Diagnosis of Chronic Fatigue Syndrome

• Tension headache
• Pseudotumor cerebri
  –Elevated ICP with no masses or abnormalities in CSF or labs
• Cluster headache
  –Unilateral nonthrobbing, periorbital pain
  –May have ipsilateral conjectival injection, lacrimation, rhinorrhea
• Subarachnoid hemorrhage
  –Sudden paroxysmal headache
  –Meningeal signs
  –An emergency requiring CT and LP
• Increased intracranial pressure
  –Tumor, abscess, hydrocephalus, hemorrhage
• Sinusitis, otitis
• Dental disease
• Systemic infection
• TMJ disease
• Postconcussive syndrome
• Trigeminal neuralgia
• Mitochondrial disorders
• Venous sinus thrombosis
• Meningitis/encephalitis
• CSF leak, post-lumbar puncture
• Hypertensive crisis
• Trauma
• Arteriovenous malformation
• Stroke
• Toxins and medication
  –Nitrites, cocaine, interferon, CO
• Fever
• Anemia

Workup and Diagnosis

• History
  –Duration (recurrent, progressive), frequency
  –Time of onset and duration
  –Location and nature of pain, warning (aura)
  –Factors that alleviate or exacerbate symptoms (e.g., stress)
  –Nausea, vomiting, photophobia, phonophobia
  –Family history, response to treatment
• Physical exam
  –Vital signs (temperature, blood pressure)
  –Height, weight, head circumference
  –Funduscopy (to rule out papilledema)
• Neuroimaging (CT, MRI) is required for certain symptoms
  –Short history of headache (<6 months) or age <5–6 years
  –Worsening headaches, no response to treatment
  –Deterioration in cognitive or motor function
  –Short stature, macrocephaly
  –Awakening at night or early morning
  –Repeated morning vomiting
  –Exacerbation by position change or cough
  –Focal neurologic symptoms during headache
  –Cluster headache in prepubertal children and adolescent girls
  –Systemic symptoms: Fatigue, weight loss
  –Abnormal neurological exam
  • Lumbar puncture with opening pressure
    –Subarachnoid hemorrhage, pseudotumor, or meningitis
  >>

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Source: In A Page: Pediatric Signs and Symptoms, 2007

HEADACHE: Approach to the Diagnosis
(Differential Diagnosis in Primary Care)

The patient presenting with a history of headaches is an exciting diagnostic challenge. If one approaches the challenge simply on the basis of what is common, the patient most likely has migraine or muscle traction headache. But, wait a minute! Shouldn’t we look for serious conditions such as brain tumor, meningitis, or subarachnoid hemorrhage to avoid a serious mistake and a malpractice suit? First, check for nuchal rigidity to rule out meningitis and subarachnoid headache. Next, do a careful neurologic examination to rule out a brain tumor or other space-occupying lesion. These steps are particularly important in a patient is experiencing his or her first serious headache. If there is nuchal rigidity or focal neurologic signs, it is wise to immediately refer the patient to a neurologist or neurosurgeon for further workup and possible hospitalization. The specialist will probably order a CT scan of the brain and follow that with a spinal tap if a subarachnoid hemorrhage or meningitis is suspected. It is clear that a CT scan should be done prior to a spinal tap if there are focal neurologic signs or papilledema. One other condition that must be considered in acute headache particularly in the elderly is temporal arteritis. A sedimentation rate will usually be positive but a neurology consult is axiomatic so that steroids can be started immediately.

In the patient with chronic or recurring headaches and no neurologic findings, it is wise to see the patient during the attack. Migraine and histamine headaches can be diagnosed by the response to sumatriptan by mouth or injection. If the headaches are due to chronic allergic or infectious rhinitis, relief can be had by spraying the turbinates with phenylephrine. Muscle traction headaches will often be relieved by occipital nerve blocks supporting the diagnosis. Compression of the superficial temporal artery will often relieve migraine temporarily supporting that diagnosis. Compression of the jugular veins will often give relief to post spinal tap headaches.

