Pathology Chapter 21 Central Nervous System and Eye

Cerebral _____ is the accumulation of excess fluid within the brain parenchyma

edema

________ edema occurs when the integrity of the blood-brain barrier is disrupted, allowing fluid to shift from the vascular compartment into the extracellular spaces of the brain.

________ edema is an increase in intracellular fluid secondary to neuronal and glial cell injury, as might follow a generalized hypoxic or ischemic insult or exposure to certain toxins.

Vasogenic (Extracellular)

Cytotoxic (Intracellular)

Cerebral Spinal Fluid is produced by the ______ ______

Choroid Plexus

Hydrocephalus is increase in the volume of the _______ within the ventricular system.

CSF

The 3 types of hydrocephalus are

______ Hydrocephalus where there is localized obstructuion

______ Hydrocephalus where CSF resorption is impaired

______ ______ due to brain volume loss

Noncommunicating, Communicating, Ex Vacuo (Secondary to brain loss)

________ is the displacement of brain tissue past rigid dural folds (the falx and tentorium) or through openings in the skull because of increased intracranial pressure.

Herniation

The 3 types of herniation are

______ (_____) caused by unilateral/asymetric expansion of cerebral hemisphere.

______ (_____) caused by medial temporal lobe displacement against the tentorium

______ Herniation caused by cerebellar tonsil displacement through foramen magnum

Subfalcine (Cingulate)

Transtentorial (Uncinate)

Tonsillar

3 types of herniation by effect and location

Subfalcine: Under falx cerebri and causes leg weakness

Transtentorial: Through temporal lobe and causes blown pupil (CN3)

Tonsillar: Through foramen magnum causing medulla compression to respiratory arrest (Very fatal)

_____ _____ are midline malformations involving neural tissues, meninges, and sometimes bone or soft tissue.

Risk factor include folate deficiency

Elevated _____ can diagnose this

Neural Tube

AFP

2 mechanism of neural tube defect are

Failure of neural tube closure (2)

Primary bony defects (3)

Anencephaly, Myelomeningocele

Encephalocele, Meningocele, Spina Bifida

Forebrain malformation include (3)

Microencephaly (Abnormal Small Brain)

Gyral Abnormalities: Lissencephaly loss of gyri and Polymicrogyria is excessive small gyri

Holoprosencephaly: Mild is absence of olfactory bulbs and severe is single cerebral hemisphere

Posterior fossa malformation include (3)

Arnold-Chiari Malformations (Chiari Type 2): Small posterior fossa

Chiari Type 1: Cerebellar tonsils extend through foramen magnum

Dandy-Walker: Enlarged posterior fossa

Several genetic diseases disrupt metabolic processes in neurons and glia, resulting in progressive disorders that present _____ in life.

early

Neuronal Storage Disease is enzyme deficiencies in degradation pathways

Mitochondrial Encephalomyopathies are dysfunction in oxidative phosphorylation in neurons (most in ____ matter) and skeletal muscle

Gray

Cerebrovascular diseases are brain disorders caused by pathologic processes involving _____ vessels.

Blood

3 pathogenic mechanisms of cerebrovascular diseases

_____ occlusion: formation of clot at site

_____ occlusion: blockage by material traveling from elsewhere

_____ rupture: bleeding into brain due to vessel breakage

_____ is the clinical term for acute symptoms of all 3

Thrombotic, Embolic, Vascular

Stroke

Difference between ischemia and hypoxia

Ischemia is lack of blood flow, depriving brain of oxygen and glucose

Hypoxia is oxygen deprivation from low oxygen levels, reduced oxygen-carrying capacity, or interference with oxygen use

Global cerebral hypoxia or ischemia occurs when there is a generalized reduction of cerebral perfusion or decreased oxygen-carrying capacity of the blood

Reduction can be due to cardiac arrest, shock, and hypotension

Reduced carry can be due to carbon monoxide poisoning

Cerebral arterial occlusion leads first to _______ and then to _______ in the distribution of the compromised vessel.

Ischemia, Infarction

Explain difference between nonhemorrhagic vs hemorrhagic

Nonhemorrhagic is ischemic and pale due to thrombosis

Hemorrhagic is embolic leading to reperfusion and damage vessel

Infarction is death of tissue due to inadequate blood supply

Infarction in anterior, middle, and posterior cerebral artery

Anterior: Motor and Sensory defects

Middle:

_______ within the brain are caused by (1) hypertension and other diseases leading to vascular wall injury; (2) structural lesions such as arteriovenous and cavernous malformations; (3) trauma; and (4) tumors.

