Usefulness of the Head-Upright Tilt Test for Distinguishing Syncope and Epilepsy in Children

PURPOSE: Episodic loss of consciousness in children, whether or not associated with hypertonia or short-duration clonic movements, presents a diagnostic challenge to the pediatrician and child neurologist. We provide some evidence of the usefulness of the head-upright tilt test for investigating the causes of transient loss of consciousness in children, and for distinguishing between syncope, convulsive syncope, and epilepsy. METHODS: We studied nine children previously diagnosed as epileptic on the basis of compatible clinical events and epileptiform findings in routine EEGs who were treated over the long term with antiepileptic drugs, but whose clinical records suggested syncope or convulsive syncope rather than epilepsy on reevaluation. All subjects underwent head-upright tilt testing. RESULTS: The tilt-test result was positive in all nine cases, with the patients reporting the same symptoms as in the previously considered epileptic attacks. CONCLUSIONS: Inadequate histories and misuse/overinterpretation of EEG results often lead to misdiagnosis of epilepsy in children. The head-upright tilt test is a useful and reliable diagnostic technique, allowing syncopal events to be induced and evaluated under controlled conditions. In a subset of patients, it may help to distinguish epilepsy from simple or convulsive syncope.     

Syncope associated with hair-grooming

We report 20 girls who experienced episodes of unconsciousness while standing for hair grooming. The episodes were syncopal in character, electroencephalograms were normal in most cases, and at least 11 of the 20 had definite episodes of syncope in other circumstances. A number of these girls underwent extensive diagnostic testing. We consider this a form of situational or reflex syncope, perhaps related to orthostatic hypotension, the recognition of which may spare unnecessary diagnostic and therapeutic interventions.     

Dreaming experience as a useful diagnostic clue for syncopal episodes

Background: The differential diagnosis between epileptic seizures and syncopes is a common occurrence in clinical practice. The manifestations of seizure and syncope sometimes overlap, and available diagnostic testing often not provides a conclusive answer. Syncope is often preceded by a symptom complex characterized by lightheadedness, generalized muscle weakness, giddiness, visual blurring, tinnitus, and gastrointestinal symptoms. These subjective symptoms are very important in guiding the diagnosis. In our experience, the impression of coming out of a dream after the syncopal episode is a subjective symptom commonly reported by patients, if questioned. Methods: To verify the occurrence of dreaming experience after syncope and after generalized tonic‐clonic seizures (GTCS) and its diagnostic value in differential diagnosis, we asked 100 patients with GTCS and diagnosis of idiopathic generalized epilepsy (Group 1) and 100 patients with a certain diagnosis of syncope (Group 2) whether they have never felt the impression of coming out of a dream after the loss of consciousness (GTCS or syncope, respectively). Results: In Group 1, nobody referred the dreaming experience, whereas in the syncope group, 19% of patients referred this subjective symptom. Conclusions: Dreaming experience seems to be an additional useful diagnostic clue for syncopal episodes, helping the clinician to differentiate them from seizures.     

Syncope as a first sign of seizure disorder

We studied the long-term follow-up of patients with the diagnosis of "syncope of unknown origin," and their progression to epilepsy to gain a better understanding of the relationship between syncope and epilepsy, and to determine whether findings of the first syncopal attack have prognostic significance in relationship to the onset of epilepsy or not. Eighteen patients with the diagnosis of syncope of unknown origin were evaluated for the possibility of becoming epileptic during a 4-year period, and four patients showed characteristic seizure disorder. There were no clinical or laboratory features that differentiated them from the nonepileptic group, except that they were all girls. The interval between the first syncopal attack and the typical epileptic seizure ranged between 7 and 19 months. Syncope of unknown origin could be the first sign of an epileptic disorder, especially in girls. Long-term follow-up extending up to 1 year is necessary to disclose the risk of becoming epileptic.     

