Search Results (121)

Background: We aimed to determine paranasal sinus volumes using 3D volumetric measurements and to evaluate the effect of anatomical variations on these volumes, ensuring balanced age and sex distribution during childhood. Methods: Thirteen age groups (0–16 years), each including 10 males and 10 females, were formed. After excluding sinus pathologies, a total of 260 subjects were randomly selected from CT head examinations. Right and left frontal, maxillary, and sphenoid sinus volumes were calculated using 3DSlicer software (version 5.6.2)following manual segmentation of axial CT slices. Also, the presence of right and left Agger Nasi cells, Haller cells, Onodi cells, and concha bullosa were recorded. Results: No significant difference was found between males and females in sinus volumes (p > 0.05). Mean right and left maxillary sinus volumes were 6.23 cm³ and 6.27 cm³ (p = 0.551); frontal sinuses were 0.79 cm³ and 0.86 cm³ (p = 0.170); and sphenoid sinuses were 1.64 cm³ and 1.85 cm³ (p = 0.041). Sphenoid sinus pneumatization appeared in 30% of the 0–6-month group and in over 75% of older groups. Frontal pneumatization began at age 2–3 and exceeded 50% after age 4. Agger Nasi, Haller, Onodi cells, and concha bullosa were detected in 58.8%, 31.2%, 10%, and 22.3% of cases, respectively. Anatomical variations showed no significant effect on sinus volumes (p > 0.05). Conclusions: We developed a paranasal sinus volume chart applicable to routine practice, showing that anatomical variations had no significant impact on the development. This is the first study to investigate the impact of anatomical variations on sinus development and volume, along with the age at which variations emerge, with a balanced distribution of age and sex. Full article

Background/Objectives: Craniopharyngiomas (CPs) are rare, generally benign tumors predominantly located in the sellar and suprasellar regions, associated with significant morbidity and complex surgical management. Despite high overall survival rates, patients frequently experience complications including visual impairment, pituitary dysfunction, diabetes insipidus (DI), and hypothalamic syndrome. Among these, hypothalamic obesity (HO) represents one of the most clinically challenging sequelae, often occurring early, lacking standardized medical treatment, and leading to substantial comorbidity and reduced quality of life. This study reports a single-center experience focusing on the relationship between skull base anatomy, surgical approach selection, and endocrinological outcomes. Methods: A retrospective analysis was conducted on patients diagnosed with CPs who underwent surgery by a dedicated team at our Department from January 2014 to January 2024. The approaches used were endoscopic (ER) and transcranial (TR). Preoperative imaging (volumetric MRI and CT scans) was analyzed using 3DSlicer (open-source software) for anatomical modeling of the tumor and skull base. Clinical outcomes were evaluated through follow-up assessments by a team of neuroendocrinologists. Data on BMI changes, DI onset, and hypopituitarism were collected. Statistical analyses consisted of descriptive comparisons and exploratory regression models. Results: Of 18 patients reviewed, 14 met the inclusion criteria. Larger sphenoid sinus volumes were associated with selection of an endoscopic endonasal approach (p = 0.0351; AUC = 0.875). In ER cases, the osteotomy area was directly related to tumor volume, independent of other anatomical parameters. Postoperatively, a significant increase in BMI (22.39 vs. 26.65 kg/m²; p = 0.0049) and in the incidence of DI (three vs. nine cases; p-value 0.0272) was observed. No clear differential association between surgical approach and endocrinological outcomes emerged in this cohort. Conclusions: Quantitative assessment of skull base anatomy using 3D modeling may support surgical approach selection in patients with craniopharyngiomas, particularly in identifying anatomical settings favorable to endoscopic endonasal surgery. Endocrinological outcomes appeared more closely related to tumor characteristics and hypothalamic involvement than to the surgical route itself. These findings support the role of individualized, anatomy-informed surgical planning within a multidisciplinary framework. Full article

