Head/Brain Diseases Flashcards
(277 cards)
1
Q
What headache does this describe: a person experiencing pain in the muscles of the region of the head and neck.
A
Tension headaches
2
Q
What headache does this describe: a severe pain in the head, un-associated with the musculature of the head, but associated with vascular disturbances.
A
Migraine headache
3
Q
What are tension headaches?
A
Primary headaches due to anxiety, stress, and tension. Characterized by tightness, pressure, or pain in the occipital or forehead area (bilateral)
4
Q
What are migraine headaches?
A
Primary headaches with paroxysmal attacks of headaches (throbbing) often preceded by psychological or visual disturbances. It can be accompanied by nausea, vomiting, drowsiness.
5
Q
What are the two types of migraine headaches?
A
Classical migraine - associated with a prodromal aura
Common migraine - not associated with a prodromal aura, but can be preceded with vague symptoms
6
Q
What are the three theories for etiology of migraines?
A
- vasodilatory theory: extracranial arterial vasodilation during an attack
- inflammation of the dural membranes
- altered normal firing of brain neurons
7
Q
What are cluster headaches?
A
Headaches with repeat occurances over weeks or months with a sudden onset of unilateral pain and short duration. The pain occurs several times per day, mostly during REM sleep.
Other symptoms: red eyes, lacrimation, rhinorrhea, stuffiness of nostrils, etc. (autonomic features)
8
Q
What are sinus headaches?
A
Headaches that mostly localized to the frontal areas of the head and around the eyes. Bending over exacerbates pain. Often accompanied by nasal congestion and rhinorrhea.
9
Q
How are tension headaches treated?
A
counseling, massage, heat application, rest, relaxation
non-narcotic analgesics, anxiolytic drugs
10
Q
What are preventive treatments for migraines?
A
propranolol - decreases frequency and severity
methysergide - serotonin antagonist
amitriptyline
calcium channel blockers
11
Q
What are non-pharmacologic treatments for migraine headaches?
A
exercise, relaxation, avoiding dietary triggers
12
Q
What are the abortive treatments for migraines?
A
- salicylates and acetaminophen (mild cases)
- triptans
- ergotamine
- narcotic analgesics
13
Q
What is the treatment for cluster headaches?
A
methysergide - prophylactic serotonin antagonist
can also use propranolol, amitriptyline, calcium channel blockers, and corticosteroids
14
Q
What is the mechanism of ergotamine?
A
Alpha-adrenoreceptor antagonist that directly constricts vascular smooth muscle
it asks as a serotonin antagonist
15
Q
What are symptoms of ergot poisoning?
A
vomiting, diarrhea, unquenchable thirst, tingling/itching/coldness of skin, rapid and weak pulse, confusion and unconsciousness, abortion in pregnant women
16
Q
What is the mechanism of methysergide?
A
Serotonin antagonist that acts as a weak adrenolytic agent, vasoconstrictor, and uterine constrictor
17
Q
What are the symptoms of methysergide toxicity?
A
retroperitoneal fibrosis, fibrous tissue adhesions on kidney/lung/heart/aorta/viscera
CNS effects (drowsiness, unsteadiness, weakness, etc)
18
Q
What is the mechanism of -triptan drugs?
A
They activate 5-HT receptors in the nerve to reduce the release of 5-HT, leading to vasoconstriction of cranial blood vessels
19
Q
What are oligodendrocytes?
A
Myelinating cells of the CNS, have perfectly round and dark nuclei with perinuclear halo
20
Q
What do astrocytes look like?
A
oblong nuclei with fine chromatin and cytoplasm that blends in with background parenchyma
21
Q
What is the appearance of microglia?
A
in “activated states” –> have thin, elongated, hyperchromatic nuclei
these are the resident macrophages of CNS
22
Q
What is the appearance of the ependyma?
A
single layer of cuboidal/columnar ciliated cells that line the ventricular system and form part of the brain-CSF barrier
23
Q
What are the effects and morphological features of acute neuronal injury?
A
occurs 12 hours after an acute, sustained neuronal injury and results in neuronal cell death
morphologic features: cell shrinkage, intensely eosinophilic (“red dead”) cytoplasm, pyknotic nucleus, loss of nucleolus
24
Q
What are the effects and morphologic features of subacute/chronic neuronal injury?
A
long-standing neuronal injury as part of progressive diseases
morphologic: progressive cell loss of functinoally associated groups, leads to hyperplasia and hypertrophy of astrocytes
25
What are the morphologic features associated with axonal injury?
rounding up and ballooning of cell body, dispersion of Nissl substance peripherally, and peripheral displacement of nucleus with enlarged nucleolus
26
What are some examples of neuronal inclusions? Proteinopathies?
Neuronal inclusions - cytoplasmic or intranuclear
Proteinopathies - aggregates of misfolded proteins that accumulate in neurodegenerative disease (ex. lewy bodies in parkinsons)
27
What changes and morphologies are associated with astrocyte gliosis?
hypertrophy and hyperplasia of astrocytes in response to CNS injury
morphologic: enlarged, eccentric nuclei with abundant, eccentric, eosinophilic cytoplasm
28
What are alzheimer type 2 astrocytes?
astrocyte changes that occur with long-standing metabolic disorders (not Alzheimer's disease)
morphologic features: enlarged nucleus, light chromatin, prominent nuclear membrane/nucleolus
29
What are rosenthal fibers? When do they occur?
morphologic features: thick and elongated, brightly eosinophilic, corkscrew-shaped structures in astrocytic processes
diseases: long-standing gliosis, slow growing tumors, some metabolic disorders of white matter
30
What is corpora amylacea?
Changes seen inaging or areas of long-standing injury, thought to represent degenerative changes in astrocytes
morphologic features: round, basophilic, concentrically lamellated structures prominent in areas of astrocytic end processes, may be calcified
31
What are the responses of microglia to injury?
