Electroconvulsive Therapy Research Articles

Addressing patient concerns: Exploring Electroconvulsive Therapy (ECT) in primary care: Review of the literature

Addressing patient concerns: Exploring Electroconvulsive Therapy (ECT) in primary care: Review of the literature

Pharmacotherapy and electroconvulsive therapy prescription for women with depressive and anxiety disorders in a psychiatric mother-baby unit.

The purpose of this study was to understand the pharmacotherapy and electroconvulsive therapy (ECT) prescription of women with depression and anxiety admitted to an Australian inpatient psychiatric mother-baby unit (MBU) and compare prescription to national clinical practice guidelines. A retrospective audit was conducted on women diagnosed with depression or anxiety admitted to a public psychiatric inpatient MBU from March 2017 to July 2019. Data was captured at three time points to assess demographic, clinical and pharmacotherapy treatment characteristics. Descriptive statistics were completed. Of the 74 women, 57 women had depression, with 73% prescribed Selective Serotonin Reuptake Inhibitors (SSRIs) and 14% provided ECT during admission. For women with anxiety (n = 17), 23% were prescribed a benzodiazepine with concurrent antidepressant prescription. SSRI prescription increased, with other antidepressant prescription up trending through admission. Atypical antipsychotic prescription was increased initially and trended downwards at discharge. This study explored the therapeutic armamentarium employed for the treatment of mothers admitted to an inpatient psychiatric MBU with depression and anxiety. The results point to the intricate prescribing practices in a naturalistic setting and highlight that prescribing practices were in line with national guidelines.

Prediction of Clinical Outcomes in Psychotic Disorders Using Artificial Intelligence Methods: A Scoping Review.

Psychotic disorders are major psychiatric disorders that can impact multiple domains including physical, social, and psychological functioning within individuals with these conditions. Being able to better predict the outcomes of psychotic disorders will allow clinicians to identify illness subgroups and optimize treatment strategies in a timely manner. In this scoping review, we aimed to examine the accuracy of the use of artificial intelligence (AI) methods in predicting the clinical outcomes of patients with psychotic disorders as well as determine the relevant predictors of these outcomes. This review was guided by the PRISMA Guidelines for Scoping Reviews. Seven electronic databases were searched for relevant published articles in English until 1 February 2024. Thirty articles were included in this review. These studies were mainly conducted in the West (63%) and Asia (37%) and published within the last 5 years (83.3%). The clinical outcomes included symptomatic improvements, illness course, and social functioning. The machine learning models utilized data from various sources including clinical, cognitive, and biological variables such as genetic, neuroimaging measures. In terms of main machine learning models used, the most common approaches were support vector machine, random forest, logistic regression, and linear regression models. No specific machine learning approach outperformed the other approaches consistently across the studies, and an overall range of predictive accuracy was observed with an AUC from 0.58 to 0.95. Specific predictors of clinical outcomes included demographic characteristics (gender, socioeconomic status, accommodation, education, and employment); social factors (activity level and interpersonal relationships); illness features (number of relapses, duration of relapses, hospitalization rates, cognitive impairments, and negative and disorganization symptoms); treatment (prescription of first-generation antipsychotics, high antipsychotic doses, clozapine, use of electroconvulsive therapy, and presence of metabolic syndrome); and structural and functional neuroimaging abnormalities, especially involving the temporal and frontal brain regions. The current review highlights the potential and need to further refine AI and machine learning models in parsing out the complex interplay of specific variables that contribute to the clinical outcome prediction of psychotic disorders.

The Role of Electroconvulsive Therapy in Posttraumatic Stress Disorder: A Systematic Review.

Posttraumatic stress disorder (PTSD) is associated with a high burden of disability and mortality. Despite standard treatments with antidepressants and/or psychotherapy, remission is often difficult to achieve. Electroconvulsive therapy (ECT) is an effective treatment for mood disorders but is currently not recognized as a treatment modality for PTSD. The literature about its potential role in the management of PTSD is growing. Thus, we aim to systematically review the available evidence for the role of ECT in PTSD.Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses 2020 guidelines, we performed a systematic literature search from 1958 to December 2023 using PubMed, Embase, Web of Science, Cochrane Central Register of Controlled trials databases, and the Clinicaltrials.gov-registry.Eighteen studies met our inclusion criteria: 1 meta-analysis, 2 randomized control trials, 2 prospective, 4 retrospective studies, 8 case reports, and 2 reviews.Accumulating evidence suggests that ECT might have a beneficial effect on the core symptoms of PTSD with comorbid conditions, such as depression or schizophrenia. Although in some studies, the effect on core PTSD symptoms was not related to an antidepressant effect of ECT, these findings need further replication. Nevertheless, in severe and intractable cases, ECT can be considered, especially in the presence of comorbid depression. Further research in patients without comorbidity is warranted.

