Block 8 (Neuro) - L9, L10 Flashcards
1
Q
Where is an epidural abscess located?
A
Space between the bone and the dura
2
Q
Where is a subdural empyema located?
A
Space between dura and leptomeninges
3
Q
What is meningitis?
A
Inflammation within the subarachnoid space (between arachnoid and pia mater)
4
Q
What is encephalitis?
A
Inflammation of brain parenchyma (meningoencephalitis when subarachnoid space is also inflamed)
5
Q
What is polio, leuko, and panencephalitis?
A
Polioencephalitis - primarily affects the gray matter
Leukoencephalitis - primarily affects the white matter
Panencephalitis - affects both
6
Q
What is ventriculitis?
A
Inflammation of the ventricles
7
Q
What are the 5 broad causes of meningitis?
A
- Bacterial
- Fungal
- Amebic and tuberculous
- Viral
- Non-infectious - chemical (e.g. post-op), meningeal carcinomatosis
8
Q
What are the most common pathogens causing bacterial meningitis?
A
S. pneumoniae
N. meningitidis
H. influenzae
9
Q
What pathogens tend to cause acute bacterial meningitis in patients <1 month old?
A
- E. coli
- Group B strep
- L. monocytogenes
10
Q
What pathogens tend to cause acute bacterial meningitis in patients who are 1 month - 16 years old?
A
- N. meningitidis
- H. influenzae
- S. pneumoniae
11
Q
What pathogens tend to cause acute bacterial meningitis in adults (>15 y/o) who are immunocompetent?
A
- S. pneumoniae
2. N. meningitidis
12
Q
What pathogens tend to cause acute bacterial meningitis in patients who are immunocompromised (age, diabetes, steroids, alcohol use, etc.)
A
- L. monocytogenes
2. Group B strep
13
Q
What is seen on the gross brain in bacterial meningitis?
A
Pus (thick, creamy exudate composed of protein, bacteria, and neutrophils)
14
Q
CSF findings - bacteria
Fluid quality? Cells present? Protein? Glucose? Pressure?
A
Fluid quality: cloudy Cells present: PMNs Protein: very high Glucose: low (compared to plasma levels) Pressure: high
15
Q
What is seen on H&E stain in bacterial meningitis?
A
Subarachnoid space is filled with inflammatory cells (normally empty)
Note - the cortical surface is largely uninvolved
16
Q
What are the 6 causative agents of chronic meningitis?
A
- Tuberculous (M. tuberculosis, rare)
- Fungal (Cryptococcus neoformans, Histoplasma capsulatum, Coccidioides immitis)
- Parasitic
- Syphilis (T. pallidum, rare)
- Borreliosis (B. burgdorferi, rare)
- Non-infectious (neurosarcoid)
17
Q
What is seen on histology in CNS tuberculosis prior to development of meningitis?
A
Rich foci (nodules) - small subpial tubercles
18
Q
What is the clinical presentation of CNS tuberculosis?
A
- CN deficits (common)
2. Signs of meningeal irritation (variable)
19
Q
CSF findings - TB
Fluid quality? Cells present? Protein? Glucose? Pressure?
A
Fluid quality: n/a Cells present: lymphocytes Protein: moderately high Glucose: mildly low (compared to plasma levels) Pressure: n/a
20
Q
What are the 4 different clinical pathologic patterns seen in CNS TB?
A
- Tuberculous meningitis
- Tuberculoma
- Tuberculous brain abscess
- Vertebral osteomyelitis (Pott’s disease)
21
Q
What is seen on the gross brain in tuberculous meningitis?
A
Thick exudate at the base of the brain
22
Q
What is seen histologically in CNS TB?
A
Characteristic lesion - necrotizing granuloma
23
Q
What is a tuberculoma?
A
Space-occupying lesion with a caseous center and granulomatous inflammation; common in patients with miliary TB
24
Q
What are the 3 clinicopathologic patterns of neurosyphillis?
A
- Aseptic meningitis
- Meningovascular syphilis
- Parenchymal neurosyphilis (general paresis and tabes dorsalis)
25
What does the CSF show in neurosyphillis?
