Genotype-specific spinal cord damage in spinocerebellar ataxias: an ENIGMA-Ataxia study.

BACKGROUND: Spinal cord damage is a feature of many spinocerebellar ataxias (SCAs), but well-powered in vivo studies are lacking and links with disease severity and progression remain unclear. Here we characterise cervical spinal cord morphometric abnormalities in SCA1, SCA2, SCA3 and SCA6 using a large multisite MRI dataset. METHODS: Upper spinal cord (vertebrae C1-C4) cross-sectional area (CSA) and eccentricity (flattening) were assessed using MRI data from nine sites within the ENIGMA-Ataxia consortium, including 364 people with ataxic SCA, 56 individuals with preataxic SCA and 394 nonataxic controls. Correlations and subgroup analyses within the SCA cohorts were undertaken based on disease duration and ataxia severity. RESULTS: Individuals in the ataxic stage of SCA1, SCA2 and SCA3, relative to non-ataxic controls, had significantly reduced CSA and increased eccentricity at all examined levels. CSA showed large effect sizes (d>2.0) and correlated with ataxia severity (r<-0.43) and disease duration (r<-0.21). Eccentricity correlated only with ataxia severity in SCA2 (r=0.28). No significant spinal cord differences were evident in SCA6. In preataxic individuals, CSA was significantly reduced in SCA2 (d=1.6) and SCA3 (d=1.7), and the SCA2 group also showed increased eccentricity (d=1.1) relative to nonataxic controls. Subgroup analyses confirmed that CSA and eccentricity are abnormal in early disease stages in SCA1, SCA2 and SCA3. CSA declined with disease progression in all, whereas eccentricity progressed only in SCA2. CONCLUSIONS: Spinal cord abnormalities are an early and progressive feature of SCA1, SCA2 and SCA3, but not SCA6, which can be captured using quantitative MRI.

Optic Disc and Retinal Architecture Changes in Patients with Spinocerebellar Ataxia Type 2.

BACKGROUND: ATXN2 is the causative gene of spinocerebellar ataxia type 2 (SCA2) and has been implicated in glaucoma pathogenesis. Therefore, studying ocular changes in SCA2 could uncover clinically relevant changes. OBJECTIVE: The aim was to investigate optic disc and retinal architecture in SCA2. METHODS: We evaluated 14 patients with SCA2 and 26 controls who underwent intraocular pressure measurement, fundoscopy, and macular and peripapillary spectral domain optical coherence tomography (SD-OCT). We compared SD-OCT measurements in SCA2 and controls, and the frequency of glaucomatous changes among SCA2, controls, and 76 patients with other SCAs (types 1, 3, 6, and 7). RESULTS: The macula, peripapillary retinal nerve fiber and inner plexiform layers were thinner in SCA2 than in controls. Increased cup-to-disc ratio was more frequent in SCA2 than in controls and other SCAs. CONCLUSIONS: Ocular changes are part of SCA2 phenotype. Future studies should further investigate retinal and optic nerve architecture in this disorder.

Fermentation of whey-derived matrices by Kluyveromyces marxianus: alcoholic beverage development from whey and fruit juice mixes.

This research paper addresses the hypotheses that Kluyveromyces marxianus can be cultured with good alcohol production on different whey-derived matrices, and that the fermented product can be used in order to develop alcoholic beverages with acceptable sensory characteristics by mixtures with yeast-fermented fruit-based matrices. Growth and fermentative characteristics of Kluyveromyces marxianus LFIQK1 in different whey-derived matrices were explored by culturing (24 h, 30°C) on reconstituted whey, demineralized whey, heat-treated whey and milk permeate media. High lactose consumption, ethanol production and yield were observed. Reconstituted whey matrix was selected for mixing with orange or strawberry juices fermented using Saccharomyces cerevisiae to obtain alcoholic beverages (W-OR and W-ST, respectively). Consumer evaluation of beverages was performed using acceptability and Check-All-That-Apply (CATA) questions. Good acceptance was observed, significantly higher for W-ST than for W-OR. CATA questions gave information about organoleptic characteristics of beverages. Penalty analysis showed W-R and W-ST were positively associated with smooth/refreshing and fruity/natural, respectively. Liking was represented, accordingly with penalty analysis, by natural/refreshing. A novel alternative for utilization of whey and whey-related matrices by alcoholic beverages production with natural ingredients is presented.

