Unit II week 1 Flashcards
1
Q
Myopathy vs. Denervation
A
Myopathy = primary disease of muscle –> PROXIMAL weakness and atrophy
- elevated CK
- EMG changes
Dennervation = DISTAL weakness and atrophy
- NORMAL CK
- Different EMG changes
2
Q
Response to Denervation
A
Atrophy of muscle
Over time, end-organ “loses” ability to receive a nerve fiber input and be functionally restored
Approx 2 years for muscle
Variable for different types of sensory endings
3
Q
PNS vs. CNS myelin
A
Myelin = 70% lipids, 30% protein
- Lipids in CNS and PNS are the same
- Protein compositions differ in CNS and PNS → allergic reaction against PNS myelin does not cause central demyelination and vice versa
4
Q
Segmental demyelination (1 characteristic feature)
A
Demyelinating type of peripheral nerve disorder
breakdown and loss of myelin over a few segments - axon remains intact and there is no change in neuronal body
- Onion bulb neuropathy: onion bulb formation (hypertrophy of nerves) with repeated attack and repair of myelin
- Have working axon, but conduction velocity decreased
EX) Inflammatory demyelinative neuropathies
EX) Charcot-Marie-Tooth disease
5
Q
Astrocyte reaction to injury
A
expansion of cytoplasmic volume and synthesis of intracytoplasmic intermediate glial filaments (GFAP+)
CANNOT fill large holes of tissue damage (do not make COLLAGEN)
Chronic gliosis results in cytoplasmic expansion and extension of cell processes, but NO EXTRACELLULAR COLLAGEN → astrocytes CANNOT fill in large holes of tissue damage
6
Q
Microglia
A
major phagocytic cell of nervous system, proliferate/respond to injury
Sentinels within brain, monitor immunologic signals, awaiting need for response to tissue injury
Replenished by blood monocytes
High level of activity –> when damage occurs, microglia to lots of cleaning up, but astrocytes cannot make collagen to fill space –> large empty hole remains
7
Q
Ischemic neuron –> ?
what appearance?
A
total necrosis –> loss of neuron and removal
Appearance: acutely damaged, “RED DEAD” neuron + loss of nucleus + loss of basophilic Nissl substance → EOSINOPHILIA
8
Q
What happens when you transect an axon?
what does it look like pathologically?
A
Wallerian degeneration
necrosis of axon distal to transection
→ Neuroaxonal swelling - Swollen axonal process by silver stains at site of transection/injury
9
Q
What is GFAP staining used for?
A
used to highlight full cytoplasmic volume of astrocyte on immunostaining
10
Q
Intracytoplasmic intermediate glial filaments (GFAP+)
A
key protein of astrocyes
-released by astrocytes in response to tissue injury
11
Q
Concussion (Mild Traumatic Brain Injury)
A
alteration in mental status caused by biomechanical forces that may or may not cause loss of consciousness
Differs from severe TBI only in degree, and regions of brain affected (confined to junction of white/gray matter immediately beneath cortex)
12
Q
Hallmarks of mild TBI (2)(aka concussion) and common symptoms
A
Hallmarks = confusion and amnesia
Common symptoms: headache, dizziness, poor attention, inability to concentrate, memory problems, fatigue, irritability depressed mood, intolerance of bright light or loud noise, and sleep disturbance
13
Q
Grading scale of concussion
A
Grade 1 = Confusion without amnesia or LOC
Grade 2 = Confusion and amnesia
Grade 3 = LOC
14
Q
Second Impact Syndrome
mechanism?
A
usually fatal, second concussion while still suffering effects of an earlier concussion
Loss of CNS vasculature autoregulation → cerebral vessels lose tone, fill with blood, ICP rises → reduced cerebral perfusion, ischemia
15
Q
Concussion management (4)
A
Observation for 24 hours
CT scan to check for intracranial bleeding if LOC occurred
Treat sleep disturbances
Acetaminophen for headaches and bodily pain
16
Q
Highest incidence of head injuries?
A
Economically disadvantaged populations within major cities
Males 2x higher risk
Peak age = 25-35yrs
Smaller peaks from 0-4 yrs (shaken baby) and over 65 yrs (falls)
17
Q
Most common causes of head injury (5)
A
- Traffic and transport injuries
- Assaults
- Homicides
- Suicides
- Falls
18
Q
Forces responsible for TBI (4)
A
1) Contact phenomena
2) Acceleration/Deceleration
3) Penetrating
4) Secondary injury (hypoxia, hypotension)
19
Q
Contact phenomena
A
results from object striking the head
→ Local effects (lacerations of scalp, fractures of skull, epidural hematomas, cerebral contusions)
20
Q
Acceleration/Deceleration
A
results from rapid head movement that can create shear, tensile, and compressive strains
Translational or rotational
21
Q
Translational (Acceleration/Deceleration)
A
(falls, restrained occupants in MVA)
Head movement in a single plane the instant after impact
Results in stretching, tearing of veins between brain and dura (subdural hematoma) and bruising of brain as it impacts skull (contusion)
22
Q
Rotational
Acceleration/Deceleration
A
(high speed MVA, ejection, auto-ped, motorcycle)
Results from head moving in more than one plane
Results in microscopic tearing of nerve cells in brain
No recognizable injury detected without microscope
23
Q
Penetrating head injury
A
(GSW, knives, tree branches)
Results from combination of contact phenomena and distant translational injury
Results in direct cranial and cerebral injury as well as translational injury
24
Q
Contact phenomena injuries
A
Skull fracture
Extradural hematoma
Epidural hematoma
25
Skull fractures
5 types of fractures
Results from contact phenomenon
1) Linear
2) Depressed
3) Basilar
4) Diastatic
5) Growing fractures of infancy
26
Linear skull fracture
crack, not displaced
27
Depressed skull fracture
depression of bone in toward the brain
comminuted bone fragments may or may not be driven into brain
28
Basilar skull fracture
crack at base of skull, common with high-velocity blunt injuries
May extend through cribriform plate or petrous bone
****→ highly associated with CSF leak, meningitis****
29
Signs of skull base fracture (6)
- CSF rhinorrhea or otorrhea
- Bilateral periorbital haematomas (racoon eyes)
- Subconjunctival hemorrhage
- Bleeding from external auditory meatus
- Battle’s sign (bruising behind ear)
- Facial nerve palsy
30
Diastatic skull fracture
traumatic separations of skull at suture lines
31
Growing fractures of infancy
skull is soft, so it gets punched in, and dura tears, and then skull pops back out
Can then have herniation of arachnoid into fracture site
32
Extradural or Epidural Hematoma
intracranial, extradural ARTERIAL bleeding often due to skull fractures (affecting middle meningeal artery)
** “LUCID INTERVAL” →progressive obtundation/coma as hematoma expands
Low mortality rate
33
Treatment of Extradural or Epidural Hematoma
TX = surgical removal of mass lesion
Prognosis depends on time from injury to evacuation
34
Translational Injuries (Acceleration injury) (2)
1) Subdural hematoma
| 2) Cerebral contusion
35
Subdural hematoma
hemorrhage into subdural space due to rupture of BRIDGING VEINS that connect cortical surface of brain with sagittal sinus
Due to translational accelerations from high velocity mechanisms
Associated with:
- Cerebral contusions
- Elevated intracranial pressure
- Distant secondary cerebral injury
36
Subdural hematoma treatment
prompt surgical removal of blood clot, control ICP, restore adequate cerebral blood flow
**High mortality rate
37
Cerebral Contusion
superficial hemorrhagic contusion of brain (often where brain hits skull at anterior cranial fossa, and greater wing of sphenoid bone)
Due to high velocity translational and impact injuries
Hemorrhage into areas of damaged brain → mass effect and herniation with secondary brain injury
38
Treatment of cerebral contusion
medical management of brain swelling, occasional surgical evacuation
39
_______ is a Rotational Injury
| Acceleration-Deceleration Injury
Diffuse Axonal Injury (DAI)
40
Diffuse Axonal Injury (DAI)
- shearing of axons → Axon spheroids, aka “retraction balls” (appear when coma exceeds 6 hours)
- Patient unconscious from moment of injury
- No evidence of injury on CT, MRI may show punctate hemorrhages over white large white matter tracts
- Corpus callosum and brainstem most commonly affected
- Axonal degeneration may continue for years after injury
41
Primary Injury vs. Secondary injury
Primary Injury: occurs at moment of impact - irreversible injury
Second injury: due to inadequate resuscitation
42
Secondary injury is often due to... (3)
1) Hypoxia
2) Altered cerebral blood flow (dysautoregulation)
3) Release of free radical mediators → break down BBB → interstitial edema → brain swelling, elevated ICM, further hypoxia, dysautoregulation, and herniation
43
Pathophysiology of traumatic brain injury
effect of a mass lesion
44
Intracranial compensation
Brain is non-compressible
| Any increase in intracranial volume decreases CSF or CBV
45
Where is CSF displaced?
