Spinal Muscular Atrophy

Abstract: Background and Objective Stroke patients with severe leg paralysis are often bedridden in the acute and subacute phase, which increases the risk of disuse muscle atrophy in the chronic phase. The evidence to date indicates that oxidative stress plays an ...

The outcomes of 55 cases of cubital tunnel syndrome treated by a partial frontal epicondylectomy are presented at a mean follow-up of 38 months follow-up. According to McGowan classification, 25 cases were grade I (45%), 12 grade II (22%) and 18 grade III (33%). The results (Wilson and Krout classification) were excellent or good in 41 patients (75%), fair in nine patients and unchanged in five, without any worsening or recurrence. Total relief was reported in 80% of grade I, 75% of grade II and 66% of grade III patients. Seven painful scars and one persistent 15° elbow extension deficit were the only complications. The satisfaction rate was 93%. This technique preserves bony protection, the blood supply and gliding tissues for the nerve and nerve recovery were comparable to other surgical procedures. Residual pain at the osteotomy site was not a serious problem.

Nusinersén es un oligonucleótido antisentido capaz de incrementar la producción de la proteína SMN funcional, cuya deficiencia está relacionada con el origen de la atrofia muscular espinal 5q, indicación para la cual ha recibido autorización, como medicamento huérfano. El fármaco aumenta la proporción de inclusión del exón 7 en los transcritos del ácido ribonucleico mensajero (ARNm) del gen de supervivencia de la neurona motora 2 (SMN2) al unirse a un sitio ISS-N1 (silenciador del proceso de corte y empalme intrónico) localizado en el intrón 7 del precursor del ácido ribonucleico mensajero (pre-ARNm) del SMN2. Al unirse, el nusinersén desplaza los factores de corte y empalme, produciendo la retención del exón 7 en el ARNm del SMN2 y, por consiguiente, cuando se produce el ARNm del SMN2, se puede traducir en su proteína SMN funcional de longitud completa, lo que se relaciona con la eficacia terapéutica. Aunque con numerosas limitaciones, no cabe duda de que nos encontramos ante un medicamento auténticamente innovador, por varios motivos. Es el primer oligonucleótido antisentido (OAS) que permite actuar sobre el fundamento genético de la atrofia muscular espinal 5q y, lo que realmente resulta más relevante, su capacidad para actuar sobre una enfermedad que actualmente carece de tratamiento etiológico. Ciertamente, los resultados no son espectaculares pero abren una puerta a la esperanza, aunque habremos de esperar los datos de los ensayos clínicos en curso para poder establecer con mayor consistencia las conclusiones definitivas.

Muscle wasting and changes in muscle protein metabolism in chronic obstructive pulmonary disease. R.T. Jagoe, M.P.K.J. Engelen. #ERS Journals Ltd 2003. ABSTRACT: Loss of skeletal muscle mass is now recognised as an important feature of chronic obstructive pulmonary disease (COPD) which contributes to symptoms and influences prognosis. The changes in skeletal muscle remain poorly understood, largely because only a few studies have been performed to define the adaptations in whole body and muscle protein metabolism in COPD.

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of diseases that share some symptoms such as muscular weakness and inflammation of skeletal muscle. Complete recovery of muscle function with pharmacological treatment does not always occur, suggesting that physical inability is a great concern for these patients. In this context, it has been speculated that physical exercise could result in functional benefits to patients with IIM, leading to an improvement in quality of life. In fact, recent studies of polymyositis (PM) and dermatomyositis (DM) support the notion that exercise training improves or at least stabilizes muscle strength and functional ability without inducing disease flares. Importantly, these benefits were observed not only during the chronic phase, but also in the course of active disease. This positive effect was found to be long term, as demonstrated by a six-month significant improvement in exercise capacity and strength. Together, these findings indicate that a well controlled exercise program can be recommended for patients with DM and PM. The optimal exercise modality training and the underlying mechanism for this encouraging response remain to be determined in future studies.

