Estimation of Ambulation and Survival in Neurodegeneration with Brain Iron Accumulation Disorders.

BACKGROUND: Neurodegeneration with Brain Iron Accumulation (NBIA) disorder is a group of ultra-orphan hereditary diseases with very limited data on its course. OBJECTIVES: To estimate the probability of preserving ambulatory ability and survival in NBIA. METHODS: In this study, the electronic records of the demographic data and clinical assessments of NBIA patients from 2012 to 2023 were reviewed. The objectives of the study and factors impacting them were investigated by Kaplan-Meier and Cox regression methods. RESULTS: One hundred and twenty-two genetically-confirmed NBIA patients consisting of nine subtypes were enrolled. Twenty-four and twenty-five cases were deceased and wheelchair-bound, with a mean disease duration of 11 ± 6.65 and 9.32 ± 5 years. The probability of preserving ambulation and survival was 42.9% in 9 years and 28.2% in 15 years for classical Pantothenate Kinase-Associated Neurodegeneration (PKAN, n = 18), 89.4% in 7 years and 84.7% in 9 years for atypical PKAN (n = 39), 23% in 18 years and 67.8% in 14 years for Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN, n = 23), 75% in 20 years and 36.5% in 33 years for Kufor Rakeb Syndrome (KRS, n = 17), respectively. The frequencies of rigidity, spasticity, and female gender were significantly higher in deceased cases compared to surviving patients. Spasticity was the only factor associated with death (P value = 0.03). CONCLUSIONS: KRS had the best survival with the most extended ambulation period. The classical PKAN and MPAN cases had similar progression patterns to loss of ambulation ability, while MPAN patients had a slower progression to death. Spasticity was revealed to be the most determining factor for death.

Transcranial sonography in neurodegeneration with brain iron accumulation disorders.

BACKGROUND: Transcranial Sonography is a non-invasive technique that has been used as a diagnostic tool for a variety of neurodegenerative disorders. However, the utility and potential application of this technique in NBIA disorders is scarce and inconclusive. METHODS: In this cross-sectional retrospective case-control study, the echogenicity of Substantia Nigra (SN), Lentiform Nucleus (LN), and Diameter of the Third Ventricle (DTV) were assessed by TCS in genetically confirmed NBIA patients referring to the movement disorder clinic. The normal echogenicity area of SN was defined based on the 90th percentile of an age-and-gender-matched control group. NBIA patients underwent neurologic examination at each visit, but their brain magnetic resonance imaging and demographics were extracted from electronic records. RESULTS: Thirty-five NBIA patients of four subtypes with a mean disease duration of 10.54 years and 35 controls were enrolled. The normally defined SN echogenicity in controls was 0.23 cm2. DTV and SN echogenicity areas were significantly higher in patients compared to the controls (P = 0.002 and < 0.001, respectively). Around 85% and 63% of the patients showed LN and SN hyperechogenicity at least on one side, respectively. Disease duration was positively correlated with DTV (r = 0.422, p = 0.015). Cases with Pantothenate Kinase Associated Neurodegeneration (n = 23) also had significantly higher DTV and SN echogenicity area compared to the controls. CONCLUSION: Despite most NBIA patients displayed increased DVT and higher SN and LN hyperechogenicity than healthy controls, the discriminatory role of TCS on different NBIA subtypes remains to be determined.

Neurodegeneration with Brain Iron Accumulation Disorders and Retinal Neurovascular Structure.

