On Spencer’s curve

2000px-znak_a-1-svg1In our recent ultrasound refresher course, I tried to give a talk on the vagaries of stenosis graduation (mainly) for extracranial stenoses. The gist of the talk is outlined in the following notes.

The Bernoulli principle

While Bernoulli’s equation is rather intricate, the underlying principle of conservation of flow along a stenosed tube is simple. Consider a tube with a short stenosis with laminar flow of a Newton fluid. Then the bigger area A1 multiplied with the flow  velocity v1 (take psv for simplicity, although this is not really correct) should be the same as the smaller area A2 multiplied with v2. Thus the increase of flow is proportional of A1 / A2, so that the reduction to a third of the area leads to an increase by the factor 3 of the flow velocity, a reduction to a tenth leads to ten times the flow velocity in the stenosis.img_7579

Adding friction

Since we usually don’t observe velocities higher than 5 m/sec, there must be a limiting principle and this is the resistance offered by the stenosis, which reduces flow in the whole vessel. This resistance can be approximated by the law of Hagen-Poiseuille and is proportional to the length of the stenosis, the inverse of r^4 and the inverse of viscosity. Again, this only holds for laminar flow and the case of blood offers some more complications, but the core message is: the longer the stenosis the higher the flow reduction. Also the flow reduction grows much more with decreasing vessel diameter than the flow velocity increase by Bernoulli’s principle can compensate. Very tight and long stenoses show a flow velocity reduction despite there high grade. If you  find a psv of only 2,4m/sec this might therefore mean either a mere medium grade stenosis or a very tight stenosis (near occlusion).img_7578

Spencer’s curve

Taking these two principles into account, Spencer and Reid (in their brilliant 1979 stroke article) deduced the famous curve now known as Spencer’s curve (see Alexandrov’s papers for a more detailled exposition).

Since at the time duplex sonography was technically not feasible, the Spencer curve is based on the theoretical assumption of a 2 mm stenosis and thus does not correct for the length of the stenosis (as well as the other factors mentioned below). This explains why the cw-doppler-data in their paper does not really fit the theoretical model. Still it is the best approximation we have to a theoretical foundation of stenosis quantification.

Measuring diameters

Diameter instead of area

Most of the studies have been done with angiographic imaging of stenoses or ultrasound measurements of the stenosis diameter rather than the area. Of course, the area could easily be calculated from the diameter (r^2 pi) if it were a circle, but then it isn’t. In ultrasound we could measure the area itself (if no shadowing artifacts are present), yet no one does really. Therefore you should remember that most of calculations of the stenosis area from the diameter are systematically invalid.

Where, when and how to measure diameters

For some absurd reason, Europeans kept to the local stenosis degree (i.e., diameter of perfused lumen divided by the original vessel diameter), at least in their ECST trial, while the NASCET trial used the more reasonable distal stenosis degree (i.e., minimal lumen diameter divided by non-stenosed distal ICA diameter). Since the ICA bulb varies in its bulbiness and distends with age and blood pressure (and with stenosis degree), the local stenosis degree is usually a shot in the dark. The distal (NASCET) degree suffers from pseudoocclusion, i.e., collapse of the distal vessel in very high grade stenosis. All attempts to calculate the NASCET stenosis degree from ECST and vice versa are irrational.

Being faithful to both traditions, I measure all the lumina (minimal lumen, original vessel lumen, distal lumen). The only really interesting number is the residual diameter (combined with the length of the minimal lumen), because this determines the hemodynamic compromise.

Other important factors


Neither is blood a Newton fluid, nor is all the viscosity (rarely measured today) explained by the hematocrit alone. Yet the hematocrit is an important number to factor into your interpretation of ultrasound data. You should note it.


Every vessel wall abnormality leads to small perturbations of flow and thus turbulence. Turbulence reduces anterograde flow and thus reduces the distal pressure after a stenosis. While very hard to quantify it is essential to mention turbulent flow when you see it. Remember that to distinguish retrograde (i.e. turbulent) flow from flow increase with aliasing you need to look at the color bar on the side of your duplex image, noting that flow increase jumps over the upper limit of the color spectrum while retrograd flow (usually) passes the black zero flow region.


decreases over the lifetime, even more if severe hypertension or calcification of vessel walls is present. This, again, is very hard to quantify, but often easy to recognize qualitatively in your duplex image, when you recognize the pulsation of the vessel wall. Reduced elasticity has to lead to increased flow velocities.


