Blennow K.,Institute of Neuroscience and Physiology |
Hampel H.,Trinity College Dublin |
Weiner M.,University of California at San Francisco |
Weiner M.,Medical Center |
Zetterberg H.,Institute of Neuroscience and Physiology
Nature Reviews Neurology | Year: 2010
Intense multidisciplinary research has provided detailed knowledge of the molecular pathogenesis of Alzheimer disease (AD). This knowledge has been translated into new therapeutic strategies with putative disease-modifying effects. Several of the most promising approaches, such as amyloid-Β immunotherapy and secretase inhibition, are now being tested in clinical trials. Disease-modifying treatments might be at their most effective when initiated very early in the course of AD, before amyloid plaques and neurodegeneration become too widespread. Thus, biomarkers are needed that can detect AD in the predementia phase or, ideally, in presymptomatic individuals. In this Review, we present the rationales behind and the diagnostic performances of the core cerebrospinal fluid (CSF) biomarkers for AD, namely total tau, phosphorylated tau and the 42 amino acid form of amyloid-Β. These biomarkers reflect AD pathology, and are candidate markers for predicting future cognitive decline in healthy individuals and the progression to dementia in patients who are cognitively impaired. We also discuss emerging plasma and CSF biomarkers, and explore new proteomics-based strategies for identifying additional CSF markers. Furthermore, we outline the roles of CSF biomarkers in drug discovery and clinical trials, and provide perspectives on AD biomarker discovery and the validation of such markers for use in the clinic. © 2010 Macmillan Publishers Limited. All rights reserved.
News Article | January 18, 2016
Andrew Petrulis is finally getting some rest. For years, he didn’t want to fall asleep. He was out of the war but sleep put him back in it. His dreams replayed scenes from 11 years of active-duty service as a member of a US Air Force explosive ordnance disposal unit. Master Sgt. Petrulis defused roadside bombs and other improvised explosives with a robot, or sometimes his own hands, throughout Iraq, Afghanistan, and Southwest Asia between 2002 and 2013. He received the Bronze Star twice. He shot at people and got blown up. Bombs went off within feet of him. The explosions rattled his brain. He relived these scenes, over and over, in nightmares. After an honorable discharge, returning home, and joining the reserves in 2013, an MRI showed scar tissue on his brain. The VA diagnosed Petrulis with traumatic brain injury, severe post-traumatic stress disorder, tinnitus, Achilles and kneecap tendonitis, and depression. The VA rated his disabilities at a combined 140 percent, with PTSD, which his life now revolves around, accounting for 70 percent of that rating. But he was still functional in the sense that he could eat and go to the bathroom on his own. The VA ultimately declared him a 90 percent disabled veteran. He was running on fumes, getting only two or three fitful hours of sleep each night. He had regular panic attacks. Weekly night terrors. Vivid nightmares every other day, or so. He locked himself in his house, alone. Sometimes he’d drink on the couch until he passed out. But mostly he was too afraid to close his eyes. “It got really, really bad,” Petrulis, now 31, tells me. “I couldn’t do anything. So I’d just stay up.” Things are different today. Three or four nights a week, after tucking himself in bed, Petrulis slides a prototype 17-pound weighted blanket over his sheets. The blanket is roughly 3 feet wide by 6 feet long and looks a bit like 60 or so 4 x 4 inch bean bags handstitched together. The pockets are each stuffed with polypropylene pellets and a sort of memory foam material. Petrulis is a big guy—6'2", 250 pounds—but the blanket’s weight spreads evenly over him. “I feel safer when it’s covering my entire body,” Petrulis explains. No one can bother him this way. “It sets my mind up for sleeping hard that night.” Which he does. What happens, exactly, while he’s under such pressure? It sounds almost too good to be true. Whatever it is, can heavy blankets help other veterans with combat-related sleep problems get some rest too? What about restless deployed troops? Can heavy blankets offer them relief? The underlying idea is dead simple: create a cocooning embrace, like being swaddled. Petrulis compares it to a firm, comforting hug. According to Gaby Badre, a leading sleep researcher who’s studied weighted blanket therapy for treating insomnia in adults, there is good reason to believe this is because the deep pressure touch of a weighted material spread over part or all of the body dials down the fight-or-flight arousals of the sympathetic nervous system. (It’s generally accepted that a weighted blanket should be at least 10 percent the person’s body weight.) There is also speculation that lying under heavy constant pressure such as a weighted blanket feels good because it somehow lights up the brain’s reward center, probably triggering the release of neurotransmitters like serotonin and dopamine. But that’s about the extent of our understanding of the science beneath weighted blankets. No one knows precisely what goes on in the