BACKGROUND: The unique neurovascular structure of the retina has provided an opportunity to observe brain pathology in many neurological disorders. However, such studies on neurodegeneration with brain iron accumulation (NBIA) disorders are lacking. OBJECTIVES: To investigate NBIA's neurological and ophthalmological manifestations. METHODS: This cross-sectional study was conducted on genetically confirmed NBIA patients and an age-gender-matched control group. The thickness of retinal layers, central choroidal thickness (CCT), and capillary plexus densities were measured by spectral domain-optical coherence tomography (SD-OCT) and OCT angiography, respectively. The patients also underwent funduscopy, electroretinography (ERG), visual evoked potential (VEP), and neurological examination (Pantothenate-Kinase Associated Neurodegeneration-Disease Rating Scale [PKAN-DRS]). The generalized estimating equation model was used to consider inter-eye correlations. RESULTS: Seventy-four patients' and 80 controls' eyes were analyzed. Patients had significantly decreased visual acuity, reduced inner or outer sectors of almost all evaluated layers, increased CCT, and decreased vessel densities, with abnormal VEP and ERG in 32.4% and 45.9%, respectively. There were correlations between visual acuity and temporal peripapillary nerve fiber layer (positive) and between PKAN-DRS score and disease duration (negative), and scotopic b-wave amplitudes (positive). When considering only the PKAN eyes, ONL was among the significantly decreased retinal layers, with no differences in retinal vessel densities. Evidence of pachychoroid was only seen in patients with Kufor Rakeb syndrome. CONCLUSION: Observing pathologic structural and functional neurovascular changes in NBIA patients may provide an opportunity to elucidate the underlying mechanisms and differential retinal biomarkers in NBIA subtypes in further investigations. © 2023 International Parkinson and Movement Disorder Society.

Olfactory status in neurodegeneration with brain iron accumulation disorders.

BACKGROUND: Olfactory dysfunction has been suggested as a diagnostic and discriminative biomarker in some neurodegenerative disorders. However, there are few studies regarding the olfactory status in rare diseases including neurodegeneration with brain iron accumulation (NBIA) disorders. METHODS: Genetically-confirmed NBIA patients were enrolled. Neurological and cognitive examinations were conducted according to the Pantothenate Kinase-Associated Neurodegeneration-Disease Rating Scale (PKAN-DRS) and the Mini-Mental State Examination (MMSE) questionnaire, respectively. Olfaction was assessed in three domains of odor threshold (OT), odor discrimination (OD), odor identification (OI), and total sum (TDI) score by the Sniffin' Sticks test. The olfactory scores were compared to a control group and a normative data set. RESULTS: Thirty-seven patients, including 22 PKAN, 6 Kufor Rakeb syndrome, 4 Mitochondrial membrane Protein-Associated Neurodegeneration (MPAN), 5 cases of other 4 subtypes, and 37 controls were enrolled. The mean PKAN-DRS score was 51.83±24.93. Sixteen patients (55.2%) had normal cognition based on MMSE. NBIA patients had significantly lower olfactory scores compared to the controls in TDI and all three subtests, and 60% of them were hyposmic according to the normative data. Including only the cognitively-normal patients, still, OI and TDI scores were significantly lower compared to the controls. The phospholipase A2-Associated Neurodegeneration (PLAN) and MPAN patients had a significantly lower OI score compared to the cognitively-matched PKAN patients. CONCLUSION: Olfactory impairment as a common finding in various subtypes of NBIA disorder can potentially be considered a discriminative biomarker. Better OI in PKAN compared to PLAN and MPAN patients may be related to the different underlying pathologies.

Investigating the prevalence of risk factors of papillary thyroid carcinoma recurrence and disease-free survival after thyroidectomy and central neck dissection in Iranian patients.

Background: Papillary thyroid carcinoma (PTC) is considered the most frequent thyroid malignancy (85-90%) with a good prognosis. However, its frequent recurrence increases mortality and morbidity. In this inquiry we investigated the prevalence of risk factors of PTC recurrence and disease free survival after thyroidectomy and central neck dissection. Method: In this retrospective study, all patients with confirmed PTC who underwent total thyroidectomy and central neck dissection in Imam Reza and Omid hospitals of Mashhad University of Medical Sciences from 2004 to 2011 were included. Total locoregional and distant recurrence rate, 5-year disease free survival rate (DFS) and contributing factors of recurrence were investigated after at least 5 years. Results: In this study 289 patients were included with a mean follow-up of 72.90 ± 11.02 months. 70.6% were female and 29.4% were male. Recurrence occurred in 58 cases from which 10 were distant and 48 were loco-regional. 5-year DFS was 80% and total-survival-rate was 99%. Our analysis showed that primary tumor size, vascular-invasion, extra-thyroid extension, and lymph node ratio (LNR) were significantly related to DFS.

