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AN64.1-3 | Histology & Embryology (Neuroanatomy) — Self-Directed Learning

Part 1: Histology of the Spinal Cord (AN64.1)

Gross structure on cross-section:
• H-shaped grey matter (posterior horn, anterior horn, lateral horn T1–L2) surrounded by white matter
• Ependymal cells line the central canal

Microscopic features:
• Anterior horn: Large multipolar neurons (alpha motor neurons, Golgi type I), prominent Nissl bodies, occasional Golgi type II interneurons
• Posterior horn: Smaller neurons, substantia gelatinosa (Rolando) = tip of posterior horn; dense small neurons (pain modulation)
• White matter: Myelinated axons + astrocytes + oligodendrocytes; no neuronal cell bodies
• Blood-spinal cord barrier: Tight junctions in spinal cord endothelium (similar to BBB)

Identifying spinal cord in practical (key features):
1. Butterfly/H-shaped grey matter
2. Large multipolar neurons in anterior horn
3. Substantia gelatinosa (dark compact area at tip of posterior horn)
4. Central canal with ependymal cells
5. At T1–L2: lateral horn present (small neurons = preganglionic sympathetic)

Part 2: Histology of the Cerebellum & Cerebrum (AN64.1)

Cerebellar Cortex — 3 Layers:

Layer	Position	Cells	Function
Molecular (outer)	Most superficial	Basket cells, stellate cells, parallel fibre axons of granule cells, Purkinje dendrites	Inhibitory interneurons; parallel fibres synapse here
Purkinje cell layer (middle)	Single row of large cells	Purkinje cells — large, flask-shaped, extensive dendritic tree	ONLY output of cerebellar cortex; GABAergic; inhibit deep nuclei
Granular (inner, deepest)	Deepest layer	Granule cells (most numerous neurons in CNS!) + Golgi cells	Granule cells = excitatory (glutamate); receive mossy fibre input; send parallel fibres up to molecular layer

Identifying cerebellum under microscope:
1. Folial pattern (folia with core of white matter)
2. Three layers: molecular (pale, outer) → single row of large Purkinje cells → granular (dark, dense, inner)
3. Purkinje cells: distinctive large flask shape, prominent nucleolus, massive dendritic tree in molecular layer

Cerebral Cortex (Neocortex) — 6 Layers:

Layer	Name	Key Cells	Function
I	Molecular (plexiform)	Few neurons, mostly neuropil	Dendritic arborisation
II	External granular	Small granule cells	Input
III	External pyramidal	Medium pyramidal cells	Corticocortical output
IV	Internal granular	Dense small granule cells	THALAMIC INPUT (main sensory input layer; best developed in sensory cortex)
V	Internal pyramidal	Betz cells (giant pyramidal)	MAIN CORTICAL OUTPUT (motor cortex: Betz cells → corticospinal tract)
VI	Multiform (fusiform)	Mixed cell types	Subcortical output, thalamocortical fibres

Regional variations:
• Primary motor cortex (area 4): Very thick layer V (Betz cells), absent layer IV — "agranular" cortex
• Primary sensory cortex (areas 1,2,3): Prominent layer IV (koniocortex — "dust cortex" with dense granule cells), thin layer V
• Visual cortex (area 17): Line of Gennari = visible stripe in layer IV from dense myelinated thalamocortical fibres; called "striate cortex"

Identifying cerebral cortex under microscope:
1. Six layers (count them)
2. Betz cells in layer V (primary motor cortex) — largest neurons in the CNS
3. Dense layer IV (sensory cortex) — koniocortex
4. Gyri with white matter cores

Part 3: Development of the Nervous System (AN64.2)

Neural Plate Formation (Week 3, days 18–19):
• Notochord induces the overlying ectoderm to become neuroectoderm → neural plate
• Neural plate thickens, edges form neural folds, midline becomes neural groove

Neural Tube Closure (Week 4, days 22–28):
• Neural folds elevate and fuse in the midline → neural tube
• Fusion begins in the middle (future cervical region) and progresses both cranially and caudally
• Cranial neuropore closes at day 25 (Carnegie stage 11)
• Caudal neuropore closes at day 28 (Carnegie stage 12)
• Neural tube = brain (rostral) + spinal cord (caudal)
• Neural crest cells = detach from the dorsal neural tube; migrate to form: dorsal root ganglia, sympathetic ganglia, Schwann cells, adrenal medulla, melanocytes, branchial arch structures

