What is the differential diagnosis for acute confusion and agitation in a patient with a prior intracerebral hemorrhage and known seizures?

Differential Diagnosis for Acute Confusion and Agitation in a Patient with Prior Hemorrhagic Stroke and Seizure History

In a patient with prior intracerebral hemorrhage and known seizures presenting with new confusion and agitation, the differential diagnosis must prioritize seizure activity (particularly nonconvulsive status epilepticus), recurrent hemorrhage, metabolic derangements, infection, and medication effects—with urgent workup including continuous EEG monitoring given the high risk of subclinical seizures in this population.

Primary Neurological Causes

Seizure-Related Etiologies (Highest Priority)

• Nonconvulsive seizures or status epilepticus represent the most critical consideration, occurring in 28-31% of ICH patients despite prophylactic antiseizure medications 1, 2.
• Electrographic seizures are detected in 28% of monitored patients during the initial 72 hours after hemorrhage, often without clinical manifestations 2.
• Patients with lobar hemorrhage location have the highest seizure risk (28-31%), particularly when blood contacts the cortical surface 2.
• Continuous EEG monitoring should be obtained immediately in patients with depressed mental status disproportionate to the degree of brain injury 1, 3, 4.
• Nonconvulsive seizures correlate with higher NIH Stroke Scale scores, greater midline shift, and poorer functional outcomes 2.

Recurrent Hemorrhage

• Recurrent stroke is a major risk factor for late poststroke cognitive decline, with the incidence of new dementia being much higher after a second stroke 1.
• Urgent brain CT or MRI is mandatory to exclude new hemorrhage, as clinical features alone cannot reliably distinguish hemorrhagic from ischemic events 1.
• Look for sudden worsening of symptoms, new focal deficits, severe headache, vomiting, or elevated blood pressure >220 mmHg systolic 1.

Delirium (Acute Confusional State)

• Delirium occurs in approximately 25% of admitted stroke patients and is characterized by acute onset, fluctuating level of consciousness, and decreased attention 1.
• The clinical hallmarks are alterations in arousal that distinguish it from other forms of cognitive impairment 1.
• Delirium is a medical emergency with mortality twice as high if the diagnosis is missed 1.

Metabolic and Systemic Causes

Essential Laboratory Workup

• Hyponatremia is a common stroke complication affecting cognitive function 1.
• Hypoglycemia or hyperglycemia must be excluded immediately, as glucose >170 mg/dL in nondiabetics increases hemorrhage risk and worsens outcomes 1.
• Renal and hepatic function tests to identify metabolic encephalopathy 1.
• Complete blood count to assess for infection or hematologic abnormalities 1.

Infectious Etiologies

• Urinary tract infections and pneumonia are the most common precipitating factors for delirium in stroke patients 1.
• CNS infection (meningitis/encephalitis) requires CSF examination if fever, nuchal rigidity, or unexplained altered mental status persists 1.
• Two or more coexisting precipitating causes are frequently encountered 1.

Medication-Related Causes

Antiseizure Drug Effects

• Prophylactic antiseizure drugs (particularly phenytoin) are associated with increased death and disability in ICH patients 1, 4.
• Antiseizure medications can cause cognitive impairment, sedation, and confusional states 1.
• Review all medications for anticholinergic effects, sedating properties, and drug-drug interactions 1.

Corticosteroid-Induced Psychiatric Disease

• If the patient received corticosteroids, steroid-induced psychiatric disease occurs in 10% of patients treated with prednisone ≥1 mg/kg, manifesting primarily as mood disorder (93%) rather than psychosis 1.

Other Important Considerations

Poststroke Depression

• Poststroke depression affects approximately one-third of individuals in the first year after stroke 1.
• Depression is often accompanied by cognitive symptoms that may resolve with treatment 1.
• Use a depression screening tool validated in stroke patients 1.

Structural Complications

• Cerebral edema with increased intracranial pressure, particularly in patients with large hemorrhages 1, 3.
• Hydrocephalus from intraventricular extension of hemorrhage 1.
• Subdural hematoma from trauma (especially if on anticoagulation or antiplatelet agents) 1.

Vascular Causes

• Ischemic stroke can present with isolated mental status changes in 7% of cases, though 66% have some focal abnormality on examination 5.
• Locations associated with confusion include right frontoparietal, bilateral occipital, and bilateral frontal regions 5.

Diagnostic Algorithm

Immediate Bedside Assessment

• Vital signs with particular attention to blood pressure, temperature, and oxygen saturation 1.
• Detailed neurological examination including NIHSS and Glasgow Coma Scale 1.
• Point-of-care glucose 1.

Urgent Imaging

• Non-contrast head CT is mandatory to exclude new hemorrhage, mass effect, or hydrocephalus 1.
• Brain MRI may be considered at qualified centers for more detailed evaluation 1.

Electrophysiological Studies

• Continuous EEG monitoring is essential given the 28% incidence of electrographic seizures in this population 1, 2, 3.
• Standard EEG if continuous monitoring unavailable, though it may miss intermittent seizure activity 1.

Laboratory Panel

• Serum electrolytes (especially sodium), renal function, hepatic function, complete blood count with platelets 1.
• Prothrombin time/INR and activated partial thromboplastin time 1.
• Thyroid-stimulating hormone and vitamin B12 to exclude reversible causes 1.
• Urinalysis and culture, chest radiography if infection suspected 1.
• Toxicology screen and blood alcohol if appropriate 1.

Critical Pitfalls to Avoid

• Do not assume confusion is simply "expected" after stroke—28% of these patients have active seizures on EEG that require treatment 2.
• Do not rely on clinical examination alone to exclude seizures; continuous EEG is necessary in patients with unexplained altered mental status 1, 2.
• Do not continue prophylactic antiseizure medications without documented seizures, as they worsen outcomes 1, 4.
• Do not miss infection—it is the most common reversible cause of delirium in stroke patients 1.
• Do not forget to assess for pain and constipation, which are frequently overlooked precipitants of delirium 1.