Infinite Potential Program

Cortical Integrative Therapy in Cortical Malformation
with Heterotopias of the Gray Matter:

Dr. Victor M. Pedro
Department of Clinical Sciences, University of Bridgeport, Bridgeport, Connecticut, U.S.A.

ABSTRACT

A case study is described of a 10-year-old left-handed Caucasian male with a neuronal migration disorder characterized by a large diffuse cortical malformation and a probable right cortical malformation with associated heterotopias of the brain's cortical substance (gray matter). Causation unknown. Born slightly premature after 371/2 week gestation. Medical condition is significant for febrile seizures. Recurrent learning disabilities included weak auditory memory skills, below normal motor coordination, poor problem-solving skills and reading comprehension, and difficulty with the language of mathematics. Intelligence tests registered in the Low Average range. Performance weaknesses noted in abstract reasoning, sequencing of socially meaningful visual stimuli, and retention of auditory stimuli. After five years of special education interventions with no significant improvement in any measurable area of function, a multimodal approach using techniques aimed at facilitating inter-hemispheric communication was provided. At completion of the Cortical Integrative Therapy program, significant improvements were observed in memory and reading comprehension skills, abstract reasoning, auditory processing, motor coordination, and sequencing of visual stimuli. There have been no febrile seizures since cessation of program.

KEY WORDS: neuronal migration disorder, cortical malformation, heterotopias, Cortical Integrative Therapy

Neuronal migration appears as a complex ontogenic step occurring early during embryonic and fetal development. As the cerebral cortex is formed, a process known as neocorticogenesis, neurons derive from the primitive neuroepithelium and migrate to their appropriate position in the cerebral mantle. In humans, migration of neocortical neurons occurs mostly between the 12th and the 24th week of gestation (Gressens P., 2000). Control of neural migration involves different cell populations including Cajal-Retzius neurons, subplate precursor neurons, and non-neural cells known as radial glia. Although the exact manner in which migrating neuronal cells find their destinations is not completely understood, the glial cells play an integral role in the development of the cortex. Apparently, the process involves the building of scaffolds or chemical trails that migrating cells follow (Rakic P., 1992). These trails are formed by glial cells, which are guided by local chemical cues, made by genes and their by-products, that serve as molecular signposts, creating barriers that restrict movement and providing adhesive surfaces. As the emerging brain expands in size, the traveling glia grow fibers that extend out from the proliferative zone (the place where the precursor cells are making neurons and glia) toward the brain surface (where the neurons need to go to form the cortex). By crawling along the glial trail, the young neurons find their way to their target (LeDoux J., 2002).

But without precise timing kept intact in order to foster these myriad ontogenic actions, the cerebral developmental plan fails. In a cascading effect, neuronal migration disorders can cause congenital cerebral malformations during the third and fourth months of gestation. Usually classified as agyria, pachygyia, schizencephaly, polymicrogyria, and heterotopic gray matter, these malformations can have deleterious effects (Orderud W. et al, 1995). Frequently, neuronal migration disorders result in epile psychomotor retardation (motor skill deficits) and cerebral palsy, auditory or visual processing deficits, or defective mental development displayed by various degrees of intellectual impairment, including severe learning disabilities and mild mental retardation.

Heterotopias of the gray matter, a neuronal migration disorder sub-type, originate between the 12th and 16th gestational week (Treguier C. et al, 1993). Because of a failure of normal migration, neurons may accumulate in unusual areas (Powell E. et al, 2003). Misplaced or displaced cortical neurons can interfere with higher level cognitive processing. Symptomology can include generalized seizures, mild mental retardation, auditory processing-related learning disabilities, and slight to moderate deficits in motor skills. Associated cortical malformations related to the heterotopias but distinct from them can also occur (Porter B. E. et al, 2002). Gray matter is the cortical substance of the brain consisting primarily of nerve cells and synaptic connections. Heterotopias, often diffuse infiltrations, are known to saturate large areas of healthy cortical tissue.

