Onset Cases Research Articles

Short-term consequences after COVID-19 in older people with epilepsy

BackgroundThis study aims to investigate the clinical characteristics and the short-term consequences of COVID-19 in older people with epilepsy. MethodsFrom January 28 to March 6,2023,a telephone follow-up survey was conducted to a group of older people with epilepsy after COVID-19 outbreak in Shanghai. Data on infection symptoms,duration,COVID-19 vaccination, and clinical characteristics and management of epilepsy were collected. ResultsEighty-two participants aged ≥50 years with SARS-CoV-2 infection were recruited. Common symptoms included fever (72.0%) and cough (63.4%).Overall, anti-seizure medication(ASM) accessibility was sufficient (95.1%),and medication adherence was good (93.9%).Three participants (3.7%)reported 1–3 seizures after virus infection. No statistically significant differences were observed in terms of clinical characteristics and consequences of COVID-19 in subgroups with participants aged <63 and ≥63years,with and without fever, antipyretic drugs users and non-users, and with ≥4 and <4 seizures/year before COVID-19. ConclusionOur study found few cases of seizure onset and good ASM adherence after SARS-CoV-2 infection in older people with epilepsy. Further prospective studies are needed to understand the long-term consequences of COVID-19.

A rare case of the late onset of Balo concentric sclerosis

A rare case of the late onset of Balo concentric sclerosis

Epidemiological characteristics of multiple sclerosis in Stavropol region

Multiple sclerosis (MS) is a chronic autoimmune, infl ammatory and degenerative disease of the central nervous system and is the most common neurological disorder in young people.Purpose: to determine the clinical and epidemiological features of multiple sclerosis usig the example of the Stavropol region (SR).Materials and methods. A retrospective analysis of 655 medical records of patients for 2021–2022, hospitalized in the neurological department of a multidisciplinary hospital with a diagnosis of MS, was carried out. The age, gender, place of residence of the patient, age of onset of the disease, type of MS, degree of disability, and rate of disease progression were assessed. Statistical processing was carried out using Microsoft Excel and Statistica 10 software.Results. The incidence of MS during this period was 22.7 per 100,000 population. The share of women was 70.2%, men — 29.8%. Average age — 40.04 ± 10.8 years. The vast majority of cases of onset of MS (83.2%) occur between the ages of 21 and 50 years — 82.8% of women and 84% of men. When analyzing the severity of neurological defi cit, the average score on the extended Kurtzke scale of disability was 3.53 ± 1.7 points. The rate of progression was 1.21 ± 1.1 points per year, which corresponds to a fast pace. Among those hospitalized, 65.4% have a disability group: third — 41.9% (275 patients), second — 21.4% (140 patients), fi rst — 2.1% (14 patients).Conclusion. The Stavropol Territory is one of the regions with a moderate risk of developing multiple sclerosis. The results of the work may be useful in planning medical and social care in certain territories of this region.

Abstract B021: Early onset uterine corpus cancer incidence rates and 5-year relative survival by histologic subtype and race/ethnicity among women aged 20-49 years