- elongated shapes ("rod cells")
- increased numbers
- microglial nodules (aggregates around areas of necrosis)
- aggregates around dying neurons (neuronophagia, prominant in polio and ALS)
32
What conditions lead to oligodendrocyte injury?
demyelinating disorders and leukodystrophies
33
What diseases are associated with oligodendrocyte inclusions?
progressive multifocal laukoencephalopathy, neurodegenerative diseases
34
What are ependymal granulations?
disruption of ependymal lining with proliferation of subependymal astrocytes and formation of pinched of ependymal canals
occurs as a nonspecific reaction to injury
35
What is vasogenic edema?
cerebral edema due to increased extracellular fluid which occurs when the normal BBB is disrupted, resulting in increased vascular permeability that can be localized or generalized
36
What are the macroscopic characteristics of cerebral edema?
flattening of gyri, narrowing of sulci, and compression of the ventricular system
37
What is cytotoxic edema?
cerebral edema due to increased intracellular fluid secondary to cell injury, leads to inability to maintain normal membrane ionic gradients
## Footnote
*common etiologies: hypoxic-ischemic injury, metabolic derangements*
38
What is noncommunicating (obstructive) hydrocephalus?
increased CSF volume in the ventricular system caused by blockage in the ventricles preventing CSF from reaching subarachnoid space
leads to enlargement of the ventricular system proximal to blockage
39
What is communicating hydrocephalus?
hydrocephalus where CSF in ventricles can communicate freely with the subarachnoid space but leads to enlargement of the entire ventricular system (due to increased production of CSF, scarring of arachnoid granulations, etc)
40
What are the effects of increased intracranial pressure?
decreased perfusion (which can further raise ICP), displacement of tissue, herniations
41
What is a subfalcine (cingulate) herniation?
herniation of the cingulate gyrus under the falx, can compress the ipsilateral anterior cerebral artery
42
What is a transtentorial (uncal) herniation?
Herniation of the uncus/medial temporal lobe through the free margin of the tentorium
## Footnote
*can lead to compression of CN III, ipsilateral posterior cerebral artery, and ipsilateral cerebral peduncle*
43
What are duret hemorrhages?
linear midline and paramedian hemorrhages that result from torn perforating vessels of the midbrain and pons
## Footnote
*occurs with progression of the transtentorial herniation*
44
What is a cerebellar tonsillar herniation?
life-threatening herniation of the cerebral tonsils through the foramen magnum with compression of vital cardiac/respiratory centers in the medulla
45
What do perforating arteries supply?
they branch off the circle of Willis and supply the deep gray and white matter structures (basal ganglia, diencephalon, and internal capsule)
46
What are causes of focal cerebral ischemia?
embolism from a distant source, in situ thrombosis (often due to atherosclerosis), inflammatory processes of vessels, pro-thrombotic conditions
47
What is global cerebral ischemia?
a condition also called diffuse hypoxic-ischemic encephalopathy, caused by generalized reduction in cerebral blood flow that may cause irreversible damage to CNS tissue
48
Which neurons are most susceptible to injury in global cerebral ischemia?
- pyramidal neurons in CA1 region of hippocampus
- cerebellar Purkinje cells
- pyramidal neurons in neocortical layers 3 and 5 (watershed areas)
49
What are the prolonged effects of global cerebral ischemia?
widespread neuronal death, liquefactive necrosis
50
What are the general characteristics of nonhemorrhagic infarcts?
nearly identical to focal and global ischemia
initially nonhemorrhagic infarcts can undergo hemorrhagic transformation
51
What are the macroscopic findings of acute nonhemorrhagic infarcts?
no abnormalities within the first 8 hours, after 8 hours can lead to subtle blurring of gray-white junctions
52
What are the macroscopic findings of subacute nonhemorrhagic infarcts?
prominent softening, blurring of gray-white junction, tissue becomes more gelatinous and friable
occurs between 2-10 days
53
What are the macroscopic findings of a resolving nonhemorrhagic infarct?
repair process begins with liquefactive necrosis that is gradually removed and leaves to progressive cavitation
occurs after 10+ days to several months
54
What are the macroscopic findings of a remote nonhemorrhagic infarct?
The repair process is complete and left with CSF-filled cystic cavity
occurs after several months
55
What are the microscopic findings of an acute nonhemorrhagic infarct?
no changes within 12 hours, "red dead" neurons appear at 12 hours and can persist for days, influx of neutrophils
56
What are the microscopic findings of a subacute nonhemorrhagic infarct?
macrophages (seen at 48 hours), reactive astrocytes and capillary proliferations appear at the periphery
57
What are the microscopic findings of a resolving nonhemorrhagic infarct?
repair process begins as liquefactive necrosis proceeds with removal of necrotic tissue by macrophages
58
What are the microscopic findings of a remote nonhemorrhagic infarct?
complete repair process, some macrophages remain
left with cystic cavity and rim of reactive astrocytes
59
What are lacunar infarcts?
small perivascular, ischemic, cavitary infarcts that are seen in hypertension
most often involve the putamen, globus pallidus, thalamus, internal capsule, deep white matter, caudate nucleus, and pons
60
What is vascular dimentia?
neurologic decline as a result of multiple, bilater gray and white matter infarcts that can mimic other neurodegenerative diseases
often due to multifocal vascular disease of different types
61
What are ganglionic hemorrhages?
deep gray and white matter hemorrhages, most often in the putamen/thalamus/pons/cerebellum, caused by hypertension
62
What are the macroscopic findings of ganglionic hemorrhages?
acute - central core of clotted blood with compression of surrounding parenchyma
subacute - resorption of hematoma, friable and gelatinous surrounding tissue
resolving - liquefactive necrosis and progressive cavitation and gliosis
remote - cavitary lesion with brown rim
63
What are the microscopic findings of ganglionic hemorrhages?
acute - central acute hemorrhage and "red dead" neurons
subacute - influx of hemosiderin and lipid-laden macrophages
resolving - removal of necrotic tissue by macrophages with progressive cavitation
remote - cavitary lesions lined by gliosis and hemosiderin-laden macrophages
64
What are lobar hemorrhages? Microscopic features?