If the patient is seen between headaches, certain prophylactic measures may help establish the diagnosis. For migraine, β-blockers may be prescribed and if the headaches are prevented, there is good support for the diagnosis. A course of corticosteroids may be initiated in patients with histamine (cluster) headaches to help establish the diagnosis. Muscle relaxants and/or tricyclic drugs may be given to help diagnose muscle contraction headaches.

The diagnostic workup of chronic headaches might include a CT scan of the brain, x-rays of the sinuses, x-rays of the cervical spine and routine blood work. Certainly if headache persists after careful follow up, these need to be done.

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Source: Differential Diagnosis in Primary Care, 2007

WEAKNESS AND FATIGUE, GENERALIZED: Approach to the Diagnosis
(Differential Diagnosis in Primary Care)

The association of other symptoms and signs with generalized weakness and fatigue is very important in pinning down a diagnosis. Generalized lymphadenopathy and fatigue suggest infectious mononucleosis, lymphoma, or tuberculosis or other chronic infection such as AIDS. Weakness and weight loss and polyphagia with polyuria and polydypsia would suggest hyperthyroidism or diabetes mellitus. Generalized weakness with polyuria and no significant weight loss suggests hyperparathyroidism. Weakness with pallor suggests some type of anemia. Weakness and weight loss without polyuria or polyphagia suggest malignancy or malabsorption syndrome. Weakness with other significant neurologic signs and symptoms prompts the consideration of muscular dystrophy, amyotrophic lateral sclerosis, or multiple sclerosis. Weakness with drug or alcohol use prompts the investigation of drug or alcohol abuse. Caffeine, especially in large quantities, can also cause significant weakness and chronic fatigue.

The initial workup of weakness and fatigue requires a CBC, sedimentation rate, drug screen, chemistry panel, thyroid profile, ANA, chest x-ray and ECG. If muscular dystrophy or dermatomyositis is suspected, urine for creatinine, creatine and myoglobin can be done. Ultimately, a muscle biopsy may be indicated. If myasthenia gravis is suspected, serum for acetylcholine receptor antibody may be done. If Addison disease is suspected, a serum cortisol may be done. A 24-hour urine aldosterone level may be done to exclude primary aldosteronism. Serum PTH may be done to exclude hyperparathyroidism.

It would be wise to consult an infectious disease specialist before ordering an expensive workup. It would also be wise to consult an oncologist when searching for a malignancy before ordering an expensive workup.

When all tests have negative findings, many clinicians have been tempted to make a diagnosis of chronic fatigue syndrome. It is questionable whether this is truly a disease or not.

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Source: Differential Diagnosis in Primary Care, 2007

Fatigue: History and physical examination
(Handbook of Signs & Symptoms (Third Edition))

Obtain a careful history to identify the patient’s fatigue pattern. Fatigue that worsens with activity and improves with rest generally indicates a physical disorder; the opposite pattern, a psychological disorder. Fatigue lasting longer than 4 months, constant fatigue that’s unrelieved by rest, and transient exhaustion that quickly gives way to bursts of energy are other findings associated with psychological disorders.

Ask about related symptoms and recent viral or bacterial illness or stressful changes in lifestyle. Explore nutritional habits and appetite or weight changes. Carefully review the patient’s medical and psychiatric history for chronic disorders that commonly produce fatigue. Ask about a family history of such disorders.

Obtain a thorough drug history, noting the use of any drug with fatigue as an adverse effect. Ask about alcohol and drug use patterns. Determine the patient’s risk for carbon monoxide poisoning, and inquire as to whether the patient has a carbon monoxide detector.

Observe the patient’s general appearance for overt signs of depression or organic illness. Is he unkempt or expressionless? Does he appear tired or sickly, or have a slumped posture? If warranted, evaluate his mental status, noting especially mental clouding, attention deficits, agitation, or psychomotor retardation.

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Source: Handbook of Signs & Symptoms (Third Edition), 2006

Headache: History and physical examination
(Handbook of Signs & Symptoms (Third Edition))

If the patient reports a headache, ask him to describe its characteristics and location. How often does he get a headache? How long does a typical headache last? Try to identify precipitating factors, such as certain foods or exposure to bright lights. Ask what helps to relieve the headache. Is the patient under stress? Has he had trouble sleeping?

