Conjugate eye deviation in acute stroke

While poorly understood, conjugate eye deviation (CED) is really quite frequent: about 20% of stroke patients, about a third of thrombolyzed patients and roughly half of thrombectomy patients have it.

In this modern era where neurological workup of stroke patients is reduced to the barest minimum for the sake of door-to-needle and door-to-groin time, the door-to-neurologist’s-brain interval and ratio suffers just as much as the patient, inflating the role of the only diagnostic measure that is properly carried out: neuroimaging. Therefore radiological signs of severe impairment gain more attention and conjugate eye deviation is one of the easy and seemingly objective signs (while, say, a Babinski is hard to capture in an image of the brain). In contrast to the rest of the neurological exam you can also find CED on CT (CT-CED) retrospectively, so there are quite a few papers on it.

Clinical aspects

In the neurological exam one would require the following semiquantitative information:

  • Any eye deviation
  • Significant eye deviation (> 15°) – increases interrater reliability of CED
  • Severe eye deviation (> 30°) – if supratentorial, highly associated with spatial neglect
  • With head deviation – usually with severe eye deviation. Note that head-on-trunk deviation cannot be seen on CT as the patient’s head is fixed in the machine.
  • Fixed: cannot be overcome by contralateral visual stimulation – this might hint at accompanying spatial/visual neglect or hemianopia
  • Supranuclear: can be overcome by VOR/OCR – if not, obviously a brainstem stroke should be suspected
  • With nystagmus, usually in the direction of the eye deviation – this is ictal mainly. In theory it could be pontine but I have never observed the combinaton of CED + nystagmus in that case and could not find any case reports.

Since the FEF is quite near to the precentral gyrus and large strokes tend to damage the pyramidal tract as well, we expect a contralateral hemiparesis to accompany the ipsilesional eye deviation in most cases of damage to the frontal eye field.

CT versus clinician?

It is noteworthy that mild forms of conjugate eye deviation may actually only be seen with eyes closed (those of the patient, silly!) – this is much harder to examine clinically than radiologically, although it requires that the CT technician consistently ask patients to keep their eyes closed and that patients be able to follow this command.

This reduces correlation between the clinical examination (as reported in the gaze palsy item of the NIHSS) and the CT finding; e.g. in this 2017 study, a kappa of only 0,34 was achieved, while the interrater reliability of CT-CED was very good (even without a predefined threshold for the degree of eye deviation). UCSD seems to be better at fitting the clinical examination to CT results, achieving a kappa of 0,89 but they have the advantage of having a cool name for CT-CED: the “DEYECOM sign”.


Usually, CED and especially severe and/or fixed CED points to large hemispheric strokes. Still there is a well documented 2002 report of a smaller cortical stroke in the region of the frontal eye field (FEF) that caused ipsilesional CED (see below for comments about the localization of the FEF) and we have seen such ourselves.

Neglect versus CED

A long-standing controversy surrounds the relation between CED and spatial neglect. Obviously a patient that ignores, say, the left world, will have his eyes or even his head turned right. Vice versa, if you cannot turn your eyes to the left, you tend to not see things on the left (although you will still recognize that something is happening on the left – something a real neglect patient would not). So if in some studies only visual cues have been used to diagnose neglect, there should be a strong correlation between the two and the more severe the neglect the worse the eyes (and head) deviate. There are definite cases of CED without neglect and the two phenomena have a different half life, with CED usually subsiding after hours to days, while neglect can take much longer. So there is a relationship but they are not married.

Wrong-way CED

There are some case series and reports on contraversional CED in supratentorial strokes, sometimes called wrong-way deviation. This can be explained by:

  • ictal CED – stimulation of the frontal eye field (see below) causes contralesional eye deviation, often with nystagmus (so-called epileptic nystagmus which really is quite specific). If in the setting of acute stroke or intracerebral hemorrhage this requires that the FEF is not in the core but in the border region of the stroke (the outer penumbra, where cells are still viable, semi-functioning but easily excitable), for instance in M2 occlusions of the temporoparietal trunc,
  • bilateral stroke – not necessarily recognized in the acute images; can hint at proximal embolic source, vasculitis and much more,
  • herniation: the well-known falsely localizing sign of ipsilesional hemiparesis in space-occupying lesians such as malignant MCA stroke or large ICH with transtentorial herniation – compression of the contralateral crus cerebri against the cerebellum through midline shift of the mesencephalon (producing Kernohan’s notch),
  • hemorrhage with contralateral lesion,
  • parietal stroke: some authors mention that spatial neglect from right parietal stroke can lead to contraversive eye deviation. I have to admit that I don’t understand it, but there you have it.

