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There is an aspect of compassion which regards a quantitative dimension, such that individual's compassion is often given a property of "depth," "vigour," or "passion." More vigorous than empathy, the feeling commonly gives rise to an active desire to alleviate another's suffering. It is often, though not inevitably, the key component in what manifests in the social context as altruism. In ethical terms, the various expressions down the ages of the so-called Golden Rule embody by implication the principle of compassion: Do to others what you would have them do to you.
Scooped by
Edwin Rutsch
onto Empathy and Compassion

subset: commoncrawl


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Olympia, WAUSA
September 12, 2013
Hello! I am new to the area (from the east coast) and have been excited about all the new adventures Washington has to offer. When I was in the Air Force I fell in love with backpacking but my close friends do not have the ability to join me.
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Just popping in to wish you all a Happy and safe Halloween! Here's our costumes this year: We have a minion, a bumble bee and a "Special Forces Commando". Black and yellow seem to be our colors this year. The little
The Peanuts Movie plus pumpkin stencil!
We're getting excited for the new Peanuts Movie to hit the big screen on November 6th, and we were thrilled to see a few of our favorite Peanuts characters at our local pumpkin patch. If you have yet to visit the pumpkin patch this season, you'll have to check out this list of pumpkin patches […]
Holy Skull-y Guacamole
We are getting excited for everything Halloween around here…including all the cute Halloween Party Food that comes with it. Since most Halloween treats seem to be on the not so healthy side, we wanted to make something festive yet healthy at the same time. How about some Holy 'skull-y' Guacamole! Isn't it so fun to […]
25+ Halloween Party Food Ideas
Halloween is almost here, which means it's time for party planning! There are dozens of ways to craft with food to create an unforgettable party experience for your guests. Take a peek at these Halloween party food ideas and add some treats (or tricks?) to your menu.
S'mores Peeps Brownies
Sometimes it's the simple ideas that are the best. We've taken s'mores + brownies + ghost peeps to make the cutest brownies on your Halloween party table. I have a thing for Peeps and S'mores…and brownies, so this was a big a-ha moment when they all came together. The funnest part of putting them all […]
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German Yule tradition comes to This Is the Place
Ben Brewer, Deseret News
SALT LAKE CITY — A German yuletide tradition was introduced to Salt Lake City on Thursday evening with the St. Martin's Lantern Parade at This Is the Place Heritage Park, an event organizers expect to be an annual tradition.
Choirs from seven elementary and junior high schools in the Granite and Salt Lake City school districts carried paper lanterns from the park's Eagle Gate replica to the plaza at the park entrance and performed German Christmas carols.
The Most Rev. John C. Wester, bishop of the Salt Lake City Catholic Diocese, narrated the program. He related the story of St. Martin, who was a soldier in the Roman Empire. He was riding his horse outside the city wall on a cold winter night, when a beggar asked him for alms.
With his sword, Martin cut his woolen cloak in two and gave half to the beggar. For kindness and compassion, Martin became well-known.
The incident was portrayed during the program with two costumed enactors, one on horseback representing Martin and the other depicting the beggar.
"The good deeds of this kindly saint bring light to our world, warming us and showing us the way," Bishop Wester said in his narration.
Later, Martin was chosen to be bishop of Tours. Legend has it that he felt he did not deserve the honor, so he hid in a goose house all day.
Adults and children searched the town to find him, lighting lanterns when it grew dark. He was found when the geese in the goose house began to squawk.
Today, German children celebrate St. Martin's Day by making lanterns and parading through town in honor of St. Martin's service.
"The children sing songs about him and later settle down to a goose dinner, which seems to me lacking in gratitude for the favor performed by the geese so many years ago," Bishop Wester said. "Tonight, our little celebration and re-enactment calls our attention to the simple yet heroic acts of kindness we are asked to perform on our journey home."
At the end of the program, to the strains of "O Tannebaum," Bishop Wester flipped a switch illuminating a colorful and brightly lit Christmas tree in the plaza.
The park's first Christkindlmarkt, with an assortment of small shops and booths, was the setting for the lantern parade. It carries forward a German tradition stemming from the Middle Ages in which German farmers sell toys, ornaments and crafts in the town center during the weeks leading to Christmas.
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text:
|Wide Receiver
|Lincoln, Neb.
|High School:
|Lincoln East
Honors & Awards
» Nebraska Scholar-Athlete Honor Roll (Fall 2014)
2016 Outlook
Sophomore Bryan Reimers heads into the 2016 campaign with hopes of contending for playing time in a deep Nebraska receiving corps. The 6-5, 210-pound Reimers has spent time in the program at both receiver and tight end, but settled in at receiver last fall, The Lincoln East graduate joined NU as a walk-on in 2014, and provides a big target in the Husker passing game.
2015 (Redshirt Freshman)
Reimers was a reserve receiver for the Huskers, but did not play in a game. He was part of the travel squad twice during the season.
2014 (Redshirt)
Reimers redshirted during his first season as a Husker and worked as a scout team receiver.
Before Nebraska (Lincoln East HS)
Reimers lined up at wide receiver for Lincoln East and had 27 receptions for 596 yards as a senior, an average of 22.1 yards per catch. Reimers also hauled in 12 touchdown catches in 2013, helping the Spartans to an 8-2 record and a trip to the Class A state playoffs. Reimers was an All-Nebraska second-team pick by the Omaha World-Herald and a second-team Super State selection by the Lincoln Journal Star. Reimers also earned All-City honors from the Lincoln Journal Star.
The son of Bryce and Suzanne Reimers, Bryan was born on May 28, 1996. He is majoring in business administration and was named to the Nebraska Scholar-Athlete Honor Roll in the fall semester. Reimers has volunteered his time with Uplifting Athletes and local hospital visits as part of NU's community outreach efforts


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Marco Rubio Lied On By Prophet Brian Carn!
Our friends over at the Preying Narcissist told us first about Carn's false prophesy of Marco Rubio and how he misled the sheep…AGAIN!
So our other friends at Pimp Preacher have further exposed Brian Carn about Marco Rubio! See below:
Well, as long as Brian Carn still wants to be unrepentant and still try to justify his false prophesies, we will continue to still report on him.
Why So Surprised About Brian Carn? He Wanted to Model After Benny Hinn!
We are seriously waiting to hear back from Brian Carn to see what he has to say about what has been found out about his FALSE prophesies he allegedly received from a psychic named Cheryl Lynn.
Street Preacher Beaten Into a Coma After Condoms Fall from His Bible
Originally posted May 30, 2013:
This is a crazy story but then again not much is crazy about the non-anointing of some false preachers. In this story, a preacher climbs onto a bus in Lagos, Nigeria and begins to preach to the passengers. Reports say he was moving the crowd so much, that many were falling out and shouting under the alleged anointing coming from his words.
Pastors Mentored By Bishop Earl Paulk Allegedly Carried The Torch of Scandal [Part 3]
Originally posted on Jan. 23, 2012:
We want to thank you all for being patient with us on this series we started late last year.
G. Craig Lewis and Ex Ministries Very Silent On Fred Price Sr.'s Jesus Committed Suicide Sermon
We at AT2W have to deal with this issue on Dr. Fred Price Sr. and his sermon about 'Jesus committing suicide' again. But we are not going to rant over how Dr. Price is faulty and in error for his use of words and terminology which we see nothing less than blasphemy. We are going to deal with a fact that G. Craige Lewis of Ex-Ministries has not allegedly addressed this particular minister and his error in addressing our savior's giving of himself to us to save our souls. Why is G. Craige Lewis so very silent about this issue?
Pastor Fred Price Jr. Allegedly Hung Up on Interview Call About Father's Jesus Suicide Sermon
We just listened to an interview The Church Folk Revolution and their talk with Crenshaw Christian Center's Senior Pastor, Fred Price Jr. The pastor was on their show to discuss his father's sermon and comments that "Jesus committed suicide and put the gun in this mouth and pulled the trigger." It was really getting to be a good show until a former church member of his joined the show and he literally hung up the phone.
Warning To Preachers: You Must Teach The Entire Word of God
There are many ministers who have been going against God's Word and this article has been written for those of you who are even guilty of following them. We will present a list of people who are in danger of judgment, thus saith the Lord.
Bishop E. Bernard Jordan's Son Manasseh Prophet Pimping with Rev. Run's Daughter
Many people know Bishop E. Bernard Jordan who is a self-proclaimed prophet has a son who is doing the same thing, Prophet Manesseh Jordan. The bishop and prophet Bernard is very known in the New York area from his long affiliation with false prophet Rev. Ike and Rev. Al Sharpton whose a regular on his radio show "Keeping it Real with Al Sharpton".


