Nervous System

AGENESIS OF CORPUS CALLOSUM (ACC)

●● Aicardi syndrome (partial/complete agenesis, retinal abnormalities, infantile spasms)

●● Non-ketotic hyperglycemia (inborn error of metabolism)

LISSENCEPHALY TYPES I AND II

●● Diffuse smooth cerebral surface, absence of gyration

●● Cerebral gray matter is thick, paucity of white matter

migration

●❑ Excessive migration of neuroglial precursors

●❑ Associated with autosomal recessive syndromes (Walker Warburg, Fukuyama)

●❑ Triad of cerebral, ocular, and muscle diseases

PACHYGYRIA

POLYMICROGYRIA

excessively folded/fused/unlayered ●● Risk factors: TORCH, intrauterine isch-

emia, metabolic diseases (Zellweger), family history

MALFORMATIONS OF CORTICAL DEVELOPMENT (FOCAL CORTICAL DYSPLASIA)

gray-white matter ●● Delamination and columnar disorganiza-

tion ●● Dysmorphic neurons: Large, neurofilament

rich, atypical coarse Nissl substance, thick dendritic processes, maloriented

●● Balloon cells: Abnormal cells with abundant glassy eosinophilic cytoplasm, eccentrically placed vesicular nucleus, prominent nucleoli

●● Dysmorphic neurons have neuronal, glial, or hybrid features (positive for GFAP and neuronal markers)

●● FCD type I: Disorganized and delaminated cortex

●● FCD type II: Delaminated cortex and dysmorphic neurons. IIA = without balloon cells. IIB = with balloon cells

●● FCD type III: Cortical delamination associated with other principal lesion

(hippocampal sclerosis, epileptogenic tumors, vascular malformations, cerebral traumatic lesion of early life)

ANTENATAL DISRUPTIVE LESIONS OF BRAIN

●● Hypoxic/ischemic/infectious insult to brain

Porencephaly

space ●● Polymicrogyria, gliosis, calcification seen at

rim of defect

Basket brain

Schizencephaly

Microcephaly

Micrencephaly

BUDD-CHIARI MALFORMATION

Chiari I

●● Herniation of tonsils through foramen magnum

Chiari II

magnum ●● Lumbar myelomeningocele ●● Tectal beaking: “S”-shaped kinking of

medulla into dorsal spinal cord ●● Vitamin A deficiency in mother

Chiari III

hydrocephalus

sinuses ●● Maternal isotretinoin usage is risk factor

BACTERIAL INFECTIONS

Acute meningitis

●● Neonatal meningitis caused by group B streptococcus and Escherichia coli

●● Infants/young children infected by Haemophilus influenzae type B

●● Older children by Streptococcus pneumoniae and Neisseria meningitidis

●● Cerebrospinal fluid (CSF) exam: Granulocytic pleocytosis, increased proteins, decreased glucose

to cranial nerve palsies), hydrocephalus

Cerebral abscess

●● Children with CHD at risk for hematogenous bacterial spread/cerebral abscess

●● Other risk factors: Penetrating head injuries, neurosurgical procedures, immunocompromised hosts

VIRAL INFECTIONS

virus common ●● Other viruses: HSV, CMV, VZV, HIV ●● Perivascular and leptomeningeal lympho-

cytic infiltrate ●● Diagnosis of fetal infection: Viral cultures,

polymerase chain reaction of amniotic fluid, fetal IgM serology

FUNGAL INFECTIONS

Aspergillus species

PARASITIC INFECTIONS

Toxoplasmosis

tal spread ●● Immunocompromised children (reactiva-

tion of dormant infection) ●● Sabin tetrad = seizures, chorioretinitis,

cerebral calcifications, and hydrocephalus ●● Encysted bradyzoites in brain easily identi-

fied compared to extracellular tachyzoites ●● Imaging: Multiple ring-enhancing lesions

Neurocysticercosis

●● CNS disease; when humans are intermediate hosts (after eating pork contaminated with Taenia solium oocysts)

●● Oocysts develop into larvae → invade gastrointestinal tract → disseminate hematogenously → reside in CNS/muscle

HYPOXIC ISCHEMIC ENCEPHALOPATHY (HIE)

