Ch 17 - CNS Pathology Flashcards
(154 cards)
1
Q
Neural crest cells become:
A
Peripheral Nervous System – includes DRG
2
Q
NEURAL TUBE DEFECTS are associated with low levels of:
A
LOW FOLATE levels PRIOR TO CONCEPTION
3
Q
DETECTION of NEURAL TUBE DEFECTS
A
ELEVATED ALPHA-FETOPROTEIN (AFP) in amniotic fluid and maternal blood
4
Q
ANENCEPHALY
A
ABSENCE OF SKULL & BRAIN – disruption of the cranial end of neural tube
5
Q
FETAL Appearance in ANENCEPHALY
A
FROG-LIKE appearance – eyes appear predominant with absence of skull and brain
6
Q
MATERNAL Condition in ANENCEPHALY
A
MATERNAL POLYHYDRAMINOS – fetal swallowing of amniotic fluid is impaired (brain centers not developed)
7
Q
SPINA BIFIDA
A
Failure of the posterior vertebral arch to close – disruption of the CAUDAL end of neural tube
8
Q
Physical appearance of SPINA BIFIDA OCCULTA
A
DIMPLE or PATCH OF HAIR overlying the vertebral defect
9
Q
MC cause of HYDROCEPHALUS in NEWBORNS
A
CEREBRAL AQUEDUCT STENOSIS – blocks draining from 3rd ventricle → 4th
10
Q
Clinical Presentation of CEREBRAL AQUEDUCT STENOSIS in NEWBORNS
A
Enlarging head circumference – due to dilation of the ventricles
11
Q
DANDY-WALKER MALFORMATION
A
FAILURE OF CEREBELLAR VERMIS to develop
12
Q
CLINICAL FEATURES of DANDY-WALKER MALFORMATION
A
Massively DILATED 4TH VENTRICLE, ABSENT CEREBELLUM, often hydrocephalus
13
Q
ARNOLD-CHIARI MALFORMATION
A
EXTENSION of CEREBELLAR TONSILS through the FORAMEN MAGNUM
14
Q
CLINICAL FEATURE OF ARNOLD-CHIARI MALFORMATION
A
HYDROCEPHALUS – from obstruction of CSF flow
15
Q
ARNOLD-CHIARI MALFORMATION is ASSOCIATED with:
A
MENINGOMYELOCELE and SYRINGOMYELIA
16
Q
SYRINGOMYELIA – pathophys, assoc, location
A
CYSTIC DEGENERATION of spinal cord assoc with TRAUMA or ARNOLD-CHIARI MALFORMATION; usually occurs at C8-T1
17
Q
CLINICAL FEATURES OF SYRINGOMYELIA
A
DEGENERATION OF ANTERIOR WHITE COMMISSURE → SENSORY LOSS OF PAIN/TEMP in UPPER EXTREMITIES (cape-like distribution)
18
Q
SYRINX Expansion in SYRINGOMYELIA
A
May expand to involve LATERAL HORN OF HYPOTHALAMOSPINAL TRACT (HORNER SYNDROME) and LOWER MOTOR NEURONS in ANTERIOR HORN (muscle atrophy, weakness, decreased tone, and impaired reflexes)
19
Q
CLINICAL FEATURES of HORNER SYNDROME
A
PTOSIS (droopy eyelid), MIOSIS (constricted pupil), and ANHIDROSIS (decreased sweating)
20
Q
POLIOMYELITIS
A
Damage to anterior motor horn due to POLIOVIRUS infection → LMN signs
21
Q
WERNDIG-HOFFMAN DISEASE
A
INHERITED DEGENERATION OF ANTERIOR MOTOR HORN; floppy baby – death within few years
22
Q
AMYOTROPHIC LATERAL SCLEROSIS
A
DEGENERATION of ANTERIOR MOTOR HORN CELLS & LATERAL CORTICOSPINAL TRACT
23
Q
ALS – UMN or LMN?
A
LMN SIGNS – from anterior motor horn degeneration and UMN SIGNS – from degeneration of corticospinal tracts
24
Q
EARLY sign of ALS
A
ATROPHY & WEAKNESS OF HANDS
25
What distinguishes ALS from SYRINGOMYELIA?
