[Interictal psychosis of epilepsy]. / Les psychoses épileptiques interictales.

Interictal psychosis (IIP) refers to psychosis that occurs in clear consciousness in persons with epilepsy (PWE) with temporal onset not during or immediately following a seizure. The pooled prevalence estimate of psychosis in PWE is 5.6%. PWE and schizophrenia have very high mortality, and more than one in four persons with both disorders die between the age of 25 and 50years. IIP can manifest in brief or chronic forms. The chronic forms of IIP may closely resemble schizophrenia. However, some authors have described the typical presence of persecutory and religious delusions, sudden mood swings and the preservation of affect, as well as rarity of negative symptoms and catatonic states, but these differences remain controversial. Typically, IIP starts after many years of active temporal lobe epilepsy. Several epilepsy-related variables are considered pathogenically relevant in IIP including epilepsy type and seizure characteristics. Risk factors for developing IIP are family history of psychosis, learning disability, early age of onset of epilepsy, unilateral or bilateral hippocampal sclerosis, history of status epilepticus, history of febrile seizures, and poorly controlled temporal lobe epilepsy. In patients with epilepsy and psychosis, structural imaging studies have shown several relevant changes leading to conflicting findings. Altered neuronal plasticity and excitability have been described in epilepsy and psychotic disorders. Neuropathological data suggest that IIP are not the result of classic epileptic pathology of the temporal lobe. Forced normalization (FN) and alternating psychosis refer to patients with poorly controlled epilepsy (focal or generalized) who have had psychotic episodes associated with remission of their seizures and disappearance of epileptiform activity on their EEGs. FN mainly occurs in temporal lobe epilepsy when patients have frequent seizures that are abruptly terminated triggered by an antiepileptic drug, vagus nerve stimulation or epilepsy surgery. Treatment is based on withdrawal of the responsible drug, and by transient use of antipsychotics for acute symptomatic control on a case-by-case basis. FN is an entity whose pathophysiology remains uncertain. Antiepileptic drugs (AEDs) may sometimes induce psychotic symptoms and psychosis could be a direct effect of the AEDs. IIP has been reported more frequently following the initiation of zonisamide, topiramate, and levetiracetam when compared with other antiepileptic drugs. However, AEDs do not appear to be the only determinant of IIP. The management of IIP requires a multidisciplinary approach with early involvement of a liaison psychiatrist associated with a neurologist. IIP are underdiagnosed and mistreated. Existing recommendations are extrapolated from those established for the treatment of schizophrenia with some additional guidance from expert opinions. A two-step procedure, not necessarily consecutive, is suggested. The first step requires reevaluation of the antiepileptic treatment. The second step requires initiation of atypical neuroleptics. Antipsychotic drugs should be selected with consideration of the balance between pharmacological profiles, efficacy, and adverse effects. Regarding pharmacokinetic interactions, AEDs with inducing properties reduce the blood levels of all antipsychotics. It is important to consider implications of combining neuroleptics and AEDs with a similar spectrum of side effects. Regarding the duration of treatment, IIP episodes are more likely to be recurrent than in primary schizophrenia. In practice, atypical neuroleptics with few motor side effects such as risperidone can be used as first choice, given the low propensity for drug-drug interactions and the low seizure risk, with the added suggestion to start low and go slow. Clozapine could be prescribed in selected cases.

[Postictal psychoses: Clinical and neurobiological findings]. / Clinique et neurobiologie des psychoses post-ictales.

