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Does thoracic outlet syndrome cause cerebrovascular hyperperfusion? -- Diagnostic markers for occult craniovascular congestion


Abstract and Figures

Thoracic outlet syndrome (TOS) is known to be associated with diffuse craniological comorbidities (CCM), such as occipital headaches, migraines, vestibular dysfunction, tinnitus and fatigue. Conventionally, these problems have been suggested to be a manifestation of positional vertebrobasilar insufficiency. Angiography tends to be normal in TOS sufferers, however, and doppler ultrasonography of the vertebral artery fails to demonstrate severe flow reduction. TOS is attributed to the brachial plexus and subclavian artery being compressed in the interscalene triangle, costoclavicular or subpectoral passages. The vertebral and carotid arteries arise from subclavian artery proximal to the sites of obstruction in TOS. Numerous reports of resolved CCM post scalenectomy and first-rib resection, despite lacking vertebral artery impairment, have been documented. TOS CCM, moreover, share many of the symptoms seen in systemic and intracranial hypertension. Reports of subclavian thromboembolus migrating to the head have been documented in incidences of TOS, showing the potential for flow retrogradation. We postulate that the blood prevented from entering the brachium due to distal subclavian compression, retrogrades to the brain via the carotid and vertebral arteries, resulting in craniovascular hyperperfusion and congestion.
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Running head:
Does thoracic outlet syndrome cause cerebrovascular
hyperperfusion? -- Diagnostic markers for occult craniovascular
Authors: Kjetil Larsen,
Felice C. Galluccio, MD,2 Sharma Karam Chand, MD3 – 12.11.2019
Injury rehabilitation specialist, MSKNeurology, Oslo, Norway
2 Department of Clinical and Experimental Medicine, Division of Rheumatology, University of
Florence, AOU Careggi, Florence, Italy
3 Director of Neurosurgery, Aashuman Hospital Dwarka sector 10, New Delhi, India
* Correspondence:; Tel.: +47 975 45 192
Thoracic outlet syndrome (TOS) is known to be associated with diffuse craniological
comorbidities (CCM), such as occipital headaches, migraines, vestibular dysfunction, tinnitus
and fatigue. Conventionally, these problems have been suggested to be a manifestation of
positional vertebrobasilar insufficiency. Angiography tends to be normal in TOS sufferers,
however, and doppler ultrasonography of the vertebral artery fails to demonstrate severe flow
reduction. TOS is attributed to the brachial plexus and subclavian artery being compressed in
the interscalene triangle, costoclavicular or subpectoral passages. The vertebral and carotid
arteries arise from subclavian artery proximal to the sites of obstruction in TOS. Numerous
reports of resolved CCM post scalenectomy and first-rib resection, despite lacking vertebral
artery impairment, have been documented. TOS CCM, moreover, share many of the
symptoms seen in systemic and intracranial hypertension. Reports of subclavian
thromboembolus migrating to the head have been documented in incidences of TOS, showing
the potential for flow retrogradation. We postulate that the blood prevented from entering the
brachium due to distal subclavian compression, retrogrades to the brain via the carotid and
vertebral arteries, resulting in craniovascular hyperperfusion and congestion.
Key words: thoracic outlet syndrome, cerebrovascular hyperperfusion, idiopathic intracranial
hypertension, cerebrovascular hypertension, hypertension, migraine, headache, vertigo, chronic fatigue
syndrome, myalgic encephalomyelitis
Thoracic outlet syndrome (TOS) is a common problem that has been implicated in many diffuse
maladies,1,2,3,4,5 amongst these, vestibular dysfunction, migraines, visual impairment, tinnitus and
fatigue are commonly mentioned. Sanders6,7,8 states that up to 86% of TOS patients may have occipital
(“hypertensive”) headaches, but the relationship between TOS and migraines and its other
cerebrological co-morbidities are not well understood.9 In this regard, it has been postulated that
vertebrobasilar insufficiency (VBI) caused by intermittent compression of the vertebral arteries may be
the cause of these problems, as several studies have demonstrated flow velocity reduction upon full
cervical rotation.5,7,10,11,12,13,14,15,16,17,18 Rotational occlusion of the vertebral artery (VA), however, is a
rare incidence, and even when found, it may still be asymptomatic due to adequate contribution from its
right or left counterpart.19,20 Even the carotid artery may be up to 70% stenosed and still be
asymptomatic.21 Further, although maximal cervical rotation may theoretically obstruct the VA, the
patient is unlikely to stay in such a position for long durations at a time, rendering the likelihood of its
continuous implication in these issues doubtful. Finally, considering that the absolute majority of TOS
patients suffer from cerebrological co-morbidities without findings of conspicuous vascular
compromise, and the fact that unilateral VA obstruction is rare and may even be asymptomatic, how
likely is it really that these problems may be attributed to vertebrobasilar insufficiency?
Several researchers have studied the vertebral arteries during cervical rotation with ultrasonographic
Doppler, and have demonstrated mild to moderate flow velocity changes, suggesting that positional
hypoperfusion may occur.22,23 This appears to be a common finding upon cervical rotation, also in our
own clinical practice. However, empirically, flow loss to the degree of ischemia is very rare. Moreover,
it has been shown that there is a poor correlation between flow velocities, occlusion and VBI.24 Also,
demonstrable flow velocity changes upon cervical rotation may represent normal and benign changes in
luminal diameter with compensatory velocity accommodation, consistent with Pousille’s law of flow
continuity, and does therefore not necessarily suggest frank obstruction.24,25,26 Further, many patients
with no proven brachial nor VA compromise still frequently resolve their cerebrological co-morbidities
post decompressive TOS surgery.6,27,28,29,30 Finally, obstruction in maximal rotation would likely cause
positional symptoms rather than symptoms appearing spontaneously and often without a distinct
pattern, as seen in Sell et al’s10 case where the patient consistently developed unilateral blindness with
excessive leftward rotation due to left-sided scalenogenic VA occlusion. Combined, it is the authors’
opinion that the prior arguments strongly suggest attribution of these cerebrological problems to an
etiology other than that of VBI.
Contrarily, we have found that Doppler waveforms of patients with TOS may resemble those of
patients with systemic hypertension, especially during cervical rotation, being evident by a slow
systolic upstroke, rounded and blunted systolic peaks, with or without diastolic attenuation. We have
found that hypertensive waveforms occur during ipsilateral cervical rotation and extension, but either
improve or spontaneously resolve (unilaterally) with contralateral rotation and flexion. This, as the
first-mentioned tightens the scalenus muscles and the latter detauts them, thus increasing or decreasing
brachial arterial resistance due to increased or decreased mechanical stress placed on the subclavian
artery in the interscalene triangle. It is our belief that the distal obstruction of the subclavian artery
caused by TOS prevents normal perfusion rates of the arm, and that the blood inhibited from entering
the brachium is forced to retrograde into the nearest vessel of lesser resistance, i.e. the vertebral and
carotid arteries, resulting in uni- or bilateral cerebrovascular hyperperfusion (CVH).
TOS is, conventionally, not regarded as a pathology that affects the cerebrum. However, many common
complaints that patients with TOS have, are quite similar to those of intracranial hypertension and
systemic hypertension. Headaches, fatigue, vestibular dysfunction, and more, are all well-known
sequelae of all three pathological conditions.31,32,33 In severe incidences, syncope,34 seizures,35 or other
sinister symptoms may develop. Currently, the cause of these co-morbidities in TOS remains
Preexisting literature has shown that patients with TOS have developed thromboembolus that have
retrograded from the subclavian artery to the head and caused stroke,36,37,38,39,40,41,42 demonstrating the
potential for subclavian to carotid retrogradation in TOS patients. We postulate that the compression
imposed on the distal subclavian artery in TOS not only inhibits some blood from entering the
brachium, but that the obstructed blood reverts toward the head, resulting in, to some extent, continuous
TOS-induced cerebrovascular hyperperfusion (CVH). In this case, systemic blood pressures will
generally be normal or may even be hypotensive. Cerebral MRI, venography, and angiographies will
also appear normal, thus rendering this problem almost entirely occult, as there will be no conspicuous
indicators of hypertension, despite the patient presenting with suggestive symptoms. Verily, the
symptoms of TOS CVH are consistent with those of hypertension or even malign hypertension, but
with normal systemic pressures.
The brain is very sensitive to both hypo- and hyperperfusion. To compensate for natural alterations in
cerebral blood supply, cerebral autoregulation is an autonomic process which, as the name suggests,
autoregulates flow rates and pressures in the cerebrovascular system, to maintain steady perfusion and
pressure. The autonomic nervous system may reduce cerebrovascular pressures mainly by inducing
intracranial and peripheral vasodilation, or by reducing the heart rate. Contrarily, pressures are
increased by inducing vasoconstriction or by increasing the heart rate. In TOS, peripheral resistance is
mechanically placed on the subclavian artery in the interscalene triangle, as well as costoclavicular and
subpectoral spaces,2 and will, therefore, override brachial vasodilation as a regulatory mechanism. We
believe that this causes a continuous increase in perfusion rates through the vertebral and carotid
arteries, especially on the right side (as the right internal carotid artery branches off the innominate
artery in the majority of the population whereas the left carotid generally branches off the aortic arch).
There will be insufficient cerebral vasodilation available to cope for this continuous, abnormal increase
in incoming blood volumes, often resulting in cerebrovascular congestion. Thus, in many incidences, as
vasodilation fails to lower the pressures, cardiac output may be decreased, resulting in compensatory
bradycardia or borderline bradycardia being induced by the autonomic nervous system.44,45 This may
result in the paradoxical but common event where systemic hypotension and intracranial hypertension
concomitantly develops, which seems to be especially prevalent in female TOS sufferers. Compatibly,
in our experience, patients with TOS and debilitating cerebrological co-morbidity frequently present
with a resting heart rate between 50-60 beats per minute despite being of non-suggestive [often poor]
cardiovascular fitness levels.