Gamma Knife stereotactic radiosurgery for cerebellopontine angle meningioma.

OBJECTIVE: Meningiomas comprise 6-15 % of cerebellopontine angle (CPA) tumors. Surgical treatment is a real challenge because this area is occupied by several critical neurovascular elements. Currently, surgery is the first choice of treatment, however several factors may be present that necessitate choosing the alternative treatments such as Gamma Knife Stereotactic Radiosurgery (GKS). PATIENTS AND METHODS: Ninety-three patients with CPA meningioma who were treated by GKS for a period of 8 years, were retrospectively reviewed. Factors affecting clinical and radiological improvement were analyzed. RESULTS: The median tumor volume was 6 cm3. The mean values for maximal and marginal dose were 20.2 and 13.6 Gy, respectively. The mean follow-up time was 31.5 months. Tumor control (lack of progression) was achieved in 96.8% of the patients and 55.9% of the patients showed tumor regression on follow-up MRI. The actuarial 3-year progression-free survival (PFS) rate was 96%. Clinical improvement was seen in 49.5% of the patients while 11.8% experienced worsening or new-onset symptoms. Adverse radiation effects were seen in 4.3% of the patients. A worse symptomatic outcome, male sex, a lower tumor coverage, and marginal doses <13.5 Gy were associated with worse radiologic outcomes. Worse radiologic outcomes and higher tumor volumes, especially tumor volumes ≥8.5 cc, were associated with worse symptomatic outcomes. The male sex was associated with a lower PFS. CONCLUSION: Gamma Knife radiosurgery, either primarily or post- operatively, offers a decent long-term tumor control in CPA meningioma, and is associated with an acceptable complication profile, especially in tumors with lower volumes.

Gamma Knife Radiosurgery for Cavernous Sinus Meningiomas: Analysis of Outcome in 166 Patients.

OBJECTIVES: The outcomes of Gamma Knife radiosurgery (GKRS) for cavernous sinus meningioma (CSM) are presented, and factors possibly affecting outcome are investigated. METHODS: The medical records and imaging and procedural reports of 166 patients with CSM were retrospectively reviewed. Demographic data, procedural data, symptomatic improvement, radiological regression, and progression-free survival (PFS) rates were evaluated. RESULTS: There were 124 women and 42 men; including 44 postoperative and 122 primary GKRS cases. Mean follow-up was 32.4 months. Mean marginal dose was 13 Gy. Symptomatic improvement was seen in 40.4%, while neurologic deterioration occurred in 9.6%; 50% remained symptomatically stable. Radiological regression was noted in 57.2%; the tumor remained stable in 35.5%, and 7.2% of the patients experienced tumor progression. The actuarial 5- and 10-year PFS rates were 90.1% (±3.3) and 75.8% (±8.8), respectively. History of previous surgery or radiotherapy were associated with lower symptomatic improvement. Higher tumor coverage and isodose lines were accompanied with better radiological prognosis. However, a history of conventional radiotherapy, presence of facial sensory deficits at presentation, a higher tumor volume, and tumor extension to the suprasellar compartment affected the radiologic outcome negatively. CONCLUSION: This study revealed a high efficacy and safety for GKRS in both postoperative and primary GKRS patients. Achievability of a good profile of tumor coverage and isodose lines at radiosurgical planning predict a better outcome.

Gold-coated magnetic nanoparticle as a nanotheranostic agent for magnetic resonance imaging and photothermal therapy of cancer.