Psychosis in epilepsy can be categorized in relation to seizures in two main categories: interictal psychosis and postictal psychosis. Postictal psychosis (PIP) is a specific syndrome in relation to seizure activity: a clear temporal relation exists between the psychotic state of sudden onset and a precipitating bout of complex partial or generalized seizures. However, this very specific syndrome is not included as such within the DSM-5, and PIP belongs to the category "Psychotic disorder due to another medical condition". Diagnostic criteria are: (1) episode of psychosis within 1 week after a seizure(s); (2) psychosis lasts more than 15hours and less than 2 months; (3) delusions, hallucinations in clear consciousness, bizarre, or disorganized behavior, formal thought disorder, or affective changes; and (4) no evidence AED toxicity, non-convulsive status epilepticus, recent head trauma, alcohol, or drug intoxication or withdrawal, prior chronic psychotic disorder. The presence of a lucid interval between the last seizure and start of changes rules out a simple postictal delirium. The outcome is characterized by a remission of the psychotic symptoms over several days (mean: 1 week), with or without any treatment. Prepsychotic EEG abnormalities persist during the psychosis. Risk factors for PIP include: long standing localization-related epilepsy, extratemporal onset, bilateral epileptiform activity, secondary generalization, slowing of the EEG background activity and personal or family history of psychiatric disorders. Brain MRI frequently shows structural abnormalities. Several functional neuroimaging studies have shown hyperperfusion in various cerebral regions during PIP, suggesting an excessive activation of particular structures of the brain rather than a postictal depression of cerebral activity. Implanted electrode studies have shown that the EEG correlate of psychotic symptoms differs from the ictal EEG correlate of epileptic seizures. The value of antipsychotic treatment in PIP requires further studies. Despite their role in symptomatic relief, there is no clear effect of neuroleptics on duration or prognosis of PIP. Different combinations of pharmaceutical interventions can be tried on a case by case basis: (1) oral administration of benzodiazepine; (2) combined oral administration of benzodiazepine and atypical neuroleptics; (3) intramuscular administration of dopamine-blockers for rapid tranquilization of violent or agitated patients. The notion that neuroleptic drugs lower the seizure threshold has no clinical significance: there is no evidence that antipsychotic drugs increase seizure frequency in epileptic patients treated with antiepileptic drugs.

International trade drives biodiversity threats in developing nations.

Human activities are causing Earth's sixth major extinction event-an accelerating decline of the world's stocks of biological diversity at rates 100 to 1,000 times pre-human levels. Historically, low-impact intrusion into species habitats arose from local demands for food, fuel and living space. However, in today's increasingly globalized economy, international trade chains accelerate habitat degradation far removed from the place of consumption. Although adverse effects of economic prosperity and economic inequality have been confirmed, the importance of international trade as a driver of threats to species is poorly understood. Here we show that a significant number of species are threatened as a result of international trade along complex routes, and that, in particular, consumers in developed countries cause threats to species through their demand of commodities that are ultimately produced in developing countries. We linked 25,000 Animalia species threat records from the International Union for Conservation of Nature Red List to more than 15,000 commodities produced in 187 countries and evaluated more than 5 billion supply chains in terms of their biodiversity impacts. Excluding invasive species, we found that 30% of global species threats are due to international trade. In many developed countries, the consumption of imported coffee, tea, sugar, textiles, fish and other manufactured items causes a biodiversity footprint that is larger abroad than at home. Our results emphasize the importance of examining biodiversity loss as a global systemic phenomenon, instead of looking at the degrading or polluting producers in isolation. We anticipate that our findings will facilitate better regulation, sustainable supply-chain certification and consumer product labelling.

Characteristics of postictal headache in patients with partial epilepsy.

Migraine-like features sometimes characterize the headache that follows epileptic seizure (postictal headache, PIH). We compared patients with different types of epilepsy to investigate the association between migraine-like PIH and seizure type. Subjects comprised 364 patients with partial epilepsy. Epilepsy types were temporal lobe epilepsy (TLE, n = 177), frontal lobe epilepsy (FLE, n = 116), and occipital lobe epilepsy (OLE, n = 71). Patients participated in a structured interview pertaining to PIH as well as interictal headache and family history of migraine. Headaches were classified according to the International Headache Society criteria, which was modified for this study. Forty percent had PIH and 26% of these patients had migraine-like PIH. Migraine-like PIH occurred significantly more often in cases of TLE and OLE than in cases of FLE. In addition, the incidence of interictal migraine headache was significantly higher in patients with migraine-like PIH. These results suggest that migraine-like PIH is related to particular regions of epileptogenic focus and that susceptibility to migraine headache predisposes to migraine-like PIH.

Glomerular crescents predominantly express cadherin-catenin complex in pauci-immune-type crescentic glomerulonephritis.

AIMS: To investigate the expression of the cadherin complex in human crescentic glomerulonephritis to elucidate the role of intercellular adherens junction molecules in crescent formation. METHODS AND RESULTS: Immunostaining revealed cadherin complexes localized in Bowman's epithelial cells, but not in podocytes, of normal human glomeruli. Eight adult cases with myeloperoxidase anti-neutrophil cytoplasmic autoantibodies (MPO-ANCA)-related (pauci-immune type) crescentic glomerulonephritis were examined on immunofluorescence microscopy with anti-pan cadherin, p120 catenin, and beta-catenin antibodies. The specimens provided six cellular crescents, 12 fibrocellular crescents, and four fibrotic crescents. Immunofluorescence was semiquantitatively estimated by the rate of the field of localization within the whole area of the crescent, according to the four-grade system [(-) - (++)]. All the tested molecules consisting of the cadherin complex were abundantly observed in cytokeratin-positive epithelial components in crescents, each with an equivalent area of localization. The expression of the cadherin complex was closely associated with that of cytokeratin and both diminished as the crescents developed from cellular to fibrotic. CONCLUSIONS: The cadherin-catenin complex is a specific marker of Bowman's epithelial cells in human glomeruli. The cellular crescents in pauci-immune-type crescentic glomerulonephritis possess adherens junction molecules, indicating a principle parietal epithelial cell phenotype.

