Spinal Muscular Atrophy Group Research Articles

Oral functions in adult persons with spinal muscular atrophy compared to a healthy control group: a prospective cross-sectional study with a multimodal approach

BackgroundOral function tests have been shown to reliably detect impaired bulbar function in adults with spinal muscular atrophy (SMA). Although not routinely recorded, it is known that persons with SMA are affected to varying degrees. Detecting differences in bite and tongue force, endurance, and maximum mouth opening has become particularly promising since the introduction of causal therapy for SMA. This study aimed to compare oral function among adult persons with SMA with different SMA types, walking abilities, and treatment status to a healthy control group.MethodsData from oral function tests conducted on 58 persons with SMA and 45 healthy individuals were analyzed. Differences in oral function between SMA subgroups were pairwise tested and compared to the healthy control group using Wilcoxon rank sum tests.ResultsIn an overall comparison, three out of five oral function tests revealed lower values for the SMA group compared to the control group. Subgroup analyses indicated lower scores for most oral function tests in non-ambulatory, untreated patients with SMA type 2 compared to controls. Ambulatory, treated patients with SMA type 3 achieved strength and endurance values comparable to those of healthy individuals.ConclusionsThe impairment of oral function varies across persons with SMA. Routine measurement of oral function is warranted to determine individual bulbar involvement stages. Further evaluation should be scheduled if indicators such as restricted maximum mouth opening arise.Trial registration DRKS, DRKS00015842. Registered 30 July 2019, https://drks.de/register/de/trial/DRKS00015842/preview.

The Alterations of Gut Microbiome and Lipid Metabolism in Patients with Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) can cause multiple system dysfunction, especially lipid metabolic disorders, for which management strategies are currently lacking. Microbes are related to metabolism and the pathogenesis of neurological diseases. This study aimed to preliminarily explore the alterations in the gut microbiota in SMA and the potential relationship between altered microbiota and lipid metabolic disorders. Fifteen patients with SMA and 17 gender- and age-matched healthy controls were enrolled in the study. Feces and fasting plasma samples were collected. 16S ribosomal RNA sequencing and nontargeted metabolomics analysis were performed to explore the correlation between microbiota and differential lipid metabolites. No significant difference was found in microbial diversity (α- and β-diversity) between the SMA and control groups, with both groups having a relatively similar community structure. However, compared to the control group, the SMA group showed an increased relativeabundance of the genera Ruminiclostridium, Gordonibacter, Enorma, Lawsonella, Frisingicoccus, and Anaerofilum and a decreased abundance of the genera Catabacter, Howardella, Marine_Methylotrophic_Group_3, and Lachnospiraceae_AC2044_group. The concurrent metabolomic analysis showed that the SMA group had 56 different kinds of lipid metabolite levels than did the control group. Additionally, the Spearman correlation suggested a correlation between the altered differential lipid metabolites and the above-mentioned altered microbiota. The gut microbiome and lipid metabolites differed between the patients with SMA and the control subjects. The altered microbiota may be related with the lipid metabolic disorders in SMA. However, further study is necessary to clarify the mechanism of lipid metabolic disorders and develop management strategies to improve the related complications in SMA.

Behavioral problems in infants and young children with spinal muscular atrophy and their siblings: A cross-sectional study.

Older children and adults with spinal muscular atrophy (SMA) have been shown to have more anxiety, depression, and other behavioral problems in a few studies. But no similar studies have been performed in infants and young children with SMA. Behavioral co-morbidities of young children with SMA were compared with healthy and children with chronic non-neurological illness control group. Infant Behavior Questionnaire-Revised (IBQ-R) and parent-report version of chid behavior checklist (CBCL) were used for infants and preschool-age children respectively. A total of 35 SMA children (age at symptom onset-5.9±2.8 months, at enrolment-21.4±7.1 months, 65% boys, 11, 19 and 5 were SMA 1, 2 and 3 respectively) and 24 siblings (38.6±11.2 months, 71% boys) were enrolled. We also enrolled 15 children with nephrotic syndrome as age and gender matched control to SMA children in age-group 2-5 years (27.7±9.1 months, 67% boys). In infants with SMA, the scale scores of IBQ-R were significantly higher for distress to limitation, fear, sadness, and falling reactivity/rate of recovery from distress (p=0.005; 0.03; 0.001, and 0.04) and lower for soothability as compared to healthy control group (p=0.04). Similarly, for the three dimensions of temperament computed from these 13 domains, the mean scale score for surgency/extraversion was lower and negative affectivity was higher (p=0.04 and 0.03), in infants with SMA as compared to healthy controls. For preschool age group, the internalizing problem scores (p=0.009 and 0.03) and stress problem scores (p=0.002 and 0.04) were higher in the SMA group, as compared to both the healthy control group and diseased control group. While assessing the syndrome scale scores, the score was higher for emotionally reactive (p=0.0002 and 0.01) and anxious domains (p<0.0001 and p=0.0002) compared to both healthy and diseased control groups. Infants and young children with SMA suffer from increased internalizing problems like anxiety, depression and probably their healthy siblings are also at increased levels of stress, depicted by increased somatic complaints.

