"Anthony G Gordon mentioned that a drop in endolymph pressure from CSF hypotension and vascular hypotension may lead to hyperactivity of the inner ear."

I think a major cause of vertigo/dizziness/lightheadedness from whatever supposed cause is in fact a reduction in perilymph pressure, with secondary expansion of the endolymphatic compartment (endolymphatic hydrops).  Causes of this reduced perilymph pressure include dehydration, weight loss, vascular hypotension, CSF or perilymph leaks, CSF hypotension, etc.  There is no plausible central nervous system origin for dizziness with postural hypotension (where is this site; why not a mass of associated neurological symptoms?).

I seem to recall that the cochlear aqueduct narrows with age, impairing any link between CSF and perilymph.  Are there age effects for the audiovestibular correlates of CSF hypotension?

The hydrops theory of postural hypotension can be easily tested by looking for other hydrops symptoms, including audiosensitivity, low tone hearing loss, nausea, tinnitus,  aural fullness/pressure.

As you can see in this paper, cerebral autoregulation may vary among patients with OH. (Autoregulation of Cerebral Blood Flow in Orthostatic Hypotension Vera Novak, Peter Novak, Judith M. Spies and Phillip A. Low 29(1)104,Stroke.1998) Different individuals have different capacity to cope with hypotension. Then, OH may be present in those with preserved SPB>90mmHg on standing. So, there is no wonder that they do not feel dizzy although they meet OH criteria. To feel "dizzy" some crucial criteria should be fulfilled: standing systemic BP low enough to cause cerebral hypoperfusion, and/or insufficient mechanisms of cerebral autoregulation. Of course, when SBP drops below 60 mmHg, it does not take long time to faint regardless of cerebral autoregulation.  On the other hand, we have seen patients on tilt who tolerated SBP of about 60 mmHg without any specific symptoms apart from tiredness. In the large population-based studies, only 10% of participants with OH at baseline were symptomatic.See: Fedorowski A, Melander O. Syndromes of orthostatic intolerance: a hidden danger. J Intern Med 2013;273(4):322-35.

You may also like to look at Cerebral autoregulation: an overview of current concepts and methodology with special focus on the elderlyJournal of Cerebral Blood Flow & Metabolism (2008) 28, 1071–1085,

Regards,

Artur

Dear Gordon,

Thank you for clarification of the physiological basis for dizziness in severe hypotension. Your further suggestions on testing of the theory are also helpful, and we will see if the opportunity for joint research present itself locally in due course.

However, I will definitely keep this in mind, especially the possible association between the narrowing of the cochlear aqueduct and loss of relationship between the perilymph and the CSF. Fascinating.

Many thanks once again for your comments and do let me know if you come across studies, past, present and future on this topic.

Much obliged,

Samuel Chew

Dear Artur,

I read your reply and article with great interest.

It brings back memories of my Specialist Registrar training years with my mentor, the late Dr Jed Rowe from Moseley Hall Hospital in Birmingham. We used a Finapress machine, which monitored non-invasively the beat-to-beat blood pressure during tilt, and performed the same protocol as described in your article. I still remember vividly the sudden drop of HR before the patient experience syncope as a result of the exaggerated cardio-inhibitory response and the ensuing circulatory collapse and syncope.

Figure 5 in your paper (Fedorowski A, Melander O. Syndromes of Orthostatic Intolerance: a hidden danger. J Intern Med 2013;273(4):322-35.) illustrates this perfectly!

I agree completely with your view that it is due to the cerebral auto regulation that some of these patients are able to be symptom free despite the severe postural hypotension.

However, for the patient to experience sudden witnessed syncope without the accompanying vestibular symptom would suggest that the auto-regulation has a finite point at which it suddenly collapses. A reactive auto-regulation capability may also explain a small cohort of patients of whom I have observed to have improved documented in-patient blood pressure and resolution of the dizziness symptoms with the trial off anti-hypertensive therapy in the setting of severe debilitating postural dizziness (unpublished data).

