Clinical features of late-onset partial cryptogenic epilepsy: toward an idiopathic temporal epilepsy?

Adult-onset epilepsy is commonly thought to be secondary to a brain lesion. However, the etiology of adult-onset epilepsy remains unknown in approximately 25% of patients, despite progress in medical and diagnostic tools. In the present study, we investigated whether late-onset partial cryptogenic epilepsies could be subgrouped based on seizure semiology and clinical characteristics. A total of 41 patients with late-onset cryptogenic epilepsy were included, and the corresponding clinical and electrophysiological data were analyzed. The following three clinical subgroups were identified: 1) a group that fulfilled the diagnostic criteria of transient epileptic amnesia (TEA); 2) a group with late-onset cryptogenic epilepsies with a temporal seizure semiology; and 3) a cryptogenic extratemporal group, which was consistent with the categorization of cryptogenic epilepsies, i.e., epilepsies involving unknown lesions. The temporal group showed homogeneous clinical characteristics, especially a rapid evolution and a greater tendency toward generalization and pharmacoresistance compared with the other two groups. Transient epileptic amnesia was associated with a higher frequency of sleep disorders than either of the other groups. Our findings argue for the clinical identification of a subgroup of late-onset temporal epilepsy that might constitute an idiopathic form. The association between TEA and sleep disorders would suggest a possible pathophysiological role of sleep apnea syndromes in TEA.

Conversion disorder and coexisting nonepileptic seizures in patients with refractory seizures.

Nonepileptic seizures (NES) are commonly observed in patients with seizures resistant to antiepileptic drugs (AEDs). However, NES may be symptomatic of different diagnoses, in particular, conversion disorder (CD) and coexisting NES and epileptic seizures (CENES). We compared the clinical characteristics of these disorders in 219 patients with refractory seizures. The prevalence of NES was similar in children (11%) and adults (16%). In both groups, CENES represented the most frequent cause of NES (75%). In adults, CD was associated with a shorter duration of illness and normal neuroimaging and interictal EEG compared with the other groups. Patients with CD represented one-quarter of all patients with AED-resistant seizures with normal presentation during interictal investigations. In both children and adults with AED-resistant seizures, NES are frequently observed and are three times more likely to be CENES than CD.

Distinct striatal targets in treating obsessive-compulsive disorder and major depression.

The ventral striatum, including the head of the caudate nucleus and the nucleus accumbens, is a putative target for deep brain stimulation (DBS) in the treatment of obsessive-compulsive disorder (OCD) and major depression (MD). However, the respective roles of these structures in the pathophysiology of OCD and MD remain to be clarified. To address this issue, DBS of the ventral striatum was tested in 2 patients with severely distressing and intractable forms of OCD and MD. Comparisons of clinical outcomes and anatomical data on electrode positioning showed that caudate nucleus stimulation preferentially alleviated OCD manifestations, whereas nucleus accumbens stimulation improved depressive symptoms. These findings suggest that the caudate nucleus and nucleus accumbens participate differently in the pathogenesis of both of these psychiatric conditions.

Neuronal correlates of obsessions in the caudate nucleus.

BACKGROUND: Metabolic overactivity of corticosubcortical loops including the caudate nucleus (CN) has been reported in obsessive-compulsive disorder (OCD) using functional imaging techniques. However, direct proof of a modification of neuronal activity within the CN of OCD patients is still lacking. We tested the hypothesis that obsessions or compulsions might be associated with particular features of neuronal activity in the CN of OCD patients. METHODS: Single unit recordings were performed peroperatively in the CN of three patients with severe forms of obsessive-compulsive disorder (OCD) who were candidates for deep brain stimulation of the CN. Severity of obsessions was assessed preoperatively with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and peroperatively with a subjective obsession score based on a visual analog scale (VAS). RESULTS: Frequency of CN discharge and variability of interspike intervals were found to be abnormally high in two patients with a high VAS score during surgery but not in one with a low VAS score. Lateralization and depth of recording influenced neuronal activity variably among patients. CONCLUSIONS: Because the three patients had high Y-BOCS scores before surgery, these findings suggest that caudate hyperactivity in OCD is concomitant with the occurrence of the obsession process.

Refractory occipital lobe epilepsy treated by surgery in a child with chronic encephalitis.

