Xiangqing Wang

This study aimed to describe the changes in the etiology of adult epilepsy in different age groups over the past 25 years, with consideration of different time periods. A retrospective study was conducted using the clinical data of patients with adult-onset epilepsy at The First Medical Center of Chinese PLA General Hospital between February 1999 and March 2024. The study included 5,712 patients from 25 provinces and 4 municipalities in China. The study found that the prevalence of unknown etiology has decreased overall, particularly after 2015, and that the proportion of epilepsy cases caused by metabolic etiologies has declined since 2016. However, since 2021, there has been an increase in immune-related epilepsy. The proportion of patients with structural epilepsy ranged from 29.7% to 90% across all age groups. Among epilepsy patients aged ≥ 51 years, structural epilepsy was predominant, accounting for the majority of cases. In particular, the proportion of epilepsy attributable to cerebrovascular disease increased with age at onset. With regard to gender, structural epilepsy was more common in males than in females. This study highlights observed trends and changes in clinical diagnosis in epilepsy etiologies, revealing an obvious decrease in unknown etiology. The recent rise in immune-related epilepsy underscores the need for increased clinical vigilance. The observed gender and age disparities in structural epilepsy, particularly cerebrovascular-related cases in elderly males, provide critical insights for targeted preventive and therapeutic strategies.

Introduction COQ4 mutation often leads to a fatal multi-system disease in infants. Recently, it was reported that the biallelic COQ4 variants may be a potential cause of hereditary spastic paraplegia (HSP). This study aims to describe the clinical features and genotype of the COQ4 associated hereditary spastic paraplegia (HSP). Methods We reported a case of HSP with COQ4 variants, and a literature reanalysis was performed. Results Three studies with a total of 1309 patients with HSP of unknown cause were included, and 13 (1%) patients were found to have biallelic COQ4 variants. Seven patients fulfilled pure HSP, and six patients fulfilled complicated HSP. The median age of these patients was 24 years (range 15 to 65 years), and the median year of disease onset was 14 years (range 1 to 55 years). The most common clinical manifestations were lower limb spasticity (100%), hyperreflexia (100%), Babinski sign (77%), reduced muscle strength (53.8%) cerebellar ataxia (23.1%), seizures (23.1%) and dysarthria (23.1%). Including our case, 16 different variants located in exon 2, exon 4, exon 5, exon 6, exon 7 and two introns of the COQ4 gene have been identified in patients with HSP. All started CoQ10 supplementation, but follow-up was reported in only one patient. Conclusion COQ4 variants were associated with childhood, adolescent, and adult onset HSP, which has a relatively mild course. The efficiency of CoQ10 supplement in patients with COQ4 associated HSP need to be classified in the future study.

Objective: To analyze the clinical characteristics, etiology, drug treatment, and related factors of patients with young adult‐onset epilepsy.Methods: The study included patients with epilepsy aged between 18 and 44 years and aimed to analyze the clinical characteristics of epilepsy in young people and their response to antiseizure medication (ASM) over a 24‐year period (February 1999 and March 2023).Results: A total of 4227 patients experienced epilepsy onset between 18 and 44 years of age. The median age of onset was 26 years (interquartile range [IQR]: 21–33), and the median duration from the first seizure to starting treatment was 3 months (IQR: 1.0–6.0). Structural etiology was the most common cause of epilepsy, accounting for 43.2% (1827/4227) of cases, of which head trauma and a history of craniotomy accounted for 64.9% (1186/1827). However, these two causes did not necessarily result in prompt medication or poor epilepsy control. Co‐morbid cognitive decline was more prevalent than headache and anxiety/depression. Multifactorial regression analysis showed that the factors associated with poor seizure control included longer seizure duration (odds ratio [OR] 1.85; 95% confidence interval [CI] 1.58‐2.16; p < 0.001), electroencephalography (EEG) epileptic discharge (OR 1.37; 95% CI 1.17–1.67; p < 0.001), focal seizure (OR 1.69; 95% CI 1.38–2.07; p < 0.001), and seizure clusters (OR 3.35; 95% CI 2.70–4.15; p < 0.001). Initiating treatment after two seizures (OR, 1.18; 95% CI 0.98–1.15; p = .08) or 6 months after the first seizure (OR 0.84; 95% CI 0.67–1.03; p = .09) did not worsen effectiveness.Significance: Young adult‐onset epilepsy was frequently caused by head trauma or craniotomies. Co‐morbid cognitive decline was more prevalent than headache and anxiety/depression. The median time from the first seizure to follow‐up treatment was 3 months (IQR: 1.0–6.0). Initiating treatment after two seizures did not necessarily indicate poor drug effectiveness.Plain Language Summary: In this article, we observed that young adult‐onset epilepsy was mainly caused by head trauma and craniotomy; co‐morbid cognitive decline was more common. The median duration from first seizure to initiation of treatment for young‐onset epilepsy was 3 months, and more than one‐third of patients experienced more than two seizures prior to treatment, but this factor had no effect on the drug effectiveness.

