Stroke/ICU Flashcards
Acute ischemic stroke histopathology
Neurons become brightly eosinophilic with loss of the Nisl substance within 6-24 hours of ischemia (“Red neurons”). (circle)
After 12-36 hours of ischemia, astrocytes increase in size and develop well-defined cytoplasm (“Reactive”). (arrow)
Subacute ischemic stroke - histopathology
Polymorphonuclear cells invade the ischemic territory within hours and peak at 48- 72 hours. (arrow)
Macrophages appear within 48 hours and last for months.
Vascular proliferation begins after 48 hours (circles)
-The blood-brain barrier is absent.
Chronic cortical ischemic stroke
Aftermonths,allthat remains is a cystic cavity surrounded by gliotic tissue with glial strands (circle)
-There is compensatory (ex- vacuo) ventricular enlargement (open arrow)
Wallerian degeneration of the cerebral peduncle and corticospinal tract in the pons. (arrows)
Lacunar infarcts
Infarctions ranging in size from 1 mm to 1.5 cm (arrow)
Classically, the walls of small arteries become thickened from the formation of hyaline membranes (lipohyalinosis) (circle)
-Caused by chronic hypertension.
-These arteries may also rupture.
Watershed infarcts
Are wedge shaped over the convexity
The depths of the sulci are most affected by ischemia (circles).
– In contrast, the crests of the gyri are most affected in traumatic injury.
Transient global hypoperfusion - gross
Transient shock or cardiopulmonary arrest causes focal ischemic injury to neurons with high metabolic rates:
– Layer 3 and 5 of cortex (laminar necrosis) (arrow)
– Hippocampus (circle)
– Purkinje cells in Purkinje layer of cerebellum
– Basal ganglia
Transient global hypoperfusion - acute histopathology
Acute ischemia of the Purkinje cells. (circle)
Chronically, there is loss of neurons and proliferation of the surviving astrocytes (gliosis).
– In the cerebellum, this is called Bergmann gliosis. (arrow)
Transient global hypoperfusion - chronic histopathology
Chronically, there is loss of neurons (circle and (arrow)
Chronically, there is proliferation of the surviving astrocytes (gliosis).
Arterial dissection
Tearing of the endothelial lining of the blood vessel with extravasation of blood into the vessel wall (arrow).
Seen in:
– Marfan’s syndrome
– Fibromuscular dysplasia,
– Ehlers-Danlos type IV – Trauma
Vasculitis
May be part of a systemic vasculitis or isolated to the CNS.
Requires transmural vessel wall inflammation (circle).
Venous sinus thrombosis
Venous congestion over the convexities (yellow arrowheads) with parietal petechial hemorrhages (circle).
Associated with: Post-partum, dehydration, hypercoagulable states, adjacent inflammation (e.g., mastoiditis).
Parenchymal hemorrhage - pathology
The blood products are absorbed by macrophages and walled off by gliosis.
Months later, the cystic cavity appears tan - brown from hemosiderin-laden macrophages.
Lobar Hemorrhages
Classically caused by amyloid angiopathy
- Amyloid accumulates in the blood vessel wall. It appears green on Congo Red stain (circle).
Other causes include: hypertension, vascular malformations
AVMs
Located in cortex
Composed of both large arteries (open arrow) and veins (solid arrow) without intervening capillaries.
Between vessels there is gliotic nonfunctional hemosiderin stained tissue (circle).
Cavernous malformation
Located in cortex or less frequently in the brainstem.
Composed of thin-walled vessels (arrow).
– These tend to bleed repeatedly.
There is no intervening parenchyma between the vessels (circle).
Developmental venous angioma
Most common vascular malformation
- Located in cortex
- Composed of dilated medullary veins
- One enlarged vein drains the blood into the normal venous circulation (circle).
Between vessels ,there is normal brain parenchyma.
Capillary Telangectasia
Commonly located in the pons
Composed of dilated capillaries (circle).
Between vessels, there is normal brain parenchyma.
Vascular malformations table
Hypertensive hemorrhage
Commonly occur in the: putamen (65%) (circle), pons (10%) (arrow), cerebellum (10%), thalamus
These are the same locations of lacunar infarctions.
Aneurysms
Appear as balloon-like out-pouching (Berry) (circle)
Commonly occur at bifurcations, where there is a defect of the elastic media (arrow)
– Carotid termination including PCOM
– Junction of the ACA and anterior communicating artery
Subarachnoid Hemorrhage
Caused by aneurysmal rupture or trauma
Overlying the blood is the arachnoid membrane (arrow).
Epidural Hematoma
Usually caused by laceration of the middle meningeal artery.
The blood is between the inner table of the skull and the outer surface of the dura (arrow).
– The blood does not cross suture lines
Subdural Hematoma
Usually caused by tearing of veins that connect venous sinuses and the cortical surface (bridging).
– In atrophied brains, these veins are stretched further making them more vulnerable.
Chronic subdural hematomas are encased by a membrane.
– Immature blood vessels develop in these membranes causing further bleeding.
Cerebral Contusion
Area of hemorrhagic necrosis
– Usually affects the crest of gyri.
– Frequently seen in subfrontal and anterior temporal lobes as the base of the brain slides over the irregular skull base (arrows).
Blood is removed by macrophages leaving an irregular tan discoloration. (circle)
Widespread ruptured axons from trauma.
– Neuroimaging is normal but patients are comatose.
On gross examination, there is white matter atrophy. (circle)
The injured axons dilate (“axon retraction balls”) (arrow).
Type of herniation?
Subfalcine: an edematous cingulate gyrus (arrow) compresses the ipsilateral anterior cerebral artery as it runs in the falx cerebri.