Objectives: To characterize the learning curve of endoscopic transsphenoidal pituitary adenoma surgery performed by a single neurosurgeon, assess how operative time, resection rates, and clinical outcomes evolved with experience, and identify tumor-related factors influencing surgical performance. Methods: This retrospective study included 123 consecutive endoscopic transsphenoidal pituitary adenoma resections performed between 2018 and 2025. Cases were divided into quartiles according to chronological order. Clinical, radiological, endocrinological, and operative variables were analyzed. Gross total resection (GTR), biochemical remission, postoperative complications, and visual and cranial nerve outcomes were compared between quartiles. A segmented linear regression model was applied to identify changepoints in the operative-time learning curve. Statistical significance was set at p < 0.05. Results: The mean operative time decreased by 31.8%, from 160.8 min in Quartile 1 to 109.7 min in Quartile 4. Segmented regression revealed two changepoints at cases 47 and 85, defining three learning phases: a steep improvement phase, a consolidation phase, and a plateau. GTR was achieved in 51.2% of patients and did not significantly differ across quartiles. For Knosp 0–2 tumors, GTR was 76.1% overall; for Knosp 3–4 tumors, 30%. Tumor diameter, Knosp grade, and sphenoid sinus invasion were strongly associated with lower GTR rates (all p < 0.05). Biochemical remission was achieved in 74.2% of patients with functional adenomas. New or worsened postoperative pituitary insufficiency significantly decreased across quartiles (p < 0.001). Rates of postoperative diabetes insipidus (30.8%) and CSF leak (6.5%) were comparable with published literature and showed no consistent temporal trend. Conclusions: A clear learning curve exists in endoscopic pituitary surgery, with operative proficiency achieved after approximately 50 cases and an experienced plateau after ~90 cases. Surgical experience significantly reduced operative time and postoperative pituitary insufficiency but did not influence GTR rates, likely due to a high and increasing proportion of large tumors with cavernous sinus invasion. Tumor size, Knosp grade, and sphenoid sinus invasion were identified as major determinants of surgical complexity and should be accounted for when evaluating learning curves and surgical outcomes. Full article

Background and Clinical Significance: Giant sphenoid wing meningiomas are generally viewed as skull base masses that compress frontal centers and their respective pathways gradually enough to cause a dysexecutive–apathetic syndrome, which can mimic primary neurodegenerative disease. The aim of this report is to illustrate how bedside phenotyping and multimodal imaging can disclose similar clinical presentations as surgically treatable network lesions. Case Presentation: An independent, right-handed older female developed an incremental, two-year decline of her ability to perform executive functions, extreme apathy, lack of instrumental functioning, and a frontal-based gait disturbance, culminating in a first generalized seizure and a newly acquired left-sided upper extremity pyramidal sign. Standardized neuropsychological evaluation revealed a predominant frontal-based dysexecutive profile with intact core language skills, similar to behavioral-variant frontotemporal dementia (bvFTD). MRI demonstrated a large, right fronto-temporo-basal extra-axial tumor attached to the sphenoid wing with homogeneous postcontrast enhancement, significant vasogenic edema within the frontal projection pathways, and a marked midline displacement of structures with an open venous pathway. With the use of a skull-base flattening pterional craniotomy with early devascularization followed by staged internal debulking, arachnoid preserving dissection, and conservative venous preservation, the surgeon accomplished a Simpson Grade I resection. Sequential improvements in the patient’s frontal “re-awakening” were demonstrated through postoperative improvements on standardized stroke, cognitive and functional assessment scales that correlated well with persistent decompression and symmetric ventricles on follow-up images. Conclusions: This case illustrates the possibility of a non-dominant sphenoid wing meningioma resulting in a pseudo-degenerative frontal syndrome and its potential for reversal if recognized as a network lesion and treated with tailored, venous-sparing skull-base surgery. Contrast-enhanced imaging and routine frontal testing in atypical “dementia” presentations may aid in identifying additional patients with potentially surgically remediable cases. Full article

