Pathology of the Nervous System

JANTIMA TANBOON,MD
¾ Central nervous system
¾ Peripheral nervous system

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missinglink.ucsf.edu/www.lab.anhb.uwa.edu.au
 Normal cells
ƒ Neuron
ƒ Glia
Macroglia: ectoderm
Microglia: mesoderm
ƒ Choroid plexus
ƒ Neuropil
ƒ Meningothelial cells Virchow-Robin space
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 Neuron
ƒ Nuclei, ganglia
ƒ Cell body (perikaryon), processes
ƒ Eccentric nucleus
ƒ Prominent nucleolus
ƒ Abundant Nissl substance
ƒ Microtubule, neurofilament, prominent golgi,
rER, synaptic specialization
ƒ16/10/51NFP, NeuN, synaptophysin
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 Glia

ƒ Macroglia <- neuroectoderm

Astrocytes,Oligodendrocytes, Ependyma

ƒ Microglia <- bone marrow

ƒ Inflammation, repair, fluid balance, energy

metabolism
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 Astrocytes
ƒ Round-oval nuclei
ƒ Pale chromatin
ƒ Gray/white matter
ƒ Protoplasmic: gray
ƒ Fibrous: gray/white
ƒ Star shape
ƒ GFAP, Golgi method

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 Astrocytes
Processes
DNeuron
ƒ Metabolic buffers
ƒ Detoxifiers
ƒ Nutrient suppliers
ƒ Electrical insulator
DCapillaries
ƒ Barriers: blood, CSF, brain
Repair, scar formation/
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fibroblast
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 Oligodendrocytes
ƒ Processses wrap neural axons
ƒ Like Schwann cells in PNS
ƒ Multiple internodes
ƒ Small round lymphocyte-like nuclei
ƒ Linear arrays

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 Ependymal cells
ƒ Line ventricular system

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 Microglia
ƒ Mesoderm- bone marrow
ƒ Macrophages of CNS
Injury response
1. Proliferation
2. Developing elongated (rod cells)- syphillis
3. Microglial nodules
4. Neuronophagia

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 Reaction of neurons to injury

ƒ Acute neuronal change (red neuron)

ƒ Subacute and chronic neuronal injury (degeneration)

ƒ Axonal reaction

ƒ Subcellular alteration in organelles and cytoskeletal

ƒ Neurodegenerative changes

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 Acute neuronal change (red neuron)

ƒ Acute CNS hypoxic/

ischemic
ƒ H+E 12-24 hrs
ƒ Shrinkage cell body
ƒ Nuclear pyknosis
ƒ Loss of nucleolus
ƒ Loss of Nissl substance
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 Subacute and chronic neuronal injury
(degeneration)
ƒ Cell loss
ƒ Reactive gliosis (early detect)
Axonal reaction
ƒ Regeneration of axon->Axonal spheroids
ƒ Increase protein synthesis-> sprouting
ƒ Enlarge, round up cell body
ƒ Peripheral nuclear displacement
ƒ Dispersion of Nissl substance to periphery
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 Subcellular alteration in organelles and
cytoskeletal
ƒ Lipofuscin, proteins, CHO
ƒ Viral inclusion
z Intranuclear

z Intracytoplasmic

Neurodegenerative changes
ƒ Neurofibrillary tangles-Alzheimer
ƒ Lewy body- Parkinson
ƒ Abnormal vacuolation- CJD
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 Reaction of Astrocytes to injury

ƒ Gliosis***-indicator of CNS injury

ƒ Cellular swelling

ƒ Rosenthal fibers

ƒ Corpora amylacea

ƒ Glial cytoplasmic inclusion

ƒ Alzheimer type II astrocyte

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 Gliosis
ƒ Astrocyte: hypertrophy hyperplasia
ƒ Nucleus: eccentric, enlarged vesicular,
prominent nucleolus
ƒ Scant->bright pink cytoplasm
ƒ Gemistocytic astrocyte
ƒ Glial fibrils
ƒ Bergmann gliosis

