Neuro Path Flashcards
1
Q
A
Astrocyte cells
Astrocytes are thought to perform a supportive role in the CNS
Astrocytes multiply and become hypertrophied in response to a variety of CNS injurious processes
2
Q
A
Oligodendrocytes: produce CNS myelin
- Diseases that damage/destroy oligodendrocytes–> loss of myelin
3
Q
A
Microglial cell:
- NOT neuroepithelial, derived from monocyte macrophage lineage incorporated into CNS during fetal development
- *Below**:
- Microglial cells form network of CNS antigen presenting cells for immune surveillance
- Activation–> proliferation, migration of microglia
- Most pronounced in viral encephalitis
4
Q
What type of injury occured to the brain specimen below?
A
- *Epidural hematoma**:
- Transtentorial herniation–> damage to vital cardio-respiratory centers in brainstem–> death due to epidural hematoma
- *Increasaed supratentorial pressure**:
- Many causes of increased intracranial pressure including intracerebral hemorrhage, tumor, liver failure, encephalitis
- Transtentorial herniation results in compression of uncus against midbrain resulting in 3rd nerve palsy
- Rostrocaudal displacement of brainstem can cause intraparenchymal (Duret) hemorrhages in brain stem
- Loss of brainstem function can result in death.
Below: compression of midbrain against tentorium–> compression of PCA–> formation of kernohan’s notch
Can also see duret hemorrhages= torsion on small blood vessels in pons/brainstem
- *Hepatic encephalopathy** can also cause herniation:
- toxic metabolites not metabolized in liver (liver failure)–> altered astrocyte function–> massive cerebral edema–> herniation
5
Q
What type of injury occured to the brain specimen below?
A
- *Subdural hematoma**:
- Accumulation of blood in subdural space (beneath dura, above leptomeninges
- Results from torn bridging veins
- Death in 74% of cases
- Good recovery in 8% of cases
- Large clinically significant subdural hematomas almost always traumatic.
- Subdural blood does not enter the subarachnoid space. - Would not be detected as blood on spinal tap.
Ex: elderly have cerebral atrophy–> bridging veins span greater distance–> more susceptible to damage
6
Q
What type of injury occured to the brain specimen below?
A
Subarachnoid hemorrhage
Bleeding into subarachnoid space
Due to:
- Trauma
- Rupture of saccular aneurysm (66%)
- Rupture of AV malformation (10-15%)
- Infection
- Vasculitis
- Tumor
Subarachnoid blood–> reactive vasospasm–> secondary ischemic brain injury
Below: see blood in subarachnoid space, below leptomeninges
7
Q
What type of injury occured to the brain specimen below?
A
Impact to head–> cerebral parenchymal hemorrhage:
Intraparenchymal hemorrhage due to severe impacts
- rupture of intracerebral blood vessels
Cerebral contusions
Head impact related cerebral contusions results from the brain forcefully hitting the interior surface of the overlying skull.
- Contusions usually occur in areas of prominence of the cerebral hemispheres including the tips of frontal, temporal and occipital lobes
- *Contusion**= Bruise on the cortical surface
- Necrosis followed by phagocytosis of damaged cortex and white matter
- Coup lesions: at site of impact
- Countercoup lesion: Located at site distant from impact. Brain moves within skull due to impact to head and slams into skull at site remote from traumatic impact on head.
- *Histo:** linear hemorrhages arranged in perpendicular surface of brain where impact occurred
- Will also see macrophages in brain tissue (phagocytize necrotic tissue)
- Formation of hemosiderin stained areas on cerebral surface
8
Q
A woman expires after getting into a MVA. There is no bruising visible on her skull or brain parenchyma, but the follow changes are noted in her brain tissue. What happened and what caused this?
A
Diffuse axonal injury:
Results from rotational acceleration of the brain within the head. (can occur in absence of impact)
Three characteristic features of the pathology of DAI in its most severe form include:
1) diffuse damage to axons
2) a focal lesion in the corpus callosum
3) focal lesions in the dorsolateral sector of the rostral brain stem adjacent to the superior cerebellar peduncles.
Can result in formation of numerous axonal spheroids
- Blocks axonal flow–> buildup in one space (indicates axonal transection)
9
Q
Below is the brain specimen from a 50 year old former heavyweight boxer who died of an MI. What types of changes have occured?
A
Chronic traumatic encephalopathy:
= progressive neurologic deterioration related to repeated traumatic brain as can occur in number of athletic activities.
- CTE is a slowly progressive tauopathy with a trauma associated etiology
Tauopathy= increased expression of Tau, neurofibrillary tangles
10
Q
A 30 year old man involved in an altercation was shot in the head. He was taken to the Emergency Department where he was still breathing and had in tact pupillary reflexes. After 10 minutes he expired- what caused his death?
A
Projectile brain injury
Damage occurs in areas in and adjacent to bullet path including blood vessels. The resultant increase in intracranial pressure can result in brainstem herniation and death.
11
Q
The following was noted on an MRI of a patient with a headache. What is the anomaly here and what would a physician be concerned about?
A
AV Malformation:
Disorganized mass of abnormal arteries and veins
- Direct connection between arterial and venous circulations
- Congenital cases result from lack of development of local capillary network
- Rate of bleeding is 2-4 % per year (with high mortality due to herniation)
See disorganized arrray of abnormal blod vessels–> abnormal communication between arteries and veins–> seizures, SAH, intraparenchymal hemorrhage
12
Q
What is grossly abnormal in this brain specimen of a 25 year-old patient who reported to the ED with the “worst headache of his life” and subsequently expired?
A
AV Malformation:
Disorganized mass of abnormal arteries and veins
- Direct connection between arterial and venous circulations
- Congenital cases result from lack of development of local capillary network
- Rate of bleeding is 2-4 % per year (with high mortality due to herniation)
- Seen more commonly in individuals age 20-40 years
See disorganized arrray of abnormal blod vessels–> abnormal communication between arteries and veins–> seizures, SAH, intraparenchymal hemorrhage
Histo: varied wall thickness and lumen caliber. Some vessels have hyalinized walls and arteries. Hemosiderin in intervening reactive brain parenchyma indicates previous bleeding. Arteries contain internal elastic lamina
13
Q
The following histologic specimen was recovered from the brain of a 70-year-old man who passed away from an MI. What types of changes are noted in the vasculature of his brain?
A
- *Cavernous hemangioma**:
- Venous vascular malformation
- Dilated vascular channels
- Large vascular spaces with fibrous walls and little or no intervening brain parenchyma
- Seizures, headaches or neurologic deficits
- Most are asymptomatic
- May rarely result in intraparenchymal bleed
14
Q
A
Telangiectasias consist of an aggregate of small thin-walled blood vessels with intervening parenchyma.
They may cause seizures but rarely rupture.
15
Q
A 79 year old man expires after developing gradual symptoms of dementia. The following is noted in a histologic specimen of his brain. What is his diagnosis?
