Hippocampal damage caused by seizures in temporal lobe epilepsy

Hippocampal damage caused by seizures in temporal lobe epilepsy

RESEARCH LETTERS Study groups Conceived (no [%]) EUP* 1st trimester miscarriage Term delivery Premature labour HTN† GDM§ IUFD‡ Treated (n=22...

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RESEARCH LETTERS

Study groups

Conceived (no [%])

EUP*

1st trimester miscarriage

Term delivery

Premature labour

HTN†

GDM§

IUFD‡

Treated (n=22) Not treated (n=24)

12 (54·5) 3 (12·5)

1 (4·5) 0

1 (4·5) 0

6 (27·3) 2 (8·3)

3 (13·6) 0

0 0

0 0

0 1 (4·2)

*Extrauterine pregnancy, †hypertension, §gestational diabetes mellitius, ‡intrauterine fetal death.

Pregnancy outcome

preventing early pregnancy loss in autoantibody seropositive patients. We found no increased incidence of preterm delivery (p=0·48), nor of gestational diabetes or hypertension. This contrasts with the recent findings of Laskin et al,4 who concluded that immunosuppression should be avoided. 1

Geva E, Amit A, Lerner-Geva L, Lessing JB. Autoimmunity and reproduction. Fertil Steril 1997; 67: 599–61. Geva E, Yaron Y, Lessing JB, et al. Circulating autoimmune antibodies may be responsible for implantation failure in in vitro fertilization. Fertil Steril 1994; 62: 802–06. Rote NS, Walter A, Lyden TW. Antiphospholipid antibodies—lobsters or red herrings? Am J Reprod Immunol 1992; 28: 31–37. Laskin CA, Bombardier C, Hannah ME, et al. Prednisone and aspirin in women with autoantibodies and unexplained recurrent fetal loss. N Engl J Med 1997; 337: 148–53.

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Sara Racine In-Vitro Fertilization Unit, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel (J B Lessing); and Sackler Faculty of Medicine, Tel Aviv University

Hippocampal damage caused by seizures in temporal lobe epilepsy Tuuli Salmenperä, Reetta Kälviäinen, Kaarina Partanen, Asla Pitkänen

Hippocampal damage is found in about 60–70% of patients with temporal lobe epilepsy (TLE) who have undergone surgery due to drug-refractory seizures.1 One of the concerns in epilepsy research has been whether the damage is already present at the time of epilepsy diagnosis, or whether it appears later in life as a consequence of recurring seizures. In clinical practice, this begs the question of whether the appearance and severity of structural damage in the brain of epileptic patients can be controlled during their lifetime with antiepileptic drug treatment.2,3 In this cross-sectional study, we measured the hippocampal volumes of 25 controls and 153 TLE patients (78 males, 75 females, age 36 [13] years) with magnetic resonance imaging (MRI). The epileptic focus was in the left temporal lobe of 90 patients, the right temporal lobe of 55 patients, and eight TLE patients had a bilateral focus. The patients were divided into four study groups based on their duration of TLE (聿 1 year, 2–10 years, 11–20 years, and 肁21 years). In addition, the patients were assigned to subgroups of either rare (聿2 seizures 70

All

60

Rare seizures

1

% of patients

Frequent seizures

**

50 40 30

** 0·001

0·001 0·01

0·01 0·01

20

2

0·01 0·01 0·05 * *

3

10 0

per year) or frequent (>2 seizures per year) seizures. Except for patients with newly diagnosed epilepsy, all TLE patients had been treated with antiepileptic drugs. The volumes of the left and right hippocampi were assessed with a 1·5 T Magnetom (Siemens, Erlangen) as previously described.4 Informed consent was obtained from each patient or control. Statistical analyses were done with the Mann-Whitney U test, the ␹2 test, Fisher’s exact test, Pearson’s correlation test, and logistic regression analysis. In patients with at least 21 years of TLE, the volume of the hippocampus was significantly reduced on the focal side (by 15% on the left, p<0·05; and 29% on the right, p<0·001) compared with controls. This reduction was apparent only in those patients who had frequent seizures. In fact, up to 50% of patients with at least 21 years of frequent seizures had at least a 2 SD volume reduction in the hippocampus (figure). Further analysis in a group of patients with at least 21 years of TLE and frequent seizures showed that patients with damage were more likely to have begun their seizures when they were 5 years old or younger than patients without damage (OR 0·14, p<0·01). Aetiology (cryptogenic or remote symptomatic including patients with prolonged febrile seizures) or epileptiform EEG did not explain the difference in the appearance of damage. The hippocampal volume in the 153 patients correlated with their lifetime number of seizures (left hippocampus r=⫺0·240, p<0·001; right hippocampus r=⫺0·246, p<0·001). A significant correlation between hippocampal volume and the duration of the disease was found only in the subgroup of patients with frequent seizures (left hippocampus r=⫺0·200, p<0·05; right hippocampus r=⫺0·312, p<0·001; n=115). Our study shows that seizure frequency, particularly when associated with the early onset of epilepsy, is the main determinant for reduction in hippocampal volume in chronic TLE patients, whereas the aetiology of TLE or epileptiform EEG is not associated with the damage. In our patient population, it took 20 years to accumulate enough seizures before the hippocampal volume reduction was apparent with MRI volumetric analysis. Although such a slow progression in hippocampal damage could easily go undetected in clinical practice, our data suggest that good seizure control in the long-term treatment of TLE is likely to diminish the subsequent loss of hippocampal neurons. Furthermore, by minimising the number of seizures, we may also reduce the functional consequences of hippocampal damage, such as memory impairment.5

4

<1

2–10 11–20 Duration of TLE (years)

>21

Percentage of patients with over 2 SD decrease in hippocampal volume in patient groups with different duration of TLE ␹ test, *p<0·05, **p<0·001 compared with controls. 2

THE LANCET • Vol 351 • January 3, 1998

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Babb TL, Pretorius JK. Pathological substrates of epilepsy. In: Wylie E, ed. The treatment of epilepsy: principles and practice. Philadelphia: Lea & Febiger, 1993: 55–70. Reynolds EH. Do anticonvulsants alter the natural course of epilepsy? Treatment should be started as early as possible. BMJ 1995; 310: 176–77. Chadwick D. Do anticonvulsants alter the natural course of epilepsy? Case for early treatment is not established. BMJ 1995; 310: 177–78. Soininen HS, Partanen K, Pitkänen A, et al. Volumetric MRI analysis of the amygdala and the hippocampus in subjects with age-associated memory impairment. Neurology 1994; 44: 1660–68. Kälviäinen R, Partanen K, Äikiä M, et al. MRI-based hippocampal volumetry and T2 relaxometry: correlation to verbal memory performance in newly diagnosed epilepsy patients with left-sided temporal lobe focus. Neurology 1997; 48: 286–87.

Departments of Neurology and Clinical Radiology, Kuopio University Hospital; and University of Kuopio, A I Virtanen Institute, P O Box 1627, FIN-70 211 Kuopio, Finland (A Pitkänen)

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