Research – Orthostatic Hypotension Causing Syncope and Hemiplegic Migraines

Diagnosis, evidenced based treatment of, and prognosis for:

• 1. Orthostatic Hypotension causing syncope
• 2. Hemiplegic Migraines

Date: October 09, 2020

Requester: Wendy s47F - pers (Assistant Director – TAB) Requester: Alicia s47F - personal privacy (Advisor – TAB)

Researcher: Craig s47F - persona (Tactical Research Advisor – TAB/AAT)

Please note:

The research and literature reviews collated by our TAB Research Team are not to be shared external to the Branch. These are for internal TAB use only and are intended to assist our advisors with their reasonable and necessary decision-making. Delegates have access to a wide variety of comprehensive guidance material. If Delegates require further information on access or planning matters they are to call the TAPS line for advice. The Research Team are unable to ensure that the information listed below provides an accurate & up-to-date snapshot of these matters.

Contents

• Related TAB Research … 2
• Summary … 2
• What is Orthostatic Hypotension and Syncope? … 3
  • Orthostatic Hypotension (OH) … 3
  • Syncope … 4
  • Orthostatic Hypotension causing Syncope (Orthostatic syncope) … 5
  • Prognosis for Orthostatic Syncope … 5
  • Diagnosis of Orthostatic Hypotension … 5
  • Treatment of Orthostatic Hypotension … 7
    • Medication management … 8
    • Non-medical management … 8
• Hemiplegic Migraines … 9
  • What are Hemiplegic Migraines? [24] … 9

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Related TAB Research

Summary

Orthostatic Hypotension Causing Syncope

• Orthostatic hypotension is also referred to as postural hypotension and is a sudden fall in blood pressure that occurs when the patient stands up quickly. It may be acute or chronic, as well as symptomatic or asymptomatic.

• Syncopal is the medical term for fainting or passing out. Syncopal episodes are typically triggered by a sudden, temporary drop in blood flow to the brain, which leads to loss of consciousness and muscle control.

• Orthostatic Hypotension can cause Syncope and is termed “Orthostatic Syncope”.

• Diagnosis for suspected Orthostatic Hypotension begins by identifying reversible causes and underlying associated medical conditions.

• Treatment of Orthostatic Hypotension depends on the cause and includes medical and non-medical management.

• Prognosis for Orthostatic Syncope depends on the underlying cause of orthostatic hypotension. The prognosis is good in non-neurally mediated orthostatic syncope once the cause of hypotension is identified and treated.

• It appears that improving the hypotension will likely reduce occurrence of syncope.

Hemiplegic Migraines

• Hemiplegic migraine (HM) is a rare type of migraine headache affecting a small number of people who get migraine with aura. Aura includes visual symptoms, like flashes of light and zigzag patterns that happen before or during a migraine.

• Diagnosis is based on characteristic symptoms, patient history, clinical evaluation and other specialized tests. There are no pathognomonic clinical, laboratory or radiological findings to diagnose HM. Generally, affected individuals must have two episodes of migraine with aura that exhibit specific signs or symptoms.

• Treatment of HM is directed toward the specific symptoms that are apparent in each individual. A Multidisciplinary management approach is taken.

• Prognosis for HM is good, where most patients recover completely between episodes. However time may effect neurologic outcomes.

What is Orthostatic Hypotension and Syncope?

Orthostatic Hypotension (OH)

Orthostatic hypotension, also called postural hypotension, is a sudden fall in blood pressure that occurs when the patient stands up quickly. Hypotension is the term for low blood pressure.

When the patient stands up, gravity pulls blood into the legs and the blood pressure begins to fall. Certain reflexes in the body compensate for this change. The patient’s heart beats faster to pump more blood and the blood vessels constrict to prevent blood from pooling in the legs.

Many drugs can affect these normal reflexes and lead to orthostatic hypotension. These reflexes may also begin to weaken as the patient ages. For this reason, orthostatic hypotension is more common in older adults.

