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

Le cubitus proximal détient une courbe sagittale unique pour chaque individu, nommée « Proximal Ulna Dorsal Angulation (PUDA) ». Une reconstruction non-anatomique du cubitus proximal, suite à une fracture complexe peut engendrer une malunion, de l’arthrose et de l’instabilité. L’objectif de cette étude était d’évaluer la magnitude de malalignement au niveau de l’angulation proximale dorsale du cubitus qui causerait un malalignement radio-capitellaire, avec et sans un ligament annulaire intact. Afin d’atteindre cet objectif, une étude biomécanique fut conduite sur six spécimens frais congelés avec un simulateur de mouvement du coude. Des fractures simulées au niveau du PUDA, furent stabilisées avec une fixation interne dans cinq configurations différentes. Des images fluoroscopiques furent prises dans différentes positions du coude et de l’avant-bras, avec le ligament annulaire intact, puis relâché. Le déplacement de la tête radiale fut quantifié avec le ratio radio-capitellaire. Une interaction significative fut découverte entre les positions du coude, les angles de malalignement et l’intégrité du ligament annulaire. La subluxation de la tête radiale fut accentuée lors de la déchirure du ligament annulaire. Une augmentation de la subluxation antérieure de la tête radiale fut observée lorsque le malalignement était fixé en extension et lors de mouvements de flexion progressive du coude. D’autre part, un malalignement en flexion et une extension graduelle du coude occasionnait une subluxation postérieure. En conclusion, les résultats ont démontré l’importance d’une reconstruction anatomique du cubitus proximal, car un malalignement de 5 degrés engendre une subluxation de la tête radiale, surtout lors d’une déchirure du ligament annulaire. / It has been shown that the proximal ulna has a sagittal bow, named the Proximal Ulna Dorsal Angulation (PUDA), unique for each individual. Non-anatomic reconstruction of the proximal ulna following a complex injury may lead to malunion, arthrosis and instability, hence the importance of understanding its initial anatomy. The purpose of this study was to evaluate the magnitude of angular malalignement at the proximal ulna dorsal angulation that would lead to radiocapitellar malalignement, with and without an intact annular ligament. In order to achieve our goal, a biomechanical study was conducted on six fresh frozen specimens, with an elbow movement simulator. Simulated fractures at the PUDA were stabilized with internal fixation at five different angles. Then, fluoroscopic images were taken in different elbow and forearm positions, first with the annular ligament intact and then released. Radial head displacement was quantified with the Radio-Capitellar-Ratio (RCR). Overall, a significant interaction was found between elbow positions, angles of malalignement and annular ligament integrity. Radial head subluxation was emphasized when the annular ligament was ruptured. Moreover, anterior subluxation of the radial head increased as malalignement was fixed into extension and with progressive elbow flexion. Furthermore, posterior subluxation increased with malalignement into flexion and with elbow extension. In conclusion, our results demonstrate the importance of obtaining an anatomic reconstruction, specific for each individual’s unique proximal ulna dorsal angulation, following a proximal ulna fracture. Indeed, malalignment of 5 degrees can lead to abnormal tracking of the radial head, especially when associated with annular ligament tear.