CASE REPORT

D.L. is a 10-year-old left-handed male, born at 6 pounds, 3 ounces following a slightly premature (371/2 weeks) gestation delivered by caesarean section due to breech positioning. (Normal gestation is 38 to 40 weeks.) Mother experienced high blood pressure and edema during pregnancy. D.L. became ambulatory at 13 months; his speech commenced at age two, short sentences spoken at age three. Toilet training attained at three years, six months. Medical history is positive for febrile seizures, ear infections, and seasonal allergies. A maternal uncle and D.L's father were also positive for febrile seizures, and the uncle's visual-spatial style of learning was subsequently equated with D.L.'s style of learning. D.L's early behavioral and developmental history seemed otherwise relatively normal to his parents. Academic issues began in kindergarten. He began experiencing difficulty with classroom activities that required language processing and verbal expression. Verbal directions often needed to be repeated when D.L. had difficulty with discrimination of letter sounds. At age 6 years, 1 month, a school psychologist administered a battery of intelligence tests, but these were inconclusive. Both his verbal (82) and performance (84) scores on the Wechsler Intelligence Scale for Children - Third Edition (WISC-III) were within the low normal range of cognitive functioning. Overall, he displayed average to low average performance in visual-spatial analysis, visual-motor integration, and visual processing speed. In fact, D.L.'s performance with tasks that required visual recall suggested no deficit and reflected no areas of relative delay. At that time there was no diagnosis, but D.L. was offered speech and language therapy, focusing on expressive language. At age 6 years, 9 months, D.L. was reassessed for purposes of evaluating progress. He was judged to be within normal limits (age appropriate) for skill areas such as oral peripheral (able to produce speech), articulation, phonological awareness, vocabulary development, expressive vocabulary, language development, and auditory processing. But he was well below normal in auditory word and number memory and interpretation of directions. Resourceful, D.L. often attempted to compensate by using meaning, structural, and visual cues to self-correct. At age 7 years 8 months, D.L. was given a central auditory processing evaluation. He was found to be easily distracted by background sounds, had difficulty recalling auditory information, and had difficulty learning through the auditory channel. He was beginning to have difficulty with reading comprehension and mathematics. In a filtered word subtest, he scored technically within the average range, but was on the verge of an auditory processing disorder. He would hear a simple word and it sounded slightly distorted or muffled. Problems on this test seemed to indicate an auditory processing disorder. A pitch pattern sequence test (PPST) proved more problematic. Instructed to listen to three tones that were in combinations of high and low pitches and then discriminate between high and low, he performed poorly, suggesting a compromise of the inter-hemispheric pathways or of the left hemisphere. Although D.L. possessed an excellent ability to understand speech in quiet listening conditions, in competing sound environments, he demonstrated a distinct right ear weakness. Specifically, he had difficulty selectively attending to speech in the presence of background noise and difficulty decoding auditory information coming from different locations. As a consequence of this evaluation, he was fitted with a "hearing aid," more precisely, a FM Auditory Assistive Listening Device, to improve signal-to-noise ratio (teacher's voice relative to the background noise) and improve D.L's comprehension in the classroom. He was also enrolled in Earobics -- an auditory enhancement program for slow listeners. It was strongly advised that a neuropsychological evaluation be performed to rule out a neurologically based language or learning disability. As a second grader, D.L. continued to have difficulty focusing and following oral directions, as well as difficulty with new concepts, in particular the language of mathematics. Despite his deficits, D.L. tested well within the normal range (42 percentile) on the Iowa Tests of Basic Skills as a second grader. At age eight years ten months, additional developmental tests revealed considerable strengths as a visual-spatial learner; for instance, he possessed very strong artistic abilities, especially in drawing and copying figures. He showed mixed dominance with left hand and right eye dominance. His gross motor function was above average, as shown by his ability to perform rapid alternating movements, hop in place, perform a sideways tandem gait, and catch a ball. As language tasks became more complex and abstract, however, D.L. had much more difficulty. Memory was another troublesome area. For instance, drawing from memory was difficult for D.L. and sequencing when drawing figures was erratic. While he was able to name the days of the week backwards, he proved unable to learn a series of seven words in four tries and could not learn a visual pattern in four tries. Reading comprehension was well below normal; he was observed to be a "very well-behaved boy who copes well with his substantial learning disabilities." A physician's comments in the evaluative summary finally observed that D.L. was afflicted with more than an auditory processing disorder. "D.L. has a much more complex processing problem, with overall processing issues of both visually and auditorially presented information." This more ominous report became a prediction of diagnosis when D.L. underwent a more conclusive Brain MRI with contrast spectroscopy at age 10 years 2 months. What the magnetic resonance scan discovered was quite significant, but not entirely unexpected from a clinician's perspective. Essentially, it revealed a large diffuse cortical malformation with associated heterotopic gray matter visible in the left hemisphere. A right subependymal nodular heterotopia and probable right frontal cortical malformation was also existent. He also was diagnosed with a variant circle of Willis vascular anatomy. The MRI detail confirmed a large area of heterotopic gray matter. In addition, focal nodular areas of similar intermediate signal intensity (positive for brain anomalies) were noted in the subependymal areas of the frontal horn of the right lateral ventricle, which was also diagnosed as likely gray matter heterotopias. The left caudate head and basal ganglia were malformed, appearing to be fused. An abnormal gyral pattern was observed in the right frontal lobe with a focal cortical malformation involving this lobe as well. The ventricles and CSF spaces were prominent, but remained within normal limits. What enabled D.L. to function at all was that his midline structures were otherwise normal with no evidence of mass or shift, and that his brainstem, cerebellum, and craniocervical junction were normal. Note was made of an azygos anterior cerebral artery arising from the right internal carotid artery, and that the left internal carotid artery terminated in the left middle cerebral artery as well. But no evidence of intraparenchymal hemorrhage or extra-axial fluid was identified. Finally, the MR spectroscopy demonstrated normal NAA, creatine, and choline ratios without evidence of abnormal metabolites.