A
Cerebral Amyloid Angiopathy:
Cortically located lobar hemorrhage
Pts older than 60 with majority (88%) > 70
Beta amyloid accumulates in media (replaces smooth muscle)- seen in adventitial tunica of arterioles, medium sized and small arteries
- *Overlap with Alzheimer’s disease**
- Both associated with Apolipoprotein e4
- CAA common in alzheimer’s dz, however, only 20-40% of CAA pts have clinical dementia
** Common cause of frontal lobe intraparenchymal bleeds in elderly (risk for intracerebral hemorrhage)
Diagnosis: Boston Criteria
- Definite: postmortem examination
- Probable with supporting pathology: Bx or evacuated hematoma c/w CAA
- Probable: MRI / CT with ≥ 2 lobar hemorrhages (microhemorrhages) in pt ≥ 55 (no other cause)
- Possible: MRI / CT with 1 lobar hemorrhage in pt ≥ 55 (no other cause)
* Microhemorrhages in deeper structure (basal ganglia)= hypertensive hemorrhage
- *Below**:
- Iron stain shows abundant iron deposition near old cerebral amyloid-related hemorrage
16
Q
An 80 year old woman expires after progressive dementia-related degeneration. Additionally she had suffered from severe headaches for the last 20 years. She had been diagnosed with Alzheimer’s disease but on autopsy the following changes were found. What is notable in the histologic sample and what is her diagnosis?
A
Cerebral amyloid angiopathy:
Cortically located lobar hemorrhage
Pts older than 60 with majority (88%) > 70
Beta amyloid accumulates in media (replaces smooth muscle)
- *Overlap with Alzheimer’s disease**
- Both associated with Apolipoprotein e4
- CAA common in alzheimer’s dz, however, only 20-40% of CAA pts have clinical dementia
** Common cause of frontal lobe intraparenchymal bleeds in elderly (risk for intracerebral hemorrhage)
Diagnosis: Boston Criteria
- Definite: postmortem examination
- Probable with supporting pathology: Bx or evacuated hematoma c/w CAA
- Probable: MRI / CT with ≥ 2 lobar hemorrhages (microhemorrhages) in pt ≥ 55 (no other cause)
- Possible: MRI / CT with 1 lobar hemorrhage in pt ≥ 55 (no other cause)
* Microhemorrhages in deeper structure (basal ganglia)= hypertensive hemorrhage
- *Histo:** focus of old infarct with hemorrhage near CAA-related cerebral hemorrhage. See old cystic necrosis due to remote hemorrhage
- Additionally see degeneration of white matter due to decreased vascularization
MRI:
Inflammatory CAA presents with marked headaches and causes patchy or confluent bright signal on T2 weighted MRI
17
Q
On post-mortem exam the following changes were noted in the circle of Willis of a patient with a family history of sudden death following painful headaches. What is noted in the arterial structure and what might have led to the death of this patient?
A
Saccular aneurysms:
Acquired lesions; loss of internal elastic lamina, muscularis at junction of artery with aneurysm
- Aneurysm has thinned fibrous wall vs normal muscular, elastic lamina
- Thin, dilated structure–> risk for rupture
** Rupture of saccular (berry) aneurysm–> life-threatening, 35% mortality during initial hemorrhage
- 2/3 of Subarachnoid hemorrhage are secondary to aneurysm rupture
- 10-15% due to AV malformations
- Blood in subarachnoid space–> vasospasm of cerebral blood vessels–> secondary cerebral ischemia
18
Q
A
Atherosclerotic brain aneurysm:
Fusiform dilitations of basilar and vertebral arteries due to severe atherosclerosis
- Major complication= thrombosis
19
Q
A 55 year old woman with a 30-year history of systemic lupus expires from an MI due to CAD. She had developed multiple manifestations of the disease (cutaneous, pulmonary “shrinking lung”). Additionally, according to her children her mental “sharpness” had declined in recent years. Based on the histology of her brain, what may she have developed?
A
Vasculitis of cerebral blood vessel:
Secondary vasculitis of the CNS (more common) can be part of a variety of systemic illnesses including generalized
autoimmune disease such as:
- SLE
- Sjogren’s syndrome
a variety of systemic vasculitides such as:
- Wegener’s Granulomatosis
- Polyarteritis nodosa
Primary CNS vasculitis (primary angiitis of CNS):
- No other disease or condition causing vessel damage
- Often granulomatous (below)
20
Q
A 74 year old man with long-standing HTN who refused to take any medications or change his lifestyle comes to the ED after collapsing in his home. He is unresponsive and demonstrates R-sided paralysis and eventually expires. At autopsy there are signs of massive hemorrhage within the thalamus and the following histologic changes are found. What is his diagnosis?
A
Hypertensive Hemorrhage
Rupture of a cerebral blood vessel as a consequence of long standing hypertension
The most common locations for hypertensive cerebral hemorrhages are:
- the basal ganglia and thalamus (65%),
- the pons (15%)
- the cerebellum (8%).
May be related to lipohyalinosis of small vessel walls–> formation of microscopic Charcot-Bouchard aneurysms
Hemorrhage in the region of the internal capsule causes paralysis of the opposite side of the body.
- Patients are usually however unconscious
An acute hemorrhage in the pons may damage cranial nerve nuclei or result in loss of consciousness due to damage to reticular formation.
A cerebellar hemorrhage may cause abrupt ataxia, severe occipital headache and vomiting and may cause life-threatening compression of medulla.
- *Histo:** hypertensive arteriosclerosis in patient with long-standing HTN
- front: Charcot-bouchard aneurysms (mural deposition of lipid, hyaline–> damage to cerebral arterioles)
21
Q
A 39 year old woman goes into labor and delivers a healthy baby, but suffers from major bleeding during delivery. During the operation to repair the bleed she suffers a stroke and expires. At autopsy the following is noted. What happened?
A
Watershed infarct:
Reduced blood flow to the brain –>
produce areas of ischemic injury in the watershed areas between:
- ACA–> MCA
- MCA–> PCA
22
Q
A 25 year old man falls into a lake while out on a boat with his friends and knocks his head on the side of the boat. He nearly drowns but is resuscitated on the beach. Afterwards, he goes to his physician because he feels like he’s having trouble remembering things that he didn’t used to have problems with. Based on the histologic specimen below, what has occured to his brain?
A
Global ischemia: Sommer’s sector:
Produces damage in areas of the brain most sensitive to anoxic/hypoxic injury. These include:
1) Sommer’s sector (CA 1) of the hippocampus- front
2) Purkinje cells of the cerebellum
3) Layers IV to VI of the cerebral cortex (below)
- may see deficits in voluntary movements, associations (between visual/sensory cues and memory)
- Neuronal death seen in cell populations sensitive to anoxic/hypoxic injury
23
Q
A 30 year old woman is in a motor vehicle accident where she is knocked unconcious and is found non-responsive and not breathing. Resuscitation is performed for 25 minutes and she eventually begins breathing again. After a long recovery in the hospital, her family notes that she seems to have trouble walking and is more clumsy. Based on the histologic changes below, what occured?
A
Global ischemia- Purkinje Fiber death:
Produces damage in areas of the brain most sensitive to anoxic/hypoxic injury. These include:
1) Sommer’s sector (CA 1) of the hippocampus
2) Purkinje cells of the cerebellum
3) Layers IV to VI of the cerebral cortex
- Neuronal death seen in cell populations sensitive to anoxic/hypoxic injury
24
Q
A 65 year old woman with a history of uncontrolled hypertension and progressive coronary artery disease suffers from a stroke. Afterwards she has difficulty forming sentences and appears extremely frustrated by her inability to answer questions or express herself. Based on the imaging below, what has occured?
A
MCA Cerebral infarct–> Broca’s aphasia (Brodmann 44 and 45)
Cerebrovascular occlusive disease (thrombotic and embolic) remains a major cause of morbidity and mortality in the United States and worldwide.
- Atherosclerosis predisposes to vascular thrombosis and embolic events.
