This is what is needed to be carefully studied in the field of outpatient and inpatient medicine , especially for patient with the syndrome of manic depressive insanity, which may most likely turn out to be a chronic example of a quiet, mixed and/or wild delirium [a progression of carbon dioxide narcosis states] ,caused by abnormal at rest breathing rate and abnormal minute ventilation worsened by [hidden] infection or hormonal disturbance.
Psychiatrists never think of the possibility of disorders of consciousness a a feature of serious mental illness. Serious mental illness is most likely a metabolic disorder of consciousness which needs to be carefully medically worked up, starting with getting the 4 basic vital signs of baseline Respiratory Rate, Blood Pressure, heartRate [and signs] and Body Temperature. Abnormal vital signs is a sign of systemic illness, including all levels of [hidden] organ failure, including respiratory pump failure and hypercapnic encephalopathy. These illnesses are hidden ONLY because doctors [including psychiatrists and neurologists] DO NOT take the baseline measurements of the vital physiological signs seriously and almost universally NEVER measure baseline respiratory rate. Without the measurement of baseline respiratory rate, the interpretation of the other vital signs will be incorrect and misleading and will not necessarily lead to the correct treatment. All people, including doctors, take the ability to move air in and out of the body as a given, when, in reality the various parts of the body needed to perform this complex motor task can easily become injured, impeding acid base balance of the blood without the patient knowing and only showing up on an arterial blood gas test, which will not be given if the doctor and patient are unaware of an respiratory acid problem, and this can easily happen and has not been studied since the time of Dr Emile Kraepelin, over 100 years ago. We discovered this discrepancy when Paula became ill, in a distressing silent confusional state. No one has measured her breathing rate even today, 20+ years later. Because it was never a part of medical practice to do so, although the four vital signs are given lip service in introductory medical textbooks.
Hence we know little about the reversible hypercapnia resulting in encephalopathy and natural distress in the syndrome called bipolar illness.
J. Claude HemphillIII, in Aminoff’s Neurology and General Medicine (Fifth Edition), 2014
Metabolic encephalopathy is the most frequent cause of disordered consciousness in systemic diseases, and is defined as an alteration in consciousness caused by diffuse or global brain dysfunction from impaired cerebral metabolism. The list of metabolic encephalopathies is extensive and includes such disparate conditions as hypoxic-ischemic encephalopathy, hepatic encephalopathy, drug overdose, bacterial meningitis, and the postseizure state. The principal reason for grouping together this wide variety of disorders is that the neurologic examination may appear quite similar regardless of the underlying etiology. Nevertheless, the cause of the metabolic encephalopathy is the fundamental determinant of treatment and prognosis. Thus, considering the biochemistry of metabolic encephalopathies is of prime importance in their differentiation.
Two common themes emerge with regard to presumptive etiologies of metabolic encephalopathies in systemic disease: impaired substrate delivery (glucose or oxygen) to the brain or release by a systemic disease of a circulating substance that crosses the blood–brain barrier (or enters through a broken blood–brain barrier) and causes neuronal and cellular dysfunction (Table 60-3). The former, implicated in hypoxic-ischemic encephalopathy and hypoglycemia, may result in irreversible brain injury.24,25 The latter, implicated in most metabolic encephalopathies associated with organ system dysfunction (e.g., hepatic, renal) or with systemic infection, may be largely reversible if the underlying disorder is treated.26–29 Although there are exceptions, this mechanistic differentiation can be of great importance in determining treatment and prognosis.
Table 60-3. Mechanisms of Metabolic Encephalopathies
|Impaired Substrate Delivery|
|Carbon dioxide narcosis|
|Circulating Cytokines (Putative)|
|Multisystem organ failure|
|Diffuse Brain Infection|
|Collagen vascular diseases|
|Diffusely Decreased Cerebral Metabolism|
HIV, human immunodeficiency virus.
When substrate delivery to the brain is globally reduced, encephalopathy and eventually coma may result. Hypoxia, and especially hypoxia-ischemia, may result in permanent cerebral damage diffusely or in selectively vulnerable areas such as the hippocampus, cerebellum, and thalamus. The degree and duration of hypoxia or decreased cerebral blood flow determine the severity and irreversibility of damage. Hypoxic-ischemic encephalopathy most commonly results from severe hypotension or cardiac arrest and is mediated by the neuronal ischemic injury cascade, which includes release of excitatory amino acids, intracellular calcium influx, lipid peroxidation, and cell breakdown.30 Two clinical trials have demonstrated a beneficial effect of immediate treatment of comatose survivors of cardiac arrest with mild hypothermia (33°C for 12 to 24 hours after out-of-hospital cardiac arrest from ventricular fibrillation or pulseless ventricular tachycardia), and this treatment is part of standard resuscitation guidelines as discussed in Chapter 9.31–33 Hypoglycemic encephalopathy is potentially reversible, but permanent damage may occur if it is not treated early. Hypertensive encephalopathy may be due to disordered cerebral autoregulation, elevated cerebral vascular resistance, and subsequent globally decreased cerebral blood flow.34,35 These substrate-delivery encephalopathies have altered cerebral oxygen and glucose delivery as a common pathway, regardless of cause, and may result in severe permanent neurologic damage if not treated urgently.
