EDAN pushes for Kenya's implementation of Disabilities Rights Convention

GENEVA, Switzerland, August 24, 2015/African Press Organization (APO)/ -- Despite significant steps taken by the Kenyan government, coordinator of the World Council of Churches (WCC) Ecumenical Disability Advocates Network (EDAN) Dr Samuel Kabue says that “more needs to be done” so that people with disability can enjoy their rights.

“They must have access to inclusive and viable environment, sign language support, feasible transport, communication, legal capacity, health care and employment, among other rights,” he reports.

Kabue adds that people with disability speak about their rights from an experiential point of view: “This point of view may not be the same as the government's, which mostly implies that all is fine.”

Kabue shared these reflections in an interview following his participation in a session of the Committee on the Rights of Persons with Disabilities (CRPD) which concluded its consideration of the initial report of the Kenyan government on its implementation of the Convention on the Rights of Persons with Disabilities on 19 August in Geneva, Switzerland.

The Kenyan state ratified the Convention in May 2008, among the early ones to do so. The Convention has been been ratified by 157 states as of the end of Geneva meeting this month.

According to Kabue, the National Council of Churches of Kenya has been instrumental in raising awareness on disability issues. However, he feels that in order to make a stronger impact, churches need to engage with the Convention for an effective implementation.

“If the churches enhance their understanding of the Convention, they will be able to advocate more strongly for the rights of people with disability,” said Kabue. This is one theme, he explained, that was discussed in an elaborate dialogue side-event organized by the EDAN and other civil society organizations that was held during the 14th Session of the CRPD Committee of Experts in Geneva.

Kabue shared that a number of significant topics were addressed at the CRPD Committee of Experts session, including issues related to men, women and children with disabilities; persons with albinism; legal capacity; accessibility both in public transport and facilities; refugees and migrant workers with disabilities; inclusion of persons with disabilities in policy-making processes; multiple discrimination and inter-sectional disabilities.

Kabue said that in Kenya, among other countries, EDAN is working with other disability organizations in pushing for an effective implementation of the Convention on the Rights of Persons with Disabilities. He explained that EDAN was among the influential “non-state actors” whose participation in the CRPD was facilitated by the International Disability Alliance.

Established in 1998, EDAN, along with churches and its partner organizations, addresses the issues affecting persons with disabilities globally, advocating for the inclusion, participation, and active involvement of persons with disabilities in the spiritual, social and development life of the church and society.

Article provided by World Council of Churches (WCC) via Mordern Ghana.

Kimbowa offers life lessons to many who take things for granted by Diana Nabiruma

Joseph Kimbowa, 23, remembers running around Villa Maria, Masaka, chasing after an old bicycle tyre.

With a stick, he would push the tyre and run until his little, sturdy legs were exhausted. His legs were sturdy, he emphasises. He would look at them and they reminded him of a footballer’s.

His arms were bulky too, like a body-builders. He maximised his athletic frame. Other than chasing after bicycle tyres, he played football and engaged in athletics.

BEGINNINGS OF MUSCULAR DYSTROPHY

But then, mysteriously, his strong beautiful legs started to betray him.

“I would fall whenever I would attempt to run,” he says.

His family was concerned. Why would a seemingly strong and healthy boy fall while running? He said he felt that his muscles were weaker, and could not properly support him. But he could still run small distances at slow speeds, couldn’t he?

He couldn’t. Doctors and herbalists were consulted and he received various treatments.

“They didn’t help me. I only started to feel worse. My bones were aching, alongside with me feeling increasingly weak.”

He soon dropped out of school. Little schoolboys thought his yet-to-be diagnosed condition was funny. They pushed him so he could fall, to their delight.
Kimbowa was not happy with their behaviour; so, he dropped out of school.

DIAGNOSED IN KAMPALA

A nun, wondering why Kimbowa was out of school, was told he was ill. She sponsored his trip to Kampala, where he was diagnosed with muscular dystrophy. His sister, Joslyn Nambatya, weeps when she talks about the doctor at Chesire Home, Katalemwa who hinted at serious trouble.

“When we got to Katalemwa, he [Kimbowa] was happy. He saw children being fitted with metals in their legs and said ‘I am going to be fine, baaba [big sister]. I will get those metals and I will be fine’,” Nambatya recalls.

