In January 2009, our family returned from a cruise and Lauren presented with what might be considered “sea legs” from being on a cruise for a week. Only things continued to get worse beginning on January 27, 2009. By the next Sunday, she could no longer walk and she had voluntary tremors that left her barely able to function. We took her to the Emergency Room at Arnold Palmer Hospital in Orlando, Florida as there are no pediatric neurologists in Ocala. They admitted her and ran multiple tests for 3 days. All the tests came back normal and so a differential diagnosis of acute post-infectious cerebellar ataxia/cerebellitis was given. This diagnosis typically resolves itself with 3 days of IV steroids and 4-8 weeks of time. An EEG was also given to check for seizures due to consistent movements of her eyes being observed. She was also diagnosed with a seizure disorder and put on meds. After a week in the hospital, she was discharged. By now, our normally developing 21 month old was functioning physically as a 6-7 month old, barely able to sit due to the tremors and ataxia. She also had ataxic dysarthria (a motor speech disorder).
Lauren began physical therapy and she took her first steps for the second time in her life a month later. She continued to make slow progress but then in April 2009 her progress came to a standstill and her symptoms began to get worse again. These symptoms included ataxia, tremors, eye movements, sleep disturbances, and rages/outbursts beyond what a typical 2 year old exhibits. Doctors told us that it is not unlikely for a patient with her diagnosis to need a second dose of IV steroids so she was re-admitted to the hospital in Orlando and began another round of steroids, which did help for the short-term. She also underwent more testing to make sure no tumors or other problems were developing. Doctors told us that all of her tests came back normal but we were waiting on one urine test to come back and that if there were any concerns, they would contact us. We never heard from anyone but my mommy instincts and my anal nature told me I needed those results to feel at peace. At a follow up with our neurologist, I asked for those results and the hospital had never sent them so they told us they would look into them and get back to us. A few days later, I got the call…..the HVA and VMA (catacholemine) levels in her urine were elevated on two separate tests and this can indicate neuroblastoma (a cancerous tumor). We saw a pediatric oncologist 3 days later and they began rigorous testing to see if they could find a tumor in her body. (Neuroblastomas generally reside in the adrenal glands above the kidneys but can be found anywhere in the body). After repeated tests over a month period, including CT scans and an MIBG test that requires radiation injected into her little body, no tumor was ever found. Her urine levels remained elevated so they said they would continue to monitor her but said her case was not typical and we would have to wait and see.
Although we were happy with the care she was receiving, we are not ones to sit around and wait so we started doing research for a pediatric oncology program in the US with someone who specialized in neuroblastoma. We figured since we were going to travel we would also get a second opinion with neurology even though the current diagnosis made sense. We finalized on Children’s Hospital-Boston who was ranked #2 in the country for neuro (now #1 for the past 2 years!) and oncology (and had a specialist for Neuroblastoma). By God’s grace I got everything together and was able to get appointments within two weeks of beginning my quest (due to cancellations-I tell you it really was an act of God since we had to coordinate 2 docs who had clinic on two different days). We went to Boston for the first time on July 14, 2009. We returned home with a new diagnosis of opsoclonus-myoclonus syndrome (OMS). We were surprised but it all made sense.
It is believed that 50% of patients get OMS from a virus and 50% get it from a neuroblastoma. Post infectious cerebellar ataxia is often the mis-diagnosis. In a nutshell, either the virus or the neuroblastoma send the individual’s immune system haywire and the antibodies that fight them off mis-communicate and detect the cerebellum of the brain as a foreign substance so they attack it causing brain damage. The steroids are used to stop the attack. A side note on the neuroblastoma is that an individual can have one and the body can fight it off and dispel it so we will never know what Lauren’s was caused by but after 2 years she just had her first normal VMA and HVA results so we are suspicious.
