PATHOLOGY OF THE CENTRAL NERVOUS SYSTEM

HERBERT Z. MANAOIS, M.D.

PATHOLOGY OF THE CENTRAL NERVOUS - ipsilateral pupillary dilatation and

SYSTEM impaired ocular movement
I. Cerebral edema, hydrocephalus, and
raised intracranial pressure and C. Tonsillar
herniation - cerebellar tonsils displaced through
II. Malformations and developmental foramen magnum
Disorders - respiratory and cardiac center
III. Trauma compromised
IV. Cerebrovascular disease
V. Infections Types of Herniation
VI. Prion diseases
VII. Demyelinating diseases
VIII. Neurodegenerative diseases
IX. Toxic and metabolic diseases
X. Tumors

Cerebral edema, hydrocephalus, and raised

intracranial pressure and herniation

I. Cerebral edema
- increased fluid leakage from vessels or CNS
cellular injury

* Two main pathways Robbins and Cotran, Pathologic Basis

1. Vasogenic edema of Disease, 9th ed., Chap 28, pp 1255
– extracellular; blood-brain barrier
disruption increased vessel Malformations and
permaeability
2. Cytotoxic edema
- intracellular; neuronal, glial or I. Neural tube defects
endothelial injury - most CNS malformations
- hypoxic or ischemic insult, metabolic A. Spinal dysraphism/spina bifida
- asymptomatic bone defect (occulta)
* Interstitial edema (hydrocephalic edema) B. Myelomenoingcele
- around lateral ventricles (meningomyelocele)
- increased intravascular pressure causing abnormal - extension of CNS tissue through a
fluid flow from intraventricular defect in the vertebral column
CSF to the periventricular white matter - when only meningeal extrusion
without CNS tissue (meningocele)
II. Hydrocephalus - lumbosacral region
* Excess fluid in the ventricular system C. Encephalocele
* Impaired flow and resorption - brain tissue extends through the
* Choroid plexus : produces CSF cranium
* Arachnoid granulations : absorbs CSF - posterior fossa, most often
* Two types: * Anencephaly
A. Noncommunicating/obstructive - absence of most of the brain and
- no communication with subarachnoid Calvarium
space
- e.g. tumor in 3rd ventricle II. Forebrain anomalies
B. Communicating * Megalencephaly
- entire ventricular system is enlarged - large brain volume
* Microencephaly
III. Raised intracranial pressure and - small brain volume, more common
herniation * Lissencephaly
A. Subfalcine (cingulate) - reduced number of gyri
- cerebral hemisphere displaces cingulate * Agyria
gyrus under falx - no gyral pattern
- anterior cerebral artery is compresses * Polymicrogyria
- small numerous cerebral convolutions
B. Transtentorial (uncinate/ * Holoprosencephaly
mesial temporal) - incompletely separated hemispheres
- medial aspect of temporal lobe - Cyclops
compressed against tentorium
- third cranial nerve is compromised
UST FMS MEDICAL BOARD REVIEW 2019 1 | PATHOLOGY
 PATHOLOGY OF THE CENTRAL NERVOUS SYSTEM
HERBERT Z. MANAOIS, M.D.