brain and throughout the body under this kind of pressure; whether the mechanism is mere placebo, or if something else altogether makes lying under a weighted blanket feel so reassuring and safe that it could bring deep, restorative sleep to those who need it but can’t otherwise get it on their own. It’s this mystery that still largely colors weighted blankets as non-evidence-based folk remedies to sleep disorders. They have shown promise as anti-anxiety and stress-relief aids in the very young and the very old. There is data and evidence to support claims that heavy blankets can help calm children with attention deficit hyperactivity disorder, autism, and other sensory disorders, as well as elderly people with dementia, added Badre, who’s been studying sleep since the late 1980s and currently oversees sleep medicine clinics at The London Clinic, the Institute of Neuroscience and Physiology at the University of Gothenburg, and SDS Kliniken. The between years, from roughly age 14 through 60, are murkier. There just isn’t sufficient data from clinical experience, at least not yet. There is hardly any supporting research, just anecdotal evidence, that shows the potential of weighted blankets having the same arousal-reducing effects as well as sleep-inducing ones in adult populations, including combat veterans like Petrulis. No small number of Iraq and Afghanistan war vets have trouble sleeping. Among patients of the Veterans Health Administration, the healthcare arm of the Department of Veterans Affairs, in 2015, 1,262,393 veterans—over 20 percent—had a sleep disorder diagnosis in the past two years, according to a VA representative. Those million-plus diagnosed sleep disorder cases, to say nothing of undiagnosed cases, are all different; various external factors like back and other muscular, skeletal, and neurological issues, plus prescription drug histories, bring unique forces and circumstances to bear on combat-related sleep disturbances. Petrulis is one veteran battling sleep after war. And one veteran reporting positive results, with no apparent side effects, from a non-evidence-based sleep aid is notable. But it’s not enough to convince the government to fund or conduct clinical research into that aid. Neither the VA nor the Department of Defense are exploring weighted blanket therapy. Petrulis and Chelsea Benard, a licensed occupational therapist who introduced him to weighted blanket therapy in the fall of 2015, wonder why not. Petrulis and Benard, who handstitched the 17-pound blanket Petrulis currently uses, don’t think the blanket is a cure-all for his sleep problems, but rather a promising, albeit under-researched supplement to other evidence-based treatment options for sleep and anxiety issues. “What’s neat is it’s a non-pharmacological approach that can be used as a complement tool to any other kind of treatment,” says Benard, who had the idea to try out weighted blankets with adult patients after she saw success using them on kids. “It’s not going to have any side effects.” She and Petrulis genuinely believe the technique can help people like him who cope with combat-related PTSD or TBI, whose core symptoms include sleep disturbances. And he says he’s tried just about everything when it comes to sleep. The VA initially prescribed him Ambien, which he tried once with no luck. The VA then upped the dosage, but still nothing; he’d sleep a few hours, then be up the rest of the night. They also put him on Valium for panic attacks, but that didn’t help either, even after an upped dosage. The VA currently has him on Prazosin, a blood pressure medication developed in the 1980s that’s been shown to stanch night terrors, and also has him on Klonopin, an anti-anxiety drug, for panic attacks. He says the Klonopin isn’t working, and is unsure whether or not Prazosin is helping. When he tries to power down at night, his brain is often going a million miles an hour. Except while he’s under the weighted blanket. He says it’s the only thing that helps him sleep. Nothing else gets him in a place at the end of the day where he can calm down and drift off. To this day, he hasn’t had a nightmare with the blanket on. But bad dreams still haunt him. They come when he isn’t sleeping under the blanket, and they often begin at home in Higganum, Connecticut, with Petrulis surrounded by family and friends. Then he’s driving a Humvee around town. He turns a corner, and suddenly he’s in Baghdad or Kandahar or some other place where he’s fighting for his life. He steps out of his vehicle and there’s a guy pointing a gun at him. Petrulis raises his M4 rifle, pulls the trigger. But it won’t fire. He keeps pulling the trigger and the guy either shoots Petrulis, or Petrulis dreams he shoots the guy. That bad dream hasn’t come around in awhile. It’s a scene from January 2, 2006, the first time Petrulis was blown up. He was driving a Humvee through Kandahar when a vehicle-borne improvised explosive device—a car bomb—detonated 10 feet from the armored vehicle. Everything went black. His gunner’s face was covered in third-degree burns. It was the first time Petrulis realized, “Hey, I’m not invincible.” He has lived with that memory—that bad dream—for years, reliving it over and over again in his sleep. Petrulis (right) with fellow bomb squad member and bomb-defusing robot (back left), near Forward Operating Base Giro, Afghanistan, May 2011. Photo: Andrew Petrulis His dreams have expanded with time. Most recently they’ve taken on an Inception-like, dream-within-a-dream quality. Petrulis will be disarming IEDs when suddenly he “wakes up.” “Oh my god,” he thinks to himself. “It was just a dream. I’m glad I’m not at war.” He’s fine. He’s in his bedroom. He gets up, walks outside, and guess what? There’s the war again. There’s nowhere for him to take cover. Enemy rounds are popping off over his head. He’s dodging RPG fire. He starts freaking out. Is this reality? Then he wakes up again. This time he’s screaming. He really is awake. “These dreams are so real,” he tells me, almost exasperated. “I can’t express how real they are, even when I wake up that second time. It’s almost like I have feelings in the dream. I physically feel in the dreams.” These layered nightmares are so visceral he has panic attacks when he surfaces from them. He’ll be soaked in sweat, unable to get back to sleep. Why would he want to? The psychologist he saw while on active duty recommended Petrulis keep a dream journal. So he writes down a lot of these nightmares. He’s found it helps his brain comprehend them. Writing this raw material down is a key stage of image rehearsal therapy, an evidence-based treatment for nightmares, said Wendy Troxel, a clinical and health psychologist who does sleep research in both civilian and military concentrations. Image rehearsal therapy involves patients “rescripting” their dreams, and is one in a range of evidence-based treatment options for enduring psychic wounds of modern war like PTSD and insomnia. These options include medications like Prazosin, the anti-nightmare drug Petrulis currently takes; prolonged exposure therapy for PTSD; and cognitive behavioral therapy for insomnia. Troxel told me she’s never heard of weighted blankets. As the co-principal investigator of an exhaustive 2015 RAND report on military sleep, she would be cautious about discussing any potential remedy for sleep disorders or PTSD that isn’t evidence-based. Which a heavy blanket is not. “If you can find science behind it, that’s one thing,” she wrote in an email. “But I would be very skeptical.” A review of the literature brings up just one randomized controlled trial examining the efficaciousness of weighted blankets on any psychological health outcome, according to Dr. Daniel Evatt, chief of research production at the Department of Defense Deployment Health Clinical Center. The study, published in 2014 in the journal Pediatrics, found that autistic children and their parents preferred weighted blankets over regular ones (the blankets were “well tolerated”). But the findings also reported that the weighted blankets did not improve overall sleep time for the children any more than the traditional blankets. In a written statement, Evatt said in light of that evidence, clinicians “might incorporate initial evidence that weighted blankets may be preferred and well tolerated and suggest that weighted blankets could be considered like any other bedding accessory and advise patients to use those bedding accessories that work for them.” “On the other hand,” Evatt added, “clinicians should be cautious of alternative treatments such as weighted blankets that are advertised with unsupported claims and that could be sought out by some patients in lieu of treatments that have the support of a body of scientific evidence." Dr. Vincent Mysliwiec, the US Army Surgeon General’s sleep medicine consultant, is aware of heavy blankets used for sleep. “From my understanding it’s kind of like a Beanie Baby,” says Mysliwiec, who authored a 2013 American Academy of Sleep Medicine study on active duty military personnel prone to sleep disorders and short sleep duration. “You’ve got this blanket with these tactile-like senses that you can, like, sense while you’re sleeping.” Mysliwiec is not familiar, however, with any scientific or medical-based studies that have established weighted blankets as an efficacious sleep therapy for any patient population, not just military. Kind of like a Beanie Baby. That’s about as good of an explanation as any. Or, maybe, kind of like floating. Gaby Badre doesn’t have problems sleeping, though he’s tried sleeping under a weighted blanket anyway. He’s also spent time soaking in a sensory deprivation tank, and thinks that somehow the two experiences can share a core operating principle. “The floating situation is really interesting,” says Badre. “You’re floating. It’s the same thing if you’re under deep pressure that is evenly distributed, so that you don’t feel a change in stimulation. You don’t get more stimulated by moving in your bed.” Badre is at the forefront of clinical weighted blanket therapy research in adult populations. He led a 2015 study on the positive effects of weighted blankets in adults aged 20 to 66 with intrinsic insomnia, or insomnia not secondary to medical or psychiatric disorders. The weighted blanket used in that study was a Swedish-designed product with adjustable metal chains (providing adequate pressure, depending on body weight). The Swedish heavy blanket used in