When Paula had her attack of what Dr Kraepelin would easily have identified as “depressive insanity” with psychomotor retardation, she was experiencing “dysfunction” of her brain.She experienced this state for over a year; it started abruptly when she awoke suddenly with a sensation of chronic fear and incredible distress. This was the start of the attack. Her arousal was super high [distress, fear] and her motor and cognitive function was significantly depressed.
In our opinion, any mood or cognitive disorder which affects one’s ability to think or remember, thereby affecting ability to do the daily tasks of living, must be carefully investigated; it might be a primary brain disorder, like a stroke or a brain tumour,. Once these possibilities and others are ruled out, it is time to begin to look at dysfunctions of organ systems other than the brain. most of which can cause secondary brain dysfunction.
This was not done for Paula.
Kraepelin, without modern tools, was at least able to measure the vital signs of his patients , finding abnormal patterns which clearly pointed to ventilatory dysfunction in bipolar attacks of depression with psychomotor retardation and mania with psychomotor excitement. Kraepelin measured resting respiratory rates, blood pressure, heart rates [and signs] and body temperature and also found peripheral and central vasoconstriction [cool, pale even cyanotic lips, hands and feet]. Kraepelin understood that these were key to the depressed and excited brain dysfunction of these patients. He also learnt that examination and measurement of vital signs can speak volumes when patients cannot speak for themselves and do not know what is wrong.
Various patterns of brain dysfunction can be triggered by external substances or poisons [including intoxicants] – such as alcohol, cocaine, amphetamines, opiates, anaethesthesia , lead poisoning, mercury poisoning , carbon monoxide poisoning, cyanide poisoning, etc..
Various patterns of brain dysfunction can also be caused by internal endogenous substances – too much or too little endogenous carbon dioxide [a normal product of cell metabolism] in the blood, too little oxygen, a buildup of ammonia due to liver issues, too much or too little iron in the blood, too little thiamine [an important co-enzyme], toxins from muscle tissue breakdown [eg. due to muscle wasting], toxins from the breakdown of tumour cells, too much or too little sugar in the blood stream, too little blood due to obvious or hidden blood loss, too much water in the body [oedema] or too little [dehydration], acid base disturbances affecting the function of enzymes and protein folding and basically everything in the body, thermodynamics and body temperature also affecting everything, much like acid base imbalance, etc..
In the case of external substances causing brain dysfunction, especially if one is specifically investigating recreational drug reactions, doctors used to [and perhaps still do] use vital signs as a guide. Different ingested substances affected breathing rate, blood pressure, heart rate and body temperature in specific patterns. Drugs creating excitement, often raise breathing rate and blood pressure and heart rate. Drugs considered to be depressants usually depress breathing, slow heart rates and lower blood pressure. These patterns of vital signs due to external toxic substances affect physiology and cause brain dysfunction and the pattern of vital signs affected are called toxidromes. There can be complex patterns of disturbance in vital signs, depending on combination of substances ingested.
The same approach should and can be used for internal substances causing secondary brain dysfunction. It is difficult, lengthy and costly to find the cause of secondary brain dysfunction, it is much like trying to find a needle in a haystack. It is useful to utilize the medical and paediatric history and physiological vital signs assessment as a basic road map to rule out some conditions and investigate other conditions further .Modern tools such as ultrasound [not necessarily of the brain – if brain dysfunction is a secondary effect of abnormal vital signs] can help. Blood tests [is the blood too thick, are there enough platelets , is there insulin resistance?- [insulin resistance suggests metabolic acidosis]-, has the patient stopped producing urine? could the distress and fear the patient is experiencing be silent dyspnea due to peripheral organ dysfunction such as heart dysfunction or lung issues or ventilatory dysfunction,- of which the patient is completely unaware – except for the suffering that is caused. The patient’s body condition and vital signs will suggest which tests might be useful.
In our opinion, doctors need to use the same approach to identify endogenous or internal toxic substances as they would to identify external poisons, by studying the pattern of vital signs presented by the patient at rest. This will help the doctor to form a hypothesis on possible organ dysfunction of the body that could be causing these secondary effects in the brain, [not dissimilar to the secondary effects of ingesting external toxic substances in cases of poisoning or intoxication or chronic exposure [to toxic indoor or outdoor environments].
In the case of Paula, her toxidrome was unusual; her respiratory rate was very depressed -we never obtained her tidal volume [depth of respiration] or her minute ventilation [the amount of air exchanged per minute-even though these are non-invasive, easy to obtain measurements], her blood pressure was very high [perhaps to raise cerebral blood flow], her heart rate raised with palpitations and occasional murmur, her extremities were cold and pale, her body temperature mildly hypothermic [hence the vasoconstriction]. Paula had clear signs of possible ventilatory failure requiring immediate supportive medical care. She may have had an infection as well since she was ill for a few weeks before her attack.
