Complex Disorder Research Articles

Expanding the Understanding of Stiff-Person Syndrome: Insights from 17 Cases in India.

Stiff-person syndrome (SPS) is a rare and complex neurologic disorder characterized by progressive muscle stiffness, painful spasms, and gait difficulties. In this report, we describe a case of SPS who presented with a relapse while on maintenance immunosuppressive treatment. In addition, we review the literature of 16 previously reported cases of SPS from India, highlighting the diverse clinical features, comorbidities, treatment response, and relapse. The occurrence of paraneoplastic SPS emphasizes the need for early recognition and diagnosis.

Mutated neuron navigator 3 as a candidate gene for a rare neurodevelopmental disorder.

Neuron navigator 3 (NAV3) is characterized as one of the neuron navigator family (NAV1, NAV2, NAV3) proteins predominantly expressed in the nervous system. The NAV3-encoded protein comprises a conserved AAA and coiled-coil domains characteristic of ATPases, which are associated with different cellular activities. We describe a Saudi proband presenting a complex recessive neurodevelopmental disorder (NDD). Whole exome sequencing (WES) followed by Sanger sequencing, 3D protein modeling and RT-qPCR was performed. WES revealed a bi-allelic frameshift variant (c.2604_2605delAG; p.Val870SerfsTer12) in exon 12 of the NAV3 gene. Furthermore, RT-qPCR revealed a significant decrease in the NAV3 mRNA expression in the patient sample, and 3D protein modeling revealed disruption of the overall secondary structure. For the time, we associate a bi-allelic variant in the NAV3 gene causing NDD in humans.

Revue critique de la littérature sur l’efficacité des interventions en Eye Movement Desensitization and Reprocessing (EMDR) chez l’enfant et l’adolescent

ObjectivesOver three decades, EMDR therapy became a gold standard treatment for post-traumatic stress disorder in adults. While a pediatric adaptation of EMDR therapy has been developed and disseminated in specialized trauma centers, its place in the management of psychotrauma in children and adolescents remains unclear. Patients and methodA literature search was conducted using PubMed and Cochrane databases to identify controlled trials evaluating the benefit of EMDR therapy in subjects under 18 years of age. ResultsFourteen studies were found (non-randomized k=3, randomized k=11) in which EMDR therapy was consistently more effective for trauma-related symptoms in children and adolescents compared to no intervention (waiting list) or non-specific interventions. None of the studies comparing EMDR to psychotrauma-focused psychotherapy (CBT-trauma-focused or writing-based) showed a significant difference on the primary outcomes. Two meta-analyses reported a medium effect size, d=0.49–0.66, i.e., in the same range as other psycho-trauma focused psychotherapies. DiscussionAlthough encouraging, one may regret the lack of studies evaluating the benefit EMDR therapy for youths with more complex trauma-related disorders (e.g., chronic form, association with suicidal behaviors, and/or developmental disabilities). ConclusionFurther research would help to assess the benefit of EMDR therapy in children and adolescents, not only in terms of efficacy but also in terms of acceptability and effectiveness compared to other interventions.

Epigenomic differences between osteoarthritis grades in primary cartilage

ObjectiveOsteoarthritis is a common and complex joint disorder that shows higher prevalence and greater disease severity in women. Here, we investigate genome-wide methylation profiles of primary chondrocytes from osteoarthritis patients. DesignWe compare genome-wide methylation profiles of macroscopically intact (low-grade) and degraded (high-grade) osteoarthritis cartilage samples matched from osteoarthritis patients undergoing knee replacement surgery. We perform an epigenome-wide association study (EWAS) for cartilage degeneration across 170 patients and separately in 96 women and 74 men. ResultsWe reveal widespread epigenetic differences with enrichments of nervous system and apoptosis-related processes. We further identify substantial similarities between sexes, but also sex-specific markers and pathways. ConclusionsTogether, we provide the largest genome-wide methylation profiles of primary cartilage to date with enhanced and sex-specific insights into epigenetic processes underlying osteoarthritis progression.

