Cross sectional study to determine the cognitive impairment among epilepsy patients

INTRODUCTION

Epilepsy is a chronic disorder manifested by recurrent, often erratic seizures which may be disconcerting and troublesome to the normal commotion of daily living affecting people of all ages. Approximately 50 million people worldwide have epilepsy, making it one of the most common neurological diseases globally nearly 80% of the people with epilepsy live in low and middle-income countries. In India there is very little data available among psychiatric morbidities amongst seizure disorders. Irrespective of the socioeconomic status and gender discrepancies all ages of epilepsy patients suffer from psychiatric morbidity. People with epilepsy respond to treatment approximately 70% of the time. About three fourths of people with epilepsy living in low- and middle-income countries do not get the treatment they need. In many parts of the world, people with epilepsy and their families suffer from stigma and discrimination.¹ Temporal lobe epilepsy (TLE) is the most frequent form of focal epilepsy in adult i.e. about 80%, neuropsychological scores worsen with advanced age, long duration of epilepsy, high seizure frequency, Antiepileptic drugs (AED’S) and presence of temporal lesion on cerebral MRI. However, high level of education seems to be protective.² Psychiatric co-morbidities are more common among unmarried, unemployed, people living from rural background, it is also more among people taking multiple AED’S.³ Epilepsy can be complicated by neurobehavioral co morbidities, which include cognitive impairment, psychiatric disorders, and social problems. Although such comorbidities are traditionally thought to arise predominantly from the effects of recurrent seizures and AED’S. Other possibilities like altered neurodevelopment of the brain, acceleration of common age-associated changes and negative treatment effects should also be considered leading to uncertain and understudied outcome in old age.^4,5 Recent studies suggest that common symptoms among cognitive decline were impairment of either verbal or figural memory and letter based verbal fluency in TLE.^6,7 Cognitive and behavioral involvement is the rule, not the exception, among patients with disorders of the central nervous system (CNS).⁸ Cognitive impairment in person leads to difficulty in performing daily day today activities, such individuals may complain of impaired attention, word-finding difficulty, verbal fluency difficulty, forgetfulness and psychomotor slowing. Memory disturbance being the most common symptom among them. Such individuals may rely on smart phones to check the dates calculate and set reminder notes and somehow accomplish all their customary tasks independently. Mild cognitive impairment is associated with a higher than normal risk of developing dementia of Alzheimer’s type.^9,10 Harmful effects of AED’s include aggression, impaired cognition, attention difficulties, depression, irritability, sexual dysfunction, confusion and sleep disturbances.¹¹ Cognitive impairment is less among newer AED’s and people adhering to single drug regimen whereas cognitive impairment is more with patients on polytherapy.¹² Phenobarbital and topiramate have known to cause more cognitive impairment.¹³ In the recent SANAD study patients with newly diagnosed but not yet treated epilepsy as well as healthy controls participated in a battery of neurocognitive tests even prior to initiating treatment, cases scored relatively worse compared to controls so these findings suggest that subtle cognitive impairments likely preceded the onset of epilepsy as these patients had only had a few seizures at the time of testing.¹⁴ Many of the neuropsychological scales and tests are of limited use for general practitioners (GPs) to detect cognitive impairment. Mini-mental state examination (MMSE) is a simple screening tool which detects dementia at the earliest and can be easily administered by GPs.^15-21For the practicing clinician, perhaps the most important message to remember is that there is no such thing as “just epilepsy.” Any patient with epilepsy should be viewed as someone who is at risk of encountering a variety of consequences including cognitive difficulties, behavioral disorders, depression, suicide, and also sudden death. There is absolutely no reason to re-stigmatize epilepsy, but there is every reason to make sure physicians, patients, families, as well as educators and others are adequately prepared to recognize any such difficulties and to manage them appropriately.²²As for the treatment of TLE early detection and seizure control is more important in preventing developmental disability in early childhood and accelerated progression of cognitive decline with ageing.²³ When cognitive issues are not addressed adequately, the morbidity of these patients may increase and this may interfere with the epilepsy treatment adherence. So present study was aimed to screen for cognitive impairment and to assess the level of cognitive impairment among epilepsy patients, to study the prevalence and the relationships between specific seizure subtype and to determine the correlation between seizure frequency, seizure duration and abnormal EEG finding with cognitive impairment among epilepsy patients.

