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The Evaluation of Spells

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The Evaluation of Spells r e V i e W the evaluation of spells I.N. van Loon1*, J. Lamberts1, G.D. Valk2, A.F. Muller1 1Department of Internal Medicine, Diakonessenhuis, Utrecht, the Netherlands, 2Department of Internal Medicine, University Medical Centre Utrecht, Utrecht, the Netherlands, *corresponding author: tel.: +31 (0)88- 25 05 901, e-mail: [email protected] a B s t r a C t the differential diagnosis of spells is broad and includes table 1. Differential diagnosis of episodic symptoms both innocent and life-threatening conditions with a endocrine pharmacological considerable overlap in clinical presentation. extensive Pheochromocytoma Abrupt withdrawal of adrener- diagnostic testing is often performed, without reaching a Thyreotoxicosis gic inhibitor final diagnosis, or resulting in false-positives. a thorough Hypogonadism (menopause) MAO inhibitor in combination Medullary thyroid carcinoma with specific food medical history, including family history and medication, Pancreatic islet cell tumours Sympathicomimetic and physical examination are required to obtain clues (e.g. insulinoma, VIPoma) Hallucinating drugs (cocaine, Gastroenteropancreatic LSD) about the cause of a spell. an overview of spells with their neuroendocrine Chlorpropamide-alcohol flush stereotypic phenotype in general internal medicine practice tumours (carcinoid syndrome) Vancomycin is presented in this article. Besides, a diagnostic approach Hypoglycaemia Calcium antagonist is proposed for the clinical evaluation of spells. Cardiovascular neurological Labile hypertension Autonomic neuropathy Pulmonary oedema Migraine Syncope Epilepsy K e y W o r d s Orthostatic hypotension Paroxysmal arrhythmias other Angina pectoris Mastocytosis Spell, flushing, pheochromocytoma, gastroentero- Renovascular disease Recurrent idiopathic pancreatic neuroendocrine tumours, mastocytosis anaphylaxis psychiatric Panic disorder (hyperventila- tion syndrome) Conversion disorder i n t r o d UC t i o n A spell is best defined as ‘a sudden onset of a symptom or symptoms that are recurrent, self-limited, and differential diagnosis short list. A description of frequently stereotypic in nature’.1 The differential diagnosis of encountered and commonly sought causes of spells is spells is challenging and includes both innocent and given. Finally, a proposed work-up for different types of life-threatening conditions with a considerable overlap spells is presented. in clinical presentation (table 1). This typically results in extensive diagnostic testing without reaching a final diagnosis, or in false-positives. In general, but especially s e a r C H s t r a t e g y in conditions with a differential diagnosis as extended as spells, testing for a particular disease should only be We searched PubMed and Embase databases for performed if the pre-test probability is high. publications on the systematic evaluation of spells in In this article we aim to provide a rational approach to the general (i.e. manuscripts focusing on specific diseases analysis of spells and spell-like symptoms for the general were excluded in this stage) using synonyms for “spell” internist. First, we carried out a systematic literature as shown in the syntaxes (figure 1). Since the terms search on the systematic evaluation of spells in general, “attack” and “attacks” resulted in many articles concerning thereby excluding manuscripts focusing on a specific neurological or cardiovascular disorders, but not in disorder. Then, we described key components of history publications concerning spells in general, we decided to and physical examination that are necessary to make a exclude these. © Van Zuiden Communications B.V. All rights reserved. july/August 2011, vol. 69, no 7/8 309 figure 1. Search strategy position). Physical or psychological stressors immediately prior to the spell suggest a vasovagal event. Unusual Pubmed: (Spell[title/abstract] OR spells[title/abstract] OR smells, visual disturbances or uncontrolled movements flush[title/abstract] OR flushing[title/abstract] OR may represent seizure activity, often referred to as an aura. flushing[MeSH] OR flushes[title/abstract] OR paroxysm[title/ abstract] OR paroxysms[title/abstract])AND If an attack starts with palpitations or tachycardia this differential diagnosis[MeSH] suggests a cardiac cause. Loss or transient alteration of Embase: (Spell:ab,ti OR spells:ab,ti OR flush:ab,ti OR flushing:ab,ti consciousness points to insufficient blood flow to the brain OR flushes:ab,ti OR paroxysm:ab,ti (syncope) or altered brain activity (generalised seizures). OR paroxysms:ab,ti )AND ‘differential diagnosis’:ab,ti Key components of the spell itself are a description of the specific symptoms, sequence of occurrence, timing, Pubmed Embase