Type of herniation?
Uncal: The medial temporal lobe (uncus) (arrow) herniates across the tentorium cerebelli compressing:
– the ipsilateral 3rd nerve
– the midbrain resulting in compression of the contralateral cerebral peduncle on Kernohan’s notch (top): a hemiparesis ipsilateral to the herniation (secondary to expanding mass in some cases) is known as Kernohan phenomenon, which is a false localizing sign
– the posterior cerebral arteries resulting in occipital lobe infarcts. (circle)
What type of herniation?
Tonsillar
With elevated posterior fossa pressure, the cerebellar tonsils (arrows) are forced downward into the foramen magnum causing hemorrhage and compression of the medulla.
Since the blood vessels are fixed by the dura, downward displacement of the brainstem causes rupture of the penetrating arteries resulting in multiple linear hemorrhages (Duret). (circles)
Atretic great vessels
Aortic aneurysm
Takayasu arteritis
Branches of the ICA
- Ophthalmic - “Amaurosis Fugax - Transient monocular visual loss”
- Posterior communicating Artery
- Anterior choroidal artery
- Anterior cerebral artery (ACA)
- Middle cerebral artery (MCA)
Figure 1 - Schematic diagram of the brain blood circulation: 1, Aortic Arch; 2, brachiocephalic artery; 3, common carotid artery; 4, posterior inferior cerebellar artery (PICA); 5, pontine arteries; 6, anterior choroidal artery; 7, anterior communicating artery; 8, anterior cerebral artery (ACA); 9, posterior communicating artery; 10, posterior cerebral artery (PCA); 11, superior cerebellar artery (SCA); 12, anterior inferior cerebellar artery (AICA); 13, anterior spinal artery; 14, arches of vertebral arteries; 15, internal carotid arteries
Segments of the internal carotid
The Internal Carotid Artery (ICA) is commonly divided into segments (Gibo classification)
(1) The Cervical segment runs from above the carotid bulb through the neck to the base of the skull;
(2) the Petrous segment runs from the base of the skull through the petrous bone;
(3) the Cavernous segment runs through the cavernous sinus (note the prominent bends)
(4) the Supraclinoid segment runs above the clinoid process through the dura into the subarachnoid space; several important branches arise from the supraclinoid carotid, among them the ophthalmic, posterior communicating, and anterior choroidal arteries.
Bouthillier et al.
C1: cervical segment
C2: petrous (horizontal) segment
C3: lacerum segment
C4: cavernous segment
C5: clinoid segment
C6: ophthalmic (supraclinoid) segment: ophthalmic artery
C7: communicating (terminal) segment: posterior communicating artery, anterior choroidal artery
anterior cerebral artery, middle cerebral artery
Anterior choroidal artery stroke
HHH: Hemiplegia, Hemisensory loss, and sometimes Hemianopia
MCA stroke
CONTRALATERAL: FACE AND ARM > LEG WEAKNESS, SENSORY LOSS, VISUAL FIELD DEFICITS, APHASIA (if dominant hemisphere) or NEGLECT (if non-dominant hemisphere)
Anterior Cerebral Artery - ACA
contralateral LEG LEG LEG> FACE AND ARM
PCA stroke
Basilar artery splits into the POSTERIOR CEREBRAL ARTERIES (PCAs)
~25% of patients have a “fetal” PCA from the PCOM
PCA strokes cause VISUAL FIELD DEFICITS: Contralateral homonymous hemianopsia
Vertebral-basilar system
VERTEBRAL ARTERIES typically arise from the subclavian arteries
• Run through the foramen in the transverse processes of the vertebrae at C-6 and exit at C-1
• Enter the skull through the foramen magnum
• Join to form the BASILAR ARTERY
Thalamic stroke
Pure motor hemiplegia: Medial medullary pyramid, cerebral peduncle, or posterior limb of internal capsule
Pure sensory stroke: Ventral posterolateral and ventral posterior medial nuclei of the thalamus
Sensorimotor stroke: Both thalamic nuclei and posterior limb of the internal capsule
Dysarthria-clumsy hand syndrome: Severe dysarthria, cortical bulbar weakness of lower face and
tongue, and slowness of fine movements of one hand. Small infarct in the dorsal basis pontis just below the medial lemniscus or internal capsule.
Ataxic hemiparesis: Slight hemiparesis with cerebellar ataxia occurs with lesions of rostral pons
Thalamic stroke
Pure motor hemiplegia: Medial medullary pyramid, cerebral peduncle, or posterior limb of internal capsule
Pure sensory stroke: Ventral posterolateral and ventral posterior medial nuclei of the thalamus
Sensorimotor stroke: Both thalamic nuclei and posterior limb of the internal capsule
Dysarthria-clumsy hand syndrome: Severe dysarthria, cortical bulbar weakness of lower face and
tongue, and slowness of fine movements of one hand. Small infarct in the dorsal basis pontis just below the medial lemniscus or internal capsule.
Ataxic hemiparesis: Slight hemiparesis with cerebellar ataxia occurs with lesions of rostral pons
Top of the basilar occlusion
Bilateral infarction of midbrain, thalamus, occipital, and medial temporal lobes causing cortical blindness, agitated delirium or even transient coma, amnestic state, third nerve palsy, fixed dilated pupils, loss of vertical gaze, loss of convergence
Hallucinations and confabulation may occur
Weber’s syndrome
Midbrain stroke syndrome
Ipsilateral third nerve palsy
Contralateral hemiplegia
Claude’s syndrome
Midbrain syndrome
Ipsilateral third nerve palsy
Contralateral limb dysmetria and tremor (red nucleus)
Benedikt’ syndrome
Midbrain syndrome
Ipsilateral third nerve palsy
Contralateral movement disorder (upper red nucleus)
Contralateral weakness (pyramidal tract)
Millard–Gubler or Foville syndrome
Pontine syndrome
Infarct of ventrocaudal pons resulting in:
• Contralateral hemiplegia (sparing the face) due to pyramidal tract involvement
• Ipsilateral CN VI palsy
• Ipsilateral peripheral facial paresis, due to cranial nerve VII involvement.
