What is Vasogenic edema and is often seen following what?
- Increased EXTRAcellular fluid due to BBB disruption and increased vascular permeability
- Fluid shifts from INTRAvascular compartments to INTERcellular spaces
- Can be either localized (i.e., adjacent to neoplasms or inflammation) or generalied often follows ischemic injury
What is Cytotoxic edema and when is it seen?
- Increase in INTRAcellular fluid secondary to neuronal, glial, or endothelial cell membrane injury
- Generalized hypoxic/ischemic insult or w/ metabolic derangment
In practice, will oftens see elements of which type of edema(s)?
What morphological characteristics of the brain will be seen and this can lead to?
- Both vasogenic and cytotoxic edema
- Gyri flattened, sulci narrowed, and ventricles compressed —> Herniation!
What type of injury is associated with localized vs. generalized vasogenic edema?
- Localized: adjacent to inflammation or neoplasms
- Generazlied: follow ischemic injury
What is the most common cause of noncommunicating (obstructive) hydrocephalus in the neonate/infant?
Aqueductal stenosis
Enlargement of the entire ventricular system (“symmetric dilation”) due to accumulation of CSF not being properly absorbed at the dural sinus level is known as?
Communicating (“non-obstructive”) hydrocephalus
What 2 congenital conditions cause ventricular system obstruction?
1) Acqueductal stenosis
2) Dandy-Walker malformation
What is Hydrocephalus Ex-Vacuo?
Whom is it seen in?
What is the CSF pressure?
- Compensatory increase in ventricular volume secondary to loss of brain parenchyma
- Atrophy with increasing age, stroke or other injury, chronic neurodegenerative disease
- CSF pressure is NORMAL!!!
Herniation is displacement of brain tissue due to _____ or ______
Mass effect or Increased intracranial pressure
What is diffuse vs. focal mass effect that is associated with herniation?
- Diffuse: generalzied brain edema
- Focal: tumors, abscesses, or hemorrhages
Subfalcine herniation involves displacement of the _______ under the _______
Cingulate gyrus under the falx cerebri
A subfalcine herniation may lead to compression of the ________ artery leading to infarction
Anterior Cerebral artery (ACA)
What symptoms would result from Subfalcine herniation with compression of the ACA?
Contralateral lower extremity weakness
Transtentorial (uncinate, mesial temporal) herniation occurs when?
Which specific part and of which lobe?
MEDIAL aspect of the TEMPORAL lobe is compressed against the free margin of the tentorium
What are 3 possible consequences of progression of transtentorial herniations?
1) Compression of CN III —> pupillary dilation; eye is “down and out” (ipsilateral to lesion)
2) Compression of PCA —> ischemia of primary visual cortex
3) Large herniation may compress contralateral cerebral peduncle —> hemiparesis ipsilateral to side of herniation = Kernohan notch = “false localizing sign”
What are Duret hemorrhages and are a result of what?
- Progression of transtentorial herniation producing secondary hemorrhagic lesions in the midbrain and pon
- “Flame-shaped” lesions
Why is it crucial to exam the eyes of a patient you expect to be suffering from increased intracranial pressure?
Look for papilledema
What are congenital causes of hydrocephalus?
- Intrauterine infections (TORCH)
- Agenesis/atresia/stenosis
- Arnold chiari malformations
- Dandy walker syndrome
- Cranial defects: Achondroplasia and Craniostenosis
Which rare type of brain tumor leads to increased CSF production, thus causing increased ICP and hydrocephalus?
Choroid Plexus Papilloma/Carcinoma
What is the most common parasitic nervous system disease in the world and can lead to hydrocephalus?
- Cysticercosis
- Taenia Solium (pork tapeworm)
What are the characteristic of normal pressure hydrocephalus and who is it seen in?
- Symmetric type usually occuring in adults >60
- Develops slowly over time; drainage of CSF is blocked gradually
- Enlarged ventricles still exert pressure on brain and can become symptomatic w/ pt’s exhibiting dementia-like manifestatons
- Dementia may be similar to Alzheimers and gait abnormalities may suggest Parkinson disease
- NPH is often misdiagnoses as one of these diseases
What is the classic triad of clinical findings exhibited by patients with normal pressure hydrocephalus?