Take a drug and alcohol history, and ask about head trauma within the past 4 weeks. Has the patient recently experienced nausea, vomiting, photophobia, or visual changes? Does he feel drowsy, confused, or dizzy? Has he recently developed seizures or does he have a history of seizures?

Begin the physical examination by evaluating the patient’s level of consciousness (LOC). Then check his vital signs. Be alert for signs of increased ICP — a widened pulse pressure, bradycardia, an altered respiratory pattern, and increased blood pressure. Check pupil size and response to light, and note any neck stiffness.

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Source: Handbook of Signs & Symptoms (Third Edition), 2006

Headache: Diagnosis
(Professional Guide to Diseases (Eighth Edition))

Diagnosis requires a history of recurrent headaches and physical examination of the head and neck. Such examination includes percussion, auscultation for bruits, inspection for signs of infection, and palpation for defects, crepitus, or tender spots (especially after trauma). Firm diagnosis also requires a complete neurologic examination, assessment for other systemic diseases — such as hypertension — and a psychosocial evaluation, when such factors are suspected.

Diagnostic tests include cervical spine and sinus X-rays, EEG, computed tomography scan — performed before lumbar puncture to rule out increased intracranial pressure (ICP) — or magnetic resonance imaging. A lumbar puncture isn’t done if there’s evidence of increased ICP or if a brain tumor is suspected because rapidly reducing pressure by removing spinal fluid can cause brain herniation.

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Source: Professional Guide to Diseases (Eighth Edition), 2005

Chronic fatigue syndrome: Diagnosis
(Professional Guide to Diseases (Eighth Edition))

Because the cause and nature of CFS are still unknown, no single test unequivocally confirms its presence. Therefore, physicians base this diagnosis on the patient’s history and the CDC’s criteria. (See CDC criteria for diagnosing chronic fatigue syndrome.) Because the CDC criteria are admittedly a working concept that may not include all forms of this disease and are based on symptoms that can result from other diseases, diagnosis is difficult and uncertain.

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Source: Professional Guide to Diseases (Eighth Edition), 2005

Fatigue: History and physical examination
(Professional Guide to Signs & Symptoms (Fifth Edition))

Obtain a careful history to identify the patient’s fatigue pattern. Fatigue that worsens with activity and improves with rest generally indicates a physical disorder; the opposite pattern, a psychological disorder. Fatigue lasting longer than 4 months, constant fatigue that’s unrelieved by rest, and transient exhaustion that quickly gives way to bursts of energy are findings associated with psychological disorders.

Ask about related symptoms and any recent viral or bacterial illness or stressful changes in lifestyle. Explore nutritional habits and any appetite or weight changes. Carefully review the patient’s medical and psychiatric history for any chronic disorders that commonly produce fatigue, and ask about a family history of such disorders.

Obtain a thorough drug history, noting use of any narcotic or drug with fatigue as an adverse effect. Ask about alcohol and drug use patterns. Determine the patient’s risk of carbon monoxide poisoning, and ask whether the patient has a carbon monoxide detector.

Observe the patient’s general appearance for overt signs of depression or organic illness. Is he unkempt or expressionless? Does he appear tired or sickly, or have a slumped posture? If warranted, evaluate his mental status, noting especially mental clouding, attention deficits, agitation, or psychomotor retardation.

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Source: Professional Guide to Signs & Symptoms (Fifth Edition), 2006

Headache: History and physical examination
(Professional Guide to Signs & Symptoms (Fifth Edition))

If the patient reports a headache, ask him to describe its characteristics and location. How often does he get a headache? How long does a typical headache last? Try to identify precipitating factors, such as eating certain foods or exposure to bright lights. Ask what helps to relieve the headache. Is the patient under stress? Has he had trouble sleeping?

Take a drug and alcohol history, and ask about head trauma within the last 4 weeks. Has the patient recently experienced nausea, vomiting, photophobia, or visual changes? Does he feel drowsy, confused, or dizzy? Has he recently developed seizures, or does he have a history of seizures?

Begin the physical examination by evaluating the patient’s level of consciousness (LOC). Then check his vital signs. Be alert for signs of increased ICP—widened pulse pressure, bradycardia, altered respiratory pattern, and increased blood pressure. Check pupil size and response to light, and note any neck stiffness. (See Differential diagnosis: Headache, pages 392 and 393.)

