Brain Surgery’s Most Feared Side Effect May Not Shorten Glioma Patients’ Lives

Neurosurgeons have long dreaded a peculiar complication that can strike patients after brain tumor surgery: the sudden inability to move or speak, despite the fact that the operation never touched the brain’s primary motor or language pathways. Known as supplementary motor area syndrome, this transient shutdown of movement initiation and speech production has been documented for nearly half a century, yet its consequences for cancer care have remained surprisingly murky. Now, a retrospective study from LMU University Hospital in Munich, published in the Journal of Neuro-Oncology, offers a reassurance that many in the field will welcome: patients who develop the syndrome after glioma resection are no more likely to have their adjuvant therapy delayed, and they do not live shorter lives than those who escape it.

The supplementary motor area, or SMA, is a strip of cortex on the medial surface of the frontal lobe, tucked anterior to the primary motor cortex and bounded by the superior frontal sulcus, the interhemispheric fissure, and the cingulate sulcus. It orchestrates the initiation and coordination of voluntary movement and contributes to speech fluency. Because frontal gliomas frequently invade or abut this region, surgeons operating there routinely risk provoking the syndrome, which classically presents as contralateral weakness or slowness of movement, impaired motor initiation, mutism or reduced verbal output, and a striking general reduction in spontaneous activity. Previous reports have placed its incidence anywhere between 23 and 100 percent depending on the tumor type and surgical definition, with one prominent series reporting 60.7 percent in SMA-involving glioma resections.

The Munich team, led by Dragan Jankovic and Darius Kalasauskas, set out to answer a question that had never been systematically addressed: does this dramatic postoperative deficit actually matter for oncological outcomes? The concern is clinically grounded. Functional status is one of the strongest prognostic factors in glioma care, because patients must be well enough to tolerate radiotherapy and chemotherapy within the narrow window of roughly four to six weeks after surgery. If SMA syndrome knocked patients below the eligibility thresholds for standard treatment protocols, it could indirectly cost them survival time even if the deficit itself was harmless.

To find out, the researchers reviewed 74 consecutive patients who underwent resection of gliomas involving, adjacent to, or approached through the SMA between 2015 and 2024. The cohort spanned World Health Organization grades 2 through 4, from slower-growing IDH-mutant tumors to aggressive IDH-wildtype glioblastoma. The team defined SMA syndrome strictly: new-onset motor deficits or language impairment without corresponding changes in intraoperative neuromonitoring, and without imaging or surgical evidence of injury to the primary motor cortex, the corticospinal tract, or ischemia. This definition matters, because it separates a network-level functional disruption from direct structural damage to the brain’s motor highways.

Half of the patients, 37 of 74, developed the syndrome after surgery. That figure alone is striking, but the recovery pattern was equally notable. By the first outpatient follow-up, at a median of 43 days, 81 percent of affected patients had fully recovered, and both groups had returned to a median Karnofsky Performance Status of 90. The syndrome, in other words, was overwhelmingly transient, consistent with the idea that the SMA’s functions are redistributed across parallel motor networks once the acute postoperative disruption subsides.

The statistical analysis, using logistic and Cox regression models adjusted for age, preoperative functional status, and tumor volume, delivered the study’s central message. Postoperative SMA syndrome was not associated with delayed initiation of adjuvant therapy, with a hazard ratio of 0.86 and a p-value of 0.617. It did not predict worse progression-free survival, with a hazard ratio of 1.21 and a p-value of 0.573, and it did not predict worse overall survival, with a hazard ratio of 1.21 and a p-value of 0.681. Kaplan-Meier curves for both survival endpoints overlapped almost completely between patients with and without the syndrome. Even the small subgroup of seven patients whose deficits persisted at follow-up showed no statistically significant survival disadvantage, although the authors caution that this exploratory finding rests on very limited numbers.

What did predict the syndrome? The extent of resection, classified according to the RANO resection system, emerged as the key risk factor. Compared with supramaximal RANO class 1 resections, class 2 resections, encompassing complete and near-total removal of contrast-enhancing or T2-FLAIR-visible tumor, carried roughly fivefold higher odds of postoperative SMA syndrome in the multivariable model, with an odds ratio of 5.05 and a p-value of 0.024. The authors interpret this not as a reason to stop short of maximal resection, but as a reflection of the anatomical reality: class 2 resections frequently represent the limit of what is safe when tumors press against eloquent motor pathways, including the corticospinal tract and the frontal aslant tract, a fiber bundle previously implicated in both the occurrence and the recovery of SMA syndrome.

Perhaps the most clinically consequential finding concerns what actually drives treatment decisions. Patients whose Karnofsky score dropped by 20 points or more after surgery were far more likely to receive modified or reduced-intensity adjuvant therapy, with an adjusted odds ratio of 13.91 and a p-value of 0.005. Yet SMA syndrome itself was not associated with treatment modification at all. The distinction is subtle but important: a global decline in functional status, which may stem from frailty, delayed recovery, reduced mobility, or systemic complications such as pneumonia, is what makes oncologists and tumor boards recalibrate therapy, not the specific neurological signature of SMA syndrome. Decision-makers, the authors suggest, calibrate treatment to overall functional reserve rather than to any particular deficit phenotype.

The study also reinforces a growing mechanistic understanding of why the syndrome occurs and why it resolves. Intraoperative neuromonitoring changes were rare and showed no association with the syndrome, supporting the concept that SMA syndrome arises from disruption of higher-order motor networks, including interhemispheric connections through the corpus callosum, rather than from injury to the corticospinal tract that standard monitoring interrogates. Previous work has shown that recovery from the syndrome is predicted by restoration of this interhemispheric SMA connectivity, a pathway that is anatomically distinct from the motor tract and invisible to conventional neuromonitoring. This network-level explanation fits neatly with the predominantly transient course observed in Munich.

The authors are candid about the limitations. The retrospective design may have undercounted subtle or short-lived manifestations, particularly mild language disturbances. Karnofsky scores are a blunt instrument for capturing SMA-specific deficits. Diffusion tensor tractography was not systematically available, leaving the spatial relationship between tumors and functional pathways unquantified. The single-center cohort of 74 patients limits statistical power, as reflected in wide confidence intervals, and the mixed tumor grades required two different RANO classification frameworks. Still, the consistency of the findings across univariate, multivariable, and Kaplan-Meier analyses lends weight to the conclusion. For patients facing glioma surgery near the supplementary motor area, the message is cautiously optimistic: the frightening postoperative shutdown that surgeons have feared since the era of Penfield is, in oncological terms, a detour rather than a dead end, and it should not deter maximal safe resection when the tumor demands it.

Subject of Research: The impact of postoperative supplementary motor area syndrome on adjuvant therapy timing and survival in intracranial glioma surgery

Article Title: Supplementary motor area syndrome in intracranial gliomas is not associated with worse survival

Article References: Supplementary motor area syndrome in intracranial gliomas is not associated with worse survival. (n.d.). https://doi.org/10.1007/s11060-026-05805-y

Image Credits: AI Generated

DOI: 10.1007/s11060-026-05805-y

Keywords: supplementary motor area, SMA syndrome, glioma, glioma surgery, adjuvant therapy, progression-free survival, overall survival, Karnofsky Performance Status, neuromonitoring, extent of resection, neuro-oncology, neurosurgery