With regards to implications, little existing evidence forelies for moderate degrees of cerebrovascular
hyperperfusion, as seen in TOS. However, its many potential symptoms are consistent with those of
systemic and intracranial hypertensive states. Headaches and migraines, chronic fatigue, and vestibular
dysfunction are perhaps some of its most common sequelae. Tinnitus, both ordinary as well as pulsatile,
is also common. Unilateral (or, rarely, bilateral), mild to moderate forms of hemifacial weakness or
ptosis, dysarthria, aphasia, and amnesia, may also be seen, in many circumstances. Rarely, usually in
incidences of cervical whiplash or concurrent [severe] anxiety disorder, sporadic syncope,34 narcolepsy
and seizures35 may develop as well, as mentioned earlier. It is known that chronic hypertension may
impair cerebral autoregulation.46,47 Continuous cerebrovascular hypertension may predispose the
patient to aneurysmic development,48 and intima-media thickening through the processed named by
Miller as lipohyalinosis,49 which may result in unexpected strokes or hemorrhages. TOS symptoms are
highly prevalent in migraineurs. This may explain why some migraineurs are at higher risk for both
ischaemic as well as hemorrhagic strokes,50,51,52,53,54,55 and also present with seemingly idiopathic
hypertensive retinal signs.56,57,58 Saxton et al.27 documented a case where a patient with migraine since
childhood, whose symptoms exacerbated with neck extension and ipsilateral rotation and brachial
elevation, and whose MRA demonstrated sole subclavian artery obstruction within the interscalene
triangle, entirely resolved post scalenectomy. Research has also suggested that chronic hyperperfusion
may result in deterioration of the blood-brain barrier (BBB). Deliberate BBB breakdown in animal
experiments have shown that secondary seizures, epilepsy and neuronal damage may occur.59,60,61 It
may also cause cerebral swelling and demyelination,48,62,63,64 Some authors have postulated that
cerebral edema may be the underlying cause of pathologies such as multiple sclerosis,65,66 although this
remains a controversial topic. Up to 69% of people living with multiple sclerosis also suffer from
migraines.67 TOS CVH often causes pronounced fatigue, and is a common co-finding in patients with
myalgic encephalomyelitis (ME) / chronic fatigue syndrome. We also believe that the compensatory
cerebroarterial vasodilation that occurs in chronic CVH may play a role in postural orthostatic
tachycardia syndrome, another common sub-component of ME.
TOS-induced cerebrovascular hyperperfusion is a hidden disorder and may, perhaps, only be directly
identified by intraluminal catheter measurements in the extracranial arteries. However, several subtle
but indicative findings may be made non-invasively through various examinations, which will be
discussed in this section. In cases where other etiologies of the patient’s problems have been excluded,
such as frank positional VA occlusion, systemic hypertension, intracranial masses, atherosclerosis or
cerebral venous drainage-deficits (CVD) (e.g., thrombosis or high-grade cerebral venous sinus
stenosis), and the patient is known to have TOS (regardless of whether or not the patient suffers from
some degree of frank brachial ischemia), a potential presence of TOS-induced cerebrovascular
hyperperfusion may be investigated. It is a common sequela in TOS patients. TOS CVH may also have
a concurrent presence in patients who also carry other, more conspicuous pathologies such as systemic
hypertension or CVD. It should also be noted that TOS CVH will be amplified by both of the latter
With regard to TOS itself, its elaborated diagnostic protocols are outside of the main scope of this
article. However, we have used a modified version of Selmonosky’s diagnostic triad68,69,70,71 to
diagnose TOS on these patients: Clinical presentation should have common denominators with TOS’
symptomology, although the brachial aspect may or may not be the most dominant ones. Chest pain,
brachialgia, dyspnea, and periscapular pain are common symptoms in TOS. Myotome testing may
frequently reveal weakness of the triceps, fifth finger, and finger abduction, as the inferior trunk of the
brachial plexus lies more susceptible to compression in the costoclavicular space. There is usually
severe pain elicited upon Morley’s test and peripheral palpation of the radial and ulnar nerves in the
medial and lateral aspects of the forearm. Moreover, naturally, craniological co-morbidities should
present such as headaches, occipital headaches, migraine, tinnitus, vestibular dysfunction, or asthenia.
There may or may not be positive vascular TOS tests such as Selmonosky’s white hand sign, military
brace (Halstead’s) or Adson’s tests, or by duplex ultrasound examination of the axillary artery, but it is
important to note that the absence of brachial flow impairment does not exclude craniovascular
involvement. Roos’ test is usually positive and may also demonstrate post-exertional palmar paleness
either uni- or bilaterally.
As stated, TOS CVH is an occult pathology, because vascular imaging will appear within normal
limits. For example, ultrasound Doppler velocities as well as magnetic resonance angiography (MRA)
of the intra- and extracranial arteries will appear normal, because these examinations conventionally
aim to detect hypoperfusion rather than hyperperfusion. However, ultrasonography still plays an
essential role in its diagnosis, but the diagnosis is made through a combination of clinical signs,
symptomology, and qualitative Doppler waveform assessments rather than typical velocity
measurements. MRA may demonstrate increased carotid contrast saturation and intensity upon raising
of the arms (fig. 5) or even in a normal, supine position, suggesting hematogenous retrogradation and
arterial congestion. Finally, fundoscopy may sometimes provide valuable, as retinal cotton wool spots,
arteriolar constriction, snail tracks, or, in some incidences, papilledema may be present despite the lack
of high brachial blood pressure56 or cerebrovenous compromise. Papillary elevation may also be seen
with transorbital ultrasonography, and duplex evaluations of the central retinal artery may demonstrate
hypertensive arterial waveforms.
Mild to moderate degrees of distal (i.e. stenosis distal to the vertebral artery’s emanation) subclavian
artery stenosis may be asymptomatic in many circumstances.1 The arm is much less sensitive to
changes in perfusion than the brain. Therefore, in TOS, cerebrological symptoms may develop far prior
to any symptoms of frank brachial ischemia, and thus a negative Doppler study of the axillary artery in
TOS provocative positions does not exclude TOS CVH. One reason for this is that the brain’s
metabolic rate is quite constant relative to that of the brachium. Another important reason is that TOS
usually causes intermittent and positional impingement of the thoracic outlet’s neurovascular bundle, of
course, depending on the degree of affliction. Either way, it will have a positional component of either
improvement or exacerbation. Scapular retraction and depression narrows the costoclavicular passage
and thus obstruct the subclavian artery or vein.72,74 Similarly, ipsilateral rotation and extension will
tauten the scalenus anticus and may consequently obstruct the subclavian artery at its passage through
the interscalene triangle. In contrast, to positionally decompress these spaces, the patient should be set
into cervical contralateral rotation and flexion (if unilateral) or just in flexion if it is bilateral, with
moderate scapular elevation and slight protraction.
Cervical retraction and extension test
The scalenus anticus muscle is a neck flexor, lateral cervical flexor and ipsilateral rotator. It will tauten
significantly with cervical extension and ipsilateral rotation. Moreover, depression of the scapulae will
further obstruct the costoclavicular passage and the subclavian vasculature. Patients with severe TOS
will experience a rapid and substantial increase in perceived intracranial pressures and pulsatility in
neck extension. The increased pulsatility may be palpated and also noted by the clinician; it is often
conspicuous when situated in the provocative position. Ipsilateral rotation will increase the pressures in
the ipsilateral carotid and vertebral arteries, and ameliorate the contralateral side due to stretching of the
ipsilateral and detauting of the contralateral scalenus muscles. Usually, mere retraction of the neck is
sufficient to demonstrate the problem, as seen in figure 1.
Figure 1: Top left- & right images demonstrate significant dilation of the temporal arteries along with redness of
the scalp and neck, in cervical extension (the pillow on the top left is very small and soft). The patient
experiences a concomitant increase in carotid pulsatility, as is also palpable by the clinician. Bottom left- &
right: Placing the patient in 45 ̊ of cervical flexion (large, hard pillow) normalizes the carotid caliber and also
remarkably reduces carotid pulsatility
Reiterated, compatible symptoms and clinical suspicion of TOS are identified before diagnosing TOS
CVH; it is not rendered based on one single test. Other, direr potential etiologies should also be
excluded. This test has limited value if used in solitude; a series of tests and clinical evaluations are
necessary to get a clear image over the patient’s situation.
Doppler ultrasonography
In hypertension, although the flow velocities may appear within normal limits, Doppler waveforms
markedly change depending on pressure severity. It has been shown repeatedly that hypertensive
patients tend to develop a less vertical systolic upstroke, i.e. delayed upstroke,75,76,77 rounding of the
systolic peak, along with increased inclination in the diastolic descent,75,78,79 and thus an increase in
pulsatility.75,80,81 Similar findings are usually seen in [milder] incidences of TOS induced CVH.
Figure 2: [Source:] Kohara et al.75 showed that slowed systolic
upstrokes with rounded peaks and reduced diastolic velocities
were common findings in patients with systemic hypertension.
Moderate cases of TOS induced CVH will frequently present with “pyramidal” systolic waveforms,82
i.e. increased pulsatility but with slow and somewhat dampened systolic upstrokes. Strong pulsatility
usually correlates with the degree of hypertension.75,80,81 In very severe incidences, decreased systolic
pulsatility may be demonstrated, as longstanding hyperdilation and loss of compliance severely dampen
the systolic upstroke. If the distal ICA is not well visualized, the common carotid artery, which should
demonstrate medium resistance waveforms, may show a gross increase in pulsatility, similar to what
would be regarded as normal in the periphery, except that it remains monophasic. The Doppler
waveforms thus change relative to the degree of luminal saturation: The higher the pressure, the more
dampened the systolic peak will become, along with turbulence (filling of the spectral window).
Initially, increased pulsatility is seen, as shown in figures 3 & 4. However, as luminal compliance
exceeds, severe systolic dampening may be visualized, as seen in figure 5. Similar findings may be
made for the VA, although, empirically, the vertebral arteries tend to appear normal more often than the
carotid arteries. When examining the vertebral arteries for signs of CVH, the distal V2, or distal V3
segments should be checked, as the congestion is greater and more evident proximal to the cranium.
