Doi:10.1016/j.mehy.2006.10.040

Medical Hypotheses (2007) 68, 1318–1327 From the nutcracker-phenomenon of the left renalvein to the midline congestion syndrome as a causeof migraine, headache, back and abdominal painand functional disorders of pelvic organs Thomas Scholbach * Authorized Outpatient Ultrasound Department of the Saxonian Association of CHI Physicians DelitzscherStrasse 141, D – 04129 Leipzig, Germany Received 11 October 2006; accepted 12 October 2006 This paper presents the hypothesis, that pain and functional disturbances of organs which lie on the midline of the body might be caused by a venous congestion of these organs. Cause of their congestion is theparticipation of these organs (vertebral column, skull, brain, spinal medullary, uterus, prostate, left ovary/testis,urinary bladder rectum, vagina, urethra) in the collateral circulation of the left renal vein. In many patients withcomplaints of the above mentioned organs the left renal vein is compressed inside the fork formed by the superiormesenteric artery and the aorta. This so called nutcracker phenomenon is incompletely understood today. It can leadto a marked reduction of left renal perfusion and forces the left renal blood to bypass the venous compression site viaabundant collaterals. These collaterals are often not sufficient. Their walls become stretched and distorted – variceswith inflamed walls are formed. These dilated veins are painful, interfere with the normal organ's function anddemand more space than usual. This way pain in the midline organs and functional derangement of the midline organscan occur. The term ‘‘midline congestion syndrome'' seems appropriate to reflect the comprehensive nature of thisfrequent disorder. The rationale for this hypothesis is based on the novel PixelFlux-technique (of renal tissue perfusion measurement. With this method a relevant decline of left renal corticalperfusion was measured in 16 affected patients before therapy (left/right ratio: 0.79). After a treatment withacetylsalicylic acid in doses from 15 to 200 mg/d within 14–200 days a complete relief of so far long lasting therapy-resistant midline organ symptoms was achieved. Simultaneously the left/right renal perfusion ratio increasedsignificantly to 1.24 (p = 0.021). This improvement of left renal perfusion can be explained by a better drainage ofcollateral veins, diminution of their wall distension, thereby decline of their intramural inflammation, reduction oftheir mass effects (especially by the replaced spinal fluid inside the spinal canal and the skull), and altogether areduction of pain and functional derangement in the affected midline organs. The proposed theory might influence the * Tel.: +49 341 909 3651; fax: +49 341 909 1517.
0306-9877/$ - see front matter  c 2006 Published by Elsevier Ltd.
From the nutcracker-phenomenon of the left renal vein to the midline congestion syndrome current understanding of such frequent and difficult to treat diseases as chronic back pain, headaches, frequentcystitis, enuresis, abdominal pain, flank pain and might spur new theories of arterial hypertension, placentalinsufficiency, prostate diseases and myelopathies.
c 2006 Published by Elsevier Ltd.
Materials and method The nutcracker phenomenon of the left renal vein (LRV) is an anatomical situation, in which the leftrenal vein shows a marked calibre reduction at 16 Patients (4–18 years; mean 12.8 years) with a the crossing with the aorta Observations of this nutcracker phenomenon of the left renal vein and situation and nephrologic sequelae date back to long lasting complaints were included. They the early decades of the 20th century (as far as suffered from a variety of symptoms including known) when first reports on the ‘‘syndrome de la migraine, flank pain, dysuria, pollakisuria, micturi- ´senterique'' were issued and forgotten la- tion disturbances, dyspareunia, back pain and ter on In the seventies of the 20th century the abdominal pain.
situation was taken up again as a cause of other-wise unexplained hematuria and was diagnosed by Color Doppler sonography evaluation of the late venous phase of renal arteri-ograms. De Schepper was the first to link the All investigations were carried out with a Sequoia calibre reduction – which he perceived as com- 512 Ultrasound equipment with a curved array pression of the left renal vein between the aorta transducer to depict the kidneys in B-mode and and the superior mesenteric artery – as a cause color Doppler mode (frequencies 4–8 MHz). To of hematuria of left renal origin whereas the link measure the flow inside the left renal vein stenosis to the orthostatic albuminuria was seen already (compression site) a vector transducer with fre- as early as 1923 He argued that this elevated quencies from 1.75 to harmonic 4 MHz was backpressure leads to a mechanical induced bleed- ing of the upper urinary tract.