NO SENSORY IMPAIRMENT IN ALS
26
CAUSE OF FAMILIAL ALS
ZINC-COPPER SUPEROXIDE DISMUTASE (SOD1) MUTATION → free radical injury in neurons
27
FRIEDREICH ATAXIA
Degenerative disorder of the cerebellum (→ataxia) and spinal cord
28
ETIOLOGY OF FRIEDREICH ATAXIA
EXPANSION of unstable TRINUCLEOTIDE REPEAT (GAA) in FRATAXIN GENE - FRiedrich FRataxin
29
FRATAXIN protein – function and loss
ESSENTIAL for MITOCHONDRIAL IRON REGULATION; Loss results in Fe buildup → free radical damage
30
FRIEDREICH ATAXIA is assoc with:
HYPERTROPHIC CARDIOMYOPATHY
31
MC Causes of MENINGITIS in NEONATES
GBS, E. coli, Listeria monocytogenes
32
MC Cause of MENINGITIS in CHILDREN & TEENAGERS
Neisseria meningitidis
33
How does N. meningitidis spread to MENINGES?
Enters nasopharynx → blood → meninges
34
MC Cause of MENINGITIS in ADULTS & ELDERLY
Strep pneumo
35
MC Cause of MENINGITIS in NONVACCINATED INFANTS
H influenza
36
MC VIRAL CAUSE of MENINGITIS – population affected and transmission
COXSACKIEVIRUS – children via fecal-oral transmission
37
MC Cause of MENINGITIS in IMMUNOCOMPROMISED Pts
FUNGI
38
CLINICAL FEATURES OF MENINGITIS
TRIAD OF HA, NUCHAL RIGIDITY & FEVER; also photophobia (esp virus – Coxsack), vomiting, altered mental status
39
How is MENINGITIS DIAGNOSED?
Lumbar Puncture
40
What LEVEL is the needle placed in a LUMBAR PUNCTURE?
between L4 and L5
41
What LAYERS are crossed during a LUMBAR PUNCTURE?
SKIN, LIGAMENTS, EPIDURAL SPACE, DURA & ARACHNOID – NOOOOT THE PIA
42
WHAT LAYER is NOT crossed during a LUMBAR PUNCTURE?
PIA
43
CSF FINDINGS in BACTERIAL MENINGITIS
NEUTROPHILS w/ DECREASED CSF GLUCOSE
44
CSF FINDINGS IN VIRAL MENINGITIS
LYMPHOCYTES w/ NORMAL CSF GLUCOSE
45
CSF FINDINGS IN FUNGAL MENINGITIS
LYMPHOCYTES w/ DECREASED CSF GLUCOSE
46
Complications of BACTERIAL MENINGITIS
Cerebral edema (pus, exudate) → herniation → death; Also fibrosis → hydrocephalus, hearing loss, and seizures
47
Repeated Episodes of HYPOGLYCEMIA (insulinoma) can produce what type of CEREBROVASCULAR DISEASE?
GLOBAL CEREBRAL ISCHEMIA – probably mild (give glucose and pt promptly recovers)
48
ETIOLOGIES of GLOBAL CEREBRAL ISCHEMIA
Low perfusion (atherosclerosis), Acute decrease in blood flow (cardiogenic shock), chronic hypoxia (anemia), or REPEATED EPISODES OF HYPOGLYCEMIA (insulinoma)
49
What type of NECROSIS occurs in PYRAMIDAL NEURONS of the CEREBRAL CORTEX following MODERATE GLOBAL ISCHEMIA?
LAMINAR NECROSIS – lines of necrosis in layers 3, 5, 6
50
What areas are affected by MODERATE GLOBAL ISCHEMIA?
WATERSHED AREAS – pyramidal neurons of the cerebral cortex (→ LAMINAR NECROSIS), pyramidal neurons of the hippocampus (affects long-term memory), Purkinje layer of the cerebellum (sensory perception with motor control)
51
THROMBOTIC STROKE – etiology, where, type of infarct
Due to RUPTURE OF ATHEROSCLEROTIC PLAQUE; develops at BRANCH POINTS (bifurcations); results in PALE infarct at periphery of cortex
52
EMBOLIC STROKE – etiology, where, type of infarct
Due to THROMBOEMBOLI; usually involves MIDDLE CEREBRAL ARTERY; results in HEMORRHAGIC INFARCT at periphery of cortex
53
MC Source of EMBOLI
Left Side of the heart (ex: Afib) --> EMBOLIC stroke
54
LACUNAR STROKE – etiology, where, findings
Occurs secondary to HYALINE ARTERIOSCLEROSIS (complication of HTN); MC involves LETINCULOSTRIATE VESSELS → SMALL CYSTIC AREAS OF INFARCTION
55
ISCHEMIC STROKE leads to what type of NECROSIS?
