Neuroregenerative and Neurorehabilitative Therapy in a Patient with Alobar Holoprosencephaly and Related Diagnoses
This case study presents a nine-month-old patient with congenital diagnoses of Alobar Holoprosencephaly, brachial plexus injury, hemi diaphragm paralysis, and malrotation of the small intestine, undergoing care at the NeuroSolution Center of Austin.
Abstract
This case study presents a nine-month-old patient with congenital diagnoses of alobar holoprosencephaly, brachial plexus injury, hemi diaphragm paralysis, and malrotation of the small intestine, undergoing care at the NeuroSolution Center of Austin. Alobar holoprosencephaly is a severe developmental anomaly characterized by incomplete separation of the cerebral hemispheres, often leading to significant neurological and functional deficits. The brachial plexus injury caused significant limitations in right upper extremity motor control and strength. Hemi diaphragm paralysis, due to phrenic nerve involvement, impacted respiratory efficiency. Lastly, malrotation of the small intestine presented risks of volvulus and obstructive complications.
The patient underwent two separate 2-week intensive rehabilitation sessions focused on the proprietary NeuroSolution Energy, Sensory, and Movement methods, as well as regenerative medicine interventions, including the SONG Laser Activated VSEL procedure with extracellular vesicle inclusion. Post-treatment results showed substantial improvements in muscle tone, coordination, voluntary motor control, core stability, and developmental milestones. The patient's ability to vocalize and interact socially also progressed, demonstrating the potential efficacy of these novel approaches.
This case highlights the safety and potential effectiveness of innovative neuroregenerative and neurorehabilitative therapies in addressing complex neurological and systemic conditions, warranting further study and broader clinical application.
Introduction
The patient, born on August 20, 2023, presented with the following congenital diagnoses:
- Alobar Holoprosencephaly: A severe neural tube defect causing failure of midline brain division, associated with fusion of cerebral hemispheres, basal ganglia, and partial thalami. The condition often leads to significant neurological impairment.
- Brachial Plexus Injury: Resulting in limited function of the right upper extremity with a mix of upper and lower motor neuron signs.
- Hemi Diaphragm Paralysis: Leading to compromised respiratory function due to phrenic nerve involvement.
- Malrotation of the Small Intestine: A congenital anomaly increasing the risk of volvulus and intestinal obstruction.
At the time of initial treatment (May 13, 2024), the patient was nine months old. A multidisciplinary approach was implemented to address her complex needs.
Initial Clinical Presentation
MRI Findings
- Mild enlargement of the supratentorial monoventricle.
- Partial effacement of sulci.
- Mild crowding at the foramen magnum, without pegging of cerebellar tonsils.
- Persistent findings consistent with holoprosencephaly.
Clinical Exam Findings (Performed by Dr. Brandon Crawford)
- General Muscle Tone: Globally low functional muscle tone, cortical fisting bilaterally, occasional leg extension when excited, and rigidity throughout.
- Right upper extremity: Cortical fisting present. Moderate to severe limitation of use with mixed upper and lower motor neuron signs. Moderate to severe reduction in range of motion. Moderate to severe rigidity noted throughout.
- Left upper extremity: Cortical fisting present. Mild to moderate limitation of use, relatively normal range of motion noted. Mild to moderate rigidity noted, mostly associated with excitement or volitional movements.
- Right lower extremity: Moderate to severe rigidity noted throughout. Mild to moderate reduction in range of motion.
- Left lower extremity: Mild to moderate rigidity noted throughout. Mild to moderate reduction in range of motion.
- Vocalization: Can produce cooing sounds, is not verbal.
- Eye contact and regard: some text
- Joint attention is not fully present.
- Does portray interest in faces of parents, family and others. Does seem to prefer looking at faces over inanimate objects.
- Tracking is present but is not always smooth.
- Core Stability: Concentric tone dominant. Reduced head / neck stability, not able to hold head upright on her own for prolonged periods of time.
Primitive Reflexes
Rooting: 4 bilaterally
Palmar: 4 bilaterally, cortical fisting noted bilaterally
Babkin: 4 bilaterally
Babinski: 4 bilaterally
TLR: Could Not Perform
ATNR: Could Not Perform
STNR: Could Not Perform
Spinal Galant: Hypotonic
Spinal Perez: Hypotonic
Fear Paralysis: Positive based on history
Moro: Smiles and enjoys vestibular inputs. May have auditory induced Moro at times.
Postural Reactions
Parachute: Not intact
Propping: Not intact
Head Righting: Not intact
Reticular Activating System / Alertness: Alert to environment and others. Will respond and turn her head to brother's voice. Will interact with Kristin and I while she was being held.
Rolling Ability: Initiates amphibian rolling, stronger from right to left. Does not initiate via the right upper extremity.
Additional Medical History
- Silent aspiration noted on swallow study.
- History of NG tube placement, which proved counterproductive. NG tube seem to make swallowing more challenging for unknown reasons.
- Low cortisol levels managed with hydrocortisone; previously high TSH normalized with levothyroxine.