Aseptic meningitis
26
Discuss the presentation of meningovascular syphilis.
Develops months-years after primary infection (earlier in HIV)
Thickened meninges leads to hydrocephalus and CN palsies
Obliterative endarteritis leads to thrombosis and infarction
27
What is seen morphologically in meningovascular syphillis?
Lymphocytic vasculitis
28
Discuss the presentation of general paresis.
Presents 5-25 years after infection
Symptoms: psychosis and dementia
29
What is seen on pathology in general paresis?
Cortical atrophy of frontal and temporal lobes; large number of spirochetes present
30
Discuss the presentation of tabes dorsalis.
Pupillary abnormalities, optic nerve atrophy with declining visual acuity, ataxia, bladder and bowel dysfunction
31
What is seen on pathology in tabes dorsalis?
Posterior spinal roots and columns atrophy; no spirochetes demonstrated
32
What patients are most likely to get fungal infections of the CNS?
Patients who are immunocompromised
33
The majority of fungal CNS infections are part of systemic infection. List some of the causes.
1. Lung (most common primary site)
2. Cutaneous mycosis
3. Sinus or mastoid (zygomycetes)
4. Infected heart valve
5. Acquired (iatrogenic)
34
What are the possible presentations of CNS fungal infections?
1. Meningitis
2. Encephalitis
3. Granuloma or abscess
4. Secondary vasculitis with intracerebral hemorrhage (vascular invasion and thrombosis can lead to infarction; mycotic aneurysm rupture can lead to hemorrhage)
35
What fungi can cause secondary vasculitis with intracerebral hemorrhage?
Aspergillus, Candida, Coccidioides
36
What are the microscopic findings of fungal infections?
Mononuclear infiltrate, variably granulomatous
37
What are the three special stains for diagnosis of fungal infections?
1. Periodic acid-Schiff (PAS)
2. GMS
3. Mucicarmine (Crypto)
38
What is the gold standard for diagnosis of fungal infections?
PCR
39
What are the 4 major causes of fungal meningitis (hyphal and pseudohypal fungi)?
1. Candida
2. Aspergillus
3. Zygomycetes
4. Fusarium
40
What are the 3 major causes of fungal meningitis (yeasts)?
1. Histoplasma
2. Blastomyces
3. Cryptococcus
41
What is the most common form of fungal meningitis?
Cryptococcus
42
How is Cryptococcus diagnosed?
India Ink stain of CSF
43
Where is Cryptococcus found and how is it transmitted?
Soil and bird feces; inhaled
44
What is seen on the gross brain in Cryptococcus?
Thickened, pale meninges
Clear cystic lesions in the white and deep gray matter
(Swiss cheese effect)
45
What is seen microscopically in Cryptococcus?
Can see oval budding yeasts with a mucoid capsule; inflammation is focal and limited
46
What are the three major causes of parasitic CNS infections?
1. Cysticercosis
2. Toxoplasmosis
3. Amoebiasis (N. fowleri, Entamoeba histolytica, Balamuthia mandrillaris)
47
What is the most common cerebral parasite?
Cysticercosis
48
Where is Cysticercosis found geographically?
SW US and Mexico
49
How is Cysticercosis transmitted?
Consumption of pork tapeworm (T. solium)
50
What is the most common manifestation of Cysticercosis and what causes the symptoms?
Seizures; death of the parasite
51
What can be seen grossly/on imaging in Cysticercosis?
Cysts containing scolexes
52
How is Toxoplasma gondii transmitted?
Consumption of cysts in meat or oocysts inc at feces
53
Most people are infected after childhood and infection remains silent in Toxoplasmosis - reactivation may follow ___.
Immunosuppression
54
How does toxoplasmosis present in the brain?
Abscess leading to seizures and focal neurologic deficits
55
What can be seen on imaging in toxoplasmosis?
Ring enhancing lesion on MRI
56
What are the TORCH infections?
Common infections associated with congenital anomalies
```
Toxoplasmosis
Others
Rubella
CMV
Herpes virus
```
57
What is the classic triad of symptoms seen in congenital toxoplasmosis?