Liquefactive
56
MICROSCOPIC FINDINGS after ISCHEMIC STROKE
Early 12hrs RED NEURONS; 24hr COAG NECROSIS; days 1-3 Neutrophils; days 4-7 Microglial cells; weeks 2-3 granulation tissue; end result is GLIOTIC CYST (fluid-filled cystic space surrounded by gliosis)
57
EARLY MICRO FINDING after ISCHEMIC STROKE
RED NEURONS 12hrs after
58
ISCHEMIC STROKE – END RESULT MICRO FINDING
GLIOTIC CYST
59
INTRACEREBRAL HEMORRHAGE – etiology, MC site
Due to RUPTURE OF CHARCOT-BOUCHARD MICROANEURYSMS OF LENTICULOSTRIATE VESSELS; MC site is BASAL GANGLIA
60
Clinical Features of INTRACEREBRAL HEMORRHAGE
Severe HA, N/V, Eventual coma
61
SAH – ETIOLOGY, MC SITE
Most due to RUPTURE OF BERRY ANEURYSM; MC located in ANTERIOR CIRCLE OF WILLIS BRANCH POINTS OF ACOM ARTERY
62
BERRY ANEURYSMS
LACK A MEDIA LAYER increasing risk for rupture → SAH
63
SAH is associated with what conditions
MARFAN SYNDROME & ADPKD (autosomal dominant polycystic kidney disease)
64
CLINICAL Presentation of SAH
Sudden HA (worst HA of all time) w/ NUCHAL RIGIDITY
65
LP Findings in SAH
XANTHOCHROMIA – yellow hue due to bilirubin breakdown
66
EPIDURAL HEMATOMA – ETIOLOGY, CT FINDINGS
Blood between dura and skull due to FRACTURE OF TEMPORAL BONE WITH RUPTURE OF MIDDLE MENINGEAL ARTERY; LENS-SHAPED LESION on CT
67
CLINICAL FEATURES OF EPIDURAL HEMATOMA
TALK & DIE SYNDROME – lucid interval may precede neuro signs; Herniation is lethal complication
68
SUBDURAL HEMATOMA – ETIOLOGY, CT FINDINGS
Blood underneath dura and covering surface of the brain due to TEARING OF BRIDGING VEINS btwn dura and arachnoid usually with trauma; CRESCENT-SHAPED LESION ON CT
69
CLINICAL FEATURES OF SUBDURAL HEMATOMA
Progressive neuro signs and herniation as lethal complication
70
TONSILLAR HERNIATION and its Clinical Features
Displacement of cerebellar tonsils into the foramen magnum → compression of brain stem → CARDIOPULMONARY ARREST
71
SUBFALCINE HERNIATION and its Clinical Features
Displacement of CINGULATE GYRUS under FALX CEREBRI → compression of anterior cerebral artery → infarction
72
UNCAL HERNIATION and its Clinical Features
Displacement of TEMPORAL LOBE UNCUS under TENTORIUM CEREBELLI → compression of CN3, posterior cerebral artery (infarct), and rupture of paramedian artery (Duret Hemorrhage)
73
METACHROMATIC LEUKODYSTROPHY
DEFICIENCY OF ARYLSULFATASE (autosomal recessive) → MYELIN CANNOT BE DEGRADED → MYELIN ACCUMULATES IN LYSOSOMES OF OLIGODENDROCYTES
74
MC LEUKODYSTROPHY
METACHROMATIC LEUKODYSTROPHY
75
KRABBE DISEASE
DEFICIENCY OF GALACTOCEREBROSIDE β-GALACTOSIDASE → GALACTOCEREBROSIDE accumulates in macrophages
76
ADRENOLEUKODYSTROPHY
IMPAIRED ADDITION OF COENZYME A TO LONG-CHAIN FAs (X-linked) → accumulation of FAs damages adrenal glands and white matter
77
MS
AUTOIMMUNE DESTRUCTION OF CNS MYELIN & OLIGODENDROCYTES
78
MC POPULATION with MS
Young WOMEN (20-30yo)
79
MS – HLA and Environmental Trigger