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 Rosenthal fibers
ƒ Thick elongated brightly eosinophilic
ƒ Irregular contour within astrocytic process
ƒ Long standing gliosis
ƒ Pilocytic astrocytoma
ƒ Craniopharyngioma
ƒ Syrinx cavities
ƒ Alexander disease
ƒ αB-crystallin, hsp27, ubiquitin
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 Corpora amylacea
ƒ Concentrically lamellated round faintly basophilic,
PAS positive 5-50µm
ƒ Heat shock protein, ubiquitin
ƒ Astrocytic end process
z Subpial
z Perivascular zone
ƒ Advance age
ƒ Adult polyglucosan body
ƒ Lafora body (cytoplasm)
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 Alzheimer type II astrocyte
ƒ Gray matter
ƒ Nucleus 2-3 times> normal
ƒ Pale staining central chromatin
ƒ Unrelated to Alzheimer disease
ƒ Hyperamonemia
ƒ Chronic liver disease
ƒ Wilson disease
ƒ Hereditary disorder of Urea cycle
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 Cerebral edema
Vasogenic edema
ƒ Disrupted normal BBB
ƒ vascular permeability
ƒ Intercellular space
ƒ Localized/generalized
Cytotoxic edema
ƒ Neuronal/glial/endothelial injury
ƒ Intracellular
ƒ Generalized hypoxic/ischemic
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Increase intracranial pressure
Herniation
ƒ Subfalcine (cingulate)
ƒ Transtentorial
(uncinate, mesial temporal)
ƒ Tonsillar herniation

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 Subfalcine (cingulate)herniation
ƒ ACA compromised

Tonsillar herniation

ƒ Life-threatening
ƒ Brain stem compression
ƒ Respiratory and cardiac center in medulla

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 Transtentorial
(uncinate, mesial temporal) herniation
ƒ CNIII compressed -> pupil dilate
z Impair ipsilateral ocular movement

ƒ PCA compressed->primary visual cortex

z Contralateral peduncle compress
z Kernohan’s notch
z Ipsilateral hemiparesis

ƒ Hemorrhage in midbrain, pons

z Secondary brain stem (Duret hemorrhage)
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 CSF
Produced: Choroid plexus
Absorbed: Arachnoid granulation

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 Hydrocephalus
Accumulation of excessive CSF
ƒ Impaired flow
ƒ Impaired absorption
ƒ Overproduction
ƒ Hydrocephalus ex vacuo

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Noncommunicating hydrocephalus
ƒ Congenital malformation
ƒ Tumor
ƒ Inflammation
ƒ Hemorrhage

Communicating hydrocephalus
ƒ Subarachnoid hemorrhage
ƒ Meningitis
ƒ Metastasis to subarachnoid space
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 Neural tube defects
1. Anencephaly
2. Encephalocele
3. Spina bifida*(spinal dysraphism)
4. Myelomeningocele
ƒ Maternal blood: AFP, acetylcholinesterase
ƒ Folate deficiency
ƒ Subsequent pregnancy 4-5%
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 Forebrain anomaly
1. Polymicrogyria
2. Megalencephaly
3. Microencephaly*
4. Lissencephaly
5. Neuronal heterotopia
6. Holoprocencephaly
7. Agenesis of corpus callosum

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 Posterior fossa anomaly
ƒ Arnold-Chiari malformation
z Type I: less severe, tonsils

z Type II: vermis

z Small posterior fossa, large foramen magnum,

low insertion of tent

z caudal displacement of medulla, tectum

malformation, aqueduct stenosis,

cerebralheterotopia, hydromyelial
ƒ Dandy-Walker malformation

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 Arnold- Chiari malformation

Type I Type II

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 Dandy-Walker malformation
ƒ Enlarged posterior fossa,
ƒ Agenesis of vermis,
ƒ Midline cyst

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ƒ Hydromyelia

ƒ Syringomyelia

ƒ Syringo bulbia

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 Direct parenchymal injury
Contusion: bruising
Laceration: tearing

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Contusion

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 Plaque jaune

Contusion

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 Diffuse axonal injury

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 Diffuse axonal injury
ƒ Deep centroaxial white matter region

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 Traumatic vascular injury

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 Epidural hematoma
¾ Associated skull fracture
¾ Middle meningeal artery
¾ Lucid interval

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 Subdural hematoma
ƒ Potential spaces-> Bridging veins Elder, infant
¾ Acute subdural hematoma
¾ Chronic subdural hematoma

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 Chronic subdural hematoma
Multiple episode of rebleeding
Organizing
ƒ 1wk -> Clot lysis
ƒ 2wks -> Fibroblast from meninges to hematoma
ƒ 2-3 months -> Early development of hyalinized
connective tissue