intraparenchymal hemorrhages involving cerebral hemispheres, most often caused by cerebral amyloid angiopathy
microscopic features: rigid leptomeningeal and intracortical vessels, vessel walls with dense/glassy pink material, positive stain for beta-amyloid
65
What are secondary hemorrhagic infarcts?
hemorrhagic transformation of an initially non-hemorrhagic ischemic infarct
leads to petechial hemorrhages
66
What is the most common non-traumatic cause of subarachnoid hemorrhage?
saccular (berry) aneurysm
67
Where do saccular aneurysms most commonly form?
arterial branch points in the anterior circulation
68
What are the macroscopic and microscopic findings of saccular aneurysms?
macroscopic: wide or narrow-necked thin walled outpouching, usually at an arterial branch point
microscopic: saccular wall that lacks internal elastic lamina and smooth muscle media (instead made of thickened intima and adventitia)
69
What are the macroscopic and microscopic findings of vascular malformations?
macroscopic: mass of irregular, tortuous, "worm-like" vessels in the subarachnoid and/or intraparenchymal
microscopic: large caliber vessels involving the subarachnoid space and/or brain parenchyma
70
Cell injury in the central nervous system is characterized by all the following EXCEPT:
a) red dead neurons
b) gliosis
c) microglial nodules
d) ciliated columnar cells lining the ventricles
d) ciliated columnar cells lining the ventricles
71
The following areas are most sensitive to hypoxic-ischemic injury EXCEPT:
a) caudate nucleus
b) CA1 region of hippocampus
c) cerebellar Purkinje cells
d) watershed cortical areas
a) caudate nucleus
72
All of the following are true about cerebral infarcts EXCEPT:
a) remote infarcts are usually cystic
b) remote infarcts can be dated based solely on histopathology
c) macrophages are a prominent feature of subacute infarcts
d) lacunar infarcts originate from arteriosclerosis of deep perforating arterial vessels
b) remote infarcts can be dated based solely on histopathology
73
What is this?
Red dead neurons
74
What is this?
axonal reaction with central chromatolysis
75
C) 12 hours
76
B) hypertension
77
D) 2 years
78
All pathways using glutamate are \_\_\_\_\_\_\_\_; all pathways using GABA are \_\_\_\_\_\_\_\_.
excitatory; inhibitory
79
What is the mainr eceiving area of the basal ganglia?
Striatum
80
The cerebral cortex sends _________ \_\_\_\_\_\_\_\_\_\_ projections to the striatum in a somatotopic fashion.
excitatory glutamatergic
81
In the basal ganglia, somatosensory and motor areas project to the __________ and association cortex to the \_\_\_\_\_\_\_\_\_.
putamen; caudate
82
What is the primary role of the substantia nigra?
Regulating dopamine production to modulate the direct and indirect pathways
83
What is the path of the indirect pathway of the basal ganglia?
D2 efferents (striatum) project to external globus pallidus (inhibitory) --\> projects to subthalamic nucleus (eGP inhibits STN, so STN is uninhibited since eGP activity is inhibited) --\> projects to GPi and SNr (STN excites them) --\> projects to venterolateral and ventral anterior nuclei of the thalamus then the cerebral cortex (inhibits them)
## Footnote
*disinhibition of STN ultimately leads to inhibition of the motor cortex and dampening of motion*
84
What is the path of the direct pathway of the basal ganglia?
D1 efferents project directly onto the GPi/SNr (inhibits them) --\> projects to the VL nucleus of the thalamus (uninhibits it, leading to motion)
85
What is the effect of a lesion of the substantia nigra pars compacta?
disruption of the pathway --\> results in loss of dopamine, loss of inhibitory effects on striatum --\> increased inhibition of the GPe, disinhibition of the STN, and therefore GPi
excitation of the GPi is also enhanced by lack of inhibition via the direct pathway
ultimate effect: slow movement, lack of movement, parkinsonism
86
What changes in the basal ganglia pathway lead to dyskinesias and hyperkinetic movements?
STN and GPi become excessively inhibited and do not suppress unwanted movements
87
What are the general criteria for parkinsonism?
brady kinesia + one other feature (rigidity and/or tremor)
88
How is parkinson's disease definitively diagnosed?
pathological confirmation of the presence of degeneration of SNc and other brain stem pigmented nuclei, and the presence of Lewy bodies
89
What are Lewy bodies?
histopathological hallmarks of parkinson's disease
intracytoplasmic inclusion bodies found in SNc, locus ceruleus, dorsal nucleus of vagus, pigmented nuclei, and cerebral cortex
90
How is parkinson's disease diagnosed clinically?
Clinical evaluation of symptoms with some imaging (MRI, PET and SPECT tracers, etc)
91
What are some other diseases that should be considered in the parkinson's disease differential?
progressive supranuclear palsy
multiple system atrophy
dementia with lewy bodies
92
What is the treatment for parkinsonism?
Levodopa - a precursor to dopamine that is capable of crossing the blood brain barrier
Also treated with dopamine agonists, COMT-inhibitors, MAO-B inhibitors, amantadine, and deep brain stimulation
93
How is levodopa converted to dopamine?
it is converted by aminoacid decarboxylase
94
What is the role of MAO-B inhibitors in treatment of parkinson's disease?
MAO-B inhibitors block reuptake of dopamine and enhance dopamine's effect in the synapse
95
What are the long term effects of levodopa treatment?
can lead to motor complications and dyskinesias
96
What are the most common clinical features of parkinsonism?
bradykinesia (required)
tremor, rigidity, postural instability, premotor symptoms (hyposomia, constipation, etc) and nonmotor symptoms (anxiety, cognitive impairment, etc)
97
How is the diagnosis of Parkinson's disease made?
