Absolutely without a doubt this one is a sleeper for the general practitioner, Anthony. We have documented thousands of keratitis obturans, external ear cholesteatoma, middle ear cholesteatoma, and otitis media presenting a potentially life threatening development. We find the majority of adult cases arise not from primary otitis issues but secondarily to jaw and tooth problems, which is why we have teamed up with dental researchers wherever possible in sorting out the etiologies and pathophysiology. Pseudomonas (anaerobic amoeba type) seems to be the worst offender, but when pseudomonas are involved we find also a lot of other microorganisms such as s. aureus, enterbacter clocae, and aspergillus favus (these latter in the external meatus). This admixture creates a septic environment that grows and grows until it finally invades the circulatory system and becomes systemic. What is amazing is how much these can grow without being discovered by the body's immunological watchdogs. Usually, the most they conjure up are a troubling cascade of proinflammatory cytokines bringing what appears to be idiopathic inflammation throughout the body. Even when bone cells are being brought up from the mastoid process into the keratosis the vascular system seems little involved, until about year five. Then, it looks like an appendecitis in blood tests with the same life threatening markers. Insidious is the word we use most often with the advancement of these conditions, because almost no one, not even the attending physician, sees it for what it is. They instead confuse the growing mass as impacted cerumen and/or simple otitis. I am attaching one of my monographs on this topic. We see so many cases in our clinic that we are puzzled as to why more professionals are not noting the dramatic increase of these in the population. 

Let me answer briefly. Yes, It is.

Absolutely without a doubt this one is a sleeper for the general practitioner, Anthony. We have documented thousands of keratitis obturans, external ear cholesteatoma, middle ear cholesteatoma, and otitis media presenting a potentially life threatening development. We find the majority of adult cases arise not from primary otitis issues but secondarily to jaw and tooth problems, which is why we have teamed up with dental researchers wherever possible in sorting out the etiologies and pathophysiology. Pseudomonas (anaerobic amoeba type) seems to be the worst offender, but when pseudomonas are involved we find also a lot of other microorganisms such as s. aureus, enterbacter clocae, and aspergillus favus (these latter in the external meatus). This admixture creates a septic environment that grows and grows until it finally invades the circulatory system and becomes systemic. What is amazing is how much these can grow without being discovered by the body's immunological watchdogs. Usually, the most they conjure up are a troubling cascade of proinflammatory cytokines bringing what appears to be idiopathic inflammation throughout the body. Even when bone cells are being brought up from the mastoid process into the keratosis the vascular system seems little involved, until about year five. Then, it looks like an appendecitis in blood tests with the same life threatening markers. Insidious is the word we use most often with the advancement of these conditions, because almost no one, not even the attending physician, sees it for what it is. They instead confuse the growing mass as impacted cerumen and/or simple otitis. I am attaching one of my monographs on this topic. We see so many cases in our clinic that we are puzzled as to why more professionals are not noting the dramatic increase of these in the population. 

The companion monograph that goes with the keratosis obturans topic (above) is attached here. This one is about how septic tooth and jaw problems cause otitis cases of the ear, both in the middle and outer ear. Overlooked 99% of the time, I would say.

"We have documented thousands of keratitis obturans, external ear cholesteatoma, middle ear cholesteatoma, and otitis media presenting a potentially life threatening development"

   I agree there can be dangerous and undetected outcomes, but the question is the temporal and causal chain.  For the purposes of this question, to keep it sharp and focussed, I think it better to exclude KO and OM secondary to tumours or jaw or teeth disorders.   I have also modified the question to focus on young adults with OM of unknown origin.

   I think cholesteatomas in the ear, and the rest of the body for that matter, represent a failed attempt to close a persistent fistula.  I do not think they are caused by OM.

   I think a good model of an infective cause of complicated OM is chronic diabetes.  This weakens bone, and lets in Pseudomonas.  However, I think this only serves to highlight the difference from a typical non-systemic case of unilateral brain abscess in a young adult, as supported by this quote from above:

"This admixture creates a septic environment that grows and grows until it finally invades the circulatory system and becomes systemic."

"Let me answer briefly. Yes, It is."

RG should be a forum where ideas are critically discussed.   If we do not understand, or worse, misunderstand, the relation between OM and brain abscess, we will continue to overlook such potentially fatal cases.  If OM is causal, there should be a dose effect, so it is then all too easy to assume that what looks like a trivial case of OM cannot have cranial co-morbidity. 

Dear Anthony. Let me add my answer specifics. We were taught at the Medical University. There anastomosis between the blood vessels of the head and neck. Thus, there anastomoses between the vasculature of the outer, middle and inner ear, on the one hand, and the vessels of the brain, on the other hand. We accept these postulates. Further, if there is inflammation in the ear, there is always a danger of infection by the vasculature to the brain. But why this occurs sparsely? Because any pathological process determined by the intensity of the pathological process and functional state of protective systems (immune, endocrine, humoral, nociceptive). If the body's defenses "weakened" the fatal inevitability.

"Thus, there anastomoses between the vasculature of the outer, middle and inner ear, on the one hand, and the vessels of the brain"

I think the lymphatic routes (eg perivascular prelymphatic pathways) are more important.

"Because any pathological process determined by the intensity of the pathological process and functional state of protective systems (immune, endocrine, humoral, nociceptive)."

If these general processes are decisive, then there should clearly be a strong dose effect.  In particular, cranial complications should be far commoner or even restricted to bilateral chronic otitis, which  is certainly not the case.

I agree, the blood and lymph systems are the preconditions for the manifestation of the infection from the ear to the brain.

Anthony, we have tracked every examined idiopathic adult case of KO to causes as diverse as jaw/teeth, unresolved pnuemonia, implanted prosthesis, ingrown toenail, or other identifiable subclinical or clinical infection. A few have been traced to external ear trauma and stand alone OME, but they were far rarer than the others I mentioned. I know it seems spread out from the topic of discussion, but my point was that these are increasing in our population as other chronic pathologies continue to increase, and that examined under the immunological lens, even down to those contributors that do not rise to clinical significance or seem unrelated, that it is almost always possible to identify origin of such conditions. When we examine other clinic's findings that tend to get a lot of etiology unknowns, and look at the same cases, we find they just didn't investigate deeply enough to make the association. That these can cascade into invasion into the bainstem and elsewhere is usually a matter of time rather than etiology. Pseudomonas, for instance, is patient and inisidious and opportunistic--nearly always revealing itself years after the initial process started. That is one reason we are so cautious about the promotions of hearing aids that are left in the ear for 30 days at a time, like the Lyric is--the interrupted desquamation added to a near anaerobic environment sets the patient up for serious ear pathologies. The same for abcessed teeth that go undetected for years--From this view, even the vestibular Schwannomas and acoustic neuromas could have an identifiable start with the infection/inflammation cascade from elsewhere in the body, genetic tendencies notwithstanding. Those are some of my thoughts on the topic, and ask your forebearance if they seem peripheral. In my work the looming question is from where did it come and how, and then our current body of knowledge in application can be expanded to include prevention.        

Practically, i met a young patient, about 5 years old, referred to me from pediatric department due to complicated severe right otitis media. The history revealed that this patient had right AOM which was not properly treated, then developed behavior change & intractable fever with right sided headache. CT-scan brain with contrast revealed right sided brain abscess with sigmoid sinus thrombosis. Fortunately this patient improved by IV antibiotherapy, heparinotherapy & strict follow up by me (ENT), pediatrician & neurologist. My diagnosis was right AOM complicated by acute brain abscess & sigmoid sinus thrombosis. This brain abscess was of otogenic origin i.e. otogenic brain abscess because its symptoms developed after AOM symptoms. I think, AOM in this case, can not be considered secondary to brain abscess because brain abcess symptoms did not precede AOM symptoms.    

In terms of young adults, I feel we will find etiologies common to both children and adults, because of their chronological proximity to both. Perhaps, in this case, primary OME further influenced on physical development and maturation relative to chronic upper respiratory infections roughly equal to those of other etiologies (environmental, pathological, etc.). You mentioned the development of diabetes, which not long ago was so far removed in any appreciable numbers in the young, but today is rapidly growing more prevalent. As a general rule, our finding is that when OM co-occurs with brain abcesses, we feel we can assume the OM was contributive, if not causal, to the brain abcesses. I doubt if many cases will be found simply coincidental. I see your point with Hippocrates' hypothesis, but in practice, I don't see the cerebral leakage into the middle ear cavity that can cause these in the numbers we see today. We know that immunological processes are highly active in the ear region and comparitively sanguine in the regions surrounding. But I feel your question is a timely one and one needing addressed on a large scale in the interdisciplines, as the co-occurence seems to be increasing in the population.    

"From this view, even the vestibular Schwannomas and acoustic neuromas could have an identifiable start with the infection/inflammation cascade from elsewhere in the body"

I think VS/ANs are the result of out-of-control nerve repair for some sort of damage, ie they are a mechanical phenomenon.  If infection is present, it is secondary to localised physical damage.   If systemic factors are involved (eg neurofibromatosis), the tumours are usually bilateral, easily separable from VS/ANs which are unilateral. 

"Those are some of my thoughts on the topic, and ask your forebearance if they seem peripheral."

I don't mind at all.  Often the breakthrough for one topic comes from thinking about another.   While it may be hard to pick up these side issues via RG, they are easily found via Google.

 "I think, AOM in this case, can not be considered secondary to brain abscess because brain abcess symptoms did not precede AOM symptoms."   

I am not claiming, nor did Hippocrates I think, that the prime mover was brain abscess.  In this case I think it was overload of the physiological CSF/lymphatic pathways around the sigmoid sinus. 