The doctor, however, suspecting muscular dystrophy, said that Kimbowa might never be cured and he would likely die a young man.

“He was speaking English and I didn’t think he [Kimbowa] understood him. But when we left, he was sad, saying that he had heard the doctor say he would never be healed,” Nambatya says.

She breaks down sobbing, nine years after being told her brother would never heal.

“Please call me back later,” she requests between sobs.

When called later, Nambatya, a mother of two, worriedly asks: “Do you think my son will get muscular dystrophy?”

She pauses, as if she is chewing on some unpleasant information.

“I was told that the condition is passed from mothers to their sons. That us [girls] we are carriers. But the boys! They suffer. I have a son and daughter. I wonder whether my son is safe.”

MUSCULAR DYSTROPHY

Dr Justus Byarugaba, a paediatrician and nuero-physician who has worked with Nakasero hospital, confirmed Kimbowa’s muscular dystrophy. He asked to study Kimbowa’s family as Kimbowa has maternal cousins with the disease.

“He wanted to do biopsies but I had been advised against them. I refused. I took my brother to Kampala School of the Physically Handicapped thereafter,” Nambatya says.

UK’s National Health Services (NHS) defines muscular dystrophy as “a group of inherited genetic conditions that gradually cause the muscles to weaken.”

Seven types of muscular dystrophy, including duchenne, myotonic, facioscapulohumeral, Becker, limb-girdle muscular dystrophy, oculopharyngeal and Emery-Dreifuss, are listed by the organisation’s website.

The condition is caused by mutation of genes “responsible for the structure and functioning of a person’s muscles. These mutations cause changes in the muscle fibres that interfere with the muscles’ ability to function. Over time, this causes increasing disability,” the website says.  

Nambatya’s fears for her son’s vulnerability are not far fetched.

“Muscular dystrophy is often inherited from parents,” Dr Enoch Kawalya of CORSU, a facility that treats disabilities, says. “I recently saw a whole family [of boys] with the condition.”

One prominent pastor’s sons are all said to have died as a result of Duchene muscular dystrophy. As this story might have shown, boys seem to be more affected by Duchene muscular dystrophy, which is sex-linked.

According to the NHS, this is because “females have two copies of the X chromosome [and] they are less likely to develop an X-linked condition because the normal copy of the chromosome [from the parent without muscular dystrophy] can usually compensate for the altered version.”

Muscular dystrophy is said to be uncommon in Uganda.

“We see one to two patients with muscular dystrophy every three weeks,” Kawalya says.

Duchene muscular dystrophy, which Kimbowa suffers from and is said to be the commonest, is symptomised by difficulty in walking, running or jumping, difficulty in standing up, learning to speak later than usual, being unable to climb the stairs without support and having behavioural or learning difficulties.

Bulkier frames, like Kimbowa’s, could also be seen in muscular dystrophy. All types of muscular dystrophy are progressive and incurable in nature, but Duchene muscular dystrophy is said to be the most severe, putting its sufferers in wheelchairs between the ages of eight and 14.

EARLY DEATH

Kimbowa’s muscular dystrophy has progressed to a point that he can no longer turn himself in bed or dress himself. His parents, who are shopkeepers, pay a minder to help him with bathing, dressing and perform other chores.

“They [children with Duchene muscular dystrophy] die a lot. We have lost four since I joined this school in 2006,” Proscovia Kajubi, a teacher at Kampala School of the Physically Handicapped, says. Kajubi taught Kimbowa.

Duchene muscular dystrophy results in damage of the lungs and heart and “once the heart and respiratory muscles are damaged, Duchene MD becomes life-threatening. With medical care, most people with Duchene MD die from heart or respiratory failure before or during their 30s,” nhs.uk says.

Muscular dystrophy is treated with physiotherapy and other interventions. Kajubi says they encourage sporting activities such as swimming, seat-volleyball and seat-ball, among others, so that the children still in school do not get depressed.

HOPES AND MISCONCEPTIONS

“Sometimes I get hope that it can be cured. Do you think those pastors can help?” Kimbowa asks me in a tired voice.

