Brain

Eyre, J. A. ; Clowry, G. J.

doi: 10.1093/brain/awf197pmid: N/A

Grünewald, Richard

doi: 10.1093/brain/awf195pmid: 12183339

Walker, M. C.; White, H. S. ; Sander, J. W. A. S.

doi: 10.1093/brain/awf203pmid: 12183340

With the growth in antiepileptic drug treatment, the question arises as to what extent we are merely treating the symptom (i.e. the seizures) rather than the underlying disease process (i.e. epileptogenesis). Epilepto genicity can be considered as the process whereby structural and functional changes occur following an insult that in some cases result in epilepsy. Epilepto genicity also describes some of the changes and processes that contribute to the progression observed in some epilepsies. These processes have been modelled in animals mostly by the kindling model of epilepsy, in which repetition of subconvulsive stimuli results in a progressive epileptic state and eventually leads to spontaneous seizures. However, it is not clear that kindling has a human correlate, so models in which an initial insult (status epilepticus, hyperthermia, hypoxia, trauma) is followed by the development of lowered seizure threshold and, in some instances, spontaneous seizures have been used. These models seem to support the ‘second hit’ hypothesis, in which there is an initial insult resulting in lowered seizure threshold, and then a later insult, the ‘second hit’, that results in the expression of epilepsy. These models also support the concept of a latent period during which there could be targeted therapies to prevent the epileptogenic process. Although the occurrence of neuronal damage is one such target, neuronal damage is not necessary for epileptogenesis, and other mechanisms are at play. At the present time, it is not known whether targeted therapies may also affect compensatory processes, such as brain repair. Clearly, this would be a potential risk of such strategies. Epidemiological evidence and trials indicate that our present antiepileptic drugs are not effective in preventing epileptogenesis; antiepileptic drugs were, however, not designed for this purpose. Data from animal experiments suggest that treatment of non‐convulsive status epilepticus following specific insults may prevent epileptogenesis. The relevance of this for the human condition remains uncertain, but non‐convulsive status epilepticus is probably an under‐recognized and probably under‐treated condition. Perhaps one of the most salutary findings has been the observation of decreased childhood epilepsy with improved neonatal care. This highlights the importance of medical care at the time of an insult, and of prevention of the insults. This review discusses the data that support the concepts underlying epileptogenesis and the model systems that are presumed to reflect the human condition. Particular attention is paid to the potential for interrupting the processes underlying epileptogenesis.

Scott, R. C.; Gadian, D. G.; King, M. D.; Chong, W. K.; Cox, T. C.; Neville, B. G. R.; Connelly, A.

doi: 10.1093/brain/awf202pmid: 12183341

The nature of the relationships between status epilepticus, acute hippocampal injury, mesial temporal sclerosis (MTS) and temporal lobe epilepsy remains unclear. The aim of this study was to investigate whether generalized status epilepticus is associated with brain abnormalities, especially in the mesial temporal lobe, within 5 days of the acute event. Such changes may be the first part of a causative pathophysiological sequence relating status epilepticus and MTS. Thirty‐five children with a history of status epilepticus, including 21 with a history of prolonged febrile convulsion (PFC), underwent qualitative and quantitative MRI investigations within 5 days of the acute episode. Quantitative assessments of the hippocampus included T 2 relaxometry and hippocampal volumetry. Hippocampal volumes were large in patients with PFC when compared with controls. In addition, T 2 relaxation time was elevated in patients with PFC compared with control subjects during the first 2 days of the acute event. No difference was observed in patients examined 3–5 days after the event. Patients with afebrile status epilepticus had a variety of imaging abnormalities including elevated hippocampal T 2 values, but no evidence of hippocampal enlargement. PFC is associated with hippocampal abnormalities, consistent with hippocampal oedema, whilst non‐febrile status epilepticus is not. A systematic longitudinal study is required to characterize the evolution of these abnormalities and to determine whether any patient develops MTS.