Color Doppler sonography encompassed an Numerous reports later on confirmed the causal overview of abdominal vessels' anatomy with spe- relationship between left renal vein entrapment cial attention to the occurrences of abnormal flow and hematuria Some reports of this constella- phenomena as displayed by the variance mode of tion referred to other complaints as well : the ultrasound equipment. This mode displays tur- abdominal pain and proteinuria. Consequently bulences as green–yellow signals thus making operations aimed successfully to correct this situa- them visible at a first glance. All examinations tion in severe cases of renal bleeding and pain (ac- were carried out with a fixed preset of the ultra- tual survey at Due to the first description of sound parameters as color gain, color frequency, the nutcracker syndrome as a syndromatic combi- type of transducer, spatial and time resolution nation of calibre reduction of the LRV and hematu- to mention the most important ones. All images ria sometimes accompanied by flank pain most of and video clips were recorded digitally (DICOM the following observations were focussed on cases with exactly this symptomatology. As hematuriais a rather infrequent symptom in a general popula-tion nutcracker syndrome as defined by De Schep- Diagnosis of nutcracker phenomenon per and followers was regarded to be a raresituation.
A nutcracker phenomenon was diagnosed when a Own routine sonographic observation of the aor- calibre reduction of the left renal vein with more to-mesenteric angle and the left renal vein in than 50% while crossing the abdominal aorta was abdominal sonograms showed that aorto-mesen- found. For measurement a longitudinal section of teric compression (what better should be termed the vein was recorded and the maximal and mini- nutcracker-phenomenon instead of nutcracker syn- mal diameter of the vein as well as the transsec- drome which includes an obligatory hematuria) is a tional diameter of the aorta were measured.
rather frequent variant of the left renal vein at Inside the compressed venous segment the flow least in children and adolescents.
velocity was measured. demonstrates a


Typical B-mode sonogram of the left renal vein entrapment between abdominal aorta and superior mesenteric artery in a transverse section of the so-called arterial nutcracker (consisting of both arteries).
Hemodynamic effects are illustrated by the flow velocity recordings below: centre: marked flow acceleration insidethe venous stenosis with profound change of flow pattern. Here venous flow is completely interrupted in the latesystole of the compressing arteries. In diastole and early systole a flow resembling an arterial jet is recorded as far asvelocity and also change of flow velocity concerns. Striking elevation of pulsatility left renal artery's perfusion in achild with nutcracker phenomenon. Left lower corner: right renal arterial perfusion.
typical example of sonographic findings in a patient product of mean perfused area and mean perfu- with nutcracker phenomenon. The abrupt calibre sion velocity of the entire sub-ROI (here the reduction is easily depicted by conventional B- proximal 20% of the ROI). Perfusion measure- mode ultrasound.
ments were done for both kidneys and a perfu-sion Renal cortical tissue perfusion measurement amount of suppression of the renal perfusion of with the PixelFlux-technique Renal cortical tissue perfusion was calculatedwith the PixelFlux-technique . Digital colorDoppler sonographic videos, which had been re- Statistical analysis corded under strictly standardized conditions,were analyzed numerically with respect to perfu- Perfusion ratios immediately before initiation of sion intensity. A standardized region of interest therapy and at the onset of relief of symptoms (ROI) consisting of the whole central renal seg- were calculated and compared by the Mann-Whit- ment fed by one interlobar artery, was investi- ney-U-test. The significance threshold was set at gated. This segment was sliced horizontally and p < 0.05.
in the proximal 20% of the ROI perfused areaand mean perfusion velocity as encoded by thepixels' color were calculated automatically bythe PixelFlux-software for each frame of a video sequence. This calculation was repeated from thebeginning to the end of a full heart cycle and In a series of 16 patients with a nutcracker phe- mean values of the aforementioned raw parame- nomenon and long lasting symptoms a variety of ters were calculated. Perfusion intensity is the symptoms was noted: From the nutcracker-phenomenon of the left renal vein to the midline congestion syndrome the diverse symptoms in these patients or if this situation is only a minor anatomical variant without any consequences.
