SPINAL MUSCULAR ATROPHY

1. SMA is a degenerative disease of motor neurons and basic lesion lies at anterior
horn cells of the spinal cord.

2. The pathological hallmark is progressive denervation of muscle.

3. It is an autosomal recessive disease.

4. Four clinical types are there:

a. Type 0: It is the most severe form and presents in fetal life. Most
children do not survive.

b. Type 1 (Werdnig-Hoffmann disease): It presents with profound

hypotonia, flaccid weakness and global areflexia, resultant delay in motor
milestones. They have frog-like position. Respiratory weakness, poor
swallowing and tongue fasciculations are common. Aspiration pneumonia
is common cause of mortality.

c. Type 2 (Dubowitz disease): Age of onset around 6-18 months of age.

They have more chronic and benign course. They are usually able to sit
unaided.

d. Type 3 (Kugelberg Welander disease): They present later in childhood

and are usually able to walk.

e. Type 4: Adult SMA

5. Diagnosis:
a. Mainly by Clinical suspicion
b. Normal / mild elevation of serum CK levels
c. Molecular genetic marker in blood
a. SMN1 deletion/ mutation
b. SMN2 copy number testing
c. Absence of SMN1 exon7 confirms the diagnosis of SMA
6. Treatment is supportive.
a. Respiratory care
b. Feeding and swallowing problems management
c. Adequate nutrition
d. Orthopedic physiotherapy
e. Rehabilitation
f. Gene therapy
g. Immunization
h. Family education
i. Counselling
 CONGENITAL MYOPATHY

1. Congenital myopathies are a diverse group of muscle disorders caused by

genetic defects in the contractile apparatus of the muscle.

2. Most of these disorders have subcellular abnormalities that can be demonstrated

only by muscle biopsy, by means of histochemistry, immunohistochemistry and
electron microscopy.

3. Myogenic regulatory genes involved are MYF5, MYF6, Myogenin, MYOD1,

myomaker, PAX3, PAX7, WNT3a, myostatin etc.

4. Majority of these disorders present as “floppy infant syndrome.”

5. Common Clinical features:

a. Hypotonia
b. Static or non-progressive muscle weakness
c. Normal or decreased deep tendon reflexes
d. Respiratory insufficiency
e. Feeding difficulties
f. Contractures and skeletal deformities

6. Types
a. Central core disease
i. Muscle biopsy – central cores devoid of mitochondrial enzyme
activity

b. Nemaline myopathy
i. Clinical – dysmorphic skeletal features such as pigeon chest,
kyphoscoliosis, pes cavus, high arched palate, long face with
prognathic jaw.
ii. Muscle biopsy – red-staining rod-like structures

c. Myotubular myopathy (centronuclear myopathy)

i. Clinical – varying degrees of limb weakness, ptosis, external
ophthalmoplegia.
ii. Muscle biopsy resembles myotubes of fetal muscle

d. Congenital fiber-type disproportion

7. Investigations:
a. Serum creatine kinase is either normal or mildly raised
b. EMG – myopathic pattern
c. Skeletal muscle biopsy
d. Molecular genetics

8. Treatment
a. Mainly supportive
b. Parental counselling
c. Care for respiratory insufficiency
d. Care for feeding and swallowing difficulties
e. Gene therapy being investigated
 CONGENITAL MUSCULAR DYSTROPHY

1. Muscular dystrophy has four obligatory criteria

a. It is a primary myopathy
b. It has a genetic basis
c. Course is progressive
d. Degeneration and death of muscle fibers occur at some stage in the
disease.

2. Congenital muscular dystrophies refer to a group of hereditary disorders with

early (prenatal or neonatal) onset and histologic features suggestive of
dystrophic process.

3. Clinical features:
a. Severe weakness – static or slowly progressive
b. Hypotonia at birth
c. Floppy baby syndrome
d. Joint contractures
e. Distal arthrogryposis
f. Poor head control
g. Tendon stretch reflexes hypoactive or absent
h. Severe dysphagia
i. Respiratory insufficiency

4. Ullrich type of CMD involves axial or proximal joint contractures. It is due to

mutation in one of three collagen VI genes.

5. Fukuyama type of CMD is second most common type in Japan. It involves

severe cardiomyopathy and malformations of the brain. Clinical features are
cardiomegaly, heart failure, intellectual disability, seizures, microcepahly.

6. Investigations:
a. Serum CK levels – normal to moderately raised
b. EMG – nonspecific myopathic features
c. Muscle biopsy – islands of muscle fibres surrounded by fat.
d. Genetic testing
e. Cardiac assessment
f. Brain imaging
7. Diagnosis:
a. Muscle biopsy is diagnostic.
b. Specific genetic testing might avoid muscle biopsy

8. Treatment
a. Mainly supportive care
b. Counselling
c. Care for respiratory insufficiency
i. Screen for respiratory function with PFT
ii. Chest physiotherapy
iii. BiPAP
iv. Invasive ventilation
d. Swallowing difficulties – G-tube feeds
e. Speech therapy
f. Physical therapist and physiatrists – manage contractures
g. Orthopaedic surgical intervention – kyphoscoliosis
h. Education plans for learning and intellectual disabilities
 MYOTONIA CONGENITA

1. Myotonia implies the continued active contraction of a muscle persisting after

cessation of voluntary effort or stimulation.

