Cerebrovascular Disease and Infections Flashcards
What deficits are seen in an anterior cerebral artery rupture?
- Upper motor neuron type weakness
- Cortical type sensory loss
- Contralateral hemiplegia initially
- Alien hand syndrome
What is alien hand syndrome? When is it seen?
- Semi Automatic movements of the contralateral arm not under voluntary control
- Seen in anterior cerebral artery rupture
What deficits are seen in posterior cerebral artery rupture?
- Contralateral homnymous hemianopia
What deficits are seen in middle cerebral artery rupture?
- Aphasia
- Hemineglect
- Hemianopia
- Face-arm or face-arm-leg sensorimotor loss
What is the gaze preference in MCA rupture?
- TOWARD side of lesion
What are lacunes?
- Small deep infarcts involving penetrating branches of MCA or other vessels
What is the difference between hypoxia and ischemia?
- Hypoxia –> decreased oxygen
- Ischemia –> decreased blood supply
What is the ultimate consequence of hypoxia and ischemia?
- Tissue infarction
What are the three major categories of cerebrovascular disease?
- Thrombosis
- Embolism
- Hemorrhage
What is a stroke?
- Clinical designation
- Applies to all classifications of cerebrovascular disease
- Acute onset and persists longer than 24 hours
What are some of the most common cerebrovascular disorders?
- Global ischemia
- Embolism
- Hypertensive intraparenchymal hemorrhage
- Ruptured aneurysm
What does survival depend on when blood flow is reduced?
- Collateral circulation
- Duration of ischemia
- Magnitude and rapidity of flow reduction
What are the two types of reduction in blood flow?
- Global ischemia
2. Focal ischemia
What are some causes of global ischemia?
- Cardiac arrest
- Shock
- Severe hypotension
What are some causes of focal ischemia?
- Embolic or thrombotic arterial occlusions
- Vasculitides
- Atherosclerosis in hypertension
What does the damage look like to watershed areas in an infarct?
- Sickle shaped band of necrosis
What can cause damage to the ACA-MCA watershed area?
- Occlusion of internal carotid artery
- Hypotension in patient with carotid stenosis
What symptoms are seen in ACA-MCA watershed infarct?
- Proximal arm and leg weakness
- Transcortical aphasia –> language issues
What symptoms are seen in MCA-PCA watershed infarct?
- Higher order visual processing
What can cause carotid stenosis?
- Atherosclerosis
What could be a consequence of atherosclerosis of the internal carotid artery?
- Thrombi can embolize distally to the MCA, ACA, or ophthalmic artery
What may be some symptoms of a thrombi that embolizes from the carotids?
- Contralateral face-arm or face-arm-leg weakness
- Contralateral sensory changes
- Contralateral visual field defects
- Aphasia or neglect
What are some sites of primary thrombosis?
- Carotid bifurcation
- Origin of middle cerebral artery (MCA)
- Either end of basilar artery
What is an atheroma?
- Intimal lesion, lipid core covered by fibrous cap
What happens if the lipid cap ruptures?
- Exposes blood to thrombogenic substance –> thrombosis/clot
What do infarcts look like in the brain?
- Wedge shaped due to distribution
What are some sources of emboli?
- A fib
- MI
- Valvular disease
- Artery-to-Artery emboli
- Dissection
- PFO
What is a marantic emboli?
- Proteinaceous emboli from marantic (non-bacterial thrombotic) endocarditis
- Hypercoagulable states such as advanced malignancy
- Amniotic fluid emboli –> child birth
Which artery is most likely affected by an emobli?
- MCA
What is a shower emboli?
- Fat after long bone fracture
What is characteristic of bone marrow embolization?
- Widespread white matter hemorrhages
What are some causes of hypercoaguability?
- Heritable coagulation factor disorders
- Dehydration
- Adenocarcinomas/malignancies
- Surgeries, trauma, childbirth
- DIC
- Hematologic disorders
- Vasculitis
What are some common causes of a transient ischemic attack (TIA)?
- Migraines
- Seizures
- Non-neurologic conditions (cardiac arrhythmias or hypoglycemia)
How long are TIAs typically? What happens if they are longer?
- Around 10 min
- Anything longer causes some permanent cell death
Why are TIAs so important to recognize?
- They are a neurological emergency
- May have a stroke causing persistent deficits within 3 months
What is the mechanism of TIAs?
- Embolus temporarily occludes then dissolves, in situ thrombus formation and/or vasospasm
What are the two types of stroke?
- Hemorrhagic
- Ischemic
What does a hemorrhagic stroke look like?
