Spinal Muscular Atrophy: Diagnosis and Global Management Considerations

Robert Rinaldi, MD FAAPMR

Co-Director, Nerve and Muscle Program

Associate Professor of Pediatrics

Division of Pediatric Rehabilitation Medicine

The Children’s Mercy Hospital and Clinics

Disclosures

*I have no financial disclosures to make

*I am not a pulmonologist

*I am not using the official CMH slide template

What is SMA?

• Spinal Muscular Atrophy• A neuromuscular disease of infancy, childhood, and adulthood, that effects

the survival and function of the anterior horn cells of the spinal cord.• It is characterized by progressive, predominantly proximal and symmetric

muscle weakness• Sensation and cognition are preserved• Broad clinical heterogeneity across phenotypes

Epidemiology

• Autosomal Recessive • Incidence – 1:100,000 live births• 95% - homozygous deletion or mutations in Chromosome 5q, SMN1

gene• SMA type 1-3

• 5% - various other deletions associated with AHC involvement• Distal SMA syndromes• Kennedy Disease (X linked, SMAX1)• SMA with respiratory distress/SMARD (11q, IGHMBP2)

Pathology

• Genetic – 2 genes, SMN1 and SMN2• Homozygous deletion or mutations in SMN1 gene• SMN2 – production of alternative SMN protein

• Unstable• Rapidly degrades• SMN2 copy # to clinical severity ratio

• Deficiency of SMN1 leads to selective motor neuron degeneration• ? Motor neurons only• ? Role of SMN1• ? Possible role in other organ systems

Anatomic Correlates - SMA

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Diagnostic Evaluation

• Clinical presentation/Physical examination• Electrodiagnostic studies

• Motor nerve conduction study – abnormal ( amplitudes, nml CV)• Sensory nerve conduction study – normal• EMG – denervation potentials

• Targeted mutation analysis • deletions of exon 7 and 8, SMN1 gene (95-98%) • SMN2 copy count

• Biopsy – grouped atrophy (motor unit loss)• not necessary anymore

Muscle Biopsy – group atrophy

Phenotypic Variants

SMA Type Age of onset Highest Function Natural Age of Death

Type 1 (severe) 0 – 6 months Never sits independently

<2 y

Type 2 (intermediate) 7-18 months Never stands independently

>2 y

Type 3 (mild) >18 months Stands and walks Adulthood

Type 4 (adult) 2nd – 3rd decade Walks during adult years

Adulthood

Phenotypic Variants

• SMA 1• Classic “floppy baby”

• Profound hypotonia• Absent reflexes• Muscle fasiculations• Marked proximal-general weakness• Intercostal weakness plus spared diaphragm

• Paradoxical breathing pattern• Bell shaped chest

• Bulbar dysfunction

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Phenotypic Variants

• SMA 2• Delayed motor milestones• Inability to maintain independent sitting • Lower extremities affected more than upper extremities• +/- bulbar weakness and swallowing difficulties • Decreased cough and tracheal clearance• Risk:

• Kyphoscoliosis • Evolving joint contractures – LE >> UE

Phenotypic Variants

• SMA 3• Subtypes:

• A – onset before 3 y• B – onset after 3y

• Late and variable onset• Independent walking achieved

• May decline with age• +/- bulbar weakness - mild• +/- cough and nocturnal hypoventilation• Risk:

• Scoliosis• Joint contractures

Treatment and Management

• A systems and functional based approach• Medical management – improve health• Functional management – improve function, independence, and QOL

• Primary considerations:• Developmental delay• Gastroeneterologic• Orthopedic / musculoskeletal• Craniofacial• Pulmonary• Mobility• Functional disabilities

Developmental

• Intelligence– normal to above normal• Verbal IQ – above average

• Gross motor milestones• SMA1 – no significant milestones achieved• SMA2 and 3 – may lose mobility as they age

• ? etiology

• Fine motor skills• Variable – based on upper extremity involvement

• School modifications to accommodate physical disabilities• PT/OT – functional skills

Gastroenterologic

• Considerations: • failure to thrive (35%)

• Dysphagia – poor coordination of swallow and airway closure• Chewing difficulties – masticatory and facial weakness• Fatigue – decreased efficiency of pre-oral, oral and pharyngeal phases

• Gastroesophageal reflux• Increased risk of aspiration

• Management:• Formal swallow evaluation (OPM)• G-tube placement• Dietary modifications• Medication management for reflux

Orthopedic

• Considerations: • Scoliosis

• SMA2 > SMA3 > SMA1• Early onset: 4-9 y • Bracing may slow progression, but wont stop it

• Bracing may decrease tidal breathing if not fit correctly• Abdominal cut-out

• Restrictive lung disease• Surgical correction

• Curves >50 dgrees• Slows rate of respiratory deterioration

Orthopedic

• Consideration:• Contractures

• SMA 2 and 3• Large joints – LE >>> UE

• Hamstrings/knees; hip flexors• Can affect laying and sitting posture, mobility, comfort

• Management• Stretching• Night time splinting• Surgical – soft tissue/tendon lengthenings and releases

Craniofacial

• Considerations:• Deformities

• Malocclusion• Jaw/mandibular deformity

• Air leaks with non-invasive ventilation face masks

• Poor dental hygiene• Open mouth posture due to facial weakness

Pulmonary

• Major cause of morbidity and mortality in SMA 1 and 2• Factors:

• Weak inspiratory and expiratory muscles• Scoliosis – older SMA 2 and 3• Progressive restrictive lung disease• Swallowing dysfunction and reflux

• Recurrent infections• Progression to respiratory failure via recurrent infection/nocturnal

desaturation and hypoventilation/daytime hypercarbia

• Pulmonary evaluations every 6 months

weakness

dec. FVC

Chest deformity aspiration

Weak coughSleep

hypoventilationinfection

Dec. compliance

fatigue

Resp failure

Pulmonary

• Considerations:• Weak Cough

• Poor airway clearance• Decreased PCF, FVC• Risk: atelectasis, pneumonia• Management:

• Adequate hydration• Assisted cough

• MI/E devices – use 2x/d for maintenance, increase to 4x/d when ill• Pressures: children tolerate 40cm/-40cm well; adjust accordingly to age/size

• Manual secretion mobilization• Chest percussion, etc….

Pulmonary

• Considerations:• Recurrent infections

• Aggressive secretion mobilization• Hydration • Monitoring for hypercapnia/inadequate ventilation• Non-invasive ventilation assistance if needed

• Sleep-disordered breathing• Routine, semiannual monitoring of CO2, and PFTs • Polysomnograpghy• Management: nocturnal BIPAP

Functional Disabilities

• The goal of rehabilitation medicine is to minimize the health impact of physical and cognitive impairments on an individual, while maximizing their functional capacity and quality of life…..regardless of diagnosis

• Typical domains addressed• Cognition• Self care and activities of daily living skills• Fine motor skills• Gross motor skills / mobility• Communication

Functional Disabilities

• Self care skills and ADLs• SMA1 – fully dependent• SMA2 – partially dependent• SMA3 – independent

• Mobility• SMA1 – fully dependent• SMA2 – partially dependent• SMA3 – independent

• Communication• SMA1 – dependent• SMA2 and 3 – independent

• Goal: INCREASE AND MAXIMIZE FUNCTIONAL INDEPENDENCE

Self care skills and ADLs

• Adaptive modifications

Mobility and Standing

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Adaptive Mobility

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Adaptive Communication Systems

Adaptive Sports

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Questions?

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