* Agenesis of corpus callosum - brain atrophy in elderly is increased

- absent white matter risk
- “bat-wing” deformity * Chronic traumatic encephalopathy (dementia
puligistica)
III. Posterior fossa anomalies - repeated head trauma
* Arnold-Chiari malformation * 50% of all neurologic disorders
(Chiari type II) * Mortality Rate:
- small posterior fossa Brain Infarct -50
- misshapen cerebellum with downward Subarachnoid hemorrhage -10
extension of vermis through foramen Brain Hemorrhage -30
magnum Others -10
* Chiari type I
- less severe Cerebrovascular diseases
- cerebellar tonsils extend down in the
vertebral canal
* Dandy-Walker malformation I. Hypoxia, ischemia and Infarction
- enlarged posterior fossa * Brain
- vermis is absent or rudimentary - 1-2% of the body weight
- 15% of the cardiac output
IV. Syringomyelia and hydromyelia - 20% of the oxygen consumption
* Hydromyelia * Hypoxia
- expanded central canal - reduced oxygen
* Syringomyelia/syrinx * Anoxia
- fluid-filled cavity in the inner portion of - total absence of oxygen
cord * Ischemia
- may extend to brainstem (syringobulbia) - interrupted blood flow
* Infarction
Trauma - localized area of ischemic necrosis in an
organ or tissue
I. Skull fracture * Global cerebral ischemia (diffuse ischemic/
* occipital: when patient is awake hypoxic encephalopathy)
* frontal: when there is loss of consciousness - generalized reduction of perfusion
* meningitis may follow - cardiac arrest, shock, and severe
* Displaced skull fracture hypotension
- distance of displacement greater than - neurons are most sensitive
bone thickness - pseudolaminar necrosis
- uneven destruction and preservation
II. Parenchymal injuries - e. g. borderzone infarcts (watershed)
* Concussion - most distal reaches of arterial blood
- clinical syndrome of altered supply
consciousness due to head injury
* Direct brain injury * Focal cerebral ischemia
1. Contusion - localized area
2. Laceration 1. Embolism
- most common cause of focal cerebral
* Crest of gyri ischemia
- most susceptible to hemorrhage - cardiac mural thrombi: most common
* Orbital ridge of frontal lobe and source
temporal lobe - middle cerebral artery: most common
- most frequent site for contusion site
* Coup: point of contact 2. Thrombotic occlusion
* Countercoup : opposite - artherosclerotic plaque
* Plaque jaune - carotid bifurcation, middle cerebal
- yellow brown patches artery origin, basilar artery
* Diffuse axonal injury 3. Inflammatory processes
- deep white matter, cerebral - vasculitis (e.g., syphilis, tuberculosis,
peduncles, deep reticular formations aspergillosis, CMV, polyarteritis
nodosa)
III. Traumatic vascular injury
* Epidural hematoma II. Hypertensive cerebrovascular disease
- trauma * Lacunar infarcts
- dural artery (middle meningeal artery) - deep penetrating vessels
- lucid interval - arteriolar sclerosis
* Subdural hematoma - lake-like small cavitary infarcts
- trauma
- bridging veins
UST FMS MEDICAL BOARD REVIEW 2019 2 | PATHOLOGY
 PATHOLOGY OF THE CENTRAL NERVOUS SYSTEM
HERBERT Z. MANAOIS, M.D.

* Slit hemorrhages * Four principal routes

- rupture of small vessels A. Hematogenous
- slitlike cavity - most common
B. Direct implantation
* Hypertensive encephalopathy - traumatic or congenital malformation
- malignant hypertension C. Local extension
- diffuse cerebral dysfunction D. Peripheral nervous system
- rabies and herpes zoster virus
III. Intracranial hemorrhage
* Intraparenchymal hemorrhage
- hypertension (most common risk factor) Infections
and cerebral amyloid angiopathy
- Charcot-Bouchard aneurysms
- chronic hypertension * Acute meningitis
- minute aneurysms that may rupture - inflammation of leptomeninges and CSF
- basal ganglia - meningoencephalitis
- Common etiologies: - inflammation of brain and meninges
A. Hypertensive intraparenchymal
hemorrhage - Classification:
- putamen (50-60%), thalamus, 1. Acute pyogenic meningitis
pons, cerebellum - bacterial
B. Cerebral amyloid angiopathy - Waterhouse-Fridrechsen syndrome
- risk factor most commonly Causes of Acute Pyogenic Meningitis
associated with lobar Neonates E. coli
hemorrhages Group B
streptococcus
* Subarachnoid hemorrhage and ruptured Elderly S. pneumonia
saccular aneurysm L. monocytogenes
- saccular (berry aneurysm) Adolescents/young N. meningitidis
- most frequent cause of clinically adults
significant subarachnoid hemorrhage - septicemia, cutaneous petechiae,
- most common type of intracranial adrenal gland hemorrhagic infarction
aneurysm - meningococcal and pneumococcal
- anterior circulation meningitis
- absent smooth muscle and internal 2. Acute aseptic (viral) meningitis
elastic lamina - absent organism on bacterial
- fifth decade; females > males culture
- associated with increased ICP like - signs and symptoms of meningitis
straining or sexual orgasm - viral (in about 80% of cases
- “worst headache” then loss of enteroviruses), bacterial, rickettsial,
consciousness autoimmune
- less fulminant than pyogenic
* Vascular malformations - viral aseptic meningitis usually self-
- Four groups: limited
A. Arteriovenous malformation - enteroviruses : most common viral
- most common type of clinically
significant vascular malformations * Acute focal suppurative infections
- 10-30 years old; males > females A. Brain abscess
- middle cerebral artery : most common - usually bacterial
site - localized
- tangled wormlike blood vessels - acute bacterial endocarditis, , R-L
- neither purely arterial nor purely shunting in congenital heart disease,
venous (“arterialized veins”) pulmonary sepsis
- pulsatile A-V shunting with high blood - Staphyloccoci and streptococci
flow - most common in
- enlarged vessels separated by gliosis no immunosuppressed
B. Cavernous malformation B. Subdural empyema
- distended loosely organized C. Extradural abscess
- no brain tissue in between - osteomyelitis
C. Capillary telangiectasia * Chronic bacterial meningoencephalitis
- dilated thin walled vessels A. Tuberculosis
D. Venous angioma (varices) - arachnoid fibrosis and obliterative
endarteritis
- most serious complication
- diffuse meningoencephalitis
- most common pattern
UST FMS MEDICAL BOARD REVIEW 2019 3 | PATHOLOGY
 PATHOLOGY OF THE CENTRAL NERVOUS SYSTEM
HERBERT Z. MANAOIS, M.D.

