Free Papers: Psychiatric Aspects


*Hideo Aiba, *Hiroatsu Hojo, *Keiko Hirano, and *Katsuhiko Oguro *Division of Pediatric Neurology, Shizuoka Children's Hospital, Shizuoka, Japan .

Purpose: Sulthiame (STM) is a carbonic anhydrase inhibitor that is effective in the control of temporal lobe epilepsy and other syndromes of localization-related epilepsy. We attempted to use STM for intractable localization-related epilepsy in patients with tuberous sclerosis (TS).

Methods: Three TS children aged from 4 to 17 years, who had daily to weekly seizures of localization-related epilepsy despite polytherapy with anticonvulsants (AEDs), were enrolled in this study. All patients fulfilled the criteria of definitive TS. The initial dose of STM was 50–100 mg/day, and the doses of other AEDs before STM treatment were not altered for 1 month.

Case Reports: Case 1: Secondarily generalized convulsions originating from the left or right upper limb during febrile episodes and recurred from age 7 months. Nonfebrile seizures, with a vacant stare and mild tonic stiffening, with or without loss of consciousness, occurred from age 18 months. Interictal scalp EEG showed left or right anterior temporal spike–waves, and ictal scalp EEG showed the same origin. Polytherapy with valproic acid (VPA), zonisamide (ZNS), and clobazam (CLB) decreased seizure frequency from daily to weekly. The seizure frequency decreased with the additional therapy of STM, 100 mg/day, and seizures were controlled with 150 mg/day STM at age 8 years. ZNS could be withdrawn. Only one recurrence occurred during a 2-year follow-up period, and the dose of STM was increased to 250 mg/day.

Case 2: Serial formation of epileptic spasms or tonic seizures occurred from age 1 year. Ictal EEG showed generalized fast waves, and interictal EEG showed multifocal spikes. Seizures and epileptic EEG abnormalities disappeared with polytherapy with VPA, ZNS, and clorazepate (CLP). Simple partial seizures with motionless stare and mild vibratory-tonic movements of the upper limbs occurred weekly from age 2 years. Interictal scalp EEG showed no epileptic discharges. The seizure frequency decreased with the substitution of CLB for CLP at age 3 years but increased to daily at age 4 years. When STM, 50 mg/day, was added, seizures ceased for 2 months. However, seizures relapsed when ZNS was discontinued. Seizures were controlled again for a year, when ZNS was reused and the dose of STM increased to 250 mg/day.

Case 3: Secondarily generalized seizures occurred from age 8 years. Interictal scalp EEG showed no epileptic discharges, and seizures were controlled with monotherapy with ZNS. Psychomotor seizures with unconsciousness, oroalimentary automatism, irrelevant speech or wandering, and secondarily generalized seizures relapsed from age 10 years. Interictal EEG showed left anterior temporal spike–waves. Ictal EEG showed paroxysmal discharges originating from the left frontocentral region and propagating to left hemisphere or both hemispheres. Complex partial seizures occurred daily, and secondarily generalized seizures occurred weekly at age 17 years, despite polytherapy with VPA, carbamazepine, and phenytoin (PHT). Seizures disappeared when STM, 100 mg/day, was added, but recurred 6 weeks later. The dosage of STM was increased gradually to 400 mg/day, and PHT was discontinued. The seizure frequency decreased compared with that before the addition of STM; complex partial seizures occurred once a week, and secondarily generalized seizures, once in 3 months.

Conclusions: Three TS patients with intractable localization-related epilepsy experienced >80% reduction in seizure frequency with the additional therapy of STM. We think it is worthwhile to use STM in these patients, although we do not know how it suppresses the seizure activity, or whether STM specifically benefits seizure control for TS. Combination of STM with VPA, CLB, or ZNS may provide better results.


*Masahiro Ito, *Hiroki Hasumi, and *Hisamitsu Tamaki *Department of Pediatrics, Tokyo Metropolitan Bokuto Hospital, Japan .

Purpose: Zonisamide (ZNS) is a broad-spectrum antiepileptic drug (AED), but renal stones and disturbance of sweating have been reported to be adverse effects (AEs) of ZNS. We report two cases of epilepsy with ZNS-related psychosis, which is rarely seen in Europe and the United States.

Case Report: Case 1: A 20-year-old man had mild developmental delay and epilepsy, with generalized seizures induced by a family computer game. Treatment with ZNS resulted in disappearance of seizures but was accompanied by severe psychotic episodes such as anxiety, insomnia, confusion, and visual and auditory hallucinations. These symptoms did not improve with administration of haloperidol and chlorpromazine. When ZNS was stopped, psychotic symptoms improved, but seizures appeared 4 days after cessation of ZNS.

