What is the management approach for an elderly patient presenting with focal onset seizures, leukocytosis (elevated White Blood Cell count) with lymphocytosis (elevated lymphocytes percentage)?

Management of Elderly Patient with Focal Onset Seizures and Marked Lymphocytic Leukocytosis

This elderly patient with focal onset seizures and WBC 45,000 with 85.5% lymphocytes requires immediate evaluation for chronic lymphocytic leukemia (CLL) with CNS involvement, followed by concurrent seizure management and hematologic workup.

Immediate Diagnostic Priorities

Hematologic Evaluation

• Obtain flow cytometry of peripheral blood immediately to diagnose CLL, as this absolute lymphocyte count of ~38,500 cells/mm³ strongly suggests lymphoproliferative disorder 1
• Perform blood smear microscopy to confirm mature lymphocyte morphology characteristic of CLL 1
• Screen for Del(17p) and/or TP53 mutations if CLL is confirmed and treatment is planned 1
• Complete blood count with differential, LDH, beta-2 microglobulin, and comprehensive metabolic panel 1

Neurologic Evaluation

• Obtain urgent brain MRI with contrast to evaluate for CNS lymphoma involvement, stroke, or structural lesions causing focal seizures 2
• Lumbar puncture with CSF flow cytometry if CNS lymphoma is suspected based on imaging or neurologic findings 1
• EEG to characterize seizure focus and assess for ongoing epileptiform activity 2

Infection Exclusion

• While this lymphocyte-predominant leukocytosis is unlikely infectious, obtain chest radiograph and blood cultures if fever is present 3, 4
• Critical distinction: Neutrophilic left shift (≥16% bands or absolute band count ≥1,500/mm³) suggests bacterial infection, whereas lymphocytic predominance points to CLL 3, 4, 5

Seizure Management

Acute Treatment

• Initiate levetiracetam 500-1000 mg twice daily as first-line antiepileptic therapy for focal onset seizures in elderly patients 6, 7
• Levetiracetam is preferred because it has minimal drug interactions, does not require hepatic metabolism, and is generally well-tolerated in elderly patients 6
• Important caveat: Levetiracetam can cause minor decreases in WBC and neutrophil counts, but this is clinically insignificant and should not be confused with the underlying lymphocytosis 6

Etiology-Specific Considerations

• In elderly patients with new-onset focal seizures, cerebrovascular disease accounts for 39% of cases, brain tumors 11%, and metabolic disorders 7% 2
• 80% of elderly patients with first seizures have focal onset, with 50% becoming secondarily generalized 2
• If CLL with CNS involvement is confirmed, seizures may resolve with treatment of the underlying lymphoma 1

CLL-Specific Management Framework

Fitness Assessment

• Use geriatric assessment to stratify patient as fit, vulnerable, or terminally ill, which determines treatment intensity 1
• Assess comorbidities, functional status (ADL/IADL), and treatment goals (curative vs palliative) 1

Treatment Based on Fitness and Genetics

For Fit Elderly Patients WITHOUT Del(17p)/TP53mut:

• Consider bendamustine plus rituximab (BR) or dose-attenuated FCR as first-line therapy 1
• Chlorambucil combinations (with obinutuzumab, ofatumumab, or rituximab) are alternatives 1

For Vulnerable Elderly Patients WITHOUT Del(17p)/TP53mut:

• Treat with obinutuzumab-chlorambucil (G-CLB), ofatumumab-chlorambucil (O-CLB), or rituximab-chlorambucil (R-CLB) 1

For ANY Patient WITH Del(17p)/TP53mut:

• Ibrutinib is the recommended first-line therapy regardless of fitness level 1

For Relapsed/Refractory CLL:

• Ibrutinib or idelalisib plus rituximab are first-line salvage options (Level I evidence, Grade A recommendation) 1

Critical Pitfalls to Avoid

Diagnostic Errors

• Do not dismiss this as seizure-induced leukocytosis: Seizures can cause transient leukocytosis, but this is typically neutrophilic (not lymphocytic) and resolves within hours 8
• Do not attribute lymphocytosis to antiepileptic drugs: While carbamazepine can cause leukocytosis, it is neutrophilic, not lymphocytic 9, 10
• Levetiracetam causes minor WBC decreases, not increases 6

Management Errors

• Do not start chemotherapy before confirming CLL diagnosis with flow cytometry and genetic testing 1
• Do not withhold antiepileptic therapy while awaiting hematologic workup—seizure control is immediate priority 7
• Do not perform bone marrow biopsy in terminally ill patients if it will not change management 1

Treatment Selection Errors

• Do not use full-dose FCR in elderly patients except in very carefully selected fit individuals 1
• Be aware that bendamustine combinations carry infection risk requiring prophylaxis consideration 1
• Exercise caution with idelalisib due to significant toxicity including diarrhea and opportunistic infections 1

Prognostic Considerations

• Provoked seizures are common in hospitalized elderly patients (63% vs 26.8% community-onset), with proconvulsant medications being a major risk factor 7
• Despite ILAE criteria, 72.5% of elderly patients with first seizures receive antiepileptic drugs, while 19% who meet criteria do not—highlighting need for standardized approach 7
• CLL prognosis depends heavily on Del(17p)/TP53mut status, fitness level, and treatment selection 1