Neuromuscular Disorders

Ma. Josefa Victoria R. Panlilio M.D.,FPPS, FPNA 4-19-18 6.03B

o Myalgias
I. NORMAL MUSCLE
 Occur in several diseases
II. SPINAL MUSCULAR ATROPHIES
– Acute dermatomyositis
III. PERIPHERAL NEUROPATHIES – Acute polyneuropathy (Guillain-Barré
IV. DEVELOPMENTAL DISORDERS OF MUSCLE syndrome)
V. MUSCLE DYSTROPHIES – Aetabolic diseases of muscle
VI. ENDOCRINE AND TOXIC MYOPATHIES – Ischemic myopathy (vascular diseases such as
VII. METABOLIC MYOPATHIES dermatomyositis)
VIII. MITOCHONDRIAL MYOPATHIES  They denote the acuity of the process
IX. DISEASES OF NEUROMUSCULAR JUNCTION – Acute stages of inflammatory myopathies and
X. INFLAMMATORY MYOPATHIES acute denervation of muscle often present with
muscular pain and tenderness to palpation
o Specific clinical features
LEARNING OBJECTIVES
 Fasciculations
 No objectives given – Best seen in the tongue
– Sign of denervation
I. NORMAL MUSCLE  Sensory abnormalities: indicate neuropath
 Fatiguable weakness: neuromuscular junctional
Neuromuscular disease: defines disorders of the motor unit disorders
and excludes influences on muscular function from the brain,  Myotonia: specific for a few myopathies
such as spasticity o Other manifestations of congenital neuromuscular
4components of the motor unit: disease in infants
o Motor neuron in the brainstem or ventral horn of the  Undescended testes
spinal cord  Funnel-shaped thorax with thin, radiolucent ribs
o Its axon: forms the peripheral nerve together with other
axons I-A. CYTOSKELETAL PROTEINS
o Neuromuscular junction
 Maintain the structural integrity of the muscle against the
o All muscle fibers innervated by a single motor neuron
physical forces of contraction exerted on the sarcolemma
Large muscles have a large number of muscle fibers innervated
membrane
by a single motor neuron, as opposed to small muscles in which
a 1:1 ratio can prevail  Dystrophin: use to provide mechanical support and structural
The motor unit is influenced by upper motor neuron control integrity to the sarcolemma.
Diseases of the motor unit are common in children  Dystrophin-Glycoprotein Complex: acts as a link between the
o Genetic, congenital, or acquired extracellular matrix and the cytoskeleton, confers structural
o Acute or chronic, progressive or static stability to the sarcolemma and protects muscle fibers from
o Overlapping clinical manifestations mechanical stress during muscle contraction.
o Specific therapy  Utrophin: increases the transcription of acetylcholine receptor,
o Laboratory confirmation is required for most diseases sodium channels and utrophin.
Clinical Manifestations  Dysferlin: function in signal transduction or in membrane
Hypotonia, decreased motor power, hypo/areflexia, trafficking, such as protein kinase C.
muscle atrophy, fasciculations  Caveolin: participate in membrane trafficking, sorting,
o Generalized hypotonia and motor developmental delay transport, and signal transduction.
are the most common presenting manifestations of
I-B. LOWER MOTOR NEURON
neuromuscular disease in infants and young children
o Assessment of muscle bulk  1. Anterior Horn Cell
o Tone  2. Peripheral Nerve
 Passive tone: range of motion around a joint  3. Neuromuscular Junction
 Active tone: physiologic resistance to movement
 4. Muscle
o Strength
 Head lag: sign of weakness, not low tone
 Hypotonia may be with normal strength or weakness
 Wasted muscles may have weak or normal strength

Table 1. Comparison between myopathies and neuropathies

MYOPATHY NEUROPATHY
Proximal distribution of Distal in distribution
weakness and muscle wasting  with the notable exception of
 with the notable exception of juvenile spinal muscular
Figure 1. Anatomy of the motor unit. 4 components: AHC
myotonic muscular dystrophy atrophy
(anterior horn cell), peripheral nerve, myoneural junction, muscle.
(+) tendon stretch reflexes (-) tendon stretch reflexes
Myalgias Myalgias
Contractures of muscles Contractures of muscles

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I-B-1. ANTERIOR HORN CELL (AHC) LESION

 Rapid progression
Figure 2. Lower Motor Neuron. We can also levelize the lesion in  Asymmetrical distribution of limb paralysis affecting proximal
the lower motor neuron whether it’s on AHC, peripheral nerve, limb muscles than distal limb muscles
NMJ, or muscle.  May lead to severe asymmetrical atrophy and skeletal
deformities
Table 2. CNS vs PNS  Fasciculation is present
CNS (UMN) PNS (LMN) I-B-2. MUSCLE DISORDERS
Strength  
Bulk (atrophy)  
Tone  
DTR  , (–)
Babinski (+) (–)
Abnormal spontaneous (–) (+)
muscle movement
(twitching, fasciculations)
How would you differentiate central nervous vs. peripheral  Involve specific muscle, usually with proximal muscles
nervous system. Weaker strength in LMN because the patient associated with muscle pain
is floppy, tone is decreased, more atrophy, DTR is absent or  Myotonia, or failure of the voluntary muscles to relax after
hyporeflexive, and Babinski is absent. Fasciculations is also contraction ceases and by slow, tonic response to mechanical
observed. In babies this can be seen in the tongue where there and electrical stimulus
is wave-like movements of the muscles of the tongue which is
 More readily observed in the hand, face, and tongue
a significant finding for AHC disease.
 Atrophy is seen in AHC diseases. In peripheral nerve, there is
also early and severe atrophy. In NMJ like Myesthenia Gravis,
Table 3. Lower Motor Neuron Lesion
there is no atrophy. In Muscle diseases, pseudohypertrophy.
AHC PN NMJ MSC
NMJ and Muscle disorders may have normal or decreased
Weakness Prox Distal episodic Prox DTRs.
Atrophy (+) early, severe (-) pseudohypertrophy
Reflexes /0 /0 N/0 N/
Sensory N /0 N N I-B-3. NEUROMUSCULAR JUNCTION
Weakness is proximal in AHC, while it is distal in peripheral
nerve. When you say proximal, it is near the axial part of the
body (upper arm)
Atrophy is seen in AHC diseases. In peripheral nerve, there is
also early and severe atrophy. In NMJ like Myasthenia Gravis,
there is no atrophy. In Muscle diseases, pseudohypertrophy.
NMJ and Muscle disorders may have normal or decreased
DTRs. Sensory is not affected except in peripheral nerve.  Proximal symmetric weakness without sensory loss and
Differential diagnoses may include weakness that is usually waxing and waning and comes with
o Endocrine diseases fatigability
o Metabolic diseases Weakness is episodic. Strong in the morning, then fluctuating
o Down Syndrome when the patient gets tired.
o Nonspecific NM signs of malnutrition or chronic systemic
illness I-C. CLINICAL LABORATORY TESTS
o A prenatal history of decreased fetal movements and
 Clinical Biochemistry
IUGR may be elicited in patients who are symptomatic at
o Creatine kinase M/B or MB
birth
 Significantly elevated in Duchenne muscular
dystrophy
Elevated in muscular dystrophies. Normal in AHC,
peripheral nerve and Myasthenia Gravis.
o Aldolase
o Enzymes: transaminases, lactate dehydrohenase,
pyruvate kinase