Primary Vesicle Formation (Week 4 end):

Vesicle	Region
Prosencephalon (forebrain)	Rostral
Mesencephalon (midbrain)	Middle
Rhombencephalon (hindbrain)	Caudal

Secondary Vesicle Formation (Week 5):

Primary	Divides into	Develops into
Prosencephalon	Telencephalon	Cerebral hemispheres, basal ganglia, hippocampus, olfactory bulb
	Diencephalon	Thalamus, hypothalamus, retina, optic nerve
Mesencephalon	(no division)	Midbrain

| Rhombencephalon | Metencephalon | Pons + cerebellum |
| | Myelencephalon | Medulla oblongata |
| Spinal cord | — | Neural tube caudal to rhombencephalon |

Development of the Cerebral Hemispheres:
• Telencephalon balloons outward from week 5 → forms the cerebral hemispheres (expand enormously)
• Cortical neuronal migration: neurons born in the ventricular zone → migrate outward along radial glial fibres → form the 6 cortical layers in an "inside-out" pattern (earliest neurons deepest, later neurons superficial)
• Gyration begins at week 20; myelination continues until adulthood
• Corpus callosum forms by week 18–20 (agenesis of CC = failure of commissural fibres to cross)

Development of the Cerebellum:
• From the rhombic lip of the metencephalon (dorsal)
• Purkinje cells migrate from the ventricular zone
• Granule cells are born in the external granular layer (EGL) postnatally → migrate inward through the Purkinje cell layer → form the internal granular layer
• Medulloblastoma is thought to arise from remnants of the external granular layer (hence its common location in the vermis)

Part 4: Neural Tube Defects (AN64.3)

Open Neural Tube Defects (NTDs) — Failure of Neural Tube Closure

Cranial NTDs (cranial neuropore fails to close by day 25):

Defect	Description	Clinical
Anencephaly	Absence of the cranial vault + cerebral hemispheres; neural tissue exposed and degenerates; not compatible with life	Detected on antenatal US; raised maternal AFP; termination often offered
Encephalocele	Herniation of brain/meninges through a skull defect	Occipital (most common in India); surgical repair
Craniorachischisis	Failure of entire neural tube to close	Severe; rare; incompatible with life

Spinal NTDs (caudal neuropore fails to close by day 28):

Defect	Contents of sac	Skin cover	Neurological deficit	Infant in hook
Spina bifida occulta	No sac; laminar defect only	Normal skin ± tuft of hair/dimple	None usually	Not this
Meningocele	Meninges + CSF; no neural tissue	Normal skin	NONE or minimal	2nd infant
Myelomeningocele	Meninges + CSF + neural tissue (spinal cord/roots exposed)	Thin membrane/open	Severe — paraplegia, bladder/bowel paralysis	1st infant
Myeloschisis (rachischisis)	Neural tissue completely open/flat (no sac)	None — open lesion	Most severe	—

Embryological basis:
• Failure of caudal neuropore closure → spinal canal remains open → spinal cord does not properly form/close
• The higher the level, the more severe the deficit (thoracic > lumbar > sacral)

Arnold-Chiari Malformation Type II (associated with myelomeningocele):
• Cerebellar tonsils + vermis + medulla herniate through the foramen magnum
• Causes obstructive hydrocephalus (kinking of aqueduct + hindbrain obstruction)
• Nearly ALL myelomeningocele patients have Chiari II

Risk Factors and Prevention:
• Folic acid deficiency — single most important preventable cause
• Prevention: 400 mcg folic acid DAILY from one month BEFORE conception until 12 weeks gestation (periconceptional supplementation)
• High-risk patients (previous NTD child, antiepileptics): 5 mg/day folic acid
• India: Government free folic acid supplementation through primary health centres; ICDS (Integrated Child Development Scheme) includes folate
• Diagnosis: Maternal serum AFP elevated (open defects); amniocentesis AFP + AChE; antenatal ultrasound (recommended 18–20 weeks anomaly scan)

Prenatal closure surgery (fetal MMC repair):
• Available in a few Indian centres; done at 22–26 weeks intrauterine; reduces hydrocephalus severity and improves leg function vs postnatal repair