primarily into spinal subarachnoid space
46
Where is blood displaced?
venoconstriction of CNS capacitance vessels displaces blood into jugular venous system
47
Exhaustion compensation
- Once limited homeostatic mechanisms are exhausted, additional small increases in volume of a mass lesion produce marked elevations in ICP
- Raised ICP may decrease CBF, resulting in vicious cycle
48
Herniation
ICP rises not equally distributed throughout skull and pressure gradients develop
49
Example of lateral herniation
cingulate herniation
50
Example of downwards herniation
Transtentorial herniation
51
Excitotoxicity
mechanical forces cause massive neuronal depolarization + massive NT release
52
Mechanism of excitotoxicity leading to vasogenic edema
Neurons damaged and killed by overactivation of receptors for excitatory neurotransmitter, glutamate
→ lots of Ca2+ into cell→ activate enzymes and free radicals→ damage to cell structures and BBB
→ Vasogenic Edema
Also cause immediate K+ spike extracellularly
53
Vasogenic edema
increased permeability due to BBB damage causes additional brain swelling
54
Mechanism in excitotoxicity leading to cytotoxic edema
Astrocytes attempt to clear glutamate and K+ extracellularly
-Glutamate transporter relies on high Na+ out, and low K+ in → pump cannot function with high K+ out → pump reverses and makes excitotoxicity worse (K+ and glutamate into cell)
→ *CYTOTOXIC EDEMA: astrocyte swelling in response to ionic shifts
55
Cytotoxic edema
astrocyte swelling in response to ionic shifts
56
What happens to cerebral blood flow when astrocytes swell due to cytotoxic edema?
Swelling of astrocytes abutting capillaries → increased capillary resistance, and decreased cerebral blood flow
57
What are the main consequences of excitotoxicity?
1) Vasogenic edema
2) Cytotoxic edema
3) Decreased cerebral blood flow (due to astrocyte swelling)
4) Lose zone of autoregulation (too much or too little blood flow)
58
Herniation Syndromes
forcible displacement of brain tissue across falx, tentorium, or foramen magnum
Secondary injury caused by mass effect (trauma, ischemia, neoplasm, infection, and hydrocephalus)
59
Classic signs of increased ICP
progressive lethargy and poor responsiveness (obtundation)
60
Subfalcine Herniation
cingulate gyrus pushed away from expanding mass and herniates beneath falx cerebri
→ Anterior cerebral artery kinked
61
Central herniation
downward pressure centrally → bilateral uncal herniation
62
Uncal herniation
uncus herniates across tentorial edge and downward into posterior fossa → compresses midbrain and ipsilateral cerebral peduncle
63
Which deficits are seen with uncal herniation?
→ third nerve palsy (pupil dilated on ipsilateral side) and contralateral hemiparesis/hemiplegia
64
Kernohan’s Notch
when uncal herniation compresses the opposite cerebral peduncle against the tentorial edge → hemiparesis IPSILATERAL to mass lesion and herniated uncus
65
Duret Hemorrhage
characteristic hemorrhage in brain stem associated with uncal herniation
66
Tonsillar Herniation
cerebellar tonsils herniate downward into foramen magnum = “Coning”
Compresses medulla → Cushing’s reflex (bradycardia, hypertension in setting of high ICP)
-Typically due to mass lesion in posterior fossa
67
Lumbar puncture in setting of intracranial mass lesion can precipitate ________
herniation syndrome
68
3 main responses assessed with the Glasgow Coma Scale
1) Eye opening
2) BEST motor response
3) Verbal response
69
Review glasgow coma scale
DO IT
70
Syndrome of delirium
- rapidly developing disorder of attention characterized by an inability to maintain a coherent line of thought
- ACUTE confusional state, with prominent attentional problems and a toxic-metabolic encephalopathy
- Fluctuating level of consciousness, incoherent speech
- Toxic and metabolic causes usually found
- Typically reversible
71
What's more common - delirium hypoaroused or hyperaroused?
