ReviewClinical utility of ictal eyes closure in the differential diagnosis between epileptic seizures and psychogenic events
Graphical abstract
The presence of ictal eye closure (IEC) has been considered to represent an additional clinical sign supporting the diagnosis of psychogenic non-epileptic events (PNEEs). The probability of PNEE is estimated by means of a nomogram describing how pre-test probability relates to post-test probability given the pLR for IEC. When in doubt between the diagnosis of seizure and that of PNEE, for instance with a pre-test probability of PNEE of 50%, the presence of IEC increases the chance that the patient had a PNEE (continuous line) (pLR = 5.524). A pooled analysis of data from the literature shows that IEC is a physical sign with high specificity and high pLR for PNEEs. A careful history of seizure semiology in an outpatient setting might help to discern between seizures and PNEE, although a video-recording of the paroxysmal event still represents the reference standard to properly differentiate between the two conditions.
Introduction
The differential diagnosis between psychogenic non-epileptic events (PNEEs) and epileptic seizures may represent a diagnostic challenge.
The differentiation is complicated by the coexistence of both conditions in some patients (Benbadis et al., 2001, Martin et al., 2003) and the high rates of psychiatric disorders in patients with epilepsy.
A clinical suspicion relies mainly on an accurate history or on a description of the event given by witnesses, and the presence or absence of physical signs may provide additional information to support or rule out the initial diagnostic suspicion. In a previous systematic review we concluded that the presence of a lateral tongue biting strongly supports the diagnosis of epileptic seizures, given the high values of specificity (100%) and positive likelihood ratio (pLR) (21.386) to seizures (Brigo et al., 2012c).
A video-EEG recording of the paroxysmal event represents however the “gold” diagnostic standard in the differential diagnosis between PNEEs and seizures (Cascino, 2002, Alsaadi et al., 2004).
The presence of ictal eye closure (IEC) has been considered to represent an additional clinical sign supporting the diagnosis of PNEEs, although a comprehensive search of the literature to determine the accuracy of this physical finding (with special regards to its positive likelihood ratio) has not yet been performed.
In this study we therefore aimed to undertake a systematic review to evaluate sensitivity, specificity and likelihood ratios (LR) of IEC in the differential diagnosis between epileptic seizures and PNEEs.
Section snippets
Methods
Our aim was to critically and systematically evaluate the literature to evaluate the sensitivity, specificity, positive LR (pLR) and negative LR (nLR) of IEC in the differential diagnosis between epileptic seizures and PNEEs.
We included only studies evaluating the presence of IEC in patients with epileptic seizures (all types) and patients with PNEEs using a video-EEG as a reference diagnostic standard. No age, race or gender restrictions were applied. Only a direct observation by means of
Results
The search strategy described above yielded 25 results (22 MEDLINE, 3 in reference lists).
After reading the abstracts, 11 studies were provisionally selected. After reading the full text of the retrieved articles, 6 studies, comprising a total of 1496 events (1021 epileptic seizures and 475 PNEEs) were included (DeToledo and Ramsay, 1996, Chung et al., 2006, Azar et al., 2008, Chen et al., 2008, Syed et al., 2008, Syed et al., 2011).
Five studies were excluded because did not report data on both
Sensitivity, specificity, pLR and nLR of IEC for the diagnosis of PNEEs
Sensitivity, specificity, pLE and nLR for each included study are reported in Table 2.
Principal investigator of one study (Syed et al., 2011) was contacted per mail (July 2012) requiring additional information to include missing data in the meta-analysis. The provided data were included in the present review.
Pooled accuracy measures were: sensitivity 58% (0.579) (95% CI 0.534–0.623), specificity 80% (0.895) (95% 0.875–0.9131)%, pLR 5.524 (95% CI 4.546–6.714) and nLR 0.47 (95% CI 0.422–0.524).
A
Discussion
The differential diagnosis between epileptic seizures and other paroxysmal events such as PNEEs is primarily clinical and relies on patient's history and an accurate witness description of the attacks, sometimes supported by the presence of absence of clinical findings, such as tongue biting or IEC. However, differentiating between epileptic seizures and PNEEs represents often a diagnostic challenge, so that a video-EEG recording of the investigated event is frequently needed to reach a
Conclusions
In conclusion, a pooled analysis of data from the literature indicates that IEC is a physical sign which might suggest PNEE. Despite the useful information provided by an evidence-based approach to the evaluation of a physical sign, the diagnosis of epileptic seizure or PNEE requires careful integration of history, ictal signs and other clinical and investigational information, and should never be driven by any single clinical sign alone. IEC and other clinical signs (such as tongue biting)
Conflict of interest
The authors have no conflicts of interest.
Acknowledgement
We are in debt with Dr. Tanvir Syed, who provided us with additional information on his study, thus allowing us to include data from this study in this review.
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