Orthostatic hypotension in the context of Pure autonomic failure

Multiple system atrophy (MSA) is a rare neurodegenerative disorder characterized by tremors, slow movement, muscle rigidity, postural instability (collectively known as parkinsonism), autonomic dysfunction and ataxia. This is caused by progressive degeneration of neurons in several parts of the brain including the basal ganglia, inferior olivary nucleus, and cerebellum. MSA was first described in 1960 by Milton Shy and Glen Drager and was then known as Shy–Drager syndrome.

Many people affected by MSA experience dysfunction of the autonomic nervous system, which commonly manifests as orthostatic hypotension, impotence, loss of sweating, dry mouth and urinary retention and incontinence. Palsy of the vocal cords is an important and sometimes initial clinical manifestation of the disorder.

Syncope (syncope), commonly known as fainting or passing out, is a loss of consciousness and muscle strength characterized by a fast onset, short duration, and spontaneous recovery. It is caused by a decrease in blood flow to the brain, typically from low blood pressure. There are sometimes symptoms before the loss of consciousness such as lightheadedness, sweating, pale skin, blurred vision, nausea, vomiting, or feeling warm. Syncope may also be associated with a short episode of muscle twitching. Psychiatric causes can also be determined when a patient experiences fear, anxiety, or panic; particularly before a stressful event, usually medical in nature. When consciousness and muscle strength are not completely lost, it is called presyncope. It is recommended that presyncope be treated the same as syncope.

Causes range from non-serious to potentially fatal. There are three broad categories of causes: heart or blood vessel related; reflex, also known as neurally mediated; and orthostatic hypotension. Issues with the heart and blood vessels are the cause in about 10% and typically the most serious, while neurally mediated is the most common. Heart-related causes may include an abnormal heart rhythm, problems with the heart valves or heart muscle, and blockages of blood vessels from a pulmonary embolism or aortic dissection, among others. Neurally mediated syncope occurs when blood vessels expand and heart rate decreases inappropriately. This may occur from either a triggering event such as exposure to blood, pain, strong feelings or a specific activity such as urination, vomiting, or coughing. Neurally mediated syncope may also occur when an area in the neck known as the carotid sinus is pressed. The third type of syncope is due to a drop in blood pressure when changing position, such as when standing up. This is often due to medications that a person is taking, but may also be related to dehydration, significant bleeding, or infection. There also seems to be a genetic component to syncope.

Amyloidosis is a group of diseases in which abnormal proteins, known as amyloid fibrils, build up in tissue. There are several non-specific and vague signs and symptoms associated with amyloidosis. These include fatigue, peripheral edema, weight loss, shortness of breath, palpitations, and feeling faint with standing.

In AL amyloidosis, specific indicators can include enlargement of the tongue and periorbital purpura. In wild-type ATTR amyloidosis, non-cardiac symptoms include: bilateral carpal tunnel syndrome, lumbar spinal stenosis, biceps tendon rupture, small fiber neuropathy, and autonomic dysfunction.

Hydrochlorothiazide, sold under the brand name Hydrodiuril among others, is a diuretic medication used to treat hypertension and swelling due to fluid build-up. Other uses include treating diabetes insipidus and renal tubular acidosis and to decrease the risk of kidney stones in hypercalciuria. Hydrochlorothiazide is taken by mouth and may be combined with other blood pressure medications as a single pill to increase effectiveness. Hydrochlorothiazide is a thiazide medication which inhibits reabsorption of sodium and chloride ions from the distal convoluted tubules of the kidneys, causing a natriuresis. This initially increases urine volume and lowers blood volume. It is believed to reduce peripheral vascular resistance.

Potential side effects include poor kidney function, electrolyte imbalances, including low blood potassium, and, less commonly, low blood sodium, gout, high blood sugar, and feeling lightheaded with standing.

Furosemide, sold under the brand name Lasix among others, is a loop diuretic medication used to treat edema due to heart failure, liver scarring, or kidney disease. Furosemide may also be used for the treatment of high blood pressure. It can be taken intravenously or orally. When given intravenously, furosemide typically takes effect within five minutes; when taken orally, it typically metabolizes within an hour.

Common side effects include orthostatic hypotension (decrease in blood pressure while standing, and associated lightheadedness), tinnitus (ringing in the ears), and photosensitivity (sensitivity to light). Potentially serious side effects include electrolyte abnormalities, low blood pressure, and hearing loss. It is recommended that serum electrolytes (especially potassium), serum CO₂, creatinine, BUN levels, and liver and kidney functioning be monitored in patients taking furosemide. It is also recommended to be alert for the occurrence of any potential blood dyscrasias.

Autoimmune autonomic ganglionopathy is a type of immune-mediated autonomic failure that is associated with antibodies against the ganglionic nicotinic acetylcholine receptor present in sympathetic, parasympathetic, and enteric ganglia. Typical symptoms include gastrointestinal dysmotility, orthostatic hypotension, and tonic pupils. Many cases have a sudden onset, but others worsen over time, resembling degenerative forms of autonomic dysfunction. For milder cases, supportive treatment is used to manage symptoms. Plasma exchange, intravenous immunoglobulin, corticosteroids, or immunosuppression have been used successfully to treat more severe cases.

Postural orthostatic tachycardia syndrome (POTS) is a condition characterized by an abnormally large increase in heart rate upon sitting up or standing. POTS in adults is characterized by a heart rate increase of 30 beats per minute within ten minutes of standing up, accompanied by other symptoms. This increased heart rate should occur in the absence of orthostatic hypotension (>20 mm Hg drop in systolic blood pressure) to be considered POTS. POTS is a disorder of the autonomic nervous system that can lead to a variety of symptoms, including lightheadedness, brain fog, blurred vision, weakness, fatigue, headaches, heart palpitations, exercise intolerance, nausea, difficulty concentrating, tremulousness (shaking), syncope (fainting), coldness, pain or numbness in the extremities, chest pain, and shortness of breath. Many symptoms are worsened with postural changes, especially standing up. POTS symptoms may be treated with lifestyle changes such as increasing fluid, electrolyte, and salt intake, wearing compression stockings, slowing down postural changes, exercise, medication, and physical therapy.

POTS is mainly caused by problems in the autonomic nervous system, which controls heart rate and blood flow. This may include blood pooling in the legs instead of returning to the heart, or the heart beating faster to make up for low blood pressure. In other cases, it develops after a viral infection, surgery, trauma, autoimmune disease, or pregnancy. It has also been shown to emerge in previously healthy patients after contracting COVID-19, in people with Long COVID (post-COVID-19 condition), or possibly in rare cases after COVID-19 vaccination, though causative evidence is limited and further study is needed. POTS is more common among people who got infected with SARS-CoV-2 than among those who got vaccinated against COVID-19. About 30% of severely infected patients with long COVID have POTS. Risk factors include a family history of the condition.