"then developed behavior change & intractable fever with right sided headache"

But was this because the ear was still discharging, or had the otorrhea stopped?   There is an inverse relation between otorrhea and cerebral mischief.  And why was the OM acute, not chronic, and why had it not spread to the other side?

There are thousands of case reports like that of Hazem in the literature. Here is a typical one briefly reported in Medical Times 1850;21:257.  I have highlighted in bold those features requiring an explanation (not ad hoc rationalisations) from those believing in the Otitis First theory:

"Dr Banks exhibited a specimen of caries in the petrous portion of the temporal bone. The subject of it, before coming into hospital, was deaf, and at one time had a copious purulent discharge from the ear.  In hospital, he complained of pain in the forehead; very intense and intermittent; feverish heat of skin; the pulse weak and very irregular, changing from 80 to 60, and as low as 54. He had delirium, became gradually heavier and more insensible, and died eighteen days after the first rigors and sickness.  At the post-mortem the temporal bone was found highly carious -- perforated in two places; a probe grating upon loose portions of it.  The dura mater corresponding to one of the apertures was perforated and sloughy; the brain also dark-coloured, with a large abscess in the left middle lobe.  There was also a large collection of "thick green and very fetid pus beween the dura mater and the mastoid and petrous portion of the temporal bone, extending to the middle line posteriorly, and downwards nearly to the foramen magnum," -- a curious but instructive instance of the amount of mischief that may go on in this locality in a very few days.  The abscess the Society seemed to consider of only five days' formation" 

Those who adhere to the Otitis First theory need to answer the following queries:

The alternative Hippocratic explanation is simple;  the prime source was bone disease and/or a knock on the head.  CSF gushed into the ear, forming a niche for secondary infection.  The CSF fistula self-healed, but as the brain was no longer able to decompress into the ear, cerebral symptoms arose.

Thank you, Anthony, for such well reasoned and thorough replies. I guess the reason I subscribe to infection first, then inflammation cascading to neurological abnormalities, is because in the models of disease I've worked on in chronic disease this is precisely the procession we see. The delayed onset of symptoms could be a bit like the last gasp effect in hair cell loss from amino gycoside use with as much as 6-12 months offset of measurable threshold changes after toxic exposure. In trauma cases the effects are almost immediately noticeable. Of course, bringing in the toxicity angle, it may at first appear to be off-topic, but in reality toxicity creates an often insidious assault followed by free radical damage to the site of lesion and eventually in other areas of the body, its main effect not far different from a chronic clinical or subclinical infection. We also see this in teeth/jaw sepsis that often follows the trigeminal route to various parts of the ear. The trigeminal being a cranial nerve, it would not be too much of a stretch to surmise that the immunological cascade could go anywhere the trigeminal goes, including the motor centers which it innervates and points between. We know the inflammatory response is there; but I am not sure we understand how the infection/free radical connection happens in that cascade. Perhaps someone does and I've just not read their work. But we have conclusively seen the effect from teeth to external meatus and tympanic membrane, but are not sure if it can or does continue from that point to elsewhere.

" But we have conclusively seen the effect from teeth to external meatus and tympanic membrane"

I am not sure I have quite got my head round temporomandibular joint syndrome (Costen), but am fairly certain it must be from some sort of mechanical effect of misplaced jaws or teeth on local lymphatic drainage or circulation, making it unnecessary to postulate any infection or inflammation.

I'm speaking of infection, Anthony, particularly sepsis hidden under crowns and bridges, and under fillings and around the gumline. In the cases of KO and OME in adults that we see we usually track these issues to teeth/jaw infections, especially in cases of periodontal disease and where they are taking those dastardly osteoporosis meds that rot the jawbone. On the TMJ problem I don't see the effects affecting the cascade we are talking about. But we do see a lot of KO and OME cases that will not resolve until the teeth problems are addressed. Maybe it is not a problem in UK, but it is a big one over here.

I am an ENT surgeon.  I have seen several cases of "otogenic" abscess of the brain.  The case you describe from 1850 is the same as the cases we see today: indeed I operated on such a case last year. 

In such cases there are typical symptoms of ear infection, and then a few days later symptoms of brain abscess.  When I have operated on these ears you can see how the pus has damaged and eroded the bone forming the roof of the middle ear (the tegmen) to spread into the ear.  However spread is also thoght to occur via local venous channels.  There is a CT scan clearly showing this process in my article on "Cholesteatoma" in the British Medical Journal (see my publications).  It is true that fluid can leak from the brain into the ear through for example previous trauma causing tegmen defects, but that is a CSF leak, not pus leaking from the brain.  You are right however to suggest that there may be anatomical variants in the structure of the tegmen that make some people more prone to otogenic abscess.

Why can the ear stop discharging before the onset of brain abscess?  This is not unusual - the immune system can fight infection better in the middle ear than it can in the brain, where it instead walls off infection as an abscess.  So the body may finally defeat the previously overwhelming ear infection, but if it has spread into the brain by then, it may not be able to get rid of that component.  The brain abscess will then slowly grow until it gets big enough to cause symptoms a few days later.  Copious pus and "fistula" (perforation of the eardrum) are simply markers of severity of ear infection.  A severe ear infection is more likely to cause copious discharge, to cause perforation, and to cause subsequent brain abscess.  Acute infection is more likely to cause this than chronic because with chronic infection the infection usually represents a stalemate where neither the bacteria nor the immune system have won.  A chronic infection does not usually overwhelm the body so much that it can spread to the brain, but having said that you do occasionally see brain abscess from chronic ear infection.

Anthony you asked for cases of symmetrical bone erosion to suggest that there is a symmetrical process in acute ear infection.  Nothing in biology is truly symmetrical, I have never seen such a case.

Yes, trauma, which I left out above, thinking in terms of pathophysiology instead.  Thank you, Dr. Bhutta.

 " A severe ear infection is more likely to cause copious discharge, to cause perforation, and to cause subsequent brain abscess."

Yes, but why on earth does this happen before the other ear becomes infected?  This makes absolutely no sense to me.  The immune system operates systemically, not just on one side of the body.

 "It is true that fluid can leak from the brain into the ear through for example previous trauma causing tegmen defects, but that is a CSF leak, not pus leaking from the brain"

I am not claiming that pus leaking from the brain initiates the process.  It will often be CSF from a traumatic leak.   Hippocrates describes a case of extradural hematoma from a slap on the head, where it was blood leaking into the middle ear that became infected. 

Cerebral-spinal fluid can also be in the mix on this in the case of head trauma. But immunology generally follows neurology in pathogenesis and progression. So it is entirely possible, even probable, to be contralateral from site of lesion in the cortex to site of infection. in the ear region. Just my two cents on the mystery.

So yes, there are cases of CSF leak into the middle ear cleft, often following trauma, sometimes spontaneous.  I have repaired  a couple of these leaks (you place new fascia or bone over the skull defect), and the reason for repair was to prevent a long-term risk of meningitis (infection in the ear can very easily spread into the brain is there is no covering).  What Hippocrates described still happens today.  We tend to repair these defects within a few weeks or months because the risk of meningitis is actually quite low, meaning immediate repair is not necessary.  The same is true of CSF leak in the anterior skull base.  In Hippocrates time such a repair could not be undertaken., surgery was a very crude art at that time

Anthony I am not sure I understand your query about why a brain abscess occurs if / before the other ear gets inflamed.  Ear infections arise from the back of the nose where the bacteria in the back of the nose ascend up the Eustachian tube and then infect the middle ear space.  Usually ear infection happens on one side, but it can happen on the other side.  It is the same as lobar pneumonia - one segement of the lung on one side gets infected.  Once an ear is infected the infection can spread directly from that ear superiorly into the brain on the same side.  The other ear getting infected is independent of the brain getting infected.  When we see both ears infected that usually happens simultaneously.  When we see the brain getting infected it is usually a few days after the onset of the ear symptoms because the infection has to have time to spread and also reach sufficient severity to cause symptoms.  Perhaps there is low grade infection in the brain in some children that the immune system clears up - if these children get better we may never know that this had happened as they may never come to medical attention.

Excellent observations, Mahmood. I am not involved in surgery, but am called upon to help with pathophysiology in some cases. Anthony has raised an excellent and thought provoking question.

"Anthony you asked for cases of symmetrical bone erosion to suggest that there is a symmetrical process in acute ear infection. Nothing in biology is truly symmetrical, I have never seen such a case"

Thanks for confirming you have not seen a bilateral case of otitic brain abscess.   I am still waiting for someone to find a well-described one in the literature.

• Otosclerosis is a bone disease, often bilateral, sometimes remarkable symmetrical.
• I have tested hundreds of cases of Meniere's disease, but only rarely found a truly unilateral one, even if lowered stapedial reflex thresholds were the only abnormality.   Cases are, however, often asymmetrical.
• Bilateral glue ear is very common.

 "Ear infections arise from the back of the nose where the bacteria in the back of the nose ascend up the Eustachian tube and then infect the middle ear space"

They go up both tubes!

Hi Anthony

Yes, otosclerosis is often a bilateral disease but the severity of disease (hearing loss) is rarely symmetrical at presentation.  Bilateral glue ear is common, but I have often coincidentally diagnosed unilateral glue ear - there must be lots of unilateral glue ear that does not come to attention.  In cases of bilateral glue ear, the degree of inflammation (measured by cytology or gene profiling) is rarely symmetrical - I have data that show this.

I guess what I mean is that the severity of disease is rarely symmetrical.  If a disease has a strong genetic basis then symmetry is more likely, if it has a strong environmental basis, symmetry is less likely.  All the disorders you mention likely have both a genetic and environmental component in aetiology.