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 Subarachnoid hemorrhage

ƒ Trauma
ƒ Aneurysm/Vascular malformation

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 Trauma sequele
ƒ Post traumatic hydrocephalus
ƒ Punch-drunk syndrome (dementia pugilistica)
z Hydrocephalus
z Thining of corpus callosum
z DAI
z Neurofibrillary tangles
z Diffuse Aβ-plaque
ƒ Epilepsy
ƒ Brain tumor (meningioma)
ƒ Infectious disease
ƒ Psychiatric disorder
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 Cerebrovascular disease
Cerebrovascular accident (CVA)
Ischemia and infarction
z Global cerebral ischemia
z Focal cerebral ischemia
Intracranial hemorrhage
z Intraparenchymal (intracerebral) hemorrhage
z Rupture Berry aneurysm
z Vascular malformation
Hypertensive cerebrovascular disease
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 Global cerebral ischemia
ƒ Diffuse hypoxic/ischemic encephalopathy

ƒ Low flow

ƒ Respirator brain

ƒ Border zone (watershed) infarction

ƒ Most susceptible

z Pyramidal cells of Sommer sector (CA1) of the

hippocampus, Purkinje cell of cerebellum,

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1. Early change: 12-24 hrs
Red neuron
Neutrophils
2. Subacute change: 24hrs-2 wks
Necrosis
Macrophage
Vascular proliferation
Gliosis
3. Repair: after 2 weeks
Remove all necrotic tissue
Loss normal organized CNS structure
Gliosis
Pseudolaminar necrosis
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 Focal cerebral ischemia
MCA*
Embolization*
z Cardiac mural thrombi: MI, valvular disease, AF

z Thromboemboli: atheromatous plaque

z Paradoxical emboli

z Emboli associated with Sx

z Other material (tumor, fat, air)

In situ thrombosis
z Atherosclerosis: carotid bifurcation, origin of

MCA, basilar artery

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 Non hemorrhagic infarcts
ƒ First 6 hrs: difficult
ƒ 48 hrs: pale soft swollen, indistinct GW junctio
ƒ 2-10 days: gelatinous, friable, distinct
ƒ 10-3 wks: liquefies, fluid filled cavity

Hemorrhagic infarcts
ƒ Reperfusion: collaterals, dissolution of
intravascular occlusion
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 Bone marrow embolization

¾ Fat embolism
¾ Fractures

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 Intraparenchymal hemorrhage
ƒ HT
ƒ Putamen* thalamus pons cerebellar hemisphere
ƒ Charcot-Bouchard aneurysm
Fusiform
Basal ganglia
ƒ Ganglionic hemorrhage
Basal ganglia
Thalamus
ƒ Lobar hemorrhage

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 Lobar hemorrhage

ƒ Hemorrhagic diathesis

ƒ Neoplasms

ƒ Drug abuse

ƒ Infectious vasculitis

ƒ Non infectious vasculitis

ƒ Cerebral amyloid angiopathy

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 Aneurysm
Saccular (berry) abeurysm
MC subarachnoid hemorrhage
Congenital
Atherosclerosis
Fusiform aneurysm, Basilar a
Mycotic
Traumatic
Dissecting
Anterior ciculation
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 Vascular malformations
1. Arteriovenous malformations*
2. Cavernous hemangiomas
3. Capillary telangiectasia
4. Venous angiomas

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 Hypertensive cerebrovascular
disease
ƒ Lacunar infarction (<15mm)
Basal ganglia, thalamus. Internal capsule, deep white
matter, pons

ƒ Slit hemorrhage
ƒ Hypertensive encephalopathy
Diffuse cerebral dysfunction
headache, confusion, vomitting, convulsion-> coma

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 Lacunar infarction
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 Tumors
ƒ Subtle histologic distinction
ƒ Low grade lesion sometimes infiltrate
ƒ Anatomic site -> prognosis
ƒ Spread through subarachnoid spaces
1. Gliomas
2. Neuronal tumors
3. Embryonal tumors
4. Meningioma
5. Metastasis