Knowing what I do about muscular dystrophy, I only grunt. There is a pause in the conversation, where thoughts are rearranged. Kimbowa is the first to speak.

“You know, for some people the disease is a curse,” he says thoughtfully.

Spiritually, that could make sense, but science disagrees. The disease is a result of gene mutations. 

Then Kimbowa speaks about his dreams.

“If I were somewhere abroad, my life would be better. But for now, I think about settling in Kampala. That is where most of my friends are.”

Kimbowa repairs mobile phones. When I first met him in 2011, he hoped to fulfill this dream and he has. Repairing phones is easiest for him, because they are light and he can lift them. He is seeking sponsors to help him attain training in mobile phone repairs.

He can be reached on 0757112101or on 0784617959. But you have to be patient. It takes him extraordinary effort to pick his mobile phone up when it rings.
Sigh! The things we do take for granted!

The conversation turns to children. Would he want any? He brightens up for the first time in the 41-minute interview.

“I always think about that. But it is not easy to be patient with someone like me. I have tried to talk to some girls. But it is not easy,” Kimbowa says.

You can feel the smile in his voice. I tell him that it is not easy for most boys and men without his condition. Kimbowa laughs and we say our goodbyes.

IMPORTANCE OF RESPIRATORY CARE

Taking care of our respirator system is very important especially when you have a neuromuscular condition which progressively wastes and weakens the muscles. This is so because it can affect your breathing making it hard for one to breath normally and cause discomfort while coughing.

According to Muscular dystrophy Canada site on respiratory care (http://www.muscle.ca/living-with-muscular-dystrophy/respiratory-care/) these are the symptoms one should look out for to know if you have respiratory complications due to MD:

• Sleeping more often
• Constant fatigue
• Occasional confusion
• Difficulty concentrating
• Muscle twitching that previously did not exist
• Constant or periodic headache
• Significant shortness of breath at rest
• Difficulty sleeping or lying down
• Unconsciousness or difficulty waking up

It is important to keep monitoring yourself and let your doctor know of the changes you feel in your body for proper care and treatment. Self advocacy is key to avoid complications that can become life threatening.

For people living with DMD breathing may become difficult during the day and they will be required to use a ventilator to breath. The lungs become weaker as the condition progresses and preventing infections of the lungs such as pneumonia is vital. It is also advisable to get pneumonia vaccination.

A cough assist can also help people with MD cough well when they have a cold or infection.

DARE TO BUST A MOVE FOR LGMD AWARENESS

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0LGMD Awareness Day Dare to bust a move challenge.

Muscle exercise in limb girdle muscular dystrophies: pitfall and advantages

This infomation has not been altered in anyway and is meant to provide information to all living with LGMD. This is the original version as it appears in:  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4478773/

GABRIELE SICILIANO,1 COSTANZA SIMONCINI,1 STEFANO GIANNOTTI,2 VIRNA ZAMPA,3 CORRADO ANGELINI,4 and GIULIA RICCI1

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Abstract

Different genetic mutations underlying distinct pathogenic mechanisms have been identified as cause of muscle fibers degeneration and strength loss in limb girdle muscular dystrophies (LGMD). As a consequence, exercise tolerance is affected in patients with LGMD, either as a direct consequence of the loss of muscle fibers or secondary to the sedentary lifestyle due to the motor impairment. It has been debated for many years whether or not muscle exercise is beneficial or harmful for patients with myopathic disorders. In fact, muscular exercise would be considered in helping to hinder the loss of muscle tissue and strength. On the other hand, muscle structural defects in LGMD can result in instability of the sarcolemma, making it more likely to induce muscle damage as a consequence of intense muscle contraction, such as that performed during eccentric training. Several reports have suggested that supervised aerobic exercise training is safe and may be considered effective in improving oxidative capacity and muscle function in patients with LGMD, such as LGMD2I, LGMD2L, LGMD2A. More or less comfortable investigation methods applied to assess muscle function and structure can be useful to detect the beneficial effects of supervised training in LGMD. However, it is important to note that the available trials assessing muscle exercise in patients with LGMD have often involved a small number of patients, with a wide clinical heterogeneity and a different experimental design. Based on these considerations, resistance training can be considered part of the rehabilitation program for patients with a limb-girdle type of muscular dystrophy, but it should be strictly supervised to assess its effects and prevent possible development of muscle damage.