Too Scared to Talk: Managing Selective Mutism in an Abandoned Girl

Selective mutism (SM) is a complex anxiety-related disorder, primarily prevalent in girls, and usually diagnosed in early childhood. The main diagnostic features include persistent failure to speak in some social situations, where there is an expectation for speaking, despite normal or near-normal speech in other social settings. AD, an abandoned girl, about 3-year-old, from a child care institute was referred for a medical examination to a tertiary care pediatric hospital. The major complaints were poor appetite, failure to speak to others, and excessive aloofness. She had no major behavioral difficulties, was cooperative, and complied with all verbal instructions. She would use gestures to communicate. The child was diagnosed with SM and a comprehensive individualized therapeutic plan was implemented. The management plan focused on enhancing attachment, cognitive stimulation, and language skills. As a first step, AD was enrolled in a day care center. An enabling and enriching environment was provided with plentiful opportunities for play and interaction with peers. Defocused communication that involved sitting alongside the child rather than face to face, creating joint attention using tasks that the child enjoyed, not asking direct questions, giving the child adequate time to reply, and continuing with the conversation even if she did not respond verbally was used as the primary treatment strategy. Collaborative teams including pediatricians and mental health professionals can play an integral role in early diagnosis and in overseeing the challenging path of overcoming SM in young children from adverse circumstances.

The Morbid Impact of Environmental Toxins on the Human Nervous System: Peripheral Neuropathy Nexus with Organic Solvents, Pesticides, and Heavy Metals

Peripheral neuropathy is a complex disorder characterized by damage to the peripheral nerves, resulting in various sensory, motor, and autonomic symptoms. This review offers a detailed examination of peripheral neuropathy, covering its prevalence, effects on individuals and society, causes, diagnosis, mechanisms, treatment, and management, focusing on its association with environmental toxins. The etiology of peripheral neuropathy is multifactorial, encompassing diverse causes such as diabetes mellitus, autoimmune diseases, infections, vitamin deficiencies, toxic exposures, and genetic factors. Notably, environmental toxins, including organic solvents, pesticides, and heavy metals, have been implicated in the pathogenesis of peripheral neuropathy. Environmental toxins exert their neurotoxic effects through various mechanisms, including disruption of neuronal membrane integrity, interference with neurotransmission, induction of oxidative stress, and promotion of inflammatory responses. Accurate diagnosis of peripheral neuropathy involves a comprehensive medical history, neurological examination, electrophysiological studies, imaging tests, and laboratory investigations to identify underlying causes, including environmental toxin exposure. Treatment strategies for environmental toxin-induced peripheral neuropathy focus on eliminating exposure, managing symptoms, and preventing further nerve damage. Pharmacological interventions, adjunctive therapies, nutritional support, regular monitoring, and patient education are integral to management. A multidisciplinary approach is fundamental for diagnosing and managing peripheral neuropathy effectively, emphasizing identifying and mitigating environmental toxin exposure to alleviate symptoms and improve quality of life.

The genomic mosaic of mitochondrial dysfunction: Decoding nuclear and mitochondrial epigenetic contributions to maternally inherited diabetes and deafness pathogenesis

AimsMaternally inherited diabetes and deafness (MIDD) is a complex disorder characterized by multiorgan clinical manifestations, including diabetes, hearing loss, and ophthalmic complications. This pilot study aimed to elucidate the intricate interplay between nuclear and mitochondrial genetics, epigenetic modifications, and their potential implications in the pathogenesis of MIDD. Main methodsA comprehensive genomic approach was employed to analyze a Sicilian family affected by clinically characterized MIDD, negative to the only known causative m.3243 A > G variant, integrating whole-exome sequencing and whole-genome bisulfite sequencing of both nuclear and mitochondrial analyses. Key findingsRare and deleterious variants were identified across multiple nuclear genes involved in retinal homeostasis, mitochondrial function, and epigenetic regulation, while complementary mitochondrial DNA analysis revealed a rich tapestry of genetic diversity across genes encoding components of the electron transport chain and ATP synthesis machinery. Epigenetic analyses uncovered significant differentially methylated regions across the genome and within the mitochondrial genome, suggesting a nuanced landscape of epigenetic modulation. SignificanceThe integration of genetic and epigenetic data highlighted the potential crosstalk between nuclear and mitochondrial regulation, with specific mtDNA variants influencing methylation patterns and potentially impacting the expression and regulation of mitochondrial genes. This pilot study provides valuable insights into the complex molecular mechanisms underlying MIDD, emphasizing the interplay between nucleus and mitochondrion, tracing the way for future research into targeted therapeutic interventions and personalized approaches for disease management.