The external carotid artery may also show signs of hypersaturation, indicated through dampening of the
systolic peaks. In some of these patients, their carotid pulsatility may be so strong that it is challenging
to hold the transducer steadily and acquire a good measurement.
There are usually two main, typical appearances seen in these patients - the ones with “pyramidal”
systolic peaks, and those with severely dampened systolic peaks. The first-mentioned findings seem to
indicate that there is some compliance of the lumen during systole, but the latter, i.e. loss of a
delineable peak, most likely indicates loss of luminal compliance due to hypersaturation and pre-
expansion. More research is needed to confirm these hypotheses, however. We have found that patients
with waveforms similar to those outlined in Kohara’s75 paper are generally seen in patients with mild to
moderate morbidity. In contrast, severe blunting of the systolic peak is often seen in patients with more
severe cerebrological issues such as seizures and frequent seemingly idiopathic syncopal events.
Figure 3: Here, we show the Doppler waveforms of a 40-year-old woman with frequent idiopathic syncope, chronic
migraine, fatigue and upper extremity pain. Severe pain was elicited during Morley’s test, and the patient had a
presyncopal event shortly after. We were able to cancel the syncopal episode by turning her neck contralaterally
and into slight flexion. The changes in waveform quality are apparent. In image A, severe turbulence (spectral
filling) diffuse rounding of the systolic peak is seen. These waveforms are not tardus parvus; note the normal
velocities. In image B, after setting the patient in cervical flexion and contralateral rotation, flow turbulence
vanishes, and a very stable flow rate is seen. The systolic peak is now delineable, and time-averaged mean flow
velocities almost double, as the distal vascular congestion has been [temporarily] resolved. Fundoscopy showed
right-sided retinal arteriolar constriction. Brachial blood pressure was 127/83.
Figure 4: Pyramidal waveforms with a subtly slowed systolic upstroke and rapid diastolic declination (increased
pulsatility) in a 34-year-old male patient with chronic fatigue, severe dizziness and periodic migraines,
indicative of distal cerebrovascular congestion. This scan was done in a neutral cervical position.
Figure 5: A 23-year-old female patient with very severe TOS and near paresis of the left arm due to plexopathy.
Duplex examination of the ipsilateral axillary artery revealed near-occlusion in the military brace test-position.
Ipsilateral internal carotid artery shows a severely dampened systolic peak, suggesting severe congestion and
loss of luminal compliance during the systolic phase. Her right arm, as such, had normal strength, and ICA on
this side had moderate “pyramidal” appearance as seen in earlier figures.
Rotational vertebral artery compromise
For the case of frank vertebrobasilar insufficiency: Strangulation of the VA by the scalenus anticus
muscle is a rare but potentially sinister sequela of TOS.10,11,12,13,14,15,16,17,18 Similarly, bow hunter’s
syndrome (BHS) is yet another problem where the VA becomes compressed in the transverse vertebral
foramen, either due to foraminal stenosis or atlantoaxial hypermobility.18,19,20 Empirically, at least at
this point in time, we have not encountered frank rotational VBI in any of our TOS patients. Its
existence is not disputed, however, but VBI should not be considered a common TOS sequela, as it is
by some, today. Be that as it may, both of these problems are serious, but, thankfully, easily excludable
through a dynamic Doppler ultrasonographic examination. To correctly interpret the examination, it is
important to understand the essential yet subtle differences between near-occlusive “tardus parvus”
waveforms, and CVH waveforms. Although they may resemble in waveform shapes, tardus parvus
flow rates will often demonstrate very low systolic and end-diastolic velocities (generally systolic
velocities below 60 cm/s21), and no focal plaque nor other stenotic causes may be demonstrated. MRA
will appear abnormal in legitimate luminal stenosis, with post-stenotic tardus parvus waveforms. In
CVH, systolic velocities are dampened, but still within normal limits. The main frank abnormality
found in CVH are waveform changes, not velocity changes. There is plentiful of diastolic flow in CVH.
MRA will appear normal to be within normal parameters. Further, although the symptoms reported of
VBI may be similar to those of severe CVH, VBI is induced rotationally, whereas CVH is usually more
constant. Sell et al.10 described a patient with rotational VBI in TOS who developed ipsilateral
blindness every time he turned his head to the right. Dynamic angiography demonstrated occlusion of
the right VA by scalenus anticus muscle, and she was cured after surgical decompression.
To reliably detect proximal flow obstruction in the VA, as seen in scalenogenic strangulation or BHS,
with Doppler ultrasonography, the VA should be measured at the supra-atlantal (distal V3) VA segment
in both the neutral position as well as in ipsilateral and contralateral cervical rotation (figure 6). Sole
V2 segment measurement does not suffice. First of all, because BHS requires measurements to be
performed distal to the site of obstruction, i.e. distal to the atlantal transverse foramen, and, secondly,
because studies have shown imaging possibility for normal perfusion rates even in VA dissection,83 the
examination’s sensitivity increases when the lumen is examined as far cranially as possible. MR or CT
Angiographies with cervical rotation will demonstrate filling defects in actual VA obstruction, whereas
in CVH, it will show abnormally high signal-intensities rather than focal hypointensity suggestive of
obstruction. With Doppler ultrasonography, in mere minutes, these rare but serious pathologies can be
quite reliably excluded.
Figure 6: Duplex examination of the distal V3 segment of the vertebral artery in a patient with TOS and
suspected vertebrobasilar insufficiency revealed tremendous pulsatility suggestive of hyper-, rather than
hypoperfusion, in both left and right cervical rotation.
Magnetic resonance angiography
A contrast-enhanced, or contrast-free “time of flight” (TOF) 3D rendered MRA may demonstrate asymmetrical
intensities within the carotid and vertebral arteries compared to the subclavian and aortic vasculature in TOS
patients, as seen in figure 7 & 8. In patients with serious TOS-CVH affliction, mere neck extension will suffice
in bringing forth the abnormal signal increase in the extracranial arteries. In patients with a lesser degree of
vascular TOS, however, provocative maneuvers may be necessary to demonstrate the asymmetrical luminal
intensities. Patients with predominant scapular dyskinesia or pronounced pectoralis minor tightness will most
likely demonstrate pathology upon brachial elevation. Forced clavicular depression (“military brace test”) will
subsequently be done if the elevation maneuver is negative, as this compresses the subclavian artery in patients
with TOS.72 The purpose of this maneuver is not necessarily to detect obstruction of the subclavian artery, but,
more importantly, to detect signal intensity increase in the VA and ICAs either in neutral position or in
provocative maneuver, suggestive of TOS CVH.
2D slices are not sensitive for delineating intensity differences between normal and abnormal vasculature, and
thus a 3D rendered MRA is preferred over 2D MRA or CTA. There may or may not be conspicuous luminal
narrowing in the subclavian arteries seen on MRA. Lacking frank subclavian obstruction does not exclude CVH.
Even severe scalenus tightness does usually not cause [significant] filling defects within the subclavian artery, on
MRA, but may still cause severe CVH. Doppler ultrasonography may also be used when evaluating the axillary
artery, but this will not allow simultaneous evaluation of relative intensities between the subclavian and
extracranial arteries.
Figure 7: A 22-year-old female with longstanding TOS and chronic migraine, dizziness, and fatigue. 3D
rendered MRA reveals slight subpectoral space narrowing in a neutral posture (A). However, multifocal areas of
signal loss within the subclavian arteries are noted upon elevation of the arms, and direct illumination of the
carotid arteries occurs due to retrogradation of contrast-infiltrated blood.
Figure 8: A 36-year-old male with chronic migraine, sporadic syncopal events, seizures, extreme fatigue,
and vertigo. Plain, supine MRA reveals significant obstruction of the left subclavian artery at the
costoclavicular passage, and conspicuous hyperintensity of the vertebral and carotid arteries at the
cervicothoracic transition, which clearly delineates themselves from the caudal vascular anatomy,
suggesting hypersaturation and congestion. Clinically, this patient’s exam suggested bilateral TOS.
However, there was also concurrent bilateral obstruction of the internal jugular veins, explaining the
bilateral hyperintensity.
Neuro-ophthalmological examination
The retina may provide subtle information with regards to occult hypertensive pathology. Early
findings may be retinal venular distention and loss of spontaneous venous pulsations of the central
retain vein. Subtle cotton wool spots (retinal ischemic spots) are somewhat common findings in patients
in TOS, and suggests early hypertensive retinopathy.56,57,58 More aggressive signs include arteriovenous
“nicking”, copper- or “silver wiring”, arteriolar constriction, papilledema, and optic disk elevation,
suggesting significant, longstanding hypertension. Moreover, the neuro-ophthalmic examination may
frequently demonstrate nystagmus, diplopia, or impairment of convergence which worsens in
provocative position. The patient may experience nystagmus when their eyes are closed when lying in
neck extension, but not when side-lying and in neck flexion. The vestibulo-ocular reflex may often be
Figure 9: Subtle hypertensive retinal appearance in a 43-year-old female patient with pronounced systemic
hypotension (90/60mmHg) and concurrent, severe TOS. Slight optic disk elevation is seen along with blurring of
its nasal borders (green arrow). Moreover, copper wiring (red arrow), early arteriovenous “nicking” (gray
arrows) and focal retinal ischemia (“cotton wool spot”) nasal to the macula (orange arrow).
Orbital ultrasonography
Transorbital ultrasonography may demonstrate papilledema with disk elevation despite a normal optic
nerve sheath diameter, suggesting arterial hypertension rather than excess cerebrospinal fluid.