●● Global insult to body (cardiac arrest/septic shock)

of gray and white matter junction, cerebral atrophy

●● Parenchymal edema, vacuolization, microglial activation, foamy macrophages

●● Neuronal cytoplasmic eosinophilia, pyknotic angulated nuclei, karyorrhexis

HIE

●● Sulcal cortical depth involved leading to ulegyria (mushroom-like)

●● HIE in prenatal life leads to malformations; polymicrogyria, schizencephaly

PERIVASCULAR LEUKOMALACIA (PVL)

maternal cardiorespiratory instability ●● Periventricular coagulative necrosis, cystic

degeneration, mineralization, and gliosis ●● Long-term sequelae: Cerebral palsy, cogni-

tive disorders, epilepsy

GERMINAL MATRIX HEMORRHAGE (GMH)

tory compromise, intrauterine growth retardation (IUGR), hypothermia

●● Germinal matrix has neuroglial precursors and is a site of fibrinolytic activity

tricle normal in size and less than 50% involved with hemorrhage)

●● Grade III: Intraventricular hemorrhage (ventricle dilated and entirely filled with hemorrhage)

●● Grade IV: Parenchymal extension of hemorrhage

PEDIATRIC STROKE

disease (CHD), thrombophilia, smoking, hypertension, oral contraceptive use

VASCULAR ANEURYSM

Berry aneurysm

lamina replaced by fibrosis, atherosclerosis

VASCULAR MALFORMATIONS

Arterio-venous malformation (AVM)

●● Veins, arteries, hybrid vessels (arterialized veins) with intervening gliotic brain tissue fragments

Cavernous hemangiomas

●● Hyalinized veins of variable caliber arranged in back-to-back pattern

Vein of Galen aneurysm

Meningioangiomatosis

ized fibrosed vessels, perivascular spindle cells

●● Surrounding brain has gliosis and dysmorphic neurons

NEURONAL LIPIDOSIS

●● Neuronal cytoplasm distended by lipofuscin-like storage material (neuronal ceroid lipofuscinosis)

LEUKODYSTROPHIES (KRABBE AND METACHROMATIC)

●● Abnormality in myelin formation and metabolism

●● Bilateral, symmetrical white matter disease, involves all parts of CNS

●● Rostral fibers involved in Alexander disease and metachromatic leukodystrophy (MLD)

●● Caudal fibers involved in Krabbe leukodystrophy (KLD) and adrenoleukodystrophy (ALD) (Luxol fast blue stain)

●● Mitochondria are known as “power houses of cell”; provide energy by ATP and electron transport chain

●● Dysfunction of electron transport chain results in cell death (due to energy deprivation/free radical toxicity/apoptosis)

ENCEPHALOMYOPATHIES

●● Skeletal muscle, cardiac muscle, and brain affected

●● Blood/CSF lactate and lactate/pyruvate, ratio increased

MELAS

●● Metabolic encephalopathy, lactic acidosis, and stroke

nucleotide

MERRF

LEIGH DISEASE

KEARNS-SAYRE SYNDROME

nopathy ●● Mitochondrial myopathy

Note: Ragged red fibers; Gomori’s trichrome stain (dark red). Succinic dehydrogenase stain (dark blue). EM: Rectangular para-crystalline arrays resembling a parking lot

●● Wernicke-Korsakoff syndrome: Vitamin B1 (thiamine) deficiency

●● Subacute combined degeneration: Vitamin B12 (cobalamin) deficiency

●● Disorders causing dysfunctioning of neocortex

MESIAL TEMPORAL SCLEROSIS

●● Ammon horn sclerosis (hippocampal sclerosis)

●● Isolated or in association with other temporal lobe diseases (neoplasm, vascular malformation, cortical dysplasia)

●● Atrophy of hippocampal formation, dilatation of adjacent inferior temporal horn of lateral ventricle

●● Neuronal loss/gliosis most prominent in CA1 and CA3 hippocampal subregions

FRIEDREICH ATAXIA

●● Autosomal recessive progressive limb and gait ataxia, multisystem disorder

●● Expanded GAA intronic nucleotide repeat, chromosome 9

●● Spinal cord shows symmetric degeneration in dorsal column, corticospinal tracts, and spinocerebellar tracts

●● Neuronal loss in dorsal root ganglion, loss of large myelinated fibers in peripheral nerves

