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<p>Cilj rada: Posmatrano je da li postoji povezanost kliničkih parametara, bihejvioralnih simptoma i postignuća na testovima kognitivnih funkcija sa karakteristikama hoda kod obolelih od Parkinsonove bolesti. Analizirana je i povezanost nalaza hiperehogenosti strukture substantia nigra dobijenog transkranijalnim parenhimskim ultrazvukom sa karakteristikama hoda.Materijal I metode: Istraživanjem je obuhvaćeno 60 obolelih od Parkinsonove bolesti (22 žene i 38 mu&scaron;karaca, sa trajanjem bolesti 5,06&plusmn;4,54 godina, ukupnim UPDRS 39,76&plusmn;36,65, UPDRS III 24,28&plusmn;15,18) koji su prema stadijumu bolesti po Hen i Jarovoj skali (H&amp;Y) podeljeni u tri podgrupe sa po 20 ispitanika: H&amp;Y 1, 2 i 3. Kontrolnu grupu činilo je 35 zdravih ispitanika (19 žena i 16 mu&scaron;karaca) koji se od grupe obolelih nisu razlikovali u pogledu godina starosti (oboleli 64,21&plusmn;6,92 godina, zdravi 63,45&plusmn;7,75, p=0,832) i godina obrazovanja (oboleli 12,63&plusmn;3,16 godina, zdravi 12,57&plusmn;2,87, p=0,954). Iz analize su isključeni ispitanici čiji je skor MMSE bio manji od 24. Procena težine motornih znakova Parkinsonove bolesti vr&scaron;ena je Unifikovanom skalom za kvantifikovanje Parkinsonove bolesti, treći deo (UPDRS III). Za globalnu procenu kognicije je kori&scaron;ćena Revidirana Adenbrukova kogntivna skala (ACE- R), a za procenu egzekutivnih funkcija su kori&scaron;ćeni baterija za procenu frontalnih funkcija (FAB) i Egzekutivni intervju (EXIT-25). Za evaluaciju depresije kori&scaron;ćene su Hamiltonova skala za procenu depresije (HAM- D) i Bekova skala depresivnosti (BDI II), za procenu anksioznosti Hamiltonova skala za procenu anksioznosti (HAM- A), a za procenu apatije Skala apatije (AS).Određivanje vremenskih i prostornih parametara hoda vr&scaron;eno je pomoću GAITRite sistema, tokom &bdquo;on&rdquo; perioda. Analizirano je osam parametara hoda: vreme dvokoraka (CT), dužina dvokoraka (SL), vreme zamaha (ST) i vreme dvostrukog oslonca (DS), kao i njihovi koeficijenti varijacija (CV). Posmatran je i uticaj dvostrukog zadatka na parametre hoda. Kao dodatni zadatak tokom hoda primenjen je kognitivni zadatak (oduzima -7 tokom hoda), motorni zadatak (nosi ča&scaron;u punu vode) i kombinovani zadatak (oduzima i nosi ča&scaron;u istovremeno). Veličina hiperehogenosti substantia nigra merena je transkranijalnim parenhimskim ultrazvukom. Rezultati: U poređenju sa zdravim vr&scaron;njacima, oboleli od Parkinsonove bolesti imali su značajno izraženiji varijabilitet koraka pri hodu bez zadatka (skraćen SL, povećan CVSL i CVCT, varijabilitet koraka bio je jo&scaron; izraženiji, dok je pri motornom zadatku postojala i značajna razlika DS i CVDS (p&lt;0,05), tj. parametara kojima se izražava ravnoteža koraka. U uslovima kombinovanog zadatka ove razlike su se potencirale. Parametri hoda (SL, VCSL, CVCT I CVST) minimalno su se razlikovali kod obolelih u najranijim stadijumima bolesti (H&amp;Y 1) u odnosu na zdrave, dok su razlike postajale izraženije kako je bolest bila u odmaklijim stadijumima (H&amp;Y 2 I H&amp;Y 3). U grupi zdravih starost ispitanika korelirala je sa varijabilitetom koraka jedino u uslovima dvostrukog zadatka. Kod obolelih ova povezanost je uočena i pri hodu bez zadatka, a povezanost je bila jača u uslovima dvostrukog zadatka. Starost ispitanika i težina motornih znakova na UPDRS III korelirali su sa parametrima hoda kod obolelih od PB. Skorovi apatije i depresivnosti korelirali su sa promenama parametara hoda kod obolelih, s tim &scaron;to je apatija bila prisutna već u najranijim, a depresija tek u kasnijim stadijumima bolesti. Niža postignuća na testovima egzekutivnih funkcija povezana su sa pogor&scaron;anjem svih parametara hoda. Sa pogor&scaron;anjem parametara hoda tokom trajanja bolesti koreliraju i niža postignuća na testovima jezičkih i vidno- prostornih funkcija, kao i deficit pamćenja. Veličina hiperehogenosti korelira sa CV svih parametara hoda. Zaključak: Kod obolelih od Parkinsonove bolesti značajno se razlikuju vremenski i prostorni parametri hoda u poređenju sa zdravim, pre svega oni kojima se opisuje varijabilitet koraka. Ovi parametri su izraženiji kada se tokom hoda obavlja i dodatni kognitivni zadatak. Kada se tokom hoda obavlja motorni ili kombinovani motorni i kognitivni zadatak, pored varijabiliteta koraka javlja se i značajno produžen DS koji ukazuje na poremećaj ravnoteže. Na parametre hoda utiču starost ispitanika, težina i stadijum Parkinsonove bolesti. Apatija i depresija takođe značajno utiču na parametre hoda kod obolelih. Apatija se javlja u najranijim, a depresivnost tek u kasnijim stadijumima bolesti, &scaron;to govori u prilog stanovi&scaron;ta da je apatija zaseban simptom bolesti povezan sa dopaminergičkom disfunkcijom. Pogor&scaron;anja parametara hoda koreliraju sa o&scaron;tećenjem kognitivnih funkcija, pre svega egzekutivnih. U odmaklim stadijumima bolesti sa pogor&scaron;anjem hoda povezana su i lo&scaron;ija postignuća na testovima vidno-prostornih funkcija i pamćenja. Hiperehogenost substantia nigra na transkranijalnom parenhimskom ultrazvuku, koja se značajno če&scaron;će javlja i značajno je veće povr&scaron;ine kod obolelih u odnosu na zdrave, korelira sa varijabilitetom koraka.