What are the primary neurologic complications of von Willebrand disease?

Neurologic Complications of Von Willebrand Disease

Von Willebrand disease rarely causes primary neurologic complications, but intracranial hemorrhage represents the most serious and life-threatening neurologic manifestation when it occurs.

Primary Neurologic Complication

1. Intracranial Hemorrhage (ICH)

• Intracranial hemorrhage is extremely rare in VWD but carries the highest mortality risk when it occurs, particularly in Type 3 VWD with virtually complete VWF deficiency 1.
• ICH can present as subarachnoid hemorrhage from ruptured intracranial aneurysms, as documented in case reports of Type 2A VWD patients 2.
• Spontaneous intracerebral hemorrhage in the basal ganglia with intraventricular extension has been reported, even following minor head trauma in pediatric VWD patients 3.
• The bleeding complications, particularly intracranial hemorrhage, are associated with the highest mortality rates in patients with bleeding disorders 4.

Secondary Neurologic Complications (Associated Conditions)

2. Stroke from Paradoxical Embolism

• Ischemic embolic stroke can occur in patients with congenital heart disease who may also have acquired von Willebrand syndrome, resulting from paradoxical embolization of venous thrombi crossing cardiac defects 4.

3. Peripheral Neuropathy (in Waldenström's Macroglobulinemia with Acquired VWD)

• Slowly progressing, demyelinating, symmetrical sensory peripheral neuropathy affecting initially the feet occurs in patients with Waldenström's macroglobulinemia who develop acquired VWD 4.
• Myelin-associated globulin antibodies (anti-MAGs) are detectable in 50% of these patients 4.
• This represents an indirect complication where the underlying lymphoproliferative disorder causes both neuropathy and acquired VWD simultaneously 4.

4. Cerebral Venous Thrombosis (Paradoxical in Acquired VWD)

• While VWD is a bleeding disorder, cerebral venous thrombosis has been reported in the context of spontaneous intracranial hypotension, which can be associated with bleeding diathesis including acquired VWD 4.

5. Seizures (Secondary to ICH)

• Seizures occur as a complication of intracranial hemorrhage in VWD patients, representing a secondary rather than primary neurologic manifestation 4, 3.

6. Altered Mental Status (Secondary to ICH)

• Altered consciousness ranging from semicomatose to comatose states occurs secondary to intracranial hemorrhage and increased intracranial pressure 3.

7. Focal Neurological Deficits (Secondary to ICH)

• Hemiparesis and other focal deficits develop as direct consequences of intracerebral hematomas, particularly in basal ganglia hemorrhages 3.

8. Headache (from ICH or Hyperviscosity in Acquired VWD)

• Severe headache is a presenting symptom of intracranial hemorrhage in VWD 4.
• In acquired VWD associated with Waldenström's macroglobulinemia, headache can result from hyperviscosity syndrome 4.

9. Visual Disturbances (from Hyperviscosity in Acquired VWD)

• Visual deficits occur in patients with acquired VWD secondary to Waldenström's macroglobulinemia due to hyperviscosity and retinal hemorrhages 4.
• Fundoscopic examination may reveal retinopathy requiring regular monitoring in these patients 5.

10. Cranial Nerve Palsies (Secondary to ICH or Mass Effect)

• Cranial nerve dysfunction can occur secondary to mass effect from large intracranial hematomas or increased intracranial pressure 3.

Critical Clinical Considerations

Key diagnostic pitfall: Intracranial hemorrhage in VWD patients may occur with minimal or no trauma, and the bleeding disorder may not be diagnosed until the hemorrhagic event occurs 3.

Preoperative screening imperative: Patients with prolonged bleeding time should be screened for VWD before any neurosurgical intervention, as unrecognized VWD significantly increases surgical bleeding risk 2.

Management of neurosurgical emergencies: Immediate administration of factor VIII/von Willebrand factor concentrate is essential for neurosurgical procedures in VWD patients, with intra- and postoperative dosing required to prevent excessive bleeding 2.

Acquired vs. congenital distinction: Screening for acquired von Willebrand syndrome should be performed in patients with aortic stenosis, lymphoproliferative disorders, or monoclonal gammopathies who present with neurologic bleeding complications 6.