Electroconvulsive Therapy Versus Aripiprazole Addition to Clozapine in Patients with Clozapine-Resistant Symptoms (EMECLO): A Protocol of a Single-Blind, Multicenter, Randomized-Controlled Feasibility Trial.

Currently, guidance on the most effective treatment for patients with clozapine-resistant schizophrenia-spectrum disorders (SSD) is lacking. While augmentation strategies to clozapine with aripiprazole and electroconvulsive therapy (ECT) have been demonstrated to be effective in patients with clozapine-resistant schizophrenia spectrum disorders (CRS), head-to-head comparisons between these addition strategies are unavailable. We therefore aim to examine the feasibility of a larger randomized, single-blind trial comparing the effectiveness, cost-effectiveness, and safety of aripiprazole addition vs. ECT addition in CRS. In this multi-center, randomized, single-blind feasibility study, the feasibility of recruiting 20 participants with CRS who will be randomized to either aripiprazole or bilateral ECT addition will be assessed. The main endpoint is the number of patients willing to be randomized. The number of screened individuals and reasons to decline participation will be recorded. Effects will be estimated for the benefit of the foreseen larger trial. To that end, differences between both arms in symptom severity will be assessed using blinded video assessments. In addition, tolerability (e. g., cognitive functioning), safety, quality of life, recovery, and all-cause discontinuation will be compared. The follow-up period is 16 weeks, after which non-responders will be given the option to switch to the other treatment. Strengths of this feasibility trial include maintaining blinding with video assessment, a possibility to switch groups in case of non-response, and a broad set of outcome measures. Identification of factors contributing to non-participation and drop-out will generate valuable information on trial feasibility and may enhance recruitment strategies in a follow-up RCT. The study has been approved by the Medical Research Ethics Committee of the Amsterdam University Medical Center, location AMC, and was registered on 1 May 2022 in the EU Clinical Trials Register (EudraCT) under the trial name 'EMECLO' (2021-006333-19).

Predicting treatment outcomes in major depressive disorder using brain magnetic resonance imaging: a meta-analysis.

Recent studies have provided promising evidence that neuroimaging data can predict treatment outcomes for patients with major depressive disorder (MDD). As most of these studies had small sample sizes, a meta-analysis is warranted to identify the most robust findings and imaging modalities, and to compare predictive outcomes obtained in magnetic resonance imaging (MRI) and studies using clinical and demographic features. We conducted a literature search from database inception to July 22, 2023, to identify studies using pretreatment clinical or brain MRI features to predict treatment outcomes in patients with MDD. Two meta-analyses were conducted on clinical and MRI studies, respectively. The meta-regression was employed to explore the effects of covariates and compare the predictive performance between clinical and MRI groups, as well as across MRI modalities and intervention subgroups. Meta-analysis of 13 clinical studies yielded an area under the curve (AUC) of 0.73, while in 44 MRI studies, the AUC was 0.89. MRI studies showed a higher sensitivity than clinical studies (0.78 vs. 0.62, Z = 3.42, P = 0.001). In MRI studies, resting-state functional MRI (rsfMRI) exhibited a higher specificity than task-based fMRI (tbfMRI) (0.79 vs. 0.69, Z = -2.86, P = 0.004). No significant differences in predictive performance were found between structural and functional MRI, nor between different interventions. Of note, predictive MRI features for treatment outcomes in studies using antidepressants were predominantly located in the limbic and default mode networks, while studies of electroconvulsive therapy (ECT) were restricted mainly to the limbic network. Our findings suggest a promise for pretreatment brain MRI features to predict MDD treatment outcomes, outperforming clinical features. While tasks in tbfMRI studies differed, those studies overall had less predictive utility than rsfMRI data. Overlapping but distinct network-level measures predicted antidepressants and ECT outcomes. Future studies are needed to predict outcomes using multiple MRI features, and to clarify whether imaging features predict outcomes generally or differ depending on treatments.

