Point mutation in a virus-like capsid drives symmetry reduction to form tetrahedral cages.

Protein capsids are a widespread form of compartmentalization in nature. Icosahedral symmetry is ubiquitous in capsids derived from spherical viruses, as this geometry maximizes the internal volume that can be enclosed within. Despite the strong preference for icosahedral symmetry, we show that simple point mutations in a virus-like capsid can drive the assembly of unique symmetry-reduced structures. Starting with the encapsulin from Myxococcus xanthus, a 180-mer bacterial capsid that adopts the well-studied viral HK97 fold, we use mass photometry and native charge detection mass spectrometry to identify a triple histidine point mutant that forms smaller dimorphic assemblies. Using cryoelectron microscopy, we determine the structures of a precedented 60-mer icosahedral assembly and an unexpected 36-mer tetrahedron that features significant geometric rearrangements around a new interaction surface between capsid protomers. We subsequently find that the tetrahedral assembly can be generated by triple-point mutation to various amino acids and that even a single histidine point mutation is sufficient to form tetrahedra. These findings represent a unique example of tetrahedral geometry when surveying all characterized encapsulins, HK97-like capsids, or indeed any virus-derived capsids reported in the Protein Data Bank, revealing the surprising plasticity of capsid self-assembly that can be accessed through minimal changes in the protein sequence.

An interaction network approach predicts protein cage architectures in bionanotechnology.

Protein nanoparticles play pivotal roles in many areas of bionanotechnology, including drug delivery, vaccination, and diagnostics. These technologies require control over the distinct particle morphologies that protein nanocontainers can adopt during self-assembly from their constituent protein components. The geometric construction principle of virus-derived protein cages is by now fairly well understood by analogy to viral protein shells in terms of Caspar and Klug's quasi-equivalence principle. However, many artificial, or genetically modified, protein containers exhibit varying degrees of quasi-equivalence in the interactions between identical protein subunits. They can also contain a subset of protein subunits that do not participate in interactions with other assembly units, called capsomers, leading to gaps in the particle surface. We introduce a method that exploits information on the local interactions between the capsomers to infer the geometric construction principle of these nanoparticle architectures. The predictive power of this approach is demonstrated here for a prominent system in nanotechnology, the AaLS pentamer. Our method not only rationalises hitherto discovered cage structures but also predicts geometrically viable options that have not yet been observed. The classification of nanoparticle architecture based on the geometric properties of the interaction network closes a gap in our current understanding of protein container structure and can be widely applied in protein nanotechnology, paving the way to programmable control over particle polymorphism.

The value of MUNIX as an objective electrophysiological biomarker of disease progression in chronic inflammatory demyelinating polyneuropathy.

INTRODUCTION/AIMS: Objective outcome measures to monitor treatment response and guide treatment are lacking in chronic inflammatory demyelinating polyneuropathy (CIDP). In this study we aimed to evaluate the motor unit number index (MUNIX) as an outcome measurement in patients with CIDP and determine the correlation of MUNIX with functional and standard electrodiagnostic tests in a single follow-up study. METHODS: We evaluated MUNIX of the abductor pollicis brevis, abductor digiti minimi, and tibialis anterior (TA) muscles bilaterally. Muscle force was assessed by Medical Research Council Sum Score (MRCSS). Functional measures used were the Overall Neuropathy Limitation Score (ONLS) and the Rasch-built Overall Disability Scale (R-ODS) score at baseline and after 6 months of treatment. Standard electrophysiology was evaluated by the Nerve Conduction Study Score (NCSS). RESULTS: Twenty patients were included at baseline, and 16 completed the follow-up study. Significant correlations were found between the MUNIX sum score and both MRCSS and NCSS at baseline, between both the pinch strength and grip and upper limb MUNIX at baseline and follow-up, and between MUNIX of TA and both lower limb MRCSSs with lower limb ONLS at baseline and follow-up. Significant correlations also were found between MUNIX sum score change and MRCSS change, R-ODS change, and ONLS change. DISCUSSION: MUNIX changes correlated with strength and electrophysiological improvements in CIDP patients. This suggests that MUNIX may represent a useful objective biomarker for patient follow-up.

