Also known as: Cree Encephalitis, Pseudo-TORCH syndrome, Microcephaly-intracranial Calcification syndrome (MICS)
Aicardi-Goutières syndrome (AGS) is a genetic brain disease which can be mistaken for the consequences of viral infections affecting a child in the womb. Most children with AGS show signs of the condition in the first few months of life. Features allowing a doctor to make a diagnosis of AGS include:
calcification in the brain
changes in the white nerve tissue of the brain
raised levels of interferon-related proteins (chemicals produced by the body to fight viral infection – but in the case of AGS found in the absence of such infection) in the blood and the cerebrospinal fluid (CSF)
distinctive ‘chilblain-like’ lesions on the hands and feet, which are usually worse in the cold
Last updated July 2018 by Professor Yanick Crow, University of Edinburgh, Edinburgh, UK.
Although great care has been taken in the compilation and preparation of all entries to ensure accuracy, we cannot accept responsibility for any errors or omissions. Any medical information provided is for education/information purposes and is not designed to replace medical advice by a qualified medical professional.
WHAT ARE THE SYMPTOMS?
In general terms there are two types of presentation in AGS. Some babies, especially those with AGS1 mutations (see ‘What are the causes?’), experience problems at or very soon after birth. Features include feeding difficulties, abnormal neurological signs, low platelets (blood cells involved in clotting), and liver abnormalities. In contrast, other children, develop normally for the first few weeks or months of life. They then experience the sudden onset of a period of intense irritability, cry a lot for hours at a time, sleep poorly, and can develop fevers without infection. During this period there is a loss of skills.
WHAT ARE THE CAUSES?
After a few months the disease process seems to ‘stop’. Many individuals with AGS are still stable in their late teens and early twenties. Typical neurological features of AGS include learning problems, stiffness of the limbs with poor body and head control, dystonia (impairment in muscle tone) of the limbs, and seizures (see entry Epilepsy). Although the neurological problems seen in AGS are often severe, a small number of children, usually those with AGS2 or AGS5-7 mutations, display good communication skills, and a few children can have completely normal intellectual development.
Seven different genes have been identified that, when damaged by a mutation, can cause Aicardi-Goutières syndrome (AGS). Only one gene is involved in any one family.
Will has a provisional diagnosis of AGS because he does not have the genetic markers for any of the known AGS genes. His diagnosis is based on his clinical presentation. He has interferonopathy, and there is at least one other child in the drug program like Will.
HOW IS IT TREATED?
The following treatments may be used for the management of AGS:
management of seizures (which are quite common in more severely affected children) using standard protocols
some children need tube or gastrostomy feeding because of difficulties with feeding secondary to the associated neurological problems
chest physiotherapy and antibiotic treatment may be needed for respiratory complications, which can occur secondary to the associated neurological problems
in some cases, treatments may be considered for chilblains
Surveillance includes the following:
assessment for glaucoma (seen in a small percentage of cases)
monitoring of the spine for the development of scoliosis (which can sometimes occur because of muscle imbalance)
monitoring for signs of insulin-dependent diabetes mellitus (IDDM) and hypothyroidism (these are rare, but treatable, associations seen in a small percentage of patients)
in the case of SAMHD1-related disease, there may be need for monitoring of the blood vessels in the brain with special scans
July 7th, 2017
Will’s 1st birthday we were driving home from a Gastroenterologist’s office after a nutrition consult. Will’s neurological condition had worsened over the course of eight weeks, and we were afraid that he would decompensate further and not eat enough to thrive. As we were driving home, Will’s neurologist called and asked to be placed on speakerphone so my husband and I could both hear what he had to say. In the next few moments, we learned that Will had been given a diagnosis of Leukodystrophy and they presumed he had Aicardi-Goutieres Syndrome (AGS) based on findings in his Cerebral Spinal Fluid (an extraordinarily high neopterin level). Neopterin is a biomarker that is present in the setting of immune system activation. Along with high neopterin levels in his CSF, they reviewed his MRI again, which was read as normal two months prior. After reviewing his MRI again, the neuroradiologist concluded that Will had mineralization in the white matter of his brain. With the high Neopterin levels and calcifications in his basal ganglia, a clinical diagnosis of AGS seemed most appropriate. It felt especially cruel to get such difficult news on Will’s 1st birthday. Some have said, ‘once you know, you’ll feel better.’ I didn’t feel better. In fact, I doubted the diagnosis. AGS is a genetic syndrome, and the genetic changes are found on one of seven genes. I remember thinking, ‘How can this be? He is our love baby.’ I still feel this way.