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I'm currently making a Java program that loads classes from a different package. It allows users to delete .class files from a package and prevent a crash. I therefore want to load all these classes using:
The only problem is that when I try that it says that the class is not found. If I put the class in the same package it works, but if I wanted to load it from the package "this.is.a" Class.forName("this.is.a.package.RandomClass"), it doesn't work. Any help appreciated!
I know I should probably be using URLClassLoaders but I don't know how I would use them to load a file inside a zipped jar.


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7-year-old girl dies after elephant at zoo throws a rock at her
The Latest: Trump slams Clinton over 'radical Islam'
Trump Jr. accuses Obama of plagiarizing a line from his speech
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Pixar movie scenes that you can visit in real life in the Bay...
Off-duty officer shoots man outside Costco in Modesto
Clinton speech draws mixed reaction on cable news
Suspected Santa Rosa molester dies after return from Mexico
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Oakland's 23rd Annual Thanksgiving Dinner will be Tuesday, November 25, 2014
The City of Oakland's just announced the 23rd annual Thanksgiving dinner, a free event to feed those who need some holiday food and cheer. Sponsored by Oakland's Human Services Department, …
Where else to go in Oakland now that the Uptown is closed
By Pilar Reyes Now that the Uptown is gone (yes, the Uptown venue on Telegraph closed November 5th, read about it here), there's a giant guitar-neck-shaped hole in the heart of Oakland. "What are we …
Oakland's Omni Commons space is where it's at
By Eric James Anderson The Omni Commons is probably the most exciting thing happening in Oakland right now, and it hasn't even opened yet. The simplest explanation of it: Omni Commons is an …
Chris Turner on the Romantic Movement, fatherhood, and Prince vs. Elsa
By Katie Schwarz It's been 12 years since Chris Turner moved to New York to study music. Since then he's toured the world, played with award-winning artists such as Bilal and Esperanza Spalding, and …
A mystified Sudanese studies his first Halloween
The first things I had to learn were Jack o' lantern, trick or treat, and you better get a costume! A week ago, I started seeing people on the bus, in grocery stores and other places, with pumpkins, …
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The grand opening of the first cat café in the country drew dozens of cat lovers and spectators to Downtown Oakland on Saturday—or rather, Caturday. …
Black & Brown Unity Short Film Showcase kicks off at Youth Impact HUB Oakland (Community Voices)
This month, the Beloved Community Event Series continues at Youth Impact HUB Oakland with the Black & Brown Unity Short Film Showcase, which highlights multicultural, inter-generational …
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A bit of Burning Man in Oakland
Have you ever wondered where Oakland's Burning Man artists go to unwind? The answer: to the Gardens at Lake Merritt, where every autumn, they display their wildly creative inventions in an …


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- Swimmer Ryan Lochte reveals one of his worst dates - US Weekly
- Get the latest on Dr. Dre's arrest - TMZ
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- Are Blac Chyna and Kylie Jenner on good terms? - Radar
- Blue Ivy is just as stylish as her mom Beyonce! - Lainey Gossip
- This Narcos star confirms he's not coming back for another season of the show - The Hollywood Reporter
20 August 2014 at 2:37 PM
Joe Manganiello Practices His 'Magic Mike 2' Dance Moves on Girlfriend Sofia Vergara!
About this photo set: Joe Manganiello puts on his dancin' shoes for the New Balance and James Jeans dance party powered by ISKO held at a private residence on Tuesday (August 19) in… Read More Here
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text: Big Bear Lake, CA, October 17, 2011, 8:00am - Big Bear's Toastmasters Club, "Bearly Speaking", is sponsoring its first Youth Leadership program for students in the Big Bear Home School Group. Developed by Toastmasters International, the eight-week program is not in competition with school programs or courses, or other established youth projects. … [Read more...]


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Top 20 Ultimate Ways to Use a Disposable Camera
Extra photos for bloggers: 1, 2, 3.
When it comes to photography, we like to root for the little guy.
He's the picture taker that works hard, is easy going and is always around when you need him.
Yep, we're talking about one of our old favorites: the disposable camera.
While we love adding filters to our phone pics and making masterpieces with our DSLRs, there's something magical about disposable cameras we can't forget…
They're cheap, fun to play with and can do almost anything!
Here's our top 20 list of didn't-know-you-could-do-that ways to use, abuse, modify, and make the most of your disposable camera!


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Welcome to Fishing Guide
Fly Fishing In Ruidoso New Mexico Article
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The Great Adventure of Alaska Fly Fishingfrom:
Can you feel the cool water coming up around your ankles? Can you feel the warm sunshine beating down on your face while watching the most beautiful Bald Eagles soar above? Then you do the only thing left to make this moment perfect, you begin to pick up your reel and step further into the water as rainbows and dollies swim just seeming to call your name. This is the experience that you can find when Alaskan fly-fishing. The experience of fishing in remote areas, soaking in some of the greenest trees you have ever seen, immersing yourself in the untouched natural surroundings, while casting your line in the cool Alaskan waters.
Alaskan fly-fishing is an adventure for anyone looking for a once in a lifetime experience. When you go fly fishing in Alaska you will find over hundreds of great fishing spots in over a 1,000 miles of streams and rivers. Anglers will have endless chances to catch dollies, rainbow trout, king salmon, and pink salmon. Though it is usually the larger than life sized fish that tends to draw anglers to the great adventure and the fun of fly fishing in Alaska, that's just the beginning of what you will experience. While on your fly fishing adventure, it is likely that you will see whales, seals, otters, bears and other varieties of wildlife wandering the countryside.
Going on an Alaskan fly fishing trip isn't just for the experienced angler either. It doesn't matter if you are a novice, or third generation fly fisherman, Alaskan fly-fishing can be for you. There are vacation packages that include private cabins and secluded islands. If you are the only angler in the family that is all right because there are a variety of other things the entire family can do. There's camping, sightseeing, and fun for the whole family. You can take a cruise on a boat, swim in the beautiful lakes, or take in any of the countless tourist attractions around. If you're an angler of any kind, it will most likely be the solitude of the waters, and the unending supply of fish that will draw you into the enjoyment of Alaskan fly-fishing.
The under exploited waters allow for plentiful fresh fish just right for the catching. Helping Mother Nature in the overflow of the fish is the Department of Fish and Game. They have a widespread planting and stocking program throughout the waters of Alaska so that when you go on your Alaskan fly fishing journey, you will find no shortage of Artic graylings, rainbow trout, lake trout, Coho salmon, king salmon, and Artic char.
Christina Gray is a recognized authority on the subject of fly fishing. Her website Fishing Secrets Revealed provides a wealth of informative articles and resources on everything you will need to know about fly fishing gear. All rights reserved. Articles may be reprinted as long as the content and links remains intact and unchanged.
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Gardening 101
Garden columnist Jessica Damiano shows you how to create a gorgeous garden.
column Jessica Damiano Garden Detective: vegetable troubleshooting Home gardeners growing vegetables are by now knee-deep in their routines: weeding, watering, fertilizing and, ... Read More »
column Jessica Damiano Using native vs. non-native plants 'using native vs. non-native plants' ... Read More »
photolist Home and Garden How to make a shoe organizer hanging garden A hanging shoe-organizer garden is a great way for anyone to grow edibles -- or ... Read More »
column Jessica Damiano Dry your own flowers For those who prefer the faded color of dried hydrangeas commonly sold at florist shops ... Read More »
column Jessica Damiano How to eliminate poison ivy Tips for identifying and removing poison ivy -- once and for all. ... Read More »
guide Home and Garden Growing fruit at home Here's what you need to know to grow and harvest ten fruits that are well-suited ... Read More »
article Home and Garden 7/29/16 How to make dried fruit at home Are you paying a premium for granola with half a cup of dried fruit? Tired ... Read More »
article Home and Garden 7/29/16 Garden Minute video: Save money on plants Keep your money in your wallet: propagating plants with cuttings is easier than you might ... Read More »
article Jessica Damiano 6/30/16 How to grow tomatoes on Long Island Follow these growing practices for a successful Long Island tomato harvest. ... Read More »
article Home and Garden 6/6/11 Gardening Minute: How to plant tomatoes This week, let's look at the best way to plant tomatoes to ensure you grow ... Read More »