Abstract Purpose: Uterine cancer, including early onset cases, is increasing among all women, particularly in minority populations. Despite nearly 25% of cancers occurring in younger women, changes in tumor characteristics (e.g., histology) by race/ethnicity remain poorly understood. We examined incidence rates and 5-year relative survival of uterine cancer among women aged 20-49, overall and by race/ethnicity and histology. Methods: We used the Surveillance, Epidemiology, and End Results Program (SEER 22) Research Plus Data, representing 47.9% of the total U.S. population. We included women aged 20-49 years with microscopically confirmed malignant uterine cancer (diagnosed 2000-2019) to calculate age-adjusted incidence and age-standardized 5-year relative survival (2000-2018) overall and by race/ethnicity and histology. Time trends were described across two time periods: 2000-2009 and 2010-2019. All analyses were conducted using SEER*Stat; incidence rates were presented for per 100,000 population. Results: We included 57,128 cases (55% Non-Hispanic [NH]-White, 9% NH-Black, 10% NH-Asian/Pacific Islander [PI], and 25% Hispanic). From the period of 2000-2009 to 2010-2019, the proportion of cases that were 20-29 and 30-39 increased by 1% and 4%, respectively. Overall, incidence increased over time for all women (8.7 in 2000-2009 to. 10.4 in 2010-2019), and increases were observed for both endometrioid and non-endometrioid subtypes. In the most recent period, rates were highest for endometrioid subtypes (8.4), followed by sarcomas (1.0), and non-endometrioid subtypes (0.7). Rates for endometrioid and non-endometrioid cancers were highest in Hispanics (9.9 and 0.8) and NH-Asian/Pacific Islanders (9.7 and 0.8), respectively and lowest in NH-Blacks (5.5 and 0.6). Rates of sarcomas were highest in NH-Blacks (1.5). 5-year relative survival remained relatively unchanged over time in most racial/ethnic groups, except NH-Blacks experienced slight improvement (57% to 60%). In terms of histology, survival increased for endometrioid (87% to 89%) and non-endometrioid cases (54% to 58%) and decreased for sarcomas (46% to 42%). Conclusions: Early onset uterine cancer is rising in all women, and for both endometrioid and non-endometrioid subtypes. Of interest is the differences in the rates by histology when compared the full U.S. population: Among women aged &amp;lt;50 years, rates of uterine sarcomas were higher compared to non-endometrioid subtypes. These findings are concerning given that sarcomas are associated with poor prognosis and were the only cases to show decreased 5-year survival in our analysis. While rates of non-endometrioid subtypes are known to be higher among NH-Black women in the U.S., we did not observe a striking racial difference among early onset cases. In fact, NH-Black women had the lowest rates of endometrioid and non-endometrioid subtypes, but highest rates of sarcomas compared to others. Next step for this analysis is hysterectomy correction, which, while expected to be relatively lower among women aged&amp;lt;50 years, is known to vary by race/ethnicity. Citation Format: Akemi T. Wijayabahu, Megan A. Clarke. Early onset uterine corpus cancer incidence rates and 5-year relative survival by histologic subtype and race/ethnicity among women aged 20-49 years [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B021.

Clinical and Pathological Features of Immune Checkpoint Inhibitor-induced Liver Injury in Comparison with Drug-induced Liver Injury and Autoimmune Hepatitis.

Immune checkpoint inhibitors may cause various types of organ damage as immune-related adverse events, of which, liver damage is the most common. Herein, we evaluated the clinicopathological features of immune checkpoint inhibitor-related liver injury and investigated the differences between immune checkpoint inhibitor-related liver injury and drug-induced liver injury or autoimmune hepatitis. We selected patients with ≥ grade 3 liver injury who were diagnosed with immune checkpoint inhibitor-related liver injury (n=15). Liver biopsies were performed in 10 of the 15 cases. We also selected cases in which a liver biopsy was performed and drug-induced liver injury (n=7) or autoimmune hepatitis [n=21: acute exacerbation (n=13) was diagnosed and cases of acute onset (n=8), in which liver function test results corresponded to ≥ grade 3]. Portal fibrosis and periportal activity scores were significantly higher in the acute exacerbation autoimmune hepatitis group than in the other groups. Portal and lobular activity were not different between the groups. Plasma cell infiltration showed a higher trend in the autoimmune hepatitis group than in the other groups. Granuloma formations were seen in 90% of immune checkpoint inhibitor-related liver injury cases. The CD4/8 ratio was significantly lower in the immune checkpoint inhibitor-related liver injury group than in the other groups. Patients with bile duct injury had poorer response to corticosteroid therapy than those without. There are some obvious differences among immune checkpoint inhibitor-related liver injury, drug-induced liver injury, and autoimmune hepatitis in liver histology. Liver biopsy is helpful for the diagnosis and severity evaluation of liver injury.

10027-CBMS-3 POSTOPERATIVE EPILEPTOGENICITY IN GLIOBLASTOMA ARE ACHIEVED AS THE RESULT OF INTERACTIVE FLUCTUATIONS OF GLUTAMATE AND STEM CELL MARKER