Clinically - based on history, exam, and sometimes imaging to rule out other conditions that can mimic PD
98
What are the diagnostic criteria for multisystem atrophy?
autonomic failure, levodopa resistant parkinsonism, and cerebellar dysfunction
99
What is the "hot cross bun" sign?
cruciform hyperintensity in an atrophied pons in multisystem atrophy due to selective loss of myelinated transverse pontocerebellar fibers
100
What are the characteristic features of progressive supranuclear palsy?
downward gaze abnormalities, postural instability, unexplained falls, bradykinesia and rigidity (symmetrical), non-motor symptoms, pseudobulbar palsy
definite diagnosis: Tau neurofibrillay tangles/straight filaments on histopathology
101
What are the core clinical features of cortico-basal syndrome?
cortical dysfunction (dementia, asymmetric apraxia, alien limb phenomena, cortical sensory loss, visual neglect)
extrapyramidal dysfunction (asymmetric parkinsonism, action tremor, focal limb dystonia, myoclonus)
102
What is the "triad" associated with dementia with lewy bodies?
visual hallucinations, fluctuating cognition, parkinsonism
103
Which PD patients are ideal deep brain stimulation candidates?
tremor is a significant symptom
unpredictable off periods
responds well to levodopa
good surgical risk
104
What is a tremor?
involuntary, rhythmic, oscillatory, sinusoidal movement about a joint produced by contractions of reciprocally innervated antagonist muscles
105
Describe benign essential tremor.
- action-kinetic, postural, during voluntary movement, rarely at rest
- worse with anxiety, fatigue, temperture extremes, older age
106
What is chorea?
excessive spontaneous movements from a flow of muscle contractions that are "dance-like": irregularly timed, randomly distributed, abrupt, and semi-directed
107
What is the treatment of chorea?
neuroleptics (dopamine receptor blockers)
dopamine depeleting agents
108
What is dystonia?
sustained, but not fixed muscle contraction that can cause twisting or repetitive movements and abnormal postures
109
What are tics?
sudden, brief, intermittent movements or utterances that are briefly suppressible and usually associated with an urge for the action
110
What is myoclonus?
brief, "lightening"-like muscle jerks
111
What is bacterial meningitis?
An acute purulent infection within the subarachnoid space, associated with increased intracranial pressure, decreased consciousness, seizures, and stroke
112
What are the most common organisms responsible for bacterial meningitis?
strep pneumonia, neisseria meningitidis, group B strep, listeria monocytogenes
113
What is the most common pathogenesis of CNS infection?
hematogenous transmission
114
What are the three main types of transmission of CNS infections?
hematogenous transmission
contiguous spread
neuronal transmission
115
What is the classic clinical presentation of meningitis?
fever, headache, meningismus (nuchal rigidity or stiff neck)
progresses to cerebral dysfunction
can also include nasuea, vomiting, shaking chills, seizures, cranial nerve palsies (rarely)
116
What are signs of increased intracranial pressure?
CN III palsy, uni- or bilateral pupillary dilatation, papilledema, Cushing's reflex, decerebrate posturing, coma
117
What are the CSF findings of bacterial meningitis?
decreased CSF glucose (due to increased glycolysis by neutrophils)
increased CSF protein (altered BBB permeability)
CSF culture and gram stain
118
What is the treatment for bacterial meningitis?
empiric antibiotic regimen (ceftriaxone + vancomycin + ampicillin)
corticosteroids
119
What are the complications of bacterial meningitis?
focal neurologic deficits, cognitive impairment, seizure disorder, hydrocephalus (communicating and obstructive)
120
121
What is aseptic meningitis?
any meningitis that does not have a clear cause after initial evaluation with stains and cultures of CSF
122
What are causes of subacute/chronic meningitis?
mycobacterium tuberculosis, cryptococcus neoformans, syphilis, systemic diseases and neoplasms
123
What is encephalitis?
inflammation of the brain parenchyma
124
What is the pathogenesis of encephalitis?
mostly hematogenous spread, but can be due to neuronal transmission (ex. reactivation of latent HSV 1)
125
What is the clinical presentation of encephalitis?
fever, headache, altered consciousness, focal/multifocal neurological signs, seizures
126
What is the most common cause of focal encephalitis? What are the associated symptoms?
HSV-1 encephalitis
fever, headache, altered consciousness, hemiparesis, seizure activity, temporal lobe dysfunction
127
What is the pathogenesis of brain abscesses?
continuous spread from untreated frontal sinusitis or other nearby source
128
What are the clinical features of brain abscesses?
classic triad: fever, headache, focal neurologic deficit
frontal lesions --\> drowsiness, inattention, deteriorated mental function
temporal lesions --\> aphasia
cerebellar lesions --\> nystagmus, ataxia, vomiting, and dysmetria
129
How are brain abscesses diagnosed?
CT, but MRI is better
## Footnote
*LP contraindicated*
130
What is the treatment for a brain abscess?
drainage - percutaneous or surgical
prolonged antibiotics
131
hat is a spinal epidural abscess?
infection that spreads in the spinal epidural space (more likely in spine than cranium because the dura is less tightly adhered)
132
What is neurocysticercosis?
disease caused by pork tapeworm in humans
can present as an intestinal infection or a neurologic infection (with seizures, hydrocephalus, and inflammation/scarring)
133
What is ciguatera fish poisoning?
foodbourne illness caused by eating reef fish contaminated with toxins
symptoms: diarrhea, vomiting, numbness, itchiness, temperature sensitivity, neurologic symptoms
134
An 18 year-old woman presents with abrupt onset of fever, chills, severe headache, and stiff neck. Examination of her cerebrospinal fluid shows an elevated opening pressure; 33 RBCs, 1,200 WBCs, protein 388, and glucose 17. Gram stain of the fluid shows rare gram-negative diplococci. She is a college freshman and lives in a dorm with three roommates. Can treatment be safely narrowed based on CSF gram stain results? How did she acquire infection? Is it vaccine-preventable? How would you counsel her roomates and college?
consistent with neisseria meningitidis - therapy narrowed to ceftriaxone alone
acquired person-to-person via respiratory droplets
it is vaccine-preventable
can be passed to close contacts
broader college population should be vaccinated
135
A 72 y.o. man presents with fever, headaches, and dsyphagia. A stat CT scan of the brain (without contrast infusion) is unremarkable. A lumbar puncture is performed and shows 3 RBCs, 48 WBCs, protein 43, and glucose 57. Is further testing necessary? What treatment is recommended? Can he be safely discharged?