METHODS

Hundred patients (52 males, 48 females) aged between 16-50 years visiting the outpatient Department of Psychiatry were randomly recruited for the study. A written informed consent was taken from all the individuals after being advised about the nature of the study according to a protocol approved by the Ethics Committee of Sambhram Institute of Medical Science and Research, KGF, Kolar, Karnataka, India.

Inclusion criteria

Patients with evidence or history of epilepsy and on treatment and whose last seizure episode was more than seven days were included in the study.

Exclusion criteria

• • Patients with other co-morbid physical illnesses such as diabetes, hypertension, ischemic heart disease, hypothyroidism,
• • Patients with known psychiatric illness before the onset of epilepsy,
• • Un-cooperative patients and who refused to participate in the research and give informed consent for assessment excluded from this study.

A semi structured proforma comprising of personal, sociodemographic profile diagnosis, EEG and radio imaging findings, seizure duration, frequency, drug history, compliance, family history, and other relevant details necessary for the study design was used. Semi structured proforma, MINI Plus neuropsychiatric interview and mini mental status examination (MMSE) were used. MINI plus neuropsychiatric interview is a short structured clinical interview which has 20 separate modules for each disorder and is used to diagnose axis I disorders according to DSM V or ICD 10 developed by Sheehan et al. It has been validated and reliability has been studied in comparison to the SCID-P (abbreviated as structured clinical Interview for DSM V) and the CIDI (composite international diagnostic interview) which is a structured discussion established by the world health organization for untrained interviewers for ICD-10. It has a high inter-rater reliability and validity. It is a clinician administered scale and can be completed within 15 minutes. M.I.N.I. Plus is allocated into modules recognized by letters with each letter agreeing to a diagnostic category. There are screening questions corresponding to the main criteria at the commencement of each diagnostic component except for psychotic illness.

Diagnostic box at the end of each module is given to indicate whether diagnostic criteria are met or not. Mini-mental state examination (MMSE) or The Folstein test is a thirty-opinion inquiry form introduced by Folstein et al, used as a detective tool for cognitive impairment. It is very often used to detect dementia in addition to evaluate the depth of cognitive decline and to track the sequence of cognitive decline in patients over time and serves as an effective way to monitor a person's reaction to treatment. It is operational as a detecting tool aimed at cognitive impairment with old age, hospitalized adults.

It is also used as an exploration instrument for screening cognitive decline in epidemiological works and follows cognitive variations in clinical trials. It has 11-questions which measures 5 zones of cognition including orientation, registration, attention, and calculation, recall and language.

Extreme tally is 30, a score of 23 or lower is indicative of cognitive impairment. It takes around 10 minutes to administer and is easy to use repeatedly and routinely. It relies primarily on verbal response and reading and writing and as a result certain group of people performs poorly even when their cognition is intact. They include patients who are blind and deaf, intubated, have low English literacy or those with other communication disorders.

Statistical analysis

Statistical analysis was performed using SPSS v15.0 statistical package (SPSS Inc., IL, Chicago USA). Descriptive analysis was performed to statistically demonstrate the correlation between different measurements. Student t test and F test was used to compare different variables.

RESULTS

The results demonstrated that out of 100, 52 % were females and the remaing 48% were males. 24% were below 26 years, 51% were from 27 to 37 years and the remaining 25 percent were above 38 years. Majority that is 42% were of primary grade literacy profile and next common was high school 27%.

Regarding the occupation majority belonged to unskilled group of workers and housewife’s which constituted 23%. Regarding marital status 77% of them were married and only 17% of them were unmarried. Majority belonged to lower, upper lower and lower middle socioeconomic status.

Regarding the type of family in which they were living, 65% of them were from nuclear family and the remaining 35% was joint family type. It was found that 56% of epileptic patients had abnormal EEG findings and the remaining 44% had normal EEG.

