Publications by authors named "Farzad Fatehi"

114 Publications

Dataset of high-throughput ligand screening against the RNA Packaging Signals regulating Hepatitis B Virus nucleocapsid formation.

Authors:
Fardokht Abulwerdi Farzad Fatehi Iain W Manfield Stuart F J Le Grice John S Schneekloth Reidun Twarock Peter G Stockley Nikesh Patel

Data Brief 2022 Jun 26;42:108206. Epub 2022 Apr 26.

Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.

Multiple ssRNA viruses which infect bacteria, plants or humans use RNA Packaging Signal (PS)-mediated regulation during assembly to package their genomes faithfully and efficiently. PSs typically comprise short nucleotide recognition motifs, most often presented in the unpaired region of RNA stem-loops, and often bind their cognate coat proteins (CPs) with nanomolar affinity. PSs identified to date are resilient in the face of the typical error prone replication of their virus-coded polymerases, making them potential drug targets. An immobilised array of small molecular weight, drug-like compounds was panned against a fluorescently-labelled oligonucleotide encompassing the most conserved Hepatitis B Virus (HBV) PS, PS1, known to be a major determinant in nucleocapsid formation. This identified > 70 compounds that bind PS1 uniquely in the array. The commercially available 66 of these were tested for their potential effect(s) on HBV nucleocapsid-like particle (NCP) assembly , which identified potent assembly inhibitors. Here, we describe a high-throughput screen for such effects using employing fluorescence anisotropy in a 96-well microplate format. HBV genomic RNAs (gRNA) and short oligonucleotides encompassing PS1 were 5' labelled with an Alexa Fluor 488 dye. Excess (with respect to stoichiometric  = 4 NCP formation) HBV core protein (Cp) dimers were titrated robotically into solutions containing each of these RNAs stepwise, using a Biomek 4000 liquid handling robot. The anisotropy values of these mixtures were monitored using a POLARstar microplate reader. NCP-like structures were challenged with RNase A to identify reactions that did not result in complete NCP formation. The results imply that ∼50% of the compounds prevent complete NCP formation, highlighting both PS-meditated assembly and the PS-binding compounds as potential directly-acting anti-virals with a novel molecular target. Importantly, this method allows high-throughput screening for assembly inhibitors in this major human pathogen.
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http://dx.doi.org/10.1016/j.dib.2022.108206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9065705PMC
June 2022

Dysregulation of Hepatitis B Virus Nucleocapsid Assembly in vitro by RNA-binding Small Ligands.

Authors:
Nikesh Patel Fardokht Abulwerdi Farzad Fatehi Iain W Manfield Stuart Le Grice John S Schneekloth Reidun Twarock Peter G Stockley

J Mol Biol 2022 May 24;434(10):167557. Epub 2022 Mar 24.

Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK. Electronic address: https://twitter.com/AstburyCentre.

RNA sequences/motifs dispersed across the genome of Hepatitis B Virus regulate formation of nucleocapsid-like particles (NCPs) by core protein (Cp) in vitro, in an epsilon/polymerase-independent fashion. These multiple RNA Packaging Signals (PSs) can each form stem-loops encompassing a Cp-recognition motif, -RGAG-, in their loops. Drug-like molecules that bind the most important of these PS sites for NCP assembly regulation with nanomolar affinities, were identified by screening an immobilized ligand library with a fluorescently-labelled, RNA oligonucleotide encompassing this sequence. Sixty-six of these "hits", with affinities ranging from low nanomolar to high micromolar, were purchased as non-immobilized versions. Their affinities for PSs and effects on NCP assembly were determined in vitro by Surface Plasmon Resonance. High-affinity ligand binding is dependent on the presence of an -RGAG- motif within the loop of the PS, consistent with ligand cross-binding between PS sites. Simple structure-activity relationships show that it is also dependent on the presence of specific functional groups in these ligands. Some compounds are potent inhibitors of in vitro NCP assembly at nanomolar concentrations. Despite appropriate logP values, these ligands do not inhibit HBV replication in cell culture. However, modelling confirms the potential of using PS-binding ligands to target NCP assembly as a novel anti-viral strategy. This also allows for computational exploration of potential synergic effects between anti-viral ligands directed at distinct molecular targets in vivo. HBV PS-regulated assembly can be dysregulated by novel small molecule RNA-binding ligands opening a novel target for developing directly-acting anti-virals against this major pathogen.
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http://dx.doi.org/10.1016/j.jmb.2022.167557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7612645PMC
May 2022

Programmable polymorphism of a virus-like particle.

Authors:
Artur P Biela Antonina Naskalska Farzad Fatehi Reidun Twarock Jonathan G Heddle

Commun Mater 2022 Feb;3

Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7A, 30-392 Krakow, Poland.

Virus-like particles (VLPs) have significant potential as artificial vaccines and drug delivery systems. The ability to control their size has wide ranging utility but achieving such controlled polymorphism using a single protein subunit is challenging as it requires altering VLP geometry. Here we achieve size control of MS2 bacteriophage VLPs via insertion of amino acid sequences in an external loop to shift morphology to significantly larger forms. The resulting VLP size and geometry is controlled by altering the length and type of the insert. Cryo electron microscopy structures of the new VLPs, in combination with a kinetic model of their assembly, show that the abundance of wild type ( = 3), = 4, D3 and D5 symmetrical VLPs can be biased in this way. We propose a mechanism whereby the insert leads to a change in the dynamic behavior of the capsid protein dimer, affecting the interconversion between the symmetric and asymmetric conformers and thus determining VLP size and morphology.
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http://dx.doi.org/10.1038/s43246-022-00229-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7612486PMC
February 2022

Guillain-Barre Syndrome and COVID-19 Vaccine: A Report of Nine Patients.

