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MikkoKallela

Differential Diagnostics of Episodic Symptoms

Essentials

  • The majority of episodic symptoms are of benign nature, but the possibility of potentially serious conditions should be taken into account.
  • Patient history is by far the most important instrument in the investigation of episodic symptoms. The onset of symptoms, provoking factors, course over time and the patient's condition after the episode are particularly important in the exploration of the symptoms. As is often the case in other contexts too, the first impression (at the start of an episode) is very important.
  • Possible further investigations are focused according to the most probable aetiology.

Classification of episodic symptoms in primary care

  • Fainting i.e. vasovagal syncope
  • Hypoglycaemic episode
  • An episode associated with heart disease or pulmonary embolism
  • An episode associated with a neurological illness or symptom
    • Epileptic seizure
      • Generalised seizure
      • Focal seizure
  • Disorders of cerebral circulation
    • TIA or stroke at the carotid region (“disturbance of anterior circulation”)
    • TIA or stroke at the basilar region (“disturbance of posterior circulation”)
  • Transient global amnesia (TGA)
  • Paroxysmal headache
    • Primary headache
    • Secondary headache
  • Migraine aura
  • Paroxysmal dizziness (”dizzy spells”)
    • Benign positional vertigo
    • Acute vestibular deficiency (vestibular neuronitis)
    • Attack of Ménière's disease
  • A collapse associated with orthostatism
  • Psychogenic causes

Typical episodic symptoms

  • Fainting can be identified by the presence of a preceding, emotionally stressful situation (taking of a blood test, emotional turmoil, standing at attention for a long time), signs and symptoms of presyncopy (paleness, sweating, feeling unwell), short duration (less than 1 minute) and short recovery period Syncope: Causes and Investigations. Dehydration, anaemia or hypoglycaemia may significantly contribute towards fainting.
  • A drop attack signifies a sudden loss of muscle tone without a loss of consciousness. A common cause of falls in the elderly. A small disturbance in the cerebral circulation will lead to the patient falling but will not cause loss of consciousness.
  • A hypoglycaemic attack is associated with, for example, rapid heart beat, sweating, feeling of hunger, tremor, headache, confusion, visual disturbances as well as irritability and other transient emotional symptoms. The symptoms will disappear as soon as the blood glucose level is restored.
  • A history of heart disease and symptoms suggestive of cardiogenic origin (awareness of cardiac arrhythmias, chest pain, dyspnoea) are indicative of cardiogenic episodes (ischaemic heart disease, valvular defect, disturbances in the conduction system, long QT syndrome, WPW syndrome, SVT, ventricular tachycardia etc.)
    • If the patient has lost consciousness, it will return quickly after normal circulation is restored. There usually are no convulsions or post-ictal confusion, but short-lasting twitching of the limbs may be noted.
    • In addition to collapse, the typical symptoms of pulmonary emboli are dyspnoea, chest pain and cough.
  • A generalised epileptic seizure is characterised by abrupt onset, loss of consciousness, rhythmic tonic-clonic convulsions, incontinence, slow recovery and post-ictal confusion. The patient may hurt himself/herself.
    • The duration of a typical uncomplicated seizure is about one minute.
  • Signs suggestive of a focal epileptic seizure include neurological prodromal symptoms (”aura”, such as a rising epigastric sensation, déjà vu, sensory disturbances, speech disorders, twitching of the limbs, abnormal tonic positions), sudden onset, blurring of consciousness and, in some cases, the progression of the symptoms to tonic-clonic convulsions.
  • Disorders of cerebral circulation (see Cerebral Infarction (Ischaemic Stroke) Intracerebral Haemorrhage) are characterised by a sudden onset of symptoms which suggest a neurological deficit. The symptoms may have improved or be totally absent when the patient presents himself/herself. Not taking into account episodes of TIAs, most patient will, however, exhibit some residual signs on examination.
    • Patients with episodes of a TIA Transient Ischaemic Attack (TIA) often have cardiovascular risk factors. A TIA symptom develops rapidly, reaches its peak within seconds or tens of seconds, and its duration is from a few minutes to a good ten minutes.
      • During a TIA affecting the carotid artery region, the patient experiences unilateral limb weakness, transient loss of vision and disturbances in speech if the dominant hemisphere is affected.
      • During a TIA affecting the vertebral artery region, the patient experiences dizziness, blurred vision, diplopia, slurred speech and drop attacks (differential diagnosis may be difficult).
  • Primary headache manifests itself as repeated episodes of headache of similar character. No abnormalities will be detected on examination. A patient with secondary headache (for example caused by disturbed cerebral circulation or a brain tumour) will typically show abnormal signs on examination and the headache will not easily fulfil the criteria of any of the causes of a primary headache (see Cluster Headache (Horton's Syndrome) Migraine Tension Headache).
  • A migraine aura is typically a visual disturbance including both positive (zigzag lines, vibrating visual field, scintillation) and negative (scotoma) features. It may also consist of a disturbance of speech or sensation.
    • An aura expands (becomes worse) within tens of minutes and gradually subsides so that the total duration is less than an hour.
    • The most characteristic feature of migraine is the recurrence of the attacks and also of the aura always in a similar way. The headache often follows the aura within an hour.
    • A TIA symptom develops more rapidly than a migraine aura, and it lacks the expansive nature and the positive features typical of an aura, and usually also the subsequent headache is absent.
  • Transient global amnesia (TGA Transient Global Amnesia (TGA)) refers to an episode lasting from a few hours to 24 hours during which time the patient is not able to formulate new memory. The patient keeps repeating the same questions, although otherwise operates appropriately.
  • In benign positional vertigo (see Benign Paroxysmal Positional Vertigo (BPPV) Vertigo) certain changes in the position of the head precipitate severe, transient vertigo which is not associated with other neurological symptoms. Intensive vertigo is typically of limited duration, usually less than a minute, and the patient feels well after that, until a change in the position of the head provokes another episode of rotatory vertigo.
    • Other causes of acute vertigo include acute vestibular neuronitis and an attack of Ménièr's disease Ménière's Disease.
  • In orthostatism Syncope: Causes and Investigations, the feelings of weakness, dizziness or near collapse are associated with getting up. The patient is often elderly and uses several different medicines. Autonomic neuropathy (for example associated with diabetes) worsens symptoms.
  • A collapse brought on by psychogenic causes is typically preceded by a fright, anxiety, panic and hyperventilation. No abnormal findings are detected in the somatic status. The patient often has a history of similar attacks Anxiety Disorder.
  • More rare causes of episodic symptoms include:
    • Hypersensitivity of the carotid sinus (carotid sinus syncope)
      • Stimulation of the carotid sinus (for example, a tight collar) will cause, via the vagal reflex, the patient to collapse.
    • Narcolepsy Narcolepsy and other Hypersomnias of Central Origin
      • The symptoms include: increased urges to sleep, cataplexy (sudden loss of voluntary muscle tone associated with, for example, laughing), sleep paralysis and hallucinations during sleep onset or upon awakening.