- gelatinous and fibrinous exudate - children or young adults

- caseating granulomas - altered measles virus

B. Neurosyphilis * Fungal meningoencephalitis

- tertiary stage of syphilis A. Mucor : vasculitis
- Distinct forms: B. Aspergillus : vasculitis
A. Meningovascular syphilis C. Candida : brain invasion
- chronic meningitis D. Cryptococcus : brain invasion
- obliterative endartertis (Huebner - AIDS
arteritis) - mucoid- encapsulated yeasts
- gummas - basal leptomeninges
B. Paretic neurosyphilis - “soap bubbles”
- brain invasion and parenchymal - expanded perivascular (Virchow-Robin)
damage spaces with organisms
- general paresis of the insane
C. Tabes dorsalis * Toxoplasmosis
- damage to the sensory neurons - ring-enhacing lesions
axons in the dorsal roots - subacute
- locomotor ataxia, Charcot joints, - cerebral cortex
lightning pains and absent deep - tachyzoites and bradyzoites
tendon reflexes
Neurodegenerative Diseases
* Viral meningoencephalitis
- parenchymal infection associated with * Amoebiasis
meningoencephalitis and - Naegleria : necrotizing encephalitis
encephalomyelitis - Acanthamoeba : chronic granulomatous
- latency period
Bacterial Viral TB
- perivascular and parenchymal
mononuclear cells infiltrates Protein High High High
- glial nodules Glucose Low Normal Reduced or
- neuronophagia normal
- clusters around foci of necrosis WBC Neutrophils Neutrophilic Mononuclears;
- inclusion bodies then mixed (neutros
A. Herpes simplex virus type I lymphocytic and lymphs)
- children and young adults
Pressure High Slightly high
- only 10% with prior herpes infection
- temporal lobes and frontal lobes
CSF Purulent Colorless
- Cowdry type A intranuclear inclusions
B. Varicella-Zoster virus
- latent phase in the sensory neurons of the meningoencephalitis
dorsal root or trigeminal ganglia * Cerebral malaria
- reactivation (shingles) - Plasmodium falciparum
C. Poliomyelitis * Prions
- anterior horn motor neurons of the spinal - abnormal cellular protein
cord - PRPC to PRPSC
- rapidly progressive neurodegenerative
Prion Diseases disease
- sporadic , familial, or transmitted
D. Rabies - “spongiform change”
- most severe in brainstem - intracellular vacuoles
- Negri bodies - rapidly progressive dementia
- cytoplasmic eosinophilic inclusion * Creutzfeldt-Jakob disease - human
bodies - most common
- ascending entry to the CNS through * Gertsmann-Straussler- - human
peripheral nerves from the wound site Scheinker syndrome
E. HIV * Fatal familial insomnia - human
- microglial nodules with multinucleated * Kuru - human
giant cells * Scrapie - sheep/goat
F. Progressive multifocal * Mink-transmissible - mink
leukoencephalopathy encephalopathy
- JC polyoma virus * Chronic wasting disease - deer/elk
- oligodendrocytes >> demyelination * Bovine spongiform - cow
Encephalopathy

G. Subacute sclerosing panencephalitis Demyelinating Disease

- cognitive decline, spastic limbs, seizures
UST FMS MEDICAL BOARD REVIEW 2019 4 | PATHOLOGY
 PATHOLOGY OF THE CENTRAL NERVOUS SYSTEM
HERBERT Z. MANAOIS, M.D.

