Journal of Neurosciences
in Rural Practice. 7.3 (July-September 2016): p405. From InfoTrac
Science Collection 2017.
BACKGROUND
Epilepsy is the commonest neurological
disorder encountered in Sub-Saharan Africa. The quality of life of patients
with epilepsy (PWEs) is adversely affected by cognitive impairments. Aim: This
study investigated the prevalence and pattern of cognitive impairments in PWE
in Ukpo community located in a South-Eastern state in Nigeria using Community
Screening Interview for Dementia (CSID) and a computer-assisted cognitive test
battery (FePsy). Methods and Patients: Fifty-one PWEs were studied and compared
with 51 age-, sex-and level of education-matched healthy controls. Diagnosis of
epilepsy was confirmed clinically with eye-witness corroboration.
Sociodemographic data and information on epilepsy variables were obtained with
the aid of a questionnaire. Cognitive domains assessed include language,
memory, orientation, attention, psychomotor speed and constructional praxis.
Results: The prevalence rate of cognitive impairment using total CSID score was
19.6%. Analysis of CSID scores revealed significant impairment in language (17.6%),
memory (29.4%), orientation (15.7%), attention (7.8%) and constructional praxis
(15.7%) compared to healthy controls. A similar pattern was observed with FePsy
but with better sensitivity indices for detecting cognitive impairment.
Conclusion: This study indicated significant prevalence rate of cognitive
impairment among treatment-naive PWE with profound affectation of memory,
mental speed and language. In addition, the FePsy was found to be more
sensitive and specific in assessment of cognitive function in PWE.
INTRODUCTION
The number of new cases of epilepsy in
Sub-Saharan Africa (SSA) is on the increase, ranging between 64 and 156 per
100,000 people per year,[sup][1] and this may be attributed to poor perinatal
management, recurrent childhood febrile convulsions, prevalent infectious
diseases and traumatic brain injury.[sup][2] This region also has very high
prevalence rates ranging between 2.2 and 58 per 1000 people, with higher rates
associated with rural communities and lack of health care facility.[sup][2],[3],[4]
A recent study compared the prevalence in a rural Nigerian community with that
of a semi-urban community and reported a rate of 20.8 per 1000 in the rural
community, higher than the rate of 4.7 per 1000 in the semi-urban
community.[sup][4] Partial epilepsies are the most common worldwide and account
for 76% of cases of epilepsy in Nigeria while generalized epilepsies account
for 20% of epilepsy cases. Of the partial seizures, 29% are simple, 57% are
complex, and 14% are with secondary generalization.[sup][5] Also, subjects with
human leukocyte antigen-A9 haplotype have been reported to be 16 times more
susceptible to develop epilepsy than the general population.[sup][6]
The wide treatment gap is characteristic of SSA constituting a
major challenge to management of epilepsy. This is further worsened by presence
of cognitive impairments which may affect the patients' vocation, education,
social life [sup][7] and medication adherence.[sup][8] The poor medication
adherence has been demonstrated to be largely due to memory disturbance in a
study of Nigerian patients with epilepsy (PWEs).[sup][8] Several studies have
demonstrated cognitive disturbances in PWEs with the prevalence varying
widely.[sup][9],[10],[11] Cognitive impairments may occur either ab initio from
recurrent epileptic attacks or due to adverse effect of antiepileptic drugs. A
study that evaluated cognitive function in Nigerians with newly diagnosed
epilepsy before commencement of antiepileptic drug therapy using an automated
cognitive test battery, the IronPsychology (acronym-FePsy),
revealed impairment of visual and auditory reaction times (ARTs), memory tasks
and attention span.[sup][12] Another study has shown significant impairment in
cognitive abilities of Nigerian PWEs using the Community Screening Instrument
for Dementia (CSID).[sup][13] This cognitive impairment pattern has been
reported by other authors.[sup][14],[15]
Despite the several studies demonstrating the cognitive
impairments in Nigerian PWE, there has been no study that assessed prevalence
among PWEs especially and define patterns of impairment in South-Eastern states
of Nigeria. Therefore, this study investigated the prevalence and pattern of
cognitive impairments in PWEs in Ukpo, Anambra State, South-East Nigeria, using
CSID and FePsy cognitive tools.
METHODS AND PATIENTS
STUDY SITE
Ukpo is a sub-urban community in Awka, the
capital of a South-Eastern state in Nigeria. It has a population of 14,300 with
estimated 65% above the age of 18 years.[sup][16] The inhabitants are mainly
Igbos, and the major religion is Christianity with a few adherents to Africa
traditional religion. The community's major diet is tuber-based with large
consumption of palm oil. Cereal meals largely are prepared on special days and
festive periods. Initial sensitization meetings with the community leaders, the
herbalists, opinion leaders, the clergy men and school heads were done before
commencement of the study.
