Electroclinical characteristics of new-onset seizures associated with neurocysticercosis
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.132359
Source of Support: None, Conflict of Interest: None
Purpose: Although seizures are the most common presentation of neurocysticercosis (NCC), the electroclinical characteristics of the seizures have not been adequately studied. Materials and Methods: The study cohort included 308 consecutive patients presenting with a new-onset seizure, both acute symptomatic or unprovoked. They were divided into two groups: Group 1 (NCC group), those in whom imaging studies revealed active or inactive NCC (N = 184 (59.7%)) and group 2 (non-NCC group), those in whom either imaging was normal or revealed abnormalities other than NCC or the diagnosis was idiopathic generalized epilepsy (N = 124 (40.3%)). Results: Clinical features significantly associated with group 1 included focal seizures (specifically, aphasic seizures (P < 0.05)), seizure clusters (P < 0.0001), postictal Todd's paresis (P < 0.05), and peri-ictal headaches (P < 0.008). In addition, somatosensory and visual seizures, and focal-clonic and focal-tonic were more frequent in this group. Generalized clonic seizures (P < 0.05) were significantly more common in the group 2. The findings of regional epileptiform abnormalities (P = 0.0001) and primary generalized epilepsy (P < 0.0001) on electroencephalography were significantly more common in group 2. Significance: In patients presenting with new-onset seizure, aphasic seizures, seizure clusters, postictal Todd's palsy and peri-ictal headaches might augur the finding of NCC, both active and inactive lesions, on imaging.
Keywords: Electroencephalograph, neurocysticercosis, new-onset epilepsy, semiology, single seizure
Neurocysticercosis (NCC) impacts the burden of seizure disorder (both acute symptomatic and unprovoked seizures) in many Taenia solium-endemic regions of the world. ,,, Seizures are the most common manifestation of NCC,  but seizure semiology in NCC has been insufficiently studied.  Aside from few cursory references to the frequency and broad categories of seizures, elaborate descriptions of electroclinical characteristics of seizures in people with NCC are not available. ,, The diagnosis of NCC in those presenting with seizures is largely based on imaging studies.  However, most of the population in the T. solium-endemic regions of the world have limited access to neuroimaging facilities because of nonavailability of the facility and poor purchasing capacity. Thus, it is of importance to clarify the demographic and electroclinical features of seizures associated with NCC and also to determine if such clinical characteristics help in differentiating the seizure disorder associated with NCC from seizure disorders associated with other etiology. This serves to distinguish these from seizures associated with other conditions.
The source population comprised 1337 consecutive patients (age >12 years) with history of epileptic seizure/epilepsy seen first time in the Neurology Outpatient Service, Dayanand Medical College, Ludhiana, India, between January 1995 and December, 2001. The relevant clinical data were prospectively entered and maintained in a database. Patients with a new-onset seizure (including a cluster of seizures within 24 hours), both acute symptomatic or unprovoked (n = 308) were studied. Patients with psychogenic non-epileptic seizures and in whom a diagnosis of epilepsy/seizure was uncertain were excluded.
Detailed semiological characteristics of the seizures according to a semiological seizure classification were noted.  Other data collected included age at presentation, gender, occurrence of seizure clusters, postictal Todd's paresis, postictal psychosis, and risk factors for epilepsy. Patients were investigated using tailored protocols that included electroencephalography (EEG), imaging (contrast computed tomography (CT) or magnetic resonance imaging (MRI)), and appropriate blood and metabolic investigations. The EEG patterns was classified into primary generalized epilepsy, regional epileptiform abnormalities, regional non-epileptiform abnormalities, and normal. Semiological, syndromic, and etiological classifications were determined and recorded during outpatient visits. However, the data were revised by consensus at the time of analysis by the two authors. ,, Postictal psychosis and postictal paresis (Todd's palsy) were defined using previously accepted operational criteria, and peri-ictal headaches were defined according to criteria of the International Classification of Headache Disorders. ,,
Diagnosis of NCC
The following imaging features were considered as consistent with NCC: (1) single or multiple actively degenerating brain parenchymal cysticerci with surrounding edema, (2) single or multiple calcific lesions consistent with the inactive stage of cysticerci, or (3) any combination of (1) and (2) with no other perceived cause for the seizure. , In establishing NCC as the cause of the seizures, emphasis was given to electroclinical localization of seizure onset and anatomical location of the cysts on imaging. Standard work-up in subjects with the imaging findings included the following: chest roentgenograms to exclude pulmonary tuberculosis, Mantoux test, hemograms, and cysticercus serology (either enzyme-linked immunosorbent assay (ELISA) or enzyme-linked immunoelectrotransfer blot assay (EITB)). However, a positive serology was not considered mandatory for the diagnosis of NCC on account of its poor sensitivity in individuals with solitary cysticercus granuloma (SCG).
