neuromuscular disease

2. • Variety of conditions that affect the CNS, PNS, or the skeletal muscle.
• Symptoms are variable: floppy infants, development delay, weakness, fatiguability, abnormal gait,
myalgia or ptosis A. Disorders of the Motor Neuron:
1-Spinal Muscular Atrophy SMA
2-Acute poliomyelitis.
B. Disorders of the Peripheral Nerve:
1- Hereditary Motor and sensory Neuropathy:
a- Charcot-Marie-Tooth Disease
b- HMNS Associated With Degenerative disease
c- Hereditary Sensory and Autonomic Neuropathy (HSAN)
2- Immune mediated/ Inflammatory Neuropathy:
a- Acute Inflammatory Demyelinating Polyneuropathy (AIDP): Guillain-Barre Syndrome
b- Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
c- Acute Motor Axonal Neuropathies
C. Disorders of the Neuromuscular Junction:
1- Myasthenia Gravis (juvenile, transient Neonatal, congenital)
2- Botulism
D. Disorders of muscle
-up to 40% of childhood chronic neuropathies.
-degeneration of the myelin sheaths and disorder of axo
-lead to a distal paralytic amyotrophy involving the lowe
upper limbs with areflexia.

3. SMA
Progressive degeneration of the spinal cord anterior horn+/-motor nuclei in the
brainstem.
Extraocular and sacral motor nerves, cardiac and smooth muscles are selectively spared.
Heterogynous group of disorders
Due to deletions in “survival motor neuron”: 2 types of genes: SMN1 and SMN2.
Homozygous deletions (95%) of SMN1 lead to more severe forms that may vary in
presentation depending on the number of SMN2 genes that are present.
2nd most common hereditary Neuromuscular disease after Duchenne muscular
Dystrophy
2nd most common AR disease in children after cystic fibrosis

4. SMA1/Werdnig-Hoffman
disease
SMA2 SMA3-Kulburg-Welander SMA4- adult form
-Onset before 6 m
-AR homozygous SMN1
deletion ( 95%), <1-2 copies
of SMN2 copies.
-severe weakness of limbs,
and intercostal muscles.
Paucity of spontaneous
movements of shoulder and
hip girdle, some antigravity
movements of hands and
feet. Tongue atrophy with
fasciculations.
-DTR are absent
-patient will never sit
-normal intellect
- mortality > 90%, few survive
to the 2nd decade
-Onset: 6-18m
-Genetics: AR Homozygous
SMN1 deletion with usually 3
SMN2 copies
-Exam: Lower Extremities
more involved than upper
extremities, Tremor, Tongue
may have fasciculations.
-DTR absent
-Patient will Sit but will never
walk.
-Normal intellect
-Prognosis is variable, most
survive to the 2nd-3rd
decade
-Onset > 18m ,
-2 subtypes with Type 3A
before 3 y, type 3B after 3y
- AR, homozygous SMN1
deletion with 3-4 SMN2
copies.
-Proximal symmetric
weakness, it might not
manifest before adult life,
limb and tongue
fasciculations
-Patient will be able to walk
-with normal intellect
-Prognosis: will survive into
adult life
-Onset: after 20y ,
-Genetics: 20% AD, AR,X-
linked
- Proximal muscle are
predominantly involved,
impaired joint mobility,
waddling gait, lumbar
lordosis and protuberant
abdomen, limb and tongue
fasciculations and tremor
-Patient will be able to walk -
with normal intellect
-Prognosis: age of symptom
onset correlates with
cessation of ambulation

5. 1. Genetic testing (Molecular genetic testing) : detection of homozygous deletion of exons 7
of SMN1 and sometimes there could be point mutation
2. EMG: spontaneous muscle activity, fibrillation, residual motor unit potentials that are
increased in amplitude and duration.
3. Muscle Biopsy: not common in practice at present (demonstrates small and large group
atrophy  non-specific)
4. CPK: normal to 5 times Upper limit
Tx:
• Symptomatic
• Monitor and support other potential complications : dysphagia, scoliosis, restrictive lung
disease and poor nutrition.
• Novel disease-modifying therapies are now available
-Nusinersen (IT: intrathecal)
-Onasemnogene (IV)
• Indications:
-Age<2y and not ventilator-dependent patient

6. Charcot marie tooth disease
• It is the Most common inherited neurologic condition
• Type 1, 2 and the primary x-linked form are the most frequent.
• Variable in age of Onset: 1st-2nd decade with speed progression.
• Classic phenotype: steppage gait, pes cavus, sensory loss in a
socking/glove distribution, inverted champagne bottle leg, and
symmetrical atrophy of the hands.
• DTR: absent or decreased.
• Proprioception impaired with sometimes Neuropathic pain.