- Intracerebral or subarachnoid hemorrhage
- Emboli associated
- Hemorrhage secondary to reperfusion of damaged vessels
What does an ischemic stroke look like?
- Bloodless
- Thrombus associated
- Hemorrhagic conversion
What is hemorrhagic conversion seen in ischemic stroke?
- Fragile vessels rupture leading to secondary hemorrhage
What are some causes of ischemic stroke?
- Embolic
- Thrombotic
- Large vessel
- Small vessel
- Lacunar infarcts
What symptoms are seen in lenticulostriate artery infarct?
- Pure motor hemiparesis
What symptoms are seen in thalamic lacune?
- Contralateral somatosensory deficits
What symptoms are seen in basal ganglia lacune?
- Hemiballismus
What are slit hemorrhages?
- Small caliber penetrating vessels –> look like slit like cavities
What surrounds a slit hemorrhage?
- Pigment laden macrophages
- Macrophages
- Gliosis
What causes hypertensive encephalopathy?
- Malignant HTN
What is seen in hypertensive encephalopathy?
- Vascular multi-infarct dementia
- Binswanger disease
- Charcot-Bouchard microaneurysms
What signs are seen in vascular multi infarct demetia?
- Dementia
- Gait
- Pseudobulbar signs
What signs are seen in binswanger disease?
- Large area of subcortical white matter with myelin and axon loss
What signs are seen in charcot-bouchard microaneurysms?
- Associated with chronic hypertension
- Minute aneurysms in the basal ganglia
What is cerebral amyloid angiopathy?
- Lobar hemorrhage
- Same B-amyloid deposited in the walls of vessels (like in Alz disease) producing microbleeds
What is CADASIL?
- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
What is seen in CADASIL?
- Recurrent strokes and dementia
- Thickening of the media and adventitia
- Loss of smooth muscle cells and basophilic PAS+ deposits
When is CADASIL detected?
- Around 35 years old and infarcts typically occur 10-15 years later
What gene is seen in CADASIL?
- Auto Dom –> NOTCH 3 gene
What are some stroke risk factors?
- HTN
- Diabetes
- Hypercholesterolemia
- Cigarette smoking
- Pos family history
- Cardiac disease
- Prior history of stroke
- Hypercoagulability
What should you think if there is a stroke in a young patient?
- Arterial dissection (like in marfan)
- PFO or hypercoagulability
- Sickle cell
What is the most frequent cause of a significant subarachnoid hemorrhage?
- Rupture of saccular (berry) aneurysm –> begins as basilar SAH
What aneurysms are seen in the anterior circulation?
- Saccular
- Mycotic
- Traumatic
- Dissection
Where in the circle of willis are saccular aneurysms found?
- Majority in ACA
- Secondary location in MCA
How can saccular (berry) aneurysms be treated?
- Clipping due to having a neck
When do aneurysms usually rupture?
- Fifth decade and slightly more in females
What increases the likelihood of ruptured aneurysms?
- Increased intracranial pressure –> straining at stool or sexual orgasm
What are some hereditary diseases that have increased incidence of aneurysms?
- If first degree relative is affected
- Infantile polycystic kidney disease
- Ehlers-Danlos type IV
- NF1
- Marfan
How do people present with a ruptured aneurysms?
- Worse headache they have ever had
- Repeat bleeding is common
What are people most at risk for a couple of days after SAH?
- Additional ischemic injury from vasospasm affecting vessels bathed in extravasated blood
What are the four groups of vascular formations?
- Arteriovenous malformations (AVM)
- Cavernous malformations/hemangiomas
- Capillary telangiectasias
- Venous angiomas
What do cavernous malformations look like?
- Distended, loosely organized vascular channels arranged back to back
- ** THERE IS NO BRAIN PARENCHYMA***
What regions of the brain are affected by cavernous malformations?
- Cerebellum
- Pons
- Subcortical regions
What is seen in cavernous malformations?
- Foci of old hemorrhage
- Infarction
- Calcification seen in surrounding area
Who is most likely affect by AVMs?
- Males more than females in their 10-30s
What are some symptoms of AVMs?
- Seizure
- Intracerebral hemorrhage or SAH
What do AVMs look like?
- Tangle, worm like vascular channels with prominent pulsatile arteriovenous shunting with high blood flow
Where are AVMs most commonly seen?
- MCA and posterior branches (subarachnoid space)
What mutation is associated with AVMs?
- KRAS oncogene
What are some causes of multifocal vascular disease?
