Anatomic and MRI bases for pontine infarctions with patients presentation

Objectives: There are scarce data regarding pontine arteries anatomy, which is the basis for ischemic lesions following their occlusion. The aim of this study was to examine pontine vasculature and its relationships with the radiologic and neuro-logic features of pontine infarctions. Materials and methods: Branches of eight basilar arteries and their twigs, including the larger intrapontine branches, were microdis-sected following an injection of a 10% mixture of India ink and gelatin. Two addi-tional brain stems were prepared for microscopic examination after being stained with luxol fast blue and cresyl violet. Finally, 30 patients with pontine infarctions underwent magnetic resonance imaging (MRI) in order to determine the position and size of the infarctions. Results: The perforating arteries, which averaged 5.8 in number and 0.39 mm in diameter, gave rise to paramedian and anteromedial branches, and also to anterolateral twigs (62.5%). The longer leptomeningeal and cere-bellar arteries occasionally gave off perforating and anterolateral twigs, and either the lateral or posterior branches. Occlusion of some of these vessels resulted in the para-median (30%), anterolateral (26.7%), lateral (20%), and combined infarctions (23.3%), which were most often isolated and unilateral, and rarely bilateral (10%). They were located in the lower pons (23.3%), middle (10%) or rostral (26.7%), or in two or three portions (40%). Each type of infarction usually produced characteristic neurologic signs. The clinical significance of the anatomic findings was discussed. Conclusions: There was a good correlation between the intrapontine vascular territories, the position, size and shape of the infarctions, and the type of neurologic manifestations. (c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Peer reviewe

Anatomic and MRI bases for medullary infarctions with patients' presentation

Objective: There is a low incidence of the medullary infarctions and sparse data about the vascular territories, as well as a correlation among the anatomic, magnetic resonance imaging (MRI) and neurologic signs. Materials and methods: Arteries of the 10 right and left sides of the brain stem were injected with India ink, fixed in formalin and microdissected. The enrolled 34 patients with medullary infarctions underwent a neurologic, MRI and Doppler examination. Results: Four types of the infarctions were distinguished according to the involved vascular territories. The isolated medial medullary infarctions (MMIs) were present in 14.7%. The complete MMIs comprised one bilateral infarction (2.9%), whilst the incomplete and partial MMIs were observed in 5.9% and 8.9%, respectively. The anterolateral infarctions (ALMIs) were very rare (2.9%). The complete and incomplete lateral infarctions (LMIs), noted in 35.3%, comprised 11.8% and 23.6%, respectively, that is, the anterior (5.9%), posterior (8.9%), deep (2.9%), and peripheral (5.9%). Dorsal ischemic lesions (DMIs) occurred in 11.8%, either as a complete (2.9%), or isolated lateral (5.9%) or medial infarctions (2.9%). The remaining ischemic regions belonged to various combined infarctions of the MMI, ALMI, LMI and DMI (35.3%). The infarctions most often affected the upper medulla (47.1%), middle (11.8%), or both (29.5%). Several motor and sensory signs were manifested following infarctions, including vestibular, cerebellar, ocular, sympathetic, respiratory and auditory symptoms. Conclusions: There was a good correlation among the vascular territories, MRI ischemia features, and neurologic findings regarding the medullary infarctions.Peer reviewe

Respiratory onset in an ALS family with L144F SOD1mutation

International audienceFamilial amyotrophic lateral sclerosis (FALS) cases linked to SOD1 mutations may sometimes present with unusual clinical features such as pure lower motor neuron involvement or sensory signs. We describe a FALS pedigree with the L144F SOD1 mutation in which all cases had respiratory involvement as a first symptom. Although atypical clinical features are not rare in ALS families, this is the first pedigree with respiratory-onset in three affected members. This unusual presentation led to delayed diagnosis in the proband and highlights the fact that respiratory-onset can occur in familial ALS cases carrying SOD1 mutation

The SOD1-mediated ALS phenotype shows a decoupling between age of symptom onset and disease duration

Superoxide dismutase (SOD1) gene variants may cause amyotrophic lateral sclerosis, some of which are associated with a distinct phenotype. Most studies assess limited variants or sample sizes. In this international, retrospective observational study, we compare phenotypic and demographic characteristics between people with SOD1-ALS and people with ALS and no recorded SOD1 variant. We investigate which variants are associated with age at symptom onset and time from onset to death or censoring using Cox proportional-hazards regression. The SOD1-ALS dataset reports age of onset for 1122 and disease duration for 883 people; the comparator population includes 10,214 and 9010 people respectively. Eight variants are associated with younger age of onset and distinct survival trajectories; a further eight associated with younger onset only and one with distinct survival only. Here we show that onset and survival are decoupled in SOD1-ALS. Future research should characterise rarer variants and molecular mechanisms causing the observed variability

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p

Cytokine Gene Polymorphisms in Patients with Chronic Inflammatory Demyelinating Polyneuropathy