Significant healthcare burden and life cost of spinal muscular atrophy: real-world data.

The aim of this study is to quantify the mortality rate, direct healthcare costs, and cumulative life costs of pediatric patients with spinal muscular atrophy (SMA) type 1, type 2, and type 3 born in Hong Kong. Data were collected from genetically confirmed SMA patients born in or after 2000 from the Hospital Authority medical database. Patients were followed up from birth until they died, left Hong Kong, reached 18years, or initiated disease-modifying treatment. Study outcomes included incidence risks of mortality, cumulative direct medical costs-attendances of special outpatient clinics, emergency department, allied health services, and mean length of stay in hospitals over time. Total direct medical costs were calculated as unit costs multiplied by utilization frequencies of corresponding healthcare services at each age. Seventy-one patients with SMA were included. Over a median follow-up period of 6years, the overall incidence rate of death was 5.422/100 person-years (95%CI 3.542-7.945/100 person-years). 67.7% and 11% of deaths occurred in SMA1 and SMA2 groups, respectively. The median age of death was 0.8years in SMA1 and 10.9years in SMA2. The mean cumulative direct medical costs in overall SMA, SMA1, SMA2 and SMA3 groups per patient were US$935,570, US$2,393,250, US$413,165, and US$40,735, respectively. Our results confirmed a significantly raised mortality and extremely high healthcare burden for patients with SMA especially SMA type 1 and 2 without disease-modifying treatment. Study evaluating health and economic impact of newborn screening and early treatment is needed.

The alteration of left ventricular strain in later-onset spinal muscular atrophy children.

BackgroundPatients with spinal muscular atrophy (SMA) may suffer from multisystem injury, including an impaired cardiovascular system. However, M-mode echocardiography, the current dominant echocardiographic modality, is limited in the detection of myocardial injury. We considered the use of left ventricular strain imaging in detecting myocardial injury and explored the serum lipid profile related to cardiovascular disease in later-onset SMA children.MethodsA case-control study involving 80 patients with later-onset SMA and 80 age-, gender-, and body surface area-matched control children was conducted in a single tertiary pediatric hospital in China. Data on the left ventricular strain measured using two-dimensional speckle tracking echocardiography, left ventricular function parameters assessed by M-mode echocardiography, and serum lipid profile of these two groups were retrospectively collected for differential analysis.ResultsThe mean age of the 80 SMA patients were (6.87 ± 2.87) years, of which 46 were type 2 and 34 were type 3 patients. The global longitudinal strain (GLS) of the SMA group (−18.7 ± 2.9%, p < 0.001) was lower than that of the control group; the time to peak longitudinal strain (TTPLS) of the SMA group (22.9 ± 13.6 ms, p < 0.001) was higher than that of the control group, while left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), measured by the Teichholz method of M-mode echocardiography, showed no significant differences between the two groups. In addition, independent indicators for cardiovascular risk, including total cholesterol (TC)/HDL, low-density lipoprotein (LDL)/HDL, and Apo B/Apo A1 levels, were higher in SMA children than in the control group.ConclusionCompared with healthy controls, later-onset SMA children presented with reduced GLS and prolonged TTPLS while the LVEF and LVFS values were within normal range. In particular, whether a reduced GLS or prolonged TTPLS in later-onset SMA compared to the control group can predict the risk of future cardiomyopathy remains to be investigated.

Protocol-driven early tracheal extubation in patients with flaccid neuromuscular scoliosis and pre-existing lung disease.