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 Gliomas

ƒ Astrocytoma

Pilocytic, Anaplastic, Glioblastoma

ƒ Oligodendroglioma

ƒ Ependymoma

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 Fibrillary (diffuse) astrocytoma
ƒ 80% of adult primary brain tumor
ƒ 4th-6th decades
ƒ Cerebral hemisphere
ƒ Histology <-> prognosis
ƒ II/IV Diffuse astrocytoma
ƒ III/IV Anaplastic astrocytoma
ƒ IV/IV Glioblastoma

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 Glioblastoma

ƒ Palisading necrosis
ƒ Vascular proliferation
ƒ Glomeruloid body

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 Pilocytic astrocytoma
ƒ Children, young adult
ƒ Cerebellum*, floor-wall of 4th ventricle
ƒ Optic nerve, cerebral hemisphere
Gross: Cystic with mural nodule
ƒ Solid well circumscribed
Micro: Hair-like process
ƒ Rosenthal fibers
ƒ Eosinophilic granular bodies
ƒ Microcysts
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 Oligodendroglioma
ƒ 4th-5th decades
ƒ Cerebral hemisphere: white matter
ƒ Better prognosis>astrocytoma
Gross: Infiltrative, gelatinous gray mass
Micro: Similar to normal oligodendrocyte
ƒ Clear cytoplasmic halo
ƒ Delicate capillary network
ƒ Calcifications (~90%)
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 Ependymoma
ƒ 1st two decades: 4th ventricle
ƒ Adults: spinal cord
ƒ Supratentorial, spinal better>cerebellum
Gross: papillary/ circumscribed solid
Micro: Rosettes
Perivascular pseudorosettes

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Perivascular pseudo rosette
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Homer-Wright pseudo rosette
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Flexner Wintersteiner rosette
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Embryonal tumor: Medulloblastoma
ƒ 20% of pediatric brain tumor
ƒ Cerebellum*
ƒ Undifferentiated
ƒ Highly malignant, dismal prognosis
ƒ Radiosensitive-> 5 yr survival 75%
Gross:
ƒ Children midline of cerebellum
ƒ Adult: lateral
Micro: Small blue cells,
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rosette
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 Meningioma
ƒ Meningothelial cell (arachnoid)
ƒ External surface, ventricle
ƒ Loss of 22q (NF2 22q12)
ƒ Slow growing
ƒ Parasagittal convexity, lateral convexity, wing of
sphenoid, olfactory groove, foramen magnum
ƒ F:M = 3:1 (10:1, spinal cord)
ƒ Rapid growth during pregnancy
ƒ MIB1 (Ki67)
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 Encapsulated mass, en plaque
Grade I – IV

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 Metastatic tumors
ƒ ¼- ½ of intracranial tumors
ƒ 5 MC primary site (80%):
z Lung

z Breast

z Skin (melanoma)

z Kidney

z GI tract

ƒ Choriocarcinoma
ƒ Intraparenchyma, meninges
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 Metastatic tumors
ƒ Sharply demarcated
ƒ Gray-white junction
ƒ Edema, reactive gliosis, central necrosis
ƒ Meningeal carcinomatosis:
z Brain, spinal cord, intracranial nerve root
z Lung: small cell CA, adenoca
z Breast CA

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 Schwannoma
ƒ Syn: Neurilemmoma
ƒ Schwann cell
ƒ Symptoms: local compression
ƒ NF2
ƒ CP angle, vestibular branch of VIII
ƒ Acoustic neuroma (vestibular schwannoma)
ƒ Gross: Circumscribed
ƒ Micro: Antoni A (Verocay body), Antoni B
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 Antoni A:
cellular area, nuclear free zone,
Verocay bodies
Antoni B:
Loose cellular, microcysts,
myxoid changes
Elongated cells, oval nuclei
Degenerative change:
nulcear pleomorphism,
xanthomatous change,
vascular hyalinization
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www.robbinspathology,www.cumc.columbia.edu
 Neurofibroma

ƒ Skin: cutaneous neurofibroma

ƒ Peripheral nerve: solitary neurofibroma

ƒ Sporadic or associated with NF1

ƒ Skin: nodules (pedunculated, hyperpigmented)

ƒ Plexiform neurofibroma: NF1-> malignant

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Malignant peripheral nerve sheath tumor

ƒ MPNST
ƒ De no vo: Neurofibroma, plexiform
ƒ Associate with NF1
ƒ NF1, p53, p16
ƒ Highly malignant
ƒ Local invasive, recurrence, metastasis
ƒ Triton tumor

