Diagnostic Workup for Suspected GBM Presenting with Peripheral Tingling
Tingling in the arms, legs, and back is an atypical presentation for glioblastoma and should prompt immediate brain MRI, but this symptom pattern more likely suggests spinal cord pathology, peripheral neuropathy, or other systemic conditions rather than an intracranial GBM.
Understanding the Clinical Context
GBM typically presents with symptoms of increased intracranial pressure (headache, vomiting), new-onset seizures, focal neurological deficits (hemiparesis, aphasia), or neurocognitive impairment 1. The characteristic presentation involves symptoms localized to the brain rather than diffuse peripheral sensory disturbances 1, 2.
Peripheral tingling in multiple extremities and the back is not a typical manifestation of GBM 1. While GBM can present atypically with focal motor weakness or coordination problems 2, 3, bilateral peripheral sensory symptoms suggest alternative diagnoses such as:
- Spinal cord compression or pathology
- Peripheral neuropathy
- Metabolic disorders
- Cervical myelopathy
Immediate Diagnostic Algorithm
Primary Imaging
Obtain brain MRI with and without intravenous contrast as the first-line imaging study 1. This should include:
- T1-weighted sequences (with and without contrast) 1
- T2-weighted sequences and/or FLAIR imaging 1
- Three-dimensional acquisition using standardized techniques 1
MRI is superior to CT scanning for detecting gliomas and should be used preferentially 1.
Concurrent Spinal Evaluation
Given the atypical symptom pattern with back and bilateral extremity involvement, obtain spinal MRI to evaluate for cord compression, myelopathy, or other spinal pathology that could explain the sensory symptoms.
Clinical Assessment
Document specific neurological findings 1:
- Focal motor deficits (paresis, weakness)
- Sensory distribution patterns (dermatomal vs. non-dermatomal)
- Signs of increased intracranial pressure (papilledema, altered mental status)
- Seizure activity
- Neurocognitive function using standardized assessment (MMSE or MoCA) 1
The Neurological Assessment in Neuro-Oncology (NANO) scale can document examination findings systematically 1.
If Brain Lesion is Identified
Tissue Diagnosis is Mandatory
Histological confirmation must be obtained because neuroimaging alone is insufficient for definitive diagnosis 1. The only exception is elderly patients with deep-seated lesions and very poor performance status where biopsy risk outweighs benefit, though this should remain exceptional 1.
Surgical Approach
- Maximal safe resection should be performed whenever feasible 1
- If major resection is too risky, perform stereotactic or open biopsy 1
- Ensure tissue samples are representative, particularly from contrast-enhancing areas 4
- Obtain postoperative MRI within 72 hours to assess extent of resection 1, 4
Essential Molecular Testing
Tissue must be processed for 1, 4:
- Histological diagnosis using 2016 WHO classification (type and grade)
- IDH1/IDH2 mutation status (required for classification)
- 1p/19q codeletion testing (particularly for oligodendroglial tumors)
- MGMT promoter methylation (predicts temozolomide response)
- Optional: Ki67, GFAP immunohistochemistry
Samples should be processed immediately by pathology, with tissue fixed in 10% formaldehyde for histology and frozen in liquid nitrogen for molecular studies 1, 4.
Critical Clinical Pitfalls
Do not assume GBM based on peripheral sensory symptoms alone - these are not characteristic presentations 1, 2. While GBM can present atypically with unusual neurological symptoms 2, 3, bilateral peripheral tingling suggests alternative pathology.
Maintain high clinical suspicion but pursue appropriate differential diagnosis including:
- Spinal cord lesions (primary or metastatic)
- Paraneoplastic syndromes (if systemic cancer present)
- Metabolic/toxic neuropathies
- Cervical spondylotic myelopathy
If brain imaging is negative but symptoms persist, continue investigation with spinal imaging and consideration of systemic causes 3. Brain tumors should be kept in mind for patients with atypical symptoms, but imaging should be performed and repeated if symptoms remain unresolved 3.
Performance Status Assessment
Document Karnofsky Performance Score (KPS), as this critically influences treatment decisions 1. KPS ≥70 generally indicates candidacy for aggressive multimodal therapy, while KPS <70 suggests consideration of palliative approaches 1.