Abnormal cardiovascular responses to carotid sinus massage also occur in vasovagal syncope – implications for diagnosis and treatment

Background and purpose: Carotid sinus massage (CSM) is commonly used to identify carotid sinus hypersensitivity (CSH) as a possible cause for syncope, especially in older patients. However, CSM itself could provoke classical vasovagal syncope (VVS) in pre disposed subjects. Methods: Retrospective analysis of CSM, cardiovascular autonomic function tests (including tilt table testing) and medical history in 388 patients with recurrent syncope to identify and characterize patients in whom an abnormal response to CSM was more likely to reflect VVS than CSH. Results: CSM was abnormal in 79 patients. In 53 patients (77.2 ± 8.7 years), CSH was the likely cause of syncope. VVS was the more likely diagnosis in 26 younger patients (59.7 ± 12.6 years) with longstanding syncope from youth, in whom fear or pain was as a trigger; 7/26 suffered from intense chronic or intermittent neck pain and one exacerbation of syncopal attacks followed a physical and emotional trauma to the neck. In VVS, 4/26 had spontaneous VVS during head‐up tilt, another six after venepuncture (performed in 17/26). In 6/26, the abnormal response to CSM was delayed, occurring 62.8 ± 28.4 s after completion of CSM. The response to CSM was predominantly of the mixed type (20/26) and abnormal on both sides in 14/26. Conclusions: An abnormal response to CSM may not indicate syncope caused by CSH and needs to be considered in the light of the patient’s age, duration of syncopal episodes and detailed history of provocative stimuli. Differentiating CSH from VVS with an abnormal response to CSM has various implications from advice on driving to treatment strategies.     

Episodic neurological dysfunction due to mass hysteria

We describe 10 students from a small rural secondary school with episodes resembling seizures or syncopal attacks. Several students were initially treated for epilepsy or syncope, but the temporal pattern of the attacks, the simultaneous resolution of the episodes during a school holiday, and the fact that 4 students subsequently had pseudoseizures confirmed by video-electroencephalography strongly suggest mass hysteria. Seven students were treated with antiepileptic medications, and most underwent multiple diagnostic studies. Prompt recognition of mass hysteria allows physicians to avoid unnecessary tests and treatments and to reassure those affected as well as the general public.     

Diagnosing epilepsy in neurology clinics: A prospective study

The certainty of the initial diagnosis of epilepsy was assessed prospectively by one neurologist in outpatients. One hundred and fifty-eight consecutive referrals with loss of consciousness or possible epilepsy were seen. The relative contributions to the initial diagnosis from the referral letter, history taking in clinic, physical examination, and investigation were compared. There was a referring diagnosis in 28.5%. The neurologist reached a diagnosis in 87% of the 158 cases: in 43% epilepsy, 25% syncope, 12% non-epileptic seizures and in 7% other diagnoses. There was a low correlation between referral and specialist diagnosis. Physical examination did not change the diagnosis in any patient. Investigations changed the diagnosis in one patient. Neuro-imaging revealed a relevant abnormality in 12/43 (27.9%) scanned. The yield from EEG was 7/25 (28%), but the EEG changed the diagnosis in only one case. Cardiac testing confirmed the type of syncope in 2/47 (4.3%) of patients. Blood tests did not contribute to the diagnosis in any patient. The neurology consultation significantly increased diagnostic certainty. The diagnosis of epilepsy remains largely clinical. It is important that patients are aware of this prior to investigation.     

Unrecognized paroxysmal ventricular standstill masquerading as epilepsy: a Stokes-Adams attack.

Recognition of cardiac syncope masquerading as epilepsy may be difficult in the Emergency Department. We report a middle-aged man with recent onset convulsions who posed a diagnostic puzzle before it was found that he had paroxysmal ventricular standstill with complete atrioventricular block: he made a complete recovery after temporary pacemaker insertion. The main lessons from this case were (1) a convulsive seizure of only seconds duration and with an abrupt return of consciousness suggests syncope not epilepsy, (2) repeated, convulsive syncopes without provocation suggest cardiac syncope, (3) a 12-lead ECG should be recorded as soon as possible after such a series of episodes and should not be discontinued until an event is captured, and (4) Emergency Department clinicians should be familiar with any automatic gain on their ECG machine, lest fast, atrial activity be mistaken for narrow complex tachycardia. In summary, a good clinical history is of prime importance in differentiating convulsive syncope from epilepsy, and a simple, non-invasive cardiovascular evaluation may help to diagnose the condition as cardiac syncope.     