2. It is a type of channelopathy. It is the most common of the nondystrophic

myotonia syndromes.

3. Inheritance
a. Autosomal dominant – Thomsen disease
b. Autosomal recessive – Becker disease

4. Genetic defect
a. Chromosome- 7q35
b. Gene- CLCN1

5. Clinical features:
a. Symptoms start in infancy.
b. Generalized weakness
c. Generalized muscular hypertrophy resemble bodybuilders (Herculean
appearance)
d. Difficulty in opening the eyes after closure on crying or sneezing
e. Difficulty in releasing grip and initiating sudden movements
f. Difficulty in starting to run or walk briskly.
g. Feeding difficulties
h. Strangled cry

6. Investigations:
a. Muscle biopsy – minimal pathologic changes
b. EMG – myotonia
c. Genetic testing

7. Treatment
a. Antimyotonia therapy
i. Mexiletine – improve stiffness as well as decrease handgrip
myotonia
b. Carbamazepine
c. Phenytoin
d. Gabapentin
e. Counselling

DIPLEGIA
1. This term suggested by Freud is used for a form of cerebral palsy in which limbs
on both sides of the body are affected, with the legs more severely affected than
the arms.

2. It is almost always congenital in origin.

3. Common causes
a. Prematurity
b. Ischemia
c. Infections
d. Endocrine / metabolic

4. Clinical features:
a. Lethargic, hypotonic, difficult to feed
b. Overactive, hypertonic, jittery
c. Seizures
d. Hypotonic stage
i. Poor head control
ii. Abnormally easily provoked neonatal automatism- moro reflex,
automatic walking, tonic neck reflexes.
e. Dystonic stage
i. Involuntary mass movements, generalized hypertonia, scissoring of
legs
f. Rigid-spastic stage
i. Hypertonia not only in erect position, but also in prone, upright
positions.
g. Brisk deep tendon reflexes, ankle clonus, bilateral babinski sign.
h. Intellectual disabilities
i. Vision, hearing problems

5. Diagnosis
a. Clinical history and examination
b. MRI Brain
i. Periventricular leukomalacia
ii. Periventricular cysts or scars in white matter, enlargement of
ventricles, squared-off posterior ventricles
c. Comprehensive evaluation including hearing, vision etc
d. Genetic testing

6. Management
a. Supportive care
 b. Parental counselling
c. Physiotherapy
d. Occupational therapy
e. Speech therapy
f. Adaptive equipments as orthoses, walkers, poles, standing frames.
g. Rhizotomy
h. For spasticity – benzodiazepines, baclofen
i. Botulinum toxin injections to manage spasticity in muscle groups
j. Deep brain stimulation

HEMIPLEGIA

1. Hemiplegia is a common manifestation in children with stroke and cerebral palsy.

2. Common causes
a. Genetic/ developmental
b. Infection
c. Thrombophilic disorders
d. Periventricular hemorrhagic infarction

3. It can be congenital or acquired.

4. Congenital hemiplegia can be demonstrated by exploitation of neonatal

responses such as Moro, automatic walking and allow comparison between the
two sides.

5. In spastic hemiplegia there are decreased spontaneous movements on the

affected side and show hand preference at an early age (1-2 yrs).

6. The physical signs are of pyramidal type with spasticity, increased tendon
reflexes, weakness particularly of antigravity muscles and difficulty with discrete
finger movements.

7. The arm is held adducted, flexed and internally rotated at the shoulder with the
elbow flexed, wrist flexed and ulnar-deviated, the forearm pronated and thumb
adducted. The leg is often held adducted, semiflexed at the knee and plantar
flexed at the ankle with equinovarus or equinovalgus deformity.

8. Homonymous hemianopia may be present on the affected side. Ipsilateral

weakness of mild degree on the face often involved.

9. Speech defects varies and Intellectual disability is less common.

10. Acquired hemiplegia

a. Involuntary movements of athetoid or choreoathetoid type are common.
b. Epilepsy is twice a common than congenital type.
c. Dysphasia is common in acquired type.

11. Diagnosis
a. Clinical history and examination
b. Neuroimaging
 i. MRI is far more sensitive than cranial CT scan for most lesions
seen with CP.
ii. Focal infarct or cortical, subcortical damage or cortical
malformations can be detected.
iii. CT scan is helpful for detecting calcifications associated with
congenital infections.
c. Comprehensive evaluation including hearing, vision etc
d. Genetic testing

12. Management
a. Supportive care
b. Parental counselling
c. Physiotherapy
d. Occupational therapy
e. Speech therapy
f. Constraint-induced movement therapy
g. Surgical tenotomy of the Achilles tendon
h. Botulinum toxin injections to manage spasticity in muscle groups