Lateral medullary syndrome
Medullary syndrome
Caused by PICA or vertebral disease most commonly
Vertigo, ataxia, loss of sensation on ipsilateral face (corneal) and contralateral body, ipsilateral Horner’s, nystagmus horizontal and rotary, ipsilateral vocal cord and palate weakness, ipsilateral facial weakness, face pain and hiccups may occur
SCA stroke
Dysarthria and ataxia with ispilateral axial lateralpulsion, ipsilateral Horner’s, contralateral loss of temp and pain
AICA syndrome
Pure vestibular syndrome, unilateral hearing loss
PICA
Vertigo, vomiting, ataxia, dysarthria and with medullary and lower pons - you get Wallenberg’s!
CADASIL
Autosomal dominant mutation in notch 3 gene results in progressive recurrent small vessel infarcts
Fabry’s disease
X-linked recessive lysosomal alpha-galactosidase A deficiency
Hyperhomocysteinuria
Impaired cystathionine B-synthase, autosomal recessive
Sickle cell disease
Can cause strokes in children, stroke rate lowered in high risk patients with exchange transfusions, associated with moyamoya
Fibromuscular dysplasia
Arterial dissection can be familial in 10-20% of cases
Polycystic kidney disease
Polycystic kidney disease is associated with berry aneurysms and SAH
Marfan’s and Ehlers-Danlos type IV
Associated with dissection
MELAS
Mitochondrial disease with metabolic stroke-like brain lesions
Bilateral fetal PCAs
Associated with relatively diminutive distal basilar
Unilateral absent ACA
May be associated with: Anterior communicating artery aneurysm, relatively smaller contralateral ICA, bilateral A2 infarcts
Moya moya
Progressive obliteration of anterior circulation intracranial vessels – ICA, MCA, ACA
Women:men - 2:1
More common in Asia
Can lead to ischemia > hemorrhage
Etiologically diverse: Accelerated atherosclerosis, infection (meningitis, VZV, HIV, leptospirosis), genetics (up to 10% have a first degree relative in Japan)
Associated with trisomy 21, neurofibromatosis I, sickle cell disease, tuberous sclerosis, and Marfan’s
MC aneurysm location
Anterior communicating–Anterior cerebral
Posterior communicating–Internal carotid
Middle cerebral artery bifurcation (M1–M2)
Internal carotid bifurcation (ACA–MCA)
Basilar (PCA–PCA)
Aneurysm treatment
Requires intervention if symptomatic (SAH, cranial neuropathies, etc), large (>5-7mm in anterior circulation, 4-5mm in posterior circulation), enlarging over time, high risk morphology: elongated axis, daughter blebs
Risk factors for aneurysm
Other risk factors include family history of SAH, smoking, uncontrolled HTN
Early infarct signs
Loss of grey-white junction
- Any lobe including insula
Obscuration of the deep grey structures
- Caudate
- Putamen
- Thalamus
Obscuration of the sylvian fissure
Sulcal effacement
Hyperdensebloodvessel
Stroke on MRI
DWI is bright in acute stroke due to cytotoxic edema and restricted diffusion
- Can be seen as early as 15 minutes into a stroke and remains bright for up to 10-14 days
- Should have corresponding area of decreased signal on ADC map
Enhancement begins at around day 3 and can remain for weeks
tPA criteria
Clinical diagnosis of ischemic stroke within 3-4.5 hours of last seen normal
No recent: 1) Trauma, major surgery (2 weeks) 2) GI or UT bleed (3 weeks) 3) Serious head trauma, brain surgery, stroke (3 months)
No rapidly improving symptoms (?TIA)
No seizure at onset (?Todd’s paralysis)
BP < 185/110 without major interventions
CT without ICH or major early infarct signs
Normal glucose (50-400) and platelets (>100k)
Normal PT or PTT if patient is on warfarin or heparin:
Re: this, tPA c/I’d if:
- Patient has received heparin within 48 hours and has an elevated aPTT (greater than upper limit of normal for laboratory)
- Current use of oral anticoagulants (ex: warfarin) and INR >1.7
- 3urrent use of direct thrombin inhibitors or direct factor Xa inhibitors
Increased risk for hemorrhagic transformation in:
Stroke severity (NIHSS)
Early CT findings of significant acute hypodensity, edema, or mass effect
Elevated serum glucose
Possibly age of patient and lower platelets
These patients were still more likely to have an excellent outcome with t-PA than with placebo
AFib and stroke
DOACs
Dabigatran (Pradaxa,adirectthrombininhibitor), rivaroxaban (Xarelto, a factor Xa inhibitor), and apixaban (Equilis, a factor Xa inhibitor), edoxaban (Savaysa, a factor Xa inhibitor) are all FDA approved
Antiplatelets mechanism of action
Timing of appearance of blood on MRI
Timing of stroke on MRI
Consciousness components
Arousal+awareness
Pathophysiology of consciousness
Requires an interaction between the Reticular Activating System (RAS) of the brain stem, thalamus and the cerebral cortex
The RAS is responsible for arousal
RAS projects to thalamus and cortex: asserts direct and indirect influences on the cortex
The cerebral cortex is responsible for the awareness of self and environment
Brain death
Death by neurologic criteria
Coma
State of unarousable unresponsiveness
Vegetative state
Describes patients who recover the arousal component of consciousness but not awareness
Minimally conscious state
Severely altered consciousness in which minimal but definite behavioral evidence of self or environmental awareness is demonstrated
Locked-in state
Describes a condition of total paralysis below the third nerve nuclei. Patients can open their eyes and can move their eyes up and down to command. The diagnosis depends on identifying that the patient can open his eyes voluntarily. Neuropathological basis for this condition is usually an infarction of the ventral pons and efferent motor tracts. Other conditions include central pontine myelinolysis, pontine hemorrhage, and tumors.