Pathological CSF levels will cause concomitant optic nerve sheath dilation > 5,8 mm Ø in the majority
of incidences.84 Such conclusions should, however, not be drawn unless everything else points in that
very same direction. Be aware that the mechanical index should be set to no more than 0,23 when
examining the eyes ultrasonographically.86
Figure 10: Orbital ultrasonography reveals papilledema in a patient with chronic migraine, memory loss, and
upper extremity pain. Normal brachial blood pressure and cerebral MRI. There is a relatively normal diameter
of the optic nerve sheath, i.e. no suspicion of concurrent venogenicity. Retinal Doppler examination, however,
demonstrated severely slowed systolic upstroke and rounded peaks. The flow velocities are normal,85 and thus
these findings are manifestations of hypertension and should not be interpreted as tardus parvus
(hypoperfusion). An ophthalmologist later confirmed hypertensive appearances of the retina upon fundoscopy.
Exclude venogenicity
An impaired cerebrovenous drainage capacity will also cause craniovascular congestion and cause
similar symptoms to that seen in TOS CVH. Recent research has shown that cerebrovenous drainage
impairment is a problem of much higher prevalence than earlier considered.87,88 A simple Doppler scan
with volume flow measurements of the internal jugular veins will help in excluding venogenic causes
of the patient’s problems, and can be done in mere minutes. Normal volume flow quantities amount to
approximately 700-1000 ml/min both sides combined.89,90,91 Even the hypoplastic side should drain
around 300 ml/min,91 and unilateral flow-deficit should not automatically be rendered insignificant if
the opposite canal demonstrates seemingly adequate perfusion. Flow rates lower than 160ml/min may
suggest thrombosis or significant stenosis.91 We have seen that cerebrovenous drainage deficits are
often concurrent in patients with TOS. In these cases, an evaluation should be done to estimate which
problem has the most likely etiology. Often both issues must be addressed. In cerebrovenous drainage
impairment, optic nerve sheath dilation hgher than 5,8mm in diameter may be expected, but
papilledema is not always present despite co-presence of pathological CSF levels.92
Figure 11: Absence of flow in the right internal jugular vein, in a patient with brachialgia, asthenia, and
migraines. Normal unilateral flow volumes tend to span between 350-700ml/min.
Both palliative and etiologically focused treatment approaches should be used when treating TOS
induced CVH. Pharmacological and daily positional considerations may ameliorate the patient’s
symptoms. Concurrently, addressing its underlying causes should be done. This part will also discuss
some important crucial contraindications, along with a brief detailing of palliative and etiological
treatment approaches.
Conservative considerations
The main aim in conservative therapy is to alleviate neurovascular compression in the interscalene,
costoclavicular, and subpectoral spaces. It is essential that common treatment fallacies that promote
scapular retraction and depression, as well as scalene muscle stretching, are avoided, as these, although
temporary relief may sometimes be experienced, will exacerbate the condition long-term.71,72,73 The
patient should be cued to keep their shoulders up in posture, at least one centimeter higher than that of
maximal depression, to decompress the costoclavicular space and disengage the pectoralis minor, as
well as gently strengthen their scalenus anticus and medius muscles twice per week.71,72
With regard to palliative considerations, cerebral blood flow increases significantly when supine.93 The
patient should, therefore, rest in slight inclination, preferably side-lying and in cervical flexion. This
will reduce the CVH and improve their quality of sleep. Contrarily, sleeping supine on a small or with
no pillow at all will severely exacerbate the CVH due to tautening of the scalenus anticus.
Further: Strength training of the upper extremities will cause increased upper extremity blood
consumption rates in up to 72 hours after adequately intensive exercise. The increased peripheral
perfusion rates may significantly reduce brachial resistance and will thus ameliorate the CVH for 24-72
hours depending on how hard the patient trained and their amount of muscle mass. Scapular dyskinesia,
if present, must be treated prior to the initiation of intensive strength training, as dyskinesia may grossly
exacerbate their symptoms due to consequent costoclavicular narrowing. Likewise, reducing cervical
extension during exercise will reduce potential scalenus muscle compression of the subclavian artery
and thus also relieve the physical vascular obstruction, reducing their symptoms.
Contraindications: Cervical manipulative procedures are commonly performed in patients with chronic
neck pain. However, TOS induced CVH will rigidize the VA due to hypersaturation, and this may
make the patient more susceptible to VA injury secondary to high-velocity manipulation. It is known
that patients with hypertension are more susceptible to VA dissection.94 Moreover, VA dissection is a
rare but acknowledged potential adverse effect of cervical manipulation.95 We believe that cervical
manipulation should be regarded as contraindicated in patients with TOS and pronounced craniological
A consensus on the appropriate pharmacological regimen for TOS remains controversial, and it varies
according to the underlying etiology of TOS. Generally, pharmacological interventions are indicated
for the control of pain and neurological symptoms, for muscle relaxation or for thromboembolic
complications or prophylaxis,96-103 but no preexisting protocol for cerebrovascular hyperperfusion
forelies in the literature. Therefore, we present our recommendation based on the treatment of other
similar conditions and our clinical experience.
The first step is to examine the patient’s blood pressure. Maintaining normal blood pressure values
could be beneficial and reduce, albeit partially, TOS symptoms. No studies demonstrating the
superiority of a class of antihypertensives, so we refer the choice of the drug (ace inhibitors, sartans,
etc.) to the clinician’s experience. Diuretics can be used both in association with antihypertensives as
add-on therapy or as needed to reduce TOS related symptoms. The most commonly used diuretics are:
Thiazides: Hydrochlorothiazide
Loop diuretics: Furosemide or torsemide
Carbonic anhydrase inhibitors: acetazolamide
Potassium-sparing agents: amiloride
Based on our experience, the administration of medium-low doses of hydrochlorothiazide plus
amiloride, are effective in reducing the continuous symptoms related to hyperperfusion, while
acetazolamide can be used in sporadic acute attacks.
In the most severe cases and especially at the beginning of treatment, it may be beneficial to combine
anti-edematous corticosteroids, such as dexamethasone. Prednisone or methylprednisolone can
obviously be used but we prefer dexamethasone, especially drops formulations that can be easily dosed.
Among the pharmacopoeia generally indicated in the treatment of TOS, we can find all the drugs that,
variably based on symptoms, can be added to the therapy of forms with cerebrovascular
hyperperfusion, and are:
Non-opioid analgesics. Nonsteroidal anti-inflammatory drugs commonly are prescribed in patients
with mild to moderate pain to control symptom flare. They inhibit inflammatory reactions and pain by
decreasing prostaglandin synthesis. Acetaminophen is a safe choice for gastrointestinal, kidney or
cardiovascular complications as well as during pregnancy or breastfeeding.96
Opioids. Generally prescribed in chronic or long-standing disease or in short-term for symptom flares
as well as for post-surgery. Low to mild dose opioids can be used as ground therapy in moderate to
severe pain. Transdermal opioids are generally well accepted and can enhance patient’s adherence to
the treatment.96
Opioids antagonist. Generally used to manage alcohol or opioid dependence. Naltrexone is a
reversible competitive antagonist at μ-opioid and κ-opioid receptors. However, it was discovered that
its use in low doses follows alternate pharmacodynamic pathways with various effects. Low dose
naltrexone has gained popularity as an off-label treatment of several autoimmune diseases including
multiple sclerosis and inflammatory bowel disease, as well as chronic pain disorders including
fibromyalgia, complex regional pain syndrome, and diabetic neuropathy and, in our experience, is
helpful also in TOS.
Antidepressants and reuptake inhibitors. This group of drugs is commonly used and well-studied in
the treatment of chronic and neuropathic pain. Tricyclic antidepressant has more cardiovascular adverse
effects than serotonin and serotonin and norepinephrine reuptake inhibitors and generally are
considered more difficult to titrate. These drugs also have sedative effects that may be beneficial in
these patients.96
Anticonvulsant and gabapentinoids. Commonly used for neuropathic pain alone or as adjuvant agent.
Structural derivative of GABA. Binds with high affinity to alpha2 -delta site (a calcium channel
subunit). In vitro, reduces calcium-dependent release of several neurotransmitters, possibly by
modulating calcium channel function.97,98
Muscle relaxants. May prove helpful to decrease spasm and usually prescribed in chronic contractures
during the rehabilitation period. Central muscle relaxants also have a sedative effect that can be
beneficial in these patients.96
Anticoagulants and thrombolytics. Only prescribed in the venous or arterial subtypes of TOS to treat
arterial of venous occlusions.99,100
Local injections. Injection of local anesthetic and steroids into the anterior scalene or pectoralis muscle
have demonstrated varying levels of success in observational studies. Scalenii hydrodissection or
blocks are a new and promising approach to the treatment of nTOS. Ultrasound guide hydrodissection
is useful to decompress the connective tissue around nerves.
Others. Cannabinoids may play an important role in nTOS due to their dual effect of neuropathic pain
relief and muscle relaxation. Pentoxyfilline and cilostazol may also be considered for their effect of
vasodilation and platelet aggregation inhibition.
Surgical intervention should be the last resort for these patients, reserved for those with severe CVH
sequelae such as seizures, debilitating dizziness, or frequent syncopal events. As mentioned earlier, it is
well-known that patients with cerebrological concomitant morbidities often experience resolution of
these issues after surgical intervention.
First rib resection is a potentially risky procedure with limited interventional value. Firstly, because the
clavicle may drop down to compress the second rib in many of these patients.104,105,106 Secondly,
costoclavicular compression is easily manageable conservatively by raising the scapulae in posture and
treating scapular dyskinesia.72 We believe that salvaging the first costal is a viable choice which also
reduces the likelihood of intra-procedural [iatrogenic] nerve damage. Removal of the scalenus anticus
will free the subclavian artery in the interscalene triangle, significantly reducing CVH. Removing the
scalenus anticus will, further, reduce cranial pulling of the first costal, widening the costoclavicular
interval.71 The scalenogenic subclavian obstruction is more constant and thus, often, more debilitating
than the positional obstruction occurring in the subpectoral and costoclavicular passages, in CVH.
Small cervical ribs are usually asymptomatic and do not require surgical resection. In circumstances
where the cervical rib is very large and physically indents the subclavian artery, resection may be
feasible. Sometimes the cervical rib ossifies during adolescence, and if the symptoms appear in the very
same period, the likelihood of it being symptomatic is high.