Chorioretinitis
Hydrocephalus
Intracranial calcifications
58
What is seen histologically in Toxoplasmosis?
Cyst with bradyzoites, background of necrosis and acute inflammation
59
What is Naegleria fowleri and what does it cause?
Free living amoeba, infects people swimming in freshwater lakes, enters via the cribriform plate
Causes fulminant acute meningoencephalitis (usually fatal)
60
What do Acanthamoeba and Balamuthia cause?
Granulomatous encephalitis with a less fulminant course (still high mortality)
61
What is the most common cause of viral meningitis?
Enteroviruses
62
CSF findings - viruses
```
Fluid quality?
Cells present?
Protein?
Glucose?
Pressure?
```
```
Fluid quality: clear
Cells present: lymphocytes
Protein: slightly high
Glucose: normal (compared to plasma levels)
Pressure: n/a
```
63
What is seen grossly in viral meningitis?
Usually nothing; may be hyperemia, congestion, and edema of the brain
64
What are the microscopic changes seen in viral meningitis?
Lymphocytic meningeal infiltrates, perivascular lymphocytic extension along Virchow-Robin spaces
65
What is encephalitis?
Inflammation of the brain parenchyma, diffuse or regional; usually accompanied by meningitis = meningoencephalitis
66
Most encephalitis is caused by ___.
Viruses
67
What viruses target the meninges?
1. Mumps
2. Enterovirus
3. Coxsackie
4. HIV
68
What viruses target motor neurons?
1. Polio
| 2. Enterovirus
69
What viruses target neurons and glia?
1. Herpes virus
2. Rabies
3. Measles
70
What viruses target neurons, glia, and endothelium?
CMV (in immunocompromised)
71
What viruses target oligodendroglia?
Papovavirus (usually in immunocompromised)
72
What viruses target microglia?
HIV
73
What viruses target dorsal root ganglia?
HSV, VZV
74
What viruses target the fetal nervous system?
Rubella, CMV
75
What viral encephalitis is prevalent in summer/early fall?
Arboviruses (WNV)
Also enterovirus, RMSF (non-viral, mimics viral encephalitis)
76
What viral encephalitis is prevalent in fall and winter?
LCMV
77
What viral encephalitis is prevalent in winter and spring?
Mumps
78
What viral encephalitis is prevalent in any season?
HSV
Also EBV, CMV, mycoplasma (non-viral), and leptospira (non-viral)
79
Which type of brain matter is involved more in viral encephalitis?
Grey>white
80
What are the microscopic findings in viral encephalitis?
1. Perivascular inflammation
2. Leptomeningeal inflammation
3. Microglial clusters (nodules)
4. Neuronophagia
T-lymphocytes predominate (some PMNs in acute phase)
81
Activated microglial cells are ___-shaped.
Comma
82
What transmits WNV?
Mosquitos
83
Most WNV infections are asymptomatic; what symptoms are seen when they are present?
Polioencephalomyelitis
| Parkinsonism
84
What three groups of neurons are targeted by WNV?
Anterior horn cells
Nigral neurons
Purkinje cells
85
How is poliovirus transmitted?
Fecal-oral, replicates in oropharynx and SI
86
What are the clinical features of polio encephalitis?
1. Asymmetrical paralysis (lower limbs >> upper limbs > trunk)
2. CN palsies (9, 10)
3. Bulbar disease
4. Reticular formation (cardiac arrhythmia, sleep apnea, abnormal breathing patterns)
87
Polio encephalitis is restricted to the ___ matter and infects/destroys ___ cells.
Grey; anterior horn (LMN)
88
Old lesions caused by polio encephalitis demonstrate what microscopic findings?
Loss of motor neurons, anterior nerve root atrophy, and neurogenic atrophy of corresponding muscles
89
What is seen on histology in polio encephalitis?
Mixed inflammatory infiltrate, neuronophagia
90
What is the incubation period of rabies?
10 days to over 1 year
91
What is seen in neurons of the brainstem, hippocampus, and cerebellum in rabies?