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 Traumatic neuroma
ƒ Morton’s neuroma
ƒ Non neoplastic proliferation
ƒ Response to injury
ƒ Disorganized proliferation of proximal stump
ƒ Firm nodule, tender, painful
Gross: circumscribed white gray nodules
Micro: haphazard proliferation of nerve fascicles
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 Traumatic neuroma

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 Type 1 Neurofibromatosis
ƒ AD
ƒ Neurofibromas (plexiform, solitary)
ƒ Gliomas of the optic nerve
ƒ Lisch nodules (iris)
ƒ Café au lait spots
ƒ Tend to have malignant transformation
ƒ NF1 17q11.2 tumor suppressor: neurofibromin

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 Type 2 Neurofibromatosis
ƒ AD
ƒ < NF1
ƒ Bilateral vestibular (acoustic) schawannoma
ƒ Multiple meningiomas
ƒ Gliomas, Ependymoma of the spinal cord
ƒ Schwannosis (spinal cord)
ƒ Meningioangiomatosis
ƒ Glial hamartia
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 Type 2 Neurofibromatosis
ƒ Heterotopia of Schawann cells, glial cells
ƒ Nonsense mutation, missense mutation
ƒ NF2 22q12: merlin

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 Tuberous sclerosis
ƒ AD
Hamartomas and benign neoplasms
ƒ CNS (cortical tubers, subependymal
hamartomas)-> epilepsy, mental retardation
ƒ Renal angiomyolipoma, retinal glial hamartomas,
cardiac rhabdomyomas
ƒ Cysts: liver kidney pancreas
ƒ Cutaneous lesion: angiofibroma, shagreen
patches, ash-leaf patches, subungual fibroma
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 Tuberous sclerosis

ƒ Disruption of tumor suppressor gene

ƒ TSC1: hamartin
ƒ TSC2: tuberlin

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 Von Hippel-Lindau Disease
ƒ AD
ƒ Hemangioblastoma: cerebellum, retina,
brainstem, spinal cord
ƒ Pheochromocytoma
ƒ Cysts; pancreas kidney, liver
ƒ Tend to develop renal cell carcinoma
ƒ Missense mutation in VHL tumor suppressor
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 Primary disease of myelin

Disruption of neuronal communication

White matter disorders

¾ Demyeliniating disease: acquired: MS

¾ Dysmyelinating disease: mutation:

leukodystrophy

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 Multiple sclerosis (MS)
ƒ MC* demyelinating disorder
ƒ Autoimmune: env+genetic
ƒ New symptoms (relapse) -> remission (incomplete)
ƒ Accumulation of increasing neurologic deficit
ƒ Any age, F:M = 2:1
ƒ HLA-DR2
ƒ T-cell, macrophage
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 Multiple sclerosis (MS)
White matter disease
Plaques:
z Ventricles*
z optic nerve, chiasm, brainstem,tracts,
cerebellum, spinal cord.
Active plaques:
z Macrophage+myelin debris
z Perivascular cuffs
z Axon preserved
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 Plaque:
well-circumscribed,irregular shape,
slightly depressed glassy gray-tan lesion

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 Multiple sclerosis (MS)
Inactive plaques:
z No inflammation
z Little-no myelin
z Prominent astrocytic proliferation+ gliosis

Shadow plaques:
z Not circumscribed border
z Thinned out myelin sheaths
z Incomplete loss/partial remyelination
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 Central pontine demyelinolysis
ƒ Loss myelin/preserve axons, neurons
ƒ Rapid correction of hyponatremia
ƒ Pons*, elsewhere
ƒ Rapidly evolving quadriplegia

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 Degenerative diseases
ƒ Gray matter disease
ƒ Progressive neuronal loss
ƒ Secondary change in white matter tracts
1. Cortex
2. Basal ganglia and brain stem
3. Spinocerebellar
4. Motor neurons

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 Alzheimer disease
MC* cause of dementia in elderly
Affecting cerebral cortex
ƒ Forgetfulness
ƒ Insidious impairment of intellectual function
ƒ Alterations in mood and behavior
ƒ Progressive disorientation
ƒ Memory loss
ƒ Aphasia
ƒ Profounded disabled
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 Alzheimer disease
ƒ Pathologic examination -> definite
ƒ Clinical + modern radiologic methods
ƒ Sporadic> familial (5-10%)
ƒ Rare before age of 50
ƒ Amyloid precursor protein (APP)
ƒ Chromosome 21 (Down syndrome>45 yr)
ƒ Apolipoprotein (ApoE4) Chr 19 -> early onset
ƒ SORL1_> late onset
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 Aβ :
Small aggregates:
ƒ Alter neuronal
transmission
ƒ Toxic to neurons
and synaptic
endings