Badre's study. Photo: Gaby Badre The results were published in the Journal of Sleep Medicine & Disorders, and found that a weighted blanket might aid in decreasing insomnia and, as such, “may provide an innovative, non-pharmacological approach and complementary tool to improve sleep quality.” Badre says there are two issues at play. “We know that deep pressure with a consistent sensory input decreases the level of arousal,” he explains. “The other aspect is that tactile stimulation can decrease the activity of the sympathetic nervous system. We know that an increase in sympathetic activity will increase arousal.” That might be the limit of our understanding of the science beneath weighted blankets, but for Badre it seems to be enough to justify using one. “I think everything that can give you this cocooning and monotonous tactile stimulation can have a positive impact,” he tells me. A positive impact is one thing. A body of evidence supporting that impact is another. Badre admits we simply need more clinical data before considering weighted blankets as anything other than an alternative approach to treating sleep disorders in adult populations. That includes active-duty military personnel and veterans. Badre says he has worked with at least one former member of the US military—a Marine who’d act out his nightmares—and thinks weighted blankets can help those with sleep problems related to PTSD. There's even a chance Badre could've been studying weighted blankets to treat such disorders in these types of patients by now, if only it were easier to convince the US military community to provide funding to rigorously research the technique. He would know. It’s unclear which branch of the military he and an American colleague were targeting. Badre says last fall they'd drawn up a weighted blanket research grant proposal, but that according to his colleague the military showed “no enthusiasm” before the idea was even formally presented. The researchers decided to not submit the proposal. What might account for that lack of enthusiasm? Troxel speculates it could be a matter of military funding. But it could also be that scant preliminary data on weighted blankets is not enough to support deeper investments from the government. There does seem to be a lack of bandwidth, time, and money among the small handful of weighted blanket providers on the market to commission clinical research. “We have been far too busy making weighted blankets to commission studies, but we would love to do so (or be part of one),” Donna Chambers, founder and CEO of Sensacalm, wrote me in an email. Sensacalm makes weighted blankets for people with autism, ADHD, Asperger’s, PTSD, sensory processing disorder, anxiety, dementia, and Alzheimer’s. Chambers added that Sensacalm has previously donated blankets to researchers studying them, but has yet to hear back any results. The irony is that the VA, at least, does offer patients weighted blankets and vests. Just not for sleep disorders. They can be ordered through the VA’s Rehabilitation & Prosthetic Services and are provided for orthopedic and neurologic balance disorders, such multiple sclerosis, Parkinson’s, ataxia, and stroke, according to a written statement from the VA. Patients must show documentation of medical necessity and how the blanket is an essential component of their treatment plans. This doesn’t extend to treating sensory processing disorders, post-traumatic stress, and anxiety, the statement adds. That's one way of putting it. “We can’t necessarily prescribe this because it’s not a medical device,” says Mysliwiec, the US Army Surgeon General’s sleep medicine consultant. That's another way. That doesn’t mean Mysliwiec thinks there’s nothing to lying under a weighted blanket, however. He thinks it can play a role in people getting better sleep. It’s OK to use one, Mysliwiec admits, so long as it doesn’t cause a person any side effects. Blankets are probably not fit for people with disruptive breathing disorders like sleep apnea, or who have underlying heart or lung conditions. In those cases Mysliwiec would not consider weighted blankets appropriate or exactly safe. But for people like Petrulis, who does not report sleep breathing disorders or any underlying heart or lung conditions, for whom sleeping under a weighted blanket helps their sleep, Mysliwiec doesn’t think using one is a problem, and he sees no significant side effects either. For their part, Petrulis and Benard are trying to get the word out and scale up production of her proprietary blanket model. Benard tells me she’s used weighted blankets with at least 200 adult patients over roughly the past five years; about 80 of them were veterans, and she says every one of them had symptoms of anxiety or disturbed sleep negatively impacting their quality of life. Others with PTSD, including rape victims, have also reached out to her, asking how they can get their hands on a blanket. Benard has 10 blankets as of this writing. She was waiting on a bulk order, paid entirely out of pocket, of 1,000 pounds of the polypropylene pellets and memory foam-like material (she did not elaborate on either) to hopefully make a bunch more blankets. At the same time, she’s trying to figure out if bulk manufacturing