Regarding drug compliance, 59% had good compliance and 26% patients had average compliance and 15% had poor compliance. It was found that majority of the participants for the study group were from GTCS which constituted 34%. complex partial seizure with secondary generalization were 23%, focal motor seizure with secondary generalization were 17%, complex partial seizure was 14% and others were 12%. Regarding grades of cognitive decline, 36% had cognitive impairment out of which 7% had definitive impairment and 29% had mild impairment (Table 1).

It was observed that the other group of seizure subtypes which included atonic, myoclonic, focal sensory, focal motor, absence seizure with secondary generalization had low mean cognitive scores signifying cognitive impairment, where as those with complex partial seizure with secondary generalization group had high mean cognitive scores signifying no cognitive dysfunction. However, the observed difference is statistically significant, since the F ratio is significant at 0.05 level (Table 2).

Those who had longer seizure duration more than 16 years and above had cognitive decline since their mean scores were low. It was also observed that those who had seizure duration between 6 to 10 years had high mean scores indicating no cognitive decline. However, the observed difference is not statistically significant, since the F ratio is not significant at 0.05 level (Table 3). It was observed that those who had higher seizure frequency had low mean cognitive scores indicating cognitive decline and those with very low seizure frequency had high mean cognitive scores indicating no cognitive decline.

P >0.05, * Significant

P <0.05, * Significant

P <0.05, * Significant

However, the observed difference is statistically significant, the F ratio is not significant at 0.05 level (Table 4). It was observed that the mean score for abnormal EEG patients was 24.68 indicating mild cognitive decline whereas for normal EEG patients the mean cognitive score was 26.27 indicating no cognitive decline. However, the observed difference is statistically significant since P<0.05 (Table 5).

DISCUSSION

The study using a cross sectional design examined and estimated the prevalence of cognitive impairment among the epilepsy patients. The findings in the study bring to light certain observations which may be generalized in spite of the limitations in the study. In our hospital the different types of seizure groups have been categorized by our expertise neurologists into focal seizures, focal seizures with secondary generalization and generalized seizures. Among focal seizures authors have focal motor seizure (FMS), focal sensory seizures (FSS), and complex partial seizures (CPS).

Among focal seizures with secondary generalization authors have focal motor seizures with secondary generalization (FMSWSG), complex partial seizures with secondary generalization (CPSWSG). Among generalized seizures authors have generalized tonic clonic` seizures (GTCS), myoclonic seizures (MYO), atonic (ATONIC) and absence seizures with secondary generalization. authors have nine different types of seizure groups and for the sake of statistics authors have merged myoclonic, atonic, focal motor, focal sensory and absence with secondary generalization into others. Majority of the participants for the study group were from GTCS which constituted 34% complex partial seizure with secondary generalization were 23%, focal motor seizure with secondary generalization were 17%, complex partial seizure was 14% and others were 12% (Table 2). 56% of epileptic patients had abnormal EEG and the remaining 44% had normal EEG.

For the sake of statistical convenience, the duration of seizure has been grouped into below 5 years. 6-10 years, 11-15 years and 16 years and above. From the study it was found that the most common was 6-10 years which constituted 37%. The second most common was below 5 years which constituted 24%. Seizure frequency was grouped into below 1 per year, 2-5 per year and 5 and above per year. It was found that majority of them had a seizure frequency of 2-5 years which constituted 41% (Table 4).

Patients who continued to take medications regularly were categorized as good compliance and those patients who skipped the medications for 2 to 3 visits were categorized as average compliance and patients who skipped their antiepileptic medications for more than 3 to 4 visits was categorized as having poor compliance. From the study it was found that 59% had good compliance and 26% patients had average compliance and 15% had poor compliance.