Plant Extracts and Phytochemicals from the Asteraceae Family with Antiviral Properties.

Asteraceae (Compositae), commonly known as the sunflower family, is one of the largest plant families in the world and includes several species with pharmacological properties. In the search for new antiviral candidates, an in vitro screening against dengue virus (DENV) was performed on a series of dichloromethane and methanolic extracts prepared from six Asteraceae species, including Acmella bellidioides, Campuloclinium macrocephalum, Grindelia pulchella, Grindelia chiloensis, Helenium radiatum, and Viguiera tuberosa, along with pure phytochemicals isolated from Asteraceae: mikanolide (1), eupatoriopicrin (2), eupahakonenin B (3), minimolide (4), estafietin (5), 2-oxo-8-deoxyligustrin (6), santhemoidin C (7), euparin (8), jaceidin (9), nepetin (10), jaceosidin (11), eryodictiol (12), eupatorin (13), and 5-demethylsinensetin (14). Results showed that the dichloromethane extracts of C. macrocephalum and H. radiatum and the methanolic extracts prepared from C. macrocephalum and G. pulchella were highly active and selective against DENV-2, affording EC50 values of 0.11, 0.15, 1.80, and 3.85 µg/mL, respectively, and SIs of 171.0, 18.8, >17.36, and 64.9, respectively. From the pool of phytochemicals tested, compounds 6, 7, and 8 stand out as the most active (EC50 = 3.7, 3.1, and 6.8 µM, respectively; SI = 5.9, 6.7, and >73.4, respectively). These results demonstrate that Asteraceae species and their chemical constituents represent valuable sources of new antiviral molecules.

Sarcoid optic neuropathy.

A 45-year-old woman presented with sudden complete vision loss in her left eye and retroorbital pain worsened by eye movements. A previous milder episode of vision loss had occurred in the same eye 1 year before, with complete recovery after high-dose intravenous methylprednisolone. She had no light perception in the left eye with a swollen optic disc, but with a normal right optic disc. There were no systemic manifestations or infections. MR scan of the brain showed extensive enlargement and enhancement of the left optic nerve and optic chiasm. After excluding infections and autoimmune markers, a left optic nerve biopsy confirmed non-caseating granulomas, leading to a diagnosis of neurosarcoidosis.

Similarities of Geobacillus bacteria based on their profiles of antimicrobial susceptibility in milk samples.

The genus Geobacillus is composed of thermophilic bacteria that exhibit diverse biotechnological potentialities. Specifically, Geobacillus stearothermophilus is included as a test bacterium in commercial microbiological inhibition methods, although it exhibits limited sensitivity to aminoglycosides, macrolides, and quinolones. Therefore, this article evaluates the antibiotic susceptibility profiles of five test bacteria (G. stearothermophilus subsp. calidolactis C953, Geobacillus thermocatenulatus LMG 19007, Geobacillus thermoleovorans LMG 9823, Geobacillus kaustophilus DSM 7263 and Geobacillus vulcani 13174). For that purpose, the minimum inhibitory concentrations (MICs) of 21 antibiotics were determined in milk samples for five test bacteria using the radial diffusion microbiological inhibition method. Subsequently, the similarities between bacteria and antibiotics were analyzed using cluster analysis. The dendrogram of this multivariate analysis shows an association between a group formed by G. thermocatenulatus and G. stearothermophilus and another by G. thermoleovorans, G. kaustophilus and G. vulcani. Finally, future microbiological methods could be developed in microtiter plates using G. thermocatenulatus as test bacterium, as it exhibits similar sensitivities to G. stearothermophilus. Conversely, G. vulcani, G. thermoleovorans and G. kaustophilus show higher MICs than G. thermocatenulatus.

Enzymatic synthesis of amlodipine amides and evaluation of their anti-Trypanosoma cruzi activity.