Authors:
Narges Karimi Reza Boostani Farzad Fatehi Akram Panahi Ali Asghar Okhovat Bentolhoda Ziaadini Keivan Basiri Siamak Abdi Farnaz Sinaei Mojtaba Rezaei Gholamreza Shamsaei Behnaz Ansari Shahriar Nafissi

Basic Clin Neurosci 2021 Sep-Oct;12(5):703-710. Epub 2021 Sep 1.

Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Introduction: Guillain-Barre Syndrome (GBS) is an autoimmune acute inflammatory demyelinating polyneuropathy usually elicited by an upper respiratory tract infection. Several studies reported GBS associated with Coronavirus Disease 2019 (COVID-19) infection. In this study, we described nine GBS patients following the COVID-19 vaccine.

Methods: In this study, nine patients were introduced from six referral centers for neuromuscular disorders in Iran between April 8 and June 20, 2021. Four patients received the Sputnik V, three patients received the Sinopharm, and two cases received the AstraZeneca vaccine. All patients were diagnosed with GBS evidenced by nerve conduction studies and/or cerebrospinal fluid analysis.

Results: The median age of the patients was 54.22 years (ranged 26-87 years), and seven patients were male. The patients were treated with Intravenous Immunoglobulin (IVIg) or Plasma Exchange (PLEX). All patients were discharged with some improvements.

Conclusion: The link between the COVID-19 vaccine and GBS is not well understood. Given the prevalence of GBS over the population, this association may be coincidental; therefore, more studies are needed to investigate a causal relationship.
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http://dx.doi.org/10.32598/bcn.2021.3565.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8818119PMC
September 2021

Iranian Consensus Recommendations for Treatment of Myasthenia Gravis.

Authors:
Shahriar Nafissi Ali Asghar Okhovat Farnaz Sinaei Behnaz Ansari Hormoz Ayramloo Keyvan Basiri Reza Boostani Bahram Haghi Ashtiani Payam Sarraf Farzad Fatehi

Arch Iran Med 2022 01 1;25(1):37-49. Epub 2022 Jan 1.

Neurology Department, Shariati Hospital, Iranian Neuromuscular Research Center (INMRC), Tehran University of Medical Sciences, Tehran, Iran.

Myasthenia gravis (MG) is an immune-mediated potentially treatable disease in which rapid diagnosis and proper treatment can control symptoms. Treatment should be individualized in each patient according to distribution (ocular or generalized) and severity of the weakness, antibody status, thymus pathology, patient comorbidities, and preferences. A group of Iranian neuromuscular specialists have written these recommendations to treat MG based on national conditions. Four of the authors performed an extensive literature review, including PubMed, EMBASE, and Google Scholar, from 1932 to 2020 before the central meeting to define headings and subheadings. The experts held a 2-day session where the primary drafts were discussed point by point. Primary algorithms for the management of MG patients were prepared in the panel discussion. After the panel, the discussions continued in virtual group discussions, and the prepared guideline was finalized after agreement and concordance between the panel members. Finally, a total of 71 expert recommendations were included. We attempted to develop a guideline based on Iran's local requirements. We hope that these guidelines help healthcare professionals in proper treatment and follow-up of patients with MG.
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http://dx.doi.org/10.34172/aim.2022.07DOI Listing
January 2022

An age-structured model of hepatitis B viral infection highlights the potential of different therapeutic strategies.

Authors:
Farzad Fatehi Richard J Bingham Peter G Stockley Reidun Twarock

Sci Rep 2022 01 24;12(1):1252. Epub 2022 Jan 24.

York Cross-disciplinary Centre for Systems Analysis, University of York, YO10 5GE, York, UK.

Hepatitis B virus (HBV) is a global health threat, and its elimination by 2030 has been prioritised by the World Health Organisation. Here we present an age-structured model for the immune response to an HBV infection, which takes into account contributions from both cell-mediated and humoral immunity. The model has been validated using published patient data recorded during acute infection. It has been adapted to the scenarios of chronic infection, clearance of infection, and flare-ups via variation of the immune response parameters. The impacts of immune response exhaustion and non-infectious subviral particles on the immune response dynamics are analysed. A comparison of different treatment options in the context of this model reveals that drugs targeting aspects of the viral life cycle are more effective than exhaustion therapy, a form of therapy mitigating immune response exhaustion. Our results suggest that antiviral treatment is best started when viral load is declining rather than in a flare-up. The model suggests that a fast antibody production rate always leads to viral clearance, highlighting the promise of antibody therapies currently in clinical trials.
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http://dx.doi.org/10.1038/s41598-021-04022-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8786976PMC
January 2022

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

Authors:
Ali Asghar Okhovat Soroor Advani Bentolhoda Ziaadini Akram Panahi Saeideh Salehizadeh Shahriar Nafissi Bahram Haghi Ashtiani Yusuf A Rajabally Farzad Fatehi

Muscle Nerve 2022 04 31;65(4):433-439. Epub 2022 Jan 31.

Neurology Department, Iranian Neuromuscular Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

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.
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http://dx.doi.org/10.1002/mus.27498DOI Listing
April 2022

Therapeutic interfering particles exploiting viral replication and assembly mechanisms show promising performance: a modelling study.

Authors:
Farzad Fatehi Richard J Bingham Pierre-Philippe Dechant Peter G Stockley Reidun Twarock

Sci Rep 2021 12 13;11(1):23847. Epub 2021 Dec 13.