Heart rate variability in children with neurocardiogenic syncope

Abstract. In order to characterize the autonomic profile of syncopal children, we have studied heart rate variability (HRV) of 73 children, ages 11–18, with neurocardiogenic syncope and a positive outcome of head-up tilt testing (HUT).HRV was calculated over a 24-hour period for the time-domain indices (SDNN, SDANNi, SDNN, rMSSD, pNN50), and over 5-minute segments from night and day for frequency-domain indices (LF, HF, LF/HF). The obtained results were compared to reference values calculated for Polish children. 55% of the children had mixed response to HUT, 41% vasodepressor and 4% cardioinhibitory. Patients with syncope had significantly lower values of rMSSD and pNN50 in comparison to healthy children. Moreover, in the frequency-domain analysis they exhibited significantly higher LF and lower HF values. The day-night rhythm of HRV and the age-related changes of HRV were, however, similar in syncopal and healthy children. In addition to this, we found a significantly lower SDNN value in children with cardioinhibitory response during HUT in comparison to children with mixed response. We concluded that 1) based on HRV analysis children with neurocardiogenic syncope had alterations in basal autonomic balance, which indicated an increased sympathetic modulation in these patients, 2) syncopal children had adequate circadian rhythm of autonomic activity, 3) the changes of HRV indices with age in these groups are not altered in comparison to healthy children, 4) syncopal children may exhibit differences in HRV indices values depending on the kind of vasovagal response observed during HUT.     

Long-Term Prognosis of Convulsive Disorders in the First Year of Life: Mental and Physical Development and Seizure Persistence

Summary: A follow-up study was made on 304 children (164 boys, 140 girls) with convulsive disorders, excluding occasional convulsions, in the first year of life. All patients except 45 who died were followed until 6 years of age or older. At the final follow-up, the subjects were divided into six groups according to the degree of mental and physical development (groups I-VI). Seizures were regarded as absent if the patient had been seizure free for more than 3 years. At the final follow-up, seizures had ceased in 57.7%, and 43.4% had normal mental and physical development (group I). As to the initial diagnosis, the percentage of group I at the final follow-up was 81.8% with febrile convulsions and 37.6% with epilepsy. In patients without seizures it was 69.7% with febrile convulsions and 55.8% with epilepsy. Some 80.6% of patients with unclassified generalized motor seizures, 11.5% of those with infantile spasms, 2.9% of those with secondary generalized epilepsy other than infantile spasms, 46.4% of those with partial seizures, and 25.0% of those with hemiconvulsive seizures were finally placed in group I. The percentage of patients without seizures was 81.4, 33.0, 34.4, 57.7, and 100%, respectively. As has been suggested, among the first-year epilepsies, a subgroup with a more favorable prognosis may exist. Further studies regarding the etiology, ictal EEGs, and effectiveness of treatment and long-term prognosis of these cryptogenic benign infantile convulsions are needed to provide a firm basis for understanding convulsive disorders in the first year of life.     

Neurocardiogenic syncope: frequency and consequences of its misdiagnosis as epilepsy

