Evaluation of the Surgical Treatment of Patients over 90 Years Old with Hip Fractures and Their Morbidity and Mortality.

Objective: Hip fractures in older adults have the highest impact on the patient's health. These injuries result in many complications, reducing functional capability, quality of life, and life expectancy. This study aimed to provide more epidemiological data on the outcomes of these fractures in nonagenarians from a large city treated at a tertiary hospital. Methods: This study consisted of medical record reviews and interviews. Results: In this study, 76 patients underwent 82 surgeries. The mean age of the patients was 92.5 years. Ninety percent of the subjects were female. The patients spent 10.4 days in hospital. Surgery occurred on average 2.3 days after hospitalization. Regarding fractures, 46 were trochanteric (56%), and 34 affected the femoral neck (41.5%). Forty-one surgeries used the short proximal femoral nail (50%), and 18 were partial hip replacements (22%). During hospitalization, 46 patients (55%) had no complications, excluding episodes of delirium, and seven patients (9%) died. Forty-two subjects completed the one-year postoperative follow-up period, with 56% alive and 44% dead. Conclusions: Treating hip fractures in older patients is challenging. Our goal must focus on helping these subjects receive the quickest and least aggressive treatment possible and start mobilization early. We hope the data presented in this study can lead to a better understanding of the characteristics of our nonagenarian population with hip fractures and seek the best possible treatment for them.

Static Balance in Hereditary Spastic Paraplegias: a Cross-sectional Study.

Motor and somatosensory pathway dysfunction due to degeneration of long tracts in hereditary spastic paraplegias (HSP) indicates that postural abnormalities may be a relevant disease feature. However, balance assessments have been underutilized to study these conditions. How does the static balance of individuals with HSP with eyes open and closed differ from healthy controls, and how does it relate to disease severity? This cross-sectional case-control study assessed the static balance of 17 subjects with genetically confirmed HSP and 17 healthy individuals, evaluating the center of pressure (COP) variables captured by a force platform. The root-mean-square of velocities and mean of displacements amplitudes in mediolateral and anteroposterior axes were correlated with disease severity. All COP parameters' performances were significantly impaired in HSP subjects compared to controls (p < 0.001 for all comparisons). COP with eyes open and closed differed for all variables within the HSP group, whereas in the control group, differences were observed only for anteroposterior velocity and amplitude. Spastic Paraplegia Rating Scale presented moderate direct correlations with the most COP variables (Rho = - 0.520 to - 0.736). HSP individuals presented significant postural instability with eyes open and to a greater extent with eyes closed, corroborating the clinical findings of somatosensorial and proprioceptive pathways dysfunction. The degrees of proprioceptive and motor impairments are mutually correlated, suggesting that similar pathophysiological mechanisms operate for the degeneration of these long tracts. COP parameters can be seen as disease severity biomarkers of HSP, and they should be assessed in future clinical trials.

Dysarthria in hereditary spastic paraplegia type 4.

OBJECTIVE: To describe the speech pattern of patients with hereditary Spastic Paraplegia type 4 (SPG4) and correlated it with their clinical data. METHODS: Cross-sectional study was carried out in two university hospitals in Brazil. Two groups participated in the study: the case group (n = 28) with a confirmed genetic diagnosis for SPG4 and a control group (n = 17) matched for sex and age. The speech assessment of both groups included: speech task recording, acoustic analysis, and auditory-perceptual analysis. In addition, disease severity was assessed with the Spastic Paraplegia Rating Scale (SPRS). RESULTS: In the auditory-perceptual analysis, 53.5% (n = 15) of individuals with SPG4 were dysarthric, with mild to moderate changes in the subsystems of phonation and articulation. On acoustic analysis, SPG4 subjects' performances were worse in measurements related to breathing (maximum phonation time) and articulation (speech rate, articulation rate). The articulation variables (speech rate, articulation rate) are related to the age of onset of the first motor symptom. CONCLUSION: Dysarthria in SPG4 is frequent and mild, and it did not evolve in conjunction with more advanced motor diseases. This data suggest that diagnosed patients should be screened and referred for speech therapy evaluation and those pathophysiological mechanisms of speech involvement may differ from the length-dependent degeneration of the corticospinal tract.