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 Electromyography
o Is the recording of the electrical activity by a needle
electrode of action potentials of muscle fibers
o Technically difficult in children
o Useful in cases of neuropathic and myopathic disorders
 Nerve Conduction Velocity
o Neuropathies are detected by decreased conduction
 Muscle Biopsy
o Definitive test for diagnosing specific muscle diseases
and is indicated in the child with suspected neuromuscular
disease
o Less likely to yield diagnostic findings if creatine kinase
and EMG readings are normal
 Muscle Imaging
o Ultrasound, computed tomography and magnetic
resonance imaging
o Used in the diagnosis and management of patients with
neuromuscular diseases
 Molecular Genetics
o Duchenne’s and Becker’s muscular dystrophy
 ECG
o Heart may be involved in muscular dystrophies and in
inflammatory and metabolic myopathies
II. SPINAL MUSCULAR ATROPHIES
These are not seen in adults as the children die before they
reach adulthood. Three kinds of SMA which involves the AHC.
II-A. SPINAL MUSCULAR ATROPHY I (INFANTILE ONSET
SPINAL MUSCULAR ATROPHY; WERDNIG-HOFFMANN
DISEASE)
Figure 3. Spinal Muscular Atrophy I. Severe weakness and
hypotonia of the limbs. High index of suspicion in a child who is
always in the hospital, weak and crying.
 Most severe form of disease
 Onset of symptoms before age 6 months
Cardinal features of SMA type 1 are severe hypotonia,
generalized weakness, thin muscle mass, absent tendon
stretch reflexes, involvement of the tongue, face, jaw muscles;
and sparing of extraocular muscles and sphincters.
Infants lie flaccid with little movement, unable to overcome
gravity. They lack head control.
Diaphragmatic involvement is late
Infants who are symptomatic at birth can have respiratory
distress and are unable to feed
 Frequently resulting in death from respiratory failure before 2
years of age
 Severe weakness of the limbs and intercostals muscles
 (+) paucity of spontaneous movement at the shoulder and hip
girdle
 (+) fine hand tremors (polyminimyoclonus)
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 Physical examination
o Frog-leg postion
o Narrowed thorax with pectus excavatum deformity and
flaring of the lower limbs (bell-shaped)
o (+) diaphragmatic or paradoxical breathing
o (+) tongue weakness and fasciculations
o (-) DTRs; sphincter and sensation remain intact
o Bilateral eventration or paralysis of the diaphragm-maybe
a presenting manifestation before the loss of DTRs or the
detection of muscle weakness
 <3 months of age, unilateral or bilateralmost
common presenting complaint in SMA with
respiratory distress
Symptomatic management. Usually, they are ventilator-
dependent. They usually die of infection.
II-B. SPINAL MUSCULAR ATROPHY II (JUVENILE SPINAL
MUSCULAR ATROPHY, CHRONIC SPINAL MUSCULAR
ATROPHY)
 Onset of weakness: 6-18 months
 Failure to walk-typical chief complaint
 DTRs may be variable
 Minipolymyoclonus may be prominent
 Distal muscles (fingers) are primarily involved
 Able to sit without support; rarely, are able to stand or walk
with aid
 Usually achieve normal milestones up to 6-8 months of age
Affected infants are usually able to suck and swallow, and
respiration is adequate in early infancy.
These children show progressive weakness, but many survive
into the school years or beyond, although confined to an
electric wheelchair and severely handicapped.
Nasal speech and problems with deglutition develop later.
Scoliosis becomes a major complication in many patients with
long survival.
GERD may lead to malnutrition or to aspiration with acute
airway obstruction or pneumonia.
Figure 4. Spinal Muscular Atrophy II. Typical problem of weakness
due to involvement of AHC. They die due to respiratory problems.
II-C. SPINAL MUSCULAR ATROPHY III (WOHLFART-
KUGELBERT-WELANDER SYNDROME)
Mildest form but still wheelchair-bound by 3-10 years of age.
 Present in late childhood or adolescence
Patients can appear normal in infancy.
 Maybe confused with limb girdle muscular dystrophy
 (+) waddling gait, lumbar lordosis, genu recurvatum and a
protuberant abdomen
 DTRs may or may not be elicited
Progressive weakness is proximal in distribution, particularly
involving shoulder girdle muscles.
Patients are ambulatory.
6.03B Neuromuscular Disorders [Dra.Panlilio]
 Prognosis for continued independent ambulation can be
correlated with age of onset of weakness
 Onset <2 years old: patient likely to stop walking by 15 years
old
 Onset >2 years old: highly likely that ambulation will be
possible into the 5th decade, but they are weak
Symptoms of bulbar muscle weakness are rare.
Cramps and myalgias of appendicular and axial muscles are
common, especially in later stages, and problems of
micturition may present.
 Distinguished from SMA I because of later onset and long
survival; and from ALS by the benign course and absence of
any involvement of corticospinal tracts
 Autosomal recessive disorder-most common form of spinal
muscular atrophy
 Clinical Laboratory Tests
o Serum muscle enzymes (creatine kinase)-may or may not
be elevated
o Electromyography- (+) acute denervation
o Muscle biopsy- indicate neurogenic atrophy or evidence of
reinnervation
 Management
o Consists of preventing or treating the complications
o No effective therapy for spinal muscle atrophy
o Complications: restrictive lung disease; poor nutrition;
orthopedic deformities; immobility and psychosocial
problems
o Scoliosis-most serious orthopedic problem
Figure 5. Spinal Muscular Atrophy III. Lordosis and problems in
spine curvature as they are always sitting down.
II-D. MOBIUS’ SYNDROME
 Facial nerve bilateral palsy with mask-like facies
 Congenital, static condition manifested by facial palsy (often
bilateral) and CN VI, impaired lateral rectus muscle with
resultant convergence
 (+) CNs impairment: V, X, XI, XII
 (+) recurrent swallowing impairment
 (+) history of exposure to cocaine or misoprostol in utero
 Differential diagnoses:
o Myotubular myopathy
o Facial scapulohumeral dystrophy
Figure 6. Mobius’ Syndrome. Masked-like fascies due to paralysis
of facial nerve. They have no expressions. They have problems in
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swallowing, and sometimes may be incompatible with life. If they
reach adult, it is probable that the involvement is unilateral only.
II-E. ARTHROGRYPOSIS MULTIPLEX CONGENITA
(This part was skipped in the lecture)
 Syndrome manifesting at birth, characterized by multiple,
fixed contractures of large joints
 Utero- (+) fetal hypokinesia or restricted movement result to
congenital contractures
 Autosomal recessive
 Manifestations:
o Decrease of the AHC population in the cervical and lumbar
spinal cord enlargements
o Arms rotated inwardly
o forearms held pronated
o ulnar deviation at the wrists
o Hands are flexed/ fingers are curled tightly
o Thighs are externally rotated
o Limbs are slender
 Absent DTRs
Figure 7. Arthrogryposis Multiplex Congenita
III. PERIPHERAL NEUROPATHIES
 Depending on whether the main disruption involves the axon
or the myelin supported by the Schwann cell.
 PNS – made up of:
o Cranial nerves III to XII
o Spinal roots
o Nerve plexus
o Peripheral nerves
o Autonomic ganglia
 Neuropathies – are demyelinating or axonal
o Depending on whether the main disruption involves the
axon or the myelin supported by the Schwann cell.
 Evaluation of PN disease:
o Clear History – distribution or rate of progression
o Thorough PE
o EMG
III-A. FACIAL NERVE PARALYSIS (BELL’S PALSY)
Common due to viral infection of facial nerve. It may remit
after treatment with steroids, Vitamin B complex and therapy.
 Caused by lesions of the facial nerve nucleus in the pons or
axial or extra axial facial nerve.
 (+) partial or complete paralysis of the upper & lower face
muscles.
 Most often results from edema and inflammation of the nerve
as it traverses the facial canal within the temporal bone.
 Commonly follows an URTI
It could also be due to cold exposure (electric fan on your
face with aircon on), and weak immune system
6.03B Neuromuscular Disorders [Dra.Panlilio]
 Lesions in the CN VII nucleus – result in the paralysis of upper
(forehead) and lower facial muscles.
o CN VII – complex nerve that has motor, sensory and
autonomic components
 Incidence: F=M
 1st manifestation: ear pain near the mastoid process
 1st motor sign: unilateral inability to close the eyelid and
maintain normal facial involvement
 Facial weakness develops rapidly – 3 hours to 3 days
 Drinking & eating are impaired (because the inability to close
the mouth on the involved site