HLA-DR2 and regions AWAY FROM EQUATOR
80
CLINICAL FEATURES OF MS
Blurred vision unilateral, Vertigo, SCANNING SPEECH, INTERNUCLEAR OPHTHALMOPLEGIA (affected MLF), hemiparesis or U/L loss of sensation
81
Dx of MS
MRI – plaques (areas of white matter demyelination) and LP – Lymphocytes, INCREASED IMMUNOGLOBULINS with OLIGOCLONAL IgG BANDS, myelin basic protein
82
Tx of Acute MS Attacks
High-dose steroids
83
Long-term Tx of MS
IFN-β
84
Subacute Sclerosing Panencephalitis (SSPE) – Etio and Population affected
Slowly progressing, persistent infection of the brain by MEASLES VIRUS – infection occurs in INFANCY and neuro signs arise years later
85
Subacute Sclerosing Panencephalitis (SSPE) Micro findings
Viral inclusions within neurons (gray matter) and oligodendrocytes (white matter)
86
Progressive Multifocal Leukoencephalopathy (PML) – Etio
JC VIRUS infection of oligodendrocytes; Immunosuppression (AIDS or leukemia) leads to reactivation of the latent JC virus
87
CLINICAL FEATURES of PML
Rapidly PROGRESSIVE neuro signs – visual loss, weakness, dementia
88
CENTRAL PONTINE MYELINOSIS – Etio
Focal demyelination of the pons due to RAPID IV CORRECTION OF HYPONATREMIA – in severely malnourished pts (alcoholics and pts with liver disease)
89
CLINCAL FEATURES of CENTRAL PONTINE MYELINOSIS
Acute B/L paralysis - “LOCKED IN” syndrome
90
DEGENERATION difference between DEMENTIA & MOVEMENT DISORDERS
DEMENTIA – degeneration of CORTEX; MOVEMENT DISORDERS – degeneration of BRAINSTEM and BASAL GANGLIA
91
MC Cause of DEMENTIA
Alzheimer disease
92
CLINCAL FEATURES of ALZHEIMER DISEASE
FOCAL NEURO DEFICITS NOT SEEN IN EARLY DISEASE, slow-onset memory loss, progressive disorientation, loss of learned motor skills and language, changes in behavior/personality, mute/bedridden
93
MC Cause of death in Alzheimer pts
Infection
94
Which ALLELE is associated with HIGHER or LOWER risk of ALZHEIMER DISEASE?
ε2 is associated with DECREASED RISK; ε4 is associated with INCREASED RISK
95
EARLY-ONSET ALZHEIMER DISEASE is seen in:
Familial Cases – PRESENILIN 1 & 2 mutations; DOWN SYNDROME – by age 40
96
ALZHEIMER DISEASE is assoc with which TRISOMY DISORDER
DOWN SYNDROME – amyloid precursor protein is also on chromosome 21 → increased Aβ amyloid
97
MORPHOLOGIC FEATURES of ALZHEIMER DISEASE
DIFFUSE CEREBRAL ATROPHY, NEURITIC PLAQUES, NEUROFIBRILLARY TANGLES
98
In ALZHEIMER DISEASE, what is a complication of DIFFUSE CEREBRAL ATROPHY?
HYDROCEPHALUS EX VACUO – the ventricles are able to expand
99
How is Aβ AMYLOID DERIVED in ALZHEIMER DISEASE?
AMYLOID PRECURSOR PROTEIN (APP) normally undergoes alpha cleavage but in AD it undergoes BETA CLEAVAGE → Aβ AMYLOID
100
AMYLOID COMPLICATION in ALZHEIMER DISEASE
CEREBRAL AMYLOID ANGIOPATHY – AMYLOID may deposit around vessels → increased risk of hemorrhage
101
What is a NEUROFIBRILLARY TANGLE COMPRISED of in ALZHEIMER DISEASE?