Dysarthria in hereditary spastic paraplegia type 4

Abstract Objective: To describe the speech pattern of patients with hereditary Spastic Paraplegia type 4 (SPG4) and correlated it with their clinical data. Methods: Cross-sectional study was carried out in two university hospitals in Brazil. Two groups participated in the study: the case group (n = 28) with a confirmed genetic diagnosis for SPG4 and a control group (n = 17) matched for sex and age. The speech assessment of both groups included: speech task recording, acoustic analysis, and auditory-perceptual analysis. In addition, disease severity was assessed with the Spastic Paraplegia Rating Scale (SPRS). Results: In the auditory-perceptual analysis, 53.5% (n = 15) of individuals with SPG4 were dysarthric, with mild to moderate changes in the subsystems of phonation and articulation. On acoustic analysis, SPG4 subjects' performances were worse in measurements related to breathing (maximum phonation time) and articulation (speech rate, articulation rate). The articulation variables (speech rate, articulation rate) are related to the age of onset of the first motor symptom. Conclusion: Dysarthria in SPG4 is frequent and mild, and it did not evolve in conjunction with more advanced motor diseases. This data suggest that diagnosed patients should be screened and referred for speech therapy evaluation and those pathophysiological mechanisms of speech involvement may differ from the length-dependent degeneration of the corticospinal tract.

Diagnostic yield of multi-gene panel for muscular dystrophies and other hereditary myopathies.

Genetic testing is being considered the first-step in the investigation of hereditary myopathies. However, the performance of the different testing approaches is little known. The aims of the present study were to evaluate the diagnostic yield of a next-generation sequencing panel comprising 39 genes as the first-tier test for genetic myopathies diagnosis and to characterize clinical and molecular findings of families from southern Brazil. Fifty-one consecutive index cases with clinical suspicion of genetic myopathies were recruited from October 2014 to March 2018 in a cross-sectional study. The overall diagnostic yield of the next-generation sequencing panel was 52.9%, increasing to 60.8% when including cases with candidate variants. Multi-gene panel solved the diagnosis of 12/25 (48%) probands with limb-girdle muscular dystrophies, of 7/14 (50%) with congenital muscular diseases, and of 7/10 (70%) with muscular dystrophy with prominent joint contractures. The most frequent diagnosis for limb-girdle muscular dystrophies were LGMD2A/LGMD-R1-calpain3-related and LGMD2B/LGMD-R2-dysferlin-related; for congenital muscular diseases, RYR1-related-disorders; and for muscular dystrophy with prominent joint contractures, Emery-Dreifuss-muscular-dystrophy-type-1 and COL6A1-related-disorders. In summary, the customized next-generation sequencing panel when applied in the initial investigation of genetic myopathies results in high diagnostic yield, likely reducing patient's diagnostic odyssey and providing important information for genetic counseling and participation in disease-specific clinical trials.

Progression of Functional Gait in Hereditary Spastic Paraplegias.

Hereditary spastic paraplegias (HSP) are characterized by progressive deterioration of axonal projections of upper motor neurons leading to abnormal locomotion. The clinical course of HSP as well as the definition of the best instruments to assess its progression is largely unknown. The aim of this study was to investigate the progression of functional gait in individuals with HSP and to define sensitivity to change, minimal clinically important difference (MCID), and validity of timed functional tests of gait (TFT). The study was constituted of two phases: a cross-sectional study and a prospective cohort of 18 months. Twenty-five patients (17 being SPG4), and twenty-five age- and sex-matched control individuals performed TFT. Spastic paraplegia rating scale (SPRS), ten-meter walking test (10MWT), timed up and go test (TUG), both at self-selected and maximal walking speeds, and six-minute walking test (6MWT) were performed on baseline in both groups and after 18 months of follow-up only in the HSP cohort. In the cross-sectional analysis, all TFTs performances were greatly impaired in HSP patients compared to controls. After 18 months of follow-up, TFTs did not differ significantly from baseline in the statistical analysis, with some tests showing more frequent improvement than worsening. We have provided effect size measures and MCID for the evaluated instruments. HSPs clearly compromised TFTs performances, which were valid instruments for assessing disease severity. However, TFTs and SPRS did not capture the very slow motor evolution of HSPs, reinforcing the necessity of additional biomarkers of disease progression.