Anticipation Can Be More Common in Hereditary Spastic Paraplegia with SPAST Mutations Than It Appears.

BACKGROUND AND OBJECTIVE: Hereditary spastic paraplegia (HSP) is a heterogeneous neurodegenerative disorder with lower-limb spasticity and weakness. Different patterns of inheritance have been identified in HSP. Most autosomal-dominant HSPs (AD-HSPs) are associated with mutations of the SPAST gene (SPG4), leading to a pure form of HSP with variable age-at-onset (AAO). Anticipation, an earlier onset of disease, as well as aggravation of symptoms in successive generations, may be correlated to SPG4. Herein, we suggested that anticipation might be a relatively common finding in SPG4 families. METHODS: Whole-exome sequencing was done on DNA of 14 unrelated Iranian AD-HSP probands. Data were analyzed, and candidate variants were PCR-amplified and sequenced by the Sanger method, subsequently checked in family members to co-segregation analysis. Multiplex ligation-dependent probe amplification (MLPA) was done for seven probands. Clinical features of the probands were recorded, and the probable anticipation was checked in these families. Other previous reported SPG4 families were investigated to anticipation. RESULTS: Our findings showed that SPG4 was the common subtype of HSP; three families carried variants in the KIF5A, ATL1, and MFN2 genes, while five families harbored mutations in the SPAST gene. Clinical features of only SPG4 families indicated decreasing AAO in affected individuals of the successive generations, and this difference was significant (p-value <0.05). CONCLUSION: It seems SPAST will be the first candidate gene in families that manifests a pure form of AD-HSP and anticipation. Therefore, it may be a powerful situation of genotype-phenotype correlation. However, the underlying mechanism of anticipation in these families is not clear yet.

Disease severity and response to treatment in Iranian patients with myasthenia gravis.

PURPOSE: Myasthenia gravis (MG) is a potentially fatal neuromuscular disorder if left untreated. In this study, we tried to address the possible demographic, clinical, and laboratory determinants of severity and outcome in Iranian MG patients over a follow-up period of more than 5 years. METHODS: Demographic and diagnostic data (age, age of onset, antibody status, thymus pathology, and duration of the disease) of the patients with MG were extracted. Maximal disease severity and post-intervention status were assessed according to the recommendations of the task force of the Myasthenia Gravis Foundation of America. RESULTS: In our series of 146 patients, MG was more severe in older, anti-muscle specific tyrosine kinase (MuSK) positive, and thymomatous patients. Seropositivity to the MuSK antibody and the presence of thymoma determined the need for immunosuppressive drugs. However, the number of patients requiring more than one immunosuppressive was not significantly different among various subtypes. CONCLUSIONS: The overall outcome was favorable in the majority of patients, despite differences in the disease course and severity. In contrary to the previous reports, anti-MuSK positive patients in our series did not need a more vigorous treatment regimen comparing other serologic subtypes of MG.

Retrospective analysis of response to rituximab in chronic inflammatory demyelinating polyneuropathy refractory to first-line therapy.