" A severe ear infection is more likely to cause copious discharge, to cause perforation, and to cause subsequent brain abscess. Acute infection is more likely to cause this than chronic"

How then to explain Wilde's outpatient caseload (Med Times 1851;23:345):

• Otorrhea, chronic:             131 cases, mostly children 
• Otorrhea, acute:                    1 case
• Otorrhea, with perforation:  19 cases (16 of these adults)   
• Otorrhea, with caries:            2 cases
• Brain abscess:                       0 cases

" When I have operated on these ears you can see how the pus has damaged and eroded the bone forming the roof of the middle ear (the tegmen) to spread into the ear"

Here and elsewhere I have commented on the fact that general otitic tissue erosion does not begin to explain why the damage is so discrete and localised.   So here is a case where there clearly was massive generalised damage, yet no intracranial complication.  Circumscribed preexisting vulnerability evidently antedates otitis with cerebral otitic complications.

**********************************************************************************

 A British Army wife in India had head pain for 20 days and a temperature of 105. Seven years before she had an abscess behind the ear which left a small discharging sinus behind. On admission, 137 extremely hungry and very active fly larvae 1.7cm long were removed from a deep post-aural cavity. "The destruction of the tissues, as will be seen from the photograph, was frightful.  Almost the entire petrous portion of the temporal bone was gone and the damage was dangerously approaching the lateral sinus. The dura mater was exposed."

Sutton EA A case of myiasis of the temporal bone J Royal Army Medical Corps 1926;47:61

In medicine, if A causes B, more A should cause more B.   Absence of this dose effect should be a red light, casting doubt on the causal nature of any correlation.  Here is a case series where brain herniation into the middle ear or mastoid, which can be associated with brain abscess, was allegedly due to otitis media (Wootten et al Laryngoscope 2005;115:1256):

Here are the facts that indicate serious ear disease; surgical disease beginning in childhood in 41%, yet average age at first surgery was 43y;  over half were actively draining purulent material at presentation; the disease was "long-standing" and "advanced"; "serious complications in people with already extensive disease"; before presentation, patients had an average of 3 prior procedures, and afterwards one needed another 4 operations.

Yet not a single one of these 12 cases had any problem on the contralateral side - they all had unilateral ear disease, quite impossible if otitis was the driving force.  Of course, had the primary trouble been some developmental problem of increased pressure in the brain and/or CSF, as Hippocrates would have it, the decompression into the ear would only need to occur on one side.

Interesting association between CSF leak and brain abscess with occurrence of OM. It's our observation in our practice that brain abscess does not occur with similar frequency as OM but I presume that if ear infection is not suppurative it is unlikely that it will be metastatic. The CSF leak may in fact be a response to suppurative inflammatory process in a setting of early encephalitic phenomenon.

Excellent analysis, Anthony and Olubunmi. 

"It's our observation in our practice that brain abscess does not occur with similar frequency as OM but I presume that if ear infection is not suppurative it is unlikely that it will be metastatic"

I am not claiming that brain abcesses cause OM, rather that both can arise from a developmental CSF leak.  If the leak is large, fluid can discharge down the E tube or out of the ear, and may not get infected.  A small leak may stop and start, and the retained fluid may get infected at the brain end (abscess), or in the ear (mastoiditis).

"The CSF leak may in fact be a response to suppurative inflammatory process in a setting of early encephalitic phenomenon."

Some of these CSF leaks have evidently been present (though unrecognised!) for decades. Any metastatic or encephalitic process is surely bilateral.

" I see your point with Hippocrates' hypothesis, but in practice, I don't see the cerebral leakage into the middle ear cavity that can cause these in the numbers we see today."

His main point was that there was physiological drainage of CSF into the lymphatic system via eyes, nose, ears, etc.  People differed as to the time at which any excess drainage and hence ear infections occur.   This obviously applies to bilateral otitis.  As for unilateral otitis, he describes a case of extradural hematoma with bloody otorrhea after a slap on the head. He also notes cases where otorrhea reduces brain symptoms.

Further evidence against the primary role of otitis:

Smith SM Chronic recurrent suppurative otitis media and its relation to mastoid and intracranial complications  Ann Otol 1908;17:723:

Smith starts by noting "Intermittent Otic Discharge More Dangerous than the Constant Variety".   This fact needs a lot of explaining.  If someone said that intermittent alcohol consumption did more damage than regular consumption, we would be rightly incredulous and demand compelling evidence against this unlikely situation.

He gives 3 typical case histories.  In case 1 "acute exacerbations occurred about every three or four months.  in the interim the ear would be entirely dry and free from pain".  No surprise that pain and discharge can co-occur.   However, in case 2 "at times the discharge would cease for a period of about one year, the membrana tympani completely regenerating in the interval, the pain, however, being much worse during the period of cessation of discharge".   In case 3 "the acute exacerbation was ushered in with characteristic headache, nausea and great lassitude, extending over a period of several days, until the discharge again appeared, which in turn relieved the pain considerably, as so often occurs".   These latter cases can only be explained by postulating a reciprocal relation between brain and ear suppuration.   This is analogous to the process in a men's urinal, where water drips into the storage cistern, which suddenly discharges when full into the urinal bowl below.

"One point of interest and importance to which I especially wish to direct your attention, is the fact that we can hardly conceive that all the bone destruction seen in this case could have occurred in the three or four days which marked the acute exacerbation of the chronic recurrent suppurative otitis media, and yet the patient and his family claimed that for eight months prior to the date of this acute exacerbation he did not suffer the slightest inconvenience from this ear and that the same remained entirely dry during that period".  

"At times we are confronted with the statement that an otorrhea has existed for many years without producing untoward symptoms.  So long, therefore, as the patient experiences no actual suffering he is content, often on the advice of his physician, "to let well enough alone"".     But is this GP advice as irresponsible as Smith thinks?

Yes, I agree with the implications you suggest, Anthony. In such cases, they do advance and eventually grow more lethal over time. We've never seen one not continue to grow and invade more surrounding tissues, so it would be indeed negligence to knowingly "let well enough alone'. 

Anthony, with respect a paper from 1908 does not hold that much relevance today.  There was very little understanding of ear disease at that time.  The observation "Intermittent Otic Discharge More Dangerous than the Constant Variety" is not at all surprising to an ear surgeon.  Pus builds up in the middle ear space (a closed space) and if this continues it needs an outlet.  It may burst through the ear drum and cause discharge in which case the pressure is relieved (and risk of intracranial spread negated).  Or it may continue to build, erode through or translocate across  the roof of the middle ear, and cause intracranial complications. Indeed one way to prevent complications of acute otitis media is to drain the ear using a "grommet".  I have never seen intracranial complications in the presence of a grommet.  Relieve the pus by allowing it to drain, and it doesn't spread anywhere else.  The draining ear reduces infectious load.

I operate on the middle ear about 6-7 times a week.  Spontaneous CSF leaks can be seen but are vanishingly rare.  Although your theory is interesting, I'm afraid it is not borne out by clinical practice.

Mahmood, excellent observations. I think, but he can correct me if I'm wrong, Anthony was referring to the progressive lethality of untreated, unreferred cases. Those being managed or treated, of course, will rarely present into the more invasive forms. But in my more than 4 decades in hearing health, research, and education, I've run into many cases of untreated or under-treated cases that festered into life threatening forms--in some cases was the primary cause of death. So much of the literature is silent on these cases, I assume, because they occur outside the realm of a healthcare system. One of my students who used to conduct post mortems on patients dying of non-ear related conditions was stunned to find so many previously undetected advanced choleatomas (outer and middle types, both), acoustic neuromas, vestibular schwannomas, and glomus tumors. I guess it goes to reinforce the cliche "the lack of evidence is not the evidence of absence".  That was a real eye-opener for me. More conditions than we see are percolating below the surface, causing early death in many cases, and the literature is silent on it, though they exist.  

"a paper from 1908 does not hold that much relevance today."

I totally disagree.   Many children died then from ear disease, so in the absence of effective diagnostic tests and treatments, all they had to fall back on were their clinical skills and observations.  Surely they had far more experience in this area than any modern clinician?  

I would be interested to know if any modern clinician has noted and pondered the crucial observation that there may be an inverse relation between otorrhea and cerebral symptoms (References please!).  I read the old literature because I cannot find such detailed descriptions in the modern literature. 

"Pus builds up in the middle ear space (a closed space) and if this continues it needs an outlet.  It may burst through the ear drum and cause discharge in which case the pressure is relieved (and risk of intracranial spread negated).  Or it may continue to build, erode through or translocate across  the roof of the middle ear, and cause intracranial complications. Indeed one way to prevent complications of acute otitis media is to drain the ear using a "grommet". "

An effusion in the middle ear is associated with reduced, not increased, middle ear pressure, as is measured with an impedance meter.  A grommet equalizes this pressure, raising the middle ear pressure to atmospheric pressure.  This allows the fluid to be absorbed or drain away, not usually via the grommet.   I have never quite understood how perforations occur in otitis media.  I think it may be the result of softening of the drum, so that it eventually ruptures at a natural weak point.

This highlights another crucial problem with the otitis-primary theory.   There is a natural centrifugal pressure gradient between brain and mastoid/tympanum, accentuated if there is any middle ear effusion or any increased CSF pressure.   Yet the otogenic theory would have us believe there is a centripetal mechanism.

These two cases of Burgess provide the reductio ad absurdum of the otogenic (centripetal) theory of brain abscess (Practitioner 1911;87:867):   [ I am not going to apologize for quoting these old cases from the days when doctors regularly went on home visits].

They were 8y old girls of good backgrounds with similar misleadingly mild initial symptoms.

Case 1 had near-fatal enteric fever. Five weeks into her recovery she became ill with a high fever. A distinguished aurist diagnosed a recovering acute unilateral otitis media with no perforation, no pus and no mastoid tenderness. An operation was therefore deferred, and she died shortly afterwards.