It was found that 36% of the epileptic patients had cognitive impairment and 64% did not have cognitive impairment. Among the 36% who had cognitive impairment 29% had mild cognitive impairment, 7% had definite cognitive impairment (Figure 1). In the present study, the findings for cognitive impairment were found to be 36% (Table 1 and Figure 1), so present study fairly correlates with the standard literature.²⁴

Seizure frequency predicts cognitive dysfunction, the study findings (Table 4) are in agreement with other studies.^25-28 Cognitive impairment may range between 30-44%. On the contrary many previous studies did not mention the prevalence about cognitive dysfunctions.^29,30 There was no statistical significance between complex partial seizure and cognitive decline (Table 3). These findings were in contrast to study done by Cynitha L et al, Harden MD et al, which shows cognitive decline is more in chronic temporal lobe epilepsy compared to other seizure variant.³¹ It is obvious from (Table 3) that cognitive decline was seen among atonic, myoclonic, focal sensory, focal motor, absence seizure with secondary generalization. But this finding was in contrast to the studies by Jokeit H et al, and Ebner A et al, which concluded that among temporal lobe epilepsies cognitive decline is more common. ³² While the cross-sectional studies hardly support the idea of an increasing impairment of memory with an increasing duration of epilepsy, there is nevertheless less evidence of significant memory decline over time from longitudinal studies in TLE. ^33,34 Likewise, from the (Table 3) it is observed that those who had longer seizure duration had cognitive impairment had low mean cognitive scores and patients who had lesser seizure duration had higher mean scores indicating no cognitive impairment, however the observed difference is not statistically significant. The results also show that cognitive decline is more among epilepsy patients with Abnormal EEG and this observed difference was statistically significant (Table 5). To our best knowledge, this is the first study to find such correlation, so this is considered as a new finding in present study, however this needs further research and future studies.

CONCLUSION

This study was intended to throw some light on cognitive aspects of epileptic patients. Most of the epileptic patients suffer cognitive impairment which goes undetected and untreated so appropriate screening and early detection of cognitive impairment will lead to better treatment outcome of epileptic patients. This study will also create some awareness and help in preventing early onset dementia to some extent.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: The study was approved by the Institutional Ethics Committee of Sambhram Institute of Medical Science and Research, KGF, Kolar, Karnataka, India