would even make sense. “I’m not sure we’ll be able to keep up with the demands,” Benard tells me. Her and a small group of volunteers still sew blankets by hand. She does hope to launch a non-profit, called Snug as a Bugz, centered on her model of “battle blanket.” She has a natural spokesperson in Petrulis, who is currently helping her raise funds to get more material to make more blankets. Since launching a GoFundMe campaign on December 5, 2015, “over 400” people have contacted Benard in support of weighted blankets or requesting more information; they have all either been combat veterans or families or friends of veterans. All the money raised through the campaign would go toward making more blankets—Benard and Petrulis would take none of the cut. The pair hopes to get blankets in the hands of as many vets as possible, including at retreat centers like Virginia-based Boulder Crest, a privately-funded rural wellness retreat for combat vets and their families. I asked Josh Goldberg, director of strategy at Boulder Crest, if the retreat would ever consider keeping a few weighted blankets onsite for guests with sleep disorders. “I would absolutely not rule it out,” said Goldberg. He was careful not to endorse weighted blankets outright, but did say Boulder Crest is “very open minded to the fact that a lot of things that are non-clinical in nature can be very, very effective at giving people the peace that they need to live the life they deserve to live in.” Lying under a heavy blanket has given Petrulis a little bit of that peace. He sleeps and feels a lot better than he did just a few years ago because of it. If the potential is there for something as dead-simple as weighted blankets to help other vets with sleep issues and perhaps even deployed troops with similar problems, Petrulis wants military brass to understand something. “I want the military to really understand that this is something—and they really don’t know about it, or talk about it, and there’s no information on this—that will drastically help people even if you just have ‘em in your mental health units,” he says. “Or bring them into every EOD shop.” If someone’s having a bad flashback or is unable to sleep, just wrap them up. “It’s such an easy thing to do.” He’s talking about people who are deployed, who are in war zones, not just vets at home. A reality of modern war is that a generation of tired troops are being raised up through the ranks, and that has a big impact on sleep and life during and after war. The 2015 RAND military sleep study Troxel co-authored included 1,957 participants from across all four branches of the armed forces, and found a “high prevalence” of sleep issues like poor sleep quality, nightmares, insufficient sleep duration, and daytime sleepiness among those subjects. The participants were “older and all married,” Troxels points out. Their battle rhythms are in stark contrast—they’re just not as zipped up—compared to the twentysomething deployed men who Troxels says are the highest-risk demographic today for, say, slugging energy drinks. And then crashing. “It’s concerning that we’re raising this population of servicemembers who are using a variety of techniques to stay awake, which then further compromises sleep,” Troxel says. “It’s a vicious, perpetuating cycle of trying to stay awake and then not being able to fall asleep at night, which perpetuates not being able to sleep the subsequent night.” “There’s something endemic to military culture that’s contributing to sleep problems,” she adds. It can be hard to sleep while at war. But adjusting to sleep long after battle can be a war unto itself. Petrulis misses the person he used to be, before the PTSD and sleepless nights. But he knows he will never be that person again. “I feel like a person who pops 30 pills a day from 10 different doctors all trying to figure out what's wrong with me and how to help me,” he says. “I used to care but now I don't. I feel like a test subject that is fed pills until my brain is numb and I don't have to think anymore.” He has good and bad days. Today, he is in the process of being medically retired from the reserves. He heads up a CrossFit gym, which recently celebrated its one-year anniversary. He brings the blanket to work sometimes, wrapping himself up there if he can’t concentrate. Or if he had a bad night sleeping. He seems somewhat relieved that sleeping with the blanket some nights is helping him sleep during nights when he doesn’t use it. The night terrors are down to once every two weeks, but he’s still having issues allowing his body to rest. He does report sleeping soundly the three or four nights per week he currently sleeps under the blanket, accepting its weight. He pulls it down toward his feet as these nights progress. Sometimes bad dreams happen after that, but never when the blanket is physically on top of him. When he wakes up it’s not on him at all. Eventually Petrulis hopes to wean himself off the blanket entirely. “I want to try and be a normal human being again,” he says. There’s a hesitance in his voice, as if staring down a long struggle ahead. “I don’t want to go to sleep still.” You’ll Sleep When You’re Dead is Motherboard’s exploration of the future of sleep. Read more stories.