To review the results of a postoperative respiratory pathway for patients with muscular dystrophy (MD) and spinal muscular atrophy (SMA) undergoing spinal surgery. With IRB approval, a retrospective review was done on all patients with SMA and MD undergoing spinal surgery on a neuromuscular protocol. Baseline demographics, perioperative results, and long-term outcomes were collected. Per the protocol, patients remained intubated after surgery and were transported to the intensive care unit (ICU) for extubation. We present the results of protocol implementation and compare patients with MD to those with SMA. Twenty-four patients were treated using the protocol. Average age was 13.1years. Severe restrictive lung disease was present in 75% of patients. Nocturnal BiPAP was required in 68% of patients. Average number of instrumented levels was 17. All patients were immediately extubated upon entering the ICU. There were three respiratory complications and only was patient was re-intubated. Average ICU stay was 1.8days and average hospital length of stay was 6.7days. No differences in postoperative inspiratory or expiratory positive airway pressures were observed between the MD and SMA groups. Through a multidisciplinary neuromuscular protocol, excellent clinical outcomes were achieved in patients with neuromuscular scoliosis and restrictive lung disease, with complication rates and length of stay significantly lower than previously published data. IV.

Neck and Trunk Muscle Strength in Children With Spinal Muscular Atrophy Is Lower Than in Healthy Controls and Depends on Disease Type.

Background: Neck and trunk muscle strength and relationship with motor function in individuals with spinal muscular atrophy (SMA) is not investigated well. Information on maximum muscle strength that children with SMA may develop considerably expands the possibilities of assessing the effectiveness of pharmacological treatment methods and therapeutic procedures. This study sought to assess neck and trunk muscle strength in patients with SMA and to compare it with values noted in healthy children.Methods: The study involved 56 individuals with SMA aged 5–16 not treated pharmacologically, including 9 patients with SMA type 1 (SMA1), 27 with SMA type 2 (SMA2), and 20 with SMA type 3 (SMA3). The control group included 111 healthy individuals aged 5–16. Neck and trunk muscle strength was assessed by means of a maximum voluntary isometric contraction method with the use of a handheld digital muscle tester MICROFET2. Moreover, relative strength was also calculated by standardising the maximum voluntary isometric contraction according to body mass. The Kruskal–Wallis test, Mann–Whitney U-test, and Spearman's rank correlation were used for statistical analysis.Results: The reliability of the neck and trunk muscle strength measurements with the handheld digital muscle tester was excellent with ICC > 0.9. The values of muscle strength in SMA groups were significantly lower than in the control group. The values of relative torque of the neck muscles expressed in percentage values calculated with regard to the control group were at the level of 47.6–51.6% in SMA1 group, 54.8–58.1% in SMA2 group and 80.6–90.3% in SMA3 group. The percentage values for upper and lower trunk muscle strength were at the level of 42.6–68.4% in SMA1 group, 56.9–75.4% in SMA2 group and 76.7–94.8% in SMA3 group.Conclusion: Handheld dynamometry provides reliable measures of neck and trunk muscle strength in SMA children. Neck and trunk muscle strength in children with SMA is lower than in healthy controls and depends on disease type, which confirms the theory based on clinical observations. Further, study is needed to investigate the effect of pharmacological treatment on the strength of the neck/trunk muscles, and relationship between neck and trunk muscle strength and motor capabilities.

Motor unit number index (MUNIX) in children and adults with 5q-spinal muscular atrophy: Variability and clinical correlations

Spinal muscular atrophy (SMA) is a motor neuron disease associated with progressive muscle weakness and motor disability. The motor unit number index (MUNIX) is a biomarker used to assess loss of motor units in later-onset SMA patients. Twenty SMA patients (SMA types 3 and 4), aged between 7 and 41 years, were clinically evaluated through the Hammersmith Motor Functional Scale Expanded and the Spinal Muscular Atrophy-Functional Rating Scale. The patients underwent compound motor action potential (CMAP) and MUNIX studies of the right abductor pollicis brevis, abductor digiti minimi and tibialis anterior (TA) muscles. Age-matched healthy controls (n = 20) were enrolled to obtain normative CMAP and MUNIX values from the same muscles. Compared to healthy controls, SMA patients showed significant reductions in MUNIX values among all muscles studied, whereas CMAP showed reductions only in the weaker muscles (abductor digiti minimi and TA). MUNIX variability was significantly higher in the SMA group than in the control group. MUNIX variability in TA correlated with CMAP variability. Motor functional scores correlated with TA MUNIX. The MUNIX study is feasible in later-onset SMA patients, and TA MUNIX values correlate with disease severity in patients with mild motor impairment.