- Cerebral atherosclerosis
- Vessel thrombosis/emboli from carotid or heart
- Cerebral arteriosclerosis from chronic hypertension
What is seen in vascular dementia?
- Multiple, bilateral gray matter and white matter infarcts
What are the four principal routes of infection?
- Hematogenous
- Direct implantation
- Local extension
- PNS
How does tuberculous meningitis develop?
- Seeding CSF from subepidural or submeningeal granulomas
How does herpes simplex and zoster infections spread?
- Produce latent infection of sensory ganglia
- Replicate in schwann cells
- Ascend to the CNS within sensory nerves
How does rabies infections spread?
- Bind at or near Ach receptors at the NMJ
- Ascend to the CNS via motor nerves
What is the CNS response to infection?
- Widespread infection –> involving all tissue elements, characteristic of bacterial meningitis and many viral encephalitides
- Functional specialization of different cell populations and of specific neuro-anatomical regions determine the characteristic neurological syndromes
What accelerates the development of cerebral edema?
- Accelerated by products released by both living bacteria and antibiotic lysed bacteria
What slows the development of cerebral edema?
- Slowed and reversed by corticosteroids
What are the symptoms of acute meningitis?
- Headache
- Meningeal irritation signs (Kernig/Brudzinski)
- High fever
- Confusion
- Coma
When do symptoms of acute meningitis develop?
- Within several days; however may develop over a few hours with a fulminant course
Where is the exudate in pneumococcal meningitis?
- Convexities near sagittal sinus
Where is the exudate in H. influenzae meningitis?
- Basal location
What is ventriculitis?
- Fulminant infection
- Inflammation may extend into ventricles
What is focal cerebritis?
- Inflammatory cells infiltrate walls of the veins and extend into the brain substance
What are some systemic signs that are caused by acute meningitis?
- Ventriculitis
- Focal cerebritis
- Phlebitis –> may lead to venous thrombosis and hemorrhagic infarction
- Leptomeningeal fibrosis –> hydrocephalus
What are the complications seen in bacterial meningitis?
- Seizures
- Encephalitis
- Hearing loss, blindness, paralysis
- Fulminant –> esp. with meningococcemia (will see adrenal hemorrhage causing death)
What is the gram neg diplococci causing meningitis?
- N. meningitidis
What is the gram pos diplococci causing meningitis?
- S. pneumoniae
What is the gram neg pleomorphic causing meningitis?
- H. influenzae
What is the gram pos cocci causing meningitis?
- S. aureus or s. epi
- Streptococci
What is the gram neg bacilli causing meningitis?
- E. coli or other gram neg
Where in the spine is the best place to do a lumbar puncture?
- Between 3rd and 4th lumbar vertebrae
How does the CSF differ between bacterial cause and viral cause?
- Bacterial: Cloudy, high neutrophil, low glucose, very high protein levels
- Virus: clear, no neutrophils, high lymphocytes, normal glucose, increased protein levels
What are some risk factors for meningitis?
- Age <5 and >60
- DM
- Immunosuppression
- Contiguous infections
- IVDA
- Bacterial endocarditis
- Sickle cell
What organisms are most likely to cause meningitis in neonates?
- E. coli
- Grp B strep
What organisms are most likely to cause meningitis in unvaccinated children under 2yo?
- H. influenzae type B
What organisms are most likely to cause meningitis in adolescents and young adults?
- N. meningitidis
What organisms are most likely to cause meningitis in elderly?
- S. pneumoniae
- Listeria monocytogenes
What organisms are most likely to cause meningitis in immunocompromised individuals?
- S. pneumoniae
- N. meningitidis
- L. monocytogenes
- P. aeruginosa
What organisms are most likely to cause meningitis in a basilar skull fracture?
- S. pneumoniae
- H. influenzae
- Grp A beta-hemolytic strep
How do patients present with an abscess?
- Progressive focal neurological deficits
- Signs of increased intracranial pressure may also develop
What does the CSF look like in an abscess?
- High WBC
- High protein
- Normal glucose
What are some complications seen in ascesses?
- Herniation
- Abscess rupture with ventriculitis or meningitis
- Venous sinus thrombosis (patient dies)
What is the treatment for most brain abscesses?
- Surgical drainage and antibiotics
What does a brain abscess look like on CT?
- Edema surrounding liquefactive necrosis
What is subdural empyema?
- Bacteria or fungus infection of skull bones or sinuses spread to subdural space
What is the treatment of subdural empyema?
- Surgical drainage
What is associated with an extradural abscess?
