Impaired Respiratory Drive and Episodes of Loss of Mind,

another summary letter to researchers! Because they have no idea!!!!

” I have some insights regarding ….. fill in the blanks with your research discovery here..… based on my knowledge of Paula’s case. Paula is a colleague and close friend.  She had a serious attack of major depression about 17 years ago or so and remembers well today what she experienced.

We have been investigating what happened to her ever since and some of what we found is similar to what Dr Emile Kraepelin found in the depressed episodes of Manic Depressive Insanity over 100 years ago.

Paula woke up very distressed, stiff,  and strange one morning after having several minor illnesses 17 years ago. She was also menopausal. [estrogen and ventilation are somehow related, we read].
 She did not realize that she suddenly had significant memory issues until she tried to do something ,  anything.  She went to work feeling strange [she did not know what else to do so off she went to work ] and found that she no longer remembered what to do at her work [she is a teacher]. She was shocked, embarrassed, even more distressed and worried about it, then forgot.  This went on all day.  [since she could not remember what she could not do-it was a nightmare].

She found that her thoughts were clear at first, then within seconds, faded-like sand disappearing in a sieve-preventing her from speaking her thoughts or acting on her thoughts.  She could not remember how to reach a doctor, what to say or what to do…so she did nothing.  That to us, was reactive inhibition.   When we tested her later with digit span, we found that she remembered 4-5 digits forward and none backward.  This from a teacher with a graduate degree.  She had to take a leave from work, as she was suddenly incompetent. 

It was assumed that she was depressed.  She was not, she was unbearably and abnormally distressed. 
She realized that something was very wrong but did not have any idea what.  

A quick check of her vital signs would have shown that she has a respiratory defect or non progressive injury most likely from her difficult birth.

She could not speak or move much because she has a depressed rate of breathing, [no medications , no yoga] which has only recently been formally tested.  She has been fine most of her life [she also has depressed ventilation in health, we learnt]  but is most likely at risk for hypercapnic respiratory failure . [which, with healthy lungs, may not result in hypoxia, just hypercapnic attacks.
 Hypercapnia causes reversible effects on brain function [if it doesn’t kill you, that is.]  In this case, a ventilatory defect [non progressive] makes acid base adjustments to the blood and brain complex and limited , especially during physical illness, with muscle weakness and during developmental biological hormonal change.  Breathing is complicated.

Kraepelin also found depressed breathing in thousands of unmedicated patients who were depressed with major psychomotor retardation. Kraepelin concluded that these patients had a ventilatory defect causing metabolic dysfunction after a major triggering event such as head injury,  loss of blood, or exposure to confinement [such as prison-with its lousy ventilation, hygienic conditions, overcrowding [causing higher indoor CO2 levels], and undernutrition and fights-causing injuries and blood loss].
Kraepelin looked to the future of medicine, to the eventual perfection of arterial blood gases [he died before this happened] and medications to rescue and support ventilation in such patients.
Kraepelin followed patients for decades and was amazed to find a remitting relapsing course of illness throughout life, once it started. Patients always spontaneously recovered their mental status, after months, years or decades of illness, and were the only ones who left the mental asylums when they recovered. Medications today can improve or impair full recovery of mental status, mood and locomotor activity .  It is hit or miss. Doctors have no idea what they are doing. 

Hypercapnia has reversible effects on brain function.   Supportive medical measures might hasten recovery and prevent future attacks.

Paula was mentally confused [quiet delirium with psychomotor retardation] and did not have the breath or memory to talk much or move much for over a year. She experienced huge distress, most likely due to chronic dyspnea- worsened by physical effort, which she did not recognize [or did and kept forgetting].   During the long attack her other normally normal vital signs were also abnormal. Instead of having normal body temperature, heart rate, heart signs, blood pressure and weight, mood and mental status in spite of her ventilatory depression;  when ill that year , her blood pressure skyrocketed [to keep brain perfused?], her heart rate became fast, with palpitations and heart murmurs, she was mildly hypothermic and vasoconstricted [hand, feet, lips pale and cold], with the same ventilatory ventilatory depression. The difference to her was that she felt too weak to do anything else but maintain her breathing, which became even slower at 2.5 breaths per minute.
She remembers when well what she could not remember when ill.

