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April2012 Vol.49 Issue:      2 Table of Contents
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Epilepsy among Dementia Subtypes

Yossri Ashour, Ahmed Abou-Hagar


Department of Neurology, Suez Canal University; Egypt



ABSTRACT

Background: Dementia has been studied as a risk for developing epilepsy. Objective: To investigate the risk of developing the first convulsive seizure among dementia subtypes. Methods: Eighty six non-epileptic dementia patients were recruited from the neurology clinic in Suez Canal University hospital between January 2006 and January 2007 with three years follow up. Patients’ data were collected through medical history, clinical examination, full laboratory investigations and brain MRI. Patients who developed convulsive seizure were further evaluated. Results: Fourteen percent of patients developed convulsive seizure equally distributed between subgroups depending on MRI findings. Conclusion: The risk for developing epilepsy in dementia is independent of the nature of the disease (vascular or degenerative). [Egypt J Neurol Psychiat Neurosurg. 2012; 49(2): 105-108].

Key Words: dementia, epilepsy, MRI, Alzheimer’s disease, vascular dementia.

Correspondence to Yossri Ashour. Neurology unit, Suez Canal University; Egypt.

Tel: +201143541776. E-mail: yossri_a@hotmail.com





INTRODUCTION

 

Alzheimer’s disease (AD) was found to be associated with increased incidence of epilepsy. Seizure activity in AD has been widely interpreted as a secondary process resulting from advanced stages of neurodegeneration, perhaps in combination with other age related factors.1 Recently, neurodegenerative hypothesis was debated by finding higher rate of incidence of seizures among the younger age of patients and earlier stage of the disease.1,2

Association of ischemic stroke with seizure has been documented, and frequency of epilepsy in connection with ischemic cerebrovascular disorder has been estimated to be between 4% and 28% in the literature.3,4

In dementia patients there were always degenerative and vascular etiologies implicated in the pathogenesis, raising the question of which process is responsible for the etiology of epilepsy. Moreover; our question is ‘could there be another unidentified process or risk factor attribute to the degenerative cognitive decline, epilepsy, and ischemic cerebrovascular disorders all together?’ To answer these inquiries we first have to figure out the distribution of epilepsy among cerebrovascular and degenerative dementia patients.

 

PATIENTS AND METHODS

 

The study included 86 dementia patients recruited from the Neurology Clinic in Suez Canal university hospital within a year [2006-2007]. All patients were followed up for three years with a minimum of one visit every three months.

Full neurological examination was done to all patients to exclude other diagnoses. Clinical information’s as age, gender, smoking habits, history of diabetes mellitus or hypertension were collected by a personal interview. Physical examination included measurement of blood pressure. Laboratory data including CBC, KFT, LFT, thyroid functions and electrolytes were done for all patients. MRI and EEG were done for all patients. During follow up period, patients who developed epilepsy were subjected to reevaluation of blood chemistry, EEG and MRI brain studies to exclude the development of vascular event and to rule out any medical causes of convulsions.

 

Diagnosis of Dementia:

Patients were diagnosed as having dementia based on Diagnostic and Statistical Manual of Mental Disorders (DSM4-R)5 criteria in addition to the Mini-Mental Scores less than 24/30 for literates and less than 22/28 for illiterates. Further clinical classification of dementia subtypes was done using Hachinski Ischemic Scale6 and was confirmed by MRI. Three groups of dementia were identified clinically (Degenerative, Vascular and Mixed). Finally, two groups of dementia subtypes were used in final statistics where mixed type group were classified as vascular according to MRI study.

 

Diagnosis of epilepsy:

Epilepsy was diagnosed based on the International league against epilepsy classification 1981.7 Confirmation of diagnosis depended on true observation of seizure on examination or clear history of actual convulsions. Further evaluation was done by EEG. Considering the diagnosis of epilepsy in our study was only in those patients who developed sure seizures after excluding the debated ones.

 

Diagnosis of Hypertension:

The diagnosis of hypertension was based on the presence of persistently elevated blood pressure (systolic ≥140 mmHg, and/or diastolic ≥ 90 mmHg) in three separate measurements at least one week apart or if the patient reported the use of a blood pressure lowering medication.8

 

Diagnosis of Diabetes Mellitus:

Diabetes mellitus was diagnosed according to the international guidelines.9 Smoking was categorized into: current smokers (those who habitually smoke cigarettes and ex- smokers < 5 years) and non smokers (those who do not smoke and ex- smokers > 5 years).10

 

Use of MRI:

MRI with a superconducting magnet with a main strength of 1.5 T (Philips Achieva R 2.5.3) was used for confirmation of initial classification of dementia and to exclude structural lesions e.g. subdural hemorrhage, tumors.

