This is the story of a parents quest to help their daughter. We hope to create a discussion about what has worked and what has failed. Our goal is to help others and give us new ideas for helping Alissa. Professional opinions welcome.
We are formally seeking professional input to this case study. This webpage contains detailed information on Alissa’s medical history as well as her therapy program. We would be glad to provide more information to anyone interested in conversing.
Alissa was born on November 1, 2000 in Singapore. The pregnancy was uneventful and the delivery was proceeding normally in the hospital until Mom’s water broke. A moment later the fetal heart monitor showed Alissa’s heart rate had dropped off the chart. Mom had suffered a very rare and typically fatal complication called an amniotic fluid embolism.
This complication occurs when the amniotic fluid somehow enters into the mother’s blood stream. It results in devastating complications such as cardio-pulmonary collapse, stroke, and failure of the mothers blood to clot. Luckily Mom was one of a small percentage of mothers that survive and survive with no permanent damage. Unfortunately, it was approximately 40 minutes before an emergency c-section could be performed. During this wait, Alissa was not receiving oxygen because of Mom’s critically ill body.
Alissa was born with Apagar scores of 1 at 1 minute and 2 at 5 minutes. She was ventilated and put on a anti-seizure medication and for the first week. She barely moved. We were told to wait and see. If she were to recover spontaneously it would typically occur in the first week. If we did not see recovery in this period then the future would be uncertain. She did not recover in that first week. However, she did improve. She was taken off the ventilator and the anti-seizure medication. She did not have any seizures, which was good. However, she still was not moving much, she was not sucking, she could barely open her eyes. She was ng-tube feed. Mom was still in intensive care for the first 10 days, so these are dark scary memories.
The rest of her first month was better with Mom getting onto her feet and Alissa staring to give us some signs of hope. The first thing we noticed were her eyes. Even before she could move her arms and legs she gave us hope in her big bright eyes. Alissa continued to make slow progress over the next several months. By three months of age we were back in the USA and Alissa had improved to the point that she was moving all her limbs with slightly high tone with underlying low tone. Her head control was improving and her sight and hearing checked out fine. Unfortunately, she still was not eating orally.
During those first moths we worked very hard to learn everything we could about Alissa’s Injury and what we could do to help her. We started with the internet. The search engine Goolge is an extremely powerful tool for learning just about anything. From Google we found the a Google Discussion Group that was dedicated to HIE – Hypoxic Ischemic Encephalopathy, which is Alissa’s official diagnosis.
I began to devour all the literature I could find on Alissa’s injury and possible treatment approaches. We quickly came to realize that the first few years of Alissa’s life are going to be her most critical. As a family we all agreed to make sacrifices to ensure that Alissa had the best possible chance in her first years. I made adjustments at work to give me more time at home, my wife won’t be returning to work as soon as we had originally planned and our 11 year old daughter is taking time out of her busy life to help her sister as well. We agreed that we would not accept compromises with Alissa’s treatment options to the fullest extent of our abilities. After giving our best shot at helping Alissa we would then settle in peacefully to accepting what God has given our family.
To get started I called upon an old collage roommate that has gone on to become a leading PhD scientist in the field of basic brain research. Through his help I began to make contact with the worlds leading scientists in the field of brain research. Through their input and guidance I was able to develop sort of a set of “guiding principles” that I am able to keep coming back to whenever I question the next step in Alissa’s treatment plan.
I have summarized our family’s current understanding of the science behind Alissa’s condition in the following points. Based on this understanding, in consultation with our clinical team, we design our home therapy program. Credit needs to be given to the enormous talent that we have in our clinical team. (Barbara Cupps/Chris Garenger-PT, Chris Cayo-OT, Rona Alexander/Linda Anderson-ST).
Based on the work of all those mentioned in this document, we are confident that significant functional improvement after brain injury is a realistic goal.
We believe that Reorganization (Plasticity) and Pharmaceuticals(Stem Cells and Growth Factors) present the two best areas offering means to achieve functional improvement.
