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Transcript of Spinal Muscular Atrophy: Diagnosis and Global Management Considerations by Dr. Robert Rinaldi,...
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
en.wikipedia.org
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
Ehealthwall.com
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
Numotion.com
1800wheelchair.com
Adaptive Mobility
Robohub.com
Melrosewheelchairs.com
Adaptive Communication Systems
Adaptive Sports
Huffingtonpost.com
Questions?
Calicospanish.com