After scalenectomy, the patient should be referred to a qualified physiatrist who understands the
pathophysiology of TOS. Cueing these patients to depress the scapulae posturally will, reiterated,
grossly exacerbate their condition even after surgery, and must be avoided at all costs. The surgeon
should ensure that the patient’s conservative health care provider understands this crucial concept.
Many patients with TOS suffer from pre-existing anxiety, neuroticism, and similar psychological
disorders. Moreover, although we do not believe that TOS is strictly psychogenic, treating such issues,
if present, is crucial to help the patient recover. As always, non-organic (purely psychogenic) causes of
pain should be differentiated from actual, organic pain-generating pathologies. Patients with TOS have
a tendency of holding their breaths and physically bracing themselves (habitually “clenching” their
muscles), and these unfortunate habits must be ceased.
Case example
A 23-year-old female patient presented in the first author’s clinic with brachialgia, periscapular & chest
pain, dyspnea, fatigue and frequent migraines since the age of twelve. The migraines, as such,
responded positively to triptans and was considered a primary migraine disorder. She also suffers from
mild anxiety disorder. Her pain problems had set her on the verge of losing her employment.
She has a healthy body habitus and is approximately 170 centimeters tall. Systemic blood pressures
were slightly hypotensive, at 110/70, with a resting heart rate of 65 beats per mine. The postural
assessment showed poor cervical posture along with severe winging of both scapulae as well as
maximal clavicular depression. Roos’, Halstead’s, and Morley’s tests were all conspicuously positive,
and the patient explains that her symptoms significantly exacerbate after carrying heavy objects,
suggestive of TOS with a dominant costoclavicular component. There was an absence of deep tendon
reflexes in both upper extremities. Selmonosky’s white hand sign seemingly was negative, but the
patient complains of “always” having cold hands. Upon myotome testing, pronounced weakness (grade
three) was demonstrated of the right fifth finger and finger abduction (C8, T1, ulnar nerve) as well as
grade four weakness of the triceps (C7, radial nerve) and shoulder abduction (C5-6, axillary nerve),
suggestive of plexopathy, and consistent with the positive TOS tests. Cervical MRI was normal.
Internal jugular vein measurements revealed completely normal flow rates of 560 ml/min of the right
(dominant) and 370 ml/min of the left (hypoplastic) sides. Waveform examination of the internal
carotid artery, however, revealed hypertensive waveforms in the neutral position, which normalized in
cervical flexion and contralateral rotation (as this detauts the scalenii). The patient felt a substantial
increase in intracranial pressure after mere seconds in the cervical extension test.
Figure 12: Upper left: Left, hypoplastic internal jugular vein drains 372 ml/min. Upper right: Right, dominant
IJV drains 563 ml/min, and thus total IJV drainage equates to 935 ml/min; perfectly normal. Lower left: Doppler
waveforms in neutral position (lying supine, head straight, neck resting on a small pillow) revealed hypertensive
waveforms with slowed systolic upstrokes and rounding of the systolic peaks, as well as loss of the spectral
window, suggestive of turbulence. Lower right: Decent normalization of the waveforms and spectral window
after setting the patient in cervical flexion and contralateral rotation, to detaut the scalenus anticus. This was
Fundoscopy showed subtle ischemic (cotton wool) spots around the macula and superior retinal artery,
suggestive of mild hypertension. Transorbital ultrasonography showed normal optic nerve sheath
diameters of Ø 4,9 mm left and 5,5 mm right side, but with some elevation of the papilla. Doppler
examinations of the axillary artery showed some velocity loss but no evidence of severe, monophasic
waveforms (not shown). Thus, this was a moderate case of TOS with concomitant CVH without
significant brachiovascular compromise.
Figure 13: Papillary elevation despite a normal optic nerve sheath diameter and normal cerebrovenous
drainage abilities, suggestive of arterial hypertension. The patient’s serology was normal and thus no systemic
etiologies were suspected.
The patient was sent home with postural corrections for the head and neck, scapular repatterning as
well as strengthening exercises for the scalenii.71,72 The author received an email from the patient three
weeks later, saying that she felt better and had not suffered any headaches since the examination. A
follow-up email three months later showed that the patient had been pain-free for two months and had
stopped all pain medications. She had suffered no migraine attacks since the initial consultation. Today
she remains fully employed and pain free.
We propose the notion that obstruction of the distal subclavian artery, as seen in thoracic outlet
syndrome, may force retrogradation of the blood that is inhibited from entering the brachium toward
the head via the vertebral and carotid arteries. This results in cerebrovascular hyperperfusion and
congestion, and may explain in the many craniological concomitant morbidities seen in thoracic outlet
syndrome, such as dizziness, headaches, migraines, asthenia and tinnitus. In severe incidences, seizures
and syncopal events may occur. TOS CVH is an occult pathology; systemic blood pressures will
frequently appear normal or even hypotensive due to compensatory bradycardia and peripheral
vasodilation. A significant degree of clinical suspicion is required, and the clinician who performs the
exams should be versed in multiple diagnostic approaches, as seen in the article. Many of the subtle
findings in CVH may be deemed as “normal variants” by an unsuspecting clinician. Systemic causes, as
well as potential arterial or venous obstructive pathologies, should be excluded before rendering the
TOS CVH diagnosis.
Study limitations
Lacking, direct, existing evidence, in combination with the inconspicuous diagnostic signs of TOS
CVH, are the two most significant limitations of this article.
Conflict of interest
1. Sanders RJ, Hammond SL, Rao NM. Diagnosis of thoracic outlet syndrome. J Vasc
Surg. 2007 Sep; 46(3):601-4.
2. Sanders RJ, Hammond SL, Rao NM. Thoracic outlet syndrome: a review. Neurologist.
2008 Nov;14(6):365-73. doi: 10.1097/NRL.0b013e318176b98d.
3. Urschel Jr HC, Razzuk MA. Upper plexus thoracic outlet syndrome: optimal therapy.
Annals of Thoracic Surgery 1997;63(4):935e9.
4. Urschel HC, Razzuk MA, Hyland JW, et al. Thoracic Outlet Syndrome Masquerading as
Coronary Artery Disease (Pseudoangina). The Annals of Thoracic Surgery Volume 16,
Issue 3, September 1973, Pages 239-248.
5. Urschel HC Jr, Kourtis H, Jr. Thoracic outlet syndrome: a 50 year experience at Baylor
University. Proc Bay Union Med Cent 2007 Apr; 20(2): 125-135.
6. Sanders RJ, Pearce WH. The treatment of thoracic outlet syndrome: a comparison of
different operations. J Vasc Surg. 1989 Dec;10(6):626-34.
7. Sanders RJ, Haug CE. Thoracic Outlet Syndrome: A Common Sequela of Neck Injuries.
Published by Richard J Sanders MD, 1991.
8. Sanders JR. Neurogenic Thoracic Outlet Syndrome and Pectoralis Minor Syndrome: A
Common Sequela of Whiplash Injuries. Journal for Nurse Practitioners, v.4, no.8, 2008
Sept, p.586(9)
9. Washington University school of Medicine. “Neurogenic TOS”. Accessed 24th of November, 2018.
10. Sell JJ, Rael JR, Orrison WW. Rotational vertebrobasilar insufficiency as a component
of thoracic outlet syndrome resulting in transient blindness. Case report. J Neurosurg
1994; 81: 617–9
11. Demos NJ, Rubenstein H, Restivo CS. Role of scalenotomy for relief of positional
vertebrobasilary ischemia. J Med Soc N J.1980;77:419-422.
12. Powers SR Jr, Drislane TM, Nevins S. Intermittent vertebral artery compression; a
new syndrome. Surgery. 1961 Feb;49:257-64.
13. Hardin CA, Poser CM. Rotational Obstruction of the Vertebral Artery Due to
Redundancy and Extraluminal Cervical Fascial Bands. Annals of Surgery: July 1963 -
Volume 158 - Issue 1 - ppg 133-137
14. Husni EA: Mechanical occlusion of the vertebral artery. JAMA 196(6):101-104. 1966
15. Riddell DH, Smith BM. Thoracic and vascular aspects of thoracic outlet syndrome. Clin
Orthop. 1986;207:316.
16. Bacquey, F., Hamon, M. Coskun, O. Coffin, O. Joidate, A. Courtheoux, P. Theron, J.
Rotational vertebro-basilar insufficiency secondary to a fibrous band of the longus colli
muscle: value of CT spiral angiography diagnosis. J. Radiol. 2002, 83, 979-982,
17. Dadsetan, M.R., Skerhut, H.E. Rotational vertebrobasilar insufficiency secondary to
vertebral artery occlusion from fibrous band of the longus coli muscle. Neuroradiology
1990, 32, 514-515.
18. Kuether, T.A. Nesbit, G.M. Clark, W.M., Barnwell, S.L. Rotational vertebral artery
occlusion: a mechanism of vertebrobasilar insufficiency. Neurosurgery 1997, 41, 3.
19. Shimizu T, Waga S, Kojima T, Niwa S. Decompression of the vertebral artery for bow-
hunter's stroke. J Neurosurg. 1988; 69: 127131
20. Dargon PT, Liang CW, Kohal A, Dogan A, Barnwell SL, Landry GJ. Bilateral mechanical
rotational vertebral artery occlusion. J vasc sur 2013:58 p1076-1079. DOI:
21. Pellerito J, Polak J. Introduction to Vascular Ultrasonography 6th Edition, 2012;
Elsevier publishing.
22. Arnold C, Bourassa T, Langer T, Stoneham G. Doppler studies evaluating the effect of
a physical therapy screening protocol on vertebral artery blood flow. Man Ther.
23. Ozdemir H, Cihangiroglu M, Berilgen S, Bulut S. Effects of Cervical Rotation on
Hemodynamics in Vertebral Arteries. JDMS 21:384391 September/October 2005.