METHOD

12-week program of Cortical Integrative Therapy

RESULTS

At the conclusion of the 12-week treatment program, D.L. showed considerable gains in his ability to understand directions as noted by an independent examiner, a school psychologist. His overall academic performance, as noted by his classroom teachers and parents, was also significantly improved especially in the areas of reading comprehension and memory. D.L.'s febrile seizures appear to have ended.

DISCUSSION

Heterotopias associated with cortical malformations are often causal for major intellectual deficits and severe learning disabilities. D.L. had been stymied throughout his academic career by these conditions and his quality of life was severely restricted. But when a multimodal approach using techniques aimed at facilitating inter-hemispheric communication was provided, evidence was produced to indicate that when such techniques are applied, the prospect of indirect neuronal or network modulation occurring as cortical pathways are stimulated becomes a real possibility worthy of further investigation. In addition, there are valuable intangibles effecting quality of life. Prior to participation in Cortical Integrative Therapy, D.L. "hesitated to speak up in almost any situation and answered in mumbled monosyllables when he had to speak," according to his mother. Subsequent to the alternative treatment regime, he is "talkative, outgoing, and happy" and "speaks in a voice that has some confidence to it."

REFERENCES

Gressens, P. (2000) "Mechanisms and Disturbances of Neuronal Migration." Pediatric Research, 48: 725-730

LeDoux, J. (2002) "Synaptic Self: How Our Brains Become Who We Are." p69 (2)

Orderud W.J., Skjeldal O.H., Stromme P. "Neuronal Migration Disorders." Radiological and Clinical Aspects, Tidsskr Nor Laegeforen. 1995 Jun 20; 115 (16): 1952-56.

Porter, B.E., Brooks-Kayal A., and Golden J.A. "Disorders of Cortical Development and Epilepsy." Arch Neurology, March 1, 2002; 59(3):361-365.

Powell, E.M., Campbell D.B., Stanwood G.D., Davis C., Noebels J.L., Levitt P. "Genetic Disruption of Cortical Interneuron Development Causes Region -And GABA Cell Type- Specific Deficits, Epilepsy, and Behavioral Dysfunction." The Journal of Neuroscience, January 15, 2003, 23(2): 622-631

Rakic P., 1992, Science 258: 1421-1422

Treguier C., Muh P., LeBerre C., Sorel L., Odent S., Dacher J.N., Carsin M. "Diffuse subcortical heterotopias of the gray matter." Pediatrie. 1993;48(3):223-227.