PBL 2

GROUP B2 (B49)
01
Differentiate
between clinical
feature of upper and
lower motor neuron
lesions
Ze Herne, Yussmetha
Dysfunction of UMN
: causes loss of voluntary control, but not total loss of movement.
: overtime spasticity and hyperreflexia develop.
: a central lesion usually results in weakness that is more pronounced in the flexors of the lower extremities than in
extensors. Patients tend to be spastic with legs extended and adducted.
: In the upper extremities, extensors are weaker than flexors, so elbows and wrists are flexed.

Dysfunction of LMN
: leads to hypotonia and total loss of movement.
: atrophy and fasciculations are common.
: deep tendon reflexes are typically decreased or absent.

Source: Nelson Essentials of Paediatrics Eighth Edition pg 693

02
Guillain-Barre
syndrome
Amisha, Sneha
 GBS ETIOLOGY
1. Campylobacter Jejuni (C jejuni infections also generate anti-ganglioside
antibodies—including to the gangliosides GM1, GD1a, GalNac-GD1a, and GD1b—that
are commonly found in patients with AMAN and AMSAN, the axonal subtypes of GBS)

2. Cytomegalovirus (CMV) (infections are significantly associated with antibodies against

the ganglioside GM2)

3. Epstein-Barr virus (EBV)

4. Mycoplasma pneumoniae

5. Varicella-zoster virus

6. Human immunodeficiency virus (HIV)

Guillain-Barre Syndrome: Practice Essentials, Background, Pathophysiology. (2020).Medscape.EMedicine.

 GBS PATHOPHYSIOLOGY
Antecedent Infectious Illness (e.g Campylobacter jejuni) Macrophage-Mediated Stripping of Myelin
↓ ↓
Induction of Immune Response Defective Propagation of Electrical Nerve Impulses
(Immune responses directed against lipopolysaccharide ↓
antigens in the capsule of C jejuni) Profound Delay or Absence of Nerve Conduction
↓ ↓
Molecular Mimicry Flaccid Paralysis
(Antibodies cross-react with gangliosides GM1, GD1b in ↓
peripheral nerves) Recovery Phase
↓ - Remyelination of affected nerves
Immune Attack on Peripheral Nervous System
↓
Lymphocytic Infiltration of:
- Spinal roots
- Peripheral nerves
- Cranial nerves (sometimes)

Guillain-Barre Syndrome: Practice Essentials, Background, Pathophysiology. (2020).Medscape.EMedicine.

 GBS PATHOPHYSIOLOGY
Severe Disease Pathway:
(severe Inflammation)
↓
Secondary Axonal Disruption and Loss
OR
Primary Immune Attack Directly on Axons (with sparing of myelin)
↓
Clinical Manifestation:
(Similar to typical GBS)

Guillain-Barre Syndrome: Practice Essentials, Background, Pathophysiology. (2020).Medscape.EMedicine.

 CLINICAL FEATURES
1. Initial Symptoms:
5. Other Symptoms:
● Tingling or “pins and needles” sensations in the extremities.
● Muscle weakness that usually begins in the legs and ascends ● Facial Weakness Affecting
to the upper body. Speech,chewing,and swallowing.
● Double Vision Or Inability To
2. Progressive Weakness: Move The Eyes
● Severe Pain That May Worsen
● Rapid progression of muscle weakness over hours to days. At Night.
● Difficulty Walking,climbing stairs,or performing fine motor
tasks

3. Autonomic Dysfunction:

● Rapid heart rate or fluctuations in blood pressure

● Difficulty breathing if respiratory muscles are affected
 MANAGEMENT
● A Clinical diagnosis can be made by a history of progressive, ascending weakness (< 4 wks)
with areflexia, and an elevated CSF protein level and normal cell count (“protein-cellular
dissociation”)
● Nerve conduction study is Confirmatory.
● Initial measures
○ Give oxygen, keep NBM if breathless
○ Monitor PEFR regularly
○ Admit for PICU / PHDU care, if having:

● Respiratory compromise (deteriorating PEFR)

● Rapidly progressive tetraparesis with loss of head control.
● Bulbar palsy.
● Autonomic and cardiovascular instability.
● Provide respiratory support early with BiPAP or mechanical
ventilation
 PROPHYLAXIS
● IV Immunoglobulins (IVIG) 2 gm /kg total over 2 weeks of illness
● 10 % of children with GBS may suffer a relapse of symptoms in the first weeks after
improvement from IVIG. Administer second dose of IVIG.
● 5 days in the first 2
● Prophylaxis for deep vein thrombosis should be considered for patients ventilated for GBS,
especially if recovery is slow.
● Liberal pain relief, with either paracetamol, NSAIDs, gabapentin or opiates.
03
Transverse
myelitis
Shavindran, Arfan
 Etiology
Transverse myelitis (TM) is an acute or subacute inflammatory disorder of the spinal cord that results in motor,
sensory, and autonomic dysfunction. In children, its aetiology can be broadly divided into:

