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Acute hyponatremia and neuroleptic malignant syndrome in Parkinson's disease.

1. The neuroleptic malignant syndrome (NMS) may occur, occasionally, in Parkinson's disease (PD) after withdrawal of antiparkinsonian drugs. However, the circumstances in which the NMS occurs and the pathophysiologic mechanisms remain uncertain. 2. The authors studied a woman with PD, who developed hyperthermia, increased muscular tone, tremor, signs of autonomic dysfunction and stupor as symptoms of acute hyponatremia due to gastrointestinal loss of sodium in excess of water. 3. The correction of hyponatremia led to a complete recovery after about 6 hours. During this period the antiparkinsonian therapy was not modified. 4. An acute imbalance of sodium in the central nervous system may play a role in the pathophysiology of NMS.

Aged↗

Bilateral periodic lateralized epileptiform discharges in Mycoplasma encephalitis.

Status epilepticus and prolonged coma developed in two patients with respiratory tract infections caused by Mycoplasma pneumoniae. Serial electroencephalography initially revealed bilateral, independent, periodic, lateralized epileptiform discharges. This pattern was replaced several days later by other electroencephalographic abnormalities.

Brain Damage, Chronic↗

Effect of an adenosine antagonist and an adenosine agonist on status entry and severity in a model of limbic status epilepticus.

Adenosine is an endogenous neuromodulator that suppresses excitatory neurotransmission. We postulated that adenosine-mediated mechanisms resist status epilepticus (SE) entry and limit SE severity. In the first experiment rats were given an adenosine agonist (2-chloroadenosine), an adenosine antagonist (aminophylline), or saline vehicle, prior to SE induction with pulsed-train current delivered to amygdala in successive 5-min current-on sessions. Saline-treated animals entered limbic SE, with predominantly exploratory behavior, after 6.0 +/- 0.9 current-on sessions. Aminophylline increased major convulsive activity during stimulation and resulted in entry into convulsive SE after only 2.1 +/- 0.1 sessions. 2-Chloroadenosine, in contrast, suppressed major convulsive activity during stimulation, and blocked (in 3/7) or delayed (4/7) SE entry, with successes requiring 12.8 +/- 0.9 stimulation sessions. In a second experiment, animals already in exploratory SE were administered a single injection of saline vehicle, aminophylline, or 2-chloroadenosine. Aminophylline converted exploratory SE into lethally severe convulsive SE. 2-Chloroadenosine suppressed SE behaviorally and electrographically, and protected recipients from the seizure-associated cerebral damage seen in saline-administered SE controls. These results support the hypothesis that endogenous adenosine mechanisms resist SE entry, modulate the severity of ongoing SE, and limit the anatomic spread of seizure activity.

2-Chloroadenosine↗

Single dose pharmacokinetics of carbamazepine-10,11-epoxide in patients on lamotrigine monotherapy.

The pharmacokinetics of a single oral dose of carbamazepine-10,11-epoxide (CBZ-E, 100 mg) were compared in 10 patients on chronic monotherapy with lamotrigine (LTG, 200-300 mg/day) and in 10 drug-free healthy control subjects. CBZ-E pharmacokinetic parameters in LTG-treated patients were found to be similar to those observed in controls (half-life: 7.2 +/- 1.6 vs 6.1 +/- 0.9 h; apparent oral clearance: 110.8 +/- 53.1 vs 120.5 +/- 29.9 ml/h/kg; apparent volume of distribution: 1.08 +/- 0.37 vs 1.04 +/- 0.25 l/kg respectively; means +/- s.d.). These data indicate that, contrary to previous suggestions, LTG has no effect on the metabolic disposition of CBZ-E.

Adult↗

Etiological heterogeneity of familial periventricular heterotopia and hydrocephalus.

Periventricular heterotopia (PH) represents a neuronal migration disorder that results in gray matter nodules along the lateral ventricles beneath an otherwise normal appearing cortex. While prior reports have shown that mutations in the filamin A (FLNA) gene can cause X-linked dominant PH, an increasing number of studies suggest the existence of additional PH syndromes. Further classification of these cortical malformation syndromes associated with PH allows for determination of the causal genes. Here we report three familial cases of PH with hydrocephalus. One pedigree has a known FLNA mutation with hydrocephalus occurring in the setting of valproic acid exposure. Another pedigree demonstrated possible linkage to the Xq28 locus including FLNA, although uncharacteristically a male was affected and sequencing of the FLNA gene in this individual revealed no mutation. However, in the third family with an autosomal mode of inheritance, microsatellite analysis ruled out linkage with the FLNA gene. Routine karyotyping and fluorescent in situ hybridization using BAC probes localized to FLNA also showed no evidence of genomic rearrangement. Western blot analysis of one of the affected individuals demonstrated normal expression of the FLNA protein. Lastly, sequencing of greater than 95% of the FLNA gene in an affected member failed to demonstrate a mutation. In conclusion, these findings demonstrate the etiological heterogeneity of PH with hydrocephalus. Furthermore, there likely exists an autosomal PH gene, distinct from the previously described X-linked and autosomal recessive forms. Affected individuals have severe developmental delay and may have radiographic findings of hydrocephalus.