Advancing with our project about the development of new antiparasitic agents, we have enzymatically synthesized a series of amides derived from amlodipine, a calcium channel blocker used as an antihypertensive drug. Through lipase-catalyzed acylation with different carboxylic acids, nineteen amlodipine derivatives were obtained, eighteen of which were new compounds. To optimize the reaction conditions, the influence of several reaction parameters was analyzed, finding different requisites for aliphatic carboxylic acids and phenylacetic acids. All synthesized compounds were evaluated as antiproliferative agents against Trypanosoma cruzi, the etiological agent of American trypanosomiasis (Chagas' disease). Some of them showed significant activity against the amastigote form of T. cruzi, the clinically relevant form of the parasite. Among synthesized compounds, the derivatives of myristic and linolenic acids showed higher efficacy and lower cytotoxicity. These results added to the advantages shown by the enzymatic methodology, such as mild reaction conditions and low environmental impact, making this approach a valuable way to synthesize these amlodipine derivatives with an application as promising antiparasitic agents.

Post-transplant lymphoproliferative disorder myeloradiculopathy.

A 56-year-old woman developed progressive subacute lower limb weakness with sensory and autonomic abnormalities. She had received a living-donor kidney transplantation 21 years before for end-stage chronic kidney disease and took mycophenolate mofetil and prednisolone. MR scan of the spinal cord showed bilateral cauda equina gadolinium enhancement and MR scan of the brain showed enhancing nodular hyperintensities in the internal capsule and globus pallidus. Cerebrospinal fluid (CSF) showed a pleocytosis with extremely low glucose, and positive DNA-PCR for Epstein-Barr virus. Her condition worsened despite empirically guided antimicrobial treatment. CSF immunophenotyping later identified mature, clonal B lymphocytes of large size, expressing CD19, CD20, CD200 antigens, and kappa light chain immunoglobulin, with absent CD5 and CD10 expression. We diagnosed a myeloradiculopathy from a monomorphic post-transplant lymphoproliferative disorder. This condition occurs after kidney transplantation and falls on the lymphoma spectrum. We review its clinical features, diagnosis and management.

Ischaemic lumbosacral plexopathy following aortic dissection.

A 57-year-old man was diagnosed with acute myocardial infarction and Stanford type A aortic dissection that had spread to the common iliac arteries. He underwent a Bentall procedure for vascular repair. Immediately after surgery, he developed numbness and severe weakness in his left leg. On examination, he had hypotonia, absent deep tendon reflexes, weakness in the left leg (Medical Research Council (MRC) scale for muscle strength - 0/5 distal, 3/5 proximal) and reduced sensation in the left leg. Electromyography confirmed subacute involvement of the left lumbar and lumbosacral plexus. MR scan of the lumbar plexus showed diffuse muscle oedema involving the left gluteus maximus. We diagnosed ischaemic lumbosacral plexopathy secondary to extensive aorta dissection and internal iliac artery occlusion. We discuss the clinical features of ischaemic plexopathy and the diagnostic approach and review the vascular anatomy of the lumbosacral plexus.

Physical function and physical activity in adults with X-linked hypophosphatemia.

We described physical function and activity in UK adults with X-linked hypophosphatemia (XLH). Our data indicate that low physical activity and impaired mobility are common in adults with XLH. Deficits in lower limbs muscle power and functional capacity contribute to the loss of physical function in adults with XLH. INTRODUCTION: There is a dearth of literature on physical function and physical activity in adults with X-linked hypophosphatemia (XLH). We described muscle strength and power, functional capacity, mobility and physical activity level and explored the relationships among these variables in adults with XLH. METHODS: Participants were recruited as part of a UK-based prospective cohort study, the RUDY Study. They underwent a clinical visit and physical examination, including assessment of handgrip strength, jump power (mechanography), six-minute walk test (6MWT) and short physical performance battery (SPPB), and completed the International Physical Activity Questionnaire (IPAQ). Performance data were analysed using parametric and non-parametric tests, whereas correlations were assessed by univariate analysis. RESULTS: Twenty-six adults with XLH (50% males) with a mean age of 44 ± 16.1 years were recruited. Jump power and 6MWT distances (p < 0.0001) were 54.4% and 38.6% lower respectively in individuals with XLH compared with normative values. These deficits were not associated with age or sex. Handgrip strength values were similar to expected values. Deficits in muscle power were more pronounced than those reported at 6MWT (p < 0.0001). Univariate analysis revealed only a correlation between total physical activity and muscle power (r = 0.545, p = 0.019). CONCLUSIONS: Adults with XLH have a marked deficit in lower limb muscle power and a reduced functional capacity, with a high incidence of impaired mobility and inactivity. In addition to metabolic effects of XLH, low physical activity may contribute to deficits in lower limb power. Further studies are required to develop novel treatment approaches to improve physical function and mobility.