Case 2 woke on Sat with a high fever. She had no problems with ear or hearing then or any time previously. By Mon night she was moribund. On Tues afternoon he found her dressed and playing with her toys on the floor. "To my look of inquiry, for I was too surprised to speak, I was told that something broke in her ear during the night and a profuse discharge flowed out on the pillows. She then went quietly to sleep...The patient is now a strong healthy young woman slightly deaf on the left side".

From Wikipedia:

"On August 1, 1890, Schliemann returned reluctantly to Athens, and in November travelled to Halle, where his chronic ear infection was operated upon, on November 13. The doctors deemed the operation a success, but his inner ear became painfully inflamed. Ignoring his doctors' advice, he left the hospital and travelled to Leipzig, Berlin, and Paris. From the latter, he planned to return to Athens in time for Christmas, but his ear condition became even worse. Too sick to make the boat ride from Naples to Greece, Schliemann remained in Naples, but managed to make a journey to the ruins of Pompeii. On Christmas Day he collapsed into a coma and died in a Naples hotel room on December 26, 1890. The cause of death was cholesteatoma."

Further information comes from Dr V Cozzolino, whom he consulted on Dec 23rd. (J Larygol Rhinol Otol 1894;8:266).  He "followed Schliemann to the hotel, and finding out who he was, immediately summoned Profs...All agreed that the cranium should be trephined in order to free the brain of pus; but unfortunately the discussion was cut short.. Schliemann had expired".

It is by looking at old cases like these that I am led to suppose that it was the recent operation (not mentioned by Cozzolino!) that killed him, by (inadvertently) blocking off the naturally established drainage route from brain to ear.   So are we absolutely sure this could not happen nowadays?   Are there any post-operative "complications"?

Anthony, you are confusing different types of otitis media.  Otitis media with effusion is a non-purulent effusion and associated with negative pressure in the ear upon resolution (reasons unclear but likely relating to poor transmucosal gaseous exchange).  Purulent otitis media is the only type that causes intracranial infection and that is pus under positive pressure.  Classically there is a bulging drum.  Indeed otitis media is a complex spectrum of disorders, for example look at the histological work of Paparella.  Cholesteatoma is a squamous form of otitis media which is linked to mucosal disease but a different entity that can cause spread into the brain through local activation of osteoclasts and bone erosion - a different mechanism to that occuring in acute (purulent) otitis media.

Incidentally all large scale epidemiological studies show that the incidence of acute otitis media and its complications have hugely reduced compared to 50 years ago, but things are perhaps now at a plateau.

"Purulent otitis media is the only type that causes intracranial infection".

If you have a brain abscess, then, yes, the OM is purulent.    But if you restrict intracranial complications to purulent OM, then you are scrambling around for other ad hoc explanations for otitis-linked conditions like tegmen dehiscences, CSF leaks, encephaloceles, otitic hydrocephalus etc.  These are no problem for the brain primacy theory, they are due to primary defects of brain or bone or drainage routes leading to leakage of CSF into ear spaces, which may or may not become secondarily infected.  One overall explanation is more likely to be correct than several disjointed ones.

One has to go back a long way to find any discussion of cerebral otorrhea, and hence to see the reasons why this theory was dismissed and finally ignored.   See Bruce J On Phlebitis fo the Cerebral Sinuses Lond Med Gaz 1841;27:608-13:--

"It is usually preceded by cessation of the discharge from the ear, and the pain, originally confined to that organ gives place to a severe general headache; fever, stupor, delirium, and symptoms of meningitis, supervene, and the patient may die...

The question relating to the organ primarily affected in co-existing suppuration of the ear and the brain, has given rise to much discussion. M. Itard, in his excellent monograph on diseases of the ear, has adopted the opinion originally maintained by Laubius, that purulent otorrhoea is in many cases merely symptomatic of disease in the brain. He believes that a primitive cerebral otorrhoea exists whenever suppuration takes place within the cranium, and penetrates into the ear by the carious openings in the temporal bone, or by the natural foramina; or, in other words, he considers the otorrhoea, in many instances, as the critical termination of an encephalitis. M. Itard has adduced several ingenious arguments in support of this opinion, but they appear to me to be completely overturned by the reasoning of Lallemand, who has almost succeeded in demonstrating that the lesion of the ear invariably precedes that of the brain... Lallemand naturally

inquires why the purulent matter, presuming it to possess corrosive properties, never effects its escape through any other bone besides the temporal, though there are some which occupy a lower position in the cranium, and which are thinner... "

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Comments:

1. I do not presume that pus has corrosive properties.

2. The objection to selective corrosion applies even more to the ear primacy theory. It seems that pus makes a bee line for the brain, often travelling along narrow fistulous tracts. If it dissolves bone, then it should do this uniformly, not selectively.                                                             3. There are many drainage routes for CSF into the ear and temporal bone.

4. Harmful organisms no doubt reach the brain from the ear, so pus may well appear first in the ear. However, this says nothing about the chain of action beforehand, the breakdown of body defences and creation of isolated fluid pools allowing the bugs to take hold.

5. There a plenty of cases, some already mentioned here above, where sufficient ear trouble does not predate the cerebral complication.

6.  Surely someone can come up with better objections to the cerebral primacy theory? Who wants to argue with Itard? (Not me!).

Dear Anthony, from your pedantic and clear explanation, I realized the main thing. Never hurt otitis.

"Lallemand naturally inquires why the purulent matter, presuming it to possess corrosive properties, never effects its escape through any other bone besides the temporal"

As it happens, there is a condition of general osseous corrosion, where it is instructive to see what happens (Milligan W Diagnosis and treatment of tuberculous disease of the middle ear and its accessory cavities J Lar Rhin Otol 1903;18:136-54):

"A distinct feature of tuberculous invasion of the middle ear is the readiness with which the underlying bone becomes eroded.  Not only does this take place at a much earlier stage than usual in non-tuberculous cases, but is prone to be more extensive, more rapid in its progress, and more likely to end in the formation of large sequestra.  Owing to this early and, at times, extensive destruction of bone, facial paralysis is a symptom of frequent occurrence...In one fatal case of double tuberculous otitis the two temporal bones were so eaten out by disease that only a thin shell remained upon which the middle fossae were poised.  Carious erosion may, and frequently enough does, destroy the stapedio-vestibular articulation, and so opens up the cavity of the internal ear."

So, exactly the conditions to expect brain abscess on the conventional theory that the pus in non-tuberculous otitis was corrosive and hence causal.  Precisely what does not happen:

"The occurrence of intracranial abscesses is, in my experience at least, not very frequent in tuberculous cases.  This is probably due to one of three causes...the destruction of bone which takes place so permits of drainage that the risks of secondary infections are minimized..."

"They were 8y old girls of good backgrounds with similar misleadingly mild initial symptoms.  Case 1 had near-fatal enteric fever. Five weeks into her recovery she became ill with a high fever. A distinguished aurist diagnosed a recovering acute unilateral otitis media with no perforation, no pus and no mastoid tenderness. An operation was therefore deferred, and she died shortly afterwards."

I mentioned this case of Burgess 13 days ago.  I have since found a strikingly similar case (J Laryngol Rhinol Otol 1903;18:440):

A 7y old girl had a slight discharge of pus from the meatus 6 weeks after the start of a severe attack of enteric fever.  A mastoid operation found no pus in the antrum, no reason to suspect intracranial mischief.  Next day, sudden onset of serious symptoms.  A further operation found a fistulous opening in the roof of the antrum from which flowed some drops of pus.  A large quantity of pus was liberated from the meninges.  The immediate results of the operation were excellent, but she later relapsed.  Autopsy found meningitis and a 7cm brain abscess.  

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Here again it is absurd to suppose that the brain abscess was secondary to otitis or mastoiditis.  The pressure gradient was clearly centrifugal.  Fortunately, we have an obvious simple alternative, a typhoidal brain abscess.

No doubt stimulated by the LMG article by Bruce a few months previously (see my summary 3 days ago), George Fife reported a "Case of Otitis, Complicated with Cerebral Disease Lond Med Gaz 1841;28:353-5:

"After continuing for some weeks in this state, and complaining of pain in her left ear, it gave exit to a foetid, muco-sanguinolent discharge, mainfestly attended with temporary relief. This was of short duration, as head symptoms became too prominent to leave any doubt as to the sensorium being implicated...

Reflection on this case suggests an interesting and, in a practical point of view, not unimportant question; viz. was the disease primarily in the ear, and the brain, &c. implicated merely in a secondary manner; or was the brain primarily affected, and the ear ultimately took on the inflammatory action? This question is difficult of decision; but one which is well deserving of consideration...

The idea that the disease originated in the brain is favoured by the fact that the child had been evidently out of health, with loss of appetite, deranged bowels, &c. for some weeks before it made any complaint of the ear; which, it must be well known, is a condition which very often precedes the unequivocal indications of cerebral disease, more especially.. hydrocephalus...That, in these cases, the ear is often affected, I can testify from personal observation; and am happy in being able to corroborate this by again referring to M. Rostan, as the following passage sufficiently proves. "D'autres fois les maladies cerebrales commencent, et l'otite n'est qu-un effet consecutif..".

In conclusion it may be observed, that whatever the primary seat of disease was in the case before us, extreme vigilance on the part of the physician is required to detect the very first appearance of cerebral symptoms.."

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Comments

1. Fife poses the crucial question perfectly, though without himself coming to any definite conclusion.

2 Autopsy on his case showed hydrocephalus, a very soft left petrous bone, and abundant pus in the left internal ear and cells.

3. If disease extended from ear to brain, then why was no pus found in or around the brain?

3 Ironically, nowadays there is much less curiosity but correspondingly much more dogmatism in these ear-brain cases.

4. Beaucoup des apologies to Francophones for my omission of accents.

I wrote in previous letter: "Never hurt otitis". This important aspect of prevention remained unaddressed. Then I shall think differently. In order to know how dangerous otitis media, otitis need to recover. But certainly it is necessary to recover.