- Osteomyelitis
Where does N. meningitidis colonize?
- Oropharynx and rhinopharynx
What agar is used to grow N. meningitidis?
- Chocolate agar
What are the clinical manifestations of N. meningitidis?
- Rapidly progressive septicemia with fever, hypotension, DIC, petechial and purpuric lesions
- Purpura fulminans
- Hemorrhagic infarction of adrenal glands
What is purpura fulminans?
- Hemorrhagic skin lesions which progress to gangrene
- Occurs in distal portion of limbs
What are the symptoms of chronic meningitis?
- Fever
- Headache
- Lethargy
- Confusion
- N/V
- Stiff neck
What does the CSF look like in chronic meningitis?
- Elevated protein
- Predominantly lymphocytic pleocytosis
- Sometimes low glucose
What are some causes of chronic meningitis?
- TB
- Neuroborreliosis
- Neurosyphilis
What is seen in mycobacterium tuberculosis diffuse meningoencephalitis?
- Gelatinous or fibrinous exudate in subarachnoid space
- Obliterative endarteritis –> inflammation infiltrates vessel walls with intimal thickening
Where is the predilection in mycobacterium tuberculosis diffuse meningoencephalitis?
- Base of brain –> CNs could be affected
- Obliterated Cisterns and encases CNs
What is needed to diagnose mycobacterium tuberculosis diffuse meningoencephalitis?
- Culture AND smear to increase chance of positive
What symptoms are seen in borrelia meningitis?
- Cranial nerve palsy and peripheral neuropathies
- CSF with antibodies
How is borrelia meningitis diagnosed?
- CSF PCR
What is meningovascular neurosyphillis?
- Chronic meningitis involving base of the brain
- Causes communicating hydrocephalus
What is seen in meningovascular neurosyphilis?
- Obliterative endarteritis = Heubner arteritis
What is paretic neurosyphilis?
- Insidious, but progressive mental deficits associated with mood alterations (delusions of grandeur) that terminate in severe dementia
- Perivascular iron deposits
- Glandular ependymitis –> proliferation of subependymal glia under damaged ependymal lining
What is tabes dorsalis?
- Damage to sensory nerves in the dorsal roots
What symptoms are seen in tabes dorsalis?
- Impaired joint position sense and resultant ataxia
- Loss of pain sensation
- Joint damage
- Lightening pains
- Absence of deep reflexes
What is the main cause of aseptic meningoencephalitis?
- Enteroviruses
What does the CSF look like in aseptic meningoencephalitis?
- Lymphocytic pleocytosis
- Moderate increase protein
- Glucose near normal
How do most viruses infect the CNS?
- Through nerves
What is the inflammatory response to viruses in the brain?
- Lymphocytes
What are some symptoms of arthropod borne viral encephalitis?
- Generalized neuro deficits
- Focal signs
What does west nile look like?
- Involves spinal cord and gives a polio like syndrome with paralysis
What does the CSF look like in arthropod borne viral encephalitis?
- Colorless
- Slight increase in pressure
- Increased protein
- Normal glucose
What is seen in the brain during arthropod borne viral encephalitis?
- Multiple foci of necrosis in both gray and white matter
- Neuronophagia
- Microglial nodules
What are the symptoms of HSV-1 encephalitis?
- Alterations in mood, memory, and behavior
What does HSV-1 encephalitis do to the brain?
- Necrotizing and hemorrhagic
What parts of the brain are most affected by HSV-1 encephalitis?
- Inferior and medial temporal lobes (cingulate gyrus destroyed)
- Orbital gyri of frontal lobes
What inclusions are seen in HSV-1 encephalitis?
- Cowdrey type A
How do neonates get HSV-2 encephalitis?
- Born by vaginal delivery to women with active primary HSV infection
What happens with the herpes zoster infection?
- Latent phase in sensory neurons of dorsal root or trigeminal ganglia
What happens when herpes zoster is reactivated?
- Shingles –> painful vesicular skin eruption limited to a single or limited dermatome
- Postherpetic neuralgia syndrome
What is postherpetic neuralgia syndrome seen in reactivated herpes zoster infection?
- Persistent pain as well as painful sensation following nonpainful stimuli
Who is most likely affected by CMV?
- Fetuses and immunocompromised ind.
What happens to the brain in a CMV infection?
- Periventricular necrosis causing severe brain destruction (mainly parenchyma)
- Microcephaly
- Periventricular calcification
Where does CMV localize in the brain?
- Paraventricular subependymal regions –> severe hemorrhagic necrotizing ventriculo encephalitis and choroid plexitis
Where does poliomyelitis attack?