People with orthostatic hypotension may feel dizzy when they stand up. The condition is often mild and lasts for just a few minutes after standing. Some people may faint or lose consciousness. [1]

According to a 2011 study, about 20 percent of people older than 65 experience orthostatic hypotension. [2]

Orthostatic hypotension may be acute or chronic, as well as symptomatic or asymptomatic. Common symptoms include:

• Dizziness
• Light-headedness
• blurred vision
• weakness
• fatigue
• nausea

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• palpitations
• headache

Less common symptoms include:

- syncope
- dyspnea
- chest pain
- neck and shoulder pain.

Causes include [2]:

- dehydration or blood loss
- disorders of the neurologic, cardiovascular, or endocrine systems
- several classes of medications

Syncope

Fainting, or passing out, is referred to medically as a syncopal episode, or syncope. Syncopal episodes are typically triggered by a sudden, temporary drop in blood flow to the brain, which leads to loss of consciousness and muscle control. The patient then falls down or over, which allows blood flow to return to the brain. Returning blood flow allows the patient to regain consciousness.

Syncope is common. It can happen at any age, including childhood, though fainting happens more frequently to people as they get older. Syncopal episodes usually last only seconds or minutes. They may be accompanied by temporary feelings of confusion when the patient regains consciousness.

Syncope can be caused by an underlying medical condition or from environmental triggers. Fainting can also result from an emotional response to a very difficult situation. Intense pain, low blood sugar, or a change in blood volume may also cause syncope. If the patient experiences a drop in blood pressure or heart rate, they may faint abruptly.

Common causes of syncope include:

- low blood pressure or dilated blood vessels
- irregular heart beat
- abrupt changes in posture, such as standing up too quickly, which can cause blood to pool in the feet or legs
- standing for long periods of time
- extreme pain or fear
- extreme stress
- pregnancy
- dehydration
- exhaustion

Syncopal episodes are often preceded by warning signs or symptoms. These may include [1]:

- nausea
- slurred speech

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• weak pulse
• changes in body temperature that make you feel suddenly flushed or chilled
• sudden, clammy sweat
• pale skin
• disturbances to your vision, like seeing spots, tunnel vision, blurry vision, or dilated pupils
• feeling as if sounds are suddenly very far away
• light-headedness, wooziness, or feeling as if your head and body are weightless
• numbness
• dizziness
• vertigo, or a sensation that the room is moving
• rapid heartbeat
• body weakness
• shakiness
• headache

Orthostatic Hypotension causing Syncope (Orthostatic syncope)

Orthostatic syncope refers to syncope resulting from a postural decrease in blood pressure termed as OH. [3]

In the general population, syncope and OH are frequent events that often lead to hospitalisation or a visit to the emergency department. However, as a broad symptom, it is currently unclear whether they are independent risk markers for adverse prognosis or if syncope and OH are actually the initial symptom leading to diagnosis of severe underlying cardiac disease. [4]

OH is an important cause of syncope, and may contribute to morbidity, all-cause mortality and reduced quality of life. [5]

Prognosis for Orthostatic Syncope

Prognosis for orthostatic syncope depends on the underlying cause of orthostatic hypotension. The prognosis is good in non-neurally mediated orthostatic syncope once the cause of postural hypotension is identified and treated - fluid resuscitation in dehydration or volume depletion, transfusion for blood loss, discontinuation of offending antihypertensive medications. In neurally mediated syncope, prognosis depends on the course of the underlying medical condition. [3]

Diagnosis of Orthostatic Hypotension

Tests used to diagnose orthostatic hypotension include [6]:

• Medical history, including medical conditions and drugs taken on a regular basis
• Physical examination
• Measuring blood pressure when lying down versus standing up

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• Blood tests to check, for example, blood sugars or adrenal hormones
• Echocardiography, an imaging scan of the heart, to check for certain heart conditions
• Other tests, depending on individual factors.