An 11-year-old boy developed catastrophic occipital lobe epilepsy with progressive neurocognitive decline which led to surgical treatment. Pathological examination of the resected epileptic area showed chronic inflammatory changes. Surgery was followed by a subacute and regressive encephalopathy although the patient did not suffer further seizures. We suggest that this occipital lobe epilepsy was related to chronic nonprogressive encephalitis consistent with a variant of Rasmussen's syndrome, and that the immune and/or inflammatory process was reactivated by surgery. This case indicates that there is no direct link between the epileptic and the encephalitic processes.

Statistical determination of the optimal subthalamic nucleus stimulation site in patients with Parkinson disease.

OBJECT: The subthalamic nucleus (STN) is currently recognized as the preferred target for deep brain stimulation (DBS) in patients with Parkinson disease (PD). If there is agreement in the literature that DBS improves motor symptoms significantly, the situation is less clear with respect to the side effects of this procedure. The goal of this study was to correlate the coordinate values of active electrode contacts with the amplitude of residual clinical symptoms and side effects using a mathematical approach. METHODS: In this study the investigators examined a cohort of 41 patients with PD who received clinical benefits from DBS after stimulating electrodes had been implanted bilaterally into the STN. The combined scores of residual clinical symptoms plus side effects, including speech disturbance, postural instability, and weight gain, were fitted by using either inverted ellipsoidal exponefitials or smooth splines. These analyses showed evidence of lower combined scores for stimulating contacts at an x coordinate approximately 12.0 to 12.3 mm lateral to the anterior commissure-posterior commissure (AC-PC) line and at a z coordinate approximately 3.1 to 3.3 mm under the AC-PC line. There was insufficient evidence for a preferred y coordinate location. CONCLUSIONS: The authors propose a "best" therapeutic ellipse area that is centered at an x, z location of 12.5 mm, -3.3 mm and characterized by an extension of 1.85 mm in the x direction and 2.22 mm in the z direction. Therapeutic electrode contacts located within this area are well correlated with the lowest occurrence of residual symptoms and the lowest occurrence of side effects independent of STN anatomical considerations. The lack of a significant result in the y direction remains to be explored further.

Verbal memory compensation: application to left and right temporal lobe epileptic patients.

This study investigates the compensatory impact of cognitive aids on left and right temporal lobe epileptic patients suffering from verbal memory disorders, who were candidates for surgery. Cognitive aids are defined in the levels-of-processing framework and deal with the depth of encoding, the elaboration of information, and the use of retrieval cues. Results indicate differential compensatory impact for left and right epileptic patients and are discussed according to the HERA model and the compensation framework.

Transient hyperthermia protects against subsequent seizures and epilepsy-induced cell damage in the rat.

Many mild preconditioning stress conditions, including physical and metabolic injuries, increase the resistance of neurons to subsequent more severe stresses of the same or different type. This "tolerance phenomenon" lasts one to several weeks, providing a unique opportunity to investigate endogenous neuroprotective mechanisms. The aim of this study was to find a physiological and easily applicable preconditioning stimulus able to confer protection against convulsant-induced neuronal damage and seizures. We found that moderate transient hyperthermic preconditioning markedly reduced kainic-acid-induced neuronal cell loss and attenuated susceptibility to bicuculline-induced seizures. Prevention of cell damage (approximately 50%) was efficient both in vitro in organotypic hippocampal slice cultures and in vivo in adult rats. This protection lasted about 1 week and peaked 3 to 5 days after pretreatment. Unraveling the mechanisms of heat shock preconditioning-induced protection against epilepsy should lead to the development of new therapeutic strategies.

Updated overview of the putative role of the serotoninergic system in obsessive-compulsive disorder.