- Mononuclear cell perivascular cuffs
- Neuronophagia of the anterior horn motor neurons of the spinal cord
What symptoms are seen in poliomyelitis?
- Flaccid paralysis
- Associated with muscle wasting and hyporeflexia
What is the incubation period of rabies?
- 1-3 months
How does rabies infect?
- Ascends along peripheral nerves from the wound site
What are some symptoms of a rabies infection?
- Paresthesias around wound
- Extraordinary CNS excitability –> violent motor responses progressing to convulsions
- Flaccid paralysis
- Hydrophobia
What happens in acute HIV aseptic meningitis?
- Mild lymphocytic meningitis
- Perivascular inflammation
- Some myelin loss
What happens in chronic HIV aseptic meningitis?
- Microglial nodules with multinucleated giant cells
What happens to the vessels in HIV aseptic meningitis?
- Abnormal prominent endothelial cells and perivascular foamy or pigment-laden macrophages
What happens to the white matter in HIV aseptic meningitis?
- Multifocal or diffuse areas of myelin pallor, axonal swelling, and gliosis
What is IRIS?
- Immune reconstitution inflammatory syndrome
What is seen in IRIS?
- Paradoxical deterioration after starting antiviral therapy
- Exuberant inflammatory response
- Paradoxical exacerbation of symptoms from opportunistic infections
What is seen in HIV-associated neurocognitive disorders?
- Mild to florid cognitive changes
- Persisting despite effective HIV treatment
What virus causes progressive multifocal leukoencephalopathy (PML)?
- JC Polypomavirus
What does the JC polyomavirus affect?
- Oligodendroglial cells
- Demyelination principle pathologic effect
What occurs in PML?
- Irregular, ill-defined destruction of white matter
- Subcortical area of demyelination with lipid-laden macrophages in the center with decreased number of axons
What causes subacute sclerosing panencephalitis (SSPE)?
- Paramyxovirus
- Seen in children months-years following early age acute infection with measles
What symptoms are seen in SSPE?
- Cognitive decline
- Spasticity of limbs
- Seizures
What happens in the brain during SSPE?
- Widespread gliosis and myelin degeneration
- Viral inclusions
- Variable inflammation of white and gray matter
- Neurofibrillary tangles
What organisms are the biggest causes of fungal meningoencephalitis?
- Candida albicans
- Mucor
- Aspergillus
- Cryptococcus neoformans
Which meningitis causing fungus is most likely found in people with diabetes?
- Mucormycosis
Who is most likely to develop chronic meningitis by cryptococcus neoformans?
- People with immune dysfunction –> Immunosuppressed
Where is cryptococcus gattii likely to cause chronic meningitis?
- Immunocompetent ind.
What is used to prep the CSF in cryptococcus meningitis?
- India ink prep
How is cryptococcus meningitis diagnosed?
- Look at CSF for the cryptococcal polysaccharide antigen and culture
What does toxoplasmosis gondii do to the brain?
- Brain abscess
Where is the brain abscess due to toxoplasmosis located?
- Near gray-white junction of cerebral cortex and deep gray nuclei
What does a toxoplasmosis brain abscess look like on CT?
- Ring enhancing lesion
What does the histology look like for toxoplasmosis?
- Central foci of necrosis
- Petechial hemorrhages surrounded by acute and chronic inflammation
- Macrophage infiltration and vascular proliferation
- Free tachyzoites and encased bradyzoites
How does naegleria fowleri (brain eating ameba) get into the brain?
- Through the nose when contaminated water goes through cribiform
- Located in warm freshwater
What does the brain look like in rocky mountain spotted fever?
- Starry sky on diffusion weighted imaging
What is the cause for prion diseae?
- PrP prion protein
What symptoms are seen in prion disease?
- Rapidly progressive neurodegenerative disorders
What does prion disease do to the brain?
- Microscopic spongiform change –> intracellular vacuoles in neurons and glia
How does someone get CJD?
- Corneal transplant
- Brain implantation of electrodes
- HGH
What are the symptoms of CJD?
- Rapidly progressive dementia with startle myoclonus
- Only about 7 months
How is the vCJD in the UK different than CJD?
- Kuru plaque –> extracellular deposits of aggregated abnormal protein
- Congo red + and PAS+
What is fatal familial insomnia?
- Sleep disturbances initially
- Aspartate substitution
What symptoms are seen in fatal familial insomnia?
- Ataxia
- Autonomic disturbances
- Stupor
- Finally coma