Because of their great scientific and technological potentials, iron oxide nanoparticles (IONPs) have been the focus of extensive investigations in biomedicine over the past decade. Additionally, the surface plasmon resonance effect of gold nanoparticles (AuNPs) makes them a good candidate for photothermal therapy applications. The unique properties of both IONPs (magnetic) and AuNPs (surface plasmon resonance) may lead to the development of a multi-modal nanoplatform to be used as a magnetic resonance imaging (MRI) contrast agent and as a nanoheater for photothermal therapy. Herein, core-shell gold-coated IONPs (Au@IONPs) were synthesized and investigated as an MRI contrast agent and as a light-responsive agent for cancer photothermal therapy.The synthesized Au@IONPs were characterized by UV-visible spectroscopy, transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential analysis. The transverse relaxivity (r 2) of the Au@IONPs was measured using a 3-T clinical MRI scanner. Through a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the cytotoxicity of the Au@IONs was examined on a KB cell line, derived from the epidermal carcinoma of a human mouth. Moreover, the photothermal effects of Au@IONPs in the presence of a laser beam (λ = 808 nm; 6.3 W/cm2; 5 min) were studied.The results show that the Au@IONPs are spherical with a hydrodynamic size of 33 nm. A transverse relaxivity of 95 mM-1 S-1 was measured for the synthesized Au@IONPs. It is evident from the MTT results that no significant cytotoxicity in KB cells occurs with Au@IONPs. Additionally, no significant cell damage induced by the laser is observed. Following the photothermal treatment using Au@IONPs, approximately 70% cell death is achieved. It is found that cell lethality depended strongly on incubation period and the Au@IONP concentration.The data highlight the potential of Au@IONPs as a dual-function MRI contrast agent and photosensitizer for cancer photothermal therapy.

Vitamin D Levels in Children with Adenotonsillar Hypertrophy and Otitis Media with Effusion.

INTRODUCTION: Vitamin D has been suggested to play a considerable role in the function of the immune system in various infectious, inflammatory, and autoimmune conditions. Otitis media with effusion (OME), defined as the presence of non-purulent fluid within the middle ear without signs or symptoms of suppurative otitis media, has a number of inflammatory predisposing factors. This study was designed to explore the association between vitamin D deficiency and OME. MATERIALS AND METHODS: In this cross-sectional study, 74 children aged 2-7 years with an obstructive indication for adenotonsillectomy were included. Patients were divided into two groups based on the need for ventilation tube insertion for OME. Thirty-two children were enrolled in the OME group and 42 in the control group. The mean vitamin D level was compared between the two groups. RESULTS: Mean vitamin D concentration in all patients was 11.96±5.85 ng/ml (9.79±4.36 ng/ml in the OME group and 13.61±6.33 ng/ml in the control group; P=0.003). There was also a significant difference in levels of vitamin D in patients referred in winter (9.0±2.94 ng/ml) compared with the summer (19.85±4.21 ng/ml; P=0.001). Data analyzed based on the season in which the patients were referred showed no significant difference between the OME and the control group. CONCLUSION: Although our results showed lower serum levels of vitamin D in OME patients, the difference was not significant when seasons were taken into consideration. Therefore, the season is an important confounding factor in any research related to vitamin D due to the effect of sun-induced vitamin D.

Impact of endoscopic endonasal pituitary surgery on nasal airway patency.

BACKGROUND: Nose is used as a corridor in endoscopic endonasal transsphenoidal approach (EETSA) for pituitary adenoma. Thus, it may affect the nasal airway patency, function and sinonasal-related quality of life. The aim of this study is to objectively and subjectively evaluate these effects. METHODS: In this prospective study, 43 patients with pituitary adenoma who were candidates for EETSA from March 2012 to October 2013 were enrolled. The patients were evaluated preoperatively using acoustic rhinometry and rhinomanometry (with/without the use of decongestant drops) and asked to complete the 22-Item Sinonasal Outcome Test (SNOT-22) questionnaire. The tests were repeated at one and three months postoperatively. The preoperative data were compared with the first and second postoperative ones using paired-sample t-test. RESULTS: Without the use of decongestant drops, the total airway resistance increased significantly (p=0.016), and the nasal airflow decreased significantly (p=0.031) in the first postoperative evaluation. However, in the 3rd postoperative month, the difference was not significant. With the use of decongestant drops, the objective parameters showed no significant changes compared to preoperative data even at the first evaluation. The SNOT- 22 scores also did not differ significantly in 1st and 3rd postoperative months. The first postoperative SNOT-22 showed a strong correlation with the second minimal cross-sectional area on simultaneous evaluation, and with the preoperative total airway resistance. CONCLUSION: EETSA has a transient adverse effect on the nasal patency that quickly improves, making it a safe approach for the sinonasal system. Rhinomanometry is the most sensitive test for detecting these nasal functional changes objectively.

