04388nas a2200385 4500008004100000022001400041245009500055210006900150260001200219300001100231490000800242520325500250653001003505653003403515653002103549653001003570653003603580653002403616653002703640653002103667653001103688653000903699653004103708653002803749100002603777700002503803700001403828700001903842700001403861700001503875700002503890700002103915700001803936856004803954 2011 eng d a1872-895200aTransition from the locked in to the completely locked-in state: a physiological analysis.0 aTransition from the locked in to the completely lockedin state a c06/2011 a925-330 v1223 a

OBJECTIVE: 

To clarify the physiological and behavioral boundaries between locked-in (LIS) and the completely locked-in state (CLIS) (no voluntary eye movements, no communication possible) through electrophysiological data and to secure brain-computer-interface (BCI) communication.

METHODS: 

Electromyography from facial muscles, external anal sphincter (EAS), electrooculography and electrocorticographic data during different psychophysiological tests were acquired to define electrophysiological differences in an amyotrophic lateral sclerosis (ALS) patient with an intracranially implanted grid of 112 electrodes for nine months while the patient passed from the LIS to the CLIS.

RESULTS: 

At the very end of the LIS there was no facial muscle activity, nor external anal sphincter but eye control. Eye movements were slow and lasted for short periods only. During CLIS event related brainpotentials (ERP) to passive limb movements and auditory stimuli were recorded, vibrotactile stimulation of different body parts resulted in no ERP response.

CONCLUSIONS: 

The results presented contradict the commonly accepted assumption that the EAS is the last remaining muscle under voluntary control and demonstrate complete loss of eye movements in CLIS. The eye muscle was shown to be the last muscle group under voluntary control. The findings suggest ALS as a multisystem disorder, even affecting afferent sensory pathways.

SIGNIFICANCE: 

Auditory and proprioceptive brain-computer-interface (BCI) systems are the only remaining communication channels in CLIS.

10aAdult10aAmyotrophic Lateral Sclerosis10aArea Under Curve10aBrain10aCommunication Aids for Disabled10aDisease Progression10aElectroencephalography10aElectromyography10aHumans10aMale10aSignal Processing, Computer-Assisted10aUser-Computer Interface1 aMurguialday, Ramos, A1 aHill, Jeremy, Jeremy1 aBensch, M1 aMartens, S M M1 aHalder, S1 aNijboer, F1 aSchoelkopf, Bernhard1 aBirbaumer, Niels1 aGharabaghi, A uhttp://www.ncbi.nlm.nih.gov/pubmed/2088829202450nas a2200397 4500008004100000022001400041245010000055210006900155260001200224300001000236490000700246520132400253653001201577653002701589653002401616653001601640653001301656653003101669653001601700653001601716653000901732653001801741653001601759653000901775653002301784653003001807653000801837100001701845700002301862700001901885700002001904700001801924700001901942700001901961856007201980 2005 eng d a0168-827800aPathways for the regulation of body iron homeostasis in response to experimental iron overload.0 aPathways for the regulation of body iron homeostasis in response c10/2005 a711-90 v433 aBACKGROUND/AIMS: Secondary iron overload is a frequent clinical condition found in association with multiple blood transfusions. METHODS: To gain insight into adaptive changes in the expression of iron genes in duodenum, liver and spleen upon experimental iron overload we studied C57BL/6 mice receiving repetitive daily injections of iron-dextran for up to 5 days. RESULTS: Iron initially accumulated in spleen macrophages but with subsequent increase in macrophage ferroportin and ferritin expression its content in the spleen decreased while a progressive storage of iron occurred within hepatocytes which was paralleled by a significant increase in hepcidin and hemojuvelin expression. Under these conditions, iron was still absorbed from the duodenal lumen as divalent metal transporter-1 expressions were high, however, most of the absorbed iron was incorporated into duodenal ferritin, while ferroportin expression drastically decreased and iron transfer to the circulation was reduced. CONCLUSIONS: Experimental iron overload results in iron accumulation in macrophages and later in hepatocytes. In parallel, the transfer of iron from the gut to the circulation is diminished which may be referred to interference of hepcidin with ferroportin mediated iron export, thus preventing body iron accumulation.10aAnimals10aDisease Models, Animal10aDisease Progression10aDNA Primers10aDuodenum10aGene Expression Regulation10aHepatocytes10aHomeostasis10aIron10aIron Overload10aMacrophages10aMice10aMice, Inbred C57BL10aPolymerase Chain Reaction10aRNA1 aTheurl, Igor1 aLudwiczek, Susanne1 aEller, Philipp1 aSeifert, Markus1 aArtner, Erika1 aBrunner, Peter1 aWeiss, Günter uhttp://www.sciencedirect.com/science/article/pii/S0168827805003168#