Abstract BACKGROUND AND OBJECTIVE In our recent Glioblastoma multiforme (GBM) cases, postoperative epilepsy mostly occurred later than twenty-eight days after surgery. CD44, a stem cell marker, is known to relate with tumor cell invasiveness, however, little are known with epilepsy nor glutamate (Glu). We investigated the relationship between CD44 and the pathophysiology of this post operative late-phase epilepsy. MATERIALS AND METHODS A total of 10 GBM cases received surgery and postoperative treatment at our institute were divided into two groups; 4 cases of epilepsy onset, group E, and 6 cases without, group NE. In each group, the tumor was separated into core and periphery, from which Glu was measured (Amino Acid Analyzer L8900; Hitachi High-Tech Corporation) with expression of xCT, EAAT2 and CD44 examined (Western blot). The same objects were also examined on our three glioma stem-like cell (GSC) lines. In addition, we figured Factor X (F-X) as a key related factor, and evaluated the same objects on the GSCs under conditioned F-X (under submission). RESULTS Group E showed higher Glu than group NE both in the core and periphery. CD44 expression was significantly higher in group E in the periphery, and xCT was higher in group E both in the core and periphery. EAAT2 was lower in group E both in the core and periphery. Among the GSCs, GSC-2 had the highest CD44 expression while having the lowest xCT and extracellular Glu, and the highest EAAT2. In addition, CD44 knockdown in GSC-2 resulted in significant increase of xCT expression and extracellular Glu. Furthermore, changing the concentration of F-X low to high led to decreased expression of CD44 and increased xCT. CONCLUSION The postoperative epileptogenicity could be gained by the increase of Glu which results from the alterations of CD44, xCT and EAAT2. F-X could enhance the ability of Glu discharge.

Incidence and Timing of Immune-Related Adverse Events in Immune-Checkpoint Inhibitor-Treated Patients: A Retrospective Observational Study.

Immune-checkpoint inhibitors (ICIs) are effective against various cancers; however, immune-related adverse events (irAEs) have been reported and the timing and risk factors are unknown. Therefore, we examined the incidence and timing of irAE occurrence. Patients who received ICIs at our hospital between 1 April 2016 and 31 March 2020 were enrolled. Patients were classified into an irAE group or non-irAE group. In addition, we examined the onset time and symptoms of irAEs for each ICI type. A total of 80 patients received ICIs, of which 27 (33.8%) developed irAEs. The incidence of irAEs was 35.3% for nivolumab, 35.5% for pembrolizumab, and 28.6% for atezolizumab. The incidence of pneumonitis was 12.5%, 8.8% for dermatologic adverse events, and 6.3% for thyroid dysfunction. The earliest case of onset was after the 1st course, and the latest cases occurred after the 66th course. By the sixth course, 69% of the irAEs occurred. The positive rates for anti-thyroid peroxidase and anti-thyroglobulin antibodies were higher in the irAE group compared to the non-irAE group. Our findings suggest a high probability of irAEs occurring early in ICI treatment, with a diverse range of symptoms. This underscores the need for vigilant monitoring and tailored patient management during the initial courses of ICI therapy.

Association of methylation risk score with incident type 2 diabetes mellitus: A nested case-control study.

To investigate the association of methylation risk score (MRS) and its interactions with environmental factors with type 2 diabetes mellitus (T2DM) risk. We conducted a nested case-control study with 241 onset cases and 241 matched controls. Conditional logistic regression models were employed to identify risk CpG sites. Simple and weighted MRSs were constructed based on the methylation levels of ATP-binding cassette G1 gene, fat mass and obesity associated gene, potassium voltage-gated channel member 1 gene, and thioredoxin-interacting protein gene previously associated with T2DM to estimate the association of MRS with T2DM risk. Stratified analyses were used to investigate interactions between MRS and environmental factors. A total of 10 CpG loci were identified from the aforementioned genes to calculate MRS. After controlling for potential confounding factors, taking tertile 1 as reference, the odds ratios (ORs) and 95% confidence intervals (CIs) for T2DM of tertile 3 was 2.39 (1.36-4.20) for simple MRS and 2.59 (1.45-4.63) for weighted MRS. With per SD score increment in MRS, the OR (95% CI) was 1.66 (1.29-2.14) and 1.60 (1.24-2.08) for simple and weighted MRSs, respectively. J-curved associations were observed between both simple and weighted MRSs and T2DM risks. Additionally, multiplication interactions for smoking and hypertension with simple MRS on the risk of T2DM were found, similarly for smoking and obesity with weighted MRS on the risk of T2DM (all Pinteraction < .05). Elevated simple and weighted MRSs were associated with increased risk of T2DM. Environmental risk factors may influence the association between MRS and T2DM.