DOI: 10.1177/8756479305278982
24. Mitchell J. Doppler insonation of vertebral artery blood flow changes associated with
cervical spine rotation: Implications for manual therapists. J physiotherapy theory
practice 2007:23:6:p303-313
25. Cavdar S, Dalcik H, Ercan F, Arbak S, Arifoglu Y. A morphological study on the V2
segment of the vertebral artery. Okajimas Folia Anat. 1996;73:133137.
26. Mitchell J. Differences between left and right suboccipital and intracranial vertebral
artery dimensions: An influence on blood flow to the hindbrain? Physiother Res
Internat. 2004;9:8595.
27. Saxton EH, Miller TQ, Collins JD. Migraine complicated by brachial plexopathy as
displayed by MRI and MRA: aberrant subclavian artery and cervical ribs. J Natl Med
Assoc. 1999 Jun; 91(6): 333341.
28. Raskin NH, Howard MW, Ehrenfeld WK. Headache as the leading symptom of the
thoracic outlet syndrome. Headache. 1985 Jun;25(4):208-10.
29. Washington University school of Medicine. “Pamela’s Story”. Accessed 24th of November,
30. Chahwala V, Tashiro J, Li X, Baqai A, Rey J, Robinson HR. Ann Vasc Surg. 2017
Feb;39:285.e5-285.e8. doi: 10.1016/j.avsg.2016.05.109. Epub 2016 Aug 13. Venous
Thoracic Outlet Syndrome as a Cause of Intractable Migraines.
31. Jensen RH, Radojicic A, Yri H. The diagnosis and management of idiopathic
intracranial hypertension and the associated headache. Ther Adv Neurol Disord.
32. Hulens M, Rasschaert R, Vansant G, Stalmans I, Bruyninckx F, Dankaerts W. The link
between idiopathic intracranial hypertension, fibromyalgia, and chronic fatigue
syndrome: exploration of a shared pathophysiology. J Pain Res. 2018;11:3129-3140.
Published 2018 Dec 10. doi:10.2147/JPR.S186878
33. Higgins JNP, Pickard JD, Lever AML. Chronic fatigue syndrome and idiopathic
intracranial hypertension: different manifestations of the same disorder of intracranial
pressure? Med Hypotheses. 2017;105:69.
34. Miller R, Kelso R. Thoracic Outlet Syndrome in a Child Presenting As Syncope. J vasc
surg 2014:60:4-p1118
35. Li Q, Tan G, Zhou J. Basilar-Type Migraine with Coma: Case Reports and Literature
Review. Pain Med. 2011 Apr;12(4):654-6. doi: 10.1111/j.1526-4637.2011.01080.x.
Epub 2011 Apr 4.
36. Urschel HC, Razzuk MA, Hyland JW, Matson JL, Solis RA, Wood RE, et al. Thoracic
outlet syndrome masquerading as coronary artery disease (pseudoangina). Ann
Thorac Surg.1973;16(3):239-48
37. Vemuri C, McLaughlin LN, Abuirqeba AA, Thompson RW. Clinical presentation and
management of arterial thoracic outlet syndrome. J Vasc Surg. 2017;65(5):1429-39
38. Arnhjort T, Nordberg J, Delle M, Borgis CJ, Rosfors S, Larfars G. The importance of the
costoclavicular space in upper limb primary deep vein thrombosis, a study with
magnetic resonance imaging (MRI) technique enhanced by a blood pool agent. Eur J
Intern Med. 2014;25(6):545-49.
39. Fiorentini C, Mattioli S, Graziosi F, Bonfiglioli R, Armstrong TJ, Violante FS.
Occupational relevance of subclavian vein thrombosis in association with thoracic
outlet syndrome. Scand J Work Environ Health. 2005;31:160163.
40. Meumann EM, Chuen J, Fitt G, Perchyonok Y, Pond F, Dewey HM. Thromboembolic
stroke associated with thoracic outlet syndrome. J Clin Neurosci. 2014
May;21(5):886-9. doi: 10.1016/j.jocn.2013.07.030. Epub 2013 Oct 4.
41. Strzelecka J, Skadorwa T, Franckiewicz M, Jóźwiak S. A case of symmetric retrograde
thromboembolic cerebral infarction in an 8-year-old child due to arterial thoracic
outlet syndrome. Childs Nerv Syst (2018) 34: 2503.
42. Sharma S, Kumar S, Joseph L, Singhal V. Cervical rib with stroke as the initial
presentation. Neurol India 2010;58:645-7
43. Cushing H. Concerning a definite regulatory mechanism of the vasomotor centre
which controls blood pressure during cerebral compression. Bull Johns Hopkins Hosp.,
1901 12: 2902.
44. Escott, Mark EA. “Understanding the cushing effect”. Accessed
4th October, 2018
45. Deepak A. Rao; Le, Tao; Bhushan, Vikas (2007). First Aid for the USMLE Step 1 2008
(First Aid for the Usmle Step 1). McGraw-Hill Medical. ISBN 0-07-149868 Page 254
46. Shekhar S, Liu R, Travis OK, Roman RJ, Fan F. Cerebral Autoregulation in
Hypertension and Ischemic Stroke: A Mini Review. J Pharm Sci Exp Pharmacol.
47. Strandgaard S, Olesen J, Skinhoj E, Lassen NA. Autoregulation of brain circulation in
severe arterial hypertension. Br Med J. 1973;1(5852):507510.
48. Moulakakis KG, Mylonas SN, Sfyroeras GS, Andrikopoulos V. Hyperperfusion
syndrome after carotid revascularization. Journal of Vascular Surgery Volume 49,
Issue 4, 2009, Pages 1060-1068.
49. Fisher CM. The arterial lesions underlying lacunes. Acta Neuropathol. 1968;12:115.
50. Schürks M, Rist PM, Bigal ME, Buring JE, Lipton RB, Kurth T. Migraine and
cardiovascular disease: systematic review and meta-analysis. BMJ. 2009;339:b3914.
Published 2009 Oct 27. doi:10.1136/bmj.b3914
51. Caplan LR. Migraine and vertebrobasilar ischemia. Neurology. 1991 Jan;41(1):55-61.
52. Sacco S., Ornello R., Ripa P., Pistoia F., & Carolei A. (2014). Migraine and
hemorrhagic stroke: A meta-analysis. Stroke, 44, 30323038.
53. Witvoet EH, Pelzer N, Terwindt GM, et al. Migraine prevalence in patients with
unruptured intracranial aneurysms: A case-control study. Brain Behav.
2017;7(5):e00662. Published 2017 Mar 30. doi:10.1002/brb3.662
54. Agostoni E, Rigamonti A. Migraine and small vessel diseases. Neurol Sci. 2012 May;33
Suppl 1:S51-4. doi: 10.1007/s10072-012-1041-x.
55. Kurth T, Kase CS, Schürks M, Tzourio C, Buring JE. Migraine and risk of haemorrhagic
stroke in women: prospective cohort study. BMJ. 2010;341:c3659. Published 2010
Aug 24. doi:10.1136/bmj.c3659
56. Rose KM, Wong TY, Carson AP, Couper DJ, Klein R, Sharrett AR. Migraine and retinal
microvascular abnormalities: the Atherosclerosis Risk in Communities Study.
Neurology. 2007 May 15;68(20):1694-700.
57. Bajaj NPS, Morrish PK. The danger of ignoring a migraine. Postgraduate medical
journal 78:915.
58. Liu G, Volpe N, Galetta S. Liu, Volpe, and Galetta’s Neuro-Ophthalmology: Diagnosis
and Management, 3rd Edition. Elsevier publishing, 2018.
59. Ivens S, Gabriel S, Greenberg G, Friedman A, Shelef I. Bloodbrain barrier breakdown
as a novel mechanism underlying cerebral hyperperfusion syndrome. Journal of
neurology. 2010;257(4):615-620. doi:10.1007/s00415-009-5384-z.
60. Marchi N, Angelov L, Masaryk T, Fazio V, Granata T, Hernandez N, Hallene K, Diglaw
T, Franic L, Najm I, Janigro D. Seizure-promoting effect of bloodbrain barrier
disruption. Epilepsia. 2007;48:732742.
61. Friedman A, Kaufer D, Heinemann U. Bloodbrain barrier breakdown-inducing
astrocytic transformation: novel targets for the prevention of epilepsy. Epilepsy Res.
62. Jha SK. Cerebral Edema and its Management. Med J Armed Forces India.
2003;59(4):326331. doi:10.1016/S0377-1237(03)80147-8
63. Adams RD, Vander Eecken HM: Vascular diseases of the brain. Ann Rev Med 4: 213-
252, 1953
64. Sierra C, López-Soto A, Coca A. Connecting Cerebral White Matter Lesions and
Hypertensive Target Organ Damage. Journal of Aging Research Volume 2011, Article
ID 438978, 7 pages doi:10.4061/2011/438978
65. Barz H, Schrieber A, Barz U. Demyelinating diseases as a result of cerebral edema?
Medical Hypotheses Volume 104, July 2017, Pages 10-14
66. Damadian RV, Chu D. The Possible Role of Cranio-Cervical Trauma and Abnormal CSF
Hydrodynamics in the Genesis of Multiple Sclerosis. Physiol. Chem. Phys. & Med. NMR
(20 September 2011) 41: 117
67. Kister I, Caminero AB, Monteith TS, et al. Migraine is comorbid with multiple sclerosis
and associated with a more symptomatic MS course. J Headache Pain. 2010;11:417-
68. Selmonosky, C.A. Byrd, R. Blood, C. Blanc, J.S. Useful triad for diagnosing the cause
of chest pain. South. Med. J. 1981, 74, 947-949.
69. Selmonosky C.A, Silva R.P. The diagnosis of thoracic outlet syndrome. Myths and
facts. Revista Chilena de Cirugia 2008, 60, 255-261.
70. Selmonosky, C.A. Thoracic outlet syndrome. The missing link in the diagnosis of non-
coronary chest pain. Italian Journal of Cardiology 2008, 9, 217S.