News Article | December 13, 2016
Faster and better recovery after stroke may be the result of a newly discovered treatment strategy that created new nerve synapses in the brain--a key factor for learning. A study at Sahlgrenska Academy showed improved ability to use the affected paw in mice that received the treatment. "More nerve sprouts and connections between nerve cells are created so that the remaining cells can take over functions that the dead cells once had," says Marcela Pekna, associate professor at the Institute of Neuroscience and Physiology at Sahlgrenska Academy. The focus is on a molecule called C3a peptide, which is produced naturally in the body and even more so with certain medical conditions. In this case, it was administered to laboratory animals through nasal drops. Of a total of 28 mice with stroke, half received C3a peptide and half a placebo. The treated mice recovered much better. "Mice have pretty good ability to recover after a stroke, even without treatment, but with C3a they got better much faster and were able to use the affected paw to a higher degree. And they remained better even four weeks after we finished the treatment," says Anna Stokowska, first author of the study and postdoctoral researcher at Sahlgrenska Academy. The results from the behavioral analysis were linked to what happened in the brains of the mice, in which treatment with C3a led to what many now consider to be more important for the recovery of function than generation of new nerve cells, namely the creation of new synapses between the cells. "Say a stroke kills ten million brain cells. Newly created cells equal less than one percent of those that died, and how much can that help? The formation of new nerve synapses is what allows a person to learn, for example, to speak or use her hands and legs again," says Marcela Pekna. Still a long way to go As C3a is inactivated if given orally or intravenously, the researchers used nasal drops. The C3a peptide is also extremely expensive to produce and would need to be replaced by a smaller, cheaper molecule with similar properties. Marcela Pekna and her research team hope that, in the future, this treatment strategy can be applied clinically in humans. The fact that, in the study, C3a began to be given first a week after onset opens for opportunities to help many people. "In principle, all stroke patients could receive the treatment. Compare that with removing the blood clot, which must be done within the first few hours. Most people arrive at the hospital too late for that treatment. We believe that a combination of this treatment and the correct type of rehabilitation can help patients improve even faster. It might also be possible to treat other illnesses than stroke, such as brain damage after traffic accidents. But that remains to be seen; there is still a long way to go," Pekna says.
News Article | December 15, 2016
Neural stem cells have been found in epileptic brain tissue--outside the regions of the brain where they normally reside. In a group of patients who underwent surgery for epilepsy, over half had stem cells where healthy individuals do not have them, according to a study from Sahlgrenska Academy. "We have confirmed what earlier studies indicated, and gained new knowledge about molecular characteristics of these neural stem cells," says Milos Pekny, professor at the Institute of Neuroscience and Physiology. Neural stem cells with the ability to form new neurons in the brain are normally present in the hippocampus (the part of the brain connected to learning and memory) and in the subventricular zone of the brain. However, in 8 of 14 patients in the study, neural stem cells were present outside these regions, namely in the epileptic brain tissue that was surgically removed. Over 50 operations of this kind are conducted in Sweden each year, of which about 20 in Gothenburg, with most patients becoming seizure-free or having significant reduction in seizure frequency. After an extensive investigation aiming at the precise localization of the epileptic focus, brain tissue that is damaged due to malformation, injury or other cause, is surgically removed. Surgeons, neurologists and neuroscientists worked side by side in the current study, which followed ethical approval and informed consent from each patient. For research purposes, the team was allowed to examine a small part of the removed tissue used for histopathological examination - in the operating room and in the research laboratory, just several minutes after removal. "About 60% of the patients had epileptic tissue that contained neural stem cells that could be converted into neurons, astrocytes and oligodendrocytes (the three types of brain cells that neural stem cells can differentiate into) when they were later grown in the laboratory," says Milos Pekny. "This may point to a greater plasticity in the epileptic tissue, which to some extent can be compared to the brain tissue of a newborn," continues Milos Pekny. Scientists have gained a better molecular understanding of the region of the brain in individuals with epilepsy which - due to a developmental abnormality, trauma, stroke, or a growing tumor - has stopped responding to control signals, and this results in recurrent seizures. "The knowledge gained in this study primarily helps to improve our understanding of the brain responses in epilepsy," outlines Milos Pekny. Scientists have long speculated that astrocytes, the cell type that controls many neuronal functions, give rise to neural stem cells in damaged brain tissue. "Our study suggest that this is not the case, at least in epilepsy, and it contributes the advancement of our understanding of what can happen in the brain in people with epilepsy," says Milos Pekny.
Mannerkorpi K.,Gothenburg University |
Mannerkorpi K.,Sahlgrenska University Hospital |
Nordeman L.,Gothenburg University |
Cider A.,Sahlgrenska University Hospital |
And 2 more authors.