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Greetings, Jean Luis and Tone! Thank you both so much for enjoying this pretty Autumn scene! Your appreciation of such beauty makes me smile. Thanks again for taking the time to comment here. WIshing you a wonderful Wednesday,
Mary Alice
Nice colors and nice place... Like... I added you to my friend list...Mary
Dear Mary Alice isn't this a fairy tale place for the Easter Bunnies?? :))) I wish you and yours a very Happy Easter Easterbunnyhugs, Peter
Thank you so much for enjoying these pretty Fall colors, **Alireza! Your kind words are greatly appreciated! Bets wishes to you! :)
Peter, Thanks so much or thinking of me this Easter! It has been a beautiful day, and I hope that yours has been just as nice! What a day to celebrate indeed! Easter bunny hugs right back to you, and thank you again for remembering me today!
Warmest regards,
Mary Alice
Very beautiful !!! Like
Best greetings from China !行者无路
Greetings, 行者无路, and thank you for your praise! I'm happy that you enjoyed this pretty view of Fall's golden colors. THanks again for visiting! Sending cheerful greetings to China from the USA,
Mary Alice
Beautiful autumn view with beautiful colours, greeting from Poland M. W. LIKE
Greetings, Mariwozn, and thank you for visiting! Your kind appreciation makes me smile! Thanks again for stopping by and enjoying this view of Fall. :)
Best regards on such a pretty Wednesday,
Mary Alice
Wonderful photo! Like!
Goldern splendor for sure,even better to no ''Bin Larden'' is no more.Well done America. Lloyd
Beautiful Capture!! LIKE+FAVORITE..Regards Mario
Thank you, Varkos! I'm happy you enjoyed this!
Mario, Your praise is greatly appreciated! Thank you! :)
Lloyd, Thank you, and Yes, God bless America! :)
Best regards to you all,
Mary Alice
É uma visão espetacular da natureza, parabéns pelo registro. F6 Saudações, de Dourados - Mato Grosso do Sul - Brasil
Greetings, Paulo Yuji Takarada, and thank you for your kind words. I couldn't agree with you more ..... Indeed, this is such a wonderful example of the beauty of nature! We are blessed with so many magnificent wonders on this good earth to enjoy. Thanks again for visiting and for your kind appreciation of this Autumn shot.
Best regards from the USA,
Mary Alice
very nice autumn scene, i like it a lot...
Pauwels Ferdi, I'm so pleased that you enjoyed this pretty view of Fall! Thank you so much for visiting and taking the time to comment. Very best regards from the USA,
Mary Alice
Very good view! LIKE!
Greetings Z.
Greetings, Zanot, and thank you so much for your enthusiastic visit. I'm so pleased that you enjoyed this beautiful Autumn view. Happy weekend wishes to you from the USA,
Mary Alice
Wonderful shot! Beautiful place! LIKE
Greetings, Pavlik90, and thank you very much for your kind words. I'm happy that you stopped by and enjoyed this Autumn view.
Best wishes to you from the USA,
Mary Alice
Photo taken in Upson County, GA, USA


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Historians Now: Founders' Son: A Life of Abraham Lincoln by Richard Brookhiser
Richard Brookhiser discusses his book, Founders' Son: A Life of Abraham Lincoln.
Richard Brookhiser discusses his book, Founders' Son: A Life of Abraham Lincoln.
David S. Reynolds talks about editing the Norton Critical Edition of Lincoln's Selected Writings.
James Oakes discusses his book, The Radical and the Republican: Frederick Douglass, Abraham Lincoln and the Triumph of Antislavery Politics.
West Virginia University historian Aaron Sheehan-Dean offers thoughts on the Library of America series The Civil War Told by Those Who Lived It at Gilder Lehrman webinar on the Civil War 150 traveling exhibition. The exhibition is co-sponsored by the Gilder Lehrman Institute, the Library of America, and the National Endowment for the Humanities.
James I. Robertson, Alumni Distinguished Professor in history at Virginia Polytechnic Institute and State University, re-examines, in Stonewall Jackson: The Man, the Soldier, the Legend, the life and the aura of Thomas "Stonewall" Jackson.


