Neurology: Cerebral Palsy · Degenerative Brain Disorders · Neuromuscular Disease

Classification of CP, leukodystrophies, mitochondrial disorders, Duchenne MD, SMA, congenital myopathies
🧠 Key concepts: CP motor subtypes (spastic, dyskinetic, ataxic), GMFCS, neurodegenerative red flags (regression, optic atrophy, white matter changes), Duchenne MD (dystrophin, Gowers'), SMA (SMN1 deletion), and multidisciplinary care.

📖 Cerebral palsy, neurodegenerative & neuromuscular disorders

🧩 Cerebral palsy (CP)
Spastic (hemiplegia/diplegia/quadriplegia), dyskinetic (choreoathetosis, dystonia), ataxic, mixed. Associated comorbidities: epilepsy, intellectual disability, hip subluxation, scoliosis, feeding difficulties.
🧬 Degenerative brain disorders
Leukodystrophies (Krabbe, MLD, Alexander), neuronal ceroid lipofuscinosis (NCL), mitochondrial disorders (MELAS, Leigh), GM2 gangliosidosis (Tay-Sachs). Red flags: regression, optic atrophy, spasticity + peripheral neuropathy.
💪 Neuromuscular diseases
Duchenne MD (X-linked, dystrophin, Gowers', high CK). Spinal muscular atrophy (SMN1 deletion; type 1 infantile → type 4 adult). Congenital myopathies (nemaline, central core). Myasthenia gravis (acetylcholine receptor antibodies).
⚠️ Clues to neurodegenerative disease: Loss of previously acquired skills (regression), progressive ataxia, optic atrophy/pale discs, seizures refractory to treatment, MRI white matter changes or basal ganglia involvement.

🩺 Diagnostic approach: CP vs neurodegenerative vs neuromuscular

1
Cerebral palsy suspicion – Non-progressive motor disorder of early brain injury. Assess tone, reflexes, primitive reflexes persistence, GMFCS level. Brain MRI (periventricular leukomalacia, basal ganglia injury, malformations).
2
Neurodegenerative red flags – Regression (loss of milestones), progressive ataxia, spasticity + neuropathy, optic atrophy, seizures. MRI white matter (leukodystrophy), basal ganglia (Leigh), cortical atrophy. Metabolic screen, enzyme assays, genetic testing.
3
Neuromuscular evaluation – Pattern: proximal (DMD/SMA) vs distal (CMT); weakness with normal sensation (myopathy, SMA) vs sensory loss (neuropathy). CK (↑ in DMD, normal in SMA). EMG/NCS, muscle biopsy, genetic (dystrophin, SMN1).
📌 Clinical pearls: Gowers' sign + calf pseudohypertrophy + CK >10× normal → Duchenne until proven otherwise. Floppy infant with tongue fasciculations + areflexia → SMA type 1 (SMN1 deletion).

📋 Management strategies: CP, neurodegeneration, neuromuscular diseases

1
Cerebral palsy – multidisciplinary – Physiotherapy, occupational therapy, speech therapy. Tone management: baclofen (oral/intrathecal), botulinum toxin, selective dorsal rhizotomy. Hip surveillance, scoliosis, feeding (gastrostomy), seizure control, pain management.
2
Degenerative disorders (supportive + specific) – Substrate reduction (miglustat for Niemann-Pick C), gene therapy (MLD), haematopoietic stem cell transplant (Krabbe, MLD if early). Seizure management, spasticity, nutritional support, palliative care.
3
Duchenne muscular dystrophy – Prednisolone/defazacort (improves strength, prolongs ambulation). Cardiac (ACE inhibitors, beta-blockers), respiratory monitoring (NIV), physiotherapy, scoliosis surgery. Ataluren (nonsense mutations), gene therapy (microdystrophin) emerging.
4
Spinal muscular atrophy (SMA) – Nusinersen (intrathecal), risdiplam (oral), gene therapy (onasemnogene abeparvovec – IV) for SMA type 1. Supportive: respiratory, nutritional, orthopedic.
5
Congenital myopathies & metabolic myopathies – Avoid triggers (malignant hyperthermia in central core). Supportive, respiratory monitoring, physical therapy, genetic counselling.
🚨 Emergency in neuromuscular disease: Acute respiratory decline (SMA, DMD) – urgent non-invasive ventilation; cardiac surveillance in DMD (annual ECG/echo, start ACE inhibitors before decline).

🧠 Reflex prompts: CP, neurodegeneration & neuromuscular disease

🦵 4-year-old boy, difficulty climbing stairs, Gowers' sign, calf pseudohypertrophy. CK 15,000. Diagnosis?
Duchenne muscular dystrophy (dystrophin gene deletion). Start prednisolone, monitor cardiomyopathy.
📉 6-month-old floppy infant, absent deep tendon reflexes, tongue fasciculations, normal CK. Most likely diagnosis?
Spinal muscular atrophy type 1 (SMN1 deletion). Genetic testing, supportive care, consider gene therapy.
🧬 Child with progressive ataxia, spasticity, optic atrophy, and MRI white matter changes. Suspected disorder?
Leukodystrophy (e.g., Krabbe, MLD, Alexander). Enzyme assays, genetic testing, haematopoietic stem cell transplant if early.
🧠 5-year-old with loss of milestones, myoclonic seizures, and visual failure. MRI shows grey matter signal changes. Diagnosis?
Neuronal ceroid lipofuscinosis (CLN disease). Skin biopsy (granular osmiophilic deposits), enzyme/genetic testing.
🦽 Most common motor type of cerebral palsy in preterm infants?
Spastic diplegia (lower limbs more affected), associated with periventricular leukomalacia.
💪 First-line medication to improve strength and prolong ambulation in Duchenne MD?
Prednisolone (0.75 mg/kg/day) or deflazacort. Monitor side-effects (weight gain, behaviour, osteoporosis).
🧬 Which metabolic disorder presents with acute decompensation (vomiting, encephalopathy) and symmetrical basal ganglia lesions on MRI?
Leigh syndrome (mitochondrial, often SURF1 or MT-ATP6). Lactate elevated, treat with thiamine/cofactors.
👶 Floppy infant with normal reflexes, delayed motor milestones, and myopathic facies. EMG: myopathic. Muscle biopsy shows nemaline rods. Diagnosis?
Nemaline myopathy (congenital myopathy). Supportive respiratory care, physiotherapy.
🩺 Child with fluctuating ptosis, diplopia, worse at end of day. Neostigmine test positive. Antibody?
Anti-AChR (acetylcholine receptor) antibodies → myasthenia gravis. Thymus imaging, pyridostigmine, immunosuppression.
🦷 What are the three cardinal features of mitochondrial disease in childhood?
Progressive encephalomyopathy, seizures, lactic acidosis, ragged red fibers on muscle biopsy, multi-system involvement.