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 Aβ :
Large aggregates:
ƒ Form plaques
ƒ Neuronal death
ƒ Local inflammatory response
ƒ Cell injury
ƒ Alter region-to-region commnication through
mechanical effect
ƒ Form tangles (Hyperphosphorelate tau protein )

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 Alzheimer disease
Gross: cerebral atrophy
ƒ Frontal/temporal/ temporal
ƒ Spare occipital
ƒ Hydrocephalus ex vacuo

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 Major microscopic abnormalities:
1.Neuritic (senile) plaques
Diffuse plaques
2.Neurofibrillary tangles
3.Amyloid angiopathy

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 Granulovacuolar degeneration:
ƒ Normal aging
ƒ AD: hippocampus, olfactory bulb
Hirano bodies
ƒ Major compotent: actin
ƒ Hippocampal pyramidal cells

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faculty.washington.edu missinglink.ucsf.edu
 Parkinsonism
ƒ Mask facies
ƒ Stooped posture
ƒ Slowness voluntary movement
ƒ Festinating gait
ƒ Rigidity
ƒ Pill-rolling tremor
ƒ 10-15%->dementia (fluctuating courses/hallucination)
ƒ Pathologic evidence of Alzheimer disease
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 Parkinsonism
Idiopathic Parkinson disease
ƒ Sporadic>familial (AD/AR)
ƒ α- synuclein/parkin
ƒ Dopaminergic neuron in substantia nigra
ƒ MPTP/ pesticide exposure
ƒ Caffeine/ nicotine -> protective
ƒ RX -> L-dihydroxyphenylalanine (L-DOPA)

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Gross: Pallor of substantia nigra, Locus ceruleus
Micro: Loss of cathecholaminergic neurons,Gliosis
Lewy body: basal nucleus of Meynert,
sympathetic
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135
 Huntington disease
ƒ AD
ƒ Trinucleotide (CAG) repeated mutation 4p16.3
ƒ huntingtin
ƒ Progressive movement disorder+dementia
ƒ Degenerate striatum (caudate+putamen)
ƒ Chorea:
ƒ Jerky, hyperkinetic, dystonic movement

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 Huntington disease

ƒ 4th-5th decades

ƒ Depend on length of CAG repeate

ƒ >70 adolescent

ƒ Motor>cognitive impairment

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 Huntington disease
Gross:
ƒ Striking atrophy on caudate/putamen
ƒ Globus pallidus
Micro:
ƒ Severe neuronal loss
ƒ Gliosis

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 Amyotrophic lateral sclerosis
ƒ ALS
ƒ MC form of neurodegeneration involving motor
system
ƒ Muscle atrophy
ƒ Hyper-reflexia (loss upper+lower motor neuron)
ƒ Degeneration of the corticospinal tract
ƒ M>F
ƒ >5th decades

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 Amyotrophic lateral sclerosis
ƒ Sporadic>familial (AD 5-10%)
ƒ Chromosome 21
ƒ Superoxide dismutase (SOD1)
ƒ Asymmetric weakness of hands
ƒ Cramping/spasticity of arms and legs
ƒ Fasciculations
ƒ Respiratory muscles-> death
ƒ 5 year survival-50%
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 Transmissible spongiform
encephalopathy (Prion disease)
Creutzfeldt-Jakob disease (CJD)
Variant CJD
Gerstmann-Straussler-Scheinker syndrome (GSS)
Fatal familial insomnia
Kuru
Scrapie: sheep/goat
Mink transmissible encephalopathy
Chronic wasting disease of deer and elk
Bovine spongiformJantima
16/10/51
encephalopathy
Tanboon, MD
(BSE) 141
 Prion disease
¾ PRNP gene chr 20 PrPc -> PrPsc,PrPres
¾ Resistant to protease digestion
¾ Other PrPc change
¾ Low rate -> sporadic
¾ High rate -> mutation