1 Post-infectious or Parainfectious:
◦ Most common cause in pediatrics.
◦ TM often follows a viral infection (e.g., Epstein-Barr virus, enteroviruses, influenza, varicella-zoster virus).
◦ It is believed to be immune-mediated, where infection triggers an aberrant immune response that attacks the spinal
cord.
2 Autoimmune diseases:
◦ TM can occur in association with systemic autoimmune diseases such as:
▪ Systemic lupus erythematosus (SLE)
▪ Sjogren syndrome
▪ Neuromyelitis optica spectrum disorder (NMOSD)
▪ Multiple sclerosis (MS)
3 Post-vaccination:
◦ Rarely, TM has been reported after vaccinations, likely via an immune-mediated mechanism.
4 Direct Infectious Causes:
◦ Less common than immune-mediated TM.
◦ Direct infection of the spinal cord by pathogens (e.g., herpesviruses, enteroviruses, Mycoplasma pneumoniae).
5 Idiopathic:
◦ In a significant number of cases (up to 60%), no clear cause is identified.
 Pathophysiology
Pathophysiology:
• The hallmark of TM is focal inflammation across one or more segments of the spinal cord.
• The inflammation involves demyelination and sometimes axonal injury, leading to:
◦ Disruption of conduction of sensory, motor, and autonomic impulses.
• Histopathology findings (though rarely biopsied) may include:
◦ Perivascular inflammatory infiltrates (mainly T-cells and macrophages)
◦ Edema
◦ Myelin loss

Mechanisms involved:
1)Molecular mimicry: Infectious agents share antigens similar to spinal cord components, leading to
cross-immune attack.
2) Cytokine-mediated injury: Inflammatory cytokines like IL-6, TNF-α cause blood-brain barrier disruption,
enhancing immune cell entry and myelin destruction.
3) Direct infection (rare): Viral replication inside glial cells or neurons can cause direct cytotoxic injury.
The damage is usually centrally located in the spinal cord, often involving both white and grey matter, leading
to motor weakness, sensory loss, and bladder/bowel dysfunction.

• Longitudinally extensive transverse myelitis (LETM) (involving three or more vertebral segments) suggests an
association with NMOSD or other systemic autoimmune diseases.
 Clinical features
1. Symptoms (typically progress over hours to days)
A. Motor Symptoms:

● Weakness (paresis or paralysis) below the lesion.

● Often bilateral, can be flaccid initially → becomes spastic later (upper motor neuron signs).

● If cervical spine involved → affects all four limbs (quadriparesis).

● If thoracic/lumbar → lower limbs only (paraparesis).

B. Sensory Symptoms:

● Sensory level — clear line below which sensation is altered.

● Paresthesia (numbness, tingling, burning)

● Loss of pain, temperature, vibration, proprioception depending on tract involvement.

 Clinical features
C. Autonomic Dysfunction:

● Bladder dysfunction: urgency, retention, incontinence.

● Bowel dysfunction: constipation, incontinence.

● Sexual dysfunction.

Function Finding

Motor ↓ Power, ↑ Tone (after initial flaccid phase), Hyperreflexia,

Babinski positive

Sensory Diminished or absent below lesion; Sensory level

Autono Bladder/bowel dysfunction, sexual dysfunction

mic
 Management
1. Acute Phase Treatment:

Treatment Details

High-dose IV Methylprednisolone 1g/day IV

corticosteroids
for 3-5 days

Plasma exchange (PLEX) If no response to steroids

IV Immunoglobulin (IVIG) Sometimes used in

autoimmune cases

Treat underlying cause Infections, autoimmune

diseases, etc.
 Management
2. Supportive Care:
● Bladder management: intermittent catheterization if retention.

● DVT prophylaxis: because of immobility.

● Pressure sore prevention: turn patients regularly.

● Pain management: neuropathic pain (e.g., gabapentin, pregabalin).

3. Rehabilitation Phase:
● Physiotherapy: strength training, mobility exercises.

● Occupational therapy: daily activity assistance.

● Psychological support: dealing with disability.