To answer this question the hemodynamic con- sequences of the venous congestion were moni- tored. With quantitative Doppler sonographic techniques (PixelFlux-method it is easy to demonstrate profound hemodynamic changes of the left renal perfusion in many patients with nut- cracker phenomenon – even if proteinuria and hematuria are absent ). It is not rare that left Nasal obstruction renal arterial perfusion is compromised. This be- comes already evident by simple comparisons of Breathing difficulties the RIs (resistance index) of both kidneys. The RI as a marker of the of perfusion pulsatility is often Pain at defecation much higher on the left than on the right side lower part, left vs. right corner). This points to the relevant obstruction of the left renal venous outflow. The resistance against the arterial influx is elevated because of the increased venous back-pressure. The first reaction of arterial flow dynam-ics is then the drop of the diastolic flow velocity The renal cortical tissue perfusion measure- because diastolic pressure is much lower than sys- ments were carried out at the day of beginning tolic one. In this unphysiologic situation counter- and at the first consultation after complete relief mechanisms aim to compensate the decreased re- of symptoms. With the relief of the individual nal perfusion of the left side, hence it is not only symptoms of any patient a significant (p = 0.021 – the perfusion velocity but also the perfusion vol- Mann-Whitney U-Test) amelioration of the left re- ume that is diminished in such cases.
nal perfusion could be found. The ratio of left to It is interesting therefore to rethink the constel- right renal proximal cortical tissue perfusion was lation of nutcracker phenomenon with respect to compared (as an individual patient's exam- possible complaints related to the disturbed perfu- ple). Initially left renal perfusion was less than at sion of the left kidney. Such a disturbance has at the right side – the mean ratio was calculated as least two aspects: the reduction of perfusion vol- 0.79. A significant increase of perfusion to a ratio ume and the collateralization of the venous flow.
of 1.24 was reached with ASA therapy simulta- Until recently it was almost impossible to quantify neously with the complete relief of the individual renal tissue perfusion by simple, reliable and symptoms. ASA dose ranged from 15 to 200 mg/d affordable means. With the introduction of the and therapeutic effect was described between 14 sonographic PixelFlux-technique to quantify tissue and 209 days of therapy. ASA was orally adminis- perfusion from conventional color Doppler videos tered as a single morning dose.
a workable method is available. We used this tocompare renal cortical perfusion of both kidneys in patients with nutcracker phenomenon. As to beexpected from the distortion of the flow pattern in- The nutcracker phenomenon of the left renal vein side the left renal artery in cases with pronounced is regarded a rather rare constellation .
nutcracker phenomenon a reduction of left renal There are numerous case reports and few larger perfusion could be established. Without therapy series published focussing on the classical symp- the perfusion intensity of the left renal cortex was only 74% compared to the contralateral kidney.
This can be regarded as a measure of the functional entrapment is but rather frequently observed. In compromise of the left kidney due to venous con- the own laboratory the prevalence of a substantial gestion. This congestion is the driving force for compression with flow acceleration above 100 cm/s the formation of collateral pathways to drain the is found in as much as 16% of children and adoles- rather high perfusion volumes of the kidney. Renal cents (unpublished data, example see perfusion is second only to the brain in the greater The question is whether the simple compression circulation. Blood flow of one kidney at rest is of the left renal vein per se might be the cause of about 11% whereas cerebral blood flow at rest


Example of a patient's renal perfusion at the time of typical complaints of midline congestion: severe headaches recurrent during more than three weeks, abdominal pain. Above left kidney, below right kidney: strikingdifferences of the cortical perfusion are highly visibly due to PixelFlux perfusion measurement: lower overall perfusion(see also of the left kidney (homogeneous cortical perfusion intensity 2.79 vs. 1.81 cm/s; ratio left/right: 0.60!)is accompanied by an obvious shift of perfusion intensity distribution towards higher perfused areas inside the rightkidney (diagrams inside the sonograms).