Characterization of Retinal Architecture in Spinocerebellar Ataxia Type 3 and Correlation with Disease Severity.

BACKGROUND: Neurodegeneration affects the brain and peripheral nervous system in spinocerebellar ataxia type 3 (SCA3). As the retina is also involved, studying the retinal architecture in a cohort of patients could reveal clinically relevant biomarkers. OBJECTIVE: The aim is to investigate retinal architecture in SCA3 to identify potential biomarkers. METHODS: We evaluated 38 patients with SCA3 and 25 healthy age-matched controls, who underwent visual acuity assessment, intraocular pressure measurement, and fundoscopy and macular and peripapillary spectral domain optical coherence tomography (SD-OCT). We measured the peripapillary retinal nerve fiber layer (pRNFL) thickness in each quadrant of the temporal-superior-nasal-inferior-temporal chart and the macular layer thicknesses in each sector of the inner circle of the Early Treatment Diabetic Retinopathy Study (IC-ETDRS) grid. Linear regression analysis was employed to test the associations between retinal parameters and age, disease duration, CAG repeats, and SARA (Scale of the Assessment and Rating of Ataxia) and ICARS (International Cooperative Ataxia Rating Scale) scores in SCA3. RESULTS: In all sectors, except for the temporal quadrant, pRNFL was significantly thinner in SCA3 patients than in controls. Average total macular, ganglion cell layer (GCL), and inner plexiform layer (IPL) thicknesses were significantly decreased in SCA3 patients in comparison to controls. The average total macular thickness and the average thicknesses of RNFL, GCL, and IPL negatively correlated with ICARS scores, whereas average GCL and IPL thicknesses negatively correlated with SARA scores. CONCLUSIONS: The retinal ganglion cells, their dendrites, and axons are selectively affected in SCA3 patients. The RNFL, GCL, and IPL thicknesses in SD-OCT correlate with the clinical phenotype and represent potential biomarkers for future clinical trials and natural history studies. © 2021 International Parkinson and Movement Disorder Society.

RFC1-Related Disorder: In Vivo Evaluation of Spinal Cord Damage.

BACKGROUND: RFC1-related disorder is a novel heredodegenerative condition with a broad phenotypic spectrum. Its neuropathological bases are not yet fully understood, particularly regarding the pattern, extent, and clinical relevance of spinal cord (SC) damage. OBJECTIVES: The objectives were to determine the SC structural signature in RFC1-related disorder in vivo and to identify potential clinical correlates for these imaging abnormalities. METHODS: We enrolled 17 subjects with biallelic RFC1 (AAGGG)n expansions and 11 age- and sex-matched healthy controls that underwent multimodal magnetic resonance imaging SC acquisitions in a 3T Philips Achieva scanner. Both global morphometry and tract-specific analyses were then performed across all cervical levels. Between-group comparisons were assessed using nonparametric tests. RESULTS: In the patient group, mean age and disease duration were 62.9 ± 9.3 and 9.3 ± 4.0, respectively. Compared to controls, patients had remarkable SC cross-sectional area reduction along all cervical levels but anteroposterior flattening only in the lower cervical levels. There was also prominent SC gray matter atrophy. Diffusivity abnormalities were identified in the dorsal columns but not in the lateral corticospinal tracts. Disease severity did not correlate with these imaging parameters. CONCLUSION: SC damage is a hallmark of RFC1-related disorder and characterized by gray as well as white matter involvement. In particular, dorsal columns are severely and diffusely affected. The clinical correlates of these imaging abnormalities still deserve additional investigations. © 2022 International Parkinson and Movement Disorder Society.

Clinical and Genetic Characterization of Brazilian Patients with Ataxia and Oculomotor Apraxia.