71. Larsen K. How to truly identify and treat thoracic outlet syndrome (TOS). Web blog.
Accessible at:
[read the 9th of November, 2019]
72. Larsen K. Postural cues for scapular retraction and depression promote costoclavicular
space compression and thoracic outlet syndrome. Anaesth Pain & Intensive Care
73. Larsen K, Chien GCC. Lumbosacral plexus entrapment syndrome. Part Two:
Symptomology and rehabilitative trials. Anaesth pain & intensiv care 2019;23(2):138-
74. Watson LA, Pizzari T, Balster S. Thoracic outlet syndrome Part 2: conservative
management of thoracic outlet. Man Ther. 2010 Aug;15(4):305-14. doi:
75. Kohara K, Jiang Y, Igase M, Hiwada K. Effect of Reflection of Arterial Pressure on
Carotid Circulation in Essential Hypertension. AJH 1999;12:10151020
76. Kelly RP, O’Rourke MF: Evaluation of arterial wave forms in hypertension and
normotension, in Laragh JH, Brenner BM (eds): Hypertension: Pathophysiology,
Diagnosis, and Management, Laven Press, New York, 1995, pp 343364.
77. Nichols WW, O’Rourke MF: McDonald’s Blood Flow in Arteries. Theoretical,
Experimental, and Clinical Principles, Arnold, London, 1998.
78. Jiang YN, Kohara K, Hiwada K: Alteration of carotid circulation in essential
hypertensive patients with left ventricular hypertrophy. J Hum Hypertens 1998;
79. Watanabe S, Okura T, Kitami Y, Hiwada K. Carotid hemodynamic alterations in
hypertensive patients with insulin resistance. American Journal of Hypertension,
Volume 15, Issue 10, 1 October 2002, Pages 851856,
80. Weisfeldt M: Aging, changes in the cardiovascular system, and responses to stress.
Am J Hypertens 1998;11: 41S45S.
81. London G, Guerin A, Pannier B, Marchais S, Benetos A, Safar M: Increased systolic
pressure in chronic uremia. Role of arterial wave reflections. Hypertension 1992;20:
82. Larsen K. Occult intracranial hypertension as a sequela of biomechanical internal
jugular vein stenosis: A case report. Anaesth Pain & Intensive Care 2018;22(2):238-
83. Pugliese F, Crusco F, Cardaioli G, Tambasco N, Boranga B, Scaroni R, et al. CT
angiography versus colour-Doppler US in acute dissection of the vertebral artery.
Radiol Med. 2007 Apr;112(3):435-43. Epub 2007 Apr 20.
84. Geeraerts T, Merceron S, Benhamou D, Vigue B, Duranteau J. Noninvasive
assessment of intracranial pressure using ocular sonography in neurocritical care
patients. Crit Care. 2008;12(Suppl 2):P117.
85. Dennis KJ, Dixon RD, Winsberg F, Ernest JT, Goldstick TK. Variability in measurement
of central retinal artery velocity using color Doppler imaging. J Ultrasound Med. 1995
86. Barnett SB. World Federation for Ultrasound in Medicine and Biology (WFUMB)
Symposium on safety of ultrasound in medicine: Conclusions and recommendations
on thermal and non-thermal mechanisms for biological effects of ultrasound.
Ultrasound Med Biol. 1998;24:155.
87. Jayaraman MV, Boxerman JL, David LM, Haas RA, Rogg JM. Incidence of Extrinsic
Compression of the Internal Jugular Vein in Unselected Patients Undergoing CT
Angiography. AJNR Am J Neuroradiol. 2012 Aug;33(7):1247-50. doi:
10.3174/ajnr.A2953. Epub 2012 Feb 9.
88. Ding JY, Zhou D, Pan LQ, Ya JY, Liu C, Yan F, et al. Cervical spondylotic internal
jugular venous compression syndrome. CNS Neurosci Ther. 2019;00:18.
89. Müller HR, Hinn G, Buser MW. Internal jugular venous flow measurement by means of
a duplex scanner. J Ultrasound Med. 1990 May;9(5):261-5.
90. Brunhölzl C, Müller HR. [Doppler sonography measurement of jugular vein blood
flow]. Vasa. 1990;19(1):26-9.
91. Özen Ö, Ünal Ö, Avcu S1. Flow volumes of internal jugular veins are significantly
reduced in patients with cerebral venous sinus thrombosis. Curr Neurovasc Res. 2014
92. De Simone R, Ranieri A, Montella S, et al. Intracranial pressure in unresponsive
chronic migraine. J Neurol. 2014;261(7):13651373. doi:10.1007/s00415-014-7355-
93. Garrett ZK, Pearson J, Subudhi AW. Postural effects on cerebral blood flow and
autoregulation. Physiol Rep. 2017;5(4):e13150. doi:10.14814/phy2.13150
94. Pezzini A, Caso V, Zanferrari C, et al. Arterial hypertension as risk factor for
spontaneous cervical artery dissection. A case-control study. J Neurol Neurosurg
Psychiatry. 2006;77(1):9597. doi:10.1136/jnnp.2005.063107
95. Refshauge KM: Rotation: a valid premanipulative dizziness test? Does it predict safe
manipulation? J Manipulative Physiol Ther 1994;17:1519.
96. Jones MR, Prabhakar A, Viswanath O, et al. Thoracic Outlet Syndrome: A Comprehensive Review
of Pathophysiology, Diagnosis, and Treatment. Pain Ther. 2019;8(1):5–18. doi:10.1007/s40122-
019-0124-2 2)
97. Wiffen PJ, McQuay HJ, Edwards JE, Moore RA. Gabapentin for acute and chronic pain. Cochrane
Database Syst Rev. 2005 Jul 20. 3)
98. Moore RA, Straube S, Wiffen PJ, Derry S, McQuay HJ. Pregabalin for acute and chronic pain in
adults. Cochrane Database Syst Rev. 2009 Jul 8 4)
99. Brooke BS, Freischlag JA. Contemporary management of thoracic outlet syndrome. Curr Opin
Cardiol. 2010;25(6):535–540 5)
100. Schneider D.B., Dimuizio P.J., Martin N.D. Combination treatment of venous thoracic outlet
syndrome: Open surgical decompression and intraoperative angioplasty. J. Vasc. Surg.
2004;40:599–603. 6)
101. Jordan S.E., Machleder H.I. Diagnosis of thoracic outlet syndrome using electrophysiologically
guided anterior scalene blocks. Ann. Vasc. Surg. 1998;12:260–264. 7)
102. Jordan SE, Ahn SS, Freischlag JA, Gelabert HA, Machleder HI. Selective botulinum
chemodenervation of the scalene muscles for treatment of neurogenic thoracic outlet syndrome.
Ann Vasc Surg. 2000 Jul. 14 (4):365-9. 8)
103. Foley JM, Finlayson H, Travlos A. A review of thoracic outlet syndrome and the possible role
of botulinum toxin in the treatment of this syndrome. Toxins (Basel). 2012;4(11):1223–1235.
Published 2012 Nov 7. doi:10.3390/toxins4111223
104. Roos DB. Experience with First Rib Resection for Thoracic Outlet Syndrome. Annals
of Surgery March 1971:429-442
105. Stallworth JM, Quinn GJ, Aiken AF. Is rib resection necessary for relief of thoracic
outlet syndrome? Ann Surg. 1977 May;185(5):581-92.
106. Wijeratna MD, Troupis JM, Bell SN. The use of four-dimensional computed
tomography to diagnose costoclavicular impingement causing thoracic outlet
syndrome. Shoulder & Elbow 2014, Vol. 6(4) 273275 2014 DOI:
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Aims This study aimed to identify the clinical profiles of cervical spondylosis‐related internal jugular vein stenosis (IJVS) comprehensively. Methods A total of 46 patients, who were diagnosed as IJVS induced by cervical spondylotic compression were recruited. The clinical manifestations and imaging features of IJVS were presented particularly in this study. Results Vascular stenosis was present in 69 out of the 92 internal jugular veins, in which, 50.7% (35/69) of the stenotic vessels were compressed by the transverse process of C1, and 44.9% (31/69) by the transverse process of C1 combined with the styloid process. The transverse process of C1 compression was more common in unilateral IJVS (69.6% vs 41.3%, P = 0.027) while the transverse process of C1 combined with the styloid process compression had a higher propensity to occur in bilateral IJVS (52.2% vs 30.4%, P = 0.087). A representative case underwent the resection of the elongated left lateral mass of C1 and styloid process. His symptoms were ameliorated obviously at 6‐month follow‐up. Conclusions This study proposes cervical spondylotic internal jugular venous compression syndrome as a brand‐new cervical spondylotic subtype. A better understanding of this disease entity can be of great relevance to clinicians in making a proper diagnosis.
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Purpose: Idiopathic intracranial hypertension (IICH) is a condition characterized by raised intracranial pressure (ICP), and its diagnosis is established when the opening pressure measured during a lumbar puncture is elevated >20 cm H2O in nonobese patients or >25 cm H2O in obese patients. Papilledema is caused by forced filling of the optic nerve sheath with cerebrospinal fluid (CSF). Other common but underappreciated symptoms of IICH are neck pain, back pain, and radicular pain in the arms and legs resulting from associated increased spinal pressure and forced filling of the spinal nerves with CSF. Widespread pain and also several other characteristics of IICH share notable similarities with characteristics of fibromyalgia (FM) and chronic fatigue syndrome (CFS), two overlapping chronic pain conditions. The aim of this review was to compare literature data regarding the characteristics of IICH, FM, and CFS and to link the shared data to an apparent underlying physiopathology, that is, increased ICP. Methods: Data in the literature regarding these three conditions were compared and linked to the hypothesis of the shared underlying physiopathology of increased cerebrospinal pressure. Results: The shared characteristics of IICH, FM, and CFS that can be caused by increased ICP include headaches, fatigue, cognitive impairment, loss of gray matter, involvement of cranial nerves, and overload of the lymphatic olfactory pathway. Increased pressure in the spinal canal and in peripheral nerve root sheaths causes widespread pain, weakness in the arms and legs, walking difficulties (ataxia), and bladder, bowel, and sphincter symptoms. Additionally, IICH, FM, and CFS are frequently associated with sympathetic overactivity symptoms and obesity. These conditions share a strong female predominance and are frequently associated with Ehlers-Danlos syndrome. Conclusion: IICH, FM, and CFS share a large variety of symptoms that might all be explained by the same pathophysiology of increased cerebrospinal pressure.
