The mutation in CNKSR2 leads to a broad spectrum of phenotypic variability and manifests as an X-linked intellectual disability. However, we reported that the male patient in this study not only had intellectual disability but also epileptic seizures. In addition, there were progressive language impairment, attention deficit hyperactivity disorder and autism. Electroencephalograms showed continuous spike-and-wave during sleep. Genetic testing revealed a de novo mutation of the CNKSR2 gene (c.2185C > T, p.Arg729Ter) in the child that was not detected in the parents. Therefore, the child was diagnosed with X-linked epilepsy aphasia syndrome. Deletion of the CNKSR2 gene has been rarely reported in epilepsy aphasia syndrome, but no de novo mutation has been found in this gene. This report not only adds to the spectrum of epilepsy aphasia syndrome but also helps clinicians in diagnosis and genetic counseling.

Rationale: Multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare inborn error of metabolism affecting fatty acid, amino acid, and choline metabolism. The clinical manifestation of MADD is heterogeneous, from severe neonatal forms to mild late-onset forms. Patient concerns: Here, we report a patient who presented with severe hypoglycemia and exercise intolerance suggestive of MADD. Serum tandem mass spectrometry analysis indicated elevated levels of various acyl carnitines at 25 days of age. Exome sequencing of the proband revealed compound heterozygous mutations, c. 413T>G (p.Leu138Arg) and c.1667C > G (p.Pro556Arg), in the ETFDH gene as the probable causative mutations. Diagnoses: Based on the patient's clinical presentation and test results, the patient was diagnosed with MADD. Interventions: A high-calorie and reduced-fat diet was given together with oral supplements of L-carnitine (150 mg/day). Outcomes: He passed away at the age of 4 months because of severe respiratory distress accompanied by muscle weakness. Lessons: He passed away at the age of 4 months because of severe respiratory distress accompanied by muscle weakness. Clinicians should consider MADD in the differential diagnosis when patients present with muscle weakness and biochemical abnormalities. Gene testing plays a critical role in confirming the diagnosis of MADD and may not only prevent the need for invasive testing but also allow for timely initiation of treatment.

Disorders of the central nervous system (CNS) constitute a significant global health concern at the moment. Most CNS disorders are characterized by severe neuronal damage with excessive production of reactive oxygen species, which induces high levels of oxidative stress and intense inflammatory responses in the affected tissues, thus aggravating disease pathology. Notably, the blood–brain barrier makes it difficult to deliver many drugs and biologics to the CNS, which creates great difficulties in the diagnosis and treatment of CNS disorders. Recent research on polydopamine nanotechnology has led to the discovery of many promising properties; it shows strong scavenging ability for reactive oxygen species, prevents activation of pro-inflammatory microglia, and its repair function can reduce brain damage and protect neurons. Moreover, polydopamine nanotechnology can improve the blood–brain barrier permeability of biologics and reduce their neurotoxicity. It is therefore a promising candidate in the treatment of CNS disorders associated with oxidative stress. In the present paper, we review the functionality of polydopamine nanotechnology as well as the potential and recent advances of polydopamine-based nanosystems in the diagnosis and treatment of various CNS disorders, including Alzheimer’s disease, Parkinson’s disease, stroke, spinal cord injury, and glioma. Finally, we predict how polydopamine nanoparticles may guide future therapeutic strategies to address CNS disorders such as epilepsy, which currently have no cure.

-OBJECTIVE: When magnetic resonance imaging (MRI) fails to detect an un-derlying epileptogenic lesion, the odds of a good outcome after epilepsy surgery are significantly lower (20%-65% compared with 60%-90% if a lesion is detected). We investigated the possible effects of introducing hybrid 18F-fluo-rodeoxyglucose positron emission tomography (18F-FDG PET)/MRI into the de-cision algorithm for patients with lesioned and nonlesioned drug-resistant epilepsy. -METHODS: Three databases were searched from January 1990 to October 2022. We registered the protocol with International Platform of Registered Systematic Review and Meta-analysis Protocols. Studies in which 18F-FDG PET/ MRI was conducted with double dagger 12 months of postsurgical follow-up in patients with refractory epilepsy. Random-effects meta-analysis was used to calculate the proportion of patients with good outcomes. Metaregression was used to investigate sources of heterogeneity. -RESULTS: We identified 8105 studies, of which 23 (1292 patients in total) were included. The overall good postoperative outcome rate was 71% (95% confi-dence interval 63.6-74.9). Good outcome was associated with the location of the refractory epileptic lesion (temporal lobe or extratemporal; risk ratio 1.27 [95% confidence interval 1.01-1.52], P [ 0.009); Length of postoperative follow-up double dagger 40 months included in the same study accounted for 0.6% of the observed heterogeneity. -CONCLUSIONS: Seventy-one percent of patients with refractory epilepsy and 18F-FDG PET/MRI epileptogenic lesion features had a good outcome of epilepsy after surgery. Our findings can be incorporated into routine preoperative con-sultations and emphasize the importance of the complete resection of the temporal lobe epileptogenic zone for 18F-FDG PET/MRI detection when safe and feasible.

Tuberous sclerosis complex (TSC) is a genetic disease characterized by seizures, mental deficiency, and abnormalities of the skin, brain, kidney, heart, and lungs. TSC is inherited in an autosomal dominant manner and is caused by variations in either the TSC1 or TSC2 gene. TSC-related epilepsy (TRE) is the most prevalent and challenging clinical feature of TSC, and more than half of the patients have refractory epilepsy. In clinical practice, we found several patients of intractable epilepsy caused by TSC1 truncating mutations. To study the changes of protein expression in the brain, three cases of diseased brain tissue with TSC1 truncating mutation resected in intractable epilepsy operations and three cases of control brain tissue resected in craniocerebral trauma operations were collected to perform protein spectrum detection, and then the data-independent acquisition (DIA) workflow was used to analyze differentially expressed proteins. As a result, there were 55 up- and 55 down-regulated proteins found in the damaged brain tissue with TSC1 mutation compared to the control. Further bioinformatics analysis revealed that the differentially expressed proteins were mainly concentrated in the synaptic membrane between the patients with TSC and the control. Additionally, TSC1 truncating mutations may affect the pathway of amino acid metabolism. Our study provides a new idea to explore the brain damage mechanism caused by TSC1 mutations.

Adenylosuccinate lyase (ADSL) deficiency is a rare autosomal-recessive defect of purine metabolism caused by mutation of the ADSL gene. It can cause severe neurological impairment and diverse clinical manifestations, including epilepsy. Here, we describe a 3-year-old Chinese boy who had both psychomotor retar dation and refractory epilepsy. Magnetic resonance imaging showed myelin hypoplasia. Electroencephalography findings supported a diagnosis of epilepsy. Whole-exon sequencing revealed the presence of a novel complex heterozygous mutation in the ADSL gene: The splicing mutation c.154-3C>G and the missense mutation c.71C>T (p. Pro24Leu). Considering the patient’s clinical presentation and genetic test results, the complex heterozygous mutation was predicted to prevent both ADSL alleles from producing normal ADSL, which may have led to ADSL deficiency. Finally, the child was diagnosed with ADSL deficiency. We identified a novel complex heterozygous mutation in the ADSL gene associated with ADSL deficiency, thus expanding the known spectrum of pa thogenic mutations that cause ADSL deficiency. Additionally, we describe epilepsy that occurs in patients with ADSL deficiency.