Analysis and Identification of Rare and Prevalent Breakpoints in Chromosomal rearrangements in Adult and Pediatric with B-Acute Lymphoblastic Leukemia (B-ALL): A Systematic Review

Background: B-cell acute lymphoblastic leukemia (B-ALL) is a complex disorder that includes multiple genetic changes, one of the main causes of which is rare and common chromosomal translocations that lead to abnormal gene fusions. This abnormal fusion produces a new protein that causes the leukemia cells. These types of rearrangements usually occur in lymphoma and result in the movement of genetic material between different chromosomes or within chromosomes. This systematic review aims to evaluate published studies and investigate the role and importance of common and rare chromosomal translocations in the occurrence of B-ALL. Material and Methods: This systematic review investigated and evaluated the evidence regarding the effect of chromosomal translocations in adults and pediatrics with B-ALL. This review was based on the preferred reporting items for systematic reviews and meta-analysis checklists. A literature search was conducted using international databases (such as PubMed, Web of Science, Scopus, Research Gate, Google Scholar, and Cochrane Systematic Reviews database). Only English-language articles published between January 2010 and January 2023 including MESH terms such as ALL, B-ALL, and chromosomal translocations were selected. Seventy-five related studies had the necessary criteria to be examined in the present study. Results: A total of 237 articles were retrieved in the online search. The excluded articles included research on other types of leukemia in adults and children, descriptive studies, case studies, studies related to animal models of leukemogenesis, and comparisons of common treatment methods of leukemia grouping cancers. Finally, seventy-five studies were identified as eligible for inclusion in this systematic review. Conclusion: This review provides a comprehensive assessment of common and rare chromosomal translocations that can lead to the development of cancer cells. Chromosomal translocations play a role as diagnostic markers and important prognostic indicators and help specialists adjust treatment approaches according to their occurrence.

Effects of Magnesium in Physiotherapy Treatment for Patients with Knee Osteoarthritis

Background: Osteoarthritis (OA) is a complex joint degenerative disorder. Pain is a dominant characteristic, becoming persistent and more limiting as the disease progresses, resulting in reduced physical function, quality-of-life. Magnesium deficiency is considered to be a major risk factor for osteoarthritis development and progression. Oral magnesium presents unique challenges for many individuals to effectively restore intracellular magnesium levels. Transdermal magnesium absorption could be more effective than oral absorption due to its greater absorption rate and presents fewer negative effects due to its gastrointestinal tract-bypassing nature. Method: Total 40 subjects with knee osteoarthritis were selected as per the inclusion and exclusion criteria and randomly assigned to either Group A (intervention) or Group B (conventional), each having 20 patients. Assessment of the outcome measures was done pre and post 8 sessions. Outcome measures used were Visual Analogue Scale (VAS), Western Ontario and McMaster Universities Arthritis Index (WOMAC), Timed up and go test (TUG), 9 Step stair climb test, Knee ROM, Quadriceps strength using pressure biofeedback. Group A was given conventional therapy along with Epsom salt foot soak and Magnesium oil application. Group B was given conventional therapy alone. Result: There was statistically significant improvement seen in all the outcome measures in intragroup analysis with p<0.05. Intergroup analysis showed statistically significant difference in VAS on activity, WOMAC, Knee ROM, Quadriceps strength with p <0.05 indicating Group A performed better than Group B. Conclusion: The study found that Magnesium when used as an adjunct to conventional therapy shows significant difference in pain levels, knee mobility, quadriceps strength and better functionality in activities of daily living. KEYWORDS: Knee osteoarthritis, Epsom salt, Magnesium, Physiotherapy.

Effectiveness of Physiotherapy Intervention for Elderly People with Diabetic Neuropathy: A Review Study

Introduction: Diabetic neuropathy (DN) is one of the most complex and progressive disorders, characterized by symmetrical distal degeneration of peripheral nerves, resulting in features of pain and sensory loss. This study aimed to find out the effects of physiotherapy intervention on physical function, balance, and postural control of persons with DN. Materials and Methods: A computerized electronic search was performed using PEDro, Pubmed, CINAHL, and EMBASE with keywords including physiotherapy intervention, physical exercise, rehabilitation techniques, balance training, diabetic neuropathy, and diabetic peripheral neuropathy. The inclusion criteria consisted of studies that were randomized clinical trials, crossover trials, or controlled trials published in the English language from 2015 to 2021, identifying DN as the primary concern, and physiotherapy intervention as one of the treatment options. Results: The primary search of the database turned up an entire set of 58 studies, among which 11 studies were selected as potentially meeting the inclusion criteria. Ultimately, four studies were retained for the final results of the review. The evaluations provided evidence to suggest that physiotherapy has positive effects on subjects with diabetic peripheral neuropathy. Conclusion: After reviewing, it has been revealed that balance and strength training are applicable for improving balance, gait, and physical function in DN patients.