BACKGROUND: Ataxia with oculomotor apraxia (AOA) is characterized by early-onset cerebellar ataxia associated with oculomotor apraxia. AOA1, AOA2, AOA3, and AOA4 subtypes may present pathogenic variants in APTX, SETX, PIK3R5, and PNKP genes, respectively. Mutations in XRCC1 have been found to cause autosomal recessive spinocerebellar ataxia-26 (SCAR26) now considered AOA5. OBJECTIVES: To examine a cohort of Brazilians with autosomal recessive cerebellar ataxia plus oculomotor apraxia and determine the frequencies of AOA subtypes through genetic investigation. METHODS: We evaluated clinical, biomarkers, electrophysiological, and radiological findings of 52 patients with AOA phenotype and performed a genetic panel including APTX, SETX, PIK3R5, PNKP, and XRCC1. RESULTS: We found pathogenic variants in SETX (15 patients), PNKP (12), and APTX (5). No mutations in PIK3R5 or XRCC1 were identified. CONCLUSIONS: AOA2 and AOA4 were the most common forms of AOA in Brazil. Mutations in PIK3R5 and XRCC1 were not part of this genetic spectrum. © 2022 International Parkinson and Movement Disorder Society.

Diagnostic Yield of Whole Exome Sequencing for Adults with Ataxia: a Brazilian Perspective.

Previous studies using whole exome sequencing (WES) have shown that a significant proportion of adult patients with undiagnosed ataxia in European and North American cohorts have a known genetic cause. Little is known about the diagnostic yield of WES in non-Caucasian ataxic populations. Herein, we used WES to investigate a Brazilian cohort of 76 adult patients with idiopathic ataxia previously screened for trinucleotide expansions in known ataxia genes. We collected clinical and radiological data from each patient. WES was performed following standard procedures. Only variants labeled as pathogenic or likely pathogenic according to American college of medical genetics and genomics (ACMG) criteria were retrieved. We determined the diagnostic yield of WES for the whole cohort and also for subgroups defined according to presence or not of pyramidal signs, peripheral neuropathy, and cerebellar atrophy. There were 41 women and 35 men. Mean age at testing was 48 years. Pyramidal signs, peripheral neuropathy, tremor, and cerebellar atrophy were found in 38.1%, 13.1%, 10.5%, and 68.3% of all subjects, respectively. Diagnostic yield of WES was 35.5%. Thirty-six distinct mutations were found in 20 different genes, determining the diagnosis of 18 autosomal recessive and 9 autosomal dominant ataxias. SACS and SPG7 were the most frequently found underlying genes. WES performed better in the subgroup with vs the subgroup without spasticity (p = 0.005). WES was diagnostic in 35.5% of cases of the Brazilian cohort of ataxia cases. These results have implications for diagnosis, genetic counseling and eventually treatment.

Dystonia, Chorea, and Ataxia: Three Challenging Cases.

Movement disorders comprise a heterogeneous and complex group of neurological disorders that increase (hyperkinetic) or decrease (hypokinetic) the speed or amplitude of movements, or disrupt their coordinated sequencing. In this article, we describe three instructive cases, exemplifying classic movement disorders, namely dystonia, chorea, and ataxia. We highlight the diagnostic approach based on clinical clues, syndromic reasoning, evaluation, and management recommendations. Each case ends with key messages for the clinicians.

Consensus in acute myeloid leukemia in Mexico.

Acute myeloid leukemia (AML) comprises a heterogeneous group of hematopoietic cell neoplasms of myeloid lineage that arise from the clonal expansion of their precursors in the bone marrow, interfering with cell differentiation, leading to a syndrome of bone marrow failure. AML is a consequence of genetic and epigenetic changes (point mutations, gene rearrangements, deletions, amplifications, and arrangements in epigenetic changes that influence gene expression) in hematopoietic precursor cells, which create a clone of abnormal cells that are capable of proliferating but cannot differentiate into mature hematopoietic cells or undergo programmed cell death. The diagnosis requires more than 20% myeloid blasts in the bone marrow and certain cytogenic abnormalities. Treatment will depend on age, comorbidities, and cytogenetic risk among the most frequent.