Severe Orthostatic Hypotension is a hidden danger, and likely to be responsible for much more burden of disease and morbidity in terms of not only cerebral and vestibular function, but also in terms of cognition, rehabilitation potential and unexplained cachexia in the very elderly.

The high burden of disease (25% per 100 patient years in our recent study) is often unrecognised in the very elderly, due to the current emphasis on very short length of in-patient stay, and great difficulty in performing lying and standing in symptomatic patients, who will naturally resist, in addition of other masking factors. Furthermore, interest has shifted to hyper and not hypo, tension.

I agree with your comments in your paper that although Midodrine has RCT-level of evidence supporting it's use, it's efficacy is often questioned. Incidently, it was also Dr Rowe who introduced me to Midodrine. We are currently working on a study to see if we can first define and standardise the disabilities caused by severe postural hypotension using the Orthostatic Grading Scale proposed by Low et al (Management of Neurogenic Orthostatic Hypotension: An Update. Lancet Neuro. 2008: 7:451-58)

Without a validated disability scale for Orthostatic Hypotension, it is hard to prove the efficacy of treatment, before and after, for this very special and vulnerable group of patients.

ps There are some reports that the relationship between history of significant hypertension in the past and predisposition to severe postural hypotension is related to over-stimulation of the baroreceptors over many years, leading to "burn-out" and hence failure to compensate for the postural haemodynamic changes in later years (Naschitz et al. "The patient with supine hypertension and orthostatic hypotension: a clinical dilemma". Postgrad Med J 2006;82:246–253. doi: 10.1136/pgmj.2005.037457)

This is another group of patients of interest to me: "Severe postural hypotension with severe supine hypertension"!

Thank you again for your time and for sharing your study.

Much obliged,

Samuel Chew

" To feel "dizzy" some crucial criteria should be fulfilled: standing systemic BP low enough to cause cerebral hypoperfusion, and/or insufficient mechanisms of cerebral autoregulation"

What part of the brain generates dizziness?  In the absence of any clear idea or evidence, why not consider the simpler explanation that it comes from the ear?

"do let me know if you come across studies, past, present and future on this topic"

I have had a quick look through my reference files, and found some papers indicating that the ear is particularly susceptible to poor blood supply, in particular displaying symptoms of hydrops.  See

• Arteriosclerosis (Practitioner 1892;2:458)
• Vascular hypotension  (J Laryngol Otol 2003;117:265)
• Exxcess blood loss (Med Times 1845;12:132)
• Syncope (Neurol 2013;80:1485)
• Low tone hearing loss (Annals ORL 2002;111:160)

Dear Gordon,

Thank you for the links. The systematic review on Midodrine by Izcovich et al (Neurology 2014;83:1170–1177) is helpful. Clearly, we have our work cut out for us, particularly form the aspect of symptom/quality of life measures using validated scales in response to treatment.

Samuel Chew

" I will definitely keep this in mind, especially the possible association between the narrowing of the cochlear aqueduct and loss of relationship between the perilymph and the CSF"

I believe the symptoms of dizziness/faintness arise from reduced blood flow in the ear (see abstract below).  However, this would not explain why more symptoms occurred in younger persons, a very unexpected finding.  So the mechanism is more likely a reduction in CSF pressure transmitted via the cochlear aqueduct, which is more patent in younger persons.

Symptoms of low blood pressure: a population study.

BMJ1990; 301 doi: http://dx.doi.org/10.1136/bmj.301.6748.362(Published 18 August 1990) Cite this as: BMJ 1990;301:362 

