CCPT311-8-Polio-GBS-XX
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Anterior Horn Cell and Spinal Muscular Atrophy (SMA)
Group of disorders associated with lower motor neuron (LMN) loss
Degeneration of anterior horn cells in the spinal cord
Presents with proximal muscle weakness and atrophy
Etiology: Homozygous deletion at 5q13 responsible for 95% of cases of SMA
Most common subtype: Proximal SMA (Type 0, 1, 2, 3, 4)
Prevalence: 1 in 6,000-11,000, carrier frequency of 1 in 40 in the general population
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Types of SMA
Type 0: Congenital SMA, presents in the neonatal period with hypotonia and early respiratory failure
Type I: Acute Werdnig-Hoffman Disease, non-sitters with limited head control and hypotonia
Type II: Chronic Werdnig-Hoffman Disease, sitters with progressive weakness and scoliosis
Type III: Kugelberg-Welander Disease, walkers with mild weakness
Type IV: Adult onset SMA, presents in adulthood with mild leg weakness
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Type III: Kugelberg-Welander Disease
Presents after 18 months with progressive weakness
Similar to Type II but without restrictive lung disease
Subtypes: Type IIIa (18 months to 3 years), Type IIIb (>3 years)
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Diagnosis and Management of SMA
Diagnosis: Electrodiagnostic testing shows motor loss consistent with loss of motor neuron function
Management:
Spinaraza (Nusinersen): Intrathecal delivery of antisense oligonucleotide (ASO) to promote functional SMN2 production
Onasemnogene Abeparvovec: One-time IV injection gene therapy to deliver the SMN1 gene
Risdiplam: Oral medication that increases functional SMN protein levels
Pulmonary, gastrointestinal, and orthopedic management strategies discussed
Differential Diagnosis: Spinobulbar Muscular Atrophy, a slowly progressive LMN syndrome with bulbar involvement and sensory neuropathy
Page 5: Poliomyelitis
Poliomyelitis is a viral disease that can range in severity from self-limiting disease to meningitis.
In its most severe form, it may present as acute flaccid paralysis.
Poliovirus is the virus causing both acute polio and post-polio syndrome (PPS).
The primary cause of the majority of the world's paralytic polio cases until vaccines became widespread is Wild Type 1 Poliovirus.
Wild Types 2 & 3 have been eradicated as of 2015.
Prevention methods include the Salk vaccine (inactivated polio vaccine) and the Sabin vaccine (attenuated oral polio vaccine).
The primary infection can lead to viral replication in oropharyngeal and gastrointestinal lymphatic tissues.
In up to 95% of cases, infections are non-paralytic, presenting as a flu-like illness.
In approximately 5% of cases, pure motor paralysis can occur.
Page 6: Poliomyelitis continued
Poliomyelitis is commonly transmitted through the oral-fecal route.
Oral-oral spread is also possible.
Clinical manifestations of poliomyelitis include pure motor deficit, headaches, myalgias, fatigue, nausea, neck stiffness, or pharyngitis.
It can progress into the spinal cord, causing severe muscle spasms and asymmetrical flaccid paralysis.
Poliomyelitis tends to have a lower-limb predominance.
The acute stage of poliomyelitis lasts for 2 years, followed by a stage of recovery that lasts for more than 2 years.
Rehabilitation plays an imperative role in preventing the development of deformities.
During the stage of recovery, non-fatiguing exercise programs are appropriate to deal with muscle weakness.
Page 7: Poliomyelitis and Post-Polio Syndrome
The stage of chronicity in poliomyelitis is characterized by recovery of muscle plateau and residual paralysis.
Approximately 60-80% of patients with a past diagnosis of polio report at least 1 fall in the past year.
Diagnosis of poliomyelitis is made through various tests such as blood, CSF, respiratory, stool tests, EMG, and brain/SC MRI to rule out other pathologies.
Post-Polio Syndrome (PPS) affects approximately 30-40% of polio patients.
PPS progression is multifactorial and depends on factors like severity of acute paralysis, age of onset, and socio-economic status.
PPS is not contagious and is characterized by the onset of new muscle weakness and persistent symptoms for at least 1 year.
Diagnosis of PPS is made by exclusion, as there are no definitive biomarkers widely accepted.
Page 8: Myasthenia Gravis
Myasthenia Gravis (MG) is an autoimmune disorder that affects the neuromuscular junction of the skeletal muscles.
