What is the differential diagnosis for a patient with fever for 10 days, slurring of speech, and a left plantar extensor response?

Differential Diagnosis for Pyrexia (10 Days), Slurring of Speech, and Left Plantar Extensor Response

The combination of prolonged fever with focal neurological signs (dysarthria and unilateral extensor plantar response) indicates central nervous system infection or inflammation, with viral encephalitis being the most critical diagnosis requiring immediate empiric treatment. 1

Primary Diagnostic Considerations

Viral Encephalitis (Most Urgent)

• Herpes simplex encephalitis (HSE) is the leading diagnosis given the triad of fever, speech disturbance, and focal neurological signs with an extensor plantar response indicating upper motor neuron involvement 1
• Fever is present in 91% of HSE cases on admission, with speech disturbances occurring in 59% and behavioral changes in 41% 1
• The presence of focal neurological signs (unilateral extensor plantar response) strongly suggests cortical involvement, typical of HSE which preferentially affects temporal lobes 1
• Empiric IV acyclovir (10 mg/kg every 8 hours) must be initiated immediately while awaiting diagnostic confirmation, as delays in treatment significantly worsen outcomes 1, 2

Bacterial Meningoencephalitis

• Ten days of fever with progressive neurological deterioration warrants consideration of partially treated or atypical bacterial infection 1
• Tuberculous meningitis presents subacutely with fever, altered mental status, and focal deficits including cranial nerve palsies and pyramidal signs 1
• Listeria monocytogenes can cause rhombencephalitis with brainstem signs and should be covered empirically in older or immunocompromised patients 1

Parasitic CNS Infections

• Neurocysticercosis can present with seizures, focal deficits including extensor plantar responses, and subacute fever, particularly in endemic areas 3
• Multiple cysts throughout the brain parenchyma can cause raised intracranial pressure and focal neurological signs 3
• Cerebral malaria should be considered with appropriate travel history, presenting with fever, altered consciousness, and focal signs 1

Autoimmune/Antibody-Mediated Encephalitis

• Anti-NMDA receptor encephalitis and other antibody-mediated encephalitides present with subacute behavioral changes, speech disturbances, and movement disorders 1
• These conditions may have fever, though typically less prominent than infectious causes 1
• Features suggesting antibody-mediated disease include orofacial dyskinesia, choreoathetosis, or intractable seizures 1

Tickborne Rickettsial Diseases

• Human monocytic ehrlichiosis (HME) can present with fever, altered sensorium (up to 20% of cases), and CNS manifestations including seizures and focal weakness 1
• Neuroimaging is usually normal or nonspecific, but CSF may show lymphocytic pleocytosis in 50% of cases 1
• Consider with appropriate exposure history (outdoor activities, tick bites) 1

Other Infectious Considerations

• Epstein-Barr virus can rarely cause acute cerebellar ataxia with fever, dysarthria, and extensor plantar responses 4
• Brain abscess (bacterial or fungal) presents with fever, focal deficits, and signs of raised intracranial pressure 1

Non-Infectious Causes to Consider

Drug-Induced Encephalopathy

• Metronidazole-induced encephalopathy presents with acute onset dysarthria, ataxia, and cerebellar signs, though fever is not typical 5
• Symptoms develop after prolonged metronidazole use and resolve completely after drug discontinuation 5

Neuroleptic Malignant Syndrome

• Presents with fever, altered mental status, muscle rigidity, and autonomic instability in patients on antipsychotic medications 6
• Requires immediate drug discontinuation and intensive supportive care 6

Still's Disease (Adult-Onset)

• Can present with prolonged fever and neurological manifestations, though CNS involvement is uncommon 1
• Typically accompanied by characteristic salmon-pink rash, arthritis, and markedly elevated ferritin 1

Critical Immediate Actions

Urgent Diagnostic Workup

• Lumbar puncture is essential unless contraindicated by signs of raised intracranial pressure or focal mass lesion 1
• Many patients require CT scan before LP to exclude contraindications; clinical assessment should guide this decision on a case-by-case basis 1
• CSF studies must include: opening pressure, glucose (with paired serum glucose), protein, cell count with differential, bacterial culture, and HSV PCR 1
• If HSV PCR not sent on first LP, repeat CSF PCR on second LP; consider HSV CSF IgG at 10-14 days 1

Neuroimaging

• MRI brain with contrast is preferred over CT for detecting encephalitis, showing temporal lobe involvement in HSE 1
• CT may show multiple calcifications (neurocysticercosis) or ring-enhancing lesions (abscess) 3

Additional Laboratory Testing

• Blood cultures (at least two sets) before antibiotics 7
• Complete blood count, comprehensive metabolic panel, liver function tests 1
• Serology for relevant pathogens based on exposure history (EBV, rickettsial diseases, endemic parasites) 1, 4
• Consider autoimmune encephalitis panel if infectious workup negative 1

Empiric Treatment Algorithm

While awaiting diagnostic confirmation:

1. Immediately initiate IV acyclovir 10 mg/kg every 8 hours for presumed HSE 1, 2
2. Add broad-spectrum antibiotics (ceftriaxone 2g IV q12h PLUS vancomycin) if bacterial meningoencephalitis cannot be excluded 1
3. Add ampicillin 2g IV q4h if Listeria is a consideration (age >50, immunocompromised) 1
4. Continue acyclovir for 14 days if HSE confirmed; stop if CSF HSV PCR negative on repeat testing 1

Common Pitfalls to Avoid

• Never delay acyclovir while awaiting LP or imaging results in suspected encephalitis—mortality increases significantly with treatment delays 1
• Do not dismiss the diagnosis of encephalitis based on normal initial consciousness level, as subtle behavioral changes may be the only early sign 1
• Avoid attributing symptoms to psychiatric illness, drugs, or alcohol without excluding organic CNS pathology 1
• Do not obtain nasopharyngeal aspirate in suspected SARS or highly infectious conditions as this generates aerosols 1
• Remember that elderly and immunocompromised patients may present atypically without prominent fever despite severe infection 7, 8
• The presence of rash, lymphadenopathy, or prominent systemic symptoms makes isolated CNS infection less likely and suggests alternative diagnoses 1