Vladimir brings up an important point: recovery and prevention are vital. We see the cognitive and developmental delays in the young, and the corrosive, serious damage to adults, as well, when otitis media forges onward undisturbed for years at a time. The most troublesome cases can be the silent insidious ones.

Two more fatal cases showing the reductio ad absurdum of supposing that otitis media acts as a boiler room or reservoir for pumping pus into the brain (Lees DB BMJ 1902;1:1247-8), though it is likely that organisms reach the brain from the outside via the ear:

"Abscess of the temporal lobe of the brain is so commonly consecutive to suppuration in the middle ear, that it is desirable to record instances where no ear lesion is present.  In the following cases there was necrosis of a small portion of the petrous bone, but the middle ear appeared to be perfectly healthy.   Septic organisms may have been conveyed to the petrous bone and to the brain from a transient otitis externa, which is not uncommon in children... 

The cases prove that necrosis of the petrous bone and temporo-sphenoidal abscess may exist when there is no otorrhoea and the tympanic membranes are normal..."   

Dear Max. There is another aspect of the problem. It is known as the common otitis media in children. Microbes from the source of inflammation fall into the cranial cavity. Formed dormant infection in certain parts of the brain. For example, in the temporal lobe. These events affect the functions of the brain, for example, in the process of remembering, learning. So, we must learn to effectively prevent ear infections at any age.

Yes, one of my subspecialties is child development, for which I emphasize in my lectures the need to diagnose and treat OME in children, particularly during their formative years. In our screenings for schools we find hosts of children with the tell tale signs of past OME and inquiring with the mothers hear repeated denials that their child ever had any ear infections. To that we suggest theirs may have been a "silent" case that did not bring fever and pain and therefore was missed by all. But the developmental delays occurred and their child struggles (especially males) to catch up cognitively and spatially with their unaffected peers. So, I agree with you on the criticality of early identification and treatment. 

"Yes, one of my subspecialties is child development, for which I emphasize in my lectures the need to diagnose and treat OME in children, particularly during their formative years."

I have always thought that OME has very important developmental consequences, but this area is very controversial and there have been a number of negative studies.  Personally, I think the resolution to this is to consider the crucial concept of a critical period.  I am not persuaded that OME at school or even preschool age has any long term consequences, because the brain is sufficiently developed to be able to compensate, but OM in infancy, often latent and undetected, can have devastating long term effects of language and behaviour.

Incidentally, I am currently reading some Victorian ENT journals, and have been surprised to find a large number of epidemiological studies, especially from Europe, showing strong correlations between minor hearing loss and poor school attainment.   This was mainly from OM, but says nothing about the time period over which the damage was done, which I suspect was in infancy.

My colleagues and I have long noted the lagging academic performance of males in particular when we see evidence of scarring on the TM. So that when we did an observational study on adults on removing scar tissues by using MiraCell Botanical Solution about 15 years ago (depending on the severity of the scarring, most are gone by day 45 with daily use), we wondered if academic and behavioral improvements would happen in school age children in the age 6-10 range. So, we suggested that the clinics involved with our study take a few in that age group and note improvements over the coming academic year. We did not specify instruments of measure or other benchmarks that might have given us a clearer picture on this, as we were thinking merely qualitatively to see if there was a trend. We were surprised by the anedcotal case histories coming out of that. The general trends were divided according to gender. The boys improved in academic performance and attentional behaviors in short order, the girls showed little difference. (Of course, when we speak of learning disorders that is predominantly the domain of the boys) In both cases, average HFA thresholds improved about 10-15 dB in low and mid frequencies and scarring either disappeared completely or mostly, and shallow A tympanograms returned to normal A. Much to my regret, as it would have been most useful information, we never ran a quantitative study on this. But over the ensuing years we still see these trends in all age groups and note threshold improvements with MiraCell. One case of gestation otosclerosis that was progressively worse with each succeeding birth improved dramatically from an 80dB PTA to about 45dB. Others to lesser degrees. Much to be looked at here. But the overriding moral to the story is that we still see such evidence. Since we've not been asked to look at this in a large population study we can only provide observations here, not data.  

"My colleagues and I have long noted the lagging academic performance of males in particular when we see evidence of scarring on the TM"

Some years ago I had a debate with Dorothy Bishop in JCPP in which I apparently failed to convince her that the reason for the male excess in dyslexia and learning disorders was because there was a higher incidence of latent OM (and resultant pneumonia and gastroenteritis) in male infants.   I suspect the reason for this is behavioral, in that male infants are harder to feed so that milk, foods or secretions end up in their middle ears.

It is well known that males have more fragile immune systems, begin life with certain parts of their brain less developed, and are subject in greater numbers to infant mortality. Aspergers is almost totally a male condition, as just about all delays in child development. The school district I just visited in central Arizona had no girls in their rather large special ed program. So, the developmental burden of OME will certainly show more problems in males. In a study we did about ten years from population data in the US we found that each year there were approximately 5% more males born than females, but by age 22 there was an equal number of each. After that, the numbers male to female grow exponentially larger into old age where women live 6-12 years longer than males. The prisons over here are packed with males (94%) versus females. The remedial classes in state colleges and universities are packed to the gills with males. Far fewer males attend graduate school than girls. The amazing thing in sharing these numbers here is that I get shocked looks from the PC crowd as if mentioning that developmental and mortality issues that affect males many times over females is taboo for some reason. The facts are the facts, and if they were allowed, they would land on your side of the debate.

"It is well known that males have more fragile immune systems, begin life with certain parts of their brain less developed, and are subject in greater numbers to infant mortality."

I am not sure about a general sex difference in immunity.  Is this the case for adult infections?

With respect to developmental disorders, we need to focus on infancy.  Looking at old data from the UK/USA when IM was high, and greater in males, there was no male excess for infectious diseases (eg measles) and many infections.  The male excess was confined to the major cause of death, latent otitis with subsequent pneumonia and gastroenteritis (the sompe syndrome).  There is unlikely to be any general immunological explanation for this, which is why I have come up with a specific mechanical/behavioral one.

The immunological differences between males and females at birth is well-known in the literature, Anthony, but has been fairly hushed up in academic circles. But it is the reason behind the push to delay vaccinations in newborns in the US, where we are seeing skyrocketing increases in autism and Asperger's, etc. The data from studies saying otherwise is tainted and biased, at best--cowtowing to the ones financing such egregious studies. The US government has shielded the drug companies from lawsuits over it even though the CDC guidelines say vaccines should be started at about 12 months of age. Nearly all the hospitals in the US give them at birth without the parent's permission and often without their knowledge. I've had parents go back in (who doubted this was the case for their child who began showing signs of autism) and ask for the record--in every case to-date they are shocked to find their son was vaccinated within a day or two of birth and now they have the distinction of having a developmental delayed child--these programs in the schools are massive and draining badly needed funding for other educational needs. Yes, boys are more fragile and we lose them in the early days at a rate at least four times as great as females. 

"I am not sure about a general sex difference in immunity. Is this the case for adult infections?"

I think the following data are pretty good evidence against a consistent and general immune weakness in males:

King TW On the frequency of cancer in the two sexes, and at different ages,  Lond Med Gaz 1845;6:597-8

Cancer was found in 85 of 451 autopsies in females, and in 41 out of 598 in males. The female excess was in young and middle aged women, no doubt in the two commonest cancer sites, breast and ovary.

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As for infants, what is the evidence for a general immune deficit in males?

I apologize that my publishing and speaking schedule is so packed that I can barely keep up at the moment and only take a moment's respite here and there to come onto RG. But had thought the evidence so strong and consensus so well-known on this topic (male vs female immunity at birth) and the state of the outcomes of such that I would not need to bring out references. But I will work on it over the next few days. The fact that there are 105 males to 100 females at birth and by age 22 the 100 males to 100 females, infant mortality rates far higher for males, developmental delays of all types, especially in terms of autism, etc. was well known everywhere. But perhaps it is not well known in some countries that are not as affected. UK is well-known for its extraordinarily high Asperger's rates among boys. And while the incidence of OME in infant males is likely about the same as in females, the delaying effects of it have always shown to be more devastating to their academic performance in school grades 1-5, if not all the way through graduate school. Of course, these are norms and there are many exceptions. But all of this ties into the differences in immune systems and the more fragile states of the males at birth and, to a lesser extent, onward in life. I will get back with you on some references, of which I'e compiled thousands over recent decades. 

Re the reference to cancer in females vs males--cancer, of course, is less tied to immunology than to other acquired and genetic factors, such as acidosis, nutrient deficiencies, environmental toxins, food additives, lifestyle and mental health issues, lingering subclinical infections, accumulated injuries, etc. So, as said above, the differences are more prominent at birth and younger ages. Longevity factors showing females outliving males by 6-12 years on average are essentially from a different set of aversive factors than immunological/developmental factors at birth.   

Here's an online snapshot of the recent data:

http://www.livescience.com/16268-female-immune-system-stronger-males-genetics.html

http://trstmh.oxfordjournals.org/content/108/7/385.full

http://blogs.discovermagazine.com/d-brief/2013/12/23/why-womens-immune-systems-are-more-sensitive-than-mens/#.Vgf6tcsrrDo

http://www.ncbi.nlm.nih.gov/pubmed/23151996

This extract taken from the PNAS article just recommended (middle link above) supports my point that there is no general immune deficiency in males 

"Numerous sex differences in susceptibility to infections have been described in the literature. Males fare worse during sepsis; they are more susceptible to certain bacterial infections such as invasive pneumococcal disease, group A streptococcal pharyngitis, and enterohaemorrhagic E. coli and campylobacter diarrhoea; and pulmonary tuberculosis is more prevalent among adult males. By contrast, females suffer more Mycoplasma pneumoniae and Bordetella pertussis infections. In general, viral infections are more prevalent among males, while the clinical outcomes are often more severe among females due to a more pronounced immune response leading to increased immunopathology. A greater male susceptibility to viral infections in childhood may reverse to a female preponderance in adulthood,although females are more susceptible to certain viruses such as herpes infections from childhood. Males are generally more susceptible to parasitic infections, including Leishmania spp., Plasmodium falciparumand P. vivax, Schistosoma mansoni and certain filarial infections. Females seem more susceptible to Toxoplasma gondii infection and possibly to Giardia lamblia and Entamoeba histolytica."