Psychogenic coma
Patients typical have tightly closed eyes and resist opening. They have intact normal caloric responses. They have normal or inconsistent motor exams. EEG is normal. (Hand drop test, Nose hair tickling)
Akinetic mutisms
Characterized by abulia, lack of spontaneous movement and eye closure. They have eye tracking, facial grimace, and blinking to threat. Sleep-Wake cycles can be seen based on eye opening. Upper motor neuron signs do not develop ( no spasticity). Caused by lesions of the cingulate gyri
Stupor
Patient appears to be asleep but when vigorously stimulated will become alert, manifested by eye opening and ocular movements. Speech and other movements are limited..
Obtundation
Patient has a mild to moderate reduction of alertness with a decrease in interest in the environment. Patients are “slow” in their response and have increased number of hours where they sleep
Clouding of Consciousness
State of reduced wakefulness or alertness characterized by hyper-excitability and irritability alternating with drowsiness. The patient is easily distracted and startled. Characterized by misjudgement of sensory perceptions
Somnolent and Lethargic
Sleepy
GCS
An objective measure of arousal.
It uses three markers of consciousness - eye opening, motor function, verbal function
Coma neuroanatomy
A direct injury to the brainstem at or above the level of the pons may result in coma, but requires that the injury occur rapidly and is of sufficient size.
Bilateral Thalamic or Hypothalamic Injury
Extensive bilateral disturbance of the hemisphere function is required to produce coma
-Drugs, metabolic disease produce coma by a depression of both cortex and RAS
-Trauma->diffuse axonal injury
Herniation syndromes
Pupils and structural lesion
Breathing pattern
Cheyenne Stokes - bilateral injury (to respiratory centers), physiological abnormalities in congestive heart failure, and is also seen in newborns with immature respiratory systems and in visitors new to high altitudes. One example is the breathing pattern in Joubert (molar tooth) syndrome and related disorders.
characterized by progressively deeper, and sometimes faster, breathing followed by a gradual decrease that results in a temporary stop in breathing called an apnea. The pattern repeats, with each cycle usually taking 30 seconds to 2 minutes.[1] It is an oscillation of ventilation between apnea and hyperpnea with a crescendo-diminuendo pattern, and is associated with changing serum partial pressures of oxygen and carbon dioxide.[2]
Breathing pattern
Biot’s - medulla
An abnormal pattern of breathing characterized by groups of quick, shallow inspirations followed by regular or irregular periods of apnea. It is distinguished from ataxic respiration by having more regularity and similar-sized inspirations, whereas ataxic respirations are characterized by completely irregular breaths and pauses. As the breathing pattern deteriorates, it merges with ataxic respirations. Biot’s respiration is caused by damage to the medulla oblongata due to strokes or trauma or by pressure on the medulla due to uncal or tentorial herniation. It generally indicates a poor prognosis.
Breathing pattern
Kussmaul breathing - DKA
A deep and labored breathing pattern often associated with severe metabolic acidosis, particularly diabetic ketoacidosis (DKA) but also kidney failure. It is a form of hyperventilation, which is any breathing pattern that reduces carbon dioxide in the blood due to increased rate or depth of respiration.
Breathing pattern
Apneustic - pontine
An abnormal pattern of breathing characterized by deep, gasping inspiration with a pause at full inspiration followed by a brief, insufficient release.
Breathing pattern
Ataxic - medulla
Ataxic respiration is an abnormal pattern of breathing characterized by complete irregularity of breathing, with irregular pauses and increasing periods of apnea. As the breathing pattern deteriorates, it merges with agonal respiration.
Good and bad prognostic signs in coma
Therapeutic hypothermia
Adult declaration of brain death
In most states 1 confirmatory exam by a physician is adequate
The declaration of brain death requires: series of careful neurologic tests, the establishment of the cause of coma, the recognition of possible confounding factors, the resolution of any misleading clinical neurologic signs ( ie dilated pupil due to atropine), the ascertainment of irreversibility: CT imaging demonstrating massive brain destruction - mimics: acute severe hydrocephalus and cerebellar hematoma
Exam (T>36, SBP>100)
Patients must lack all evidence of responsiveness - based on evaluation for motor response to noxious stimulation
- Key is to distinguish spinal reflexes from true response - things that hint at spinal reflexes: 1) They may occur with neck flexion and nail bed compression but are absent with supraorbital nerve compression 2) These responses are not classifiable as decorticate or extensor responses 3) These responses are uncommon, but include triple flexion responses, finger flexion or extension, head turning, and slow arm lifting 4) May be upsetting to family or caregivers -> critical to explain that these come from the spinal cord
Absence of all brainstem reflexes
- Pupils should be mid-position (4-6mm) and unreactive
- Absent corneal reflex
- Absent ocular-cephalic reflex (fast head turning)
- Absent ocular-vestibular reflex: The head should be elevated 30 degrees -> 50 cc of ice water is then infused in the external auditory canal -> No eye movement should be observed after 2 minutes of observation.