 Decreased lacrimation & taste distorted on ipsilateral side
Figure 8. Bell’s Palsy. Ipsilateral peripheral facial palsy. Results
from damage to the motor nucleus of CN VII or its axons. A LMN
lesion results in the paralysis of all muscles of facial expression
ipsilateral to the lesion. Unable to wrinkle the forehead,
asymmetrical nasolabial fold.
Figure 9. (L) Central Palsy- UMN facial weakness, the patient can
still wrinkle the forehead. The lesion is above the facial nerve vs (R)
Peripheral Facial Palsy- LMN facial weakness, all muscles in the
given side are affected.
III-A-1. DIFFERENTIAL DIAGNOSIS
 Trauma, acute & chronic infections of the inner ear, herpes
simplex infection, herpes zoster infection, Mycoplasma
pneumoniae infection, EPV infection & Lyme disease.
 Mobius Syndrome –bilateral, congenital facial paralysis usually
in conjunction with ophthalmoplegia involving CN VI
o Result of aplasia or hypoplasia of cranial nerves nuclei of
VI & VII
 Cayler’s syndrome – simple asymmetry of facial expression
when infants & children cry
o Due to congenital hypoplasia of the depressor anguli oris
o Associated with CHD
o Links to chromosome 22
III-A-2. MANAGEMENT
• Laboratory Findings:
o Blood count & ESR – normal
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o CSF analysis – pleocytosis
o EMG – assess severity of facial nerve involvement and
predicting outcome.
• Treatment & Prognosis
o Good
o Prednisone – widely used for 1 week
• Recovery:
o 2-4 weeks; maximum within 6-12 months
III-B. BRACHIAL PLEXUS PALSY
• Birth related injuries: 0.5-1 of 1000 live births
• Associated with excessive traction to the affected extremity
during breech delivery or traction to the head and neck during
vertex delivery – due to shoulder dystocia
• Associated with:
o Clavicular fracture – 10%
o Humerus fracture – 10%
• Erb’s Palsy
o Most common brachial plexus injury, (80-90%)
o Due to the damage of the 5th & 6th cervical nerves or the
upper trunk of the brachial plexus  paralysis of the upper
arm
o PE:
 Humerus adducted and internally rotated with the
elbow extended, forearm pronated and wrist flexed.
 Deltoid, biceps, brachialis, supinator and extensors of
the wrist and finger muscles are paralyzed.
• Klumpke’s paralysis (not discussed)
o Injury to the lower trunk of the plexus involving the 8th
cervical nerve and the 1st thoracic nerve
o Rare, <1%
o Manifestations:
 Weakness of the forearm extensors
 Flexors of the wrist and fingers
o PE:
 Elbow is flexed
 (+) clawlike deformity of the hand
 Hyperextension of the wrist and fingers
 Triceps and grasp reflex
There is a good outcome with conservative management. If
there is a good function of the hand before 6 months – good
prognosis. Any residual problem afterwards would mean a
probable difficult return to normal function.
Management:
o Putting the forearm in the sling
o Passive range of motion after 2-3 wks to prevent
contracture
o X-ray – for fractures
o Physiotherapy
IV. DEVELOPMENTAL DISORDERS OF MUSCLE
(The lecturer skipped this section in her discussion and was taken from
her powerpoint)
• Congenital Muscle Fiber-type Disproportion (CMFTD)
o May occur independently or associated with nemaline rod
disease, Krabbe disease, cerebellar hypoplasia and other
brain malformations, fetal alcohol syndrome, etc.
o Associated with cerebellar hypoplasia
o CM: referred for dev’tal delay and hypotonia.
6.03B Neuromuscular Disorders [Dra.Panlilio]
 Present with dolichocephalic head, facial weakness,
high-arched palate, thin muscles, but respiratory and
bulbar muscles usually not affected.
o Diagnosis: Muscle biopsy - type I fibers are small, type II
are hypertrophic; type I are more numerous than type II.
o Genetics: sporadic, autosomal recessive
o Treatment: physiotherapy
• Nemaline Rod Myopathy
o Nemaline rods consist of excessive Z-band material made
of actin, α-actinin, tropomyosin-3, and the protein nebulin
o CM:
 Neonatal- severe and usually fatal because of
respiratory failure since birth
 Infantile- generalized hypotonia and weakness which
can include bulbar-innervated and respiratory
muscles, and a very thin muscle mass
 Decreased fetal movements, neonates may suffer
from hypoxia and dysphagia, arthrogryposis may be
present
 juvenile forms- mildest and not associated with
respiratory failure
o Lab: serum CK is normal or mildly elevated
o Muscle biopsy: show nemaline rods (EM) and CMFTD
o Genetics: AD and AR, and X-linked dominant in girls; 5
genes have been identified (NEM1-5)
o Treatment and Prognosis: Supportive; gastrostomy may
be needed; pneumonia is common
• Central Core disease and Minicore Myopathy
o Transmitted as either AD or AR with the same abnormal
gene at the 19q31.1 locus
o This gene programs the ryanodine receptor (RYR1)
o Mutations in this gene also cause malignant
hyperthermia. This may precede the diagnosis of central
core disease. Pretreatment with dantrolene before
anesthesia.
o CM: infantile hypotonia, proximal weakness, muscle
wasting, and involvement of facial and neck flexor
muscles. Kyphoscoliosis may develop. High incidence of
cardiac abnormalities.
o Patho: central core within muscle fibers in which only
amorphous, granular cytoplasm is found.
o Treatment with salbutamol is still controversial
o Variants: minicores (different genetic disease) and
multicores
• Myofibrillar myopathies
o Most are not symptomatic in childhood, but occasionally
older children and adolescents may show early symptoms
of proximal and distal weakness
o An infantile form also occurs and may cause mild neonatal
hypotonia and weakness with disproportionately severe
dysphagia and respiratory insufficiency, at times leading
to death
o Non-progressive and some show improvement in later
infancy and early childhood; cardiomyopathy may occur
o Muscle biopsy: some sarcomeres of myofibers are
disorganized or show dissolution
V. MUSCULAR DYSTROPHIES
 Progressive, inherited skeletal muscle disorders resulting in
muscle degeneration and loss of strength
 Clinical onset: Neonatal to Late Adulthood
 Mod of Inheritance:
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o Autosomal dominant
o Autosomal recessive
o X-linked (Most Common)
Muscular dystrophy is distinguished from all other
neuromuscular diseases by 4 obligatory criteria:
1. Primary myopathy
2. Has a genetic basis
3. Progressive course
4. Degeneration and death of muscle fibers occur at some
stage in the disease
o This definition excludes neurogenic diseases
V-A. DUCHENE MUSCULAR DYSTROPHY
(Note: This part was focused on during the discussion AND given as a
reading assignment)
Most common hereditary neuromuscular disease affecting all
races and ethnic groups
 Incidence: 1:3600 live born infant boys
 Relentlessly progressive skeletal muscle disorder
Disorder of organization – insult occurred on the 5th to 7th
month AOG
 Caused by genetic mutation in the X-linked Dystrophin gene,
resulting in absence of a protein, Dystrophin (<3% compared
to normal)
Abnormal gene is at the Xp21 locus
o X-linked recessive pattern of inheritance, but
approximately 30% of cases are new mutations
o Female carriers usually are asymptomatic, but affected
girls are occasionally encountered, manifesting milder
weakness in boys. This is explained by the Lyon
hypothesis – in which the normal chromosome becomes
inactivated, and the one with the gene deletion is active
Rarely symptomatic at birth. Early gross motor skills are
usually achieved at appropriate ages
 Present in infancy with muscle fiber necrosis & high serum
creatine kinase level
Common presentation in toddlers: delayed walking, falling, toe
walking, and trouble running or walking upstairs,
developmental delay, and, less often, malignant hyperthermia
after anesthesia
 Symptoms are recognizable at 3 years old
o More falling attacks
o Progressive muscle weakness
Poor head control (neck flexors) in infancy may be
the first sign of weakness
o Hip girdle weakness
o Gower’s sign
o By age 5-6 y/o,Trendelenburg, or hip waddle appears
o Hypertrophy of calves (pseudohypertrophy) – prominent
at 3 or 4 years old
o Wasting of the thigh muscles, later also involving the
tongue and forearm muscles
o Progression of weakness later involves the respiratory
muscles, bulbar muscles, and extraocular muscles.
o Patient may be confined to a wheelchair by 10 yr old
 Pulmonary involvement
o Weakness of intercostal & diaphragmatic muscles 
Disruption of lung function
 Cardiac involvement
o Persistent tachycardia and myocardiac failure
o Risk for cardiomyopathy at ages 5 - 6 years old
Seen in 50-80% of patients
6.03B Neuromuscular Disorders [Dra.Panlilio]