HYPOAROUSED with lethargy and somnolence more common than type with hyperarousal + agitation and restlessness
72
Pathophysiology of Delerium
diffuse brain dysfunction due to disruption of normal brain homeostasis
Widespread neuronal dysfunction affecting arousal systems in brainstem and diencephalon, and cortical regions
If insult is corrected within a few days, normal brain function can be restored - prolonged insult may damage neurons irreversibly
73
Common etiologies of delirium (7)
1) Drugs and toxins (intoxication and withdrawal) = # 1 cause
2) Metabolic disorders
3) Cardiac, pulmonary, renal, hepatic, endocrine, and nutritional diseases also possible causes
4) Infections/Inflammatory causes
- Meningitis, encephalitis, CNS vasculitis, systemic infection
5) Traumatic brain injury
6) Stroke, hemorrhage, edema
7) Seizure disorders
74
Evaluation of a patient with delirium
1) History and physical (complete mental status exam not necessary)
2) Lab tests (metabolic panel, CBC, urinalysis, urine tox screen, EKG, CXR, CT/MRI of brain)
3) Lumbar puncture possible
4) Electroencephalogram
75
Treatment of delirium
1) Prompt attention to etiology
2) Provide adequate sleep
- Avoid daytime sedation and naps
3) Environmental manipulations (clock, calender, pictures of family, TV)
4) Can give drugs for agitation
76
Syndrome of dementia
-acquired and persistent impairment in intellectual function with deficits in at least three domains - memory, language, visuospatial skills, complex cognition, and emotion/personality - that is of sufficient severity to interfere with usual social and occupational function
CHRONIC
- Normal level of consciousness and normal attention
- Aphasia
- Toxic and metabolic causes not usually found
- Typically irreversible - but does NOT NEED to be progressive or irreversible
77
Reversible causes of dementia
10-20% of dementia cases
Drugs and toxins, mass lesions (tumor, subdural hematoma), hydrocephalus, systemic illness, inflammatory disease, infectious disease, depression, mild TBI
78
Irreversible causes of dementia
80-90% of dementia cases
Alzheimer's, frontotemporal lobal degeneration, vascular dementia, Lewy Body Dementia, Parkinson’s, Huntington’s, Creutzfeldt-Jakob Disease, HIV-associated dementia, severe TBI
79
Evaluation of dementia
History and physical (mental status, general, neurologic)
CMP, CBC, TSH, B12, RPR
MRI or CT scan of brain
80
Cortical Dementia
2 examples of diseases
cerebral cortex bears major burden of neuropathology
1) Alzheimer's
2) Frontotemporal Dementia (FD)
81
Alzheimer's Disease onset, survival, patient population
Cortical Dementia
most common dementia in elderly
5-10% prevalence over age 65, more common in women
Survival after onset = 6-12 years
82
Three typical stages of Alzheimer's
Stage I (1-3 years): amnesia most notable, mild anomia, apathy
Stage II (2-10 years): dementia obvious, fluent aphasia, visuospatial dysfunction, anosognosia, neuropsychiatric features
Stage III (8-12 years): severe mental and physical incapacity
83
Neuropathology of Alzheimer's
Cerebral atrophy, loss of cortical neurons/synapses
Neuritic (amyloid) plaques and neurofibrillary tangles
84
Etiology of Alzheimer's (2 possible theories)
1) Amyloid precursor protein (chromosome 21) overproduces amyloid
- APOE gene epsilon allele
2) Relative deficiency in acetylcholine → cholinergic hypothesis
85
Frontotemporal Dementia (FD)
degenerative disease of frontal/temporal lobes → changes in behavior and comportment, but not significant changes in memory
-Presents with disinhibition, apathy, and executive dysfunction while memory still normal
86
Subcortical Dementia
2 examples of diseases
subcortical gray matter structures (basal ganglia, thalamus, brainstem nuclei) bear burden of neuropathology
1) Parkinson's Disease
2) Huntington's Disease
87
Parkinson’s Disease (PD)
sx (4) and neuropathology (2)
Sx: tremor, bradykinesia, rigidity, postural instability
Neuropathology:
1) Lewy bodies found in substantia nigra
2) Dopamine deficiency
88
Huntington’s Disease (HD)
typically shows atrophy in what brain region?
2 symptoms?
genetics?
Typically shows caudate atrophy
Sx = dementia and chorea (jerky involuntary movements)
AD
Increased polyglutamine repeats (CAG) in Huntington gene on chr4
89
White Matter Dementia
2 diseases?
cerebral white matter bears burden of neuropathology
1) Binswanger's Disease
2) Normal Pressure Hydrocephalus (NPH)
90
Binswanger's Disease
vascular dementia caused by long standing HTN and lacunar infarction of cerebral white matter
91
Normal pressure hydrocephalus (NPH)
Increased CSF → dilated ventricles → stretching of corona radiata
- LP improves symptoms
- “Wet, wobbly, and wacky”
- causes symptoms of dementia
92
Mixed Dementia
2 diseases?
affects many different brain regions
1) Multi-infarct dementia
2) Creutzfeldt-Jakob Disease (CJD)
93
Multi infarct dementia
vascular dementia with repeated strokes that erode cognitive function progressively
94
Creutzfeldt-Jakob Disease (CJD)
rapidly progressive, fatal, potentially transmissible
RAPIDLY progressive dementia, myoclonus
Human prion disease, often sporadic
95
Treatment of Dementia
-Irreversible dementia → avoid drugs that worsen mental status, use low dose atypical antipsychotic drugs for neuropsych symptoms, antidepressants, informed counseling
96
Neurodegenerative Disorders
spontaneous death of neuronal populations with location of neurons determining clinical presentation
We categorize these illnesses by clinical presentation, but there is considerable interaction and overlap between their mechanisms
-Characterized by intra/extracellular abnormal protein accumulation
Appear to be disorders of protein conformation and metabolism
Genetic and environmental effects
97
Prion Disease
conformational change in protein constitutes the transmissible agent → propagation of abnormal protein conformation
98
Prion
small infectious pathogen, contains proteins, but no nucleic acid
99
Clinical features of prion diseases
- Ataxia, abnormal movements, neuropsychiatric features
- Sporadic, heritable, or transmissible
- Uniformly fatal
100
Alzheimer's Disease
**early memory and visuospatial problems**
- BOTH amyloid plaques and neurofibrillary tangles
- Acetylcholine deficit
- Typically see changes in cortex and hippocampus (relative sparing of deeper structures)
- Results in diffuse atrophy
101
Frontotemporal Dementia (FTD) (4)
-early behavioral, executive and/or language problems
- May manifest with: neurofibrillary tangles, ubiquitin inclusions, tau reactive intra-neuronal inclusions, or CDP-43 deposition
- ->Pick Bodies = Tau-reactive intraneuronal inclusions
No specific findings on autopsy
Higher incidence of psychosis
102
Lewy Body dementia
early parkinsonian features, psychosis, fluctuating consciousness
- Lewy bodies with synuclein protein
- Dopamine and ACh deficit
103
Progressive supranuclear palsy (PSP)
bradykinesia, rigidity, falls, abnormal vertical eye movements
Lose volitional eye movements, retain reflex eye movements
104
Delirium (10 features)
1) Develops over short period of time (hours to days)
2) Change from baseline that FLUCTUATES during course of day (fluctuating arousal)
3) ATTENTION deficits
4) Alterations in memory, language, construction, perception, and mood
5) Spontaneous speech may be incoherent, rambling, shifting
6) Sleep disturbances
7) Possible psychosis
8) Neurological motor signs (tremor, altered tone, asterixis, myoclonus, hyperreflexia)
9) Autonomic disturbances (tachycardia, diaphoresis, pupillary dilation)
10) Bottom up impairment
105
11 features of dementia
1) Cognitive deficits interfere with independence in everyday activity
2) Top down impairment
3) Normal level of arousal and attention
4) Insidious onset GRADUALLY, over years
5) Changes in personality language, and complex cognition prior to memory problem
6) Perceptual disturbances
7) Impaired VISUOSPATIAL skills
8) Impaired recognition in given sensory modality (agnosia)
9) Decreased motivation (apathy)
10) Disturbances of emotion (Depression)
11) Disturbances in sleep
106
Long term outcomes of in-hospital delirium (4)
1) Longer hospital stays
2) Increased risk of death
3) Increased risk of disability and functional dependence
4) Increased risk of future cognitive impairment
107
Infarction can be ____ or ______
Infarction differs from hemorrhage how?