Adult↗

Subregions of human MT complex revealed by comparative MEG and direct electrocorticographic recordings.

OBJECTIVE: To locate the visual motion complex (MT+) and study its response properties in an epilepsy surgery patient. METHODS: A 17-year-old epilepsy patient underwent invasive monitoring with subdural electrodes in the right temporo-parieto-occipital area. MT+ was investigated by cortical electric stimulation and by epicortical visual evoked potentials time-locked to motion onset of sinusoidal gratings (motion VEP). Motion-related visual evoked magnetic field (motion VEF) was also recorded before the electrode implantation to complement the invasive recording. RESULTS: Motion VEPs revealed two subregions within MT+, generating early and late potentials respectively. The early activity with a peak around 130 ms was localized at a single electrode situated immediately caudal to the initial portion of the ascending limb of the superior temporal sulcus (AL-STS). The late activity, peaking at 242-274 ms, was located ventro-rostrally over three electrodes. Among the four electrodes with motion VEPs, cortical stimulation at the most caudal pair elicited motion-in-depth perception involving the whole visual field. In addition to two subregions revealed on the gyral crown, magnetoencephalography (MEG) demonstrated another subregion with a late motion VEF in AL-STS immediately rostral to the electrode with the early motion VEP. CONCLUSIONS: In combination with MEG recording, the present invasive exploration demonstrated human MT+ in a focal area of the temporo-parieto-occipital junction and delineated possible three subregions as indicated by the different latencies and distributions of the motion VEP/VEFs. SIGNIFICANCE: Comparative MEG and direct electrocorticographic recordings delineated possible subregions within the human MT complex.

Adolescent↗

Fine spatiotemporal structure of phase in human intracranial EEG.

OBJECTIVE: To transfer to the clinic for humans the technology and theory for high-resolution EEG analysis that have been developed in the laboratory with animals. METHODS: EEGs were recorded at high spatial resolution from a 1 x 1 cm 8 x 8 electrode array on the right inferior temporal gyrus of a patient undergoing preoperative monitoring for epilepsy surgery. Cosines were fitted to EEG segments to measure frequency and phase and compute location, size, latency, phase velocity, duration, and recurrence rate of radially symmetric spatial patterns called phase cones. The Hilbert transform was also used to get high temporal resolution. RESULTS: In the awake state, the power spectral density (PSD) showed power-law decrease in log power with log frequency at 1/falpha, alpha approximately 2, but with peaks in the standard empirical ranges. The phase in beta and gamma ranges had spatial gradients in conic form. Resetting of these stable spatial patterns of phase cones was spatially coincident at intermittent discontinuities ('phase slip') recurring at theta rates. Cones had half power diameters from 2 to 50+ mm; their durations had power-law distributions with values ranging from 6 to 300+ ms depending on length of the analysis window. In slow wave sleep PSD decreased at 1/falpha, alpha approximately 3,with loss of beta-gamma spectral peaks and diminished or absent oscillations and spatiotemporal phase structure. CONCLUSIONS: Spatiotemporal structures in awake human and rabbit EEG showed striking similarities. The only clear differences were ascribable to differing scales of measurement. These fine spatiotemporal structures of EEG were diminished or lost in slow wave sleep. SIGNIFICANCE: The fine structure indicates that neocortical stability is sustained at self-organized criticality; that synaptic input in the awake state drives neocortex away from criticality causing beta-gamma oscillations in re-stabilizing 'neural avalanches'; and that diminished input in slow wave sleep allows return toward criticality but with some added risk of instability and seizure.

Adult↗

The novel antiepileptic drug lacosamide blocks behavioral and brain metabolic manifestations of seizure activity in the 6 Hz psychomotor seizure model.

Brain metabolic activation after 6 Hz electrical stimulation (32 mA, 3s stimulus duration) was assessed by autoradiographic analysis of 14C-2-deoxyglucose (2-DG) uptake. In addition, effects of the new antiepileptic drug lacosamide were examined on the stimulation-induced metabolic activation. The 6 Hz stimulation via corneal electrodes induced a robust increase 2-DG uptake in cerebral cortical regions, lateral amygdala, and the caudate-putamen. Many other brain regions were not affected by the stimulation, including the hippocampal formation, medial nuclei of the amygdala, thalamus, and hypothalamus. Lacosamide (20 mg/kg) injected i.p. 30 min before application of electrical stimulation antagonized completely the seizure-induced brain metabolic activation but did not affect basal 2-DG uptake. The data provide evidence that lacosamide antagonizes the neural activation induced by an electrical seizure stimulus, without suppressing normal brain metabolic activity.