BACKGROUND: Neurocardiogenic syncope (NCS) can be mistaken as a seizure. We reviewed the frequency and diagnostic consequences of this misdiagnosis. METHODS: A retrospective review of outpatient adult epilepsy clinic charts (QEII Health Sciences Centre, Halifax, NS) was conducted to identify NCS patients referred with a provisional diagnosis of seizures. Charts were reviewed in detail with an emphasis on the consequences of misdiagnosis. RESULTS: Of 1506 consecutive referrals to the epilepsy clinic, 194 (12.9%) ultimately had a clinical diagnosis of NCS. Mean age was 38 +/- 16 years (mean age of syncopal onset was 28 +/- 16 years). Two-thirds of referrals were from primary care physicians (including emergency departments) and 18% from neurologists. Thirty-five percent were prescribed antiepileptic drugs (AEDs) prior to referral with eight patients (4.1%) experiencing hypersensitivity reactions. Three of five women had adverse pregnancy outcomes while taking AEDs. One-third of patients had restrictions placed on their driving privileges while 11 patients (5.7%) had their employment interrupted. Diagnostic modalities used in the work-up included EEG (90%), CT head (51%), and MRI head (15%). CONCLUSIONS: NCS is commonly misdiagnosed as epilepsy. Some patients had an incorrect diagnosis for > 10 years. Patients with this misdiagnosis are often excessively investigated, inappropriately treated, and have unnecessary restrictions placed on driving and employment.     

Tilt table testing in patients with suspected epilepsy

Background –  Approximately 20–30% of patients with epilepsy are misdiagnosed and syncope often seems to be the mistaken cause. We re-evaluated patients referred to an epilepsy clinic where suspicion of neurally mediated (reflex) syncope were raised using tilt table testing (HUT).
Methods –  HUT laboratory results and medical records of 120 consecutive patients were reviewed retrospectively over a period of 27 months.
Results –  HUT was positive in 59 (49%) patients. Seventeen of 38 (45%) patients previously diagnosed with epilepsy and taking antiepileptic drugs were found to be misdiagnosed. Four of 21 patients with epilepsy (19%) had dual diagnoses of reflex syncope and epilepsy.
Conclusion –  HUT is an informative investigation when suspicions of reflex syncope are raised in patients referred to an epilepsy clinic. Reflex syncope is an important and common differential diagnosis of epilepsy.     

Epidemiologic features of isolated syncope: the Framingham Study

To obtain epidemiologic information regarding syncope, 2336 men and 2873 women aged 30 to 62 years at entry to the study were evaluated for syncope. During 26 years of surveillance, evidence of cardiac or neurologic morbidity and mortality was also recorded. At least one syncopal episode was reported by 71 (3.0%) of the men and 101 (3.5%) of the women during the course of the study. Criteria for isolated syncope (i.e., transient loss of consciousness in the absence of prior or concurrent neurologic, coronary, or other cardiovascular disease stigmata) were met by 56 (79%) of the 71 men and by 89 (88%) of the 101 women with syncope. During 26 years of follow-up isolated syncope was not associated with any excess of stroke (including transient ischemic attack) or myocardial infarction. Similarly, isolated syncope was not associated with any excess of all-cause or cardiovascular mortality (including sudden death).     

Familial vasovagal syncope and pseudosyncope: Observations in a case with both natural and adopted siblings

This report describes an 11-year-old girl with recurrent syncope beginning at the age of 2 1/2 years. Her paternal grandmother, father, and three of her five natural siblings had similar symptoms, often linked to emotional upsets. There were three adopted children from a single family, and none of these had syncope. Prior to referral there was an increase in attacks, some with convulsions, but with no other features of epilepsy. Vasovagal syncope was confirmed. However, continuous electroencephalogram, blood pressure, and heart rate recordings during attacks indicated that in some episodes there was neither cardiovascular change nor epileptiform activity, implying feigned syncope (pseudosyncope) with pseudoseizures. A psychological origin was sought, found, and in part rectified. The separation of vasovagal syncope from pseudosyncope, in the context of the family history, is discussed.     