Thrombotic or Embolic
Hemorrhage → blood dissects along planes of least resistance
Infarction/occlusion → deficits in territories of vascular distribution
108
Ischemic Stroke vs. TIA
Ischemic Stroke (ischemic injury to brain, persistent clinical deficit at 24 hrs)
TIA (ischemic neurological deficits, completely resolved by 24 hours)
109
Large Vessel Ischemic stroke
results in what deficits?
partial or complete occlusion of a major artery causes deficits in multiple systems
MCA → Hemiparesis, hemisensory deficit, hemianopsia
Aphasia (Dominant) and Neglect (non-dominant)
110
Small Vessel Ischemic stroke
results in what deficits?
occlusions (atheromatous, lipohyalinosis) of small penetrating vessels deep in the brain) cause isolated motor (or sensory) deficit on one side of body (hemiparesis/hemisensory loss)
Can also be caused by hypoperfusion due to systemic hypotension, cardiopulmonary bypass, isolated major vessel stenosis, vasospasm, hypercoagulation, or inflammatory processes
Small vessels are too small for a catheter
111
Lacunar infarct
1 cm or less in size
due to small vessel infarcts
Can be caused by chronic HTN or arteriosclerotic vascular disease
Many lacunar infarcts can eventually result in multi-infarct dementia
112
Types of hemorrhage (5)
1) Intracerebral Hemorrhage
2) Intraparenchymal hemorrhages
3) Subarachnoid hemorrhage
4) Subdural hemorrhage
5) Epidural hemorrhage
113
Types of intracerebral hemorrhage?
Deep (ganglionic, putamenal, striatocapsular)
Lobar: Frontal > Parietal > Occipital > Temporal
114
Etiology of Deep Intracerebral Hemorrhage
causes?
outcome?
most common in what races?
HTN and age
Poor outcome
Non-white and asians at higher risk
115
Etiology of Lobar Intracerebral Hemorrhage
causes?
outcome?
most common in what races?
Age, dementia, coagulation
HTN
Surprisingly well tolerated
White/Asian higher risk
116
Intraparenchymal hemorrhages
formed blood clots that dissect into brain
most commonly due to HTN and age
117
Causes of Intraparenchymal Hemorrhage (9)
1) HTN and age = #1 cause
2) Coagulation disease, or therapeutic anticoagulation
3) AVMs (arteriovenous malformations)
4) Cavernous (venous) Angioma
5) Aneurysms
6) Vasculitis
7) Hemorrhage into tumors
8) Infection
9) Amyloid angiopathy
118
AVMs (arteriovenous malformations)
No arteriovenous SHUNT = no intervening bed of capillaries between arteries and veins → blood builds up in veins --> hemorrhage
Associated with aneurysms
Responsible for 2% of all intracranial hemorrhages
Thought to be congenital
119
Cavernous Angioma
AD mutation (cerebral cavernous malformation 1, CCM1) common in denver
No arterial component, only venous leaks
120
Aneurysm common locations in brain
Most commonly on anterior cerebral artery (40%)→ middle cerebral artery (34%) → posterior communicating artery (20%) → basilar artery (4%)
121
Amyloid angiopathy
recurrent lobar hemorrhage typical in elderly→ progressive dementia and disability
122
Typical location of intraparenchymal hemorrhages (4)
basal ganglia, thalamus, pons, and cerebellar deep gray matter
Atypical = deep white “lobar” hemorrhages
123
Presentation of intraparenchymal hemorrhages
mild headache, deficit, nausea → progress over minutes to hours adding decreased level of consciousness
Hemiparesis progressing to hemiplegia
124
Subarachnoid hemorrhage
right next to brain under arachnoid layer, typically involves aneurysms
125
Causes of subarachnoid hemorrhage (3)
trauma, aneurysmal rupture, arteriovenous malformations
126
Why do we get aneurysms?
Branch points lack media
127
Presentation of subarachnoid hemorrhage
cataclysmic, “firecracker” explosion in head, severe headache
Cranial nerve palsy (III especially)
Hemiparesis
Sudden onset of neurological deficits + headache, nausea, vomiting, depressed level of consciousness
High mortality rate
128
Subdural hemorrhage
causes?
appearance?
between dura and arachnoid layer, typically torn/ruptured bridging vein, looks like a banana (CONCAVE) hematoma
Causes: “trivial traumas”, small brain in big skull
129
Epidural hemorrhage
causes?
appearance?
between skull and dura, typically ARTERIAL (middle meningeal)
collect in CONVEX (lemon/lens) shaped hematoma
Causes: “trivial traumas”, small brain in big skull
“LUCID INTERVAL”
Associated with skull fractures
130
Nontraumatic brain hemorrhage
often is what type of hemorrhage?
what are common causes (elderly vs. young)?
More often involvement of brain parenchyma (see intraparenchymal hemorrhage section above)
Think first - CHRONIC HTN
Elderly → Cerebral amyloid angiopathy
Young patient → recreational drug use, immunocompromised, cancer pt receiving chemo, patients with vaso-invasive infections, patient with iatrogenic or intrinsic coagulation deficits
131
Non-Atherosclerotic causes of stroke in young patients (5)
1) Vasculopathies:
- Fibromuscular Dysplasia (FMO)
- Moya-Moya
- Spontaneous arterial dissection
2) Hematological disorders
3) Inflammatory mechanisms
4) Venous infarction
5) Vasospasm
132
Fibromuscular Dysplasia (FMO)
Vasculopathic cause of non-atherosclerotic stroke in young patients
-arterial media hypertrophies causing areas of segmental occlusion/stenosis
Typically involves renal artery, carotid, and vertebral
Associated with arterial dissection and intracranial saccular aneurysms
Possible association with HSV-1
Women in 30s and 40s
133
Moya-Moya
Vasculopathic cause of non-atherosclerotic stroke in young patients
non-atherosclerotic focal occlusion of middle cerebral artery
Children, and women in 30s and 40s
Intimal hyperplasia
Possible association with EBV
Associated with secular aneurysms and dissection
134
Spontaneous Arterial Dissection
tear in endothelial lining of artery → blood dissects between endothelium and adventitia → occlusion or stenosis of artery, with emboli distally
Possible association with HSV-1
135
Hematological disorders (6)
1) Protein C deficiency, Protein S deficiency, Antithrombin deficiency, or Factor V Leiden, or Prothrombin gene → venous thrombosis
2) Malignancies
3) Sickle Cell Anemia
4) Hyperviscosity states
5) Oral contraceptive
6) Antiphospholipid antibodies (triad = spontaneous miscarriage, thrombocytopenia, recurrent large vessel thrombosis-arterial or venous)
136
Prevention of hemorrhage (2)
1) Control BP and other vascular risk factors
- Smoking cessation
- HTN is number one risk factor for nontraumatic brain hemorrhage
2) Manage initial ischemic event with antiplatelet or anticoagulants to prevent hemorrhagic transformation
137
Emergency Management of Intracranial Hemorrhage
1) Rapid diagnosis
2) Place intracranial pressure monitoring device or drainage device
3) Emergency surgery (+/-)
4) Support patients before definitive procedure can be performed
5) Diuresis
6) Reduction of blood CO2
138
Prevention of stroke (5)
1) Modify risk factors
2) Aspirin
3) Thienopyridines (Clopidogrel, Prasugrel, Ticlopidine)
4) Anticoagulants
5) Endarterectomy in symptomatic patients with high grade (70-90%) stenosis)
139
Emergency management of stroke
1) Thrombolytic agents (TPA)
2) Rehydration (lowers blood viscosity, prevent stroke progression)
3) Lumbar puncture:
4) Aspirin (+/- Clopidogrel)
5) IV Heparin
140
What happens if you give TPA too late?