Acetamides↗

Source analysis of interictal spikes in polymicrogyria: loss of relevant cortical fissures requires simultaneous EEG to avoid MEG misinterpretation.

PURPOSE: Multiple source analysis of interictal EEG and MEG spikes was used to identify irritative zones in polymicrogyria (PMG). Spike onset times and source localization were compared between both modalities. PMG is characterized by a marked loss of deep cortical fissures. Hence, differences between EEG and MEG were expected since MEG signals are predominantly generated from tangentially orientated neurons in fissures. PATIENTS: We studied 7 children and young adults (age 7.5 to 19 years) with localization-related epilepsy and unilateral polymicrogyria (PMG) as defined from anatomical MRI. METHODS: 122-channel whole-head MEG and 32-channel EEG were recorded simultaneously for 25 to 40 min. Using the BESA program, interictal spikes were identified visually and used as templates to search for similar spatio-temporal spike patterns throughout the recording. Detected similar spikes (r > 0.85) were averaged, high-pass filtered (5 Hz) to enhance spike onset, and subjected to multiple spatio-temporal source analysis. Source localization was visualized by superposition on T1-weighted MRI and compared to the lesion. RESULTS: Nine spike types were identified in seven patients (2 types in 2 patients). Eight out of nine EEG sources and seven MEG sources modeling spike onset were localized within the visible lesion. EEG spike onset preceded MEG significantly in two spike types by 19 and 25 ms. This was related to radial onset activity in EEG while MEG localized propagated activity. In one case, the earliest MEG spike activity was localized to the normal hemisphere while the preceding radial EEG onset activity was localized within the lesion. Distances between EEG and MEG onset sources varied markedly between 9 and 51 mm in the eight spike types with concordant lateralization. CONCLUSION: Interictal irritative zones were localized within the lesion in PMG comparable to other malformations, e.g., FCD. Discrepancies in MEG and EEG were related to the lack of deep fissures in PMG. In two cases, MEG was blind to the onset of radial interictal spike activity and localized propagated spike activity. In two other cases, MEG localized to the more peripheral parts of the irritative zone. Simultaneous EEG recordings with MEG and multiple source analysis are required to avoid problems of MEG interpretation.

Adolescent↗

Processing stages underlying word recognition in the anteroventral temporal lobe.

The anteroventral temporal lobe integrates visual, lexical, semantic and mnestic aspects of word processing, through its reciprocal connections with the ventral visual stream, language areas, and the hippocampal formation. We used linear microelectrode arrays to probe population synaptic currents and neuronal firing in different cortical layers of the anteroventral temporal lobe, during semantic judgments with implicit priming and overt word recognition. Since different extrinsic and associative inputs preferentially target different cortical layers, this method can help reveal the sequence and nature of local processing stages at a higher resolution than was previously possible. The initial response in inferotemporal and perirhinal cortices is a brief current sink beginning at approximately 120 ms and peaking at approximately 170 ms. Localization of this initial sink to middle layers suggests that it represents feedforward input from lower visual areas, and simultaneously increased firing implies that it represents excitatory synaptic currents. Until approximately 800 ms, the main focus of transmembrane current sinks alternates between middle and superficial layers, with the superficial focus becoming increasingly dominant after approximately 550 ms. Since superficial layers are the target of local and feedback associative inputs, this suggests an alternation in predominant synaptic input between feedforward and feedback modes. Word repetition does not affect the initial perirhinal and inferotemporal middle layer sink but does decrease later activity. Entorhinal activity begins later (approximately 200 ms), with greater apparent excitatory post-synaptic currents and multiunit activity in neocortically projecting than hippocampal-projecting layers. In contrast to perirhinal and entorhinal responses, entorhinal responses are larger to repeated words during memory retrieval. These results identify a sequence of physiological activation, beginning with a sharp activation from lower level visual areas carrying specific information to middle layers. This is followed by feedback and associative interactions involving upper cortical layers, which are abbreviated to repeated words. Following bottom-up and associative stages, top-down recollective processes may be driven by entorhinal cortex. Word processing involves a systematic sequence of fast feedforward information transfer from visual areas to anteroventral temporal cortex followed by prolonged interactions of this feedforward information with local associations and feedback mnestic information from the medial temporal lobe.

Adult↗

The neural correlate of (un)awareness: lessons from the vegetative state.