I have signally failed to generate in the modern otological literature any critical discussion of the relation between ear and brain disease. This extract here perfectly encapsulates the unresolved problem (Abscess of the Brain, Lond Med Gaz 1846;37:609-10):

"In the discussion which ensued, great difference of opinion existed among the members as to whether the disease of the ear, and the abscess in the substance of the brain, had any direct connexion, in the relation of cause and effect, to each other; and also to the period of formation of the brain abscess"

Facts of this case

* Woman age 26y, had measles as a child, discharge from right ear ever since.

* Complained of right earache which became most intense, "screaming at times from the violence of the pain, which extended over the entire right half of the head. At his time there was no discharge from the ear, or so trifling as to be of no consequence."

* Death about a month after she first complained of this earache

* There was a large abscess within the substance of the brain, occupying the whole upper part of the right hemisphere

* The dura mater was discoloured, but apparently intact

* The petrous bone was carious, the mastoid cells full of pus, the bone extremely thin with several apertures

* " Dr Merriman argued, that in this case the abscess was produced by transmission of inflammation from the bone through the membranes to the brain itself..."

Comment

As Merriman noted, there was frequent connexion between brain abscesses and disease of the temporal bone, so their co-occurrence here was not accidental. But if the abcess was caused in the last month by ear infection so severe it made her scream, why did the eardrum not rupture and thus decompress the middle ear? Would someone here today like to draw up a timeline for ear and brain infection and their interaction that makes more sense than the simple alternative Hippocratic version, ie: measles produced localised bone/tissue/membrane damage, (no problems ever occurred on the left side, excluding any general immunological mechanism). The resultant fistula(s) (presumably CSF) from brain to ear cavities continued for about 20 years, and only ending fatally when the leak(s) self-healed.

Anthony, the odd thing about this case is that it appears to be an external ear cholesteatoma and middle ear cholesteatoma co-occurring--possibly even connected. We see the external ear cholesteatoma drawing in the mastoid bone cells, but this case seemed to have provided a pathway for the middle ear portion of the infection to get into the brain from there. Possibly anaerobic pseudomonas? I recall a case of a 46 year-old male that I saw personally some 25 years ago, which I referred to Carle Clinic (Illinois) that became lethal almost to the description you provided on the 26 yo female. It was unilateral and extremely progressive.   

"the odd thing about this case is that it appears to be an external ear cholesteatoma and middle ear cholesteatoma co-occurring--possibly even connected"

I don't think postulating cholesteatoma helps understand the sequence of events in this case.  I think cholesteatomata, wherever they occur in the body, are a result of the failure to close a wound caused by a persistent fistula, and are never caused by ear infection.   In this case, measles could easily have caused a persistent CSF fistula into the ear.

Did your 46y old male have any condition liable to cause a fistula?  Head injury?  Bone disease?  Diabetes?

I would not normally pick an argument with Sir William Wilde, but in the absence of any modern commentator, his opinion deserves an airing, although in his 506 page textbook of Aural Surgery, he does not go into great detail;

" Authors speak also of abscesses and collections of matter within the cranium finding their way through the petrous portion of the temporal bone, into the external auditory tube.  This is a doctrine I cannot subscribe to -- it is unsupported by facts; it is much more probable, that if the brain was the original seat of disease, that death would have ensued long before this matter could find an outlet through the very hardest bone in the whole body."   

Comment

• The most curious and strongest fact in support of the cerebral origin is the striking inverse relation so often seen between otorrhea and brain abscess, as he himself noted:  "A case of otorrhoea may continue for years without causing greater inconvenience than the loss of hearing and the pollution from the discharge; the patient, however, becomes suddenly unwell...From about the period of the commencement of the attack the discharge from the ear generally lessens..."
• He was not around to witness the miserable death of his son from ear disease in a Paris hotel.  Oscar's head was said to have "exploded" after death, with fluid pouring out of every aperture.  Had this happened sooner, he may well have recovered.
• I agree that pus will not go through hard bone from brain to ear, nor, indeed, from ear to brain.  However, there are physiological CSF drainage routes through the bone, and often larger congenital holes or traumatic defects.  cf the ethmoid bone (Greek for perforated).
• I agree that brain disease would normally be short-lived, but not if there is a release mechanism for raised CSF pressure.  Hence (otitic) hydrocephalus can decompress around the sigmoid sinus into the ear. 

 As I recall the 46 year old male, and I need to clarify that my role was in assisting an audiology clinic at the time to referrals patients in that area for cochlear implantation and helping identify candidates. So, this particular case was one of long-standing history of being in and out of ENT practices and being prescribed repeated courses of antibiotics for acute and chronic externa otitis which failed to resolve his problem. His health profile was one of long term prediabetes, jaw sepsis (periodontal disease from dental health neglect), repeated keratosis obturans masquerading as impacted cerumen that was removed about annually.

His coming to this particular clinic was two-fold: 1) what did we suggest to stop this merry-go-round of externa otitis/keratosis formation cycle, and 2) would be be a possible cochlear implant candidate. The answer to the second question was that he had too much hearing in the opposing ear to be a CI candidate and just needed appropriate hearing aid amplification.

To the first question in this case--we really could not address all the issues in that practice setting--but in three visits spread over a six-month period, we noticed a pattern of under-treatment and misdiagnosis by the attending ENTs (using the same mild Amoxycillin course repeatedly was totally ineffective and we suggested they needed to find the agent as it appeared to be, and later turned out to be pseudomonas, not simple s aurea as first diagnosed) and that the cerumen impaction was likely keratosis obturans inspired from jaw (periodontal) sepsis--with really no cerumen involved. I made a note to the attending otologist to consider Augmentin (topical suspension as well as oral prescription) as a more prudent choice of antibiotic, and to see if the sepsis-destroyed are of the mastoid surrounding the offending area of the mastoid needed surgical attention.

Instead, the same mild (belated) course of amoxycillin was carried on, no attention whatsoever to the dental/otological connection, and the audiologist directly involved with the case reported in a CE class to me and the other attendees (I was leading the discussion) that this patient (identify protected) ended up with major surgery around that region of concern, that the infection had invaded past the temporal bone into the brainstem area and caused a slow and painful death to the patient. I've seen a number of similar cases going back to the 1970s--where the otological cascade was under-estimated and therefore undertreated--but this was probably the worst one in terms of the number of physician visits and years of treatment involved. I noted above that in the last six months the destruction was rapid and apparently unstoppable. But I brought this case out only because it matched a great deal the one described of the younger female.

While this was not a brain abcess cascading into the oto-region case--neither did the female case you shared seemed to be. So, I agree with you that it probably was not the case. Forgive me if I am misunderstanding your question. But I think the highly active immunology of the ear can affect the brain, but I strongly doubt it goes the other way, at least not in any predictable manner.   

" I think the highly active immunology of the ear can affect the brain"

Any immunological mediation is superfluous, and not just because it does not address the unilaterality.  We have in one case tissue destruction by virulent measles, in the other diabetic bone destruction, creating a fistula or amplifying a route between brain and ear.   In Malignant Otitis Externa, I think Pseudomonas is an opportunistic invader, making use of the altered metabolic environment created by diabetes, and not the prime mover.  

"While this was not a brain abcess cascading into the oto-region case--neither did the female case you shared seemed to be."

In Oscar Wilde's case, and that of others mentioned here and in the literature, the cascade occurred at a late stage, either leading to sudden cure, or making only a temporary respite in a fatal case, or coming too late (OW is the only such post mortem case I know of, and that witness account has therefore been much ridiculed).   In "otogenic" abscess in general, the trouble starts many years previously with a drip-drip from brain to ear.  Cascading only occurs when the leak has been temporally sealed, and centrifugal pressure from brain to ear has built up. 

That's most interesting to know, Anthony. There seems to be a lot of shared knowledge and understanding missing in the field on such cases--possibly because at the clinical level these really need a lot of parsing through to understand how things transpired and what course of action at the causal level might prevent or reverse it. You've shined a light here on some very important considerations.

To show a causal link between infection and any complication, it is necessary to demonstrate a dose effect (Bradford Hill), ie the worse the disease, the worse the complication.  Kafka (Laryngoscope 1935;45:790) looked at cerebral complications (mainly brain abscess/meningitis) in 3225 cases of mastoiditis.  Since there were only 33 brain abscesses, this should have make it even more predictable that cases with brain complications must have had particularly virulent ear disease.   So how did such predictions from the theory that the ear infection was primary hold up?

     This supports the Hippocratic view that there is primary mischief in the circulation and/or drainage of CSF, with secondary effects in the ear.

Here is an example of reductio ad absurdum of the idea that there is a dose relation between severity of OM and intracranial complications therefrom.   The 45y old man had only had unilateral intermittent OM for 10y.

"Chronic otitis media (COM) is a common clinical entity, but the incidence of COM complications has declined recently due to broad use of antibiotics.

Independent of this, these complications are still a significant challenge in otorhinolaryngology practice because of high morbidity and

mortality rates. The most common etiologic diagnosis was cholesteatomatous COM. Simultaneous coexistence of complications of COM in the same case is a rare situation, and the present report describes a case with mastoiditis, Bezold abscess, lateral sinus thrombophlebitis, meningitis, and paraspinal abscess.

