Allelieh sma

Allelieh Javier Capistrano, RTAllelieh Javier Capistrano, RTPediatric Respiratory TherapistPediatric Respiratory TherapistSection of Pulmonary MedicineSection of Pulmonary Medicine

Philippine Children’s Medical CenterPhilippine Children’s Medical Center

Spinal Muscular Spinal Muscular AtrophyAtrophy

What is SMA?What is SMA? Spinal muscular atrophy (SMA) is a group of Spinal muscular atrophy (SMA) is a group of

inherited neuromuscular diseases that attack motor inherited neuromuscular diseases that attack motor neurons, which control the movement of voluntary neurons, which control the movement of voluntary muscles. This disease causes anterior horn cells muscles. This disease causes anterior horn cells (lower motor neurons) in the base of the brain and (lower motor neurons) in the base of the brain and spinal cord to gradually disintegratespinal cord to gradually disintegrate. .

TThe disorder causes weakness and wasting of the he disorder causes weakness and wasting of the voluntary muscles. voluntary muscles.

WWeakness is often more severe in the legs than in eakness is often more severe in the legs than in the arms. the arms.

What is SMA?What is SMA? Loss of function of spinal motor neurons causing progressive weakness of Loss of function of spinal motor neurons causing progressive weakness of

musclesmuscles Muscles include extremities, respiratory musclesMuscles include extremities, respiratory muscles Sensation is normalSensation is normal Brain function is rain function is

normalnormal

http://kidshealth.org/parent/medical/bones/sma.html#http://kidshealth.org/parent/medical/bones/sma.html#

What is the lower motor What is the lower motor neuron?neuron?

Types of SMATypes of SMA Infantile progressive spinal

muscular atrophy (SMA Type 1)

Intermediate SMA (SMA Type 2)

Juvenile SMA (SMA Type 3)

Adult SMA (SMA Type 4)

SMARD1

Congenital SMA with arthrogryposis

SMA Type 1SMA Type 1

Also known as, Also known as, Werdnig-HoffmannWerdnig-Hoffmann acute acute infantile, non-sitters, occur birth up to 6 infantile, non-sitters, occur birth up to 6 months (95% by 3 months)months (95% by 3 months)

Severe, progressive muscle weakness and Severe, progressive muscle weakness and flaccid or reduced muscle tone (hypotonia). flaccid or reduced muscle tone (hypotonia).

Bulbar dysfunction includes poor suck ability, Bulbar dysfunction includes poor suck ability, reduced swallowing, and respiratory failure. reduced swallowing, and respiratory failure.

Patients have no involvement of the Patients have no involvement of the extraocular muscles, and facial weakness is extraocular muscles, and facial weakness is often minimal or absent.often minimal or absent.

They have no evidence of cerebral They have no evidence of cerebral involvement, and infants appear alert.involvement, and infants appear alert.

SMA Type 1SMA Type 1 Impaired fetal movements are observed in 30% of Impaired fetal movements are observed in 30% of

casescases 60% of infants with SMA type I are floppy babies at 60% of infants with SMA type I are floppy babies at

birth. Prolonged cyanosis may be noted at delivery. birth. Prolonged cyanosis may be noted at delivery. In some instances, the disease can cause fulminant In some instances, the disease can cause fulminant

weakness in the first few days of life. Such severe weakness in the first few days of life. Such severe weakness and early bulbar dysfunction which has a weakness and early bulbar dysfunction which has a mean survival of 5.9 months.mean survival of 5.9 months.

Affected children never sit or stand.Affected children never sit or stand. In 95% of cases, infants die from complications of In 95% of cases, infants die from complications of

the disease by 18 months.the disease by 18 months.

SMA Type 2SMA Type 2

SMA type II (intermediate SMA, sitters) usually begin SMA type II (intermediate SMA, sitters) usually begin between 6 - 18 months.between 6 - 18 months.

Most common form of SMAMost common form of SMA Most common manifestation is developmental motor Most common manifestation is developmental motor

delay. Infants with SMA type II often have difficulties delay. Infants with SMA type II often have difficulties with sitting independently or failure to stand by 1 with sitting independently or failure to stand by 1 year of age. year of age.

These children may learn to sit but will never be able These children may learn to sit but will never be able to stand or walk.to stand or walk.

