Postictal mania versus postictal psychosis: differences in clinical features, epileptogenic zone, and brain functional changes during postictal period

PURPOSE: To clarify the differences between postictal mania (PIM) and postictal psychosis (PIP). METHODS: Five patients with PIM were compared to 17 patients with PIP, with respect to clinical, epileptological, electrophysiological, and neuroimaging features. PIM was distinguished from PIP by the symptoms observed in the postictal period based on the ICD-10 criteria. RESULTS: Postictal manic episodes lasted for a longer period than postictal psychotic episodes. Patients with PIM had more recurrent postictal episodes than patients with PIP. The age at onset of epilepsy in patients with PIM was older than that in patients with PIP. PIM was associated with frontal lobe and temporal lobe epilepsies, whereas PIP was associated with temporal lobe epilepsy. The estimated epileptogenic zone was on the language dominant side in PIM, whereas there was no predominant hemispheric laterality in PIP. Electroencephalography (EEG) performed during the early period of postictal manic and psychotic episodes showed decreased frequency of interictal epileptiform discharges in both PIM and PIP. Single-photon emission computed tomography (SPECT) during postictal manic and psychotic episodes showed increased perfusion in the temporal and/or frontal lobes in both PIM and PIP. Three patients with PIM showed increased perfusion during postictal episodes on bilateral or the language nondominant side, which were contralateral to the estimated epileptogenic zone, whereas three patients with PIP showed increased perfusion on the areas, which were ipsilateral to the estimated epileptogenic zone. CONCLUSIONS: PIM has a distinct position among the mental disorders observed in the postictal period.     

Single Photon Emission Computed Tomography (SPECT) in a Patient with Bilateral Temporal Seizures: Correlation Between Ictal EEG and Postictal/Ictal SPECT

Summary: We report a patient with bilateral independent temporal lobe seizures in whom two [^99mTc]HMPAO single photon emission computed tomograph (SPECT) scans were performed during two different seizures. In the first perüctal SPECT, [^99mTc]HMPAO was injected in the interval between two closely spaced seizures (one localized in the left temporal lobe and the other in the right temporal lobe). SPECT images showed hypoperfusion in the left lateral temporal lobe, hyper-perfusion of the left mesial temporal region, and pronounced hyperperfusion in the right anterior temporal lobe. These results suggest both a postictal left temporal SPECT pattern and an ictal right temporal pattern. In the second periictal SPECT, [^99mTc]HMPA was injected immediately after a right temporal lobe seizure and showed right lateral temporal lobe hypoperfusion and right mesial hyperperfusion, suggesting a postictal right temporal SPECT pattern. Interpretation of the periictal SPECT should take into account EEG changes at the time or in the minutes immediately after injection of [^99mTc] HMPAO.     

A longitudinal functional connectivity analysis of the amygdala in bipolar I disorder across mood states

Cerullo MA, Fleck DE, Eliassen JC, Smith MS, DelBello MP, Adler CM, Strakowski SM. A longitudinal functional connectivity analysis of the amygdala in bipolar I disorder across mood states. Bipolar Disord 2012: 14: 175–184. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective: Bipolar I disorder is characterized by affective symptoms varying between depression and mania. The specific neurophysiology responsible for depression in bipolar I disorder is unknown but previous neuroimaging studies suggest impairments in corticolimbic regions that are responsible for regulating emotion. The amygdala seems to play a central role in this network and is responsible for appraisal of emotional stimuli. To further understand the role of the amygdala in the generation of mood symptoms, we used functional magnetic resonance imaging (fMRI) to examine a group of patients with bipolar I disorder longitudinally. Methods: fMRI was used to study regional brain activation in 15 bipolar I disorder patients followed for up to one year. Patients received an fMRI scan during an initial manic episode and a subsequent depressive episode. During the scans, patients performed an attentional task that incorporated emotional pictures. Fifteen healthy comparison subjects were also scanned at baseline and then at four months. Whole‐brain functional connectivity analysis was performed using the left and right amygdala as seed regions. Results: Significant changes in amygdala functional connectivity were found between the manic and depressed phases of illness. The right amygdala was significantly more positively correlated with the left inferior frontal gyrus during mania and with the right insula during depression. There were no significant differences in left amygdala correlations across mood states in the bipolar I disorder group. Conclusions: In the transition from a manic/mixed episode to a depressive episode, subjects with bipolar I disorder showed unique changes in cortical–amygdala functional connectivity. Increased connectivity between the insula and right amygdala may generate excessive positive feedback, in that both of these regions are involved in the appraisal of emotional stimuli. Increased correlation between the right amygdala and the inferior frontal gyrus in mania is consistent with previous findings of decreased prefrontal modulation of limbic regions in mania. These differences in connectivity may represent neurofunctional markers of mood state as they occurred in the same individuals across manic and depressive episodes.     

