What is the differential diagnosis for a patient with blurring of vision, vomiting, headache, and fever, and a positive familial history?

Differential Diagnosis: Blurred Vision, Vomiting, Headache, Fever with Positive Family History

The constellation of fever, headache, vomiting, and blurred vision with a positive family history demands immediate consideration of CNS infections (meningitis/encephalitis), followed by evaluation for inherited conditions that may predispose to intracranial pathology, and exclusion of other life-threatening secondary causes.

Priority 1: Life-Threatening CNS Infections

Viral or bacterial meningitis/encephalitis must be ruled out first given the classic presentation of fever with headache, vomiting, and altered neurological function (blurred vision). 1

Key Clinical Features Supporting CNS Infection:

• Fever with altered mental status, behavior changes, or focal neurological signs (including visual disturbances) strongly suggests encephalitis 1
• Headache with nausea, vomiting, and fever represents the classical triad of CNS infection 1
• Visual disturbances occur from dural irritation and localized encephalitis affecting cranial nerves or visual pathways 1
• The presence of nuchal rigidity, photophobia, or altered consciousness would further support this diagnosis 1

Immediate Actions Required:

• Do not delay empiric antimicrobial therapy while awaiting diagnostic confirmation, as delays worsen outcomes and increase mortality 1, 2
• Obtain blood cultures, complete blood count, hepatic transaminases, and serum sodium before antibiotics 1
• Neuroimaging (CT or MRI) before lumbar puncture if focal neurological signs, altered consciousness, or concern for increased intracranial pressure 1

Priority 2: Inherited/Familial Conditions with CNS Manifestations

The positive family history is a critical red flag that must be explored:

Acute Disseminated Encephalomyelitis (ADEM):

• Can present with encephalopathy, fever, and visual disturbances (optic neuritis) 3
• Bilateral optic neuritis is common in ADEM 3
• Often follows viral infections or vaccinations 3
• MRI shows large, confluent T2 brain lesions 3

Familial Hemiplegic Migraine or Other Genetic Conditions:

• Family history may indicate inherited migraine variants with severe aura
• However, fever is not typical of primary migraine and should raise suspicion for secondary causes 1

Inherited Metabolic Disorders:

• Past history of similar episodes, symmetrical neurological findings, or lack of fever would suggest metabolic causes over infection 1
• Consider if presentation is subacute (weeks to months) rather than acute 1

Priority 3: Other Secondary Causes Requiring Urgent Evaluation

Increased Intracranial Pressure:

• Brain abscess, subdural empyema, or epidural empyema can present with fever, headache, vomiting, and visual changes 1
• Subdural empyema in older children often results from sinusitis or otitis media extension 1

Tickborne Rickettsial Diseases:

• Rocky Mountain spotted fever presents with fever, headache, and can mimic meningitis 1
• Consider if there is tick exposure history or outdoor activities 1
• Requires immediate doxycycline therapy regardless of age 1

Subarachnoid Hemorrhage:

• Thunderclap headache with vomiting should trigger immediate CT evaluation 1
• CT has 98% sensitivity for acute SAH 1
• Less likely with fever unless complicated by meningitis

Diagnostic Algorithm

Step 1: Immediate Assessment

• Vital signs including fever documentation 4
• Complete neurological examination including cranial nerves, mental status, focal deficits, and signs of meningeal irritation 1, 4
• Fundoscopic examination for papilledema (increased ICP) or optic neuritis 3

Step 2: Red Flag Identification

Red flags requiring immediate imaging include: 1, 4

• Unexplained fever with focal neurological symptoms
• Altered consciousness, memory, or personality
• Neck stiffness or limited neck flexion
• Progressive worsening over time

Step 3: Neuroimaging Decision

• MRI with and without IV contrast is preferred for suspected CNS infection, showing superior sensitivity for encephalitis, meningeal enhancement, and abscess formation 1
• Non-contrast CT if MRI unavailable or if immediate imaging needed before lumbar puncture 1
• MRI sequences (T2 FLAIR, DWI, post-contrast T1) help identify vasogenic/cytotoxic edema and meningeal enhancement 1

Step 4: Lumbar Puncture (if safe after imaging)

• CSF analysis for cell count, protein, glucose, Gram stain, culture 5
• PCR testing for HSV, enteroviruses, and other viral pathogens 5
• Consider fungal stains and cryptococcal antigen if immunocompromised 5
• Lymphocytic pleocytosis and elevated protein suggest viral encephalitis or ADEM 3

Step 5: Family History Exploration

• Detailed three-generation pedigree focusing on similar neurological episodes, migraine patterns, metabolic disorders, or autoimmune conditions
• Consider genetic testing if metabolic or inherited condition suspected after acute infection excluded 1

Critical Pitfalls to Avoid

• Never delay empiric antimicrobial/antiviral therapy while awaiting diagnostic studies in suspected CNS infection 1, 2
• Do not dismiss fever as incompatible with migraine—this is a red flag for secondary headache 1
• Do not perform lumbar puncture before imaging if focal signs, altered consciousness, or papilledema present 1
• Do not overlook tickborne diseases in endemic areas or with outdoor exposure history 1
• Do not assume benign primary headache with the combination of fever, vomiting, and visual changes—this warrants full workup 1