CSF suggests mild asceptic/viral meningitis, but focal neurologic deficits suggest focal encephalitis
differential includes HSV-1 encephalitis
further testing necessary, empiric treatment indicated
not safe to discharge
136
What are gliomas? What are the two main histologic subgroups?
primary CNS tumors from neuroepithelial tissue
subgroups: astrocytoma and oligodendroglioma
137
What are the WHO grades for tumors?
Graded I-IV based on severity
I and II = low grade
III/IV = high grades
138
What are the four grades of astrocytic tumors?
Grade I = pilocytic astrocytoma
Grade II = astrocytoma
Grade III = anaplastic astrocytoma
Grade IV = glioblastoma multiforme
139
What are the types/grades of oligodendroglial tumors?
grade II = oligodendroglioma
grade III = anaplastic oligodendroglioma
140
What are the types/grades of ependymal tumors?
Grade II = ependymoma
Grade III = anaplastic ependymoma
141
What staining can identify astrocytic tumors?
glial fibrillary acidic protein
142
What is the prognosis of glioblastoma multiforme?
very poor - most common malignant primary brain tumor
143
What is the gross and microscopic appearance of glioblastoma multiforme?
gross: necrotic, yellowish mass that diffusely infiltrates the normal brain
microscopic: increased cellularity, pleomorphism, atypia, mitoses, pseudo-palisading necrosis, and microvascular proliferation
144
What is the treatment for glioblastoma multiforme?
neurosurgery to improve patient function and improve effectiveness of radiotherapy and chemotherapy
other targeted therapy (ex. anti-VEGF antibody)
145
What are oligodendrogliomas?
tumors of glial cells that are usually supratentorial and arise in the frontal lobes and are often heavily calcified
146
What are the gross and microscopic findings of oligodendroglioma?
gross: similar to astrocytomas but calcified
microscopic: fried egg appearance (cleared cytoplasm), distinct cell borders, and small bland hyperchromatic nuclei
chicken wire branching vessels
147
What are the main markers for oligodendrogliomas?
loss of heterozygosity for chromosomes 1p and 19q (1p19q codeletion)
148
What is the cause of death associated with oligodendrogliomas in most patients?
transformation into anaplastic oligodendrogliomas
149
What are meningiomas?
slow-growing often benign tumors that arise from the meningothelial cap cells of the meninges
150
What are the risk factors for meningiomas?
genetic predisposition (neurofibromatosis type 2) and prior exposure to ionizing radiation
151
What is the gross morphology of meningiomas?
lobulated tumors with a rubbery consistency
they separate easily from brain tissue (but can invade sinuses and encase arteries)
152
What are the most common presenting symptoms associated with meningiomas?
focal seizures, neurologic deficits, and other location-specific signs
153
What type of tumor is this most consistent with?
meningioma
154
What is the treatment for meningiomas?
monitoring if small or asymptomatic/medically controlled
surgery (can be curative if completely resected)
unresectable tumors get radiation therapy
155
What is a schwannoma?
A tumor that arises from the nerve sheath (can occur anywhere in the body, but most common in the vestibular part of the CN VIII)
156
What is the main risk factor for schwannoma?
unilateral = sporadic
bilateral = almost always neurofibromatosis type 2 (mutation in the merlin gene)
157
What is the clinical presentation of vestibular schwannomas?
gradual, unilateral hearing loss sometimes preceded or accompanied by tinnitus and a vague feeling of dizziness/unsteadiness while walking
can also present with hemifacial spasm and facial numbness
158
What are the physical exam findings and imaging findings associated with schwannomas?
exam: ipsilateral decreased facial sensation, cerebellar ataxia, nystagmus, increased ICP
imaging: on MRI, characteristically isointense with nerve on T1-weight, isointense with CSF on T2- weight (harder to see), contrast intensely
159
What is the treatment for vestibular schwannomas?
surgical resection and radiosurgery to cure tumor and preserve function
160
What are pituitary adenomas?
tumors of pituitary tissue that alters endocrine function (either directly or by compressing normal tissue)
as it grows, it can cause headaches and compression of cranial nerves
161
How are pituitary tumors diagnosed?
Imaging: contrast enhanced MRI (hypointense on T1) and calcification seen on CT
Blood: hormone levels measured in the blood
162
How are pituitary adenomas treated?
Surgically, may also be treated with suppression of hormone hypersecretion
163
What is a primary central nervous system lymphoma?
a non-Hodgkin's lymphoma that arises within the CNS, predominantly a large B cell tumor with a multifocal angiocentric pattern of growth
immunodeficiency is a risk factor
164
What are the imaging findings of a primary central nervous system lymphoma?
usually involves the frontal lobes, corpus callosum, and deep periventricular brain structures
MRI: hypointense on T1 and hypo/isointense on T2, usually homogenous enhancement with IV contrast
165
What are the symptoms of primary central nervous system lymphoma?
cognitive impairment, behavioral changes
seizures
headache, hemiparesis/hemisensory loss
*note: do not have classic lymphoma B cell symptoms like fever, night sweats, weight loss, etc.*
166
How are primary central nervous system lymphomas diagnosed?
requires histology for diagnosis (imaging can help, but not definitive)
167
What is the treatment for primary CNS lymphoma?
radiotherapy and chemotherapy (sensitive to both) on the whole brain + systemic methotrexate at a high dose
NOT corticosteroids - can make them undetectable for a bit, but then they come back
168
What are the risks associated with therapy for primary CNS lymphoma?
neurotoxicity that can lead to dementia, ataxia, and urinary incontinence
169
What are medulloblastomas? Where do they usually localize?
malignant childhood tumor
normally localized to the vermis of the cerebellum, but can seed in the leptomeninges and cause widespread metastases
170
What are the histological features of medulloblastoma?