Loss of muscle mass after stroke has implications for strength and functional ability and may also contribute to impaired glucose metabolism. Therefore, prevention of muscle loss is desirable. Before interventions to prevent loss of muscle can be designed and evaluated, the expected rate, magnitude and timing of muscle loss need to be understood. A systematic search was undertaken to identify all studies that investigated changes in skeletal muscle mass, volume or crosssectional area in people after stroke. Studies that used either direct measures of muscle size (computer tomography, magnetic resonance imaging or ultrasound) or measures of lean tissue mass (dual X-ray absorptiometry) were included. Fourteen trials were found and the results were pooled for differences in lean tissue mass between the paretic and the nonparetic leg and arm as well as differences in the midthigh cross-sectional area. In individuals at least 6-month poststroke, there was significantly less lean tissue mass in the paretic compared with the nonparetic lower limb (MD 342 . 3g, 95% confidence interval 247 . 0-437 . 6 g) and upper limb (MD 239 . 9 g, 95% confidence interval 181 . 7-298 . 2 g), and significantly less midthigh muscle cross-sectional area (MD 15 . 4cm 2 , 95% confidence interval 13 . 8-16 . 9cm 2 ). There were insufficient data to pool with regard to change in muscle mass over time. There is a significant difference in the regional muscle mass in the paretic vs. the nonparetic limb in individuals greater than 6-months poststroke but little is known about how early and how quickly changes in muscle mass occur.

Objective. To investigate the frequency of structural changes in the vastus medialis muscle in patients with osteoarthritis (OA) of the knee. Methods. Specimens of vastus medialis muscle from 78 patients with end-stage OA of the knee undergoing total joint arthroplasty were examined histopathologically. Morphologic changes were assessed in relation to clinical features that might have contributed to muscle injury. Results. All muscle specimens exhibited atrophy of type 2 fibers. In 32% of the patients, atrophy of type 1 fibers was also noted. Fiber type grouping of type 1 fiber in 15% of the patients and type 2 fiber in 37%, indicating reinnervation, led to the diagnosis of neurogenic muscular atrophy in 32% of the patients; selective atrophy of type 2 fiber in 68% of the specimens was interpreted as possibly resulting from pain-associated disuse. Signs of muscle degeneration and regeneration were found in 65% and 96% of the samples, respectively. Soft tissue changes indicating long-term disease, such as calcification, fibrosis, and lipomatosis, were frequently observed (in 69%, 71%, and 94% of the patients, respectively). Statistical analysis of clinical and morphologic parameters revealed a significant association between degenerative muscle changes and the presence of a varus deviation of the leg axis. Conclusion. Patients with OA of the knee frequently exhibit muscle changes, with probable multifactorial etiology. Selective atrophy of type 2 fibers might

Tetanic electrical stimulation applied over human muscle or peripheral nerve generates contractions by depolarizing motor axons beneath the stimulating electrodes. However, the simultaneous depolarization of sensory axons can also contribute to the contractions by the synaptic recruitment of spinal motoneurons. Maximizing this central contribution may be beneficial for reducing muscle atrophy or restoring movement for persons with movement disorders.

Cap analogs are chemically modified derivatives of the unique cap structure present at the 5´ end of all eukaryotic mRNAs and several non-coding RNAs. Until recently, cap analogs have served primarily as tools in the study of RNA metabolism. Continuing advances in our understanding of cap biological functions (including RNA stabilization, pre-mRNA splicing, initiation of mRNA translation, as well as cellular transport of mRNAs and snRNAs) and the consequences of the disruption of these processes - resulting in serious medical disorders - have opened new possibilities for pharmaceutical applications of these compounds. In this review, the medicinal potential of cap analogs in areas, such as cancer treatment (including eIF4E targeting and mRNA-based immunotherapy), spinal muscular atrophy treatment, antiviral therapy and the improvement of the localization of nucleus-targeting drugs, are highlighted. Advances achieved to date, challenges, plausible solutions and prospects for the futu...

Spinal muscular atrophy (SMA) is the most common human genetic disease resulting in infant mortality. SMA is caused by mutations or deletions in the ubiquitously expressed survival motor neuron 1 (SMN1) gene. Why SMA specifically affects motor neurons remains poorly understood. We have shown that Smn deficient PC12 cells have increased levels of the neuronal profilin IIa protein, leading to an inappropriate activation of the RhoA/ROCK pathway. This suggests that mis-regulation of neuronal actin dynamics is central to SMA pathogenesis. Here, we demonstrate an increase in profilin IIa and a decrease in plastin 3 protein levels in a SMA mouse model. Furthermore, knock-out of profilin II upregulates plastin 3 expression in a Smndependent manner. However, the depletion of profilin II and the restoration of plastin 3 are not sufficient to rescue the SMA phenotype. Our study suggests that additional regulators of actin dynamics must also contribute to SMA pathogenesis.