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Interventions
Intensive Rehabilitation Outline:
The patient underwent an intensive rehabilitation program spanning 4 weeks in total, divided into two 2-week sessions conducted in the summer and fall of 2024. Each session comprised 18-hour therapy weeks, with care provided 5 days per week. The therapy sessions utilized the proprietary NeuroSolution Energy, Sensory and Movement methods, which integrate multiple innovative strategies and modalities to promote neuroplasticity and functional recovery.
The goal of care, as with every patient in our office, is to establish and promote one or all four types of functional neuroplasticity. There are at least four major forms of functional neuroplasticity that can be studied in humans: homologous area adaptation, cross-modal reassignment, map expansion, and compensatory masquerade. Homologous area adaptation is the assumption of a particular cognitive process by a homologous region in the opposite hemisphere. Cross-modal reassignment occurs when structures previously devoted to processing a particular kind of sensory input now accepts input from a new sensory method. Map expansion is the enlargement of a functional brain region on the basis of performance. Compensatory masquerade is a novel allocation of a particular cognitive process to perform a task. By focusing on these four forms of functional neuroplasticity, several fundamental questions about how functional cooperation between brain regions is achieved can be addressed (1). What we have noted in the clinical setting for the past several years is that there are many complex cases that require an integrated and more complete approach to care. The NeuroSolution Methods were born out of this need and are defined to include protocols and modalities that were designed to achieve more sustainable and rapid results for this complex demographic of patients. We are now also applying these same methods and procedures to optimize individuals seeking to improve their health, wellness and overall neurological prowess; not only those seeking help due to pathology.
In addition to these rehabilitative approaches, the patient also underwent advanced regenerative medicine procedures aimed at supporting and enhancing the therapeutic gains:
SONG Laser Activated VSEL Procedure: We performed the proprietary SONG Laser activated VSEL procedure once during each intensive care setting for a total of two procedures performed. This procedure has been pioneered by Dr. Todd Ovokaitys PhD. Dr. Marcella Madera, MD is a neurosurgeon that has continued to develop this procedure. Dr. Madera was our medical director overseeing the administration of these procedures in this case study. Dr. Brandon Crawford, Dr. Jeri LaVigne, Katie Volkers, and a licensed pediatric anesthesiologist performed the regenerative medicine procedures on the patient. This procedure leverages the activation of the human very small embryonic-like stem cells that are generated from the plasma generating process. Human very small embryonic-like (hVSEL) stem cells are pluripotent stem cells found in peripheral blood and most tissues, and represent a unique and readily available source of stem cell for regenerative medicine procedures. Other authors have also confirmed the presence of hVSEL stem cells in peripheral blood and that these cells may be envisioned as “cellular paramedics” that are involved in immune surveillance or tissue and organ rejuvenation. It is generally agreed that hVSEL stem cells are a population of epiblast-derived cells created during embryonic gastrulation which further highlights their important role in normal physiology as well as their role in rejuvenation and longevity. The possible role of hVSEL stem cells in disease modulation is under intense study, including research on cardiovascular disease, neurogenesis, Crohn’s disease and even reproductive biology. Given this background, it is clear that hVSEL stem cells play an important role in both normal physiology and disease. An enhanced understanding of how we may improve the biological potential of these cells by using modulated laser light will lay the ground-work for future exciting collaborations between healthcare scientists and quantum physicists to develop a unified understanding of cell biology at the finite level (2) (3).
Extracellular Vesicle Therapy: Administered to reduce systemic inflammation and improve cellular communication, this therapy facilitated an optimal environment for neuroplastic changes and tissue healing. “Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising exosomes and microvesicles, which originate from the endosomal system or which are shed from the plasma membrane, respectively. They are present in biological fluids and are involved in multiple physiological and pathological processes. Extracellular vesicles are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material. Knowledge of the cellular processes that govern extracellular vesicle biology is essential to shed light on the physiological and pathological functions of these vesicles as well as on clinical applications involving their use and/or analysis. However, in this expanding field, much remains unknown regarding the origin, biogenesis, secretion, targeting and fate of these vesicles.” (4)
This combined approach of intensive rehabilitation and regenerative medicine reflects an integrative care model designed to maximize recovery potential in patients with severe neurological and systemic conditions.
Additionally, we created a comprehensive home care plan tailored to the patient's findings and needs to ensure continued progress outside of the clinical setting. The home care plan involved five days of care per week with two rest days, incorporating strategies from our NeuroSolution ESM Methods. This included specific exercises to support neuroplasticity, sensory integration, and movement patterns, as well as targeted laser and photobiomodulation protocols to sustain and enhance the therapeutic gains achieved during intensive therapy.
Results
Updated Clinical Exam Findings per Dr. Brandon Crawford:
- General Muscle Tone: Globally improved functional muscle tone as indicated by improvements in range of motion and volitional movement and reductions in rigidity, cortical fisting reduced and largely eliminated in her left hand, occasional leg extension when excited reduced and largely eliminated.
- Right upper extremity: Cortical fisting present but is reduced. Moderate limitation of use with mixed upper and lower motor neuron signs. Moderate reduction in range of motion. Moderate rigidity noted throughout.