York Cross-disciplinary Centre for Systems Analysis, University of York, York, YO10 5GE, UK.

Defective interfering particles arise spontaneously during a viral infection as mutants lacking essential parts of the viral genome. Their ability to replicate in the presence of the wild-type (WT) virus (at the expense of viable viral particles) is mimicked and exploited by therapeutic interfering particles. We propose a strategy for the design of therapeutic interfering RNAs (tiRNAs) against positive-sense single-stranded RNA viruses that assemble via packaging signal-mediated assembly. These tiRNAs contain both an optimised version of the virus assembly manual that is encoded by multiple dispersed RNA packaging signals and a replication signal for viral polymerase, but lack any protein coding information. We use an intracellular model for hepatitis C viral (HCV) infection that captures key aspects of the competition dynamics between tiRNAs and viral genomes for virally produced capsid protein and polymerase. We show that only a small increase in the assembly and replication efficiency of the tiRNAs compared with WT virus is required in order to achieve a treatment efficacy greater than 99%. This demonstrates that the proposed tiRNA design could be a promising treatment option for RNA viral infections.
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http://dx.doi.org/10.1038/s41598-021-03168-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8668974PMC
December 2021

The Transition of Mild Cognitive Impairment Over Time: An AV45- and FDG-PET Study of Reversion and Conversion Phenomena.

Authors:
Amir Ashraf-Ganjouei Kamyar Moradi Shahriar Faghani AmirHussein Abdolalizadeh Mohammadreza Khomeijani-Farahani Farzad Fatehi Alzheimer's Disease Neuroimaging Initiative

Curr Alzheimer Res 2021 ;18(9):721-731

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Background: Mild cognitive impairment (MCI) is a state between normal cognition and dementia. However, MCI diagnosis does not necessarily guarantee the progression to dementia. Since no previous study investigated brain positron emission tomography (PET) imaging of MCI-- to-normal reversion, we provided PET imaging of MCI- to-normal reversion using the Alzheimer's Disease Neuroimaging Initiative (ADNI) database.

Methods: We applied comprehensive neuropsychological criteria (NP criteria), consisting of memory, language, and attention/executive function domains, to include patients with a baseline diagnosis of MCI (n=613). According to the criteria, the year 1 status of the patients was categorized into three groups (reversion: n=105, stable MCI: n=422, conversion: n=86). Demographic, neuropsychological, genetic, CSF, and cognition biomarker variables were compared between the groups. Additionally, after adjustment for confounding variables, the deposition pattern of amyloid-β and cerebral glucose metabolism were compared between three groups via AV45- and FDG-PET modalities, respectively.

Results: MCI reversion rate was 17.1% during one year of follow-up. The reversion group had the lowest frequency of APOE ε4+ subjects, the highest CSF level of amyloid-β, and the lowest CSF levels of t-tau and p-tau. Neuropsychological assessments were also suggestive of better cognitive performance in the reversion group. Patients with reversion to normal state had higher glucose metabolism in bilateral angular and left middle/inferior temporal gyri, when compared to those with stable MCI state. Meanwhile, lower amyloid-β deposition at baseline was observed in the frontal and parietal regions of the reverted subjects. On the other hand, the conversion group showed lower cerebral glucose metabolism in bilateral angular and bilateral middle/inferior temporal gyri compared to the stable MCI group, whereas the amyloid-β accumulation was similar between the groups.

Conclusion: This longitudinal study provides novel insight regarding the application of PET imaging in predicting MCI transition over time.
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http://dx.doi.org/10.2174/1567205018666211124110710DOI Listing
April 2022

Recommendations for Infantile-Onset and Late-Onset Pompe Disease: An Iranian Consensus.

Authors:
Farzad Fatehi Mahmoud Reza Ashrafi Marzieh Babaee Behnaz Ansari Mehran Beiraghi Toosi Reza Boostani Peyman Eshraghi Atefeh Fakharian Zahra Hadipour Bahram Haghi Ashtiani Hossein Moravej Yalda Nilipour Payam Sarraf Keyhan Sayadpour Zanjani Shahriar Nafissi

Front Neurol 2021 21;12:739931. Epub 2021 Sep 21.

Department of Neurology, Neuromuscular Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Pompe disease, also denoted as acid maltase or acid α-glucosidase deficiency or glycogen storage disease type II, is a rare, autosomal recessive lysosomal storage disorder. Several reports have previously described Pompe disease in Iran and considering increased awareness of related subspecialties and physicians, the disease's diagnosis is growing. This guideline's main objective was to develop a national guideline for Pompe disease based on national and international evidence adapting with national necessities. A group of expert clinicians with particular interests and experience in diagnosing and managing Pompe disease participated in developing this guideline. This group included adult neurologists, pediatric neurologists, pulmonologists, endocrinologists, cardiologists, pathologists, and physiatrists. After developing search terms, four authors performed an extensive literature review, including Embase, PubMed, and Google Scholar, from 1932 to current publications before the main meeting. Before the main consensus session, each panel member prepared an initial draft according to pertinent data in diagnosis and management and was presented in the panel discussion. Primary algorithms for the diagnosis and management of patients were prepared in the panel discussion. The prepared consensus was finalized after agreement and concordance between the panel members. Herein, we attempted to develop a consensus based on Iran's local requirements. The authors hope that disseminating these consensuses will help healthcare professionals in Iran achieve the diagnosis, suitable treatment, and better follow-up of patients with infantile-onset Pompe disease and late-onset Pompe disease.
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http://dx.doi.org/10.3389/fneur.2021.739931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490649PMC
September 2021

Zytux in Refractory Myasthenia Gravis: A Multicenter, Open-Labeled, Clinical Trial Study of Effectiveness and Safety of a Rituximab Biosimilar.