PATIENTS WITH EPILEPSY
Fifty-one patients (33 males and 18 females)
aged 16–75 years diagnosed with epilepsy were selected by snowball
technique from the Ukpo community clinic. Structured questionnaires designed to
obtain demographic information on the age, sex, level of education, age at
onset of seizures, history of fever, head injury, drug or alcohol abuse,
systemic diseases that can result in symptomatic seizures, and seizure
variables (frequency, duration and type of seizures) were completed for all
study participants. The duration of epilepsy was estimated as the historic time
interval between the first attack ever and the initial presentation at the Ukpo
community clinic. The clinical diagnosis of epilepsy was based on history of
two or more recurrent afebrile seizures and eye witness corroboration with
electroencephalogram (EEG) confirmation. The seizure types were classified
clinically based on the International League Against Epilepsy
criteria.[sup][17] The exclusion criteria included subjects <16 years of
age, patients with co-morbidities (i.e., diabetes mellitus, hypertension, and
associated intracranial disorders, e.g., brain tumor, and other metabolic
diseases), major axis 1 psychiatric illness, presence of clinical signs of
cardiac, hepatic or renal failure, alcohol intake above 120 g/week or 13
units/week, history of previous head injury with loss of consciousness and
patients on anticholinergic medications. Patients with visual and hearing
impairment (because of interference with psychometric analysis), those who are
unable to understand, communicate and follow instructions for the psychometric
test were also excluded from the study.
CONTROLS
Fifty-one healthy controls (comprising 33
males and 18 females) were recruited from the neighborhood of the PWEs within
the same community. These were age-, sex- and level of education-matched with
the PWEs. They had neither personal nor family history of seizures.
RECRUITMENT
Snowball sampling technique was used to ensure
identification of all cases of epilepsy in the community. The snowball
technique involved finding the people who knew about the diseases in the
community including herbalists, community leaders, opinion leaders, the clergy,
and school heads to assist in identifying PWEs. Identified people with epilepsy
were also asked to assist in further identifying other people with epilepsy.
This continued until all the people with epilepsy were identified. The study
lasted for about 3 months. EEG was done on all the patients.
Seventy-five PWE were identified by the
snowball method. Eighteen of them were aged <16 years; two had hearing and
speech impairments; two had severe physical disability, and two were severely
mentally impaired (they could not cope with the cognitive assessment). The
remaining 51 satisfied the inclusion criteria and thus formed the sample of the
study.
COGNITIVE TESTING
Community Screening Interview for Dementia
(CSID) composed of 48 items with a 32-item cognitive test and a 16-item
informant interview. The cognitive test covers the domains of memory (recall,
registration), language (expression, naming, repetition and fluency), attention
and calculation, orientation (to place and time), praxis and abstract thinking.
It takes an average of 15 min to administer. CSID has been used in many
populations from different socioeconomic backgrounds and has been translated
and used among the African-Americans, Chinese, Taiwanese and Nigerian
Yorubas.[sup][18]
The CSID instrument was translated into the
traditional Igbo language and back translated to ensure consistency. The
translation was done by a university graduate secondary school teacher who
holds a first degree in Igbo language. The CSID was administered to all PWEs
and controls by one of the authors (A.E) in a room free of distractions. The
CSID administration per participant lasted 15–25 min. The subtotal scores
for each cognitive domain were calculated and the aggregate score was also
calculated. Cognitive impairment cut-offs were determined by subtracting 2
standard deviation (SD) from mean values of the control subjects' subtotal
scores of language, memory, orientation, and attention domains and total CSID
score as previously documented by Salawu et al .[sup][19] The cut-off values
therefore were; 12.14 for language score, 3.72 for memory score, 4.15 for
orientation score, 1.70 for attention score and 23.02 for total CSID score.
Therefore, any value below these cutoffs were considered as cognitively
impaired. In contrast, 2 SD was added to the mean control praxis score to
obtain the cut-off score of 4.57 because the cognitive performance is inversely
related to the praxis score. Any value above this cut-off was considered
impaired.
The Iron Psychology (acronym-FePsy)[sup][20]
cognitive test battery was used to assess the following tasks:
THE SIMPLE REACTION TIME
This has two components-the visual and
auditory. The essence of this task is to assess the mental (psychomotor) speed
of the individual. The reaction time for simple auditory and visual stimuli
were measured. In the visual version, the testee was expected to react as
quickly as possible on seeing a white square in the middle of the computer
screen by pressing the space bar. The auditory version involves the
presentation of sound stimuli of 800 Hz generated by the computer and the
testee was asked to react as quickly as possible on hearing the sound by
pressing the space bar.