Systemic vasculitis in Kazakhstan: a complex research approach

Rare diseases known as systemic vasculitides involve the inflammatory destruction of blood vessels, leading to complex disorders that can affect a single organ or multiple organs and systems. The challenges in diagnosis, coupled with the lack of awareness among healthcare providers, particularly primary care physicians, and delayed treatment, often result in disability and worsen the prognosis of systemic vasculitis patients. We have conducted a comprehensive research approach to understand the features of systemic vasculitis, considering demographic, clinical, and laboratory data in Kazakhstan (Shymkent city and the Turkestan region). This approach, which encompasses a retrospective research method, an analytical research method, and a one-stage cross-examination (online survey), is essential in our quest to improve the understanding and management of systemic vasculitis in Kazakhstan.

Ambient Particulate Matter Induces In Vitro Toxicity to Intestinal Epithelial Cells without Exacerbating Acute Colitis Induced by Dextran Sodium Sulfate or 2,4,6-Trinitrobenzenesulfonic Acid.

Inflammatory bowel disease (IBD) is an immunologically complex disorder involving genetic, microbial, and environmental risk factors. Its global burden has continued to rise since industrialization, with epidemiological studies suggesting that ambient particulate matter (PM) in air pollution could be a contributing factor. Prior animal studies have shown that oral PM10 exposure promotes intestinal inflammation in a genetic IBD model and that PM2.5 inhalation exposure can increase intestinal levels of pro-inflammatory cytokines. PM10 and PM2.5 include ultrafine particles (UFP), which have an aerodynamic diameter of <0.10 μm and biophysical and biochemical properties that promote toxicity. UFP inhalation, however, has not been previously studied in the context of murine models of IBD. Here, we demonstrated that ambient PM is toxic to cultured Caco-2 intestinal epithelial cells and examined whether UFP inhalation affected acute colitis induced by dextran sodium sulfate and 2,4,6-trinitrobenzenesulfonic acid. C57BL/6J mice were exposed to filtered air (FA) or various types of ambient PM reaerosolized in the ultrafine size range at ~300 μg/m3, 6 h/day, 3-5 days/week, starting 7-10 days before disease induction. No differences in weight change, clinical disease activity, or histology were observed between the PM and FA-exposed groups. In conclusion, UFP inhalation exposure did not exacerbate intestinal inflammation in acute, chemically-induced colitis models.

Inflammasome activation in patients with Kaposi sarcoma herpesvirus–associated diseases

AbstractKaposi sarcoma herpesvirus (KSHV)–associated diseases include Kaposi sarcoma (KS), primary effusion lymphoma (PEL), KSHV-associated multicentric Castleman disease (MCD), and KS inflammatory cytokine syndrome (KICS). PEL, MCD, and KICS are associated with elevated circulating inflammatory cytokines. However, activation of the inflammasome, which generates interleukin-1β (IL-1β) and IL-18 via active caspase-1/4/5, has not been evaluated in patients with KSHV-associated diseases (KADs). Herein we report that patients with HIV and ≥1 KAD present with higher plasma levels of IL-18 and increased caspase-1/4/5 activity in circulating monocytes compared with HIV-negative healthy volunteers (HVs) or people with HIV (PWH) without KAD. Within KAD subtypes, KICS and MCD shared enhanced caspase-1/4/5 activity and IL-18 production compared with HVs and PWH, whereas patients with PEL showed remarkably high levels of inflammasome complex formation (known as apoptosis–associated speck-like protein containing a caspase recruitment domain). Moreover, caspase-1/4/5 activity and IL-18 plasma levels correlated with KSHV viral load, indicating KSHV-driven inflammasome activation in KAD. Accordingly, factors released by cells latently infected with KSHV triggered inflammasome activation and cytokine production in bystander monocytes in vitro. Finally, both supervised and unsupervised analyses with inflammasome measurements and other inflammatory biomarkers demonstrate a unique inflammatory profile in patients with PEL, MCD, and KICS as compared with KS. Our data indicate that detrimental inflammation in patients with KAD is at least partially driven by KSHV-induced inflammasome activation in monocytes, thus offering novel approaches to diagnose and treat these complex disorders. These trials were registered at www.ClinicalTrials.gov as #NCT01419561, NCT00092222, NCT00006518, and NCT02147405.