Innate and adaptive immune responses exert their role in CIDP pathogenesis through cytokine production. Single-nucleotide polymorphisms (SNPs) may alter cytokine gene expression, with a potential influence on the pathogenesis of autoimmune diseases. However, cytokine gene SNPs have not been assessed in CIDP patients yet. We assessed functional SNPs in the genes encoding IL-10 (rs1800896, rs1800871, rs1800872 and rs3024505), IL-6 (rs1800795), TNF (rs1800629 and rs361525), IL-12B (rs3212227), IFN-γ (rs2430561), GM-CSF (rs25882) and IL-17F (rs11465553) in a cohort of 88 CIDP patients and 486 healthy controls (HCs) via qPCR. We found an association of SNP in the IL10 promotor and CIDP occurrence. Major homozygotes (AA) were more frequent in the HCs compared to CIDP patients (p = 0.049), but the GA genotype prevailed among the patients (p = 0.032). A lower frequency of the C allele was observed for rs1800871 and rs1800872 in CIDP patients compared to the HCs (p = 0.048). A higher proportion of A carriers at position -1082 (rs1800896) (presumed to be a low IL-10 producer) was noted in patients with milder disability (low INCAT). All mild-INCAT patients were C carriers for rs1800871 and rs1800872 in IL10 (p = 0.038). Furthermore, the IL6 rs1800795 GG genotype was more frequent in patients (p = 0.049) and the CG heterozygote in the HCs (p = 0.013). Among the CIDP patients, being a G carrier for this SNP was associated with a higher frequency of type 2 diabetes (T2D) compared to being a non-carrier (p = 0.032). Our data indicate a possible association of the IL10 and IL6 SNPs with CIDP, but also with disease severity and T2D occurrence. Given the paucity of CIDP patients, multicentric studies are necessary to draw definite conclusions on these associations

Association between the SMN2 gene copy number and clinical characteristics of patients with spinal muscular atrophy with homozygous deletion of exon 7 of the SMN1 gene

Background/Aim. Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by degeneration of alpha motor neurons in the spinal cord and the medulla oblongata, causing progressive muscle weakness and atrophy. The aim of this study was to determine association between the SMN2 gene copy number and disease phenotype in Serbian patients with SMA with homozygous deletion of exon 7 of the SMN1 gene. Methods. The patients were identified using regional Serbian hospital databases. Investigated clinical characteristics of the disease were: patients' gender, age at disease onset, achieved and current developmental milestones, disease duration, current age, and the presence of the spinal deformities and joint contractures. The number of SMN1 and SMN2 gene copies was determined using real-time polymerase chain reaction (PCR). Results. Among 43 identified patients, 37 (86.0\%) showed homozygous deletion of SMN1 exon 7. One (2.7\%) of 37 patients had SMA type I with 3 SMN2 copies, 11(29.7\%) patients had SMA type II with 3.1 +/- 0.7 copies, 17 (45.9\%) patients had SM\_A type III with 3.7 +/- 0.9 copies, while 8 (21.6\%) patients had SMA type IV with 4.2 +/- 0.9 copies. There was a progressive increase in the SMN2 gene copy number from type II towards type IV (p < 0.05). A higher SMN2 gene copy number was associated with better current motor performance (p < 0.05). Conclusion. In the Serbian patients with SMA, a higher SMN2 gene copy number correlated with less severe disease phenotype. A possible effect of other phenotype modifiers should not be neglected.Hungary-Serbia IPA Cross-Border Co-Operation Program: Research Cooperation to Improve Symptoms in Neurological Disorders, and Quality of Life of Patients {[}HU-SRB/0901/214/052

Validation of the Serbian version of inflammatory Rasch-built overall disability scale in patients with chronic inflammatory demyelinating polyradiculoneuropathy

Inflammatory Rasch-built overall disability scale (I-RODS) seems to be a valid activity measure for use in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Our aim was to translate and validate the I-RODS for use in CIDP patients from Serbia. Study comprised 83 patients diagnosed with CIDP. I-RODS was translated and cross-culturally validated using the standard guidelines. Following scales were also administered: Medical Research Council (MRC) sum score, Inflammatory Neuropathy Cause and Treatment (INCAT) sensory and disability scores, Krupp's Fatigue Severity Scale, Beck Depression Inventory, Visual Analogue Scale for pain, and health survey-36 (SF-36) as a quality of life measure. According to the I-RODS, significant proportion of our patients reported that "running" (51%), "dancing" (41%), and "standing for hours" (40%) were impossible tasks to perform, while "teeth brushing" (94%), "eating" (88%), and "reading a newspaper/book" (82%) were noted as the easiest items. Patients with more muscle weakness (lower MRC sum score) and more severe INCAT sensory score had lower I-RODS score (P 1 (P <.01). I-RODS score correlated with the total SF-36 score (rho = +0.73, P <.01), as well as with all SF-36 domain scores. Serbian version of the I-RODS seems to be a valid activity measure for use in CIDP patients. I-RODS was able to assess different levels of disability, it was in association with impairment measures, INCAT disability scale and quality of life. Further studies are needed to assess its responsiveness