Understanding Neurological Complications in Sickle Cell Disease: A Patient's Case Study

Table of Contents

• Case Presentation
• Medical History and Background
• Initial Examination Findings
• Diagnostic Testing Results
• Brain Imaging Findings
• Differential Diagnosis
• Clinical Impressions
• What This Means for Patients
• Source Information

Case Presentation

A 21-year-old man with sickle cell disease arrived at the emergency department after losing consciousness and falling. He had been experiencing his typical sickle cell pain in the chest, back, arms, and legs for the previous week, which he managed with hydromorphone infusions as an outpatient.

On the day of the incident, he used oral oxycodone and supplemental oxygen for chest pain. His family found him lying on his bedroom floor after hearing a thud from upstairs. The patient woke up when spoken to but was confused for about one minute before returning to his normal mental state. He remembered feeling dizzy upon waking from a nap and trying to walk across his room just before the fall.

Emergency medical services recorded a normal blood sugar level and a perfect Glasgow Coma Scale score of 15 (indicating full consciousness). They placed a cervical collar around his neck as a precaution and transported him to the hospital for evaluation.

Medical History and Background

The patient had homozygous sickle cell disease with multiple complications including:

• Vaso-occlusive events (pain crises caused by blocked blood vessels)
• Pulmonary embolism and inferior vena cava blood clots
• Retinal artery occlusion (eye artery blockage) requiring regular blood transfusions for stroke prevention
• Sickle cell nephropathy (kidney damage)
• Avascular necrosis of the hip (bone death from poor blood supply)
• Gallstones, iron overload, and splenic sequestration that required spleen removal

His medications included apixaban (blood thinner), deferasirox (iron chelator), amoxicillin, gabapentin, cetirizine, montelukast, famotidine, oxycodone as needed, and several inhalers. He used supplemental oxygen when needed and received regular blood transfusions.

Notably, his mother had multiple sclerosis and a history of petit mal seizures as a child. Multiple family members had hypertension, and his paternal grandfather had suffered a stroke.

Initial Examination Findings

Upon examination, doctors noted:

• Heart rate: 123 beats per minute (elevated)
• Blood pressure: 149/95 mm Hg (mildly elevated)
• Oxygen saturation: 97% on room air (normal)
• Abrasion on the right forehead and right cheek swelling from the fall
• Slightly yellowed eyes (mild jaundice)
• Rapid heartbeat with a midsystolic murmur
• Chronic right arm weakness
• Otherwise normal neurological examination

Diagnostic Testing Results

Laboratory tests revealed important findings shown in Table 1. The patient had moderate anemia with hemoglobin at 9.8 g/dL (normal 13.5-17.5) that dropped to 8.2 g/dL the next day. His white blood cell count was elevated at 20,860 cells/μL (normal 4,500-11,000), increasing to 22,380 cells/μL, indicating possible infection or inflammation.

His blood smear showed sickle cells, target cells, burr cells, and Howell-Jolly bodies—all consistent with sickle cell disease after spleen removal. The reticulocyte count was significantly elevated at 14.2% (normal 0.5-2.5%), indicating his bone marrow was working hard to produce new red blood cells.

After his seizure episode, additional tests showed:

• Creatine kinase: 4,431 U/L (normal 60-400) - indicating muscle breakdown
• Lactate: 12.7 mmol/L (normal 0.5-2.0) - significantly elevated, consistent with seizure activity
• D-dimer: >10,000 ng/mL (normal <500) - markedly elevated, suggesting blood clotting activity

Urine toxicology was negative except for oxycodone, which he had taken as prescribed.

Brain Imaging Findings

Approximately 7 hours after the witnessed seizure, doctors performed magnetic resonance imaging (MRI) of the head. The MRI revealed several important findings:

T2-weighted FLAIR imaging showed regions of increased signal intensity in the brain's posterior regions, including the bilateral posterior frontal, parietal, occipital, and temporal lobes. The left lenticulocapsular region and right cerebellar hemisphere also showed abnormalities. These findings suggested vasogenic edema (fluid accumulation in brain tissue) with mild mass effect.

