Syncope/fainting

Definition: Syncope is a common clinical syndrome defined by sudden transient total loss of consciousness and postural tone caused by global cerebral hypoperfusion with spontaneous and complete recovery without neurologic sequelae.  It manifests in the form of a symptom complex characterized by light-headedness, generalized muscle weakness, giddiness, visual blurring, tinnitus, and gastrointestinal (GI) symptoms.

Pre-syncope refers to a situation in which there is reduction of cerebral blood flow and a sensation of impending loss of consciousness, although the patient does not actually looses consciousness.

Pathophysiology: Syncope occurs secondary to acute transient decrease in cerebral blood flow due to a variety of mechanisms. 

In order for a person to lose consciousness, the reduction of blood flow must affect the reticular activating system of the brain stem, thalamus, or both cerebral hemispheres simultaneously. Normally, with assumption of an upright posture, there is a transient reduction in blood pressure that is soon counteracted by an increase in heart rate mediated by inhibition of the parasympathetic nervous system and activation of the sympathetic nervous system. Splanchnic, renal, and skeletal muscle blood vessels vasoconstrict. The increase in heart rate is maximal at the 15th beat and a mild reflex bradycardia is noted at the 30th beat. During syncope there is a sudden transient failure of the autonomic nervous system to maintain BP against the force of gravity at a level of cerebral perfusion.

History: presyncopal, syncopal, and recovery phases.

Presyncopal phase: Patient is awake and able to related to an accurate history. Pt. is usually standing, experiences a sensation of light-headedness, dizziness, weakness, yawning,  a feeling of warmth, nausea, vomiting, and profuse sweating. Patient may have transient blindness. 

Syncopal phase: LOC, loss of postural tone, resulting in fall to the ground from muscle weakness. If syncope truly occurred, the patient will not have any memory of the events of this phase and will not provide an accurate history. Collateral information from witnesses regarding onset of syncope, duration of LOC, seizure activity, circumstances around the fall, likely trauma. A complete lack of muscle tone or myoclonic jerks is common in syncope, unlike seizure activity where tonic-clonic activity and post-ictal confusion is seen. LOC is brief, followed by immediate recovery. 

Recovery phase: Ask regarding rate of recovery from patient or/and witnesses. Confusion or delayed recovery to normal suggests post-ictal state, hypoglycemia, or CNS lesion. Patient with syncope usually regains normal mental function rapidly, with near normal mentation. Check VS, BS, ECG to provide some insight into the cause of syncope.

PMH: Risk factors - HTN, CAD, DM, VTE, CVA. Meds (anti-HTN, QT-prolonging agents, proarrhythmics, psychotropic, vasodilators) may lead to syncope secondary to dysrhythmia and hypotension. 

Temporary loss of consciousness:

Classification and Etiology of Syncope:

Cardiac:

Hypovolemia

Hypotension:

Cerebrovascular:

Metabolic:

Hyperventilation

Multifactorial:

Recurrent, unexplained syncope, particularly in an individual with structural heart disease, and is associated with a high risk of death  (40% mortality in 2 years).

Pregnancy and syncope

Epidemiology:

Seizures vs syncope.

Convulsive syncope:

The frequency of myoclonic or tonic activity during syncope is high (approximately 70%–90%). Myoclonus associated with syncope tends to be asynchronous, multifocal rather than generalized, and brief (less than 30 seconds). Tonic movements are less frequent and less pronounced in syncope, and more common after profound cerebral hypoxia (e.g., prolonged asystole, breath-holding spells). Even after a prolonged syncope lasting 1 to 2 minutes, the postictal confusion rarely lasts more than 30 seconds. Thus, longer-lasting disorientation suggests an epileptic seizure, although an exception would be frontal lobe seizures, which can be associated with very brief postictal periods. EEG during syncope shows a sequence of changes: diffuse high-amplitude slowing at the onset of unconsciousness; suppression; reappearance of slow activity; and return of normal background activity. This sequence represents the final common path for global cerebral hypoxia, and is independent of the mechanism of syncope and of the clinical presentation as convulsive or nonconvulsive syncope. 

