Neurological manifestations of Erdheim–Chester Disease

Abstract

Objective: To characterize the spectrum of neurologic involvement in Erdheim-Chester Disease (ECD), a treatable inflammatory neoplasm of histiocytes. Methods: Sixty-two patients with ECD were prospectively enrolled in a natural history study that facilitated collection of clinical, imaging, laboratory, neurophysiologic, and pathologic data. Results: Ninety-four percent of the patients had neurologic abnormalities on examination or imaging, and 22% had neurologic symptoms as the initial presentation of ECD. The most common neurologic findings were cognitive impairment, peripheral neuropathy, pyramidal tract signs, cranial nerve involvement, and cerebellar ataxia. Imaging revealed atrophy and demyelination along with focal lesions that were located throughout the nervous system, dura, and extra-axial structures. The BRAF V600E variant correlated with cerebral atrophy. Brain pathology revealed lipid-laden, phagocytic macrophages (histiocytes) accompanied by demyelination and axonal degeneration. Interpretation: In patients with ECD, neurologic morbidity is common and contributes significantly to disability. Since neurologic symptoms can be the presenting feature of ECD and, given the mean delay in ECD diagnosis is 4.2 years, it is critical that neurologists consider of ECD and other histiocytosis in patients with inflammatory, infectious, or neoplastic-appearing white matter. Furthermore, given the broad spectrum of neurologic involvement, neurologists have an important role in a team of specialists treating ECD patients.

Erdheim-Chester Disease Involving the Central Nervous System with Latent Toxoplasmosis

“…Referring to previous studies, clinical and radiologic features of ECD with CNS involvement and TE are summarized in Table . In our case, the clinical presentations of cerebellar ataxia, abnormal mental status, and cognitive change were compatible with both diseases (8)(9)(10)(11)(12)(13). Regarding MRI findings, previous studies have reported similar types of abnormalities in both diseases, including nodular lesions, diffuse T2-hyperintense lesions, and brain Key clinical and radiologic features of Erdheim-Chester disease (ECD) with central nervous system (CNS) involvement and toxoplasmic encephalitis (TE) with comparison between previous studies and our case (8)(9)(10)(11)(12)(13). MRI: magnetic resonance imaging, N/A: not available atrophy (9)(10)(11)(12)(13).…”

Pituitary Imaging Abnormalities and Related Endocrine Disorders in Erdheim–Chester Disease

“…Additionally, CNS involvement was an independent, poor prognostic factor for mortality in ECD subjects at five years in their study [18]. Neurologic symptoms can be the presenting feature of ECD, and given the mean delay in ECD diagnosis of 4.2 years, ECD must be considered in patients with inflammatory, infectious or neoplastic-appearing white matter [26]. Clinicians treating ECD should be aware of the high prevalence of API and the association between CNS lesions and mortality.…”

“…Central nervous system involvement in ECD remains a major cause of morbidity and mortality [26]. For instance, a survival analysis of 53 cases of ECD reported CNS involvement in 51%; these were directly responsible for 29% of reported deaths [18].…”

“…We did not perform evaluation for growth hormone deficiency with serum GH or IGF-1 levels. Furthermore, neurological screening was performed by experienced neurologists using appropriate clinical and imaging assessments listed in detail elsewhere [26]. Cognitive impairment, neuropathies, and cranial nerve involvement were classified as 'neurodegeneration/cognitive impairment' while coordination impairment and pyramidal tract involvement were classified as 'cerebellar syndrome' due to their distinct clinical features [26].…”

“…Furthermore, neurological screening was performed by experienced neurologists using appropriate clinical and imaging assessments listed in detail elsewhere [26]. Cognitive impairment, neuropathies, and cranial nerve involvement were classified as 'neurodegeneration/cognitive impairment' while coordination impairment and pyramidal tract involvement were classified as 'cerebellar syndrome' due to their distinct clinical features [26]. Overall, neurological abnormalities reflect any neurological involvement by ECD including 'neurodegeneration/cognitive impairment' and/or 'cerebellar syndrome'.…”