Hemorrhages

_______ is the most common risk factor for deep brain parenchymal hemorrhages

Hypertension

______ is a disease in which amyloidogenic peptides, similar to those found in Alzheimer, deposit in wall of meningeal cortical vessels

CAA (Cerebral Amyloid Angiopathy)

The most frequent cause of clinically significant nontraumatic ________ hemorrhage is rupture of a saccular (berry) aneurysm.

Subarachnoid

4 types of vascular malformation of CNS

_____ are most significant and leading cause of hemorrhage

Cavernous malformation present with chronic issues like small hemorrhages

Capillary telangiectasias and venous angiomas are incidental finding and rarely problems

AVM

Hypertension causes ______ aeteriolar sclerosis

Hyaline

Weakens vessels making more prone to rupture and occlusion

Vasculitis in the CNS is most often the result of _______ or systemic autoimmune diseases. Causes impaired blood flow leading to infarction

Infections

Vascular Dementia is ______ ischemia due to infarcts

Chronic

Coup vs Contrecoup Injury

Coup is injury at site of impact

Contrecoup is injury on opposite of brain when brain rebound against skull

Contusion vs Laceration

Also what is concussion

Contusion are bruises and Laceration are tissue tearing

Concussion is reversibly altered brain function

_______ is a progressive neurodegenerative condition associated with repeated head trauma

CTE Chronic Traumatic Encephalopathy

Show Tau distribution and common in football and boxer

Vascular injury is a frequent component of CNS trauma; it results from disruption of the ______ wall and leads to hemorrhage in different anatomic sites

Vessel

Comparison between epidural and subdural

Epidural is arterial Subdural is venous

Epidural is lens-shaped and Subdural is crescent shaped

Epidural is rapid and Subdural is gradual

Epi for emergency require urgent surgery

Cerebral palsy is a term for ________ neurologic motor deficits characterized by injury occurring during the prenatal and perinatal periods.

Two major types of injury are hemorrhages and infarcts

nonprogressive

Hematogenous spread is the most ______ infections of nervous system

common

_______ is an inflammatory process typically induced by an infection involving the leptomeninges within the subarachnoid space; if the infection spreads into the underlying brain, it is termed ______.

Meningitis, Meningoencephalitis

Examination of _____ is used to identify cause of meningitis

Types are

Acute pyogenic (Bacterial)

Aseptic (Viral) (Not bacteria involved)

Chronic (Tuberculosis)

CSF

In acute pyogenic meningitis

E. Coli and Group B streptococci in common in neonates

Neisseria is common in young adults

S. pneumoniae and L. monocytogenes are common in older adults

Think as E. coli common in neonates because birth canal

When pathogens are identified, ______ are the most common in aseptic meningitis

Enterovirus

How to distinguish bacterial vs viral meningitis

If glucose is low, bacterial

If glucose normal and lymphocyte dominate, viral

______ meningitis can include tuberculosis, spirochetal (syphilis), and fungal

Chronic

A brain ______ is a localized focus of necrotic brain tissue with accompanying inflammation, usually caused by a bacterial infection.

Abscess

Big difference between brain abscesses and meningitis

Brain abscesses are normal glucose but high white cell and protein

Meningitis has low glucose

This is because CSF is involved in meningitis and abscess is usually local. Abscess will involve glucose if rupture into subarachnoid space

Viral _________ is a parenchymal infection of the brain that is almost invariably associated with meningeal inflammation

encephalitis

More severe than viral meningitis

Common virus include rabies and poliovirus

Arbovirus are a major cause of epidemic encephalitis caused by ______ borne virus

Arthropod

Difference between HSV-1 and HSV-2 (Herpesviruses)

HSV-1 most comon in children and young adults

HSV-2 usually in adults as meningitis

Rabies causes hydrophobia and is almost always ______

fatal

HAND is HIV-associated neurocognitive disorder associated with _____ cell infection. When effective anti-HIV therapy, there is a risk for IRIS (Immune reconstitution inflammatory syndrome)

microglial

ML is caused by JC virus and causes _________

demyelination

Epidural Abscess vs Subdural Empyema

Epidural (Dura and skull) abscess can cause spinal cord compression

Subdural (Dura and arachnoid) can spread and cause infections

Because of its high metabolic demands, the ______ is particularly vulnerable to nutritional imbalances and alterations in the body’s metabolic state.

brain

Wernicke Encephalopathy is ______ and due to thiamine deficiency and causes psycnosis, eye movement abnormalities. Korsakoff Syndrome is more ______ and can cause severe memory impairment

Acute, Chronic

Remember Thiamine also cause beriberi

In addition to anemia, deficiency of vitamin _____ may cause demyelination and axonal loss of _____ matter of spinal cord

B12, White

Myeline is produced by ______ in the CNS and ______ in the PNS. Typically affect ______ matter

Oligodendrocytes, Schwann, White

Demyelinating vs Leukodystrophy or dysmyelinating

Demyelinating is damage to healthy myelin such as multiple sclerosis

Luekodystrophy is myelin not formed properly

Multiple sclerosis (MS) is an autoimmune demyelinating disorder characterized by episodes of disease activity, separated in time, that produce _____ matter lesions that are separated in space.