Background: The pterygomaxillary region is a complex anatomical area formed by the junction of the maxillary, palatine, and sphenoid bones and contains critical neurovascular structures. Accurate assessment of this region during Le Fort I osteotomy is essential, particularly to prevent hemorrhage and nerve injury that may occur during the pterygomaxillary separation phase. This study aims to investigate the morphometric characteristics of the pterygomaxillary region using cone-beam computed tomography (CBCT) and to evaluate the effects of age, sex, and laterality on these anatomical parameters. Materials and Methods: In this retrospective study, CBCT scans of 200 individuals (100 males and 100 females) aged 20–80 years were analyzed. Axial measurements included distances between the piriform rim, the descending palatine artery, the pterygomaxillary osteotomy line, and the pterygomaxillary fissure. Additionally, the thickness and width of the pterygomaxillary region and pterygoid process, lengths of the medial and lateral pterygoid laminae, and the distance between the greater palatine canal and the medial pterygoid lamina apex were recorded. Measurements were statistically evaluated by sex, age group, and laterality. Results: The following parameters demonstrated statistically significant differences based on the conducted measurements: The distance between the piriform rim and the descending palatine artery was significantly greater on the left side (p < 0.001). The length of the lateral pterygoid lamina increased with advancing age (p = 0.048). The thickness of the pterygomaxillary region was significantly greater in females (p = 0.014). Additionally, the distance between the greater palatine canal and the terminal point of the medial pterygoid lamina was significantly higher in males (p < 0.001). Conclusions: The pterygomaxillary region exhibits anatomical variations that may lead to serious complications during Le Fort I osteotomy. Detailed preoperative evaluation of this area using CBCT can guide surgical planning and help prevent potential vascular and neural complications. Full article

Evaluation of pituitary neuroendocrine tumors remains complex depending on the exact growth pattern, involvement of critical neurovascular structures, pituitary function and endocrinological activity of the tumor. A predominant growth into the sphenoid sinus and clivus poses specific challenges. We reviewed 557 surgeries for pituitary neuroendocrine tumors in an endonasal endoscopic technique performed between 1 January 2015 and 31 August 2025 to identify 13 cases (2.3%). Clinical, radiological and surgical data were selected by chart review. Thirteen cases aged from 31 to 68 years with almost exclusively non-functioning or clinically silent tumors (92%) were identified. Clival infiltration was restricted to the dorsum sellae in 2/13 (15%), spread to the floor of the sphenoid in 6/13 (46%) and extended inferior to the sphenoid in 5/13 (38%) cases with a high rate of cavernous sinus (62%) and sphenoid sinus infiltration (69%). Complete resection was achieved in 31%, and the residual tumor was clival/sphenoidal in 5/13 cases or within the cavernous sinus in 6/13 cases. The diaphragma sellae was reported to be intact in 92% of cases, and postoperative transient arginine vasopressin deficiency did not occur. Pituitary neuroendocrine tumors predominantly growing below the sella and infiltrating the clivus and sphenoid present specific challenges with a high rate of preoperative pituitary insufficiency, frequent cavernous sinus infiltration and postoperative tumor residuals in the cavernous sinus, sphenoid bone and clivus which are sometimes difficult to delineate. The surgical approach must be tailored specifically to treat the clival infiltration zone to reduce the risk of recurrence. Full article

Background: The sphenoid sinus is essential for transsphenoidal surgical accesses to the sellar and parasellar regions because of its anatomic proximity to vital vascular and neurologic structures such as the internal carotid artery, optic nerve, and cavernous sinus. The high degree of morphological variability of the sphenoid sinus has a significant impact on surgical technique and the risk of intraoperative complications. Detailed knowledge of individual anatomy is therefore crucial for the safety and efficacy of transsphenoidal approaches. Objectives: This review aims to conduct a systematic analysis of the current scientific literature on anatomical variations in the sphenoid sinus and their clinical relevance in surgical interventions to the skull base. Special attention is paid to the influence of morphological features on surgical strategies to pathological processes in this area and postoperative outcomes. Materials and Methods: A systematic review of the literature was conducted according to PRISMA 2020 guidelines. The PubMed, Scopus, Web of Science, and Google Scholar databases were searched for the period March 2010 to March 2025. Keywords such as “sphenoid sinus”, “anatomical variations”, “transsphenoidal surgery” and “skull base” were used. Original studies, systematic reviews, and meta-analyses focused on the anatomy, pneumatization, and surgical significance of sphenoid sinus variations are included. Quality and relevance criteria for published material were considered in the selection of articles. Results: The most commonly identified anatomic variations included sellar and lateral pneumaticity, the presence of Onodi cells, multiple and deviated septa, and dehiscence of the posterior wall of the sphenoid sinus and prolapse into its cavity of the internal carotid artery. These variations are associated with an increased risk of intraoperative vascular injury, visual deficit, and postoperative liquorrhea. Accurate preoperative assessment by high-resolution computed axial tomography and magnetic resonance imaging, as well as the use of intraoperative neuronavigation, are critical to reduce surgical risk. Conclusions: Anatomic variations in the sphenoid sinus are an essential factor to consider when planning and performing transsphenoidal surgical accesses. An individualized approach based on detailed diagnostic imaging analysis and neuronavigation technologies contributes to a higher safety of the performed surgical interventions, a better radicality of tumor resection and more favorable postoperative outcomes. Full article