Characterization of the longitudinal effects of electroconvulsive therapy on mitochondrial bioenergetics in immune cells from patients with major depressive disorder

Characterization of the longitudinal effects of electroconvulsive therapy on mitochondrial bioenergetics in immune cells from patients with major depressive disorder

Refractory Pediatric Catatonia Following Treatment for an Intracranial Mass: Safe and Effective Use of Electroconvulsive Therapy.

Refractory Pediatric Catatonia Following Treatment for an Intracranial Mass: Safe and Effective Use of Electroconvulsive Therapy.

Does Electroencephalography Seizure Duration Account for an Adequate Treatment of Magnetic Seizure Therapy for Schizophrenia?

A seizure lasting >15 s has been considered to indicate treatment for magnetic seizure therapy (MST), a modification of electroconvulsive therapy (ECT), without much validation. This study aimed to investigate whether this seizure duration was suitable for the treatment of schizophrenia. Altogether, 34 and 33 in-patients with schizophrenia received 10 sessions of MST and ECT, respectively. Clinical symptoms were assessed using the Positive and Negative Symptom Scale at baseline and at the 4-week follow-up. Electroencephalogram (EEG) was monitored during each MST or ECT treatment using bifrontal electrodes. The proportion of participants who achieved the 15-second threshold was only 28.6% in the MST group, with a significant difference between responders and nonresponders. For patients receiving MST, the average EEG seizure duration correlated with the percentage of Positive and Negative Symptom Scale reduction (t(32) = 2.51, P = 0.017, uncorrected; t(32) = 2.00, P = 0.055, corrected with clinical characteristics). The average EEG seizure duration predicted the clinical response at a trend level (Z = 1.76, P = 0.078) with an optimal cutoff of 11.3 seconds. All patients in the ECT group achieved the 15-second threshold. However, their average EEG seizure duration was uncorrelated with clinical improvement. The duration of EEG seizures may be associated with the antipsychotic effects of MST. This association may have been influenced by various clinical and technical factors. More research is needed to define the specific criteria for adequate MST in schizophrenia in order to achieve personalized dosing.

Leukocyte Telomere Length and Mitochondrial DNA Copy Number in Treatment-Resistant Depression and Response to Electroconvulsive Therapy: A Pilot Longitudinal Study.

In this study, we investigated if changes in leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNA-cn), 2 markers of cellular aging, are associated with treatment-resistant depression (TRD) and with response to electroconvulsive therapy (ECT). LTL and mtDNA-cn were measured in 31 TRD patients before (T0), 1 week (T1), and 4 weeks (T2) after the ECT course, as well as in a sample of 65 healthy controls. TRD patients had significantly shorter LTL and higher mtDNA-cn compared with healthy controls at baseline. In the TRD sample, LTL was inversely correlated with Montgomery-Åsberg Depression Rating Scale scores at baseline. Baseline levels of LTL or mtDNA-cn were not correlated with response to ECT. Similarly, changes in LTL or mtDNA-cn were not associated with response to ECT either when considered as a dichotomous trait (responders vs nonresponders) or as a percentage change in symptoms improvements. Ours is the first longitudinal study exploring the role of LTL and mtDNA-cn in response to ECT. Findings of this pilot investigation suggest that LTL and mtDNA-cn may constitute disease biomarkers for TRD but are not involved in response to ECT.

Depression and Parkinson’s disease

Parkinson's disease is a progressive neurodegenerative disease with motor symptoms and non-motor impairments, including depression, observed in 2.7-90% of cases. Depression is frequently underestimated and diagnosed late due to its similarity with symptoms of Parkinson's disease, such as fatigue, sleep disturbances, hypomimia, etc. In approximately 25% of patients, depression precedes motor symptoms, which may indicate its connection with the pathogenesis of Parkinson's disease. The purpose of the study was to analyze current data on the pathophysiology, diagnosis, and treatment of depression in patients with Parkinson's disease. The study results have demonstrated that the pathophysiological mechanisms of depression in Parkinson's disease include neurodegeneration of dopaminergic, noradrenergic, and serotonergic neurons, neuroinflammation, and impaired neuroplasticity. For timely treatment, patients, especially those with changes in motor or non-motor symptoms, should be regularly examined. Treatment is based on a multimodal approach and includes the use of supportive psychotherapy and pharmacotherapy. Alternative methods such as exercise, cognitive behavioral therapy, transcranial magnetic stimulation, and electroconvulsive therapy are also being explored. Thus, treatment of patients with depression and Parkinson's disease requires an individualized approach. Further research into this problem is crucial to develop and improve patient management algorithms.