</p> / <p>Objectives: The aim of the study was to assess the contribution of clinical presentation, behavioral symptoms and cognitive functioning to gait characteristics in Parkinson&rsquo;s disease (PD). Hyperechogenicity of the substantia nigra on transcranial parenchimal ultrasound and its correlations with gait characteristics was also analyzed. Material and Methods: The experimental group consisted of 60 patients suffering from Parkinson&rsquo;s disease (22 women and 38 men, disease duration 5.06&plusmn;4.54, Unified Parkinson&#39;s Disease Rating Scale (UPDRS) total 39.76&plusmn;36.65, and UPDRS III 24.28&plusmn;15.18), who were classified into three subgroups according to the Hoehn and Yahr (H&amp;Y) stage of the disease: H&amp;Y 1, H&amp;Y 2 and H&amp;Y 3, with each subgroup containing 20 patients. The control group included 35 healthy subjects (19 women and 16 men) who were matched for years of age (64.21&plusmn;6.92 years PD vs 63.45&plusmn;7.75 healthy; p= .832) and formal education (12.63&plusmn;3.16 years PD vs 12.57&plusmn;2.87 healthy, p= .954). The subjects with MMSE&lt;24 were concerned demented and excluded from further analysis. The disease severity was assessed by the UPDRS, motor part (UPDRS III). Addenbrooke&rsquo;s Cognitive Examination-Revised (ACE-R) was used in assessment of global cognition, while executive functions were examined by Frontal Assessment Battery (FAB) and Executive Interview (EXIT-25) Hamilton&rsquo;s Depression Rating Scale (HAM-D) and Beck&rsquo;s Depression Inventory (BDI II) were used to screen for symptoms of depression, and the Apathy Scale (AS) and Hamilton&rsquo;s Anxiety Rating Scale (HAM- A) were used to assess apathy and anxiety. The measurements of spatial and temporal parameters of gait were performed using the GAITRite system, during the &ldquo;on&rdquo; state. The following eight parameters were analyzed: Cycle Time (CT), Stride Length (SL), Swing Time (ST) and Double Support Time (DS), as well as their coefficients of variation (CV). The impact of dual task on gait parameters was also observed. The subjects were asked to walk and simultaneously perform cognitive task (subtracting -7), then motor task (carrying a glass of water) and eventually combined task (subtracting and carrying a glass of water), while walking on the GAITRite electronic pathway. Transcranial parenchymal ultrasound was used to measure hyperechogenicity of substantia nigra. Results: Compared to healthy controls, PD patients had significantly higher gait variability during gait without additional tasks (decreased SL, increased CVSL and CVCT; p&lt; .05), whereas with a cognitive task the variability was even higher. During the motor task DS and CVDS were significantly increased as well, implying gait instability. A combined task had similar effects as the motor task, affecting all parameters. When the experimental group was divided into subgroups, variability of gait (SL, VCSL, CVCTandCVST) was minor in subgroup H&amp;Y 1, but more pronounced in later stages (H&amp;Y 2 and H&amp;Y 3). The age correlated with gait variability (CVCT and CVSL) only during the dual task in healthy subjects, whereas in PD patients the association was significant during normal gait and increased on the dual task. The age and severity of the disease on the UPDRS III also correlated with gait parameters. Apathy and depression were also associated with gait variability. Symptoms of apathy were significant in the earliest stages (H&amp;Y 1), whereas depression was notable in the later stages (H&amp;Y 3). Worse scores on tests of executive functions correlated with impairment of gait parameters. The impact of diminished language, visuo-spatial and memory functions on gait was also significant. Hyperechogenicity of the substantia nigra on transcranial parenchymal ultrasound occurred more frequently and was larger in PD patients and correlated well with gait variability. Conclusion: There is a significant impairment of temporal and spatial gait parameters in PD patients compared to healthy subjects, particularly the parameters of gait variability. These parameters become even more impaired during a simultaneous cognitive task. When a motor or combined task is performed, there is additional increase of DS, implying impairment of stability. Also, age and disease severity affect gait in PD patients. Apathy is significant in early stages (H&amp;Y 1) and depression in later stages (H&amp;Y 3), the finding which may be explained by the dopaminergic origin of apathy. Impairment of cognitive functions, most importantly executive dysfunction, are also associated with gait variability. Lower scores at visuo-spatial, language and memory tests are associated with worsened gait parameters of gait in later stages of PD. Finally, hyperechogenicity of the substantia nigra on transcranial parenchymal sonography, which occurs more frequently and is larger in PD patients, correlates with gait variability.</p>

Introdução: As mucopolissacaridoses (MPSs) são doenças de deposito lisossômico causadas por deficiências enzimáticas envolvidas na degradação das glicosaminoglicanas. O catabolismo das glicosaminoglicanas pode ser bloqueado isoladamente ou em combinações, podendo ocorrer o acúmulo de dermatan sulfato, heparan sulfato, queratan sulfato, e o acido hialurônico. Existem sete tipos de MPSs (tipos I, II, III, IV, VI, VII e IX) causados por onze deficiências enzimáticas conhecidas; o comprometimento multissistêmico progressivo é uma característica comum à maioria dos tipos. O espectro de manifestações neurológicas é amplo e o diagnóstico precoce de tais manifestações é fundamental para um melhor prognóstico. A terapia de reposição enzimática (TRE) é atualmente disponível para o tratamento de alguns tipos de MPS, entretanto não há evidências de melhorias dos sintomas neurológicos com o uso da TRE. Objetivo: O objetivo deste estudo foi descrever as alterações neurológicas e de neuroimagem nos diversos tipos de MPSs. Métodos: Vinte pacientes com diagnóstico de mucopolissacaridoses (MPS) foram incluídos no estudo e avaliados conforme o protocolo clínico e de neuroimagem pré-estabelecido. Os pacientes foram submetidos à ressonância magnética (RM) de crânio e coluna em aparelhos de 1,5 Tesla. Resultados: Dentre os 20 pacientes da amostra, dois pacientes apresentavam MPS I (10%), três MPS II (15%), nove MPS IV (45%) e seis MPS VI (30%). As idades variaram de três a 26 anos (12,5 ± 6,1) e 13 (65%) pacientes eram do sexo masculino. Os pacientes com MPSs tipo I e II apresentaram uma ampla diversidade clínica e de neuroimagem. Desde casos oligossintomáticos com exame neurológico normal