- Geographic location of occluded vessel defines area of infarction and clinical symptoms.
Examples:
- Occlusion of the trifurcation of the MCA results in cortical infarction with motor and sensory loss and often aphasia (front).
- Striate branch occlusion causes damage to the internal capsule with subsequent motor defects.
HTN–> Narrowing (arteriosclerosis) of brain parenchymal arteries and arterioles–>
small cystic ischemic infarcts referred to as lacunar infarcts.
Severe disease with numerous lacunar infarcts can result in the clinical entity multi-infarct dementia.
Histology:
- Coagulative necrosis with acute inflammation
- Phagocytosis of cellular debris by macrophage
- Eventual cyst formation and surrounding reactive astrocytosis.
Below: Anterior cerebral artery (ACA) infarct
25
A 73 year old man has suffered from multiple strokes over the past several years. Recently his daughter has noted that his behavior has progressively worsened- he can't remember the names of his grandchildren and has had several emotional outbursts. Based on the changes below, what may have occured?
**Cerebral infarct- Lacunar infarct**:
Cerebrovascular occlusive disease (thrombotic and embolic) remains a major cause of morbidity and mortality in the United States and worldwide.
- Atherosclerosis predisposes to vascular thrombosis and embolic events.
- Geographic location of occluded vessel defines area of infarction and clinical symptoms.
Examples:
- Occlusion of the trifurcation of the MCA results in cortical infarction with motor and sensory loss and often aphasia.
* *- Striate branch occlusion causes damage to the internal capsule with subsequent motor defects.**
HTN--\> Narrowing (arteriosclerosis) of brain parenchymal arteries and arterioles--\>
small cystic ischemic infarcts referred to as lacunar infarcts.
**Severe disease with numerous lacunar infarcts can result in the clinical entity multi-infarct dementia.**
Histology:
- **Coagulative necrosis with acute inflammation
- Phagocytosis of cellular debris by macrophage**
- Eventual cyst formation and surrounding reactive astrocytosis.
26
A 40 year old woman delivers a baby via C-section. While in the hospital she develops a massive headache and subsequently expires. At autopsy the following change is noted. What happened?
**Sagittal sinus thrombosis**
The Sagittal sinus receives the venous drainage from the superior portions of the cerebral hemispheres. Venous infarcts of the brain result from thrombosis of the dural sinuses and cerebral veins.
_Primary aseptic thromboses_ of the sagittal sinus usually are associated with hypercoagulable states or circulatory slowing. Underlying conditions include:
- dehydration
* *- pregnancy,**
- oral contraceptives
- hemolytic anemias
- **postoperative period**
Secondary or septic venous thrombosis is
seen with pyogenic infection of the face
or sinuses, subdural abscesses and meningitis.
27
A 2 day old baby is rushed to the emergency room by her parents when she develops a fever and is screaming and crying. A spinal tap reveals PMNs in her CSF. Based on the presence of PMNs, what is happening and what are some likely causes of this infection?
**Bacterial meningitis**:
Infections of the leptomeninges may be caused by many bacterial species as well as some viruses, fungi and amebas
Acute bacterial meningitis is an infection of the meningeal spaces.
Bacterial organisms are the most common cause of acute leptomeningitis:
- E. coli
- H. influenzae
- Streptococcus pneumoniae
- Neisseria meningitidis
_Frequent causes in newborn:_
- Streptococcus agalactiae (Lancefield's group B)
- Escherichia coli K1
- Citrobacter
- Klebsiella species
- Listeria monocytogenes.
**Histo**: see PMNs in CSF of subarachnoid space
28
After a few days of vomiting and diarrhea, a woman comes to the hospital complaining of a headache and a stiff neck. She says her GI symptoms are resolving but she wants to know why she has these new symptoms. What can you tell her?
**Viral meningitis- lymphocytes**
Viral meningitis is _frequently a benign, short-lived illness characterized by:_
- Meningitic symptoms and signs (head ache, photophobia and neck stiffness)
- CSF pleocytosis consisting predominantly of lymphocytes. Meningitis is the most common viral disease of the CNS.
Viruses causing meningitis:
- Most commonly caused by enteroviruses.
- Mumps virus
- EBV
- Herpes simplex
- Lymphocytic Choriomeningitis Virus (rodents)
\* 50-75,000 cases/year
Other infectious causes of aseptic meningitis (lymphocytic) other than viruses include:
- Borellia burgdorferi
- Mycobacterium tuberculosis,
- Cryptococcus neoformans
- Treponema pallidum.
**Histo: s****ee lymphocytes in CSF:****Virchow-Robin** space and subarachnoid space
29
A 65 year old man from India comes to the physician with his wife who complains that her husband seems to be more forgetful and he has decreased coordination. An MRI of the brain reveals the following. What might be the cause of these CNS changes?
**Tuberculous meningitis**:
Tuberculous meningitis is the most common form of TB of the CNS.
TB meningitis frequently involves the leptomeninges at the base of the brain. **Arteritis** associated with the tuberculous meningitis may lead to **parenchymal infarcts**.
Rare cases M. tuberculosis organisms can infect the brain parenchyma with the formation of a tuberculoma.
- **Tuberculomas = spherical masses with central areas of caseous necrosis surrounded by granulomatous tissue.**
- Pott's disease= destructive lesions in vertebral column--\> spinal cord compression
30
A 50 year old woman with a history of HIV infection comes the hospital after experiencing a seizure. She states she has been having intermittent headaches and a stiff neck. Based on the CSF sample below, what is her diagnosis?
**Cryptococcal meningitis**:
Most commonly seen as opportunistic infection in immunocompromised hosts.
Cryptococcus neoformans= fungus usually harbored in soil and manure of some birds.
- Organisms gain entry to the CSF --\> disseminate in leptomeninges and in the Virchow-Robin spaces.
- Sparse host tissue response is characteristic compared to other infections
* *Histo:**
- Cryptococcus are encapsulated organisms that reproduce by budding.
- Carbohydrate-rich capsule (india-ink positive, PAS, mucicarmine stains)
31
A 45 year old man who has worked as a sex worker for the last 20 years comes to a doctor after experiencing worsening headaches, neck stiffness, and is now having progressive weakness. Based on his symptoms and the gross image below, what might his diagnosis be?
**Cerebral syphillis**:
In approximately 25% of patients with Syphilis, blood-borne spirochetes, Treponema pallidum, transiently reside in the leptomeninges during secondary syphilis.
\* Years later some of the patients display tertiary neurologic manifestations including meningovascular syphilis, general paresis and tabes dorsalis.
Meningovascular syphilis = subacute or chronic meningitis characterized by spirochetes in the meninges.
- Subsequent invasion of the brain parenchyma by the spirochetes can produce chronic meningoencephalitis designated general paresis
Tabes dorsalis= myelopathy thought to result from meningeal fibrosis secondary to spirochete infection with involvement of the dorsal roots followed by degeneration of the posterior columns.
32
A 45 year old needle-drug user with dental caries comes to the hospital after being hit by a car. An MRI of his brain reveals the following lesion. What is a possible diagnosis?
**Cerebral abscess**:
Blood-borne bacteria can lodge in capillaries in the brain and elicit an acute inflammatory reaction termed cerebritis.
Further development of the lesion with multiplication of organisms and inflammatory response--\> focus of acute inflammation and necrosis consistent with an abscess.