Few case reports/series describe the efficacy of rituximab in refractory chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), which is preferred in the presence of anti-nodal/paranodal antibodies. We aimed at evaluating the clinical response to rituximab in a subset of patients with refractory CIDP for whom the anti-nodal/paranodal antibodies status was unknown, as not available in Iran. We retrospectively analyzed the response to rituximab in 14 Iranian patients with refractory CIDP (3 children, 11 adults), in whom the anti-nodal/paranodal antibodies status was unknown. The subjects were evaluated with the Medical Research Council (MRC) sum score (MRCSS), Inflammatory Neuropathy Cause and Treatment (INCAT) disability scores, and electrophysiology, before and after treatment. Mean age was 34.4 ± 20.7 years, disease duration pre-rituximab treatment was 27.8 ± 18.8 (range: 6-60) months, and mean follow-up duration was 18.5 ± 11.0 (range: 4-36) months. Considering the INCAT sum score, one worsened during post-rituximab treatment, and three patients did not change. Considering MRCSS, notably, four patients achieved normalization of their MRCSS. Regarding the corticosteroid dose, two patients could discontinue prednisolone. As rated by a pre-defined scoring system, nerve conduction parameters improved significantly post-rituximab in the treated cohort (P = .006). All patients tolerated rituximab infusions without adverse effects. Rituximab may be effective in refractory CIDP, even though worsening may occur in some patients. Anti-nodal/paranodal antibodies assay, when available, and other criteria may help drive therapeutic decision-making on rituximab as second-line treatment.

Application of muscle ultrasound for the evaluation of patients with amyotrophic lateral sclerosis: An observational cross-sectional study.

INTRODUCTION: We evaluated the association between muscle ultrasound, number of motor units, and clinical parameters, and assessed their utility for distinguishing amyotrophic lateral scleorisis (ALS) patients from healthy individuals. METHODS: Three muscle pairs (abductor pollicis brevis, abductor digiti minimi, and tibialis anterior) of 18 ALS patients and 18 controls underwent muscle ultrasound (echointensity and thickness) and assessment of motor unit number index (MUNIX). The clinical and functional status of participants were also assessed. RESULTS: Mean age of the patients was 53.8 ± 12.1 years, and score on the ALS Functional Rating Scale-Revised was 38.9 ± 4.1. Echointensity of all tested muscles of ALS participants was significantly higher than that of controls, but there was no significant difference in muscle thickness. Muscle echointensity correlated significantly with clinical and electrophysiological parameters. CONCLUSION: Echointensity of muscles was highly associated with clinical scales and MUNIX, confirming its relevance as an ancillary diagnostic test in ALS patients.

The second mutation of SYCE1 gene associated with autosomal recessive nonobstructive azoospermia.

PURPOSE: It is estimated that 40-50% of infertility among human couples is due to male infertility. Azoospermia is estimated to occur in 1% of all men and to be the cause of 10-20% of male infertility. Genetic defects, including single gene effects, maybe cause of azoospermia in 20-30% of affected males. Here, we aim to identify the genetic cause of azoospermia in a man who is also affected by hereditary spastic paraplegia. METHODS: The proband was subjected to whole-exome sequencing, followed by a comprehensive in silico analysis to identify the azoospermia causative gene. RESULTS: A novel splice site mutation c.375-2A > G in SYCE1 that is thought to be the cause of azoospermia was identified. This variant co-segregated with azoospermia status in the family that has three additional affected males. CONCLUSION: SYCE1 gene encodes synaptonemal complex (SC) central element 1 protein which contributes to the formation of the synaptonemal complex during meiosis. Syce1 null male and female mice have been shown to be infertile. There have only been two reports on the effects of SYCE1 mutations in humans; it was shown as the cause of primary ovarian failure (POI) in one and as the cause of nonobstructive azoospermia (NOA) in another. We suggest that the mutation 375-2A > G, which affects the acceptor splice site within intron 6 of SYCE1, is the likely cause of azoospermia and subsequent infertility in the family studied. The finding constitutes the third report of SYCE1mutations that affect infertility in humans and further supports its contribution to this condition.

Type 1 FSHD with 6-10 Repeated Units: Factors Underlying Severity in Index Cases and Disease Penetrance in Their Relatives Attention.