Blunted activation in orbitofrontal cortex during mania: a functional magnetic resonance imaging study.

BACKGROUND: Patients with bipolar disorder have been reported to have abnormal cortical function during mania. In this study, we sought to investigate neural activity in the frontal lobe during mania, using functional magnetic resonance imaging (fMRI). Specifically, we sought to evaluate activation in the lateral orbitofrontal cortex, a brain region that is normally activated during activities that require response inhibition. METHODS: Eleven manic subjects and 13 control subjects underwent fMRI while performing the Go-NoGo task, a neuropsychological paradigm known to activate the orbitofrontal cortex in normal subjects. Patterns of whole-brain activation during fMRI scanning were determined with statistical parametric mapping. Contrasts were made for each subject for the NoGo minus Go conditions. Contrasts were used in a second-level analysis with subject as a random factor. RESULTS: Functional MRI data revealed robust activation of the right orbitofrontal cortex (Brodmann's area [BA] 47) in control subjects but not in manic subjects. Random-effects analyses demonstrated significantly less magnitude in signal intensity in the right lateral orbitofrontal cortex (BA 47), right hippocampus, and left cingulate (BA 24) in manic compared with control subjects. CONCLUSIONS: Mania is associated with a significant attenuation of task-related activation of right lateral orbitofrontal function. This lack of activation of a brain region that is usually involved in suppression of responses might account for some of the disinhibition seen in mania. In addition, hippocampal and cingulate activation seem to be decreased. The relationship between this reduced function and the symptoms of mania remain to be further explored.     

Distinct neurophysiological mechanisms for manic and cycloid psychoses: evidence from a P300 study on manic patients

Pathologically asymmetrical P300 fields with right lateralized peaks were described in core schizophrenia as an expression of left-temporal functional deficits, while higher than normal amplitudes were found in cycloid psychosis. This latter finding appeared to be specific for cycloid psychosis and was explained by a generalized cerebral hyperarousal. Based on some psychopathological analogies with cycloid psychosis, and on the comparable pharmacological treatment of the acute episodes, a group of 19 manic patients was investigated immediately after remission and clinical stabilization of an episode. Patients with psychotic features were excluded to avoid overlaps with cycloid psychosis. Patients showed normal P300 amplitudes and no pathological asymmetries of the field, but more posterior positive areas compared to age- and sex-matched controls. This indicates that the neurophysiological changes underlying mania are different from both core schizophrenia and cycloid psychosis. Based on previous three-dimensional source location studies, this finding indicates that disinhibition due to reduced frontal lobe activity, and not hyperarousal, is the basic functional mechanism of manic disorders.     

Magnetoencephalographic Analysis of Secondary Bilateral Synchrony

To assess the clinical value of magnetoencephalography (MEG) in investigating the origin of secondary bilateral synchrony (SBS) in patients with partial epilepsy. MEG and simultaneous electroencephalography (EEG) were recorded with a 204-channel whole-head MEG system in 2 patients. The equivalent current dipoles (ECDs) for epileptic discharges on MEG were calculated according to a single dipole model. In patient 1, the ictal EEG showed bursts of bilateral synchronous 3-Hz spike-and-slow-wave complexes. ECDs obtained from the ictal MEG localized to the right medial frontal lobe. On the second patient's MEG recordings, epileptic discharges corresponding to prolonged EEG bursts of bilateral synchronous spike-and-slow-wave complexes were obtained. ECDs calculated from the prolonged bursts were clustered in the left medial frontal lobe. MEG detected the sources of SBS in the medial frontal lobe. MEG is extremely useful for the identification of the source of SBS.     