Other clinical features Consistently elevated even at birth. Normal levels

o CNS manifestations – dystrophin is also expressed in the incompatible with diagnosis of DMD
brain, but in lower levels than in muscle 2. Genetic testing
 Intellectual impairment – occurs in all patients; 20- PCR for dystrophin gene mutation is the primary test
30% with IQ <70 If the blood PCR is diagnostic, muscle biopsy may be
 Epilepsy – slightly more common than in normal deferred
population 3. Muscle biopsy – diagnostic
 Autism-like behavior – uncommon  (+) Large, opaque fibers distinguished by intense staining
o Proliferation of connective tissue in muscle are prominent
o Pharyngeal weakness: aspiration, nasal regurgitation of
liquids, airy or nasal voice quality
o Preserved ankle DTRs
 Knee DTRs present until 6 yr but are less brisk, and
are eventually lost
 Brachioradiallis DTRs >> biceps or triceps DTRs
• Complications
o Contractures: ankles, knees, hips, elbows
o Scoliosis
Death occurs usually at about 18-20 yr of age
o Respiratory failure during sleep
o Intractable heart failure
o Pneumonia
o Aspiration and airway obstruction

Figure 12. Duchenne muscular dystrophy on muscle biopsy.

Variation in fiber diameter, numerous hyalinized fibers and
replacement of muscle by fat and fibrous tissue.

V-A-2. TREATMENT

No medical cure nor a method to slow down its progression

1. Multidisciplinary setting
 Physicians (neurologist, psychiatrists, orthopedic
surgeons, cardiologists, pulmonologists)
 PTs/OTs
 Nutritionists
 Physiologists
 Social workers
2. Family Counselling
3. Pharmacologic treatment
 Corticosteroids: Prednisone
o Given during the ambulatory stage of the disease
o 0.75 mg/kg/day prednisone for the first 10 days of
each mo
o Stabilizes or improves the strength
Figure 10. Clinical Manifestations o The only demonstrated treatment for this disease
o MOA: Not entirely known and likely involves
immunosuppressive actions, gene transcription and
modulation
Decrease the rate of apoptosis of myotubes and
can decelerate myofiber necrosis
Improved long-term prognosis in muscle and
myocardial outcome
Deflazacort may be more effective than prednisone.
Avoid dexamethasone or triamcinolone
(fluorinated steroids) because they induce myopathy.
Figure 11. Gower’s Sign
Digoxin – for cardiac decompensation
V-A-1. CLINICAL & LABORATORY TEST Prompt treatment of pulmonary infections
• Avoid contact with children with contagious diseases;
1. Serum creatine kinase level: 15-35,000 IU/L immunizations for prevention
 Greatly elevated from 10,000-30,000x normal

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6.03B Neuromuscular Disorders [Dra.Panlilio]

Preservation of good nutritional state. No need for  Most patients become unable to walk about 25 years after
megavitamins. Adequate calcium to minimize osteoporosis symptom onset.
and fluoride supplements. Avoid obesity. Reported in Amish families and in families from French
Physiotherapy delays contractures, but contributes little to Reunion Island and from Brazil
muscle strengthening Slowly progressive

V-B. BECKER MUSCULAR DYSTROPHY

V-C-3. LIMB GIRDLE MUSCULAR DYSTROPHY 2B:
 X-linked recessive condition with mutation at Xp21 DYSFERLINOPATHY
 MW of dystrophin is reduced to 20-90% of the normal in 80% of
 Allelic mutations of dysferlin gene, which expresses a protein
patients. In 15%, the dystrophin is normal size but reduced in
essential to the structural integrity of the sarcolemma
quantity. 5% have an abnormally large protein
 Late teens
 Same as Duchenne with a genetic defect at the same locus, but
follows a milder and more protracted course  Progress slowly
 Onset: 7 years old  (+) Serum creatine kinase levels
 Characteristics: V-D. EMERY DREIFUSS MUSCULAR DYSTROPHY
o Ambulation is typically maintained beyond 30 years old
o (+) calf pseudohypertrophy, proximal hip weakness (The lecturer skipped this section in her discussion and was taken from
o Cramps & myalgia (Initial manifestation) her powerpoint)
 Creatine kinase levels are normal and slightly elevated (2,000-  Scapuloperoneal or scapulohumeral MD
20,000U/L)  Triad:
 Muscle biopsy: similar with DMD but less pronounced 1. Early contractures
 Treatment: same as DMD 2. Muscle wasting & weakness in a humeroperoneal
distribution
V-C. LIMB GIRDLE MUSCULAR DYSTROPHY 3. Cardiomyopathy
 Rare X-linked recessive dystrophy, the locus is on the long arm
(The lecturer skipped this section in her discussion and was taken from
within the large Xq28 region
her powerpoint)
May also be autosomal dominant (more than 1 pattern of
 Characterized by progressive muscle weakness
inheritance)
 Affecting the large muscles around the shoulder & pelvic
 Manifestations (begin at 5-15 yr of age):
girdles
o Contractures – elbows, Achilles tendon & posterior
Distal muscles also eventually become atrophic and weak
cervical muscles
16 genetic forms
 Contractures of elbows and ankles develop early
Clinical manifestations rarely appear before middle or late
o Arms are semi-flexed
childhood
o Muscles becomes wasted in a scapulohumeroperoneal
Low back pain d/t lordotic posture from gluteal muscle
distribution
weakness
o Cardiac symptoms: palpitations, syncope, diminished
Weakness of neck flexors and extensors is universal
exercise tolerance
EMG and muscle biopsy show confirmatory evidence of
Dilated cardiomyopathy is severe and is often the
muscular dystrophy, but none of the findings is specific enough
cause of death
to make the definitive diagnosis without additional clinical
Stroke secondary to cardiac arrhythmia
criteria
(–) pseudohypertrophy, facial weakness, myotonia,
impaired intellectual function
V-C-1. LIMB GIRDLE MUSCULAR DYSTROPHY 1C:  May survive to late adult life because of slow progression
CAVEOLINOPATHY Diagnosis and Investigations
o Emerin deficiency
 Caveolins – small transmembrane proteins with intracellular o ECG, echocardiogram
domains that undergo extensive oligomerization to form o Serum CK – may be moderately elevated; baseline for
membrane complexes known as caveolae. comparison with future measurements
 Autosomal dominant o Muscle biopsy – diagnostic
 Symptoms:  Management – directed to the symptoms
o Slowly progressive weakness o Special attention to cardiac conduction defects – may
o Calf hypertrophy require medications or a pacemaker
o Elevated creatine kinase levels (4-20 fold)
V-E. FACIOSCAPULOHUMERAL MUSCULAR DYSTROPHY
V-C-2. LIMB GIRDLE MUSCULAR DYSTROPHY 2A:
CALPAINOPATHY (The lecturer skipped this section in her discussion and was taken from
her powerpoint)
Primary calpain-3 defect  Autosomal dominant
 Frequent, childhood-onset LGMD (8-15 yr)  Manifestations:
 Autosomal recessive o Bifacial weakness – difficulty in whistling, sipping straw or
 Causes symmetric weakness of the pelvic & girdle; involvement blowing balloons
of the posterior part of the thighs o Weakness of the scapula

