Neurology · Year 3 · from Neurology
Case 2: Brain Metastases with Unknown Primary
Patient Demographics
- Age: 58 years
- Sex: Female
- Occupation: Administrative assistant
Chief Complaint
"Terrible headaches and I feel off-balance for 2 weeks."
History of Present Illness
The patient presents with 2 weeks of progressively worsening headaches, initially mild and intermittent but now constant and severe. The headaches are worse when lying down and first thing in the morning. She has had persistent nausea and has vomited three times this week. She has noticed difficulty with balance and coordination, walking into door frames, and feeling "drunk." Her husband reports she has been confused at times and had word-finding difficulties. She had a 30 pack-year smoking history, quit 5 years ago. She has had an unintentional 15-pound weight loss over the past 3 months, which she attributed to stress. No prior cancer diagnosis.
Neurological Examination Findings
Vital Signs:
- BP: 138/82, HR: 88, RR: 16, Temp: 37.0C
Mental Status Examination:
- Alert, oriented to person and place, vague on date
- Mild word-finding difficulty
- MMSE: 26/30
Cranial Nerves:
- Pupils: Equal, reactive
- Papilledema present (bilateral disc swelling)
- Visual fields: Right superior quadrantanopia
- Eye movements: Full, no nystagmus at rest
- Gaze-evoked nystagmus on lateral gaze
- Facial sensation and movement intact
Motor Examination:
- 5/5 strength throughout
- Normal tone
Sensory Examination:
- Intact
Reflexes:
- 2+ symmetric
- Plantar responses flexor
Coordination:
- Dysmetria on finger-to-nose bilaterally (left > right)
- Dysdiadochokinesia
- Impaired heel-to-shin bilaterally
Gait:
- Wide-based, ataxic gait
- Unable to tandem walk
- Positive Romberg (falls backward)
Localization
- Bilateral cerebellar involvement (ataxia, dysmetria, gait instability)
- Possible left temporal/parietal involvement (quadrantanopia, word-finding)
- Elevated ICP (headache, papilledema, vomiting)
Neuro Workup
MRI Brain with Contrast:
- Multiple (>10) ring-enhancing lesions throughout the brain
- Largest lesion: 3.2 cm in left cerebellar hemisphere
- Additional lesions in: Right temporal, left parietal, bilateral frontal lobes
- Gray-white matter junction predominance
- Surrounding vasogenic edema
- Hydrocephalus from cerebellar mass effect on fourth ventricle
CT Chest/Abdomen/Pelvis:
- 3.5 cm spiculated mass in right upper lobe of lung
- Hilar and mediastinal lymphadenopathy
- No liver or adrenal metastases
PET-CT:
- Hypermetabolic right upper lobe lung mass
- Hypermetabolic mediastinal lymph nodes
- Brain lesions show increased uptake
Laboratory Studies:
- CBC: Normal
- CMP: Normal
- CEA: Elevated (12.5 ng/mL)
CT-guided Lung Biopsy:
- Non-small cell lung cancer - adenocarcinoma
- Molecular testing:
- EGFR mutation: Negative
- ALK rearrangement: Negative
- ROS1: Negative
- PD-L1: 60% (high)
- KRAS G12C: Positive
Diagnosis
Metastatic Non-Small Cell Lung Cancer (Adenocarcinoma) to Brain
- Stage IV (cT2N2M1b)
- Multiple brain metastases (>10 lesions)
Management
Immediate Treatment:
- Dexamethasone 10mg IV load, then 4mg q6h - reduce edema, improve symptoms
- Levetiracetam - seizure prophylaxis (supratentorial lesions)
- PPI for GI prophylaxis while on steroids
Neurosurgical Consultation:
- Posterior fossa decompression NOT indicated given multiple lesions
- No role for surgical resection with diffuse metastatic disease
Radiation Oncology:
- Whole-brain radiation therapy (WBRT) recommended
- 30 Gy in 10 fractions OR 37.5 Gy in 15 fractions
- Hippocampal-sparing technique considered to reduce cognitive effects
- Memantine added to reduce cognitive decline
- Stereotactic radiosurgery (SRS) not appropriate given >10 lesions
Medical Oncology:
- Systemic therapy initiated after WBRT:
- First-line: Pembrolizumab (anti-PD-1) + chemotherapy given high PD-L1
- KRAS G12C inhibitor (sotorasib) as potential later option
- Tyrosine kinase inhibitors not indicated (no actionable mutations)
Supportive Care:
- Physical therapy for ataxia and fall prevention
- Occupational therapy
- Speech therapy if needed
- Palliative care consultation for goals of care discussion
- Advanced care planning
Prognosis Discussion
Prognostic Assessment:
- Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for NSCLC:
- Multiple brain metastases, no targetable mutation
- Estimated median survival: 4-7 months with WBRT
Factors in This Case:
- Unfavorable: Multiple metastases, no EGFR/ALK mutation, symptomatic
- Favorable: Good performance status, high PD-L1 (may respond to immunotherapy)
Goals of Care Discussion:
- Discussed palliative nature of treatment
- Focus on quality of life and symptom control
- Established healthcare proxy
- Discussed hospice as future option
Clinical Image
Image Description: T1-weighted MRI with contrast showing multiple ring-enhancing brain metastases at the gray-white matter junction with surrounding vasogenic edema, characteristic of metastatic disease.
Attribution: Image from Wikimedia Commons. Licensed under CC BY-SA 3.0. Source: https://commons.wikimedia.org/wiki/File:Hirnmetastase_MRT-T1_KM.jpg
Key Teaching Points
Glioblastoma
- Most common and most aggressive primary brain tumor
- Characteristic imaging: Ring enhancement, central necrosis, edema
- IDH-wildtype defines glioblastoma (poor prognosis vs IDH-mutant)
- MGMT methylation predicts temozolomide response
- Standard treatment: Maximal safe resection + Stupp protocol (RT + temozolomide)
- Median survival ~15 months despite treatment
Brain Metastases
- More common than primary brain tumors (10:1 ratio)
- Most common primaries: Lung, breast, melanoma, renal, colorectal
- Imaging: Multiple lesions at gray-white junction, ring-enhancing
- Always search for primary if unknown
- Treatment based on number, size, primary tumor, molecular markers
- Options: Surgery (single, accessible), SRS (limited number), WBRT (multiple)
- Systemic therapy increasingly important (targeted therapy, immunotherapy)