It is more common among patients with a history of thymoma or tumor on the thymus.
MG is more prevalent in females than males and affects individuals over 50 years old.
Clinical manifestations of MG include fluctuating weakness, extraocular muscle weakness, diplopia, bulbar muscle weakness, limb weakness, and myasthenic crisis.
Diagnosis of MG can be done through the Edrophonium (Tensilon) Test, which is a short-acting acetylcholinesterase inhibitor that increases the availability of ACh in the neuromuscular junction.
Another quick bedside technique for diagnosing MG is placing a small cube of ice over the ptotic eyelid for 2 minutes, which can indicate a disorder of neuromuscular transmission.
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Clinical Correlation in Physical Therapy - Poliomyelitis & Guillain Barre Syndrome Management
Acetylcholinesterase inhibitors increase the level of ACh at the NMJ by preventing its enzymatic degradation.
Neostigmine
Pyridostigmine
Physostigmine
Immunosuppressive Treatment
Intravenous immunoglobulins (IVIG)/Plasmapheresis
Thymectomy
Cholinergic Crisis
Overstimulation at a NMJ due to an excess of Ach
Weakness due to drug intake due to accumulation of Ach in the synaptic cleft.
Lambert Eaton Myasthenic Syndrome (LEMS)
Fluctuating weakness that improves with exercise.
Paraneoplastic Phenomenon or Primary Autoimmune disorder.
Underlying malignancy, most commonly small-cell lung cancer.
Affects voltage-gated Ca channels in the presynaptic membrane.
Epidemiology
LEMS is 46 times less prevalent than Myasthenia Gravis (MG).
More common in males (75% of patients are males).
Poor prognosis.
Peak age of onset at 35 years and a second larger peak at 60 years.
Clinical Manifestation
Muscle weakness:
Proximal to Distal; Caudal to Cranial.
Lower extremities more affected than upper extremities.
Symmetrical pattern of progression - proximal to distal, and caudal to cranial, finally reaching the oculobulbar region.
Dull aching or stiffness.
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Clinical Correlation in Physical Therapy - Poliomyelitis & Guillain Barre Syndrome
Areflexia is present in the absence of significant muscle atrophy.
Postexercise or post-activation facilitation characterized by the return of tendon reflexes and muscle strength with repeated muscle contractions.
Oculobulbar Weakness:
70% of patients.
Ocular symptoms, particularly ptosis and diplopia.
Dysphagia and dysarthria are seen in later stages of the disease.
Autonomic dysfunction is reported in 80-96% of patients.
Most common symptom: Dry mouth.
Other symptoms: Erectile dysfunction, constipation, orthostatic dysfunction, altered perspiration.
Respiratory failure infrequently occurs in the later stages.
Triad of LEMS:
Areflexia
Muscle weakness with a typical distribution
Autonomic dysfunction.
Management
Drug of choice: Guanidine
Oral medication used to treat the symptoms of LEMS.
Botulism
Rare, potentially fatal syndrome of diffuse, flaccid paralysis caused by botulinum neurotoxin (BoNT) elaborated by the bacterium Clostridium botulinum.
Mode of Transmission: Foodborne botulism is acquired by the ingestion of inadequately cooked food or processed or refrigerated foods in which toxin has formed, particularly canned and alkaline foods.
Epidemiology
Average of 162 annual cases of botulism.
Distribution:
71-88% for infant botulism
1-20% for foodborne botulism
5-10% for wound botulism
1-4% for botulism of other or unknown origin.
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Clinical Correlation in Physical Therapy - Poliomyelitis & Guillain Barre Syndrome
Overall mortality was 3.0% with 109 botulism-related deaths among 3,618 botulism cases.
Total Nerve Blockage
Classically begins with cranial nerve palsies.
Diplopia (visual disturbances), dysphagia (difficulty swallowing), dysphonia (voice change), and dysarthria (slurred speech).
Progresses to symmetrical descending weakness of the trunk, extremities, and smooth muscle, with eventual flaccid paralysis.
No sensory deficits except for blurred vision, although paresthesias are occasionally seen.
Medication
Heptavalent Botulinum Antitoxin (HBAT)
Mixture of immune globulin fragments indicated for the treatment of symptomatic botulism following documented or suspected exposure to botulinum neurotoxin.