SMA type 2SMA type 2

An unusual feature of the disease is a postural An unusual feature of the disease is a postural tremor affecting the fingers. This is thought to be tremor affecting the fingers. This is thought to be related to fasciculations in the skeletal musclesrelated to fasciculations in the skeletal muscles

Pseudohypertrophy of the gastrocnemius muscle, Pseudohypertrophy of the gastrocnemius muscle, musculoskeletal deformities, and respiratory musculoskeletal deformities, and respiratory failure can occur.failure can occur.

The lifespan of patients with SMA type II varies The lifespan of patients with SMA type II varies from 2 years to the third decade of life. from 2 years to the third decade of life. Respiratory infections account for most deaths.Respiratory infections account for most deaths.

SMA Type 3SMA Type 3

SMA type IIISMA type III (Kugelberg-Welander, (Kugelberg-Welander, chronic chronic juvenile, walkersjuvenile, walkers)) appear 18 months – adult. appear 18 months – adult.

Slowly progressive proximal weakness. Most Slowly progressive proximal weakness. Most can stand and walk but have trouble with can stand and walk but have trouble with motor skills, such as going up and down motor skills, such as going up and down stairs.stairs.

Bulbar dysfunction occurs late in the Bulbar dysfunction occurs late in the disease. disease.

SMA Type 3SMA Type 3

Patients may show evidence of Patients may show evidence of

pseudohypertrophy.pseudohypertrophy.

The disease progresses slowly, and the The disease progresses slowly, and the

overall course is mild. Many patients overall course is mild. Many patients

have normal life expectancies. have normal life expectancies.

SMA Type 4SMA Type 4

is the adult form of the disorder. Most people is the adult form of the disorder. Most people affected by this type start having symptoms after affected by this type start having symptoms after age 35, and these symptoms slowly get worse over age 35, and these symptoms slowly get worse over time. Because it develops slowly, many people with time. Because it develops slowly, many people with type IV SMA don't know that they have it until years type IV SMA don't know that they have it until years after symptoms begin.after symptoms begin.

Spinal Muscular Atrophy with Spinal Muscular Atrophy with Respiratory Distress Type 1 (SMARD1)Respiratory Distress Type 1 (SMARD1)

In SMARD1, the predominating symptom is a severe In SMARD1, the predominating symptom is a severe respiratory distress due to a paralysis of the diaphragm. respiratory distress due to a paralysis of the diaphragm. Most patients present show symptoms at the age of 1 to Most patients present show symptoms at the age of 1 to 6 months with respiratory failure and progressive muscle 6 months with respiratory failure and progressive muscle weakness with predominantly distal lower limb muscle weakness with predominantly distal lower limb muscle involvement.involvement.

Spinal Muscular Atrophy with Spinal Muscular Atrophy with Respiratory Distress Type 1 Respiratory Distress Type 1

(SMARD1)(SMARD1)

In SMARD1, the predominating symptom is a In SMARD1, the predominating symptom is a severe respiratory distress due to a paralysis of severe respiratory distress due to a paralysis of the diaphragm. Most patients present show the diaphragm. Most patients present show symptoms at the age of 1 to 6 months with symptoms at the age of 1 to 6 months with respiratory failure and progressive muscle respiratory failure and progressive muscle weakness with predominantly distal lower limb weakness with predominantly distal lower limb muscle involvement.muscle involvement.

Congenital SMA withCongenital SMA with arthrogryposisarthrogryposis

Congenital SMACongenital SMA withwith arthrogryposisarthrogryposis (p (persistent ersistent contracture of joints with fixed abnormal posture contracture of joints with fixed abnormal posture of the limb) is a rare disorder. Manifestations of the limb) is a rare disorder. Manifestations include severe contractures, curvature of the include severe contractures, curvature of the spine, chest deformity, respiratory problems, an spine, chest deformity, respiratory problems, an unusually small jaw, and drooping upper eyelids. unusually small jaw, and drooping upper eyelids.

Congenital SMA withCongenital SMA with arthrogryposisarthrogryposis

A Genetic CauseA Genetic Cause SMA is usually inherited. This means that both SMA is usually inherited. This means that both

parents must have an altered (mutated) or parents must have an altered (mutated) or missing copy of the gene involved in the disorder missing copy of the gene involved in the disorder for a child to develop it.for a child to develop it.

