What are the differential diagnoses for a 75-year-old male with hypertension (HTN), type 2 diabetes mellitus (T2DM), and chronic kidney disease (CKD) presenting with a 10-day history of bifrontal headache, worsening headache, lower extremity weakness, difficulty ambulating, and paucity of speech?

Differential Diagnoses for 75-Year-Old Male with Bifrontal Headache, Lower Extremity Weakness, and Speech Difficulty

Most Likely Diagnosis: Acute Stroke (Ischemic or Hemorrhagic)

This patient requires immediate neuroimaging (CT or MRI brain) to rule out acute stroke, given the acute worsening of neurological symptoms (lower extremity weakness, speech difficulty) in a patient with multiple vascular risk factors. 1

Rule In:

• Acute focal neurological deficits (lower extremity weakness, paucity of speech) developing over hours in a patient with HTN, T2DM, and CKD are highly suggestive of stroke 1
• Bifrontal headache can occur with stroke, particularly hemorrhagic stroke or large vessel occlusion 1
• Vascular risk factors (HTN, T2DM, CKD) dramatically increase stroke risk, with CKD patients having significantly elevated cardiovascular risk 2, 3
• Obtain immediate non-contrast CT head to differentiate ischemic from hemorrhagic stroke 1
• Check blood pressure - severe elevation (>200/120 mmHg) with neurological symptoms suggests hypertensive emergency with end-organ damage 1
• Brain MRI with diffusion-weighted imaging is more sensitive for acute ischemic stroke, particularly in posterior circulation 1

Rule Out:

• Normal CT/MRI brain effectively excludes acute stroke as primary diagnosis 1
• Absence of vascular territory distribution of symptoms makes stroke less likely 1
• Symmetric bilateral symptoms without clear vascular distribution pattern would be atypical for stroke 1

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Second Diagnosis: Hypertensive Encephalopathy / Posterior Reversible Encephalopathy Syndrome (PRES)

Hypertensive encephalopathy presents with headache, altered mental status, and neurological deficits in the setting of severe hypertension, and is particularly common in CKD patients. 1, 4

Rule In:

• Severe hypertension (typically >180/120 mmHg) with acute neurological symptoms (headache, weakness, speech difficulty) 1
• CKD patients are especially vulnerable to PRES due to frequent exposure to uremia and hypertension 4
• MRI brain showing T2/FLAIR hyperintensities in posterior brain regions (parieto-occipital areas) is diagnostic of PRES 1, 4
• Fundoscopy showing papilledema, flame hemorrhages, or cotton wool spots indicates hypertensive end-organ damage 1
• Symptoms may include headache, visual disturbances, somnolence, lethargy, and seizures 1
• Check blood pressure immediately - this is a hypertensive emergency requiring urgent but controlled BP reduction 1

Rule Out:

• Normal or only mildly elevated blood pressure (<160/100 mmHg) makes hypertensive encephalopathy unlikely 1
• Normal fundoscopic examination without retinopathy changes argues against malignant hypertension 1
• MRI without characteristic posterior white matter edema excludes PRES 1, 4
• Complete reversibility with BP control and dialysis confirms PRES diagnosis retrospectively 4

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Third Diagnosis: Uremic Encephalopathy with Cognitive Impairment

CKD patients are at high risk for cognitive impairment and uremic encephalopathy, which can present with altered mental status, speech difficulties, and motor dysfunction. 3, 5

Rule In:

• Advanced CKD (eGFR <30 mL/min/1.73 m²) with uremic symptoms 2, 3
• Check BUN and creatinine - markedly elevated BUN (>100 mg/dL) with uremic symptoms suggests uremic encephalopathy 2
• Cognitive impairment affects 30-60% of CKD patients, with executive function, attention, and orientation most commonly affected 3, 5
• Subacute progression over days rather than acute onset (though acute worsening can occur) 3, 5
• Asterixis, myoclonus, or altered mental status in addition to focal deficits 2
• Check electrolytes (sodium, potassium, calcium, phosphate) - severe derangements can cause encephalopathy 2
• EEG showing diffuse slowing supports metabolic encephalopathy 2

Rule Out:

• Acute onset over hours (rather than days to weeks) makes pure uremic encephalopathy less likely 3
• Focal neurological deficits (unilateral weakness, speech difficulty) are atypical for uremic encephalopathy alone and suggest structural lesion 2
• Normal or only mildly elevated BUN/creatinine argues against uremic encephalopathy 2
• Lack of improvement with dialysis suggests alternative diagnosis 4
• Brain imaging showing structural lesion indicates stroke or other pathology rather than pure metabolic encephalopathy 2, 4

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Critical Additional Workup Required Immediately:

• Non-contrast CT head (or MRI brain if available) to exclude stroke, hemorrhage, or mass lesion 1, 4
• Blood pressure measurement - severe elevation requires urgent management 1
• Complete metabolic panel including BUN, creatinine, electrolytes, glucose 2
• Fundoscopic examination to assess for hypertensive retinopathy or papilledema 1
• ECG to evaluate for acute cardiac ischemia (can present with neurological symptoms) 2

Common Pitfalls to Avoid:

• Do not assume symptoms are solely metabolic/uremic without excluding stroke - CKD patients have dramatically elevated stroke risk and require immediate neuroimaging 1, 3
• Do not delay imaging for laboratory results - acute stroke requires time-sensitive intervention 1
• Do not attribute all symptoms to "chronic" conditions - acute worsening demands acute evaluation 2
• Do not overlook subdural hematoma - elderly patients with multiple comorbidities are at risk for falls and intracranial bleeding 2