Cervical rotation, chest deformity and pelvic obliquity in patients with spinal muscular atrophy

BackgroundMusculoskeletal disorders are often observed in patients with spinal muscular atrophy (SMA). The aim of the study was to assess passive ranges of rotation in the cervical spine, chest deformity and pelvic obliquity in SMA patients, and to compare these results to the norms obtained in the group of healthy individuals. The second aim was to review these measurements and Cobb angle values for correlations in SMA patients.MethodsThe study included 74 patients with SMA and 89 healthy individuals aged 2 to 18 years. Cervical Rotation (CR), Supine Angle of Trunk Rotation (SATR) and Pelvic Obliquity (PO) tests were carried out.ResultsCervical rotation ranges were significantly higher in the control group than in SMA patients (p < 0.05). Differences between cervical rotation ranges to the left and to the right were significantly larger in SMA I and SMA II groups than in healthy individuals (p = 0.000). Chest asymmetry and pelvic obliquity were bigger in SMA groups than in the control (p < 0.05). Significant correlations between cervical rotation measurements, chest deformity, pelvic obliquity and Cobb angle were found in SMA individuals, depending on the type.ConclusionsThe results of the study suggest that CR, SATR and PO tests may assist in the assessment of SMA patients in addition to the radiographic evaluation of the spine. Biomechanical relationships between disorders located in various skeletal structures should be taken into account in the treatment of SMA patients. Special attention should be given to assessing postural parameters in non- sitters and sitters. Treatment of patients with SMA and associated musculoskeletal disorders requires a multi-specialist approach.

Validity and Reliability of the 32-Item Motor Function Measure in 2- to 5-Year-Olds with Neuromuscular Disorders and 2- to 25-Year-Olds with Spinal Muscular Atrophy.

IntroductionTo investigate the validity and reliability of the 32-item Motor Function Measure (MFM32) in individuals with neuromuscular disorders (NMD), including spinal muscular atrophy (SMA), aged 2–5 years, and in non-ambulant individuals with Types 2 or 3 SMA, aged 2–25 years.MethodsTest–retest reliability (intraclass correlation coefficient [ICC]), internal consistency (Cronbach’s alpha [α]), convergent validity (Spearman rank-order correlations), and known-groups validity (analysis of covariance comparing groups defined by the Clinical Global Impression of Severity [CGI-S] scale and Vignos grade) were calculated. The analysis was performed on a dataset provided by Hospices Civils De Lyon, extracted from the multinational MFM32 database. A total of 165 individuals were included in the analyses, of whom 84 were in the NMD group (aged 2–5 years) and 81 were in the SMA group (aged 2–25 years).ResultsStrong evidence of test–retest reliability (ICC: 2- to 5-years’ population = 0.94–0.95; 2- to 25-years’ population = 0.97), internal consistency (Cronbach’s α: 2- to 5-years’ population = 0.96; 2- to 25-years’ population = 0.95), convergent validity (2- to 5-years’ population: CGI-S rho = − 0.84, Vignos grade rho = − 0.79; 2- to 25-years’ population: CGI-S rho = − 0.49), and known-groups validity (all P < 0.001) were demonstrated.ConclusionsThese analyses provide supportive evidence of the validity and reliability of the MFM32 in younger individuals with NMDs, aged 2–5 years, and in non-ambulant individuals with Types 2 or 3 SMA, aged 2–25 years, supporting the use of the MFM32 across a wide age range.

Neurochemical markers in CSF of adolescent and adult SMA patients undergoing nusinersen treatment.

Background:There is limited information on neurochemical markers being used to support and monitor the affection of motoneurons in patients with spinal muscular atrophy (SMA). The objective of this study was to examine neurochemical markers in cerebrospinal fluid (CSF) under treatment with the antisense-oligonucleotide (ASO), nusinersen.Methods:We measured markers of axonal degeneration [neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH)] along with basic CSF parameters in 25 adolescent and adult SMA type 2 and 3 patients at baseline and after four intrathecal injections of nusinersen. Neurochemical markers were compared with controls. In addition, neurochemical markers in SMA patients were related to the Hammersmith Functional Rating Scale Expanded (HFMSE).Results:No significant difference in neurofilament (Nf) values was observed between SMA and control group, neither at baseline nor after four injections of nusinersen. NfL, protein and quotients of albumin (Qalb) increased slightly in SMA patients after the fourth injection. The slight increase of NfL could be related to the development of mild CSF flow change. No relations were observed between changes in Nf and HFMSE.Conclusion:We assume that Nf levels in CSF in these patients may result from slow disease progression in this stage of disease, pre-existing loss of motoneurons due to long disease duration besides affection of the LMN only. Therefore, we conclude that Nf levels in CSF do not seem useful as diagnostic and monitoring markers in adolescent and adult SMA type 2 and 3 patients.