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Contributed equally to work.
Full-Length Original Research
Autoantibodies to neuronal antigens in children with new-onset seizures classified according to the revised ILAE organization of seizures and epilepsies
Version of Record online: 23 OCT 2013
DOI: 10.1111/epi.12405
Wiley Periodicals, Inc. © 2013 International League Against Epilepsy
Volume 54, Issue 12, pages 2091–2100, December 2013
Additional Information
How to Cite
Epilepsia, 54(12):2091–2100, 2013
Publication History
- Issue online: 4 DEC 2013
- Version of Record online: 23 OCT 2013
- Manuscript Accepted: 3 SEP 2013
Funded by
- National Health and Medical Research Council (NHMRC), Australia
- The Wellcome Trust
- Clinical Research Training Fellowship
- Epilepsy Research United Kingdom
- NIHR Oxford Biomedical Research Centre
- Pediatrics;
- Epilepsy;
- Autoimmune;
- N-methyl-d-aspartate receptors;
- Glutamic acid decarboxylase;
- Top of page
- Summary
- Methods
- Results
- Discussion
- Acknowledgments
- Disclosures
- References
- Biographies
- Supporting Information
Potentially pathogenic autoantibodies are found increasingly in adults with seizure disorders, including focal seizures and those of unknown cause. In this study, we investigated a cohort of children with new-onset seizures to see whether there were autoantibodies and the relationship to any specific seizure or epilepsy type.
We prospectively recruited 114 children (2 months to 16 years) with new-onset seizures presenting between September 2009 and November 2011, as well as 65 controls. Patients were clinically assessed and classified according to the new International League Against Epilepsy (ILAE) organization of seizures and epilepsies classification system. Sera were tested for autoantibodies to a range of antigens, blind to the clinical and classification details.
Key Findings
Eleven (9.7%) of 114 patients were positive for one or more autoantibodies compared to 3 of 65 controls (4.6%, p = ns). Patients had antibodies to the voltage-gated potassium channel (VGKC) complex (n = 4), contactin-associated protein-like 2 (CASPR2) (n = 3), N-methyl-d-aspartate receptors (NMDARs) (n = 2), or VGKC-complex and NMDAR (n = 2). None had antibodies to glutamic acid decarboxylase, contactin-2, or to glycine, 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl) propionic acid (AMPA), or γ-aminobutyric acid B receptors. Ten of these 11 patients were classified as having epilepsy according to the new ILAE organization of seizures and epilepsy. Although, there were no significant differences in the demographic and clinical features between antibody-positive and antibody-negative patients, the classification of "unknown cause" was higher in the antibody positive (7/10; 70%) compared with the antibody negative subjects (23/86; 26.7%; p = 0.0095, Fisher's exact test). Furthermore, four of these seven patients with epilepsy (57.1%) were classified as having predominantly focal seizures compared with 12 of the 86 antibody-negative patients (13.9%; p = 0.015).
Because autoantibodies were more frequent in pediatric patients with new-onset epilepsy of "unknown cause," often with focal epilepsy features, this group of children may benefit most from autoantibody screening and consideration of immune therapy.
A clear clinical diagnosis of patients who present with seizures and the subsequent accurate classification of their epilepsies is extremely important to the neurologist for treatment and prognosis and to the neuroscientist for facilitation of focused, robust research. To meet these dual needs, the revised International League Against Epilepsy (ILAE) system for the organization of seizures and epilepsies, published in 2010, presented a conceptualized framework for everyday clinical practice that also tried to reflect the advancement of basic epilepsy research (Berg et al., 2010). The most important and subsequent controversial recommendation, involved the replacement of the terms "idiopathic, symptomatic, and cryptogenic" with "genetic, structural/metabolic, and unknown cause" when describing etiology (Shinnar, 2010; Panayiotopoulos, 2011, 2012).
It is estimated that epilepsies of unknown cause account for approximately one third of all cases of epilepsy in adults (Berg et al., 2010) and 23–35% in children (van Campen et al., 2013). They are an important group for the identification of new etiologies, and an area in which the emerging identification of specific antibodies may be increasingly important. Antibodies (Abs) directed against neuronal surface proteins such as the voltage-gated potassium channel (VGKC) complex and its associated proteins, leucine-rich, glioma inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2) and contactin-2, the N-methyl-d-aspartate receptor (NMDAR), γ-aminobutyric acid B receptor (GABABR), and 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl) propanoic acid receptor (AMPAR) and against intracellular proteins such as glutamic acid decarboxylase (GAD) have already been described. The association between these antibodies and seizures is manifest in patients with limbic encephalitis who often have temporal lobe seizures, and NMDAR-Ab encephalitis in which patients can have focal or generalized seizures. In addition, each of the antibodies has been identified in a proportion of patients with epilepsy but without other encephalitic clinical signs or symptoms, such as cognitive impairment or neuropsychiatric features (Peltola et al., 2000; McKnight et al., 2005; Majoie et al., 2006; Irani et al., 2008; Niehusmann et al., 2009; Barajas et al., 2010; Quek et al., 2012; Brenner et al., 2013), prompting the increased recognition of "autoimmune epilepsy" (Palace & Lang, 2000; Bien & Scheffer, 2011; Irani et al., 2011a; Vincent et al., 2011; Nabbout, 2012; Quek et al., 2012). The identification of a putative autoimmune etiology in some forms of epilepsies suggests that early identification of specific autoantibodies and subsequent treatment with immunotherapy could lead to reduced seizure frequency and may improve outcomes (Irani et al., 2011b; Quek et al., 2012).
In children, NMDAR-Ab encephalitis and VGKC-complex-Ab–associated encephalitis have also been recognized, with seizures being an important presenting symptom (Dale et al., 2009b; Florance et al., 2009; Haberlandt et al., 2011; Suleiman et al., 2011a). Fewer reports are available regarding the association of neuronal antibodies in defined pediatric epilepsies (e.g., Dhamija et al., 2011; Suleiman et al., 2011b, 2013). Here, we recruited a prospective cohort of children with new-onset seizures, recorded their clinical features, and classified them according to the revised ILAE organization of seizures and epilepsies. At the end of the study period, and blinded to the clinical and classification details, the sera taken at admission were tested for autoantibodies.
- Top of page
- Summary
- Methods
- Results
- Discussion
- Acknowledgments
- Disclosures
- References
- Biographies
- Supporting Information
Recruitment criteria of patients with new-onset seizures
We prospectively recruited children aged 2 months to 16 years with new-onset seizures presenting to the Children's Hospital at Westmead Hospital, Sydney between September 2009 and November 2011. One hundred fourteen children were included in the study (58 females, mean age 4.39 years, median 2.55 years, range 0.13–15.25 years). All patients with a well-described paroxysmal episode compatible with a clinical seizure and who had serum collected within 6 months of seizure onset were included (in and outpatients). Neonates (0–60 days), and patients with clear etiologies for their seizures such as brain tumor, bacterial meningitis, and brain injury (traumatic or ischemic) were excluded from the study.
Control group
The control group for antibody testing consisted of hospital patients (n = 65, 27 female, mean age 9 years, median 9.14 years, range 1–16 years) who had serum collected as part of their routine investigations during 2007. The underlying medical problems were immunologic/inflammatory or allergic (n = 28); hematologic/oncologic (n = 20); or other medical condition such as respiratory, gastrointestinal, and endocrine (n = 17). Recruitment of the patients and control groups for this study was approved by the hospital ethics committee, and written consent was obtained from the patients or their families.
Antibody assays
Patients were tested for antibodies to VGKC complex and NMDAR (n = 114); LGI1, CASPR2, and GAD (n = 113); glycine receptor (GlyR), AMPAR, contactin-2 (n = 112); and GABABR (n = 92). The antibodies to VGKC complex and GAD were tested by radioimmunoassays as described previously (McKnight et al., 2005). VGKC-complex-Abs and GAD levels >100 pM and 100 >U/ml, respectively, were considered positive. All other neuronal antibodies were tested by cell-based assays (CBAs) (for full descriptions see Irani et al., 2008, 2010a,b; Dale et al., 2009b). The CBAs were scored on a visual scale 0 (no binding), 1 (low but specific binding)-4 (strong binding to all transfected cells) by two independent observers. If positive, samples were titrated by serial dilution, and the final dilution at which the sample remained positive (score of 1) was given. The 65 controls were tested at the same time as the new-onset seizure patients for the following antibodies: LGI1, CASPR2, contactin-2, NMDAR, AMPAR, GABABR, GAD, and GlyR (n = 65) and VGKC complex (n = 62). Assays were performed and read by SW who was blinded to the clinical data, and re-scored by an additional reader. Incomplete testing was due to insufficient sample available. Cerebrospinal fluid testing could not be performed in this study owing to limited sample availability.
Epilepsy classification
Classifications of seizure types, epilepsy, electroclinical syndrome, and etiology were performed by the primary investigator, a pediatric neurologist (JS), and were cross-checked by a pediatric neurologist and epileptologist (DG). Both were blinded to the results of the antibody testing at the time of performing the classification. The seizure type at presentation was determined for the 114 patients and classified where possible using the new ILAE organization of seizures and epilepsies (Engel, 2006; Berg et al., 2010) and terminology for ictal semiology (Blume et al., 2001). Classification of a patient's condition into an epilepsy syndrome was made by reviewing the child's age, neurologic and developmental state, seizure semiology (at onset and on follow up), electroencephalography (EEG), imaging, and other relevant investigations findings. The structure of the latest proposed ILAE organization of seizures and epilepsies (Berg et al., 2010) was used for this purpose in addition to previous ILAE classification when required (including Commission, 1989; Engel, 2001; Engel, 2006). Patients who had features compatible with one of the electroclinical syndromes described in the new ILAE organization of seizures and epilepsies were classified as such irrespective of the etiology of their epilepsy. For example, patients with epileptic spasms and hypsarrhythmic EEG were classified as West syndrome, despite some of these patients having a known structural or metabolic cause. Patients who did not fit into any electroclinical syndrome were classified (as per the ILAE 2010 recommendation) on the basis of presence of metabolic diseases or structural abnormalities. The term "epilepsy of unknown cause" was used to classify those patients who did not fit into an electroclinical syndrome and who had no structural or metabolic cause found for their epilepsy. Patients with seizures that are traditionally not diagnosed as a form of epilepsy including febrile seizures were kept in a separate group as per Berg et al. (2010). We also added patients with acute symptomatic (provoked) seizures (Beghi et al., 2010; Beleza, 2012) and with single unprovoked seizures to this group.
Statistics and data analysis