From the nutcracker-phenomenon of the left renal vein to the midline congestion syndrome ranges at 14% of cardiac output . Thus even of the midline therefore play a major role in the minor obstruction leads to relevant volumes which redirecting left renal blood to the tributaries of have to be bypassed. Such bypasses are embryolog- the caval veins. Midline organs such as vertebral ically preformed and consist mainly of the left column, spinal cord, urinary bladder, uterus (pros- ovarian (spermatic) vein, the so called tronc tate), rectum, vagina, urethra and the pelvic ve- reno-rachidien (a large tributary connecting the nous plexus fed via lumbar veins and the left left renal vein with the hemiazygos vein) and the spermatic (ovarian) vein have naturally venous epidural plexus, and lumbar veins draining the re- connections to both hemispheres. They can bridge nal blood down to the pelvic organs as urinary blad- renal blood to inferior or superior caval veins via der, urethra, vagina, uterus, prostate and rectum.
their proprietary venous network. But these veinsare not laid out to receive large volumes of blood Physiology of nutcracker phenomenon from the left kidney. Many of these organs have ausually low perfusion due to a high flow resistance The obstruction of left renal venous outflow ele- as they are muscular organs (urinary bladder, vates the blood pressure inside the proximal venous uterus) or they are metabolically weakly active segment thus leading to the diagnostically impor- (vertebral column, spinal cord, prostate) or of tant dilation of the vein ) and hematuria.
small size (urethra, ovary). These potential collat- Own series (unpublished data) nevertheless show, eral pathways are connected in parallel and are ex- that nutcracker phenomenon without hematuria is posed to the same pressure as they all have direct much more frequent and accounts for about 16% venous circuit with the left renal vein. Individual of all sonograms in a tertiary ultrasound center.
disposition then decides which pathway will be- In 8% of an unselected series of renal venograms come the main route of pressure alleviation. This ureteral varices were found – always on the left disposition is predefined by embryological struc- side . Both prevalences are much higher than tures (remnants of the abundant venous predeces- that of hematuria and stresses that enlarged collat- sors in the region of the left retroperitoneum).
erals occur more frequently than hematuria which Some individuals have a relatively large lumbar ve- has been so far regarded the guiding symptom of nous system draining the blood towards the pelvis.
nutcracker phenomenon. All collaterals have to Others have a markedly developed pathway direc- fulfil the purpose of directing blood from the left ted to the hemiazygos vein and giving rise to a hemisphere of the body to its right side. Organs remarkable influx into the spinal canal (see ‘‘Sea-horse-sign''– large collateral vein (so called ‘‘tronc reno-rachidien''), connecting the dilated left renal vein (tail of the sea-horse) with the venous network of the spine – the ‘‘snout'' of the Sea-horse is directed to anintervertebral foramen draining the blood into the epidural plexus.
Some exhibit a spacious dilation and even in an adolescent of our small series), congestion umbilical cord-like tortuosity of the left spermatic of the urethra and urinary bladder may lead to (ovarian) vein, leading to a pronounced ovarian hematuria and urgent voiding, despite only small varicosis or varicocele of the left scrotum. Many urinary volumes, and burning pain at the end of women with such a condition develop large vari- micturition .
cose uterus veins or an enlarged retropubic ve- Venous congestion of the spine may have seque- nous network often also encompassing the distal lae so far not associated with renal blood flow rectum and the urethra The rectum is swollen obstruction. The vertebral column has large capac- and the hemorrhoidal plexus is filled with blood.
itive vascular pools. These are the lumbar veins, Even the urinary bladder may show atypically large hemiazygos and azygos vein, and the epidural ve- veins often with knot-like focal distensions.