Arthritis Research and Therapy | Year: 2010
Introduction: The objective of this study was to investigate the effects of moderate-to-high intensity Nordic walking (NW) on functional capacity and pain in fibromyalgia (FM).Methods: A total of 67 women with FM were recruited to the study and randomized either to moderate-to-high intensity Nordic Walking (n = 34, age 48 ± 7.8 years) or to a control group engaging in supervised low-intensity walking (LIW, n = 33, age 50 ± 7.6 years). Primary outcomes were the six-minute walk test (6MWT) and the Fibromyalgia Impact Questionnaire Pain scale (FIQ Pain). Secondary outcomes were: exercise heart rate in a submaximal ergometer bicycle test, the FIQ Physical (activity limitations) and the FIQ total score.Results: A total of 58 patients completed the post-test. Significantly greater improvement in the 6MWT was found in the NW group (P = 0.009), as compared with the LIW group. No between-group difference was found for the FIQ Pain (P = 0.626). A significantly larger decrease in exercise heart rate (P = 0.020) and significantly improved scores on the FIQ Physical (P = 0.027) were found in the NW group as compared with the LIW group. No between-group difference was found for the change in the FIQ total. The effect sizes were moderate for the above mentioned outcomes.Conclusions: Moderate-to-high intensity aerobic exercise by means of Nordic walking twice a week for 15 weeks was found to be a feasible mode of exercise, resulting in improved functional capacity and a decreased level of activity limitations. Pain severity did not change over time during the exercise period.Trial registration: Clinicaltrials.gov identifier NCT00643006. © 2010 Mannerkorpi et al.; licensee BioMed Central Ltd.
Edelvik A.,Institute of Neuroscience and Physiology |
Rydenhag B.,Institute of Neuroscience and Physiology |
Olsson I.,Gothenburg University |
Flink R.,Uppsala University Hospital |
And 3 more authors.
Neurology | Year: 2013
Objective: To investigate prospective, population-based long-term outcomes concerning seizures and antiepileptic drug (AED) treatment after resective epilepsy surgery in Sweden. Methods: Ten- And 5-year follow-ups were performed in 2005 to 2007 for 278/327 patients after resective epilepsy surgery from 1995 to 1997 and 2000 to 2002, respectively. All patients had been prospectively followed in the Swedish National Epilepsy Surgery Register. Ninety-three patients, who were presurgically evaluated but not operated, served as controls. Results: In the long term (mean 7.6 years), 62%of operated adults and50%of operated children were seizure-free, compared to 14% of nonoperated adults (p , 0.001) and 38% of nonoperated children (not significant). Forty-one percent of operated adults and 44% of operated children had sustained seizure freedom since surgery, compared to none of the controls (p , 0.0005). Multivariate analysis identified $30 seizures/month at baseline and long epilepsy duration as negative predictors and positive MRI to be a positive predictor of long-term seizure-free outcome. Ten years after surgery, 86% of seizure-free children and 43% of seizure-free adults had stopped AEDs in the surgery groups compared to none of the controls (p , 0.0005). Conclusions: This population-based, prospective study shows good long-termseizure outcomes after resective epilepsy surgery. The majority of the patients who are seizure-free after 5 and 10 years have sustained seizure freedomsince surgery.Many patientswho gain seizure freedomcan successfully discontinue AEDs, more often children than adults. Classification of evidence: This study provides Class III evidence that more patients are seizure-free and have stopped AED treatment in the long term after resective epilepsy surgery than nonoperated epilepsy patients. © 2013 American Academy of Neurology.
Sundelin K.,Institute of Neuroscience and Physiology |
Petersen A.,Institute of Neuroscience and Physiology |
Soltanpour Y.,Gothenburg University |
Zetterberg M.,Institute of Neuroscience and Physiology
Open Ophthalmology Journal | Year: 2014
Aim: Inter-individual differences in intrinsic proliferative capacity of lens epithelial cells may have importance for the risk of developing posterior capsule opacification (PCO) after cataract surgery. The purpose of the present study was to determine growth of human lens epithelial cells (HLEC) in culture and investigate possible associations with clinical characteristics of the donors, such as age, sex, pseudoexfoliation, uveitis and diabetes. Methods: Pieces of lens capsule and adhering lens epithelial cells were obtained through capsulorhexis at cataract surgery. Specimens were cultured in a humidified CO2-incubator using standard culture medium and 5% fetal calf serum for two weeks after which cultured cells were stained with carboxy-fluorescein diacetate succinimidyl ester. Image processing software was used to determine the area of the confluent epithelial cell layer in relation to the size of the original capsule specimen. Results: The increase in area of confluent HLEC showed a negative correlation with diabetes at the first week after surgery. Lower age and female sex showed border-line significant associations with a higher rate of cell proliferation. The presence of pseudoexfoliation in vivo did not significantly affect cell growth in culture postoperatively. Nor did installation of xylocain in the anterior chamber during surgery. Conclusion: Diabetes is associated with lower rate of proliferation of lens epithelial cells in culture. The lack of strong correlations between in vitro growth and known risk factors for PCO in the donors suggest that other factors than the proliferative capacity of the cells per se are important for PCO formation. © Sundelinet al.; Licensee Bentham Open.