Given the current pace of progress in pharmaceuticals, we believe that plasticity models may yield better short term approaches. (Macklis, Merzenich)
We recognize the importance of self motivation in the learning process and understand why traditional medical therapy models often fail.
The severity of the injury is obviously a critical factor in determining the effectiveness and focus of the treatment. (Urban, Macklis)
Focused assistance on the targeted functional areas is the key to recovery. (Hogan, Ulrich, Taub, etc.) However, treatment must be based on understanding how that injury results in a “undesired” movement pattern becoming the stable attractor. Opportunities must be presented and facilitated to allow new more desirable patterns to de-stabilize the undesirable pattern and become the stable pattern.
Plasticity is not time dependent. (Taub, Hogan) However, once abnormal patterns become stable they become very difficult to replace. (Thelen, Ulrich) Therefore, early intervention is critical. With the first year of life being the most important. The second year less so, and so on.
Functional achievement and intervention strategy needs to be matched to appropriate developmental opportunity windows. (For example, unsupported walking can not be expected until sufficient muscle strength is achieved)
Measurement and understanding of the factors leading to undesirable patterns is the key to developing a treatment program. Stable patterns are almost always the optimized solution to the interplay of all factors (neurological, physiological, environmental, etc.) The intervention program should provide focused intervention to the factors that are allowing an undesirable pattern to emerge. (Thelen, Ulrich, Hogan, Taub, Merzenich)
The complexity of the functional skill and degree of stability that the abnormal pattern has achieved, are the two factors determining the level of intensity and duration needed in order to de-stabilize the undesirable pattern and establish the desirable pattern. (Thelen, Ulrich, Hogan, Taub, Merzenich)
Currently our major difficulty in Alissa’s program is that as parents we do not understand in detail the complex interplay of factors driving undesirable patterns to become the stable patterns. Therefore, we have not been able to develop optimal intervention techniques to overcome some of Alissa’s more undesirable patterns.
Personally, I believe a possible next step is to improve our ability to measure the degree to which critical variables are having a normal or abnormal influence on development. However, I am not sure how to go about identifying, isolating and measuring the critical variables.
Admittedly, the options presented in the literature for effective intervention strategies are extremely limited. (A representative list includes hands on therapy which can be very powerful in the hands of an experienced therapist but limited with the parent, robotic assistance which is limited by the complexity of the functional skills needing focus in a typical infant hypoxic injury, tread mill gait training which can only be used after the child has met certain challenging developmental milestones, Constraint Induced Therapy which is best applied to a child with Hemiplegia. This list is very limited and significant work needs to be done to increase the assistive tools that are available to parents and therapists)
Finally, none of the above research cited has specifically addressed global hypoxic brain injuries and very little has addressed rehabilitation in the context of the childhood developmental phase. The research has been verified on Stroke, Downs Syndrome, Spinal Cord injury, TBI and generally in adulthood. However, we have not found significant research on the more complex situation of a injury resulting from global hypoxic injuries early in life. However, based on the principles of dynamics systems theory we believe that the results of the research can be effectively extended to the more complex situation of a injury resulting from global hypoxic injuries early in life. This position is shared by Hogan and Taub and Ulrich is currently conducting research to verify this position.
Below is a detailed accounting of the historical progression of our research.
Next, I will retrace our journey over the last 12 months to help your understand how we have come to the our current state of understanding. We stated by contacting an old college room mate of mine, Nathan Urban ref1 who went onto to research basic brain function. He gave us a good foundation of understanding the complexity of the problem we faced given the nature of Alissa’s Injury. (Alissa suffered an hypoxic injury due to amniotic fluid embolism in mom, apgars of 1 @ 1 min and 2 @ 5 min, CT scan at 4 months showed calcification in the basil ganglia, MR was good at 8 months but showed mylination at low end of scale, microcephaly, feeding disorder, 100% g-tube feed). Nathan also stressed to us the importance of understanding the nature of how people learn. The importance of the natural sequence of learning. And finally, the importance of self motivation in the learning (and rehabilitation) process.
Nathan, directed us to the work of Mike Merzenich of UCSF ref2 ref3 who promotes plasticity as a key mechanism for brain re-organization. Mike stressed to us that our challenge was more complex than those he has worked successfully with, which included children with language learning deficiencies.