The MRI images of the subjects were randomly stored and interpreted by radiology consultant blinded to subject clinical diagnosis. Vascular insult was diagnosed when a low-signal-intensity area detected on T1-weighted images that is also visible as a hyper intense lesion on T2-weighted images

 

Exclusion criteria:

-        Patients with history suggestive of epilepsy at the initial assessment were not included in the study.

-        Patients who failed to attend the follow ups visits ( 11 patients) were dropped out of the study and their data were excluded from the study.

 

Statistical Analysis 

Data was collected, coded, entered and analyzed using PASW (Predictive Analytics Software) Statistics version 18.0.0. Quantitative data were expressed as means ± SD. While, qualitative data were expressed as numbers and percentages. Unpaired t test was used to test significance of difference between 2 means; while Chi square was used to test significance of difference between qualitative data. Multiple logistic regression was used to assess risk of developing seizure. A probability value (P-value) < 0.05 was considered statistically significant; while a probability value (P-value) < 0.01 was considered statistically highly significant.

 

RESULTS

 

A total of 12 (14%) patients developed convulsive seizure at anytime throughout the three years follow up period. In the subgroups; 13.3% of the patients with vascular dementia developed convulsive seizure, while 15.4% of patients with degenerative dementia developed convulsive seizure as cumulative percentage throughout the follow up period. No statistical significant association was found between dementia subtypes and the development of epilepsy among these groups (Table 1).

Demographics and clinical characteristics of both groups (according to epilepsy) are shown in (Table 2).

Epilepsy had a significant association to hypertension (controlled or not) among total dementia patients.

Vascular dementia had a highly significant association to Diabetes Mellitus and hypertension among total population. DM was found in 28 patients with vascular dementia (46.7%) versus 2 patients with degenerative dementia (7.7%) with P-value < 0.01. Hypertension was found in 40 patients with vascular dementia (66.7%) versus 8 patients with degenerative dementia (30.8%) with P-value < 0.01.


 

 

Table1. Incidence of epilepsy according to dementia subtypes.

 

 

Vascular

N=60 (%)

Degenerative

N=26 (%)

P-value

epilepsy

8 (13.3)

4 (15.4)

0.521

Chi square test, statistically not significant at the 0.05 level

 


Table 2. Clinical characteristics of patients (epileptic vs. non-epileptic).

 

 

Epileptic

N=12 (%)

Non epileptic

N=74

P-value

Age ( Mean±SD)

68.8±8.41

67.5±7.61

0.573

Gender

Male

Female

4 (33.3)

8 (66.7)

32 (43.2)

42 (56.8)

0.376

Hypertension

10 (83.3)

38 (51.4)

0.036*

DM

4 (33.3)

26 (35.1)

0.590

Smoking

4 (33.3)

18 (24.3)

0.365






* Statistically significant (P < 0.05).

 

 


DISCUSSION

 

Elderly were always found to have higher prevalence of epilepsy.(11) Dementia patients had a higher risk for developing epilepsy compared to the total elderly population.1 That risk of epilepsy in dementia raised a lot of debates and questions trying to find out a mutual pathogenesis for both.  

In a recent cohort study; epileptiform activities had been developed in the electroencephalographic follow ups among patients with cognitive decline. Those epileptiform activities were non-specific and had no association with the diagnosis. But a moderate risk of first-ever seizures in dementia patients was found.3

In the current study convulsive fits by history or observation was the only solid diagnosis for epilepsy where the debated EEG findings did not play a significant role in confirmation of diagnosis.

In the current study; Age had no significant association to the development of seizures neither among the total study population nor among the MRI subgroups. Some studies found higher risk of seizures in younger patients with AD12,13 which was explained by the hypothesis that younger patients with AD may have more aggressive disease(10) and another study found a lack of association between patient age at AD onset and seizures.14 Our study had a smaller range of age than those study maybe due to the smaller life expectancy  in our community.

Epilepsy was associated with degenerative dementia(1) and vascular dementia15 with controversy regarding both pathogenesis. In the current study, no statistical significant difference was found between epilepsy development among definite (MRI-confirmed) vascular dementia and degenerative dementia patients which raised another question about the probability of another unknown pathogenesis linking both dementia and epilepsy in one syndrome. And what backed up this hypothesis, is the fact that some anti-epileptics are already under study to be used in treatment of dementia.16

However, uncovering that process may play a role in developing the future drugs for dementia.

Conclusion and Recommendations

Dementia imposes a risk for developing epilepsy independent of the nature of its underlying pathogenesis (vascular or degenerative) which raises a new question about the pathogenesis of dementia and needs further longitudinal large population studies with more subjective investigations to clarify the relation between dementia and epilepsy.