Since blood flow is not continuous but pulsatile and this in varying shapes, we should really be using mean flows in our stenosis calculations. This has historically not been done. As a consequence, valve abnormalities (aortic stenosis, insufficiency) have to be factored in, when we try to calculate the stenosis degree from peak systolic velocities.

Blood pressure and atrial fibrillation

The (pulsating) blood pressure is the driving force of cerebral blood flow, trying to overcome venous and intracerebral pressure as well as the distal blood pressure offered by collaterals (see below). At least, you should note the blood pressure and relativize your stenosis graduation in cases of extreme values. When the patient has atrial fibrillation, you probably should use an “average” heartbeat rather than the extreme values. But bear in mind that absolute arrhythmia is a risk factor for arterioarterial embolization in itself.

The geometry of the stenosis

usually is far from being that of a tube. Rather, the blood flow curves around plaques, rotating and hitting small plaques on the distal wall. Again, the effects are impossible to quantify, but at least the geometry should be noted. The shape of the stenosis area should be remarked upon, if it isn’t circular.

The role of collaterals

The pressure difference along a stenosis is not only determined by the resistance of the stenosis itself, but also by the collateral blood flow which leads to an increase of distal pressure (mostly but not only in diastole). This leads to a reduction of the blood flow velocity in the case of good collateralization, thus also reduced flow velocities.

The danger of a stenosis

In the neurovascular clinic, I try to estimate four risks of a stenosis: the hemodynamic risk (what happens if the stenosis were to increase?), the embolic risk (how high is the risk of an embolic event from the stenosis?), risk factors and other risks.

Hemodynamic risk

The hemodynamic risk is determined by

  • the current hemodynamic compromise (jet flow velocity, CCA flow vs. ICA flow, pulsatilities, MCA flow, CO2 reserve)
  • the dynamics of the stenosis (how long has this been going on? was there time to develop collaterals?)
  • the completeness of the circle of Willis (variations such as A1 hypoplasia, Pcomm hypoplasia)
  • secondary stenoses in the collateral circulation.

The problem is that we cannot foresee whether the stenosis will be slowly progressive or suddenly close up (as in plaque rupture). At least in asymptomatic stenoses I require CT- or MR-angiography to determine the completeness of the circle of Willis.

Embolic risk

The embolic risk is determined by

  • Plaque morphology and
  • Plaque type
  • Whether the atherosclerotic process is active or burnt out.
    As in coronaries, it is not reasonable to revascularise every severe asymptomatic stenosis. But in a patient where the overall atherosclerotic process is currently active (after an NSTEMI, say), we can expect the plaques to rupture.
  • Previous embolic events can be noted on MRI.
  • Emboli detection
  • Is the anti-platelet medication working? Multiplate or similar tests.

Risk factors

  • Did the patient stop smoking? How long ago?
  • Can we use high dose statins in this patient? Statins are highly effective against plaque deterioration, but also have serious side effects (less exercise tolerance, diabetes, muscle problems), especially in the high doses we like to use for severe stenosis.
  • Is the patient’s blood pressure controllable? Note that severe stenosis lead to very labile blood pressures as one of the most important sensors of the system is damped.
  • Exercise? Although this has not been studied properly in carotid artery stenosis, I surmise that health by fitness should improve the prognosis of carotid artery stenosis.

Other risks

  • Central or mixed sleep apnea syndrome – very prevalent among ICA stenosis patients, leading to a bag of systemic problems, not the least being poor blood pressure control.
  • Bad blood pressure control (see above)
  • Development of secondary stenoses in the collateral vessels (contralateral, ECA, …)
  • Development of a collateral rete with its danger of bleeding


I don’t see any better physical theories coming. Also, we can never expect better data than NASCET and this is a bad foundation. Therefore you have to tackle all the complexities outlined above and refrain from simplifying an ICA stenosis to a mere number (always the worst approach).




