Ennapadam S Krishnamoorthy and Michael R Trimble
A 32-year-old medically retired civil servant was referred to our clinic by his general practitioner. He had a history of epilepsy from the age of 16 years, and 3 years earlier, on referral to a university hospital, he had been correctly diagnosed with frontal lobe epilepsy. Neuroimaging studies had shown right frontal pathology. Therapy with topiramate had been instituted, which led to complete cessation of seizures. However, over the 18-month period between then and his consultation with us, he had developed a very prominent lack of motivation, though he remained seizure-free. This was diagnosed as depression and treated with fluoxetine for 18 months with little effect. In addition there was a complaint of erectile dysfunction and impaired ejaculation that appeared to predate these complaints.
While waiting to be seen in our clinic his clinical condition worsened significantly. He became profoundly withdrawn, stopped taking care of himself, did not eat for days on end, had not opened his mail, and had not washed for a considerable time. While he was somewhat depressed, the most prominent feature was his profound lack of will to engage in goal-directed behavior (abulia). Unlike people with depression that is severe enough to result in significant self-neglect, he did not have mood-congruent delusions or hallucinations, nor did he entertain nihilistic or suicidal ideas.
His general practitioner replaced fluoxetine with reboxetine, and his family intervened and took care of him. He was also seen by a local psychiatrist, who documented these developments, and by the uroneurologist in our hospital, who recommended sildenafil for the erectile dysfunction.
With the institution of reboxetine, and perhaps the use of sildenafil (on one occasion), his seizure control was destabilized and he developed a flurry of seizures. Nonetheless, his motivation improved, he began to engage in purposeful goal-directed behavior, his appetite became better, and he began to gain weight. Although there was no change in his mood and he remained somewhat miserable, his clinical state improved markedly and his abulia ceased.
When examined in the clinic, the patient was somewhat anxious and he reported long-standing low self-esteem. He attributed his low self-esteem, as well as his sexual dysfunction, to epilepsy. There were no psychotic features or major depressive ideation. He did, however, give a good account of the very prominent syndrome characterized by lack of motivation that he had suffered from, in the absence of seizures, while on treatment with topiramate, and which had remitted when his seizures returned.
Alternative psychosis in a patient with frontal lobe epilepsy presenting as a frontal lobe syndrome characterized by abulia.
Because the patient's symptoms had remitted with the reemergence of seizures, it was recommended that the dose of anticonvulsant drugs should be titrated to allow the occasional breakthrough seizure. The patient was referred to a sexual dysfunction clinic. When last reviewed in our clinic, his improvement with regard to abulia was maintained and he continued to have the occasional seizure.
This case clearly illustrates the complex relationships between epilepsy and psychiatric disorders, ranging from the more common and better-accepted agonistic relationship, to the less common and often hotly debated antagonistic relationship — the forced normalization of Landolt1 and the alternative psychoses of Tellenbach.2
This case also shows that distinct, possibly localization-related, neuropsychiatric syndromes do exist in epilepsy and are often mistaken for common psychiatric disorders such as depression.
Furthermore, this case aptly demonstrates the significance of the disability that sometimes results from anticonvulsant-induced neuropsychiatric disorders, which may arise, paradoxically, as a consequence of seizure control.
What did we learn from this case?
First, it is automatically assumed that good seizure control is the panacea for all the patient's ills. While this is certainly true for the vast majority of patients, there is a distinct subset of patients in whom we see an antagonistic relationship between seizure control and mental health. We learned from this case that it may be better for some patients to have the occasional seizure, rather than aggressively pursuing the ideal of
Abulia in a Seizure-Free Patient with Frontal Lobe Epilepsy 265
complete seizure control. As Landolt somewhat crudely put it: "It appears that there are some patients with epilepsy who need to have seizures in order to be mentally sane."3
Secondly, a number of people fail to recognize the distinct behavioral syndromes that accompany neurological and neuropsychiatric disorders. Abulia, the inability to engage in goal-directed behavior, is one such syndrome, commonly seen with lesions of the basal ganglia and frontal lobes.4 According to experts that we have surveyed, the syndrome does have some very distinct characteristics, such as difficulty in initiating and sustaining purposeful actions, reduced social interactions and reduced interest in usual pastimes, reduced emotional responsiveness and spontaneity, and reduced spontaneous speech and movement.5 Abulia is often mistaken for depression and treated as such. In this case, treatment with antidepressant drugs was beneficial in that it destabilized the patient's seizure control, leading to remission of the abulia.