Patients were grouped into group 1 (NCC group), those in whom imaging studies revealed active or inactive NCC (N = 184 (59.7%)) and group 2 (non-NCC group), those in whom either imaging was normal or revealed abnormalities other than NCC or the diagnosis was idiopathic generalized epilepsy (N = 124 (40.3%)). A comparison of frequency and distribution of various variables, age and gender, semiologic seizure types, seizure clusters, postictal Todd's paresis, postictal psychosis, and types of EEG abnormalities in the two groups, was determined.
Univariate comparisons of categorical variables were performed using the Chi-square test. Continuous variables such as mean age at onset and presentation and duration of seizures were examined with the Student's t test. A P < 0.05 was considered significant. Variables for which P was < 0.1 were entered into multivariate regression analysis model. Those with P < 0.05 were considered significant.
Of the 308 patients presenting with a new-onset seizure, 184 (59.7%) (median age: 20 years; 95% confidence intervals (CI), 22-25 years; 118 (64.1%) males and 66 (35.9%) females) were categorized to group 1 (NCC group) and 124 (40.3%) (median age: 24 years; 95% CI, 24-29 years; 89 (71.8%) males and 35 (28.3%) females) in group 2 (non-NCC group). The etiologies in the group 2 (non-NCC) included the following: Neoplasms (1; 0.8%), gliosis (15; 12.1%), hematoma (2; 1.6%), acute infarction (5; 4.0%), and hypodense lesions of indeterminate etiology (5; 4.0%). Imaging was not undertaken in 15 (12.1%) patients as these patients had the diagnosis of idiopathic generalized epilepsy and was normal in 85 (68.5%) in this group. The imaging profile in group 1 (NCC group) included SCG (156; 84.8%), single calcified lesion with contrast enhancement and surrounding edema (13; 7.1%), single calcified lesion without contrast enhancement or surrounding edema (10; 5.4%), multiple active NCC (7; 3.8%), and mixed active and calcified NCC (1; 0.5%). No significant difference was noted in the median age of onset of seizure and gender distribution of the two groups [Table 1].
Focal seizures were significantly more common in the NCC group (group 1) (P < 0.0001), whereas generalized-onset seizures were significantly more common in the non-NCC group (group 2) (P < 0.0001) [Table 1]. Among various seizures semiologies, aphasic seizures were significantly more common in the NCC group (P < 0.05) (group 1). Somatosensory, focal-clonic, focal-tonic, and occipital seizures were more frequent in NCC group (group 1), though the difference between the two groups was not statistically significant. Generalized seizures were more common in the non-NCC group (P = 0.03). Seizure clusters (within 24 h) (P < 0.0001), postictal Todd's paresis (P < 0.05), history of childhood febrile seizures (P < 0.05), and peri-ictal headaches (P < 0.008) were significantly more common in the NCC group (group 1). Regional epileptiform abnormalities (P < 0.0001) and primary generalized epilepsy (P < 0.0001) on electroencephalography were significantly more common in non-NCC group (group 2) patients when compared with patients in NCC group (group 1).