Life’s simple 3

When a stroke patient with symptomatic intracranial stenosis has been worked up, we SAMMPRIS him, by which we mean ASS, Clopidogrel and high dose statin. This is, of course, not the whole story – more important than drugs are the necessary lifestyle adjustments. We use this example to develop a system for stepwise improvement of risk factors and health behaviour.

In my view, the standard risk factors (pressure, sugar, fat and weight) can all be improved by concentrating on the simple three:

  1. Get active and work out
  2. Eat healthy
  3. Don’t smoke

This sounds reasonable, although the science behind 1 and 2 is not so simple. Just staying active (e.g. walking every day for at least 30 mins or running for 3 x 25 mins) might be healthy but need not really lower your blood pressure. Vastly more efficient are more intense workouts such as muscle strengthening (resistance) exercises or even high intensity interval training. The evidence for these measures is quite good. With regard to healthy eating, there seems to be no golden way to a good diet (in fact, most diets studied have been harmful), yet the mere fact that you are trying to be conscious about your food has a proven health promoting effect.

The current decade is probably the best to initiate health promoting behaviour, as smartphone/smartwatch/fitness bands abound and make it easier to watch your health without investing too much time. In particular these applications

  • can help to find out what improves weight or fitness
  • introduce a gamification factor to the otherwise boring issue
  • might lead to more insight about how your blood pressure, sugar or cholesterol react to specific measures
  • might allow to identify those patients where high dose statins are harmful by reducing fitness effects


Climate change


The earth might be warming up and so might our patients in the ICU. It is easy to fall into the Fever ➝ CRP ➝ antibiotics trap, but our goal is to be more responsible.


  • Raised temperature: fever vs. hyperthermia
  • Central fever
  • Stroke and fever
  • Temperature management strategies for stroke
  • Infectious causes of fever
  • Noninfectious causes of fever
  • References

Raised temperature

might be fever or hyperthermia.

Fever is more common and defined by a raised hypothalamic setpoint, due to

  • infectious or
  • other inflammatory reasons, or due to
  • central stimulation

of the hypothalamus (“central fever”, e.g. blood in brain, see below). Note that CRP does not really distinguish between the three causes of fever, while procalcitonin might at least hint at an infectious etiology. Also there is no proper consensus as to what constitutes fever.

Non-fever hyperthermia is failure of heat regulation with intact setpoint, e.g. in exsiccosis. Typically, antipyretics are ineffective in pure hyperthermia.

Fever control in the ICU has been studied, if not extensively, and never been shown to be helpful. Most recently, Acetaminophen was not effectively in improving anything (Young NEJM 2015). It may be harmful, especially in septic patients (see Schulman 2005 and Lee 2012).

Central fever

(see this 2016 review on the subject) is always suspected in neuro patients, but hard to prove.

Pathophysiology, it is due to damage to the hypothalamus or contact of this structure to blood 0r pus (this can be reproduced in animals). In brain injury, diffuse axonal damage and frontal lesions indicate shear stress on the hypothalamus and correlate with central fever.

Clinically, central fever might have less diaphoresis and tachycardia, but this is not very specific. The diagnosis relies on exclusion of other infectious and inflammatory causes. The literature (Predicting central fever in NICU, Hocker 2013) says

The combination of negative cultures; absence of infiltrate on chest radiographs; diagnosis of subarachnoid hemorrhage, intraventricular hemorrhage, or tumor; and onset of fever within 72 hours of admission predicted central fever with a probability of .90.

Therapywise, central fever is harder to treat, so that physical measures and endovascular cooling are often employed. I grew up with the lytic cocktail (blocking every neurotransmitter you know), but there is no proper literature on that.

You should bear in mind that there is another central neurologic complication with fever that complicates severe brain injury, namely paroxysmal sympathetic hyperactivity – this is a chapter on its own.

Stroke and fever

  • Very common: (40-61%) in the first 2d of stroke have elevated temperatures, depending on the definition
  • Very bad: Raised temperature correlates with bad outcome, both in animal experiments (40° x 3h leads to 3 times the stroke volume) and patients (e.g., Greer 2008).
  • Early is worse: Stroke is more vulnerable to fever in the first 24 hours – it accelerates the conversion of penumbra to stroke and all bad pathophysiologic cascades (apoptosis, inflammatory).
  • Can be controlled: Fever control is feasible in principle and regarded as one of the active components of stroke unit care.