In a research paper focusing on the evaluation and management of OH the following diagnostic steps were indicated [2]: - Identify reversible causes and underlying associated medical conditions - Elicit symptoms of autonomic dysfunction involving the gastrointestinal and genitourinary systems - Assess motor nervous system - Measure blood pressure and pulse rate - Test with head-up tilt-table

Evaluation of suspected OH begins by identifying reversible causes and underlying associated medical conditions.

The table below lists historical features that suggest a specific diagnosis in the patient with orthostatic hypotension. [7, 8]

Historical features	Possible etiology
Abnormal uterine bleeding, fatigue, rectal bleeding	Anemia
Amaurosis fugax, aphasia, dysarthria, unilateral sensory and motor symptoms	Stroke
Bradykinesia, pill-rolling tremor, shuffling gait	Parkinson disease
Burns	Intravascular volume depletion
Chest pain, palpitations, shortness of breath	Congestive heart failure, myocardial infarction, myocarditis, pericarditis
Chills, fever, lethargy, nausea, vomiting	Gastroenteritis, sepsis
Extremity swelling	Congestive heart failure, venous insufficiency
High-risk sexual behavior	AIDS, neurosyphilis
Progressive motor weakness	Guillain-Barré syndrome, multiple system atrophy
Relapsing neurologic symptoms in various anatomic locations	Multiple sclerosis
Symptoms after a meal	Postprandial hypotension
Witnessed collapse	Cardiac arrhythmia, seizure

In addition to assessing for symptoms of orthostasis, the physician should elicit symptoms of autonomic dysfunction involving the gastrointestinal and genitourinary systems. [7]

Key physical examination findings in the evaluation of suspected orthostatic hypotension are listed in the table below. [9, 10]

Treatment of Orthostatic Hypotension

Treatment of OH depends on the cause where options may include [6]:

• Fluids to treat dehydration
• Management of diabetes, such as regular insulin injections
• Changes in medication or altered doses if drugs are the cause (sometimes, however, stopping or altering the dose of a particular medication may cause more harm than good and must be carefully considered in consultation with your doctor)
• Medication, surgery or both to treat heart conditions
• Medication to increase blood volume or pressure, including corticosteroids
• Medications to treat orthostatic hypotension including pyridostigmine, a drug used in the treatment of myasthenia gravis
• A range of treatments, since orthostatic hypotension may have two or more causes
• In some cases, a lower body pressure suit is required.

Medication management

A 2017 research review [14] published by the Royal Australasian College of Physicians suggested the following medications are used in treatment:

• Midodrine, an α1 agonist, stimulates arterial and venous adrenoceptors [15]

• Droxidopa is a noradrenaline prodrug with a short life of 2–3 h. It is not yet available in Australia but has been used in Japan for more than a decade and was recently approved in the United States for neurogenic OH. However, its efficacy is unclear in diabetes [15]

• Fludrocortisone, a synthetic mineralocorticoid, acts by improving circulating blood volume and blood vessel sensitivity to pressor agents. Although it is suggested as the first-line treatment in some guidelines, given salt and water retention and its long half-life, it may not be suitable for patients with heart failure and nocturnal hypertension [16]

• Pyridostigmine, a cholinesterase inhibitor, has the advantage of not aggravating supine hypertension. However, its pressor effect is modest, and it is less well-tolerated due to gastrointestinal side effects [17]

• Atomoxetine, a noradrenaline reuptake inhibitor, has been shown to increase standing BP in a single-dose crossover trial, with improvement in BP and symptoms compared to midodrine and placebo. [18] However, its long-term effects are not known.

• Caffeine inhibits peripheral vasodilatation and thus increases standing BP [19]

Non-medical management

The Royal Australasian College of Physicians research review [14] suggested the following for non-medical management:

• Patients should be advised to stand slowly in stages to prevent sudden falls in BP.

Hemiplegic Migraines

What are Hemiplegic Migraines? [24]

Hemiplegic migraine (HM) is a rare type of migraine headache. Like other migraines, hemiplegic migraine causes intense and throbbing pain, nausea, and sensitivity to light and sound. It also causes temporary weakness, numbness and tingling, and paralysis on one side of the body. These symptoms start before the headache.

HM affects a small number of people who get migraine with aura. Aura includes visual symptoms, like flashes of light and zigzag patterns that happen before or during a migraine. Aura also includes other sensory problems and trouble speaking. In people with hemiplegic migraine, the weakness or paralysis happens as part of the aura.

There are two types of HM which are based on family history of migraines:

1. Familial hemiplegic migraine (FHM) affects at least two close relatives in the same family. If a patient has FHM, each of their children will have a 50 percent chance of inheriting the condition.

2. Sporadic hemiplegic migraine (SHM) affects people who don’t have any family history of the condition.

HM is caused by changes (mutations) to genes. A few genes have been linked to hemiplegic migraine, including:

• ATP1A2
• CACNA1A
• PRRT2
• SCN1A

Diagnosis

A diagnosis of hemiplegic migraine is based upon [25]:

• Identification of characteristic symptoms,
• A detailed patient history,
• A thorough clinical evaluation
• A variety of specialized tests.

There are no pathognomonic clinical, laboratory or radiological findings to diagnose HM. [26]

Two proposed diagnostic criteria have been published (The International Classification of Headache Disorders, 3rd edition [25] and a population-based study of familial hemiplegic migraine [26a] suggests revised diagnostic criteria, to help physicians diagnose hemiplegic migraine.

Generally, affected individuals must have two episodes of migraine with aura that exhibit specific signs or symptoms. By definition, fully reversible muscle weakness on one side of the body (hemiplegia) that occurs with at least one other type of aura symptom (vision, sensory, speech or brainstem) must be present for a diagnosis. For the familial form, at least one first- or second-degree relative must also have the disorder. [25]

Brain imaging is usually normal in individuals with hemiplegic migraine. A minority of individuals affected by hemiplegic migraine associated with permanent cerebellar symptoms have an atrophy of the cerebellum. [25]

Molecular genetic testing can confirm a diagnosis of familial hemiplegic migraine in some individuals. Molecular genetic testing can detect mutations in specific genes known to cause the disorder, but is available only as a diagnostic service at specialized laboratories. [25]

The table below gives the diagnostic criteria according to the International Classification of Headache Disorders, third edition. [27]

Type	Diagnostic criteria ICHD-3
Hemiplegic migraine	A. At least two attacks fulfilling criteria
B. One or more of the following fully reversible aura symptoms:

1. visual
2. sensory
3. speech and/or language
4. motor
5. brainstem
6. retinal C. At least three of the following six characteristics:
7. at least one aura symptom spreads gradually over 5 minutes
8. two or more aura symptoms occur in succession
9. each individual aura symptom lasts 5–60 minutes
10. at least one aura symptom is unilateral
11. at least one aura symptom is positive
12. the aura is accompanied, or followed within 60 min, by headache D. Aura consisting of both of the following:

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Diagnostic criteria ICHD-3

Type

Type	Diagnostic criteria ICHD-3
	1. fully reversible motor weakness
	2. fully reversible visual, sensory and/or speech/ language symptoms.

Familial hemiplegic migraine (FHM)

A. Attacks fulfilling criteria for Hemiplegic migraine B. At least one first- or second-degree relative has had attacks fulfilling criteria for Hemiplegic migraine.

Familial hemiplegic migraine type 1 (FHM1)

A. Attacks fulfilling criteria for Familial hemiplegic migraine B. A mutation on the CACNA1A gene has been demonstrated

Familial hemiplegic migraine type 2 (FHM2)

A. Attacks fulfilling criteria for Familial hemiplegic migraine B. A mutation on the ATP1A2 gene has been demonstrated.

Familial hemiplegic migraine type 3 (FHM3)

A. Attacks fulfilling criteria for Familial hemiplegic migraine B. A mutation on the SCN1A gene has been demonstrated.

Familial hemiplegic migraine, other loci

A. Attacks fulfilling criteria for Familial hemiplegic migraine B. Genetic testing has demonstrated no mutation on the CACNA1A, ATP1A2 or SCN1A genes

Sporadic hemiplegic migraine (SHM)

A. Attacks fulfilling criteria for Hemiplegic migraine B. No first- or second-degree relative fulfils criteria for Hemiplegic migraine.

Treatment

The management of HM relies on the control of triggering factors and sometimes severe attacks can require hospitalisation to ensure fluid balance and food intake. Fever and seizures can be treated symptomatically. [26]

The treatment of HM is directed toward the specific symptoms that are apparent in each individual. Multidisciplinary management may require the coordinated efforts of a team of specialists [25:

• Paediatricians
• Physicians who specialize in diagnosing and treating disorders of the brain and central nervous system in children (paediatric neurologists)
• Neurologists
• Physicians who specialized in treating headaches or migraines
• Pain specialists
• Physicians who specialize in diagnosing and treating eye disorders (ophthalmologists)
• Social workers
• Psychosocial support for the entire family may be beneficial as well
• Genetic counselling may be of benefit for affected individuals and their families

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Prognosis

Although most people with familial hemiplegic migraine (FHM) recover completely between episodes, neurological symptoms such as memory loss and problems with attention can last for weeks or months. The occurrence of FHM attacks tends to decrease with age. The eventual neurologic outcome is often benign; however, about 20 percent of individuals with FHM develop mild but permanent difficulty coordinating movements (ataxia), which may worsen with time, and nystagmus (rapid, involuntary eye movements). Unusually severe migraine episodes have been reported in some people with FHM. These episodes may include fever, seizures, prolonged weakness, coma, and, rarely, death. [28]

References

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9. Gross CR, Lindquist RD, Woolley AC, Granieri R, Allard K, Webster B. Clinical indicators of dehydration severity in elderly patients. J Emerg Med. 1992;10(3):267-274.
10. Gorelick MH, Shaw KN, Murphy KO. Validity and reliability of clinical signs in the diagnosis of dehydration in children. Pediatrics. 1997;99(5):E6.

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Podoleanu C, Maggi R, Brignole M, Croci F, Incze A, Solano A et al. Lower limb and abdominal compression bandages prevent progressive orthostatic hypotension in elderly persons: a randomized single-blind controlled study. J Am Coll Cardiol 2006; 48: 1425–32.

Smeenk HE, Koster MJ, Faaij RA, de Geer DB, Hamaker ME. Compression therapy in patients with orthostatic hypotension: a systematic review. Neth J Med 2014; 72: 80–5.

Healthline [Internet]. Healthline Media a Red Ventures; 2020. What Is a Hemiplegic Migraine? [Date cited 09 October 2020] . Available from: https://www.healthline.com/health/migraine/hemiplegic-migraine

National Organisation for Rare Disorders [Internet]. NORD - National Organization for Rare Disorders, Inc; 2020. Hemiplegic Migraine [Date cited 09 October 2020] . Available from: https://www.healthline.com/health/migraine/hemiplegic-migraine

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26 Di Stefano V, Rispoli MG, Pellegrino N, et al. Diagnostic and therapeutic aspects of hemiplegic migraine. Journal of Neurology, Neurosurgery & Psychiatry 2020;91:764-771.

26a Thomsen L, Eriksen M, Roemer S, Andersen I, Olesen J, Russell M. A population-based study of familial hemiplegic migraine suggests revised diagnostic criteria. Brain. 2002;125(6):1379-1391.

27 The International Classification of Headache Disorders, 3rd edition [Internet]. Ichd-3.org. 2020 [Cited 09 October 2020]. Available from: https://ichd-3.org/wp-content/uploads/2018/01/The-International-Classification-of-Headache-Disorders-3rd-Edition-2018.pdf

28 Genetic and Rare Diseases Information Centre [Internet]. Genetic and Rare Diseases Information Center (GARD); 2020. Familial hemiplegic migraine [Date cited 09 October 2020] . Available from: https://rarediseases.info.nih.gov/diseases/10975/familial-hemiplegic-migraine