La leucemia mieloide aguda (LMA) comprende un grupo heterogéneo de neoplasias de células hematopoyéticas de linaje mieloide que surgen de la expansión clonal de sus precursores en la médula ósea, interfiriendo con la diferenciación celular, lo que conlleva a un síndrome de falla medular. La LMA es una consecuencia de cambios genéticos y epigenéticos (mutaciones puntuales, rearreglos de genes, deleciones, amplificaciones y arreglos en cambios epigenéticos que influyen en la expression del gen) en las células hematopoyéticas precursoras, la cual crea una clona de células anormales que son capaces de proliferar, pero no se pueden diferenciar en células hematopoyéticas maduras ni sufrir una muerte celular programada. El diagnostic requiere más del 20% de blastos mieloides en médula ósea y ciertas anormalidades citogénicas. El tratamiento dependerá de la edad, comorbilidades, riesgo citogenético entre las más frecuentes.

Physical function in UK adults with osteogenesis imperfecta: a cross-sectional analysis of the RUDY study.

We describe the physical function in adults with osteogenesis imperfecta (OI) and explored clinical and non-clinical factors related to its impairment. Our data showed that physical dysfunction is a common feature of adults with OI, varying by OI severity, and mediated by the presence and quality of pain and fatigue symptoms. INTRODUCTION: There is a paucity of data describing physical function in adults with osteogenesis imperfecta (OI). We investigated the effects of OI and its severity on physical function and explored the relationship between physical function and number of fractures and symptomatology. METHODS: Adults with OI of different types were recruited from the RUDY study, an ongoing UK-based prospective cohort study. Participants completed demographic and clinical questions and questionnaires. These assessed physical function (SF-36), mobility (EQ-5D-5L and NEADL), fatigue (FACIT-F), and pain (SF-MQ-2). Scores were compared using parametric or non-parametric statistical analyses, whereas correlations between outcomes were examined using univariate and multivariate regression analysis. RESULTS: Seventy-eight adults with OI aged 43.5 ± 14.5 years were enrolled (type I, 32; type III, 11; type IV, 10; unknown type, 26). Physical function (PCS, SF-36) was significantly lower in all participants than normative values (p < 0.001) and in type III than type I (p = 0.008). Mobility was significantly different across the types (EQ-5D-EL, p = 0.007; NEADL, p < 0.001), with type III having more severe problems, followed by types IV, unknown, and I. Physical function was associated with OI type (r = 0.26; p = 0.021), presence and quality of pain (r = - 0.57; p < 0.0001), and fatigue (r = - 0.51; p < 0.0001). Multivariate analysis revealed that physical function correlated independently with age, OI type, fatigue, and non-neuropathic pain. CONCLUSIONS: Individuals with OI display a marked deterioration in physical function during adulthood. This impairment varies in severity according to the OI phenotype and is associated with the presence of non-neuropathic pain and fatigue.

Brain Structural Signature of RFC1-Related Disorder.

BACKGROUND: The cerebellar ataxia, neuropathy, and vestibular areflexia syndrome was initially described in the early 1990s as a late-onset slowly progressive condition. Its underlying genetic cause was recently mapped to the RFC1 gene, and additional reports have expanded on the phenotypic manifestations related to RFC1, although little is known about the pattern and extent of structural brain abnormalities in this condition. OBJECTIVE: The aim is to characterize the structural signature of brain damage in RFC1-related disorder, correlating the findings with clinical symptoms and normal brain RFC1 expression. METHODS: We recruited 22 individuals with molecular confirmation of RFC1 expansions and submitted them to high-resolution 3T magnetic resonance imaging scans. We performed multimodal analyses to assess separately cerebral and cerebellar abnormalities within gray and white matter (WM). The results were compared with a group of 22 age- and sex-matched controls. RESULTS: The mean age and disease duration of patients were 62.8 and 10.9 years, respectively. Ataxia, sensory neuronopathy, and vestibular areflexia were the most frequent manifestations, but parkinsonism and pyramidal signs were also noticed. We found that RFC1-related disorder is characterized by widespread and relatively symmetric cerebellar and basal ganglia atrophy. There is brainstem volumetric reduction along all its segments. Cerebral WM is also involved-mostly the corpus callosum and deep tracts, but cerebral cortical damage is rather restricted. CONCLUSION: This study adds new relevant insights into the pathophysiological mechanisms of RFC1-related disorder. It should no longer be considered a purely cerebellar and sensory pathway disorder. Basal ganglia and deep cerebral WM are additional targets of damage. © 2021 International Parkinson and Movement Disorder Society.