Temperature management strategies for stroke

  • Hypothermia: Bi 2011, de Georgia 2004, Ictus-L 2006, Ovesen 2013 show no benefit
    EuroHyp-I (ongoing), Ictus 2/3 (terminated; no results yet) – endovascular methods, no evidence (but very effective)
  • Prophylactic
    • antipyretics: PAIS (den Hertog 2009), PISA (Dippel 2003) – only modest effect on temperature, no benefit (NRO, survival)
    • antibiotics: EPIAS, PANTHERIS – reduced infection rates, no benefit (NRO, survival)
  • Fever treatment: blankets/air cooling probably not better than drugs, endovascular highly effective – no benefit shown
    QASC trial shows that the combination of controlling fever, dysphagia and glucose is beneficial

Infectious causes of fever

  • Head: meningitis/encephalitis, brain abscess, ventriculitis, sinusitis, dental, HEENT (including epiglottitis)
  • Circulatory: CVC, endocarditis/myocarditis, peripheral cannula, aortitis, mediastinitis
  • Respiratory: pneumonia/bronchitis, empyema, VAP
  • GI: esophagitis, pancreatitis, diverticulitis, rectal/anal abscess, C. diff
  • Urogenital: prostatitis, pyelonephritis, cystitis, PID
  • Hematological: malaria, HIV
  • Integument: Osteomyelitis, cellulitis, fasciitis, myositis

Noninfectious causes of fever

  • Vascular: stroke, IVH, ICH, SAH, MI, ischemic bowel, DVT
  • Idiopathic inflammatory: Gout, postoperative, acalculous cholecystitis, pancreatitis, aspiration pneumonitis, GI bleed, ARDS
  • Traumatic: Hematoma, Ulcers
  • Toxic
    • Drug fever: high spiking fever, chills, maybe leucocytosis, eosinophilia; drugs are beta-lactams, PHE, iv contrast
    • Malignant neuroleptic syndrome, Serotonin syndrome (beware: linezolid, MCP, setrons), malignant hyperthermia
  • Autoimmune: vasculitis, hemolysis, transplant rejection, transfusion
  • Psychiatric: Withdrawal
  • Neoplastic: renal cell CA, tumor lysis, lymphoma, leucemia
  • Endocrine: Ovulation, Thyroiditis, Thyreotoxicosis, adrenal insufficiency




First described in 1883, the concept of watershed strokes was further developed pathophysiologically in the 50s and 60s. (There is a proud  article in Stroke this week, discussing the  history of the concept.)


Several terms are used in the literature: border-zone stroke, watershed stroke, misery perfusion, Letzte Wiese. Watershed is probably the best term, as it describes the idea that the land most distal to two supplying rivers suffers from even slight variations in flow in either. I personally apply the name Letzte Wiese only in specific cases – it captures an area  insufficiently supplied by just one vessel and thus can be applied only to internal border zone strokes.


For watershed strokes you need either quite severe hypoperfusion (as in hemorrhagic shock) or only minor hypoperfusion but at least one severely stenosed vessel.

  • The most frequent stenosis affects the proximal ICA, leading to the ACA/MCA and PCA/ACA border zones, as well as (sometimes) strokes in the MCA internal border zone.
  • High grade MCA stenosis can lead to watershed strokes in the internal border zone along and above the lateral ventricles (rosary pattern). In this case the region between the supplied region of the deep penetrating endarteries (mainly basal ganglia) and the small branches of the MCA main branches (which enter the brain from the cortex down) suffers, which amounts to the white matter in the centrum semiovale.
  • Finally the cerebellum knows watershed zones between the 3 feeding vessels, but this is not of practical relevance because treatment is similar to embolic strokes.