额叶癫痫的诊断—形态与功能定位的对比

本文对２８例额叶癫痫病人的ＥＥＧ，ＣＴ，ＳＰＥＣＴ检查定位结果进行了对比研究，结果显示：８５．７％的病人发作间期和／或发作期ＥＥＧ有额叶定位征象，两者结合可提高定位诊断阳性率及准确率。ＣＴ检查仅４２．９％发现额叶损害，仍是重要辅助诊断手段。     

Correlation of SPECT, EEG and CT in patients with epilepsy. A preliminary report

Single photon emission computed tomography (SPECT) were performed in 14 patients with epilepsy. Among 6 patients with GTC, five had no focal abnormalities in EEG and CT scan, SPECT also showed no changes of regional cerebral perfusion. In another one patient EEG was normal, CT scan showed hypodensity in right frontal area, SPECT showed decreased regional cerebral perfusion in right frontotemporal area. AVM in frontal lobe was found at operation. In 3 patients with complex partial seizures and 5 patients with complex partial seizures and GTC, SPECT showed regional cerebral perfusion coincided with the area of focal epileptic form discharges in EEG. In one patient with complex partial seizures and GTC EEG showed right antero-temporal focal sharp wave discharges, discrete calcification in superior suprasella cisterna on CT, SPECT showed decreased regional perfusion in right temporal area, pathological examination revealed hematoma in right temporal lobe. SPECT is useful for localizing epileptogenic foci in epileptics.     

Postictal SPECT in Epileptic Versus Nonepileptic Seizures

Despite advances in video-electroencephalogram (EEG) technology, in many patients distinguishing epileptic seizures from nonepileptic seizures (NES) remains a challenge. Reliable methods to make this distinction are needed. In a pilot study, we performed postictal and interictal single photon emission computed tomography (SPECT) in 22 patients undergoing video-EEG monitoring who had altered responsiveness during an episode. Eleven had seizures, defined as episodes associated with EEG seizure patterns or postictal prolactin (PRL) elevations greater than 1.5 times the highest interictal baseline PRL; 11 had NES. Among the 11 seizures, postictal SPECT was abnormal in seven (regions of hypoperfusion in six and hyperperfusion in one) and normal in four. In six cases (55%), the interictal and postictal SPECT changed. Among the 11 NES cases, postictal SPECT was abnormal in three cases (all hypoperfusion abnormalities) and normal in eight cases. In no case did the interictal and postictal SPECT change. This small sample revealed a trend toward greater hypometabolism (postictal versus interictal) on SPECT for epileptic seizures compared to NES (p < 0.12). There were postictal SPECT changes in two of five seizures unassociated with postictal PRL elevation. Prolactin was elevated in two cases unassociated with change on SPECT. Comparision of postictal to interictal SPECT may help distinguish epileptic seizures from NES. Results from SPECT may also help identify epileptic seizures unassociated with PRL elevation.     

Ictal/postictal SPECT in the pre-surgical localisation of complex partial seizures.

Single photon emission computed tomography (SPECT) used in conjunction with HM-PAO (Ceretec-Amersham International) was used to image regional cerebral blood flow (rCBF) in 28 patients with medically intractable complex partial seizures during or soon after a seizure, and interictally. Changes from interictal rCBF were seen in 26/28 (93%) patients. The main findings were; 1) During the seizure--hyperperfusion of the whole temporal lobe; 2) Up to 2m postically--hyperperfusion of the hippocampus with hypoperfusion of lateral temporal structures; 3) From 2-15m postically--hypoperfusion of the whole temporal lobe. When compared with EEG and MRI data, correct localisation to one temporal lobe was obtained in 23 patients. In one further patient bilateral temporal foci, and in a further two patients frontal foci, were correctly identified. There were no disagreements between EEG and SPECT localisation. Temporal lobe surgery was successful (by the criterion of at least 90% reduction in seizure frequency) in all but one of the 23 patients operated on. It is concluded that ictal/postictal SPECT is a reliable technique for the presurgical localisation of complex partial seizures. The data indicate a likely sequence of changes in rCBF during and after complex partial seizures of temporal lobe origin.     