densely packed cells with round, oval nuclei surrounded by scanty cytoplasm
homer wright rosettes found 40% of the time
171
What are the most common presenting symptoms of medulloblastoma?
presents in children with headache and vomiting (often projectile and without preceding nausea)
symptoms often only present in the morning after first waking up
also includes gait ataxia (vermis controls balance) --\> children appear "drunk"
also have other cerebellar abnormalities on exam
hydrocephalus is often present at diagnosis
172
What imaging findings are associated with medulloblastoma? Histology findings?
imaging: intense, homogenously enhancing mass in the vermis without evidence of cyst formation or necrosis
histology: small, round undifferentiated cells with mild/moderate nuclear pleomorphism
173
How are medulloblastomas categorized?
either histologically (classic, desmoplastic/nodular, medulloblastoma with extensive nodularity, large cell/anaplastic medulloblastoma)
OR
genetically (WNT activated, SHH activated, non WNT or SHH group 3 and 4)
174
What is the treatment for medulloblastoma?
surgical resection of as much as possible, followed by whole-neuraxial radiation and sometimes chemotherapy
175
What are pilocytic astrocytomas?
low-grade astrocytic tumors in children and young adults that are found in the cerebellum, optic nerve/chiasm, hypothalamus (in kids) or the cerebral hemispheres or cerebellum (in adults)
176
What are the gross and histological features of pilocytic astrocytoma? Imaging?
Gross: well-demarcated and cystic
histology: has long rosenthal fibers (brightly eosinophilic) and microcysts
imaging: solid and cystic mass, usually contrast enhancing
177
What are the typical symptoms of pilocytic astrocytomas?
gait and ipsilateral limb ataxia (if in cerebellum)
cognitive and behavioral abnormalities with endocrine dysfunction (if in hypothalamus)
visual field defects and blindness (if in optic nerve)
178
What is craniopharyngioma?
tumors believed to arise from the remnants of Rathke's pouch (embryonic precursor of anterior pituitary, oral mucosa, and teeth)
usually in a pseudocapsule above the sella turcica and include compression of third ventricle, increased ICP, and endocrine dysfunction
179
What characteristic visual abnormality accompanies craniopharyngioma?
bitemporal hemianopsia
180
What is the pathophysiology of metastatic/secondary CNS tumors?
must develop its own blood supply --\> invade local tissues --\> enter circulation and reach venous circulation --\> hits the lung first (usually first spot of metastases) --\> must grow in lung and seed the pulmonary venous circulation to be sent to the brain by the heart
181
What two factors promote metastases to the brain?
- brain gets a ton of the body's overall blood flow
- brain is a good spot for arrest and growth (protected from immune, good blood supply)
182
What are supportive care tools for metastatic brain cancer?
corticosteroids - for symptoms
anticonvulsants - for symptoms
anticoagulants - thromboembolic disease more likely with cancer
183
What are disease modifying treatments for brain metastases?
- surgery
- radiation therapy
- radiosurgery
- chemotherapy
* prognosis is usually very poor*
184
Which of the following frequently present with seizures:
high grade glioma, low grade glioma, PCNSL, meningioma
low grade glioma = meningioma \> high grade glioma
## Footnote
*PCNSL can also cause seizures*
185
Which of the following frequently present with focal neurologic deficits:
high grade glioma, low grade glioma, PCNSL, meningioma
high grade glioma \> PCNSL
## Footnote
*low grade glioma and meningioma can also cause this but less likely*
186
Which of the following frequently present with cognitive/behavioral changes:
high grade glioma, low grade glioma, PCNSL, meningioma
PCNSL \> high grade glioma \> meningioma (least likely)
187
How do brain tumors present clincally?
both focal neurologic symptoms as well as generalized neuro symptoms from high ICP
188
What does contrast enhancement on neuro-imaging indicate?
blood brain barrier breakdown
189
Why should brain tumor patients with seizures not receive enzyme inducing anticonvulsants?
these may interfere with chemotherapy
190
What genetic abnormality/tumor marker is seen in oligodendroglioma?
1p19q codeletion
191
Why does glioblastoma often have a classic "butterfly" appearance on MRI?
it grows and spreads via white matter tracks, including the corpus callosum that gives the "butterfly" appearance
192
Why do meningiomas enhance homogenously after the administration of IV contrast?
because they lie outside the BBB
193
Why can't many gliomas be surgically resected completely?
because they may be growing in "eloquent" cortex that can't be cut without damaging the patient's neurologic state
194
Why aren't gliomas treated with focal radiotherapy instead of whole brain radiotherapy?
because wbrt would cause more risks without benefit
195
What is the standard surgical approach for a patient suspected of having a primary CNS lymphoma?
biopsy only
196
Where do medulloblastomas originate from?
vermis of the cerebellum usually
197
How can you differentiate craniopharyngioma from pituitary adenoma on imaging?
calcification with craniopharyngioma (best seen on CT head)
198
What visual field defects do patients with pituitary adenoma present with?
bitemporal hemianopsia
199
What syndrome is bilateral CN VIII schwannomas pathognomonic for?
neurofibramatosis type 2
200
In what tumor are Rosenthal fibers found?
pilocytic astrocytoma
201
Why do patients with medulloblastoma often present with signs of increased intracranial pressure?
from obstruction of the 4th ventricle due to tumor growth
202
Which tumor type has "pseudopallisading necrosis" microscopically?
glioblastoma
203
What is the mechanism whereby corticosteroids reduce symptoms in primary or secondary brain tumors?
by reducing vasogenic edema
204
How do leptomeningeal metastases present?
with both focal and generalized symptoms, also classically cranial nerve and spinal nerve findings/symptoms
205
hy do patients with leptomeningeal metastases develop headache and signs of increased intracranial pressure?
because of abnormal CSF absorption from tumors interfering with arachnoid granulations and normal CSF reabsorption
206
Which tumor type has psammomabodies on histology?
meningioma
207
What are signs of increased intracranial pressure?
headache, nausea, vomiting
208
What is the appearance of a meningioma on MRI?
homogenously enhancing dural based tumor with enhancing dural tails
209
What is the role of surgery in gliomas?
for diagnosis and treatment
greater extent of resection leads to better prognosis
210
What are the most common pediatric tumors?
medulloblastoma, ependymoma
211
What is nystagmus?
rhythmic pattern of a slow phase of eye movement, followed by a fast phase of eye movement that is oppositely directed
*direction of nystagmus designated by the direction of the fast phase movement*
212
What is vestibular neuritis?
inflammation of the vestibular nerve
213
What is the physiology of the vestibular sensory cells?