 S Wessely,J Nickson,B Cox

Abstract

OBJECTIVE--To establish whether an association exists between blood pressures in the "low normal" range and common symptoms such as tiredness, dizziness, headache, and palpitation, as suggested by French and German medical practice but not English or American medical practice. DESIGN--Cross sectional population based survey (the health and lifestyle survey) of blood pressure measurements and self reported common symptoms. Results were analysed by combined stratification and logistic regression. SUBJECTS--7383 (82%) Adults aged 18 and over chosen from the electoral register in England, Wales, and Scotland for the health and lifestyle survey, in whom satisfactory physiological measurements were taken, from 9003 in the interviewed sample. MAIN OUTCOME MEASURES--Body mass index, smoking, social class, exercise, self declared physical illnesses, hours slept, use of drugs, and psychological illness as determined with the general health questionnaire assessed as potential confounders. RESULTS--True confounders were sex, age, taking of drugs, physical illness, exercise, and body mass index. A negative association was found between systolic blood pressure and self reported tiredness and feeling faint, which persisted after adjustment for the confounders. The association was strongest in women aged under 50...

If this interpretation is correct, otological symtoms of intracranial hypotension and post lumbar puncture are predicted to be greater in younger persons.

What part of the brain generates dizziness? In the absence of any clear idea or evidence, why not consider the simpler explanation that it comes from the ear?

Dear Anthony,

Thank you for your question. This topic is not an easy one, of course. During hypotension you may feel "dizzy", "blurred vision", imbalance, lightheadedness etc. We have seen people report dizziness both due to hypotension and with appropriate haemodynamic parameters during the same examination session. They were not able to tell the difference. However, when the hypotension sequence is in operation they feel tired first, then they used to lose their vision, and then, quite abruptly, they faint. Dizziness may appear in any moment during this sequence. Maybe you are right that it comes from the local hypoperfusion in the balance organ. So, it might be a warning signal coming from the brain and telling the subject to get down as soon as possible. So, according to your idea, first the retina perfusion is compromised (blurred vision), and then the cochlear perfusion. When the global tissue saturation decreases (we can see it through cerebral oxymetri) below a threshold value, the subject faints. Do you agree?

Best,

A

Dear Gordon,

The population study you quote from Wessely et al seems to support the link between aging and patency of the cochlear aqueduct, and the working hypothesis of dizziness as a result of endolymphatic hydrops due to a contraction of the perilymph volume due to significant hypotension.

The following website illustrates the relationship between the perilymph, endolymph, organ of Corti and Hair Cells beautifully. Hence the activation of the inner ear leading to dizziness, is due to a pressure disequilibrium between the endolymph and periplymph, rather than as a direct effect of lack of vascular perfusion per se.

Thank you once again for the clarifications. I have learnt something new.

Even though we may not have hard evidence to prove the connections between the reduction in the incidence of dizziness as age progresses in the setting of severe hypotension to the narrowing of the Cochlear Aqueduct, this seems the most plausible explanation at present.

It would be most interesting if there are are further input from others working in this field to further share their insight.

This relationship between the inner ear and blood pressure actually have pertinent clinical ramifications, as I have observe a series of cases where elderly patients have been treated with sequentially increasing multitude and doses of anti-hypertensives in the presence of severe dizziness with progressively worsening dizziness and secondary hypertension as result of the distress from the dizziness.

Gradual reduction of the multiple anti-hypertensives in this setting have resulted in resolution of the dizziness and normalisation of the blood pressure, to everyone's surprise. In some occasions, cessation of anti-hypertensives have led to the unmasking of severe postural hypotension requiring pharmacological treatment before the symptoms of dizziness are resolved.

I would assume that in this subgroup of patients, their Cochlear Aqueduct is still patent despite their advanced age.

I apologise that these are unpublished observations due to the small numbers at present, but I will endeavour a case series report in due course.

I wonder if other clinicians have seen similar clinical phenomenon in the very elderly in their practice?

http://www.cochlea.eu/en/cochlea

"So, according to your idea, first the retina perfusion is compromised (blurred vision)"

Blurred vision is such a common accompaniment of endolymphatic hydrops, Meniere's disease and vertigo, that I think it is a direct vestibular effect on eye movement control.  See Goto et al (2012), sixth posting after this one, for an example of probable hydrops with blurred vision due to syncope.

" When the global tissue saturation decreases (we can see it through cerebral oxymetri) below a threshold value, the subject faints. Do you agree?"