Thirdly, even those clinicians who acknowledge the existence of the antagonistic relationship between epilepsy and psychiatric disorders often believe that the only presentation of the psychiatric disorders is with psychotic symptoms. This could not be further from the truth. The alternative psychoses, often accompanied by forced normalization of the EEG, are a spectrum of disorders that range from traditional psychosis to affective disorder, anxiety disorder and even non-organic complaints.6 In our experience, alternative psychoses can also present as discrete neuropsychiatric syndromes such as abulia and even the syndrome of episodic dyscontrol. Putative mechanisms include kindling in subcortical structures, secondary epileptogenesis and alternating states of GABAergic and glutaminergic preponderance, influenced by complex interactions with dopamine.7 Anticonvulsant drugs, particularly those such as topiramate that increase Y-aminobutyric acid levels, are well known to lead to alternative psychosis with or without forced normalization of the EEG.8
Furthermore, although the alternative psychoses are usually acute, they often develop insidiously. We have proposed criteria for the diagnosis of this condition that we hope will encourage epileptologists to establish prospective studies.9
Fourthly, most anticonvulsant drugs (both new and old) do produce neuropsychiat-ric symptoms or syndromes in some patients that are often ignored or remain undiag-nosed. These syndromes can cause a significant level of disability, as this case highlights, and need to be identified and managed properly.
Finally, this case serves to remind us that psychotropic drugs, especially antidepres-sants, are proconvulsant and may precipitate seizures. On this occasion the offending agent was reboxetine, a newer antidepressant. The seizure, however, ironically proved helpful in the patient's diagnosis and remission.
1. Landolt H. Serial EEG investigations during psychotic episodes in epileptic patients and during schizophrenic attacks. In: Lorentz De Haas AM, ed. Lectures on epilepsy. Amsterdam: Elsevier, 1958: 91-133.
2. Tellenbach H. Epilepsie als Anfallsleiden und als Psychose. Nervenar 1965;36:190-202.
3. Schmitz B. Forced normalization: history of a concept. In: Trimble MR, Schmitz B, eds. Forced normalization and alternative psychoses of epilepsy. Petersfield: Wrightson, 1998: 7-24.
4. Bhatia KP, Marsden CD. The behavioural and motor consequences of focal lesions of the basal ganglia in man. Brain 1994;117:859-76.
5. Vijayaraghavan L, Krishnamoorthy ES, Brown RB, Trimble MR. Abulia: a survey of British neurologists and psychiatrists. Mov Disord 2002;17(5):1052-7.
6. Wolf P. Acute behavioural symptomatology at disappearance of epileptiform EEG abnormality: paradoxical or forced normalization. In: Smith D, Treiman D, Trimble MR, eds. Neurobehavioural problems in epilepsy. NY: Raven Press, 1991: 127—42.
7. Krishnamoorthy ES, Trimble MR. Mechanisms of forced normalization. In: Trimble MR, Schmitz B, eds. Forced normalization and alternative psychoses of epilepsy. Petersfield: Wrightson, 1998: 193—207.
8. Trimble MR. Forced normalization and the role of anticonvulsants. In: Trimble MR, Schmitz B, eds. Forced normalization and alternative psychoses of epilepsy. Petersfield: Wrightson, 1998: 169—78.
9. Krishnamoorthy ES, Trimble MR. Forced normalization: clinical and therapeutic relevance in mood disturbances, psychoses and epilepsy. Epilepsia 1999;40(suppl 10):S57—S64.
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