Authors:
Farzad Fatehi Kamyar Moradi Ali Asghar Okhovat Ghazaleh Shojatalab Behnaz Sedighi Reza Boostani Payam Sarraf Bahram Haghi Ashtiani Majid Ghasemi Soussan Moussavi Nassim Anjidani Shahriar Nafissi

Front Neurol 2021 26;12:682622. Epub 2021 Aug 26.

Neurology Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Myasthenia gravis (MG) is an immune-mediated neuromuscular disorder responsive to immunomodulatory treatments. 10-20% of MGs are not responsive to conventional first-line therapies. Here, we sought to investigate the efficacy and safety of rituximab therapy in the treatment of patients with refractory MG. In a 48-week, multicenter, open-labeled, prospective cohort setting, 34 participants with refractory MG were assigned to receive infusions of Zytux, which is a rituximab biosimilar, according to a validated protocol. Clinical, functional, and quality of life (QoL) measurements were recorded at baseline, and seven further visits using the Myasthenia Gravis Foundation of America (MGFA), Myasthenia Gravis Composite (MGC), Myasthenia Gravis Activities of Daily Living profile (MG-ADL), and Myasthenia Gravis Quality of Life (MGQoL-15) scales. Besides, the post-infusion side effects were systematically assessed throughout the study. The correlation analysis performed by generalized estimating equations analysis represented a significant reduction of MGC, MG-ADL, and MGQoL-15 scores across the trial period. The subgroup analysis based on the patients' clinical status indicated a significant effect for the interaction between time and MGFA subtypes on MG-ADL score, MGC score, and pyridostigmine prednisolone dose, reflecting that the worse clinical condition was associated with a better response to rituximab. Finally, no serious adverse event was documented. Rituximab therapy could improve clinical, functional, and QoL in patients with refractory MG in a safe setting. Further investigations with larger sample size and a more extended follow-up period are warranted to confirm this finding. The study was registered by the Iranian Registry of Clinical Trials (IRCT) (Code No: IRCT20150303021315N18).
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http://dx.doi.org/10.3389/fneur.2021.682622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427762PMC
August 2021

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

Authors:
Farzad Fatehi Ali Asghar Okhovat Akram Panahi Bentolhoda Ziaaddini Yusuf A Rajabally Shahriar Nafissi

J Peripher Nerv Syst 2021 12 10;26(4):469-474. Epub 2021 Sep 10.

Neurology Department, Neuromuscular Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

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.
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http://dx.doi.org/10.1111/jns.12461DOI Listing
December 2021

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

Authors:
Seyyed-Saleh Hashemi Reza Hajati Atefeh Davarzani Mohammad Rohani Fardad DanaeeFard Mohammad Masoud Rahimi Bidgoli Farzad Fatehi Ariana Kariminejad Hossein Najmabadi Shahriar Nafissi Afagh Alavi

Can J Neurol Sci 2021 Aug 6:1-11. Epub 2021 Aug 6.

Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.

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.
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http://dx.doi.org/10.1017/cjn.2021.188DOI Listing
August 2021

Thigh and Leg Muscle MRI Findings in GNE Myopathy.

Authors:
Farzad Fatehi Soroor Advani Ali Asghar Okhovat Bentolhoda Ziaadini Hosein Shamshiri Shahriar Nafissi

J Neuromuscul Dis 2021 ;8(4):735-742

Neurology Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Background: Muscle MRI protocols have been developed to assess muscle involvement in a wide variety of muscular dystrophies. Different muscular dystrophies can involve muscle groups in characteristic patterns. These patterns can be identified in muscle MRI in the form of fatty infiltration.

Objective: This study was conducted to add the existing knowledge of muscle MRI in GNE myopathy and evaluate the correlation of muscular involvement with different gene mutations.

Methods: The MRI scans of the 18 GNE patients were analyzed retrospectively. Cluster analysis was done for grouping the muscles and patients.

Results: The four muscles with the highest fat infiltration were adductor magnus, tibialis anterior, semitendinosus, and semimembranosus. Furthermore, three clusters of muscle involvement were found, including cluster 1, typical muscle involvement indicating muscles with the highest infiltration: extensor digitorum longus, gracilis, biceps femoris, soleus, gastrocnemius medial, adductor longus, tibialis anterior, adductor magnus, semimembranosus, semitendinosus; cluster 2, less typical muscle involvement indicating muscles with intermediate fat infiltration, peroneus longus, gastrocnemius lateral, and minimal fat infiltration in most of the patients, i.e., tibialis posterior; and cluster 3, atypical muscle involvement with low-fat infiltration: rectus femoris, sartorius, vastus intermedius, vastus medialis, and vastus lateralis.

Conclusions: This study found three clusters of muscle involvement and three groups of patients among GNE patients. Hamstring muscles and the anterior compartment of the lower leg were the muscles with the highest fat infiltration. Moreover, a weak genotype-muscle MRI association was found in which tibialis posterior was more involved in patients with the most frequent mutation, i.e., C.2228T > C (p.M743T) mutation; however, this finding may be related to longer disease duration.
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http://dx.doi.org/10.3233/JND-210629DOI Listing
December 2021

Myasthenia gravis associated with novel coronavirus 2019 infection: A report of three cases.

Authors:
Narges Karimi Ali Asghar Okhovat Bentolhoda Ziaadini Bahram Haghi Ashtiani Shahriar Nafissi Farzad Fatehi

Clin Neurol Neurosurg 2021 Sep 23;208:106834. Epub 2021 Jul 23.

Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Several neurological presentations have been reported following coronavirus 2019 (COVID-19) infection. This case report describes three myasthenia gravis (MG) patients presented following COVID-19 infection. We report three adult patients with myasthenic Gravis and COVID-19 infection. The patients are between 38 and 61 years old. Case 1 is a 61-year-old woman with progressive dysphagia, nasal speech, ocular ptosis, diplopia, and proximal muscle weakness for 10 days. She had a COVID-19 infection 6 weeks ago. Case 2 is a 57-year-old man with clinical symptoms of muscular fatigability, diplopia, ptosis, and dysphagia for a week and a positive COVID-19 infection 10 days ago. Case 3 is a 38-year-old woman with fatigability, ptosis, dysphagia, and a diagnosis of COVID-19 infection 4 weeks ago. All patients had a positive RT-PCR for COVID-19 infection by nasopharyngeal swab test and a high-level acetylcholine receptor antibody in the serum. All patients were treated with pyridostigmine and prednisolone with a favorable outcome. MG may appear following COVID-19 infection, and the role of molecular mimicry and latent MG activation should be considered the cause of the disease onset.
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http://dx.doi.org/10.1016/j.clineuro.2021.106834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299214PMC
September 2021

Comparison of Clinical, Ultrasound, and Electrophysiologic Changes in Chronic Inflammatory Demyelinating Polyneuropathy: A Prospective Study.

Authors:
Ali Asghar Okhovat Shahriar Nafissi Kamyar Moradi Bentolhoda Ziaadini Akram Panahi Bahram Haghi Ashtiani Farzad Fatehi

J Clin Neurophysiol 2021 Jul 6. Epub 2021 Jul 6.

Neurology Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran; and Department of Neurology, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran.

Purpose: The follow-up and monitoring of response to immunomodulatory therapy in patients with chronic inflammatory demyelinating polyneuropathy are still challenging. Various outcome measures have been proposed in recent years, and some are now frequently used in daily clinical practice; however, reliable biomarkers for the disease activity and treatment response are lacking.

Methods: Cross-sectional nerve area of the bilateral vagus, fifth and the sixth cervical spinal, median, ulnar, tibial, peroneal, and sural nerves were measured at 2 time points with an interval of 6 months using nerve ultrasound. The results were used to calculate the ultrasound pattern sumscore (UPSS). The correlation between UPSS change (ΔUPSS) and changes in functional and nerve conduction studies measures over the study period were assessed.

Results: Sixteen patients completed this prospective, observational study. General linear model showed that ΔUPSS is significantly associated with ΔMedical Research Council sumscore (β = -0.72, P = 0.003), Δhandgrip strength (β = -0.57, P = 0.014), ΔRasch-built overall disability scale (β = -0.57, P = 0.010), and Δoverall neuropathy limitations scale (β = 0.75, P < 0.001), after adjustment of confounding variables. Nevertheless, ΔUPSS was not correlated with other clinical measures, including Δpinch power, Δ9-hole peg test, Δ10-m walking test, and Δnerve conduction study sumscore (P values > 0.05).

Conclusions: Nerve ultrasound might be an efficient method for monitoring the functional status of patients with chronic inflammatory demyelinating polyneuropathy over time because the alterations in its scores could significantly reflect clinical changes.
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http://dx.doi.org/10.1097/WNP.0000000000000883DOI Listing
July 2021

Prevalence of mild behavioral impairment in patients with mild cognitive impairment.

Authors:
Gilda Kianimehr Farzad Fatehi Maryam Noroozian

Acta Neurol Belg 2021 Jun 30. Epub 2021 Jun 30.

Department of Neuropsychiatry and Cognitive Neurology, Roozbeh Hospital, Tehran University of Medical Sciences, South Kargar Street, Tehran, Iran.

Over the past years, increasing attention has been paid to the frequency of neuropsychiatric symptoms (NPS) in dementia, also known as the behavioral and psychological symptoms of dementia. This study's main goal was to determine the prevalence of Mild Behavioral Impairment (MBI) and its subdomains in patients with Mild Cognitive Impairment (MCI) in Iran. Participants included 96 patients with MCI who attended the memory clinic between July and December 2020. Global cognitive function was evaluated using the Persian version of the Montreal Cognitive Assessment (MoCA). To assess MBI, the Persian version of the MBI checklist (MBI-C) was completed by the patient or a close caregiver. The mean age of patients was 71.4 ± 9.3 years, and 56 patients (58.3%) were female. Regarding the cutoff point of 6.5, 48 patients (50%) had MBI. In both groups of MBI and non-MBI, 28 (58%) were female. There was no significant difference in MBI subdomains scores and total MBI scores between the two genders. In addition, we found no significant difference in total MBI in patients with different risk factors. There was no significant difference in MoCA score between MBI and non-MBI patients (24.1 ± 3.9 versus 23.7 ± 4.0) (p = 0.59). NPS are highly prevalent in MCI patients, with the most common ones being impulse dyscontrol, emotional dysregulation, and decreased motivation. Psychotic symptoms and social inappropriateness are rare. New-onset psychiatric symptoms and behavioral changes in older adults, even in a mild form (MBI), should increase the suspicion of subsequent cognitive impairment.
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http://dx.doi.org/10.1007/s13760-021-01724-zDOI Listing
June 2021

Burnout and clinical learning environment among residents in Tehran: A cross-sectional study.

Authors:
Nastaran Maghbouli Farzad Fatehi Mahboobeh Khabaz Mafinejad Saeed Pourhassan Amir Ali Sohrabpour Jemal Haidar Ali

Heliyon 2021 Jun 8;7(6):e07238. Epub 2021 Jun 8.