Objective Sialidosis type 2 has variants that are both catalytically inactive (severe), while sialidosis type 1 has at least one catalytically active (mild) variant. This study aimed to discuss the structural changes associated with these variants in a newly reported family carrying N-acetyl-α-neuraminidase-1 (NEU1) variants and explore the clinical characteristics of different combinations of variants in sialidosis type 1.Methods First, whole-exome sequencing and detailed clinical examinations were performed on the family. Second, structural analyses, including assessments of energy, flexibility and polar contacts, were conducted for several NEU1 variants, and a sialidase activity assay was performed. Third, previous NEU1 variants were systematically reviewed, and the clinical characteristics of patients in the severe-mild and mild-mild groups with sialidosis type 1 were analyzed.Results We report a novel family with sialidosis type 1 and the compound heterozygous variants S182G and V143E. The newly identified V143E variant was predicted to be a mild variant through structural analysis and was confirmed by a sialidase activity assay. Cherry-red spots were more prevalent in the severe-mild group, and ataxia was more common in the mild-mild group. Impaired cognition was found only in the severe-mild group. Moreover, patients with cherry-red spots and abnormal electroencephalographies and visual evoked potentials had a relatively early age of onset, whereas patients with myoclonus had a late onset.Conclusion Changes in flexibility and local polar contacts may be indicators of NEU1 pathogenicity. Sialidosis type 1 can be divided into two subgroups according to the variant combinations, and patients with these two subtypes have different clinical characteristics.

Objective: This study aimed to analyze the clinical characteristics, etiology, and treatment of midlife‐onset epilepsy in a real‐world setting at a single center in China.Methods: The clinical data of patients who attended the epilepsy clinic of the Department of Neurology, First Medical Center of Chinese PLA General Hospital from February 1999 to March 2023 were retrospectively analyzed. The clinical characteristics, etiology, and risk factors for midlife‐onset epilepsy over the past 24 years were analyzed.Results: Of the 969 patients with onset at 45–64 years of age, 914 were diagnosed with epilepsy with at least two unprovoked seizures 24 h apart. Of those, 99.7% (911) were of focal origin. The median duration from the initial seizure to follow‐up treatment was 2 months (interquartile range [IQR]: 1.0–6.0 months). Before commencing treatment, 30.2% (207/683) of patients experienced more than two seizures. A structural etiology was found in 66.3% (606/914) of patients. Cerebrovascular disease (CVD) and traumatic brain injury (TBI) accounted for 19.9% (182/914) and 16.6% (152/914) of the cases, respectively. Logistic regression analysis showed that patients with abnormal imaging (odds ratio [OR] 2.04; 95% confidence interval [CI] 1.25–3.32; p = .004), focal seizures (OR 2.98; 95%CI 1.82–4.87; p < .001), and seizure clusters (OR 2.40; 95%CI 1.21–4.73; p = .01) had poor drug responses. Treatment outcomes were generally better in patients with epilepsy after CVD (OR .49; 95%CI .28–.85; p = .01). Treatment initiation after two seizures (OR .70; 95%CI .42–1.15; p = .16) or 6 months after the first seizure (OR 1.17; 95%CI .66–2.09; p = .58) did not result in poor drug effectiveness.Significance: Midlife‐onset epilepsy is typically of focal etiology, with CVD being the most common cause, and tends to respond well to medication. The median duration from the initial seizure to follow‐up treatment was 2 months. Over 30% of patients experienced more than two seizures before commencing treatment, but this did not affect subsequent outcomes.