Differential effects of milnacipran and fluvoxamine, especially in patients with severe depression and agitated depression: a case-control study.

We attempted to compare the antidepressant efficacy of milnacipran and fluvoxamine in 202 outpatients with major depression, using the 17-item Hamilton Depression Rating Scale (HDRS). Special attention was paid to the difference of responsiveness as a function of the severity of depression and individual HDRS factors. As a result, while no significant difference between the treatment groups was found overall, a positive response (50% or more decrease in total score from the baseline) was recorded significantly more often with milnacipran than fluvoxamine recipients whose baseline HDRS total score was greater than 19 points. Furthermore, there was a significant difference of response for the 'agitation' and 'insomnia' factors in favour of milnacipran. In both treatment groups, the incidence of adverse events, characteristic of tricyclic antidepressants such as dry mouth, constipation, somnolence and postural hypotension, was low. While complaints concerning the upper intestinal tract, such as epigastric distress, were predominant in the fluvoxamine group, urological complications and palpitations were reported only in the milnacipran group. In conclusion, we suggest that milnacipran is preferred to selective serotonin reuptake inhibitors for the treatment of depressed patients with agitation as well as severely depressed patients.

Acute pancreatic damage associated with convulsive status epilepticus: a report of three cases.

Three cases involving a previously unreported association of acute pancreatic damage following convulsive status epilepticus (SE) are presented. A review of literature failed to reveal a similar association between SE and acute pancreatic damage. As possible pathophysiological mechanisms of this so far unknown sequel of SE, increased intraduodenal pressure during SE leading to the reflux of the duodenal contents into the pancreatic duct, along with altered metabolism of oxygen-derived free radicals during a prolonged seizure with hypoxia and ischemia resulting in acinar cell injury are suggested. We believe that SE should be considered as an additional risk factor of acute pancreatitis and that pancreatic enzymes should be monitored in patients who have prolonged seizures.

Long-term follow-up study of Lennox-Gastaut syndrome in patients with severe motor and intellectual disabilities: with special reference to the problem of dysphagia.

A long-term follow-up study of Lennox-Gastaut syndrome (LGS) ( > 10 years) was conducted with 38 patients with severe motor and intellectual disabilities (SMID) to clarify the relationship between the rapid development of dysphagia and epileptic seizures, and to elucidate the long-term evolution of LGS in patients with SMID. Those who showed a relatively favourable seizure outcome were compared to those with a poor seizure outcome. Poor seizure outcome correlated strongly with: (a) an early appearance of dysphagia and additional deterioration of the already retarded mental function; (b) a predominance of atypical absence seizures; and (c) persistent frequent epileptiform discharges during electroencephalographic evaluations. Neither age at seizure onset nor intelligence level at the time of the last examination was correlated with seizure prognosis. Further, seizure prognosis was not related to the aetiology of LGS. Repeated seizures apparently caused development of progressive epileptic encephalopathy, in addition to the underlying severe brain damage. Since development of dysphagia burdens an already severely handicapped patient with intensive medical care, efforts to reduce the seizures and design a long-term care plan are of great importance.

Presurgical postictal and acute interictal psychoses are differentially associated with postoperative mood and psychotic disorders.

The authors studied 52 patients who had undergone surgery because of intractable temporal lobe epilepsy. Investigation of postoperative psychiatric illnesses focused on psychotic disorder (293.81 and 293.82) and mood disorder (293.83) due to a general medical condition diagnosed according to DSM-IV criteria. Presurgically, two episodic psychotic syndromes, acute interictal and postictal psychosis, were defined operationally. A correlation was confirmed between presurgical acute interictal psychosis and postsurgical psychotic disorder, as well as between presurgical postictal psychosis and postsurgical mood disorder. An excellent final outcome for postoperative mood disorder in contrast to a less favorable one for psychotic disorder was also suggested.