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Vasovagal syncope (66%): A prodrome of presyncope marked by dizziness pallor is the rule. Bradycardia may be seen shortly after the episode, and recovery is usually rapid. If the clinical picture is not clear, the tilt table study is done to provoke vasovagal syncope in order to establish the diagnosis with the sensitivity and specificity of approximately 80%. Sudden head up tilting in patient with vasovagal syncope produces an increase in myocardial contractility, which in turn leads to excessive stimulation of left ventricle and mechanical receptors (C fibers) and an exaggerated reflex vagal response. No specific intervention is required and the prognosis is excellent. Up to 80% the patient with recurrent vasovagal syncope and positive tilt test respond to treatment with a beta blocker such as atenolol 25-100 mg PO q.d. This blunts the cardiac inotropic response to a fall in BP and prevents the overly sensitive reflex vagal response. Approximately half of patients who do not respond to a beta blocker or other agents will respond to paroxetine 20 mg p.o. daily, a selective SSRI.

Carotid sinus syncope: Is unusual disorder seen exclusively in older individuals and results from hypersensitivity or baroreceptors in the carotid sinus. External pressure of the neck (like turning the head while wearing a tight collar, results in an exaggerated vagal response and fall in BP. Carotid massage can be used with ECG monitoring to establish the diagnosis, but this should be performed with caution since patient may end up getting a stroke.

Neurologic cause:

Transient ischemic attack. The vertebrobasilar stenosis or occlusion is a rare cause of syncope. The diagnosis as suggested by symptoms or signs of focal brainstem ischemia (diplopia, vertigo, ataxia, nystagmus, dysarthria, dysphagia, facial numbness, unilateral or bilateral weakness, or sensory loss) either before or after the event. Deficits referable to posterior cerebral artery, particularly hemianopia may also occur. Syncope following prolonged head extension ("beauty pallor syncope") in patients with atherosclerotic vertebrobasilar disease has been described. Transcranial and duplex Doppler ultrasonography, CT or MRA, or conventional angiography is used to establish the diagnosis.

Subclavian steal. is an unusual cause of vertebrobasilar insufficiency. It results from occlusion of one of the subclavian arteries proximal to the origin of the vertebral artery. The distal subclavian artery is hence supplied by retrograde flow from the ipsilateral vertebral artery, which steal flow from the basilar and contralateral vertebral arteries, resulting in intermittent hemodynamic flow failure in the posterior circulation.

Unilateral carotid stenosis or occlusion does not cause syncope. However, in very rare instances, syncope may result from severe bilateral disease, particularly with superimposed reduction of blood pressure.

Primary autonomic failure: Shy-Drager or Riley-Day syndrome; MSA.

Autonomic ganglionopathy: Autoimmune (antecedent viral illness) or paraneoplastic (SCLC).  Sx develop over weeks. Dysfunction in autonomic system. Antibody to ganglionic nictoninic ACh-rcp in serum. 

Pure autonomic failure (Bradbury-Eggleston syndrome): Attributed to loss of intermediolateral cell column neurons.  Alpha-synucleinopathy with Lewy bodies seen. In men earliest sx is impotence. No an acute condition. 

Neuropathies:  DM, amyloidosis, BGS, AIDS, alcoholic neuropathy, hepatic prophyria, beriberi, and autoimmune subacute autonomic neuropathy and small fiber neuropathies.

POTS

It is a heterogenous condition with orthostatic intolerance due to dysautonomia and is characterized by rise in heart rate above 30 bpm from base line or to more than 120 bpm within 5-10 min of standing with or without change in blood pressure which returns to base line on resuming supine position.

This condition present with various disabling symptoms such as light headedness, near syncope, fatigue, nausea, vomiting, tremor, palpitations and mental clouding, etc . However there are no identifiable signs on clinical examination and patients are often diagnosed to have anxiety disorder. The condition predominantly affects young women between the ages of 15-50 years but is rarely described in older people.

Pathophysiology: The various pathophysiological mechanisms involved in POTS are:

Not all of these mechanisms present in any one patient and treatment should be tailored accordingly. Symptoms are most likely due to cerebral hypoperfusion.

Types of POTS:

The primary form is not associated with or caused by other chronic disorders. Here the onset is usually abrupt particularly when it occurs following viral illness, immunisation, pregnancy or surgery. An exception is the developmental form which occurs following a period of rapid growth. In this case it runs a slow progress to reach a peak within 2 years. Two major types of primary forms are identified. They are partial dysautonomic and hyperadrenergic forms:

Secondary POTS can occur in conditions that affect the peripheral autonomic nervous system such as diabetes mellitus, amyloidosis, sarcoidosis, and paraneoplastic syndromes, or following chemotherapy.

Management of POTS is multifaceted and includes discontinuation of any medications that could contribute to orthostatic intolerance, such as α-adrenoceptor antagonists, diuretics, cGMP-specific phosphodiesterase type 5 inhibitors (sildenafil), and organic nitrates and nitrites, along with identifying those conditions that may cause secondary POTS.

Treating POTS patients comprises non-pharmacological and pharmacological interventions. Conservative measures for patients with mild POTS symptoms include plasma volume expansion and increasing dietary salt and fluid intake. Pharmacotherapy is needed for patients with moderate to severe POTS, and, currently, no drug has been officially approved by the US Food and Drug Administration (FDA) for treating POTS. In fact, most drugs that are given to POTS patients are usually prescribed “off label” and include fludrocortisone, desmopressin, and, sometimes, erythropoietin. Other drugs which can also be therapeutically beneficial in patients with POTS are (1) drugs that increase peripheral vascular resistance such as midodrine, a prodrug whose active metabolite is an α-adrenoceptor antagonist, and somatostatin analogs; (2) drugs that can modify the central and peripheral activity of the sympathetic nervous system such as β-adrenoceptor antagonists (mainly propranolol), serotonin and norepinephrine uptake inhibitors, and combined α- and β-adrenoceptor antagonists; and (3) drugs that reduce the sympathetic tone such as clonidine.

Investigations: Head up tilt (HUT) is the investigation of choice although some studies suggest that standing haemodynamics is more specific. It is important to rule out other conditions which cause tachycardia such as phaeochromocytoma, carcinoid, thyrotoxicosis, cardiac arrhythmia, etc. Tachycardia in these conditions is not related to change in posture. Important investigations are blood tests which should include full blood count, renal function, thyroid function, calcium level, glucose, catecholamines on standing from supine position. Twenty-four hours urine collection for 5HIAA, catecholamines, sodium level are relevant investigations in POTS to rule out other causes of tachycardia and aim treatment options. Routinely an ECG should be performed and further investigations such as 24 h monitoring and echocardiogram are carried out if indicated.

Management: Review of medications which can aggravate POTS and appropriately stopping these medications; these include: drugs that enhance vasodilatation-alpha adrenoreceptor blockers, angiotensin converting enzyme inhibitor (ACEI), calcium channel blockers and nitrates; drugs that enhance tachycardia-beta adrenoreceptor stimulants, tricyclic antidepressants; and drugs that worsens volume depletion-diuretics and ACEI.

Treatment of POTS is challenging due to the potential for adverse effects from the above mentioned drugs and the limited effectiveness of non-pharmacologic treatments. Many POTS patients have difficulty achieving adequate control of their symptoms. In addition, none of the abovementioned medications are tailored specifically to blunt the increase in HR that underlies the many symptoms of POTS.

Vasoconstrictors: Fludrocortisone is the most commonly used drug in orthostatic intolerance. Its action is mediated by improving peripheral sensitivity of alpha adrenoceptors, fluid and salt retention. Midodrine is an alpha-1 adrenoreceptor agonist not only increases the peripheral vascular resistance but also helps orthostatic intolerance by having an effect on heart rate. Other vasoconstrictors used with variable results are: methylphenidate - increases vasoconstriction by increasing catecholamine release and inhibiting monoamine oxidase; erythropoietin: increases the sensitivity of angiotensin II; clonidine is a central sympatholytic and increases peripheral vascular resistance; and octreotide: somatostatin analogue is potent vasoconstrictor.

Heart rate limiting drugs: Beta blockers are the main group of drugs and among them propranolol is favored by clinicians. There are limited studies with regards to the dosage at which it is effective in treating POTS. Moderate dose of propranolol (20 mg) not only reduces heart rate but also improves symptoms, whereas higher dose (80 mg) is effective in reducing heart rate but does not improve symptoms. In fact it has been reported to worsen symptoms. Other drugs which can reduce heart rate and alleviate symptoms are selective serotonin reuptake inhibitors (SSRI) and selective noradrenalin reuptake inhibitors. SSRI have been used for cardiogenic syncope and orthostatic hypotension. Serotonin plays and important role in central control of heart rate.

There is some anecdotal evidence that some POTS patients can be successfully treated with ivabradine, an anti-anginal agent designed to slow the HR. Ivabradine is a selective antagonist of the If channel, an ionic current that determines the slope of diastolic depolarization (phase IV action potential). Accordingly, ivabradine controls the time interval between successive action potentials and the HR. Ivabradine also reduces the firing rate of pacemaker cells in the sinoatrial (SA) node, where it mainly influences the intrinsic HR at concentrations that do not affect other cardiac currents, and has no negative inotropic or lusitropic effects. In view of its ability to slow the HR without affecting other cardiovascular functions, we posited that ivabradine may be an ideal medication for treating POTS patients. We report herein on the results of an investigation in which the effect of ivabradine on the hemodynamics and sympathovagal balance of POTS patients was studied.

Anticipatory guidance to patients:

Cause of Orthostatic Hypotension:

Non-neurogenic causes: hypovolemia, cardiac failure, chronic illness with deconditioning and medication side-effects.

Medications causing orthostatic hypotension by impairing sympathetic tone:

Neurogenic causes: failure of autonomic nervous system, neurodegenerative diseases (PD, PAF, DLB, MSA), peripheral neuropathies (diabetes), autoimmune disorders.

History:

The clinical features should be established, with emphasis on precipitating factors, posture, type of onset of the faint (including whether it was abrupt or gradual), position of head and neck, the presence and duration of preceding and associated symptoms, duration of loss of consciousness, rate of recovery, and sequelae.  Whether patient has fainted or fallen before. If possible, question an observer about clonic movements, color changes, diaphoresis, pulse, respiration, urinary incontinence, and the nature of recovery.

In the elderly, syncope may cause unexplained falls lacking prodromal symptoms.

Vital signs: Check for orthostatics. 

SFSR

ROSE STUDY

Lab: 

Head Up Tilt test  

Method:  HUT is a method to simulate a prolonged passive stand without the active contraction of the calf muscles and is aimed to reproduce the pooling in the lower extremities that occurs upon standing. The patient lies flat on

the tilt table; HR is monitored with ECG and BP is monitored continuously both with a photoplethysmographic device and manually.  Baseline measurement is obtained after 30 minutes of recumbence.  The table is then tilted up rapidly at 60° to 80° for various periods of time, according to the clinical question to be addressed.  For patients with autonomic failure and OH, the test duration is typically 5 minutes, as patients typically develop OH within 3 minutes.  For patients with suspected POTS, test duration is extended to 10 minutes, as some patients may develop delayed hypotension.  For patients with suspected reflex (neurally mediated, vasovagal) syncope, the test duration typically is 20 to 45 minutes followed by the administration of a provocative agent, typically intravenous isoproterenol (a beta adrenergic agonist that increases cardiac contractility and elicits vasodilation) or nitroglycerin (a potent venodilator).

Normal and Abnormal Responses:  In normal conditions, the net effect of assuming the upright posture is a 10 to 20 beat-per-minute increase in HR, negligible changes in systolic BP, and an approximate 5 mm Hg increase of diastolic BP.  The initial BP decrement is modest (less than 10 mm Hg of mean BP), with recovery within 1 minute.  There are three main patterns of abnormal responses during HUT:

The first pattern is typical neurogenic OH characterized by a fall of systolic BP ≥ 20 mm Hg and/or diastolic BP ≥ 10 mm Hg within 3 minutes of standing or HUT.  Neurogenic OH is typical of autonomic failure and is mainly the consequence of impaired sympathetically mediated reflex vasoconstriction.  In these patients, the HR response is typically attenuated, but may be intact or even increased if cardiac sympathetic innervation is preserved.  OH contrasts to indices of mild adrenergic impairment which include excessive oscillations of BP; an excessive decrease (>50 percent) of pulse pressure; a transient (less than 1 min) decrease in BP; or excessive increment of HR (> 30 beats per min).  A variant called “delayed OH” may occur in some patients.

 

The second pattern is exaggerated and symptomatic orthostatic tachycardia which indicates POTS.  This is defined by an HR increase ≥ 30 beats per minute and/or HR ≥ 120 beats per minute with standing.  These criteria are applicable to patients older than 19 years of age; for younger patients, a 40 beats per minute HR increase is considered the cutoff point.  POTS is multifactorial and may result from selectively impaired adrenergic vasoconstriction resulting in venous pooling (neuropathic POTS), hyperadrenergic state (hyperadrenergic POTS), as well as hypovolemia, and deconditioning, in various combinations.

The last pattern is reflex (neurally mediated, vasovagal) syncope, in which an initially stable (or slightly increased) BP and HR is followed by a sudden drop of BP (vasodepressor response) and HR (cardioinhibitory response).  The mechanisms are poorly defined.  It is due to an abrupt decrease in cardiac output and peripheral resistance triggered by activation of ventricular or other receptors.

Cardiac cine MRI provide an alternative noninvasive modality that may be useful for patient in whom diagnostic-quality echocardiographic images cannot be obtained. Also, this test is useful for patients who have right ventricular outflow tract ventricular tachycardia, since the right ventricular structural abnormalities are better visualized better on MR imaging done by echocardiogram.

If a neurologic cause of syncope as suggested by history or examination, specific testing may include the following:

3 minute trial of hyperventilation, EEG without sleep, head CT or MRI, transcranial Doppler ultrasound to check intracranial vertebral and basilar arteries, duplex doppler ultrasonography, MRA or CTA, cerebral angiography, EMG/NCS.

HRCT, V/Q scan, or pulmonary angiography indicated in patients with syncope that maybe due to pulmonary embolus.

Doppler ultrasound studies of the carotid, MRI of the brain MRA of the head and neck without without contrast in patient with possible cerebrovascular syncope.

Treatment

Obtain a fingerstick blood glucose level. Administer IV D5W. Place the patient onto the left side. Order a stat Foley ECG and rhythm strip.

The treatment of orthostatic hypotension is approached by nonpharmacological means and with pharmacological treatments. 

Nonpharmacological approaches would include compression stockings or an abdominal binder. 

Other approaches include volume-expanding agents such as increased salt intake or fludrocortisones acetate. 

Erythropoietin can also expand blood volume, but its longterm safety and efficacy for this indication has not been established. 

Nonetheless, volume-expanding agents would be contraindicated in a person with supine hypertension who is also being treated for essential hypertension. Midodrine is an alpha-agonist that has been known to worsen supine hypertension as noted in this patient. In contrast, pyridostigmine bromide has been shown to have efficacy in patients with both orthostatic hypotension and coexisting supine hypertension.

A population-based CAMERA  (Cerebral Abnormalities in Migraine, an Epidemiologic Risk Analysis) study demonstrated an elevated prevalence of syncope and orthostatic intolerance in migraineurs without clear interictal signs of autonomic nervous system dysfunction.  NEUROLOGY 2006;66:1034–1037