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.


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.