ICA stenosis

  • In chronic near occlusion of the ICA, the borderzone region can move if you give it enough time, with the PCA/MCA region moving forward and the ACA/MCA region backward.
  • To complicate matters further, the borderzones are variable depending on the localization of the stenosis and the integrity of the ECA collateral as well as the Circle of Willis (e.g., if A1 or the anterior communicating artery is hypoplastic or the PCA has the fetal variant).
  • In my experience you need at least 2 patent collaterals (out of ECA, ACA, PCA) to ensure hemodynamic stability even in near occlusion.
  • In the last years we learnt more about degenerative distal ICA stenosis just below the carotid T which is not well collateralized via the ECA pathway – this region unfortunately is not well imaged with CTA due to calcification-related artifacts, being  better amenable to duplex ultrasound and MRA.
  • Similar problems can arise with dissections extending to the intracranial sections of the ICA.
  • In very slowly progressive combined distal ICA and MCA stenosis (degenerative, vasculitis, Moya Moya disease) a web of tiny collaterals can form (Moya Moya picture), which has its own intricate pathophysiology.

Pathophysiology of hypoperfusion

Local hypoperfusion can be graded as follows:

  • Grade I: reduced CBF, enhanced CBV, functionally intact or only slightly compromised, near normal oxygen extraction, reduced vasodilatatory reserve
  • Grade II: severely reduced CBF, reduced CBV, reduced function, no or negative local vasodilatatory reserve (the latter is called the reverse Robin Hood phenomenon)

Practical management

  • When faced with an imaging pattern of watershed strokes, duplex ultrasound and angiography (CTA, MRA or even conventional angiography) are urgent to get as much information as possible about the flow patterns and the collateral situation.
  • Perfusion imaging: Severe proximal stenoses leads to difficulties in interpreting perfusion imaging, but this can be used to try to differentiate between grade I and II hemodynamic compromise.
  • To judge how imminent the danger is, functional ultrasound of the MCA (using CO2, apnea or – easier – acetazolamide 1g) is used.
  • If  in doubt, I recommend a trial of therapeutic hypertension (usually with 25-50-100µg Noradrenaline, only with intact coronaries!) to see whether the neurologic deficit fluctuates with blood pressure.
  • In this case, an emergency revascularization is necessary and without alternative. To bridge the time to surgery or stenting, you can use continuous therapeutic hypertension, aiming for an RR of > 180 or 200 mmHg.
  • Sensitivity to blood pressure drops: Quite often the reverse happens – someone accidentally treats an impressively high RR of 220 mmHg (which might actually be due to the brains own reaction to hypoperfusion) with an iv bolus of labetalol or urapidil and the patient deteriorates. If this happens, quickly counteract your medication (Noradrenaline again) and due your vascular studies.
  • Remember that patients with severe misery perfusion, the danger of hyperperfusion syndrome after revascularization is quite real and this is difficult to treat.


The thalamus of secrets

thalmusThe thalamus is a  tightly packed collection of nuclei and fibres in the center of the brain that is involved in everything sensory (except olfactory) and extrapyramidally expressive. It is connected to everyone and his mother. Any proper neuropsychological problem can be caused by thalamic lesions – neglect, aphasia, dementia, delirium, visual, sensory, motor disturbances, ataxia, pain. Thus as the caudate nucleus, the thalamus is always a good answer if you are asked for localization of your lesion. It helps immensely to organize the connections and deficits into a simple system in order to understand thalamic stroke deficits. I follow the literature on thalamic strokes and distinguish 4 vascular regions.

The four arteries

Bildschirmfoto 2016-03-07 um 07.15.12

Polar artery region (anterior thalamoperforating artery). The anterior nucleus is involved in cognition, episodic memory, language and emotion with connections to the limbic system (the corpora mamillaria, the hippocampus, the cingulum and all else) and the frontal lobes (see this cool article). Together with parts of the lateral nuclei the region is supplied by the A. thalamoperforans anterior (also called polar or tuberothalamic artery) which arises from the mid of the posterior communicating artery, although in about a third of people the paramedian artery replaces it. Strokes in this region are etiologically diverse (as e.g. in the anterior choroidal artery) and lead to thalamic aphasia as well as diverse neuropsychological deficits that resemble caudate strokes, such as change in personality, abulia, apathy and – via its mamillary connections – memory deficits.

Bildschirmfoto 2016-03-07 um 07.51.10

Posterior choroidal artery region. This artery arises from  (P1 or) P2 and supplies the pulvinar and the geniculate bodies, all of which connect to the auditory (temporal lobe) and visual system (occipital lobe). Resulting deficits are visual field defects (hemianopia, wedge shaped), hearing deficits and more rarely aphasia and other neuropsychological deficits. Since the artery also sometimes reaches the posterior and even lateral ventral nuclei, its occlusion can also lead to hemihypesthesia.