Neurological Damage Measured by S-100b and Neuron-Specific Enolase in Patients Treated with Electroconvulsive Therapy.

Electroconvulsive therapy (ECT) is considered one of the most effective treatments for psychiatric disorders. ECT has proven effective in the treatment of depression, mania, catatonia and psychosis. It is presumed that seizures induced during ECT administration cause toxicity and potentially neuronal and glial cell death. A broad range of neurological disorders increase cerebrospinal fluid and serum levels of neuron-specific enolase (NSE) and S-100b protein. This study aims to investigate the effect of ECT on NSE and S-100b levels, which, together, serve as a proxy for neuronal cell damage. Serum concentrations of S-100b and NSE of adult patients who received ECT were measured by immunoluminometric analysis before and after treatment. A two-way ANOVA test was used to estimate the statistical differences in marker concentrations between the subgroups of the study population. Results: A total of 55 patients were included in the analysis: 52.73% (n = 29) were diagnosed with depression, 21.82% (n = 12) with schizophrenia or other psychosis, 16.36% (n = 9) with mania and 9.09% (n = 5) with catatonia. There were no statistically significant changes in NSE (p = 0.288) and S-100b (p = 0.243) levels. We found no evidence that ECT induced neuronal damage based on NSE and S-100b protein levels measured in the serum of patients before and after treatment.

Bipolar Disorder: A Comprehensive Analysis of its Etiology, Impact, and Treatment Options

Bipolar disorder (BD) is a disorder significantly impacts individuals worldwide, marked by alternating episodes of mania and depression. The onset and progression of the disease are impact by a interplay of genetic factors, neurobiological differences, environmental stressors, hormonal imbalances, and circadian rhythm disruptions. These factors collectively contribute to the manifestation and exacerbation of the disorder. The disorder profoundly affect both mental and physical health. The pervasive impact on daily life can be overwhelming, resulting in severe emotional distress. This distress is compounded by the high risk of suicide associated with the disorder, underscoring the critical need for vigilant care and comprehensive support to ensure the well-being of affected individuals. Effective treatment requires a holistic approach combining pharmacological interventions, psychotherapy, and lifestyle adjustments. Mood stabilizers, antipsychotics, and antidepressants, alongside Cognitive Behavioral Therapy (CBT), psychoeducation, and family therapy, form the cornerstone of treatment. Lifestyle modifications, including regular exercise, adequate sleep, and balanced nutrition, are crucial for symptom management. Electroconvulsive Therapy (ECT) is considered for severe cases. This review underscores the need for continuous research and innovation in therapeutic strategies and emphasizes bridging global disparities in mental health services to ensure equitable care and improve the well-being of people with bipolar disorder.

Exploring suicidal attempts in a rare case of Klinefelter syndrome comorbid with autism spectrum disorder: Unveiling the underdiagnosed nexus and noble intervention of electroconvulsive therapy

Exploring suicidal attempts in a rare case of Klinefelter syndrome comorbid with autism spectrum disorder: Unveiling the underdiagnosed nexus and noble intervention of electroconvulsive therapy

Clinical and sociodemographic characteristics associated with relapse following electroconvulsive therapy for bipolar disorder.