IBC‐Ab002 Fc modifications for fast clearance are associated with advantageous safety profile

AbstractBackgroundImmune checkpoint inhibitors (ICI) have been suggested as a unique therapy for treating neurodegenerative diseases. IBC‐Ab002 is a novel fully human anti‐PD‐L1 monoclonal antibody developed by ImmunoBrain Checkpoint (IBC) for the treatment of Alzheimer’s disease (AD).In cancer patients, ICI treatments are often associated with immune‐related adverse events (irAEs), which are side effects that manifest as either temporary or permanent autoimmune conditions caused by drug administration. One example of such an event is T cell‐mediated pancreatic tissue damage leading to autoimmune diabetes. The management of irAE often involves treatment discontinuation until symptoms relief, which has unwanted impact on the effectiveness of therapies that depend on continuous drug exposure.Unlike common ICI used in oncology, PD‐L1 blockade mechanism of action in mouse models of neurodegenerative diseases was shown to be dependent on transient immune system stimulation. Accordingly, IBC‐Ab002 antibody was designed with modifications on its Fc backbone that shorten its circulation half‐life, to meet the pharmacokinetic and pharmacodynamic characteristics needed for treating AD.MethodSurrogate antibodies that block mouse PD‐L1 and share the same hIgG1 Fc‐modifications as IBC‐Ab002 were generated and tested for their propensity to accelerate the onset of autoimmune diabetes in NOD transgenic mice, which spontaneously develop type 1 diabetes. Mice were monitored for their blood‐glucose levels, weight, and survival – for both the acute and long‐term duration following antibody administration.ResultWe found that administration of a therapeutically effective dose of IBC‐Ab002’s surrogate antibody led to fewer cases of premature diabetes onset in NOD mice, when compared with an antibody variant that contains no Fc‐modifications. Furthermore, no excessive weight loss, change in the time‐course of spontaneous diabetes onset or early mortality, were found following IBC‐Ab002’s surrogate treatment, compared with isotype‐control treated mice, in a 200‐days follow‐up assessment.ConclusionWe demonstrate that the clearance rate of the antibody inversely‐relates to the probability of developing an adverse immune response, and that no delayed long‐term irAEs are expected once full clearance of the antibody was achieved. Overall, these findings suggest that shortening the half‐life of anti‐PD‐L1 antibodies in treatments that do not necessitate continuous exposure can considerably increase the safety profile.

Slower clozapine titration is associated with delayed onset of clozapine-induced fever among Japanese patients with schizophrenia

Clozapine-induced fever marks the beginning of its inflammatory and potentially life-threatening adverse effects, such as myocarditis. We retrospectively analyzed the correlation between clozapine titration rate and fever onset date in 254 Japanese patients, including 55 with treatment-resistant schizophrenia who developed clozapine-induced fever. Pearson’s product-moment correlation indicated a significant delay in the fever onset date with slower titration. Most fever onset cases occurred within 4 weeks, even with slow titration. Therefore, clinicians should remain vigilant in monitoring clozapine-induced fever within 4 weeks of clozapine initiation, regardless of the titration rate.

Potential Modifying Effect of the APOEε4 Allele on Age of Onset and Clinical Manifestations in Patients with Early-Onset Alzheimer's Disease with and without a Pathogenic Variant in PSEN1 in a Sample of the Mexican Population.

In Alzheimer's disease (AD), the age of onset (AoO) exhibits considerable variability, spanning from 40 to 90 years. Specifically, individuals diagnosed with AD and exhibiting symptoms prior to the age of 65 are typically classified as early onset (EOAD) cases. Notably, the apolipoprotein E (APOE) ε4 allele represents the most extensively studied genetic risk factor associated with AD. We clinically characterized and genotyped the APOEε4 allele from 101 individuals with a diagnosis of EOAD, and 69 of them were affected carriers of the autosomal dominant fully penetrant PSEN1 variant c.1292C>A (rs63750083, A431E) (PSEN1+ group), while there were 32 patients in which the genetic cause was unknown (PSEN1- group). We found a correlation between the AoO and the APOEε4 allele; patients carrying at least one APOEε4 allele showed delays, in AoO in patients in the PSEN1+ and PSEN1- groups, of 3.9 (p = 0.001) and 8.6 years (p = 0.012), respectively. The PSEN1+ group presented higher frequencies of gait disorders compared to PSEN1- group, and apraxia was more frequent with PSEN1+/APOE4+ than in the rest of the subgroup. This study shows what appears to be an inverse effect of APOEε4 in EOAD patients, as it delays AoO and modifies clinical manifestations.

