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Patients undergoing hematopoietic stem cell transplantation may experience a range of neurological complications; moreover, etiologies for neurological complications may be difficult to differentiate but may occur from the conditioning regimen, the interval of pancytopenia lending to infection and bleeding, prophylactic drugs, or from recurrence. Here we present a complex case of chronic GVHD involving the Central Nervous System (CNS cGVHD).
CASE REPORT
A 16-year old African American male underwent mismatched unrelated allogeneic double UCBT for biphenotypic leukemia. At day +25, the patient developed rash to his palms and soles along with abdominal cramping, voluminous diarrhea, nausea, vomiting, and fever. Biopsies of the upper and lower GI tract were consistent with acute GVHD. He was treated accordingly. Diarrhea only improved with diet restriction.
His clinical course was further complicated by progressive neurologic issues (anomic aphasia, confusion, agitation and hallucinations). A new ill-defined T2/FLAIR signal abnormality was seen in the bilateral cerebral hemispheric white matter (serum/CSF negative for infection or relapse). Brain biopsy was considered but not performed, during patient’s course of altered mental status. Unfortunately he succumbed to complications, the etiology of which was debated ad-nauseam.
Examination of brain at autopsy revealed immune mediated encephalitis, vasculitis, and CNS demyelination. A diagnosis of “possible chronic CVHD of the CNS” was rendered at the patient’s M&M.
DISCUSSION
Neurological complications (regimen-related toxicities, infections, cerebrovascular events and metabolic disorders) pose a significant source for morbidity and mortality following allogeneic HSCT with the incidence varying between 10 to 55% in reported studies. This case's autopsy findings revealed immune mediated encephalitis, multifocal CNS demyelination, and vascular changes.
The neurological manifestations of CNS cGVHD are rare and can affect both the peripheral and central nervous system. However, CNS chronic GVHD remains controversial. There have been at least 18 reported cases of presumed CNS cGVHD since 1990 of which findings included demyelinating disease, angiitis, vasculitis and immune-mediated encephalitis. The diagnostic criteria for chronic GVHD of the CNS requires that all six of the following criteria for a definitive diagnosis of CNS GVHD: (1) a-priori chronic GVHD affecting other organs, (2) Neurological signs of CNS involvement, (3) MRI abnormality, (4) Abnormal CSF studies, (5) Pathological brain biopsy or post-mortem examination, and (6) Response to therapy.
While the criteria allows for a very specific diagnosis of CNS cGVHD, the criteria are too stringent. Herein, a modified criteria stratified by pathologic examination of involved neural tissue is proposed.