Bevacizumab (Avastin) (see Bevacizumab, [[Bevacizumab]])
Calcineurin Inhibitors
General Comments
Multiple Case Series Have Been Reported (Medicine, 2016) [MEDLINE] and (Transplant Proc, 2014) [MEDLINE]
May Be Associated with Calcineurin Levels Above or at the High End of Therapeutic Ranges, Although Cases Have Been Reported with Therapeutic Calcineurin Levels
Cyclosporine A (see Cyclosporine A, [[Cyclosporine A]]): commonly-reported etiology
Exact Mechanism is Unclear (Although the Following are Probably the Predominant Mechanisms)
Disordered Cerebral Autoregulation
As Upper Level of Cerebral Autoregulation is Exceeded, Cerebral Blood Flow Increases Proportional to Systemic Blood Pressure with Resulting Brain Hyperperfusion (Especially in Arterial Border Zones) with Breakdown of the Blood-Brain Barrier and Extravasation of Fluid/Blood into the Brain Parenchyma (i.e. Cerebral Edema)
Although Less Likely, Disordered Cerebral Autoregulation May Alternatively Result in Focal Vasoconstriction: resulting in local hypoperfusion, cytotoxic edema, and cerebral infarction
Endothelial Dysfunction: probably plays a role (especially in cases associated with eclampsia or cytotoxic therapies)
Damage to Vascular Endothelium with Capillary Leak, Blood-Brain Barrier Disruption, and Axonal Swelling Resulting in Vasogenic Edema
PRES May Occur with Normal Blood Pressure and with Normal Levels of the Cytotoxic Drugs
Anatomic Distribution
Predilection for Edema of the White Matter: cortex is structurally more tightly packed than the white matter and is therefore more resistant to the accumulation of cerebral edema
Predilection for Edema in Posterior Brain Regions: not clearly understood, but may involve a lesser concentration of adrenergic nerves around pial and intracerebral vessels in the posterior regions of the brain (this results in less protection of posterior region of the brain from marked increases in systemic blood pressure)
T2-Weighted Images: typically localized subcortical edema in bilateral posterior hemisphere and occipital areas
Note: In general, T1 and T2-weighted images can be easily differentiated by looking at the CSF -> CSF is dark on T1-weighted images and bright on T2-weighted images
Fluid-Attenuated Inversion Recovery (FLAIR) Images: typically localized subcortical edema in bilateral posterior hemisphere and occipital areas
Note: the Flair sequence is similar to a T2-weighted image except that the time to echo (TE) and repetition time (TR) times are very long
Diffusion-Weighted Images: usually normal
Localization (Am J Roentgenol, 2007) [MEDLINE] and (Mayo Clin Proc, 2010) [MEDLINE]: based on the extent of localization by brain MRI, the term “posterior” is probably a misnomer
Parieto-Occipital Lobe Involvement: 94%-98% of cases
Frontal Lobe Involvement: 77%-79% of cases
Temporal Lobe Involvement: 64%- 68% of cases
Clinical Manifestations
Cardiovascular Manifestations
Hypertension (see Hypertension, [[Hypertension]]): frequent, but not universally present
Importantly, the Hypertensive Crisis May Precede the Neurologic Syndrome by ≥24 hrs
Neurologic Manifestations
Altered Level of Consciousness (see Altered Mental Status, [[Altered Mental Status]]): wide range of presentations
Headache (see Headache, [[Headache]]): usually constant, non-localized, moderate-severe, and unresponsive to analgesics
Funduscopic Exam: often normal (especially in patients with chronic hypertension or eclampsia), but may demonstrate papilledema/retinal flame hemorrhages or exudates
Hyperreflexia (see Hyperreflexia, [[Hyperreflexia]]): often
Neurologic Symptoms Suggestive of Upper Cervical Spinal Cord Involvment: has been described in some cases
Hemodialysis (see Hemodialysis, [[Hemodialysis]]):
Dexamethasone (see Dexamethasone, [[Dexamethasone]]): not recommended
References
A reversible posterior leukoencephalopathy syndrome. N Engl J Med 334(8):494-500, 1996 [MEDLINE]
Posterior reversible encephalopathy syndrome: Incidence of atypical regions of involvement and imaging findings. Am J Roentgenol 189(4):904-912, 2007 [MEDLINE]
Posterior reversibleencephalopathy syndrome: Associated clinical and radiologic findings. Mayo Clin Proc 85(5):427-432, 2010 [MEDLINE]