Background: Combined oxidative phosphorylation deficiency (COXPD) is a severe disorder with early onset and autosomal recessive inheritance, and has been divided into 51 types (COXPD1–COXPD51). COXPD14 is caused by a mutation in the FARS2 gene, which encodes mitochondrial phenylalanyl-tRNA synthetase (mt-PheRS), an enzyme that transfers phenylalanine to its cognate tRNA in mitochondria. Since the first case was reported in 2012, an increasing number of FARS2 variations have been subsequently identified, which present three main phenotypic manifestations: early onset epileptic encephalopathy, hereditary spastic paraplegia, and juvenile-onset epilepsy. To our knowledge, no adult cases have been reported in the literature. Methods: We report in detail a case of genetically confirmed COXPD14 and review the relevant literature. Results: Approximately 58 subjects with disease-causing variants of FARS2 have been reported, including 31 cases of early onset epileptic encephalopathy, 16 cases of hereditary spastic paraplegia, 3 cases of juvenile-onset epilepsy, and 8 cases of unknown phenotype. We report a case of autosomal recessive COXPD14 in an adult with status epilepticus as the only manifestation with a good prognosis, which is different from that in neonatal or infant patients reported in the literature. c.467C > T (p.T156M) has been previously reported, while c.119_120del (p.E40Vfs*87) is novel, and, both mutations are pathogenic. Conclusions: This case of autosomal recessive COXPD14 in an adult only presented as status epilepticus, which is different from the patients reported previously. Our study expands the mutation spectrum of FARS2, and we tended to define the phenotypes based on the clinical manifestation rather than the age of onset.

Background: To date, no large-scale analysis has been conducted examining the association between PFO and epilepsy, especially in the Chinese population. The purpose of this study is to investigate the demographic characteristics of PFO patients, the clinical characteristics of PFO in patients with epilepsy, and the effect of PFO embolization in seizure attack. Methods: Consecutive patients who are diagnosed as PFO, are recruited for this study. All patients had performed the brain MRI examination, transesophageal echocardiograpy (TEE), EEG, ECG, transthoracic echocardiogram with bubble contrast (TTE). Epilepsy patients has a definite diagnosis of epilepsy determined by at least two epileptologists. Results: One hundred and ten patients finished the entire estimation. The patients went to see the doctor with different chief complaints, which included seizure, headache, dizziness, cerebral infarction or TIA, chest pain or palpitation and conventional examination. The proportion of chief complaints of chest tightness or palpitation is higher in the group less than 18 years old, and the proportion of headache and seizure are higher in the group older than 18 years old (pConclusion: No difference between PFO closure or not. Due to the small number of cases, it is necessary to further expand the sample size to obtain accurate results.

Background: Adrenoleukodystrophy is a rare neurogenetic disease, AMN is the most common adult phenotype, such patients in China have not gotten enough attention. This article aims to study the features of AMN in Chinese patients and expand the gene spectrum of Chinese X-linked adrenoleukodystrophy (X-ALD) patients. Methods: We applied clinical analysis, radiology, plasma levels of very long chain fatty acids (VLCFA) and genetic analysis to test the 6 Chinese AMN patients. Results: All 6 patients are men. Ages of neurological symptom onset are distributed between 21 and 38. Sexual dysfunction occurred in 5 of 6 patients. Three patients had positive family history. Five patients had Addison’s disease. Four patients were diagnosed as pure AMN, while the other two patients were with cerebral involvement. Four patients had abnormalities of nerve conduction studies. There were four patients with central conduction defects in somatosensory evoked potential tests. All 6 patients were found diffuse cord atrophy in spinal MRI. Brain MRI showed abnormal signals in 2 of the 6 tested patients, which indicated the clinical phenotypes. Plasma levels of VLCFA, as well as C24:0/C22:0 and C26:0/C22:0 ratios were elevated in 5 tested patients. Five different ABCD1 mutations were identified in 5 tested patients, one of which was a de novo mutation, and the other four have been reported previously. Conclusion: This research described the clinical, neuroimaging, biochemical, and genetic sides of Chinese AMN patients. A de novo mutation in the ABCD1 gene sequence was identified. Emotional trauma may trigger or aggravate the development of cerebral demyelination in AMN patients. Regular evaluation of brain MRI is important for AMN patients, especially for ‘pure AMN’ patients. When encountering patients with ‘myeloneuropathy-only’, neurologists should not ignore the tests of VLCFA or/and the ABCD1 gene.