Use TPA too late → can get reperfusion injury (especially in gray matter)
141
Why do you do a lumbar puncture in setting of suspected stroke/hemorrhage or AMS (altered mental status)?
Used to exclude neurosyphilis, vasculitis, or other inflammatory conditions that can mimic stroke
Determine if there is a subarachnoid hemorrhage
142
Modifiable risk factors for stroke
1) Hypertension
2) Lipid disorders (high LDL, low HDL)
3) Insulin resistance
4) Homocysteine elevation
- Treat with folate, B6, and B12
5) Smoking
6) Obesity
7) Physical inactivity
8) Diabetes
9) Alcohol abuse
143
Structural risk factors for stroke
mostly cardiac
Afib, CHF, valvular disorders (arterial stenosis), atrial septal defect (PFO), infectious endocarditis, intravascular/cardiac tumors (Atrial myxoma)
144
Main difference between ischemic and hemorrhagic stroke?
= TEMPO
Large ischemic stroke - mass effect and elevated ICP takes days to evolve
Large hemorrhagic stroke- mass effect and elevated ICP evolves in minutes to hours (headache, nausea, vomiting, lethargy, progressive LOC + focal neurodeficit)
145
_______ fusion is associated with pilocytic astrocytoma which is a grade ____ glioma
BRAF
grade I
146
IDH mutations are present in which 5 gliomas (2 lineages)
1) Oligodendroglioma --> Anaplastic oligodendroglioma
| 2) Diffuse astrocytoma --> anaplastic astrocytoma --> secondary glioblastoma
147
what mutation results in a primary glioblastoma
EGFR amplification
148
IDH + ______ are the mutations associated with oligodendrogliomas (and anaplastic oligodendrogliomas)
1p19q codeletion
149
Astrocytoma, oligodendroglioma, ependymoma, ganglioma =________, derived from the ___________
GLIOMAS
NEUROECTODERM
150
Pilocytic astrocytoma
Most common glioma seen in childhood
| Well circumscribed, non-infiltrative, minimal tendency to undergo malignant upgrading
151
Typical locations of pilocytic astrocytoma
Cerebellum, optic nerves/chiasm, and hypothalamic region
*Children often have tumors in POSTERIOR FOSSA
152
Treatment of pilocytic astrocytoma
surgical excision alone (some locations require other therapy as well)
153
Appearance (gross + microscopic) of pilocytic astrocytoma
Grossly = cystic
Microscopic = hair-like “piloid” astrocytes and Rosenthal fibers (eosinophilic intracytoplasmic glial filaments)
-May have vascular calcifications
154
Genetics of pilocytic astrocytomas
BRAF-KIAA fusion → Constitutive activation of BRAF gene = FAVORABLE feature in slow growing tumors
155
Ganglioglioma
location?
grade?
Location: usually in temporal lobe
Well demarcated = grade I
156
Ganglioglioma appearance (gross + microscopic)
Grossly = cystic, more likely to be calcified
Microscopic = increased number of jumbled, cytologically abnormal neurons mixed into a low grade glial background
-Microcysts with mucin
157
Ganglioglioma genetics
may have BRAF mutation
158
Choroid plexus papilloma typical location in children vs. adults
can result in what complication?
grade?
Children → Lateral ventricles
Adults → 4th ventricle
Produce HYDROCEPHALUS by BLOCKING CSF flow (not by CSF overproduction)
grade I
159
Choroid plexus papilloma appearance
intraventricular, closely mimic choroid plexus but more “papillary formations”, more abundant/crowded cells covering surface
Low mitotic rate, mild nuclear atypia
160
Grade I brain tumors (3)
tumors of low proliferative potential, possibility of cure with surgical resection alone
1) Pilocytic Astrocytoma
2) Ganglioglioma
3) Choroid plexus papilloma
161
Grade II brain tumors (3)
infiltrative, low proliferative level, but often recur.
Tend to progress to higher grade
TX: watchful waiting or external beam cranial irradiation
1) Diffuse Astrocytoma
2) Oligodendroglioma
3) Ependyoma
162
Diffuse Astrocytoma
what age?
progression/infiltration?
Common glioma
Occur in young adults, Age = 30s-50s
Potential to progress in grade
Infiltrative, no borders, cannot be surgically resected, only debulked
163
Location of diffuse astrocytomas
white matter of cerebral hemisphere
164
Appearance of diffuse astrocytomas (5)
1) Mild hypercellularity
2) Mild nuclear pleomorphism
3) Irregular distribution of tumor astrocytes
4) Variations in nuclear features and cytoplasmic content
* *5) Absence of necrosis, mitotic activity, and microvascular proliferation
- Main difference between anaplastic astrocytoma
165
Genetic anomolies in Diffuse astrocytoma (3)
how does this differ from the genetic anomolies found in oligodendrogliomas?
Diffuse Astrocytoma:
IDH1/2 mutation + no LOH 1p, 19q + p53/ATRX mutation
Oligodendroglioma:
IDH1/2 mutation + LOH 1p, 19q + no p53/ATRX mutation
166
Oligodendroglioma
age?
infiltration?
prognosis?