Retinal Architecture in Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS): Insights into Disease Pathogenesis and Biomarkers.

BACKGROUND: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) causes unique retinal abnormalities, which have not been systematically investigated. OBJECTIVE: To deeply phenotype the retina in ARSACS in order to better understand its pathogenesis and identify potential biomarkers. METHODS: We evaluated 29 patients with ARSACS, 66 with spinocerebellar ataxia (SCA), 38 with autosomal recessive cerebellar ataxia (ATX), 22 with hereditary spastic paraplegia (SPG), 21 cases of papilledema, and 20 healthy controls (total n = 196 subjects). Participants underwent visual acuity assessment, intraocular pressure measurement, fundoscopy, and macular and peripapillary optical coherence tomography (OCT). Macular layers thicknesses in ARSACS were compared with those of age-matched healthy controls. Ophthalmologists analyzed the scans for abnormal signs in the different patient groups. Linear regression analysis was conducted to look for associations between retinal changes and age, age at onset, disease duration, and Scale for the Assessment and Rating of Ataxia (SARA) scores in ARSACS. RESULTS: Only patients with ARSACS exhibited peripapillary retinal striations (82%) on fundoscopy, and their OCT scans revealed foveal hypoplasia (100%), sawtooth appearance (89%), papillomacular fold (86%), and macular microcysts (18%). Average peripapillary retinal nerve fiber layer (pRNFL) was thicker in ARSACS than in SCA, ATX, SPG, and controls; a cut-off of 121 µm was 100% accurate in diagnosing ARSACS. All macular layers were thicker in ARSACS when compared to healthy controls. RNFL thickness in the inferior sector of the macula positively correlated with SARA scores. CONCLUSIONS: Retinal abnormalities are highly specific for ARSACS, and suggest retinal hyperplasia due to abnormal retinal development. OCT may provide potential biomarkers for future clinical trials. © 2021 International Parkinson and Movement Disorder Society.

Clinical and trichoscopic features in various forms of scalp psoriasis.

BACKGROUND: Scalp psoriasis is often undiagnosed or inadequately treated. The patient himself underestimates the seriousness of this hair disease and consults too late to a dermatologist. OBJECTIVES: The aim of our study was to create a correlation between the clinical patterns and trichoscopy of scalp psoriasis such in a way to help the clinician to make the diagnosis and select the appropriate therapy. MATERIAL AND METHODS: We gathered all patients affected of scalp psoriasis afferent to Outpatient's hair consultation of the Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, from January 2012 to December 2018. All patients were evaluated through clinical, trichoscopic examination and a skin biopsy only in doubtful cases. We quantified the severity of the disease with several objective and subjective parameters every 4 months, up to 1 year. We recorded therapies, outcome data and quality of life. RESULTS: We collected 156 patients affected by scalp psoriasis, identifying seven clinical patterns with specific trichoscopical correlation. In the order of frequency, the clinical patterns were as follows: plaque psoriasis (with a prevalence of erythema, silver-white scales and twisted red loops vessels and red dots); thin scales (with silvery-white scales, simple red lines and signet red ring vessels); sebopsoriasis (with greasy scales, erythema with red dots, globules and twisted and bushy red loops at high magnification); psoriatic cap (with silver-white scales, erythema and polymorphic vascular pattern); pityriasis amiantacea (with yellowish adherent scales, erythema and simple red loops capillaries); cicatricial psoriatic alopecia (with erythema associated with yellowish, silver-white scales with twisted and bushy red loops capillaries) and pustular psoriasis (with 'flower shape' pustular lesions, erythema simple red loops capillaries). CONCLUSIONS: The description of different clinical patterns of scalp psoriasis and its trichoscopical correlations may help the clinician to make the diagnosis also in atypical presentations and to prescribe an adequate therapeutic regimen.