A case of early-onset, severe spinal muscular atrophy is reported. Normal fetal breathing movement patterns and heart rate accelerations were observed in spite of the severe hypotonia evident at birth. KEY w o~~s S p i n a l muscular atrophy (SMA), hypotonia, cardiotocography, breathing movements.

Although it is known that deletions or mutations of the SMN1 gene on chromosome 5 cause decreased levels of the SMN protein in subjects with proximal autosomal recessive spinal muscular atrophy (SMA), the exact sequence of pathological events leading to selective motoneuron cell death is not fully understood yet. In this review, new Wndings regarding the dual cellular role of the SMN protein (translocation of -actin to axonal growth cones and snRNP biogenesis/pre-mRNA splicing) were integrated with recent data obtained by detailed neuropathological examination of SMA and control subjects. A presumptive series of 10 pathogenetic events for SMA is proposed as follows: (1) deletions or mutations of the SMN1 gene, (2) increased SMN mRNA decay and reduction in full-length functional SMN protein, (3) impaired motoneuron axonoand dendrogenesis, (4) failure of motoneurons to form synapses with corticospinal Wbers from upper motoneurons, (5) abnormal motoneuron migration towards ventral spinal roots, (6) inappropriate persistence of motoneuron apoptosis due to impaired diVerentiation and motoneuron displacement, (7) substantial numbers of motoneurons continuing to migrate abnormally ("heterotopic motoneurons") and entering into the ventral roots, (8) attracted glial cells following these heterotopic motoneurons, which form the glial bundles of ventral roots, (9) impaired axonal transport of actin, causing remaining motoneurons to become chromatolytic, and (10) eventual death of all apoptotic, heterotopic and chromatolytic neurons, with apoptosis being more rapid and predominating in the earlier stages, with death of heterotopic and chromatolytic neurons occurring more slowly by necrosis during the later stages of SMA. According to this model, the motoneuron axonopathy is more important for pathogenesis than the ubiquitous nuclear splicing deWcit. It is also supposed that individually variable levels of SMN protein, together with inXuences of other phenotype modiWer genes and their products, cause the clinical SMA spectrum through diVerential degree of motoneuron functional loss.

Gene expression profiles of LM from beef cattle that underwent significant postweaning undernutrition were studied using complementary DNA (cDNA) microarrays. After 114 d of undernutrition, the RNA from LM showed 2-to 6-fold less expression of many genes from the classes of muscle structural proteins, muscle metabolic enzymes, and extracellular matrix compared with animals on a rapid growth diet. The expression levels of these genes had mostly returned to pretreatment levels after 84 d of realimentation. The gene expression changes associated with undernutrition and BW loss showed an emphasis on downregulation of gene expression specific to fast-twitch fibers, typical of starving mammals, with a preferential atrophy of glycolytic fast-twitch fibers. We also identified a

Mutations in the gene encoding the heavy chain subunit (DYNC1H1) of cytoplasmic dynein cause spinal muscular atrophy with lower extremity predominance, Charcot-Marie-Tooth disease and intellectual disability. We used the legs at odd angles (Loa) (DYNC1H1 F580Y) mouse model for spinal muscular atrophy with lower extremity predominance and a combination of live-cell imaging and biochemical assays to show that the velocity of dynein-dependent microtubule minus-end (towards the nucleus) movement of EGF and BDNF induced signalling endosomes is significantly reduced in Loa embryonic fibroblasts and motor neurons. At the same time, the number of the plus-end (towards the cell periphery) moving endosomes is increased in the mutant cells. As a result, the extracellular signal-regulated kinases (ERK) 1/2 activation and c-Fos expression are altered in both mutant cell types, but the motor neurons exhibit a strikingly abnormal ERK1/2 and c-Fos response to serum-starvation induced stress. These data highlight the cell-type specific ERK1/2 response as a possible contributory factor in the neuropathological nature of Dync1h1 mutations, despite generic aberrant kinetics in both cell types, providing an explanation for how mutations in the ubiquitously expressed DYNC1H1 cause neuron-specific disease.

