Data from subjects receiving intrathecal laronidase for cervical spinal stenosis due to mucopolysaccharidosis type I.

Five subjects with mucopolysaccharidosis type I and symptomatic cervical spinal stenosis received intrathecal laronidase in a 4-month pilot study and/or a 12-month extension study [1]. Clinical descriptions of study subjects, nonserious adverse events, individual data tables, and scoring system methods are provided. There were ten nonserious adverse events that occurred in more than one study subject. Somatosensory evoked potentials were absent in two subjects and normal in two subjects, limiting their utility as an endpoint. There were no significant changes in magnetic resonance imaging of cervical spinal cord or brain, pulmonary function tests, or cerebrospinal fluid opening pressure. These data are presented along with the scoring methods used in evaluation of the study subjects.

Multiply charged thorium crystals for nuclear laser spectroscopy.

We have produced laser-cooled crystals of 232Th3+ in a linear rf Paul trap. This is the first time that a multiply charged ion has been laser cooled. Our work opens an avenue for excitation of the nuclear transition in a trapped, cold 229Th3+ ion. Laser excitation of nuclear states would establish a new bridge between atomic and nuclear physics, with the promise of new levels of metrological precision.

Advances in the pathophysiology of status epilepticus.

Status epilepticus (SE) describes an enduring epileptic state during which seizures are unremitting and tend to be self-perpetuating. We describe the clinical phases of generalized convulsive SE, impending SE, established SE, and subtle SE. We discuss the physiological and biochemical cascades which characterize self-sustaining SE (SSSE) in animal models. At the transition from single seizures to SSSE, GABAA (gamma-aminobutyric acid) receptors move from the synaptic membrane to the cytoplasm, where they are functionally inactive. This reduces the number of GABAA receptors available for binding GABA or GABAergic drugs, and may in part explain the development of time-dependent pharmacoresistance to benzodiazepines and the tendency of seizures to become self-sustaining. At the same time, 'spare' subunits of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-D-aspartic acid) receptors move from subsynaptic sites to the synaptic membrane, causing further hyperexcitability and possibly explaining the preserved sensitivity to NMDA blockers late in the course of SE. Maladaptive changes in neuropeptide expression occur on a slower time course, with depletion of the inhibitory peptides dynorphin, galanin, somatostatin and neuropeptide Y, and with an increased expression of the proconvulsant tachykinins, substance P and neurokinin B. Finally, SE-induced neuronal injury and epileptogenesis are briefly discussed.

Advances in the pathophysiology of status epilepticus.

Status epilepticus (SE) describes an enduring epileptic state during which seizures are unremitting and tend to be self-perpetuating. We describe the clinical phases of generalized convulsive SE, impending SE, established SE, and subtle SE. We discuss the physiological and biochemical cascades which characterize self-sustaining SE (SSSE) in animal models. At the transition from single seizures to SSSE, GABA(A) (gamma-aminobutyric acid) receptors move from the synaptic membrane to the cytoplasm, where they are functionally inactive. This reduces the number of GABA(A) receptors available for binding GABA or GABAergic drugs, and may in part explain the development of time-dependent pharmacoresistance to benzodiazepines and the tendency of seizures to become self-sustaining. At the same time, 'spare' subunits of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-D-aspartic acid) receptors move from subsynaptic sites to the synaptic membrane, causing further hyperexcitability and possibly explaining the preserved sensitivity to NMDA blockers late in the course of SE. Maladaptive changes in neuropeptide expression occur on a slower time course, with depletion of the inhibitory peptides dynorphin, galanin, somatostatin and neuropeptide Y, and with an increased expression of the proconvulsant tachykinins, substance P and neurokinin B. Finally, SE-induced neuronal injury and epileptogenesis are briefly discussed.

Computer enhancement of scalp-sphenoidal ictal EEG in patients with complex partial seizures.

Color topographic maps of scalp/sphenoidal ictal EEG records were computer-generated in 5 patients with medically refractory complex partial seizures of suspected temporal lobe origin. Seven ictal EEG records were analyzed by parsing them into a series of 1.28 sec epochs. User-interactive, computer techniques were utilized to replace eye movement and other artifactual segments in the peri-ictal records with nearby uncontaminated EEG segments. Artifact replacement techniques were designed to minimize or eliminate EEG discontinuities in those epochs in which artifact was removed. Significance probability maps consisting of z scores were constructed by comparing theta band power for each 1.28 sec epoch composing the peri-ictal period with the mean and standard deviation of theta power computed from a pre-ictal baseline period consisting of 50-75 epochs. The resulting maps were compared with available independent clinical measures in order to validate their usefulness. The independent measures consisted of non-invasive data (visual impressions of raw scalp/sphenoidal ictal EEGs and positron emission tomography) and invasive data (depth ictal recordings, pathological findings in resected temporal lobes, and surgical outcome). Ictal topographic maps appeared to either confirm or provide new localizing information in all 5 patients. In 3 of 5 patients, several seconds of localized theta suppression preceded localized theta augmentation during the peri-ictal period. The transition between the 2 states was very rapid (approximately 2 sec). The spatial locus of suppression was always in agreement with the spatial locus of augmentation. In general, the maps were considerably easier to interpret than the raw scalp/sphenoidal ictal EEGs: (1) Localized theta suppression in the maps was not evident from visual inspection of the raw ictal scalp/sphenoidal EEG. (2) Clear localized theta augmentation in the maps occurred well before the appearance of unambiguous phase reversals in the raw scalp/sphenoidal ictal EEG. (3) Mapping data were correctly lateralizing in 1 patient in whom visual interpretation of the raw scalp/sphenoidal ictal EEGs was considered non-localizing but often suggestive of a seizure origin in the hemisphere contralateral to that implicated by depth recordings, PET, and pathological data. These results suggest that topographic mapping of scalp/sphenoidal ictal EEGs in patients with complex partial seizures may eventually prove to be a useful adjunct to the interpretation of raw ictal recordings.