Background: The sphenoidal emissary foramen (SEF) is an inconstant foramen of the sphenoid bone that facilitates venous communication between the pterygoid venous plexus and the cavernous sinus. Understanding its prevalence and laterality is crucial to preventing vascular injury during skull base procedures. Methods: A cross-sectional observational study was conducted on 133 adult Chilean dried skulls. Each specimen was examined both internally and externally to record SEF presence and laterality. Three independent observers performed the assessments under direct lighting, achieving excellent interobserver agreement (κ = 0.87, 95% CI = 0.81–0.92). Descriptive statistics, Chi-square tests, and Cramer’s V coefficients were calculated to evaluate side dominance and effect size at a significance level of p < 0.05. Results: The SEF was present in 40.17%. Bilateral foramina were observed in 26.79%, and unilateral SEF in 13.38%. Left-sided SEF (9.12%) was more common than right-sided SEF (4.26%), showing a significant difference (p = 0.03; Cramer’s V = 0.19, 95% CI = 0.02–0.33). This mild but significant left-sided prevalence indicates slight directional asymmetry rather than functional lateralization. Conclusions: The Chilean prevalence of the SEF lies within the mid-range of international data and closely aligns with Brazilian osteological reports. Although a minor left-sided predominance was observed, the effect size was weak (Cramer’s V = 0.19), reinforcing the interpretation of the SEF as a normal morphological variability rather than a true anatomical variant. Precise preoperative identification of the SEF is crucial to reduce the risk of venous injury and avoid unintentional penetration. Full article

Background and Clinical Significance: Mucormycosis is a rare but potentially fatal opportunistic fungal infection with high morbidity and mortality rates despite aggressive treatment. Rhinocerebral mucormycosis represents the most common form, requiring prompt recognition and multidisciplinary management. Case Presentation: We report a 60-year-old female with glucose intolerance who developed extensive rhinocerebral mucormycosis involving the right maxillary sinus, orbit, and skull base. Despite initial antifungal therapy with amphotericin B, rapid disease progression necessitated radical surgical intervention including complete right hemimaxillectomy, orbital enucleation, and partial sphenoid bone resection with carotid siphon exposure. Initial reconstruction using a free scapular osteocutaneous flap failed due to vascular compromise, requiring salvage coverage with a temporalis muscle flap. Postoperatively, the patient recovered without cerebrovascular complications. Long-term rehabilitation involved implant-supported prosthetic reconstruction with osseointegrated implants placed in the remaining maxilla and fabrication of a custom obturator prosthesis to restore facial support and masticatory function. Conclusions: This case demonstrates the aggressive nature of mucormycosis requiring extensive surgical resection and highlights the challenges of reconstruction in infected tissues. While free flap reconstruction offers theoretical advantages, local tissue options provide reliable coverage when microvascular procedures fail. Comprehensive multidisciplinary care including prosthetic rehabilitation can achieve satisfactory functional outcomes following radical resection. Full article

Sex estimation is a cornerstone of biological profiling in forensic anthropology. However, in cases involving badly decomposed, burnt, or fragmented remains, traditional assessments may be unfeasible, requiring alternative approaches, such as radiological and medical imaging. The cranium is a valuable indicator of sex, yet its dimorphic traits may be fragmented or altered, hindering interpretation. In such scenarios, radiological techniques targeting protected cranial structures—such as the paranasal sinuses—offer a promising alternative. Although these sinuses exhibit sexual dimorphism, their full potential for sex estimation remains partially underexplored. This study aimed to develop a logistic regression model for sex estimation in a contemporary Italian population based on volumetric measurements of the frontal, maxillary, and sphenoid sinuses, combined with selected cranial linear dimensions (biorbital breadth, upper facial height, and nasal spine length). CT scans from 222 individuals were analyzed. Volumetric measurements were obtained from 3D sinus models individually segmented from the CT scans, while linear cranial dimensions were measured on volume-rendered 3D skull reconstructions. Two predictive models were developed on a training subset and subsequently validated on an independent validation subset, both achieving an overall accuracy of approximately 80% in both phases. The most predictive variables were the volumes of the right frontal and maxillary sinuses, upper facial height, and nasal spine length, which showed the most significant sexual dimorphism. These findings are consistent with the literature on sexual dimorphism of paranasal sinuses and reflect the anatomical variability of structures like the sphenoid sinus. This study demonstrates that volumetric assessment of paranasal sinuses combined with selected cranial dimensions can provide more reliable sex estimation in forensic contexts. The integration of radiological imaging with statistical modelling offers a practical framework for situations where conventional skeletal analysis is compromised, reinforcing the role of advanced radiology in expanding the methodological toolkit of forensic anthropology. Full article