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o Ankle dorsiflexor muscles
o Sparing the deltoid, neck flexor & calf muscles
o Hearing loss
o Retinal vasculopathy
 Exclusion criteria:
1. Eyelid ptosis
2. Extraocular muscle weakness
3. Sensory loss
4. Elbow contractures
5. Cardiomyopathy
 Creatine kinase - Normal or slightly elevated
 No treatment
V-E. CONGENITAL MUSCULAR DYSTROPHY
(The lecturer skipped this section in her discussion and was taken from
her powerpoint)
• Used to encompass several distinct diseases with a common
characteristic of severe involvement at birth but follow a
benign course
• AR inheritance is the rule
• CM: infants often have contractures or arthrogryposis at birth
and are diffusely hypotonic. Muscle mass is thin. Head control
is poor. Facial muscles may be involved.
• Fukuyama type of congenital muscular dystrophy- 2nd most
common MD in Japan after DMD. Severe cardiomyopathy and
malformation of the brain usually accompany the skeletal
muscle involvement.
o (+) cardiomegaly and heart failure, mental retardation,
seizures, microcephaly, and failure to thrive
• Lab: CK- mod elevated; EMG- myopathic changes; cardiac
assessment and neuroimaging of the brain should be included
• Dx: Muscle biopsy: extensive proliferation of endomysial
collagen envelops individual muscle fibers
• Tx: Supportive
VI. ENDOCRINE AND TOXIC MYOPATHIES
(The lecturer skipped this section in her discussion and was taken from
her powerpoint)
• Thyroid Myopathies
o Thyrotoxicosis causes proximal weakness and wasting
 EMG- myopathy
 Thyroxine binds to myofibrils and impairs contractile
function
 Hyperthyroidism may also induce MG and hypoK PP
o Hypothyroidism produces hypotonia and proximal
weakness
o Muscle biopsy: hypothyroidism reveal acute myopathic
changes; in hyperthyroidism, only mild, nonspecific
myopathic changes
o Clinical and pathologic features resolve with treatment
• Hyperparathyroidism
o Develop weakness, fatigability, fasciculations and muscle
wasting that are reversible after removal of parathyroid
adenoma
o Muscle biopsy show nonspecific myopathic changes
• Steroid-induced Myopathy
o Natural and iatrogenic Cushing syndrome may cause
painless, symmetrical, progressive proximal weakness
o Labs: increased CK, myopathic EMG and muscle biopsy
o Most likely 2˚ to 9α-fluorinated steroids: dexamethasone,
betamethasone, triamcinolone
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• Hyperaldosteronism (Conn syndrome) – episodic and
reversible weakness similar to that of periodic paralysis;
elevated CK and myoglobinuria may occur during acute attacks
VII. METABOLIC MYOPATHIES
(The lecturer skipped this section in her discussion and was taken from
her powerpoint)
• Periodic paralyses (K-related)
o Usually associated with hypokalemia, but occasionaly
hyperkalemia
o All familial forms of PP are caused by mutations in genes
encoding voltage-gated ion channels in muscle: Na, Ca,
and K
o Inherited as AD
o Hyperkalemia: 17q13.1-13.3; hypokalemia: 1q31-32
o Precipitated by a high CHO meal, insulin, adrenaline,
hyperaldosteronism or hyperthyroidism, ampho B, licorice
o Attacks often begin in infancy, and is always symptomatic
by 10 years, with usual attacks of once a week. The
attacks become more frequent in adulthood, causing
progressive myopathy with permanent weakness
o Muscle biopsy: vacuolar myopathy during an attack
o Treatment: administration of K or fruit juice, low Na
intake, acetazolamide, spironolactone
VIII. MITOCHONDRIAL MYOPATHIES
(The lecturer skipped this section in her discussion and was taken from
her powerpoint)
• Ragged red fiber diseases
o Kearns-Sayre syndrome – triad of progressive external
ophthalmoplegia, pigmentary degeneration of the retina,
and onset before age 20.
o MELAS (mitochondrial encephalopathy, lactic acidosis,
and strokelike symptoms) and MERFF (myoclonic epilepsy
and ragged red fibers) – stunted growth, episodic
vomiting, seizures, and recurrent cerebral insults causing
hemiparesis, hemianopia or even cortical blindness, and
dementia. Degenerative course and children die within a
few years.
o Progressive external ophthalmoplegia – may be isolated
or accompanied by limb muscle weakness, dysphagia, and
dysarthria
• Non-ragged fiber diseases
o Leigh encephalopathy
o Leber hereditary optic atrophy
• EM of muscle biopsy: abnormal shaped cristae to form
paracrystalline structures
• No effective treatment for mitochondrial cytopathies but
various cocktails are often used: carnitine, riboflavin, coE Q, vit
C and E.
IX. DISEASES OF THE NEUROMUSCULAR JUNCTION
IX-A. AUTOIMMUNE MYASTHENIA GRAVIS
(Note: This part was focused on during the discussion AND given as a
reading assignment)
 Autoimmune disease with antibodies directed against the
skeletal muscle AchR.
 Characterized by fluctuating weakness and rapid fatigability of
ocular, bulbar and extremity striated muscles.
6.03B Neuromuscular Disorders [Dra.Panlilio]

o Ocular (ptosis, diplopia) – MG is the most common cause  birth

of unilateral/bilateral ptosis  infancy
o If there is ptosis with pupillary problem then that is not MG o Diagnosis
o Bulbar ( dysarthria, dysphagia & dyspnea)  IV (immediate action) or SC (10 mins action)
 Symptoms tend to worsen with stress & exertion. Edrophonium HCl 0.15 mg/kg
 Thymus gland- 75% of MG patients (15% are tumors, 85% o Treatment
lymphoid hyperplasia)  Long term with Neostigmine or pyridostigmine
 Thymoma – 15% adult, less than 5% in children  Thymectomy and immunosuppressive – NOT
 Clinical Classification – Osserman (1958)- according to disease beneficial
severity  Juvenile MG
o Group I – Ocular o Most common
o Group IIA – Mild generalized o Represents the childhood onset of autoimmune MG in
o Group IIB – Moderate to severe generalized adults
o Group III – acute, severe, developing over weeks to  Presently, the term juvenile myasthenia gravis is
months being discarded (denotes immune mediated)
o Group IV – late, severe with marked bulbar involvement because disorder is similar in children and adults
o Onset at 10 years old
IX-A-1. CATEGORIES OF MG IN CHILDHOOD o Female >> Male (6:1)
o Postsynaptic site: decreased no of Ach receptors, Abs
 Neonatal Transient MG against Ach Receptor (postsynaptic fold)
o 10 – 15 % born to myasthenic mothers o Muscles innervated by CN affected first
o Passive placental transfer of anti-AChR antibody or o 2 Clinical Forms
immunocytes results in transient impairments of  Ocular MG – eye muscles primarily or exclusively
neuromuscular transmission in neonate affected but facial and limb may be mildly involved
o Signs and symptoms occur hours after birth or may be – More common
delayed up to 3rd day of life – First symptoms appear after 6 mos.
o Physical Examination – After age 10 – 75 %
 Weak suck/cry
– Prepubertal – male greater than female
 Ptosis
- ocular only
 Limited facial and ocular movements
- They usually do not consult if the problem is
 Dysphagia
 Generalized weakness only in the eyelid but they consult when the
 Decreased spontaneous movement eyelids do not move d/t 3rd and 6th cranial
 Respiratory distress nerve problem
o HYPOTONIA – primary symptom - seronegative Ach receptor Abs
 +/- intrauterine hypotonia (dev. Arthrogryposis) – Post pubertal – female greater than male
o Resolves in the first 4 weeks – complete recovery - generalized
 Mean duration of weakness is 18 days (5 days – 2 mo) - seropositive
o Diagnosis - severity of disease female greater than male
 Born to myasthenia gravis mother – +/- spontaneous remission
 Increase in AChR binding antibody  Generalized MG – weakness of bulbar and limb
 response to Edrophonium HCL (0.15 mg/kg) muscles is moderate to severe
(Tensilon test) – Have increased incidence of other autoimmune
o Treatment diseases esp. thyroiditis and collagen vascular
 Exchange transfusion diseases
 Neostigmine (0.1 mg) via NGT before feeding – No spontaneous remission
 Genetic (Congenital) MG o Clinical manifestations:
o Autosomal recessive  Ptosis
o Seronegative for Ab against Ach R – must be – Most common clinical finding
distinguished from autoimmune MG – Accompanied by Ophthalmoparesis
Genetic disorder of receptors on the postsynaptic  Facial & Oropharyngeal weakness
membrane of the neuromuscular junction – Leads to Dysarthria & Dysphagia
o In 50%: symptoms present at birth or within 1st 2 years of  Extremity weakness
– Proximal > Distal
life
 Bulbar weakness
o 2 Clinical Syndromes
– Characterized by slow chewing, dysphagia,
 Congenital MG – predominantly ocular finding
nasal dysarthria, and weak cough
 Familial Infantile
– prominent respiratory and feeding difficulties
IX-A-2. DIFFERENTIAL DIAGNOSIS
– lasts +/o infancy and childhood
o Onset  Botulism
 intrauterine (+/- arthrogryposis) o May manifest as weakness

