we performed computational analyses to explore the cellular processes, molecular mechanisms, and molecular pathways related to ZIKV infection. Therefore, in this review, we comprehensively describe the morphological abnormalities caused by congenital ZIKV infection and, through the analysis noted above, propose common molecular pathways altered by ZIKV that could explain both central nervous system and craniofacial skeletal alterations.

Background and objectives

In 2024, the sequalae of the acute phase of coronavirus disease-19 (COVID-19) infection, which include neurological symptoms and are commonly referred to as long COVID or post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC), continue to be a substantial health concern; however, similar symptoms are observed in individuals with no previous COVID-19 infection.

Methods

This was a single-center, retrospective, descriptive case series study. Data were obtained from patients who visited our outpatient clinic specializing in PASC between June 1, 2021, and May 31, 2023. We compared antibody test results between patients with confirmed acute phase infection and those without. We compared differences in demographic and clinical characteristics between patients with positive results during the acute phase of COVID-19 infection and positive anti-SARS-CoV-2 antibody tests (true-PASC), and those with neither (PASC-mimic).

Results

Of 437 patients diagnosed with PASC according to World Health Organization criteria, 222 underwent COVID-19 antibody tests. Of these, 193 patients (86.9%) had a history of confirmed acute phase infection, whereas 29 (13.1%) did not. Of the former, 186 patients (96.4%) were seropositive for anti-nucleotide SARS-CoV-2 antibodies (true-PASC), whereas 19 of the latter tested seronegative for anti-nucleotide SARS-CoV-2 antibodies (PASC-mimic). There were no significant differences in symptom characteristics between true-PASC and PASC-mimic participants.

Conclusions

It was difficult to identify any clinical features to aid in diagnosing PASC without confirmation of acute COVID-19 infection. The findings indicate the existence of a “PASC-mimic” condition that should be acknowledged and excluded in future PASC-related research studies.

Parkinson's disease (PD) is a neurodegenerative disorder resulting from the loss of dopamine-producing neurons in the brain, causing motor symptoms like tremors and stiffness. Although current treatments like medication and deep brain stimulation can alleviate symptoms, they don't address the root cause of neuron loss. Therefore, cell replacement therapy emerges as a promising treatment strategy. However, the generation of engraftable dopaminergic (DA) cells in clinically relevant quantities is still a challenge. Recent advances in cell reprogramming technologies open up vast possibilities to produce patient-specific cells of a desired type in therapeutic quantities. The main cell reprogramming strategies involve the enforced expression of individual or sets of genes through viral transduction or transfection, or through small molecules, known as the chemical approach, which is a much easier and safer method. In our previous studies, using a small molecule approach (combinations of epigenetic modifiers and SMAD inhibitors such asDorsomorphin and SB431542), we have been able to generate DA progenitors from human mesenchymal stem cells (hMSCs). The aim of this study was to further improve the method for the generation of DA progenitors and to test their therapeutic effect in an animal model of Parkinson's. The results showed that the addition of an autophagy enhancer (AE) to our DA cell induction protocol further increased the yield of DA progenitor cells. The results also showed that DA progenitors transplanted into the mouse model of PD survived, integrated, and improved PD motor symptoms. These data suggest that chemically-produced DA cells can be very promising and safe cellular therapeutics for PD.

Purpose

Infantile epileptic spasms syndrome (IESS) with epileptic spasms as the main seizure type, is treated with adrenocorticotropic hormone (ACTH). This study, for the first time, examines the effects of epileptic spasms and ACTH on blood-brain barrier (BBB) permeability in patients with IESS of unknown etiology.

Methods

We prospectively evaluated the changes in BBB permeability in patients with IESS of unknown etiology at the Saitama Children's Medical Center between February 2012 and February 2024. We compared the levels of serum-albumin, cerebrospinal fluid (CSF)-albumin, Q-albumin, and CSF-neuron-specific enolase (NSE) before and after ACTH therapy. We also assessed the correlation between the frequency of epileptic spasms and these markers.

Results

Overall, 16 patients with IESS (8 males) were included in the study. The median age at IESS onset was 5 (range, 2–9) months. The median duration between the epileptic spasms onset and the serum and CSF sample examination before ACTH therapy was 26 (range, 1–154) days. After ACTH therapy, CSF-albumin and Q-albumin levels significantly decreased (CSF-albumin: 13.5 (9.0–32.0) mg/dL vs 11.0 (7.0–19.0) mg/dL, p = 0.001. Q-albumin: 3.7× 10⁻³ (2.2 × 10⁻³-7.3 × 10⁻³) vs 2.8× 10⁻³ (1.9 × 10⁻³-4.5 × 10⁻³), p = 0.003). No correlation was observed between the epileptic spasms frequency and levels of serum-albumin, CSF-albumin, Q-albumin, and CSF-NSE (Spearman's coefficient: r = 0.291, r = 0.141, r = 0.094, and r = −0.471, respectively).

Conclusion

ACTH therapy is one of the factors that play a role in restoring BBB permeability in patients with IESS of unknown etiology. Our findings may be useful in elucidating the mechanism of ACTH action and IESS pathophysiology.