Fisher's exact test was used to compare categorical data and the Mann-WhitneyU test to compare continuous data variables.
- Top of page
- Summary
- Methods
- Results
- Discussion
- Acknowledgments
- Disclosures
- References
- Biographies
- Supporting Information
Demographic, clinical features, investigations, and treatment of total cohort
One hundred one of the 114 patients in the study were admitted to the hospital during their initial presentation or during the first 6 months after seizure onset (median length of stay 4.5 days, range 1–360 days). Eighteen patients required admission to intensive care. Thirty-six patients had one or more preexisting developmental, motor, or psychiatric abnormalities including 33 with developmental delay and/or learning difficulty, 14 with motor deficits, and 4 with behavioral or psychiatric disturbance. There was a positive family history of seizures or epilepsy (including febrile seizures) in the first-degree relatives of 19 patients (16.7%).
Nearly half of the patients (n = 56) presented with focal seizures (Table S1) including 12 with focal dyscognitive seizures. Twenty-one patients presented in status epilepticus and 77 patients had an early recurrence of seizures (occurring within 48 h of first seizure onset). At the time of presentation, 32 patients had intercurrent infections including 21 with fever (defined as 37.8°C or higher [axillary temperature]), 7 of whom fulfilled the definition of febrile seizures (Berg et al., 1992). Seizures were associated with other features in 48 patients including encephalopathy (n = 33), behavioral or psychiatric alteration (n = 27), motor impairment (n = 17), cognitive alteration (n = 12), and movement disorder (n = 5).
EEG findings were abnormal in 86 (76.1%) of 113 patients, and contributed significantly to the epilepsy diagnosis and classification in 22 patients (19.5%). Brain magnetic resonance imaging (MRI) scans were abnormal in 52 of 105 patients and were diagnostic or suggestive of a cause of the epilepsy in 30 patients (28.6%). CSF analysis for pleocytosis, protein, neopterin, or infections was performed in 66 (57.9%) of 114 patients and contributed to epilepsy diagnosis in 13 patients (19.7%). Other investigations were performed as clinically indicated including metabolic, genetic, infectious, and immunologic investigations, and contributed to the epilepsy diagnosis in six patients.
Forty-six patients received acute seizure treatment and 85 patients received long-term (7 days or longer) antiepileptic drugs (AEDs). Twenty-three patients received variable regimens of immunotherapy; including steroids alone (oral prednisolone, intramuscular synthetic adrenocorticotropic hormone [ACTH] and intravenous methyl prednisolone) in 18 and steroids and intravenous immunoglobulins (IVIGs) in 5. In all cases the decision to treat with immunotherapy was made on the basis of a clinical presentation suggestive of an immune-mediated cause (e.g., Rasmussen encephalitis); a recognized immunotherapy responsive seizure syndrome (e.g., West syndrome); or as adjunctive treatment in intractable epilepsy, prior to and independent of autoantibody test results. A positive clinical response, seen in 15 of 23, was defined as clinical improvement in seizures and/or encephalopathy as judged by the treating clinician. Thirteen of 18 patients given steroids alone showed improvement, including West syndrome (n = 5), epilepsy of unknown cause (n = 4), Lennox-Gastaut syndrome (n = 2), epilepsy attributed to malformation of cortical development (n = 1), and epilepsy attributed to perinatal insult, encephalomalacia (n = 1). Two of five patients who received steroids in combination with IVIG also showed a positive clinical response (Rasmussen encephalitis, n = 1; and basal ganglia encephalitis, n = 1).
Ten (8.8%) of the 114 patients had no follow-up information available; for the remaining 104 patients, the mean length of follow-up (from seizure onset) was 11.7 months (median 11 months, range 1–36 months) at the time of assessment. Eighty-four patients had ongoing epilepsy, including 23 with drug-resistant (refractory) epilepsy (Kwan et al., 2010). Thirty-two patients had new long-term deficits (other than epilepsy), including one or more of the following: developmental delay or cognitive impairment (n = 24), behavioral/psychiatric impairment (n = 18), and motor deficits (n = 13).
Epilepsy subgroups separated by classification
The 114 patients with new-onset seizures were classified according to the structure of the latest proposed ILAE organization of seizures and epilepsies (Berg et al., 2010), Eighteen patients had seizures not traditionally diagnosed as a form of epilepsy; the remaining 96 patients had epilepsy: 30 with electroclinical syndromes, 33 with epilepsy attributed to structural-metabolic causes, and 33 with epilepsy of unknown cause (Table 1).
|Conditions with epileptic seizures that are traditionally not diagnosed as a form of epilepsy (n = 18)
|No. of patients
|Febrile seizures
|Acute symptomatic (provoked seizures)
|Infection mediated
|Posterior reversible encephalopathy syndrome (PRES) secondary to hypertension
|Single unprovoked seizure
|ILAE classification/electroclinical syndrome (n = 96)
|No. of patients
|Electroclinical syndrome (n = 30)b
|West syndrome
|Benign infantile epilepsy
|Dravet syndrome
|Myoclonic epilepsy in infancy (MEI)
|Lennox-Gastaut syndrome (LGS)
|Febrile seizures plus (FS+)
|Panayiotopoulos syndrome
|Epilepsy with myoclonic–atonic seizures
|Benign epilepsy with centrotemporal spikes (BECTS)
|Childhood absence epilepsy (CAE)
|Late-onset childhood occipital epilepsy (Gastaut type)
|Autosomal dominant epilepsy with auditory features (ADEAF)
|Epilepsy attributed to structural-metabolic causes (n = 33)
|Rasmussen syndrome
|Malformation of cortical development (MCD)
|Perinatal insults
|Neurocutaneous syndrome
|Epilepsies of unknown cause (n = 33)
Antibodies and clinical features of positive patients and controls
Eleven (9.7%) of 114 patients with new-onset seizures were positive for one or more of the tested antibodies: VGKC-complex (n = 4), CASPR2 (n = 3), NMDAR (n = 2), and VGKC-complex and NMDAR (n = 2) (Fig. 1A). None of the patients or controls were positive for GAD, GlyR, AMPAR, GABABR, LGI1, or contactin-2 antibodies.
All antibody-positive patients had been admitted to hospital on presentation, compared to 87.4% of the antibody-negative group. The mean duration of hospital stay for the positive patients was 3.72 days (median 3 days, range 2–11 days), but none required admission to the intensive care unit. Two of the antibody-positive patients had preexisting developmental delay, which was severe in one. There was a positive family history of epilepsy in two patients. One of the patients (case 8) had status epilepticus of 45 min duration at presentation. Early seizure recurrence in the first 48 h of presentation occurred in 7 of the 11 patients. Features associated with seizures on presentation are presented in Table 2. Overall there were no significant differences in the demographic and clinical features between antibody-positive and antibody-negative patients (Table 3). The timing of the samples from symptom onset for the positive patients was less but not significantly different from that of the antibody-negative patients (mean 17.5; median 4, range 1–75 days vs mean 40; median 20 and range 1–180 days, respectively). The mean age was 4.39 years for both positive and negative patients; median was 3.4 years for antibody-positive patients and 2 years for antibody-negative patients.
|Age and sex
|Seizure type at onset/early seizure recurrence
|Associated features
|Seizure type on follow-up
|Number of AED on follow-up (mo)
|ILAE classification
|Ab positivity titration
|Focal dyscognitive/+
|Epileptic: left frontotemporal. Seizure: left temporal
|Focal dyscognitive, atypical absence
|1 (11)
|Epilepsy of unknown cause (focal-temporal lobe)
|Focal versive/−
|Epileptic: generalized with bifrontal lead
|Generalized tonic–clonic
|1 (6)
|Epilepsy of unknown cause (undetermined)
|Generalized tonic clonic/+
|Slowing: right posterior
|Generalized tonic– clonic, atonic
|2 (6)
|Epilepsy of unknown cause (generalized)
|Focal dyscognitive/+
|Motor deficit
|Focal dyscognitive, atypical absence
|1 (17)
|Epilepsy of unknown cause (focal)
|Focal tonic with secondary generalization/+
|Intercurrent infection
|Slowing: right temporal Epileptic: central
|Focal tonic with secondary generalization
|1 (11)
|Epilepsy of unknown cause (focal)
|CASPR2 (1 in 200b)
|Focal tonic– clonic/−
|Intercurrent infection, fever
|Not done
|Not done
|No follow-up
|Acute symptomatic (provoked) seizure
|CASPR2 (1 in 100)
|Focal myoclonic/+
|Encephalopathy, motor deficit (hemiparesis)
|Slowing: generalized Epileptic: left parietal
|Left parietal hyperintensity
|2 (13)
|Epilepsy attributed to metabolic cause
|CASPR2 (1 in >400)
|Focal dyscognitive/−
|Slowing: right occipital.
|No follow-up
|Epilepsy of unknown cause (focal-occipital lobe)
|NMDAR (1 in 100)
|Generalized myoclonic/+
|Encephalopathy, behavioral alteration
|Slowing: generalized Epileptic: right frontal
|Corpus callosal dysgenesis, frontal heterotopia
|Mixed (myoclonic, tonic, atonic)
|4 (12)
|Lennox–Gastaut syndrome
|NMDAR (1 in 100)
|Generalized tonic/−
|Preceding infliximab infusion
|High voltage generalized spike and slow wave
|Generous ventricles
|1 (10)
|Epilepsy of unknown cause (generalized)
|VGKC (368) NMDAR (1 in 80)
|Generalized tonic–clonic/+
|Intercurrent infection
|Asymmetric hippocampi
|Generalized tonic–clonic
|2 (7)
|Febrile seizure plus (FS+)
|VGKC (233) NMDAR (1 in 80)
|ILAE classification
|Presence of characteristic in Ab-positive patients (%) n = 11
|Presence of characteristic in Ab-negative patients (%) n = 103
|(A) Epileptic seizures not diagnosed as a form of epilepsy (n = 18)
|1 (9.1)
|17 (16.5)
|Patients with epilepsy
|n = 10
|n = 86
|Electroclinical syndrome (n = 30)
|2 (20)
|31 (36)
|Epilepsy attributed to structural-metabolic causes (n = 33)
|1 (10)
|32 (37)
|Epilepsy of unknown cause (n = 33)
|7 (70)
|23 (26.7)
|Epilepsy of unknown cause (focal) (n = 16)
|4 (40)
|12 (13.9)
|ns (0. 059)
|Epilepsy of unknown cause (generalized) (n = 10)
|2 (20)
|5 (5.8)
|Epilepsy of unknown cause (spasms) (n = 4)
|0 (0)
|4 (4.7)
|Epilepsy of unknown cause (undetermined) (n = 3)
|1 (10)
|2 (2.3)
|(B) Clinical characteristic
|Medical history
|Previously normal (n = 78)
|9 (81.8)
|69 (67.0)
|First seizure
|7 (63.6)
|49 (47.6)
|4 (36.4)
|38 (36.9)
|Status epilepticus
|1 (9.1)
|20 (19.4)
|Early seizure recurrence
|7 (63.6)
|70 (68.0)
|Hospitalization (n = 101)
|11 (100)
|90 (87.4)
|Intensive care (n = 18)
|0 (0)
|18 (17.5)
|Associated features
|1 (9.1)
|20 (19.4)
|3 (27.3)
|28 (27.2)
|2 (18.2)
|31 (30.1)
|Movement disorder
|0 (0)
|5 (4.8)
|Behavioral abnormality
|1 (9.1)
|26 (25.2)
|Cognitive abnormality
|0 (0)
|12 (11.8)
|Motor deficit
|2 (18.2)
|15 (14.6)
|Ongoing epilepsy
|9 (81.8)
|75 (72.8)
|New deficit
|2 (18.2)
|30 (29.1)
|Developmental delay
|0 (0)
|16 (15.5)
|Behavioral/psych impairment
|2 (18.2)
|16 (15.5)
|Cognitive impairment
|0 (0)
|17 (16.5)
EEG and MRI brain were performed in 10 of 11 antibody-positive patients. The EEG results were abnormal in 8 and MRI abnormalities were recorded in 4 (Table 2). CSF was tested in only 4 of the 11, and it was normal apart from CSF neopterin, which was elevated in 1 of 3 tested at 68 nm (normal <30; case 1), suggestive of central nervous system (CNS) inflammation (Dale et al., 2009a).
Nine of the positive patients received long-term antiepileptic drugs, but none of the antibody-positive patients received immunotherapy during the period of disease course studied. Two antibody-positive cases were lost to follow-up (cases 8 and nonepileptic case 6). The mean length of follow-up for the remaining nine cases was 10.33 months (median 11 months, range 6–11 months), and was not different from the remaining antibody-negative cases. All of the nine patients with follow-up had ongoing epilepsy, and one had drug-resistant epilepsy (case 9). Five patients were on one AED, three were on two AEDs, and one was on four AEDs. Two patients had a new neurologic or developmental deficit (other than epilepsy) including speech impairment and hyperactivity (case 3), and motor deficit and behavioral alteration (case 5).