We began treatment in the beginning of August 2009 with high doses of daily oral steroids and IVIg (IV Immunoglobulins) every 4 weeks. Another EEG was done and determined she was not having seizures but that the eye movements were indeed the opsoclonus. Her opsoclonus got worse before it got better with eye movement episodes lasting as long as 30-45 minutes each time. She would cry and whine and I could only imagine what it would be like to have your eyes going side to side and up and down with no control. I would just sit and hold her until the episode was over. She could not talk to me at this time either. Over time with the treatments, the number of opsoclonus episodes decreased and some became shorter. Part of the steroid treatment is to do high doses for a couple months to stop the attack of the antibodies on the brain, then begin to taper but continue to do the IVIg which we hope will “reset” her immune system. Unfortunately, we were only able to get down to a certain dose with the steroids and could not go any further as Lauren would have a re-emergence of symptoms. So the next step was to do a course of Rituxan/Rituximab (chemo) to try to kill off all the B-cells that were not healthy and hope that the new ones produced by the body would come back healthy so they would not attack her brain. We did this in June 2010 once a week for 4 weeks. It was successful and allowed us to slowly taper the steroid further for many months. After getting to a certain amount of steroids, she was showing a slight re-emergence of symptoms in October 2010 (which means you can’t taper anymore and may have to increase the dose and taper again). We tried a few other things and then decided in January 2011 that a second round of Rituxan was needed (what they are finding now is that a second dose seems to help in that it makes the B cells less susceptible to being re-trained to attack; so a good analogy is like the phone game where one person tells another something and the further away the message gets from the original person, the more it has changed; so the more doses of Rituxan one is given the new B cells coming back should be less like the original ones. Of course, one doesn't want to have too much chemo so is used with discretion) We just completed this round of chemo in February 2011 and are hoping it will help stabilize those cells so that we can continue to taper her off the steroid. We will continue doing the IVIg every 3-4 weeks during the taper. Lauren is looking much better on the outside, but inside her body is continuing to battle a war against itself. We go to Boston every 3 months to see her doctor who specializes in immunology neurology. He is one of about 20 doctors in the US who specialize in OMS and one of an even smaller number doing research on OMS. Lauren was his 11th OMS patient ever in 2009.
1 in 10 million get OMS and it generally has an onset in early childhood but there have been rare cases of adult onset. Prognosis for OMS patients is unknown as it depends on many factors including how long it takes to get the diagnosis (it took us 6 months—one of the biggest issues is awareness), any initial treatment given even if wrong diagnosis (we were very lucky to get steroid treatments or she would be much worse! Not all docs give steroids for cerebellar ataxia.), etc. Lauren is still in physical therapy once a week to keep her skills developmentally appropriate. She was at age level but is having a little difficulty getting up to her next big range. Her biggest difficulties are in gross, fine and visual motor skills. Due to the early IV steroid treatments, her language and speech skills are doing well. We will not know if she has any learning disabilities for a few more years. I possibly see some auditory processing issues but not too bad. She also has difficulty regulating her loudness (whether too loud or too soft) which they have found indicates cerebellar involvement.
In 2011, Lauren has continued to receive IVIg treatments every 3 weeks and taper her prednisolone gradually. She was down to .5mL once a day when her journey took a drastic turn on November 3, 2011. During a routine follow-up in Boston, Alicia had requested an MRI scan of Lauren. We had read recently of other OMS families who had tumors found a couple years after OMS onset. A tumor was detected from an MRI in her upper abdominal cavity near the aorta and vena cava. It is believed this was the trigger for her OMS, however she will continue to battle OMS as her system has already been disrupted.
On November 21, 2011, a ganglioneuroma was removed from a complex intersection of gastric blood vessels between her pancreas and liver at Arnold Palmer Hospital in Orlando. The surgery took over 4 hours as the location of her tumor was very difficult to access. After surgery Lauren went on to recover for the next week in the hospital, then went home. After being home for 3 days, Lauren's pain continued to get worse and she had a high fever. On November 30th, she was taken back to the ER at Arnold Palmer and admitted. She was diagnosed with pancreatitis, a fluid pocket and a pseudocyst that was filled with fluid. This was caused when removing the tumor as it was attached to part of the pancreas and some tissue from the pancreas had to be removed with the tumor.