A Genetic CauseA Genetic Cause

Most cases of SMA are caused by a deficiency of a special Most cases of SMA are caused by a deficiency of a special protein called SMN ("survival of motor neurons"). Motor protein called SMN ("survival of motor neurons"). Motor neurons need this protein to function. The gene that carries neurons need this protein to function. The gene that carries this protein is called SMN1. When each parent passes onto this protein is called SMN1. When each parent passes onto their child a chromosome with a mutated or missing SMN1 their child a chromosome with a mutated or missing SMN1 gene, the protein is not produced and motor neurons die, gene, the protein is not produced and motor neurons die, leading to SMA. leading to SMA.

A Genetic CauseA Genetic Cause

The genetic defects associated with SMA types I-III are localized on The genetic defects associated with SMA types I-III are localized on chromosome 5q11.2-13.3.chromosome 5q11.2-13.3.

Mutations in the Mutations in the SMN SMN gene result in a loss of function of the SMN protein. gene result in a loss of function of the SMN protein.

Clinical Features (general for all Clinical Features (general for all types of SMA)types of SMA)

Progressive degeneration and loss of the lower Progressive degeneration and loss of the lower motor neurons (anterior horn cells) in the spinal motor neurons (anterior horn cells) in the spinal cord and sometimes in the brainstem nuclei.cord and sometimes in the brainstem nuclei. Results in muscle weakness and atrophyResults in muscle weakness and atrophy The onset varies from before birth until adulthoodThe onset varies from before birth until adulthood The weakness is symmetric and progressiveThe weakness is symmetric and progressive

Contractures, usually mildContractures, usually mild Anterior horn cell involvement, apparent due to Anterior horn cell involvement, apparent due to

tongue fasciculations and absent deep tendon tongue fasciculations and absent deep tendon reflexesreflexes

Respiratory failureRespiratory failure Variable cranial nerve involvement: Variable cranial nerve involvement:

opthalmoplegia, facial diplegiaopthalmoplegia, facial diplegia

DiagnosisDiagnosis

DiagnosisDiagnosis

A diagnosis usually comes only after the child undergoes A diagnosis usually comes only after the child undergoes several tests that rule out other diseases that cause similar several tests that rule out other diseases that cause similar symptoms. These tests usually include:symptoms. These tests usually include:

nerve conduction tests, such as an electromyogram nerve conduction tests, such as an electromyogram (EMG)(EMG)

computed tomography (CT) scancomputed tomography (CT) scan magnetic resonance imaging (MRI)magnetic resonance imaging (MRI) muscle tissue biopsymuscle tissue biopsy

DiagnosisDiagnosis

To confirm an SMA diagnosis, the doctor will usually recommend To confirm an SMA diagnosis, the doctor will usually recommend a blood test to look at the child's genes. If the SMN1 gene is a blood test to look at the child's genes. If the SMN1 gene is missing or imperfect, it will confirm the diagnosis of SMA. The missing or imperfect, it will confirm the diagnosis of SMA. The doctor might also recommend that parents and other members doctor might also recommend that parents and other members be screened for the disorder, even if they've never had any be screened for the disorder, even if they've never had any symptoms.symptoms.

TreatmentTreatment

Unfortunately, there is no cure for SMA. The treatment that Unfortunately, there is no cure for SMA. The treatment that children receive for SMA varies, depending on their age and children receive for SMA varies, depending on their age and the severity of symptoms. The goal of treatment is to the severity of symptoms. The goal of treatment is to relieve specific symptoms, maintain function and enhance a relieve specific symptoms, maintain function and enhance a child's mobility for as long as possible, and maximize the child's mobility for as long as possible, and maximize the child's independence and quality of life.child's independence and quality of life.

Prevention and MaintenancePrevention and Maintenance

Today, much can be done for SMA patients in terms of Today, much can be done for SMA patients in terms of medical and in particular respiratory, nutritional and medical and in particular respiratory, nutritional and rehabilitation care.rehabilitation care. Physical therapy and occupational therapy Physical therapy and occupational therapy to promote and maintain motor skills.to promote and maintain motor skills.