Three of the 65 controls (4.6%) were positive for antibodies. Control 1 (VGKC-complex-Abs 497 pm) was a 3-year-old boy with type 1 diabetes mellitus. Control 2 (VGKC-complex-Abs 200 pm) was a 2-year-old boy with vomiting illness and poor weight gain. Control 3 (NMDAR score 2, end point dilution 1 in 100) was an 8-year-old boy with an acute lymphocytic leukemia relapse treated with bone marrow transplantation, complicated by chronic graft-versus-host disease. No neurologic abnormality was noted in any of these controls, although no natural follow-up was recorded in control 2.
Patients with antibody-positive new-onset epilepsy according to the new ILAE organization of seizures and epilepsies
One patient with low levels of CASPR2 antibodies had nonepileptic (provoked) seizures (patient 6, Table 2). The remaining 10 antibody-positive patients with epilepsy had the following ILAE epilepsy classifications: electroclinical syndrome (n = 2), epilepsy attributed to structural metabolic causes (n = 1), and epilepsy of unknown cause (n = 7). In the total epilepsy cohort, after exclusion of nonepileptic patients (n = 96), only 2 of 30 patients with electroclinical syndromes (6.7%) had positive antibodies (cases 9 and 11). Case 9 had Lennox-Gastaut syndrome (LGS) and antibodies to NMDAR, and case 11 had febrile seizures plus with antibodies to both the NMDAR and VGKC-complex. Similarly, only one of 33 patients with epilepsy attributed to a structural-metabolic cause (3%) had positive antibodies (case 7), again not significantly different from the controls; this case had mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) and was positive for CASPR2 antibodies.
In comparison, 7 of 33 patients from the epilepsy cohort with epilepsy of unknown cause (21.2%) had positive antibodies, which was different from the controls (4.6%; p = 0.03, Fisher's exact test) (Fig. 1). Overall, the proportion of antibody-positive patients classified with epilepsy of unknown cause (7/10; 70%) was significantly higher than the remaining proportion of antibody-negative epilepsy subjects (23/86; 26.7%; p = 0.0095, Fisher's exact test) (Fig. 1B). Furthermore, 4 (57%) of these 7 patients had focal epilepsy compared with 12 of the 86 antibody-negative patients (13.9%; p = 0.059, Table 3).
Of these seven antibody-positive patients with epilepsy of unknown cause, four had VGKC-complex-Abs only (cases 1–4), three of whom presented with focal seizures, and three had early seizure recurrence (cases 1, 3, and 4) (Table 2). Case 5 had CASPR2 antibodies, presented with focal tonic–clonic seizures and had intercurrent infections. Case 8 was positive for NMDAR-Abs and had focal dyscognitive seizures and focal status epilepticus on presentation. Case 10 was double positive for NMDAR and VGKC-complex and had a number of comorbidities. She presented with seizures following an infliximab infusion given for her treatment-resistant Crohn's disease. Infliximab is a monoclonal antibody used in the treatment of some autoimmune diseases and previously described to be associated with seizures (Brigo et al., 2011).
- Top of page
- Summary
- Methods
- Results
- Discussion
- Acknowledgments
- Disclosures
- References
- Biographies
- Supporting Information
The finding of pathologically relevant autoantibodies to neuronal proteins in a small but significant minority of patients with epilepsy (9–13%, McKnight et al., 2005; Majoie et al., 2006; Brenner et al., 2013) is becoming increasingly recognized, but there have been limited studies in children with epilepsy. Herein we studied a large group of children presenting with new-onset seizures to a tertiary children's hospital and related the results to the recently revised ILAE organization of seizure and epilepsy. The cohort included a heterogeneous group of patients with a wide spectrum of seizure severity and etiology. Overall antibody positivity was detected in 9.6% of the cohort, and surprisingly in 4.6% of the controls. Nevertheless, in patients with epilepsy of "unknown cause," often with focal seizures, antibodies were more frequent than in the other categories of seizures.
Many patients in the cohort were young and complicated, required intensive acute treatment, or had ongoing refractory epilepsy, as they represented an inpatient sample rather than a community outpatient sample.
The cohort description and classification represented a challenging exercise, particularly at a time when the ILAE classification and terminology is still evolving. It is notable that the patients were classified with investigators blinded to the result of antibody testing. Nearly one third of the patients were determined to have an "unknown cause" for their epilepsy, as also noted in a recent study comparing the new and old systems (van Campen et al., 2013). Of note, 7 of the 10 antibody-positive results were in this epilepsy category. The most frequently found antibody was to the VGKC-complex (4/10). These four patients, however, were negative for the VGKC-complex proteins LGI1, contactin-2, and CASPR2. The lack of an identified complex protein has been reported previously in children (Dhamija et al., 2011; Ilingworth et al., 2011; Suleiman et al., 2011b) and contrasts with adults in whom antibodies to LGI1, and less frequently to CASPR2, are often found (Irani et al., 2008, 2010a,b; Lai et al., 2010), although not inevitably (Patterson et al., 2013). It is likely that the VGKC-complex antibodies bind to other antigenic targets that are yet to be identified in children (Hacohen et al., 2013). On the other hand, three patients were positive for CASPR2 antibodies, which have not been identified before in children, but were negative for VGKC-complex antibodies in the radioimmunoassay, so would have been missed with standard VGKC-complex-Ab screening.
None of the VGKC-complex or CASPR2 antibody-positive patients had a phenotype typical of limbic encephalitis, although most of them presented with focal seizures, suggesting that neuronal antibodies can be present beyond the spectrum of this recognized syndrome, especially in children. Two patients with positive NMDAR antibodies had epilepsy in the absence of classic autoimmune NMDAR-Ab encephalitis: one presented with focal dyscognitive seizures and one had mixed seizure types. This is similar to adult cases described with new-onset epilepsy associated with NMDAR Abs (Niehusmann et al., 2009; Brenner et al., 2013). In addition, two patients in our cohort, both presenting with generalized seizures, were positive for both NMDAR and VGKC-complex-Abs. The finding of two or more neuronal Abs is beginning to be recognized (Irani et al., 2010a; Pellkofer et al., 2010; Haberlandt et al., 2011) and may reflect a wider activation of the immune system, perhaps by infections or possibly as a secondary response to neuronal damage. NMDAR-Abs have recently been reported in one patient with MELAS (Finke et al., 2012), and secondary activation may be a possible explanation for the finding of two antibody-positive patients with known structural or metabolic cause for their epilepsy (cases 7 and 9).
Nine of the 11 positive patients with recorded follow-up had on going epilepsy and/or seizures, but unfortunately none of the 11 positive patients received immunotherapy. These patients did not develop long-term cognitive or behavioral impairment, although the follow-up was short and detailed neuropsychology was not done. Because this was a prospective observational cohort study, we can only hypothesize that immunotherapy, if given, might have improved the epilepsy outcome in these patients.
The control group consisted of children with various immunologic, oncologic, and medical conditions, and three controls were positive for one of the tested antibodies, although they did not have apparent neurologic symptoms. This level of positivity appears to be higher than in adult control cohorts (e.g., McKnight et al., 2005; Brenner et al., 2013). However, few other reports have used childhood controls; indeed all children in this cohort had been hospitalized, and approximately one third of the patients had infectious/inflammatory conditions. The ability to develop antibodies in response to circulating pathogens or environmental factors may be higher in children, particularly in those who are already unwell. However, if antibody levels are sustained, it is possible that these children could be at risk of future neurologic dysfunction.
This study is the first to describe a relatively large prospective cohort of pediatric patients with new-onset seizures, apply the new ILAE system for the organization of seizures and epilepsies (as for Berg et al., 2010), and test them for neuronal antibodies within 6 months of seizure onset. We found that specific neuronal antibodies were more common, and these may play an etiologic role in children with epilepsy of unknown cause, indicating that the new ILAE system may "facilitate the identification of nongenetic determinants of epilepsy" (Berg 2010). We suggest that further antibody testing could be performed in pediatric epilepsy patients classified in this "unknown" category, particularly those with focal epilepsy; it has already been suggested that increasing the number of investigations should help to identify the etiologies of this group (van Campen et al., 2013). Moreover, because the new ILAE organization does not incorporate autoimmune forms in the epilepsy or etiology classification, the possibility of including "immune-mediated epilepsy" as a separate category (Brenner et al., 2013) needs to be considered. However, it is also possible that the presence of neuronal antibodies are, in some circumstances, an epiphenomenon or secondary to structural damage or generalized immune activation. Further studies should concentrate on identifying antibodies in children with epilepsy of unknown cause closer to disease onset, with systematic testing of the effects of immune therapies, and applying the recent guidelines to determine whether these seizure-related antibodies define forms of "autoimmune epilepsy."
- Top of page
- Summary
- Methods
- Results
- Discussion
- Acknowledgments
- Disclosures
- References
- Biographies
- Supporting Information
The study was supported by research awards from the National Health and Medical Research Council (NHMRC), Australia (RD, JS); The Wellcome Trust (Clinical Research Training Fellowship to SW) Epilepsy Research United Kingdom (BL), and the NIHR Oxford Biomedical Research Centre (PW, AV). In addition, we would like to thank Philippa Pettingill, Rosie Pettingill, Mark Woodhall, Leslie Jacobson, and Sian Peach (Oxford) for technical support.
- Top of page
- Summary
- Methods
- Results
- Discussion
- Acknowledgments
- Disclosures
- References
- Biographies
- Supporting Information
AV, PW, BL, and the Nuffield Department of Clinical Neurosciences in Oxford receive royalties and payments for antibody assays. JS, SW, DG, FB, KP, PP, AN, and RD do not report any conflict of interest with respect to this study. We confirm that the authors have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.
- Top of page
- Summary
- Methods
- Results
- Discussion
- Acknowledgments
- Disclosures
- References
- Biographies
- Supporting Information
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Supporting Information
- Top of page
- Summary
- Methods
- Results
- Discussion
- Acknowledgments
- Disclosures
- References
- Biographies
- Supporting Information
|Word document
|Table S1. Seizures types at onset for the total cohort (as Blume et al., 2001).
Please note: Wiley Blackwell is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.