No.  I still don't see the brain has any part in this.   When the vestibular system has lost control of the vascular system, I think it simply operates the Off switch.   It is similar to concussion from a sharp rotatory blow that overstimulates the acceleration sensors in the ear, causing a sudden shutdown (knockout).

"This relationship between the inner ear and blood pressure actually have pertinent clinical ramifications, as I have observe a series of cases where elderly patients have been treated with sequentially increasing multitude and doses of anti-hypertensives in the presence of severe dizziness with progressively worsening dizziness and secondary hypertension as result of the distress from the dizziness.  Gradual reduction of the multiple anti-hypertensives in this setting have resulted in resolution of the dizziness and normalisation of the blood pressure, to everyone's surprise"

I am not surprised, as I cannot find any evidence for a causal link between hypertension and dizziness.  In fact I am going to put up a question about this on RG, to flush out those who think that there is a connection but cannot supply the evidence.  When I reviewed the literature on musical hallucinations and drugs, it was striking how often antihypertensives were involved, evidently by lowering pressure so much that a hydrops was induced, with attendant audiovestibular hyperexcitation. 

When I reviewed the literature on musical hallucinations and drugs, it was striking how often antihypertensives were involved, evidently by lowering pressure so much that a hydrops was induced, with attendant audiovestibular hyperexcitation.

Excuse my unqualified question ( I am a cardiologist): how a low blood pressure may induce hydrops in the vestibular system?

When the vestibular system has lost control of the vascular system, I think it simply operates the Off switch. It is similar to concussion from a sharp rotatory blow that overstimulates the acceleration sensors in the ear, causing a sudden shutdown (knockout)

This is very interesting. I have seen hundreds of patients faint during provocation tests (such as HUT). Yes, you are right, they faint in an on/off manner (=switch). The problem with your theory is that Gert van Dijk noticed that EEG flattening is a typical global response form the brain (link below). I do not say it is impossible but your hypothesis should be able to explain these encephalographic phenomena, which are synchronised with the global hypoperfusion according to Gert.

I would like to know more about the symptom-generating (=dizziness) and switch-like (=syncope) function of the vestibular system. If I understand you properly, the vestibular system is a warning and control system in regard to global cerebral hypoperfusion + skull trauma? Is it a sort of cerebral guardian?

http://www.ncbi.nlm.nih.gov/pubmed/24343112

Dear Artur,

Thank you for the reference to the work of J. Gert van Dijk et al. It is fascinating to see the direct correlation between the haemodynamic and EEG changes on one graph. It clearly shows what happens at the point of syncope when the cardiovascular function collapses catastrophically.

I must apologise for any confusion, but perhaps there is more than one system which functions as "protective" in the event of severe hypotension:

1. severe dizziness (leads to self-preserving behaviour to seek the supine position) and

2. syncope (leads to a supine position which will optimise the chances of survival of the individual)

The lack of symptoms of dizziness makes severe postural hypotension even harder to pick up and leads to more physical damage from the resultant fall secondary to the syncopal attack from cerebral hypo-perfusion, as the patient would not have had any warning of the impending collapse (i.e. no warning to sit oneself down or hold on to something or brace for the fall).

In evolutionary terms, syncope must be the fail-safe system of self-preservation of "last-resort", as the individual is bound to sustain some injury from the fall. From the design perspective, it would not be surprising for these 2 protective mechanisms (dizziness and syncope) to have completely different activating triggers.

I have read the paper by J. Gert van Dijk. I wonder if they have some data on the symptoms of dizziness, as the ages of their cohort ranged from 7 to 84 years old? It would be really helpful to see if there was any correlation at all between the EEG changes, age and symptoms of dizziness.

Regards,

S.Chew

It was known for us otorhinolarynglogists that in approximately 15% of dizzy patients having a mixed types of vertigo in the same time e.g. presence of BPPV & vestibular neuritis side aside. So in case of dizziness due to orthostatic hypotension, it is advised to rule out presence of another type of vertigo by referring such patient  to an otorhinolarynglogist to apply VFT including Dixhalbike test, VNG & caloric test. Hearing assessment is indicated if there is true vertigo of vestibular origin.