Absent Gag and Cough reflex
Apnea
Apnea test
Before performing the apnea test, the physician must determine that the patient meets the following conditions:
• Core temperature > 36°C or 96.8°F.
• PaCO2 35-45 mm Hg.
• Normal PaO2. Option: pre-oxygenation for at least 10 minutes with 100% oxygen to PaO2 > 200 mm Hg.
• Normotension. Adjust fluids and (if necessary) vasopressors to a systolic blood pressure ≥ 100 mm Hg (option: mean arterial pressure ≥ 65 mm Hg).
After determining that the patient meets the prerequisites above, the physician should conduct the apnea test as follows:
• Connect a pulse oximeter.
• Disconnect the ventilator.
o Apnea can be assessed reliably only by disconnecting the ventilator, as the ventilator can sense small changes in tubing pressure and provide a breath that could suggest breathing effort by the patient where none exists.
• Deliver 100% O2, 6 L/min by placing a catheter through the endotracheal tube and close to the level of the carina. Option: use a T-piece with 10 cm H20 CPAP and deliver 100% O2, 12 L/min.
• Draw a baseline arterial blood gas.
• Look closely for respiratory movements (abdominal or chest excursions that produce
adequate tidal volumes) for 8-10 minutes.
• Measure PaO2, PaCO2, and pH after approximately 8-10 minutes and reconnect the ventilator.
• If respiratory movements are absent and PaCO2 is ≥ 60 mm Hg (option: 20 mm Hg increase in PaCO2 over a baseline normal PaCO2), the apnea test supports the diagnosis of brain death.
• If respiratory movements are observed, the apnea test result is negative (i.e., does not support the diagnosis of brain death).
• Connect the ventilator if, during testing, the systolic blood pressure becomes < 90 mm Hg (or below age-appropriate thresholds in children less than 18 years of age) or the pulse oximeter indicates significant oxygen desaturation (< 85% for > 30 seconds), or cardiac arrhythmias develop; immediately draw an arterial blood sample and analyzearterial blood gas. If PaCO2 is ≥ 60 mm Hg or PaCO2 increase is ≥ 20 mm Hg over baseline normal PaCO2, the apnea test result supports the diagnosis of brain death; if PaCO2 is < 60 mm Hg and PaCO2 increase is < 20 mm Hg over baseline normal PaCO2, the result is indeterminate. If adequate blood pressure and oxygenation can be maintained, the apnea test can be repeated for a longer period of time (10-15 minutes) or an ancillary test can be considered if the result is indeterminate.
Pediatric declaration of brain death
Two examinations including apnea tests performed by different attending physicians
24 hour waiting period prior to first exam is suggested after the insult
Observation intervals between exams: 24 hours in 37 week gestation to 30 day olds, 12 hours in 30 day to 18 year olds
Ancillary tests not required
May assist examiner when apnea test or part of exam can not be performed, uncertainty regarding neurologic exam, medication effect, or to shorten observation interval.
Ancillary testing for brain death
Electroencephalography: an absence of brain electrical activity
Cerebral Angiogram: a catheter dye study of brain showing absence of blood flow
Transcranial Doppler ultrasound: absence of blood flow detected by sound
Cerebral scintigraphy: radionuclide study showing absence of blood flow
All have limitations
ABCD2 score
Age of 60 years or more (1 point); Blood pressure of 140/90 mm Hg or greater (1 point); Clinical symptoms (1 point for speech impairment without weakness and 2 points for focal weakness); Duration of symptoms (1 point for 10 to 59 minutes and 2 points for 60 minutes or more); Diabetes (1 point).
Field cuts in LGN
Anterior choroidal
Lateral choroidal from posterior choroidal of posterior circulation
What causes thalamic dementia?
Infarct of paramedian artery or other lesion of DM nucleus
Bilateral thalamic infarcts from single occlusive event?
Artery of Percheron
Blood supply to spinal cord
The spinal cord is supplied by a single anterior spinal artery and a pair of posterior spinal arteries.
These arteries arise from the vertebral arteries. The anterior spinal artery supplies the anterior 2/3 of the cord, which includes the anterior horn, ALS, and corticospinal tracts. The posterior spinal arteries supply the dorsal columns. The spinal arteries narrow in the thoracic cord (may even be noncontiguous).
As a result, the spinal arteries can be divided into 3 longitudinal segments based on their blood supply
– C1-T2: supplied by radicular arteries from the vertebral and ascending cervical arteries
– T3-T7: spinalarteriesfromT3-T7aresuppliedby radicular arteries from intercostal arteries
– T8-conus: suppliedby radicular arteries from the artery of Adamkiewicz
Blood flow to these segments is reconstituted by radiculomedullary arteries. The radiculomedullary arteries originate from radicular arteries.
Radicular arteries
Radicular arteries originate from segmental arteries, which include the ascending cervical, intercostal, lumbar, and sacral arteries. There are thirty-one pairs of radicular arteries, each passing through the neural foramina to supply each spinal nerve, the vertebral body and the dura via a small dural branch. Only 6 to 10 radicular arteries have radiculomedullary branches
– Their exact number and anatomic location is quite variable.
