CNS Pathology

CSF blockage which causes __

hydrocephalus

what are the 3 causes of hydrocepalus?

1. obstruction (congenital or acquired) - most common

2. impaired absorption by arachnoid villi

3. overproduction of CSF by choroid plexus neoplasms (rarest)

CNS __ often directly disrupts vessel walls, leading to hemorrhage.

trauma

Hematoma foramtion can be caused by...

epidural, subdural, subarachnoid, or interparenchymal

what vessels cause an epidural hematoma? what is the usual cause?

Tear in the dural vessels (especially the middle meningeal artery), secondary to a skull fracture

what demographic is susceptiple to epidural hematoma?

infants- deformable/ soft skull

children and adults- tears almost always stem from skull fractures

Once a vessel is torn, blood accumulating under arterial pressure can dissect the tightly applied dura away from the inner skull surface producing a ___

hematoma

why is a hematoma so dangerous to the brain?

compresses the brain surface

what are the symptoms of an epidural hematoma?

Clinically, patients can be lucid for several hours between themoment of trauma and the development of neurologic signs

how is an epidural hematoma tx?

may expand rapidly and constitutes a neurosurgical emergency necessitating prompt drainage and repair to prevent death

what causes a subdural hematoma?

Rapid movement of the brain during trauma tears the bridging veins that extend from the cerebral hemispheres through the subarachnoid and subdural space to the dural sinuses > bleeding in subdural space

what population has a higher rate of subdural hematomas?

Elderly patients with brain atrophy- bridging veins are stretched out, and the brain has additional space within which to move

infants- bridging veins are thin-walled

Subdural hematomas typically become clinically evident within the __(time)__ after injury

first 48 hours

where is the typical location of subdural hematomas?

They are most common over the lateral aspects of the cerebral hemispheres and may be bilateral

what are symptoms of subdural hematomas?

Neurologic signs: headache, confusion, and slowly progressive neurologic deterioration.

how are subdural hematomas tx?

surgical removal of the blood and associated reactive tissue.

what are chronic subdural hematomas?

when subdural hematomas re-bleed

a collection of freshly clotted blood apposed to the contour of the brain surface, without extension into the depths of sulci

acute subdural hematoma

With a subdural hematoma, the underlying brain is __, and the subarachnoid space is often clear.

flattened

what is the process of healing for a subdural hematoma?

1. 1 wk lysis of clot

2. 2 wks- granulation tissue from dural surface into hematoma

3. 1-3 mo fibrosis

4. fibrosing lesions can retract and leave thin layers of CT

injury to the brain asa result of altered blood flow is called...

cerebrovascular disease; usually a Cerebrovascular accident (CVA) or "Stroke"

what are the 2 mechanisms of a CVA? what is the most common CVA?

1. Hypoxia, ischemia, and infarction via embolism

-embolism more common than thrombosis

2. hemorrhage (rupture of CNS vessels) via HTN, aneurysms, malformation

what causes cerebral infarctions? (Cut off of O2)

1. Atherosclerotic thrombi- carotid artery atherosclerotic disease

2. Emboli of cardiac origin- secondary to valvular pathology, MIs, cardiac arrhythmias

emboli that lead to cerebral infarctions are secondary to what conditions?

- valvular (esp mitral valve) pathology

- acute anterior myocardial infarctions or congestive cardiomyopathies (DCM> CHF) resulting in cardiac mural hypokinesias or akinesias with thrombosis

- cardiac arrhythmias (typically atrial fibrillation)

-valve disease

-MI

-AFIB

what is the appearance of cerebral infarctions with time?

1st 6 hrs- little change in appearance

1st 48 hrs- pale, soft, and swollen tissue

2-10 days- gelatinous and friable brain; distinct location of injury

10 days - 3 wks- liquefaction necrosis

what is the most common risk factor associated w/ intracerebral hemorrhage?

HTN

what causes vessel wall abnormalities (making them weaker and more vulnerable to rupture) in intracerebral hemorrhages? what are the 3 types of vessel wall abnormalities?

Hypertension

-accelerated atherosclerosis in larger arteries

-hyaline arteriosclerosis in smaller arteries

-frank necrosis of arterioles

what is the most common sites of Intracerebral (Intraparenchymal) Hemorrhage?

putamen (50 - 60% of cases), thalamus, pons, cerebellar hemispheres (rarely), and other regions of the brain

what is the most common cause of subarachnoid hemorrhage?

rupture of a saccular aneurysm in a cerebral artery

what is the most common type of intracranial aneurysm? which vessels are most commonly effected?

Saccular ("berry") aneurysm; vessels within the circle of Willis

what are other causes of subarachnoid hemorrhages?