In contrast, systemic organ failure is a common cause of metabolic encephalopathy and carries a different prognosis than the substrate-delivery encephalopathies. Kidney (uremia) and liver failure are common causes.36–38 Carbon dioxide narcosis from pulmonary failure and, rarely, pancreatic failure can also cause encephalopathy.39,40 The biochemical mechanism of uremic encephalopathy is not known precisely, but decreased ability to utilize adenosine triphosphate by the uremic brain and elevated calcium content in the cerebral cortex and hypothalamus have been suggested.41 In hepatic encephalopathy, endogenous benzodiazepine-like substances may play a role, as suggested by animal studies and from experience in humans with improvement after administration of flumazenil.42 In hepatic failure, elevated levels of α-ketoglutaramate in the cerebrospinal fluid (CSF) correlate with systemic elevations in ammonia as well as depth of coma.43Patients with fulminant hepatic failure may also have severe diffuse cerebral edema,44 and the acutely increased intracranial pressure provides a structural basis for the coma in this situation. Abnormal function of endocrine organs may cause encephalopathy through primary mechanisms (e.g., myxedemacoma,45 thyrotoxicosis,46 hypocortisolemia) or through changes in electrolytes or the cerebral acid-base environment (e.g., hypercalcemia in hyperparathyroidism).
Encephalopathy frequently accompanies sepsis, especially when associated with multisystem organ failure.47,48 Critically ill patients may have multiple reasons for encephalopathy including primary organ failure (especially of kidneys and liver), electrolyte abnormalities, and concurrent use of sedative agents to facilitate interventions such as mechanical ventilation.49 However, sepsis itself is associated with a metabolic encephalopathy. Although proposed mechanisms of septic encephalopathy range from multiple microabscesses throughout the brain to alterations in cerebral blood flow mediated by nitric oxide, circulating cytokines that cross the blood–brain barrier and are released during sepsis or the systemic inflammatory response syndrome are likely to be implicated.50 In contrast to substrate-delivery metabolic encephalopathies, these alterations in consciousness are generally thought to be reversible if the underlying organ pathologic process or sepsis is reversed.
Electrolyte and acid-base disturbances are a common cause of encephalopathy. Among these, hyponatremia, hypernatremia, and hypercalcemia are most commonly associated with a decreased level of consciousness.51 In most circumstances, these encephalopathies are reversible, although rapid correction of hyponatremia should be avoided to decrease the potential of osmotic demyelination(central pontine myelinolysis).52
A global decrease in the cerebral metabolic rate of oxygen consumption may occur during profound hypothermia and following sedative drug overdose.53,54 This is reversible if substrate delivery is maintained. Thus, general anesthesia itself can be viewed as a cause of reversible metabolic encephalopathy or coma. Metabolic encephalopathy, often without a markedly decreased level of consciousness, may be caused by numerous prescription medications and may be mistaken for dementia in the elderly.55,56 Encephalopathy may also be a manifestation of collagen vascular disease (e.g., systemic lupus erythematosus, SLE), or systemic cancer.57,58 Although the latter may be mediated by electrolyte disturbances in the setting of the syndrome of inappropriate secretion of antidiuretic hormone or through paraneoplastic antibodies59 or circulating cytokines, these disorders may also cause alterations in consciousness from focal processes related specifically to the underlying cancer or collagen vascular disease.
The term delirium refers to a state of globally disturbed consciousness in which a subject has decreased attention and an altered sensorium, usually developing over hours to days and often with fluctuating symptoms.60 Agitation and hallucinations may be present but are not required for the diagnosis. Delirium has historically been a general descriptive term akin to metabolic encephalopathy and distinguished from dementia by its fairly abrupt onset, altered sensorium, and association with other medical conditions. However, within the past decade, delirium has been used specifically to describe a state of fluctuating confusion in hospitalized patients, often in those who are critically ill.19,61 The presence of delirium has been associated with worsened clinical outcome in these patients, and some studies have suggested that delirium is itself an independent condition with a pathophysiology and treatment distinct from the many other systemic diseases known to cause metabolic encephalopathy. The neurotransmitter acetylcholine is particularly implicated in delirium.62 Predisposing factors include older age, dementia, sensory impairment, sleep deprivation, and the use of sedative medications.63,64Inflammatory serum markers and genetic polymorphisms of the apolipoprotein E gene have also been suggested as predictors of presence or duration of delirium.65,66 In the intensive care unit, the use of the sedative medication dexmedetomidine has been associated with less delirium than benzodiazepineinfusions.63 Long-term cognitive impairment has been associated with delirium in acutely hospitalized patients, especially those with preexisting cognitive impairment.67 It is distinctly uncommon, however, for delirium to lead to a chronic vegetative or minimally conscious state. It remains controversial whether delirium is principally an indicator of the need for aggressive treatment of underlying medical problems and minimization of sedative usage in the hospital.68