KEYWORDS: Chronic otitis media, cholesteatoma, complications, abscess, sinus thrombophlebitis, meningitis"

Cite this article as: Zer Toros S, Tepe Karaca Ç, Kalaycık Ertugay Ç, Şenbayrak S, Çağatay Ertugay Ö, Şeneldir L. Simultaneous Coexistence of Complications

of Chronic Otitis Media in the Same Case. J Int Adv Otol 2017; DOI: 10.5152/iao.2017.3486

My question was intended to highlight the contrast between two opposing theories of the link between ear infections and brain complications:

"Destructive Otomastoiditis by MRSA from Porcine Origin

Helen Van Hoeck...

    A 63-year-old female pig farmer was referred to

our department with a protracted course of otomastoiditis

with destruction of the tympanic roof and cerebrospinal

fluid leakage. The patient underwent a

cortical mastoidectomy with closure of a large dural

defect. Cultures of the middle ear effusion yielded a

methicillin-resistant Staphylococcus aureus (MRSA),

which upon further analysis was found to be from

porcine origin. To our knowledge, this is the first

report of a complicated case of otomastoiditis caused

by a pig-type MRSA...

Laryngoscope, 119:137–140, 2009"

Comment

  The Hippocratic theory is clearly favored, since

  I think this perfectly sums up the situation today, nearly two centuries later.   Whilst I have continually stressed the absence of a dose effect, I had overlooked this powerful argument against such a dose effect, crucial if otitis is being posited as the primary agent.

"Instances like the above, in which abscesses within the cranium communicate with the ear, are by no means very uncommon ; and it is therefore of importance that we should keep in mind the necessity of a guarded prognosis in such cases. It has generally been assumed that the disease originates in the ear, and spreads to the parts within the cranium ; but this is by no means well ascertained, and some of the circumstances would rather lead us to believe that the disease travelled in an opposite direction.  We allude particularly to the fact that these cases in which the ear is unequivocally the primary seat of disease (as from cold, from the inflammation spreading along the Eustachian tube in scarlatina, or from foreign bodies irritating the external meatus), we very seldom hear of the brain becoming affected in this manner, although the internal ear may be so much disorganised as to produce permanent deafness."

Lond Med Gaz 1836;17:156

    This paper allows some checks on predictions from the theory that ear disease causes brain diseases, including abscesses, by comparing those groups with and without intracranial complications:   

"Laryngoscope. 2009 Aug;119(8):1610-5. doi: 10.1002/lary.20259.

Advanced pediatric mastoiditis with and without intracranial complications.

Zevallos JP...

Abstract

OBJECTIVES/HYPOTHESIS:

Recently, several groups have noticed an increase in cases of advanced pediatric mastoiditis and intracranial complications. The objective of this study was to review the bacteriology of advanced mastoiditis in pediatric patients, with the hypothesis that a difference in bacteriology might explain the development of an intracranial complication.

STUDY DESIGN:

Retrospective chart review.

METHODS:

All pediatric patients with coalescent mastoiditis requiring surgery treated at a tertiary care children's hospital between 2002 and 2007 were reviewed. Every patient included was treated either with mastoidectomy alone (for coalescent mastoiditis without an intracranial complication) or with transtemporal craniotomy (for coalescent mastoiditis with an intracranial complication). All patients had surgical specimens sent for pathology, Gram stain, and aerobic and anaerobic cultures.

RESULTS:

One hundred eight pediatric patients with coalescent mastoiditis were identified: 58 (53%) presented with coalescent mastoiditis alone, 17 (16%) presented with coalescent mastoiditis and an intracranial complication, and 33 (31%) were excluded because they were treated with myringotomy and tubes alone, had incomplete data, or had an unclear diagnosis. Streptococcus pneumoniae was the most commonly cultured organism in patients with and without intracranial complications. Anaerobic isolates were present in 29.4% of patients with intracranial complications and 5.7% of patients without intracranial complications (P = .015).

CONCLUSIONS:

Nearly a quarter of pediatric patients with coalescent mastoiditis presented with a simultaneous intracranial complication. There was an increased incidence of anaerobic organisms in patients with intracranial complications compared to those without, indicating the importance of culture and antibiotic coverage appropriate for anaerobes. This series demonstrates the role of aggressive surgical management and close collaboration with the infectious disease service for long-term intravenous antibiotic therapy in treating pediatric patients with advanced mastoiditis."

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Predictions (from conventional ear primacy theory):

So how did these predictions fare:

Conclusion

       No dose response, so a definite red card for the ear primacy theory.

   Here is an example where the cause of the mastoiditis is clear, ie a systemic immune disorder.  As expected, the mastoiditis is bilateral.  Both the known cases had some minor secondary involvement of the brain, but no abscess: 

"J Investig Med High Impact Case Rep. 2014 Jul-Sep; 2(3): ...

IgG4-Related Disease Presenting as Recurrent Mastoiditis With Central Nervous System Involvement

April L. Barnado, MD1 and Melissa A. Cunningham, MD, PhD...

Abstract

We report a case of a 43-year-old female who presented with right ear fullness and otorrhea. She was initially diagnosed with mastoiditis that was not responsive to multiple courses of antibiotics and steroids. She was then diagnosed with refractory inflammatory pseudotumor, and subsequent treatments included several mastoidectomies, further steroids, and radiation therapy. The patient went on to develop mastoiditis on the contralateral side as well as central nervous system involvement with headaches and right-sided facial paresthesias. Reexamination of the mastoid tissue revealed a significantly increased number of IgG4-positive cells, suggesting a diagnosis of IgG4-related disease..."

  Yet another example below of the absence of the dose/severity effect expected if intracranial complications were secondary to ear/mastoid disease.   A crucial prediction of this theory is that the ear disease should be bilateral, but I can find no indication here that it was in any of the cases.

"Acute mastoiditis: The role of imaging for identifying intracranial complications†

Authors  Michal Luntz...

First published: 7 September 2012 Full publication history DOI: 10.1002/lary.22193 ... 

Abstract

Objectives/Hypothesis:

Brain CT is performed in patients presenting with acute mastoiditis (AM) to identify intracranial complications (ICC). Recently, however, the need for CT scans in such patients has been questioned owing to concerns regarding long-term effects of brain irradiation, with some clinicians claiming that the decision to scan should be based on a patient's clinical presentation. This study was aimed at characterizing the typical clinical presentation of patients who already have ICCs when diagnosed with AM, and to compare it to that of AM patients presenting without ICCs...

Methods:

All patients hospitalized with AM between July 1997 and December 2009 in an otologic tertiary referral center were divided into those with and those without ICCs on presentation. Prereferral clinical characteristics and the signs, symptoms, and inflammatory indexes at presentation were compared between the two groups.

Results:

Of 71 patients presenting with AM, 10 had at least one ICC (sigmoid sinus thrombosis [nine patients], perisinus empyema [five patients], subdural abscess [one patient], and epidural abscess [one patient]). Patients with and without ICCs did not differ regarding most clinical characteristics or presenting signs and symptoms. None presented with neurological signs or cranial nerve deficits.

Conclusions:

It is not possible to define an evidence-based index of suspicion for ICCs in patients with AM." 

  See   G Fife A case of otitis, complicated with cerebral disease  Lond Med Gaz 1841;28:353-5.   Fife gives a good discussion of the two rival theories, but without coming to a definite conclusion: 

"E.T., aet. two years and three months, had for some time seemed unwell...

Her left ear ... gave exit to a foetid, muco-sanginolent discharge, manifestly attended with temporary relief...

Considerable serous effusion about the base of the brain.  The substance of the brain ... was found quite healthy... Serous effusion in considerable quantity in both ventricles... The internal ear and cells were filled with pus, which exuded abundantly so soon as the saw penetrated the cellular structure...

Was the disease primarily in the ear, and the brain, &c. implicated merely in a secondary manner;  or was the brain primarily affected, and the ear ultimately took on the inflammatory action?  This question is difficult of decision...

The idea that the disease originated in the brain is favoured by the fact that the child had been evidently out of health... before it made any complaint of the ear... which very often precedes the unequivocal indications of cerebral disease, more especially that form of hydrocephalus to which the term chronic is not perhaps justly applicable, but which is de facto subacute.  That, in these cases the ear is often affected, I can testify from personal observation;  and am happy in being able to corroborate this by again referring to M. Rostan..."D'autres fois les maladies cerebrales commencent, et l'otite n'est qu'un effet consecutif."   

**********************************************

Further points which Fife could mentioned in favour of the brain origin are

This is an excellent reference. But, I must add, Anthony that unilaterality is not exclusive to brain orientation of a disease. Much middle ear and mastoid, even EAC otopathology is notorious for presenting unilaterally. 

 "Much middle ear and mastoid, even EAC otopathology is notorious for presenting unilaterally."

  I am not arguing that because OM is unilateral, it must be of cerebral origin.    What I am saying is that any theory that postulates OM is due to an infectious organism, immunological disorder, systemic disease, smoking, etc, cannot explain unilateral disease.  Thus, in an adult presenting for the first time with a unilateral OM, cancer obstructing the E tube should be suspected.

   Are there any good counter-examples of this principle, ie systemic or general known causes of OM where it is inexplicably unilateral?