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balmnoun [ C or U ]uk /bɑːm/ us /bɑːm/
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I know the "Big Game" is a huge thing for us guys. Testosterone at it's highest level. Watching men put punishing hits on other men. Wings & Beer. Laughing at the crazy commercials. Let's be honest ladies. Why do you watch the Super Bowl???
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Test of the Month
Serum transferrin receptor
Version of Record online: 28 AUG 2008
DOI: 10.1002/ajh.21279
Copyright © 2008 Wiley-Liss, Inc.
American Journal of Hematology
Volume 83, Issue 11, pages 872–875, November 2008
Additional Information
How to Cite
Skikne, B. S. (2008), Serum transferrin receptor. Am. J. Hematol., 83: 872–875. doi: 10.1002/ajh.21279
Publication History
- Issue online: 24 OCT 2008
- Version of Record online: 28 AUG 2008
- Accepted manuscript online: 28 AUG 2008 12:00AM EST
- Manuscript Accepted: 20 AUG 2008
- Manuscript Revised: 19 AUG 2008
- Manuscript Received: 23 MAY 2008
- Abstract
- References
- Cited By
Transferrin receptors (TfRs) are the conventional pathway by which cells acquire iron for physiological requirements. Under iron-deficient conditions there is an increased concentration of surface TfR, especially on bone marrow erythroid precursors, as a mechanism to sequester needed iron. TfRs are also present in the circulation, and the circulating serum TfR (sTfR) level reflects total body TfR concentration. Under normal conditions erythroid precursors are the main source of sTfR. Disorders of the bone marrow with reduced erythroid precursors are associated with low sTfR levels. The sTfR concentration begins to rise early in iron deficiency with the onset of iron-deficient erythropoiesis, and continues to rise as iron-deficient erythropoiesis progressively worsens, prior to the development of anemia. The sTfR level does not increase in anemia of chronic inflammation, but is increased when anemia of chronic inflammation is combined with iron deficiency. The sTfR level is also increased in patients with expanded erythropoiesis, including hemolytic anemias, myelodysplastic syndromes, and use of erythropoietic stimulating agents. The ratio of sTfR/ferritin can be used to quantify the entire spectrum of iron status from positive iron stores through negative iron balance, and is particularly useful in evaluating iron status in population studies. The sTfR/log ferritin ratio is valuable for distinguishing anemia of chronic inflammation from iron deficiency anemia, whether the latter occurs alone or in combination with anemia of chronic inflammation. Am. J. Hematol., 2008. © 2008 Wiley-Liss, Inc.