Subacute postictal aggression in patients with epilepsy

Three men with epilepsy (age range, 38-62) who exhibited brief episodes of violent behavior during the postictal period are described. Disease duration ranged from 27 to 44 years. Patients had both complex partial seizures and secondarily generalized tonic-clonic seizures, which were refractory to antiepileptic drugs. Postictal aggression occurred shortly after a seizure and lasted 5-30 minutes. The patients displayed physically and verbally aggressive behavior toward others, but regained consciousness promptly and showed regret afterward. Interictal EEGs revealed temporal spikes, SPECT showed hypoperfusion in the temporal and frontal areas in two patients, and neuropsychological examination revealed poor frontal lobe function in two patients. Characteristics of our cases are consistent with subacute postictal aggression (SPA) reported previously. Epilepsy of prolonged duration and brain dysfunction involving a broad area including the temporal and frontal lobes may be associated with the occurrence of subacute postictal aggression.     

Supplementary motor area epilepsy associated with ADHD in an abused history

A 6-year-old girl with attention-deficit hyperactivity disorder (ADHD) who had been abused by her mother in infancy developed supplementary motor area (SMA) epilepsy. The seizure was characterized by bilateral tonic seizure of the upper and lower extremities, speech arrest, preserved consciousness and a lack of postictal confusion. The duration of the seizure was usually 10-60 seconds. The seizures sometimes clustered. She was diagnosed as having SMA epilepsy based on the characteristic clinical symptoms, interictal EEG, ictal video-EEG and ictal SPECT. Though her seizure was initially improved by anti-epileptic drugs, the symptoms appeared again after discharge. Since her clinical course indicated that her seizure was aggravated by her mental state, treatment included both medication with anti-epileptic drugs and the adjustment of her living environment in cooperation with a child guidance clinic. Thereafter both her epileptic seizure and ADHD symptoms improved. These changes may be related to each other, because both conditions are associated with frontal lobe dysfunction. It was interesting that the adjustment of the environment improved frontal lobe epilepsy, which in turn ameliorated ADHD symptoms.     

SPECT findings during postictal psychoses: predominance of relative increase of perfusion in right temporal lobe

To identify brain regions activated during episodes of postictal psychoses (PIP), we investigated single-photon emission computed tomography (SPECT) data obtained from five patients treated at our institutions and also reviewed four previous studies. Therefore, SPECT findings in a total of 19 cases were analyzed, including 16 patients with temporal lobe epilepsy (TLE). During nonpsychotic states, the laterality of epileptic foci was judged as left-sided in nine episodes, right-sided in six episodes, and nonlateralized in four episodes. In PIP states, 88% of the patients showed a relative increase of right temporal perfusion (increased right temporal or decreased left temporal perfusion). Regardless of whether right- or left-sided pathology was suspected during a nonpsychotic state, SPECT findings obtained during PIP episodes revealed a trend of right-sided temporal predominance.     