The lesions of MS are caused by an autoimmune response directed against components of the ______ sheath in genetically predisposed individuals.

White

Myelin

Multiple Sclerosis is 15 fold higher in 1st degree relative and 150 times higher in monozygotic twin. Strong effect in HLA-DRB1×1501 allele

In autoimmunity, the disease is initiated by ___ and ___ T cells and B cells that react against myelin antigens and secrete cytokines

Also associated with Epstein-Barr Virus

Th1 and Th17

Leukodystrophies are _______ dysmyelinating diseases characterized by abnormal myelin synthesis or turnover.

____ is X-linked and Krabbe and Metachromatic are autosomal recessive

Inherited

ALD

Neurodegenerative diseases are characterized by the progressive loss of ______, typically affecting groups of neurons with shared functions.

______ aggregation underlies most of these and toxic _____ are responsible of damage

neurons

Protein, Oligomer

_____ diseases are rapidly progressive neurodegenerative disorders caused by aggregation and intercellular spread of a misfolded prion protein.

Mechanism is PrP undergoes a conformation change from ______ (a-helix) to _____ (B-sheet).

Prion

PrPc, PrPsc (PrPsc can also induce PrPc to become more PrPsc)

CJD vs vCJD

vCJD is in younger adults and slower and linked to bovine exposure

Alzheimer Disease is the most common cause of dementia in older adults, with increasing incidence as a function of age.

The principal abnormality in AD is the accumulation of two proteins, ___ and __, in the forms of plaques and tangles, respectively, in specific brain regions; these changes result in secondary effects including neuronal dysfunction, neuronal death, and inflammatory reactions.

Ab and tau

Ab plaque is extracellular and tau tangles are intracellular

Frontotemporal lobar degeneration (FTLD) is a heterogeneous group of disorders associated with focal _____ of the frontal and/or temporal lobes.

Types include FTLD tau and TDP.

Pick disease is a subtype with pronounced lobe atrophy and presence of pick bodies

degeneration

Main difference between AD and FTLD

Alzheimer is early memory disturbances

Frontotemporal lobar degeneration is language problem first and memory loss later

_____ disease is a neurodegenerative disease marked by a hypokinetic movement disorder due to loss of dopaminergic neurons from the substantia nigra.

May be induced by dopamine antagonist or toxins also heroin and pesticide

Parkinson

Parkinson is associated with protein accumulation, mitochondrial dysfunction, and neuronal loss in substantia nigra.

Hallmark is presence of _____ bodies that contain a-synuclein

Lewy

Initial treatment for Parkinson

L-DOPA is initially effective in improving motor function, but it becomes less effective over time, leading to motor fluctuations. Does not slow down disease progression

Deep brain stimulation can help reduce need

When dementia arises within 1 year of onset of motor symptoms in parkinson, it is referred to Lewy Body ______

Dementia (LBD)

Atypical Parkinsonian Syndromes often have more rapid progression, _____ L-DOPA response, and distinct pathologies

Poor

Progressive supranuclear palsy, Corticobasilar degeneration, Multiple system atrophy

Huntington disease (HD) is an autosomal ______ movement disorder associated with degeneration of the striatum (caudate and putamen).

HD is caused by repeat expansions of a _____ trinucleotide (encoding glutamine) in a gene that encodes the protein huntingtin

Dominant

CAG

Spinocerebellar ataxias (SCAs) are a heterogeneous group of several dozen autosomal _______ diseases with clinical findings that include a combination of cerebellar and sensory ataxia, spasticity, and sensorimotor peripheral neuropathy.

Friedreich ataxia is an autosomal _______ disorder that generally manifests in the first decade of life with gait ataxia, followed by hand clumsiness and dysarthria

Dominant

Recessive (GAA repeat)

Amyotrophic lateral sclerosis (ALS) results from the _____ of lower motor neurons in the spinal cord and brain stem and upper motor neurons in the cerebral cortex.

death

Unique Characteristics of CNS Tumors

No premalignant lesion

Anatomical influence outcome

Even highly malignant rarely spread outside CNS

Cerebral Edema vs Hydrocephalus

Cerebral edema is fluid accumulation within brain parenchyma

Hydrocephalus is accumulation of CSF

Ischemic vs. Hemorrhagic Stroke

Ischemic due to embolism

Hemorrhagic due to ruptured blood vessels