The pathophysiology of obsessive-compulsive disorder (OCD) remains unknown. However, increasing attention has been paid to the putative role of the serotoninergic system, the strongest evidence being based on the widely demonstrated efficacy of serotonin (5HT) reuptake inhibitor antidepressants in the treatment of OCD. The therapeutic effects are correlated with changes in peripheral parameters of 5HT function, which have been found to be altered in OCD, suggesting the possibility of reduced 5HT reuptake capacity. This could reflect a compensatory mechanism presumably due to decreased availability of extracellular 5HT, as evidenced by data derived from direct assessment of central 5HT neurotransmission. The development of new neurochemical probes that explore the sensitivity of various 5HT receptor subtypes has provided precious information. m-Chlorophenylpyperazine (m-CPP), an agonist to 5HT1A, 5HT1D, and 5HT2C receptors, and which also blocks 5HT3 receptors, exacerbates OC symptoms. In contrast, neither MK-212 (6-chloro-2-[1-piperazinyl]-pyrazine), a 5HT1A and 5HT2C receptor agonist, nor ipsapirone or buspirone, which acts as an agonist to 5HT1A receptors, have any effect on OC symptom severity. This suggests the potential implication of the 5HT1D receptor, as shown by the aggravation of OC manifestations in response to sumatriptan, a selective 5HT1D receptor agonist. The 5HT3 plays no specific role, given the lack of influence of the 5HT3 antagonist ondansetron, on OC symptom intensity. Further studies are required to elucidate the pharmacological molecular determinants of the putative 5HT1D receptor dysfunction.

Deep brain stimulation of the ventral caudate nucleus in the treatment of obsessive-compulsive disorder and major depression. Case report.

Obsessive-compulsive disorder (OCD) is an anxiety disorder associated with recurrent intrusive thoughts and repetitive behaviors. Although conventional pharmacological and/or psychological treatments are well established and effective in treating OCD, symptoms remain unchanged in up to 30% of patients. Deep brain stimulation (DBS) of the anterior limb of the internal capsule has recently been proposed as a possible therapeutic alternative in treatment-resistant OCD. In the present study, the authors tested the hypothesis that DBS of the ventral caudate nucleus might be effective in a patient with intractable severe OCD and concomitant major depression. Psychiatric assessment included the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the Hamilton Depression Rating Scale (HDRS), the Hamilton Anxiety Rating Scale (HARS), and the Global Assessment of Functioning (GAF) Scale for determining the symptom severity of OCD, depression, and anxiety as well as the quality of pychosocial and occupational functioning, respectively. Neuropsychological assessment consisted of a wide range of tests primarily exploring memory and executive functions. Deep brain stimulation of the ventral caudate nucleus markedly improved symptoms of depression and anxiety until their remission, which was achieved at 6 months after the start of stimulation (HDRS < or = 7 and HARS < or = 10). Remission of OCD (Y-BOCS < 16) was also delayed after 12 or 15 months of DBS. The level of functioning pursuant to the GAF scale progressively increased during the 15-month follow-up period. No neuropsychological deterioration was observed, indicating that DBS of the ventral caudate nucleus could be a promising strategy in the treatment of refractory cases of both OCD and major depression.

Pathophysiology of obsessive-compulsive disorder: a necessary link between phenomenology, neuropsychology, imagery and physiology.

Obsessive-compulsive disorder (OCD) is characterized by repetitive intrusive thoughts and compulsive time-consuming behaviors classified into three to five distinct symptom dimensions including: (1) aggressive/somatic obsessions with checking compulsions; (2) contamination concerns with washing compulsions; (3) symmetry obsessions with counting/ordering compulsions; (4) hoarding obsessions with collecting compulsions; and (5) sexual/religious concerns. Phenomenologically, OCD could be thought of as the irruption of internal signals centered on the erroneous perception that "something is wrong" in a specific situation. This generates severe anxiety, leading to recurrent behaviors aimed at reducing the emotional tension. In this paper, we examine how the abnormalities in brain activity reported in OCD can be interpreted in the light of physiology after consideration of various approaches (phenomenology, neuropsychology, neuroimmunology and neuroimagery) that contribute to proposing the central role of several cortical and subcortical regions, especially the orbitofrontal cortex (OFC), the anterior cingulate cortex (ACC), the dorsolateral prefrontal cortex (DLPC), the head of the caudate nucleus and the thalamus. The OFC is involved in the significance attributed to the consequences of action, thereby subserving decision-making, whereas the ACC is particularly activated in situations in which there are conflicting options and a high likelihood of making an error. The DLPC plays a critical part in the cognitive processing of relevant information. This cortical information is then integrated by the caudate nucleus, which controls behavioral programs. A dysfunction of these networks at one or several stages will result in the emergence and maintenance of repetitive thoughts and characteristic OCD behavior.