- “Wet, wacky, and wobbly”
- Often exhibit a magnetic gait
- Dementia-like sx’s; impaired recognition (often not severe)
- Urinary incontinence; appears late in illness and is generally of the spastic hyperreflexic, increased-urgency type
A right hemisphere trans-tentorial herniation, causes a Kernohan’s notch in the _____ cerebellar peduncle, which results in ________ motor impairment.
A right hemisphere trans-tentorial herniation, causes a Kernohan’s notch in the left cerebellar peduncle, which results in right-sided motor impairment.
What is a tonsillar herniation and why is it life threatening?
- Displacement of the cerebellar tonsils through the foramen magnum
- Can can brainstem compression and compromises vital respiratory and cardiac centers in the medulla
What is Cerebral Palsy and what are the clinical manifestations of this disease?
Occurs due to insults during which period?
- Non-progressive neurologic motor deficits characterized by combination of spasticity, dystonia, ataxia/athetosis, and paresis
- Pre-natal and perinatal periods (are present from birth)
What type of hemorrhage is seen in the germinal matrix of premature infants?
Often found near which junction; may extend where and cause?
- Intraparenchymal hemorrhage
- Junction between thalamus and caudate nucleus
- May extend into ventricles —> subarachnoid space —> hydrocephalus (obstructive)
Infarcts may occur in the supratentorial white matter of premature infants and are known as?
Characteristic finding?
- Periventricular leukomalacia
- Chalky yellow plaques = white matter necrosis and calcification
Extensive ischemic damage of both white and gray matter leading to large cystic lesions during the perinatal period is known as?
Risk factor for developing?
- Multicystic encephalopathy
- Cerebral Palsy
Perinatal ischemic lesions of the cerebral cortex leading to thinned-out, gliotic gyri is known as?
Ulegyria
Diastatic fracture
Fracture that crosses a suture
If the head is immobile at the time of trauma, what time of injury will be found?
Only a coup injury
Clinical term for altered consciousness secondry to a head injury typically brough about by a change in momentum of the head
Concussion
Which intracranial location is most susceptible to a direct parenchymal injury which results from trauma to the head?
Crests of the gyri = greatest amt. of force
What is the morphology of a brain contusion?
What is seen early on and within 24 hours?
- Wedge shaped w/ a broad base lying along the surface at the point of impact
- Early stages: pericapillary edema and hemorrhage
- 24 hours: pyknosis of the nucleus, eosinophilia of cytoplasm and disintegration of the cell
What is the characteristic appearance of old traumatic lesions on the surface of the brain?
Where is the morphology most commonly seen?
- Depressed, retracted, yellowish-brown patches involving the crest of the gyri (plaque jaune)
- Most commonly located at the sites of countercoup injuries
Diffuse axonal injury is best demonstrated using what lab techniques/stains?
- Silver impregnantion (silver stain)
- Immunoperoxidase stains for amyloid precursor protein and α-synuclein
As many as 50% of individuals who develop coma shortly after trauma, even without cerebral contusions, are believed to have?
Diffuse axonal injury
Sudden onset of severe headache (“worst headache of my life”), often with rapid neurologic deterioration is consistent with a _________ hemorrhage
Subarachnoid
Secondary injury associated seen in subarachnoid hemorrhage is often associated with what?
Vasospasm
A patient presents after a direct blow to the head which initially knocked him unconscious, after a couple hour lucid interval he begins to exhibit neurological deterioration, what do you suspect?
Epidural hematoma
What type of hematoma is associated with rupture of the bridging veins?
Subdural hematoma
Which patient populations are at higher risk for subdural hematomas?
- Elderly w/ brain atrophy due to increased stretching of the bridging vein
- Infants due to thin-walled bridging veins
What is the sequence/timeline for breakdown and organization of a subdural hematoma?
- Lysis of the clot (about 1 week)
- Growth of fibroblasts from dural surface into the hematoma (about 2 weeks)
- Early development of hyalinized CT (1-3 months)
*Typically retracts to a thin layer of CT called subdural membranes
What is seen in the brains of individuals with CTE (dementia pugilistica) during a post-mortem autopsy?