Haginoya, Kazuhiro; Munakata, Mitsutoshi; Kato, Rie; Yokoyama, Hiroyuki; Ishizuka, Masaharu; Iinuma, Kazuie

doi: 10.1093/brain/awf213pmid: 12183342

Near‐infrared spectrophotometry (NIRS) is a new technique that allows continuous non‐invasive monitoring of tissue oxygenation and haemodynamics in the brain. We used NIRS in various types of paediatric epileptic seizures in order to understand the pathophysiology of epileptic seizures in childhood epilepsy. This study examined 15 children ranging in age from 1.5 months to 16 years (nine males and six females), with different types of epilepsy. Six series of tonic spasms and 67 isolated seizures were recorded. The results demonstrated that several pathophysiological processes exist during epileptic seizures in childhood. (i) Convulsive seizures were associated with a remarkable increase in cerebral blood volume (CBV), while absence seizures were associated with a mild decrease or no change in CBV of the frontal cortex. (ii) An initial transient decrease in CBV was observed in some types of convulsive seizures. (iii) An ictal increase in CBV changed to an ictal decrease in the course of tonic status epilepticus. (iv) There was definite heterogeneity in the CBV changes during tonic spasms in patients with West syndrome. NIRS is easily applicable to paediatric patients with epilepsy and may provide new insights into the pathophysiology of various types of epileptic seizure.

Charles, Perrine; Reynolds, Richard; Seilhean, Danielle; Rougon, Geneviève; Aigrot, Marie S.; Niezgoda, Adam; Zalc, Bernard; Lubetzki, Catherine

doi: 10.1093/brain/awf216pmid: 12183343

Multiple sclerosis is affecting ∼1 out of every 1000 individuals in the western world. After axons are denuded of myelin in the early stages of the disease, remyelination occurs, but eventually this process fails, and permanent disability is the result. During development, the polysialylated form of the neural cell adhesion molecule NCAM, PSA‐NCAM, is expressed at the axonal surface and acts as a negative regulator of myelination, presumably by preventing myelin‐forming cells from attaching to the axon. Removal of PSA‐NCAM from the axonal surface is a prerequisite for the initiation of myelination. We questioned whether, in multiple sclerosis, re‐expression of PSA‐NCAM by axons could occur, and therefore account for the failure of remyelination. Forty multiple sclerosis lesions from 24 different post‐mortem multiple sclerosis cases were selected by histological methods and analysed by immunohistochemistry. Demyelinated lesions and partially remyelinated lesions (shadow plaques) were studied. Controls consisted of post‐mortem brain tissue from patients with amyotrophic lateral sclerosis and without neurological disease. We showed that PSA‐NCAM, normally absent from adult brain, is re‐expressed on demyelinated axons in the plaques. Within shadow plaques, remyelinated axons do not express PSA‐NCAM. Re‐expression of PSA‐NCAM could act as an inhibitor of remyelination and participate in disease progression in multiple sclerosis.

Low, Kathy A.; Miller, Jeff; Vierck, Esther

doi: 10.1093/brain/awf206pmid: 12183344

The mechanisms responsible for reaction time slowing in Parkinson’s disease were investigated using movement‐related potentials in a choice reaction time task. Parkinson’s disease patients and control subjects were required to respond with the left or right hand to indicate whether a visual stimulus was relatively large or small. The difficulty of the size discrimination was manipulated, as was the complexity of the manual response (single key press versus sequence of three key presses). Behavioural responses of Parkinson’s disease patients were slower than those of control subjects, especially when complex responses were required. Moreover, the timing of movement‐related potentials indicated that motor processes clearly required extra time, relative to control subjects, for Parkinson’s disease patients making complex responses. In addition, delayed onset of the movement‐related potentials indicated that one or more premotor processes are also slowed in these patients.