Levels of processing with free and cued recall and unilateral temporal lobe epilepsy.

This study investigates the role of the temporal lobes in levels-of-processing tasks (phonetic and semantic encoding) according to the nature of recall tasks (free and cued recall). These tasks were administered to 48 patients with unilateral temporal epilepsy (right "RTLE"=24; left "LTLE"=24) and a normal group (n=24). The results indicated that LTLE patients were impaired for semantic processing (free and cued recall) and for phonetic processing (free and cued recall), while for RTLE patients deficits appeared in free recall with semantic processing. It is suggested that the left temporal lobe is involved in all aspects of verbal memory, and that the right temporal lobe is specialized in semantic processing. Moreover, our data seem to indicate that RTLE patients present a retrieval processing impairment (semantic condition), whereas the LTLE group is characterized by encoding difficulties in the phonetic and semantic condition.

[Two cases of neurocysticercosis mimicking brain tumor]. / Deux cas de neurocysticercose intracérébrale à révélation pseudo-tumorale.

Neurocysticercosis is an infectious disorder of the central nervous system caused by Taenia solium larvae. We report two misleading cases, mimicking high grade glioma on radiology. Two patients, aged 14 and 29 respectively, developed seizure, associated with left facial paralysis in the second. For each case, radiological data revealed a solitary lesion highly suggestive of high grade glioma. Microscopically, within an important inflammatory process, a characteristic cystic formation allowed a definite diagnosis of cysticercosis. Then, for both patients, a history of migration from endemic area was demonstrated later. These cases highlight the necessary pathological examination when neurocysticercosis mimics a brain tumor.

Complications and adverse effects of deep brain stimulation in Parkinson's patients.

Deep brain stimulation of subcortical structures, such as the subthalamic nucleus, internal pallidum or ventral intermediate nucleus of the thalamus, are currently used for the treatment of advanced Parkinson's disease with motor fluctuations or during resistant tremor. This review discusses the various adverse events occurring with this surgery by focusing on each stage of the procedure and the various stimulated targets. Intraoperative complications are rare whichever technique or type of target is used. The most frequent postoperative side effects are observed during stimulation of the subthalamic nucleus. It is likely that the small size of the nucleus and the possible spreading of current to the surrounding functional areas contribute to this phenomenon. However, these side effects are generally mild and transient compared with the dramatic improvement in motor symptoms and fluctuations. Deep brain stimulation of the internal pallidum and thalamus are not effective on all the motor symptoms in Parkinson's disease but adverse effects appear less frequently. Whatever the target, intraoperative complications and secondary side effects are being reduced by the use of new neuroimaging technology associated with an accurate intraoperative neurophysiological investigation.

Delayed kindling epileptogenesis and increased neurogenesis in adult rats housed in an enriched environment.

Environmental risk factors such as stressful experiences have long been recognized to affect seizure susceptibility, but little attention has been paid to the potential effects of improving housing conditions. In this study, we investigated the influence of an enriched environment on epileptogenesis. Epileptic susceptibility was assessed in animals housed in an enriched environment either before and during (group I) or only during (group II) a kindling procedure and in animals placed in isolated conditions (group III). The kindling paradigm provides a reliable assessment of the capacity to develop seizures following repeated daily low-frequency electrical stimulations. As both enriched environment and seizures are known to interfere with hippocampal neurogenesis, the number of newly generated dentate cells was assessed before and after the kindling procedure to investigate in more detail the relationship between epileptogenesis and neurogenesis. We found that susceptibility to developing epilepsy differed in animals housed in complex enriched environments and in those housed in isolated conditions. Kindling epileptogenesis occurred significantly later in animals housed in enriched conditions throughout the procedure (group I) than in animals from groups II and III. We also demonstrated that cells generated during kindling survived for at least 42 days and that these cells were more numerous on both sides of the brain following environmental enrichment than in rats housed in isolated conditions. As similar values were obtained regardless of the duration of the period of enrichment, these cellular changes may not play a major role in delaying kindling development. We suggest that the increase response in neurogenesis following seizures may be an adaptative rather an epileptogenic response.

Inflammatory reactions in human medial temporal lobe epilepsy with hippocampal sclerosis.