- **Below:** _Fibroblasts from around blood vessels proliferate and deposit collagen with eventual development of a fibrous capsule around the abscess._
- Growth factors secreted by immune response--\> fibrotic tissue formation
Cerebral abscesses can follow sinus or dental infections or otitis media.
33
A 55 year old man with a 20-year diagnosis of HIV comes to his physician complaining of headaches and changes in his memory. The physician is aware of complications arising from his patient's immune function and asks him if he has ever lived in a home with cats. Additionally, he orders an MRI that reveals the following. What is his possible diagnosis and what would be visible on histology?
**Toxoplasmosis**:
Infection by this protozoan is frequent cause of _CNS symptoms in AIDS patients_
- Responds to therapy
\* Usually due to _reactivation of previously acquired infection of Toxoplasma gondii_ rather than a newly acquired infection
Definitive host: cats
- Infection is acquired from undercooked meat or from cat feces.
Prevalence of antibodies ranges from 20-40% in US.
- Most primary infections in immunocompetent humans are asympsomatic
34
A 45 year old woman from Columbia comes to the physician after experiencing a seizure. An MRI reveals multiple lesions and the specimen from brain biopsy reveals the following. What is her diagnosis and how did she get this?
**Cysticercosis**:
Most common parasitic disease of the CNS worldwide
Humans serve as intermediate host for pork tapeworm= Taenia solium
Usually results from ingestion of ova in fecally contaminated food or water
- Larvae of pork tapeworm
35
A 40 year old woman comes the hospital after experiencing a massive headache and her husband states she has been acting strangely. The physician notes a few lesions around her lips and her husband said she recently had a cold. On MRI the following is found. What is a possible etiology for her symptoms?
**Herpes encephalitis**:
Herpes virus= sporadic encephalitis
- hemorrhagic necrotizing encephalitis and
- most important sporadic viral infection of the human nervous system in immunocompetent individuals.
- focus of the necrotizing pathology in the temporal lobes.
Symptoms:
- features of encephalitis and focal neurologic signs due to involvement of temporal and frontal lobes
- Fever, headache and confusion are common
**histo:** lymphocytes
36
A 15 year old deveops a massive headache, is rushed to the hospital and suffers a seizure and dies. On autopsy, the following histologic sample is recovered from the boy's brain. What occured and what is his diagnosis?
**Herpes encephalitis**:
Herpes virus= sporadic encephalitis
- hemorrhagic necrotizing encephalitis and
- most important sporadic viral infection of the human nervous system in immunocompetent individuals.
- focus of the necrotizing pathology in the temporal lobes.
Symptoms:
- features of encephalitis and focal neurologic signs due to involvement of temporal and frontal lobes
- Fever, headache and confusion are common
* *Histo**: Cowdry type A intranuclear inclusion seen in HSV encephalitis
* *Below**: gross hemorrhage following HSV encephalitis
37
A 60 year old man is found collapsed on his front porch in July. His wife states he had been complaining of worsening headaches and was thinking about going to see his doctor. On physical exam, he has decreased reflexes and appears lethargic and largely non-responsive. His lab panels reveal no serum electrolyte imbalances and he is hydrated. A brain biopsy is performed that reveals the following. What is his possible diagnosis based on the changes?
**West nile encephalitis**:
\* Arbovirus= epidemic encephalitis, mosquito-borne disease
- flavivirus, ssRNA
- IgM antibody in serum/CSF
- can invade brainstem--\> neuronophagia (immune system attacks neurons)
Histo: **reactive gliosis (front)**, **microglial nodules (below),** PMN inflammation
38
A 30 year old woman delivers a premature baby who has demonstrable microcephaly, a petechial rash and soon after delivery suffers a seizure and expires. Based on the histologic specimen below, what happened to the newborn?
**CMV encephalitis**
_Infection during 1st trimester-_-\> congenital CMV encephalitis
- See areas of calcification
- Hydrocephalus
Adults (HIV/AIDS):
- Periventricular encephalitis (smoldering)
- "Owl's eye" nucleus
39
A 15 year old girl from India is rushed to the hospital when her parents find her in bed, unable to move and hardly breathing. The following histologic sample is recovered from her brain. What is her diagnosis?
**Poliom****yelitis: neuronophagia, microglial nodule**
non-enveloped ssRNA virus
- Drinking contaiminated water
- Infects neurons--\> spinal cord/brainstem
- 5-25% mortality (respiratory failure)
40
A raccoon is found on the street foaming at the mouth and lashing out at a dog. Animal control is called and they euthanize the animal. The following changes are noted in its salivary gland. What is the animal's diagnosis and where else would physiologic changes be noted?
**Rabies**:
Enveloped RNA virus
- Transmitted to humans through bite
- Bat strains
Variable incubation
- "flu-like" symptoms
- The incubation period for rabies virus is variable (about 3 months)
- 70-90% of patients go on to develop "furious (encephalitic) rabies characterized by:
- insomnia, episodes of agitation and aggressive behavior, autonomic dysfunction, hallucinations, hydrophobia, dysphagia, dysarthria and nystagmus.
- 20-30% of patients can have "dumb" or paralytic rabies characterized by paralysis of one or more limbs
**Histo**: Salivary glands: Virus replicates in ganglion cells of salivary glands--\> retrograde transport--\> pyramidal neurons in hippocampus
**Below: Negri bodies** are eosinophilic cytoplasmic inclusions identified in cerebellar Purkinje cells, brainstem neurons and pyramidal neurons of the hippocampus in Rabies.
41
A 10 year old boy is brought to the physician by his mother because she thinks his personality seems to be changing and he is getting clumsier- he has fallen down the stairs twice in the last week. Additionally he doesn't seem to want to go outside when it is sunny. The pediatrician looks at the boy's medical records and sees that he suffered from a measles infection at age 2, as his parents refused to have him vaccinated. Based on the changes in the brain tissue specimen below, what is his diagnosis?
**Subacute sclerosing panencephalitis**:
Encephalitis of insidious onset following measles virus infection
- Occurs in children
- Caused by measles virus defective in terms of M protein (can't bud) or abnormal immune response
Symptoms: gradual, progressive psychoneurological deterioration, consisting of personality change, seizures, myoclonus, ataxia, photosensitivity, ocular abnormalities, spasticity, and coma.
characterized by astrogliosis of gray and white matter, myelin loss, perivascular lymphocytes and a protracted course
**Below:** measles virus inclusions within neuron
42
A 45 year old man with a 20-year diagnosis of HIV is brought to the physician by his partner after he notices cognitive changes in his partner. On neurological exam, the physician notes unilateral weakness. An MRI is ordered that reveals the following changes. What is the patient's probably diagnosis given his presentation and underlying conditions?
**Progressive multifocal leukoencephalopathy**:
- demyelination secondary to viral destruction of oligodendroglia by JC virus.
JC virus is a polyoma virus that causes a lytic infection of oligodendrocytes in immunocompromised persons.
70-80% of adults worldwide are seropositive for JC virus.
- Patients with _compromised immune status especially AIDS patients are at risk for PML._
Histo:
_- macrophage infiltration of white matter
- breakdown and phagocytosis of myelin
- loss of oligodendrocytes_
- enlarged oligodendrocytes with intranuclear inclusions
- “Bizarre” astrocytes.
43
A 55 year old woman with a 10 year history of HIV infection comes to her physician after having trouble moving the left side of her body. She fears she may have had a stroke. Additionally her husband states that her behavior has been strange for the past few months and she has trouble remembering things. A brain biopsy is taken after the MRI fails to reveal an area of ischemia. Based on the histologic sample below (contents of macrophages in neural tissue), what might her diagnosis be?
