Multiple plasmocytoma - a rare case of three atypical presentations

Introduction: The solitary plasmocytoma represents less than 5% of all plasma cell neoplasms. The multiple plasmocytoma is 20 times rarer than solitary plasmocytoma. Progression to multiple myeloma is common. Methods: Case study Results: We report a very rare case of multiple plasmocytoma developed in the bone and two atypical sites - renal and gastric. The patient was treated with radiotherapy, surgery and chemotherapy. The case is presented due to its rarity. Conclusion: The high risk of a progression towards a multiple myeloma justifies a comprehensive initial assessment and regular monitoring of all plasmocytomas. The management of a patient with multiple plasmocytomas will be determined by the sensitivity and the site of the tumor

Hipertensiunea pulmonară primară

Este prezentat un caz (bărbat, 26 de ani) de hipertensiune pulmonară severă, complicată cu suferinţa ventriculară dreaptă, clasa funcţional 2/3 NYHA. Investigaţiile efectuate au fost neinvazive şi invazive. Diagnosticul clinic de suferinţă al ventriculului drept era susţinut electrocardiografic; radiografia toracică era compatibilă cu diagnosticul de HP. Singura metoda noninvazivă care a stabilit cu certitudine diagnosticul de HP a fost examenul ecocardiografic - era esenţial pentru diagnosticarea şi aprecierea severităţii hipertensiunii pulmonare. Scintigrafia pulmonară de perfuzie a exclus embolismul pulmonar. Au fost excluse multiple cauze cardiace care pot determina creşterea presiunii sistolice in artera pulmonară (hipertensiunea pulmonară secundară). Cateterismul cardiac a confirmat hipertensiunea pulmonară şi tipul de hipertensiune. Evoluţia imediată ar putea fi relativ bună, prognosticul tardiv este nefavorabil, dar tratamentul medicamentos este limitat. Complicaţiile în viitor depind direct de accentuarea hipertensiunii pulmonare şi de agravarea insuficienţei ventriculare drepte

Familial epilepsy – clinical-epidemiological characteristics and next-generation sequencing in the Republic of Moldova’s population

Background: Although several theories are implicated in the origin of epilepsy, its cause is still unknown in about 50% of cases. To associate a gene with epilepsy for the first time, families with multiple affected members are needed. The aim of our study is carrying out a clinical-genetic study of multiplex families from the Republic of Moldova, for estimating the genetic biomarkers and establishing their weight in epileptogenesis. Material and methods: An epidemiological, descriptive study (2018 – 2023) started with lancing a National Epilepsy Registry for multiplex families. Whole Exome Sequencing (WES) was performed on the first 11 families. Preliminary statistical methods were applied. Results: Our National registry counts now 74 families including 186 members. First 11 families’ WES results showed that the most involved chromosomes with candidate epileptogenic variants are the 1, 2, 3, 4, 7, 12, and 17. Top affected genes are the AUTS2, ATXN1, KCNMA1, IRF2BPL, SUFU, CENPE, SACS, EDC3, RYR2, ANKRD11, PTPRD, CHL1, MYH1, CC2D2A, LIAS, TBCD and AARS. From all the detected variants, 20.3% were classified as deleterious and probably pathogenic, 38.9% were marked as tolerated and benign and 22.8% were variants of unknown significance (VUS). Conclusions: Our results represent an absolute novelty for our country, such studies having been never previously performed. Subjects continue to be recruited and the National Register of presumed genetic epilepsy is constantly being updated

Înțelegerea caracteristicilor genetice ale familiilor multiplex cu epilepsie din Moldova folosind secvențierea întregului exom