Addis Ababa University, College of Health Sciences, School of Public Health, Addis Ababa, Ethiopia.

Purpose: This study aimed to evaluate the quality of the educational environment in Tehran University of Medical Sciences across different medical specialties and its correlation with residents' burnout.

Materials And Methods: This cross-sectional study was conducted at Tehran University of Medical Sciences among residents drawn from three largest teaching hospitals affiliated. The Maslach Burnout Inventory and Postgraduate Hospital Educational Environment Measure (PHEEM) questionnaire were used to collect data through web-based, as well as paper-and pencil questionnaires. The data was analyzed using SPSS.

Results: A total of 221 residents completed the survey, with a response rate of 82%. Burnout was reported by 67.4% of medical residents. The total PHEEM score had a negative correlation with emotional exhaustion (r = - 0.57, P < 0.001), depersonalization (r = - 0.40, P < 0.001), and a positive one with personal accomplishment (r = 0.42, P < 0.001). Perception of social support significantly predicted burnout subscales (P < 0.05). PHEEM subscales also explained a small proportion of variance in emotional exhaustion (R = 0.55, R = 0.308, P < .001). Clinical learning environment independent of personal characteristics was associated with residents' burnout according to multivariate regression analysis [OR = 0.567 (0.170-0.883), P = 0.012].

Conclusion: Clinical learning environment independent of personal characteristics was associated with residents' burnout in Iran. We suggest some initiatives to be introduced ranging from improving the clinical environments, reduce workloads and provide social support to all residents as well as encouraging them to involve in other extracurricular activities like music and physical exercise.
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http://dx.doi.org/10.1016/j.heliyon.2021.e07238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215171PMC
June 2021

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

Authors:
Farnaz Sinaei Farzad Fatehi Shahram Oveis Gharan Soroush Ehsan Koorosh Kamali Shahriar Nafissi

Neurol Sci 2022 Feb 18;43(2):1233-1237. Epub 2021 Jun 18.

Department of Neurology, Shariati Hospital, Neuromuscular Research Center, Tehran University of Medical Sciences, Tehran, Iran.

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.
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http://dx.doi.org/10.1007/s10072-021-05382-0DOI Listing
February 2022

Association of HLA Class II Alleles with Disease Severity and Treatment Response in Iranian Patients with Myasthenia Gravis.

Authors:
Farnaz Sinaei Farzad Fatehi Shahram Oveis Gharan Soroush Ehsan Koorosh Kamali Aliakbar Amirzargar Mahdi Mahmoudi Alaleh Vaghefifar Shahriar Nafissi

J Neuromuscul Dis 2021 ;8(5):827-829

Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Myasthenia gravis is an autoimmune neuromuscular disease with a multifactorial etiology. A major part of the genetic susceptibility belongs to the HLA encoding genes. In this study, we investigated the role of HLA class II polymorphism in disease severity, and treatment response. In our 146 patients, 15 DRB1, 7 DQA1, and 9 DQB1 alleles, and 19 haplotypes were found. Adjusted p-values did not show any significant associations between these loci, disease severity and treatment outcome. Further studies in different populations with a larger number of patients are needed to determine the exact contribution of HLA class II alleles to MG prognosis.
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http://dx.doi.org/10.3233/JND-210700DOI Listing
November 2021

Novel Mutations of the TYMP Gene in Mitochondrial Neurogastrointestinal Encephalomyopathy: Case Series and Literature Review.

Authors:
Helia Mojtabavi Farzad Fatehi Sepideh Shahkarami Nima Rezaei Shahriar Nafissi

J Mol Neurosci 2021 Dec 6;71(12):2526-2533. Epub 2021 Apr 6.

School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a multi-system disorder caused by several homozygous or compound heterozygous mutations, mostly in the nuclear gene of TYMP. Our current knowledge on the underlying pathology of the disease is derived through the study of about 200 cases of different ethnicities. Clinical presentations include severe cachexia, weakness, ptosis, diplopia, abdominal cramps or digestive tract disorders, hearing impairment, and paresthesia.Herein, we aim to present five novel mutations of the nuclear gene of TYMP in six Iranian patients diagnosed with MNGIE. In our population, age at the time of diagnosis was 18 to 49 years, while the onset of the symptoms varied from 13 to 20 years. We detected two pathogenic non-frameshift nonsense premature stop codon mutations (c.1013C > A, and c.130C > T), one variant of uncertain significance (VUS) non-frameshift missense mutation (c.345G > T), one likely pathogenic frameshift insertion (c.801_802insCGCG), and one likely benign homozygous non-frameshift deletion (c.1176_1187del) from two siblings. Our findings also confirm the autosomal recessive inheritance pattern of MNGIE in the Iranian population. The lack of knowledge in the area of nuclear gene-modifier genes shadows the genotype-phenotype relationships of MNGIE.
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http://dx.doi.org/10.1007/s12031-021-01822-wDOI Listing
December 2021

Persian adaptation of Edinburgh Cognitive and Behavioural Screen (ECAS).

Authors:
Helia Mojtabavi Shahriar Nafissi Behrooz Mahmoodi-Bakhtiari Davood Fathi Farzad Fatehi

Amyotroph Lateral Scler Frontotemporal Degener 2021 08 17;22(5-6):426-433. Epub 2021 Feb 17.