- Common glioma
- Mostly adults
- Infiltrative, no clear borders, cannot be surgically resected
- Better overall prognosis that diffuse astrocytoma
167
Location of oligodendrogliomas
cerebral
White matter of cerebral hemisphere but quickly spread to overlying cortex → seizures
168
Appearance of oligodendrogliomas (5)
1) Calcified significantly
2) Vascular (“Chicken wire”) vascular pattern)
3) Round monotonous nuclei, equal spacing, minimal cytoplasm
4) “Fried egg” appearance
5) Minimal/absent mitotic activity
169
Genetics of oligodendrogliomas
IDH1/2 mutation + LOH 1p, 19q + no p53/ATRX mutation
Can be diagnostic in differentiating oligodendroglioma or anaplastic oligodendroglioma from an astrocytoma
170
Ependymoma
location in adults vs. children
prognosis?
mostly, but not always in ventricles
Children → 4th ventricle → HYDROCEPHALUS
**Less favorable diagnosis
Adults → Spinal cord
-Typically well demarcated, full excision may be possible
171
Appearance of ependyomas
Gross:
1) Calcified
2) Masses protrude up from 4th ventricle as exophytic masses
Microscopic:
1) ependymal differentiation
2) mild-moderate cell density
3) few mitotic figures
4) Minimal necrosis or microvascular proliferation
172
Grade III brain tumors (3)
histological evidence of malignancy (nuclear atypia, high mitotic activity)
TX: adjuvant radiation and/or chemo
1) Anaplastic Astrocytoma
2) Anaplastic Oligodendroglioma
3) Anaplastic ependyoma
173
Anaplastic Astrocytoma
Common glioma, progression from diffuse astrocytoma
174
What can be used to label mitotic rate?
what would this stain be important for differentiating?
MIB-1+ nuclear labeling → important, used to look at cells undergoing mitosis
Increased mitotic rate = difference between diffuse/anaplastic astrocytoma
175
Appearance of anaplastic astrocytoma (5)
1) increased mitotic rate
2) DOES NOT show necrosis or microvascular proliferation
3) Crowded tumor cells
4) Nuclear hyperchromatism
5) variation in cell shape and size
**DO NOT show enhancement on preop imaging studies
176
Anaplastic Oligodendroglioma appearance (2)
1) Round, uniform nucleus, scant cytoplasm, “fried egg” appearance
2) microvascular proliferation present
DO show enhancement on preop imaging studies
177
Anaplastic ependymoma
difference with ependyoma?
location/age?
recurrence?
Higher mitotic activity than ependyoma
Typically in childhood and in 4th ventricle
Histological criteria not very indicative of prognosis
Can recur in distant sites due to CSF dissemination
178
Grade IV brain tumors (2)
cytologically malignant, mitotically active, necrosis prone neoplasms
Rapid disease, often fatal
1) Glioblastoma
2) Medulloblastoma
179
Glioblastoma
Most common and most malignant glioma
Most occur in 50s and 60s
Not surgically curable, debulking only
180
Primary vs. secondary GBM
Typically arise de novo (“primary GBM”) --> via EGFR pathway
But if diagnosis with lower grade astrocytoma first → “secondary GBM” (via IDH+ pathway)*
181
Genetics of primary GBM
EGFR typical mutation (diagnostic) in high grade GBM
182
Appearance of GBM
Hemorrhagic, necrotic, multifocal
Deceptively well demarcated, but microscopically infiltrative
183
WHO criteria for GMB (4)
need 3/4
1) Nuclear abnormalities (nuclear atypia, hyperchromatism, variation in nuclear size and shape)
2) Mitotic activity
3) Microvascular proliferation
4) Necrosis
184
Medulloblastoma
location?
age?
spread?
- Malignant embryonal tumor of cerebellum (primitive neuroectodermal tumor)
- Usually in children (3-8 years old) - most common malignant brain tumor in children
- Spreads throughout CSF pathways
- -> Outcome is better if it has not spread in CSF
185
Medulloblastoma presenting symptoms
Increased ICP → headache, vomiting, papilledema
Disturbances of gait, nystagmus, and dysmetria (cerebellar involvement)
186
Appearance of medulloblastoma?
Patternless sheets of small embryonal cells with scant cytoplasm (“small blue cells”)
minimal differentiation
187
Meningiomas (4)
Typically grade I, but can be life-threatening if in a location difficult to resect from
Peak incidence is WOMEN IN THEIR 50’S
Arise from arachnoid “cap” cell within arachnoid villus
May penetrate dura, occlude venous sinuses, invade bone, and cause hyperostosis
188
Hemangiopericytoma
meningeal-based tumor
Less favorable prognosis than meningioma, high recurrence rate
Accumulates more mutations as grade increases
189
Schwannomas (3)
(aka neurofibromas)
- Benign, can rarely degenerate into malignant form (neurofibrosarcoma)
- Slow growing
- Found on cranial nerve 8, other cranial nerves, and spinal nerve roots
190
Most brain tumors are ______ and of _______ etiology
SPORADIC
UNKNOWN
191
Metastases into brain come from where?
appearance? location?
Typically mets from breast, lung, kidney, melanoma, and GI tract cancer
Usually discrete, non-infiltrating tumors with variable surrounding edema
Typically allows complete surgical resection
Typically occur in cortex
192
Grade I treatment vs. Grade II-IV treatment?
Grade I: surgical cure
Grade II-IV:
- Only surgical debulking, rather than surgical cure is achievable
- Radiation + chemo
--> + second resection when tumor recurs (especially in grade III-IV)
193
IDH1 and IDH2
isoforms of enzyme Isocitrate dehydrogenase
Frequently mutated in gliomas
IDH1 → mutated in 70-80% of grade II and III astrocytomas, oligodendrogliomas, oligoastrocytomas, and secondary (but not primary) glioblastomas
NOT present in pilocytic astrocytomas
Mutation → make tumor cells less viable, increase susceptibility to oxidative damage
BETTER PROGNOSIS with IDH mutation
194
Glial tumors in pediatric vs. adults
Look similar, but have different genetic markers
Peds = pilocytic astrocytoma, no IDH mutation - BRAD-KIAA fusion
Adults = IDH mutation +/- LOH 1qp19 +/- p53/ATRX mutation
195
LOH 1pq19
unbalanced translocation, fusion → fusion protein
All adult oligodendrogliomas defined by presence of LOH 1p19q AND IDH mutation (either IDH1 or IDH2)
Prognostic, diagnostic, and predictive
196
Tumors that tend to spread via CSF (2)
Medulloblastoma
Anaplastic Ependyoma
197
Demyelinationg diseases
group of diseases, primarily acquired, and associated with myelin destruction with RELATIVE sparing of axons
198
Five subtypes of MS
1. Relapsing-remitting (RRMS)
2. Primary progressive (PPMS)
3. Secondary progressive (SPMS)
4. Clinically Isolated syndrome (CIS)
5. Radiologically Isolated Syndrome (RIS)
199
Relapsing Remitting MS
sporadic episodes of new or worsened symptoms and signs (over 2-10 days), with variable improvement over 1-6 months