"Excuse my unqualified question ( I am a cardiologist): how a low blood pressure may induce hydrops in the vestibular system?"

By reducing the perilymphatic and/or CSF pressure, giving relative predominance to the endolymphatic system.   The same mechanism explains audiovestibular symptoms after lumbar puncture, CSF leaks, etc.  The case history below indicates prominent symptoms or peripheral audiovestibular disorder with sudden lowering of blood pressure (most likely due to hydrops).  See also my previous RG responses.

Auris Nasus Larynx. 2012 Oct;39(5):531-3. doi: 10.1016/j.anl.2011.10.003. Epub 2011 Nov 6.

Neurally mediated syncope presenting with paroxysmal positional vertigo and tinnitus.  Goto F1, Tsutsumi T, Nakamura I, Ogawa K.

Abstract

A 72-year-old man with positional vertigo and tinnitus was referred to us. He did not want to perform provoking test except once due to his fear. No positional nystagmus was provoked. He found that his attacks usually occurred when he lay on his right ear. From his clinical history, benign paroxysmal positional vertigo was suspected. Conventional pharmacotherapy as well as non-specific physical therapy did not have significant effect. His feeling of positional vertigo with pyrosis was actually presyncope. We suspected cardiovascular disorders, and referred him to a cardiologist. Portable cardiogram monitoring revealed paroxysmal bradycardia. He was diagnosed with neurally mediated syncope, and a pacemaker was implanted. His paroxysmal dizziness soon disappeared. It is important to study the clinical history of the patients in detail, as they are not always able to accurately explain their symptoms. We should carefully rule out cardiovascular disorders, especially when we see the patients with suspected BPPV without the characteristic positional nystagmus.

" The problem with your theory is that Gert van Dijk noticed that EEG flattening is a typical global response form the brain (link below). I do not say it is impossible but your hypothesis should be able to explain these encephalographic phenomena, which are synchronised with the global hypoperfusion according to Gert."

I don't see that this is a problem.  If the vestibular system is as important as I think it is in regulating arousal and autonomic control, than it will be driving many EEG rhythms.  When we want to get some sleep, we tone down the vestibular system by lying quietly in bed.  In near-death experiences, we retain vestibular sensations in the absence of EEG traces.

"I would like to know more about the symptom-generating (=dizziness) and switch-like (=syncope) function of the vestibular system."

Look up Drop Attacks, as occur in peripheral ear disease, especially Meniere's disease.

Dear Samuel,

Please, see the email address to Gert. I think you can ask him this question directly.

[email protected]

Dear Anthony,

Do you mean that drop attacks (when people remain conscious but suddenly fall) are the vestibular system disease? It is really intriguing. I do not remember that I heard such an explanation. I haven't heard either that Meniere's disease is linked to drop attacks. What I heard was that drop attacks are due to "sudden neural uncoupling" with unexplained underlying mechanisms. They are much less frequent than previously believed. But tell me more about your theory how people faint due to cerebral hypoperfusion. It is true that they faint abruptly. You suggest that the hypoperfusion of the vestibulocochlear system(let us say with SBP below 60 mmHg), when the critical value is reached, starts an active process of switching the brain off? But how? Which brain structures are involved? Another question is "dizziness". Some people feel rotatory vertigo, some a nautical one. Which one is due to hypoperfusion of the vestibular system? Logically, it should be the nautical one.

Finally, the switching off process (fainting) is very rapid. How can a hydrops be responsible for that? Or do you mean dizziness only?

Thank you for your answers.