Spinal AVMs
Oculosympathetics
Aniscoria
Physiologic (same in dark/light)
Small pupil (greater in dark) - Horner’s
Large pupil (greater in light) - CN III
None in PURE afferent disease! This has APD
Testing for Horner’s - confirming the dx
Topical cocaine is used to confirm the clinical diagnosis of ocular sympathetic denervation, or Horner Syndrome (HS). Cocaine blocks re-uptake of norepinephrine (NE) by sympathetic nerve terminals in the iris dilator muscle, transiently increasing its concentration in the synaptic junction. Norepinephrine activates alpha1 receptors in the iris dilator to cause pupil dilation. In HS, cocaine fails to dilate the affected pupil as much as the unaffected pupil, but its indirect action makes it a weak dilator, and the test can give equivocal results. Cocaine is also a controlled substance and therefore difficult to obtain. A practical and reliable alternative to cocaine is apraclonidine, an ocular hypotensive agent that has a weak direct action on alpha1 receptors and therefore minimal to no clinical effect on the pupils of normal eyes. Patients with HS have denervation supersensitivity of the alpha1 receptors in the iris stroma of the affected eye, making the pupil dilator responsive to apraclonidine. In patients with HS, reversal of anisocoria occurs after bilateral instillation of apraclonidine 1% or 0.5%. Urine drug test for cocaine will be positive for a few days after testing
(5) Apraclonidine Denervation must be present long enough for receptor upregulation to have occurred (14) Positive tests have been noted within hours of a carotid dissection but the onset of denervation sensitivity are variable (15) False negatives can occur in the setting of acute Horner syndrome or in long-standing cases if strict “reversal of anisocoria” criteria used (16, 17) Apraclonidine has limited use in pediatric Horner syndrome due to the risk of CNS and respiratory depression (18)
https: //www.ophthalmologyreview.org/articles/horner-syndrome-pharmacologic-diagnosis
Horner’s localization
HYDROXYAMPHETAMINE
Hydroxyamphetamine remains a useful tool for localization of the lesion once a diagnosis of Horner syndrome has been confirmed (20). However, it is limited by accessibility and some considerations detailed below. Since it’s still tested (and important to understand from a mechanistic and historical perspective), you still need to know how it works and what it does. Mechanism of action: increases the release of norepinephrine from the presynaptic neuron (21). In intact presynaptic (3rd order, postganglionic) neurons, this results in pupil dilation; if this neuron is not intact, the pupil does not dilate. Note anisocoria (which pupil is small, which pupil is larger) Instill 1 drop of hydroxyamphetamine (1%) in each eye Wait 45-60 minutes Re-evaluate anisocoria Results: In patients with normal pupils, there is a symmetric 2 mm dilation of each pupil (anisocoria remains) (22). In patients with Horner syndrome, the reaction is based on whether or not there is an intact 3rd-order (postganglionic) neuron (23): Both pupils dilate: intact 3rd-order neuron (localizes to 1st- or 2nd-order neuron) Only non-Horner pupil dilates: not intact 3rd-order neuron (localizes to 3rd-order neuron)
https://www.ophthalmologyreview.org/articles/horner-syndrome-pharmacologic-diagnosis
Tonic pupil
Adie tonic’s pupil denotes a pupil with parasympathetic denervation that constricts poorly to light but reacts better to accommodation (near response)
Light-near dissociation causes
Pupils in coma
Metabolic - small, reactive
Midbrain - mid position, fixed
Pons - pinpoint
Third nerve (uncal) - dilated, fixed
Pupils in coma
Metabolic - small, reactive
Midbrain - mid position, fixed
Pons - pinpoint
Third nerve (uncal) - dilated, fixed
CN IV
Innervates superior oblique - acts to depress, best in ADduction
Inferior oblique
CN III
Action elevation, best in ADduction
Actions of extraocular muscles
Fourth nerve palsy signs
If nerve - ipsilateral eye, if nucleus/fascicle before decussation- contralateral eye
Bincoular, vertical/oblique diplopia, worse in contralateral and down gaze. Fourth nerve palsy often presents with a head tilt away from the affected eye.
With ipsilateral head tilt, the medial utricle is excited.The medial utricle projects to the contralateral trochlear and oculomotor nucleus through the MLF. With ipsilateral head tilt, the ipsilateral eye elevates (sup rectus) and intorts (sup rectus and sup oblique) while the contralateral eye depresses (inf rectus) and extorts (inf rectus and inf oblique). The ocular counterrolling reflex (top) causes a compensatory cyclorotation of both eyes to maintain the subjective visual vertical. On left head tilt, the right eye infraducts and excyclotorts and the left eye supraducts and incyclotorts relative to the position of the head and true vertical. Head velocity signals are encoded by the semicircular canals. The eyes maintain this position tonically because of otolithic inputs from the utricle and saccule on the side of the lower ear. In a right superior oblique palsy (middle right), the right eye is extorted because of the lack of intorsion from the paretic superior oblique. Increased activity to the other intorter—the right superior rectus—causes a hypertropia that worsens when more intorsion is demanded by tilting the head to the right (middle left). A left ocular tilt reaction caused by abnormalities in the vertical vestibulo-ocular reflex projections from the left vestibular system causes a left hypotropia with bilateral torsion in the direction of head tilt (lower right). For each eye, the line through the cornea represents the torsional vertical axis.
Sixth neve palsy
Binocular, horizontal diplopia
Increased in ipsilateral gaze
Worse at distance
Acute papilledema
Nonarteric ischemic optic neuropathy
Nonarteric ischemic optic neuropathy
Ischemic optic neuropathy
Aniscoria
Pathologic Anisocoria is always an Efferent Problem
Midbrain syndromes
CN III: nerve vs. nucleus
Ptosis and superior rectus are bilateral in lesions of the nucleus
CN IV palsy
Innervates the superior oblique that intorts the eye and depresses the adducted eye. Superior oblique dysfunction results in an elevated eye (hypertropia) in primary gaze, which increases with eye adduction. The axons from the trochlear nucleus decussate to form the contralateral trochlear nerve.
