Forced normalization phenomena in outpatient clinic for epilepsy

Forced normalization phenomena in outpatient clinic for epilepsy


Trevisol-Bittencourt PC 1,2,3, Tomaselli PJ1, Nahoum RG1, Collares CF4, Bittencourt FS2, Tournier MB1, Pioner LM1.
1 Federal University of Santa Catarina, Florianópolis/SC, Brazil
2 Hospital Santa Teresa, São Pedro de Alcântara/SC, Brazil
3 Epilepsy Centre of Santa Catarina, São Pedro de Alcântara/SC, Brazil
4 Intoxication Control Center of the Sao Paulo City Hospital, Brazil

Backgrounds: Epilepsy is a syndrome complex in which the impairment include seizures, sometimes cognitive regression and psychiatric illness as well. The relationship between epilepsy and behavior disorders it’s not clear, but it had been suggested that epilepsy, especially temporal lobe epilepsy, plays an important role in the genesis of manic states. Forced normalization (FN) is an unique condition characterized by brief interictal psychosis or important mood disorders encountered in people suffering from epilepsy. It was first described in 1953 by the Swiss neuropsychiatrist Heinrich Landolt. According to Landolt’s description it is the occurrence of psychiatric symptoms in association with suppression of seizures and EEG becomes more normal or entirely normal, as compared with previously abnormal EEG. Obviously symptoms like these must be distinguished properly from to the well know anti epileptic drugs (AED) side effects.

Methods: A transversal retrospective study of epileptic individuals that presents the FN phenomena. We reviewed the medical records of 1617 patients, who have been followed up as outpatients at a multidisciplinary centre for epilepsy care in southern Brazil. All patients had established diagnosis of epilepsy based on clinical history, EEG and imaging, presented behavior disturbance after a reduction in the total number of spikes by over 50%, or complete seizure control registered associated with normalization of EEG. All patients whose symptoms were attributed to undesirable side effects of AEDs were not included as suffers of this peculiar condition. The psychoses and mood disorder were diagnosed according to criteria in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Epileptic seizures and epileptic syndromes were classified according the proposed by the Commission on Classification and Terminology of the International League Against Epilepsy (ILAE).


Results: FN were found in 18(1,11%) of the 1617 outpatients included; 10 men and 8 women. The mean age was 38,1 ± 9,1 years at the time of examination (Table 1).

The family history of epilepsy, history of status epilepticus, febrile convulsion and handedness were verified (Table 2).

Their epilepsy onset was 9,3 years, presenting FN at 34,4 years (Table 3).

The mean of years between epilepsy onset and FN was 25,1 years, stay 31,4 days without seizures or reduction in the total number  before the manifestation of FN (Table 4).

The etiology were established based in the clinical history, EEG and imaging – Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) (Table 5).

Etiology of epilepsy. Other (one each) Mesial temporal sclerosis, Mesial hippocampal sclerosis, left temporal atrophy, left frontal atrophy and left enlargement ventricle.

Most of the patients have severe partial epilepsy. Episodic mood liability with intense aggressivity; major depression complaints and also schizophreniform were seen in the sample (Table 6).

EEG previously showed a frontal and temporal area predominance (Table 7); and during the period of psychiatric disorder showed that their focal epileptiform discharges had disappeared or became close to normal.

The epilepsy syndrome was partial in 16, symptomatic in 5 and cryptogenic in 11. The other 2 patients presented generalized syndrome. Ten patients had complex partial seizures (55,7%) as the predominant seizure type, 3 had simple partial and 2 generalized seizure. Eight (44,5%) were on polytheraphy in the moment of FN. Carbamazepine was the most used (72,2%), sodium valproato (22,2%), phenytoin (16,7%).


Conclusions: Complex partial was the commonest seizure type associated with FN in our sample. EEG previously showed a frontal and temporal area predominance. The symptoms we found were acute psychosis-like;  mood disturbances; schizophreniform and behavioral disturbances and delusional disorder. Most probably FN  was the cause of their episodic misbehavior disturbances seen among these persons suffering from active epilepsy. Curiously their behavior became normal after a major epileptic fit. It could be inferred that some people, epileptic or not, may inherently need paroxysmal cortical discharges to keep their normal cognitive functioning. The successful use of electroconvulsive therapy described by some investigators in the treatment of severe depression is good argument in favor of this idea. FN seems  to form a part of the functional changes during the whole course of psychiatric disorder, and may be based on the pathogenesis of interictal psychosis. The mechanisms of the antagonistic relation between electrical activity and psychiatric symptoms are not clear yet, but the hypothesis that subcortical and subclinical electrophysiological activity may be responsible for the development of FN. The variable time between seizures control and manifesting behavior disorder, 5 to 72 days, shows an uncertain epileptogenic discharges and clinical relationship. Keep controversial whether we should discontinue AEDs or not, in patient with that phenomena.  Suppression the AED treatment used to be  sufficient to reverse the clinical symptoms and this was our strategy.  However we recommend the decision should be taken after an interdisciplinary team assessment. Although FN phenomena is not so common in general neurological practice, we believe this condition should not be neglected by doctors connected to epileptology.


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Endereço para correspondência:
Dr.Paulo César Trevisol Bittencourt
Neurologia/Departamento de Clínica Médica/UFSC
88040-970 – Florianópolis/Santa Catarina/Brasil