Monitoring of respiratory function, ventilatory support.Monitoring of respiratory function, ventilatory support.

Respiratory SupportRespiratory Support

Children with SMA commonly need help breathing when Children with SMA commonly need help breathing when muscle weakness begins to affect the respiratory muscles. muscle weakness begins to affect the respiratory muscles. Different therapies can help a child breathe. Different therapies can help a child breathe. Oxygen therapyOxygen therapy Non-invasive positive pressure ventilation (NIPPV) Non-invasive positive pressure ventilation (NIPPV) BiPAPBiPAP tracheostomytracheostomy

Respiratory SupportRespiratory Support

A critical factor in respiratory care is preventing A critical factor in respiratory care is preventing infection, especially pneumonia. Pneumonia is infection, especially pneumonia. Pneumonia is common in children with SMA and is life common in children with SMA and is life threatening.threatening.

Respiratory AidsRespiratory Aids

Cough AssistCough Assist Chest physiotherapyChest physiotherapy Home suctionHome suction Pulse oximeterPulse oximeter AmbubagAmbubag Nebulizer Nebulizer

Bronchodilator, mucolytics,Bronchodilator, mucolytics,

anticholinergicsanticholinergics

Conventional Respiratory Conventional Respiratory therapytherapy

1. Oxygen administrated arbitrarily in concentrations that maintain SaO2 well above 95%.

2. Frequent airway suctioning via the tube. 3. Supplemental oxygen increased when

desaturations occur. 4. Ventilator weaning attempted at the expense

of hypercapnia. 5. Extubation not attempted unless the patient

appears to be ventilator weaned.

Conventional Respiratory Conventional Respiratory therapytherapy

6. Extubation to CPAP or low span bi-level positive airway pressure and continued oxygen therapy.

7. Deep airway suctioning by catheterizing the upper airway along with postural drainage and chest physical therapy.

8. With increasing CO2 retention or hypoxia supplemental oxygen is increased and ultimately the patient is reintubated.

9. Following re-intubation tracheostomy is thought to be the only long-term option or following successful extubation bronchodilators and ongoing routine chest physical therapy are used.

10. Eventually discharged home with a tracheostomy, often following a rehabilitation stay for family training.  

Protocol for SMAProtocol for SMA

1. Oxygen administration limited only to approach 95% SaO2. 2. Mechanical insufflation-exsufflation used via the tube at 25 to 40

cm H2O to -25 to -40 cm H2O pressures up to every 10 minutes as needed to reverse oxyhemoglobin desaturations due to airway mucus accumulation and when there is auscultatory evidence of secretion accumulation. Abdominal thrusts are applied during exsufflation. Tube and upper airway are suctioned following use of expiratory aids as needed.

3. Expiratory aids used when desaturations occur. 4. Ventilator weaning attempted without permitting hypercapnia.

Protocol Protocol for SMAfor SMA

5. Extubation attempted whether or not the patient is ventilator weaned when meeting the following:

A. Afebrile B. No supplemental oxygen requirement to

maintain SaO2 >94% C. Chest radiograph abnormalities cleared or

clearing D. Any respiratory depressants discontinued E. Airway suctioning required less than

1-2x/eight hours

Nutritional SupportNutritional Support

SMA can affect the muscles used for chewing, SMA can affect the muscles used for chewing, sucking, and swallowing. This can cause a child to sucking, and swallowing. This can cause a child to become malnourished or develop pneumonia if the become malnourished or develop pneumonia if the child inhales food or liquids while eating. Some child inhales food or liquids while eating. Some children do better by eating small, frequent meals children do better by eating small, frequent meals throughout the day instead of having three large throughout the day instead of having three large meals.meals.

Some children with SMA are at risk for obesity if they Some children with SMA are at risk for obesity if they consume too many calories for their activity levels consume too many calories for their activity levels and they can't exercise to effectively burn the and they can't exercise to effectively burn the calories. Ongoing consultation with a nutritionist is calories. Ongoing consultation with a nutritionist is necessary to ensure adequate nutrition that doesn't necessary to ensure adequate nutrition that doesn't overload a child with unnecessary calories.overload a child with unnecessary calories.