até um atraso significativo do desenvolvimento neuropsicomotor (DNPM), com alterações cognitivas, motoras e sensitivas persistentes foram encontrados. Os exames de RM dos pacientes com MPSs I e II apresentaram alterações tais como espessamento da díploe, alargamento dos espaços perivasculares, dilatação ventricular e comprometimento da substância branca. Alterações degenerativas na coluna vertebral estiveram presentes em todos os pacientes com MPSs I e II, a despeito da maioria estar em regime de TRE. Compressão medular foi observada em apenas um paciente com MPS I e em nenhum paciente MPS II. Dos nove pacientes com MPS IV, dois apresentaram atraso do DNPM, um deles com alterações cognitivas persistentes; em todos os pacientes encontramos déficits motores e seis dentre os nove apresentaram alterções de sensibilidade profunda. Na RM dos pacientes com MPS IV, observamos hipoplasia do processo odontóide em todos os pacientes, e em oito foram encontrados sinais de compressão medular. Subluxação atlanto-axial foi vista em seis pacientes. Estenose do canal e lipomatose epidural também contribuíram para compressão medular, e três pacientes apresentaram dois níveis de compressão. Na RM do crânio, dois pacientes com MPS IV apresentaram alterações da substância branca. Nos pacientes com MPS VI, a cognição esteve preservada e alterações de reflexos e sensibilidade profunda foram encontradas. Além das alterações clássicas encontradas em outros pacientes com outros tipos de MPSs, a RM dos pacientes com MPS VI mostrou alterações morfológicas dos diâmetros do crânio e da fossa média. Mesmo apresentando força muscular normal, todos os pacientes com MPS VI apresentaram algum grau de compressão medular. Em quatro pacientes encontramos subluxação atlanto-axial e em três estenose do canal medular. Conclusões: A heterogeneidade clínica e de neuroimagem foram marcantes nos pacientes com MPSs tipos I e II. Alterações degenerativas do coluna vertebral estiveram presentes em todos os pacientes destes grupo, a despeito da TRE. Os achados clínicos e de neuroimagem nos pacientes com MPS IV reforçam o comprometimento primário do sistema nervoso central neste tipo de MPS. Além disso, os efeitos secundários da doença sobre o medula requerem avaliação neurológica e RM da coluna total periodicamente. Nos pacientes com MPS VI, apesar do exame clínico mostrar apenas alterações sutis, o comprometimento do neuroeixo foi um achado universal pela RM, demonstrando a necessidade de seguimento radiológico mesmo em pacientes oligossintomáticos em regime de TRE / Introduction: Mucopolysaccharidosis (MPS) are lisosomal storage disorders caused by deficiencies of glycosaminoglycans catabolism enzymes, leading to deposition of mucopolysaccharides; over time, there is cellular damage affecting several organs and systems. There are seven distinct phenotypes of MPS (types I, II, III, IV, VI, VII e IX) with eleven known enzymatic defects, which may result in accumulation of dermatan sulfate, heparan sulfate, queratan sulfate, and hyaluronic acid. Neurological manifestations are broad, and an early detection of these manifestations is essential to ensure a better prognosis of MPS patients. Enzymatic replacement therapy (ERT) is currently available to treat some types of MPS, albeit there is no evidence of direct neurological improvement with ERT. Objective: The objective of this study was to describe the clinical neurological abnormalities and neuroimaging findings in a sample of patients with diagnosis of MPS. Methods: Twenty patients previously diagnosed with distinct types of MPS were enrolled in the clinical and MRI protocol. Brain and spinal cord MRI were performed in 1.5 Tesla machines. Results: Amongst the 20 patients, two had diagnosis of MPS I (10%), three had MPS II (15%), nine had MPS type IV (45%), and six had MPS type VI (30%). The ages ranged between three and 26 years-old (mean 12,5 ± 6,1) and 13 pacients (65%) were male. Clinical findings in patients with MPS I and II were broad, ranging from an unremarkable neurologic examination to severe milestones delay, and cognitive, motor, and sensitive impairment. Neuroimaging features in patients with MPS I and II showed diploe thickness, enlargement of perivascular spaces, hydrocephalus and white matter abnormalities. Degenerative abnormalities in the spine were present in all patients with MPS I and MPS II. On the other hand, spinal cord compression was found in only one patient with MPS I and in none of the MPS II patients. Among the nine MPS IV patients, two had delayed milestones and one of those exhibited persistent cognitive impairment. All patients with MPS IV had motor deficits and six of them presented impairment of deep sensory modalities. Neuroimaging of patients with MPS IV showed white matter abnormalities in two and spinal cord compression in eight patients, with three of them presenting two levels of spinal cord compression. The main mechanism of compression was atlantoaxial subluxation; in addition, other abnormalities such as spinal stenosis and epidural lipomatosis also contributed to spinal cord compression in MPS IV patients. Patients with MPS VI had preserved cognition, but sensory exam and deep tendon reflex were abnormal. Other than classical brain MRI abnormalities, patients with MPS type VI also presented with changes in the middle cranial fossa and increased anteroposterior skull diameter. Even though all six patients with MPS VI presented normal muscle strength, all of them had some degree of spinal cord compression; four patients had atlantoaxial subluxation and three had spinal stenosis. Conclusions: Clinical and neuroimaging heterogeneity was remarkable in patients with MPS types I and II. Degenerative features in vertebrae were found in all patients with MPS I and II, despite ERT. Our clinical and neuroimaging findings in patients with MPS IV support the central nervous system impairment in these patients; additionally, it was possible to understand the underlying spinal cord compression mechanisms in MPS. Although clinical abnormalities were not meaningful in patients with MPS VI, they presented significant MRI abnormalities despite ERT. Routine assessments including neurologic examination and spinal cord MRI is extremely important in MPS patients