To establish the prevalence of sarcopenia in older Americans and to test the hypothesis that sarcopenia is related to functional impairment and physical disability in older persons. DESIGN: Cross-sectional survey. SETTING: Nationally representative cross-sectional survey using data from the Third National Health and Nutrition Examination Survey (NHANES III). PARTICIPANTS: Fourteen thousand eight hundred eighteen adult NHANES III participants aged 18 and older.

Our knowledge on altered neurological control of walking due to weakness of various muscle groups of the lower extremities is limited. The aim of this study was to assess kinematic, kinetic and electromyographic (EMG) walking patterns in a functionally homogeneous group of seven subjects with spinal muscular atrophy, type III (SMA group) and compare them with normal data obtained from nine healthy subjects (CONTROL group) in order to identify characteristic compensatory changes. Muscle strength at the ankle and knee joints was assessed using isokinetic dynamometry to determine variability in muscle strength: this was found to be similar in the two groups. Kinematic, kinetic and EMG patterns were assessed during walking in the SMA and CONTROL groups. The results showed changes in the activity of ankle plantarflexors and associated control of the center of pressure during loading response and midstance, which facilitated minimization of the external flexion moment acting on the knee and hip in the SMA group. Additionally, we identified distinct and consistent changes in the control of hip rotators that act to rapidly extend the hip early in stance phase and in the control of contralateral hip abductors that act delay weight shift onto the leg entering the stance phase. From these results we can conclude that the most important muscle groups compensating for reduced strength in knee and hip muscles are the ankle plantarflexors, hip rotators and hip abductors. This finding would have direct application in rehabilitation treatment programs. #

Purpose: There is significant debate concerning the morbidity of hamstring harvest for use during anterior cruciate ligament (ACL) reconstruction. We hypothesized that harvest of the semitendinosus and gracilis tendons for ACL reconstruction would result in no measurable hamstring weakness, but that abnormalities of the semitendinosus and gracilis muscle would be observed on magnetic resonance imaging (MRI) scans. Type of Study: Case series. Methods: Nine patients undergoing ACL reconstruction with doubled semitendinosus and gracilis tendons had MRI cross-sectional area measurements of both limbs made from axial images and muscle contour was studied on coronal images at 3 and 12 months. The semitendinosus, semimembranosus, gracilis, sartorius, and biceps muscles were evaluated. Isokinetic testing was performed on the operative and nonoperative legs at 60°and 180°per second at 6 and 12 months postoperatively. Results: The gracilis cross-sectional area at 1 year averaged 2 cm 2 on the operative side and 3.7 cm 2 on the contralateral side. The semitendinosus averaged 2.1 cm 2 on the operative side and 6.6 cm 2 on the contralateral side at 1 year. Both of these differences were statistically significant (P Ͻ .05). In most cases, the semitendinosus muscle was retracted. Distally, the gracilis and occasionally the semitendinosus were blending with the gastrocnemius or sartorial fascia. The gracilis and semitendinosus in 1 case extended to near the original attachment site. Hamstring strength testing revealed a 26% deficit on the operative side at 60°/second at 6 months and 16% at 180°/second. At 12 months the mean 60°/second deficit was 21% and the deficit at 180°/second was 13%. Conclusions: At 1 year, the semitendinosus and gracilis muscles showed significant and persistent atrophy on the operative side and frequent retraction of the semitendinosus muscle belly. There were also hamstring strength deficits persisting at 1 year after the use of the tendons for ACL reconstruction. Level of Evidence: Level IV.

Spinal muscular atrophy (SMA) is a severe autosomal recessive disease caused by a genetic defect in the survival motor neuron 1 (SMN1) gene, which encodes SMN, a protein widely expressed in all eukaryotic cells. Depletion of the SMN protein causes muscle weakness and progressive loss of movement in SMA patients. The field of gene therapy has made major advances over the past decade, and gene delivery to the central nervous system (CNS) by in vivo or ex vivo techniques is a rapidly emerging field in neuroscience. Despite Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis being among the most common neurodegenerative diseases in humans and attractive targets for treatment development, their multifactorial origin and complicated genetics make them less amenable to gene therapy. Monogenic disorders resulting from modifications in a single gene, such as SMA, prove more favorable and have been at the fore of this evolution of potential gene therapies, and results to date have been promising at least. With the estimated number of monogenic diseases standing in the thousands, elucidating a therapeutic target for one could have major implications for many more. Recent progress has brought about the commercialization of the first gene therapies for diseases, such as pancreatitis in the form of Glybera, with the potential for other monogenic disease therapies to follow suit. While much research has been carried out, there are many limiting factors that can halt or impede translation of therapies from the bench to the clinic. This review will look at both recent advances and encountered impediments in terms of SMA and endeavor to highlight the promising results that may be applicable to various associated diseases and also discuss the potential to overcome present limitations.