7. • History and Physical exam remain the core of the diagnosis.
• Nerve Conduction studies: Demyelinating, axonal or intermediate group. It shows significant reduction in the
conduction velocity of motor and sensory nerves.
• Biopsy: Demyelination that affects primarily the large nerves. Characteristic nerve biopsy appearance in CMT1 is -
onion bulb appearance (repeat cycle of demyelination)
• Genetic panel key to confirm the diagnosis.
• HMSN associated with Metabolic and Degenerative CNS disorders:
-Vitamin E and B12 deficiency.
-Amyloidosis,
-Abetalipoproteinemia,
-Mitochondrial diseases
-Metachromatic Leukodystrophy
• Hereditary Sensory and Autonomic Neuropathies (HSAN)
TX:
• Rehabilitation
• Periodic screening of further disorder that might exacerbate neuropathy: Diabetes, vitamin deficiency, AND Immune
mediated Neuropathy
• Avoidance of drugs: Vincristine, Amiodarone, Colchicine, Metronidazole
• Investigational therapies: Introducing extra copies of the PMP22 expression.

8. GBS
• (Acute Inflammatory Demyelinating Polyneuropathy

11. • Autoimmune disease: antibodies are directed at the postsynaptic
membrane of the NM junction, leading to various degrees of muscle
weakness and fatigability.
• 80-90% of patients have autoantibodies against the AChR
• Seronegative AChR antibodies have positive antibodies directed against
another target on the surface of the muscle-specific receptor tyrosine
kinase (MuSK)protein a transmembrane component of the postsynaptic
NM junction
• 6-12% of MG patients are seronegative
• Asian Populations: 50% peak at 5 to 10 y of age.
• Caucasian: more common in adulthood, prepubertal is only <10%
• Male=female

12. • Symptoms may be Insidious or start rapidly after an acute febrile
illness.
• Ocular symptoms: unilateral or asymmetric ophthalmoplegia,
strabismus, lid twitch with sustained gaze
• Generalized weakness, painless fatiguability of bulbar (relating to
brainstem) and limb musculature, dysphonia, dysphagia,
• Symptoms tend to fluctuate: they are more pronounced as day goes
on, and they improve with rest.
• Myasthenic crisis: respiratory impairment associated with
respiratory muscle involvement needing ventilatory support

13. 1- Tensilon Test: IV edrophonium will prevent the breakdown of A-choline and increase its concentration in the
N-M junction: observe for transient improvement in weakness, ptosis
2-NCS and EMG: repetitive stimulation will show decrement by > 10%.
3-Serum antibodies Anti ACHR, MuSK (0-49%, female predominance), and leucine-rich protein4 (LRP4)
4-MRI of thymus: patients with AChR antibodies + have hyperplasia in 60-70% , and thymoma in 10-12%.
• Tx:
1-Acethylcholine esterase inhibitors (pyridostigmine): 0,5-1 mg/kg every 4-6h
2-Rapid Immunosuppressive therapies: Plasma exchange and IVIG
3-Chronic immunosuppressive therapy
4- Avoid drugs that might worsen the symptoms: chloroquine, magnesium sulfate, yearly seasonal influenza
vaccination and pneumococcal vaccine.
5-Thymectomy
• Px:
• Children have higher rate of remission: spontaneous and post therapy

14. Transient neonatal Myasthenia
• Presents in 1/5 infants born to mothers suffering from acquired MG.
• Its related to transfer of maternal Ach antibodies across the placenta.
• Onset in the first 24h of life: the baby is normal at birth and
subsequently develops hypotonia, weak cry, poor suck, reduced
movements, ptosis, facial weakness.
• The diagnosis is clinical: we may and may not detect anti AChR
• Treatment: Short term treatment with anticholinesterase inhibitors is
usually sufficient. Illness will last less than 5 weeks even if untreated.
IVIG are ineffective Dx is clinical: MG mom + newborn with
presentation of MG