Clinical evaluation of the patients with epilepsy following febrile convulsions

We studied clinical, EEG and developmental features of 46 epileptic children following febrile convulsions. Incidence of developing epilepsy was 9.9 percent. Eleven patients (group G) out of 46 had generalized epileptic seizures, and 34 patients (group P) had partial seizures. Febrile convulsions of early onset, partial seizures and postictal neurological symptoms were more striking in group P (p less than 0.05), whereas febrile convulsions of late onset and prolonged seizures were slightly dominant in group G. And EEG abnormalities were more frequent in group P (p less than 0.05). Group P patients had significant number of risk factors (complex features of febrile convulsions) than group G patients (p less than 0.01). The interval between the last febrile convulsion and subsequent epileptic seizures was shorter in group G (p less than 0.01). Although subsequent epileptic seizures were well controlled in the both groups (91% in group G and 82% in group P), intractable seizures were recognized in 9% of group P patients. The patients who had risk factors of prolonged seizures, postictal neurological symptoms and early onset manifested poor controlled epileptic seizures (p less than 0.01). Motor or mental deficits were more frequently associated with group P: in some patients they had been observed before the onset of febrile convulsions. These results suggest that pathogenesis of epilepsy following febrile convulsions may be different among various seizure types of subsequent epilepsy. And the risk factors during febrile convulsions may be related to the prognosis of subsequent epileptic seizures as well as the incidence of developing epilepsy.     

Brain‐type Natriuretic Peptide Secretion Following Febrile and Afebrile Seizures—A New Marker in Childhood Epilepsy?

PURPOSE: Markers for epileptic seizures are rare and their use has not been established in the evaluation of seizures and febrile convulsions (FC). Brain-type natriuretic peptide (BNP) is a natriuretic, diuretic, and vasodilator compound first discovered in the hypothalamus but mainly synthesized in the myocardium. The aim of this study was to assess whether epileptic seizures or FC are related to increased secretion of the N-terminal fragment of BNP (NT-proBNP). METHODS: Sixty-five postictal children (43 boys, 22 girls) and 31 children with epilepsy (20 boys, 11 girls) after a seizure-free period for at least 2 months serving as controls were enrolled. Postictal NT-proBNP levels were analyzed and controlled 24-48 h thereafter. RESULTS: Plasma concentration of NT-proBNP was significantly higher 4 h postictal compared to 24-48 h postictal (p < 0.001). Subgroup analysis revealed increased NT-proBNP levels in children with tonic-clonic seizures and FC compared to children with partial motor seizures (p < 0.001), syncope (SYN; p < 0.01), or control population (p < 0.001). CONCLUSIONS: Our results suggest that elevated plasma NT-proBNP levels are not specific for cardiac dysfunction. Postictal measurement of plasma NT-proBNP seems to be useful in discriminating different types of epilepsy, FC, and SYN in childhood.     

A Prospective Study of Epilepsy Following Neonatal Convulsions

In a prospective study of 130 infants with neonatal convulsions, the frequency and type of epilepsy and the relationship between the presumptive etiology of neonatal convulsions and subsequent epilepsy were investigated in 82 survivors excluding those dying and lost to follow-up. Of these 82 children, 15 (18.2%) were found to have epilepsy, which was of generalized type in seven (8.5%), infantile spasm in four (4.9%), focal seizures in three (3.6%) and myoclonic seizures in one (1.2%). Febrile convulsions were noted in two children (2.5%). The presumed causes of neonatal convulsions were asphyxia, intracranial hemorrhage or neonatal meningitides in most instances, but no particular relationship was noted between the presumptive etiology of neonatal convulsions and the type of subsequent epilepsy. In 11 (73.3%) of the 15 epileptic children, concurrent mental retardation, cerebral palsy and postmeningitic hydrocephalus were noted. Evidence from RI cisternography, pneumo-encephalography and cerebral angiography indicated that perinatal or neonatal brain damage responsible for epilepsy might be organic in nature. The fact that epilepsy occurred later in many of cases of neonatal convulsions of unidentified etiology suggests that brain damage incurred during fetal life might also be implicated at least in some instances. The onset of epilepsy in this series was relatively early, invariably before three years of age.     

Epidemiologic Survey of Epilepsy Among Army Draftees in Lombardy, Italy

We conducted an epidemiological survey of epilepsy among males born in 1967 who were called for selection for military service from the Lombardy region in northern Italy. Of 54,520 subjects, 258 had active epilepsy (prevalence, 0.47%). Idiopathic partial epilepsy was most common (29.1%), and generalized idiopathic and/or symptomatic epilepsy was least common (3.8%). In the year preceding the interview, 66.9% of the subjects had been free of generalized tonic-clonic seizures, 57.6% had been free of minor seizures, and 36.9% were seizure-free. Case histories revealed a background of febrile convulsions in 18.9% of subjects, status epilepticus in 11.3%, and a family history of epilepsy in 18.9%. Physical and mental development was normal in 75.5% of the subjects. Education level of subjects was lower than a control group, and the unemployment rate was the same as the local rate.     