- Left upper extremity: Cortical fisting no longer present. Mild limitation of use, relatively normal range of motion noted. Mild rigidity noted, mostly associated with excitement or volitional movements.
- Right lower extremity: Mild to moderate rigidity noted throughout. Mild reduction in range of motion.
- Left lower extremity: Mild rigidity noted throughout. Mild reduction in range of motion.
- Vocalization: Has experienced an increase in ability to vocalize and has said “mama”, “dada”, and “brother”.
- Eye contact and regard: some text
- Joint attention is not fully present.
- Does portray interest in faces of parents, family and others. Does seem to prefer looking at faces over inanimate objects. Has continued to increase in her interest in others.
- Tracking is present and appears to be more smooth.
- Core Stability: Enhanced isometric tone.
Primitive Reflexes
Rooting: 4 bilaterally with improved tone
Palmar: 4 Right / 3 Left
Babkin: 4 Right / 3 Left
Babinski: 4 Right / 3 Left
TLR: Could Not Perform
ATNR: Could Not Perform
STNR: Could Not Perform
Spinal Galant: 4, lower tone noted in right paraspinals. Great improvements in spinal tone.
Spinal Perez: 4, lower tone noted in right paraspinals. Great improvements in spinal tone.
Fear Paralysis: Negative
Moro: Smiles and enjoys vestibular inputs.
Postural Reactions
- Parachute: Intact with mild to moderate lag
- Propping: Intact with mild to moderate lag
- Head Righting: Intact with mild to moderate lag
- Turtle Pose: Can perform with assistance
- Lion Pose: Can perform with assistance
- Quadraped Pose: Can perform with assistance
- Rolling Ability: Can now initiate amphibian rolling with the right upper extremity.
Visual bedside inspection of eyes
- Mild right exotropia noted when fatigued per parents, not currently present.
Optokinetic Evaluation
- Downward: hypometria noted, mild to moderate
- Upward: hypometria noted, mild
- Left: Hypometria noted, mild to moderate
- Right: hypometria noted, mild
Functional Milestones
Quoted from the mom of the patient on December 30, 2024:
“Before our first visit I never would’ve suggested Millie was lethargic, wouldn’t have said she didn’t move around. I would’ve only mentioned lack of head control. After 3 days of therapy, Millie’s spine straightened out, she felt stronger (I didn’t know how to explain that and I believe you told me, that’s her muscle tone kicking in!) can vocal turn take, with new sounds everyday. Shes said mama, dada and “brother”. She brings her hands to her mouth, toys to midline, her mouth and switches between hands, she eats some solid solids and loves to taste all the things! She has gained a whole pound since we left! She gets stronger and stronger every day with head control and core strength. She can do tummy time now. This morning she rolled from back to belly to back unprompted by herself! She splashes her legs in the bath. She belly laughs. She participates in her Bible study class. She knows what and who she wants when she wants it/them.”
Discussion
This case demonstrates the potential for functional neuroplasticity in severe neurological conditions such as alobar holoprosencephaly. By targeting the four major types of neuroplasticity—homologous area adaptation, cross-modal reassignment, map expansion, and compensatory masquerade—the NeuroSolution ESM methods promoted notable advancements in the patient’s motor control, sensory processing, and overall development.
The SONG Laser Activated VSEL procedure with the inclusion of extracellular vesicles derived from human amniotic fluid is a promising regenerative therapy that appears to amplify these gains by facilitating cellular repair and neuroregeneration. Further research is warranted to validate these findings and explore broader applications of these techniques.
Conclusion
The results clearly demonstrate improvement in this patient. She experienced notable advancements in muscle tone, movement patterns and coordination, vocalization, core stability, vestibular function, energy levels, and overall developmental progress. The methods used on this patient and others in our office demonstrate safety and efficacy and should be studied further. This represents great potential for those with severe neurological compromise, even of genetic origin, such as alobar holoprosencephaly. Furthermore, we are now applying these methods to individuals seeking to optimize their neurology and overall health. This expansion beyond treating pathology allows us to provide advanced neurorehabilitative and neuroregenerative techniques to those aiming to enhance their functional capabilities and achieve peak neurological performance.
References
- Grafman, J. (2000). Conceptualizing functional neuroplasticity. *Journal of Communication Disorders, 33*(4), 345-356. DOI: 10.1016/s0021-9924(00)00030-7
- A Theoretical Mechanism for the Action of SONG-Modulated Laser Light on Human Very Small Embryonic-Like (hVSEL) Stem Cells in Platelet Rich Plasma (PRP). *CellR4* 2021; 9: e3201. DOI: 10.32113/cellr4_20216_3201
- Human Very Small Embryonic Like (hVSEL) Stem Cells: Little Miracles. *CellR4* 2022; 10: e3304. DOI: 10.32113/cellr4_20225_3304
- van Niel G, D'Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol. 2018 Apr;19(4):213-228. doi: 10.1038/nrm.2017.125. Epub 2018 Jan 17. PMID: 29339798.
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