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 Prion disease
ƒ Accumulation of PrPsc in neural tissue -> cell injury
Creutzfeldt-Jakob disease (CJD)
ƒ Rapidly progressive dementia
ƒ 85% sporadic 1: 1,000,000
ƒ Familal form
ƒ 7th decades
ƒ Subtle changes in memory and behavior -> Rapidly
progressive dementia
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 Creutzfeldt-Jakob disease (CJD)

ƒ Startle myoclonus, cerebellar dysfunction

ƒ Fatal in 7 months
Spongioform transformation:
ƒ Cerebral cortex/deep gray matter structures
ƒ Neuronal loss, reactive gliosis
ƒ Expansion of vacuoles -> cyst (status spongiosus)

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Variant Creutzfeldt-Jakob disease (vCJD)

ƒ Young adults
ƒ Exposure to BSE (cattle)
ƒ Behavioral disorders in early stage
ƒ Neurologic syndrome progress slowly
ƒ Pathologic/molecular finding: the same

ƒ + Abundant cortical amyloid plaques

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16/10/51 Jantima Tanboon, MD 146
Gerstmann-Straussler-Scheinker syndrome
(GSS)
ƒ Mutation in PRNP gene
ƒ Chronic cerebellar ataxia
ƒ Progressive dementia
ƒ Clinical slower than CJD
ƒ Death in several years
Micro: the same
ƒ + numerous amyloid (Kuru) plaques/ tangles
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 Fatal familial insomnia
ƒ Initial stage->Sleep disturbance
ƒ <3 yr: neurological signs
ƒ Ataxia, autonomic disturbance, stupor, coma
ƒ Fatal sporadic insomnia
Micro: NO spongioform pathology
ƒ Neuronal loss, reactive gliosis
ƒ Anterior ventral/dorsomedial nuclei of thalamus
ƒ Inferior olivary nuclei
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 Infection

Routes of infection:

1. Hematogenous spread

2. Direct implantation

3. Local extension

4. Peripheral nervous system

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ƒ Meningitis
ƒ Meningoencephalitis
ƒ Chemical meningitis
ƒ Meningeal carcinomatosis
ƒ Meningeal lymphomatosis
Infectious meningitis
ƒ Acute pyogenic (bacterial)
ƒ Aseptic meningitis (viral)
ƒ Chronic meningitis (tuberculous, spirochetal,
cryptococcal)
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Acute pyogenic (bacterial) meningitis
ƒ Escherichia coli*
ƒ Streptococcus group B*
ƒ Streptococcus pneumoniae**-> over convexities
ƒ Listeria monocytogenes
ƒ Neiseria meningitidis***
ƒ Haemophilus influenza -> basal
ƒ Meningeal impairment, stiffness, headache,
photophobia
ƒ CSF: Protein, ‚ glucose
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 Aseptic (viral) meningitis
ƒ Less fulminant
ƒ Viral, NSAIDS, chemical
ƒ CSF: lymphocytosis, protein, sugar <->
ƒ Self limiting, symptomatic treatment
Gross: mild edema
Micro: mild-mod leptomeningeal L infiltration

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 Acute focal suppurative infection
Brain abscess:
ƒ direct implant, local extension
ƒ Frontal>parietal>cerebellum
ƒ CSF: protein <->sugar

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 Subdural empyema: bacteria, fungus
Extradural / spinal epidural abscess : osteomyelitis

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Chronic bacterial meningoencephalitis

Tuberculosis:
ƒ Base of the brain: gelatinous, fibrinous exudate
ƒ Meningoencephalitis*, Obliterative endarteritis,
Tuberculoma
Cpx:
Arachnoid fibrosis -> hydrocephalus
Obliterative endarteritis -> infarction
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16/10/51 Jantima Tanboon, MD 157
 Neurosyphilis = Tertiary syphilis
1. Meningovascular neurosyphilis
2. Paretic neurosyphilis
3. Tabes dorsalis
Meningovascular:
ƒ Chronic meningitis: base/convexities/spinal cord
ƒ Obliterative (Heubner) endarteritis
ƒ Plasma cell/ lymphocytes
ƒ Cerebral gumma
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Paretic neurosyphilis
ƒ Invasion T. pallidum
ƒ Granular ependymitis ->hydrocephalus
ƒ General paresis of the insane: delusion of
grandeur, dementia, loss mental/physical
Tabes dorsalis
ƒ Damage sensory nerves in dorsal root
ƒ Loss Joint position sense -> ataxia
ƒ Loss of pain sensation
-> Chacot joint
-> lightning pain
ƒ Loss DTR