Where is the FEF is located?

This question has bothered generations of researchers, starting with neurosurgical observations of patients in ancient times, somewhat later primate studies, then human semi-invasive studies (including direct cortical stimulation) and more recently PET, SPECT and fMRI research. The conclusion of this detailled review is that the precise localization depends on the setting of the experiment (which stimulus is used? what is required from the patient to do?), but it should be somewhere between the dorsal third of the midfrontal gyrus, the deeper parts of the precentral sulcus, and maybe the frontal parts of the precentral gyrus around that region.

Our best guess for the frontal eye field (blue area): in the dorsal third of the middle frontal gyrus, down into the precentral sulcus (green), perhaps to the anterior part of the precentral gyrus. Note the left central sulcus in yellow, the left superior frontal sulcus in pink and the Omega for the hand knob on the right side (we did not put it on the left as not to further confuse the reader).

Finding it on CT/MRI

Remember that one of the various (and not always successful) ways to localize the central sulcus is by walking along the easily recognized superior frontal sulcus from front to back, parallel to the falx, until you hit the precentral gyrus.

Laterally you should find the hand knob (with the Omega sign), more medially and inferiorly the paracentral lobule which closes the ring formed around the central sulcus: precentral gyrus -> paracentral lobule -> postcentral gyrus -> subcentral gyrus and back again. The frontal eye field should be slightly lateral to the corner of the L formed by the superior frontal sulcus and the precentral sulcus (see Image).

Since the FEF is near the precentral gyrus and large strokes tend to injure the pyramidal tract as well, we expect a contralateral hemiparesis to accompany the ipsilesional eye deviation in most cases of damage to the frontal eye field.

Subcortical causes

The most common pattern of caudate stroke today: s/p thrombectomy M1 right – note the hypodense demarcation in the striatum as well.

Besides the cortical structures the caudate nucleus, thalamus und the subinsular basal ganglia can cause neglect and thereby conjugate eye deviation, thus contradicting the dogma that CED is a strictly cortical sign. But remember that this holds true not only for neglect and CED but also for aphasia. While most of the acute cases with these so-called “cortical deficits” that end up with only a subcortical stroke do have cortical hypoperfusion in the acute phase  there are definite (if rare) cases of isolated strokes in either of the three regions with either of the three symptoms. Perhaps we should call them the gray (substance) deficits.

Significance of cortical signs

Why bother? Because cortical signs accompanying a hemiparesis strongly suggest a large vessel occlusion, thus necessitating CT angiography.

As an aside, many strokeologists count visual field disturbances as cortical signs. I hesitate to do so, as most quadrantanopias are probably caused by MCA strokes in the temporal or parietal subcortical visual radiation and then there is also the case of the anterior choroidal artery strokes causing hemianopia.

Differential for acute stroke

If taken as a sign of cortical dysfunction the differential for CED in the acute setting of presumed stroke is narrow: stroke/ICH, postictal (or ictal if ipsilateral to the paresis), dysglycemic. The other classic differentials for acute CNS focal deficit (such as migraine, MELAS, …) have not been reported to cause clinically consistent CED. Remark that if only the radiological sign of CED is used then a lot of false positives (50% in this series) will arise, because patients can and will look around at times during CT.


Ocular eye movements are mediated through various brainstem pathways, nuclei and cranial nerves. Lesions of these structures lead to nystagmus (gaze evoked, upbeat or downbeat), diplopia, internuclear ophthalmoplegia etc. CED is among the more rare signs of brainstem strokes:

  • Sometimes pontine lesions to the medial longitudinal fascicle (near median pontine, as in this case report) lead to contraversion of the eyes rather than the more frequent sign of internuclear ophthalmoplegia.
  • There are also some reports of medullary strokes (both dorsolateral – aka Wallenberg – and dorsomedial) with CED, in which case malfunction of the olivocerebellar pathways, the nucleus prepositus hypoglossi (taking care of gaze holding) or the MLF have been implicated, with ipsilesional eye deviation.
  • A non-systematic study of cerebellar strokes found subclinical (only radiographic) CED in about a third of patients, mostly contraversional.
  • In my personal experience, bilateral lesions to the pyramidal tract in the medulla have led to protraced (> 1 year) conjugate eye and head deviation.

Take home messages

  • Note eye and gaze position clinically in all your acute stroke patients – it is a sign of badness.
  • Note eye and gaze position on CT and try to verify it clinically.
  • In gaze deviation think 1) cortical 2) brainstem 3) subcortical 4) contralateral.

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.

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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:

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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.