In the multivariate analysis, focal seizures, aphasic seizures, seizure clusters, and peri-ictal headaches were associated with NCC on imaging studies (group 1). Generalized seizures, generalized clonic seizure semiology, antecedent history of trauma, and generalized and regional epileptiform discharges were significantly associated with non-NCC group (group 2) [Table 2].
Our study suggests that in patients in the second-third decade with new-onset seizures, focal seizure semiologies and seizure clusters, and peri-ictal headaches, neuroimaging is likely to show image morphology consistent with NCC.
Focal seizures with aphasic semiology were exclusively reported in the NCC group [Table 1] and [Table 2]. This can go with the common location of solitary cysticercus granulomas in parietal and frontal lobes.  Abdominal auras are extremely rare in patients with NCC with epilepsy and if present should suggest the possibility of dual pathology, NCC with secondary mesial temporal sclerosis.  Focal ictal symptoms and signs in seizure disorder associated with NCC are consistent with localized involvement of the cerebral cortex in NCC. Theoretically, other semiological characteristics that might be associated with the finding of NCC on imaging studies might be the occurrence of multiple varieties of focal seizures, presumably due to multiple sites of localization of the cysticerci. However, these were not noted in our study as majority of the patients had solitary granulomas.
The reported frequency of seizure clusters in patients with NCC has been 22-76%. ,, In the cohort of patients with NCC and new-onset of seizures reported by Carpio and Hauser, recurrent seizures within the first 24 h occurred in 22%.  The International League Against Epilepsy (ILAE) definition of seizure clusters is the occurrence of seizures within a given period (usually one or a few days), which exceeds the average frequency of seizures over a longer period.  Seizure clusters are not specific to NCC can occur in chronic epilepsies and rarely at the onset of epilepsy.  However, our study demonstrates that seizure clusters are significantly more common in patients with NCC. It has been conjectured elsewhere in a different context that seizures in NCC are provoked by a localized cerebral inflammatory response to the phasic release of antigenic material from the degenerating cysticercus.  Hence, clustering of seizures in NCC might be linked to the phasic release of the antigenic material and ensuing inflammation. Likewise, the occurrence of peri-ictal headaches in people with NCC might be linked to the phasic release of antigen leading to vascular headaches. In this context, population based studies in T. solium-endemic regions have demonstrated an association between NCC and migraine. ,
Calcified lesions are known to be associated with contrast enhancement and perilesional edema and correlates with seizure relapse. Nash et al., found perilesional edema around calcified lesions in 50% of their patients associated with episodic seizure activity. On the contrary, 7% of patients in NCC group showed calcified lesions with contrast enhancement in our study. 
Some of the limitations of our study are as follows: Retrospective nature of the study, clinic cohort and not a population-based cohort, and there might have been some selection bias among cases and controls. Besides, the non-NCC group included patients with different etiologies including idiopathic generalized epilepsies. The epilepsy with different etiologies may have affected the comparative features. Majority of patients in NCC group had solitary cysticercus granuloma. So the results cannot be generalized to all forms of NCC. In 15 (12.1%) subjects in non-NCC group, the diagnosis of idiopathic epilepsy has been established based on the clinical and EEG findings, and these patients did not undergo imaging studies. It might be argued that a proportion of these patients might have shown findings of NCC on the imaging studies, which we feel very unlikely. Finally, semiological characteristics of the seizures were inferred on the basis of historical descriptions provided by the patients and eye witnesses. Although admittedly, the gold standard for characterizing semiology is by the use of video EEG, the latter was impractical on account of infrequent seizures in those with NCC.
In conclusion, certain features such as focal seizures, aphasic seizures, seizure clusters, and peri-ictal headaches are associated with the finding of NCC on neuroimaging in people presenting with a new-onset seizure. On the other hand, patients with generalized tonic-clonic seizures and focal and generalized epileptiform discharges are very unlikely to have finding of NCC on neuroimaging studies. These differences might be utilized to prioritize imaging studies in people presenting with a new-onset seizure in T. solium-endemic regions. Prospective validation studies are needed to confirm the findings of our study.
[Table 1], [Table 2]