CP mimics.pptx
- 1. MIMICS OF CEREBRAL PALSY D Kalpana Sr. Consultant Pediatric Neurologist KIMSHEALTH hospitals, Trivandrum
- 2. WHAT IS CEREBRAL PALSY • disorders of movement and posture, • causing activity limitation • Due to non-progressive disturbances that occurred in the developing fetal or infant brain. • often accompanied by disturbances of sensation, cognition, communication, perception, and/or by a seizure disorder Rosenbaum 2005
- 3. CP is not a clinical diagnosis No common pathology or aetiology Even when there is antecedent cause like prematurity or perinatal asphyxia, it can have a metabolic or genetic cause cause All children with a diagnosis of cerebral palsy should be investigated and followed up. • A specific diagnosis identifies treatable causes early. • Helps in prognostication • Aids in genetic counselling • Can be included in the emerging genetic treatment trials • AVOID LITIGATION REGARDING NEGLIGENCE IN MANAGEMENT. R Gupta and R E Appleton;Cerebral palsy:not always what it seems Arch Dis Childhood 2001
- 4. Carr and Cogil:Mimics of cerebral palsy: Pediatrics and Child health 2016 RED FLAGS IN THE DIAGNOSIS OF CEREBRAL PALSY • History and examination – No risk factors for CP – Positive family history or consanguinity – History of developmental regression after normal attainment of early motor milestones, such as independent sitting and walking – Dysmorphic features – Fluctuating neurologic signs – Episodic decompensation – Dyskinetic or ataxic cerebral palsy – Persisting hypotonia – Eye movement abnormalities – Neurocutaneous markers – Organomegaly
- 5. RED FLAGS IN THE DIAGNOSIS OF CEREBRAL PALSY cont…. • Imaging – Normal neuroimaging – Structural abnormalities – Cerebellar atrophy – Typical radiologic findings of metabolic disorder • Glutaric aciduria • Maple syrup urine disease – If scan shows findings which are NOT concordant with the clinical history
- 6. DEVELOPMENTAL REGRESSION • one of the cardinal features of neurodegenerative or metabolic disorders.- • In many cases there will be a mild developmental delay initially, and regression starts later only • In severe CP or severe degenerative disease baby may not attain any milestone • In cerebral palsy also, transient regression occurs – following severe infection – with epileptic encephalopathy – due to fixed contractures, dislocation of joints • Definite regression in all the milestones is the key
- 7. DYSMORPHIC FEATURES Angelman syndrome Fragile X syndrome
- 8. HEAD SIZE • Microcephaly – HIE – Lissencephaly – Schizencephaly – Intrauterine infections – Aicardi Goutiere syndrome – Krabbe’s disease – Rett syndrome • Macrocephaly – Alexander – Canavan – Storage diseases – Vander Knapp disease
- 9. SKIN CHANGES Icthyosis in Sjogren Larssen syndrome Seborrheic dermatitis in botinidase deficiency
- 10. HYPOPIGMENTED SKIN AND HAIR Hypopigmented skin and hair Global developmental delay Hypotonia with brisk reflexes Seizures Menkes disease
- 12. HYPOPIGMENTED SKIN AND HAIR Cataract Myocardial dysfunction Immunodeficiency Hypotonia with retained DTR Global developmental delay Vici syndrome homozygous mutations in the KIAA1632/mEPG51 gene
- 13. HYPERTRICHOSIS 20 month old with mild delay development, stagnation, ataxia, tremor, hypertrichosis,MR brain involvement of brain stem and subthalamic nucleus Leigh syndrome due to SURF1 mutation
- 14. SELF MUTILATION Child with dystonic cerebral palsy h/o constant rubbing of lips with the hand Death of maternal uncle at 6 yrs of age s. Uric acid 12 mg% Leisch Nyhan syndrome
- 15. EYE ABNORMALITIES • Cataract – galactosemia, Aicardi Goutieres syndrome • Telengiectasia – ataxia telangiectasia • Retinitis pigmentosa – Refsum, SCA2 &7 • Pendular nystagmus- PMD • Ophthalmoplegia – Leigh’s disease • Oculogyric spasm – neurotransmitter diseases – AADC, Infantile parkinsonism dystonia
- 16. PENDULAR NYSTAGMUS American academy of neurology: teaching video Pelizaeus Merzbacher disease
- 17. OPHTHALMOPLEGIA AND NYSTAGMUS Leigh’s syndrome