Intracellular aggregates of fibers composed of HYPERPHOSPHORYLATED TAU PROTEIN → can no longer organize microtubule → tangles
102
Dx of Alzheimers
Made clinically after excluding other causes; Confirmed by histology at autopsy
103
VASCULAR DEMENTIA
2nd MC cause of dementia; multifocal infarction and injury due to HTN, atherosclerosis, or vasculitis – consequence of moderate global cerebral ischemia to layers 3,5,6 (gray) and hippocampus of temporal lobe (memory)
104
PICK DISEASE – location
degenerative disease of FRONTAL & TEMPORAL CORTEX
105
PICK DISEASE – morphology
ROUND AGGREGATES OF TAU PROTEIN (Pick bodies) in neurons in cortex
106
CLINICAL FEATURES of PICK DISEASE
Behavioral (Frontal) and Language (Temporal) Sx arise early → progresses to dementia
107
PARKINSON DISEASE – Pathophys
DEGENERATIVE LOSS of DOPAMINERGIC NEURONS in the SUBSTANTIA NIGRA PARS COMPACTA of basal ganglia
108
What Drug can CAUSE PARKINSONS?
MPTP
109
CLINICAL FEATURES OF PARKINSONS
TRAP – Tremor (pill rolling), Rigidity (cogwheel), Akinesia/bradykinesia (slowing of voluntary movement, expressionless face), Postural instability (shuffling gait)
110
PARKINSON DISEASE – histo findings
LOSS OF PIGMENTED NEURONS IN SUBSTANTIA NIGRA and round eosinophilic inclusions of α-SYNUCLEIN (LEWY BODIES)
111
What are LEWY BODIES COMPRISED of?
round eosinophilic inclusions of α-SYNUCLEIN
112
DIFFERENCE between LEWY BODY DEMENTIA and PARKINSONS
LEWY BODY DEMENTIA – EARLY onset dementia; PARKINSONS – LATE onset dementia
113
HUNTINGTON DISEASE – etio
Autosomal DOMINANT disorder characterized by EXPANDED TRINUCLEOTIDE REPEATS (CAG) IN HUNTINGTON GENE (Chromosome 4) → DEGENERATION of GABAergic neurons in CAUDATE NUCLEUS
114
HUNTINGTON DISEASE – pathophys of chorea
Degeneration of GABAergic neurons in CAUDATE NUCLEUS → disinhibition → random firing → random muscle movements
115
HUNTINGTON DISEASE – further nucleotide expansion
Further expansion of CAG repeats DURING SPERMATOGENESIS leads to ANTICIPATION – Grandfather Dx at age 60, father at age 55, son at 50, etc
116
CLINICAL FEATURES OF HUNTINGTON DISEASE
Presents with CHOREA, can progress to dementia and depression, ATHETOSIS (slow writhing movements of fingers)
117
NORMAL PRESSURE HYDROCEPHALUS – pathophys
INCREASED CSF → dilated ventricles → STRETCHING OF CORONA RADIATA NERVE FIBERS → classic triad
118
CLINICAL FEATURES of NORMAL PRESSURE HYDROCEPHALUS
Wet, Wobbly, Wacky – URINARY INCONTINENCE, GAIT INSTABILITY, DEMENTIA
119
LP in NORMAL PRESSURE HYDROCEPHALUS
IMPROVES Sx
120
Tx in NORMAL PRESSURE HYDROCEPHALUS
Ventriculoperitoneal shunting
121
SPONGIFORM ENCEPHALOPATHY – Pathophys
Degenerative disease due to prion protein; Disease arises with conversion to a β-pleated conformation (PrPsc) which is not degradable → converts normal (PrPc) to pathologic form
122
SPONGIFORM ENCEPHALOPATHY – Morphologic features
Damage to neurons and glial cells is characterized by intracellular vacuoles (spongy degeneration)
123
MC SPONGIFORM ENCEPHALOPATHY
CREUTZFELDT-JAKOB disease (CJD)
124
CREUTZFELDT-JAKOB DISEASE (CJD) – Etio
usually sporadic – rarely can arise due to exposure to prion-infected human tissue (HGH or corneal transplant)
125
CLINICAL FEATURES of CJD
