What is the recommended approach for a patient with a history of cancer, heart failure, or autoimmune diseases who may be at risk for CNS complications?

Detailed CNS Examination in High-Risk Patients

For patients with cancer, heart failure, or autoimmune diseases at risk for CNS complications, immediately rule out CNS disease progression, infection, metabolic derangement, and seizure activity before attributing symptoms to immune-related or systemic causes. 1

Initial Critical Assessment

Immediate Exclusions Required

• Rule out CNS progression of underlying malignancy through neuroimaging with contrast, particularly leptomeningeal metastases via CSF cytology 1
• Exclude active infection including bacterial meningitis, viral encephalitis (especially HSV), and opportunistic infections in immunocompromised patients 1
• Identify metabolic derangements such as hypoglycemia, hyperglycemia, ketoacidosis, thyroid dysfunction, and electrolyte abnormalities 2
• Assess for seizure activity using EEG if encephalopathy is present, as seizures can present with atypical aura or altered consciousness 1

Symptom-Specific Localization

For headache presentations, distinguish between aseptic meningitis (headache, photophobia, neck stiffness with normal mental status) versus encephalitis (confusion, altered behavior, seizures, memory loss, depressed consciousness) as this fundamentally changes workup and management 1

For focal neurological deficits, perform NIH Stroke Scale assessment and consider vascular causes including stroke/TIA, particularly in patients with cardiovascular disease history 3

For progressive symptoms, evaluate for space-occupying lesions (brain tumors, chloromas) that worsen with Valsalva, wake patients from sleep, or cause papilledema 2

Comprehensive Diagnostic Workup

Neuroimaging Protocol

• MRI brain and/or spine with and without contrast is the preferred initial imaging modality for subacute presentations, providing superior resolution for inflammatory processes, tumors, and demyelinating lesions 1
• Include pituitary/sellar protocol cuts to evaluate for hypophysitis and adrenal insufficiency 1
• Non-contrast CT head only if presentation is <6 hours from acute severe headache onset (95% sensitivity for subarachnoid hemorrhage on day 0) 2
• MRI spine with thin axial cuts through suspected abnormality if considering transverse myelitis or nerve root involvement 1

Lumbar Puncture Indications and Analysis

Perform lumbar puncture when suspecting:

• Encephalitis, aseptic meningitis, or sensorimotor neuropathy 1
• Any patient with headache plus altered mental status, fever, or meningeal signs 1

Essential CSF studies include:

• Opening pressure measurement (normal 6-25 cm H₂O; <6 suggests CSF leak, elevated suggests increased intracranial pressure) 2
• Cell count with differential, protein, glucose 1
• Cytology for malignant cells to definitively rule out leptomeningeal metastases 1
• Gram stain, bacterial and viral cultures 1
• PCR for HSV and other viral pathogens based on clinical suspicion 1
• Oligoclonal bands if demyelinating disease suspected 1
• Autoimmune encephalopathy and paraneoplastic antibody panels (anti-Hu/ANNA-1, anti-MAG, ganglioside antibodies, anti-ganglionic AChR) 1

Expected CSF findings:

• Immune-related meningitis/encephalitis: elevated WBC with lymphocytic predominance, elevated protein, normal glucose, negative cultures, possible reactive lymphocytes on cytology 1
• Guillain-Barré syndrome: elevated protein with normal or mildly elevated WBC (albuminocytologic dissociation) 1

Electrodiagnostic Studies

• Nerve conduction studies (NCS) and electromyography (EMG) for any sensory symptoms, weakness, or suspected peripheral neuropathy 1
• EEG to rule out subclinical seizures in encephalopathy presentations 1

Laboratory Evaluation

Mandatory initial labs:

• Complete metabolic panel, CBC with differential 1
• Morning cortisol and ACTH to exclude adrenal insufficiency 1
• Thyroid function (TSH, free T4) if symptoms of thyroid dysfunction present 2
• Cardiac enzymes and 12-lead ECG given high incidence of cardiac disease 3

Autoimmune and infectious screening:

• ANA, ESR, CRP, ANCA, anti-smooth muscle, SSA/SSB, RNP, anti-dsDNA 1
• Serum protein electrophoresis for paraproteinemia 1
• HIV, hepatitis B/C, Lyme serology, thiamine level 1
• Blood cultures if febrile 1

For neuropathy evaluation:

• Diabetic screening (HbA1c, fasting glucose), vitamin B12, folate 1
• Serum antiganglioside antibodies for Guillain-Barré syndrome subtypes 1

Grading Severity and Management Thresholds

Grade 1 (Mild)

• No interference with function, symptoms not concerning to patient
• Exception: Any cranial nerve involvement automatically escalates to Grade 2 management 1
• Hold immune checkpoint inhibitors (if applicable) and monitor closely for progression 1

Grade 2 (Moderate)

• Some interference with activities of daily living, concerning symptoms
• Mandatory neurology consultation 1
• Hold immunotherapy until return to Grade 1 1
• Consider prednisone 0.5-1 mg/kg/day if progressing 1

Grade 3-4 (Severe)

• Limiting self-care, aids required, weakness limiting ambulation, respiratory compromise
• Permanently discontinue immune checkpoint inhibitors 1
• Admit to hospital with ICU-level monitoring capability 1
• Initiate methylprednisolone 1-4 mg/kg/day (or pulse-dose 1 gram IV daily for 3-5 days for encephalitis/transverse myelitis) 1
• Consider IVIG 0.4 g/kg/day for 5 days (total 2 g/kg) or plasmapheresis for Guillain-Barré syndrome 1

Critical Pitfalls to Avoid

Do not empirically treat as immune-related adverse event without:

• Excluding CNS malignancy progression via contrast imaging and CSF cytology 1
• Ruling out HSV encephalitis—initiate empiric IV acyclovir until PCR results return 1
• Considering paraneoplastic syndromes in cancer patients, which may mimic immune-related toxicity 1

For autonomic dysfunction symptoms:

• Screen for diabetic neuropathy, adrenal insufficiency, HIV, paraproteinemia, amyloidosis, and botulism 1
• Obtain orthostatic vital signs 1
• Recognize this may occur with concurrent polyneuropathy requiring EMG/NCS 1

In heart failure patients with neurologic symptoms:

• Measure blood pressure carefully—do not aggressively treat elevated BP unless diastolic >120 mmHg or systolic >220 mmHg 3
• Consider posterior reversible encephalopathy syndrome (PRES) in setting of severe hypertension 1

Monitor for rapid progression:

• Guillain-Barré syndrome can progress to respiratory failure—frequent neurochecks and pulmonary function monitoring are mandatory 1
• Transverse myelitis requires evaluation for urinary retention and constipation 1