Half of people with delirium [hypo, hyper, mixed locomotor states] can remember their delirium.
In any case, it seems her motor responses were muted because of the need to conserve energy during hidden ventilatory failure.

More astute physicians would have noticed stiffness of the facial muscles making speech slightly more difficult, her active exhalation [indicating respiratory or muscle issues] and her inability to say more than 2 or 3 words [a clear indication of respiratory difficulties].
Please look at our ongoing investigations into mind, loss of mind and impaired respiratory drive, in order to help doctors, researchers and scientists.

We are not scientist or writers and have recently gotten help from a lung doctor/physiology professor to help us improve our understanding of respiratory physiology and he has also given Paula special lung function tests to verify her respiratory rate- which is 3-5 breaths per minute, astonishingly,her  tidal volume, which is 750-85- ml  and her minute ventilation -which is sufficient , when she is well.  [Regular spirometry does not measure minute ventilation].  She has had a sleep study years ago and does not have sleep apnea [when well anyway].

Doctors never look at the pattern of vital signs, and certainly do not measure respiratory rates , or minute ventilation in ambulatory patients who suddenly become depressed, demented , delirious or begin acting strangely.

People are not aware of their own respiratory rate at rest since it is orchestrated by the brain and periphery in order to regulate acid base balance of the blood and of the brain. High PaC02 is a cerebral vasodilator and can cause increased intracranial pressure, which cannot be measured noninvasively.
Anyway, we wished to tell you about Kraepelin’s studies and Paula’s case in particular.

Best Brigitte and Paula

PS. Although Paula only received medication from a psychiatrist, we evaluated what he prescribed using a simple test which was key for Paula.

We realized that Paula’s gaps in her autobiographical memory was evident in her inability to remember her own address every day.

So we tested medications based on whether or not they helped return this ability to her, even a little.
It took a long time of trial and error [her psychiatrist was clueless as to how we were evaluating treatment]  but we discovered that a serotonin agonist [Paxil] helped a little, then over a period of months…a little more…ec..

It took 10 years to reliably restore her memory for her address [to this day, we test for this in case of relapse] and has completely restored her baseline mental status.  [Serotonin and serotonin agonists are known to help babies avoid death from SIDS; no one yet understands how].   Those babies may have impaired respiratory drive also and no one follows them to see if their respiratory drive is still impaired when they are adults.  It will be a pretty cool thing to study, I think.   Paula was born in Paris France where babies were swaddled and put to sleep on their backs [like is recommended today] so perhaps this is why she survived infancy.  [after successful suctioning, resuscitation and transfusion at birth]. 

Her respiratory rate is still 3-5 breaths per minute today, but the hypercapnia [still a hypothesis, but a logical one] has finally cleared-it has been 15 years with the help of the serotonin agonist.
The side effects of the medication have also disappeared with time.

Please share with other scientists.

Hope this helps.

It is time Kraepelin’s hypothesis is replicated [or not].

No one has measured vital signs [especially minute ventilation]  in unmedicated neurological or neuropsychiatric patients since.  They are known to have breathing disturbances though.
And you will find most doctors to be ignorant and negligent regarding impaired respiratory drive. 
Even though, it was known by the pioneers of respiratory physiology [JS Haldane, etc..] that the range of respiratory rates were very wide in healthy adults, from as low as 3 breaths per minute at rest to as high as 28 breaths per minute at rest  [my nephew, a smoker-lungs still normal], for example].
The brain works it all out with the voluntary [?] skeletal muscles, but it is obvious that  the otherwise healthy people on both extremes are at risk for ventilatory failure with difficulty recovering,  if they cannot muster the appropriate ventilatory response to a metabolic or respiratory challenge.

The only thing that matters to the brain and all neural networks is the ability to take that next breath and management of pH and PaC02. 

And no one will be the wiser, if minute ventilation is not monitored in the patients, and if their acute attack turned chronic mental confusion [or chronic pattern of delirium-all locomotor and mood types] or distressed mood [hypercapnia is very unpleasant unless it becomes intoxicating and euphoric, depending on the stage] will never be investigated scientifically or treated medically. 
Paula is very well now and we both think this is very very cool, just like Kraepelin did.

Hope this helps you in your ongoing brain research.


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