- Atrophic w/ enlarged ventricles
- Accumulation of tau-containing neurofibrillary tangles
- Characteristic pattern involving superficial frontal and temporal lobe cortex
After some time following an injury to the spinal cord what is seen in cord sections above and below the injury?
Secondary ascending and descending wallerian degeneration, involving the long white-matter tracts
What is Penumbra?
Animal models have shown that this area may be rescued how?
- Area of “at-risk” tissue at the region of transition between necrotic tissue and the normal brain
- May be rescued by anti-apoptotic meaures, implying that cells in areas of ischemia may die by apoptosis
Which neurons are the most sensitive to global cerebral ischemia?
- Pyramidal cell layer of hippocampus (especially area CA1, Sommer sector)
- Cerebellar purkinje cells
- Pyramidal neurons in cerebral cortex
The border zone between which arteries in the cerebral hemispheres are most at risk for an infarct following global ischemia?
Between ACA and the MCA
Border zone (“watershed”) infarcts are usually seen after ________ episodes
Hypotensive
Which pattern of injury is seen in the cerebral neocortex following global ischemia?
Pseudolaminar necrosis
What are the subacute changes seen 24 hours to 2 weeks after global ischemia?
- Tissue necrosis
- Influx of Macrophages and Reactive gliosis (10 days)
- Vascular proliferation
Following global ischemia you see ______ of the gyri and _____ of the sulci
- Widening of the gyri
- Narrowing of the sulci
*Edema
Global cerebral ischemia occurs after which events?
Cardiac arrest, shock, or severe hypotension
What is the most common cause of Embolism to the brain?
Important predisposing factors?
- Cardiac mural thrombi (often form post-MI) > atheromatous plaques (carotid arteries)
- MI, valvular disease, and atrial fibrillation (pre-disposing factors)
Which artery is most frequently affected by embolic infarction?
MCA — direct extension of the internal carotid artery
Widespread hemorrhagic lesions involving the white matter are characteristic of embolization of _______ after trauma
Bone marrow
Most common sites for thrombotic occlusions in the brain
- Carotid bifurcation
- Origin of MCA
- Either end of Basilar artery
Infectious vasculitis of small and large vessels occurs w/ syphilis and tuberculosis, but is now more common in the setting of?
- Immunosuppression
- Opportunistic infection (i.e., aspergillosis or CMV encephalitis)
Primary angiitis (aka granulomatous angiitis) of the CNS is characterized by?
Chronic inflammation, multinucleated giant cells, and destruction of the vessel wall
Thrombolytic therapy following an infarct is contraindicated in?
Hemorrhagic infarcts –> may cause extensive intracerebral hematomas
Infarcts are often initially nonhemorrhagic, but secondary hemorrhage can occur from ______ injury
Ischemia-reperfusion
What are the most common locations for lacunar infarcts?
- Lenticular nucleus
- Thalamus
- Internal capsule
- Deep white matter
What are the cytoplasmic bodies seen in myoclonic epilepsy?
Lafora Bodies
How can HTN lead to the development of lacunar infarcts?
Cerebral vessesl develop arteriolar sclerosis and may become occluded —> Lacunes
Small slit like cavity that is surrounded by a brownish discoloration after reabsorption of a hemorrhage is known as what?
Slit hemorrhage
What is Binswanger disease?
Pattern of injury from multifocal vascular diseases involving large areas of subcortical white matter w/ myelin and axon loss
Hypertensive encephalopathy is a consequence of?
Malignant hypertension
Patients who have bilateral gray and white matter infarcts over many months and years may develop what distinct clinical syndrome characterized by dementia, gait abnormalities, pseudobulbar signs and other focal neuro deficits?
Vascular (multi-infarct) dementia
What is the risk factor most commonly associated with deep brain parenchymal hemorrhages?
HTN
What causes Charcot-Bouchard microaneurysms?
Chronic HTN
What is a Charcot-Bouchard microaneurysm vs. Saccular (berry) aneurysm?
Where is each most commonly seen?