The two tests were done using the dominant
hand and nondominant hands. It had two phases: The learning phase and the test
phase. In the learning phase (trial run) the testee was taught how to do the
test according to the instructions on the computer screen. In the test phase,
the testee carried out the instructions exactly as taught. Failure to do this
after three consecutive trials disqualified the testee for the test. The
interstimulus interval was randomly varied from 2.5 to 4 s. For both the
dominant and nondominant hands of each subject, 30 stimuli were presented for
the auditory version and another 30 stimuli for the visual version. The results
showed accuracy and speed of response in milliseconds. The evaluation of the
results was done within the context of speed of information processing and
alertness functions. The average of the scores in milliseconds was then
analyzed and recorded automatically by the computer. The normal control
reference values of ARTs for both dominant and nondominant hands were 492.02 ms
and 484.85 ms respectively. For visual reaction times (VRTs) the values were
464.71 and 542.26 ms for dominant and nondominant hands respectively. Scores
higher than the normal reference values were taken as abnormal.
THE RECOGNITION MEMORY TASK
This comprised the words and figures sections
which were presented simultaneously to assess recall. The study items consisted
of 4 figures (nonsense figures) or 6 words which were presented for 1 s. In
this test, the participant was shown an array of words and figures respectively
and was expected to detect among subsequent words and figures, the
words/figures, that appeared before. The task comprised of the learning phase
and testing phase. One of the authors (A.E.) administered the learning phase to
the participant, before the test phase. This task lasted for an average of 20
min per participant.
As mentioned earlier, the task was divided
into a study phase in which the material to be remembered was presented and a
test phase in which recognition (recall of study items) was tested. In the
study phase, the subject was presented with 3 or 4 figures, or 4 or 6 words to
study and memorize. In the recognition phase, different sets of 3 or 4 figures
or 4 or 6 words were presented again and one of these matched one of the study
items. The testee was required to identify the word or figure in the second
presentation that matched one of the study items presented initially.
Patients with primary and secondary education
were tested using the 3 figures and 4 words for visual and verbal memory
respectively, while those in tertiary education were tested using the 4 figures
and 6 words. Words were randomly selected from a pool of about 100 words. Figures
were randomly built up from basic elements of triangles (?) and rectangles
() and were difficult to label. The results were calculated as a
percentage of correct responses. The evaluation of the recognition task was
performed in the context of the recognition process within the memory function.
The cut-off values for figure and word recognition were 59 and 73%
respectively.
DATA ANALYSIS
Analysis of data was aided by the use of SPSS
(SPSS Inc. Chicago, USA) for Windows software (version 16.0). Descriptive data
were expressed as mean and SD for continuous variables and as percentages for
categorical variables. Comparative analysis of cognitive scores between PWE and
controls was analyzed for significance using Student's t -test. Categorical
variables between PWE and controls were analyzed using Chi-square distribution.
Statistical significance was set at P < 0.05.
RESULTS
Fifty-one PWEs participated in the study. The
mean age of the 51 PWE was 29.60 [+ or -] 12.01 years while that of the 51
matched controls was 31.43 [+ or -] 12.85 ( t = 0.74; P = 0.46). There were 33
males and 18 females in the test group (PWE) similar to the distribution in the
control group [Table 1]. Similarly, there was no significant difference in
level of education of both groups ( P < 0.5). Most of the PWEs were
privately employed. Eighty-two percent of the PWEs had localization-related
(focal) seizures. Long duration of epilepsy of >6 years was observed in 39
(76.4%) of the PWEs [Table 2].{Table 1}{Table 2}
Analysis of the mean CSID total scores
revealed significantly higher scores for the controls than the PWEs ( P <
0.001). Similarly, a similar trend was observed for the subtotal scores for
language scores ( P < 0.001), memory scores ( P < 0.001), attention
scores ( P < 0.01) but lower constructional praxis scores ( P < 0.001)
was expectedly recorded for the controls because of its inverse scoring
technique [Table 3]. However, no significant difference was observed in
orientation scores between healthy controls and PWE [Table 3].{Table 3}
[Table 4] shows the cognitive impairment
status in PWE using CSID scores. The prevalence of cognitive impairment using
total CSID score was 19.6%. The prevalence rates of cognitive impairment based
on the cognitive domains using the CSID scores were as shown in the table.
[Table 5] shows the scores of the PWEs and controls with FePsy. The PWEs
performed worse than the controls in all FePsy cognitive domains.{Table
4}{Table 5}
Independent sample t -test indicated
significantly higher mean scores on testing of dominant ART (ART-D),
nondominant ART (ART-ND), dominant VRT (VRT-D) and nondominant VRT (VRT-ND) in
PWE compared to healthy control ( P < 0.001). However significantly higher
mean recognition scores were observed among control subjects than the PWE ( P
< 0.001) indicating impaired memory ability among PWEs [Table 5].
