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Detection and Evidence-Based Treatments for Likely Neuropsychiatric Outcomes from Brain Tumor Surgery are Critical

‘We need better evaluations, timeframes, diagnostic rigor, and metrics’

Systematically assessed neuropsychiatric outcomes in central nervous system oncology—similar to what exists in other neurosurgical domains such as epilepsy—are critical.

Such assessments preoperatively may indicate likely improvement or intensification of neuropsychiatric symptoms postoperatively.

Neuropsychiatric outcomes—cognition, depression, anxiety—are common after surgical resection of brain tumors, and their incidence varies across time.

Better methodology with standardized preoperative and postoperative evaluations, timeframes, diagnostic rigor, and measurable outcomes, including for quality of life, are required to inform discussions of outcomes for these patients.

“As patients with brain tumors live longer, neuropsychiatric disorders are increasingly relevant, requiring early identification and tailored evidence-based treatments for optimal outcomes,” say researchers at the Department of Psychiatry, and the University Health Network Centre for Mental Health, University of Toronto.


One of the research team, Alvin Keng, MD

Their findings from a scoping review are in the May/June issue of Psychosomatics.


Improving brain tumor survival rates have drawn increasing focus on neuropsychiatric and psychological outcomes, say researchers Alvin Keng, MD, and colleagues. Using a scoping method, they reviewed nearly 10,000 articles describing patients with adult brain tumor, who underwent partial or total brain resection, and examined major neuropsychiatric domains after intervention.

Most articles centered on survivorship within the first year. Cognition was most widely studied—showing a transient global worsening during the first month and usually recovery or improvement thereafter. Depression increased in frequency during survivorship and was associated with frontotemporal location, time to survival, quality of life, cognitive and physical parameters, and functional status. Anxiety, independent of depression, related to tumor histology and grading and had a weaker association with cognition and quality of life.

Obsessive-compulsive symptoms, psychosis, mania, and delirium received little attention. Most studies did not include preoperative neuropsychiatric assessment, and treatment was poorly addressed.

“This review highlights key gaps,” say the researchers. “A better understanding of postresection neuropsychiatric outcomes can inform our ability to prognosticate and tailor management for patients at risk for these life-impairing conditions.”

They add: “Until recently, most studies investigating outcomes after neurosurgery have focused on mortality and physical outcomes. With improved detection and treatments for brain tumors, survival rates have improved accompanied by increasing attention to patient-centered outcomes, such as neuropsychiatric and psychological symptoms.”

Clinical care

Brain tumors and related treatments may impact neuropsychiatric and psychological symptoms thus:

  • The disease and treatment cause localized damage to brain tissue and neurocircuitry.
  • Treatment may involve surgical resection, adjuvant chemotherapy, and radiotherapy, all of which can impact global physical and mental functioning. Chemotherapy agents are neurotoxic and specific agents (e.g., carmustine and methotrexate) have been associated with delayed leukoencephalopathy and neurocognitive dysfunction.
  • Commonly used medications for management (e.g., steroids and antiepileptic drugs) have well-known psychiatric side-effects.
  • Psychosocial factors, such as changes to social and occupational life and existential distress, play an integral role in outcomes.

Few studies in their research examined short-term and longer-term outcomes postoperatively. “Better understanding of neuropsychiatric outcomes postoperatively could lead to improved patient care and clinical outcomes,” say the researchers.

Cognition—Transient worsening of multiple cognitive domains (including verbal memory, figural memory, working memory, executive function, psychomotor function, information processing speed, attention, language, learning, and visuoconstruction) can occur in the first three months postoperatively, and are likely in relation to perioperative injuries and edema.

Recovery of function may be linked to neuroplasticity. Attention, language, working memory, and executive function appear to be the most sensitive domains.

Tumor location is more important than histology, and cognition may be preserved with, or deficits replaced by, intraoperative imaging guidance and functional mapping.

Unsurprisingly, language is related to laterality, with left- and right-sided deficits showing different patterns on neuropsychological testing.

“There are no established timelines for when cognitive outcomes are deemed chronic, and available studies are inadequate to draw conclusions about late outcomes,” say the researchers. “Future research focusing on treatment is needed, although some studies indicate that stimulants may have a role to play in improving processing speed and executive function, as well as the physical symptoms of depression.”

Depression—Risk factors for depression in this population include premorbid depression, lower education, and women (as in the general population). Not surprisingly, malignancy impacted depression scores, although other tumor factors have not been reliably demonstrated.

“As depression is associated with other neuropsychiatric symptoms, functional and physical recovery, quality of life, and survival, implementing a screening program may improve clinical outcomes,” say the researchers.

Although several screening tools have been used and validated in patients with brain tumor postoperatively, the HADS (clinician-rated tool) best approximated prevalence found in structured-clinical interviews.

However, depression concordance between clinicians and patients was very low, perhaps explained by:

  • Mismatched definitions among patients and clinicians.
  • Surgeons not asking, or
  • Subthreshold symptoms.

“Treatment of depression in this population is poorly studied and requires further investigation given potential side-effects (e.g., selective serotonin re-uptake inhibitors (SSRIs) increasing bleeding risk, hyponatremia, and falls.)”

Anxiety—Anxiety was shown to impact poor health, quality of life, and emotional and physical functioning. Reported prevalence was highly variable among studies, likely related to:

  • The six-month criteria of anxiety disorders in the Diagnostic and Statistical Manual of Mental Disorders – Fifth Edition.
  • Limitations of specific screening tools.
  • Failure to distinguish anxiety from depressive disorders.

Risk factors for anxiety included a history of psychiatric illness, women, and lower education level, as well as some tumor factors including malignancy and laterality.


A better understanding of neuropsychiatric outcomes can inform our ability to prognosticate and tailor-manage patients at risk for these life-impairing conditions.


Other symptoms—Several other clusters of neuropsychiatric symptoms, such as delirium, psychosis, mania, and obsessive-compulsive symptoms, received little attention in studies. “This is especially concerning,” say the researchers, “as the existing literature suggests that confusion and delirium are common postoperatively in neurosurgical patients.”

Psychosomatics journal coverThe full paper, Examining the Neuropsychiatric Sequelae Postsurgical Resection of Adult Brain Tumors Through a Scoping Review, by Alvin Keng, MD, Donna Stewart, MD, FRCPC, and Kathleen Sheehan, MD, FRCPC, is here.



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