04
Duchenne
Muscular
Dystrophy
Megha, Pujya
 Clinical features
Symptoms usually appear between 2-5 years of age
● Progressive muscle weakness (especially starting from lower limb then
to upper limbs )
● Waddling gait- due to hip muscle weakness
● Calf pseudohypertrophy- calves appear enlarged because muscle is
replaced by fat and connective tissue
● Gower’s sign - child uses hands to “walk up” their own body when
standing up from the floor .
● Cardiomyopathy
● Respiratory complications ( breathing problems due to weakness of
diaphragm and other respiratory muscles)
Clinical features
 Diagnosis :
1. Clinical Presentation :
- Onset: Early childhood (usually 2-5 years).
- Symptoms: Delayed motor milestones (e.g., walking ), frequent falls, difficulty climbing stairs,
waddling gait, Gower's sign , enlarged calves ( pseudohypertrophy ).
2. Laboratory Tests:
- Creatine Kinase (CK): Markedly elevated 10-100 times , indicating muscle breakdown
- Aldolase, AST, ALT: May also be elevated.
3. Genetic Testing:
- Primary Test: Multiplex PCR or MLPA (Multiplex Ligation-dependent Probe Amplification) to
detect mutations/deletions in the DMD gene (Xp21).
- If initial test negative: Full gene sequencing to identify smaller mutations
- Carrier testing for mothers is important.

4. Muscle Biopsy (if genetic tests inconclusive):

- Shows absence or severe reduction of dystrophin protein , confirmed by
immunohistochemistry or Western blot .
5. Cardiac Evaluation: Baseline ECG and echocardiogram , cardiomyopathy is common

6. Pulmonary Evaluation: Pulmonary function tests like vital capacity starting around age 6- 8 , to
monitor respiratory decline.
 Management
1. Physiotherapy and Posture Management
● Regular exercise maintains muscle strength, mobility, and delays scoliosis.
● Good sitting posture reduces scoliosis risk.
● Passive stretching and night splints prevent contractures, especially at ankles.

2. Orthopedic Intervention
● Orthoses prolong walking by aiding side-to-side leaning
● Achilles tendon lengthening may facilitate ambulation.
● Scoliosis management:
- Truncal brace
- Moulded seating
- Surgical insertion of spinal rods if needed

3. Respiratory Support :
● Nocturnal hypoxia (due to intercostal muscle weakness) may present with lassitude or
irritability.
Management:
- CPAP (Continuous Positive Airway Pressure).
- NIPPV (Non-invasive Positive Pressure Ventilation).
4.Pharmacological Therapy : Chronic corticosteroid therapy (e.g., prednisolone for 10 days per month) to :
• Slow disease progression.
• Delay loss of mobility.
• Improve longevity.
• Prevent scoliosis progression.
• Exact mechanism of glucocorticoids remains unclear.

5. Genetic Counseling for Carrier detection:

• Mildly elevated CPK levels.
• DNA analysis for DMD gene deletions.
• Antenatal diagnosis available if mutation is known.

6. Multidisciplinary Supportive Care

• Physical therapy, bracing, appropriate wheelchair selection.

• Early cardiac management:
• ACE inhibitors (e.g., enalapril) and/or beta-blockers (e.g., carvedilol) started early, even before
symptoms.
• Regular follow-up at specialist neuromuscular centers.
• Psychological support and parent self-help groups for ongoing family support.
05
Spinal
Muscular
Atrophy
Sharania, Sufiah
 Etiology
- Progressive degeneration of anterior horn cells
- Genetic disease with signs and symptoms that may begin in intrauterine or any time thereafter
- One of the most frequent autosomal recessive diseases

- Three types:

SMA Type 1 ~25%

Werdnig-Hoffman disease Severe infantile form

SMA Type 2 ~50%

Kugelberg-Welander syndrome Late infantile
More slowly progressive form

SMA Type 3 ~25%

Juvenile form
 Clinical Features
The earlier in life the signs develop,
1. Hypotonia
the more severe the progression
2. Generalised weakness
3. Facial involvement Type 1 Most die within 2 years
4. Fasciculation
Type 2 Survive to adulthood
- Quivering muscle movement, best seen on
lateral aspect of the tongue Type 3 Initially appear normal
- Best identified when child is asleep with slower progression
5. Absent deep tendon reflexes of weakness
Normal life expectancy
6. Rapid, shallow, and predominantly
abdominal breathing pattern
7. Respiratory compromise lead to
- Atelectasis
- Pulmonary infection
- Death
 Diagnosis
● The diagnosis is made by genetic testing.
● Creatine phosphokinase maybe normal or mildly elevated
● The electromyogram (EMG) shows fasciculations,
fibrillations and other signs of denervation
● Muscle biopsy shows grouped atrophy
 Treatment
Symptomatic therapy is directed toward:
● minimizing contractures
● Preventing scoliosis
● Maximizing nutrition
● Avoiding infections

The use or nonuse of artificial ventilation and tube feeding must be individualized for
each patients in each stages of illness