Modeling the phenotype of spinal muscular atrophy by the direct conversion of human fibroblasts to motor neurons.

Spinal muscular atrophy (SMA) is a lethal autosomal recessive neurological disease characterized by selective degeneration of motor neurons in the spinal cord. In recent years, the development of cellular reprogramming technology has provided an alternative and effective method for obtaining patient-specific neurons in vitro. In the present study, we applied this technology to the field of SMA to acquire patient-specific induced motor neurons that were directly converted from fibroblasts via the forced expression of 8 defined transcription factors. The infected fibroblasts began to grow in a dipolar manner, and the nuclei gradually enlarged. Typical Tuj1-positive neurons were generated at day 23. After day 35, induced neurons with multiple neurites were observed, and these neurons also expressed the hallmarks of Tuj1, HB9, ISL1 and CHAT. The conversion efficiencies were approximately 5.8% and 5.5% in the SMA and control groups, respectively. Additionally, the SMA-induced neurons exhibited a significantly reduced neurite outgrowth rate compared with the control neurons. After day 60, the SMA-induced neurons also exhibited a liability of neuronal degeneration and remarkable fracturing of the neurites was observed. By directly reprogramming fibroblasts, we established a feeder-free conversion system to acquire SMA patient-specific induced motor neurons that partially modeled the phenotype of SMA in vitro.

G.P.33 - Clinical and pathological features in SMA patients, confirmed by genetic analysis

Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by degeneration of the anterior horn cells of the spinal cord, resulting in symmetrical limb muscle atrophy and weakness. It is difficult to diagnose SMA patients in some cases, because of its clinical presentations mimicking muscular dystrophies. We aimed to describe clinical and pathologic characteristics of SMA patients, confirmed by genetic test. We reviewed clinical and pathological features of 14 patients, who were completely done with electrodiagnostic study (EDX) and muscle biopsy, and diagnosed as SMA with genetic study from November 1, 2005 to December 31, 2013. Among 14 patients, 8 patients (57.1%) were male. The mean age of symptom onset was 35 months old. Mean age at final genetic diagnosis was 21.1 years old and mean duration between clinical and genetic diagnosis was 7.3 years. All patients showed proximal dominant weakness and their most common first symptoms were both leg weakness. With clinical, EDX and muscle biopsy findings, 10 patients (71.4%) were diagnosed as SMA, but other 4 patients (28.6%) were diagnosed as myopathy. Those 4 patients showed proximal dominant weakness and their first symptoms were both leg weakness, meaning their CK levels were 395 U/L, higher than clinical and pathologically SMA group (45 U/L). Among them (9 patients), EDX showed chronic neurogenic process of 3 patients and myopathic change in 1 patient. Muscle biopsy presented myopathic change with 3 patients, no pathologic diagnosis with 1 patient and neurogenic change in 1 patient. Even though the results of muscle biopsy and electrodiagnostic study show ‘myopathic change’, genetic study of SMN1 gene may show ‘exon 7, 8 deletions’. It is helpful to consider the genetic test for SMN1 gene when we diagnose patients with unspecified neuromuscular disease.

Motor unit loss estimation by the multipoint incremental MUNE method in children with spinal muscular atrophy – A preliminary study

Quantitative EMG reflects denervation of muscles after lower motor neuron degeneration in spinal muscular atrophy (SMA) but does not reflect actual motor unit loss. The aim of our study was to assess the value of the multipoint incremental motor unit number estimation (MUNE) method in the modification by Shefner in estimating motor unit loss in SMA. The number of motor units, the mean amplitude of an average surface-detected single motor unit potential (SMUP), and the amplitude of compound motor action potentials (CMAP) were estimated in 14 children with SMA in the abductor pollicis brevis (ABP). Significant differences in MUNE values and SMUP and CMAP amplitude were found between the SMA and control groups (P < 0.0001). MUNE values correlated with Hammersmith Functional Motor Scale (HFMS) scores (P < 0.05). Increased SMUP amplitude values correlated with decreased HFMS scores (P < 0.05). The study confirms that MUNE method in the modification by Shefner is a useful tool reflecting motor unit loss in SMA, and it is easy to perform and well tolerated. MUNE and SMUP amplitude seemed to be sensitive parameters reflecting motor dysfunction in SMA but a longitudinal study in a larger number of subjects is needed.