Diffusion-weighted imaging showed no restricted diffusion, ruling out acute stroke. Contrast-enhanced T1-weighted imaging revealed irregular enhancement in some areas, suggesting breakdown of the blood-brain barrier. Susceptibility-weighted imaging showed numerous tiny spots consistent with microhemorrhages throughout the brain tissue.

Magnetic resonance angiography showed normal blood vessels without evidence of blockages or constrictions. The overall imaging pattern was most consistent with posterior reversible encephalopathy syndrome (PRES), a condition where brain swelling occurs due to changes in blood vessel function.

Differential Diagnosis

The medical team considered several possible explanations for the patient's symptoms:

Syncope vs. Seizure: The initial event could have been either fainting (syncope) or a seizure. The brief confusion afterward (about 1 minute) can occur with both conditions. The absence of tongue biting or incontinence doesn't rule out seizure.

Traumatic Injury: The fall could have caused bleeding in the brain, especially concerning since the patient was on blood thinners (apixaban).

Fat Embolism Syndrome: A rare complication of sickle cell disease where fat particles enter the bloodstream and reach the brain. However, this typically causes respiratory symptoms first, which this patient didn't have.

Posterior Reversible Encephalopathy Syndrome (PRES): This condition involves brain swelling, often associated with high blood pressure, certain medications, or underlying conditions like sickle cell disease. The symmetric pattern on MRI and the clinical presentation made this the most likely diagnosis.

Other conditions like cerebral venous sinus thrombosis, reversible cerebral vasoconstriction syndrome, autoimmune encephalitis, or infectious processes were considered but ruled out based on imaging and clinical findings.

Clinical Impressions

The medical team concluded that the patient most likely experienced posterior reversible encephalopathy syndrome (PRES) related to his sickle cell disease. Several factors supported this diagnosis:

Patients with sickle cell disease have a 24% risk of having at least one stroke by age 40. However, PRES can mimic stroke and must be considered in the differential diagnosis. The patient's pre-existing conditions—sickle cell disease and kidney dysfunction—are both risk factors for developing PRES.

The imaging findings showing symmetric vasogenic edema in the posterior brain regions, combined with the clinical presentation of seizure and altered consciousness, strongly suggested PRES. The markedly elevated d-dimer level indicated significant vascular activity and endothelial dysfunction, which are involved in both sickle cell crises and PRES pathophysiology.

Although epilepsy is two to three times more common in patients with sickle cell disease, and the patient had a family history of seizures, the overall presentation was more consistent with PRES than with new-onset epilepsy.

What This Means for Patients

This case illustrates several important points for patients with sickle cell disease and their families:

Neurological symptoms require immediate attention: Any loss of consciousness, seizure, or significant neurological changes in patients with sickle cell disease should prompt immediate medical evaluation. These symptoms could represent serious complications including stroke, PRES, or other neurological emergencies.

PRES is a recognized complication: Patients and providers should be aware that posterior reversible encephalopathy syndrome can occur in sickle cell disease. Symptoms may include headache, visual changes, seizures, and altered mental status. Early recognition is important for proper management.

Monitoring and prevention: Regular follow-up with hematology and other specialists is crucial for managing sickle cell disease complications. Blood pressure control, appropriate hydration, and avoiding triggers for sickle cell crises may help reduce the risk of neurological complications.

Emergency preparedness: Patients with sickle cell disease should have an emergency plan that includes information about their condition, medications, and specific complications they might experience. This information can help emergency providers make appropriate decisions quickly.

While this case had a positive outcome with appropriate diagnosis and management, it highlights the serious nature of neurological complications in sickle cell disease and the importance of comprehensive care for these patients.

Source Information

Original Article: "Case 2-2025: A 21-Year-Old Man with Loss of Consciousness and a Fall"

Authors: Eric F. Shappell, M.D., Brooks P. Applewhite, M.D., Sharl S. Azar, M.D., and David J. Lin, M.D.

Publication: The New England Journal of Medicine, January 16, 2025, Volume 392, Issue 3, Pages 268-276

DOI: 10.1056/NEJMcpc2412511

This patient-friendly article is based on peer-reviewed research from The New England Journal of Medicine. It preserves all significant medical findings, data points, and clinical interpretations from the original case study while making the information accessible to patients and caregivers.