Large language model-driven sentiment analysis for facilitating fibromyalgia diagnosis

BackgroundFibromyalgia (FM) is a complex disorder with widespread pain and emotional distress, posing diagnostic challenges. FM patients show altered cognitive and emotional processing, with a preferential allocation of attention to...

Pills of Multi-Target H2S Donating Molecules for Complex Diseases.

Among the various drug discovery methods, a very promising modern approach consists in designing multi-target-directed ligands (MTDLs) able to modulate multiple targets of interest, including the pathways where hydrogen sulfide (H2S) is involved. By incorporating an H2S donor moiety into a native drug, researchers have been able to simultaneously target multiple therapeutic pathways, resulting in improved treatment outcomes. This review gives the reader some pills of successful multi-target H2S-donating molecules as worthwhile tools to combat the multifactorial nature of complex disorders, such as inflammatory-based diseases and cancer, as well as cardiovascular, metabolic, and neurodegenerative disorders.

PCSK9 inhibition: from effectiveness to cost-effectiveness.

Dyslipidaemia is a complex disorder characterised by abnormal lipid levels in the blood, including cholesterol and triglycerides, and plays an important role in the development of atherosclerotic cardiovascular disease. Most risk factors for cardiovascular disease are modifiable, and dyslipidaemia is a key factor among them. It can result from a combination of genetic and environmental factors. A distinction is made between primary dyslipidaemia, which is mainly caused by inherited genetic changes, and secondary dyslipidaemia, which is due to underlying diseases or certain medications. The treatment of dyslipidaemia has evolved over the years. In the past, statins were the first choice, but newer drugs, such as proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, have gained prominence due to their effectiveness in lowering lipids. Although recent guidelines recommend PCSK9 inhibitors for high-risk patients and patients who cannot tolerate statins, their widespread use is limited because of cost. Several meta-analyses have confirmed the efficacy and safety of PCSK9 inhibitors and have shown a significant reduction in low-density lipoprotein (LDL) cholesterol levels. However, the long-term side effects and interactions with other risk factors for cardiovascular disease remain uncertain. In addition, cost-effectiveness analyses have shown mixed results, with some countries considering PCSK9 inhibitors to be cost-effective for certain patient groups, while others consider them less economical. Meanwhile, initial data from patients using PCSK9 inhibitors support the results of the clinical trials. To summarise, PCSK9 inhibitors represent a revolutionary solution for lowering LDL cholesterol, but their cost-effectiveness remains controversial. Despite the controversy, they offer clear benefits for high-risk patients and should therefore be considered in the treatment of dyslipidaemia.

Dietary intervention rescues a bone porosity phenotype in a murine model of Neurofibromatosis Type 1 (NF1).

Neurofibromatosis type 1 (NF1) is a complex genetic disorder that affects a range of tissues including muscle and bone. Recent preclinical and clinical studies have shown that Nf1 deficiency in muscle causes metabolic changes resulting in intramyocellular lipid accumulation and muscle weakness. These can be subsequently rescued by dietary interventions aimed at modulating lipid availability and metabolism. It was speculated that the modified diet may rescue defects in cortical bone as NF1 deficiency has been reported to affect genes involved with lipid metabolism. Bone specimens were analyzed from wild type control mice as well as Nf1Prx1-/- (limb-targeted Nf1 knockout mice) fed standard chow versus a range of modified chows hypothesized to influence lipid metabolism. Mice were fed from 4 weeks to 12 weeks of age. MicroCT analysis was performed on the cortical bone to examine standard parameters (bone volume, tissue mineral density, cortical thickness) and specific porosity measures (closed pores corresponding to osteocyte lacunae, and larger open pores). Nf1Prx1-/- bones were found to have inferior bone properties to wild type bones, with a 4-fold increase in the porosity attributed to open pores. These measures were rescued by dietary interventions including a L-carnitine + medium-chain fatty acid supplemented chow previously shown to improve muscle histology function. Histological staining visualized these changes in bone porosity. These data support the concept that lipid metabolism may have a mechanistic impact on bone porosity and quality in NF1.

