Neurologic Manifestations of Glioblastoma Multiforme Clinical Presentation

Updated: Nov 07, 2021
  • Author: Gaurav Gupta, MD, FAANS, FACS; Chief Editor: Stephen A Berman, MD, PhD, MBA  more...
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Though the initial presentation of glioblastoma multiforme (GBM) is very non-specific, more than half of cases present to the emergency department with acute symptoms. [22]  Because of the rapidity of growth, GBM patients present with features of acutely raised intracranial tension (ICT). Many times, it is difficult to localize the symptoms due to extensive invasion, edema, hydrocephalus, and vascular compromise. [23]

Headache is one of the most common symptoms, especially if the tumor is arising in the posterior fossa. Incidence varies between 23% and 56%. [3, 4]  However, only 1–2 in 100 patients with headaches will harbor a brain tumor and GBMs are most common in supratentorial locations. Headache can be initially localized depending on the location and typically progresses over time to become holocranial. It is more common in the early morning, aggravated by lying down, coughing, and the Valsalva breathing maneuver. Also, it is usually associated with persistent nausea, vomiting, and blurring of vision in most patients. [22, 23, 3, 24]

Seizures are the other common non-specific manifestation of any brain tumor, seen in ~20% cases of GBM at presentation. Over the course of the disease, another 20% of these patients may develop seizures. However, some seizures can have peculiar features aiding the tumor localization. Patients can present with focal seizures, generalized seizures (GTCS), and complex partial seizures with preceding visual or gustatory or auditory auras. Many patients may have post-seizure transient motor weakness of the affected limbs (Todd’s paresis). [25]  New-onset seizures are found to be one of the main predictors of survival in studies. [4]

Progressive focal neurological deficits can develop typically over weeks to months in GBM patients. However, they can rarely present with acute deficits secondary to cerebrovascular ischemia or hemorrhage within the tumor. [23, 3, 25]

As an intra-axial tumor, GBMs can cause varied neurological, psychiatric, and cognitive disabilities depending on the location and extent of the tumor within the brain. Patients can present with motor weakness, cranial nerve palsies, ataxia or cerebellar symptoms, and other focal neurological deficits. Occasionally, these patients can present with solely psychiatric symptoms like mood disorders, schizophrenia, anorexia, and neurobehavioral disorders. Among patients presenting with purely psychiatric symptoms, depression is the most common presentation seen in more than 60% of patients followed by manic-like states and anxiety. Psychotic symptoms were noted in 35% of patients. Mood disorders were seen in patients with tumors of the frontal lobe, temporal lobes, and limbic structure. Psychotic symptoms are common with temporal lobe tumors and rarely with the frontal lobes and corpus callosum. Neurological disorders of diminished motivation (DDM) are the most common confusing disease. These patients present with a continuum of impairments in goal-directed behaviors arising from damage to dopaminergic neurons within the frontal lobes, basal ganglia, thalamus, substantia nigra, and mesolimbic structures. DDM encompasses apathy in its milder form, followed by abulia, and at the extreme end may present as akinetic mutism. These can resemble the psychomotor retardation of depression. However, they can be distinguished by lack of sadness, negative thoughts, irritability, and vegetative symptoms. [23]

Also, differentiating a psychiatric disorder from depression can be challenging especially during the early stages of tumor growth when symptoms are subtle. Late-onset, atypical psychiatric symptoms, negative family history of psychiatric diseases, and symptoms refractory to medications should raise suspicion of underlying organic causes like brain tumor/GBM. [23]



Physical findings depend on the location, size, and rate of growth of the glioblastoma multiforme (GBM) tumor, as with any other CNS tumor. Tumors in less critical areas (eg, anterior frontal or temporal lobe) may present with subtle personality changes and memory problems. Similarly, motor weakness and sensory hemineglect are the hallmarks of tumors arising in the frontal or parietal lobes and thalamic regions. Sensory neglect is more prominent in right hemispheric lesions. Note the following:

  • Seizures are a common presentation of small tumors in the frontoparietal regions (simple motor or sensory partial seizure) and temporal lobe (simple or complex partial seizure).

  • Occipital lobe tumors may present with visual field defects. Although these tumors are less frequent than tumors originating at other sites, patients generally are unaware of the slow onset of a cortically based hemianopsia.

  • Brainstem GBMs are rare in adults. However, they may present with bilateral crossed neurological deficits (eg, weakness on one side with contralateral cranial nerve palsy). Alternatively, they may present with rapidly progressive headache or altered consciousness.