Diagnostics

History, status and first-line investigations

  • It is most important to obtain a clear description of the events. In addition to the history submitted by the patient, the description of the events by witnesses forms the cornerstone of diagnostics. The patient's past medical history, current medication (antihypertensives, antipsychotics and other vasoactive drugs) and family history (for example epilepsy, migraine, sudden death, known long QT syndrome) should all be taken into consideration before deciding which investigations to carry out.
  • Physical examination
    • General condition
    • Signs of trauma (may be the cause of an episode of impaired consciousness or secondary falling)
    • Bite marks on the lateral sides of the tongue, incontinence (suggestive of a seizure)
    • Oedema, other signs of heart disease (suggestive of cardiogenic aetiology)
  • Cardiovascular status
    • A five point memory aid:
      1. History, medication
      2. Clinical findings: general state, jugular venous pulse, arterial pulse, blood pressure, heart auscultation
      3. ECG
      4. Chest X-ray
      5. Laboratory tests (see below).
    • An orthostatic test is important when examining a patient with a history of collapse. The patient has orthostatism if his/her systolic blood pressure is > 20 mmHg lower or diastolic blood pressure > 10 mmHg lower when taken with the patient standing up (often heart rate increases > 30 beats per minute). At least 2 (2-5) minutes should be allocated when waiting for the possible fall in blood pressure.
    • A careful examination of the ECG is very important (ischaemic changes, rhythm, ectopic beats, PR time, QT time etc.)
  • Neurological status
    • A five point memory aid:
      1. History
      2. Clinical findings: level of consciousness, nuchal rigidity, bite marks on the tongue, cranial nerves (eyes, face, speech), neurological deficits / side differences
      3. CT scan of the head
      4. Cerebrospinal fluid sample (+ other laboratory tests)
      5. EEG
    • Impaired level of consciousness and inability to cooperate are suggestive of epilepsy or other neurological aetiology. Laboratory and other tests should be carried out after careful consideration has been given to the patient's history and examination findings.
    • If the patient's collapse, based on history and physical examination, is suspected to have been caused by an acute neurological condition (for example, disturbed cerebral circulation), an emergency CT scan of the head is an essential investigation.
    • A lumbar puncture Lumbar Puncture may be carried out, as necessary, in addition to the CT scan, for example if subarachnoid bleed is suspected Intracranial Aneurysm and Subarachnoid Haemorrhage (SAH).
    • An EEG should be considered if an epileptic mechanism is suspected to be the cause of collapse.
  • The following investigations should be considered:
    • Routine tests:
      • ECG, blood glucose, CRP, basic blood counts with platelets, creatinine, electrolytes
      • If considered necessary: TSH, free T4, drug tests (ethanol, methanol, illicit drugs, medicines), serum cortisol
    • Tests to examine cardiogenic aetiology or possible pulmonary embolism:
      • ECG, CK, CK-MB, arterial blood gases, fibrin D-dimer, TnT, CRP
    • Tests after a seizure:
      • CK, blood concentration of antiepileptic medication (if known epileptic and if a test for the measurement of the concentration of the particular drug is available), possibly plasma calcium, liver function tests, ammonium ion

Further investigations

  • If the first-line investigations are suggestive of cardiogenic origin, the following should be considered: echocardiogram, ambulatory ECG monitoring and exercise tolerance test Diagnosis of Syncope.
  • Ambulatory blood pressure monitoring may be useful if the patient is suspected to have orthostatism.
  • The following neurological investigations should be considered individually for each patient: angio-CT, MRI, MR angiography or EEG (sleep, video or ambulatory EEG monitoring).
  • Testing the function of the autonomic nervous system may be useful in evaluating the state of the autonomic nervous system. The tilt table test may provide more information in cases of recurrent syncope.