Gamma Knife Radiosurgery in Sphenopetroclival Meningiomas: Preliminary Experience at the Iran Gamma Knife Center.

OBJECTIVE: The aims of this study were to characterize the epidemiologic, histologic, and radiologic aspects of sphenopetroclival meningiomas (SpPCMs) and to evaluate the outcome of Gamma Knife radiosurgery (GKRS) either as an adjunct to microsurgery or as a primary SpPCM treatment modality. METHODS: In this retrospective study, medical records of patients with SpPCM who underwent GKRS at the Iran Gamma Knife Center between April 2003 and March 2012 were analyzed. RESULTS: We assessed 122 patients with SpPCMs, including 101 women and 21 men, aged 24-94 years. The mean tumor volume was 12.24 ± 9.30 mL. Patients received 22.32 ± 3.29 Gy and 13.18 ± 1.02 Gy maximal and average marginal dose of GKRS, respectively. The most common complaint was visual impairment, followed by facial sensory impairment and headache. The most frequently involved cranial nerves were III, IV, and VI in 72.1% of patients, followed by II in 52.9%, and V in 35.5%. After radiosurgery, headaches improved in 90.0%, diplopia in 75.0%, and ptosis in 63.0% of patients. On magnetic resonance imaging, tumor size was reduced, unchanged, or increased in 77, 44, and 1 patient, respectively. Progression-free survival at the 5-year follow-up was 56.6%. Younger age (hazard ratio = 0.972, P = 0.011) and lower tumor volume (hazard ratio = 0.959, P = 0.009) were the main prognostic factors for progression-free survival. CONCLUSION: GKRS can be an effective alternative treatment for controlling the progression of SpPCM tumors, producing appropriate clinical outcomes and few complications.

Impact of nasoseptal flap elevation on sinonasal quality of life in endoscopic endonasal approach to pituitary adenomas.

To evaluate the impact of nasoseptal flap (NSF) elevation on sinonasal quality of life (QOL) in patients with pituitary adenomas who underwent endoscopic endonasal trans-sphenoidal approach (EETSA), the data of 106 eligible patients were included from February 2011 to December 2014. The scores of Sinonasal Outcome Test (SNOT-22) Questionnaire were assessed in case (that received reconstruction with NSF) and control groups preoperatively as well as 1, 3, 6, and more than 12 months postoperatively. Nine most related sinonasal questions were evaluated separately (9Q). There were no significant inter-group differences in the mean SNOT-22, 9Q, and sense of taste/smell scores in preoperative and all postoperative assessments. Within each group, a significant improvement of SNOT-22 and 9Q scores were noted after 12 months of surgery compared to preoperative data. In the NSF group, comparison of the pre- and first postoperative evaluation revealed a significant deterioration in 9Q score (p = 0.007) and "sense of taste/smell" (p < 0.001) which both returned to baseline in the 3rd month. Patients who used nasal paper mask for more than 100 "hour-days" showed a better SNOT-22 scores at 1st (p = 0.04) and 3rd (p < 0.001) months after surgery. Patients with adrenocorticotropic hormone (ACTH) secretory adenomas showed significantly higher scores of SNOT-22 in all postoperative assessments compared to the others. Although nasal symptoms deteriorated at first postoperative month (compare to preoperative data) in the NSF group, no negative impacts on the sinonasal QOL was showed comparing to the control group. ACTH-secreting adenomas could be assumed as a risk factor for poorer sinonasal QOL in EETSA.

Early onset of tuberous sclerosis with chylous ascites: a case report.

BACKGROUND: Tuberous Sclerosis Complex (TSC) is an autosomal-dominant hereditary disorder. This syndrome is characterized by tumor-like malformations in several organs, as well as the heart. This report summarizes a case of TSC in a premature infant, born at 34 weeks' gestation with ascites. After birth, multiple cardiac mass, subependymal cysts and hypopigmented macules were detected. To our knowledge, this is the first case report of early onset of TSC with chylous ascites in Iran.