85% of patients present with this type
200
Primary Progressive MS
never have relapses, just slow progression
15% present with this type
201
Secondary progressive MS
relapsing-remitting MS, which converts to progressive disease
202
__% of RRMS will convert to SPMS
50+%
203
Clinically isolated syndrome
“first attack”, don’t fit criteria for full dx yet
204
Radiologically isolated syndrome
individuals scanned for “non”-MS symptoms, yet have apparent MS on MRI scans
205
Age of presentation MS
75% between 15-45 years
206
MS: males or females
2/3 are women
207
Race most commonly affected by MS
Caucasians
208
Neuropathology of MS: Early and late
Lesions evolve over time
1. Early → perivascular lymphocytic infiltrate with T/B cells, macrophages, complement, IgG, and complement
a. Demyelination with RELATIVE axonal sparing
2. Later → more of a glial scar, modest inflammation
3. Condition CHANGES with age - relapsing, to stable, etc.
209
In MS: ___ matter lesions seen early pathologically/on MRI
Grey
210
What is seen in the meninges, especially in progressive MS
Lymph node-like structure with B cells
211
MS is both ____ and _____
inflammatory and degenerative
Inflammation wanes with time
212
Criteria for MS diagnosis
i. Multiple lesions of CNS disseminated in time and space
- 2 or more symptoms lasting at least 24hrs, 30+ days apart (RRMS) or minimum of 12 months of progression of sx (PPMS)
- 2 separate locations in brain/spinal cord
ii. No other cause identified
iii. Objective abnormalities on neurological exam
213
Clinical symptoms of early MS (6)
1. UNIFOCAL, paresthesias (numbness, tingling)
2. Monocular loss of vision (optic or retrobulbar neuritis)
3. Gait problems, weakness
4. Diplopia (double vision)
5. Urinary urgency/frequency
6. Constipation
214
Clinical symptoms of late MS (7)
Symptoms above + ...
1. Multifocal symptoms
2. Fatigue, depression
3. Sexual dysfunction
4. Cognitive dysfunction
5. Pain
6. Dysphagia
7. Problems due to immobility (e.g. infections and DVT)
215
Neurologic exam in MS
i. Usually ASSYMMETRIC “upper motor neuron” / pyramidal tract signs (weakness, spasticity, Babinski sign)
ii. Decreased visual acuity, optic atrophy, and afferent pupillary defect
iii. Eye movement abnormalities (nystagmus, internuclear ophthalmoplegia)
iv. Sensory loss
v. Cerebellar signs (ataxia, tremor, dysarthria, balance, coordination)
vi. Mood - depression, labile affect
vii. Cognitive dysfunction
216
MRI in MS
lesions in periventricular regions, corpus callosum, juxtacortical, spinal cord, and brainstem/cerebellum
1. T1 “holes” = axonal damage,**bad long term prognostic sign**
- Chronic sign
2. T1 with contrast-enhancing lesions=BBB breakdown (early stage lesion)
- Leakage of dye that lights up in brain due to BBB damage
3. T2 hyperintense/bright lesions = acute or chronic lesions, many bright dots on T2 and FLAIR images
4. Atrophy (especially gray matter) = **bad long-term prognostic sign**
217
```
CSF analysis MS:
protein-?
WBC-?
Glucose-?
IgG-?
Myelin basic protein-?
```
1. Protein mild elevations
2. WBC mild elevations (lymphocytes)
3. Glucose = ALWAYS NORMAL
4. Abnormal IgG production + oligoclonal bands
5. Myelin basic protein elevations (nonspecific)
218
Evoked potentials MS
prolonged conduction times consistent with demyelination
219
Goal of therapy in MS
lifelong brain health
220
Behavioral changes in MS treatment
good sleep, exercise, no smoking, vitamin D, low salt diet
221
Aggressive treatment of comorbidities in MS treatment
HTN, diabetes, spine disease, hip/knee disease, primary sleep disturbances
222
Treatment of acute attacks in MS treatment
high dose corticosteroids, plasma exchange (in severe cases, unresponsive to steroids)
223
Symptomatic therapy in MS treatment
physical, occupational, speech, rehab psychological therapies, etc.
224
Immunotherapy in MS treatment
goal = reduce relapses, reduce progression to disability as related to relapses, and reduce MRI changes = No Evidence of Disease Activity (NEDA)
225
Acute alcohol intoxication --> what CNS effect?
Cerebral edema
226
Chronic alcohol use --> what CNS effects (2)
1) Cerebellar degeneration, neuronal loss
- Purkinje cells in cerebellum particularly susceptible
2) Cerebral atrophy, especially damage to white matter early in disease
* Vitamin deficiency in alcoholics may also play a role in addition to direct toxicity
227
Fetal Alcohol Syndrome symptoms
hyperreactivity, poor motor skills, learning difficulties
Severely affected kids have mental retardation
228
Hepatic Encephalopathy is due to...
elevation of blood ammonia, above 200 ug/dL
229
Hepatic encephalopathy is precipitated by events that cause ammonia levels to rise. These causes include... (2)
GI hemorrhage, severe cirrhosis
230
Ammonia is derived from ______________________ and produced in _____________________
with liver failure...
with portal hypertension...
- derived from catabolism of proteins
- produced in colon from protein by urease-containing bacteria
With liver failure, ammonia NOT converted to urea
With portal hypertension, ammonia bypasses the liver completely
231
Pathogenesis of hepatic encephalopathy
Ammonia readily crosses BBB → taken up by Alzheimer type II astrocytes → astrocytes rich in glutamine synthetase
→ convert Glutamate + NH4+ → glutamine → glutamine then taken up by neurons and converted back to glutamate
=EXCITOTOXICITY
Results in edema and damage to the cortex and basal ganglia
232
Treatment of hepatic encephalopathy (3)
restrict protein
suppress bacteria with abx
use lactulose to acidify colon contents
233
Symptoms of hepatic encephalopathy (2)
1) confusion
| 2) asterixis
234
Non-Wilsonian Hepatocerebral Degeneration
Form of Chronic Hepatic Encephalopathy
-due to repeated bouts of HE --> hronic liver failure and irreversible neurological damage
235
Wilson’s Disease
inherited disorder of copper metabolism → liver cirrhosis
Produces identical neurological changes to HE (damage to basal ganglia)
Damage due to repeated bouts of HE and NOT due to direct brain toxicity by copper
236
Symptoms of Wilson's Disease (2)
Jaundice (around 12 yrs old) and/or movement disorder (due to basal ganglia damage)
237
Wernicke-Korsakoff Syndrome
oculomotor abnormalities and mental symptoms
Vitamin B1/Thiamine deficiency
Most common in alcoholics or patients with hyperemesis
Example of toxic-metabolic problem that shows selective vulnerability
238
Wernicke's Encephalopathy (3 symptoms)
1) Ocular disturbances (nystagmus, ocular motility problems)
2) Changes in mental state (confusion)
3) Unsteady gait (ataxia)
due to thiamine (B1) deficiency
239
Korsakoff's Psychosis
1) severe memory impairment without any intellectual disabilities
- often accompanies wernicke's encephalopathy
Due to thiamine (B1) deficiency
240
Wernicke-Korsakoff Synfrome effect on brain
Mammillary bodies involved in almost all cases
Also involves hypothalamus, medial thalamus, periaqueductal grey, floor of 4th ventricle
Causes hemorrhage and necrosis especially in mamillary bodies
Histology varies with stage and severity
Edema, necrosis, demyelination, neuron loss, gliosis
241
Cobalamin Deficiency
3 main consequences
vitamin B12 deficiency
1) Megaloblastic anemia
2) Neurological complications → cognitive deficits, subacute combined degeneration
3) Spinal cord disease → involvement of ascending (sensory) and descending (motor) tracts in spinal cord (myelin tracts)
242
Vitamin B12 absorption
B12: main dietary source is animal products (meat, dairy)
Intrinsic Factor: glycoprotein produced by parietal cells in stomach
IF binds B12 in stomach
--> Without IF, less than 1% of dietary B12 absorbed
B12-IF complex transported to terminal ileum
→ binds receptors, absorbed
243
How to get B12 deficiency (3)
1) Strict vegan diet
2) Problem with malabsorption
3) Autoimmune disorder - ab to gastric parietal cells / intrinsic factor = Pernicious Anemia
**Vitamin stored in many tissues, depleted in 3-4 years
244
Symptoms of Cobalamin Deficiency (3)
symptoms develop over weeks
initial:
1) slight ataxia
2) numbness in LE
3) tingling in lower extremities
Can progress rapidly to spastic weakness or complete paraplegia
245
Central Pontine Myelinolysis caused by...