Key words: limb girdle muscle dystrophies, muscle fatigue, muscle exercise

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Introduction

In limb girdle muscular dystrophies (LGMD), different genetic mutations, through distinct pathogenic mechanisms, determine a failure of muscle fibers in maintaining their physical structure during contraction, leading to sarcolemma breakdown, progressive muscle fibers degeneration and strength loss. Depending on that, exercise tolerance is affected in patients with LGMD, either as a direct consequence of loss of muscle fibers, but also secondary to the sedentary lifestyle due to the motor impairment. However, the cellular mechanisms that triggers skeletal muscle dysfunction and, ultimately, leads to muscle necrosis is still unclear, and available therapies are consequently inadequate.

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Pathophysiology of fatigue and exercise intolerance in muscular dystrophies

Muscular dystrophies are genetic muscle diseases characterized by a progressive loss of motor unit constituents, due to different degeneration mechanisms, and by a wide range of phenotypes. Like dystrophinopathies (Duchenne and Becker muscular dystrophy, DMD, BMD), the majority of LGMD, that result from mutations in genes encoding specific structural protein, are prototypes of failure of the muscle fiber to maintain its physical structure during contraction, leading to sarcolemma breakdown, myofiber degeneration and necrosis.

As a consequence, more than 60% of dystrophic patients experiences severe fatigue as a common and precocious symptom of disease manifestation. Muscle fatigue occurs when the intended physical activity can no longer be continued or is perceived as excessive effort and discomfort, depending on the interaction between the required force, the maximum force that the myofiber produces, as well as its endurance, also defined as fatigue resistance. At molecular level, although the loss of skeletal muscle mass accompanying the dystrophic process may be considered as a pathogenic factor in reduced muscle force generation in LGMD, several other and often interconnected mechanisms, as excitationcontraction coupling or energy breakdown, are involved in the genesis of muscle fatigue. However, the exact mechanism of the progressive muscle fibers necrosis in muscular dystrophies is still unknown, as well as the role of energy production in the cascade of events ending with muscle fiber degeneration. Related to that, evidence that the tricarboxylic acid cycle and some reactions in glycolysis are dependent on the integrity of cytoskeletal organization may suggest a role for defective energy metabolism in muscle fiber degeneration. In the clinical setting, a careful analysis of the muscle function is important to characterize the "phenomic" of muscle force impairment and fatigue in muscular dystrophies and to design outcome measures and optimal strategies to treat patients with decreased fatigue resistance (1).

A better knowledge of the muscle metabolic changes during exercise may be useful in understanding the role energy utilization plays in contractile insufficiency and pathogenic mechanisms. For these purposes, 31Phosphorus (31P) magnetic resonance spectroscopy (MRS) may be used to study skeletal muscle metabolismin vivo. The technique has become an important tool in the study of the pathophysiology of muscle diseases. 31P-MRS is used for providing information about the biochemical composition and metabolism of tissue without invasive sampling, and it has the unique ability to measure intracellular pH. Given that MRS is well tolerated and examinations are easily repeated, it may also be applied in longitudinal studies of disease progression or outcomes. Interestingly, studies performed by muscle 31P-MRS have shown significant differences in several metabolite ratios in dystrophic patients indicating a lower energy state (2). In particular, the reduced cytosolic acidification during exercise suggests a defective glycolytic activity in skeletal muscle of patients with Becker muscular dystrophy. A recent work performed by our group studied the exercise-related muscle metabolism in mildly affected BMD patients assessed by muscle 31P-MRS during an incremental workload. We observed that BMD patients, compared with normal controls, showed downregulation of resting pH and intramuscular membrane breakdown, an increased anaerobic metabolism during sustained submaximal contraction and the maintenance of oxidative function during recovery (3).