The human sphenoid bone (SB), centrally located at the cranial base, is structurally and developmentally complex. It arises from multiple cartilaginous precursors and undergoes both endochondral and intramembranous ossification, forming essential elements such as the sella, orbital walls, and numerous foramina. This review integrates embryological, anatomical, and radiological findings to present a comprehensive view of SB development and variation. Embryological studies reveal a layered ossification sequence, with accessory centers in the presphenoid and basisphenoid that influence adult morphology and variants, such as the caroticoclinoid foramen. In adulthood, the SB consists of a central body, paired greater and lesser wings, and the pterygoid processes, which articulate with key craniofacial bones and transmit vital neurovascular structures. Notable variants include duplication or absence of foramina, ossification of ligaments such as the pterygoid and pterygospinous ligaments, and the formation of bony bridges among the clinoid processes. These variants may affect cranial nerve trajectories and surgical access, posing potential risks during neurosurgical, endoscopic, and dental interventions. Emissary structures such as the sphenoidal emissary foramen and the newly described sphenopterygoid canal underscore the region’s vascular complexity. Additionally, variations in the optic and Vidian canals, as well as the superior orbital fissure, can also impact surgical approaches to the orbit, sinuses, and skull base. Understanding the full spectrum of sphenoid bone embryogenesis and morphology is essential for safe clinical practice and practical radiological imaging. Full article

Background: The varied shape and size of the sphenoid sinuses result in a highly variable degree of extension, described in different ways in the literature. The aim of the study was to create the authors’ classification of the sphenoid sinus extensions into the sphenoid bone processes. Methods: The study was retrospective, based on the results of head CT scans. The study group comprised 432 children, aged from birth to 18 years. Three types of sphenoid sinus extension into the sphenoid bone processes were proposed. Pneumatization of the lesser wing (type I), of the greater wing (type II), and of the pterygoid process (type III). Three subtypes were defined for each type. Pneumatization of the lesser wing in relation to the optic canal: only above (Ia), only below (Ib), and simultaneously above and below (Ic). Pneumatization of the greater wing in relation to the foramen rotundum: only above (IIa), only below (IIb), and simultaneously above and below (IIc). Pneumatization of the pterygoid process in relation to the pterygoid canal: only laterally (IIIa), only medially (IIIb), and simultaneously laterally and medially (IIIc). Results: Pneumatization of the lesser wings was observed in 19.44%, of the greater wings in 36.11%, and of the pterygoid processes in 25.00 of % children. As a result of the analysis conducted in accordance with the proposed classification, bilateral pneumatization of the lesser wings (type I), greater wings (type II), and pterygoid processes (type III) were found to occur more frequently than unilateral pneumatization. In the case of rare subtypes (Ia, Ic, IIa, Iic, or IIIb), a given subtype was observed to occur more frequently unilaterally. Conclusions: In the conducted analysis, we presented the authors’ classification of sphenoid sinus extensions into the sphenoid bone processes. Full article