Introdução: O aperfeiçoamento da assistência pré-natal e dos cuidados intensivos neonatais contribuiu para a redução da mortalidade dos recémnascidos (RN) com riscos para alterações do desenvolvimento neuromotor. Apesar destes avanços, a difícil previsão e prevenção de danos neurológicos está associada ao aumento de crianças com problemas graves como a Paralisia Cerebral (PC). Das avaliações disponíveis atualmente, a que possui melhor valor preditivo de danos neurológicos em bebês até os cinco meses de idade é a \"Avaliação Qualitativa dos Movimentos Generalizados (MGs)\" de Prechtl. No entanto, apresenta pouca aderência na prática clínica devido à sua subjetividade e necessidade de treinamento prévio para aplicação. Objetivos: Desenvolver e analisar a confiabilidade de uma escala de avaliação baseada nos MGs caracterizados a partir da avaliação qualitativa de Prechtl em recémnascidos e lactentes com riscos para alterações no desenvolvimento neuromotor. Método: Estudo observacional transversal com a participação de 30 RNs e lactentes com idade compreendida entre 31 semanas pós-menstrual e 17 semanas pós-termo avaliados no Hospital Universitário da USP. Os MGs normais e anormais foram avaliados segundo a análise qualitativa dos MGs de Prechtl seguindo as três fases: pré-termo (n=7), writhing movements (n=13) e fidgety movements (n=10). A escala foi construída baseando-se nestas fases e foram elaboradas duas versões, sendo analisadas as confiabilidades inter e intra-examinador por meio do ICC e do índice de Kappa. A consistência interna da versão final foi analisada através do alfa de Cronbach. Resultados: Foram analisadas duas versões da escala com três diferentes sistemas de pontuação: respostas do tipo \"SIM ou NÃO\"; do tipo \"SEMPRE, ALGUMAS VEZES e NUNCA\"; e \"SEMPRE, QUASE SEMPRE, ALGUMAS VEZES, QUASE NUNCA E NUNCA\". Os resultados mais significativos foram obtidos com as respostas binárias (SIM ou NÃO), sendo que nas fases pré-termo e writhing movements a pontuação máxima é de 32 pontos e na fase dos fidgety movements é de 12 pontos. A análise da confiabilidade da versão final da escala evidenciou concordância excelente tanto para a confiabilidade intra-avaliador (ICCs: 0.914 a 0.999; Kappa: 0.6 a 1 e 0.606 a 1, considerando a escala binária), como para confiabilidade inter-avaliadores (ICCs: 0.871 a 0.966 para avaliação 1; Kappa: 0.682 a 0.775 para avaliação 1, considerando novamente a escala binária). Apenas o índice Kappa neste caso apresentou concordância boa. Os valores de alfa de Cronbach se mostraram de bons a excelentes (0.866 a 0.980). Verificou-se também que os bebês com MGs anormais apresentaram pontuação abaixo de valores entre 20 e 25 na fase pré-termo e dos writhing movements, e abaixo de valores entre 8 e 12 na fase dos fidgety movements. Conclusão: Foi possível desenvolver uma escala capaz de quantificar os MGs, com pontuação capaz de diferenciar MGs normais de anormais, com excelente confiabilidade inter e intra-avaliador e alta consistência interna. A escala apresenta grande relevância clínica e, aliada ao treinamento no método qualitativo, torna-se um instrumento promissor para a detecção precoce de riscos para atraso do desenvolvimento neuromotor e seleção dos RNs e lactentes para acompanhamento e intervenção precoce / Introduction: The technological improvement of neonatal care and intensive care contributed to reduction of preterm newborn (PTNB) mortality. Despite these improvements, is still difficult to predict and prevent neural damage and neurobehavioral impairments, which are associated to higher proportion of children with severe neurological problems, such as Cerebral Palsy (CP). Between all the available methods of babies\' assessment and examination, the Prechtl´s Method of Qualitative Assessment of General Movements (GMs) shows the higher predictive value to neurological damage. Nevertheless, this assessment is not widely used because of its subjectivity and the necessity of training of the examiners. Objective: To develop a quantitative scale based on GMs in the newborn and infant, and to verify its reliability. Method: Crosssectional observational study involving 30 newborns and infants aged between 31 weeks postmenstrual age and 17 weeks post term age assessed at university hospital of University of São Paulo. The normal and abnormal GMs were evaluated based on the Prechtl´s Method of Qualitative Assessment of GMs following the three phases: preterm GMs (n=7), writhing movements (n=13) and fidgety movements (n=10). The scale was developed based on these phases and Kappa and ICC statistics were applied in the reliability analysis (inter- and intra-observer agreement). Cronbach alpha was applied in the internal consistency analysis. Results: Two versions of the scale were analyzed with three different scoring systems: \"YES or NO\"; \"ALWAYS, SOMETIMES and NEVER; \"ALWAYS, OFTEN, SOMETIMES, ALMOST NEVER and NEVER\". The most significant results were obtained with \"YES or NO\" answers. The total score obtained in preterm and writhing movements phases was 32 points and in the fidgety movements phase was 12 points. Considering the assessment with the final version of the scale, high to very high inter- (ICCs 0.871-0.966; Kappa 0.682-0.775 for the first evaluation, considering \"YES or NO\" answers) and intra-observer reliability (ICCs: 0.914-0.999; Kappa: 0.6-1, considering \"YES or NO\" answers) was found. High to very high Cronbach alpha values was also found (0.866-0.980). The infants showed abnormal GMs score below values between 20 and 25 in preterm phase and writhing movements, and below values between 8 and 12 at fidgety movements age. Conclusion: It was possible to develop a scale able to quantify GMs, with scores that can differentiate normal from abnormal GMs, with excellent inter- and intra-observer reliability and internal consistency. The scale has great clinical relevance and, combined with training in qualitative method, it is a promising tool for early detection of risks for delayed neuromotor development and screening of newborns and infants for monitoring and early intervention