Electroconvulsive therapy (ECT) is an effective treatment for bipolar disorder, but relapse following a successful ECT series is common. We aimed to identify clinical and sociodemographic characteristics associated with the risk of relapse following ECT in bipolar disorder. Using data from nationwide Danish registers, we identified all patients receiving their first ECT series with an indication diagnosis of bipolar disorder between 2006 and 2018. We then followed these patients for relapse, defined as either psychiatric admission or a new ECT series, for 6 months following ECT. Associations between clinical and sociodemographic characteristics and relapse were examined via multivariable Cox proportional-hazards regression, yielding adjusted hazard rate ratios (aHRR). Of the 1473 patients receiving ECT for bipolar disorder (62% females, mean age = 53 years), 34% met the relapse criterion. The following characteristics were associated with an elevated risk of relapse; age <40 (aHRR = 1.54, 95% CI = 1.05-2.26); being a pensioner (aHRR = 1.73, 95% CI = 1.29-2.32), indication diagnosis for ECT being psychotic mania (aHRR = 1.63, 95% CI = 1.16-2.28), psychotic bipolar depression (aHRR = 1.37, 95% CI = 1.06-1.80), mixed episode (aHRR = 1.51, 95% CI = 1.13-2.02), or other bipolar episodes (aHRR = 1.68, 95% CI = 1.28-2.21); and treatment with antipsychotics prior to the course of ECT (aHRR = 1.32, 95% CI = 1.04-1.67). Patients with bipolar disorder face a particularly high risk of relapse following ECT if they present with the following characteristics when initiating ECT: age <40, being a pensioner, having received treatment with an antipsychotic before initiating ECT, or having psychotic bipolar depression, psychotic mania, mixed episodes, or other bipolar episodes as the indication for ECT. These findings may guide relapse monitoring following ECT in bipolar disorder.

Electroconvulsive therapy modulates loudness dependence of auditory evoked potentials: a pilot MEG study.

Electroconvulsive therapy (ECT) remains a critical intervention for treatment-resistant depression (MDD), yet its neurobiological underpinnings are not fully understood. This pilot study aims to investigate changes in loudness dependence of auditory evoked potentials (LDAEP), a proposed biomarker of serotonergic activity, in patients undergoing ECT. High-resolution magnetoencephalography (MEG) was utilized to measure LDAEP in nine depressed patients receiving right unilateral ECT. We hypothesized that ECT would reduce the LDAEP slope, reflecting enhanced serotonergic neurotransmission. Depression severity and cognitive performance were assessed using the 24-item Hamilton Depression Rating Scale (HDRS24) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), respectively. Contrary to our hypothesis, findings indicated a significant increase in LDAEP post-ECT (t 8 = 3.17, p = .013). The increase in LDAEP was not associated with changes in depression severity or cognitive performance. The observed increase in LDAEP suggests a more complex interaction between ECT and neurobiological systems, rather than a direct reflection of serotonergic neurotransmission. Potential mechanisms for this increase include ECT's impact on serotonergic, dopaminergic, glutamatergic, and GABAergic receptor activity, neuroplasticity involving brain-derived neurotrophic factor (BDNF), and inflammatory modulators such as TNF-α. Our results highlight the multifaceted effects of ECT on brain function, necessitating further research to elucidate these interactions.

Role of methanogenesis and methanotrophy in CH4 fluxes from rice paddies under elevated CO2 concentration and elevated temperature

The differential responses of methanogenesis and methanotrophy to elevated carbon dioxide concentrations ([CO2]) (e[CO2]) and elevated temperature ([T]) (e[T]) may lead to dramatic changes in the response of CH4 emissions from rice paddies to global warming. In this study, we systematically investigated the responses and mechanisms of CH4 flux from rice paddies to e[CO2] and e[T] based on the production and oxidation of CH4. The CH4 flux, soil properties, and soil methanogenesis and methanotrophy were observed under CK (ambient [CO2] + ambient [T]), EC (e[CO2] by 200 μmol mol−1 + ambient [T]), ET (ambient [CO2] + e[T] by 2 °C), and ECT (e[CO2] by 200 μmol mol−1 + e[T] by 2 °C) treatments. The results revealed that EC, ET, and ECT significantly increased the cumulative amount of CH4 (CAC) in the rice paddies by 10.63, 15.20, and 11.77 kg ha−1, respectively, compared with CK. ECT increased the CAC in the rice paddies by 1.14 kg ha−1 compared with EC. Moreover, EC, ET, and ECT significantly enhanced the methane production potential (MPP) and methane oxidation potential (MOP) and tended to increase the mcrA gene abundance of the methanogens. EC tended to prompt the pmoA gene abundance of the methanotrophs, but the effect of ET on the pmoA gene abundance was less consistent across the growth stages. ECT significantly decreased the relative abundances of Methanosarcina and Methylocystis (Type II) by 4.9 % and 14.2 %, respectively, while it increased the relative abundance of Methylosarcina (Type I) by 24.0 % compared with CK. Overall, the increased MPP/MOP, mcrA/pmoA, and microbial biomass carbon under climate change increased the CH4 flux from the rice paddies. The contribution of e[CO2] to the CH4 flux was significantly enhanced by e[T], which could further exacerbate the risk of global climate change induced by e[CO2].