Cardiogenic syncope. Seizure versus syncope

Our recommendations for the evaluation of the patient with suspected cardiogenic syncope are as follows: An initial thorough history and physical examination of the patient will suggest the diagnosis of cardiogenic syncope in at least 50 per cent of patients. A sudden occurrence of syncope, or "drop attack", is most suggestive of an arrhythmic cause for syncope. If there is no evidence of neurologic, metabolic, or obvious cardiac (for example, aortic stenosis) cause for syncope, a 24-hour ambulatory ECG should be performed. If the patient has had repeated syncopal episodes or if the patient has had seizures that are difficult to control with anticonvulsant therapy, ambulatory ECG monitoring may reveal an arrhythmia in these preselected patients. If the initial 24-hour ambulatory ECG is negative and if the patient has had multiple episodes of syncope, multiple days of recording will be necessary before typical symptoms occur that correlate with arrhythmias. Seventy-two hours of ambulatory ECG monitoring should be sufficient in most instances to establish an arrhythmic cause for syncope. Echocardiography and exercise stress testing are not routinely indicated in the evaluation of syncope unless the clinical history and examination suggest valvular or coronary disease. Rarely, an atrial myxoma will be visualized by echocardiography that is not apparent clinically. Those patients who still have unexplained recurrent syncopal episodes, despite all noninvasive studies, can benefit from invasive electrophysiologic studies, although the expected yield from electrophysiologic testing is low.     

Role of endogenous adenosine in vasovagal syncope

Adenosine may be a potential mediator in the pathogenesis of vasovagal syncope. Intravenous adenosine increases sympathetic discharge and provokes vasovagal syncope in sensitive subjects. No data are available for endogenous adenosine. The authors compared the results of head-up tilt-table testing (HUT) (45 minutes at 60°) of three arbitrary groups of subjects: sensitive (n=25, age 34 y, vasovagal syncope, positive HUT), moderately sensitive (n=28, age 34 y, vasovagal syncope, negative HUT), and nonsensitive (n=19, age 30 y). A positive test result produced syncopal symptoms with hypotension and/or bradycardia. Single-lead electrocardiogram (ECG) was recorded, and arterial pressure was measured noninvasively. Fourier transform was used for power-spectral heart rate variability (HRV) analysis of 5-minute ECG data. In the nonsensitive and moderately sensitive groups, HUT was repeated with intravenous dipyridamole, and adenosine transport blocker. In the sensitive group, HUT was repeated with oral theophylline, an adenosine receptor blocker, or placebo. In the moderately sensitive group, a third HUT was performed with dipyridamole and oral theophylline. If adenosine plays a role in vasovagal syncope, then dipyridamole would induce more positive HUT responses, a positive HUT response would be prevented by theophylline, and hemodynamic and HRV data in positive HUT responses induced by dipyridamole should reproduce those observed during spontaneous positive HUT responses. Dipyridamole induced positive HUT responses in 57% of the moderately sensitive group and 21% of the nonsensitive group (p<0.05). Theophylline treatment was not efficient in preventing HUT-induced syncope in sensitive subjects; however, it prevented dipyridamole-induced syncope in 75% of the moderately sensitive group. Dipyridamole immediately increased arterial pressure, heart rate, and total HRV in all (p<0.05). In sensitive subjects, these responses were different: small for arterial pressure and for total and low-frequency HRV, and large for heart rate. It is concluded that endogenous adenosine, like exogenous adenosine, may induce vasovagal syncope. However, the mechanism of adenosine-induced syncope is probably different from that of HUT-induced vasovagal syncope. This study complies with the Declaration of Helsinki. The state ethics committee (No. 171/94) approved the research protocol; informed consent was obtained from the subjects.