Unlike most regulatory mechanisms, protein degradation is inherently irreversible. Destruction of a protein can lead to a complete, rapid, and sustained termination of the process involving the protein as well as a change in cell composition. The rapid degradation of specific proteins permits adaptation to new physiologic conditions. Regulation of Gene Transcription Ub conjugation affects transcription by multiple mechanisms (11). Many transcription factors are ubiquitinated and degraded by the proteasome. In fact, in many cases, transcriptional activation domains and signals for Ub conjugation di

There is a growing need for a robust clinical measure to assess upper limb motor function in spinal muscular atrophy (SMA), as the available scales lack sensitivity at the extremes of the clinical spectrum. We report the development of the Revised Upper Limb Module (RULM), an assessment specifically designed for upper limb function in SMA patients. An international panel with specific neuromuscular expertise performed a thorough review of scales currently available to assess upper limb function in SMA. This review facilitated a revision of the existing upper limb function scales to make a more robust clinical scale. Multiple revisions of the scale included statistical analysis and captured clinically relevant changes to fulfill requirements by regulators and advocacy groups. The resulting RULM scale shows good reliability and validity, making it a suitable tool to assess upper extremity function in the SMA population for multi-center clinical research. This article is protected by c...

Morphologic characteristics of the long-term denervated muscle in animals suggest that some original fibers are lost and some of those seen are the result of repeated cycles of fiber regeneration. Muscle biopsies from lower motoneuron denervated patients enrolled in the EU Project RISE show the characteristics of long-term denervation. They present a few atrophic or severely atrophic myofibers dispersed among adipocytes and connective tissue (denervated degenerated muscle, DDM). Monoclonal antibody for embryonic myosin shows that regenerative events are present from 1-to 37-years postspinal cord injury (SCI). After 2-to 10-years FES-training the muscle cryosections present mainly large round myofibers.

It has always been a desire of mankind to conquest Space. A major step in realizing this dream was the completion of the International Space Station (ISS). Living there for several months confirmed early observations of short-term spaceflights that a loss of gravity affects the health of astronauts. Space medicine tries to understand the mechanism of microgravity-induced health problems and to conceive potent countermeasures. There are four different aspects which make space medicine appealing: i) finding better strategies for adapting astronauts to weightlessness; ii) identification of microgravity-induced diseases (e.g. osteoporosis, muscle atrophy, cardiac problems and others); iii) defining new therapies to conquer these diseases which will benefit astronauts as well as people on Earth in the end; and iv) on top of that, unveiling the mechanisms of weightlessness-dependent molecular and cellular changes is a requirement for improving space medicine. In mammalian cells, microgravity induces apoptosis and alters the cytoskeleton and affects signal transduction pathways, cell differentiation, growth, proliferation, migration and adhesion.

Spinal muscular atrophy (SMA) is a common fatal autosomal recessive disorder characterized by degeneration of lower motor neurons, leading to progressive paralysis with muscular atrophy. The gene for SMA has been mapped to chromosome 5q13, where large-scale deletions have been reported. We describe here the inverted duplication of a 500 kb element in normal chromosomes and narrow the critical region to 140 kb within the telomeric region. This interval contains a 20 kb gene encoding a novel protein of 294 amino acids. An highly homologous gene is present in the centromeric element of 95% of controls. The telomeric gene is either lacking or interrupted in 226 of 229 patients, and patients retaining this gene (3 of 229) carry either a point mutation (Y272C) or short deletions in the consensus splice sites of introns 6 and 7. These data suggest that this gene, termed the survival motor neuron (SMN) gene, is an SMA-determining gene.