- Charcot-Bouchard occur in vessels less than 300 um in diameter; most often within basal ganglia
- Saccular (berry) aneurysms occur in larger intracranial vessesl in the subarachnoid space
What is the risk factor most commonly associated with lobar hemorrhages?
Cerebral amyloid angiopathy (CAA)
The presence of which alleles may increase the risk of repeat bleeding from sporadic CAA?
ε2 or ε4
Where are the vascular abnormalities of CAA most often seen and how does CAA differ from arteriolar sclerosis?
- Leptomeningeal and cerebal cortical arterioles
- In CAA, there is no fibrosis
What is the mutation associated with Cerebral Autosomal Dominant Arteriopathy w/ Subcortical Infarcts and Leukoencephalopathy (CADASIL)?
NOTCH3
Cerebral Autosomal Dominant Arteriopathy w/ Subcortical Infarcts and Leukoencephalopathy (CADASIL) is characterized clinically how?
Recurrent strokes (usually infarcts, less often hemorrhages) and dementia
Most frequent cause of clinically significant subarachnoid hemorrhage is rupture of?
Saccular (berry) aneurysm
What is the structural abnormality of vessels that lead to saccular (berry) aneursyms?
Absence of smooth muscle and intimal elastic lamina = developmental disorder
There is an increased incidence of saccular (berry) aneursyms in people with what disorders?
- AD polycystic kidney disease
- Ehlers-Danlos type IV
- NF1
*Smoking and HTN are risk factors
What is the most common site for Arteriovenous Malformations?
MCA; particularly its posterior branches
Who is most at risk for Arteriovenous Malformations?
How does it present?
- Males twice as frequently; between ages 10-30
- Presents as seizure disorder, intracerebral hemorrhage, or subarachnoid hemorrhage
Morphology of Arteriorvenous Malformations
Tangled vessels (“worm-like”) that show prominent, pulsatile arteriovenous shunting with high blood flow – bypass a capillary bed
Waterhouse-Friderichsen syndrome results from?
Occurs most commonly due to meningitis caused by?
- Meningitis-associated septicemia w/ hemorrhagic infarction of the adrenal glands and cutaneous petechiae
- Meningococcal and pneumococcal meningitis
What is chemical meningitis?
Nonbacterial irritant introduced into the subarachnoid space
How can hydrocephalus result from pyogenic meningitis?
Particularly with what organism?
- Capsular polysaccharide of pneumococcal meningits produces a gelatinous exudate that promotes arachnoid fibrosis
- Referred to as chronic adhesive arachnoiditis
What are predisposing conditions for the development of a brain abscess?
- Acute bacterial endocarditis
- Congenital heart disease (w/ right to left shunting)
- Loss of pulmonary filtration of organisms
Discrete lesions in the brain with central liquefactive necrosis surrounded by brain swelling, exuberant granulation tissue w/ neovascularization surrounding the necrosis is characteristic of?
Brain Abscess
Most common bacteria in brain abscesses of non-immunosuppressed patients?
- Streptococci
- Staphylococci
What type of edema is associated with brain abscesses?
- Vasogenic edema
- Newly formed vessels that are very leaky
Extradural abscess are commonly associated with?
Osteomyelitis
What are the common causes of chronic bacterial meningoencephalitis?
- Mycobacterium tuberculosis
- Treponema pallidium
- Borrelia species
What are the CSF findings with tuberculosis meningitis?
- Pleocytosis of mononuclear cells (sometimes mixed with neutrophils)
- Elevated protein
- Normal to moderately reduced glucose
The most serious complications of chronic tuberculosis meningitis are ________ producing hydrocephalus, and ________ producing arterial occlusion and infarction of underlying brain
The most serious complications of chronic tuberculosis meningitis are arachnoid fibrosis producing hydrocephalus, and obliterative endarteritis producing arterial occlusion and infarction of underlying brain
What stain is used to look for TB infection?
Acid-fast
Which form of neurosyphilis involves the base of the brain and may contain cerebral gummas (plasma cell-rich mass lesions) in the meninges and extending into the parenchyma?
Meningovascular neurosyphilis
Which organism causes Paretic neurosyphilis and how does it clinically manifest?