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Source: Professional Guide to Signs & Symptoms (Fifth Edition), 2006

Fatigue: History
(The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter)

A thorough medical, social, and family history must be conducted to identify comorbid or contributing conditions that require treatment or suggest lifestyle modification.

A. The fatigue should be assessed in terms of duration, onset, level of impairment, and character. Specifically, fatigue should be distinguished from weakness and hypersomnolence.

B. A complete review of systems may point to a cardiovascular, neurologic, psychiatric, infectious, autoimmune, hematologic, pulmonary, endocrine, or malignant cause to pursue.

 C. Attention should also be given to medication—both prescription and over-the-counter—and to diet, exercise, substance abuse, and sleep disturbance.

 D. Lifestyle issues to explore include caretaking for young children, an elderly or ill relative, and the number of hours worked outside the home. Life stresses or major family transitions such as relocation, death, divorce, financial difficulties and past or current abuse or trauma should also be assessed.

Physical examination

A thorough physical examination should be done to investigate findings of underlying disease. This is also an important prerequisite to satisfy the patient’s concern regarding the possibility of an organic cause if a psychiatric diagnosis is made. Particular attention should be given to the presence of pallor, cardiac arrhythmia, dyspnea, fever or other indication of infection; weight loss; lymphadenopathy; evidence of inflammatory arthritis, occult blood loss, organomegaly, or abdominal masses; neurologic signs of impaired coordination; hypertension; edema; generalized pruritus; obesity; peripheral neuropathy; goiter; dry hair or skin; hemoptysis; or pregnancy. Conduct a mental status examination to identify abnormalities in mood, intellectual function, memory, and personality. Pay special attention to assessment of symptoms of depression or anxiety, suicidal ideation, and psychomotor retardation.

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Source: The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter, 2000

Headache: History
(The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter)

A. Characteristics of the headache. What is the type of pain, its location, its duration, and its intensity? What symptoms precede or accompany the pain? Does anything trigger the headache or make the pain better or worse? Tell about a typical headache from beginning to end.

 1. Migraine food triggers include alcohol, aged cheese, chocolate, and aspartame.

 2. Approximately 20% to 30% of migraineurs will report an aura, typically visual in nature.

3. Patients with cluster headache report unilateral temporal headache, occurring generally once daily, usually in the evening and associated with ipsilateral nasal stuffiness and conjunctival injection.

4. Chronic daily headache (CDH) patients will describe headaches at least 10 to 15 days/month and usually report heavy use of relief drugs.

 5. Red flags that might suggest intracranial pathology (section I.B) include a loss of consciousness, persistent visual loss, seizures, staggering, or hearing loss.

 B. Chronology of the headache. Most primary headaches recur periodically for years, with only subtle changes over time. If the headache is getting worse, the cause might be psychosocial stressors, medication overuse, or evolving intracranial pathology (Table 2.5). Ask women whether the headache seems related to the menses. Past and current medication use and how they affect the headache can be important clues to headache severity and how the patient may respond to treatment.

 C. Family history. Migraine headaches often exhibit a familial pattern; the causes of secondary headaches generally do not. Tension headache can represent a family pattern of reacting to stress.

D. Psychosocial aspects of the headache. What does the patient believe is the cause of the headache? What life events might be playing a role? How does the patient’s family react to the headache? Ask: “If you did not have the headache, how would your life be different?” The key to management of recurrent primary headaches often lies in the responses to these questions, which can reveal unanticipated stressors, secondary gain, or family discord.

E. Other information. Important data include use of tobacco, alcohol, or coffee; response to exercise; a history of head trauma; or exposure to toxic fumes or chemicals. Have there been symptoms of fever, or fatigue? Ask about depression, which is often seen in migraineurs.

Physical examination

 A. Focused physical examination (PE). This should include vital signs (notably blood pressure) and an examination of the scalp; eyes, including funduscopic examination; ears; nose; paranasal sinuses; throat; and neck. A screening neurologic examination, including cranial nerves, coordination (finger-to-nose test), and deep tendon reflexes, is sufficient in most instances. In the migraineur, the examination findings should be all normal in the absence of a current headache; a positive finding warrants further testing (section IV).