Next we found the work of the Christopher Reeves foundation ref4. What impressed us about the work of the foundation was the focused research that was happening with a clear goal to allow Christopher to walk again before his death. Here we spoke with John McDonald who explained the differences and commonalties between spinal cord injury and hypoxic injury. We learned the value of muscle conditioning via Electrical Stim and the role that passive movement of effected limbs seems to play on creating spinal and neural representation that serve as a building block for further recovery.
Next we learned of the work of Ed Taub in stroke victims ref 5 ref6, again we learned the differences between stroke and Alissa’s injury. Ed’s work on CI confirmed that directed, intense therapy on specific muscle groups produced functional improvement.
Around this time we studied the work of Glenn Doman and the Institutes For Advancement Of Human Potential (IAHP) ref7. In general we found that many of their principles were quite in line with what we were learning from the scientists, so we were very hopeful about working with them. When we started this foundation we ran into many more success stories and parents who would swear by the program. We highlight just one of these success stories in our case study section. ref7a. The overwhelming support that some parents give to the IAHP continues to intrigue us. We hope that we will be able to report personally on the IAHP some day soon.
We looked at Conductive Education, and other intervention programs. We found that all of them seemed to have some common threads that made sense to us.
Based on these threads and the science we developed a set of guiding principles that we used to help us to focus: These principles are summarized here:
We studied and tried Hyperbaric Oxygen Treatment. We talked to many doctors about the possible mechanisms at play. We talked with Maurine Packard a Neurologist at Cornell U. Hospt who was seeing some success in treating CP children with HBOT, we talked with HBOT Society, etc. There was a double blind study conducted by the Canadian Government. The results showed that HBOT produced no significant functional improvement Vs the control group. However, the interesting thing in this study is that both groups improved significantly (see text below if link does not work ref8). Therefore, we began to realize that the very act of participating in a study can produce results. The HBOT study required daily intensive 2-3 hour sessions. The control group underwent HBOT sessions as well but with pressurized room air, rather than O2. Our thought is that these participants were engaged, and motivated during the study period. This alone was capable of producing results.
We studied the work of the Autism community. What we took away from them was the fact that only a few short years ago, Autism was viewed as untreatable. Now in Wisconsin, Autism is treated with intensive Behavioral Modification programs for 40 hours per week and paid for by Medicare ref9. We set this as one of our goals, “to develop a similarly accepted treatment program that would be accepted and paid for by insurance”.
We met the founders of Project ALS ref10. They have raised millions for research into ALS. Like Christopher Reeves they have funded their own directed research team and seen great results. We have a strong desire to have the same resources and influence as the Christopher Reeve and the Estess Sisters but regarding hypoxic brain injuries.
We then turned our focus to the work of Stem Cells and Neruotrophins. We contacted Jeff Macklis of Harvard ref11, Clive Svendsen of UWM ref12, and Doug Kondziolka of Pitt ref13. In particular I talked with Doug about the first implantation of Neural Cells into the adult brain. Doug’s study proved that cells could be implanted in the brain safely. It also showed using FDG Pet that the area around the implantation showed increased metabolism. Doug and I quickly came to the same conclusion that this did not imply that the implanted cells grew. It only implied that something caused increased metabolic activity. We agreed that it could be a placebo effect caused by the stroke victims desire to recover and hope that the surgery has done something to help them. Also, it appears that the implantation of cells triggered the production of neurotrophins. Finally, the most important finding of this study is that even with new brain tissue, rehabilitation was needed to teach the cells how to be functional. This conclusion has been the most powerful finding that has come out of my stem cell research. It is shared by all those that I speak to… new cells are not enough, you must teach them to regain any function lost.