Frontal lobe psychopathology: mania, depression, confabulation, catatonia, perseveration, obsessive compulsions, and schizophrenia

The frontal lobes can be subdivided into major functional neuroanatomical domains, which, when injured, surgically destroyed, or reduced in activity or volume, give rise to signature pathological and psychiatric symptomology. A review of case reports and over 50 years of research, including magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography scans, indicates that apathy, "blunted" schizophrenia, major depression, and aphasic-perseverative disturbance of speech and thought are associated with left lateral as well as bilateral frontal (and striatal) abnormalities. Impulsiveness, confabulatory verbosity, grandiosity, increased sexuality, and mania are associated with right frontal (as well as bilateral) disturbances. Gegenhalten, catatonia, and disturbances of "will" are indicative of medial frontal injuries. Disinhibitory states and obsessive-compulsive perseverative abnormalities are more frequently observed with orbital frontal lobe dysfunction, including frontal-striatal disturbances. These associations, however, are not always clear-cut as patients with the same diagnosis may demonstrate different symptoms that may be due to an additional abnormality in a different region of the brain. Moreover, as the frontal subdivisions are richly interconnected, and as frontal lobe abnormalities are not always discrete or well localized, a wide array of seemingly divergent waxing and waning symptoms may be manifest, sometimes simultaneously, including manic depression and what has been referred to as the "frontal lobe personality."     

Ictal MEG in two children with partial seizures

We report on the successful identification of epileptic foci in two children with partial epilepsy using ictal magnetoencephalography (MEG). Case 1 is a 12-year-old male suffering with simple partial seizures with leftwards nystagmus. Ictal SPECT revealed a hyperperfusion area in the right lateral occipital area, and MRI revealed cortical dysplasia in the same area. Interictal EEG dipoles were concentrated in the right mesial occipital lobe. Both interictal and ictal MEG dipoles were concentrated in the right mesial occipital lobe, which corresponded well with neuroimaging data and his clinical features. Case 2 is a 5-year-old female suffering with simple partial seizures with left-side facial twitching. Interictal EEG dipoles were located in her left motor area, the pre-sylvian fissure, close to the location of the interictal MEG-estimated dipoles. Ictal EEGs showed no remarkable changes associated with her clinical manifestations. However, ictal MEG showed high-voltage slow waves over her left hemisphere, and ictal MEG iso-contour maps revealed a clear dipolar pattern, which suggested that the MEG dipole was located in the area of the sylvian fissure. Ictal SPECT revealed hyperperfusion areas around the left sylvian fissure. Conclusion: Ictal MEG is useful for determining the precise location of epileptic focus in patients with motionless seizures, including children.     

Patterns of postictal cerebral blood flow in temporal lobe epilepsy: qualitative and quantitative analysis

We used single-photon emission computed tomography (SPECT) to study postictal cerebral blood flow (CBF) in 51 patients with temporal lobe epilepsy. There were 78 seizures studied, 77 by early postictal injection of Tc-99m HMPAO (delay from seizure onset = 4.3 +/- 4.5 min) and one by ictal injection. Increased focal temporal lobe uptake, predominantly confined to the anteromesial region, was present in 83% and declined rapidly over 5 minutes. Reduced activity in the lateral temporal lobe accompanied the mesial increase in 80% of studies, extending over much of the ipsilateral hemisphere and closely associated with the degree and extent of postictal EEG slow waves. These patterns enabled correct seizure localization by blinded analysis in 69% (31/45) of the patients with a unilateral EEG focus. The remainder showed bilateral or no changes. One of six patients with bitemporal EEG foci had unilateral perfusion changes. The positive predictive value for the correct localization of a unilateral focus by postictal SPECT was 97% (31/32). Postictal CBF imaging with SPECT can be used to support noninvasive electrographic localization and may decrease the need for invasive electrode studies.     

Efficacy of Thyrotropin-Releasing Hormone in the Treatment of Intractable Epilepsy