Laboratory of Neurobiology and Medical Genetics, Department of Neurology no. 2, Nicolae Testemitanu SUMP, Department of Neuromuscular Diseases, Institute of Neurology, UCLBackground. Although several theories have been proposed to explain the origin of epilepsy, its cause is still unknown in about half of cases. In most cases, the link between a gene and the condition is not yet clear and studying multiple affected members of a family is needed. Objective of the study. To estimate the genetic biomarkers of multiplex epilepsy families from the Republic of Moldova and their role in epileptogenesis. Material and Methods. Whole Exome Sequencing (WES) was performed on the first 11 epilepsy families from a newly started National Epilepsy Registry. It was followed by a descriptive analysis of the data. Results. Our National registry counts now 74 families including 186 members. WES results of the first 11 Moldovan multiplex epilepsy families revealed that the most prevalent epileptogenic variants are those involving the 1, 2, 3, 4, 7, 12, and 17 chromosomes. Top genes affected by candidate variants include AUTS2, ATXN1, KCNMA1, IRF2BPL, SUFU, CENPE, SACS, EDC3, RYR2, ANKRD11, PTPRD, CHL1, MYH1, CC2D2A, LIAS, TBCD and AARS. From the detected variants, almost 23 % were classified as of unknown significance (VUS), 20% were identified as deleterious and probably pathogenic by two known predictors (SIFT and Polyphen), and 39% are known as tolerated and benign. Conclusion. The preliminary results of our studies are truly revolutionary, as they represent an absolute novelty for the country and the eastern “genetically virgin” territories.Introducere. Deși au fost propuse mai multe teorii pentru a explica originea epilepsiei, cauza sa rămâne necunoscută în aproximativ jumătate dintre cazuri. În majoritatea acestora, legătura dintre genă și afecțiune nu este clară și se impune studierea mai multor membri afectați ai unei familii. Scopul lucrării. De a estima biomarkerii genetici ai familiilor multiplex cu epilepsie din Republica Moldova și rolul lor în epileptogeneză. Material și Metode. Secvențierea întregului exom (WES) a fost efectuată în cadrul primelor 11 familii cu epilepsie dintr-un Registru Național nou constituit. Ulterior, a fost efectuată o analiză statistică descriptivă a datelor obținute. Rezultate. Registrul nostru național numără acum 74 de familii și 186 de membri. Rezultatele WES ale primelor 11 familii cu epilepsie multiplex au arătat că cele mai răspândite variante epileptogene sunt cele care implică cromozomii 1, 2, 3, 4, 7, 12 și 17. Genele de top afectate de variantele candidate include: AUTS2, ATXN1, KCNMA1, IRF2BPL, SUFU, CENPE, SACS, EDC3, RYR2, ANKRD11, PTPRD, CHL1, MYH1, CC2D2A, LIAS, TBCD și AARS. Dintre variantele detectate, doi predictori de patogenitate cunoscuți (SIFT și Polyphen) au clasificat aproape 23% ca având o semnificație necunoscută (VUS), 20% ca dăunătoare și probabil patogene, iar 39% ca fiind tolerate și benigne. Concluzii. Rezultatele preliminare ale studiilor noastre sunt cu adevărat revoluționare, întrucât reprezintă o noutate absolută atât pentru țară, cât și pentru teritoriile estice, considerate „virgine genetic”

Aplicabilitatea testării genetice de nouă generație în epilepsie prin prisma secvențierii întregului exom

Background. Epilepsy affects around 1% of the general population. With strong genetic contributions >50% of cases still remain undiagnosed. Recently, novel genetic testing lead to massive gene discovery, epilepsy included. Objective of the study. Our review highlights the progress in the field of epilepsy genetics and discusses how the genetic architecture of common epilepsies is starting to be unraveled. Material and Methods. Relevant studies were searched using key-words: epilepsy genetics, next-generation sequencing (NGS), whole exome sequencing (WES) – in the PubMed and Google Scholar databases. A study was included if at least 2 of the key-words matched. Results. Since the 1995 finding of CHRNA4 mutation, more than 500 genes were estimated to play a role in epilepsy. To date, WES’s diagnostic rate varies from 12,5% in focal epilepsies to 33% in overall cohorts. The remaining undiagnosed forms are likely multifactorial. However, NGS introduces new challenges, yet to be resolved. Conclusion. Over the past decade, WES studies have increasingly been used to uncover the role of the coding genetic material in the human genome, being a prerequisite for personalized treatment approaches and reducing the epilepsy patient’s “diagnostic odyssey”. Introducere. Epilepsia afectează aproximativ 1% din populația generală. Cu contribuții genetice marcante, >50% din cazuri rămân încă nediagnosticate. Recent, testarea genetică de nouă generație a dus la descoperirea masivă de noi gene, inclusiv în epilepsie. Scopul lucrării. Review-ul nostru evidențiază progresul în domeniul geneticii epilepsiei și discută modul în care arhitectura genetică a epilepsiilor comune începe treptat să fie dezvăluită. Material și Metode. Studii relevante au fost căutate folosind cuvintele-cheie: genetica epilepsiei, secvențierea de nouă generație (NGS), secvențierea întregului exom (WES) - în bazele de date PubMed și Google Scholar. Un studiu a fost inclus dacă au corespuns cel puțin 2 dintre cuvintele-cheie. Rezultate. De la constatarea în 1995 a mutației în gena CHRNA4, peste 500 de gene au fost descrise având un rol în epilepsie. Până în prezent, rata diagnosticului în WES variază de la 12, 5% în epilepsiile focale la 33% în cohortele generale. Cazurile rămase nediagnosticate sunt probabil multifactoriale. Cu toate acestea, NGS lansează noi provocări, care încă necesită să fie rezolvate. Concluzii. În ultimul deceniu, WES a fost utilizată tot mai mult pentru a descoperi rolul secvențelor codificatoare din genomul uman, fiind o premisă indispensabilă pentru abordarea personalizată și reducerea „odiseei diagnostice” a pacientului cu epilepsie

Applicability of next generation genetic testing in epilepsy through whole exome sequencing