Molecular defects in type 1 facioscapulohumeral muscular dystrophy (FSHD) are caused by a heterozygous contraction of the D4Z4 repeat array from 1 to 10 repeat units (RUs) on 4q35. This study compared (1) the phenotype and severity of FSHD1 between patients carrying 6-8 vs. 9-10 RUs, (2) the amount of methylation in different D4Z4 regions between patients with FSHD1 with different clinical severity scores (CSS). This cross-sectional multicenter study was conducted to measure functional scales and for genetic analysis. Patients were classified into two categories according to RUs: Group 1, 6-8; Group 2, 9-10. Methylation analysis was performed in 27 patients. A total of 99 carriers of a contracted D4Z4 array were examined. No significant correlations between RUs and CSS (r = 0.04, p = 0.73) and any of the clinical outcome scales were observed between the two groups. Hypomethylation was significantly more pronounced in patients with high CSS (>3.5) than those with low CSS (<1.5) (in DR1 and 5P), indicating that the extent of hypomethylation might modulate disease severity. In Group 1, the disease severity is not strongly correlated with the allele size and is mostly correlated with the methylation of D4Z4 regions.

Late-onset pompe disease in Iran: A clinical and genetic report.

INTRODUCTION: Pompe disease is characterized by absence or deficiency of acid α-glucosidase, and several causative mutations are known. In this study we report clinical and laboratory data in Iranian patients with late-onset Pompe disease (LOPD), focusing on population-specific mutations. METHODS: Clinical and laboratory data of 14 patients from 10 families with the diagnosis of LOPD were recorded. All had reduced enzyme activity on dried blood spot (DBS) analysis. Genetic investigation was performed to identify the underlying mutations. RESULTS: The age of onset ranged from <2 to 38 years. The clinical presentations were heterogeneous. Two siblings presented with foot drop. The most common mutation was c.(-32-13T>G). There were 4 novel mutations: c.(2040 + 2dup); c.(1650delG); c.(1837T>G); and c.(2596delG). CONCLUSION: This is a comprehensive report of LOPD in Iranian patients. Distinct phenotypic and genotypic features in this population are highlighted. Muscle Nerve 55: 835-840, 2017.

Validation of the 15-item myasthenia gravis quality of life questionnaire (MG-QOL15) Persian version.

INTRODUCTION: The 15-item Myasthenia Gravis Quality Of Life (MG-QOL15) questionnaire is a valid and reliable instrument for evaluation of myasthenia gravis (MG) associated disability. Our study aim was to assess its validity and reliability in the Iranian population. METHODS: We enrolled 75 consecutive patients with established MG at 2 neuromuscular clinics in Tehran, Iran. All 75 patients completed the Persian MG-QOL15 and SF-36 questionnaire initially, and 30 filled out the MG-QOL15 questionnaire from 2 to 4 weeks after the initial visit. Concurrent and construct validity, internal consistency, and test-retest repeatability of the questionnaire were evaluated. RESULTS: The Persian MG-QOL15 showed satisfactory internal consistency (Cronbach alpha = 0.94) and test-retest reliability(r = 0.98; P < 0.001). It also demonstrated adequate concurrent and construct validity; moreover, the MG-QOL15 scores were higher in patients with more severe conditions. CONCLUSIONS: The Persian MG-QOL15 is a valid and reliable questionnaire for determination of quality of life in Iranian MG patients. Muscle Nerve 54: 65-70, 2016.

International clinimetric evaluation of the MG-QOL15, resulting in slight revision and subsequent validation of the MG-QOL15r.

INTRODUCTION: The MG-QOL15 is a validated, health-related quality of life (HRQOL) measure for myasthenia gravis (MG). Widespread use of the scale gave us the opportunity to further analyze its clinimetric properties. METHODS: We first performed Rasch analysis on >1,300 15-item Myasthenia Gravis Quality of Life scale (MG-QOL15) completed surveys. Results were discussed during a conference call with specialists and biostatisticians. We decided to revise 3 items and prospectively evaluate the revised scale (MG-QOL15r) using either 3, 4, or 5 responses. Rasch analysis was then performed on >1,300 MG-QOL15r scales. RESULTS: The MGQOL15r performed slightly better than the MG-QOL15. The 3-response option MG-QOL15r demonstrated better clinimetric properties than the 4- or 5-option scales. Relative distributions of item and person location estimates showed good coverage of disease severity. CONCLUSIONS: The MG-QOL15r is now the preferred HRQOL instrument for MG because of improved clinimetrics and ease of use. This revision does not negate previous studies or interpretations of results using the MG-QOL15. Muscle Nerve 54: 1015-1022, 2016.