Defining Retinal Vasculitis

PurposeTo assess the validity of retinal vasculitis as the preferred diagnostic term for multiple conditions. DesignPerspective MethodsExpert opinion and review of literature focused on the current nosology and pathology of retinal vasculitis. Interpretation of the subset of intraocular inflammation named retinal vasculitis based on fundamental knowledge of the blood-retinal barrier, the neurovascular unit and pathological and functional responses to a variety of stimuli. Correlation with multimodal imaging and known mechanisms of immunologically mediated disease. ResultsA search of Medline in early 2024 for the phrase “retinal vasculitis” resulted in 2041 citations encompassing immunologic, genetic, neoplastic, infectious, drug- and ischemia-related disorders. Classification schemes and angiographic grading systems are descriptive and do not address pathologic mechanisms adequately, in part due to lack of histologic confirmation. Although OCT angiography holds promise for better imaging of retinal vascular changes, it does not reveal the key feature of leakage and only partially improves understanding of pathophysiology. Diagnosing catastrophic retinal vascular occlusion after intravitreal injections as a retinal vasculitis is the most recent example of speculative application of the term to complex and rare disorders. ConclusionsRetinal vasculitis is a diagnostic term that is over-used and imprecise. Revised nosology should limit the term to primary inflammation of the retinal vasculature itself that results in opening of the blood-retinal barrier with or without retinal vascular occlusions. Pending new histologic or mechanistic evidence, the provisional term of retinal vascular inflammation or retinal vasculopathy should be used for leakage or occlusion occurring in the context of intraocular inflammation.

Understanding Gut Health: Probiotics, Dysbiosis, and their Connection to Type 2 Diabetes - A Review

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by hyperglycaemia resulting from defects in insulin secretion, insulin action, or both. The pathophysiology of T2DM involves a multifaceted interplay of genetic, behavioural, and environmental factors. Beta cells play a central role in regulating blood glucose levels through intricate mechanisms involving insulin secretion triggered by elevated glucose concentrations and other factors. Dysfunction of beta cells in T2DM encompasses various molecular pathways influenced by factors such as hyperglycaemia, hyperlipidaemia, chronic inflammation, and genetic susceptibility, leading to impaired insulin secretion and insulin resistance. Recent research has highlighted the role of gut dysbiosis in the pathogenesis of T2DM, with alterations in gut microbiome composition impacting glucose metabolism. Dysbiosis-induced intestinal permeability can lead to systemic inflammation, contributing to insulin resistance and diabetes progression. Conversely, a diverse and rich gut microbiome has been associated with protection against obesity, diabetes, and metabolic syndrome. Probiotics, defined as live bacteria conferring health benefits when administered in adequate amounts, hold promise in mitigating T2DM-related metabolic derangements through various mechanisms, including modulation of gut microbiota, regulation of the gut-brain axis, and reduction of chronic low-grade inflammation. This provides a comprehensive overview of the mechanisms through which probiotics may positively impact glucose metabolism and discusses current evidence on the efficacy of probiotic supplementation in improving glycemic parameters and highlights the need for further research to elucidate strain-specific effects, optimal dosages, and long-term outcomes. Additionally, the translation of research findings into clinical practice and the potential of microbiome-targeted therapies for precision management of T2DM are explored, underscoring the importance of evidence-based guidelines for healthcare practitioners.

Brain organoid as a model to study the role of mitochondria in neurodevelopmental disorders: achievements and weaknesses.

Mitochondrial diseases are a group of severe pathologies that cause complex neurodegenerative disorders for which, in most cases, no therapy or treatment is available. These organelles are critical regulators of both neurogenesis and homeostasis of the neurological system. Consequently, mitochondrial damage or dysfunction can occur as a cause or consequence of neurodevelopmental or neurodegenerative diseases. As genetic knowledge of neurodevelopmental disorders advances, associations have been identified between genes that encode mitochondrial proteins and neurological symptoms, such as neuropathy, encephalomyopathy, ataxia, seizures, and developmental delays, among others. Understanding how mitochondrial dysfunction can alter these processes is essential in researching rare diseases. Three-dimensional (3D) cell cultures, which self-assemble to form specialized structures composed of different cell types, represent an accessible manner to model organogenesis and neurodevelopmental disorders. In particular, brain organoids are revolutionizing the study of mitochondrial-based neurological diseases since they are organ-specific and model-generated from a patient's cell, thereby overcoming some of the limitations of traditional animal and cell models. In this review, we have collected which neurological structures and functions recapitulate in the different types of reported brain organoids, focusing on those generated as models of mitochondrial diseases. In addition to advancements in the generation of brain organoids, techniques, and approaches for studying neuronal structures and physiology, drug screening and drug repositioning studies performed in brain organoids with mitochondrial damage and neurodevelopmental disorders have also been reviewed. This scope review will summarize the evidence on limitations in studying the function and dynamics of mitochondria in brain organoids.