REFERENCES

1. 1. Epilepsy world Health organization. Accessed at: https://www.who.int/news-room/fact-sheets/detail/epilepsy.
2. 2. Nouha F, Sawsan D, Salma S, Olfa H, Hanen H, Mariem D et al. Cognitive impairment in patients with temporal lobe epilepsy. J Neuropsychia. 2018;2(2):5.
3. 3. Singh P, Pandey AK. Psychiatric morbidity in epilepsy. Int J Res Med Sci. 2017;5:4267-70.
4. 4. Wieser HG. ILAE commission on neurosurgery of Epilepsy. ILAE commission report. Mesial temporal lobe epilepsy with hippocampal sclerosis. Epilepsia. 2004;45(6):695-714.
5. 5. Hermann B, Seidenberg M, Jones J. The neurobehavioural comorbidities of epilepsy: can a natural history be developed? Lancet Neurol. 2008;7:151-60.
6. 6. Tailby C, Kowalczyk MA, Jackson GD. Cognitive impairment in epilepsy: the role of reduced network flexibility. Annals Clinic Translational Neurol. 2018;5(1):29-40.
7. 7. Helmstaedter C. Effects of chronic epilepsy on declarative memory systems. Prog Brain Res. 2002;135:439-53.
8. 8. Butler C, Zeman AZJ. Neurological syndromes which can be mistaken for psychiatric conditions. J Neurol Neurosurg Psychiat. 2005;76(I)i31-8.
9. 9. Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004;256:183-94.
10. 10. Portet F, Ousset PJ, Visser PJ, Frisoni GB, Nobili F, Scheltens P, et al. Mild cognitive impairment (MCI) in medical practice: A critical review of the concept and new diagnostic procedure. Report of the MCI working group of the European Consortium on Alzheimer's Disease. J Neurol Neurosurg Psychiat. 2006;77:714-8.
11. 11. Nadkarni S, Devinsky O. Current review in clinical science. Epilepsy Curr. 2005;5(5):176-81.
12. 12. Besag FM. Behavioural effects of the new anticonvulsants. Drug Saf. 2001;24:513-36.
13. 13. Hermann B, Meador BJ, Gaillard WD, Cramer JA. Cognition across the lifespan: antiepileptic drugs, epilepsy, or both? Epilepsy Behav. 2010;17:1-5.
14. 14. Taylor J, Kolamunnage-Dona R, Marson AG, Smith PEM, Aldenkamp AP, Baker GA. Patients with epilepsy: Cognitively compromised before start of antiepileptic drug treatment? Epilepsia. 2009;51:48-56.
15. 15. Almkvist O, Brane G, Johanson A. Neuropsychological assessment of dementia: state of the art. Acta Neurol Scand. 1996;168:45-9.
16. 16. Albert M, Cohen C. The test for severe impairment: an instrument for the assessment of patients with severe cognitive dysfunction. J Am Geriat Society. 1992;40(5):449-53.
17. 17. Carlesimo GA, Caltagirone C, Gainotti G. The mental deterioration battery: normative data, diagnostic reliability and qualitative analyses of cognitive impairment. The group for the standardization of the mental deterioration battery. Eur Neurol. 1996;36(6):378-84.
18. 18. Gottfries CG, Brane G, Steen G: A new rating scale for dementia syndromes. Gerontol. 1982;28(2):20-31.
19. 19. Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer's disease. Am J Psychiat. 1984; 141(11):1356-64.
20. 20. Roth M, Tym E, Mountjoy CQ, Huppert FA, Hendrie H, Verma S, Goddard R. CAMDEX: a standardised instrument for the diagnosis of mental disorder in the elderly with special reference to the early detection of dementia. British J Psychiat. 1986;149(6):698-709.
21. 21. Bracco L, Amaducci L, Pedone D, Bino G, Lazzaro MP, Carella F, et al. Italian multicentre study on dementia (SMID): a neuropsychological test battery for assessing Alzheimer's disease. J Psychiatr Res. 1990;24(3):213-26.
22. 22. Berg A.T. Epilepsy, Cognition, and behavior: The clinical picture. Epilepsia. 2011;52(1):7-12.
23. 23. Helmstaedter C. Effects of chronic temporal lobe epilepsy on memory functions. Prog Brain Res. 2002;135:439-53.
24. 24. Jones R, Rickards H, Cavanna AE. The prevalence of psychiatric disorders in epilepsy: a critical review of the evidence. Funct Neurol. 2010;25(4):191-4.
25. 25. Thompson, Duncan JS. Cognitive decline in severe intractable epilepsy. Epilepsia. 2005;46(11):1780-7.
26. 26. Ozmenek OA, Nazliel B, leventoglu A, Bilir E. The role of event related potentials in evaluation of subclinical cognitive dysfunction in epileptic patients. Acta neurol Belg. 2008;108:58-63.
27. 27. Albert P, Aldenkamp. Effect of seizures and epleptiform discharges on cognitive function. Epilepsis. 1997;38(1):S52-S55.
28. 28. Kimford J. Meador. Cognitive and memory effects of the new antiepileptic drugs. Epilepsy Res. 2006;68(1):63-7.
29. 29. Schouten A, Oostrom KJ, Pestman WR, Peters AC, Jennekens-Schinkel A. Learning and memory of school children with epilepsy: a prospective controlled longitudinal study. Developmental medicine and child neurology. 2002;44(12):803-11.
30. 30. Seidenberg M, Pulsipher DT, Hermann B. Cognitive progression in epilepsy. Neuropsychol Rev. 2007;17(4):445-54.
31. 31. Cynthia L Harden, MD. New evidence supports cognitive decline in temporal lobe epilepsy. Epilepsy Curr. 2007;7(1):12-14.
32. 32. Jokeit H, Ebner A. Long term effects of refractory temporal lobe epilepsy on cognitive abilities: A cross sectional study J Neurol Neurosurg Psychiat. 1999;67(1):44-50.
33. 33. Helmstaedter C, Kurthen M, Lux S, Reuber M, Elger CE. Chronic epilepsy and cognition: a longitudinal study in temporal lobe epilepsy. Ann Neurol. 2003;54(4):425-32.
34. 34. Rausch R, Kraemer S, Pietras CJ, Le M, Vickrey BG, Passaro EA. Early and late cognitive changes following temporal lobe surgery for epilepsy. Neurology. 2003;60(6):951-9.