Cerebral Venous Sinus Thrombosis May Follow a Seasonal Pattern.

BACKGROUND: Several studies have demonstrated seasonal and temporal variations in the incidence of arterial stroke; however, for cerebral venous sinus thrombosis (CVST), such study seems lacking. The main aim of this study was to investigate whether there is any seasonal variation for CVST, and association between CVST occurrence and temperature. METHODS: This retrospective study was conducted from January 2004 to July 2015 in 2 referral centers for the patients with cerebrovascular disorders. One hundred and sixty-six consecutive patients with a hospital admission or discharge diagnosis of definite CVST were included. The incidence of CVST was compared between high-temperature and low-temperature months. RESULTS: The mean age of patients was 36.71 ± 12.44 and 130 (78.31%) subjects were female. The highest frequency of CVST was seen in 3 months of July to September (1.69/month per year); and the lowest frequency of CVST was seen from December to April (.83/month per year). Additionally, there was a significant correlation between the mean average of temperature in each month and the frequency of CVST occurrence (r = .60, P = .03). Moreover, we found a cluster of patients, mostly females, in whom CVST occurred in cold months and accompanied visible cerebral infarct with higher occurrence of seizure, focal neurological deficit, and loss of consciousness. CONCLUSIONS: It seems that the incidence of CVST increases in high-temperature months of the year and dehydration and ensuing consequences may play an important role in such augmentation; however, the visible cerebral infarct is again more observed in low-temperature months.

The effect of low-dose combined oral contraceptive pills on brachial artery endothelial function and common carotid artery intima-media thickness.

BACKGROUND: Combined oral contraceptives (COCs) are considered for their thrombogenicity and the risk of premature atherosclerosis and the stroke caused by them. The aim of this study was to evaluate the relationship between chronic use of low-dose COCs (ethinyl estradiol 30 mcg + levonorgestrel 150 mcg) and endothelial dysfunction and intima-media thickness. METHODS: In a cross-sectional study, in 2011-2012, 60 healthy premenopausal women (30 cases of COC consumers and 30 controls as nonconsumers), aged between 25 and 45 years, participated in this study. They were current users for at least a 3-year period. Brachial artery flow-mediated dilatation (FMD) and common carotid artery intima-media thickness (CCA-IMT) were measured for the patients. RESULTS: The mean duration of COC consumption was 54.03 ± 27.27 months in the case group. There was a significant FMD% difference between 2 groups of cases and controls: 11 ± 3.53 versus 15.80 ± 9.22 (P = .01). In addition, a significant mean CCA-IMT thickness difference was detected: .53 ± .07 versus .44 ± .08 (P = .00). However, after multiple regression analysis and adjusting for body mass index (BMI), in COC users, no significant association between COC consumption duration and FMD% and mean CCA-IMT was observed. CONCLUSIONS: Prolonged used of low-dose COCs may cause changes in both endothelial function (measured by FMD%) and endothelial structure (measured by CCA-IMT). There was a nonsignificant inverse relationship between the duration of COC ingestion and FMD% and a nonsignificant positive relationship with CCA-IMT. Our results are in favor of early atherosclerotic changes in prolonged users of COCs.

Putamen iron quantification in diseases with neurodegeneration: a meta-analysis of the quantitative susceptibility mapping technique.

