Plasticity in the developing brain: neurophysiological basis for lesion-induced motor reorganization.

The plasticity of the developing brain can be observed following injury to the motor cortex and/or corticospinal tracts, the most commonly injured brain area in the pre- or peri-natal period. Factors such as the timing of injury, lesion size and lesion location may affect a single hemisphere's ability to acquire bilateral motor representation. Bilateral motor representation of single hemisphere origin is most likely to occur if brain injury occurs before the age of 2 years; however, the link between injury aetiology, reorganization type and functional outcome is largely understudied. We performed a retrospective review to examine reorganized cortical motor maps identified through transcranial magnetic stimulation in a cohort of 52 patients. Subsequent clinical, anthropometric and demographic information was recorded for each patient. Each patient's primary hand motor cortex centre of gravity, along with the Euclidian distance between reorganized and normally located motor cortices, was also calculated. The patients were classified into broad groups including reorganization type (inter- and intrahemispheric motor reorganization), age at the time of injury (before 2 years and after 2 years) and injury aetiology (developmental disorders and acquired injuries). All measures were analysed to find commonalities between motor reorganization type and injury aetiology, function and centre of gravity distance. There was a significant effect of injury aetiology on type of motor reorganization (P < 0.01), with 60.7% of patients with acquired injuries and 15.8% of patients with developmental disorders demonstrating interhemispheric motor reorganization. Within the interhemispheric motor reorganization group, ipsilaterally and contralaterally projecting hand motor cortex centres of gravity overlapped, indicating shared cortical motor representation. Furthermore, the data suggest significantly higher prevalence of bilateral motor representation from a single hemisphere in cases of acquired injuries compared to those of developmental origin. Functional outcome was found to be negatively affected by acquired injuries and interhemispheric motor reorganization relative to their respective counterparts with developmental lesions and intrahemispheric motor reorganization. These results provide novel information regarding motor reorganization in the developing brain via an unprecedented cohort sample size and transcranial magnetic stimulation. Transcranial magnetic stimulation is uniquely suited for use in understanding the principles of motor reorganization, thereby aiding in the development of more efficacious therapeutic techniques to improve functional recovery following motor cortex injury.

Image-guided TMS is safe in a predominately pediatric clinical population.

OBJECTIVE: The safety of transcranial magnetic stimulation (TMS) has been previously evaluated in healthy volunteers and clinical adult populations. We sought to fill the gap in safety of TMS functional mapping in a clinical, predominately pediatric cohort. METHODS: In a retrospective chart review, we assessed TMS motor and language mapping studies in persons with epilepsy or brain tumor for adverse events and safety of TMS, and in patients with cranial metal. RESULTS: Out of 500 TMS sessions attempted in 429 individual patients (51% males, 82% ≤ 18 y), seizures occurred in 29 sessions (5.8%) during or after TMS with semiology consistent with their typical presentation and 53 patients (10.6%) experienced pain during stimulation. TMS was completed safely in 276 patients with cranial metal. CONCLUSIONS: Most TMS-related adverse events were benign and transient; the most serious safety events were seizures that could not be conclusively attributed to TMS. However, useful mapping results were obtained in almost all patients. Presence of cranial metal did not adversely affect TMS mapping. We show that TMS functional mapping is safe in a largely pediatric clinical cohort. SIGNIFICANCE: This study demonstrates the safety of TMS functional mapping in patients with refractory epilepsy, brain tumor or cranial metal and fills a gap in knowledge for TMS safety in pediatric clinical population.

Clinical Utility of Transcranial Magnetic Stimulation (TMS) in the Presurgical Evaluation of Motor, Speech, and Language Functions in Young Children With Refractory Epilepsy or Brain Tumor: Preliminary Evidence.

Accurate presurgical mapping of motor, speech, and language cortices, while crucial for neurosurgical planning and minimizing post-operative functional deficits, is challenging in young children with neurological disease. In such children, both invasive (cortical stimulation mapping) and non-invasive functional mapping imaging methods (MEG, fMRI) have limited success, often leading to delayed surgery or adverse post-surgical outcomes. We therefore examined the clinical utility of transcranial magnetic stimulation (TMS) in young children who require functional mapping. In a retrospective chart review of TMS studies performed on children with refractory epilepsy or a brain tumor, at our institution, we identified 47 mapping sessions in 36 children 3 years of age or younger, in whom upper and lower extremity motor mapping was attempted; and 13 children 5-6 years old in whom language mapping, using a naming paradigm, was attempted. The primary hand motor cortex was identified in at least one hemisphere in 33 of 36 patients, and in both hemispheres in 27 children. In 17 children, primary leg motor cortex was also successfully identified. The language cortices in temporal regions were successfully mapped in 11 of 13 patients, and in six of them language cortices in frontal regions were also mapped, with most children (n = 5) showing right hemisphere dominance for expressive language. Ten children had a seizure that was consistent with their clinical semiology during or immediately following TMS, none of which required intervention or impeded completion of mapping. Using TMS, both normal motor, speech, and language developmental patterns and apparent disease induced reorganization were demonstrated in this young cohort. The successful localization of motor, speech, and language cortices in young children improved the understanding of the risk-benefit ratio prior to surgery and facilitated surgical planning aimed at preserving motor, speech, and language functions. Post-operatively, motor function was preserved or improved in nine out of 11 children who underwent surgery, as was language function in all seven children who had surgery for lesions near eloquent cortices. We provide feasibility data that TMS is a safe, reliable, and effective tool to map eloquent cortices in young children.

Presurgical language mapping in bilingual children using transcranial magnetic stimulation: illustrative case.

BACKGROUND: Presurgical mapping of eloquent cortex in young patients undergoing neurosurgery is critical but presents challenges unique to the pediatric population, including motion artifact, noncompliance, and sedation requirements. Furthermore, as bilingualism in children increases, functional mapping of more than one language is becoming increasingly critical. Transcranial magnetic stimulation (TMS), a noninvasive brain stimulation technique, is well suited to evaluate language areas in children since it does not require the patient to remain still during mapping. OBSERVATIONS: A 13-year-old bilingual male with glioblastoma multiforme involving the left parietal lobe and deep occipital white matter underwent preoperative language mapping using magnetic resonance imaging-guided TMS. Language-specific cortices were successfully identified in both hemispheres. TMS findings aided in discussing with the family the risks of postsurgical deficits of tumor resection; postoperatively, the patient had intact bilingual speech and was referred for chemotherapy and radiation. LESSONS: The authors' findings add to the evolving case for preoperative dual language mapping in bilingual neurosurgical candidates. The authors illustrate the feasibility and utility of TMS as a noninvasive functional mapping tool in this child. TMS is safe, effective, and can be used for preoperative mapping of language cortex in bilingual children to aid in surgical planning and discussion with families.