Negri bodies (cytoplasmic inclusions)
92
What is the shape of rhabdovirus?
Bullet-shaped
93
What type of herpes virus causes herpes encephalitis and how is it transmitted?
HSV-1 (usually)
| Saliva
94
Herpes encephalitis is an example of a focal encephalitis - where is it found?
Medial temporal lobes (edema, hemorrhage, and necrosis)
95
Describe the gross findings of herpes encephalitis.
Bilateral, usually asymmetrical hemorrhagic necrosis of the temporal lobes, especially anteriorly and inferiorly, and to a lesser extent, the insulae, cingulate gyri, and thalamus
Usually brain edema
96
What is seen histologically in herpes encephalitis?
Owl's eye intranuclear inclusion
97
Describe the gross findings of chronic herpes encephalitis.
"Burnt-out"
| Hemorrhagic necrosis will progress to cavitation and atrophy; brain appears shriveled and brown
98
___ is a common opportunistic infection in AIDS and fetal/neonates.
CMV
99
What is seen histologically in CMV?
Large intracytoplasmic and intranuclear inclusions
100
What is seen grossly in congenital CMV encephalitis?
Moderately dilated ventricles and several foci of calcifications in the periventricular region
101
What is seen microscopically in congenital CMV encephalitis?
Meningoencephalitis
| Inclusions in all cellular elements of the brain, including neurons; most numerous in the periventricular regions
102
What is seen in postnatal congenital CMV infection?
Numerous microglial nodules, only occasional cytomegalic cells with inclusions
103
What causes progressive multifocal leukoencephalopathy (ML)?
JC virus (genus Polyomavirus)
104
What is seen histologically in PML?
1. Loss of myelin with axonal sparing
2. Bizarre astrocytes
3. Oligodendroglial inclusions (ground glass)
105
PML usually affects what patient population?
Immunocompromised (reversal of immunosuppression can stop progression of PML)
106
What is seen grossly in PML?
Multiple small or larger confluent foci of grey discoloration in the white matter and at the junction of the white matter and cerebral cortex
107
What happens in HIV encephalitis?
Widespread microglial nodule encephalitis with multinucleated giant cells with predilection to grey matter
108
What happens in HIV leukoencephalopathy?
Subacute onset of cognitive impairment and apathy
Diffuse white matter myelin pallor microglial nodules and multinucleated giant cells
Oligodendrocytes not infected
109
What happens in vacuolar myelopathy?
Spastic paraparesis with hyperreflexia and ataxia due to vacuolation of SC white matter
110
What is a brain abscess?
Space-occupying focal CNS infection
111
What is the most common cause of brain abscess?
Hematogenous spread
Heart (endocarditis, congenital heart defect with shunt)
Lung (bronchiectasis)
Can also be local extension (teeth, ear, frontal sinus), or direct introduction (penetrating head trauma, neurosurgery)
112
Lumbar puncture is not helpful in brain abscess - it may even cause ___.
Herniation
113
What is the diagnostic tool of choice for brain abscess?
Neuroimaging
114
Definite diagnosis and pathogen identification of brain abscess can be achieved by __.
Stereotactic biopsy
115
What is seen on MRI in brain abscess?
RIng-enhancing lesion
116
What are 3 other causes of ring-enhancing lesions in the brain?
1. Toxoplasmosis
2. Glioblastoma
3. Metastasis
117
What is seen grossly in a brain abscess?
Well-circumscribed areas of softening at grey-white junction or in white matter, where collateral circulation is poorest
118
How does an abscess evolve?
1. Early cerebritis (focal encephalitis) - days 1-3
2. Late cerebritis - day 4-9 (necrotic center surrounded by rim of inflammatory cells, microvascular damage)
3. Early encapsulation (days 10-13)
4. Late encapsulation (2+ weeks)
119
What provides anterior (70% of CBF) and posterior (30% of CBF) flow to the brain?
Anterior - internal carotid artery
Posterior - vertebral arteries
120
The brain receives ___% of CO and ___% of oxygen consumption - there is no oxygen reserve in the brain.