**HIV infection causing neurological changes**:
_Dementia_ associated with HIV may be related to actions of _cytokines released by macrophages_ (front) in response to HIV virus infection of these cells.
- HIV in the brain is characterized histologically by the presence of _perivascular multinucleated giant cells that have been shown to contain HIV._
Also associated with a **vacuolar myelopathy. (below)**
- The pathogenesis of the vacuolar myelopathy may also be cytotoxic cytokine release.
- The posterior and lateral columns of the spinal cord show marked vacuolization.
- Clinically patients with vacuolar myelopathy demonstrate **ataxia and spastic paraparesis.**
- The immunosuppression caused by HIV predisposes the CNS to infection by numerous infectious agents and to the development of CNS B cell lymphomas
44
A 35 year old man diagnosed with HIV returns to the hospital after geeling sick for a few weeks and then having a seizure. An MRI reveals a tumor in his brain, and a biopsy reveals the following. What is his diagnosis?
**HIV infection with EBV--\> CNS lymphoma**:
Low CD4 count--\> immune system can’t suppress CNS lymphoma
- Additionally, EBV enhances cell proliferation (early neoplastic event)--\> lymphoma
- B-cell lymphomas also increasing in incidence in elderly with no known immune-suppressing event
Symptoms:
- presents with seizure, headache, cranial nerve findings, altered mental status, or other focal neurological deficits typical of a mass effect.[7][8]
- Systemic symptoms may include fever, night sweats, or weight loss
- Can also have: monocular vision loss, diplopia, dysphagia
45
A 40 year old woman presents to the emergency department after experiencing what she believes may have been a stroke. She is having trouble controlling the movements of her extremities on her left side and she is worried that this is permanent. An MRI is taken which shows the following isolated lesion. What is her diagnosis and why are physicians concerned about prompt treatment?
**Multiple sclerosis: acute and chronic demyelination**
Disease of oligodendrocyte and myelin loss plus severe axonal loss and grey matter injury (degenerative process)
Dawson's finger= areas of slow blood flow around neurons
* *_Types of MS:_**
* *CIS**= _clinically isolated syndrome_ (first attack, demyelinating in nature) **Front slide**
- Can be optic neuritis, brainstem sydrome,
**RRMS**_= relapsing, remitting MS_ (**below)**
SPMS= Secondary progressive MS; Starts with attacks, progression of disability without clear attacks
PPMS= primary progressive MS; starts out with just progressive disability, no attacks
RIS= radiographically isolated syndrome
- Find "MS" lesions (asymptomatic) at time of MRI (or autopsy)
**MS lesions**:
Periventricular
Intratentorial (cerebellar)
Juxtacortical
Gadolinium+ lesion
\*\* Significant small vessel involvement, rich in periventricular and juxtacortical areas
Also see lesions in cortex- not visible in conventional imaging (need post-processing)
- Axons in cortex have small amount of myelination--\> gray matter can still be demyelinated
Neuroaxonal injury persists for life
- _After first attack, significant chance of repeat attacks--\> must start immunomodulatory therapy quickly_
46
A 45 year old woman presents with sudden transient loss of vision in her left eye. On MRI, lesions are found in other sites of her brain and a biopsy is taken that reveals the following. What is her diagnosis and how will she be treated?
**Diagnosis of MS:**
Primary diagnosis based on dissemination in space:
1. First attack or progression of \> 6 months
2. Two or more lesions in appropriate locations:
- periventricular,
- juxtacortical (inferior, posterior fossa)
- cord lesion or asymptomatic infratentorial lesion
Lesions over time:
1. Presence of asymptomatic enhancing and nonenhancing lesions at any time
2. \>= 1 new T2 or enhancing lesion
\* Can now diagnose patient at first attack
\*\* risk of having another attack increases based on location of lesions (in diagnostic areas, risk is ~90%)
\*\* Fewer lesions, less likely to have disability at 5 years (10%)
**Biomarkers**: NONE detected thus far
**Pathogenesis**:
Demyelination--\> if it stops, axon will re-myelinate
In progression of MS:
Axonal transection and degeneration
- Axon is cut in half before it can regenerate the myelin sheath **(See chronic plaque on front**)
**Treatment**:
Reduce likelihood of another attack after precipitating event by administering:
- IFN-beta-1b: reduced risk of new lesion formation
- S1P receptor antagonists
- Anti-VLA4
- Anti-metabolites
- Anti-neoplastic agents
47
A 85 year old woman was brought to the emergency room after being found in her house unconcious. She was evidently dehydrated and malnourished. The ER technician started her on saline and her symptoms began to improve. Two days later, she showed apparent confusion again in spite of nutrition and saline administration. An MRI was ordered to rule out a stroke and the following was noted in the pons. What happened?
**Central Pontine Myelinolysis**:
= selective demyelination of discrete areas in the pons and at times in extra-pontine locations
May be related to damage of oligodendrocytes by electrolyte imbalances in areas of close association of gray and white matter tracts
- _Hyponatremia--\> rapid correction--\> neuronal cells lose water--\> demyelination
- Symptoms: confusion, delirium, hallucinations, difficulty with swallowing, lethargy, coma_
* *Histo**:
- Macrophages breakdown myelin
- Preservation of axons/neurons
48
A 4 month old is brought to the pediatrician for a well visit. His mother states that he has gotten much more irritable over the last month and that after they thought he could sleep through the night he has started waking her up again several times a night. Additionally he has had a couple of fevers that have necessitated going to the Emergency room, where they were unable to find any signs of infection. The pediatrician's exam reveals developmental delays. Based on the brain biopsy below, what is his diagnosis and prognosis?
**Krabbe disease (Globoid Cell Leukodystrophy**):
_Deficiency of the lysosomal enzyme beta galactocerebrosidase;_
- autosomal recessive
Onset and symptoms:
- Late infancy most common (80%), usually before 6 months
- _developmental arrest
- extreme irritability and crying followed by rigidity and spasms;_
_- frequent episodes of pyrexia (fever)_
**Prognosis**: _death by 1-2 years with continued seizures and opisthotonus_
CNS pathology due to accumulation of psychosine--\> loss of oligodendrocytes, myelin
- May also affect the peripheral nervous system
Histo:
- numerous globoid cells, paucity of intact myelin and oligodendrocytes and variable loss of axons.
49
A 5 month old boy is brought to the pediatrician for a wellness visit. On physical exam the physician notes that the infant's head in in the 99th percentile. Additionally he seems to be showing signs of delayed motor development. An MRI is ordered that reveals a mass lesion. A brain biopsy is performed that reveals the following. What is the diagnosis?
**Alexander's Disease**:
Occurs sporadically (usually)
- More common in males
- autosomal recessive
Presenation:
- Most often presents in _infancy with increased head size,
- psychomotor retardation, spasticity; rapidly progressive_
Path:
- _widespread demyelination in CNS with **Rosenthal fibers** in astrocytic processes_
usually sporadic;
- majority of patients have mutations in **glial fibrillary acidic protein** (**GFAP)**, an intermediate filament protein of astrocytes
50
A 65 year old homeless man is brought to the emergency room for severe alcohol intoxication. He is given IV fluids and glucose for ressucitation and he appears to improve. On exam the next day however, he has developed some palsy of the lateral rectus muscles and has an inward gaze (esotropia). While interviewing the patient, the physician asks him what year it is, to which the patient replies, "1975". Out of curiousity, the physician then asks him what color the dog standing next to him is. The patient confidently replies, "that's a beautiful golden retriever". Based on the symptoms and gross specimen below, what has happened?