Quantitative susceptibility mapping (QSM) is an MRI technique that accurately measures iron concentration in brain tissues. This meta-analysis synthesized evidence from 30 studies that used QSM to quantify the iron levels in the putamen. The PRISMA statement was adhered to when conducting the systematic reviews and meta-analyses. We conducted a meta-analysis using a random-effects model, as well as subgroup analyses (disease type, geographic region, field strength, coil, disease type, age, and sex) and sensitivity analysis. A total of 1247 patients and 1035 controls were included in the study. Pooled results showed a standardized mean difference (SMD) of 0.41 (95% CI 0.19 to 0.64), with the strongest effect seen in Alzheimer's disease (AD) at 1.01 (95% CI 0.50 to 1.52). Relapsing-remitting multiple sclerosis (RRMS) also showed increased putaminal iron at 0.37 (95% CI 0.177 to 0.58). No significant differences were observed in Parkinson's disease (PD). No significant differences were found between subgroups based on geographic region, field strength, coil, disease type, age, and sex. The studies revealed significant heterogeneity, with field strength as the primary source, while other factors, such as disease type, location, age, sex, and coil type, may have contributed. The sensitivity analysis showed that these factors did not have a significant influence on the overall results. In summary, this meta-analysis supports abnormalities in putaminal iron content across different diseases with neurodegeneration, especially AD and RRMS, as measured by QSM. This highlights the potential of QSM as an imaging biomarker to better understand disease mechanisms involving disturbances in brain iron homeostasis.

MRI biomarkers and neuropsychological assessments of hippocampal and parahippocampal regions affected by ALS: A systematic review.

BACKGROUND AND OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a progressive motor and extra-motor neurodegenerative disease. This systematic review aimed to examine MRI biomarkers and neuropsychological assessments of the hippocampal and parahippocampal regions in patients with ALS. METHODS: A systematic review was conducted in the Scopus and PubMed databases for studies published between January 2000 and July 2023. The inclusion criteria were (1) MRI studies to assess hippocampal and parahippocampal regions in ALS patients, and (2) studies reporting neuropsychological data in patients with ALS. RESULTS: A total of 46 studies were included. Structural MRI revealed hippocampal atrophy, especially in ALS-FTD, involving specific subregions (CA1, dentate gyrus). Disease progression and genetic factors impacted atrophy patterns. Diffusion tensor imaging (DTI) showed increased mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and decreased fractional anisotropy (FA) in the hippocampal tracts and adjacent regions, indicating loss of neuronal and white matter integrity. Functional MRI (fMRI) revealed reduced functional connectivity (FC) between the hippocampus, parahippocampus, and other regions, suggesting disrupted networks. Perfusion MRI showed hypoperfusion in parahippocampal gyri. Magnetic resonance spectroscopy (MRS) found changes in the hippocampus, indicating neuronal loss. Neuropsychological tests showed associations between poorer memory and hippocampal atrophy or connectivity changes. CA1-2, dentate gyrus, and fimbria atrophy were correlated with worse memory. CONCLUSIONS: The hippocampus and the connected regions are involved in ALS. Hippocampal atrophy disrupted connectivity and metabolite changes correlate with cognitive and functional decline. Specific subregions can be particularly affected. The hippocampus is a potential biomarker for disease monitoring and prognosis.

An uncommon presentation of early brainstem high-grade glioma in a 33-year-old male: A case study and review of literature.

INTRODUCTION AND IMPORTANCE: Unlike children, high-grade brainstem glioma (HG-BSG) in adults is a rare and diverse group of tumors. They can be classified based on their location and physical characteristics, which distinguishes them from pediatric brainstem gliomas. They are rare in adults, constituting only 1 % to 2 % of intracranial gliomas. They are often aggressive and have a poor prognosis, with a median survival time of 24 months. The diagnosis of brainstem gliomas typically involves a combination of clinical evaluation and imaging studies, mainly magnetic resonance imaging (MRI), which provides detailed images and can help identify the characteristics of the tumor. CASE PRESENTATION AND METHODS: We present a case study of an uncommon presentation of an early stage of HG-BSG in a 33-year-old male, who had a contrast-enhancing lesion in the ventrolateral medulla that extended to the lower aspect of the fourth ventricle and caused ventricular compression. CLINICAL DISCUSSION: The findings were consistent with the literature on the current state of HG-BSG MRI findings, which typically show contrast-enhancing, hyperintense, and infiltrative lesions that involve the pons, midbrain, or medulla oblongata. The diagnosis of HG-BSG was based on clinical and radiological criteria, as the patient refused to undergo a surgical biopsy. We also performed a literature review on the current state of brainstem HG-BSG MRI findings, summarizing the main features and patterns of these tumors. CONCLUSION: MRI can offer useful information regarding the tumor's location, size, and features, as well as its impact on surrounding tissues and cerebrospinal fluid circulation.