Association of community-level social capital with dementia: A multilevel nine-year longitudinal study using data from the Japan Gerontological Evaluation Study

BackgroundIndividual-level social capital prevents cognitive decline. However, a few studies have focused on the effects of community-level social capital on dementia. Therefore, we investigated the association between community-level social capital and dementia onset based on longitudinal study data on older adults in Japan. MethodsWe used longitudinal data from the Japan Gerontological Evaluation Study, obtained over nine years (2010–2019). In total, 35,921 physically and cognitively independent individuals (16,848 males and 19,073 females) aged ≥65 years and nested within 308 communities in seven municipalities participated in the study. Dementia onset was assessed using the public long-term care insurance registration. Social capital was assessed using three dimensions: civic participation, social cohesion, and reciprocity. We performed a two-level multilevel survival analysis stratified by sex, calculated hazard ratios (HRs), and 95% confidence intervals (CIs). ResultsDuring the follow-up, 6245 (17.4%) dementia onset cases were identified. The cumulative incidence of dementia was 16.2% in males and 18.4% in females. After adjusting for covariates, individual-level civic participation was associated with a lower incidence of dementia in both males and females (HR, 0.84; 95% CI, 0.77–0.92; HR, 0.78; 95% CI, 0.73–0.84). Community-level civic participation and social cohesion were associated with a lower incidence of dementia among females (HR, 0.96; 95% CI, 0.93–0.99; HR, 0.93; 95% CI, 0.88–0.98) and cross-level interaction on social cohesion among females (HR, 0.95; 95% CI, 0.90–0.99). ConclusionsLiving in a community with high civic participation and social cohesion is associated with a lower incidence of dementia among older females. Therefore, promoting civic participation and social cohesion in the community may be a useful population-based strategy to delay or prevent the onset of dementia.

Integration of Biomarker Polygenic Risk Score Improves Prediction of Coronary Heart Disease

There are several established biomarkers for coronary heart disease (CHD), including blood pressure, cholesterol, and lipoproteins. It is of high interest to determine how a combined polygenic risk score (PRS) of CHD-associated biomarkers (BioPRS) can further improve genetic prediction of CHD. We developed CHDBioPRS, combining BioPRS with PRS of CHD in the UK Biobank and tested it on FinnGen. We found that BioPRS was clearly predictive of CHD and that CHDBioPRS improved the standard CHD PRS. The largest effect was observed with early onset cases in FinnGen, with HRs above 2 per standard deviation of CHDBioPRS.

A Compendium of Late-onset Darier with an Unusual Report

Abstract Darier disease is an autosomal dominant inherited skin disorder with complete penetrance and variable expressivity due to mutation in the ATP 2A2 gene. It usually develops from childhood and persists through adolescence. Late onset of this genodermatosis has been infrequently reported and found to have minimal findings compared to the classical cases. Classical disease presents with greasy keratotic yellowish-brown papules over the seborrheic areas with palmar pits and nail changes. We hereby report a case of late onset comedonal darier disease with extensive hypopigmented lesions, involvement of palms and nails which is rarely reported in this setting. A thorough review of literature was done and a compendium prepared of late onset darier and no other case report was found to have such extensive involvement as the case reported. It will be interesting to compare more such late onset cases to see if they have a common pattern which can suggest them to be a separate entity from the classical darier.

The impact of hypothyroidism and levothyroxine treatment on preeclampsia risk: unraveling the connection for improved maternal and neonatal outcomes

Aims: Preeclampsia, a pregnancy-related complication, may develop in women with hypothyroidism. Possible risk factors may include comorbidities, predisposition to diabetes, obesity, advanced maternal age, and prior infertility treatments. The study aims to investigate the relationship between hypothyroidism and the risk of preeclampsia in pregnant women receiving levothyroxine by examining its application period. &#x0D; Methods: This is a retrospective cohort included pregnant women who gave birth between December 2022-April 2023. Women with 110 preeclampsia and those without preeclampsia (152 controls) were identified and compared in terms of hypothyroidism status, type of hypothyroidism, and levothyroxine treatment.&#x0D; Results: The results showed a significant association between the severity of the preeclampsia and its onset that early onset cases were more likely to be severe, while late onset cases were predominantly mild (p

Referral odyssey plot to visualize causes of surgical delay in mesial temporal lobe epilepsy with hippocampal sclerosis