Along those lines I contacted Neville Hogan of MIT ref14 I found the following paper to be particularly enlightening ref15. Neville has worked on robotic assisted therapy. His work is wonderfully “application” focused. He arrives at all his conclusions by data. I find he approaches the task with a refreshing enthusiasm and confidence, suggesting that initial successes in stroke victims should be extendable to more complex situations. Suggesting “were there is a will there is a way”. His work has confirmed a few important things. 1.) That current therapeutic tests are too course to measure fine improvements. 2.) That focused assisted exercise provided improved results over general therapy. 3.) That improvements tend to come only in the targeted muscle groups. Along those same lines the work done by Beverly Ulrich on treadmill assistance for children with downs syndrome proved the exact same three items.
So how to teach? I turned back to one of the original factors I knew to be critical – “Understanding how people learn”. For this I turned to Esther Thelen ref16 and Beverly Ulrich ref17 and their work with Dynamics Systems Theory. I was very comfortable with the Dynamics Systems Theory approach to learning and understanding how it could explain the abnormal movement patterns that develop in brain injured children. Our next step hopefully, is to use their work to produce an effective “predictive model” to take our therapy program to the next level. So that is were I am today.
Brief Summary: Alissa was born full term with an hypoxic Brian injury secondary to an amniotic fluid embolism in her mother. She presented typical of Stage 2 Hypoxic Ischemic Encephalopathy. Neurological she has progressed steadily but significantly delayed in an all-major areas. She is alert, communicates with cries and coos, can roll, sit with minimal assistance, reach for toys and grasp simple objects. She has underlying low tone and dominate extension movement patterns. She has been healthy aside from contracting rotovirus and 2 upper respiratory infections. She has never had seizures or phenomena.
Birth: At 37 weeks gestation, Alissa was born via emergency C-section secondary to fetal distress and bradycardia. Her mother suffered an amniotic fluid embolism and had cardio respiratory collapse prior to delivery. It was approximately 40-45 minutes from the mother’s collapse to the point of delivery. Apgars were one at 1 min and 2 at five minutes. Birth weight was 2940 gm, length 50 cm and head circumference 32 cm.
Finding at birth indicated Stage 2 Hypoxic Ischemic Encephalopathy. She was on a ventilator for 1 week. She received Phenobarbital for one week for precautionary reasons. No overt seizures were noted. Head ultrasound x 2 was W.N.L. She was started on NG Tube feedings because she had little oral muscular activity. She remained in the Gleneagles NICU until two months of age. During this period she showed gradual improvement in her neurological status. She received daily PT and ST. Her weight and head growth during this period was approx. 28 gm per day and 0.5 cm per week. She regained the ability to move her arms and legs and began to cry. She was suctioned frequently during the first month and developed a strong oral aversion. Suctioning was reduced to a minimum after the first month and her cardiorespiratory status remained very stable with consistent SaO2 of 100% even during crying episodes. Alissa was receiving oral feeding during this period that averaged between 15-20 ml per feed.
Third Month: Alissa was transported to the USA at 2 months of age via medical transport. She was transported directly to Yale New Haven Hospital with the plan of receiving a full evaluation, however due to an RSV epidemic she was discharged to the home with-in 36 hours. A nasal culture showed she was negative for RSV but positive for CMV.
She was then re-admitted to Norwalk hospital almost immediately because of diarrhea and fever symptoms. She was rotovirus positive and remained hospitalized until 1/29/01 when she was medically transported to Rainbow Babies Hospital in Cleveland to participate in an FDA study.
Fourth Month: The objective of the study was to use electrical stimulation to strengthen and stimulate the swallow reflex. She responded mixed to the treatments, in that she began to desaturate for the first time ever. We stopped the e-stim and conducted a series of tests to determine the cause of the desaturation. A PH probe showed mild reflux (appx 5%). A video EEG showed no abnormal brain activity and an apnea sleep study showed no apnea episodes. After the several weeks to complete the tests the problem corrected itself. It is our belief the e-stim increased the movement of the throat and tongue muscles. Unfortunately Alissa did not have adequate control over these muscles but over the course of two weeks she gained experience and control and the de-sat episodes stopped. She was put on Zantac and Reglan to treat her reflux.