Purpose : The ictal EEG and magnetoencephalogram (MEG) for gelastic seizures were recorded in a 4-year-old girl with tuberous sclerosis. The sites of origin for the seizure activities were investigated by using an equivalent current dipole (ECD) with the MEG.
Methods : EEG and MEG were recorded simultaneously under the administration of diazepam (DZP). The MEG recording was performed on a system consisting of an array of 64 sensors uniformly distributed over the patient's whole head (CTF, Canada), and the estimated ECDs were superimposed on the magnetic resonance imaging (MRI) images (Siemens, 1.5 Tesla).
Results : Two laughing attacks lasting 5 s each were documented. The ictal EEG showed gradually increasing 11–Hz rhythmic α activities with dominance over the frontocentral areas bilaterally, followed by irregular spike-and-wave discharges. The ictal MEG detected bilateral frontal rhythmic sharp waves before the appearance of the activities on the EEG. The estimated ECDs were localized in the deep white matter of the right frontal lobe on the MRI. However, those dipoles did not coincide with the locations of her cortical tubers.
Conclusions : Although gelastic seizures accompanied with hypothalamic hamartomas are well known, several reports have suggested a temporal or frontal lobe origin for gelastic seizures. In this patient, the ECD indicated that the seizures originated in the frontal lobe, although ictal scalp EEG recordings could not determine the precise focus. Thus, in cases in which the use of ictal scalp EEG fails to show the sites of origin for the seizures, it is recommended that the origins be estimated by using the non-invasive method of ictal MEG analysis.     

Symptom profile consistency in recurrent manic episodes

Few studies have addressed whether symptom profiles remain consistent between episodes of mania. Those that have done so focused on mood only and adopted the strictly categorical approach. We evaluated 77 subjects during two discrete manic episodes (mean interval, 2 years, 2 weeks). Episodes were characterized on five established symptom factors of mania and on overall severity of classic manic symptoms (i.e., excluding dysphoric symptoms). Pearson correlation coefficients were computed to compare symptom profiles across episodes. Four symptom factors (dysphoria, hedonic activation, psychosis, and irritable aggression) were significantly correlated across episodes, as was manic severity. Psychomotor symptoms were not significantly correlated. Manic symptomatology remains generally similar in bipolar subjects during different episodes. The characterization of manic episodes by the empirical dimensions of symptom factors, as suggested by Kraepelin nearly a century ago, may provide additional information for biological and treatment response studies of manic states that is not captured by categorical subtype diagnosis focused solely on mood symptoms (i.e., mixed v pure manic episodes).     

Combined imaging of epileptic foci and brain metabolism using MEG and FDG-PET]

A 17-year-old woman developed left hemiparesis at the age 6 months. She had suffered from focal motor seizures associated with tonic extension of her left extremities since the age of 10 years. The interictal scalp EEG demonstrated frequent spike-and-slow-wave complexes dominantly in the right frontal area. MRI showed an old cerebral infarction in the right frontal lobe. Simultaneous recordings of magnetoencephalography (MEG) and EEG were obtained by using a 204-channel whole-head MEG system. Equivalent current dipoles (ECDs) calculated from epileptic spikes on MEG were scattered in the cortex adjacent to the lesion in the right frontal lobe. Positron emission tomography with 18-fluoro-2-deoxyglucose (FDG-PET) in the interictal state showed hypometabolism in the lesion and its adjacent area. The super-imposed images of the dipole and PET showed that epileptic foci surrounded the lesion. The multimodality imaging is useful for evaluation of patients with epilepsy for possible indication of surgery.     

Ictal and Interictal Activity in Partial Epilepsy Recorded with Multichannel Magnetoelectroencephalography: Correlation of Electroencephalography/Electrocorticography, Magnetic Resonance Imaging, Single Photon Emission Computed Tomography, and Positron Emission Tomography Findings

Ictal and interictal epileptic activity was recorded for the first time by multichannel magnetoencephalography (MEG) in three patients with partial epilepsy. Pre- and intra-operative localization of the epileptogenic region was compared. The interictal epileptic activity was localized at the same region of the temporal or frontal lobe as the ictal activity. Main zones of ictal activity were shown to evolve from the tissue at the centers of interictal activity. Pre- and intra-operative electrocorticography (ECoG) as well as postoperative outcome confirmed localization in the temporal and frontal lobe. Results also correlated with findings from scalp EEG, interictal and ictal single photon emission computed tomography (SPECT), positron emission tomography (PET), and magnetic resonance imaging (MRI). Combined multichannel MEG/EEG recording permitted dipole localization of interictal and ictal activity.