Loss of Eupnea

Eupnea is defined as normal relaxed breathing at rest.

Paula has lost this ability, that is what counting her baseline respiratory rate at rest indicates. She probably sustained this focal damage at birth, when she was born not breathing [from having swallowed meconium]. Other latent pathways must have been activated when she was revived. At least, that is our current thinking.

What is so beautiful about all this is that it all worked out so well. She had no other motor damage [thanks to the quick thinking of the doctors who resuscitated her] and except for loss of eupneic breathing, she was perfect [using the idea of perfection as a metaphor here]. Her subsequent intellectual and physical development was normal. I have read research papers showing that periods of hypoxia or hypercapnia can cause lesions affecting the neural fibres of the spinal cord involved in breathing.

With the help of my assistant, Chat GPT from https://chat.openai.com, we learnt that

” Apparently periods of hypoxia or hypercapnia can cause lesions affecting the neural fibres of the spinal cord involved in breathing.

In some cases, periods of hypercapnia or hypoxia at birth can affect the phrenic motor system, but with subsequent recovery, ambulatory patients can often lead relatively normal lives. Here’s a general overview of how this process can unfold:

1. Perinatal Hypercapnia or Hypoxia: [This is what Paula had]..” During the perinatal period, which includes the time immediately before and after birth, infants may experience episodes of hypercapnia (elevated carbon dioxide levels) or hypoxia (oxygen deficiency). These events can be caused by various factors, such as birth asphyxia, respiratory distress syndrome, or complications during delivery.”
2. Impact on the Phrenic Motor System: Hypercapnia and hypoxia during this critical period can potentially affect the development and function of the phrenic motor system. The precise effects depend on the severity and duration of the oxygen or carbon dioxide imbalance, as well as individual factors. In some cases, there may be temporary dysfunction or injury to the phrenic motor neurons or the neural pathways involved in controlling the diaphragm.
3. Recovery and Ambulatory Status: Fortunately, the phrenic motor system has the potential for recovery and plasticity, particularly during early development. Over time, with appropriate medical management and support, many infants who experienced hypercapnia or hypoxia at birth can regain normal function of the phrenic motor system.

Recovery may involve various processes, such as neuroplasticity, compensatory mechanisms, and adaptation. The body can create alternative neural pathways or strengthen existing ones to ensure proper diaphragmatic function. Additionally, the development of collateral innervation or recruitment of adjacent motor neurons can occur, allowing for functional recovery of the diaphragm.

As a result of this recovery, many individuals who experienced periods of hypercapnia or hypoxia at birth can lead ambulatory lives, meaning they can walk and engage in regular activities. However, the extent of recovery can vary among individuals, and some may still experience residual effects or challenges related to respiratory function.

It’s important for individuals who have had perinatal hypercapnia or hypoxia to receive appropriate medical follow-up, including regular assessments of respiratory function and potential interventions to address any ongoing respiratory issues. Rehabilitation, physiotherapy, and respiratory therapy may also be beneficial to optimize respiratory function and overall well-being.“

I think that Kraepelin and I discovered a population of seemingly normal developing “individuals who experienced periods of hypercapnia or hypoxia at birth can lead ambulatory lives, meaning they can walk and engage in regular activities. However, the extent of recovery can vary among individuals, and some may still experience residual effects or challenges related to respiratory function”.

I think that this explains the regular and extensive range of syndromes of manic depressive illness. I think that the brain stem was spared and has extensive experience with co-ordinating cardiorespiratory function if individuals with permanent motor phrenic fibre damage and regular but abnormal respiratory rates and normal homeostasis. And the system seems to work great till the significant size and hormonal changes after adolescence or later, depending on the respiratory challenges and/or injury they experience.

The cardiorespiratory and circulatory system is amazing and adapts and adapts well; until it requires mechanical and/or pharmacological help to strengthen it. It will most likely need some kind of tweaking in order to do its job through a lifetime.

To be continued……

At one stage of hormonal change, Paula got into physiological trouble and needed treatments to tweak the system and restore stability and homeostasis and normal gas exchange.