Consciousness has two main components: wakefulness and awareness. The vegetative state is characterized by wakefulness without awareness. Recent functional neuroimaging results have shown that some parts of the cortex are still functioning in 'vegetative' patients. External stimulation, such as a painful stimulus, still activates 'primary' sensory cortices in these patients but these areas are functionally disconnected from 'higher order' associative areas needed for awareness. Such studies are disentangling the neural correlates of the vegetative state from the minimally conscious state, and have major clinical consequences in addition to empirical importance for the understanding of consciousness.

Agnosia↗

Nonconvulsive status epilepticus on treatment with levetiracetam.

In several studies the efficacy and tolerability of levetiracetam (LEV) have been demonstrated. We report two patients who developed nonconvulsive status epilepticus on treatment with LEV. Both patients never experienced status epilepticus before. One patient had a symptomatic epilepsy with complex partial seizures following radiotherapy of astrocytoma in 1985; the second patient had complex partial seizures due to mesial temporal sclerosis. Both patients received LEV 2000 mg/day. We postulate a correlation between occurrence of nonconvulsive status and treatment with LEV. This has not been described before apart from a single report of mentally retarded patients with status epilepticus on high dosages of LEV.

Adult↗

Older adults with epilepsy demonstrate cognitive impairments compared with patients with amnestic mild cognitive impairment.

Little is known about the cognitive effects of chronic epilepsy in older adults. To better characterize cognitive impairment in seniors with epilepsy, we compared cognitive performance of 26 seniors with epilepsy with that of 26 well-matched patients with mild cognitive impairment (MCI) and 26 well-matched healthy older adults. Participants completed neuropsychological testing with the Dementia Rating Scale (DRS), Logical Memory, and CFL Word Fluency. There were no significant demographic group differences, although seniors with epilepsy had higher self-reported depression. Seniors with epilepsy performed below controls on virtually all neuropsychological tests, and performed below patients with MCI on DRS Total score, Initiation/Perseveration, and CFL Fluency. Seniors with epilepsy on antiepileptic drug (AED) polytherapy had the most severe cognitive deficits, whereas seniors with epilepsy on AED monotherapy were comparable to cholinesterase inhibitor-naïve patients with MCI. This study emphasizes the clinical importance of cognitive impairment in seniors with epilepsy and highlights the need for future studies addressing causes and treatment of cognitive impairment.

Age Factors↗

Neurochemical effects of vagus nerve stimulation in humans.

An implanted stimulating device chronically stimulated the left cervical vagus nerve in epileptic patients. Cerebrospinal fluid concentrations of free and total gamma-aminobutyric acid, homovanillic acid, 5-hydroxyindoleacetic acid, aspartate, glutamate, asparagine, serine, glutamine, glycine, phosphoethanolamine, taurine, alanine, tyrosine, ethanolamine, valine, phenylalanine, isoleucine, vasoactive intestinal peptide, beta-endorphin, and somatostatin were measured before and after 2 months of chronic stimulation in six patients. Significant increases were seen in homovanillic acid and 5-hydroxyindoleacetic acid in three patients, and significant decreases in aspartate were seen in five patients. These changes were associated with a decrease in seizure frequency.

Adult↗

The effects of vagus nerve stimulation on decision-making.

Subcortical and brainstem structures are increasingly becoming recognized as important contributors to higher cognitive functioning. Decision-making is one such function, particularly as viewed within the framework of the somatic marker hypothesis (SMH). The SMH views the participation in decision-making by the body proper as integral to emotional biasing and hence key to choosing in an advantageous manner. This study focuses on the vagus nerves as a possible conduit for somatic afferent signals pertinent to decision-making. We tested eight epileptic patients with implanted left vagus nerve stimulators. To assess decision-making we used the gambling task, which is sensitive to real-life decision-making deficits. Using a counterbalanced design, each participant performed the gambling task under a condition in which low-level vagus nerve stimulation (VNS) was covertly delivered, and another condition in which no VNS was delivered. Participants showed improved performance, that is, made more advantageous choices, in the stimulated relative to the unstimulated condition. Although these results should be viewed as preliminary, they suggest that the vagus nerve is a conduit for afferent somatic signals that can influence decision-making.

Adult↗

The role of the right temporal lobe in card sorting: a case study.

It has been demonstrated previously that performance on the modified Wisconsin Card Sorting Task (Nelson, 1976) is compromised by hippocampal sclerosis, particularly of the right hemisphere (Corcoran and Upton, 1993). Further evidence in support of this claim is presented here in the form of a case study. The findings from this case demonstrated that performance on the same task was not impaired following a right sided frontal lobectomy but was found to be deficient consequent to seizure recurrence in the right temporal lobe and following right temporal lobe removal. The clinical and theoretical significance of this case is discussed.

Adult↗