Lodi and coworkes in 1997 (4) used MR imaging and 31P-MRS to study skeletal muscle in seven patients with LGMD with a variable deficiency of the alpha- (D), beta- (E), and gamma- (C) sarcoglycan but normal dystrophin expression on muscle biopsy. In LGMD patients, the authors observed that calf muscle phosphorylated compound content did not differ from controls, but the cytosolic pH was increased. Notably, the degree of calf muscle fat replacement inversely correlatedwith cytosolic pH and directly with phosphocreatin/adenosine triphosphate (PCr/ATP). Muscle oxidative metabolism was normal in LGMD2-C,- D,-E patients. The authors concluded that primary deficits of sarcoglycan complex lead to specific morphological and metabolic patterns of skeletal muscle involvement. In a recent study, we assessed exercise-related muscle metabolism by muscle 31P-MRS during an incremental workload in 10 mildly affected LGMD2A (6 males, 4 females, mean age 31.4 ± 9.5) patients and 3 LGMD2B patients, and 20 healthy controls (unpublished data). The incremental workload exercise test consisted of isometric intermittent plantar flexions of the dominant leg through an MR-compatible ergometer. Test normalization was obtained with reference to individual isometric maximal voluntary contraction (MVC), a valuable force indicator in contracting muscles. The inmagnet exercise protocol was made up of an incremental workload starting from 20% of the mean MVC (re-measured at rest 1 hour before the examination) and progressively increased by 10% MVC every 30 seconds until the subject's exhaustion (3). 31P MRS data were acquired from calf muscles. At rest, LGMD-2A and -2B subjects had a significantly higher cytosolic pH (p < 0.03), an increase in phosphodiesters (PDE), as markers of membrane rupture, and adenosine diphosphate (ADP) (p < 0.02), while they showed a reduction of phosphocreatine (PCr) (p < 0.01) compared with controls. No significant differences were found in mean values of metabolic variables during exercise between LGMD subjects and controls, while, at the end of exercise, PCr recovery rate in PGMD2A was significantly reduced (p < 0.02) in comparison with LGMD2B subjects and healthy controls, suggesting an alteration of oxidative metabolism.

However, when considering metabolic pathway related to fatigue in muscular dystrophies, reports have shown that lactic acid does not have always a deleterious influence on muscle contraction and it does not cause muscle fatigue. In fact, althought the reduced intracellular pH may alter muscle performance, given that the glycogen storage is more rapidly depleted when consumed anaerobically, producing lactic acid, it is also likely that its deleterious effects have been overestimated (5).

Alternatively, it has been proposed that the effects of ionic changes, i.e. the changes in the homeostasis of Ca2+ and reactive oxygen species (ROS) in the myoplasm, cause muscle fatigue.

Failure in calcium release is one of the major contributor to fatigue. Sarcoplasmic reticulum (SR) Ca2+ stores decline during fatigue. It has been demonstrated that the increased inorganic phosphate (Pi) affect fatigue development by acting on SR Ca2+ handling, by reducing cross-bridge force and the Ca2+ sensitivity of the myofilaments, with secondary early drop in force (1). According to the "Ca2+ precipitation theory", if Pi goes into the SR during fatigue, this can result in Ca-Pi precipitation and decrease of the Ca2+ available for release.

There is also a growing literature that indicates the "oxidative stress" as major source of signal pathway in the generation of muscle fatigue (6, 7). The superoxide anion (O2•–) is one of the major reactive oxygen species (ROS). In addition, O2•– reacts with nitrogen oxide (NO), with the production of peroxynitrite (ONOO–), a reactive nitrogen species (RNS). Muscle contraction requires a large amount of ATP. The majority of ATP is produced by mitochondrial oxidative phosphorylation (OXPHOS); during exercise, mitochondria utilize an amount of O2 which is up to 100-fold higher than the one used during resting. The high rate of O2 consumption in skeletal muscles determines also an electron dispersion from the electron transfer chain during OXPHOS, with secondary generation of O2•– (8). ROS/RNS production in muscles causes oxidative stress that is dangerous for cellular DNA, proteins and lipids. ROS have been identified as endogenous mediators of muscle fatigue, highlighting the importance to develop antioxidants as therapeutic interventions for fatigue treatment (8).