RAPIDLY PROGRESSIVE DEMENTIA assoc with ATAXIA and STARTLE MYOCLONUS (little stim); death usually <1 yr
126
EEG findings of CJD
SPIKE-WAVE COMPLEXES
127
VARIANT CJD
Related to exposure to bovine spongiform encephalopathy (mad cow) – younger pts and consumption of meat
128
FAMILIAL FATAL INSOMNIA
Inherited form of prion disease characterized by severe insomnia and exaggerated startle response
129
METASTATIC CNS TUMORS
make up 50% of CNS tumors, present as multiple, well-circumscribed lesions at gray-white junction; LUNG, BREAST and KIDNEY are common sources
130
Location of PRIMARY CNS TUMORS in KIDS vs ADULTS
KIDS – INFRAtentorial; ADULTS – SUPRAtentorial
131
MC Primary MALIGNANT CNS TUMOR
GBM
132
GLIOBLASTOMA MULTIFORME (GBM) – cell type, location
Malignant, high grade tumor of astrocytes; arises in CEREBRAL HEMISPHERE and CROSSES CORPUS COLLOSUM (butterfly lesion)
133
GLIOBLASTOMA MULTIFORME (GBM) – morphologic features
PSEUDOPALISADING – regions of necrosis surrounded by tumor cells, ENDOTHELIAL CELL PROLIFERATION; tumor cells are GFAP POSITIVE (intermediate filament in glial cells)
134
MENINGIOMA – population affected
WOMEN (EXPRESSES ESTROGEN RECEPTORS), rare in children
135
CLINICAL PRESENTATION of MENINGIOMAS
May present as seizures – tumor compresses but does not invade the cortex
136
MENINGIOMA – histo features
WHORLED PATTERN, PSAMMOMA BODIES (whorled pattern → calcify → psammoma)
137
SCHWANNOMA – clinical presentation
most frequently involves CN VIII at cerebellopontine angle → hearing loss and tinnitus
138
SCHWANNOMA – tumor marker
S-100 positive
139
BILATERAL SCHWANNOMAs are assoc with:
NEUROFIBROMATOSIS TYPE 2
140
CAs assoc with NF2
MISME – Multiple Inherited Schwannoma, Meningioma, Ependymoma
141
OLIGODENDROGLIOMA – morphologic features and location
CALCIFIED tumor in white matter usually involving FRONTAL LOBE; FRIED EGG appearance of cells
142
PILOCYTIC ASTROCYTOMA – location, morphology, marker
Usually arises in CEREBELLUM – CYSTIC LESION w/ MURAL NODULE, ROSENTHAL FIBERS; GFAP POSITIVE
143
MC BENIGN CNS tumor in ADULTS
Meningioma
144
MC CNS tumor in CHILDREN
Pilocytic astrocytoma
145
What are ROSENTHAL FIBERS?
thick eosinophilic processes of astrocytes seen in PILOCYTIC ASTROCYTOMA
146
MEDULLOBLASTOMA – population and derivation
Children; malignant tumor derived from GRANULAR CELLS of CEREBELLUM (NEUROECTODERM)
147
MEDULLOBLASTOMA – histo
small, round blue cells; HOMER-WRIGHT ROSETTES – blue cells surrounding neuritic processes
148
MEDULLOBLASTOMA – mets
Tumor grows rapidly and SPREADS VIA CSF; DROP METASTASIS – mets to cauda equina
149
EPENDYMOMA – population, location
Children – MC arises in 4th ventricle
150
EPENDYMOMA – clinical presentation and morphologic findings
Present with HYDROCEPHALUS (obstructed 4th ventricle); PERIVASCULAR PSEUDOROSETTES
151
CRANIOPHARYNGIOMA arises from
EPITHELIAL REMNANTS of RATHKE's POUCH; tends to recur after resection
152
CRANIOPHARYNGIOMA – clinical presentation
Presents as SUPRATENTORIAL MASS in CHILD or YOUNG ADULT; may compress optic chiasm leading to BITEMPORAL HEMIANOPSIA
153
BILATERAL HEMIANOPSIA is assoc with which tumors?
Pituitary tumors (adenomas) but in children think Craniopharyngioma
154
CRANIOPHARYNGIOMA – morphologic findings
CALCIFICATIONS seen on imaging