Sustained hyponatremia due to excessive secretion of ADH (vasopressin), which prevents water diuresis when serum Na+ levels low
→ occurs when chronically hyponatremic patients have their serum Na+ rapidly corrected
246
Symptoms of central pontine myelinolysis
pontine dysfunction with pseudobulbar palsy
247
Acute Bacterial Meningitis
infection of subarachnoid space
Medical emergency - start empiric abx urgently (within 60 min of arrival to ER)
248
Clinical presentation of acute bacterial meningitis (9)
Classic triad:
1) fever
2) headache
3) neck stiffness
4) +/- altered mental status
5) Seizures
6) nausea/vomiting
7) myalgia
8) cranial nerve palsies (III, VI, VII, VIII)
9) Focal deficits (hemiparesis, ataxia, gaze preference)
249
Bacteria can enter the subarachnoid space via what 3 routes
1) bloodstream (most common)
2) adjacent intracranial infection (sinusitis, otitis, etc.)
3) congenital / traumatic / surgical defects in skull/spinal column
250
Causes of acute bacterial meningitis (5)
Less than 2 months old
1) Strep agalactiae (group B strep)
2) Gram-Negative Rods (E. Coli)
3) Listeria monocytogenes (in really young, really old, or alcoholics - must add Ampicillin to abx therapy)
4) Strep pneumoniae
5) H. Influenzae
251
Causes of acute bacterial meningitis (4)
2-23 months old
1) Strep pneumoniae (50%)
2) Neisseria meningitides (10-15%)
3) Strep agalactiae (group B strep) (10-15%)
4) H. Influenzae (5-10%)
252
Causes of acute bacterial meningitis (3)
23-34 years old
1) Neisseria meningitides (40%)
2) Strep pneumoniae (40%)
3) H. Influenzae (5-10%)
253
Causes of acute bacterial meningitis (3)
> 35 years old
1) Strep pneumoniae (50-70%)
2) Neisseria meningitides (10-25%)
3) H. Influenzae (1-10%)
254
Lumbar puncture in acute bacterial meningitis
1) Low glucose
2) High protein
3) Pleocytosis
4) > 80% Neutrophils
255
When you gram stain your LP and it says...
Gram negative diplococci = ?
Gram positive diplococci = ?
Gram positive cocci in chains = ? or ?
Gram negative rod = ?
Gram positive rod = ?
Gram negative diplococci = Neisseria
Gram positive diplococci = Strep (pneumococcus)
Gram positive cocci in chains = Strep (pneumococcus or Group B) or enterococcus
Gram negative rod = enteric GNs
Gram positive rod = Listeria
256
Diagnosis of acute bacterial meningitis
1) LUMBAR PUNCTURE is key
2) Culture and gram stain LP
3) Blood culture
4) Neuroimaging (CT/MRI)
257
If you get neuroimaging prior to doing an LP in the setting of suspected acute bacterial meningitis what should you do first?
Neuroimaging prior to LP:
Get blood cultures and begin EMPIRIC ABX + CORTICOSTEROIDS started first
258
Corticosteroids in treatment of acute bacterial meningitis
can be given prior to first dose of abx
continue if pneumococcus identified
259
Treatment of acute bacterial meningitis:
Neonates, infants (1-3 months)
Ampicillin + Cefotaxime
260
Treatment of acute bacterial meningitis:
3 months - 50 years
Ceftriaxone, Cefotaxime, Vancomycin
261
Treatment of acute bacterial meningitis:
Greater than 50 years
Ceftriaxone + Vancomycin + Ampicillin
262
Treatment of acute bacterial meningitis:
Any nosocomial acquired infection, recent head trauma/neurosurgery, immunocompromised, alcoholics
Vancomycin + Meropenem +/- Ampicillin
263
LP of viral vs. bacterial meningitis
```
WBC
Cell type
Glucose
Protein
Cultures
Useful stains/tests
```
```
Bacterial:
WBC = 100-10,000
Cell type = PMN (80-95%)
Glucose = low
Protein = elevated
Cultures = + (bacteria)
Useful stains = gram stain
```
```
Viral:
WBC = 10-2,000
Cell type = mononuclear (lymphocyte)
Glucose = normal
Protein = normal/slightly elevate
Cultures = + (viral) - (bacterial)
Useful stains = PCR
```
264
LP in encephalitis
```
WBC
Cell type
Glucose
Protein
Cultures
Useful stains/tests
```
```
WBC = 10-2,000
Cell type = Mononuclear (lympocyte)
Glucose = normal
Protein = elevated
Cultures = + viral, +/- Bacterial
Useful stains = PCR, MRI
```
265
3 of the most common causes of viral meningitis
Enteroviruses
HSV-2
Arboviruses (west nile virus, WNV, Zika virus)
266
Clinical Features of viral meningitis (3)
Headache, fever, meningeal irritation (stiff neck)
Milder than with bacterial meningitis
267
Diagnosis of viral meningitis
CSF → normal glucose + lymphocytic pleocytosis + high protein
PCR amplification of viral genomic material from CSF = MOST important diagnostic test for viral meningitis
268
Viral encephalitis
infection of brain tissue rather than just subarachnoid space
269
Clinical features of viral encephalitis
1) Altered consciousness
2) fever
3) headache
4) Seizures
5) Focal neurological signs
- -> Personality changes, AMS, aphasia, hemiparesis, ataxia, cranial nerve palsies, visual field loss, tremors, myoclonus, Parkinsonism
270
Causes of viral encephalitis
1) 60% of cases have unknown cause
2) Autoimmune encephalitis (ab to NMDA receptor) possible cause
3) Most important causes in US = Arboviruses (WNV, Zika), and HSV-1
271
Diagnosis of viral encephalitis
1) CSF pleocytosis
2) EEG abnormalities
3) CT and MRI showing focal encephalitis
4) PCR amplification of viral nucleic acid from CSF
5) WNV IgM in CSF (diagnostic of WNV encephalitis)