A nuclear lesion causes a contralateral hypertropia (vs nerve, which causes ipsilateral)
Foville syndrome
Foville Syndrome: Infarction of the dorsal pontine tegmentum involving: 6th nerve nucleus: Ipsilateral horizontal gaze palsy (“nuclear” 6th nerve palsy) 7th nerve branchial nucleus (or fascicle): ipsilateral facial weakness with forehead involvement. +medial lemniscus and corticospinal tracts ->contralateral hemisensory loss, hemiparesis
CN VI: Lesion of peripheral nerve vs nucleus
Peripheral nerve - atrophy of ipsilateral LR, ipsilateral eye deviated medially, diplopia
Nucleus - inability to move moves both eyes past midline to look ipsilateral to the lesion, atrophy of ipsilateral LR, but not contralateral medical rectus
Nuclear VI vs 1 and 1/2 syndrome
Nuclear VI affects both the ipsilateral lateral rectus muscle and the contralateral MLF
1 and ½ syndrome affects the ipsilateral abducens nucleus or PPRF (thereby affecting the ipsilateral later rectus and contralateral MLF) and the ipsilateral MLF
Pontine syndromes involving the 6th nerve
Cavernouos sinus
ICA, III, IV, Vi, V1, V2
Cavernous sinus vs superior orbital fissure vs orbital apex
Lesions involving 3rd, 4th, 6th nerves and V1 (2)
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Trochlear head tilt
Occurs contralateral to the affected eye
With ipsilateral head tilt, the medial utricle is excited. The medial utricle projects to the contralateral trochlear and oculomotor nucleus through the MLF. With ipsilateral head tilt, the ipsilateral eye elevates (sup rectus) and intorts (sup rectus and sup oblique) while the contralateral eye depresses (inf rectus) and extorts (inf rectus and inf oblique)
The ocular counterrolling reflex (top) causes a compensatory cyclorotation of both eyes to maintain the subjective visual vertical. On left head tilt, the right eye infraducts and excyclotorts and the left eye supraducts and incyclotorts relative to the position of the head and true vertical. Head velocity signals are encoded by the semicircular canals. The eyes maintain this position tonically because of otolithic inputs from the utricle and saccule on the side of the lower ear. In a right superior oblique palsy (middle right), the right eye is extorted because of the lack of intorsion from the paretic superior oblique. Increased activity to the other intorter—the right superior rectus—causes a hypertropia that worsens when more intorsion is demanded by tilting the head to the right (middle left). A left ocular tilt reaction caused by abnormalities in the vertical vestibulo-ocular reflex projections from the left vestibular system causes a left hypotropia with bilateral torsion in the direction of head tilt (lower right). For each eye, the line through the cornea represents the torsional vertical axis.
Skew deviation
Low-Low: Disruption of the medial utricle fibers prior to decussation in the pontomedullary junction, results in an imbalance of tonic signal from the utricles simulating a contralateral head tilt.
The ipsilateral eye is depressed and extorted (“hypotropia”)
High-High: Disruption of the medial utricle fibers after decussation as they ascend in the MLF, also results in an imbalance of tonic signal from the utricles. However, since the fibers have already crossed, this simulates an ipsilateral head tilt. < The ipsilateral eye is elevated and intorted (hypertropia). With ipsilateral head tilt, the medial utricle is excited. The medial utricle projects to the contralateral trochlear and oculomotor nucleus through the MLF. With ipsilateral head tilt, the ipsilateral eye elevates (sup rectus) and intorts (sup rectus and sup oblique) while the contralateral eye depresses (inf rectus) and extorts (inf rectus and inf oblique).
The ocular counterrolling reflex (top) causes a compensatory cyclorotation of both eyes to maintain the subjective visual vertical. On left head tilt, the right eye infraducts and excyclotorts and the left eye supraducts and incyclotorts relative to the position of the head and true vertical. Head velocity signals are encoded by the semicircular canals. The eyes maintain this position tonically because of otolithic inputs from the utricle and saccule on the side of the lower ear. In a right superior oblique palsy (middle right), the right eye is extorted because of the lack of intorsion from the paretic superior oblique. Increased activity to the other intorter—the right superior rectus—causes a hypertropia that worsens when more intorsion is demanded by tilting the head to the right (middle left). A left ocular tilt reaction caused by abnormalities in the vertical vestibulo-ocular reflex projections from the left vestibular system causes a left hypotropia with bilateral torsion in the direction of head tilt (lower right). For each eye, the line through the cornea represents the torsional vertical axis.
Brainstem lesions and CN deficits - laterality
Localized in the vertical plane by the cranial nerve nuclei or cranial nerve axons that are affected. With the exception of the 4th cranial nerve, the lesion is ipsilateral to the cranial nerve deficit.
EOMI
Primary and secondary action
Superior oblique: Depression/intorsion - CN IV
Inferior oblique: Elevation/extorsion
Superior rectus: Elevation/intorsion
Inferior rectus: Depression/extorsion
Only act in the horizontal plane no secondary action
Medial rectus: Adduction
Lateral rectus: Abduction - CN VI
Others all CN III
Horner’s syndrome - clinical
Horner’s syndrome is characterized by:
- Ptosis of the upper eyelid (due to impaired superior tarsal and Müller’s muscles, which normally contribute to upper eyelid elevation).
- Slight elevation of the lower eyelid (due to impaired inferior tarsal muscle function, which normally contributes to lower eyelid depression).
- Pupillary miosis (impaired pupillodilator function).