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o Weakness does not have a waxing and waning character IX-B-2. TREATMENT
o EMG and ECVv findings are nonspecific
o Neuromuscular junction disorder cannot be ruled out 1. Anticholinesterase agents
o Pupillary problem 2. Prednisone
o History of intake of honey in infants 3. Guanidine hydrochloride
 Any type of honey (even imported, organic, etc) is
not recommended for infants of any age because the X. INFLAMMATORY NEUROPATHIES
boiling point of honey is very high
(The lecturer skipped this section in her discussion and was taken from
her powerpoint)
IX-A-2. CLINICAL & LABORATORY TEST

1. Edrophonium (Tensilon) Test X-A. ACUTE INFLAMMATORY DEMYELINATING

 IV 0.15 mg/kg (max 10 mg IV) POLYRADICULOPATHY (GUILLAIN-BARRE SYNDROME)
 Positive result:
o Increase the palpebral fissure aperture • Inflammatory, demyelinating disorder of spinal nerve roots and
o Improves the ocular motility peripheral nerves of acute to subacute onset.
o Improves the dysarthria & swallowing • Acute monophasic demyelinating neuropathy in which
2. Repetitive Stimulation (EMG: Jolly Test) abnormal immune responses are directed against peripheral
 (+) Decremental response of the compound muscle nerves
action potential to repetitive stimulation of a motor nerve • Cellular and humoral immune mechanism induced by a viral
3. Single fiber EMG infection (50% with a previous viral infection)
4. Anti-AChR antibodies (greater than 10 nmol/L) o CMV
o EPV
 Most specific & definitive for supporting the diagnosis
o M. pneumoniae
 Generalized MG – 90%
o C. jejuni , H.Pylori
 Ocular MG – 0 or low
 3 days to 6 weeks before the onset of symptoms
 18% of cases secondary to C. jejuni
IX-A-3 TREATMENT • Characteristics:
o Muscle pain of the lower extremities- initial manifestation
1. Neostigmine
o Pain and paresthesias
o 0.04 mg/kg IM q 4-6 hrs o Progressive symmetrical weakness of extremity and facial
o Oral neostigmine bromide, 0.4 mg/kg every 4-6 hrs muscles (Landry Ascending Paralysis)
2. Pyridostigmine bromide (Mestinon) o Bladder dysfunction, mental alterations, headache, ataxia
o 15 mg bid-tid or 0.5-1.0 mg/kg and meningismus.
3. Thymectomy o Tendon reflexes are diminished or lost
4. Corticosteroids (Prednisone) – start at 1 mg/kg/day This paralysis usually follows a nonspecific gastrointestinal or
5. Azathioprine respiratory infection by approximately 10 days.
6. Cyclosporine Due to consumption of undercooked poultry, unpasteurized
7. Cyclophosphamide milk, and contaminated water.
8. Plasmapheresis This is also reported following administration of vaccines
9. IVIG against rabies, influenza, and poliomyelitis (oral) and
conjugated meningococcal vaccine, particularly serogroup C.
IX-B. LAMBERT EATON MYASTHENIC SYNDROME • Progress for days to several weeks before plateaus in 1-28 days
• Pathology: demyelination and mononuclear cell infiltration of
 An acquired autoimmune disorder of neuromuscular junction peripheral nerve
transmission in which the defect is in the presynaptic nerve • Macrophage invasion of Schwann cells
terminal (presynaptic block) • Axonal degeneration
 Rarely encountered in children • CSF analysis:
 Seen after IV antibiotics, surgical procedures, acute leukemia o Protein- elevated within the 1st week
o Other causes of blocks: immunosuppresants, arthropod o “cyto-albumino dissociation”
venoms, some insect bites, phenytoin, trimethadione,
X-A-1. CLINICAL FEATURES OF GBS
antibiotics (polymyxim B & E, aminoglycosides)
 Characterized by: I. Required for diagnosis
o Fatigability & weakness in the limb girdle distribution o Progressive motor weakness of more than 1 limb
o Cranial nerves & respiratory symptoms are less prominent o Areflexia – loss of ankle jerk reflex
o (+) Malignancy in 50% of cases (Small Cell Carcinoma) II. Strongly supportive of the diagnosis
o Progression – weakness may develop rapidly but
IX-B-1. CLINICAL & LABORATORY TEST cease to progress after 4 weeks
o Relative symmetry
1. Electrophysiology (Triad) o Mild sensory signs & symptoms
 Low amplitude compound muscle action potential o CN involvement: facial weakness (50%)
 Decremental response at 2-5 Hz o Autonomic dysfunction
 Incremental response at 20-50 Hz
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o Absence of fever at the onset of neurologic o Acute onset of ascending weakness,

symptoms hyporeflexia
2) Acute Motor &
o Recovery – begins 2-4 wks after progression ceases o Elevated CSF protein
Sensory Axonal
o Sphincter dysfunction o EMG (+) axonal involvement with
Neuropathy
III. Features casting doubt on diagnosis reduction of CMAP
(AMSAN)
o Marked persistent asymmetry in motor function o Triphasic course; poor or limited
o Persistent bowel & bladder dysfunction recovery
o Discrete sensory level o Clinical syndrome similar to AIDP or
IV. Features that exclude the diagnosis 3) Acute Motor AMSAN
o Evidence of porphyria Axonal o Elevated CSF protein
o Recent diphtheria Neuropathy o Electrophysiologic and
o Pure sensory syndrome (AMAN) histopathologic evidence of
o Features consistent of lead intoxication degeneration to sensory axons
o Acute onset of ophthalmoplegia,
X-A-2 LABORATORY FEATURES OF GBS 4) Miller Fisher hyporeflexia/areflexia and ataxia
Syndrome o Elevated CSF protein
 CSF – (+) albuminocytologic dissociation or a disproportionate o Subsequent recovery
elevation of CSF protein in the absence of significant evidence of o Acute onset of multiple cranial
inflammation after the 1st week to 80-200mg/dl (N <40mg/dl) nerve palsies (usually bilateral CN
 Electrophysiologic testing 5) Polyneuritis VII and sparing of CN II)
o Pathologic hallmark: multifocal, immune-mediated Cranialis o Elevated CSF protein
demyelination within spinal roots & peripheral nerves o Slowing of motor conduction
o (+) multifocal slowing of nerve conduction or conduction velocities and recovery
block o Acute onset of sensory loss,
 MRI – look for the enhancement in spinal roots after contrast areflexia
administration(sign of inflammation) 6) Acute Sensory
o Elevated CSF protein
 EMG: Neuropathy
o Slowing of motor conduction
o Distal motor and F wave latencies are prolonged to more velocities and recovery
than 150% o Subacute or indolent onset of
 NCV: weakness and hyporeflexia
o Reduced to 70% below the normal. 7) Chronic o Elevated CSF protein
Inflammatory o EMG showing demyelinating
X-A-3. TREATMENT Demyelinating neuropathy
 Excellent for spontaneous recovery Polyneuropathy o Symptoms persists for >8 weeks and
 Mainstay: supportive may remain chronic or become
o Ventilatory support, nutritional, fluid and electrolyte progressive
balance is necessary o Acute or subacute onset of weakness
 Plasmapheresis – remove circulating antibody directed 8) Chronic and hyporeflexia with elevated CSF
toward peripheral nerve antigens. Inflammatory protein
o Side effects: hemorrhage, hypotension, transfusion Relapsing o EMG showing demyelinating
reaction, transmitted infections, septicemia, Demyelinating neuropathy
hypocalcemia, arrhythmias, cardiac arrest Polyneuropathy o Symptoms persists >8 weeks and
follow a chronic relapsing course
 IVIG – act by binding anti-idiotypic antibodies, absorbing
complement, or down-regulating B-cell-mediated antibody o Subacute or indolent onset of
production. 9) Chronic weakness and hyporeflexia
Inflammatory o Elevated CSF protein
X-A-4. OTHER TYPES Axonal o EMG consistent with an axonal
Polyneuropathy neuropathy
 Acute Inflammatory Demyelinating Polyardiculoneuropathy o Sural nerve biopsy is normal
(AIDP) o Acute onset of weakness and
 Acute Motor And Sensory Axonal Neuropathy 10) Guillain-Barre
hyporeflexia
 Acute Motor Axonal Neuropathy (AMAN) o Elevated CSF protein
Syndrome with
 Acute Sensory Neuropathy o EMG showing demyelinating
Encephalopathic
 Miller Fischer Syndrome neuropathy
Features
o Encephalopathic and brainstem
Table 4. GBS Variants symptoms
1) Acute o Acute onset of ascending weakness,
Inflammatory hyporeflexia X-B. CHRONIC INFLAMMATORY DEMYELINATING
Demyelinating o Elevated CSF protein POLYARDICULOPATHY
Polyneuropathy o EMG (+) demyelinating neuropathy
(AIDP) o Triphasic course with good recovery • Immune-mediated polyneuropathy of more than 2 months
duration