Bildschirmfoto 2016-03-07 um 07.50.38

Paramedian artery/arteries. Does the name Percheron ring a bell? He is the one discussing the various anomalies in the paramedian (or posterior thalamoperforating artery): it usually arises from P1 but often one side misses and this side  is supplied from the contralateral one, so that a thrombus in one P1 can lead to inferomedial strokes in both thalami (artery of Percheron). As one of the first arteries after the basilar head, basilar artery embolism often leads to paramedian artery  and thus to inferomedial thalamic strokes. The most prominent version is Caplan’s top-of-the-basilar-syndrome (a short aside: have you ever read up on the embryology of the vertebrobasilar system? if not – look here).

The artery reaches the medial nuclei (which somehow interact with all other thalamic nuclei) as well as intralaminary nuclei (these lie inside the internal medullary lamina that crosses the thalamus longitudinally), also parts of the pulvinar and sometimes the ventral lateral nuclei. More importantly, a branch of the paramedian artery goes off to the mesencephalon and pons and leads to disturbances in vertical ocular motor control (damaging the rostral = interstitial nucleus of the MLF aka riMLF). In principle a stroke in the paramedian artery can affect the functions of all other thalamic nuclei, but mainly it causes coma or somnolence, vertical gaze paralysis or skew deviation, and neuropschological deficits (“thalamic dementia”).

The thalamogeniculate artery arises from P2 and irrigates the ventral nuclei, including the anterior, lateral, intermediate, posterolateral, posteromedial nuclei. Functionally this implies sensory deficits (hemihypesthesia or hemianalgesia, but also wedge shaped sensory disturbance) via the vental posterolateral (body below face) and ventral posteromedial (trigeminal) nuclei. Interestingly the sensory disturbance in thalamic strokes can be limited exactly in the median (as a counter example for functional deficits) and tends to give rise to intractable pain syndromes (thalamic pain syndrome) later. Through deafferentation the hand moves in a weird dystonic way (with flexion of the wrist and the MCPs, adduction of the thumb and athetosis of the fingers) when the patient is asked to hold up his hands with eyes closed (thalamic hand). Through the ventral anterior and lateral nuclei as well as the subthalamic nucleus connections to the basal ganglia, the premotor cortex and the cerebellum can be harmed – this leads to atactic hemiparesis and hyper- or hypokinetic movement disorders. As the name of the artery suggests, it can also reach the genu and the posterior limb of the capsulae internae, causing the lacunar syndrome sensorimotor hemiparesis. Strokes in this region are – as those in the capsule – mainly (70%) microangiopathic.

Powell’s cross

The following scheme has been adapted from Powell’s wonderfully concise article:

Bildschirmfoto 2016-03-07 um 07.18.43Bildschirmfoto 2016-03-07 um 07.14.55

Specific thalamic syndromes

Thalamic dementia. Although it occurs frequently after paramedian artery strokes, it can also happen in anterior (through the connection to the Hippocampus and Corpora mamillaria) or even medial thalamic lesions. The neuropsychological profile is different from Alzheimer’s and akin to caudate dementia with reduced initiative, recall, short term memory (resembling Korsakoff’s), spontaneity, vigilance. Patients seem indifferent more than incapable of answering. Social intelligence may be affected more severely than formal intelligence.

Thalamic aphasia may be quite diffferent from cortical aphasia; similar to the dementia syndrome patients seem to be less interested in producing speech rather than severely handicapped. Word finding difficulties (as in any aphasia), reduced spontaneous speech, perseverations dominate, with grossly intact grammar and often preserved reading and writing capabilities as well as repetition.

Thalamic sensory  deficits. From the full blown syndrome of Déjerine-Roussy with complete hemianesthesia giving way to hypersensitivity, paresthesias and a thalamic pain syndrome to more restricted variants of hypesthesia – dissociated, face or body only, pain only, the lateral thalamic strokes can lead to severely disabling pain syndromes. Sensory deficits can be associated with (usually temporary) hemiparesis (sensorimotor stroke) or atactic hemiparesis.