- 18. FLUCTUATING SYMPTOMS • Characteristic diurnal fluctuation is seen in dopa responsive dystonia and other neurotransmitter diseases • GLUT1 deficiency manifests as seizures or dystonia manifesting at the time of fasting. Even EEG changes aggravate with fasting. • Episodic decompensation in response to fever or protein rich diet is characteristic of organic aciduria, urea cycle defects etc • Vanishing white matter disease shows deterioration with fever or trauma
- 19. NEUROIMAGING • Common imaging findings in CP due to perinatal asphyxia – Periventricular leukomalacia – Cystic encephalomalacia – Intraventricular Hemorrhage(porencephalic cyst) – Basal ganglia and thalamus injury (status marmoratus) – Globus pallidus involvement in BIND – Acute infarct (arterial or venous) – Normal MRI in 10 % • At least one imaging should be done in all cases of cerebral pasy
- 20. NEUROIMAGING • Genetic tests are indicated in – Normal imaging – Structural malformations – Specific pattern in certain genetic/metabolic conditions • Glutaric aciduria – Bat’s wing appearance • Maple syrup urine disease – myelin splitting edema • Hypomyelination in PMD and related disorders • Dilated and tortuous vessels in Menke’s disease • Basal ganglia calcification and cysts – Aicardi Goutiere syndrome
- 21. NORMAL NEUROIMAGING • Occur in about 10% of cerebral palsy cases • Think about – Hereditary spastic paraplegia – Neurotransmitter diseases – Creatine deficiency disorders – MRS will reveal the diagnosis
- 23. IMAGING Aicardi Goutieres syndrome Bilirubin induced neurological disease Methyl malonic acidemia Symmetrical Globus Pallidus T2 hyperintensity CT head- symmetrical BG calcification and cystic changes in white matter
- 24. VAN DER KNAAPS DISEASE • Siblings with large head • Delay in development • Progressive spasticity • Ataxia • Dysarthria • Occasional seizures Megalencephalic leukoencephalopathy with subcortical cysts
- 25. HYPOMYELINATION AND DYSMYELINATION Hypomyeliination - PMD Dysmyelination Symmetrical not involving U fibres – MLD Symmetrical anteriorly dominant involving U fibres – Alexanders disease
- 26. GLUTARIC ACIDURIA TYPE1 • Large head • Hypotonia followed by dystonia • Episodic fluctuation • Characteristic MRI brain • Riboflavin • Carnitine • Protein restricted diet BATS WING APPEARANCE
- 27. OTHER INVESTIGATIONS • Investigations should be focused – to get the maximum yield • Thrust should be for treatable/curable conditions • Plan costly investigations after MRI – as we can get useful clues • Metabolic testing – – if there is family history – History of recurrent encephalopathy – Suggestive MRI findings – Abnormal odour, failure to thrive, fast breathing. (ABG, glucose, ammonia, lactate, pyruvate, urinary ketones, uric acid Urine organic acids,TMS for aminoacid, organic acids, fatty acid oxidation disorders) • Thyroid function tests – T3, T4,TSH • Enzyme assay • Genetic tests
- 28. GENETIC TESTS • In dysmorphism – Karyotype – FISH for specific deletions – Chromosomal microarray • Trinucleotide repeat sequencing – fragile X,SCA • Clinical exome sequencing • Whole exome sequencing • Whole genome sequencing Now a days genetic testing is having the highest yield and is relatively cheaper
- 29. MIMICS OF SPASTIC CP • Spinal dysraphism – Imaging of spine • Hereditary spastic paraplegia- pure or complicated • Arginase deficiency – s.ammonia • Sjogren Larssen syndrome • Biotinidase and multiple carboxylase deficiency – seborrheic dermatitis and alopecia • Leukodystrophy – Nerve conduction studies, imaging genetics
- 30. HEREDITARY SPASTIC PARAPLEGIA • Mild developmental delay with spasticity • Spasticity may be noted by 2 or 3 years • Very slowly progressive • Pure type – spasticity severe than degree of weakness – SPG 3a, SPG 4,SPG11(associated with thin corpus callosum) • Complicated type – associated with seizures, dysarthria, learning problems and peripheral neuropathy • Regression, +/-neuropathy with normal MRI or with thin corpus callosum • Examine both parents for spasticity or hyperreflexia even if asymptomatic
- 31. SJOGREN LARSSEN SYNDROME • Often born preterm • Spastic diplegia or quadriplegia • MRI brain – bilateral periventricular T2 hyperintensity • Ichthyosis over legs and flexures • Macula crystallina • Mutation in ALDH3A2 gene Nagappa M, Bindu PS, Chiplunkar S, Gupta N, Sinha S, Mathuranath PS, et al. Child Neurology: Sjögren- Larsson syndrome. Neurology. 2017 Jan 3;88(1):e1–4.