School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

: To adapt the Edinburgh Cognitive and Behavioral screen (ECAS) English version into Persian. The ECAS test was adapted and implemented to 30 ALS patients and 31 healthy volunteers in Tehran, Iran. The ECAS results were compared to MoCA and ALS-FRS-r, the other standard tools to determine whether the translated version is reliable and valid in the new language. In addition, the patients' caregivers were interviewed for behavioral and psychiatric changes. The Persian version of ECAS revealed high internal consistency (α = 0.791), alongside the strong correlation of ECAS and its subscales with MoCA and ALS-FRS. Moreover, Persian ECAS discriminated against the patients and the healthy population well. Sensitivity analysis revealed promising results of Persian ECAS with an area under the curve of 0.871 in ROC curve analysis. Cognitive impairment was observed in 43.33% of patients. The Persian version of the ECAS, exclusively designed for the Iranian population, is the first screening tool to assess multiple neuropsychological functions, which provides a rapid and inclusive screen of cognitive and behavioral impairments specifically in ALS patients.
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http://dx.doi.org/10.1080/21678421.2021.1883665DOI Listing
August 2021

Quality of Life in Patients with Cerebral Venous Sinus Thrombosis: A Study on Physical, Psychological, and Social Status of Patients in Long-term.

Authors:
Danesh Kajbaf Kamyar Moradi Hossein Shamshiri Sayna Bagheri Reza Rikhtegar Askar Ghorbani Farzad Fatehi

Arch Iran Med 2021 01 1;24(1):15-21. Epub 2021 Jan 1.

Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Background: Cerebral venous sinus thrombosis (CVST) causes significant problems for patients in the working age and may therefore negatively affect their quality of life (QOL). In the present study, we sought to evaluate the QOL and its predictors in subjects with CVST.

Methods: This observational, prospective study investigated several outcomes of 56 CVST patients after thrombosis onset. Demographic characteristics, medical history, neurological signs and symptoms during hospitalization, and the employment status of the patients were retrospectively collected. Stroke-related functional scales, including the modified Rankin Scale (mRS) and Barthel Index (BI) were employed. For physical and mental aspects of the QOL, we used the validated Persian version of the Stroke Specific Quality of Life (SS-QOL) scale.

Results: The physical and functional outcomes in the long-term were promising according to mRS and BI tools, as well as the improved rate of return to work. Mental domains of the SS-QOL, such as energy and personality represented the lowest scores. According to the multiple linear regression analysis, lower mRS score, and longer time interval between CVST onset and interview were associated with higher physical function of the patients while their better mental function was correlated with lower mRS score and thrombosis in merely one cerebral venous.

Conclusion: CVST patients experience an acceptable alleviation of the primary physical disabilities, while residual symptoms, mostly in psychologic/mental domains, impair their QOL.
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http://dx.doi.org/10.34172/aim.2021.03DOI Listing
January 2021

Application of CMAP scan for the evaluation of patients with chronic inflammatory demyelinating polyneuropathy: a prospective study.

Authors:
Ali Asghar Okhovat Soroor Advani Kamyar Moradi Bentolhoda Ziaadini Akram Panahi Shahriar Nafissi Bahram Haghi Ashtiani Farzad Fatehi

Neurophysiol Clin 2021 Mar 7;51(2):175-181. Epub 2021 Jan 7.

Neurology Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Aims: We aimed to assess the compound muscle action potential (CMAP) scan in the follow-up of chronic inflammatory demyelinating polyneuropathy (CIDP) patients and investigate the correlation of CMAP scan parameters with functional and standard electrodiagnostic tests.

Methods: We evaluated four parameters of abductor pollicis brevis (APB) CMAP scan (i.e., step numbers, step percentage, S10, S90), functional measures (e.g., Medical Research Council Sum Scores), and electrodiagnostic tests, including nerve conduction study (NCS) and motor NCS of the median nerve in the baseline and after six months of treatment.

Results: Twenty patients completed baseline clinical and electrodiagnostic studies. However, sixteen patients completed the follow-up study. The median of step numbers at baseline was 3.5 (2-4.2), which decreased to 2.5 (0-3) (p = 0.005). After the treatment, step percentage reduced from 28.6 (23.9-38.7) to 13.4 (0-23.6) (p = 0.001). The scores obtained from the clinical scales showed significant recovery of most of the functions, while the alterations of NCSS and NCS of the median nerve were not significant.

Conclusions: We found a significant reduction in step number and step percentage after follow-up. This alteration was not reflected in standard electrodiagnostic values. The improvement of functional scales alongside the CMAP scan parameters suggests that the CMAP scan could be considered an appropriate outcome measurement in research and clinical fields.
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http://dx.doi.org/10.1016/j.neucli.2020.12.005DOI Listing
March 2021

An Intracellular Model of Hepatitis B Viral Infection: An In Silico Platform for Comparing Therapeutic Strategies.

Authors:
Farzad Fatehi Richard J Bingham Eric C Dykeman Nikesh Patel Peter G Stockley Reidun Twarock

Viruses 2020 12 23;13(1). Epub 2020 Dec 23.

York Cross-Disciplinary Centre for Systems Analysis, University of York, York YO10 5GE, UK.

Hepatitis B virus (HBV) is a major focus of antiviral research worldwide. The International Coalition to Eliminate HBV, together with the World Health Organisation (WHO), have prioritised the search for a cure, with the goal of eliminating deaths from viral hepatitis by 2030. We present here a comprehensive model of intracellular HBV infection dynamics that includes all molecular processes currently targeted by drugs and agrees well with the observed outcomes of several clinical studies. The model reveals previously unsuspected kinetic behaviour in the formation of sub-viral particles, which could lead to a better understanding of the immune responses to infection. It also enables rapid comparative assessment of the impact of different treatment options and their potential synergies as combination therapies. A comparison of available and currently developed treatment options reveals that combinations of multiple capsid assembly inhibitors perform best.
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http://dx.doi.org/10.3390/v13010011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823939PMC
December 2020

Sporadic late-onset nemaline myopathy with monoclonal gammopathy of undetermined significance: Report of four patients.