frequency and duration. Besides all of the above, it is 470 151 important to determine factors which provoke, exacerbate or relieve the attack, such as heat, medications or alcohol. Inclusion criteria: Filtering doubles Exclusion If the attack is accompanied by flushing, one should - Concerning criterion: determine whether it is a ‘wet’ or a ‘dry’ flush. A ‘wet’ evaluation of 552 - Concerning spell symptoms a specific flush – e.g. the postmenopausal hot flash – is accompanied - Adults (> 18 diagnosis by sweating and is of a neurogenic nature (mediated Screening title/abstract years) by sympathetic cholinergic neurons that also stimulate 17 sweat glands) whereas a ‘dry’ flush is the result of direct vasodilatation due to either endogenous (e.g. histamine, Full text available prostaglandin and polypeptides) or exogenous (e.g. nicotinic acid an amyl nitrite) substances and is not 81-8 associated with perspiration.1 Patients presenting with evident neurological spell-like symptoms are generally referred to the neurologist. It is important to realise When searching PubMed, we used Medical Subject that a number of internal diseases, such as porphyria Headings (MeSH terms) for differential diagnosis and and carcinoid syndrome, can also be accompanied by flushing to broaden our search. Articles were considered neurological or psychiatric symptoms. Hypoglycaemia relevant if they described a clinical syndrome fulfilling may present with neurological symptoms due to the criteria of a spell and the study subjects were at least neuroglycopenia. Loss of, or decreased consciousness, may 19 years of age. The search resulted in 17 apparently be triggered by cerebrovascular diseases, hypoglycaemia relevant articles, of which eight were available in full or cardiac arrhythmias. A period of lethargy after the text.1-8 Two of the articles were obtained by contacting the spell can indicate mastocytosis or epilepsy. Listing authors.2,4 Three publications extensively describe the current medication including recent changes can give clinical evaluation of flushing.5,7,8 Four articles describe a important clues pointing to a correct diagnosis, especially clinical case of a patient presenting with spells and work in the geriatric population with polypharmacy. Medication out the differential diagnosis.3,6-8 Young et al. in particular associated with flushing is shown in table 2. describe pheochromocytoma, carcinoid syndrome and Regarding family history special attention should be paid mastocytosis.1 None of the publications found focus on the to sudden death, hormonal, neurological, psychiatric and approach to the wide spectrum of spells in general internal sleep disorders. medicine, including both rare and frequently observed conditions. physical examination A key element of the physical examination of a patient presenting with episodic symptoms is the measurement of M a K i n g a d i a g n o s i s blood pressure and pulse rate, preferably during the attack. Attention should be paid to the presence of orthostasis, History tachycardia and/or an irregular heartbeat. The classical The value of a detailed description of the spell cannot be presentation of a pheochromocytoma is intermittent overemphasised. Frequently the patient is able to provide hypertension, but orthostatic hypotension may also occur.9,10 sufficient information but, if this is not the case, it is Orthostatic hypotension may cause episodic dizziness. imperative to obtain a detailed account from those who The thyroid is examined for goitre or palpable nodules. witnessed the event. Cardiac murmurs and pulmonary wheezing may be an Establish what the patient was doing prior to the event, indication of carcinoid syndrome, which is associated with e.g. activities and position (upright, lying or changing pulmonary valve stenosis and tricuspid regurgitation, Van Loon, et al. The evaluation of spells. july/August 2011, vol. 69, no 7/8 310 table 2. Medical history and findings table 3. Medication associated with flushing (Izikson et al.)2 spell history Description of specific symptoms All vasodilators: Cholinergic drugs Vancomycin Sequence of occurrence, timing, frequency, duration of nitroglycerin Bromocriptine Rifampicin symptoms and nitric oxide Chemotherapeutics: Contrast media Wet flush, dry flush or episodic pallor releasers: e.g. cyclosporine, doxo- Combination anaes- Hypertension over time sildenafil rubicin, cisplatin, thesia of isoflurane Lethargy after the spell All calcium channel interferon alfa-2 and fentanyl Provoking, exacerbating or relieving factors blockers Anti-androgens: Morphine and other Cardiac complaints: chest pain, fatigue, dyspnoea, dizziness Calcitonin flutamide, opiates Neurological complaints: weakness, sensory loss, altered states Beta-blockers cyproterone Antiemetics: e.g. of consciousness Angiotensin-
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