20; 15
121
How long does normal brain function last after cerebral ischemia? When does irreversible damage occur?
8-10 seconds;
6-8 minutes
122
What can cause cessation of blood flow to the brain?
1. Hypotension (reduction in perfusion pressure)
| 2. Small or large vessel occlusion
123
List brain cells most sensitive to ischemia (most to least).
Neurons > oligodendrocytes > endothelial cells > astrocytes
124
What is a stroke?
Abrupt onset of focal or global neurological symptoms caused by ischemia or hemorrhage
125
What causes 85% of strokes? The other 15%?
85% - cerebral ischemia
15% - intracranial hemorrhage
126
What is cerebral ischemia and what are the two major types?
Lack of blood flow to the brain (global and focal)
127
What are the two major types of intracranial hemorrhage?
Intraparenchymal and subarachnoid
128
What are the major causes of global cerebral ischemia?
1. Low perfusion (atherosclerosis, etc.)
2. Acute decrease in blood flow (cardiogenic shock, etc.)
3. Chronic hypoxia (anemia, etc.)
4. Repeated episodes of hypoglycemia
129
Discuss the magnitude of insult of mild, moderate, and severe global cerebral ischemia.
Mild - no permanent damage
Moderate - watershed infarcts and selectively vulnerable regions
Global - diffuse damage
130
Describe the timing and appearance of histologic changes in global cerebral ischemia.
Appear 6-12 hours after insult
"Red dead" neurons = cytoplasmic eosinophilic, loss of Nissl substance, dark, pyknotic nuclei
131
What areas are selectively vulnerable to global cerebral ischemia in adults?
1. Pyramidal neurons in cerebral cortex (layers 3 and 5)
2. Pyramidal neurons of hippocampus (CA1)
3. Purkinje cells of cerebellum
132
Global cerebral ischemia in the pyramidal neurons in cerebral cortex layers 3 and 5 leads to ___.
Laminar necrosis (area of necrosis with preserved superficial cortex)
133
What areas are selectively vulnerable to global cerebral ischemia in infants?
1. Subiculum
2. Thalamus
3. Pontine nuclei
134
What is a watershed zone in the brain?
Between ACA and MCA circulations
135
What is an ischemic infarction?
Regional ischemia resulting in focal neurologic defects lasting >24 hours
136
What are the 3 major causes of ischemic infarct?
1. Thrombotic (in situ or atherosclerotic plaque at bifurcation of internal carotid and MCA)
2. Embolic (cardioembolic, atheroembolic)
3. Small vessel disease (HTN, diabetes, vasculitis)
137
Where does a pure sensory stroke occur?
Thalamus
138
Where does a pure motor stroke occur?
Internal capsule
139
What are the symptoms of a large ischemic stroke in the MCA territory?
1. Contralateral hemiparesis affecting the lower face and upper extremity more than the leg
2. Similar distribution contralateral hemisensory loss
3. Contralateral visual field deficits
140
How do embolic and thrombotic ischemic infarcts differ in appearance?
Embolic - red
Thrombotic - pale
141
Describe the gross and microscopic appearance of the brain after acute cerebral ischemia.
(6-48 hours)
Gross: pale, soft, swollen, indistinct border, blurred grey-white junction
Micro: neuronal ischemia, red dead neurons, pallor/edema after 6-12 hours, infiltration by neutrophils after 1-3 days
142
Describe the gross and microscopic appearance of the brain after subacute cerebral ischemia.
(4 days to 3 weeks)
Gross: gelatinous, friable, distinct border, tissue liquefaction
Micro: neutrophils (early), macrophages (4-7 days), vascular proliferation (2-3 weeks)
143
Describe the gross and microscopic appearance of the brain after chronic cerebral ischemia.
(>3 weeks)
Gross: cystic, +/- hemosiderin staining, secondary degeneration
Micro: astrocytic gliosis, residual macrophages
144
Describe the gross appearance of an embolic infarction; where is it most common?