http://stm.sciencemag.org/content/2/35/35ra42.full.html figures, can be found at: and other services, including high-resolution A complete electronic version of this article http://stm.sciencemag.org/content/suppl/2010/06/07/2.35.35ra42.DC1.html "Supplementary Material" can be found at: Supporting Online Material http://stm.sciencemag.org/content/2/35/35ra42.full.html#ref-list-1

Interest in muscle MRI has been largely stimulated in the last few years by the recognition of an increasing number of genetic defects in the field of inherited neuromuscular disorders. Muscle ultrasound (US) and computed tomography (CT) have been used to detect the presence of muscle involvement in patients affected by these disorders, but until recently the use of muscle MRI has been, with a few exceptions, limited to detecting inflammatory forms. The aim of this review is to illustrate how muscle MRI, in combination with clinical evaluation, can contribute to the selection of appropriate genetic tests and more generally in the differential diagnosis of genetically distinct forms of neuromuscular disorders. Possible future applications of muscle MRI are also discussed.

Cervical spondylosis that causes upper-extremity muscle atrophy without gait disturbance is called cervical spondylotic amyotrophy (CSA). The distal type of CSA is characterized by weakness of the hand muscles. In this retrospective analysis, the authors describe the clinical features of the distal type of CSA and evaluate the results of surgical treatment. The authors performed a retrospective review of 17 consecutive cases involving 16 men and 1 woman (mean age 56.3 years) who underwent surgical treatment for the distal type of CSA. The condition was diagnosed on the basis of cervical spondylosis in the presence of muscle impairment of the upper extremity (intrinsic muscle and/or finger extension muscles) without gait disturbance, and the presence of a compressive lesion involving the anterior horn of the spinal cord, the nerve root at the foramen, or both sites as seen on axial and sagittal views of MRI or CT myelography. The authors assessed spinal cord or nerve root impingement...

This international nutrition accolade, including a $10,000 cash prize, is presented for the most outstanding ORIGINAL work directly relevant to the field of nutrition and metabolism accepted each year for publication in Nutrition: The International Journal of Applied and Basic Nutritional Sciences. All manuscripts published during 1995 were eligible and were reviewed by the Award Selection Committee. The selection was made on the basis of their recommendation.

A growing body of evidence supports the use of moderate blood flow restriction (BFR) combined with lowload resistance exercise to enhance hypertrophic and strength responses in skeletal muscle. Research also suggests that BFR during low-workload aerobic exercise can result in small but significant morphological and strength gains, and BFR alone may attenuate atrophy during periods of unloading. While BFR appears to be beneficial for both clinical and athletic cohorts, there is currently no common consensus amongst scientists and practitioners regarding the best practice for implementing BFR methods. If BFR is not employed appropriately, there is a risk of injury to the participant. It is also important to understand how variations in the cuff application can affect the physiological responses and subsequent adaptation to BFR training. The optimal way to manipulate acute exercise variables, such as exercise type, load, volume, inter-set rest periods and training frequency, must also be considered prior to designing a BFR training programme. The purpose of this review is to provide an evidence-based approach to implementing BFR exercise. These guidelines could be useful for practitioners using BFR training in either clinical or athletic settings, or for researchers in the design of future studies investigating BFR exercise.

The Portuguese Society of Human Genetics (SPGH - Sociedade Portuguesa de Genética Humana) was founded in 1996 by a group of 68 medical and clinical laboratory geneticists. Its mission, statutes and governance resemble those of societies of similar ilk. Aligned with these and with the European Society of Human Genetics, so too the SPGH has organized annual meetings, constituting a major event that brings together professionals and students from all over the Country. In 2018, from the 15th to the 17th November, Porto hosted the SPGH's 22nd Annual Meeting. Recent developments in several fields of human genetics were brought to discussion, with the spotlight on epigenetic regulation and dysregulation, the revolutionary role of immunotherapy in cancer treatment, advances in etiologic diagnosis and therapy of neurological disorders, as well as the ethical implications of genome editing. These were addressed in the format of plenary lectures, thematic sessions or Panel discussions (detailed proceedings available at www.spgh/net/reuniao-anual/22a-reuniao/). The programme included several Satellite meetings and three sessions each of oral and poster presentations, selected from a total of 97 Abstracts. The high scientific standard was set by the excellence of the guest speakers, all renowned experts in the respective fields, while the vivid discussions, exchange of ideas and new collaborations are a measure of the meeting's success. The event was rounded off with the usual SPGH prize-giving ceremony, with five awards: best presentations in Basic Research, Clinical Research, Clinical Case Reports, the Amândio Tavares Young Scientist Award and the ESHG Fellowship Award.