Jaraj D.,Institute of Neuroscience and Physiology |
Rabiei K.,Institute of Neuroscience and Physiology |
Marlow T.,Institute of Neuroscience and Physiology |
Jensen C.,Gothenburg University |
And 2 more authors.
Neurology | Year: 2014
Objectives: The aim of this study was to determine the prevalence of idiopathic normal-pressure hydrocephalus (iNPH) in elderly persons in a large population-based sample using radiologic and clinical examinations. Methods: We examined representative elderly populations aged 70 years and older that had undergone neuropsychiatric evaluations and CT of the brain between 1986 and 2000 (n = 1,238). Gait was evaluated by clinical examination and history of walking difficulty. Cognitive function was evaluated with the Mini-Mental State Examination and urinary incontinence by self-report. iNPH was diagnosed in concordance with the American-European iNPH guidelines. Exclusion criteria were history of meningitis, severe head trauma, and subarachnoid hemorrhage. Results: The prevalence of probable iNPH was 0.2% in those aged 70-79 years (n = 2) and 5.9% (n = 24) in those aged 80 years and older, with no difference between men and women. Only 2 of these persons had been treated for iNPH. Hydrocephalic ventricular enlargement, i.e., a CT image consistent with NPH, was found in 56 persons (4.5%). An Evans Index >0.3 was found in 256 (20.7%) and occluded sulci at the high convexity in 67 persons (5.4%). All of these findings were more common in the older age groups. Conclusions: Many elderly possess clinical and imaging features of iNPH, especially those older than 80 years. The number of persons with iNPH is probably much higher than the number of persons currently treated. © 2014 American Academy of Neurology.
Bjellvi J.,Institute of Neuroscience and Physiology |
Flink R.,Uppsala University Hospital |
Rydenhag B.,Institute of Neuroscience and Physiology |
Malmgren K.,Institute of Neuroscience and Physiology
Journal of Neurosurgery | Year: 2015
Object Detailed risk information is essential for presurgical patient counseling and surgical quality assessments in epilepsy surgery. This study was conducted to investigate major and minor complications related to epilepsy surgery in a large, prospective series. Method s The Swedish National Epilepsy Surgery Register provides extensive population-based data on all patients who were surgically treated in Sweden since 1990. The authors have analyzed complication data for therapeutic epilepsy surgery procedures performed between 1996 and 2010. Complications are classified as major (affecting daily life and lasting longer than 3 months) or minor (resolving within 3 months). Results A total of 865 therapeutic epilepsy surgery procedures were performed between 1996 and 2010, of which 158 were reoperations. There were no postoperative deaths. Major complications occurred in 26 procedures (3%), and minor complications in 65 (7.5%). In temporal lobe resections (n = 523), there were 15 major (2.9%) and 41 minor complications (7.8%); in extratemporal resections (n = 275) there were 9 major (3.3%) and 22 minor complications (8%); and in nonresective procedures (n = 67) there were 2 major (3%) and 2 minor complications (3%). The risk for any complication increased significantly with age (OR 1.26 per 10-year interval, 95% CI 1.09-1.45). Compared with previously published results from the same register, there is a trend toward lower complication rates, especially in patients older than 50 years. Con clusion s This is the largest reported prospective series of complication data in epilepsy surgery. The complication rates comply well with published results from larger single centers, confirming that epilepsy surgery performed in the 6 Swedish centers is safe. Patient age should be taken into account when counseling patients before surgery. © AANS, 2015.
Martensson L.,Institute of Neuroscience and Physiology |
Andersson C.,Institute of Neuroscience and Physiology
Scandinavian Journal of Occupational Therapy | Year: 2015
Background: In bibliotherapy, the therapeutic gains of reading fiction are ascribed to the literature. Viewing reading fiction as an occupation may give other explanations of its therapeutic function. Aim: The aim of this qualitative study was to explore the experiences of reading fiction among women during a period of sick leave. Material and methods: A qualitative approach was applied. Eight women who had been reading fiction during sick leave were interviewed. Results: An overarching theme: Supporting one's active self, comprised five categories of experiences: a prospect of ordinary life, a place of refuge, a life together with others, a source of power, and as supporting an active life. Conclusion and significance: Based on the categories, reading fiction is seen to comprise intentional, functional, mental, relational, and personal dimensions. A tentative model of supporting one's active self is proposed, which may be helpful in clarifying the mechanisms of the process of change. The health-related dimensions of reading fiction suggest that reading fiction should be regarded as a significant occupation comparable with other, more highlighted ones. Understood in this way, it is argued that the results add to the knowledge base in occupational therapy focusing on how meaningful occupations connect to occupational life trajectories. © Informa Healthcare.