Of course, in Paula’s case, doctors did not obtain any of this information and so had no idea that her distress and heightened arousal [fear] and psychomotor retardation were due to ventilatory failure, poor body condition, involuntary loss of weight and muscle wasting. Paula had possible retention of endogenous carbon dioxide [a normal product of cell metabolism and life]. The mystery is why such patients are robust in that they can have brain dysfunction for years, decades even and yet most will not die or even have permanent brain damage. Kraepelin was fascinated by this also. Why, in most cases, did [unmedicated] patients spontaneously remit and return to normal brain function [but most likely not normal ventilation] ?
Paula and I knew that she had a good chance of recovering her normal brain function because of what Kraepelin found in his studies over 100 years ago.
Paula recovered her brain function and normal vital signs [except for respiratory rate, which seems permanently depressed] over a period of 10 years with the help of Paxil, a serotonin agonist].
In our opinion, an investigative stage in a new neuropsychiatric critical care unit may be necessary to monitor the patient’s vitals [including minute ventilation and arterial blood gas tests or venous blood gas tests if accurate to obtain PaC02 and pH and 02 levels] and a catheter to measure urine output, and ammonia tests and ferric iron tests and other tests of iron and thiamine metabolism, tests of alternative hemoglobin [methemoglobinemia, cyanide, etc..] , tests of heart function, kidney function, liver function, inflammation, and whatever other modern investigations that could possible cause the motor and cognitive secondary changes affecting the brain. Intracranial pressure can be hypothesized with the help of ABG’s and other tests but remains too invasive to check further.
Once we have a better understanding of the exogenous [external] and endogenous [internal] substances involved in affecting the brain, then we can transfer the patient to an ordinary ward with the appropriate treatments [such as temporary dialysis, if needed to support kidney function, CPAP or other machines to help support the ventilation part of breathing, antibiotics for infection, etc…] .with the goal of restoring brain function and normal vital signs, in as much as is possible. Our current knowledge about peripheral organ dysfunction will suggest which organs need support and which vital signs have been permanently injured and needing permanent or occasional support.
In Paula’s case, just as Dr Kraepelin reported, her ability to raise her breathing rate at rest or in the face of respiratory challenges[ including exercise], has been permanently damaged in a non progressive manner. This is easy to see with a quick, non invasive examination of her vital signs, especially her respiratory rate at rest [see other blogs] . Paula uses active exhaling [exhaling is normally passive-like letting air out of a balloon ] in order to augment her depth in each breath she takes. She uses the same technique during exercise. Or should we say that the brain orchestrates this in order for her to be alive and functioning. This abnormal manner of ventilation has worked for her since her dramatic and problematic birth [see other blogs]; but during chronic exposure of allergy [eg to mould] or overcrowded, poorly ventilated conditions and illness [viruses and other infections] and poor body condition [physical illness causing loss of appetite, involuntary loss of weight, dehydration, nausea, lethargy, etc..] and especially during risky hormonal changes [like those of adolescence and menopause]; her [involuntary and unconscious] accommodations can be overwhelmed, leading to abnormal respiratory acid base metabolism, and secondary effects affecting her brain function.
During these debilitating attacks of chronic but mild [it is never mild] critical illness, it is important to do a workup and investigation in a neuropsychiatric critical care unit in order to limit the length of time that the brain is secondarily affected.
This is key because 1] these attacks must be brought to an end as quickly as possible with proper and effective treatments because during attacks patients cannot function effectively due to brain dysfunction [which can easily be measured by timed tests suck as those invented by Dr Wundt and Dr Kraepelin as well as modern tests like the Montreal Cognitive Test] and cannot do her work or look after herself or look after others [if a parent]. and 2] the longer and more frequent these attacks [Dr Kraepelin said they had a natural remitting relapsing pattern] the more likely that the brain dysfunction becomes permanent brain damage that is more difficult to treat and the more likely other organs like the heart and the kidneys will become damaged as well.
Doctors need to change their thinking about so called “mental illnesses” and begin to look for evidence of organ dysfunction, other than the brain, causing serious secondary brain dysfunction which renders a person instantly disabled and reversibly [its never mild] mildly demented, in order to better treat these poor patients, many in what should be the prime of their lives at ages between 17 and 30.
Instead, doctors let these patients linger at home or in psychiatric wards, doing nothing at all for them except talk, and talk is useless for a disabled, dyspneic, silent, lethargic patient with secondary brain dysfunction they do not understand.
We have the modern medical tools to investigate and change this in the 21st century.
It is time for doctors to change their approach, consider the role of secondary brain dysfunction and participate in the miracles of 21st century medicine.