**Wernicke's Encephalopathy**:
Petechial hemorrhages present in the mamillary bodies and walls of the third ventricle. (**infarction of mamillary bodies**)
- _Due to thiamine deficiency._
- Thiamine in the form of thiamine pyrophosphate is a cofactor for various enzyme systems such as the pyruvate dehydrogenase complex and transketolase.
- Areas affected in Wernicke’s encephalopathy have highest activity of transketolase.
Symptoms:
- Conjugate gaze and lateral rectus palsies, nystagmus, ataxia and mental confusion are classic features.
51
A 95 year old man passes away after experiencing an MI in his sleep. An autopsy of his brain reveals the following changes. His wife states that over the past year he had developed severe memory problems and seemed to have increasing difficulty expressing himself. What is his diagnosis and what types of pathologic changes have occured?
**Alzheimer's disease**:
**Clinical features:**
Memory impairment plus:
- Aphasia= paucity of speech
- Apraxia
- Agnosia= simultagnosia, eye movement changes, predominant parietal atrophy
Other symptoms:
- Difficulty planning
- Paranoia
- Hallucinations
- Nocturnal wandering
- Myoclonus in up to 20% in late stages
Continued gradual cognitive and functional decline, interfere significantly with social/occupational functioning (decline from past functioning)
- Accounts for 60-70% of cases of progressive cognitive impairment in elderly
**Hypothesis:**
Hallmarks on microscopic exam:
- Loss of neurons/synapses in neocortex, hippocampus
- loss of pyramidal cells
- **Extracellular amyloid plaques= senile plaque (front)**
- **Intracellular neurofibrillary tangles** (below)
Amyloid protein: APP
- Protective in plasma membrane
- Pathogenic (amyloidogenic) when full-length protein internalized
**Plaques form first--\> Neurofibrillary tangles**
1. Amyloid plaques:
- Extracellular accumulation of A-beta (fragment of the amyloid precursor protein)
- Abnormal processing of APP critical to pathophysiology of Alzheimer’s disease
2. Neurofibrillary tangles:
- Intracellular, paired helical structures composed of hyperphosphorylated tau.
- Correlate well with disease severity and neuronal death.
52
A 95 year old man passes away after experiencing an MI in his sleep. An autopsy of his brain reveals the following changes. His wife states that over the past year he had developed severe memory problems and seemed to have increasing difficulty expressing himself. What gross changes have occured in the specimen below, what was the pathophysiology of these changes, and what types of treatments could have been used for his symptoms?
**Alzheimer's disease: cortical and hippocampal degeneration**:
**Pathophys**:
Presenilin 1 (PS1) and presenilin 2 (PS2):--\> **cleave amyloid precursor protein (APP)
- Mutations in PS1/PS2--\>**A-beta42 and A-beta43 peptides (insoluble forms of A-beta amyloid)
- neurodegeneration due to A-beta 42 and 43 accumulation
* *Aβ42 i**s thought to **polymerize** as oligomers and trigger an inflammatory / oxidative response
- Soluble monomers ok, **oligomers are toxic,** and salt-linked polymer plaques are thought not to be intrinsically toxic so much as indication of dysfunction
- This in turn results in **hyperphosphorylation of tau**, a microtubule-associated protein
- Phosphorylation of tau _renders it insoluble and causes it to precipitate in the form of paired helical filaments called **neurofibrillary tangles (NFTs).**_
This cascade and polymerization is toxic to neurons resulting in the death of neurons that produce neurotransmitters.
\*\* Inheritance of apoE4 polymorphism enhances Beta-amyloid stability--\> accumulation of beta-amyloid
* *Gross:**
- Widespread cortical atrophy
- Generalized atrophy, hippocampal atrophy, hydrocephalus ex vacuo
**Below: neurofibrillary tangles**
* *Treatment**:
1. Enhancing cholinergic transmission
- Cholinergic neurons degenerate in AD: found in basal forebrain nuclei
- **Increase Ach using Ach-esterase inhibitors: donepezil, rivastigmine, galantamine**
2. Blocking excitotoxicity:
- Excitatory molecules toxic in neurodegeneration
- **Memantine= NMDA receptor antagonist**
3. Supportive treatment for pt and family
4. In the pipeline:
- Drugs clearing amyloid plaques (bapineuzemab vaccine)
- Drugs stabilizing tau (Davunetide)
- Drugs stablizing SORL1
- IVIG
- Basal forebrain DBS, hippocampal prosthetic, entorhinal cortex DBS
53
A 55 year old woman who has developed dementia and personality changes over the last 2 years is found in her apartment after an apparent suicide. Autopsy reveals the following changes in her brain. What is her likely diagnosis?
**Huntington's disease: atrophic caudate nucleus**
HD is an autosomal dominant disorder characterized by:
- chorea,
- problems with personality and affect
- dementia.
Trinucleotide disease involving a CAG repeat in the Huntingtin gene on Chromosome 4.
- Greater than 35 repeats is diagnostic.
- The prevalence is 4-8 in 100,000.
Presentation:
- Typically presents in the 40’s-50’s but may present at any age.
- Insidious, beginning with subtle motor signs and depression and apathy and progressing to total loss of motor function and dementia.
Pathology:
**- Loss of neurons in caudate, putamen, globus pallidus**
* *Treatment= supportive.**
- There are no effective treatments to stop or slow the disease.
- **Antidepressants** are used for mood issues
- _Dopamine depleting agents, including tetrabenazine, may be tried to ameliorate the chorea._
\*\* _Patients are at a marked risk for suicide,_ accounting for up to 10% of deaths of patients with HD.
54
A 75 year old man begins to develop tremors and his wife notices that he seems to walk slower around the house. On neurological exam her demonstrates slower movements and writes in smaller handwriting than normal. Based on the gross speciment below, what would his diagnosis be?
**Parkinson's disease:**
Four cardinal features:
- Tremor (3-6 Hz rest tremor);
- Bradykinesia;
- Rigidity (cogwheeling);
- Postural instability.
Supportive features:
- Hypomimia and hypophonia,
- micrographia
- stooped-flexed posture
- shuffling gait and festination
- constipation, anosmia, mood and sleep disorders
**Pathology:**
Loss of pigmented dopaminergic cell in the substantia nigra pars compacta and the formation of Lewy bodies in the brainstem.
* *Lewy bodies** (below) are cytoplasmic inclusion bodies that contain alpha-synuclein.
- Synucleinopathy?
**Treatment**:
The goal of treatment is to keep the patient functional for as long as possible.
Nonpharmacological treatment such as physical and speech therapy.
Pharmacological treatment aims at replacing or increasing dopamine levels in the brain. Drugs include Carbidopa/Levodopa, dopamine agonists, COMT inhibitors (that increase serum levodopa levels), and MAO-B inhibitors (that inhibit the breakdown of dopamine).
Complications of levodopa therapy include motor fluctuations and dyskinesias.
Deep brain stimulation is an option for select PD patients who have developed motor complications and medically refractory PD.
55
A 50 year old man notices that he is becoming clumsier over the past few months and he continues to trip and drop things. On a doctor's visit, he complains of his symptoms and the physician performs a neurological test that reveals a positive Babinski sign on the left foot. What might his diagnosis be based on the motor neuron changes (seen below)?