We transported Alissa uneventfully via private car to Connecticut and began caring for her in a home environment for the first time. We began PT, OT and ST both privately and through Birth To Three. We also conducted 28 Hyperbaric Oxygen Treatments at Hudson Valley Hyperbaric under the direction of Dr. Jo Fiengold. Alissa tolerated the treatments well not suffering any barotrauma or seizure activity. However, she was not happy with the plastic hood and would sometimes be cry inconsolably and cause the session to end prematurely. During this period she was in good health and her gross motor skills progressed rapidly. She began rolling and assisted sitting. We ended hyperbaric oxygen when Alissa caught a cold and was very congested at the end of her fifth month.
Sixth and Seventh Months: Alissa has suffered from a two upper respiratory infection during much of these two months. Her pediatrician, Dr. Jenine Freliech and her pulmonalogist Dr. Sadeghi, monitored her during this period. On exmination by Dr. Sadgehi both tympanic membranes were clear. Lungs had adequate air entry with expiratory wheeze and transmitted upper airway sounds. She was prescribed Xopenex and Pulmicort as needed. Alissa’s developmental progression was slower during this period with below normal head growth.
Eighth Month: After Alissa’s cold symptoms dissipated we were surprised that her gagging, vomiting and excess secretions continued. We consulted Dr. Mark Glassman, GI and he recommended increasing the Zantac and reglan per her weight increase. This actually seemed to aggravate her symptoms of gagging and vomiting. In addition, Alissa began to desaturate again. The episodes always occurred in the evening about one to two hours after going to bed. She would quickly desat to the mid 80″s before we administered blow-by oxygen and stimulated her out of sleep. She would cough and clear secretions and remain fine for the rest of the evening.
Ninth Month: We moved permanently to Milwaukee, WI. We stopped the Reglan as we did not see that it was helping and Alissa responded very well. The gagging and vomiting was reduced significantly. We began an intensive program of 3x PT, 3x OT and 1x Speech using a combination of Birth to Three and Private Therapists. In addition we employed 2 Marquette University PT students for approximately 15 hours per week. Alissa progressed very rapidly during this period. She had above average head growth. Overall motor skills improved with increased strength increased random movement, voluntary reaching and the beginning of a voluntary grasp. After a very productive period of about three weeks we noticed that Alissa began to arch and thrust her head back more frequently. Occasionally, the gagging and subsequent vomiting returned. These abnormal movements became significant enough that it negatively effected her progress in her therapy. Therefore we began to examine alternatives to address the problem.
Tenth Month: We scheduled a FEES Study to visualize the upper throat, determine the anatomical cause of Alissa’s pooling of secretions and determine if Alissa is aspirating. Unfortunately due to the doctor suffering a leg injury we will not conduct the test till late August. We also made the decision to replace the NG tube with a G-tube. We decided to place the g-tube entirely on the hope that removal of the ng-tube will decrease Alissa’s secretions and improve her interest in oral feeding. Endoscopic evaluation of Alissa’s esophagus showed no irritation. Our goal in this month is to eliminate Alissa’s desire to thrust her head back and to the side.
This is our largest area of concern.. Alissa’s desaturation episodes, oral motor aversion and pooling of secretions all cause worries of long term aspiration risk. Alissa had one cyanotic episode due to a mucus plug during her second respiratory infection. This was a serious incident that required overnight hospitalization. As a positive note, Alissa has never shown any issues on her chest x-rays the latest conducted during her second respiratory infection.
Alissa had an Apnea Evaluation Study completed on 2/26/01 there were no prolonged obstructive or central apneas or evidence of respriatory dyshythima. The baseline saturation was >96%. A single transient period of SaO2 was noted with values in the mis 90% without a change in respiratory pattern and resolved spontaneously. Alissa had a second study completed on 6/12/01 after experiencing de-sat episodes at night. No significant episodes occurred during the study.
Alissa received Synagis (RSV vaccine) on 3/8/01 and second dose on 4/24/01. Alissa’s last Pulmonary evaluation was conducted on May 29, 2001 by Dr. Sadeghi. Nares were clear. Lungs had adequate air entry with transmitted upper airway sounds. There was no wheezing or crackles. Cardiovascular examination was unremarkable. Alissa was expected to return for follow-up in the fall.