Attitudes and Knowledge of Electroconvulsive Therapy: An Exploration of Medical Students' Perspectives.

To explore knowledge and attitudes of medical students before and after exposure to a technology-enhanced learning and teaching (TELT) session about electroconvulsive therapy (ECT). Adequate knowledge of and attitudes toward ECT is essential for medical students. However, the impact of teaching on knowledge and attitudes is infrequently studied. Fourth- and fifth year medical students at the University of Glasgow were provided with an online questionnaire before and after engaging in a remote TELT session, led by a consultant psychiatrist with expertise in ECT. The online teaching session used resources developed by a multidisciplinary team who specialize in ECT. The teaching session lasted around 1 hour. The questionnaire contained 3 sections: baseline demographics, knowledge of ECT, and attitudes toward ECT. Changes in scores were analyzed. Sixty-seven students completed the teaching session. Response rate to the precourse questionnaire was 68.7% (n = 46), and the postcourse questionnaire was 44.8% (n = 30). Prior to engaging with the learning materials, 9 students reported no knowledge of ECT and a third believed that ECT did not cause a seizure. In general, students who had personal experience of mental illness (friend, relative, or self) had more positive attitudes toward ECT and higher knowledge scores. In general, an increase in knowledge and attitude scores was found in the postcourse questionnaire. Exposing medical students to a TELT session focused on ECT during their psychiatric placement appeared to improve knowledge and attitudes surrounding ECT.

Electroconvulsive Therapy for Psychogenic Polydipsia and Hyponatremia in Chronic Schizophrenia: A Case Report and Literature Review.

Compulsive drinking of excessive quantities of water, called psychogenic polydipsia (PP), is a challenging complication of chronic psychotic disorders, which can lead to hyponatremia and downstream morbidity or mortality. Treatments include behavioral modifications such as free water restriction, medications to modify free water excretion, and psychotropic medications to target psychotic symptoms. However, in many cases, these options remain ineffective and/or intolerable, necessitating chronic institutionalization with poor patient quality of life. Here we report the use of an acute course of 8 sessions of bilateral electroconvulsive therapy (ECT) in a 57-year-old man with chronic schizophrenia, PP, and moderate hyponatremia refractory to standard treatments in an inpatient psychiatric setting. Serum sodium normalized and remained stable during and immediately following his ECT course, despite chronic hyponatremia with high variability for months prior to ECT initiation. A literature review found remarkably few reported cases of ECT for PP in chronic schizophrenia, a surprising result given the use of this modality for patients with psychotic illness in many countries. Our findings support future investigation into the clinical utility and mechanism of ECT for PP in this patient population.

Successful Electroconvulsive Therapy in Aicardi-Goutières Syndrome Presenting Psychiatric Symptoms: An Unprecedented Clinical Case.

Aicardi-Goutières syndrome (AGS) is a rare genetic disorder that primarily affects the central nervous system and is characterized by severe intellectual and physical disabilities. Although AGS traditionally exhibits nonpsychiatric symptoms, our case challenges this norm by presenting an 18-year-old male with AGS who developed distinctive psychiatric manifestations that required hospital admission.The patient, diagnosed with spastic cerebral palsy and thrombotic vasculopathy, displayed abrupt behavioral disturbances, insomnia, and food aversion. Standard assessments revealed basal ganglia calcifications and chilblain-like lesions, and AGS was confirmed via genetic studies that showed a mutation in the SAMHD1 gene. Despite initial treatment with aripiprazole and diazepam, psychiatric symptoms persisted. This led to the initiation of electroconvulsive therapy (ECT) with substantial success, marking its first documented use in AGS.In conclusion, this unique case broadens the comprehension of AGS, introducing psychiatric symptoms and pioneering the successful application of ECT. The intricate interplay of neurovascular involvement, genetic nuances, and innovative treatments underscores the complexity of AGS, encouraging further exploration of its diverse clinical spectrum and evolving therapeutic strategies.