The “odyssey plot” was used to visualize referral delays in epilepsy surgery. Participants were 36 patients (19 males; 13–67 years, median 27 years) with mesial temporal lobe epilepsy with hippocampal sclerosis (HS) who underwent resection surgery. The “referral odyssey plot” included five clinical episodes: seizure onset (T1), first visits to a non-epileptologist (T2) and to an epileptologist (T3), first admission to our epilepsy monitoring unit (EMU) (T4), and resection surgery (T5). For each patient, we identified the first seizure type: the physician who first diagnosed focal aware seizure (FAS), focal impaired awareness seizure (FIAS), focal to bilateral tonic-clonic seizure (FBTCS), and radiologically suspected HS. Within the overall delay (T1-T5, median 18 years; interquartile range [IQR] 14), non-epileptologist’s delay (T2-T3, 11.5 years; IQR 12.25) was far (p < 0.0001) longer than patient’s (T1-T2, 0 year; IQR 2.25), epileptologist’s (T3-T4, 1 year; IQR 4), or after-EMU delay (T4-T5, 1 year; IQR 1). FAS onset cases had significantly longer T1-T2 (N = 5, median 7 years; IQR 6) than FIAS (N = 22, 0 year; IQR 1, p < 0.005) or FBTCS onset cases (N = 9, 0 year; IQR 0, p < 0.001). FAS was correctly diagnosed first by non-epileptologists in 17.9%, by out-patient epileptologists in 35.7%, and at the EMU in 46.4%. FIAS was correctly diagnosed first by non-epileptologists in 94.4% and by out-patient epileptologists in 5.6%. Non-epileptologists diagnosed FBTCS in all cases. HS was diagnosed by non-epileptologists in 13.9%, by out-patient epileptologists in 47.2%, and at the EMU in 38.9%. Early referral to epileptologists is most critical for early surgery. Early utilization of the EMU is highly recommended because FAS is often overlooked by outpatient epileptologists. The odyssey plot will be useful to improve the healthcare system for other types of epilepsy.

Evaluation of the efficacy and safety of percutaneous transforaminal endoscopic discectomy for multi-segmental lumbar disc herniation.

To investigate the clinical efficacy and safety of percutaneous transforaminal endoscopic discectomy (PTED) in the treatment of multi-segmental lumbar disc herniation (msLDH). From January 2021 to December 2021, 75 patients with msLDH admitted to Baoding No.1 Hospital of Traditional Chinese Medicine were selected and divided into PTED group (n=40) and posterior lumbar interbody fusion (PLIF) group (n=35) according to different surgical methods. The operative time, intraoperative blood loss, surgical complications, Oswestry disability index (ODI) and Japanese Orthopedic Association score (JOA) scores were compared between the two groups. In the PTED group, the average operation time was 57.45±12.01minutes, and the average intraoperative blood loss was 50.57±16.69ml. There were three patients with surgical complications, including one case of hematoma, one case of aggravation of neurological symptoms and one case of new onset of neurological symptoms. In the PLIF group, there were 12 cases undergoing single-segment operation, 15 cases undergoing double-segment operation and 8 cases undergoing three-segment operation, the average operation time was 137.26±34.64minutes, and the average intraoperative blood loss was 456.06±33.06ml, there were four cases of wound fat liquefaction or delayed healing, two cases of hematoma, and three cases of exacerbation of original neurological symptoms or new neurological symptoms. At one month, six months, and one year of postoperative, the ODI and JOA scores of the two groups were significantly improved compared with those preoperative, and the ODI scores of the PTED group were better than those of the PLIF group (t=3.131, 2.263, 3.768, all P<0.05). The surgical effect of PTED in the treatment of LDH is similar to that of PLIF. However, PTED has the advantages of short operation time, less blood loss, fewer surgical complications, and high surgical safety. It is worthy of clinical promotion.