Immune Mediated Neuropathy - Guillain-Barre Syndrome (GBS)
Also known as "Landry's Paralysis"
Demyelinating Disease of the Peripheral Nervous System.
Acute inflammatory demyelinating polyneuropathy/post-infectious immune-mediated (IgG) neuropathy.
Most common cause of acute flaccid paralysis.
Idiopathic but self-limiting.
Progressive symmetrical weakness of the limbs with hyporeflexia or areflexia, with or without sensory abnormalities.
Numbness, tingling, and weakness that can progress to paralysis.
Epidemiology
Rare but affects 0.4 to 2 per 100,000 individuals.
More common in males.
Approximately 100,000 patients worldwide.
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Clinical Correlation in Physical Therapy - Poliomyelitis & Guillain Barre Syndrome
Etiology/Pathology
Molecular mimicry:
Campylobacter jejuni: Lipooligosaccharide of Campylobacter jejuni is similar to the gangliosides of peripheral nerve membranes.
Cytomegalovirus
Epstein Bar Virus
Post-infection: Most common antecedent illnesses are gastrointestinal or respiratory illnesses.
70% of patients have reported an antecedent illness in the 1-6 weeks before the presentation of GBS.
Clinical Manifestation
Ascending Symmetrical Weakness
Monophasic (not relapsing or remitting course)
1-6 weeks of antecedent illness.
Non-length-dependent sensory symptoms (dysesthesias in the hands followed by the feet)
Facial diplegia due to the involvement of both facial cranial nerves.
Dysphagia due to the involvement of glossopharyngeal, vagus, and hypoglossal cranial nerves.
Dysautonomia is a primary etiology of the morbidity and mortality attributable to GBS.
Respiratory failure can occur in up to 30% of patients, usually leading to prolonged hospitalization and recovery.
Diagnosis
Lumbar Puncture
Normal within 48 hours
Elevated CSF protein (>0.55 g/dL) by the end of the week.
Electrodiagnostic Testing
Confirmatory test for GBS and can differentiate between the more common demyelinating form (AIDP) and axonal forms (AMAN and AMSAN).
Main clinical method of distinguishing subtypes.
Page 13: Clinical Correlation in Physical Therapy - Poliomyelitis & Guillain Barre Syndrome
GBS subtypes:
Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP)
Primarily motor inflammatory demyelination or secondary axonal damage
Clinical features: symmetrical weakness of all limbs, hyporeflexia, mild sensory symptoms, respiratory involvement, facial nerve palsy
Acute Motor-Sensory Axonal Neuropathy (AMSAN)
Motor and sensory involvement with severe course respiratory and bulbar involvement
Primary axonal degeneration with poorer prognosis
Similar to AMAN but affects sensory nerves and roots
Acute Motor Axonal Neuropathy (AMAN)
Primary axonal degeneration
Motor only with early and severe respiratory involvement
Often affects children and young adults
Miller-Fisher Variant
Pharyngeal-cervical-brachial variant of GBS
Acute Pandysautonomia
Page 14: Clinical Correlation in Physical Therapy - Poliomyelitis & Guillain Barre Syndrome
Miller-Fisher Syndrome:
Triad: ophthalmoplegia, sensory ataxia, areflexia
Rare disorder
Sensory loss unusual, but proprioception may be impaired
Demyelination and inflammation of CN 3 & 6, spinal ganglia, and peripheral nerves
Resolution: 1-3 months
Pharyngeal-cervical-brachial variant:
Often associated with IgG anti-GT1a
Presents with proximal descending weakness
Must distinguish from botulism and diphtheria
Acute Panautonomic Neuropathy:
Rarest variant
Widespread sympathetic and parasympathetic failure
Involvement of SNS & PNS
Cardiovascular involvement: postural hypotension, tachycardia, HTN, dysrhythmias
Autonomic dysfunctions:
Sinus tachycardia or bradycardia
Fluctuating HTN or hypotension
Flushing of the face
Loss of or excessive sweating
Bickerstaff Brainstem Encephalitis:
Ophthalmoplegia, ataxia, areflexia, pyramidal tract signs, and impaired consciousness, often overlapping with sensorimotor GBS
GBS variants: pattern of symptoms management
Intravenous Immunoglobulin (IVIG) or Plasma Exchange
5% of patients achieving independent ambulation with