- 32. WITH PROMINENT DYSTONIA OR CHOREA • DOPA responsive dystonia- CSF neurotransmitters • Mitochondrial disease- serum/CSF lactate, MRS • Lesch Nyhan- s. urate • Glutaric aciduria – imaging, urine organic acids • GLUT 1A deficiency – CSF glucose/s.glucose ratio • Rett’s syndrome- MECP2 mutation • Neurodegeneration with brain iron accumulation- imaging Genetic tests
- 33. NEUROTRANSMITTER DISEASES • Lower limb spasticity • Dystonia • Diurnal fluctuation • ? Trial of l- dopa in all children with spasticity with or without dystonia • AD • GTP cyclohydrolase deficiency • Tyrosine hydroxylase deficiency • Sepiapterin reductase deficiency – Dystonia – Oculogyric crises – Diurnal fluctuation • Aromatic aminoacid decarboxylase deficiency • VMAT2(infantile dystonia parkinsonism 2) –DOPA agonist responsive Dopa responsive dystonia (Segawa) Other Dopa responsive syndromes
- 34. ALLAN-HERNDON-DUDLEY SYNDROME • 2 male children in the family affected • Prominent dystonia • S TSH – low • S.T4 – low • S.T3 – very high • No response to thyroxin • Monocarboxylate transporter 8 deficiency • X linked recessive
- 35. OCULOGYRIC SPASM Infantile dystonia parkinsonism type 2 VMAT 2 mutation
- 37. ATAXIA • Angelmans – FISH, deletion/duplication/methylation • Jouberts – imaging, associated findings • Friedreich’s ataxia- trinucleotide repeat • Ataxia telangiectasia – S.AFP,immunoglobulin • Spinocerebellar ataxia – SCA 2&7- trinucleotide repeat • Cockayne syndrome – photosensitivity, microcephaly • Pelizaeus-Merzbacher disease –clinical, imaging • Non-ketotoc hyperglycinaemia – CSF glycine • Maple syrup urine disease –imaging, urine organic acids
- 38. TREATABLE CAUSES OF CEREBRAL PALSY • Glut 1 deficiency – Ketogenic diet • Biotinidase and holocarboxylase synthetase deficiency – biotin • Urea cycle defect – protein restricted diet, sodium benzoate, phenyl acetate • Methyl malonic academia – protein restriction, vitamin B12 • Glutaric aciduria- riboflavin, carnitine, lysine restricted diet • Neurotransmitter disease – L Dopa and Dopa agonists
- 39. PRACTICE POINTS • Be mindful of ‘Red Flags’ when reviewing a child with CP. • MRI scan changes can evolve over time, so imaging should be repeated if the child shows unusual progression of symptoms or signs. • MRI scan features NOT concordant with the clinical history think of another underlying condition. • A trial of levodopa should still be considered in all children presenting with dystonia, where causation is not established. Carr LJ, Coghill J, Mimics of cerebral palsy, Paediatrics and Child Health (2016)
- 40. HOW THE DIAGNOSIS IS MADE? • Concentrate on atypical/unique findings in history, physical examination and imaging. • Do an extensive literature search • Investigations should be focused. • Careful follow up may reveal the nature of the disease. • Accept mistakes and learn from mistakes • Take each case as a challenge and get excited in getting the correct diagnosis. Half hearted attempts are going to fail. • Never miss treatable causes
- 41. The clinical diagnosis of cerebral palsy should not be changed, whatever the cause. The diagnosis of cerebral palsy makes the children eligible for all the support services including financial support Registry available in many countries.Monitoring of children becomes easy Many of these diseases are slowly progressive and need support The International Cerebral Palsy Genomics Consortium 2018 Very few have a definitive treatment