Posterior Reversible Encephalopathy Syndrome (PRES)
Clinical Features
PRES presents with a characteristic tetrad: seizures (occurring in 60-90% of cases), headache, visual disturbances, and altered mental status ranging from confusion to stupor 1, 2. The seizures can be focal or generalized tonic-clonic 3. Visual symptoms include blurred vision and decreased visual acuity 4, 5. The neurological symptoms develop acutely or subacutely 6.
Key Clinical Pitfall
Despite its name, PRES is not always posterior and not always reversible—mortality ranges from 10-19%, and 40-44% of patients develop persistent neurological deficits or residual radiologic lesions 1. This makes early recognition critical.
Pathophysiology
The syndrome results from endothelial dysfunction and blood-brain barrier disruption, leading to vasogenic edema 1, 7. When blood pressure rises markedly and cerebral autoregulation fails, intracranial pressure increases, causing cerebral edema particularly in posterior brain regions where sympathetic innervation is less pronounced and BP oscillations are less effectively dampened 8.
Triggers and Associated Conditions
The most common precipitants include:
- Severe hypertension (most common) 8, 1
- Renal dysfunction 1, 6
- Eclampsia/preeclampsia 1, 3
- Cytotoxic or immunosuppressive agents 1, 6
- Autoimmune conditions 7, 6
- Sepsis 1
Rare but Important Trigger
Extreme fluctuations in blood glucose—specifically an abrupt drop from severe hyperglycemia (e.g., 700 to 75 mg/dL)—can precipitate PRES 4. This is an uncommon but documented etiology that clinicians must recognize.
Diagnostic Approach
Neuroimaging
MRI is the diagnostic modality of choice, showing characteristic vasogenic edema with increased signal intensity on T2-weighted or FLAIR imaging 8, 1. The classic pattern involves bilateral posterior cerebral white matter, particularly the parieto-occipital regions 6, 5. However, atypical patterns are frequently observed, including involvement of anterior temporal and parietal lobes 5.
CT is useful primarily to exclude intracranial hemorrhage 8 but is less sensitive than MRI for detecting the characteristic edema patterns.
Clinical Evaluation
Focus on:
- Emergency symptoms: headache, visual changes, focal or generalized neurological symptoms 8
- Blood pressure: document current BP and rate of increase (rate matters more than absolute value) 8
- Medication history: steroids, NSAIDs, cyclosporin, sympathomimetics, cocaine, anti-angiogenic therapy 8
- Underlying conditions: hypertension control, renal disease, autoimmune disorders, pregnancy status 8, 1
Diagnostic Challenge
PRES is commonly misdiagnosed due to overlap with stroke, encephalitis, and other acute neurological syndromes 1. The key distinguishing feature is the reversible vasogenic edema pattern on MRI combined with an identifiable precipitant.
Management
Treatment is primarily supportive and directed at controlling the underlying precipitant 1, 7:
Blood Pressure Control
Stabilize blood pressure gradually—avoid precipitous drops that could worsen cerebral perfusion 8, 1. The goal is controlled reduction, not emergency normalization.
Seizure Management
Provide short-term antiseizure therapy 1. Based on the ESETT trial, there is no superior agent among levetiracetam, fosphenytoin, and valproate for acute seizure management 9. Choose based on patient-specific factors and side effect profiles.
Address Precipitants
- Withdraw or adjust offending medications (immunosuppressants, cytotoxic agents) 1
- Avoid abrupt glucose fluctuations in diabetic patients 4
- Deliver fetus emergently in eclampsia cases, with IV magnesium sulfate and antihypertensive therapy 3
- Treat underlying renal dysfunction or autoimmune disease 1
Airway Management
Consider early intubation in patients with eclampsia and significantly altered mental status to protect the airway 3.
Prognosis and Follow-up
Most patients show clinical and radiologic recovery within days to weeks if diagnosed and treated early 4, 7, 6. However, complications can occur:
- Intracranial hemorrhage
- Cerebral infarction
- Recurrent PRES 1
Frequent neurological evaluations and repeat neuroimaging are required to assess disease progression and recovery 6.
Hyperglycemic Seizures
Mechanism and Clinical Context
Hyperglycemia itself can precipitate seizures through multiple mechanisms: hyperosmolarity causing neuronal hyperexcitability, metabolic derangements, and in the specific context described above, the rapid correction of severe hyperglycemia can trigger PRES, which then manifests with seizures 4.
The Critical Connection
An abrupt decrease in blood glucose from extreme hyperglycemia (e.g., 700 mg/dL) to normal or low levels creates osmotic shifts that can precipitate PRES 4. This represents a dangerous intersection where metabolic emergency management can inadvertently trigger a neurological emergency.
Clinical Presentation
Patients may present with:
- Visual changes (blurred vision, decreased acuity) 4
- Seizures (focal or generalized)
- Altered mental status
- Headache
These symptoms develop after rapid glucose correction, not necessarily at the peak of hyperglycemia 4.
Management Principles
The key is avoiding abrupt fluctuations in blood glucose 4:
Glucose Correction Strategy
- Lower glucose gradually in patients with extreme hyperglycemia
- Avoid precipitous drops exceeding 100 mg/dL per hour
- Monitor neurological status closely during glucose correction
- If PRES develops, stabilize glucose and avoid further rapid changes 4
Seizure Treatment
Follow standard seizure management protocols with antiseizure medications, but address the underlying metabolic derangement as the definitive treatment 4.
Prognosis
Symptoms typically improve with avoidance of further abrupt glucose fluctuations 4. The PRES component commonly resolves within days if the metabolic trigger is controlled and no complications develop.