The nitric oxide (NO) pathway has also been implicated in the genesis of muscle fatigue in muscular dystrophies. NO synthesized from L-arginine catalyzed by NO synthase is a widespread biological mediator with many functions, including cell signaling and protection from reactive oxygen intermediate superoxide. Loss of normal NO production in dystrophic muscle is expected to have a broad, disruptive effect on muscle function (9). Neuronal nitric oxide synthase (nNOS) is a key muscle enzyme in the production of NO, that is involved n the regulation of vasorelaxation and muscle blood supply. NOS is associated with dystrophin-associated protein complex at the sarcolemmal level, where it provides stability to the myofiber membrane during contraction. In the absence of dystrophin, as observed in dystrophinopathies, the concentration of NOS at the cell membrane and in the cytoplasm decreases, and the concentration of NOS mRNA is also reduced (10). It has been hypothesized, both in mdx mice and boys with Duchenne muscular dystrophy (11-13), that the displacement and the secondary loss of nNOS and abnormalities in the levels of its expression in muscle significantly contribute to fatigue by inducing muscle ischemia during contraction. Interestingly, nNOSnull mice display a specific deficit in adapting to exercise and develop profound fatigue upon repeated muscle contraction (14). nNOS levels were also reduced in other genetic forms of muscle disease, including those resulting from defects in extracellular matrix proteins laminin a2 and collagen VI. Mutations in dysferlin are also shown to be characterized by reduced levels of nNOS. Loss of the sarcoglycan–sarcospan complex in muscle, as observed in sarcoglicanopathies, causes a reduction in the levels of nNOS expression at the membrane, even in the presence of normal dystrophin expression (15).

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Effects of exercise training in muscular dystrophies

In healthy individuals physical exercise training is considered one of best intervention to improve muscle strength, endurance and cardiorespiratory function. Regular exercise can also prevent diseases such as diabetes mellitus, arteriosclerosis, some forms of cancer, bone fractures, overweight, and it may improve cognition and mood. Moreover, it can avoid the age-related loss of muscle, called sarcopenia. Physical fitness training is a planned and structured regimen of regular physical exercise. In particular, strength training is defined as a training performed primarily to improve muscle strength and endurance and it is typically carried out making repeated muscle contractions against resistance. Indeed, aerobic exercise training, or cardiorespiratory fitness training, is a training that consists of an activity or combination of activities that uses large muscle groups, that can be continuously maintained, and that is rhythmical and aerobic, for example walking, running, cycling, or swimming (Fig. 1).

Fig. 1.

Studies of exercise training in patients with different neuromuscular diseases seem to suggest a positive effect without susceptibility to muscle injury (16- 18). In fact, strength training, which is performed to improve muscle strength and muscle endurance, or aerobic exercise programs, which involve training at moderate levels of intensity for extended periods of time (for example, distance cycling) might maximize muscle and cardiorespiratory function and prevent additional disuse atrophy (19). Previous studies demonstrated a beneficial effect of low- to moderate-intensity resistance and aerobic training in slowly progressive myopathies (20). An improvement in aerobic capacity may prevent type 2 diabetes, cardiovascular disease, and other lifestyle diseases. Patients with neuromuscular disorders are known to have a higher risk of developing disorders associated with obesity and a sedentary lifestyle, such as metabolic syndrome, when compared with the general population. Therefore, the positive effect of a training program on aerobic capacity in these patients is of substantial importance for their long-term health and quality of life (21, 22). However, clinicians are still afraid about muscle overuse during exercise in people with muscle disease and have a cautious approach to training. Limitations in patient number, design, and, most importantly, lack of supervision have often precluded any firm conclusion from previous studies (23). Importantly, as the pathophysiology of muscular dystrophies and myopathies differs, their reaction to training intervention might be different.

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Muscle damage and exercise in LGMD

The damage of skeletal muscle during exercise may be caused by metabolic or mechanical mechanism. The metabolic damage is the result of ischemia or hypoxia during prolonged exercise, resulting in changes in ion concentration, accumulation of ROS and deficiency of ATP. Mechanical stimuli can determine muscle damage as direct consequence of overload of muscle fibers or inappropriate balance of exercise variables, with a secondary disruption of the sarcomeric Z lines (24) and plasma membrane with loss of muscle proteins, such as creatine kinase (CK), lactate dehydrogenase, aldolase, myoglobin, troponin.