Prevalence of oropharyngeal dysphagia in hereditary spastic paraplegias / Prevalência de disfagia orofaríngea nas paraparesias espásticas hereditárias

ABSTRACT Hereditary spastic paraplegias (HSP) are a group of genetic diseases characterized by lower limb spasticity with or without additional neurological features. Swallowing dysfunction is poorly studied in HSP and its presence can lead to significant respiratory and nutritional complications. Objectives: The aim of this study was to evaluate the frequency and clinical characteristics of dysphagia in different types of HSP. Methods: A two-center cross-sectional prevalence study was performed. Genetically confirmed HSP patients were evaluated using the Northwestern Dysphagia Patient Check Sheet and the Functional Oral Intake Scale. In addition, self-perception of dysphagia was assessed by the Eat Assessment Tool-10 and the Swallowing Disturbance Questionnaire. Results: Thirty-six patients with spastic paraplegia type 4 (SPG4), five with SPG11, four with SPG5, four with cerebrotendinous xanthomatosis (CTX), three with SPG7, and two with SPG3A were evaluated. Mild to moderate oropharyngeal dysphagia was present in 3/5 (60%) of SPG11 and 2/4 (50%) of CTX patients. A single SPG4 (2%) and a single SPG7 (33%) patient had mild oropharyngeal dysphagia. All other evaluated patients presented with normal or functional swallowing. Conclusions: Clinically significant oropharyngeal dysphagia was only present in complicated forms of HSP Patients with SPG11 and CTX had the highest risks for dysphagia, suggesting that surveillance of swallowing function should be part of the management of patients with these disorders.

RESUMO As paraparesias espásticas hereditárias (PEH) são um grupo de doenças genéticas caracterizado por espasticidade dos membros inferiores com ou sem características neurológicas adicionais. A disfunção da deglutição é pouco estudada nas PEH e sua presença pode levar a complicações respiratórias e nutricionais significativas. Objetivo: O objetivo deste estudo foi avaliar a frequência e a caracterização clínica da disfagia em diferentes tipos de PEH. Métodos: Foi realizado um estudo transversal em dois centros. Os pacientes com PEH confirmados geneticamente foram avaliados pelo Northwestern Dysphagia Patient Check Sheet e pela Escala Funcional de Ingestão Oral. Além disso, a autopercepção da disfagia foi avaliada pelo Eat Assessment Tool-10 e pelo Swallowing Disturbance Questionnaire. Resultados: Trinta e seis pacientes com paraplegia espástica tipo 4 (SPG4), cinco com SPG11, quatro com SPG5, quatro com xantomatose cerebrotendinosa (CTX), três com SPG7 e dois com SPG3A foram avaliados. Disfagia orofaríngea leve a moderada estava presente em 3/5 (60%) dos pacientes com SPG11 e 2/4 (50%) dos pacientes com CTX. Um único SPG4 (2%) e um único SPG7 (33%) apresentaram disfagia orofaríngea leve. Todos os outros pacientes avaliados apresentaram deglutição normal ou funcional. Conclusão: Disfagia orofaríngea clinicamente significativa estava presente apenas nas formas complicadas de PEH. A SPG11 e CTX apresentaram maiores riscos de disfagia, sugerindo que a avaliação da deglutição deve fazer parte do manejo dos pacientes com essas condições.

Are Cognitive Changes in Hereditary Spastic Paraplegias Restricted to Complicated Forms?