Case 2: A 14-year-old girl had mild developmental delay, hearing impairment, and occipital lobe epilepsy with vomiting and status epilepticus. Treatment with ZNS resulted in disappearance of seizures but was accompanied by psychotic episodes, such as delusions of persecution, emotional incontinence, hyperactivity, and school refusal. These symptoms gradually improved with cessation of ZNS.

Conclusions: Attention should be paid to psychosis as an adverse effect of ZNS, when used in adolescents with al delay.


*Hironari Sue, *Chikako Takahashi, *Kazuhiko Nakayama, and *Sadanobu Ushijima *Department of Psychiatry, Jikei University School of Medicine, Tokyo, Japan .

Purpose: Epileptic prodromes are warnings of a seizure and are observed hours or days before seizure onset. They are restricted to the phenomena that do not form part of an actual seizure. The prodromes commonly seen are subjective symptoms, such as irritability, anxiety, and headache. However, little attention has been given to these phenomena. The purpose of this study was to investigate the contents and the frequency of the prodromes.

Subjects and Methods: Patients with epilepsy (197; 90 men and 107 women), ages 12–71 years, were studied. The onset age was 0–70 years (mean age, 19.3 years). The epilepsies were categorized as generalized epilepsies in 44 (22%), partial epilepsies in 132 (67%), and unclassified (UEs) in 21 (11%). Thirty-nine of 44 patients who had generalized epilepsies were classified as idiopathic (IGE), and five, as symptomatic (SGE). All patients with partial epilepsy were symptomatic; 79 were categorized as temporal lobe epilepsy (TLE), and 53, as non-TLE. The term prodrome was defined as follows: It is seen before a habitual seizure happens, so the prodrome per se is not an actual seizure but is related to the epileptic condition; it often lasts for several hours to about a week before the occurrence of a seizure, regardless of whether it is repeated often or continues during this period; and it can be distinguished from a simple partial seizure (SPS).

Results: Of the 197 patients, prodromes were found in 14 (7%). These comprised only one (2%) of 39 patients with IGE, eight (10%) of 79 patients with TLE, and five (9%) of 53 patients with non-TLE. Thus prodromes were not found in SGE and UE patients. The contents of prodromes were as follows. Irritability followed by a headache was described by one IGE patient. Of eight TLE patients, one patient each experienced irritability, irritability and talkativeness, an uncomfortable feeling difficult to express, overeating, and a decline of concentration, whereas three patients felt a headache. Of five non-TLE patients, one patient each described a depressive mood, a headache, irritability, getting restless and talkative like a hypomanic state, and irritability developing into a drinking bout. Among the 14 patients with prodromes, three were hardly aware of these premonitory symptoms (overeating, a decline of concentration, and becoming restless and talkative like a hypomanic state). However, their families often worried that a seizure would come within a week. In other words, the prodrome observed in the three patients may be called an “objective prodrome,” whereas the others may be called a “subjective prodrome,” which the patient can feel.

Case Reports: Case 1 (subjective prodrome) was a 38-year-old man diagnosed as having TLE. The first seizure, in the form of a generalized tonic–clonic (GTC) seizure, occurred at age 28 years and was followed by seizures once every year. From age 32, several days before a seizure, he would be irritated for a few days, and then he repeatedly did a great deal of drinking, which often led to a seizure. Memory was preserved.

Case 2 (objective prodrome) was a 45-year-old man diagnosed as having TLE. The first seizure, in the form of SPS with psychic symptoms, occurred at age 10 years. He also experienced CP and GTC seizures. After a while, he experienced increased appetite before the occurrence of a seizure. He was not aware of this state, but he would excessively eat. During the time of such overeating, his mother would tell him, “Be careful; a seizure may occur.”

Conclusions: The prodromes can be classified into two types: subjective and objective. The incidence of prodromes, especially of objective prodromes, is low. Nevertheless, prodromes are important as the anticipation factor of a forthcoming seizure, and more attention to them is needed.


*Itsuki Jibiki, *Shinzou Iwasaki, *Sachiko Kamoda, and †Hisao Tonami Departments of *Neuropsychiatry and †Radiology, Kanazawa Medical University, Uchinada, Kahokugun, Japan .