A week later we met Will’s neurologist to discuss the diagnosis. I remember not talking about the diagnosis because it took my breath away. A genetic test was pending, and we were told that AGS was an autosomal recessive syndrome passed onto Will from my husband and I. I asked, ‘what happens when Will’s genetic test does not show the gene changes associated with AGS?’ The doctor looked at me sympathetically and softly said, ‘I think we will, but if for some reason we don’t see the genetic markers for AGS, we will look for mimics of AGS.’ We asked, ‘what would you do if this was your child?’ He replied, ‘I would take him to the experts, and in this case, they are in Philadelphia at CHOP.’ Our neurologist had reached out to an expert at CHOP who runs the Leukodystrophy clinic and had information about their program, specifically the compassionate use program at CHOP. There is currently a compassionate use trial for AGS kids at CHOP and they have seen clinical improvements with the drug they have been using. To be included in the trial, there is a list of criteria each patient needs to meet. There has to be genetic confirmation of AGS to be included in the study. As awful as we felt, we envisioned a hand reaching to us from Philadelphia. We thought, ‘this won’t cure him, but it could help him in some ways.’ A week later the genetic test results came back, and his Whole Exome Sequence (WES) was normal. No sign of AGS, and a denial from CHOPs compassionate use trial head researcher.
Fast forward to September (two months after Will’s provisional diagnosis of AGS), and we were meeting the Leukodystrophy team at Clinic Day in Philadelphia. We met with a renowned pediatric neurologist, Dr. Vanderver, and her team. We had consultations with a developmental pediatrician, nutritionist, physical and occupational therapists, and a rehabilitation doctor. The therapists recommended many pieces of adaptive equipment. Some things I had heard of, some I had not. Over the next three months, we were managing flares in Will’s condition; he was hospitalized, traveled back to CHOP for follow up care, and focused on Will’s nutrition. Will was growing longer, and I began feeling like we would need options for safe seating (supportive chairs, adaptive feeding chairs, adaptive strollers, a stander, etc.). We also lost our childcare because Will became too much to care for in a traditional daycare setting. Will wants to be carried and cuddled while he is awake. His favorite place is snuggled against our chest, heart-to-heart. My husband and I rearranged our work schedules, and with the support of our colleagues, we have managed to piece things together week-to-week. I have been working most weekends and one day a week, and my husband works two full-time jobs around my schedule. We also have five children and manage their interests simultaneously. Children have been getting rides from family and friends, waiting patiently for their turns, and learning that there are some things that we just cannot do. Everyone is adapting.
We are fortunate to have good insurance. Our insurance company is billing the in-network rate for our specialists in Philadelphia because there isn’t anyone in Maine who specializes in Leukodystrophy. One of the things I did not realize is that even though we have great insurance, there will be equipment and resources that are not covered. In Maine, people who do not have insurance or have disabilities can apply for MaineCare. Without MaineCare, it isn’t possible to access many of the services you rely on when faced with a complex medical condition; specifically in-home services. As we wrestled with the reality of our child being disabled, we didn’t realize that we should be applying for MaineCare (as soon as possible). It had been ten months since we first saw our neurologist, we were already behind the eight ball. We were adapting to our new life and were completely overwhelmed with grief and shock. I was (am still) looking for a treatable cause. I was slowly adapting to his new physical and cognitive limitations; not at all ready to accept this was the fate of our boy, completely disabled.
Late September 2017:
Applying for MaineCare
What a cumbersome process. We have a family friend who is familiar with the forms, and she assisted us step-by-step. We faxed hundreds of pages to DHHS so they could review our application and financial documents. They often misplaced things that were sent and faxed to their office. More than once we called them, or they called us looking for additional information. This went on over the course of several weeks. Two months later the phone call from DHHS came: ‘Hi, this is Michelle, I want to let you know that we have deemed William completely disabled as of August 1st, 2016.’ That wasn’t something I could repeat without feeling constriction in my throat and chest that made it too difficult to speak. We should be excited at this point, we have moved through the MaineCare process. It feels awful. I’m not excited; I feel immense pain. At this point, MaineCare has been denied because we both work and do not meet the financial requirements for approval. Once denied access to MaineCare, families can apply for Katie Beckett, another way to access resources through MaineCare.
The next step, applying for Katie Beckett
To get this benefit we needed to complete a Goold Assessment at DHHS. The State of Maine requires both a financial and functional assessment to determine an individual’s eligibility for most In-Home Services. The Goold assessment helps individuals and families understand what services are available to them through MaineCare.