B. Additional PE. Other PE maneuvers are appropriate if the medical history suggests specific secondary headache causes: palpation of the superficial temporal arteries (temporal arteritis), audiometry (acoustic neuroma), transillumination of the paranasal sinuses (“sinus headache”), or checking for nuchal rigidity plus Kernig’s and Brudzinski’s signs (meningeal irritation).

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Source: The 10-Minute Diagnosis Manual: Symptoms and Signs in the Time-Limited Encounter, 2000

Fatigue: Differential Overview
(Field Guide to Bedside Diagnosis)

❑ Infectious mononucleosis

❑ Depression

❑ Diabetes

❑ Hypothyroidism

❑ Drugs

❑ Chronic sleep deprivation

❑ Congestive heart failure

❑ Occult infection

❑ Iron deficiency anemia

❑ Obstructive sleep apnea

❑ Renal failure

❑ Chronic fatigue syndrome

❑ Cushing syndrome

❑ Occult cancer

❑ Addison disease

❑ Myasthenia gravis

Diagnostic Approach

Organic fatigue is characterized by physical weakness or exhaustion, which is exacerbated by activity and partially relieved by sleep, short duration (,2 months), unintentional weight loss of greater than 10%, and an ill appearance. Most organic causes have associated signs and symptoms, specific and few in number.

Psychological fatigue is characterized by a primary inertia to initiation of physical activity, which when undertaken, can be performed. The patient is tired all the time, but fatigue is not exacerbated by exertion or relieved by rest. A protracted course, multiple and nonspecific associated symptoms, relation to stressful life events, and an anxious or depressed appearance are other clues. The sick role response to prior minor illness can indicate likely response to the current illness.

A medical or psychiatric diagnosis can be found in over two-thirds of patients with more than one month of fatigue. Psychiatric diagnoses, especially depression, panic disorder, or somatization disorder are the most common.

A diagnostic approach that involves careful history-taking and physical examination, assiduous avoidance of early closure, and a clear orientation to the reality of the patient’s perceptions whatever the cause (i.e., never implying “It’s all in your head”), is most rewarding. The differential is wide, and identification of the unusual organic causes among the many psychophysiological ones takes great skill.

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Source: Field Guide to Bedside Diagnosis, 2007

Headache: Differential Overview
(Field Guide to Bedside Diagnosis)

❑ Migraine

❑ Tension

❑ Acute sinusitis

❑ Acute glaucoma

❑ Postconcussive

❑ Cluster

❑ Meningitis

❑ Drugs

❑ Hypoglycemia

❑ Benign exertional headache

❑ Temporomandibular joint inflammation

❑ Subdural hematoma

❑ Subarachnoid hemorrhage

❑ Acute epidural hematoma

❑ Lumbar puncture

❑ Brain tumor

❑ Headache in HIV

❑ Pseudotumor cerebri

❑ Hypertensive encephalopathy

❑ Carbon monoxide intoxication

❑ Giant cell arteritis

❑ Psychogenic

❑ Brain abscess

❑ Encephalitis

❑ Arteriovenous malformations

❑ Cavernous sinus thrombosis

❑ Pituitary apoplexy

❑ Carotid artery dissection

Diagnostic Approach

Red flags to serious causes include: Sudden onset of “the worst headache of my life,” especially in a non—headache-prone person; headache different from previous headaches; headache precipitated by position change, cough, or exertion; a history of trauma or fever; abnormal mental status or other neurological findings; a headache that disturbs sleep or is present immediately on awakening; immune deficiency such as HIV.

The time course helps in diagnosing headache. A “thunderclap” headache of a ruptured aneurysm peaks instantly. Cluster headache peaks over 3 to
5 minutes, remains at maximum for 45 minutes, and then gradually recedes. Migraine builds over hours, lasts hours to days, and is improved with sleep.

In evaluating patients with recurrent migraine, it is critical to ascertain whether the present headache differs from prior migraines and whether fever is present or spontaneous retinal venous pulsations are abnormally absent. These should prompt a search for alternative causes. If fever is present with headache, rule out meningitis.