Thalamic hand. This is more or less a deafferentation syndrome. Without proper feedback on the position of the fingers and hand (eyes closed), the wrist and fingers assume a dystonic posture with flexed wrist, flexed MCPs, straight PIPs and DIPS and hyperadducted thumb. When holding out the hand, deafferentation athetosis may occur, the finger wandering up and down.



An update on thrombolysis

perfusion mapDespite the recent upheaval in the emergency medicine community about the ACEP tPA-for-stroke guidelines, thrombolysis is one of the two foundations of modern stroke medicine. In a local stroke symposium, I gave a talk about new developments and folklore in tpa-ology. It also exposes our Augsburg data on thrombolysis with bleeding rate and all you could wish in a real life tpa setting. The talk introduced a new acronym for remembering the various causes of tpa-related ICH (I love acronyms). It reads CORTEX

  • C erebral amyloid angiopathy (extraischemic ICH)
  • O ld stroke (old meaning > 6h)
  • R ecanalization (recanalized vessels to dead tissue)
  • T rauma (bleeding into contusions)
  • E ndocarditis (rare but sometimes fatal)
  • X – coagulation (think of factor X, anticoagulants, ASS and the like)

If you can read German, you might want to give the presentation a try – here is the prezi link.

The colorful art and science of perfusion imaging

Deconvolution in action

Do you know what deconvolution is and how it works? Although I seriously doubt that any Neurologist is richer knowing that, it certainly is reassuring to understand why CT perfusion has so many variations, interpretations and limitations.

In my view, CT perfusion has many applications in Neurology (not to speak of Oncology):

  • Determine the penumbra of a stroke: this deserves some comments. As a quantitative method CT perfusion fails. You just cannot expect to quantify the proportion of the penumbra, because there are too many unknowns in the computation and interpretation. But you can determine the mere existence of a penumbra quite reliably (and it is still the best thing we have apart from CT+CTA).
  • Distinguish status epilepticus from postictal paralysis: the former shows hyper perfusion, while the latter looks like a stroke without core (total mismatch).
  • Recognize migraines that you would otherwise treat with tPA (again, this looks like a stroke without core, but the hypoperfusion does not respect the boundaries of the arteries and the arteries are open!).
  • Prove hyperperfusion in a hyperperfusion syndrome
  • Show the downstream effects of vasospasm in SAH
  • Determine the vascular reserve with acetazolamide – ok, this is easier done with duplex ultrasound…

Here is how I use CT-perfusion in acute stroke:

  • Indications: unknown time window, stroke mimics in tpa situations
  • Require the clinician to determine the exact region where to look
  • Use MTT or TTP to screen for ANY problems in the perfusion of the brain – wherever it is slowed, you have to do the CBF/CBV magic
  • Where CBF is quite low (don’t rely on absolute values!) and CBV is also down, there is some infarct core. Now go back to the NCCT – there should be some early ischemic signs here.
  • Where CBF is not so low as in the core and CBV is only slightly down or up there is penumbra
  • If in doubt, do exact ROI comparisons (left vs. right)
  • Now decide: is the clinical picture dominated by the infarct core or the penumbra? How much cortical structures are in the core, prone to bleed if you open up the artery? Does CTA vessel occlusion (sometimes you find the occluded vessel easier, if you know where the problem sits in perfusion CT) correspond to the perfusion deficit?

Now to the gory details:

  • Arterial input function: You should use a good arterial vessel to get the arterial input function, often the ACA is in the slice studied. But the problem is that the ACA might take part in the supply of your stroke via collateralization and it might also be disturbed by stenosis (say A1 or ICA). This can lead to very bad data.
  • Without arterial input function you cannot do deconvolution (which basically shows you how your tissue perfusion would look like if the fuzzy contrast bolus would look like a perfect rectangle-shaped push of contrast agent, not a wave) properly, so you have to use things like maximum-slope-methods and so forth.
  • Same for venous outflow.
  • The choice of algorithm is quite important – there seem to be optimal ones, if you believe this paper.
  • There are plenty of assumption underlying most of the algorithms, such as intact blood brain barrier, which usually hold in acute stroke, but are violated in things like post-CEA-hyperperfusion or SAH.
  • Sometimes, the cardiac output is so bad that the perfusion curve ends too early. You can often still use TTP in that case, but all deconvolution methods must fail.

For many more details see