Purpose: We examined the usefulness of functional MRI (fMRI) for studying the pathophysiology of memory function and as a presurgical assessment in neurosurgical treatment of epilepsy. Activated areas in the fMRI during verbal and visual memory tasks were investigated in patients with partial epilepsy and compared with activated areas in normal subjects.

Methods and Subjects: The partial epilepsy group consisted of five men and five women, ranging in age from 24 to 58 years. Seven patients had temporal lobe epilepsy, with left (four cases) and right (three cases) temporal foci; two patients had frontal lobe epilepsy with left (one case) and right (one case) frontal foci, and the remaining patient had partial epilepsy of undetermined origin. Nine patients were right-handed, and the remaining female patient with frontal lobe epilepsy and a left frontal focus was left-handed. The normal control group comprised 32 subjects (18 men and 14 women), ranging in age from 19 to 56 years. Of the 32 subject, 28 were right-handed, and the remaining four were left-handed. Verbal memory tasks were covert and overt recall tasks of 10 words presented auditorily, whereas visual tasks entailed recall tasks of six figures presented visually. Each task was performed for 10 s and repeated five times, with interposing resting baseline periods. Significant differences in signal intensity between the repeated tasks and baseline periods were acquired as activated areas during tasks on T2-weighted MRI of 1.5 Tesla. The slice thickness was 3 mm in horizontal sections parallel to an AC-PC line. Results were analyzed by using a Z-score threshold ranging from 4.2 to 6.0.

Results: In the normal subject group, fMRI during the covert recall tasks of verbal memory demonstrated activated areas mainly on the left side–dominant medial frontal lobes, including the superior frontal and anterior cingulate gyri in all but one left-handed man. During the overt recall tasks, additional activated areas were seen in the left side–dominant inferior frontal and precentral gyri as motor language areas. Furthermore, bilateral occipital lobes were activated during the recall tasks of visual memory. Also in the patient group, all but one left-handed woman showed activated areas in the same left side–dominant cortical regions as mentioned earlier, especially in seven patients with temporal lobe epilepsies, regardless of the lateralization of temporal foci during the covert or overt recall tasks of verbal memory. Both the left-handed normal man and the woman with epilepsy showed activated areas in the same cortical regions as mentioned earlier, but with right-side dominance, during the verbal memory tasks.

Conclusions: These results suggest that the memory lateralization in verbal memory function is associated with the side of handedness, perhaps in the same manner as the language function. Furthermore, fMRI is useful for the determination of lateralization of the cerebral hemisphere contributing to verbal memory function and is consequently important for presurgical assessment of memory function in neurosurgical treatment of epilepsy.


*Tatsuya Kudo and †Shirou Ishida *National Epilepsy Center, Shizuoka Medical Institute of Neurological Disorders ; and †Shizuoka Prefectural Mental Care and Rehabilitation Center, Shizuoka, Japan .

Purpose: Mental disorders with psychogenic factors as the major pathogenetic mechanism (psychogenic mental disorder, PMD) occasionally coexist with epilepsy. The clinical features and risk factors of PMDs coexisting with epilepsy were studied.

Methods: This study was based on three groups: a group of 50 patients with epilepsy coexisting with PMD (epilepsy-PMD group), a group of 176 patients with only epilepsy (epilepsy group), and a group of 55 patients with only PMD (PMD group). All patients in the epilepsy-PMD group and the epilepsy group were admitted to the National Epilepsy Center, and all patients in the PMD group were treated in the outpatient clinic of Shizuoka Prefectural Mental Care and Rehabilitation Center. The epilepsy-PMD group was further divided into a group of 32 patients whose PMD was misinterpreted by patients as epileptic seizures (misinterpreted subgroup) and a group of 18 patients whose PMD was not misinterpreted (nonmisinterpreted subgroup).