Usually smaller, centered at gray-white junction; single or multiple, may involve >1 vascular territory; MCA
145
What is a lacunar infarct?
Small infarct, up to 1.5 cm, affects areas with end arterial supply (basal ganglia, thalamus, pons, and subcortical white matter), often due to hypertensive small vessel disease
146
What can be seen on histology in a lacunar infarct?
Arterial hyalinosis
147
What are the causes of hemorrhagic infarction?
Usually embolic, can be secondary (reperfusion)
148
Where can hemorrhage occur intracranially and what are the various causes?
1. Above the arachnoid (epidural and subdural hematomas, typically caused by trauma)
2. Below the arachnoid (subarachnoid hemorrhages - aneurysms, parenchymal hemorrhages - HTN)
149
What is a subarachnoid hemorrhage?
Bleeding into the subarachnoid space
150
What is a common cause of non-traumatic spontaneous subarachnoid hemorrhage?
Berry aneurysm
Other: AVM, anticoagulated state
151
What is seen in the CSF due to a subarachnoid hemorrhage?
Xanthochromia (yellow hue due to bilirubin)
152
Describe the pathology of a subarachnoid hemorrhage.
Gross - "berry-like" thin-walled (no media) outpouchings from arterial branching points; ruptures at the dome
Associated vascular spasm produces global cerebral ischemia
153
Discuss the etiology of saccular (berry) anuerysms.
Etiology unclear
Congenital defect in media hypothesized
Genetic component - associated with AD polcystic kidney disease, Ehlers-Danlos, Marfan's, etc.
Female>Male (2:1)
154
Where are saccular aneurysms most common?
Anterior circle of willis (anterior communicating artery)
155
What are common locations of intraparenchymal hypertensive hemorrhage?
1. Putamen
2. Thalamus
3. Pons
4. Cerebellum
156
What is an IPH secondary to rupture of pseudoaneurysms?
Charcot-Bouchard (caused by chronic HTN)
157
What are some other causes of IPH?
CAA
Vasculitis
Neoplasms
158
What is seen grossly due to a hypertensive hemorrhage?
Circumscribed hematoma surrounded by brain tissue, may extend into subarachnoid space or to the ventricles
159
What is seen on microscopy due to a hypertensive hemorrhage?
Blood products surrounded by cerebral edema, minimal tissue necrosis, resolution leads to a cystic space with macrophages containing hemosiderin (orange tinge)
160
Primary intraventricular hemorrhages are rare in adults, but common in ___.
Premature infants
161
Where do intraventricular hemorrahges occur?
Germinal matrix located beneath the ependyma which easily ruptures into the ventricles; instantaneously fatal
162
What are duret hemorrhages?
Secondary to compression from herniation of the medial temporal lobe that leads to stretching and ischemia of perforating arterioles; compression can result from a variety of mass lesions (hemorrhages, inflammation, neoplasms)
163
What is an epidural hematoma?
Blood between dura and the skull, classically due to fracture of temporal bone with rupture of middle meningeal artery
164
What is seen on CT in an epidural hematoma?
Lens-shaped lesion
165
What is an subdural hematoma?
Blood underneath the dura covering brain surface, secondary to tearing of bridging veins between dura and arachnoid, usually due to trauma
166
What is seen on CT in an subdural hematoma?
Crescent-shaped lesion
167
What are the symptoms of subdural hematoma?
Progressive neurologic signs
168
What is herniation?
Displacement of the brain due to mass effect or increased intracranial herniation
169
What are the 3 types of herniation?
1. Tonsillar
2. Subfalcine
3. Uncal
170
What is a tonsillar herniation?
Displacement of cerebellar tonsils into the foramen magnum, causes compression of brain stem and cardiopulmonary arrest
171
What is a subfalcine herniation?
Displacement of the cingulate gyrus under falx cerebri, compression of ACA leads to infarction
172
What is an uncal herniation?
Displacement of uncus (medial temporal lobe) under tentorium cerebelli, compression of CN III (eye down and out + dilated pupil), compression of PCA - occipital lobe inarct, rupture of paramedian artery (duret hemorrhages)