Intraosseous hemangiomas (IH) are rare intrabony lesions that represent less than 1% of intraosseous tumors. IH are mostly seen in the axial skeleton and skull. Most commonly, the frontal bone, zygomatic, sphenoid, maxilla, ethmoid, and lacrimal bone can manifest IH. Currently, IH is classified as a developmental condition of endothelial origin. According to WHO, the five histological types of IH are cavernous, capillary, epithelioid, histiocytoid, and sclerosing. IH of the zygoma is an extremely rare condition with female predominance. A systematic review recently estimated that there were 78 cases published in the literature until 2023. The lesion is usually asymptomatic and presents with a gradually deteriorating deformity of the malar area, and the patient might be able to recall a history of trauma. Numbness due to involvement of the infraorbital nerve might also be present; however, atypical skin and bone sensations might also occur. Other symptoms include painful swelling, bone asymmetry, skin irritation, sinus pressure, paresthesia, diplopia, enophthalmos, or atypical neuralgia. A bony lesion with a trabecular pattern in a radiating formation (sunburst pattern) or a multilocal lytic lesion pattern created by the multiple cavernous spaces (honeycomb pattern) is commonly observed during radiologic evaluation. We present a rare case of IH of the zygoma in a 65-year-old generally healthy woman. A cyst-like bone tumor was revealed from the CT scan, which made preoperative biopsy of the lesion problematic. A careful radiological diagnostic differentiation of the lesion should always be conducted in such cases to outline a safe surgical plan and possible alternatives if needed. The patient underwent total tumor resection in the operating room, and the defect was reconstructed with the use of a titanium mesh and a synthetic hydroxyapatite bone graft based on a 3D surgical guide printed model. Full article

Background: Invasive aspergillosis with orbital apex and intracranial involvement is rare and often misdiagnosed due to nonspecific imaging findings. Misinterpretation may lead to inappropriate therapies, such as corticosteroids, which can exacerbate fungal infections. Case Presentation: A 50-year-old immunocompetent woman with diabetes mellitus presented with right ptosis and systemic malaise. Magnetic resonance imaging (MRI) performed three months prior had shown a subtle low-signal lesion in the right orbital apex. The lesion was small and thought to represent a granulomatous process, with minimal systemic inflammation and only mild surrounding changes on imaging. Biopsy was considered too invasive at that stage, and the patient was placed under observation. Over time, her condition progressed, and repeat imaging revealed intracranial extension, including involvement of the cavernous sinus and frontal lobe. Differential diagnoses included granulomatous diseases such as sarcoidosis or tuberculosis, prompting empirical anti-tuberculosis treatment. However, the patient’s condition worsened, and biopsy of the sphenoid sinus revealed septated fungal hyphae consistent with Aspergillus species on Grocott staining. Voriconazole therapy was initiated, resulting in significant clinical and radiological improvement. Discussion: This case highlights the diagnostic challenge of identifying orbital apex aspergillosis with early MRI changes and demonstrates the risk of misdiagnosis as granulomatous disease. Differentiating fungal infections from other inflammatory etiologies based on subtle imaging features is critical, especially when considering immunosuppressive therapy. Conclusion: Clinicians should maintain a high index of suspicion for fungal infections in patients with progressive orbital apex lesions, even in the absence of classic immunosuppression. Early imaging review and biopsy are essential to prevent misdiagnosis and inappropriate treatment. Full article

Background: Cholesteatoma, characterized by the abnormal growth of keratinizing squamous epithelium in ectopic locations, most commonly arises in the middle ear. Its occurrence in the sinonasal tract is rare and presents significant diagnostic and management challenges. These lesions can lead to severe complications like bone erosion, intracranial involvement, and orbital spread. This narrative review aims to summarize the current knowledge on cholesteatomas in these regions, focusing on epidemiology, pathophysiology, diagnosis, and treatment. Methods: A comprehensive review of the English literature was conducted, focusing on reported cases of cholesteatomas in the nasal cavity and paranasal sinuses. This review examines key aspects, including epidemiological data, imaging findings, surgical strategies, and postoperative outcomes. The role of diagnostic tools, particularly computed tomography and diffusion-weighted magnetic resonance imaging, in distinguishing cholesteatomas from other sinonasal lesions is also discussed. Results: As of March 2025, 51 cases of paranasal sinus cholesteatoma were reported. The frontal sinus is the most commonly affected site, followed by the maxillary, ethmoid, and sphenoid sinuses. Diagnosis is often delayed due to nonspecific symptoms, such as nasal congestion and recurrent infections. Surgical excision is the primary treatment, with endoscopic techniques being favored for their minimally invasive nature. Recurrence remains a major concern, and although very rare, cases of squamous cell carcinoma have also been observed in association with cholesteatoma. Conclusions: Nasal and paranasal sinus cholesteatomas require early recognition and intervention to prevent complications. Advances in imaging and surgery have improved outcomes; however, further research is needed to refine therapies and understand disease mechanisms. Full article