DISCUSSION
This study demonstrated significant cognitive
impairment in PWEs residing in a well-defined suburban community in Awka, South
Eastern part of Nigeria, with a prevalence rate of 19.6%. The demographic
information of the PWEs in this locality were similar to that reported by
previous authors in the literature, an important reflection that younger adults
bear the brunt of epilepsy in developing countries.[sup][2],[3],[4] Not
surprisingly, the prevalence of epilepsy in this suburban community was low as
this may be related to the presence of a comprehensive health facility in the
community. Previous studies have associated presence of health facility to low
prevalence of epilepsy in Nigeria.[sup][3],[21] Similarly, the long duration of
epilepsy may be explained by late presentation of PWEs to health facilities as
a previous study showed that more than 60% of PWEs seek traditional healers for
assistance.[sup][22]
Cognitive dysfunctions associated with
epilepsy include memory impairment, psychomotor retardation, inattention and
lack of concentration, reduced motor speed and in patients with significant
brain damage impaired visual scanning task.[sup][14],[15],[19] Memory impairment
was demonstrated among PWEs in this study, corroborating what has been reported
by other workers in the literature.[sup][23],[24],[25] It has also been
established that cognitive deterioration in people with epilepsy is associated
with poor quality of life, academic disruption and social stigma.[sup][26]
Attention and calculation were impaired in PWE
when compared with control subjects. This is in agreement with previous
studies.[sup][9],[12],[14],[15] Constructional praxis has been reported to be
impaired in PWE.[sup][13],[26] Most workers thought that this was due to
dysfunction of visuo-spatial, visuo-attentional and visuo-constructional
neuronal circuitry which may occur secondary to either recurrent seizures or an
underlying brain disease.[sup][27] The performance on the orientation subscale
of the CSID does not show statistical significant difference between PWE and
the control. This is in agreement with the previous study by Imam and
Ogunniyi.[sup][28] The reason for this is not obvious from this study.
The performance of the PWEs revealed higher
percentages of cognitive impairment with FePsy tasks than with CSID. The
severity of cognitive impairments observed with FePsy was significantly higher
than what has been reported by several other authors. This may be due to
differences in cognitive tools used and the methodological approach of the
previous studies. For instance, the higher sensitivity of the FePsy, being a
computer-assisted test battery, may explain the higher prevalence figures for
cognitive impairment observed in our study when compared to earlier reports.
The FePsy assesses the working memory of
individuals because the memory task utilized for this study is the Recognition
Memory Test which measures recall ability of the testee. Recall deficiency has
been previously described in epilepsy, especially with verbal memory.[sup][29]
It is responsible for the poor quality of life in epilepsy especially with
regards to medication adherence, educational achievement and coping with
vocational skills.[sup][7],[8] Though the effect of medication use on quality
of life in epilepsy is complex to evaluate,[sup][30] the contribution of
antiepileptic drugs to cognitive impairments may negatively affect quality of
life.[sup][31] Unfortunately, this study did not evaluate the effects of
seizure variables on the cognitive performances of the PWEs.
The deterioration of psychomotor ability is a
common finding in PWE especially those with generalized seizures. This is
depicted in this study by the prolonged auditory and VRTs which corroborate
observations of other authors.[sup][12],[32],[33] Interestingly, the dominant
hand ART was more prolonged than the VRT in the controls. This was similar to
the report by Ogunrin et al .[sup][12] However this is at variance with FePsy
scores obtained among Europeans in which ARTs are at least 60 ms faster than
visual.[sup][34] This may be related to the higher prevalence of recurrent
childhood febrile seizures in Nigeria, which have been linked with mesial
temporal sclerosis, thereby affecting the temporal lobes functioning of PWEs in
Nigeria more severely.
CONCLUSION
This study revealed that the prevalence of
cognitive impairment using total CSID score was 19.6% and for the cognitive
domains, using FePsy, the rate was 100% for ART-D, 94.9% for ART-ND, 97.4% for
(VRT-D and VRT-ND hand) and 86.4% for recognition memory task. There is
significant cognitive decline affecting the domains of language, memory,
attention and constructional praxis in PWE when compared to controls. FePsy is
particularly more sensitive in assessment of cognitive function in PWE. The
appreciation of the pattern of these cognitive impairments will aid academic,
vocational and social counseling, and encourage regular cognitive assessment of
PWEs to prevent the adverse consequences of cognitive dysfunction.
LIMITATIONS
The limitations of this study include the
small sample size which does not allow for application of sophisticated
statistical methods to improve fundamental understanding of the effects of
different medical and sociodemographic variables on cognitive function in PWEs
and may be difficult to generalize the findings to other suburban communities.
Furthermore, we did not evaluate the impact of the various seizure variables
like type, duration, and frequency of seizures on cognitive performance as this
is beyond the scope of this paper.
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