Spinal muscular atrophy (SMA) is characterized by degenerating lower motor neurons and an increased incidence of congenital bone fractures. Survival motor neuron (SMN) levels are significantly reduced due to deletions/mutations in the telomeric SMN1 gene in these patients. We utilized the Smn −/− SMN2 mouse model of SMA to determine the functional role for SMN in bone remodelling. μCT analysis of lumber vertebrae, tibia and femur bones from SMA mice revealed an osteoporotic bone phenotype. Histological analysis demonstrated a thin porous cortex of cortical bone and thin trabeculae at the proximal end of the growth plate in the vertebrae of SMA mice compared to wild-type mice. Histochemical staining of the vertebrae showed the presence of abundant activated osteoclasts on the sparse trabeculae and on the endosteal surface of the thin cortex in SMA mice. Histomorphometric analysis of vertebrae from SMA mice showed an increased number of osteoclasts. Serum TRAcP5b and urinary NTx levels were elevated, consistent with increased bone resorption in these mice. SMA mice showed a significant decrease in the levels of osteoblast differentiation markers, osteocalcin, osteopontin and osterix mRNA expression; however, there were no change in the levels of alkaline phosphatase expression compared to WT mice. SMA mouse bone marrow cultures revealed an increased rate of osteoclast formation (54%) and bone resorption capacity (46%) compared to WT mice. Pre-osteoclast cells from SMA mice showed constitutive upregulation of RANK receptor signalling molecules critical for osteoclast differentiation. Our results implicate SMN function in bone remodelling and skeletal pathogenesis in SMA. Understanding basic mechanisms of SMN action in bone remodelling may uncover new therapeutic targets for preventing bone loss/fracture risk in SMA.

Purpose: To develop and evaluate an expanded version of the Hammersmith Functional Motor Scale allowing for evaluation of ambulatory SMA patients. Procedures: Thirty-eight patients with SMA type II or III were evaluated using the Gross Motor Function Measure and the Hammersmith Functional Motor Scale. Based on statistical and clinical criteria, we selected 13 Gross Motor Function Measure items to develop an expanded HFMS. The expanded Hammersmith Functional Motor Scale was validated by comparison with the Gross Motor Function Measure minus the 13 items (GMFM-75) and an assessment of clinical function. The reliability of the expanded Hammersmith Functional Motor Scale in 36 patients was established. Findings: The expanded Hammersmith Functional Motor Scale was highly correlated with the GMFM-75 and the clinical function assessment (p = 0.97, and p = 0.90). The expanded Hammersmith Functional Motor Scale showed excellent test-retest reliability (International Coordinating Committee = 0.99).

Nutrition screening is usually administered by nurses. However, most studies on nutrition screening tools have not used nurses to validate the tools. The 3-Minute Nutrition Screening (3-MinNS) assesses weight loss, dietary intake, and muscle wastage, with the composite score of each used to determine risk of malnutrition. The aim of the study was to determine the validity and reliability of 3-MinNS administered by nurses, who are the intended assessors. In this cross-sectional study, 3 ward-based nurses screened 121 patients aged 21 years and over using 3-MinNS in 3 wards within 24 hours of admission. A dietitian then assessed patients' nutrition status using Subjective Global Assessment within 48 hours of admission, while blinded to the results of the screening. To assess the reliability of 3-MinNS, 37 patients screened by the first nurse were rescreened by a second nurse within 24 hours, who was blinded to the results of the first nurse. The sensitivity, specificity, and best ...

Brachial amyotrophic diplegia (BAD) is a subtype of sporadic lower motor neuron disease (LMND) presenting with adult onset, mainly in men, and remaining largely restricted to proximal arm and shoulder girdle muscles without involvement of the lower limbs or appearance of pyramidal signs. 1,2 Mutations in the copper/zinc superoxide dismutase (SOD1) gene have been described in familial cases of ALS and occurring in sporadic cases of ALS, [3][4] but not in patients with BAD. We describe here a patient with BAD syndrome associated with a novel SOD1 mutation.