Quantitative susceptibility mapping in amyotrophic lateral sclerosis: automatic quantification of the magnetic susceptibility in the subcortical nuclei.

Objective: Previous studies have suggested a link between dysregulation of cortical iron levels and neuronal loss in amyotrophic lateral sclerosis (ALS) patients. However, few studies have reported differences in quantitative susceptibility mapping (QSM) values in subcortical nuclei between patients with ALS and healthy controls (HCs). Methods: MRI was performed using a 3 Tesla Prisma scanner (64-channel head coil), including 3D T1-MPRAGE and multi-echo 3D GRE for QSM reconstruction. Automated QSM segmentation was used to measure susceptibility values in the subcortical nuclei, which were compared between the groups. Correlations with clinical scales were analyzed. Group comparisons were performed using independent t-tests, with p < 0.05 considered significant. Correlations were assessed using Pearson's correlation, with p < 0.05 considered significant. Cohen's d was reported to compare the standardized mean difference (SMD) of QSM. Results: Twelve patients with limb-onset ALS (mean age 48.7 years, 75% male) and 13 age-, sex-, and handedness-matched HCs (mean age 44.6 years, 69% male) were included. Compared to HCs, ALS patients demonstrated significantly lower susceptibility in the left caudate nucleus (CN) (SMD = -0.845), right CN (SMD = -0.851), whole CN (SMD = -1.016), and left subthalamic nucleus (STN) (SMD = -1.000). Susceptibility in the left putamen (SMD = -0.857), left thalamus (SMD = -1.081), and whole thalamus (SMD = -0.968) was significantly higher in the patients. The susceptibility of the substantia nigra (SN), CN, and pulvinar was positively correlated with disease duration. Conclusions: QSM detects abnormal iron accumulation patterns in the subcortical gray matter of ALS patients, which correlates with disease characteristics, supporting its potential as a neuroimaging biomarker.

A 65-year-old woman with ALS and bilateral precentral motor band sign.

Advanced MRI techniques, including SWI, MinIP, and QSM, are instrumental in detecting the "motor band sign" in ALS, aiding in the early diagnosis and assessment of upper motor neuron involvement, which is critical for therapeutic interventions.

Neutral lipid storage disease with myopathy: clinicopathological and genetic features of nine Iranian patients.

The rare disorder known as Neutral Lipid Storage Disease with Myopathy presents with a variety of clinical manifestations, including myopathy, cardiac dysfunction, and other organ complications. Early diagnosis is crucial due to the increased risk of cardiomyopathy. We describe the clinical, histopathological, muscle imaging, and genetic findings of nine neutral lipid storage myopathy patients. Proximal weakness and asymmetric involvement may suggest lipid storage myopathy. While skeletal muscle weakness was the main manifestation in our patients, one case presented only with hyperCKemia. Additionally, three patients had fertility issues, two suffered from diabetes mellitus, two had cardiomyopathy, and one had a history of hypothyroidism. Muscle histopathology revealed lipid depositions and rimmed vacuoles, prompting peripheral blood smears to detect Jordan Anomalies. All muscle biopsies and peripheral blood smear showed lipid droplets, rimmed vacuoles, and Jordan anomaly. Identifying PNPLA2 gene mutations is important for diagnosing neutral lipid storage myopathy; our cases showed some novel mutations. This study highlights the importance of early diagnosis and comprehensive evaluation in managing neutral lipid storage myopathy cases.