P.13.1 Molecular biomarker of angiogenesis in neuromuscular disorders

In patients with neuromuscular disorders, microcirculation abnormalities in muscle tissues and angiogenesis affect pathomechanism. A total of 57 patients from 1.3 to 47.7years old with Duchenne muscular dystrophy (DMD), a total of 19 patients from 1.7 to 67.7years old with myotonic dystrophy (DM), a total of 31 patients with spinal muscular atrophy (SMA) from 3.0 to 58.3years old and 14 healthy controls (HC) from 6.9 to 48.7years old participated. We measured peripheral blood levels of circulating CD34+ cells and serum levels of creatine kinase (CK) in all participants, and serum levels of angiogenin and matrix metalloproteinase-9 (MMP-9) in 39 DMD and 13 HC. Levels of CD34+ cells of DMD were 1.94±1.20 count/μl, and those of DM were 0.86±0.47 count/μl, and those of SMA were 1.59±1.16 count/μl, and those of HC were 1.52±0.92 count/μl. Levels of CD34+ cells in DMD and SMA showed higher tendency than HC. Levels of CD34+ cells in DM were significantly lower than others. Levels of CD34+ cells were higher in younger DMD group, but not correlated with CK. In SMA group, cases with unstable respiratory condition showed higher levels of CD34+ cells. Levels of angiogenin in DMD were significantly lower than those in HC (1467.0±524.2pg/ml, 1885.8±325.6pg/ml, respectively), while levels of MMP-9 in DMD were significantly elevated as compared to HC (4.25±2.65ng/ml, 2.90±1.27ng/ml, respectively). Angiogenin and MMP-9 showed higher tendency in elder DMD group, and there was no significant correlation between levels of CD34+ cells and angiogenin or MMP-9 in DMD. Muscle disintegration in DMD and respiratory insufficiency in SMA may be related with CD34+ cells. As a source of angiogenesis factor, circulating CD34+ cells and angiogenin have pivotal role in angiogenesis. CD34+ cells seem to play an important role in pathomechanism in DMD, but angiogenin does not.

Pattern of motor neurone disease in eastern India.

A clinical study about the pattern of motor neurone disease in eastern India was carried out from July 1993 to June 1995 at Bangur Institute of Neurology, Calcutta and SSKM Hospital, Calcutta. A total of 110 cases were studied and they constituted 0.11% of all neurological cases seen in the general OPD. Of 110 cases, amyotropic lateral sclerosis (ALS) constituted 43.6%, progressive muscular atrophy (PMA) 10.9%, post-polio progressive muscular atrophy (PPMA) 1.8%, spinal muscular atrophy (SMA) 20%, atypical form Madras pattern of MND (MMND) 0.9% and monomelic amyotrophy (MMA) 22.7% of cases. Disease is more common in males than females and average duration of symptoms before presentation varied from 1 to 12 months. Most of the patients were either agricultural labourers or manual workers in ALS variety whereas MMA variety was evenly distributed in both hard labourers and sedentary workers. Most of the patients in MMA and SMA groups presented before 30 years of age whereas ALS and PMA group presented after 30 years. Trauma was the commonest antecedent event in ALS and MMA followed by electrocution in the same two groups. Family history was found to be absent in SMA group though the disease is considered as a hereditary one. Weakness of the limbs and wasting of the muscles were common presenting symptoms and signs. Bulbar symptoms and signs were found only in the ALS group. EMG showed neurogenic pattern and mixed pattern in most of the patients in all groups. Only a few patients showed myopathic pattern. Neuroimaging study helped in exclusion of compressive lesion excepting two cases of MMA where facetal hypertrophy was present. Monomelic amyotrophy, a special variety of motor neurone disease, is not rare in this part as compared to other parts of India and Asia.