SPINAL MUSCULAR ATROPHY

muscle fibers ●● Type I more common

GLIOMAS

Pilocytic astrocytoma

mus ●● Seen in relation to optic pathway (NF1) ●● Imaging: Cystic lesion with enhancing

mural nodule ●● World Health Organization (WHO) grade I ●● Sharp tumor/normal brain interface ●● Biphasic solid/microcystic architecture ●● Spindle-shaped cells, bipolar hair-like

processes ●● Smaller cells with short cytoplasmic

processes ●● Rosenthal fibers (RF) and eosinophilic

granular bodies (EGB) ●● Positive staining with GFAP, low MIB-1

index

Pilomyxoid astrocytoma

background, perivascular pseudorosettes

Anaplastic astrocytoma

nuclei, scant cytoplasm ●● Nuclear atypia, high mitotic activity ●● Diffusely infiltrative

Glioblastoma multiforme

cular proliferation, geographic necrosis with pseudopalisading

Ependymomas

microvilli ●● Positive staining with GFAP, EMA, and

CD99

Pleomorphic xanthoastrocytoma

Oligodendroglioma

EMBRYONAL TUMORS

Medulloblastoma

tion ●● WHO grade IV ●● Small, round, blue cell tumor, high grade ●● Positive for synaptophysin ●● Large cell anaplastic medulloblastoma has

prominent cell wrapping

ATRT (Atypical teratoid rhabdoid tumor)

neoplastic lymphocytes/endothelial cells retain positivity)

●● Triad stain positivity: Vimentin, SMA, and EMA

Medulloepithelioma

membrane ●● Divergent differentiation

Hemangioblastoma

GFAP ●● Negative for epithelial markers

TUMORS RELATED TO THE THIRD VENTRICLE/SUPRASELLAR SPACE

Craniopharyngiomas

lium, squamoid cells lining cysts ●● Papillary pattern is less common in children

Intracranial germinoma

●● Biphasic histology; mitotically active epithelioid cells and reactive lymphocytes

Pineocytoma

Wright rosettes)

Pineoblastoma

NEURONAL AND MIXED GANGLIONEURONAL TUMORS

Ganglioglioma

plastic neurons ●● Vacuolated and bi-nucleated neurons ●● Eosinophilic granular bodies, perivascular

lymphocytic cuffing, microcalcifications ●● GFAP stain positive in glial portion

highly ramifying cytoplasmic processes

Dysembryoplastic neuroepithelial tumor (DNET)

cells (S-100+) ●● Cortical dysplasia adjacent to tumor (disor-

ganized and dyslaminated cortex)

Desmoplastic infantile glioneuroma (DIG)

Dysplastic infantile astrocytoma

Dysplastic gangliocytoma of the cerebellum

inside out) ●● Cerebellar cortex replaced by two layers;

outer layer composed of parallel arrays of myelinated axons, inner layer composed of abnormal smaller/larger neurons

malignancies

CHOROID PLEXUS TUMORS

nailing of surface

Choroid plexus papilloma

of tumor than normal choroid plexus

Choroid plexus carcinoma

MENINGIOMA

●● Uncommon tumors in children (compared to adults)

●● Slow growing, derived from arachnoid cap cells

●● Grade I: Meningothelial, fibroblastic, transitional, angiomatous, psammomatous

whorls, uniform round cells, intranuclear inclusions, psammoma bodies

●● Stain positive with vimentin and EMA stains

●● NF1: Neurofibromas (diffuse, nodular, plexiform), optic/hypothalamic gliomas, diffuse astrocytomas

●● NF2: Bilateral vestibular schwannomas, schwannomas, multiple meningiomas, meningioangiomatosis

●● Ataxia-telangiectasia: Cerebellar degeneration, intracranial hemorrhage, cytomegaly, nuclear atypia, lymphomas

●● Nevoid basal cell carcinoma syndrome (Gorlin): Desmoplastic medulloblastoma, meningioma

●● VH-Lindau: Hemangioblastoma of cerebellum

tumors ●● Turcot: GBM, medulloblastoma ●● Retinoblastoma: Bilateral retinoblastoma and

pineoblastoma (ectopic intracranial retinoblastoma) = trilateral retinoblastoma