Schroeder, U.; Kuehler, A.; Haslinger, B.; Erhard, P.; Fogel, W.; Tronnier, V. M.; Lange, K. W.; Boecker, H.; Ceballos‐Baumann, A. O.

doi: 10.1093/brain/awf199pmid: 12183345

The subthalamic nucleus (STN) has generally been considered as a relay station within frontal‐subcortical motor control circuitry. Little is known about the influence of the STN on cognitive networks. Clinical observations and studies in animals suggest that the STN participates in non‐motor functions which can now be probed in Parkinson’s disease patients with deep brain stimulation of the STN, allowing selective and reversible modulation of this nucleus. Using PET, we studied changes in regional cerebral blood flow (rCBF) associated with a response conflict task (Stroop task) in Parkinson’s disease patients ON and OFF bilateral STN stimulation. The Stroop task requires subjects to name the font colour of colour words (e.g. ‘blue’) printed in an incongruent colour ink (e.g. yellow). During STN stimulation, impaired task performance (prolonged reaction times) was associated with decreased activation in both right anterior cingulate cortex (ACC) and right ventral striatum. Concomitant increased activation in left angular gyrus indicative of ongoing word processing during stimulation is consistent with an impairment to inhibit habitual responses. ACC and ventral striatum are part of the ACC circuit associated with response conflict tasks. The decreased activation during STN stimulation in the ACC circuit, while response conflict processing worsened, provides direct evidence of STN modulating non‐motor basal ganglia‐thalamocortical circuitry. Impairment in ACC circuit function could account for the subtle negative effects on cognition induced by STN stimulation.

Jahn, Klaus; Strupp, Michael; Krafczyk, Siegbert; Schüler, Olaf; Glasauer, Stefan; Brandt, Thomas

doi: 10.1093/brain/awf204pmid: 12183346

The aim of this study was to investigate the possible interaction of vestibulo‐ocular and vestibulo‐spinal functions. Spontaneous eye movements and anterior–posterior and lateral body sway were recorded simultaneously in 10 patients with vestibular neuritis (Experiment 1) and in 11 healthy subjects (Experiment 2) while all subjects wore a mask that allowed fixation of a head‐fixed target. For the healthy subjects, there was no significant difference in postural sway for the conditions of eyes open in darkness and fixation of the head‐fixed target. For the patients, the question was whether transient suppression of the spontaneous nystagmus by fixating the target affected excessive body sway or whether modulation of nystagmus and postural sway were largely independent. The mean peak slow‐phase velocity of the spontaneous nystagmus decreased from 13.5 ± 5.6 to 4.3 ± 2.4°/s during fixation. The suppression of nystagmus also reduced postural sway while standing on foam rubber. Mean value decreased from 25.2 ± 7.6 to 16.2 ± 7.7 mm (right–left root mean square values; ANOVA, P = 0.003). Since a head‐fixed target was used to suppress spontaneous eye movements, the data cannot be explained by any stabilizing effect of afferent visual cues. Instead, ocular motor efference copy signals or reafferences may have contributed to the postural instability of patients with vestibular neuritis, which would explain the reduction of postural sway during fixation suppression of the nystagmus. Thus, ocular motor signals rather than afferent visual cues about retinal slip are used for visual control of postural sway, at least in this experimental paradigm.

Bjoertomt, Otto; Cowey, Alan; Walsh, Vincent

doi: 10.1093/brain/awf211pmid: 12183347

Localized repetitive transcranial magnetic stimulation was used to disrupt visuospatial perception in the near and far space of six healthy volunteer subjects. In addition to the baseline condition, they were stimulated over the right posterior parietal cortex, the right or left dorsal occipital cortex or the right ventral occipital cortex, during the brief presentation of a transected horizontal line. Subjects had to indicate whether the part of the line to the left or right of the transection appeared longer. The stimulus display was back‐projected on a screen at a viewing distance of either 50 or 150 cm (‘near’ and ‘far’ space, respectively). Reaction times and choices were measured. In a forced‐choice paradigm, subjects showed ‘pseudoneglect’, the natural tendency of neurologically intact subjects to perceive the left side of a centrally transected line as slightly longer than the right. These errors occurred more for lines in near space than for lines in far space. Magnetic stimulation of the right posterior parietal cortex or the right ventral occipital lobe selectively induced a significant shift to the right in the perceived midpoint for near‐ and far‐space lines, respectively. The results reproduced in normal subjects the dissociation between neglect in near and far space that has been described in patients with different right‐hemisphere lesions. This dissociation supports the contention that there is a dorsal/near space–ventral/far space segregation of processing in the visual system which reflects the behavioural goals of the two putative visual streams.