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This Titanfall: Expedition TV spot shows off all three DLC maps
Titanfall: Expedition is out on Xbox One and PC now, but is coming to Xbox 360 in June. EA's new TV spot shows all three of the maps in action.
It follows my Titanfall: Expedition review and gameplay videos. Check it out for some raw footage of War Games, Swampland and Runoff.
Here's the clip, via MP1st:
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Enter your stay dates and any discounts you qualify for to see Jerusalem, Israel rates found only on HotelPlanner!
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I need to an algorithm, to write frames (Pictures) into a file, which can be read by some Video-Cutting/Producing-Software to work with.
So I got frames, and I want to give them a input into a function/Method. Let's do i in Java.
How can I do this? Is there a simple way, I can write videofiles without using any systemcodecs?
I just need a uncompressed video with a constant Framerate (25 fps or 50 fps) that will take my true-Color pictures (2D-arrays of Colors), so that I can use that video in my Videoprogramm to work with.
I never found any fileformat that fits to that.
Can You help me?
Greetings from Austria, and thanks. Flo.


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three comments
great set :)
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CHARLOTTE WATER FACTS AND FIGURES(Facts and figures current until June 30, 2017.) The largest public water and wastewater utility in The Carolinas, Charlotte Water proudly serves more than 954,644 customers in the City of Charlotte and greater Mecklenburg County -- including the towns of Matthews, Mint Hill, Pineville, Huntersville, Davidson, and Cornelius. WATER OPERATIONS Water Treatment Capacity = 242 million gallons per day (mgd) Number of Treatment Plants = 3 Franklin 181 mgd capacity Vest 36 mgd capacity Lee S. Dukes 25 mgd capacity FY16 Average Daily Pumped = 111.61 mgd FY16 Highest Daily Pumped = 146.37 mgd All-time Highest Pumped = 169.229 mgd (record set August 20, 2007) Active Water Service Connections = 279,609Water Mains = 4,269 miles WASTEWATER OPERATIONS Wastewater Treatment Capacity = 123 mgd Number of Treatment Plants = 5 Sugar Creek 20 mgd capacity Irwin Creek 15 mgd capacity McAlpine Creek 64 mgd capacity Mallard Creek 12 mgd capacity McDowell Creek 12 mgd capacity Average Daily Treatment = 88 mgd Active Wastewater Service Connections = 246,299Wastewater Mains = 4,244 miles Lift Stations = 80


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Jobs Bill OK'd By Senate
Legislation that aims to boost job growth by giving employers tax breaks if they hire the unemployed just passed the Senate in a 70-28, fairly bipartisan vote.
The $35 billion plan is much smaller than a House-approved $174 billion measure, so there's some reconciling still to be done.
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