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6.03B Neuromuscular Disorders [Dra.Panlilio]

• Can present as an indolently progressive, predominantly motor D. All of the above

neuropathy and closely resemble hereditary motor and sensory
neuropathy 3. A clinical feature of Spinal Muscular Atrophy
• Typical symptoms: A. Extraocular muscle weakness with cardiomyopathy
o Lower extremities weakness – most common complaint B. Muscle weakness is distal
o Precipitous onset of weakness C. Normal tendon stretch reflexes
o Sensory loss D. Tongue fasciculation
o Diminished tendon reflexes
• Pathologic findings: 4. Which of the following medications is given to delay the
o Loss of myelinated axons; evidence of segmental and progression of spinal muscular atrophy type I
remyelination; regional variability in the severity of fiber loss A. Gabapentin and oral phenylbutyrate
and inflammation B. Stem cell therapy
o CSF – protein is elevated with normal cell count C. Valproic acid
• Management: D. None of the above
o Plasmapheresis + prednisone
o Prednisone alone 5. What diagnostic test is used to document Duchenne Muscular
o IVIG Dystrophy
o Immunosuppressive agents A. Muscle biopsy
B. PCR for the dystrophies gene mutation
SUMMARY C. Serum CK level
D. All of the above
 Clinical manifestations of neuromuscular disorder in a child:
o Hypotonia 6. What is the diagnostic test that you will order to check for
o Decreased motor power Myasthenia Gravis?
o Hyporeflexia/areflexia A. CPK
o Muscle atrophy B. Electromyography
o Fasciculations C. Muscle Biopsy
REFERENCES D. Nerve Conduction Velocity
ADDADB
 Panlilio, MJVR, Lecture. April 19, 2018. UERMMMCI, Quezon
City. MOTIVATIONAL QUOTES
 Kliegman, Robert., et al. Nelson Textbook of Pediatrics. Edition
20. Phialdelphia, PA: Elsevier, 2016.

REVIEW QUESTIONS

1. For Duchenne Muscular Dystrophy, corticosteroids are

recommended as treatment at what stage of the disease?
A. During the ambulatory stage
B. During the onset of cardiac symptoms
C. Once the patient is wheelchair bound
D. Prenatally once a genetic predisposition in the family is
suspected

2. What is/are differential diagnosis for Myasthenia Gravis:

A. Botulism
B. Organophosphate toxicity
C. Tick paralysis
APPENDIX
The following section was taken from the other powerpoint on  Course: slowly progressive to fulminating (the more rapid the
neuromuscular disorders not used in the lecture. progression, the more severe the eventual involvement)
 AHC: prime target of the virus
I. INFECTIOUS DISEASE OF THE AHC  Motor weakness: hallmark
o 1st year-quadriplegia
I-A. POLIOMYELITIS  Clinical Laboratory Tests
o CSF: (+) pleocytosis with mononuclear and a normal or
 Viral disease of motor neurons caused by poliovirus
slightly elevated protein
o 25% nonparalytic
o glucose- normal
o 50% spinal poliomyelitis
 Management: Supportive
o 12% bulbar poliomyelitis
o 10% bulbospinal involvement
 Triad: fever, nuchal rigidity, spasm of the back muscles
 Spinal involvement more common than bulbar involvement
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o Strengthening exercises of the foot- early course of the