- T. pallidum (spirochete)
- Progressive cognitive impairment associated with mood alterations (including delusions and grandeur)
- Terminates in severe dementia (general paresis of the insane)
Iron deposits seen in Paretic neurosyphilis are demonstratable using what stain and where?
Prussian blue stain perivascularly and in the neuropil
Tabes dorsalis results from damage to?
Dorsal column medial lemniscus system (posterolateral columns, fasciculus cuneatus and gracilis)
Which condition presents with widened gait, impaired joint position sense and ataxia, loss of pain sensation leading to skin and joint damage (Charcot joints), characteristic “lightning pains,” and absence of DTRs w/ corresponding atrophy and pallor in the dorsal columns of the SC?
Tabes dorsalis
What are the neurologic symptoms associated w/ Neuroborreliosis (Lyme Disease)
- Aseptic meningitis
- Facial nerve palsies
- Encephalopathy
Which virus is an important cause of epidemic encephalitis, especially in tropical regions of the world?
Arbovirus
Which CNS pathology shows multiple foci of necrosis of gray and white matter; with evidence of single-cell neuronal necrosis w/ phagocytosis of the debris (neuronopahgia)?
Encephalitides caused by various arboviruses
Involvement of the spinal cord in West Nile encephalitis can lead to ________ syndrome w/ paralysis
Polio-like syndrome w/ paralysis
Increased incidences of HSV encephalitis have been observed in patients with rare inherited loss-of-funtion mutations in the ________ pathway
TLR3 signaling
HSV-1 has a tropism for which lobes of the brain; what type of injury is seen when infected?
- Temporal lobes and orbital gyri of the frontal lobe
- Hemorrhagic lesions w/ Cowdry type A intranuclear viral inclusion bodies within neuron and glia
What does HSV-2 cause particularly in neonates born by vaginal delivery to a woman with active primary HSV genital infections?
Severe encephalitis
In immnosuppressed individuals, CMV most commonly causes?
Subacute encephalitis
Periventricular leukomalacia is characteristc of infection by which virus?
CMV
Poliovirus has a tropism for which neurons of the spinal cord?
Anterior horn motor neurons
CMV infection is confirmed by?
Immunohistochemistry
How does CNS infection by poliovirus present initially and what are the CSF findings?
- Meningeal irritation
- CSF consistent w/ aseptic meningitis (pleocytosis of lymphocytes, moderately elevated protein, nearly normal glucose)
What is post-polio syndrome?
- Happens to pt’s 25-35 years after the resolultion of initial illness
- Characterized by progressive weakness and decreased muscle mass and pain in the affected area
Negri bodies associated with rabies infection are found where in the brain?
- Pyramidal neurons of the hippocampus
- Purkinje cells of the cerebellum
*Sites usually devoid of inflammation
Which symptoms/findings are virtually diagnostic for rabies infection?
Malaise, headache and fever in conjunction w/ local paresthesias around the wound
What is seen during the acute phase of HIV infection of the CNS?
Mild lymphocytic meningitis, perivascular inflammation, and some myelin loss
What are the only CNS cell type to express both the CD4 coreceptor and the chemokine receptors (CCR5 or CXCR4) that are required in combination for efficient infection by HIV?
Microglia
What is immune reconstitution inflammation syndrome (IRIS)?
- Seen in AIDS patients
- Paradoxical deterioration after starting therapy and consists of an exuberant “reconstituted” inflammatory response while on antiretroviral therapy
- Intense inflammation w/ influx of CD8+ lymphocytes
What type of encephalitis is associated with widely distributed microglial nodules, often containing macrophage-derived multinuclated giant cells?
HIV encephalitis
Which virus causes Progressive Multifocal Leukoencephalopathy (PML)?
This virus has tropism for which cell, and what is its principle pathologic effect?
- JC polyomavirus
- Tropism for oligodendrocytes —> demyelination is its principal pathologic effect
Progressive Multifocal Leukoencephalopathy (PML) occurs almost exclusively in who?
Immunosuppressed individuals
Which encephalitis is characterized by patches of irregular, ill-defined white matter injury w/ enlarged oligodendrocyte nuclei containing glassy amphopilic viral inclusions?