-traumatic hematoma extending

-rupture of a hypertensive intracerebral hemorrhage into the ventricular system

-vascular malformations

-hematologic disturbances and CNS tumors

inflammation of the meninges

meningitis

what is the most serious form of meningitis?

bacterial

Acute pyogenic (bacterial) meningitis is infection of the __, and the CSF, which diffusely affects the whole meninges and subarachnoid space

leptomeninges (pia and arachnoidmater)

infection of leptomeninges caused by mainly Neisseria meningitidis and Streptococcuspneumoniae

Acute pyogenic (bacterial) meningitis

common bacteria ass w/ acute pyogenic meningitis?

neisseria meningitis and streptococcus pneumoniae

About _% of those who develop bacterial meningitis have symptoms that develop over _ hours. The remainder generally become ill over __ days

25%, 24hrs, 1 to 7 days

what are common symptoms associated with bacterial meningitis?

headache, stiff neck, fever and chills, vomitting, photophobia, confusion, seizures and recent URT infection

what bacteria can cause multiple organ involvement and start as which meningitis? what is it called when it spreads to multiple organs? what are the signs/ symptoms of this?

Meningitis caused by N. meningitidis may progress to a meningococcemia with multiple organ involvement, and may be associated with maculopapular, petechial, or purpuric skin rash

a rare, life-threatening condition defined by acute adrenal gland failure caused by massive bleeding into the glands, usually triggered by a Meningococcus bacteria (Neisseria meningitidis) is the most frequent cause.

Waterhouse-Friderichsen syndrome

how is bacterial meningitis dx?

The CSF is cloudy due to increased numbers of neutrophils (>1000 cells/mm 3 ). CSF protein levels increase andglucose concentrations fall.

how is bacterial meningitis tx?

vigorous intravenous antibiotic therapy

how is bacterial meningitis prevented?

a vaccine is available for meningitis caused by Neisseria meningitidis

what is the mortality rate for bacterial meningitis? Who is most effected?

3% for H. influenzae to 60% for Strep. pneumoniae, and it is highest in the very young and the elderly

what are long term complications of bacterial meningitis?

most are subtle but can have: nerve deafness, cortical blindness, muscular hypertonia, complex seizures

what is the most common cause of meningitis? what causes this type?

viral (Aseptic) meningits- mumps/ measles (paramyxovirus), enteroviruses (echoviruses, Coxsackie viruses, and polioviruses)

what are the symptoms of viral meningits?

acute onset of headache,fever, nuchal rigidity; irritability, and rapid development ofmeningeal irritation

how is viral meningitis dx?

SF is clear and colorless, w/ excess lymphocytes, increased protein, and normal glucose concentration

how is viral meningitis tx? what is the prognosis?

palliative care, complete recovery

what is a severe focal infection of the brain and is typically __ cm across

brain abcess; 1 to 2 cm across

how does a brain abscess start as?

starts as an area of cerebritis [inflammation of the brain parenchyma] and develops into a pus-filled cavity walled off by gliosis and surrounded by cerebral edema

what are the main causes of brain abcesses?

-middle ear infections

-frontal sinus infections

-bacteremia / septicemia

what organisms lead to brain abcesses?

Streptococcus viridans, Staphylococcus aureus and Klebsiella, but it may also becaused by fungal infection.

what are common signs/ symptoms of a brain abscess? Tx?

-similar to meningitis but more focal signs: epilepsy, and fever

-aggressive antibiotic therapy early, with surgical aspiration or excision of the capsule.

what is the mortality rate for brain abcesses?

10%

what are common complications of brain abcesses?

-Meningitis

-Intracranial herniation

-Focal neurological deficit

-Epilepsy

what is the most common of the demyelinating disease? When does it begin?

multiple sclerosis; 20-30 yrs old and more common in women

relapsing and remitting episodes of immunologically mediated demyelination within the CNS

multiple sclerosis

multiple sclerosis (MS) is characterized by irregularly scattered, focal areas of demyelination in the __ and __.

brain and spinal cord.

what are clinical manifestations/ signs of MS?

weakness of the lower extremities, visual disturbances and retrobulbar pain, sensory disturbances, and possible loss of bladder control

what is the classic Charcot triad? what disease is it associated with?

-nystagmus (eye movement), intention tremor (tremor worsens with targeted movements), and dysarthria (pauses in speech)

-MS

what is Uhthoff's Phenomenon? what disease is it associated with?

hot bath, messed up vision = MS

what are some oral manifestations of MS? what dental problems can this lead to?

-facial weakness/ paralysis

-dysphagia > aspiration risks

-trigeminal neuralgia >oral hygiene problems

-tongue/ motor dysfunction

-TMD

-chronic sys inflammatino and immune dysregulation

unusual muscle movement that resembles movement ofa "bag of worms". What nerve is affected? what disease is it associated with?

facial myokymia

CN VII

MS

ms pts have a 15-20 fold increased risk for dev __

trigeminal neuralgia

what are the degenerative diseases of the CNS?

prototype of cortical degenerative diseases and accounts for the majority (50 - 75%) of all cases of dementia

Alzheimer disease

AD affects __% of those over age 65, and __% overage 80. Risk of developing AD doubles every __ yrs

-10 - 15% of those over age 65

-20% of those over 80

-risk doubles after every 5 yrs after age 65

-females 2:1

AD affects what 3 processes that keep neurons healthy?

communication, metabolism, and repair

__ and __ tangles are the two major risk factors for AD

Beta-amyloid senile plaques and neurofibrillary tangles

amyloid plaque

autophagy dysfunction

cholinergic dysfunction

mitochondrial dysfunction

neurofibrillary tangles

neuroinflammation

AACMNN

What 2 proteins accumulate in the brain in AD pts?