Adult Onset Nevus of Ota: Dermoscopic Characterization of a Rare Entity - A Case Report

Introduction: Nevus of Ota (NOO) is a benign dermal melanocytic pigmentary disorder, which is characterized by abnormal blue hyperpigmentation of the skin of the face and oral cavity and it usually follows the distribution of the ophthalmic and maxillary division of the trigeminal nerve. It is comparatively rare in the Indian population. The onset of nevi can occur either at or soon after birth, but there are very few rare cases with it onset in the adulthood. We report the case of a 40-year-old female with the adult onset of NOO. Methods: A 40-year-old female born out of nonconsanguineous marriage presented with a chief complaint of hyperpigmentation over the right half of the face for 6 years. The family history was noncontributory. Cutaneous examination revealed a unilateral, diffuse, homogeneous, slate colored, macular pigmented lesion over the right upper, and middle one-third of the face with an irregular border. Ophthalmological examination revealed similar pigmentation in the right sclera. Results: Dermoscopic findings corroborated with the diagnosis of NOO. Conclusion: Very few cases of late onset (beyond 30 years) NOO have been reported in the literature. It is a rare entity in the Indian sub-continent, more so in adults. This case highlights the importance of keeping an eye out for such diagnoses even in patients with the late onset of the disease as the psychological impact of the disease is high and the lesion, although benign, can rarely transform into malignant melanoma.

A novel ELOVL4 variant, L168S, causes early childhood-onset Spinocerebellar ataxia-34 and retinal dysfunction: a case report

Spinocerebellar ataxia 34 (SCA34) is an autosomal dominant inherited disease characterized by age-related cerebellar degeneration and ataxia caused by mutations in the Elongation of Very Long Chain Fatty Acid-4 (ELOVL4) gene. The ELOVL4 enzyme catalyzes the biosynthesis of both very long chain saturated fatty acids (VLC-SFA) and very long chain polyunsaturated fatty acids (VLC-PUFA) that are important for neuronal, reproductive, and skin function. Several variants in ELOVL4 have been shown to cause different tissue-specific disorders including SCA34 with or without Erythrokeratodermia Variabilis (EKV), a skin condition characterized by dry, scaly skin, Autosomal Dominant Stargardt-Like Macular Dystrophy (STGD3), and seizures associated with neuro-ichthyotic disorders. What is puzzling is how different mutations in the same gene seem to cause different tissue-specific disorders. To date, no SCA34 patients have presented with both SCA34 and STGD3 pathology that is caused by ELOVL4 variants that cause truncation of ELOVL4. Here, we report a novel case of an early childhood onset and rapidly progressive cerebellar degeneration and retinal dysfunction in a Belgian-Italian girl who developed severe dysarthria and gait problems starting at about 3.5 years of age and progressed to immobility by 4.5 years of age. Brain magnetic resonance imaging (MRI) revealed progressive vermian, cerebellar, cortical atrophy, progressive corpus callosum slimming, and hot cross bun sign visible on the MRI. Ophthalmological examinations also revealed progressive macular dysfunction as measured by electroretinography. Using exome sequencing, we identified a novel heterozygous ELOVL4 variant, c.503 T > C (p. L168S) in the patient. To understand the enzymatic function of this novel ELOVL4 variant and how it alters the levels of VLC-PUFA and VLC-SFA biosynthesis to contribute to cerebellar and retinal dysfunction, we expressed wild-type ELOVL4 or the L168S ELOVL4 variant in cell culture and supplemented the cultures with VLC-PUFA or VLC-SFA precursors. We showed that the L168S ELOVL4 variant is deficient in the biosynthesis of VLC-SFA and VLC-PUFA. Our work suggests that differential depletion of these fatty acids may be a contributing factor to the pathogenic mechanism of SCA34 with or without EKV. Further studies will help further define how the different ELOVL4 variants cause different tissue-specific disorders with variable ages of onset.

АУТОСОМНО-ДОМИНАНТНАЯ ПОЛИКИСТОЗНАЯ БОЛЕЗНЬ ПОЧЕК С ОЧЕНЬ РАННИМ НАЧАЛОМ

Both autosomal dominant polycystic kidney disease and autosomal recessive polycystic kidney disease may occur at any age starting infancy and up to adulthood. Manifestations of autosomal dominant polycystic kidney disease usually occur in adult patients with a risk of development of end-stage renal failure after the fifth decade of life. However, an increase in the number of pediatric cases of a very-early onset of the disease, in utero or during the first 18 months of life, had been registered recently, that were characterized by severe clinical manifestations which in tis turn had mimic the autosomal recessive polycystic kidney disease. The three infant cases of autosomal dominant polycystic kidney disease are observed in the Article with perinatal period features, clinical manifestations of the disease, tests’ results and its interpretation given. Children with very-early onset of autosomal dominant polycystic kidney disease are in the high-risk group for nephromegaly, severe hypertension and the early end-stage renal failure.