On June 27th Alissa had a PEG tube placed. We made the decision to remove the NG-tube in the hope that removal of the NG would reduce Alissa’s secretions and irritation and thus reduce her respiratory risk and improve her oral interest.
Gastrointestinal: Alissa had two Ph Probe studies as she presents as a high risk for reflux. The first study was conducted on 1/24/01. No medications were in her system and she was fed pedialyte. The study showed 69 acid refluxes in a 17 hour period, 6 lasting more than 5 minues, the longest being 36 minutes, the fraction of time below 4% Ph was 10.9%. The second Ph probe test was done one month later with Zantac and Reglan in the system. This study resulted in 5% reflux.
In an effort to address Alissa’s thrusting her head back and to the side Alissa was perscribed Zantac and Reglan. Alissa was taken off Reglan on June 12th because of noted side effects of increased gagging and vomiting. We also tried 0.2 ml x4 of Eryromythican however this also did not seem to improve anything and it was stopped as well. Currently Alissa is only on 1.5ml Zantac 2x daily.
On June 27th Alissa had a PEG tube placed. We made the decision to remove the NG-tube in the hope that removal of the NG would reduce Alissa’s secretions and irritation and thus reduce her respiratory risk and improve her oral interest. During the procedure endoscopic evaluation of the esophagus showed no irritation. Biopsies were taken but no results as of this writing.
Neuroligical: No active seizures have been noted. Alissa received a CT scan in January. The scan showed some calcification in the Basil Ganglia.
She had a 24 hour Video EEG on 3/9/01. Four desaturation events were recorded with no electrographic change. Back arching and jaw quivering was noted with no EEF change. A single eye-rolling event was noted with no EEG change. There were sleep spindles that were asynchronous as well as asymmetric during the sleep portion of the study with no asymmetries noted. The automatic spike detection program found 0 events, none of which were associated with EEG changes. In summary the background waking record was age appropriate and the sleep portions were age appropriate as well.
An evaluation/assessment was conducted as part of the Birth To Three process. The test used was the Mullen Scales of Early Learning and was conducted on 1/24/01. Findings were that Gross, Fine and Oral Motor skills are all areas of concern. The scores were as follows: Gross Motor T Score 37, Percentile Rank 10%. Visual Reception 38 / 12%. Fine Motor 33/ 4%. Receptive Language 44 / 27%. Expressive Language 38 / 12%.
Lori Overland, a noted private therapist in the Connecticut area, conducted an Oral Motor evaluation on 4/12/01. Recommendations were to receive oral-motor/feeding therapy at least twice per week. We presented this to our Birth to Three program but unfortunately no therapy session were ever provided. We tried to work with-in the birth to three system to resolve the problem but were continually rejected. We let Connecticut before the problem was resolved. We now receive 1x per week ST via Birth To Three and work privately with Rona Alexander, PhD, ST as she is available. Alissa is not currently oral feeding, however she is rapidly overcoming her oral aversion and routinely places her thumb into her mouth.
An Occupation Therapy evaluation was conducted on 4/30/01. Weakness and underlying hypotonicity with bursts of movement into extension were noted. Shoulder retraction, trunk and neck extension, and fisted posturing of hands limit midline skills and development of fine motor milestones. Intensive therapy was recommended.
As of this writing Alissa has progressed well in the area of Fine Motor skills. Gross motor and oral motor continue to lag developmentally. In fine motor she now routinely bring both hands to mid-line to reach and grasp for objects. She has a voluntary grasp and shows less shoulder retraction. As noted elsewhere neck extension and twisting continue to pose a problem.
Alissa developmental strengths have been listed by her therapists as follows: Extremely alert and responsive to surroundings. Highly motivated during sessions. Very consistent, hardly ever has a bad day.
Her head growth continues to lag per the charts. She was born at the 3rd percentile with a HC of 32cm, currently she is at 40cm while the 3rd percentile would be 41.8 cm. It has been noted that periods of above average head growth have corresponded very well to periods where Alissa was feeling well and participating in a highly stimulating environment. We believe this is not a coincidence and consider it another piece of evidence to support our program of intensive therapy.