disease
o Orthopedic surgery

II-B. TYPE II

• Autosomal Recessive
• Characteristics:
o Muscle atrophy and weakness are milder & more prominent
Figure 13. Poliomyelitis. o Rapid progression of weakness to almost complete paralysis
• Pathology: marked axonal degeneration
I-B. TRANSVERSE MYELITIS ASSOCIATED WITH IMMUNE- o No palpable nerve enlargement
MEDIATED PROCESSES, INFECTION OR BOTH o “Onion bulb” – rare
• Onset: before 5 y/o
 Usually viral in origin • CSF analysis: normal
 Thoracic area is most often affected
 Begins and progresses quickly for 1 to 2 days. II-C. TYPE III (DEJERINE-SOTTAS DISEASE)
 Manifestations: fever, lethargy, malaise & myalgia weakness
& flaccidity of legs with subsequent loss of rectal and bladder • Hypomyelinating neuropathy
sphincter control. Interstitial hypertrophic neuropathy
 Recovery – evident within a week of onset. Autosomal dominant
 CSF exam: Pleocytosis with Lymphocytosis, Glucose & protein • Characterized by the presence of thin myelin sheaths, often
are normal with few or poorly compacted myelin lamellae and basal lamina
 EMG- normal remnants.
 MRI- (+) hyperintensity & patchy enhancement with Symptoms develop in early infancy and are rapidly progressive
gadolinium with:
o Hypotonia
II. HEREDITARY NEUROPATHIES o Breathing
o Feeding difficulties
• Hereditary Motor and Sensory Neuropathy
o Pupillary abnormalities (Argyll Robertson Pupil)
o Types I- V
o Kyphoscoliosis
• Charcot-Marie-Tooth disease
o Pes Cavus
o Belongs to Type I & Type II
This is a more slowly progressive variant with onset usually
o Characterized by weakness of the extremities and foot
before age of 5.
deformities including pen cavus and “hammer” toes.
• Congenital amyelinating neuropathy (recessive form)
o (+) variable loss of sensation
o Arthrogryposis because of lack of limb movements in utero
o (+) respiratory/swallowing difficulties
II-A. TYPE 1 HEREDITARY MOTOR AND SENSORY o Die very young
NEUROPATHY o NCV: unrecordable or extremely low
o Histopathology: no or very little myelin and absent onion
• Heterogenous disorder causing a progressive motor and sensory
bulbs
demyelinating neuropathy.
• Hypotonia
• Autosomal dominant
st nd • Delay in developmental milestone
• Onset: 1 or 2 decade of life o Onset of walking beyond 2y/o
• Peripheral nerves - often palpated because they are • (+) Ataxia probably due to proprioceptive deficit
hypertrophied as a result of excessive Schwann cell and • DTRs are absent
fibroblast activity. “onion bulb” • Scoliosis often occurs early and tends to progress.
• Neurophysiology:
o Motor & sensory conduction velocity – within demyelinating II-D. FRIEDREICH’S ATAXIA
range
• Characteristics: • Autosomal recessive
o Distal lower extremity muscle wasting & weakness • Characterized by slowly progressive ataxia commencing in
o Development of pen cavus (high arch of the foot) childhood.
o Hammer toe deformity • Ataxia affects all motor functions
o Gradual loss of sensation, proprioception causing unsteady • Intellect is preserved
gait in darkness and a positive Romberg sign • Cardiomyopathy
o Diminished vibration & position sense • Skeletal deformities are typical:
o Absence of tendon reflexes- ankleknee o Pes cavus
o Muscle wasting lower >upper extremities o Hammer toes
o (+) kyphosis and scoliosis- 10% of cases o Kyphoscoliosis
 Management: • Principal cause: sensory neuropathy resulting from progressive
o Supportive degeneration of dorsal root ganglion cells
• Biopsy:
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o Axonal degeneration with some secondary demyelination III-C. ACUTE INTERMITTENT PORPHYRIA
o Linked to chromosome 9
 A rare inborn error of metabolism
II-E. GIANT AXONAL NEUROPATHY  Autosomal dominant
 Caused by defects in the gene encoding hydroxymethylbilane
• Initial descriptions of children: (+) kinky hair synthase on the long arm of chromosome 11.
• Autosomal recessive inheritance  (+) marked increase of aminolevulinic acid, porphobilinogen,
• Gigaxonin- responsible gene; located in chromosome 16q24 uroporphyrin
o Cytoskeletal protein that may play a role in neurofilament  Sural Biopsy: primarily axonal
architecture  Typical manifestation: acute, severe, colicky abdominal pain
• Hallmarks:  No successful treatment has been described
o Progressive gait disturbances  DDx: GBS and Lead poisoning
o Kinky hair
o Long curly eyelashes III-D. VITAMIN DEFICIENCY
o Prominent high forehead
o Variable CNS involvement (optic atrophy, abnormal  Thiamine or Vitamin B1 – coenzyme in carbohydrate
motility, mental retardation, spasticity metabolism
• Neuroimaging: (+) leukoencephalopathy  Causes peripheral neuropathy, encephalopathy and high
• NCVs: (+) axonal, motor sensory neuropathy output cardiac failure
• Rapid progression of the sensory motor neuropathy leads to  (+) cranial nerve dysfunction, ptosis, optic atrophy and
early death. laryngeal paralysis
• Postmortem exam:  Treatment: allows for reversal of symptoms with or without
o Severe cerebellar degeneration and optic atrophy caused sequelae
by degeneration & gliosis of the optic nerves.
III-E. CONGENITAL PERNICIOUS ANEMIA
II-F. INFANTILE NEUROAXONAL DYSTROPHY
 2 forms:
o Congenital or early onset disease
 Progressive central and peripheral nervous system disorder
 Occurs before 5 y/o
 Characterized pathologically by the presence of axonal
 Result of a vitamin B12 deficiency caused by isolated
spheroids.
absence of gastric intrinsic factors
 Onset: 1-2y/o
 (+) adequate gastric free acid and a normal gastric
 Manifestations: mucosa
o Loss of mental and motor milestones  Patient has macrocytic anemia, decreased vitamin
o Loss of sensation B12 level
o Hypotonia  (+) delay in acquiring motor milestone & growth
o Diminished reflexes failure
o Urinary retention  Treatment: parenteral B12
 MRI: cerebellar atrophy and cerebellar hyperintensity on T2  Recovery: within 4-6 weeks
weighted images o Later onset form of PA- seen in adults
 Histamine-fast achlorhydria associated with gastric
III. METABOLIC NEUROPATHIES mucosal atrophy
 Pathologic changes occurs in the spinal cord > periph
III-A. DIABETES MELLITUS
nerve & brain
 10% of children caused by peripheral neuropathy due to DM  Infants who are breastfed by strict vegan mothers-
 30-50% of children with DM has impaired autonomic nervous Risk for developing megaloblastic anemia, Loss of
system acquired milestone & neurologic regression
 Heart rate variation during Valsalva maneuver and a maximum
III-F. ABETALIPOPROTEINEMIA (BASSEN-KORNZWEIG
to minimum ratio of 30:15 are the most sensitive indexes to
SYNDROME)
detect autonomic abnormalities in children.
 Characterized by:
III-B. UREMIC NEUROPATHY
o progressive ataxic neuropathy
 Rarely diagnosed in children o Retinitis pigmentosa
 Characterized by: o Steatorrhea
o Burning sensations in the feet o Hypolipidemia
o Symmetric motor sensory neuropathy o Acanthocytosis
o Progressive muscle weakness  Autosomal recessive
 Motor & sensory nerve conduction velocities are decreased  Causes:
early in the course of the disease o Absence of lipoproteins
 Facial nerve- sensitive indicator of uremic neuropathy o Absence of intestinal fat absorption from birth 
progressive deficiency in Vit A, D, E, K
 Biotin therapy- recommended to patients with advanced renal
failure

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6.03B Neuromuscular Disorders [Dra.Panlilio]

III-G. Α-LIPOPROTEIN DEFICIENCY (TANGIER DISEASE) o Muscle weakness (pelvic girdle)

o Developmental delay
 Uncommon familial disorder of lipoprotein metabolism o Scoliosis
 PE: o Pes cavus
o Patches of yellow-orange lymphoid tissue in the  Manifests in infancy or early childhood ion
tonsils/pharynx  Muscle biopsy: (+) Corelike lesions with denervation
o Hepatosplenomegaly
o Asymmetric sensory involvement V-B. MULTI-MINI CORE DISEASE
o Progressive development of weakness of both distal &
 Autosomal recessive
proximal muscles.
o Loss of pain and temperature may occur  Characterized by multiple small areas of sarcomeric
disorganization
 Treatment:
o Restriction of dietary fat  Present at birth or within 18 months
 Manifestations:
III-G. KRABBE’S DISEASE (GLOBOID CELL LEUKODYSTROPHY) o Severe neonatal hypotonia
o Delayed motor development
 Galactosylceramide lipidosis o Severe scoliosis
 Autosomal recessive neurodegenerative disorder o Significant respiratory involvement
 Due to deficiency of galactosylceramide β-galactosidase o No cardiac problem
 Manifestations:  Normal creatine kinase
o Irritable
o Spasticity V. INFLAMMATORY MYOPATHIES
o Optic atrophy
o Intellectual delay V-A. DERMATOMYOSITIS
o Polyneuropathy  Occur between 5 & 14 years
 Leads to: loss of milestone, microcephaly, severe failure to  Female > Male
thrive & progressive demyelinating peripheral neuropathy
 More acute
 13 months – average age of death
 Fulminant onset
 Peripheral neuropathy- charac by uniform marked slowing of
 Slowly progressive course
conduction velocities.
 Manifestations:
 Patho: (+) hypomyelination
o Rash frequently precedes the muscle symptoms
o Affects the neck flexors and shoulder and pelvic girdle 
IV. TOXIC NEUROPATHIES
difficulty getting up from the floor, riding a bicycle,
running, climbing stairs.
IV-A. DIPHTHERIA
o “Heliotrope rash”- purplish discoloration on the eyelids
 (+) systemic radiculoneuropathy with onset 1-16 weeks after o “Gottron’s sign”-papular, erythematous, scaly lesions over
infection cardiomyopathy & neuropathy the knuckles
 Diphtheric neuropathy V-A-1. CLINICAL &LABORATORY TEST
o Blurred vision
o Swallowing difficulties 1. Creatine kinase
o Generalized motor sensory demyelinating - Most reliable, sensitive & specific
polyneuropathy, distal & symmetric - Elevated (90%)
 Recovery – complete within several months 2. Electomyography
- (+) increased spontaneous activity with fibrillation
IV-B. HEAVY METAL POLYNEUROPATHY potentials
- Positive sharp waves
IV-B-1 LEAD TOXICITY
V-B. POLYMYOSITIS
 Cause motor & lesser sensory neuropathy
 Weakness is typical  Common in adults; rarely in children
 Encephalopathy maybe present  Manifestations
 Chelation therapy with penicillamine o Muscle pain and tenderness are common;
o Dysphagia occur secondary to oropharyngeal involvement
IV-B-2-ARSENIC POISONING  Corticosteroids is the mainstay treatment

 Produce axonal, primarily sensory neuropathy

V. CONGENITAL MYOPATHIES

V-A. CENTRAL CORE DISEASE

 Autosomal dominant
 Clinical features:
o Hypotonia
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