Laboratory of Neurobiology and Medical Genetics, Department of Neurology No 2 Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, the Republic of Moldova, Department of Neuromuscular Diseases, Queen Square Institute of Neurology, University College London, Great Britain, The 75th anniversary of Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova (1945-2020)Background: Epilepsy affects around 1% of the general population. With already acknowledged strong genetic contributions, >50% of epilepsy cases still remain undiagnosed. This is primordially due to the multifactorial condition of epilepsy that makes it a challenge to select the optimal genetic test for each specific case. Recently, next-generation sequencing (NGS) led to massive gene discovery, including epilepsy that also imposed serious financial burdens on healthcare systems. This study review highlights the progress in the field of epilepsy genetics and argues on how the genetic architecture of common epilepsies is progressively being unraveled. Since the 1995 finding of CHRNA4 mutation, more than 500 genes were estimated to play a significant role in epilepsy. To date, the majority of diagnostic genetic testing is conducted in the pediatric population, while the utility of such testing is less well understood in adults with epilepsy. A broad range in the diagnostic rate of NGS, especially of the Whole Exome Sequencing (WES), in epilepsy has been described. However, NGS introduces new challenges, yet to be resolved. Conclusions: Epilepsy’s genetic background is nowadays undeniable; however, the complexity of this condition makes it difficult to be solved. WES has increasingly been used to uncover the role of the coding genetic material in the human genome and is nowadays considered one of the most costeffective genetic tests for epilepsy, being a prerequisite for personalized treatment approaches and for reducing the epilepsy patient’s “diagnostic odyssey”

Aplicarea clinică a marcherilor cardiaci în sindromul coronarian acut

Marcherii cardiaci au devenit un element esenţial şi indispensabil, de o importanţă majoră în evaluarea pacienţilor cu sindroame coronariene acute. Utilitatea clinică a determinărilor biochimice la pacienţii cu sindrom coronarian acut este dată, pe de o parte, de diagnosticarea infarctului miocardic acut la pacienţii cu electrocardiogramă fără modifi cări sugestive sau cu electrocardiogramă difi cil de interpretat, datorită unor blocuri ventriculare preexistente sau pasing ventricular; pe de altă parte, de confi rmarea precoce a infarctului miocardic acut la pacienţii cu electrocardiograma sugestivă pentru infarct miocardic acut şi stratifi carea riscului

Multiple system atrophy

This is a practical guide to diagnosing and managing multiple system atrophy (MSA). We explain the newly published Movement Disorders Society Consensus Diagnostic Criteria, which include new ‘Clinically Established MSA’ and ‘Possible Prodromal MSA’ categories, hopefully reducing time to diagnosis. We then highlight the key clinical features of MSA to aid diagnosis. We include a list of MSA mimics with suggested methods of differentiation from MSA. Lastly, we discuss practical symptom management in people living with MSA, including balancing side effects, with the ultimate aim of improving quality of life

Drug-resistant epilepsy: modern concepts, integrative mechanisms, and therapeutic advances

Background: Drug-resistant epilepsy is the cause of severe disability. Multiple questions remain unanswered both in terms of pathogenesis and therapeutic management. For this narrative review, PubMed database and Infomedica library were searched by using “drug-resistance in epilepsy” and “treatment of drug-resistant epilepsy” as key words. The following filters were applied: “Clinical Trial”, “Meta-analysis”, “Multicenter Study”, and “Randomized Controlled Trial”, covering the period of 01.01.2005–06.01.2021.Several hypotheses have been proposed, i.e., pharmacokinetic, intrinsic severity, gene, target, transporter, and neural network hypotheses. Many controlled trials showed different results in terms of seizure control after combined methods of therapies. Immunotherapy, palliative epilepsy surgery alone or associated with neurostimulation procedures including vagus nerve, trigeminal nerve, or deep brain stimulation may be efficient, however, seizure freedom is not always achieved. Genetic epilepsies might benefit from gene and exosome therapy; however, further studies are needed to verify their safety. Conclusions: Neuroscience of drug-resistant epilepsy faces many challenges. Inflammatory mediators, biomarkers, and genes might allow the identification of new treatment targets, contribute to an earlier diagnosis, and assess the clinical outcomes

Not to Miss: Intronic Variants, Treatment, and Review of the Phenotypic Spectrum in VPS13D-Related Disorder

VPS13D is one of four human homologs of the vacuolar sorting protein 13 gene (VPS13). Biallelic pathogenic variants in the gene are associated with spastic ataxia or spastic paraplegia. Here, we report two patients with intronic pathogenic variants: one patient with early onset severe spastic ataxia and debilitating tremor, which is compound-heterozygous for a canonical (NM_018156.4: c.2237−1G > A) and a non-canonical (NM_018156.4: c.941+3G>A) splice site variant. The second patient carries the same non-canonical splice site variant in the homozygous state and is affected by late-onset spastic paraplegia. We confirmed altered splicing as a result of the intronic variants and demonstrated disturbed mitochondrial integrity. Notably, tremor in the first patient improved significantly by bilateral deep brain stimulation (DBS) in the ventralis intermedius (VIM) nucleus of the thalamus. We also conducted a literature review and summarized the phenotypical spectrum of reported VPS13D-related disorders. Our study underscores that looking for mutations outside the canonical splice sites is important not to miss a genetic diagnosis, especially in disorders with a highly heterogeneous presentation without specific red flags