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 Viral meningoencephalitis
ƒ Meningoencephalitis
ƒ Encephalomyelitis
Histology:
ƒ Perivascular/parenchymal mononuclear cell
infiltrates
ƒ Glial reaction: microglial nodule
ƒ Neuronophagia

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 Herpes simplex virus type 1
ƒ Encephalitis
ƒ Any age group: children/young adult*
ƒ Alterating mood, memory, behavior
ƒ Orbital gyri of frontal lobe
ƒ Medial regions of temporal lobe
ƒ Necrotizing and hemorrhagic
ƒ Perivascular cuffing
ƒ Cowdry type A in neurons/glia
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 Herpes simplex virus type 2
ƒ Meningitis-Adult
ƒ Encephalitis-vaginal delivered neonate
ƒ AIDS-acute hemorrhagic necrotizing encephalitis
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Varicellar-zoster virus (Herpes zoster)
ƒ Immunosuppressed – herpes zoster encephalitis
ƒ Inclusion bodies in in glia and neuron

Cytomegalovirus
ƒ Immunosuppressed-subacute encephalitis
ƒ Fetus - In utero
-> periventricular necrosis + severe brain destruction
-> microcephaly + periventricular calcification

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 Cytomegalovirus

ƒ Virus: paraventricular subependymal region

ƒ Severe hemorrhagic necrotizing
ventriculoencephalitis
ƒ Choroid plexitis

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 Poliomyelitis
ƒ Anterior horn cell motor neuron of spinal cord
ƒ Perivascular cuff, neuronophagia
ƒ Posterior horn/ motor cranial nuclei
ƒ Long term: neuronal loss, gliosis, atrophy

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 Rabies

Neuronal degeneration + inflammation

ƒ Midbrain, floor of 4th ventricle, medulla

ƒ Basal ganglia, spinal cord, dorsal root ganglia

Negri body – inflammation:

ƒ Pyramidal neuron – hippocampus

ƒ Purkinje cell - medulla

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 HIV

ƒ Direct effect/ opportunistic infection/ tumors

Aseptic HIV-1 meningitis

ƒ 10%: 1-2 wks after seroconversion

ƒ mild lymphocytic meningitis

ƒ perivascular cuffing

ƒ myelin loss
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 HIV
HIV-1 meningoencephalitis (subacute encephalitis)
ƒ AIDS dementia complex: mental slowing,
memory loss mood disterbance
ƒ Chronic inflammatory cell infiltration
ƒ Microglial nodule + multinucleated giant cells
Vacuolar myelopathy
ƒ Tracts of spinal cord

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Progressive multifocal leukoencephalopathy

ƒ PML: JC polyomavirus
ƒ Immunosuppressed: CML, chemoRX, AIDS
ƒ 65% of normal people: exposure by 14 yr
ƒ Reactivation
ƒ Oligodendrocyte-> demyelination
CT:
ƒ extensive multifocal ring enhancing lesion in
hemispheric/ cerebellar white matter
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16/10/51 Jantima Tanboon, MD 172
 Fungal encephalitis
ƒ Granulomas, abscesses, meningitis
Candida albicans
Multiple microabscesses w/wo granuloma
Mucor
Aspergillus fumigatus
Septic hemorrhagic infarction
Cryptococcus neoformans
Histoplasma capsulatum

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 Cerebral toxoplasmosis
ƒ Toxoplasma gondii
ƒ AIDS
CT/MR: multiple ring enhancing lesion
Gross:
ƒ Abscesses, Gray-white junction, deep gray nuclei
Micro:
ƒ Central necrosis, petichiae hemorrhage,
tachyzoite, bradyzoite
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 Cysticercosis
Tenia solium

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 Amebic meningoencephalitis

Naegleria spp

ƒ Swimming in nonflowing fresh water

ƒ Fatal encephalitis

Acanthamoeba spp

ƒ Chronic granulomatous meningoencephalitis

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16/10/51 Jantima Tanboon, MD 180
www.fujita-hu.ac.jp
Thank
16/10/51 you for your attention
Jantima Tanboon, MD 181