nous plexus. They are fed by an inconstant but fre-quent major tributary connecting the pressured leftrenal vein to these pools – the so called tronc re From nutcracker phenomenon towards a more rachidien (reno-spinal trunk) or ‘‘canal re comprehensive understanding – the ‘‘midline go-lombaire'' Increase of pressure inside the congestion syndrome'' spinal canal will produce sensations not only at the Such a volume overload has consequences for the lumbar spine, the entrance of the additional volume affected ones. Forced venous dilation in the above to the fixed space of the spinal canal, but also at dis- mentioned organs may affect their function and tant places due to an upward shift of cerebrospinal may cause pain emanating from the distended and fluid. The dominant reaction are headaches, often convoluted veins which develop an inflammatory reported as tension-like headaches but also very of- response to the damaging effect of shear stress ten described as typical migraine or most often as a The common goal of all compensatory mecha- mixture of a variety of painful discomfort. Some pa- nisms is to transport blood from the left kidney to tients describe their headaches as commencing in the inferior or superior caval vein. All organs of the nape of the neck and many complain of worsen- the central axis may serve as a bridge to the right ing with physical activity. This hypotheses is sup- side, where the caval veins are situated. Many ported by the observation that a 30 s lasting symptoms seem to arise from their involvement obstruction of the cervical venous outflow by means in an unphysiological transport of venous renal of the Queckenstedt manoeuvre (compression of blood. The midline organs may become congested both internal jugular veins thus raising intracranial too. Thus many of the fancy symptoms of the pa- and cerebrospinal pressure) leads to aggravation tients with nutcracker phenomenon can be traced of migraine-type headaches pointing to a causal to the fact of venous congestion of midline organs.
relationship . It is interesting that with a From my point of view it is suitable therefore to ex- shorter duration of venous obstruction by the Quec- pand our view from the nutcracker phenomenon of kenstedt manoeuvre (10 s) such an effect on head- the left renal vein to a more comprehensive ache could not be provoked and that the appreciation of the complex situation. The term effect was more pronounced in a supine than in a sitting position which stresses the causative appropriate as pain and functional compromise or at least aggravating role of venous congestion for may occur in all midline organs.
migraine. It is known that a tight relationship be- Examples for this are as follows: tween intracranial venous pressure and cerebrospi- The congested pelvic veins become painful – a nal fluid pressure exists. In patients with tension- situation which is well known as pelvic congestion type headaches a withdrawal of cerebrospinal fluid syndrome . Pain is one consequence of the led to an improvement of their complaints whereas inflammatory cascade triggered by congestion a head-down tilt amplified headache . Lumbar and venous wall distension This is injections of only small epidural volumes can pro- predominantly reported in multiparous women, duce relevant rises of cerebro-spinal fluid (CSF) some of them also demonstrating external (vulvar and thigh varices) in addition to their With the aforementioned relations of headache, internal pelvic varicosis Only recently the venous drainage of the skull and their interrelation- ties between left renal vein obstruction and this ships with CSF pressure changes it is easily compre- syndrome have been clarified .
hensible that an injection of greater volumes of The blood assembly inside the rectal wall sup- left renal blood towards the lumbar epidural space ports the genesis of haemorrhoids . Congestion can produce headache via compression of the lum- of the vagina may contribute to painful sexual bar dural sac upward shift of CSF and a congestion intercourse (a condition reported even of the intracranial structures due to the following From the nutcracker-phenomenon of the left renal vein to the midline congestion syndrome rise of intracranial CSF-pressure and may be re- (see ). Moreover acetylsalicylic acid is effec- tive for migraine therapy and prophylaxis in children and adults . Many patients with Overfilling of the epidural plexus can also pro- nutcracker phenomenon just suffer from diverse voke radicular symptoms and may even mimic forms of headaches including migraine.
disk protrusion Some reports link sciatica to In cases of nutcracker phenomenon with long such a venous congestion of the spine in cases of lasting and otherwise therapy resistant complaints inferior caval vein obstruction and even myel- in 16 cases a prophylactic treatment with ASA was opathies are reported in chronic venous conges- started after informed consent was given. The tion of the spine no matter if the congestion symptoms consisted predominantly of headaches was caused be caval or renal vein obstruction and pain sensations of the lower trunk. All patients received a low dose acetylsalicylic acid treatment Individual collateralization patterns lead to a within the range of 15–200 (mean 54) mg/day as broad spectrum of symptoms which may baffle a single oral dose in the morning. Therapeutic ef- the clinical investigator about their true nature.
fects were documented in questionnaires. Addi- Their origin in left renal vein obstruction is there- tionally a global statement of the patients and fore easily overlooked. The extraordinary diversity their parents was requested as whether a signifi- of complaints, their distant locations and the often cant relief of symptoms had occurred. All patients picturesque descriptions may mock the physician.
