DEVELOPMENTAL MILESTONES

DEVELOPMENTAL MILESTONES OF BRAIN

1. DEVELOPMENTAL MILESTONES DR . PRADEEP PATIL Prof . Department of Radio-diagnosis, DY Patil medical college, hospital & research institute Kolhapur

2. DEVELOPMENTAL REGRESSION • Delayed achievement of developmental milestones is one of the most common problems evaluated by child neurologists. – Is developmental delay restricted to specific areas, or is it global? – Is development delayed or regressing? • Loss of developmental milestones previously attained usually indicates a progressive disease of the nervous system.

3. • Rapidly assesses 4 different components of development: • Personal- Social • Fine motor adaptive • Language and • Gross motor.

4. • A progressive deterioration of neurological functions - loss of speech, vision, hearing or locomotion ,often associated with seizure, feeding and intellectual impairment. • Neuroregressive / Neurodegenerative Disorders - a group of heterogeneous diseases which results from specific genetic, biochemical defect, chronic viral infection and toxic substances. • May involves both the grey matter and white matter

5. White matter: Contains mostly myelinated axons connect various grey matter areas (the locations of nerve cell bodies) of the brain to each other, and carry nerve impulses between neuron   White matter controls the involuntary functions of the body such as blood pressure, heart rate, and body temperature. Grey matter: Consists of neuronal cell bodies, dendrites and glial cells. The grey matter includes regions of the brain involved in muscle control, sensory perception such as seeing and hearing, memory, emotions, and speech.

6.  Grey matter Disease White matter Disease  Processing center Represents networking between these centers Primarily involve neurons± histologic evidence of abnormal metabolic products--> neuronal death and secondary axon degeneration Myelin is disrupted either destruction of normal myelin or biochemically abnormal myelin production

7. APPROACH TO A CHILD WITH MILESTONE REGRESSION IMPORTANT CONSIDERATION • Regression AND NOT Delay • Age above 2 Years OR Less than 2 Years • Is only the Central nervous system involved, or are other organs involved? – Other organ involvement suggests lysosomal, peroxisomal , and mitochondrial disorders.

8. • Nerve or muscle involvement suggests mainly lysosomal and mitochondrial disorders. • Does the disease affect primarily the grey matter or the white matter ?

9. CLASSIFICATION OF NEURODEGENERATIVE/REGRESSION DISORDERS

10. ACQUIRED CAUSES Infections Subacute sclerosing panencephalitis Progressive Rubella Syndrome Toxoplasma Chronic HIV infection Metabolic Hypothyroidism Vit B-12 & E deficiency

11. INHERITED CAUSES • Grey matter involvement: Grey matter involvement with visceromegaly – GM1 Gangliosidosis – Sandholf disease – Niemann pick Disease – MPS – Gaucher disease Grey matter diseases involvement without visceromegaly – Tay Sach disease – Rett Syndrome – Menke’s kinky hair disease

12. WHITE MATTER INVOLVEMENT Leukodystrophies – Metachromatic leukodystrophy – Krabbe disease – Adrenoleukodystrophy – Alexander disease

13. OBJECTIVE OF EVALUATION • Confirmation of Developmental regression (history, clinical & neurological examination and biochemical test) • Categorization of domains involved • Identification of possible underlying etiology

14. ROLE OF MRI : The abnormalities of metabolic disease are characteristically bilateral and symmetrical. Assessment on MRI should include analysis of grey and white matter structures. Calcification is much better assessed on ct. Inherited hypomyelination .

15. Progression of myelination occurs in: Central to periphery Caudal to cranial Dorsal to ventral Sensory then motor

16. Myelination milestones Term at birth- brainstem, cerebellum, posterior limb of IC, perirolandic region First changes- increase in T1 signal , later decreased signal on T2 2-3 months- anterior limb of IC T1 bright 3 months- cerebellar WM T1 bright 3-6 months- splenium of CC T2 dark 6 months – genu of CC T1 bright 8 months- subcortical WM T1 bright, genu of CC T2 dark 1yr 2 months – occipital WM T2 dark 1yr 4months – frontal WM T2 dark 3 yrs – almost entire WM becomes T2 dark

17. Basic principles of myelination on MRI: Unmyelinated WM: Hypointense on T1 W Hyper intense on T2 W. Myelinated WM : Hyper intense on T1 W Hypointense on T2 W. Increase in signal intensity on T1W images precede the decrease in signal intensity on T2W images.

18. Terminal zones

19. Leukodystrophies with diffuse white matter involvement Canavan’s disease Alexander Disease Glutaric Aciduria Type 1 & 2

20. 2 year with canavan disease Leukodystrophy Macrocephaly Diffuse WM involvement ↑↑ NAA levels

21. Leuko dystrophy Macrocephaly Predominant frontal WM involvement Frontal rim sign Contrast enhancement ↑ GFAP glial fibrillary acidic protein levels in CSF Alexander disease

22. 7 months child with Glutaric Aciduria Type 1

23. Leuko dystrophies with subcortical white matter involvement Hydroxy glutaric aciduria Kearns sayer syndrome

24. Leuko dystrophies with deep white matter involvement Metachromatic Leuko dystrophy Krabbe’s Disease Vanishing White Matter Disease Peroxisomal disorders - Adreno leukodystrophy (ALD)

25. Metachromatic Leuko dystrophy

26. Krabbe disease

27. Axial T2W shows dark regions of myelination in the posterior limb of internal capsule,splenium and genu of corpus callosum. The rest of the cerebral hemisphere are not myelinated(white matter is too bright).

28. 5 years of age with learning and behavioural problems, a deteriorating gait - adrenoleucodystrophy

29. Thank you.