I don't think the idea that drop attacks originate in the vestibular system is controversial - see this from Wikipedia:

A Drop attack is defined as a sudden fall without loss of consciousness. Drop attacks stem from diverse mechanisms including leg weakness and knee instability but have also been attributed to transient vertebrobasilar insufficiency, epilepsy and unstable vestibular function among other reasons. Those afflicted typically experience abrupt leg weakness, sometimes after sudden movement of the head. The weakness may persist for hours. The term drop attack is used to categorize otherwise unexplained falls encompassing a wide variety of etiology and is considered ambiguous medical terminology. Drop attacks are currently reported much less often than in the past, possibly as a result of better diagnostic precision.[1][2] In neurology, the term drop attack is used to describe certain types of seizure which occur in epilepsy.[3][4] Certain debilitating conditions associated with Ménière’s disease are also called drop attacks or Tumarkin drop attacks by some authors.

I don't pretend I know the precise vestibular mechanism involved (sudden membrane rupture?).   But is is quite clear there are switches inside the inner ear, hence drop attacks and sudden loss of consciousness.

This below is a good way to investigate the labyrinthine reflexes involved in vascular control and consciousness.

High-G training is done by aviators and astronauts who are subject to high levels of acceleration ('G'). It is designed to prevent a g-induced Loss Of Consciousness (abbreviated G-LOC), a situation when g-forces move the blood away from the brain to the extent that consciousness is lost. Incidents of acceleration-induced loss of consciousness have caused fatal accidents in aircraft capable of sustaining high-g for considerable periods. (from Wikipedia)

"But how? Which brain structures are involved?"

Don't know, but the vestibular system has very large inputs into the reticular activating system, and is heavily involved in sleep regulation for example. 

"Another question is "dizziness". Some people feel rotatory vertigo, some a nautical one. Which one is due to hypoperfusion of the vestibular system?"

This is an easy one.  I think rotatory dizziness (vertigo) probably only originates in the labyrinth. All other types dizziness, lightheadedness, etc, etc, usually also start in the ear.  I do not think they originate in the brain unless accompanied by obvious neurological signs.   I think trying to localise disorder by type of giddiness is a misleading waste of effort. 

Hi,

I join the discussion a bit late... I am ENT and i use since 2004 a mechanical assistance (TRV chair) to improve my BPPV's management. I received since ten years many patients that were diagnosed as hypotensive linked dizzy symptoms. I would like to propose an hypothesis to explain these symptoms.

Most of the time the observation of the dizziness occurs during waking up or standing up from a chair and that leads to the diagnostic of hypotension. In fact it could be a misunderstanding of the cause of the symptoms: during some of the BPPV the particles located in the semicircular canals are sometimes very little (5 to 10 micrometers) and then will be very few sensitive to the gravity and will not produce a real postional vertigo but unsteadiness (mild BPPV). These particles make increasing the weight/density of the endolymphatic liquid in the canal and the whole canal becomes sensitive to the gravity. If by exemple it is a lateral canal, the patient will feel dizzy during looking downward and upward because of the vertical position of the canal. In a so situation the collumn of liquid in the canal pushes or pulls the ampulla and makes a response of the canal.

It could be interresting to test the hypotensive patients by sitting up with the lateral canals plane always in horizontal position to avoid its stimulation.

These mild BPPV are not easy to treat and the addition of kinetic energy thanks to the chair is very helpfull to permit to the particles to move toward the exit of the canal...

This hypothesis could explain the inconstant link between the observed hypotention and the dizzy symptoms...perhaps two coexisting pathology...

"These particles make increasing the weight/density of the endolymphatic liquid in the canal"

BPPV is far more logically and simply explained by by microbubbles of air than by inert heavier-than-water particles.

Hi Anthony

Is it your hypothesis? The air is disolved in the endolymphatic liquid in few days or weeks...not the calcium carbonat. Why therapeutic maneuvers would work with a so origin?

"Is it your hypothesis?"

Yes -- see my pub list.  The air is in bubbles, at least to begin with, not dissolved, ie micropneumolabyrinth.   I do not think these minute bubbles can be in the endolymph, otherwise vertigo would occur immediately on head turning.  They must be moving around with difficulty in the perilymph, which accounts for the longish latency.  This also explains the occurrence of BPPV after head trauma when it is very likely perilymph leaks out of small cracks/fistulae, enabling air bubbles to be sucked back into the perilymph.