 

[Disclosure: Authors report no conflict of interest]

 

REFERENCES

 

1.      Palop JJ, Mucke L. Epilepsy and cognitive impairments in Alzheimer disease. Arch Neurol. 2009; 66(4): 435-40.

2.      Scarmeas N, Honig LS, Choi H, Cantero J, Brandt J, Blacker D, Albert M, Amatniek JC, Marder K, Bell K, Hauser WA, Stern Y. Seizures in Alzheimer Disease: Who, When, and How Common?.  Arch Neurol. 2009; 66: 992-7.

3.      Liedorp M, Stam CJ, van der Flier WM, Pijnenburg YA, Scheltens P.Prevalence and Clinical Significance of Epileptiform EEG Discharges in a Large Memory Clinic Cohort. Dement Geriatr Cogn Disord. 2010 May 26; 29(5): 432-7.

4.      Hornig CR, Büttner T, Hufnagel A, Schröder-Rosenstock K, Dorndorf W. Epileptic seizures following ischaemic cerebral infarction. Clinical picture, CT findings and prognosis. Eur Arch Psychiatry Neurol Sci. 1990; 239 (6): 379-83.

5.      American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed, text rev. Washington, DC: American Psychiatric Association. 2000.

6.      Molsa PK, Paljarvi L, Rinne JO, Rinne UK, Sako E.  Validity of clinical diagnosis in dementia: a prospective clinicopathological study. J Neurol Neurosurg Psychiatry. 1985; 48: 1085-90.

7.      Commission on Classification and Terminology of the International League Against Epilepsy: Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia. 1981; 22: 489-501.

8.      Chobanian AV, Bakris GL, Black H.R. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure. The JNC 7 report. JAMA. 2003; 289 (19): 2560-72.

9.      Expert committee on the diagnosis and classification of Diabetes Mellitus: Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 2000; 23: S4-19.

10.    Gelfland EV, Cannon CP. A cannabinoid receptor type I blocker for management of multiple cardioembolic risk factors. Am J coll Cardiol. 2006; 47: 1919-26.

11.    De La Court  A, Monique MB, Breteler B, Meinardi H, Hauser WA, Hofman A. Prevalence of epilepsy in elderly: the Rotterdam study. Epilepsia. 1996; 37: 141-7.

12.    Amatniek JC, Hauser WA, DelCastillo-Castaneda C, Jacobs DM, Marder K, Bell K, Albert M, Brandt J, Stern Y Incidence and predictors of seizures in patients with Alzheimer’s disease. Epilepsia. 2006; 47(5): 867-72.

13.    Jacobs D, Sano M, Marder K, Bell K, Bylsma F, Lafleche G, Albert M, Brandt J, Stern Y. Age at onset of Alzheimer's disease: relation to pattern of cognitive dysfunction and rate of decline. Neurology. 1994 Jul; 44(7): 1215-20.

14.    Romanelli MF, Morris JC, Ashkin K, Coben LA. Advanced Alzheimer’s disease is a risk factor for late-onset seizures. Arch Neurol. 1990; 47(8): 847–50.

15.    Cordonnier C, Hénon H, Derambure P, Pasquier F, Leys D. Infuence of pre-existing dementia on the risk of post-stroke epileptic seizures. J  Neurol  Neurosurg  Psychiatry.2005;  76: 1649-53.

16.    Guay DR. Newer antiepileptic drugs in the management of agitation/aggression in patients with dementia or developmental disability. Consult Pharm. 2007; 22(12): 1004-34.


 

 

 

الملخص العربي

 

الصرع ونتائج التصوير بالرنين المغناطيسي فى داء الخرف

 

يعتبر داء الخرف من العوامل المنذرة لحدوث الصرع. أجريت هذه الدراسة لمعرفة عوامل الخطورة بين أنواع داء الخرف المتسببة في حدوث النوبة الصرعية اعتمادا على التغيرات في أشعة الرنين المغناطيسي. أجريت هذه الدراسة بكلية الطب جامعة قناة السويس حيث تم متابعة 86 مريض بداء الخرف لمدة 3 سنوات حيث أجرى للمرضى فحص إكلينيكي كامل, تحاليل مختبريه وأشعة رنين مغناطيسي على المخ. وعند حدوث نوبة صرعيه يتم إجراء مزيد من الفحوصات. النتائج: 14% من المرضى أصيبوا بنوبات صرعيه دونما اختلاف بين نوع داء الخرف أو وجود أو عدم وجود تغيرات بأشعة الرنين. نستخلص من ذلك أن عوامل الخطورة لحدوث نوبات صرعيه في داء الخرف غير مرتبطة بمسبباته.

 



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