Pancreatitis in children is not very common. The course of treatment for her was basically a wait-and-see approach to see if it healed itself. This did not happen and eventually enough fluid built up that they were able to install a drain into the fluid pocket, which resolved that one piece of the puzzle. We still had the pseudocyst and pancreatitis to work on. Since she was unable to eat or drink anything (this would make pancreatitis symptoms worse), a central line was surgically placed in her chest and she was put on TPN (total paraneal nutrition) and lipids to account for her nutrition. After 3 more weeks of wait-and-see and a hole in her pancreatic duct being detected by an MRI, we decided to transfer Lauren to a specialist at Children's Hospital Boston on January 3, 2012 for more specialized care and difficulties more rare than her OMS. Lauren and mommy rode in a very small air ambulance plane with a nurse, paramedic, 2 pilots and some medical equipment.
Within a few days, her pseudocyst had grown to 3 times the size it was and after drain placement was determined to contain 90% puss. They started her on additional medications to clear the infection up. Several less invasive endoscopic procedures (ERCP) were attempted to correct Lauren's pancreatic duct, but were not successful due to anatomical differences from how it should be. The physicians said this was a very unique case and they had not seen one like it at CHB in the last 10 years they had been there, so they were working with the best they could. The initial plan at the end of February was to wait 12 weeks and then attempt surgery. However, one last test done by the interventional radiology team changed everything as it showed that the pseudocyst was indeed matured as they could inflate it. This was great news and finally, on March 2nd, she received another full surgery, which created a bypass for the leaking pancreatic duct to the duodenum of her intestine. Her gallbladder and appendix also needed to be removed due to complications from the last couple months. This was a very major surgery with her being in the operating room for over 8 hours. She was only supposed to be in the PICU for 24-48 hours until she was stable but became very unstable overnight and the next day had to be put on a ventilator. Days later she had a severe drug reaction and her whole body broke out in a horrible rash. Thus, she ended up spending 2 1/2 weeks in the PICU, most of that time on the ventilator. This was a very difficult time for us as we were not sure if she would make it for about 24 hours. She also experienced some big drug withdrawals after coming off the After leaving the PICU, she returned to our beloved 9 South room where we had spent the previous 2 months. She spent another 3 weeks there as they weaned her from sedation medications. We are happy to report that as of April 2012, her surgery appears to have worked and after 4 months of not being able to eat or drink Lauren is able to successfully eat and drink without adverse effect.
Lauren spent another week in the hospital in Orlando in May 2012 for another bout of pancreatitis. She recovered and remains on a strict low-fat diet. As of January 2013, she has recovered from her surgery, has to monitor what she eats as too much fat content does present some gastrointestinal problems. Her OMS was generally being controlled with daily oral steroids and IV infusions every three weeks. Her goal now is to get her OMS under enough control to be able to discontinue these infusions and daily medicines. In February 2013, her oral steroids were decreased by .2 mL and we began seeing some OMS symptoms re-emerge. We are currently collaborating with her physicians in Boston as to what the next steps might be if she continues to have a re-emergence of symptoms during the taper. Unfortunately, she will most likely have to do another round of chemo. There are 3 chemo drugs that can be used and one has been removed due to GI issues as a side effect (and Lauren already has enough of those!). The other two options are Rituxan (which she has done previously and they are not sure if will work) and Cytoxan (which she has not done and has some possibly devastating long term effects). We are praying God will guide us in this important decision.
Unfortunately, very little research is being done on OMS mostly due to funding issues. My husband and I started the Lauren Mantz OMS Research Fund at Children’s Hospital-Boston as her doctor was very interested in doing further research. He has already begun but could do so much more with more research funding. The money raised from this fundraiser would not go toward Lauren’s treatment but toward OMS research that would benefit every child with OMS, including our “Little Lauren”.