Background: Little is known about the cognitive profile of Hereditary Spastic Paraplegias (HSP), where most scientific attention has been given to motor features related to corticospinal tract degeneration. Objectives: We aimed to perform a broad characterization of the cognitive functions of patients with pure and complicated HSP as well as to determine the frequency of abnormal cognitive performances in the studied subtypes. Methods: A two-center cross-sectional case-control study was performed. All individuals underwent cognitive assessment through screening tests (Mini Mental State Examination-MEEM and Montreal Cognitive Assessment-MOCA) and tests to assess specific cognitive functions (Verbal fluency with phonological restriction-FAS; Verbal categorical fluency-FAS-cat and Rey's Verbal Auditory Learning Test -RAVLT). Results: Fifty four patients with genetically confirmed HSP diagnosis, 36 with spastic paraplegia type 4 (SPG4), 5 SPG11, 4 SPG5, 4 cerebrotendinous xanthomatosis (CTX), 3 SPG7 and 2 SPG3A, and 10 healthy, unrelated control subjects, with similar age, sex, and education participated in the study. SPG4 patients had worse performances in MOCA, FAS, FAS-cat, and RAVLT when compared to controls. Most SPG4 patients presented cognitive changes not compatible with dementia, performing poorly in memory, attention and executive functions. SPG5 patients scored lower in executive functions and memory, and SPG7 patients performed poorly on memory tasks. All evaluated cognitive functions were markedly altered in CTX and SPG11 patients. Conclusions: Cognitive abnormalities are frequent in HSP, being more severe in complicated forms. However, cognitive impairments of pure HSPs might impact patients' lives, decreasing families' socioeconomic status and contributing to the overall disease burden.

Prevalence of oropharyngeal dysphagia in hereditary spastic paraplegias.

OBJECTIVES: Hereditary spastic paraplegias (HSP) are a group of genetic diseases characterized by lower limb spasticity with or without additional neurological features. Swallowing dysfunction is poorly studied in HSP and its presence can lead to significant respiratory and nutritional complications. The aim of this study was to evaluate the frequency and clinical characteristics of dysphagia in different types of HSP. METHODS: A two-center cross-sectional prevalence study was performed. Genetically confirmed HSP patients were evaluated using the Northwestern Dysphagia Patient Check Sheet and the Functional Oral Intake Scale. In addition, self-perception of dysphagia was assessed by the Eat Assessment Tool-10 and the Swallowing Disturbance Questionnaire. RESULTS: Thirty-six patients with spastic paraplegia type 4 (SPG4), five with SPG11, four with SPG5, four with cerebrotendinous xanthomatosis (CTX), three with SPG7, and two with SPG3A were evaluated. Mild to moderate oropharyngeal dysphagia was present in 3/5 (60%) of SPG11 and 2/4 (50%) of CTX patients. A single SPG4 (2%) and a single SPG7 (33%) patient had mild oropharyngeal dysphagia. All other evaluated patients presented with normal or functional swallowing. CONCLUSIONS: Clinically significant oropharyngeal dysphagia was only present in complicated forms of HSP Patients with SPG11 and CTX had the highest risks for dysphagia, suggesting that surveillance of swallowing function should be part of the management of patients with these disorders.

Clinical and molecular characterization of hereditary spastic paraplegias: A next-generation sequencing panel approach.

BACKGROUND: Molecular diagnosis of hereditary spastic paraplegias (HSP) is a difficult task due to great clinical and genetic heterogeneity. We aimed to characterize clinical and molecular findings of HSP families from Rio Grande do Sul, Brazil; and to evaluate the diagnostic yield of a next-generation sequencing (NGS) panel with twelve HSP-related genes. METHODS: A consecutive series of HSP index cases with familial recurrence of spasticity, consanguinity or thin corpus callosum (TCC) were included in this cross-sectional study. RESULTS: Among the 29 index cases, 51.7% (15/29) received at least a likely molecular diagnosis, and 48.3% (14/29) a defined diagnosis. NGS panel diagnostic yield was 60% for autosomal dominant HSP (6/10, all SPG4), 47.4% for autosomal recessive HSP (9/19: 5 SPG11, 2 SPG7, 1 SPG5 and 1 cerebrotendinous xanthomatosis), and 50% for patients with TCC (3/6, all SPG11). Remarkably, 2/6 SPG11 patients presented keratoconus, and tendon xanthomas were absent in the patient with cerebrotendinous xanthomatosis. CONCLUSION: A likely molecular diagnosis was obtained for more than half of families with the NGS panel, indicating that this approach could be employed as a first-line investigation for HSP. SPG4 is the most frequent form of autosomal dominant and SPG11 of autosomal recessive HSP in Southern Brazil.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay: a family report from South Brazil.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset, neurodegenerative disorder caused by mutations in SACS, firstly reported in Quebec, Canada. The disorder is typically characterized by childhood onset ataxia, spasticity, neuropathy and retinal hypermyelination. The clinical picture of patients born outside Quebec, however, is often atypical. In the present article, the authors describe clinical and neuroradiological findings that raised the suspicion of an ARSACS diagnosis in two female cousins with Germanic background from Rio Grande do Sul, Brazil. We present a review on the neuroimaging, ophthalmologic and neurophysiologic clues for ARSACS diagnosis. The early-onset, slowly progressive, spastic-ataxia phenotype of reported patients was similar to ARSACS patients from Quebec. The SACS sequencing revealed the novel homozygous c.5150_5151insA frameshift mutation confirming the ARSACS diagnosis. ARSACS is a frequent cause of early onset ataxia/spastic-ataxia worldwide, with unknown frequency in Brazil.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay: a family report from South Brazil / Ataxia espástica autossômica recessiva de Charlevoix-Saguenay: relato de uma família do sul do Brasil

ABSTRACT Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset, neurodegenerative disorder caused by mutations in SACS, firstly reported in Quebec, Canada. The disorder is typically characterized by childhood onset ataxia, spasticity, neuropathy and retinal hypermyelination. The clinical picture of patients born outside Quebec, however, is often atypical. In the present article, the authors describe clinical and neuroradiological findings that raised the suspicion of an ARSACS diagnosis in two female cousins with Germanic background from Rio Grande do Sul, Brazil. We present a review on the neuroimaging, ophthalmologic and neurophysiologic clues for ARSACS diagnosis. The early-onset, slowly progressive, spastic-ataxia phenotype of reported patients was similar to ARSACS patients from Quebec. The SACS sequencing revealed the novel homozygous c.5150_5151insA frameshift mutation confirming the ARSACS diagnosis. ARSACS is a frequent cause of early onset ataxia/spastic-ataxia worldwide, with unknown frequency in Brazil.

RESUMO A ataxia espástica autossômica recessiva de Charlevoix-Saguenay (ARSACS) é uma doença neurodegenerativa de início precoce causada por mutações no gene SACS que foi inicialmente descrita na região de Quebec, Canadá. A apresentação típica de ARSACS é caracterizada por ataxia, espasticidade, polineuropatia e hipermielinização das fibras nervosas da retina de início infantil. No presente artigo, descrevemos os achados clínicos e neurorradiológicos que levaram à suspeita de ARSACS em duas primas descendentes de alemães naturais do Rio Grande do Sul, Brasil e revisamos os achados de neuroimagem, oftalmológicos e neurofisiológicos de ARSACS. O fenótipo de ataxia-espástica de início infantil precoce apresentado pelas pacientes era similar ao classicamente descrito em Quebec. O sequenciamento do SACS revelou a mutação nova c.5150_5151insA (mudança na matriz de leitura), em homozigose, confirmando o diagnóstico de ARSACS. A ARSACS é uma causa frequente de ataxia/ataxia-espástica de início precoce mundialmente, entretanto sua frequência é desconhecida no Brasil.

Bioactive gel-glasses with distinctly different compositions: Bioactivity, viability of stem cells and antibiofilm effect against Streptococcus mutans.

In this study, an evaluation was performed to determine the in vitro bioactivity, viability of stem cells, and antibiofilm effect against Streptococcus mutans of two bioactive gel-glass 60SiO2-36CaO-4P2O5 (BG-A) and 80SiO2-15CaO-5P2O5 (BG-B) compositions. Both materials were bioactive and undergo the formation of hydroxycarbonate apatite (HCA) on their surfaces when immersed in simulated body fluid (SBF) after 12h, but the BG-A composition showed a more significant formation rate. The pH variation of the samples during the test in SBF indicated that an abrupt change had occurred for the BG-A composition within the first few hours, and the pH was subsequently maintained over time, supporting its stronger antibacterial effects against S. mutans. For the in vitro viability test using mesenchymal stem cells (MSCs), the BG-B showed significantly higher cell viability compared to the BG-A composition at concentrations of 0.125, 1.25 and 12.50mg/mL for 2days. These results indicated that the higher solubility of the BG-A glass favors bioactivity and antibacterial effects. However, as a result of rapid degradation, the increase in the concentration of ions in the cell culture medium was not favorable for cell proliferation. Thus, by varying the composition of glasses, and consequently their dissolution rate, it is possible to favor bioactivity, antimicrobial activity or stem cell proliferation for a particular application of interest.