I agree, it is a dillemma in terms of being a principle of unilaterality. In our work at DigiCare, going back to the 1970s when we were exploring psuedomonas and other newer phenomenon, we began noting an increase of keratosis obturans vs cerumen impaction and the field's utter lack of understanding in differentiating between the two. We looked far and wide for the source of such infections--most were unilateral, and after years of examining uncountable cases decided to look at the bacteria of the teeth and jaw, and immediately found identical cultures. But, alas, the field of hearing health was still asleep--much as it is today since it has become a business based on symptoms not an effort in looking for causal factors--and these discoveries have been lopped aside in both the literature and in practice. We also associated that source with glomus tumors albeit more indirect and secondary. Now, we wonder if anyone cares...hence, the value of your question, though it has been on RG for some time, is still far undervalued in the literature, but should be a front burner question for anyone involved in oto-related research.

Other infectious diseases are unilateral, and it is indeed intriguing why that should be the case.  Lobar pneumonia is often unilateral too.  For ear disease uniltaeral versus bilateral OM is well recognised, and indeed our treatment guidelines differ because bilateral OM is seen as a marker of severity.  See http://www.medscape.com/viewarticle/561121.   Unilateral glue ear in an adult is seen as a potential indicator of nasopharyngeal carcinoma, and ENT surgeons all check for that, but rarely find that to be the cause.  It is strange that even in genetic mutant mouse models of OM sometimes the disease is also only unilateral - I don't know why.

To suggest that the majority of OM is not due to an infectious agent arising from the nasopharynx is not supported by the wealth of evidence - you need to check pubmed for huge amount of literature on this.  For example, bacterial serotypes can be traced from the nasopharynx and matched to those causing OM.  Vaccination against the common bacterial serotypes found in episodes of OM has been shown in meta-analyses to reduce population risk.  There may be some cases of OM that are not due to bacterial ingress into the middle ear from the nasopharynx, but it will be an very small minority.

"Lobar pneumonia is often unilateral too."

I do not see any problem with this.  The lungs are anatomically asymmetrical.  Also, some pneumonia is due to stuff falling down from the mouth or nose.  It can also depend on lying position, etc, etc. 

"bilateral OM is seen as a marker of severity."

   Precisely the main point I have been trying to make.   So why is it that the more likely some intracranial complication, the less likely the ear disease is to be bilateral?

"To suggest that the majority of OM is not due to an infectious agent arising from the nasopharynx is not supported by the wealth of evidence".

   I am mainly concerned here with rare cases where there are serious cerebral complications associated with OM, still a problem in many parts of the world.

   I agree that nasopharyngeal organisms are involved in most cases of OM, in which cases the OM should be bilateral. However, an extra factor(s) is required, as otherwise we would have OM all the time.  For the usual OM, Hippocrates says all children get OM at some time in their life depending on developmental variations in drainage of CSF into the cranial lymphatic system.  In other words, at some periods (fluid) niches arise in which organisms can escape the body's defences and thrive.

 "Now, we wonder if anyone cares...hence, the value of your question, though it has been on RG for some time, is still far undervalued in the literature, but should be a front burner question for anyone involved in oto-related research."

    Which is why I put up contributions from centuries ago at a time when doctors recognised there was a problem of directional cause, and thought about it.  Here is another example, including an excellent literature review with references:

J Bruce  On Phlebitis of the Cerebral Sinuses, as a result of Purulent Otorrhoea.  Lond Med Gaz 1841; 27: 608-12, 636-41

"The most frequent and dangerous complication of purulent otorrhoea is that which arises from metastasis of the inflammation to the brain or its membranes.  It is usually preceded by cessation of the discharge from the ear...

The question relating to the organ primarily affected in co-existing suppuration of the ear and the brain, has given rise to much discussion.   M. Itard...has adopted the opinion originally maintained by Laubius, that purulent otorrhoea is in many cases merely symptomatic of diseases in the brain.   He believes that a primitive cerebral otorrhoea exists whenever suppuration takes place within the cranium, and penetrates into the ear by the carious openings in the temporal bone, or by the natural foramina... 

  Lallemand naturally inquires why the purulent matter, presuming it to possess corrosive properties, never effects its escape through any other bone besides the temporal...

The pain continued without intermission , for several days;  and during that time he cried almost incessantly, and seemed drowsy and stupid.  A discharge than took place from the ear, at first small in quantity, but afterwards rather abundant, and followed by a gradual mitigation of all symptoms...

   Right temporal bone in many places rough and dark coloured, with matter betwixt it and dura mater... Left pleural cavity contained fully a pound of purulent fluid."

Comment

        Contrary to Bruce, I see a brain disorder as primary

Here is some interesting contemporary laterality data relevant to the two previous LMG papers above:

J Yearsley  On Deafness  Lon Med Gaz 1842; 29: 654

From JY's last 1000 cases of deafness at all ages seen in private practice:

Left ear affected;    54

Right ear            :   41

Both ears           :  905

Cause   Cold, various diseases :  828

              Acoustic trauma, accidents:  65

              Bathing:  67

-----------------------------------------------

From 1000 cases in the Ear Institution:

Left ear only:  48

Right ear only: 23

Both ears:   929

****************************

Comments

J Paget   On the relation between the Symmetry and the Diseases of the body  Lon Med Gaz 1841; 29; 525

"The law of constitutional diseases is, to affect both sides of the body equally and simultaneously" 

Your mention of Hippocrates made me think of the way Aspergillus behaves on shins (fibia) of those with peripheral or diabetic neuropathy. It is indeed corrosive to the bones and eats away at it in pockets of CO2 gather. Since we've seen so many cultures of aspergillus in EAC that your mention of the infection theory comes very much to mind on the more easily dissolved mastoid bone cells. The same with the amoeba and protozoa class microbes.  

"It is indeed corrosive to the bones"...

    ...because the bones have been weakened by the diabetes, as in malignant otitis externa.

Yes, and the acidosis state of the diabetic body causes more loss of bone mass, while also providing an environment conducive to parasitic and fungi growths on the bones. The ear-related bones would be as susceptible to those cause and effect dynamics as the rest of the skeletal frame. 

• Diabetes weakens bones, making them susceptible to infectious agents.
• OM is said to erode bones.

          Hence, it should be the case that the pattern and distribution of bone erosion in the ear should be similar in both conditions.   I have not checked in detail, but surely it is the case that the complications of diabetic and non-diabetic ear disease are quite different?

Conclusion:   OM and otorrhea do not generally erode bone.

On bone susceptibility the differences are degree of acidosis and the types of parasites or infections that are engendered by those states. In behavioral medicine, we look at causal factors and etiology of diabetes (variations in cellular pH or acidosis, infection, function and survival of islets of Langerhans, blood sugar levels, interruption of glycolysis, insulin, etc.) as we consider diabetes as more of a syndrome of symptoms than a strict or definable pathology. Hence, something like bone effects would vary a great deal from individual to individual. One area of variability in diabetic cases is the acidosis level, another is immunological response to ongoing infection (tooth/jaw sepsis, while common, is often overlooked in general practice, as are interstitial parasites). So bone tissue might be significantly affected by diabetes in one case and very little in another. Having said that, the most basic level of what we know affects bones is the acid dimension, but also immunological compromise, heretotopic parasitic growth, nutrition deficiency, heavy metal toxicity in the marrow, hydration levels, interruption of adult stem cell, etc.

All of these can affect mastoid bone cells as well as the bones of the limbs. The fungi (often Aspergillus) of the toenails, for instance, rarely originates in the toenails, but is usually an outgrowth of Aspergillus fungi growth along the shins of the tibia down into the bones of the feet into the toenails. Only rarely do we find it in the bone itself, in most cases confined to the outside (exostosis). The same with the flora of an infected external auditory canal: the infection can reach deeply into the mastoid bone tissue or it might originate in the subclinically septic jaw and tooth region, trapped under a root canal or rotted tooth. The variations are great between individuals.

So we are both correct here: at a causal level, it could be the multiple effects of diabetes or it could be simply a localized immunological breakdown due to non-diabetic involved states.       

Another case here which was controversial in its time, but is likely to provoke zero interest nowadays, not that there is any satisfactory modern explanation for the underlying processes:

" A woman, aged 26, of scofulous diathesis, had measles when a child, and suffered from discharge from the right ear ever since...

She first complained of ear-ache on that side, which became of a most intense description, and defied all remedial art...screaming at times from the violence of the pain which extended over the entire right half of the head... At this time there was no discharge from the ear , or so trifling as to be of no consequence...

On examination, a quantity of offensive pus came from the head, while sawing through the temporal bone; this was found to proceed from a large abscess within the substance of the brain, occupying the whole upper part of the right hemisphere... The petrous portion of the bone being examined was found to be extensively carious, the mastoid cells being full of dark pus... the bone was extremely thin, and several apertures in it were noticed...

In the discussion which ensued, great difference of opinion existed among the members as to whether the disease of the ear, and the abscess in the substance of the brain, had any direct connexion, in the relation of cause and effect, to each other; and also, as to the period of formation of the brain abscess."

Lond Med Gaz 1846;37;609

*************************************

There is a perfectly satisfactory Hippocratic formulation of this case:

The rival otogenic theory is a non-starter -- there was no dose effect, and an inverse correlation between otorrhea and brain mischief. And why the unilaterality?

Addendum

This case was also abstracted in Med Times 1846;13:509. Some differences were noted:

Another example where brain infection was out of all proportion to the ear disease, again emphasising the lack of a dose effect:

A 14y old trumpeter presented with cerebral symptoms but no otorrhea nor any sign or symptom of ear disease (Caries of the temporal bone, terminating in inflammation of the brain J Parratt Medical Times 1839;1:150-1).

"Upon removing the brain, the base of the organ was discovered extensively coated with pus, in which the origin of the nerves appeared immersed -- that part of the dura mater covering a large part of the petrous portion of the left temporal bone was quite detached, and apparently gangrenous, the bone softened, and when broken into of a greenish hue... I obtained some information before the patient's death, as to his being occasionally subject to earache and slight discharge... It had not, however, appeared of sufficient importance to induce him to apply for advice until the last fatal lighting up of the latent disease."