Serotonin agonists such as Paxil are known locomotor stimulants. Paula’s doctors gave her Paxil and after 8 months of treatment, Paula became manic. The Paxil suddenly worked to make Paula’s breathing rate much faster, in fact too fast, using other [I think] alternate pathways of neurons. Paula still did not have eupneic breathing at baseline. Along with the increased speed of the ventilatory muscles, all locomotor muscle activity increased in speed as well. As well as her thoughts and her speech. All increased to levels usually induced by stimulant drugs such as amphetamines and cocaine. Clearly, this was bad. Mania ……to be continued…..

Why is this important?

It is important because it means that she must have sustained permanent and incomplete and focused damage to parts of the neural cervical spinal cord concerned with the motor act of breathing.

It is important because she [involuntarily and unconsciously] uses other muscles to compensate for the damage.

Let us turn again to my assistant Chat GPT for details about the phrenic motor responses involved in breathing;

“The phrenic motor responses refer to the electrical signals and resulting muscle contractions that occur within the phrenic motor system. These responses are responsible for the activation and control of the diaphragm muscle, which plays a crucial role in breathing. Here are the primary phrenic motor responses:

1. Phrenic Nerve Activation: The phrenic nerve is a mixed nerve that arises from the cervical spinal cord segments C3 to C5. It carries motor signals from the brainstem to the diaphragm muscle. When the phrenic nerve is activated, it sends electrical impulses to the diaphragm, initiating muscle contraction.
2. Phrenic Motor Neurons: Phrenic motor neurons are located in the spinal cord, specifically in the cervical segments C3 to C5. They receive input from various sources, including the brainstem respiratory centers and peripheral chemoreceptors. These motor neurons integrate and process the incoming signals and generate motor outputs that control the contraction of the diaphragm muscle.
3. Diaphragmatic Contraction: The primary phrenic motor response is the contraction of the diaphragm muscle. When the phrenic motor neurons are activated, they transmit signals along the phrenic nerve, leading to the contraction of the diaphragm. This contraction causes the diaphragm to move downward, expanding the thoracic cavity and drawing air into the lungs during inhalation.
4. Respiratory Rate and Depth Modulation: The phrenic motor responses are finely regulated to modulate the respiratory rate and depth according to the body’s oxygen and carbon dioxide levels. Feedback mechanisms involving chemoreceptors in the brainstem and peripheral tissues continuously monitor blood gas levels. In response to changes in oxygen and carbon dioxide concentrations, the phrenic motor system adjusts the frequency and intensity of phrenic nerve signals to modulate breathing.
5. Reflex Responses: The phrenic motor system also participates in reflex responses to various stimuli. For example, when the diaphragm senses stretch due to lung inflation, a reflex called the Hering-Breuer reflex can be triggered, which inhibits further inspiratory efforts and promotes exhalation. This reflex helps regulate the respiratory cycle and prevents overinflation of the lungs.

Overall, the phrenic motor responses are essential for the control of breathing and the proper functioning of the diaphragm. The coordination and modulation of these responses ensure the effective exchange of gases in the lungs, allowing for optimal oxygen uptake and carbon dioxide elimination.“

Given Paul’s defect in her breathing, the “coordination and modulation of these responses ensure the effective exchange of gases in the lungs, allowing for optimal oxygen uptake and carbon dioxide elimination“. is amazing and makes her a physiological superstar.

The fact that Kraepelin found spontaneous periods of recovery in between manic depressive attacks which were then completely untreated is spectacular!!!

We need to explore this phenomena further because as long as someone is breathing, supportive medical and nutritional and pharmacological help may help them get through when the system falters and their mental status gets altered due to further and most likely [with help] temporary breathing impairment.

Paula did not want to wait until she somehow spontaneously recovered because that could mean being mentally impaired for years.

She recovered with pharmacological help by following the cues that her mental capacities were improving…..and it still took 10 years for her to be completely OK.

And she did this by being lucky and by trial and error rather than by science.