"hair cells" function as motor sensors by converting movement into an electrical signal
each hair cell has a specific orientation (meaning movement one way may lead to increased firing while movement another way may lead to decreased firing) and is paired with a cell with the opposite polarity
the difference in firing rates between each hair cell is processed by the vestibular nuclei and sends signals to oculomotor nuclei to drive eye movements
214
What is the effect of rotation of the head around the vertical axis on hair cells in the horizontal semicircular canals?
turning head causes increased firing ipsilaterally and decreased firing on the contralateral side (push-pull relationship)
215
What is the pathophysiology of eye movement in vestibular neuritis?
damage to vestibular nerve reduces rate of electrical signaling coming from the inner ear on that side
this causes eyes to drift towards the side affected by vestibular neuritis at first, and then snapping back to the target (the snap back direction = direction of the nystagmus)
216
What is the treatment for vestibular neuritis?
acute phase: manage symptoms (dizziness, anti-emetics)
later: vestibular rehabilitation therapy
217
What is the dix-hallpike maneuver?
A maneuver to test for vestibular function where a patient's head is tilted and then the patient's upper body is lowered flat quickly
tests for benign paroxysmal positional vertigo
218
What is the pathophysiology of benign paroxysmal positional vertigo?
otoconia (crystals) reside in the parts of the inner ear labrynth (utricle and saccule) under normal conditions
sometimes the crystals can break off and enter the semicircular canals and stimulate the cristae ampullaris of the semicircular canals, leading to the sensationof dizziness and nystagmus
219
What is the treatment for benign paroxysmal positional vertigo?
vestibular maneuvers that guidethe patient's head through a series of positions to use gravity to coax loose otoliths out of the semicircular canal and back to the saccule/utricle
most common maneuver called the Epley maneuver (for the posterior canal)
220
What is gentamicin ototoxicity?
gentamicin (and some other aminoglycoside antibiotics) are preferentially vestibulotoxic
they accumulate slowly and can have toxic effects that persist to weakness or complete loss of the vestibular hair cells
symptoms can improve despite permanent loss of cells due to multisensory integration
221
What is the physiology of multisensory integration?
incorporation of multiple sensory modalities (vestibular function, vision, somatic sensation, proprioception) to understand the body's orientation and movement through space
normally these inputs are prioritized and weighted based on what position is most likely, but if one of them is lost the others can help compensate
222
What is the pathophysiology of motion sickness?
a nauseous feeling that can arise when multisensory integration fails to reconcile inter-sensory discrepancies
223
What is the treatment for motion sickness?
vestibular suppressants (dimenhydrinate, meclizine)
224
What is the histologic criteria for grading glial tumors?
AMEN
Atypia
Mitoses
Endothelial/vascular proliferation
Necrosis
225
What are the histologic findings of infiltrating astrocytomas?
increased cellularity, infiltration of cortex by atypical astrocytes
mitoses, vascular proliferation and necrosis (higher grade tumors)
226
What genes are associated with astrocytomas?
isocitrate dehydrogenase genes
227
What is the most common location of pilocytic astrocytomas?
cerebellum (most common)
can also be in thalamus/hypothalamus/third ventricle, optic nerves, cerebral hemisphere, and spinal cord
228
What are the imaging, gross, and histologic findings of pilocytic astrocytoma?
imaging: cyst with enhancing mural nodule
gross: well-circumscribed, well-demarcated from adjacent brain parenchyma
histologic: well-circumscribed, minimal infiltration at edges of tumors, biphasic (compact areas of rosenthal fibers, loose/microcystic areas)
229
What are the histologic findings of grade 2 and grade 3 oligodendrogliomas?
Grade 2: sheets of cells with round, uniform nuclei with a moderate amount of clear cytoplasm with a background of "chicken wire" capillaries with microcalcifications
Grade 3: same as 2 but with increased nuclear atypia, increased mitoses, epithelial proliferation and/or necrosis
230
What are the histologic findings of ependymomas?
round to oval, uniform nuclei and eosinophilic cytoplasm
forms perivascular "pseudorosettes" or true ependymal rosettes
231
What are the histologic features of medulloblastoma?
large, hyperchromatic nuclei and scant cytoplasm, nuclear molding
may form Homer-Wright rosettes
232
What genetics are associated with atypical teratoid/rhabdoid tumors?
loss/mutation of hSN5/INI1 gene on chromosome 22
233
Which of the following tumors shows increased mitoses, microvascular proliferation, and pseudopalisading necrosis?
a) glioblastoma, WHO grade 4
b) oligodendroglioma, WHO grade 2
c) diffuse astrocytoma, WHO grade 2
d) anaplastic astrocytoma, WHO grade 3
e) ependymoma, WHO grade 2
a) glioblastoma, WHO grade 4
234
Which of the following primary neuroepithelial neoplasms represents a non-infiltrating lesion:
a) anaplastic astrocytoma
b) anaplastic oligodendroglioma
c) glioblastoma
d) diffuse astrocytoma
e) pilocytic astrocytoma
e) pilocytic astrocytoma
235
Perivascular pseudo-rosettes and true rosettes are most diagnostic of:
a) oligodendroglioma
b) ependymoma
c) pilocytic astrocytoma
d) diffuse astrocytoma
e) glioblastoma
b) ependymoma
236
What type of tumor is this?