Progressive Multifocal Leukoencephalopathy (PML)
Which encephalitis is characterized by widespread gliosis and myelin degeneration; viral inclusions, largely within the nuclei of oligodendrocytes and neurons; variable inflammation of white and gray matter; and neurofibrillary tangles?
Subacute Sclerosing Panencephalitis (SSPE)
How do most fungi reach the brain; what is another way they may invade?
- Most by hematogenous dissemination
- Direct extension may also occur, particularly mucormycosis in the setting of diabetes mellitus
What are the 3 main forms of injury to the CNS caused by fungal infections?
1) Chronic meningitis
2) Vasculitis
3) Parenchymal invasion
Vasculitis associated with fungal infections is most frequently seen with what organisms?
Mucormycosis and Aspergillosis
What are the most commonly encountered fungi that invade the brain?
Candida and Cryptococcus
Gelatinous material within the subarachnoid space and small cysts within the parenchyma (“soap bubbles”), especilly within the basal ganglia are characteristic of what type of infection?
Chronic meningitis associated w/ cryptococcal infection
What may be seen on CT with cerebral toxoplasmosis infection?
Ring enhancing lesions
What is the morphology of cerebral toxoplasmosis abscesses; most often seen where?
- Mostly affect the cerebral cortex (near the gray-white junction) and deep gray nuclei
- Central necrosis, petechial hemorrhage surrounded by acute and chronic inflammation, macrophage infiltration, and vascular proliferation
Which stain is used for Naegleria species to confirm a diagnosis of cerebral amebiasis?
PAS or Methenamine silver
Cerebral malaria is a rapidly progressing encephalitis caused by what organism?
Plasmodium falciparum
What are the clinical implications of infection with Taenia Solium causing cysticercosis?
- Form cysts within the subarachnoid space
- May obstruct CSF flow, leading to life threatening hydrocephalus
- Hemiplegia, severe headaches, and papilledema
Heterozygosity at which codon is protective against the development of diseases associated with prion protein (PrP)?
129
What are the clinical manifestations of Creutzfeldt-Jakob Disease (CJD)?
Subtle changes in memory/behavior followed by a rapidly progessing dementia, often associated with pronounced involuntary jerking muscle contractions on sudden stimulation (startle myoclonus)
Creutzfeldt-Jakob Disease (CJD) has a peak incidence during what decade?
How is it transmitted?
Average survival time?
- During the seventh decade
- Iatrogenic transmission, notably by corneal transplantation, deep implantation of electrodes in the brain, and administration of contaminated preparations of naturally derived GH
- Average survival = 7 months
Onset of the variant form of CJD is linked to consumption of?
Bovine spongiform encephalopathy agent in contaminated foods or blood transfusion
How does vCJD differ clinically from CJD?
- Behavioral changes early in the disease
- Slower progression of neurologic symptoms
What is seen on electron microscopy with CJD and vCJD?
How are they stained?
- Kuru plaques: extracellular deposits of aggregated abnormal protein (will have halo of spongiform in vCJD); usually seen in the cerebellum, but are abundant in the cerebral cortex in cases of vCJD
- Congo red and PAS-positive
Fatal Familial Insomnia (FFI) is caused by what specific mutation in the PRNP gene?
Aspartate substitution at residue 178 or PrPc
What is the characteristic morphology of Fatal Familial Insomnia (FFI)?
- Neuronal loss and reactive gliosis in the anterior ventral and dorsomedial nuclei of the thalamus
- Neuronal loss is also prominent in the inferior olivary nuclei
What are the clinical manifestations of Fatal Familial Insomnia (FFI)?
- Sleep disturbances in the initial stages
- Ataxia, autonomic disturbances, stupor, and finally coma
Polymorphisms at which codon influence the development of prion diseases?
Codon 129 encoding either Met or Val
How does FFI differ from the other prion diseases, morphologically?
Does not show spongiform pathology
Where are the densest amounts of exudate found with acute meningitis caused by P**neumococcal meningitis and H. influenzae?
- P. meningitis: often densest over convexities near sagittal sinus
- H. influenzae: usually basal location