Serum levels of vascular endothelial growth factor elevated in patients with muscular dystrophy

In patients with muscular dystrophy, such as Duchenne muscular dystrophy (DMD), microcirculation abnormalities and hypoxic ischemic conditions in muscle tissues are suspected to be induced by non-symptomatic coagulation fibrinolysis abnormalities and vascular dysfunction. Vascular endothelial growth factor (VEGF) is a critical regulating factor in angiogenesis that is known to be induced by hypoxic and/or ischemic conditions. To examine whether VEGF is associated with muscular dystrophy, we measured serum levels of VEGF in 52 patients with DMD, 15 with Becker muscular dystrophy (BMD), 20 with Fukuyama congenital muscular dystrophy (FCMD), eight with myotonic dystrophy (DM), and four with spinal muscular atrophy (SMA), as well as in 15 healthy and eight disease controls. The serum level of VEGF in the DMD patients was 267.7 ± 25.3 pg/ml (10.5–800.0), while it was 358.8 ± 96.3 pg/ml (0.2–1320.0) in the BMD patients, 261.4 ± 45.6 pg/ml (0.1–758.0) in the FCMD patients, 165.0 ± 63.4 pg/ml (2.6–479.0) in the DM patients, 96.0 ± 30.3 pg/ml (41.0–168.0) in the SMA patients, 148.3 ± 20.1 pg/ml (46.5–298.0) in the healthy controls, and 154.1 ± 54.0 pg/ml (7.2–343.0) in the disease controls. The level of VEGF in BMD was significantly elevated, as compared with DM, SMA, and control groups. Further, the level of VEGF in the bedridden sub-group of DMD patients was significantly elevated as compared with chair-bound DMD, DM, SMA, and control groups. We concluded that VEGF may reflect hypoxic and/or ischemic conditions in muscle tissue, and have a relationship with the process of disease progression in DMD and BMD patients.

Sporadic ALS with early-onset respiratory failure is not associated with IGHMBP2 gene mutations

Few distinct motor neurone disease (MND) variants—for example, familial amyotrophic lateral sclerosis (fALS) and spinal muscular atrophy (SMA)—are caused by definitive gene mutations. Within the phenotypic spectrum of the superoxide...

Physical capacity in non‐ambulatory people with Duchenne muscular dystrophy or spinal muscular atrophy: a longitudinal study

The purpose of this study was to describe functional ability, muscle strength, forced vital capacity, and clinical events in participants with Duchenne muscular dystrophy (DMD) or spinal muscular atrophy (SMA) in the non‐ambulatory stages of the diseases. Nineteen non‐ambulatory participants with DMD (all males; 13 to 24 years) and 13 with SMA (six males, seven females; 11 to 57 years) were assessed once a year over 5 years. The assessments comprised functional ability measured with the EK scale and upper extremity grade, muscle strength measured with the manual muscle test, and forced vital capacity defined as a percentage of normal values (FVC%). In the DMD group all variables measured deteriorated and there was a direct correlation between them. In the SMA group only muscle strength and FVC% deteriorated and there was no close relation between the variables measured. In the DMD group, 16 participants had cardiorespiratory clinical events leading to death in five cases. In the SMA group only four participants had respiratory clinical events, none leading to death. Although the participants with SMA had been extremely weak and non‐ambulatory since early childhood they were older and less exposed to life‐threatening events than the participants with DMD.

Physical capacity in non-ambulatory people with Duchenne muscular dystrophy or spinal muscular atrophy: a longitudinal study.

The purpose of this study was to describe functional ability, muscle strength, forced vital capacity, and clinical events in participants with Duchenne muscular dystrophy (DMD) or spinal muscular atrophy (SMA) in the non-ambulatory stages of the diseases. Nineteen non-ambulatory participants with DMD (all males; 13 to 24 years) and 13 with SMA (six males, seven females; 11 to 57 years) were assessed once a year over 5 years. The assessments comprised functional ability measured with the EK scale and upper extremity grade, muscle strength measured with the manual muscle test, and forced vital capacity defined as a percentage of normal values (FVC%). In the DMD group all variables measured deteriorated and there was a direct correlation between them. In the SMA group only muscle strength and FVC% deteriorated and there was no close relation between the variables measured. In the DMD group, 16 participants had cardiorespiratory clinical events leading to death in five cases. In the SMA group only four participants had respiratory clinical events, none leading to death. Although the participants with SMA had been extremely weak and non-ambulatory since early childhood they were older and less exposed to life-threatening events than the participants with DMD.