- Facial anhidrosis (if dissection or other lesion extends proximal to the region of the carotid bifurcation, because sweating fibers travel primarily with the ECA and would not be involved in an ICA dissection).
- Enophthalmos (appearance of enophthalmos from decrease in palpebral fissure).
Horner’s syndrome - sympathetic pathway
3 neuron pathway
1) 1st order: central - originate in the posterior hypothalamus and descend through brainstem to the first synapse located in the lower cervical and upper thoracic spinal cord (C8 to T2, aka clilospinal center of Budge)
2) Second order neurons exist spinal cord, travel near apex of lung, under subclavian artery, and ascend the neck and synapse in the superior cervical ganglion, near the bifurcation of the carotid artery at the level of the angle of the mandilbe
3) The third order neurons travel with the carotid artery - vasomotor and sweat fibers branch off at the superior cervical ganglion near the level of the carotid bifurcation and travel to the face with the ECA. The oclumosympathetic fibers continue with the ICA through the cavernous sinus to the orbit, where they travel with V1 division of the trigeminal nerve to their destinations.
Differentiation and localization in Horner’s syndrome
Differentiation between causes of Horner’s syndrome can be difficult and depends on the location along the pathway.
- In general, a lesion to the first-order neurons (central neurons) will be associated to brainstem or other focal neurologic findings from a central lesion.
- A second-order (preganglionic) lesion is often associated with lesions of the neck, mediastinum, or lung apex.
- A third-order (postganglionic) lesion is often associated with pain or headache, caused by conditions such as a skull base tumor, or carotid dissection.
Cocaine 4% or 10% eye drops are sometimes used for confirmation of a Horner’s syndrome. Cocaine blocks the reuptake of norepinephrine released at the neuromuscular junction of the iris dilator muscle, allowing more local availability of norepinephrine. Following instillation of cocaine, the sympathetically denervated eye will not respond and the anisocoria will become more pronounced. (The Horner’s pupil will not change, but the unaffected pupil will become more dilated).
Hydroxyamphetamine 1% eye drops will differentiate between a lesion affecting the first- or second- order neurons from a third-order neuron. There is no pharmacologic test to distinguish between a first-and second-order lesion. Hydroxyamphetamine causes release of stored norepinephrine in the third-order neurons. Following instillation, if the Horner’s pupil dilates, the lesion is either involving the first- or second-order neurons. If the Horner’s pupil does not dilate, there is a third-order neuron lesion.
Complete pupil-sparing oculomotor nerve palsy
Most often caused by ischemia to the oculomotor nerve. This is frequently associated with diabetes, especially in the setting of other vascular risk factors.
The pupillomotor fibers travel along the peripheral aspects of the oculomotor nerve, whereas the somatic fibers to the muscles innervated by the oculomotor nerve travel centrally. The terminal branches of the arterial supply to the nerve are most affected by microvascular changes from diabetes and other risk factors as the vessels decrease in diameter from the periphery of the nerve to the central regions. Therefore, the supply to the periphery of the nerve (where the pupillomotor fibers reside) is spared, whereas the central fibers are affected. Compressive lesions (such as posterior communicating artery aneurysms) typically affect the peripheral pupillomotor fibers, leading to pupil dilatation with poor response to light (although rarely there may be some pupil sparing).
Nuclei of CN III
At the level of the superior colliculus in the dorsal midbrain
There are paired and separate oculomotor subnuclei for the inferior rectus, medial rectus, and inferior oblique—all providing ipsilateral innervation. The superior rectus subnucleus is also paired but provides contralateral innervation. It is rare for these subnuclei to be affected in isolation from central lesions without also affecting nearby subnuclei and nuclei.
The paired midline Edinger–Westphal subnuclei provides parasympathetic innervation to the iris sphincters and ciliary muscles. There is also a midline subnucleus providing innervation to both levator palpebrae superioris muscles. Therefore, a lesion to this single midline nucleus can cause bilateral ptosis, but it would be rare to affect only this nucleus without affecting nearby structures, and other clinical findings are expected to be present.
Anterior ischemic optic neuropathy (vs PION)
AION is considered to be the most common optic nerve disorder in patients older than age 50. It can also affect the retrobulbar optic nerve in isolation, in which case it is termed posterior ischemic optic neuropathy (diagnosis of exclusion). AION is a result of ischemic insult to the optic nerve head. Clinically, it presents with acute, unilateral, usually painless visual loss, although 10% of patients may have pain that can be confused with optic neuritis. Fundoscopic examination shows optic disc edema (unless retrobulbar), hyperemia with splinter hemorrhages, and crowded and cupless disc.The painless vision loss is one key feature in differentiating AION from optic neuritis, which is often associated with painful eye movements.
Anatomic landmarks for posterior circulation
Posterior circulation vascular territories
The SCA supplies most of the superior half of the cerebellar hemisphere, including the superior vermis, the superior cerebellar peduncle, and part of the upper lateral pons.
The anterior inferior cerebellar artery (AICA) supplies the inferolateral pons, middle cerebellar peduncle, and a strip of the ventral cerebellum between the posterior inferior cerebellar and superior cerebellar territories.
The posterior inferior cerebellar artery (PICA) supplies the lateral medulla, most of the inferior half of the cerebellum and the inferior vermis.
ICA branches
AICA infarct
Dejerine-Roussy syndrome
Recurrent artery of Heubener
Watershed infarcts
Top of the basilar syndrome
Pure motor lacunar stroke
NOTCH3
Cavernous malformation
Hypertensive intracranial hemorrhage
CAA
“Puff of smoke”
Stupor
Coma
Locked-in state
Unresponsive wakefulness
Delirium