Muscle contractions may determine mild and nosignificant damage of muscle fibers during daily common activities (25). More severe injuries accompanied by myalgias are also possible, especially during predominantly lengthening (eccentric) contractions. There are three different types of contractions. If the force developed by the muscle is greater than the load on the muscle, a shortening (concentric) contraction occurs. When the force developed by the muscle and the load are equivalent, or the load is immovable, a fixed length, or isometric contraction, results.

The third type of contraction occurs when the load on the muscle is greater than the force developed by the muscle and the muscle is stretched, producing a lengthening (eccentric) contraction. Depending on the severity of the injury, complete recovery may require from 7 to 30 days. Training with protocols of lengthening (eccentric) contractions produces a hypertrophic and stronger muscle. The "trained" muscle is then able to perform the protocol of repeated lengthening contractions that previously caused injury without sustaining an injury. It may be hypothesized that tear and load due to exercise on a sick muscle could accelerate the disease process in muscular dystrophies, in which sick fibres of different sizes, with disorganised myofibrillar structure, often undergoing regeneration or necrosis, in association with fibrosis and adipose tissue, does not seem for contractile activity. Based on the above considerations, patients with neuromuscular disorders in the past have been advised to refrain from strenuous exercise. But, one of the consequences of this is that patients develop severe deconditioning, with potential acceleration of the primary muscle disease process.

However, in last decade, a growing number of studies has shown that exercise can be safe and beneficial for several muscle diseases, but, to date, it is still unknown what kind of exercise (aerobic versus strength training) should be recommended, and at what duration, frequency and intensities it should be performed. Starting from actual knowledge, there is the need to plan future studies aimed at addressing if motor training for muscle disease can play a therapeutic effect (26).

Endurance training in LGMD2I (Sveen et al., 2007) (27)

Sveen and coworkers (27) analyzed the effect of lowintensity aerobic training in 9 patients with limb-girdle muscular dystrophy type 2I (LGMD2I), caused by mutation of fukutin-related protein, that is a cytosolic protein that glycosylates alpha-dystroglycan. Aplha-dystroglycan and integrin alpha-7beta-1D are the two main laminin receptors in skeletal muscle, playing a major role for the integrity of the sarcolemma. Exercise could be deleterious in patients with LGMD2I, considering the importance of alpha-dystroglycan in linking the sarcolemma to the extracellular matrix. The AA also evaluated the effect of a training program consisted in fifty 30-minute training sessions on cycle ergometer for 12 weeks, at a heart rate corresponding to 65% of their maximal oxygen uptake (VO2max). As a marker of exercise-inducing muscle damage, plasma CK was measured before and after a 12-week training period, 24 to 48 hours after the final training session. Plasma lactate and heart rate were used to validate the degree of exhaustion during cycle tests before and after training. Training improved VO2max and maximal workload in patients with LGMD2I. Plasma lactate levels and heart rate at rest and at VO2max did not differ significantly before and after training. Plasma CK levels tended to increase after training in patients, but also increased in nine matched healthy controls. Self-reported questionnaires showed that the majority of subjects with LGMD2I felt an improvement in physical endurance, leg muscle strength, and walking distance. No worsening of their condition or adverse events were reported.

The authors concluded that 12 weeks of low intensity aerobic training was effective and safe in increasing fitness in patients with LGMD2I. Training raised the patient's VO2max and workload capacity in watts by 21% and 27%, corresponding to the normal physiologic response to training in the healthy subjects. Increased work capacity was paralleled by self-reported improvements in endurance, leg muscle strength, and walking distance (27).

Resistance training in patients with LGMD2I and LGMD2A (Sveen et al., 2013) (28)

Sveen and coworkers presented the results of two pilot studies on the effect of resistance training in patients with LGMD2I, LGMD2A and Becker muscular dystrophy (BMD) (28). In particular, in one study they investigated the effect of low-intensity strength training (LOIT) in 2 patients with LGMD2A, in 4 patients with LGMD2I and 2 patients with BMD; in the other, they assessed the effect of high-intensity strength training (HIT) in 4 patients with LGMD2A, in 2 patients with LGMD2I and 1 patient with BMD. All recruited patients were ambulatory and considered to be mildly-moderately affected.