C-reactive protein frequently localizes in the kidney in glomerular diseases.

AIM: In recent reports, C-reactive protein (CRP) has emerged as a component that may play important roles in atherogenesis. Based on the analogies set out in a previous report between focal-segmental sclerosis and atherosclerosis, we hypothesized that CRP contributes to the pathogenesis of glomerular diseases. To our knowledge, no immunohistochemical study of CRP localization in the kidneys has been previously reported. PATIENTS AND METHODS: In the present study, we investigated 106 kidney biopsy specimens from children with various types of glomerular diseases and minor glomerular abnormalities. Of the 106 cases, 74 were proliferative diseases, 17 were non-proliferative diseases, and 15 were minimal-change nephrotic syndrome (MCNS). Immunohistochemical staining was performed using monoclonal antibody to CRP. RESULTS: CRP immunoreactivity was found in 48 of 106 (45.3%) specimens. CRP deposition was encountered more often in patients with proliferative diseases (56.8%) than in those with non-proliferative diseases (23.5%) (p < 0.01). CRP deposition, most frequently observed along the capillary walls of glomeruli, was found in 33 of 46 (71.7%) cases with positive expression of CRP. CRP was also located in the peritubular capillary walls and small vessels in the interstitium in 13 of 46 cases (28.3%). CRP deposition was also found in 2 of 15 cases of MCNS. The two MCNS specimens showing positive CRP immunoreactivity were both from patients who had undergone cyclosporin therapy. CRP deposition was not shown in any cases treated with steroids or cyclophosphamide. The cases of patients who had undergone renal biopsies within 6 months after onset revealed a tendency toward positive CRP deposition. The clinical outcomes at the latest follow-up were quite similar between the groups of patients with and without CRP deposition. CONCLUSIONS: We surmise that circulating CRP may deposit at the site of endothelial injury, and may not be relevant to the progression of renal lesions.

Rub epilepsy: a somatosensory evoked reflex epilepsy induced by prolonged cutaneous stimulation.

To delineate rub epilepsy--a type of reflex epilepsy induced by prolonged or repetitive cutaneous stimulation in a circumscribed area of the body--three cases are presented, as well as one of tooth brushing epilepsy for comparison. In all three cases of rub epilepsy, cutaneous stimuli in a particular body area on the left side initially induced a sensory jacksonian march in the middle of, or in close vicinity to, the trigger zone, which led to subsequent unilateral tonic contractions with intact consciousness. By contrast, a motor jacksonian seizure without sensory aura was induced in the patient with tooth brushing epilepsy. A review of cases with rub epilepsy, including those in this paper, disclosed a striking consistency in clinical manifestations. The symptomatology of the induced seizures indicates a propagation of epileptic discharges from the postcentral gyrus to the supplementary motor area. Rub epilepsy is proposed as a separate clinical entity, clearly demarcated from other somatosensory evoked reflex epilepsies such as startle and tooth brushing epilepsy.

Reexamination of interictal psychoses based on DSM IV psychosis classification and international epilepsy classification.

We sought to examine interictal psychoses based on the international epilepsy classification and DSM IV criteria, with special attention paid to epilepsy types as well as to subcategories of psychoses. One hundred thirty-two outpatients were studied, each with definite evidence of both epilepsy and interictal psychosis clearly demarcated from postictal psychosis. We compared them with 2,773 other epilepsy outpatients as a control. Risk factors for psychosis were examined within the temporal lobe epilepsy (TLE) group and the more extended group of symptomatic localization-related epilepsy. Further, nuclear schizophrenia and other nonschizophrenic psychotic disorders were compared. We confirmed a close correlation between TLE and interictal psychoses. Within the TLE group, only early epilepsy onset and a history of prolonged febrile convulsions were revealed to be significantly associated with interictal psychosis. Within the symptomatic localization-related epilepsy group, such parameters as complex partial seizures, autonomic aura, and temporal EEG foci were closely associated with psychoses. There was also a significant difference between groups as to ictal fear and secondary generalization. Whereas patients with early psychosis onset and a low intelligence quotient were overrepresented in the nuclear schizophrenia group, drug-induced psychosis and alternative psychosis were underrepresented. TLE proved to be preferentially associated with interictal psychoses. Within the TLE group, medial TLE in particular was found to be more closely associated with psychosis. Our data support the original postulation of Landolt, stating that alternative or drug-induced psychoses constitute a definite subgroup of interictal psychoses, which are different from chronic epileptic psychoses that simulate schizophrenia.