1. Beta-amyloid (Aβ) that form senile plaques (SPs)

2. Tau: which form neurofibrillary tangles (NFTs) > neural inflammation and death accompany the progression and cognitive decline

what is the primary critical initiating event for the development of AD and precedes the clinical(symptomatic) onset of AD? What are these plaques made of?

accumulation of SPs- formed from beta-amyloid plaques

what are beta-amyloid plaques formed from?

Beta-amyloid (Aβ) is formed from the transmembrane protein amyloid precursor protein (APP) > aggregate and form senile plaques

amyloid has what effect on neurons?

directly neurotoxic; sm amt > neuronal synaptic dysfunction by blocking long-term potentiation

inflammatory response from microglia and astrocytes in the brain, stimulating their secretion of mediators that cause damage to neurons.

what are the proteins and composition of nuerofibrillary tangles (NFTs)?

filaments of hyperphosphorylated tau protein; hyperphosphorylated tau loses ability to bind to microtubules and forms NFTs that accumulate in pyramidal neurons

what are the 2 ways the NFT injures neurons?

1. tau aggregates elicit stress response leading to neuronal death

2. microtubule stabilizing function of tau is lost leading to neuronal toxicity and death

what enzyme and product contributes to memory and attention deficits seen in AD patients?

Choline acetyltransferase (ChAT) and its product, acetylcholine, is decreased

what are clinical symptoms of AD pts?

-difficulty learning, judgement impairment to agitation and psychosis in later stages

what are the gross pathological findings in AD pt?

-cortical atrophy and widening of cerebral sulci.

-Atrophy causes compensatory ventricular enlargement (hydrocephalus ex vacuo)

-brain wt reduced from 1400g to 1000g

the cortical atrophy seen in Alzheimer disease leads to compensatory __ known as "hydrocephalus ex vacuo".

dilation of the cerebral ventricles

what cells surround beta-amyloid plaques in a senile plaque?

microglial cells and reactive astrocytes

intraneuronal cytoplasmic granule-containing vacuoles occurring within the pyramidal cells of the hippocampus

Granulovacuolar degeneration

elongated, glassy, eosinophilic bodies consisting of paracrystalline arrays of beaded filaments, with actin as their major component. They are found most commonly within hippocampal pyramidal cell

Hirano bodies

distorted, twisted and dilated dendritic processes and axons of cerebral cortex found around Aβ plaques.

Neuropil threads

what is the arrow pointing at?

neurofibrillary tangle- composed of insoluble cytoskeletal-like hyperphosphorylated tau (paired helical) fibrils.

The presence of a large burden of SPs and NFTs is highly associated with slight, moderate or severe cognitive dysfunction?

severe

what are the biochemical markers of dimentia?

decrease of choline acetyltransferase activity (ChAT) and beta-amyloid

Parkinson disease (PD) is a slowly progressive, debilitating, degenerative disorder of the __ characterized resting tremor, bradykinesia, rigidity, postural changes, and often mental changes

basal ganglia

what is the epidemiology and demographics of PD?

0.3% of gen pop, 3% of those over 65, females (3:2)

what is the etiology of the 2 types of PD?

primary: idiopathic- genetic and environmental factors (75%)

secondary: acquired- inherited, trauma, drugs/ toxins, Shy-Drager syndrome (25%)

what neurons and where are these neurons degenerated in Parkinson's disease (PD)?

-pigmented dopaminergic neurons

-substantia nigra (midbrain- upper part of brainstem)

what does degeneration of pigmented dopaminergicneurons lead to in PD?

reduced amt of dopamine in the corpus striatum

Surviving cells in the substantia nigra contain eosinophilic spherical inclusions called...

Lewy bodies

When these α-synuclein proteins misfold, they aggregate into rigid, insoluble filaments (about 5 to 10 nanometers in diameter). These toxic clumps gather inside neurons to form the dense spherical masses known as....and in what disease is this a hallmark for?

lewy bodies; PD

What are the clinical signs of PD?

Is an autosomal dominant, fatal, progressive movement disorder associated with degeneration of the striatum (caudate and putamen

Huntington's disease - degenerative disease

HD especially affects __ and __ neurons, and which part of the brain?

cholinergic and GABA-ergic neurons

caudate and putamen- striatum

when do symptoms of Huntington's disease (HD) become apparent?

Is characterized by the delay of clinical abnormalities until age 30 to 40; course extends 15 to 20 years

what are the nucleotides seen in HD pts?

-increased copies (more than the normal 11 to 34) of CAG trinucleotide repeats within the HD gene on the short arm of chromosome 4 (4p16.3) that encodes the huntingtin protein

what proteins are toxic and lead to HD?

huntingtin protein- subject to ubiquitination and proteolysis yielding fragments that can form intranuclear aggregates > toxic and injurious to neurons