In LOIT study, the resistance-training program lasted 6 months. Two muscle groups were included in the training program: quadriceps (knee extension) and biceps brachii (elbow flexion). During the first 4 months of training the dominant side was trained, while both sides were trained for the final 2 months of training. The weight lifted during knee extension and elbow flexion started at 40% and was increased by 5% a week. Subjects were tested before and after 4 and 6 months of training for maximal strength and endurance (number of repetitions possible at 60% of maximal strenght). They also completed a questionnaire, named Sickness Impact Profile (SIP), for assessment of their daily function and quality of life. As a marker of exercise-induced muscle damage, plasma CK was monthly measured during the training period. At the end of the training period, elbow flexion and knee extension showed a significant increase in muscle strength and endurance; there was no change in the results from the SIP questionnaire regarding daily activities.

In HIT study, the training program lasted for 3 months. Additional muscle groups were included for testing, including wrist flexion and extension and plantar flexion, and both the right and left extremities were trained from the beginning. Subjects followed a strength training program with 3 sessions per week over the course of 12 weeks, with at least one day of rest between each training session. Supervision was provided during each session by a personal instructor. Patients were tested for maximum strength monthly. In order to measure endurance, patients performed as many repetitions as possible at 60% of their repeat maximun, which was found at the initial strength test. Each training session started with a 5-minute warm-up on a stationary cycle ergometer at low intensity, followed by three sets of each exercise performed with a 90-150-second interval between sets. In each set, the patient performed the maximum number of repetitions possible. Two patients with LGMD2A dropped out of the study because of training-induced CK elevations and myalgias. After 12 weeks of training, the strength of the patients improved in wrist flexion and extension, while the improvement in the other muscle groups was not significant. It was not observed a correlation between the initial strength level of the muscles and the percentage increase seen in the muscles. SIP questionnaire did not show changes in patient's self-reported daily status and quality of life.

In conclusion, the preliminary results of this work indicated that resistance training could be safe and effective in increasing muscle strength and endurance in muscular dystrophies with proximal weakness, such as LGMD. The authors highlighted, however, that, until more knowledge is convened, training should be carefully supervised in order to recognize potential adverse effects, particularly in high-intensity protocols (28).

Aerobic training in patients with LGMD2L (Vissing et al., 2014) (29)

LGMD2L is a recessively inherited dystrophy caused by mutations in ANO-5 gene, that encodes for the putative calcium-sensitive chloride channel anoctamin 5, which is thought to play a role in membrane repair. In this study, 6 ambulant patients with LGMD2L were selected in order to evaluate the effect of home-based, pulse-watch monitored, moderate-intensity exercise at home on a cycle ergometer for 30 minutes, 3 times weekly, for 10 weeks. Also in the present work, plasma CK was assessed as a marker of muscle damage. Training was performed at a heart rate interval corresponding to 70% of their VO2max. Primary outcome measures were VO2max and time in the 5-repetitions-sit-to-stand test (FRSTST), requiring patients to rise and sit from a chair 5 times as rapidly as possible. The authors reported a significant improvement in oxidative capacity and muscle function (evaluated by VO2max and FRSTST time), with stable CK levels and no reports of adverse effects (29).

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Conclusions

In LGMD, because muscle weakness is the main problem, muscular exercise can help to counteract the loss of muscle tissue and strength in LGMD. Although it is accepted that exercise has a positive role in many diseases, it is not possible to generalize this finding to muscular dystrophy, including LGMD, and there is the need to conduct a systematic search to point out the effects of muscular exercise in experimental settings. To date, there is no certain evidences about the type (endurance or strength), frequency and intensity of muscle exercise. However, a training with moderate (below 70% of predicted maximal aerobic capacity) aerobic exercise seems to play an useful and safe effect in muscular dystrophies (23, 26).

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Acknowledgements

We are thankful to all patients and their associations, in particular the "Unione Italiana Lotta alla Distrofia Muscolare, UILDM" (www.uildm.org) and the "Beta- Sarcoglicanopatie" Italian association (beta-sarcoglicanopatie. it). We wish to acknowledge the Italian Association of Myology (AIM), and Telethon Italy for its support GUP10006.

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Articles from Acta Myologica are provided here courtesy of Pacini Editore