If a parent or guardian works and has insurance, they are not eligible for MaineCare assistance. However, all of the services provided by the many mental health agencies are only available to those whose children receive the MaineCare benefit. Some families have gone years without help or services because they didn’t know they existed or they didn’t know there was a way for the child to become eligible. There is an answer, and many families can qualify for services paid by MaineCare through the Katie Beckett Option. The Katie Beckett Option is a MaineCare option for children with serious health conditions. It is one of the many ways a child can get MaineCare. Katie Beckett has a monthly premium, just like our primary insurance. This secondary insurance will cover co-pays and hopefully, pick up where our insurance leaves off. We had our Goold Assessment at DHHS January 3rd, and the nurse conducting the assessment said we would hear from our contact within DHHS about our premium within a week or two. We heard nothing from DHHS despite calling and leaving messages twice a week for almost four weeks. At this point, we have several thousand dollars paid to medical doctors and hospitals and have been denied equipment and nursing services for our sweet boy. We have been anxious to welcome home nursing care into Will’s life because, with the right caregiver, my husband and I can leave him in loving arms and go to work.
To get coverage through the MaineCare Katie Beckett option:
•You must fill out a MaineCare application;
•Your child must be 18 or younger; and
•Your child must meet financial and medical rules.
YOU must also have the stamina of a Pronghorn Antelope because the ball will be dropped so many times during the process.
I assumed that anyone who has a significant medical disability would encounter the initial steps of acquiring these services with the aid of their primary care provider. That was incorrect.
I assumed that Child Development Services (CDS) would interject and get the MaineCare Labrinth started with our family; that was also incorrect. What I learned is that the average person has no idea where to begin with this process.
The reality of the situation is that some people have to seek out case management services on their own. Or, someone recommends applying for MaineCare and they go home and search the internet. Some people post a general question on Facebook to a private group; something along the lines of, ‘What is MaineCare and how do I get it? Or this, ‘I’m told I need MaineCare but none of the doctors have mentioned it.’ Someone may even mention that they should obtain a case manager. How do you do that??
People who are involved or work with individuals in mental health or other medical services recommend case management services to the patients, and it’s up to the patient to agree with receiving this help. There are people who have submitted their application (DHHS has 45 days to make their determination of approval/denial), and they hear nothing from DHHS about their decision. I have heard stories about people who didn’t realize that if DHHS doesn’t make their determination on time, that they automatically receive temporary benefits until a decision is made. There are some people who didn’t realize they had received temporary coverage because they got lost in the system. It’s only when a case manager keeps track of ‘the clock’ that people get their coverage faster because DHHS is hounded by the case manager to complete their file.
Where things get lost in the land of DHHS:
DHHS Office of Family Independence (OFI) receives the application and has two days to process it into their system and then sends it forward to the medical review team to determine disability. Once the DHHS OFI confirms receipt of the application, the 45-day clock begins. The Medical Review Team (MRT) sends medical requests to all providers involved in the individuals care. Once they have the file completed, they send it to an independent medical reviewer (medical doctor or psychiatrist) to determine disability. Once the MRT receives the determination from the reviewer, they immediately acknowledge it in the system and send the determination back to DHHS OFI. I have learned that the two systems (MRT and DHHS OFI) do not interact and that is where the biggest GAP is. There have been instances where the MRT has approved the individual for disability, but DHHS has sent out a denial letter; completely erroneous and leaving people desperate for care and resources in limbo.
February 2nd, 2018
Where we are in the process: almost 5 months after getting started with our MaineCare application.
We talked with DHHS yesterday, and our point person gave us information about our premium for Katie Beckett. She is ‘pushing the information through the system’ and we should receive our paperwork so we can begin paying our premiums and using the benefit as secondary insurance. To get reimbursed for out-of-pocket expenses and the insurance co-pays we have already paid, we need to contact every provider and have them submit Will’s MaineCare information to their billing department; they would get reimbursed from MaineCare once the bills are processed. Once they are reimbursed, the providers would then reimburse us. We would need to hire someone for this process alone; I can barely keep groceries in the house; let alone find time to shuffle all this paperwork. Going forward, we will have the Katie Beckett benefit, and this will help us with future co-pays and out-of-pocket expenses.
Don’t complain if you can’t recommend a solution:
When given a disabling diagnosis it would be helpful for the primary provider to immediately connect families and patients with a case manager who can begin the process of applying for benefits. In my opinion, this should be done at the initial encounter because we are doing patients a disservice by letting this fall by the wayside. It’s not enough to have follow-up appointments with specialists and not have this piece in place. Specialists are charging between $350-$600 per visit; some thought should go into the social, emotional, and medical wellbeing of patients and their families. Assigned case managers should be following up with patients while the approval process is underway. Even with my effort and the effort of our family friend, it was an overextended process that went on for months on end.
We can and should do better for our families in crisis.
A year ago Will, our newest member of the household was five months old. He was wide-eyed and curious, attempting to turn the pages of his board books. In the next three months, we noticed gradual changes in Will which later became obvious signs of a severe neurological problem.
Over the last eight months, we have turned every stone, looked for every known condition that might lead us to a cause for Will’s symptoms. Will has symptoms of Leukodystrophy, a general diagnosis for a disease process in the white matter of his brain. He has central hypotonia, dystonia, is globally delayed, unable to speak, and a quadriplegic.