Introdução: Transplantes de órgãos ocorrem principalmente devido a doações provenientes de pacientes que apresentam morte encefálica (ME). Algumas situações limitam o diagnóstico de ME baseado apenas no exame neurológico, sendo necessário utilizar um exame de imagem ou gráfico para esta confirmação. No Brasil, o exame complementar é obrigatório por lei para todos os casos suspeitos. A maioria dos métodos complementares utilizados para confirmação de ME não está disponível em muitos locais do Brasil. Neste contexto, a angiografia por tomografia computadorizada (ATC) representaria uma alternativa, devido à presença de equipamentos de tomografia em diversos hospitais brasileiros. Porém, a capacidade de este exame reconhecer a interrupção da circulação intracraniana é desconhecida. Métodos: Realizou-se revisão sistemática para verificar evidência na literatura sobre o uso de ATC como teste avaliador de ME. Foram seguidas diretrizes de busca e extração de dados, sendo o QUADAS 2 utilizado para verificar risco de vieses e qualidade dos estudos. Os dados foram sumarizados para produzir metanálise. Resultados: Dez estudos com alto risco de vieses foram encontrados. Devido à falta de estudos controlados, não se obteve dados de especificidade. Trezentos e vinte e dois pacientes foram elegíveis para metanálise, a qual revelou 84,7% de sensibilidade. Houve variação de protocolos de avaliação das imagens de ATC entre os estudos, sobre a definição de resultados positivos ou negativos. Conclusão: ATC apresenta alta sensibilidade para detectar interrupção de circulação intracraniana entre pacientes com avaliação clínica compatível com ME. Este nível de evidência é similar ao de outros métodos utilizados no mundo. Há falta de estudos bem desenhados neste tema / Background: Organ transplantation depends more often of donation from brain dead (BD) individuals. Several complications make the diagnosis of BD medically challenging and a complimentary method is needed for confirmation. Additionally, in Brazil, the complimentary diagnosis is mandatory by law, despite there are still many areas where these methods are not available. In this context, computed tomography angiography (CTA) could represent a valuable alternative, because of its widespread presence. However, the reliability of CTA for confirming brain circulatory arrest remains unclear. Methods: A systematic review was performed to identify relevant studies regarding the use of CTA as ancillary test for BD confirmation. Guidelines for online search were followed, and the QUADAS 2 tool was used to verify study quality. Data from the studies retrieved were extracted aiming to perform the meta-analysis. Results: Ten low quality studies were found. Due to the absence of controls in all studies, specificity could not be calculated. Three hundred twenty-two patients were eligible for the meta-analysis, which exhibited 84,7% sensitivity. CTA image evaluation protocol exhibited variations between medical institutions regarding which intracranial vessels should be considered to determine positive or negative test results. Conclusions: For patients who were previously diagnosed with BD according to clinical criteria, CTA demonstrated high sensitivity to verify intracranial circulatory arrest. The current evidence that supports the use of CTA in BD diagnosis is comparable to other methods applied worldwide. Considering the importance of this subject, high quality studies are currently missing and needed

O mecanismo de controle da secreção de GnRH inclui diversas vias neuronais. Estudos em modelos animais identificaram genes que codificam fatores de transcrição, tais como TTF-1 (thyroid transcription factor 1) e EAP1 (enhanced at puberty), que atuam no controle transcricional de genes codificadores de fatores excitatórios (KiSS1 e GnRH) e inibitórios (preproencefalinas) regulando a secreção de GnRH. Em primatas, a expressão de EAP1 e TTF-1 aumenta, no início da puberdade, nas regiões hipotalâmicas envolvidas na secreção de GnRH. Nos modelos animais, a deleção pós-natal de TTF-1 e o silenciamento do EAP1 provocam atraso puberal e prejuízo na função reprodutiva. TTF-1 também está envolvido na morfogênese diencefálica, por meio da via de sinalização da família Sonic-Hedgehog. Anormalidades na secreção de GnRH resultam em distúrbios puberais, que variam de puberdade precoce central (PPC) a hipogonadismo hipogonadotrófico. Hipotetizamos que anormalidades genéticas no TTF-1 e EAP1 estejam envolvidas na patogênese dos distúrbios puberais centrais. A PPC pode ser idiopática ou devido a causas orgânicas, sendo o hamartoma hipotalâmico, uma malformação congênita não neoplásica, a mais conhecida. Os pacientes com PPC devido a hamartoma hipotalâmico podem cursar com alterações neurológicas e cognitivas. Nossos objetivos foram: estudar as regiões codificadora do TTF-1 e do EAP1 e a região promotora do TTF-1 em pacientes com distúrbios puberais centrais; estabelecer a prevalência, taxa de penetrância e modo de herança da forma familial de PPC e caracterizar as manifestações neurológicas e neurocognitivas de pacientes com PPC devido a hamartoma hipotalâmico. Foram selecionados 133 pacientes com distúrbios puberais centrais - PPC idiopática (n=71), PPC devido a hamartoma hipotalâmico (n=15) e hipogonadismo hipogonadotrópico isolado normósmico (HHIn) (n=47) - e controles (n=53). Os genes TTF-1 e EAP1 foram amplificados e submetidos a sequenciamento automático. Os tratos de poliglutamina e polialanina no EAP1 foram estudados por software de análise de tamanho de fragmento (GeneScan). A avaliação neurológica e neurocognitiva dos pacientes com PPC devido a hamartoma hipotalâmico consistiu de exame neurológico, eletroencefalograma, ressonância magnética de encéfalo e aplicação da escala de inteligência (WISC-III, WAIS-III, WPPSIR). Identificamos 25% de casos familiais de PPC, com modo de herança autossômica dominante e taxa de penetrância de 67,5%. Variantes alélicas no TTF-1 não foram identificadas nos pacientes estudados. No gene EAP1 foram identificadas quatro variantes alélicas sinônimas: p.E87E, p.A163A, p.Y415Y e uma nova variante alélica p.C758C, encontradas em pacientes com PPC e HHIn. A distribuição das frequências alélica e genotípica das variantes alélicas do EAP1 não diferiram entre pacientes com PPC, HHIn e controles (p >0,05). Nas regiões poliglutamina e polialanina 5 distal foi identificada variação similar no número de repetições glutamina e alanina em pacientes e controles. Não houve diferença significativa da frequência alélica em relação ao número de repetições glutamina e alanina entre os grupos PPC e HHIn (p >0,05). A avaliação neurológica dos pacientes com PPC devido a hamartoma hipotalâmico revelou epilepsia gelástica e crises focais com generalização em 3/15 (20%) pacientes. Não houve diferença significativa entre a mediana do maior diâmetro dos hamartomas dos pacientes com PPC com e sem epilepsia (13 e 10 mm, respectivamente). Quanto à forma, 10 hamartomas eram sésseis e 5 pedunculados, sendo que a forma pedunculada foi detectada exclusivamente em pacientes sem epilepsia. A avaliação neurocognitiva em 11 dos 15 pacientes com PPC devido a hamartoma hipotalâmico detectou 2 pacientes com epilepsia com QI significativamente menor que o grupo sem epilepsia (p <0,05). Em conclusão, (i) a considerável prevalência de casos familiais de PPC reforça a influência dos fatores genéticos na puberdade humana; (ii) mutações germinativas no TTF-1 e no EAP1 não estão envolvidas na patogênese dos distúrbios puberais centrais; (iii) a função neurocognitiva reduzida nos pacientes com hamartoma e epilepsia sugere um efeito deletério das crises convulsivas no sistema nervoso central / GnRH secretion control involves multiple neuronal pathways. Animal studies have identified genes which codifies transcription factors, such as TTF-1 (thyroid transcription factor 1) and EAP1 (enhanced at puberty), that act in the transcriptional control of genes that codifies excitatory (KiSS1 and GnRH) and inhibitory factors (preproenkephalines) regulating GnRH secretion. In nonhuman primates, expression of EAP1 and TTF-1 are increased at the hypothalamic regions involved in GnRH secretion, at the beginning of puberty. In animal models, post-natal TTF-1 deletion and silencing of EAP1 lead to pubertal delay and damage of reproductive function. TTF-1 is also involved in diencephalic morphogenesis, through signalization via Sonic-Hedgehog family. Abnormalities in GnRH secretion are responsible for pubertal disorders, varying from central precocious puberty (CPP) to hypogonadotropic hypogonadism. We hypothesized that genetic anomalies at TTF-1 and EAP1 are involved in the pathogenesis of central pubertal disorders. CPP may be idiopathic or due to organic alterations and hypothalamic hamartoma, a non-neoplasic congenital malformation, is the most frequent known organic cause. Patients with CPP due to hypothalamic hamartoma may have neurological and cognitive disfunctions. Our aims were: to evaluated the codifying region of TTF-1 and EAP1 and the promoter region of TTF-1 in patients with central pubertal disorders; to establish the prevalence, penetrance rate and inheritance mode of familial CPP and to characterize neurologic and neurocognitive aspects of patients with CPP due to hypothalamic hamartoma. We selected 133 patients with central pubertal disorders idiopathic CPP (n=71), CPP due to hypothalamic hamartoma (n=15) and normosmic isolated hypogonadropic hypogonadism (nIHH) (n=47) - and controls (n=53). TTF-1 and EAP1 genes were amplified and sequenced. Polyglutamine and polyalanine tracts of EAP1 were studied by a fragment size analyser software (GeneScan). Neurologic and neurocognitive evaluation of CPP patients due to hypothalamic hamartoma consisted of neurologic exam, electroencephalogram, brain magnetic resonance and application of intelligence scale (WISC-III, WAIS-III, WPPSI-R). We identified 25% of familial CPP cases with autosomal dominant mode of inheritance and penetrance rate of 67.5%. No TTF-1 allelic variants were identified in the patients analysed. At EAP1 gene, four synonimous allelic variants were identified: p.E87E, p.A163A, p.Y415Y and a new allelic variant p.C758C, found in CPP and nIHH patients. The allelic and genotypic distribution of theses variants of EAP1 did not differ among patients with CPP and nIHH, and controls (p >0.05). At polyglutamine and 5 distal polyalanine region, similar glutamine and alanine repeats variation was found. No significative difference of allelic frequency distribution regarding the number of glutamines and alanines repeats was found among the studied groups (p >0.05). Neurologic evaluation of CPP patients due to hypothalamic hamartoma revealed epilepsy and focal crisis with generalization in 3/15 (20%) of the patients. No significant difference between the median of the larger diameter of hypothalamic hamartoma of CPP patients with and without epilepsy was found (10 mm and 13 mm, respectively). Regarding the shape, 10 hamartomas were sessile and 5 pedunculated, and the pedunculated shape was found only in non epileptic patients. Neurocognitive evaluation performed in 11 of the 15 patients with CPP due to hypothalamic hamartoma detected 2 patients with epilepsy whose IQ were significantly lower than the IQ found in the group without epilepsy (p <0.05). In conclusion, (i) the considerable prevalence of familial CPP cases reinforce the influence of genetic factors in human puberty; (ii) germinative mutations in TTF-1 and EAP1 are not involved in the pathogenesis of central pubertal disorders; (iii) reduced neurocognitive function in patients with hypothalamic hamartoma and epilepsy suggests a deleterious effect of crisis at the central nervous system

Introdução: As mucopolissacaridoses (MPSs) são doenças de deposito lisossômico causadas por deficiências enzimáticas envolvidas na degradação das glicosaminoglicanas. O catabolismo das glicosaminoglicanas pode ser bloqueado isoladamente ou em combinações, podendo ocorrer o acúmulo de dermatan sulfato, heparan sulfato, queratan sulfato, e o acido hialurônico. Existem sete tipos de MPSs (tipos I, II, III, IV, VI, VII e IX) causados por onze deficiências enzimáticas conhecidas; o comprometimento multissistêmico progressivo é uma característica comum à maioria dos tipos. O espectro de manifestações neurológicas é amplo e o diagnóstico precoce de tais manifestações é fundamental para um melhor prognóstico. A terapia de reposição enzimática (TRE) é atualmente disponível para o tratamento de alguns tipos de MPS, entretanto não há evidências de melhorias dos sintomas neurológicos com o uso da TRE. Objetivo: O objetivo deste estudo foi descrever as alterações neurológicas e de neuroimagem nos diversos tipos de MPSs. Métodos: Vinte pacientes com diagnóstico de mucopolissacaridoses (MPS) foram incluídos no estudo e avaliados conforme o protocolo clínico e de neuroimagem pré-estabelecido. Os pacientes foram submetidos à ressonância magnética (RM) de crânio e coluna em aparelhos de 1,5 Tesla. Resultados: Dentre os 20 pacientes da amostra, dois pacientes apresentavam MPS I (10%), três MPS II (15%), nove MPS IV (45%) e seis MPS VI (30%). As idades variaram de três a 26 anos (12,5 ± 6,1) e 13 (65%) pacientes eram do sexo masculino. Os pacientes com MPSs tipo I e II apresentaram uma ampla diversidade clínica e de neuroimagem. Desde casos oligossintomáticos com exame neurológico normal até um atraso significativo do desenvolvimento neuropsicomotor (DNPM), com alterações cognitivas, motoras e sensitivas persistentes foram encontrados. Os exames de RM dos pacientes com MPSs I e II apresentaram alterações tais como espessamento da díploe, alargamento dos espaços perivasculares, dilatação ventricular e comprometimento da substância branca. Alterações degenerativas na coluna vertebral estiveram presentes em todos os pacientes com MPSs I e II, a despeito da maioria estar em regime de TRE. Compressão medular foi observada em apenas um paciente com MPS I e em nenhum paciente MPS II. Dos nove pacientes com MPS IV, dois apresentaram atraso do DNPM, um deles com alterações cognitivas persistentes; em todos os pacientes encontramos déficits motores e seis dentre os nove apresentaram alterções de sensibilidade profunda. Na RM dos pacientes com MPS IV, observamos hipoplasia do processo odontóide em todos os pacientes, e em oito foram encontrados sinais de compressão medular. Subluxação atlanto-axial foi vista em seis pacientes. Estenose do canal e lipomatose epidural também contribuíram para compressão medular, e três pacientes apresentaram dois níveis de compressão. Na RM do crânio, dois pacientes com MPS IV apresentaram alterações da substância branca. Nos pacientes com MPS VI, a cognição esteve preservada e alterações de reflexos e sensibilidade profunda foram encontradas. Além das alterações clássicas encontradas em outros pacientes com outros tipos de MPSs, a RM dos pacientes com MPS VI mostrou alterações morfológicas dos diâmetros do crânio e da fossa média. Mesmo apresentando força muscular normal, todos os pacientes com MPS VI apresentaram algum grau de compressão medular. Em quatro pacientes encontramos subluxação atlanto-axial e em três estenose do canal medular. Conclusões: A heterogeneidade clínica e de neuroimagem foram marcantes nos pacientes com MPSs tipos I e II. Alterações degenerativas do coluna vertebral estiveram presentes em todos os pacientes destes grupo, a despeito da TRE. Os achados clínicos e de neuroimagem nos pacientes com MPS IV reforçam o comprometimento primário do sistema nervoso central neste tipo de MPS. Além disso, os efeitos secundários da doença sobre o medula requerem avaliação neurológica e RM da coluna total periodicamente. Nos pacientes com MPS VI, apesar do exame clínico mostrar apenas alterações sutis, o comprometimento do neuroeixo foi um achado universal pela RM, demonstrando a necessidade de seguimento radiológico mesmo em pacientes oligossintomáticos em regime de TRE / Introduction: Mucopolysaccharidosis (MPS) are lisosomal storage disorders caused by deficiencies of glycosaminoglycans catabolism enzymes, leading to deposition of mucopolysaccharides; over time, there is cellular damage affecting several organs and systems. There are seven distinct phenotypes of MPS (types I, II, III, IV, VI, VII e IX) with eleven known enzymatic defects, which may result in accumulation of dermatan sulfate, heparan sulfate, queratan sulfate, and hyaluronic acid. Neurological manifestations are broad, and an early detection of these manifestations is essential to ensure a better prognosis of MPS patients. Enzymatic replacement therapy (ERT) is currently available to treat some types of MPS, albeit there is no evidence of direct neurological improvement with ERT. Objective: The objective of this study was to describe the clinical neurological abnormalities and neuroimaging findings in a sample of patients with diagnosis of MPS. Methods: Twenty patients previously diagnosed with distinct types of MPS were enrolled in the clinical and MRI protocol. Brain and spinal cord MRI were performed in 1.5 Tesla machines. Results: Amongst the 20 patients, two had diagnosis of MPS I (10%), three had MPS II (15%), nine had MPS type IV (45%), and six had MPS type VI (30%). The ages ranged between three and 26 years-old (mean 12,5 ± 6,1) and 13 pacients (65%) were male. Clinical findings in patients with MPS I and II were broad, ranging from an unremarkable neurologic examination to severe milestones delay, and cognitive, motor, and sensitive impairment. Neuroimaging features in patients with MPS I and II showed diploe thickness, enlargement of perivascular spaces, hydrocephalus and white matter abnormalities. Degenerative abnormalities in the spine were present in all patients with MPS I and MPS II. On the other hand, spinal cord compression was found in only one patient with MPS I and in none of the MPS II patients. Among the nine MPS IV patients, two had delayed milestones and one of those exhibited persistent cognitive impairment. All patients with MPS IV had motor deficits and six of them presented impairment of deep sensory modalities. Neuroimaging of patients with MPS IV showed white matter abnormalities in two and spinal cord compression in eight patients, with three of them presenting two levels of spinal cord compression. The main mechanism of compression was atlantoaxial subluxation; in addition, other abnormalities such as spinal stenosis and epidural lipomatosis also contributed to spinal cord compression in MPS IV patients. Patients with MPS VI had preserved cognition, but sensory exam and deep tendon reflex were abnormal. Other than classical brain MRI abnormalities, patients with MPS type VI also presented with changes in the middle cranial fossa and increased anteroposterior skull diameter. Even though all six patients with MPS VI presented normal muscle strength, all of them had some degree of spinal cord compression; four patients had atlantoaxial subluxation and three had spinal stenosis. Conclusions: Clinical and neuroimaging heterogeneity was remarkable in patients with MPS types I and II. Degenerative features in vertebrae were found in all patients with MPS I and II, despite ERT. Our clinical and neuroimaging findings in patients with MPS IV support the central nervous system impairment in these patients; additionally, it was possible to understand the underlying spinal cord compression mechanisms in MPS. Although clinical abnormalities were not meaningful in patients with MPS VI, they presented significant MRI abnormalities despite ERT. Routine assessments including neurologic examination and spinal cord MRI is extremely important in MPS patients

Equine herpesvirus type-1(EHV-1) is a complex virus known for inducing various forms of disease in horses. In recent years, the number of cases of neurological disease caused by this virus has increased. While there are a number of possible sources for this recent surge, this project set out to determine if a genotypic shift in the latent population of the virus in favor of the neuropathogenic form of EHV-1 is the basis for the recent increase in frequency of EHV-1 neurologic disease. To ascertain if such a shift has in fact occurred, 450 EHV-1 isolates were obtained from fetal tissues resulting from single, sporadic cases of abortion in Thoroughbred broodmares in central Kentucky. Furthermore, the isolates utilized were from different decades (1951-2006) to determine if the genotypic shift was time-related. The isolates were propagated in cell culture, purified and the viral DNA isolated. Real-time allelic discrimination PCR analysis was performed on the DNA samples to identify the genotype of EHV-1. Statistical analysis of the PCR data indicates that the latent mutant population does appear to be increasing. Therefore, the recent increase in the number of outbreaks of EHV-1 neurological disease will most likely continue unless measures are devised to curtail further spread of the pathogen.

Spasticity is highly prevalent in neurological conditions involving upper motor neuron lesions (UMNL). Lower limb spasticity is known to impair gait and limit participation in physical activity. Multimodal interventions including botulinum toxin A, orthoses, and physiotherapy have shown longer lasting improvements compared to unimodal interventions. Studies to date, however, have not examined the long term efficacy of this multimodal intervention nor have they examined the impact across a breadth of domains necessary to comprehensively and fully understand its impact. The aim of this study was to investigate the efficacy of a multimodal intervention to treat lower limb spasticity in adults using a longitudinal mixed-methods approach, including a comprehensive set of outcome measures spanning the domains of the International Classification of Functioning, Disability and Health (ICF) model. Seven-teen participants with chronic UMNL were included in the analysis as per inclusion criteria and showed improvements at 6 and 12 months, compared to baseline, within all domains of the ICF model. / Graduate / 0571 / 0382 / 0384 / jazkim@uvic.ca

Spasticity is highly prevalent in neurological conditions involving upper motor neuron lesions (UMNL). Lower limb spasticity is known to impair gait and limit participation in physical activity. Multimodal interventions including botulinum toxin A, orthoses, and physiotherapy have shown longer lasting improvements compared to unimodal interventions. Studies to date, however, have not examined the long term efficacy of this multimodal intervention nor have they examined the impact across a breadth of domains necessary to comprehensively and fully understand its impact. The aim of this study was to investigate the efficacy of a multimodal intervention to treat lower limb spasticity in adults using a longitudinal mixed-methods approach, including a comprehensive set of outcome measures spanning the domains of the International Classification of Functioning, Disability and Health (ICF) model. Seven-teen participants with chronic UMNL were included in the analysis as per inclusion criteria and showed improvements at 6 and 12 months, compared to baseline, within all domains of the ICF model. / Graduate / 2015-04-24 / 0571 / 0382 / 0384 / jazkim@uvic.ca