mitochondrial abnormality, and neuronal

- preferential damage to myelin loss
- relative preservation of axons  α-synuclein
 Lewy body : diagnostic hallmark
* Multiple sclerosis
 most common * Huntington disease
 autoimmune demyelinating disorder  autosomal dominant
relapsing and remitting of variable duration  fourth and fifth decade
 neurologic deficits, separated in time  progressive movement disorders and
 white matter lesions, separated in space dementia
 any age, mostly young adults  chorea and writhing movement
 women > men  progressive and fatal
 unilateral optic neuritis/retrobulbar neuritis  prototype of trinucleotide repeat expansion
 paresthesia; motor and sensory deficits (CAG)
 incoordination, paraplegia, ataxia, mental  protein huntingtin
dysfunction  atrophy of caudate nucleus
 sclerosis and plaques
 CSF: mildly elevated protein, moderate * Amyotrophic lateral sclerosis
pleocytosis, increased IgG,oligoclonal bands  most common form of neurodegenerative
motor neuron disease
* Central pontine myelinolysis  loss of upper motor neuron in the cerebral
 loss of myelin due to damage of cortex and lower motor neurons in the
oligodendrocytes spinal cord and brainstem
 symmetric  muscle denervation, fasciculation, and
 rapid correction of hyponatremia weakness
 loss of neurons  toxic protein accumulation
 hallmark : accumulation of protein  copper-zinc superoxide dismutase
aggregates
Toxic and Acquired
* Alzheimer disease Metabolic Disease
 most common cause of dementia in adults
 insidious impairment of higher cognitive * Thiamine deficiency
function,progressive disorientation, memory  Wernicke encephalopathy
loss and aphasia  acute psychotic symptoms and
 over 5 – 10 years, profoundly disabled, ophthalmoplegia
mute, and immobile  reversible
 cortical atrophy  mammillary bodies
 frontal, temporal and parietal lobes  Korsakoff syndrome
 hydrocephalus ex vacuo  prolonged and irreversible if Wernicke
 accumulation of Aβ and tau proteins encephalopathy is untreated and
 plaques (Aβ peptide) and tangles (tau) unrecognized
contribute to neural dysfunction  short term memory disturbance and
confabulation
 chronic alcoholism
Tumors
*  majority are primary tumors
Parkinson disease  ¼ to ½ are metastatic
 most common neurodegenerative  70% of childhood tumors are in the
 hypokinetic movement disorder posterior fossa
 prominent hypokinetic movement disorder  rarely metastasize outside to the CNS
 masked facies, stooped posture, slow  may spread through CSF
voluntary movement, festinating gait,
rigidity and “pill-rolling” tremor * Gliomas
 loss of dopaminergic neurons in substancia  most common group of primary brain
nigra tumors
 pallor of substancia nigra and locus ceruleus  Two major categories:
 damage to nigrostriatal dopaminergic 1. diffusely infiltrating
system 2. localized
 triad (in the absence of toxic or other known  Groups:
etiology): A. Astrocytoma
1. tremor 1. Infiltrating astrocytoma
2. rigidity - 80% of adult primary brain
3. bradykinesia tumors
- cerebrum (most), cerebellum,
 associated with MPTP (opioid mepiridine) brainstem
 protein accumulation and aggregation, - and spinal cord
UST FMS MEDICAL BOARD REVIEW 2019 5 | PATHOLOGY
 PATHOLOGY OF THE CENTRAL NERVOUS SYSTEM
HERBERT Z. MANAOIS, M.D.

- 4th to 6th decade  associated with von Recklinghausen’s

a. Diffuse astrocytoma disease
- grade 2 of 4  rounded mass and dural-based
- poorly defined, gray,  psammoma bodies
infiltrative  express progesterone receptors
- greater cell density,  rapid growth during pregnancy
variable pleomorphism
b. Anaplastic astrocytoma * Metastatic tumors
- grade 3 of 4  mostly carcinomas
- more densely cellular,  from lung, breast, skin (melanoma),
greater pleomorphism, kidney and GIT
mitotic  sharply demarcated
c. Glioblastoma  gray-white matter junction
- grade 4 of 4  well-defined boundary
- primary : older, more
common * Familial tumor syndromes
- secondary : younger 1. Turcot syndrome
- necrosis, hemorrhage and - Medulloblastoma
cysts - Glioblastoma
- necrosis and 2. Gorlin syndrome
endothelial/vascular - Medullobastoma
proliferation 3. Von Hippel-Lindau disease
- pseudopalisading - Hemangioblastoma
2. Localized astrocytoma - cerebellum and retina
a. Pilocytic astrocytoma - chromosome 3
- most common of the localized - increased erythropoietin
astrocytomas (polycythemia)
- grade 1 of 4 - vascular neoplasm
- relatively benign - associated with renal cell carcinoma and
- children and young adults pheochromocytoma
- cerebellum
- Rosenthal fibers
- eosinophilic granular bodies
- Biphasic -- Fin --

B. Oligodendroglioma
 grade 2 of 4 The mind is its own place, and in itself
 cerebral hemisphere (white matter) Can make a heaven of hell, a hell of heaven.
 “fried egg appearance” - John Milton
 better prognosis than astrocytoma

C. Ependymoma
 grade 2 of 4
 ventricular system
 perivascular pseudorosettes

* Poorly differentiated neoplasms

A. Medulloblastoma
 most common poorly differentiated or
embryonal tumor
 grade 4 of 4
 children
 exclusively in the cerebellum
 Homer-Wright rosettes
 highly malignant
 “drop metastases”
 exquisitely radiosensitive

* Meningioma
 benign, grade 1 of 4
 adults, female > male (3:2)
 attached to the dura
 arise from meningothelial cells of the
arachnoid
 prior radiation therapy is a risk factor
 loss of chromosome 22
UST FMS MEDICAL BOARD REVIEW 2019 6 | PATHOLOGY