Raised intracranial pressure should be suspected with blurred vision upon bending the head forward, headache upon awakening that improves with sitting up, double vision, loss of coordination and balance, or daily
progressive headache with nausea. Pain originating above the tentorium is referred to the frontal, temporal, or parietal region. Pain from the posterior fossa and below is referred to the occiput. Pain from the posterior sagittal and transverse sinuses may be referred to the eye or forehead.

Lumbar puncture, subdural hematoma, or benign intracranial hypertension can cause orthostatic headache. Occipital headache radiating to the vertex and forehead is usually a result of cervical spondylosis but can also be caused by basal subarachnoid hemorrhage, posterior fossa tumor, or meningitis.

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Source: Field Guide to Bedside Diagnosis, 2007

Headache: Diagnosis
(Handbook of Diseases)

An accurate diagnosis requires a history of recurrent headaches and physical examination of the head and neck. Such examination includes percussion, auscultation for bruits, inspection for signs of infection, and palpation for defects, crepitus, and tender spots (especially after trauma).

A firm diagnosis also requires a complete neurologic examination, assessment for other systemic diseases (such as hypertension), and a psychosocial evaluation (when such factors are suspected).

Most patients may be diagnosed by a thorough history and physical examination. Magnetic resonance imaging, computed tomography scans, lumbar puncture, and serology may be beneficial. Neurologic deficits, such as stroke or brain tumors; metabolic processes, such as thyroid disease or diabetes; and an aneurysm must be ruled out if the headache is explosive and “the worst” in their lives.

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Source: Handbook of Diseases, 2003

Chronic fatigue and immune dysfunction syndrome: Diagnosis
(Handbook of Diseases)

The cause and nature of CFIDS are still unknown, and no single test unequivocally confirms its presence. Therefore, the diagnosis is based on the patient’s history and the CDC criteria. Because the CDC criteria are admittedly a working concept that may not include all forms of this disease and are based on symptoms that can result from other diseases, diagnosis is difficult and uncertain. Considerable overlap exists between CFIDS and fibromyalgia syndrome, with many patients having features of both.

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Source: Handbook of Diseases, 2003

Fatigue: History
(Signs & Symptoms: A 2-in-1 Reference for Nurses)

Obtain a careful history to identify the patient’s fatigue pattern. Fatigue that worsens with activity and improves with rest generally indicates a physical disorder; the opposite pattern indicates a psychological disorder. Fatigue lasting longer than 4 months, constant fatigue that’s unrelieved by rest, and transient exhaustion that quickly gives way to bursts of energy are other findings associated with psychological disorders.

Ask about related symptoms and any recent viral or bacterial illness or stressful changes in lifestyle. Explore nutritional habits and any appetite or weight changes. Carefully review the patient’s medical and psychiatric history for chronic disorders that commonly produce fatigue. Ask about a family history of such disorders.

Obtain a thorough drug history, noting use of any opioid or drug with fatigue as an adverse effect. Ask about alcohol and drug use patterns. Determine the patient’s risk of carbon monoxide poisoning, and inquire as to whether the patient has a carbon monoxide detector.

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Source: Signs & Symptoms: A 2-in-1 Reference for Nurses, 2007

Headache: History

(Signs & Symptoms: A 2-in-1 Reference for Nurses)

If the patient reports a headache, ask him to describe its characteristics and location. How often does he get a headache? How long does a typical headache last? Try to identify precipitating factors, such as certain foods or exposure to bright lights. Ask what helps to relieve the headache. Is the patient under stress? Has he had trouble sleeping?

Take a drug and alcohol history, and ask about head trauma within the last 4 weeks. Has the patient recently experienced nausea, vomiting, photophobia, or visual changes? Does he feel drowsy, confused, or dizzy? Has he recently developed seizures, or does he have a history of seizures?

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Source: Signs & Symptoms: A 2-in-1 Reference for Nurses, 2007

Fatigue: Clinical Features and Diagnosis
(The Diagnostic Approach to Symptoms and Signs in Pediatrics)

Physiologic Causes

Pathologic Causes

Anemia