```
**Amyotrophic lateral sclerosis**:
Familial Variants (\< 10%): Cu Zn SOD 1 gene
```
Linked to Frontotemporal dementia (FTLD)
Sporadic (\> 90%); 1.5-2 per 100,000
- Man \> woman
- Onset 40-60 years
- Survival 2-6 years
Etiology unclear; pathological inclusions (ubiquitin, Bunina bodies, TDP-43) in motor neurons
- Muscle fibers are disconnected from dying nerve cells in brain and cord
- TDP-43= link betweeen sporadic and familial ALS
* *Signs and Symptoms:**
- Progressive degeneration of motor neurons in anterior horn of spinal cord, brainstem and motor cortex
- ALS= _Upper and Lower motor neuron signs in same segment; asymmetric weakness and atrophy (amyotrophy) with corticospinal tract signs (hyperreflexia)_
* *- Starts as hand/foot muscle weakness**
- Normal extraocular movements, sensory and sphincter function; normal mentation
- Cognitive impairment in 40%
- Dysphagia, dysarthria, resp. muscle involvement
- Hyperreflexia, Babinski sign, pseudobulbar affect- emotional lability
Treatment:
No effective therapy: Riluzole and supportive care, ventilatory support
56
**Astrocytoma**:
```
Astrocytoma (grade II lesion)
Anaplastic Astrocytoma (grade III= more malignant)
Glioblastoma (grade IV= generally fatal, can arise de novo)
Pilocytic astrocytoma (occur in children, Grade I= surgically curable, seen in cerebellum)
Pleomorphic xanthoastrocytoma (PXA)
```
**Diffuse astrocytomas** occur throughout the CNS generally in adults and most frequently in the cerebral hemispheres.
Diffuse astrocytomas tend to progress to a higher grade (to grades III and IV)- can infiltrate brain and spinal cord
- _The cellular density and anaplastia of the astrocytic tumors increase with tumor grade._
**Grade II= Cellular pleomorphism (mitoses- front)**
- Reaches surface of brain (gray and white matter involvement
**Prognosis:**
-Tumors of young adulthood
(3rd –4th decade)
-Typically present with seizure
-Diffuse, non-enhancing mass
-Highly infiltrative
-Median survival 5 years
-Most patients die from progression
of their disease to high-grade glioma
**Grade III (below)** = Anaplastic astrocytoma= cellular pleomorphism, mitotic figures
Grade IV= cellular pleomorphism, mitotic figures, tumor necrosis and or microvascular proliferation
57
* *Astrocytoma grade IV= Glioblastoma**:
* *Primary glioblastoma** (\> 90% glioblastomas) develop very rapidly with a short clinical history without clinical or histopathological evidence of a preexisting less malignant precursor lesion.
- They develop in older patients (mean age of diagnosis is 62 years old).
* *- EGFR, p10, chrom 10 loss**
**Secondary glioblastomas** develop through progression from diffuse astrocytoma (WHO grade II) or anaplastic astrocytoma (WHO grade III).
- Mean age of diagnosis is 45 years old.
\* Genetic differences seen between primary/secondary
- **p53, IDH1**
80% of malignant gliomas are glioblastomas
Male to female ration: 3/2
Peak age of onset 6th-7th Decades
Primary- age 55
Secondary- age 45
Median survival- 1 year
**Front:** **MRI**: Irregular enhancing periphery with central necrosis is characteristic for a glioblastoma
\* Infiltrate throughout brain, NOT surgical removal not curative
58
**Glioblastoma multiforme**:
High grade astrocytic tumor cellular pleomorphism, mitotic activity, necrosis and vascular proliferation
**Front: pseduopalisading necrosis**
Genome-wide analysis of gliomas= somatic mutations of Isocitrate Dehydrogenase 1 (12%)- 5/6 of secondary gliobastomas
* *Below:** vascular proliferation driven by VEGF= diagnostic feature in glioblastoma
- Treated with avastin (Bevacizumab)
59
Giant cell glioblastoma
- De novo clinical onset
- Average age of diagnosis-42
- M/F ratio - 1.1
- Distinct genetic profile
Pleomorphic and multinucleated giant cells in a Glioblastoma multiforme
Despite the apparent circumscription of the tumor, infiltration of the adjacent brain is often evident microscopically. Better prognosis than routine glioblastoma multiforme?
**Associated with Tuberous sclerosis**
60
Gliosarcoma:
Biphasic glioblastoma with alternating areas displaying
glial and mesenchymal differentiation. Constitute 2% of
glioblastomas. Age at diagnosis-56 years, M/F ratio 1.65.
Distinct genetic profile compared to classic GBMs
- See mitotic figures, necrosis, vascular proliferation
- Abundant reticulin deposition
- Mitotic figures in sarcomatous component
\*\* High propensity for metastases
- Patient survives long enough to manifest mets
61
```
Pleomorphic Xanthoastrocytoma (PXA)
- WHO grade II, generally circumscribed cerebral cortical tumor of children and young adults that often manifests with seizures and generally associated with favorable clinical outcome
```
62
**Pilocytic astrocytoma:** WHO 1
Cystic lesion with contrast enhancing nodule in 10 year old
Circumscribed, well differentiated neoplasms of childhood.
Annual incidence: 0.3/100,000
In children, most common glioma, median age 13
63
**Oligodendroglioma**:
Represent 15% - 20% of gliomas.
Most encountered in adulthood.
Infiltrating gliomas that most often occur in adults and typically involve the cerebral hemispheres
Often slow clinical evolution with long history of seizures,
the result of their tendency to infiltrate cortical grey matter
\*\* Patients with 1p19q deletion fare better, respond better to chemotherapy
\* Can become malignant: 6 mitoses/HPF--\> worse survival
64
**Ependymoma**:
Ependymomas: May occur in a wide age range, the peak incidence is between 10-15 years of age.
- Their most common sites of origin are in decreasing order of frequency:
- the fourth ventricle,
- lateral ventricles,
- third ventricle and the
- cerebellopontine angle.
**Histo: perivascular pseudorosettes**
Often see lesions within spinal cord: relatively well-circumscribed (confined to central canal), surgical excision possible (vs astrocytoma--\> infiltrates through spinal cord)
65
* *Subependymoma:** rare, benign non-enhancing lesions
- Occasionally removed due to compression, pressure in fluid spaces
- **Histo**: see nests of tumor cell nuclei in fibrillary matrix with mirocysts
66
Gangliogliomas
Tumor composed of both neoplastic neurons and neoplastic glia.
```
Well circumscribed (benign) and usually cured by surgical resection
- Contrast enhancing
```
67
**Dysembryoplastic neuroepithelial tumor (DNET)**:
Benign usually supratentorial glial neuronal
neoplasm occurring in children or young adults
characterized by cortical location and history of
drug resistant seizures
68
**Medulloblastoma= PNET:**
Malignant, invasive, embryonal
tumor of the **cerebellum** with
preferential manifestation in
children.
Predominant neuronal differentiation.
Can be cured
Combined radiotherapy and chemotherapy
60-70% 5 year survival
69
Atypical Teratoid Rhabdoid tumor:
Highly malignant CNS tumor of young children typically
containing rhabdoid cells. Often contains primitive
neuroectodermal cells with divergent differentiation along
Epithelial, mesenchymal, neuronal and glial lines.
Mutation or loss of the INI 1 (hSNF5.SMARCB1) locus at
22q11.2 is the genetic hallmark of AT/RT
\* Mean survival= 17 months
70
**Central neurocytoma** is a rare intraventricular brain tumor that affects young adults and presents with increased intracranial pressure secondary to obstructive hydrocephalus.