This year our ‘together baby’ should be tearing the paper off of every present under the tree, a real terror! He would likely have stripped off the ornaments and lights while I was busy tending to the other children. I wanted that so very much; the craziness of a larger than life toddler. I know that we don’t always get what we ask for; things don’t always turn out as we had planned. As magical as Christmas can be, it can also be a painful reminder of the journey we had in mind. I came across an important reminder of how holidays or other times of the year can trigger feelings of anxiety and depression. Though my feelings are mostly grief and anxiety; I have to be honest with myself and others and acknowledge that these reactions are very real and important to process properly. Take a look at the blog post by Jacqueline Bogg or this piece by M. Lin. Remember to be present with the feelings you encounter along your journey; it’s important to work on all of the pieces of you, especially the not so pretty pieces.
Will’s gift to me is bigger than the sadness and fear I feel about his condition. Though I cry most days leading up to events like Christmas, I have to remember that he has shown me much more than sadness in the last eight months of his neurological mystery. The community who support our family by giving the gift of time, phone calls, messages, and food has lifted our family along this journey. Because of Will we have better seen the beauty of others. Our children have learned compassion, patience, and empathy because of Will. The work that I call my own is part of my ‘iWill’ story. The beauty I see as a result of Will’s gift to others is the ‘WeWill’ mantra I write about. Self-care is the personal work I do to stay strong for Will. My infrequent opportunities to exercise or get my nails done are ‘iWill’ moments. The words I write to help me process and accept this new normal are my ‘iWill’ moments as well. What are your ‘iWill’ moments like? Do you take a moment to think about how self-care fills your own cup?
How lucky are we to have the chance to see the world through Will’s eyes? What does he experience as a little boy with so much love and activity around him?
My husband works two full time jobs and has two boys from his previous marriage. I have three children from my previous marriage and work part time as an Emergency Room nurse. I am the CEO of the Hagar-Christensen household. In 2014 we welcomed our ‘together baby’ to our blended family. Our toddler Will is disabled and suffers from a form of Leukodystrophy; he requires 1:1 care at home.
Being a mom of a blended family is full of fun, adventure, and…in reality, it’s mostly organized chaos. It had been three years since our last family photograph and we have a new addition to add to the gallery, Baby Will. This year our family photo was about capturing all of us together, without sweatpants or yoga pants! I won’t lie, it took me about three weeks to come up with clothing that everyone would wear. A couple of the kids are stuck in their groove of wearing Target cotton pants and my girls are most often found wearing breeches to the barn.
I was able to find a cozy blanket from Target for a couple outside shots. The women’s footwear were Lucky Brand Basel Booties. My girls put on their booties and towered over me.
Let’s all take a moment to marinate in the glory (reality) of what it takes to pull of a family session like this: 2 different child contact schedules, hoping that someone doesn’t dye their hair blue with kool-aid at their other parent’s house, horseback riding schedules and caring for the beloved horse, Octavia. My adorable husband refuses to wear sweaters and I have a child who I hold 14 out of 16 hours of the day. The boys have various hobbies and my girls are avid dressage enthusiasts.
We live in a small house in Maine, it’s packed full of kids, stuff, and two dogs. The best room for a photo session is blocked by the Christmas tree. I agonized over how I would talk the boys into nice sweaters and JEANS. Then, I came to the last minute detail of THE VENUE. A family friend had offered to do our session for us and I had incorrectly assumed that she had an indoor setup in her barn. Well, she does, but it isn’t heated in the winter. In a six-week block, we had one opportunity that all the kids would be together for a brief window of time. We had 8am-10:30am on a Saturday morning, that’s it! Then it was off to basketball, followed by a swim meet, then a kid headed to New Hampshire for a wrestling match. The date and time could not move because if it snowed or someone got sick, we were going to have to postpone. The day before the photo shoot, my friend offered up her living room for our session. I was thrilled because she has a photographers dream of a living room. The natural light is phenomenal in her home. The best part, she lives around the corner. Winning!
The morning of the shoot my son got dressed in the previously approved wardrobe I had set out for him. He comes into the master bedroom and says, ‘there is no way I’m wearing these pants.’ My head implodes. I gave him the peaceful answer all my positive parenting friends recommend…no, I didn’t. I said, ‘man, you told me we were good to go with the pants. You’re wearing them! Do you realize how hard I worked on this?’ Yes, I was projecting, but good grief, wear them for an hour and shush your mouth! The others decided that my rage looked a lot like something they wanted no part in, so they did exactly as they were asked. After helping six kids with their camera-ready look, I had time for a power shower, but there was no time to wash and dry my own hair.
Complaining aside, I had the opportunity to help my 13-year-old with her makeup and my 15-year-old with her eye makeup and hair: