Adult Brain Reshapes Language Areas After Tumor Removal

Daniel M. Keller, PhD

July 05, 2012

July 5, 2012 (Prague, Czech Republic) — Contrary to earlier beliefs, the adult human brain has remarkable potential for functional reorganization after excision of a progressive tumor mass, new findings suggest.

Reporting a study of patients with surgically resected gliomas, Janpeter Nickel, MD, senior physician in the stroke unit at the Neurological Clinic of the Protestant Hospital Duisburg-North of the Heinrich-Heine-University Düsseldorf in Duisburg, Germany, presented evidence of a variety of patterns of language reorganization, demonstrating cortical plasticity.

Dr. Nickel said that besides Broca's and Wernicke's areas in the left hemisphere — the classical language areas of the brain – several other areas contribute to the language system and together "constitute an executive and perceptive system within the fronto-temporal lobes," with the right hemisphere providing understanding on a contextual level.

Their results were presented here at the 22nd Meeting of the European Neurological Society (ENS).

Eloquent Cortex

Functional magnetic resonance imaging (fMRI) is routinely used to plan surgical resections, estimate potential deficits caused by resection of tumor growth, and map structure-function relationships in patients.

Dr. Nickel and colleagues studied language function in patients with gliomas near the eloquent cortex using fMRI as patients completed sentences with inflectional processing of verbs. They looked for correlations of the fMRI and language abilities, asking whether changes in cortical topography necessarily lead to impairment.

The investigators studied 11 patients with a mean age of 36 ± 13 years with left hemisphere low- and high-grade gliomas, defined as World Health Organization (WHO) grade II or III, in a variety of locations. The patients had good function with modified Rankin Scale scores of 0 to 2.

Investigators performed 1 to 4 imaging, language, and neuropsychological measurements on the same day over a period of 3 to 39 months and did both cross-sectional and longitudinal analyses. The language and neuropsychological tests measured behavioral memory, aphasia, reading and dictation, and semantic/categorical verbal fluency.

Dr. Nickel told delegates that the tests for each individual patient "remained relatively stable over time, and although they show a wide variation between the patients...most of the patients showed good functional compensation of language, and if they showed dysfunction...this is normally restricted to single aspects of language and not generally." Major changes in cortical activation patterns of an individual patient were associated with partial resection or with growth of the glioma.

He cited 1 patient who underwent surgery and later radiation therapy for a WHO grade II glioma as an example of the plasticity of language localization, with fMRI showing areas of activity.

"You see that activation remains pretty much stable, and even after resection there was, of course, a change in the pattern, but if you look at the [language] test results, they remained pretty stable," Dr. Nickel said. Another patient, with a WHO grade III anaplastic glioma, also showed a similar pattern, with good and stable language function after surgery and radiation.

The investigators found in general an intrahemispheric shifting of language activation to regions adjacent to the lesion mass if the mass was in the language regions. All the tumors in this series were in the left hemisphere, and the main regions of activation occurred in the left frontal and temporal lobes, similar to the locations seen in healthy volunteers. There was also frequent coactivation of homologous areas in the right hemisphere, Dr. Nickel reported.

"The altered pattern of language activation we see in these tumor patients may reflect compensatory mechanisms of functional reorganization or cortical plasticity of the adult human brain in the face of progressive mass lesion," Dr. Nickel concluded. "As compared to patients with vascular lesions, of course, even if they are of similar size and position, these patients with gliomas seem to perform better on the performance level as seen in the tests."

He suggested that the rate of lesion growth may play a critical role in patients' adaptability and function.

In their abstract, the authors note that "most of the work contributing to this investigation was done as part of her doctoral thesis by Mrs. Daniela Kopp, nee Will, who was a diligent and really likeable MD student in our [neuroimaging] lab.

"In August 2011, just a few days before submission of her virtually completed manuscript to our Medical Faculty, she died in a tragic car accident," they write. "Since a posthumous submission of her dissertation is not allowed, this contribution to the ENS meeting is meant to commemorate and honor her work."

Histologically Benign

Session chairman Jacques De Reuck, MD, PhD, retired head of the Department of Neurology at Ghent University in Belgium and now working in neuroimaging at Lille University in Lille, France, commented to Medscape Medical News that he was not surprised by the results because many of the tumors were of grade II, "a still histologically benign tumor, but in which there is a long preservation of neurons," meaning that such tumors generally contain neurons that still function.

"So it's not surprising that the language function didn't change from the place and that you have only a very late compensatory mechanism, including using the other hemisphere and extending [to adjacent regions]," he said.

He noted that the problem with gliomas is that it is nearly impossible to remove all the tumor tissue unless one is willing to perform a very extensive resection and "do a lot of damage." But grade II tumors grow very slowly. "It can go over 10 or 15 years even. Grade III on the other hand...this group is accelerating," Dr. De Reuck said.

The slower growing tumors are much less damaging. "So it's an infiltrating tumor, not a compressing tumor, not a destructive tumor," he said. Neurons in and around the tumor can still function.

As Dr. Nickel reported, deficits were seen only in specific language test subdomains and not in language overall. Dr. De Reuck said these deficits become apparent with sensitive enough tests, but "in speech, you will not detect it. We'll have a more or less normal conversation,'" he noted.

There was no commercial funding for the study. Dr. Nickel and Dr. De Reuck have disclosed no relevant financial relationships. Dr. De Reuck had no involvement in the study.

22nd Meeting of the European Neurological Society (ENS). Abstract # O-238. Presented June 10, 2012.

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