Nutritional SupportNutritional Support

Children who can't swallow or suck must be fed in Children who can't swallow or suck must be fed in another way to ensure that they're receiving another way to ensure that they're receiving enough nutrition. Sometimes, they have a tube enough nutrition. Sometimes, they have a tube inserted into the stomach to help them eat. inserted into the stomach to help them eat. Through this tube, called a gastrostomy tube, Through this tube, called a gastrostomy tube, they can receive a nutritionally sound liquid diet.they can receive a nutritionally sound liquid diet.

Function and MobilityFunction and Mobility

Function and MobilityFunction and Mobility

Many children with SMA benefit greatly from Many children with SMA benefit greatly from physical and occupational therapies, which help to physical and occupational therapies, which help to maintain function and mobility and enhance quality maintain function and mobility and enhance quality of life for as long as possible. In some cases, tools of life for as long as possible. In some cases, tools can help make these tasks easier, such as:can help make these tasks easier, such as: leg braces, standing frames, canes, and walkers, which leg braces, standing frames, canes, and walkers, which

provide stability and improve mobilityprovide stability and improve mobility electric wheelchairs with customized controlselectric wheelchairs with customized controls specialized seats to use in schoolspecialized seats to use in school tools for using computers and phones and controlling tools for using computers and phones and controlling

other home electronics, such as the TVs and lightsother home electronics, such as the TVs and lights tools to aid educational activities, such as writing and tools to aid educational activities, such as writing and

drawingdrawing

Spinal DeformitySpinal Deformity

Children who develop spinal deformities need to Children who develop spinal deformities need to wear a splint, brace, or corset to straighten their wear a splint, brace, or corset to straighten their backs as toddlers or adolescents. Sometimes, backs as toddlers or adolescents. Sometimes, surgery (called a spinal fusion) is done to correct surgery (called a spinal fusion) is done to correct the spinal deformity in children who are done the spinal deformity in children who are done growing and whose respiratory systems can growing and whose respiratory systems can tolerate sedation with anesthesia.tolerate sedation with anesthesia.

OutlookOutlook

Scientists who are researching SMA have made Scientists who are researching SMA have made dramatic breakthroughs in the past few years, dramatic breakthroughs in the past few years, including identifying the genes and the protein including identifying the genes and the protein associated with the disorder.associated with the disorder.

Research is now focused on finding drugs and Research is now focused on finding drugs and other therapies that can help to keep motor other therapies that can help to keep motor neurons functioning as long as possible, enhance neurons functioning as long as possible, enhance muscle tone and function, and even modify gene muscle tone and function, and even modify gene function. Many scientists are optimistic that function. Many scientists are optimistic that ongoing research will lead to better treatment of ongoing research will lead to better treatment of SMA.SMA.

My ReferencesMy References

Web referencesWeb references

1.1. http://www.ninds.nih.gov/news_and_events/news_articles/sensory-http://www.ninds.nih.gov/news_and_events/news_articles/sensory-motor_synapses_lost_in_SMA.htmmotor_synapses_lost_in_SMA.htm

2.2. http://en.wikipedia.org/wiki/Spinal_muscular_atrophyhttp://en.wikipedia.org/wiki/Spinal_muscular_atrophy

3.3. http://www.fsma.org/http://www.fsma.org/

4.4. http://healthfinder.gov/FindServices/Organizations/Organization/HR2292/families-of-http://healthfinder.gov/FindServices/Organizations/Organization/HR2292/families-of-spinal-muscular-atrophy spinal-muscular-atrophy

5.5. http://en.wikibooks.org/wiki/Handbook_of_Genetic_Counseling/http://en.wikibooks.org/wiki/Handbook_of_Genetic_Counseling/Spinal_Muscular_Atrophy_(SMA1)Spinal_Muscular_Atrophy_(SMA1)

Guidelines/booksGuidelines/books

1.1. Guide to the Evaluation and Management of Patients with Neuromuscular Disease Guide to the Evaluation and Management of Patients with Neuromuscular Disease by Dr John Bach (2004)by Dr John Bach (2004)

2.2. Facts about Spinal Muscular Atrophy. Muscular Dystrophy AssociationFacts about Spinal Muscular Atrophy. Muscular Dystrophy Association

3.3. Handbook of Genetic CounselingHandbook of Genetic Counseling

Thank you!!Thank you!!