\*\* Typically, it has a favorable prognosis after adequate
surgical intervention, but in some cases the
clinical course is more aggressive.
\* resembles oligodendroglioma with more favorable prognosis (WHO grade II- young adults)
**EM:** Ultrastructural evidence of neuronal differentiation and diffuse immunohistochemical for synaptophysin and Neu-N
71
* *Choroid plexus papilloma**:
- Rare, less than 1% of brain tumors.
- Most often encountered in first decade of life and may be congenital.
- In decreasing order of frequency they occur in the fourth, lateral and third ventricles and the CP angle.
- Can cause hydrocephalus possibly due to overproduction of CSF
72
**Meningioma**:
Relatively common neoplasms accounting for approximately 15% of all primary intracranial tumors. Occur in middle life, usually after the third decade. Tumors originate from arachnoidal cap cells
\* Arises from meninges--\> pushes INTO brain
**Histo: meningioma whorls**
73
Pituitary adenomas are neoplasm of the Adenohypophysis
- Approximately 15% of intracranial neoplasms.
- Predominantly affect women in third to sixth decades.
- No age is exempt
74
**Craniopharyngioma**:
Epithelial tumor of suprasellar region
- 2-5% of primary intracranial neoplasms
**Histo:** can infiltrate into hypothalamus, but can be surgically excised if confined to capsule
- Epithelial tumor _within brain_
75
**B cell lymphoma**:
Not all malignant CNS neoplasms are neuroglial. Radiologic differential diagnosis of tumor as left includes malignant glioma, metastatic tumor, abscess and lymphoma
High grade B cell lymphomas that occur in the substance of the brain with no systemic component
In immunocompetent patients:
- PCNSLs account for approximately 3% to 5% of primary brain tumors.
PCNSL show features of late germinal center exit B-cell phenotype
The mean age of onset of PCNSL patients is 58 years
in immunocompetent patients and 38 years in
immunodeficient patients
**Treatment:** Chemo for immunocompetent, Antivirals for HIV patients (enhance immune system--\> fight off lymphoma)
**Histo:** stains positive for **CD20**
76
**Metastatic carcinoma of the brain**:
Arise most commonly from:
- Lung cancer
- Breast cancer
- Melanoma
Occurs in 20-40% of patients with cancer
**Treatment:**
Possible therapies include surgery for removal of
metastases vs. whole brain radiation followed by
stereotactic radiosurgery.
- Stereotatic radiosurgery is an appropriate form of therapy for patients who have 1 to 4 metastases no
larger than 4 cm in diameter.
77
Neurofibromatosis Type 1:
- Autosomal dominant, affecting 1:3000-1:4000 persons
- High new mutation rate.
- Tumors involving the CNS include optic gliomas, astrocytomas and rarely ependymomas.
- Malignant peripheral nerve sheath tumors arise from neurofibromas in approximately 5% of affected patients.
**Front**: Neurofibromas along spinal cord
78
**Schwanomas of NFT2**:
Autosomal dominant
Occurs in 1:135,000 persons
Gene located on chromosome 22
Bilateral “acoustic neuromas” (schwannomas).
Other common tumors include meningiomas and low grade gliomas.
**Schwannoma= nuclear palisading**
79
**Tuberous Sclerosis**:
Autosomal dominant disorder
1: 10,000-100,000
- Characteristic CNS lesions are multiple firm hamartomatous masses involving the cortex
- SEGAs (subependymal giant cell astrocytomas) = coat ependyma
80
**Von HIppel-Lindau Syndrome**:
Autosomal dominant disorder (VHL gene on Chrom 3= tumor suppressor gene- may play role in exit from cell cycle)
Prevalence of approximately 1:40.OOO.
Tumors include:
- “retinal angioma” (hemangioblastoma),
- hemangioblastomas of brain and spinal cord
- renal cell carcinoma
- pheochromocytomas.
**Below: renal cell carcinoma**
81
Man with Port-wine stain on face. Gross specimen from brain
**Sturge-Weber Syndrome**:
Facial port wine stain of the upper face in the distribution of the ophthalmic branch of the trigeminal nerve
- In complete form the cutaneous lesion is accompanied by ipsilateral venous angiomas of the leptomeninges, the choroid of the eye and the choroid plexus
- Usual clinical features include:
seizures, motor and sensory deficits, below normal cognitive ability and congenital glaucoma.
**Gross**: brain blood vessel abnormalities--\> calcification--\> brain changes (occured UNDER port wine stain
**Histo**: vascular changes in brain with calcification
82
**Anencephaly**:
Cranial vault is absent and cerebral hemisphere are replaced by a mass of highly vascularized, disorganized neural tissue (area cerebrovasculosa)
Folic acid now reduces chance of developing neural defects
83
Rachischisis= most severe spinal cord defect
84
**Spina bifida aperta=** can see into spinal cord at base
85
* *Arnold Chiari Malformation Type II:**
- Chiari type II malformation: Brainstem and cerebellum are compacted into small, abnormally shaped posterior fossa
- Structural abnormalities include polymicrogyria, hydrocephalus, stenosis of cerebral aqueduct, herniation of cerebellar tonsils, quadrigeminal plate “beaking” and kinking of medulla
\*\* _Unknown etiology_
**Gross**:
Arnold-Chiari II: Stenosis of cerebral aqueduct, herniation of cerebellar tonsils, quadrigeminal plate “beaking” and kinking of medulla
**Below**:
The caudal aspect of the cerebellar vermis is
herniated through an enlarged foramen magnum
and protrudes as a tongue on the dorsal aspect of
the cervical spinal cord
86
**Chiari Type I:**
Conical elongation of cerebellar tonsils and neighboring parts of cerebellar hemispheres into vertebral canal.
Often asymptomatic
87
**Hydrocephalus**:
**Congenital**:
Congenital Hydrocephalus- The cerebral aqueduct represents the narrowest part of the ventricular system.
Obstruction at this site either from
maldevelopment
acquired-following infection or hemorrhage
**Below**: communicating hydrocephalus
Obstructive= hemispheric ventricals enlarge
- Commonly obstructed at cerebral aqueduct
- Lateral and 3rd ventricles enlarge
88
**Migrational disorders**: Polymicrogyria
Disturbances in the migration of neurons from
the germinal matrix to the cerebral cortex
results in marked structural and
functional abnormalities in the brain
Migrational defects include:
- Polymicrogyria (extra gyri)
- Pachygyria (few gyri)
- Lissencephaly (no division of lobes)
89
**Holoprocencephaly**:
Disordered development of telencephalic or diencephalic structures.
Alobar holenprocencephaly
Semilobar holenprocencephaly
Arrhinencephaly
Disordered development of telencephalic or diencephalic structures from the prosencephalon.
**Alobar holoprosencephaly**-most severe form, forebrain is small consisting of an undivided spherical structure with irregularly disposed gyri.
Absent olfactory bulbs and tracts.
Optic nerve anomalies common.
One ventricular cavity in place of two lateral ventricles.
**Causes**:
Several etiologic factors have been associated including
Genetic defects (trisomy 13-15, trisomy 18 and other chromosomal disorders)
Familial cases
Maternal diabetes
90
**Agenesis of corpus callosum**
May be part of a more extensive malformation complex or may occur in isolation in an otherwise normal brain.
Agenesis of the corpus callosum can be entirely asymptomatic