Authors:
Ali Asghar Okhovat Yalda Nilipour Reza Boostani Fahimeh Vahabizad Safa Najmi Shahriar Nafissi Farzad Fatehi

Neuromuscul Disord 2021 01 12;31(1):29-34. Epub 2020 Nov 12.

Neurology Department, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Sporadic late-onset nemaline myopathy (SLONM) is a rare, acquired muscle disease presenting with subacute progression in adulthood. It can be accompanied by a monoclonal gammopathy of undetermined significance (MGUS). We describe clinical and histopathological findings of four SLONM patients with MGUS. In all patients, nemaline rod, inter-myofibrillary network disruption, atrophic changes, peripheral basophilic discoloration, vacuole without rim, and cytoplasmic body without inflammation were seen. Three out of four patients were treated with prednisolone in combination with IVIG monthly and had an appropriate response to the treatment. The optimal first-line treatment remains unclear in SLONM-MGUS, although corticosteroids plus IVIg is associated with favorable clinical response. These treatment modalities might be used as an optional treatment before autologous stem cell transplantation; however, further studies with a higher number of patients are required.
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http://dx.doi.org/10.1016/j.nmd.2020.11.004DOI Listing
January 2021

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

Authors:
Sahebeh Rajabkhah Kamyar Moradi Ali A Okhovat Nens Van Alfen Davood Fathi Leila Aghaghazvini Amir Ashraf-Ganjouei Shahram Attarian Shahriar Nafissi Farzad Fatehi

Muscle Nerve 2020 10 14;62(4):516-521. Epub 2020 Aug 14.

Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Jalal al Ahmad, Tehran, 1411713135, Iran.

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.
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http://dx.doi.org/10.1002/mus.27036DOI Listing
October 2020

The association of SARS-CoV-2 infection and acute disseminated encephalomyelitis without prominent clinical pulmonary symptoms.

Authors:
Siamak Abdi Askar Ghorbani Farzad Fatehi

J Neurol Sci 2020 09 18;416:117001. Epub 2020 Jun 18.

Associate Professor of Neurology, Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran (ORCID ID: 0000-0002-6774-7825). Electronic address:

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http://dx.doi.org/10.1016/j.jns.2020.117001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301801PMC
September 2020

Description of combined ARHSP/JALS phenotype in some patients with SPG11 mutations.

Authors:
Marzieh Khani Hosein Shamshiri Farzad Fatehi Mohammad Rohani Bahram Haghi Ashtiani Fahimeh Haji Akhoundi Afagh Alavi Hamidreza Moazzeni Hanieh Taheri Mina Tolou Ghani Leila Javanparast Seyyed Saleh Hashemi Ramona Haji-Seyed-Javadi Matineh Heidari Shahriar Nafissi Elahe Elahi

Mol Genet Genomic Med 2020 07 8;8(7):e1240. Epub 2020 May 8.

School of Biology, College of Science, University of Tehran, Tehran, Iran.

Background: SPG11 mutations can cause autosomal recessive hereditary spastic paraplegia (ARHSP) and juvenile amyotrophic lateral sclerosis (JALS). Because these diseases share some clinical presentations and both can be caused by SPG11 mutations, it was considered that definitive diagnosis may not be straight forward.

Methods: The DNAs of referred ARHSP and JALS patients were exome sequenced. Clinical data of patients with SPG11 mutations were gathered by interviews and neurological examinations including electrodiagnosis (EDX) and magnetic resonance imaging (MRI).

Results: Eight probands with SPG11 mutations were identified. Two mutations are novel. Among seven Iranian probands, six carried the p.Glu1026Argfs*4-causing mutation. All eight patients had features known to be present in both ARHSP and JALS. Additionally and surprisingly, presence of both thin corpus callosum (TCC) on MRI and motor neuronopathy were also observed in seven patients. These presentations are, respectively, key suggestive features of ARHSP and JALS.

Conclusion: We suggest that rather than ARHSP or JALS, combined ARHSP/JALS is the appropriate description of seven patients studied. Criteria for ARHSP, JALS, and combined ARHSP/JALS designations among patients with SPG11 mutations are suggested. The importance of performing both EDX and MRI is emphasized. Initial screening for p.Glu1026Argfs*4 may facilitate SPG11 screenings in Iranian patients.
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http://dx.doi.org/10.1002/mgg3.1240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336765PMC
July 2020

Quantifying the Role of Stochasticity in the Development of Autoimmune Disease.

Authors:
Lindsay B Nicholson Konstantin B Blyuss Farzad Fatehi

Cells 2020 04 2;9(4). Epub 2020 Apr 2.

Department of Mathematics, University of York, York YO10 5DD, UK.

In this paper, we propose and analyse a mathematical model for the onset and development of autoimmune disease, with particular attention to stochastic effects in the dynamics. Stability analysis yields parameter regions associated with normal cell homeostasis, or sustained periodic oscillations. Variance of these oscillations and the effects of stochastic amplification are also explored. Theoretical results are complemented by experiments, in which experimental autoimmune uveoretinitis (EAU) was induced in B10.RIII and C57BL/6 mice. For both cases, we discuss peculiarities of disease development, the levels of variation in T cell populations in a population of genetically identical organisms, as well as a comparison with model outputs.
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http://dx.doi.org/10.3390/cells9040860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226790PMC
April 2020
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