Astrocytoma
## Footnote
*top = diffuse GII, bottom = anaplastic GIII*
237
What type of tumor is this?
oligodendroglioma
238
What type of tumor is associated with ependymal rosettes/pseudorosettes?
Ependymoma
239
What type of tumor is this?
Ependymoma
240
Which type of tumor is associated with bi- and multinucleate, dysmorphic neurons?
Ganglioglioma
241
What type of tumor is associated with Homer-Wright rosettes?
Medulloblastoma
242
What type of tumor is this?
Medulloblastoma
## Footnote
*homer-wright rosettes*
243
What type of tumor is this?
Meningioma
244
a) glioblastoma
## Footnote
*pseudo palisading necrosis associated with higher grade tumors*
245
D) oligodendroglioma
246
Perivascular pseudorosettes and true rosettes are most diagnostic of:
a) oligodendroglioma
b) ependymoma
c) pilocytic astrocytoma
d) medulloblastoma
e) glioblastoma
b) ependymoma
247
E) meningioma
248
Which of the following primary neuroepithelial neoplasms represents a relatively discrete type of lesion?
a) anaplastic astrocytoma
b) anaplastic oligodendroglioma
c) glioblastoma
d) medulloblastoma
e) pilocytic astrocytoma
e) pilocytic astrocytoma
249
What are the two types of territories affected by an arterial occlusion stroke?
- area of brain entirely supplied by the artery (core of the ischemic stroke)
- area fed jointly by more than one arteries (perfusion lesion)
250
What are the treatments for an acute stroke?
reopen the occluded artery: thrombolytic agents by vein (main approach), can also do a more aggressive revascularization therapy (less common, reduced evidence)
251
How are recurrent strokes prevented?
Identify the cause of the first stroke and alleviate the cause (ex. reduce clotting if the problem was an emboli)
252
What is the mechanism of a small vessel occlusion stroke?
occlusion due to microatheroma or lipohyalinosis of penetrating arteries in the basal ganglia, internal capsule, thalamus, or pons
occurs due to hypertension, diabetes, and smoking
253
What is the treatment for small vessel occlusion strokes?
antiplatelet medications (aspirin), statins, and blood pressure control
254
What is the mechanism of large vessel cervical artery disease?
Occlusion or stenosis of the cervical carotid or vertebral arteries
255
What is the treatment for large vessel cervical artery disease?
risk factor control
if carotid stenosis, endarterectomy or stenting
256
What is the mechanism of intracranial atherosclerosis? Treatment?
mechanism: occlusion or stenosis of the intracranial vessels of the circle of Willis
treatment: risk factor control, antiplatelet therapy, and (rarely) angioplasty and stenting
257
What is the mechanism of cardioembolic strokes? Treatment?
mechanism: stroke due to embolization of thrombus or other material from the heart, often secondary to afib, low ejection fraction, cardiac thrombus, recent MI, or tumors
treatment: anticoagulation with warfarin (or others)
258
What is the typical presentation of a stroke patient?
older man with hypertension and afib, not on blood thinners
suddenly stops speaking, limp on one side, fall out of chair
awake patient, no speech, no comprehension, no blinking on weakened side, hemiplegia
259
What are clinical predictors of stroke risk at 90 days post-transient ischemic attack?
- age \> 60
- BP \> 140/90
- clinical features (hemiparesis, speech)
- diabetes
- duration \> 10 min
260
What is a lacunar stroke?
A stroke from one of the small arteries that provides blood to the brain's deep structures
261
What are the symptoms of a left anterior cerebral artery stroke?
right leg weakness (motor cortex medially)
right leg numbness (sensory cortex)
difficulty initiating verbal responses (prefrontal cortex and supplementary motor area)
262
What are the symptoms of a left middle cerebral artery stroke?
right face and arm \> leg weakness (motor cortex/CST)
right sided sensory neglect (sensory cortex/parietal dysfunction)
global aphasia (Broca's and Wernicke's area)
263
What are the symptoms of a right posterior cerebral artery stroke?
left visual field homonymous vision loss (visual cortex)
left sided numbness (thalamus)
264
What are the symptoms of a left retinal artery stroke?
left eye painless vision loss (amaurosis fugax)
265
What are the symptoms of a lacunar stroke of the right internal capsule, posterior limb?
pure motor hemiparesis
pure sensory loss
ataxic hemiparesis
clumsy-hand dysarthria
266
What are the symptoms of a basal artery penetrator stroke?
left hemiparesis (from right corticospinal tract)
right hemiataxia (from right pontine nuclei)
dysarthria (right corticobulbar tract)
267
What are the symptoms of a right posterior inferior cerebral artery stroke?
right dysmetria and ataxia (cerebellum)
headache (pressure)
nausea/vomiting (area postrema)
dizziness (vestibular connections)
268
What are the locations of intracranial hemorrhage?
subarachnoid, subdural, intraventricular, intraparenchymal
269
What is the most common risk factor for intracranial hemorrhage?
hypertension
270
What is a traumatic brain injury?
nondegenerative, noncongenital insult to the brainfrom anexternal mechanical force, possibly leadingto permanent or temporary impairment of cognitive, physical, and psychosocial functions, with an associated diminished or altered state of consciousness
271
How are potential traumatic brain injuries evaluated?
quick neuro exam, CT scan without contrast, consider intubating if neuro exam shows significant findings
272
What are the components of the Glascow coma score?
eye opening (4 - spontaneous, 1 - none)
motor response (6 - follows commands, 1 - none)
verbal function (5 - oriented x3, 1 - no response)
*consider intubation if \< 8*
273
What are intraparenchymal hemorrhages?
"bruising" of the brain, often of the bilateral frontal lobe
can "blossom" over time
274
What is the most common etiology of subdural hematoma?
bridging veins
275
What is the usual cause of epidural hematoma?
injury to middle meningeal artery from temporal bone fracture
276
What are the imaging features of diffuse axonal injury?
CT looks pretty normal
need specialized imaging to see
277
What is chronic traumatic encephalopathy?
progressive neurodegeneration associated with repetitive head trauma