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A 27-year-old woman presented with dominant symptoms including chronic migraine, dizziness and nausea with suspected intracranial hypertension (ICH). The patient also had a purpuric (cyanotic) facial discoloration, suggestive of compromised cerebral perfusion. However, her lumbar puncture opening pressure (LPOP) was borderline high, with 20 cm H2O. There was no evidence of partially empty sella turcica nor obliteration of the cerebral cisterns upon MRI. She was initially diagnosed with chronic migraines by her neurologist. However, closer inspection revealed posterior scleral flattening, flattened pons, and most importantly stenosis of the internal jugular veins (IJV) between the C1 transverse processes and styloid processes, due to anterior subluxation of the atlanto-occipital facets. Doppler waveforms of the internal carotid arteries were abnormal and suggestive of ICH, with a significantly delayed systolic upstroke but with normal speeds. Manual compression of the IJVs reproduced her symptoms within 7 sec. Occult biomechanical ICH may have severe and long-lasting consequences for the patient and thus its detection, and distinguishing from the "common migraine" is necessary, so that the patient may receive proper treatment.
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A commonly used postural corrective measure is to pull the shoulders back and down. This corrective measure is most likely based upon the idea that postural acromial protraction is a frequent tendency in neck and shoulder patients, as is excessive clavicular elevation during shoulder movement. However, this corrective measure is based upon logical fallacies, firstly because it will cause scapular depression and downward rotation, which has been associated with scapular dyskinesis (SD), shoulder impingement syndrome (SIS) and neck pain. Secondly, biomechanically it will set the patient in the Halstead’s costoclavicular compression (“military brace”) test position, which may result in plexopathy and thoracic outlet syndrome (TOS). The corrective measure thus opposes what it is intended to do, as it may exacerbate neck and shoulder problems rather than ameliorating them. Based on the anatomy and evidence, as well as personal clinical experience with 115 TOS patients, it is my impression that the cue in question is harmful and that its use should be discontinued. Conversely, the patient should be cued to raise his or her scapulae until the superior scapular angles are levelled with the T2 vertebra, and learn to stay there, as this will upwardly rotate the scapulae as well as decompress the costoclavicular space.
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Arterial type of thoracic outlet syndrome belongs to the most unusual mechanisms of stroke in children in the first decade of life. We present a case diagnosed for bilateral and symmetric changes due to retrograde thromboembolic phenomenon. Regarding the age of the patient, the appropriate diagnostics and management are still a matter of debate in pediatric and neurological literature.
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Though not discussed in the medical literature or considered in clinical practice, there are similarities between chronic fatigue syndrome and idiopathic intracranial hypertension (IIH) which ought to encourage exploration of a link between them. The cardinal symptoms of each – fatigue and headache - are common in the other and their multiple other symptoms are frequently seen in both. The single discriminating factor is raised intracranial pressure, evidenced in IIH usually by the sign of papilloedema, regarded as responsible for the visual symptoms which can lead to blindness. Some patients with IIH, however, do not have papilloedema and these patients may be clinically indistinguishable from patients with chronic fatigue syndrome. Yet IIH is rare, IIH without papilloedema (IIHWOP) seems rarer still, while chronic fatigue syndrome is common. So are the clinical parallels spurious or is there a way to reconcile these conflicting observations?
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Objectives Migraine is a suggested risk factor for aneurysmal subarachnoid hemorrhage (aSAH). An increased risk of aSAH in migraineurs may be explained by an increased prevalence of unruptured intracranial aneurysms (UIA). We performed a case–control study to compare lifetime migraine prevalence in patients with UIA, patients with a history of transient ischemic attact (TIA) or ischemic stroke and controls without a history of aSAH, TIA or ischemic stroke. Materials and Methods Patients with UIA were recruited from two university hospitals. Data on patients with TIA/stroke were retrieved from a previous study. Partners of patients with UIA or TIA/stroke were included as controls. Migraine history was assessed via a telephone interview based on the International Classification of Headache Disorders, second edition criteria. We calculated odds ratios (OR) for migraine with univariable and multivariable logistic regression analyses, adjusted for age, sex, hypertension and smoking. Results We included 172 patients with UIA, 221 patients with TIA or stroke, and 164 controls. In UIA patients, migraine prevalence was 24.4% compared with 14.6% in controls (UIA vs. controls; OR 1.9; 95% confidence interval [CI] 1.1–3.5) and 22.2% in TIA/stroke patients (UIA vs. TIA/stroke; OR 1.1; 95% CI 0.7–1.8). After adjustments, the OR for migraine in UIA patients versus controls were 1.7 (95% CI 1.0–3.1) and 0.9 (95% CI 0.5–1.0) versus TIA/stroke. Results were comparable for migraine with and without aura. Conclusions Migraine prevalence is possibly increased in patients with UIA compared with controls and comparable with the prevalence in patients with TIA or stroke. Further studies are needed to confirm our findings and to investigate the underlying pathophysiology.
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Cerebral autoregulation (CA) is thought to maintain relatively constant cerebral blood flow (CBF) across normal blood pressures. To determine if postural changes alter CA, we measured cerebral blood flow velocity (CBFv) in the middle cerebral arteries, mean arterial blood pressure (MABP), cardiac output (Q), and end-tidal carbon dioxide (PETCO2) in 18 healthy individuals (11 female and seven male; 26 ± 9 years) during repeated periods of supine and seated rest. Multiple regression was used to evaluate the influence of PETCO2, MABP, Q, and hydrostatic pressure on CBFv. Static CA was assessed by evaluating absolute changes in steady-state CBFv. Dynamic CA was assessed by transfer function analysis of the CBFv response to spontaneous oscillations in MABP. In the seated versus supine posture, MABP (67.2 ± 7.2 vs. 84.2 ± 12.1 mmHg; P < 0.001), CBFv (55.2 ± 9.1 vs. 63.6 ± 10.6 cm/sec; P < 0.001) and PETCO2 (29.1 ± 2.6 vs. 30.9 ± 2.3 mmHg; P < 0.001) were reduced. Changes in CBFv were not explained by variance in PETCO2, MABP, Q, or hydrostatic pressure. A reduction in MABP to CBFv transfer function gain while seated (P < 0.01) was explained by changes in the power spectrum of MABP, not CBFv. Our findings suggest that changes in steady-state cerebral hemodynamics between postures do not appear to have a large functional consequence on the dynamic regulation of CBF.
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Objective: Arterial thoracic outlet syndrome (TOS) is a rare condition characterized by subclavian artery pathology associated with a bony abnormality. This study assessed contemporary clinical management of arterial TOS at a high-volume referral center. Methods: A prospectively maintained database was used to conduct a retrospective review of patients undergoing primary or reoperative treatment for arterial TOS during an 8-year period (2008 to 2016). Presenting characteristics, operative findings, and clinical and functional outcomes were evaluated. Results: Forty patients underwent surgical treatment for arterial TOS, representing 3% of 1401 patients undergoing operations for all forms of TOS during the same interval. Patients were a mean age of 40.3 ± 2.2 years (range, 13-68 years), and 72% were women. More than half presented with upper extremity ischemia/emboli (n = 21) or posterior stroke (n = 2), including eight that had required urgent brachial artery thromboembolectomy. The presentation in 17 (42%) was nonvascular, with 11 having symptoms of neurogenic TOS and six having an asymptomatic neck mass or incidentally discovered subclavian artery dilatation. All patients underwent thoracic outlet decompression (25 supraclavicular, 15 paraclavicular), of which there were 30 (75%) with a cervical rib (24 complete, 6 partial), 5 with a first rib abnormality, 4 with a clavicle fracture, and 1 (reoperation) with no remaining bone abnormality. Subclavian artery reconstruction was performed in 70% (26 bypass grafts, 1 patch, 1 suture repair), and 30% had mild subclavian artery dilatation (<100%) requiring no arterial reconstruction. Mean postoperative length of stay was 5.4 ± 0.6 days. During a mean follow-up of 4.5 ± 0.4 years (range, 0.9-8.1 years), subclavian artery patency was 92%, none had further dilatation or embolism, and chronic symptoms were present in six (4 postischemic/vasospasm, 2 neurogenic). Functional outcomes measured by scores on the 11-item version of the Disability of the Arm, Shoulder and Hand Outcome Measure improved from 39.1 ± 3.8 to 19.2 ± 2.7 (P < .0001). Conclusions: This relatively large single-institution series demonstrates the diverse clinical presentation of arterial TOS coincident with a spectrum of bony and arterial pathology. Current surgical protocols can achieve excellent outcomes for this rare and often complicated condition.
Aging and chronic hypertension are associated with dysfunction in vascular smooth muscle, endothelial cells, and neurovascular coupling. These dysfunctions induce impaired myogenic response and cerebral autoregulation, which diminish the protection of cerebral arterioles to the cerebral microcirculation from elevated pressure in hypertension. Chronic hypertension promotes cerebral focal ischemia in response to reductions in blood pressure that are often seen in sedentary elderly patients on antihypertensive therapy. Cerebral autoregulatory dysfunction evokes Blood-Brain Barrier (BBB) leakage, allowing the circulating inflammatory factors to infiltrate the brain to activate glia. The impaired cerebral autoregulation-induced inflammatory and ischemic injury could cause neuronal cell death and synaptic dysfunction which promote cognitive deficits. In this brief review, we summarize the pathogenesis and signaling mechanisms of cerebral autoregulation in hypertension and ischemic stroke-induced cognitive deficits, and discuss our new targets including 20-Hydroxyeicosatetraenoic acid (20-HETE), Gamma-Adducin (Add3) and Matrix Metalloproteinase-9 (MMP-9) that may contribute to the altered cerebral vascular function.