Many experimental studies suggest that NFkappaB, a transcription factor involved in acute inflammation, and cytokines participate in neuronal excitability and/or glial scar formation in epilepsy. In this report, we looked for the expression of NFkappaB in hippocampi surgically removed in patients with medial temporal lobe epilepsy (MTLE) and hippocampal sclerosis (HS) who had an history of febrile convulsions. We analyzed 18 hippocampi from epileptic patients with MTLE and HS, and we used as control specimens three hippocampi from non-epileptic patients and four hippocampi from patients with cryptogenic MTLE without HS. We used antibodies raised against the NFkappaB-p65 subunit and we identified glial cells with specific antibodies. Hippocampi from patients with MTLE and HS displayed severe neuronal loss surrounded by gliosis in CA1 area and more or less in CA3/CA4 areas. Double immunolabeling showed that reactive astrocytes of lesioned areas over-expressed NFkappaB-p65 (significantly when compared to control specimens). Moreover, some surviving pyramidal neurons in these areas and numerous dentate granule cells were strongly positive for NFkappaB-p65 in cytoplasm and nucleus, whereas control hippocampi showed a faint basal cytoplasmic staining in neurons. These results suggest that in epileptic hippocampi with typical sclerosis, inflammatory processes are chronically active or transiently re-induced by recurrent seizures. Whether NFkappaB over-expression reflects protective or deleterious mechanisms in the epileptic focus remains to be elucidated.

Lack of agreement between direct magnetic resonance imaging and statistical determination of a subthalamic target: the role of electrophysiological guidance.

OBJECT: The goal of this study was to determine the most suitable procedure(s) to localize the optimal site for high-frequency stimulation of the subthalamic nucleus (STN) for the treatment of advanced Parkinson disease. METHODS: Stereotactic coordinates of the STN were determined in 14 patients by using three different methods: direct identification of the STN on coronal and axial T2-weighted magnetic resonance (MR) images and indirect targeting in which the STN coordinates are referred to the anterior commissure-posterior commissure (AC-PC) line, which, itself, is determined either by using stereotactic ventriculography or reconstruction from three-dimensional (3D) MR images. During the surgical procedure, electrode implantation was guided by single-unit microrecordings on multiple parallel trajectories and by clinical assessment of stimulations. The site where the optimal functional response was obtained was considered to be the best target. Computerized tomography scanning was performed 3 days later and the scans were combined with preoperative 3D MR images to transfer the position of the best target to the same system of stereotactic coordinates. An algorithm was designed to convert individual stereotactic coordinates into an all-purpose PC-referenced system for comparing the respective accuracy of each method of targeting, according to the position of the best target. CONCLUSIONS: The target that is directly identified by MR imaging is more remote (mainly in the lateral axis) from the site of the optimal functional response than targets obtained using other procedures, and the variability of this method in the lateral and superoinferior axes is greater. In contrast, the target defined by 3D MR imaging is closest to the target of optimal functional response and the variability of this method is the least great. Thus, 3D reconstruction adjusted to the AC-PC line is the most accurate technique for STN targeting, whereas direct visualization of the STN on MR images is the least effective. Electrophysiological guidance makes it possible to correct the inherent inaccuracy of the imaging and surgical techniques and is not designed to modify the initial targeting.

Effect of age of onset of temporal lobe epilepsy on the severity and the nature of preoperative memory deficits.

The nature and severity of pre-operative memory deficits observed in unilateral temporal lobe epilepsy depend upon a number of variables. Among these variables, age of seizure onset seems to be important. The age at which the lesion is sustained could modify the normal functional organization of the brain. Many studies have examined the effect of age of onset on the severity of memory deficits but have seldom focused on the nature of such deficits (verbal/nonverbal) as a function of epileptic focus laterality. This study investigates the effect of age of onset on the nature and severity of memory impairments. Fifty-six epileptics with unilateral temporal lobe epilepsy and 20 normal subjects were administered a neuropsychological evaluation. Four groups of patients were constituted: left or right temporal lobe epilepsy with early (0-5 years) or late (10 years and over) age of seizure onset. The early group showed major verbal and nonverbal memory deficits. The late group presented minor specific deficits: essentially verbal deficits with left temporal lobe seizures and nonverbal deficits with right temporal lobe seizures. These results may be interpreted in the framework of ontogenesis theories of hemispheric specialization.