Results: 1: The epilepsy-PMD group showed significantly higher rates of conversion disorder (p < 0.01), adjustment disorder (p < 0.05), and dissociative disorder without symptoms of conversion disorder (p < 0.05), compared with the PMD group. Episodes of conversion disorder were accompanied by psychogenic amnesia of events during episodes in 27 of 29 patients in the epilepsy-PMD group. When psychogenic amnesia accompanied by conversion disorder was considered as dissociative amnesia, 62% of patients in the epilepsy-PMD group showed signs of dissociative disorder. In contrast, the PMD group showed significantly higher rates of undifferentiated somatoform disorder (p < 0.01) and anxiety disorder (p < 0.01), compared with the epilepsy-PMD group. 2: The misinterpreted subgroup showed a significantly (p < 0.01) higher rate of conversion disorder accompanied by psychogenic amnesia, compared with the nonmisinterpreted subgroup. In contrast, the nonmisinterpreted subgroup showed significantly (p < 0.01) higher rates of dissociative disorder and adjustment disorder compared with the misinterpreted subgroup. Symptoms of PMD resembling epileptic seizures were observed in 26 patients in the misinterpreted subgroup (81.2%), but not in the nonmisinterpreted subgroup. Twenty-two (84.6%) of 26 patients with epileptic seizure–like symptoms of PMD showed nonconvulsive seizure-like symptoms, and five (19.2%) patients showed convulsive seizure–like symptoms. 3: Only 40% of the patients in the epilepsy-PMD group compared with 89.1% in the PMD group were able to identify the psychogenic factors causing the initial episode of PMD and to remember the time of initial onset of PMD. Aggravation of PMD symptoms was observed, not only in all patients in the PMD group, but also in all patients in the epilepsy-PMD group. Zonisamide and sulthiame were involved in the PMD of one patient each in the epilepsy-PMD group. Psychotic disorder was observed in two patients in the epilepsy-PMD group. The number of patients with neurologic deficits was significantly greater (p < 0.01) in the epilepsy-PMD group than in the PMD group. Dependent personality was observed in 76% of patients in the epilepsy-PMD group. 4: No significant differences were found in epileptic syndromes, frequency of epileptic seizures, and number of antiepileptic drugs used for controlling epileptic seizures between the epilepsy-PMD group and the epilepsy group.

Conclusions: The results showed that many factors, such as misinterpretation of PMDs as epileptic seizures, dependent personality disorder, brain damage, antiepileptic drugs, and psychotic disorder were involved in the generation of PMDs that occur under a chronic condition of epilepsy. Individualized multifaceted therapies including control of epileptic seizures, correction of misinterpretation of PMDs as epileptic seizures, psychological therapy, training, rehabilitation, and antipsychotic therapy are necessary for the treatment of PMDs.


*Kazuya Goto *Department of Pediatrics, Nishibeppu National Hospital, Nishibeppu, Japan .

Purpose: Epileptic seizures frequently are reported in pervasive developmental disorder (PDD). The present study was designed to investigate the epileptic syndrome, seizure frequency, EEG characteristics, and evolution of seizures in patients with epilepsy and PDD. We especially focused on the relation between seizure manifestations and cognitive function in this study.

Methods: We conducted a retrospective study on patients with PDD and epilepsy, nine male and four female patients, ages from 6 to 31 years. The diagnosis of PDD was made according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Patients with PDD secondary to congenital or acquired encephalopathy were excluded. Epileptic syndromes were classified according to the seizure manifestation and interictal EEG. Epileptic features included seizure type, frequency, age at onset, and evolution. Characteristics of EEG paroxysmal activities were analyzed through medical records. The relation between epileptic features and cognitive function and behavioral problems also was investigated. According to the Ohta scale, cognitive function was classified as stage I for pointing at objects described by name; stage II for pointing at objects described by use; stage III for discrimination of large and small circles; and stage IV for recognition of spatial relations. Behavioral problems such as self-injurious behavior and aggression were assessed by the Nakashima Behavior Checklist.

Results: Among 13 patients, nine patients were diagnosed as having localization-related epilepsy, including three with frontal lobe epilepsy, one with benign childhood epilepsy with occipital paroxysms, and five with undetermined localization. Two patients were diagnosed as having generalized epilepsy, one with the Lennox–Gastaut syndrome and one with myoclonic–astatic seizures. Two other patients were classified as having undetermined epilepsy. Although the ages at the initial seizure ranged from 3 months to 19 years, there seemed to be a bimodal age distribution with one peak in infancy and the other in adolescence. No correlation was noted between age at onset and cognitive function. Seizure frequencies throughout the course varied from daily to yearly. One patient with the Lennox–Gastaut syndrome, one patient with undetermined epilepsy, and two patients with localization-related epilepsy had daily or weekly seizures. All stage III or IV patients did not have seizures daily or weekly. In spite of low seizure frequencies, seizures relapsed with intervals varying from 1 to 10 years in seven patients. Interictal EEG recording showed focal paroxysmal abnormalities in nine patients, with frontal region localization in seven patients.

Conclusions: Although the most prevalent epileptic syndrome was localization-related epilepsy, many seizure types and epileptic syndromes may be associated with PDD. Seizure control is mostly related to the severity of each epileptic syndrome. In addition, seizure control may more readily be achieved in PDD patients with higher levels of cognitive function.