Late recurrence of small-cell lung cancer: a case report.

A 67-year-old man was admitted with small-cell lung cancer (SCLC). The patient was given four courses of platinum-containing chemotherapy followed by chest irradiation, and good partial response (PR) was obtained. The patient did well for 4 years, until he sought treatment for a painful subcutaneous tumor. Chest computed tomography scan revealed the mass extending from the tumor in lung parenchyma with osteolytic lesion of the third rib bone. Pathologic examination of the subcutaneous lesion revealed SCLC. The patient was given two courses of the same combination chemotherapy administered as initial therapy. Regression of the mass was observed, and the response was evaluated as a good PR. How to approach late recurrence of SCLC is discussed.

Familial aphasic episodes: another variant of partial epilepsy with simple inheritance?

We report on a family having partial epilepsy with simple inheritance. The affected members commonly have aphasic episodes with secondary generalization; onset occurred either in adolescence or adulthood. Patients' response to medication has varied greatly. No neurological defects or decline in intelligence were found. The case represents another variety of rare familial partial epilepsy with neocortical epilepsy features.

A case of post-anoxic encephalopathy with initial massive myoclonic status followed by alternating Jacksonian seizures.

To contrast stimulus-sensitive generalized myoclonus with ensuing multifocal localized myoclonus in a patient with post-anoxic coma, we stressed the clinical as well as electroencephalographical differences between his initial generalized and subsequent focal myoclonus. While generalized myoclonus was presumably of extracortical origin and responsive to valproic acid, alternating Jacksonian seizures were definitely cortical and suppressed with phenytoin. These two different types of myoclonus should not be confused in post-anoxic coma.

Prolonged post-ictal confusion as a manifestation of continuous complex partial status epilepticus: a depth EEG study.

We report a peculiar depth-EEG recording of prolonged post-ictal confusion which proved to be continuous complex partial status epilepticus. A 33 year old male with intractable medial temporal lobe epilepsy exhibited this ictal EEG recording. After repetitive habitual complex partial seizures, and an ensuing short lucid interval with intact memory and full communicability, the patient became more and more unresponsive and, finally, even cataleptic. Concurrent with this change in responsiveness, an EEG revealed a gradual and steady increase of ictal EEG activity. Immediately after intravenous diazepam infusion, this ictal EEG activity was suppressed and the patient began to move. This case confirms that a paradoxical excitation can occur after clustered complex partial seizures, instead of the well-known neuronal exhaustion.

Steroid-sensitive nephrotic syndrome associated with Kimura disease.

We report an 11-year-old Japanese boy with Kimura disease and associated nephrotic syndrome. Before the diagnosis of Kimura disease was established, the patient had three episodes of swelling on the left cheek with subsequent nephrotic syndrome. Steroids were effective for both conditions. However, both conditions recurred within months of discontinuation of steroids. For the fourth episode of swelling on the left cheek, cyclosporine (CsA) was used. The subcutaneous tumor responded to CsA and disappeared within a few days. There has been no subsequent relapse of the nephrotic syndrome to date.

Interleukin (IL)1beta, IL-1alpha, and IL-1 receptor antagonist gene polymorphisms in patients with temporal lobe epilepsy.

Proinflammatory cytokines, including interleukin (IL)-1beta, are known to modulate effects of neurotoxic neurotransmitters discharged during excitation or inflammation in the central nervous system (CNS). They also regulate development of glial scars at sites of CNS injury. To elucidate a genetic predisposition of temporal lobe epilepsy with hippocampal sclerosis (TLE-HS+), we studied polymorphisms in the IL-1beta, IL-1alpha, and IL-1 receptor antagonist (IL-1RA) genes in 50 patients with TLE-HS+ and in 112 controls. Fifty-three patients who had TLE without HS were also examined (TLE-HS-) as disease controls. The distribution of the biallelic polymorphism in the promoter region at position -511 of the IL-1beta gene (IL-1B-511) was significantly different both between TLE-HS+ patients and controls and between TLE-HS+ and TLE-HS- patients. The differences were due to overrepresentation of the homozygotes for IL-1B-511*2, which is suggested to be a high producer of IL-1beta, in TLE-HS+ patients compared with both controls and TLE-HS- patients. In contrast, there was no difference between TLE-HS- patients and controls. Our data suggest that, in the homozygotes for IL-IB-511*2, minor events in development such as febrile convulsions could set up a cascade leading to HS.