showed a complete resolution of their symptomswithin 14–209 days. Moreover, simultaneously a Therapeutic strategies significant increase of left renal perfusion wasmeasured which is a strong argument for a causal In the case of nutcracker phenomenon the symp- link of both phenomena.
toms can be traced back to the obstruction of the A decrease of blood viscosity may contribute to left renal vein. As a logical consequence all mea- the higher perfusion volumes across the stenotic sures are promising which improve the drainage venous segment. Besides this the perfusion through of the left kidney. To restore the anatomical situa- smaller collateral veins may be eased. Both will de- tion interventions are necessary and effective.
crease the prestenotic left renal venous pressure Complete symptomatic relief after dissection and and reduce wall shear stress which is a known pro- caudal reinsertion of the left renal vein into the moter of vessel wall inflammation, oedema and inferior caval vein has been repeatedly reported thrombosis. Afterwards perfusion across the collat- but internal and external stenting of the erals will augment because of increasing distensi- stenotic segment as well as gonadocaval bypass bility of the venous walls. The capacity of the proved to be successful too . Transposi- collateral pathways will thus increase further. Both tion of the superior mesenteric artery was less suc- factors promote each other and initiate a steadily cessfully performed . Nonsurgical therapies flow augmentation away from the hypertensive ve- have not been proposed so far.
nous segment. Suppression of the venous wallinflammation will reduce direct inflammatory painsensations. Along with the drop of venous pressurein and around the spine the compression of the dur- Acetylsalicylic acid (ASA) as an al sac and the raised intracranial and intraspinal alternative non-invasive therapy pressure will drop. This might explain the allevia-tion and full reversal of headaches and back pain Given the high prevalence rate of nutcracker phe- in these patients.
nomenon in the general population and the overall Larger series are necessary to follow the traces high rates of complaints from a variety of organs explained above. If the concept of midline conges- the need of a remedy on the one hand as well as tion syndrome holds true many nowadays imper- the demand of a non-invasive therapy on the other fectly understood diseases and phenomena might hand is obvious. With respect to the etiology of the find a new explanation. Tissue perfusion measure- complaints as a primarily obstructive vascular dis- ment is a valuable tool to describe venous conges- ease with low-flow states in enlarged venous seg- tion in the midline organs – as far as they are ments, elevated shear stress, increased wall accessible for ultrasound. Its principles are useful tension (which can promote thrombogenetic path- for other radiological techniques too as the soft- ways ) and varix formation and known inflam- ware can work with MR, DSA and CT images as matory venous wall infiltration in varices well. With a more refined appreciation of living therapy with acetylsalicylic acid suggests itself tissues and their perfusion we could overcome


Significant rise of left renal perfusion (p = 0.021) simultaneously with symptom relief during ASA therapy.
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Source: http://wp12612379.server-he.de/wp-content/uploads/2015/12/Scholbach-From-nutcracker-phenomenon-to-midline-congestion-syndrome-and-treatment-with-aspirin.pdf

dmat.ua.es

Society for Industrial and Applied Mathematics3600 Market Street, 6th Floor • Philadelphia, PA 19104-2688 USAwww.siam.org • siam@siam.org 5/7/2012 1:41:13 PM The cover image illustrates the results of a fluid flow calculation over an airplane. For this design, there is little flow separation occurring on the wing except near the wingtips and near the side of the body. In addition, the flowfield streamlines from the nacelle up over the wing show vortex shedding from "chines" which are structures mounted on the nacelles that are specifically designed and optimized to shed this vortex. Without them, installing the nacelle forward of the wing as in this design would compromise both the efficiency of the wing as well as its maximum lift capability. See [Konigs 2005]

sbri.fr

The Journal of Neuroscience, December 16, 2009 • 29(50):15675–15683 • 15675 Frontal Feedback-Related Potentials in Nonhuman Primates:Modulation during Learning and under Haloperidol Julien Vezoli1,2 and Emmanuel Procyk1,21Inserm, U846, Stem Cell and Brain Research Institute, 69500 Bron, France, and 2Universite´ de Lyon, Lyon 1, UMR-S 846, 69003 Lyon, France