Causes of Neurologic Decline in Patients with Histiocytic Neoplasms with Suspected Neurodegenerative Disease
Amir Barmada1, Ronald Go2, John benson3, Gaurav Goyal5, W. Tobin4
1Mayo Clinic Alix School of Medicine, 2Division of Hematology, 3Department of Radiology, 4Department of Neurology, Mayo Clinic, 5Division of Hematology-Oncology, University of Alabama at Birmingham
Objective:
Evaluate the causes of suspected neurodegeneration in adults with histiocytic neoplasms.
Background:
Neurodegenerative disease has not been well defined in Erdheim–Chester disease (ECD) or Rosai-Dorfman disease (RDD).
Design/Methods:
Patients with histiocytic neoplasms seen at our institution between February 1998 and April 2024 were identified. Inclusion criteria were: 1. Diagnosis of histiocytic neoplasm 2. The treating subspecialist hematologist suspected neurodegeneration and 3. Patients were 18 years or older. Active CNS histiocytic neoplasm was defined as new or enlarging T2 lesions, or gadolinium enhancing lesions on brain or spine MRI.
Results:

Neurodegeneration was suspected in 23/478 patients (16/23 male, mean age at diagnosis 49 years [5 - 68 years]). Diagnoses were ECD (13/23), Langerhans cell histiocytosis (LCH) (7/23), mixed LCH/ECD (2/23), and RDD (1/23). Median time from diagnosis to suspicion of neurodegeneration was 1.3 years (range 0-19 years). Median follow-up from histiocytic neoplasm diagnosis was 4.5 years (range 1 month- 20.5 years). Symptoms included ataxia (18/23), dysarthria (16/23), urinary dysfunction (16/23), cognitive impairment (14/23), and dysphagia (14/23).  

A progressive neurologic disorder was confirmed in 15/23, of which all were associated with an underlying active (12/15) or inactive (3/15) histiocytic neoplasm, (7/15 ECD, 5/15 LCH, 2/15 mixed, and 1/15 RDD). Of the 8 patients without a progressive neurologic disorder, diagnoses included fixed deficit from histiocytic neoplasm (3/8), depression (2/8), fatigue (1/8), pain (1/8), and stroke (1/8). Of the 3/15 patients with progressive neurologic dysfunction and inactive CNS histiocytic neoplasm, all had progressive pontocerebellar dysfunction. Progressive pontocerebellar atrophy on MRI was present in 10/13 patients with progressive symptoms, and 2/6 patients with no progressive symptoms.

Conclusions:

Progressive neurologic dysfunction in adult patients with histiocytic neoplasms is most frequently due to an active histiocytic neoplasm, or non-histiocytic etiology. A minority of patients have a presumed non-neoplastic progressive neurologic dysfunction, primarily associated with pontocerebellar atrophy.

10.1212/WNL.0000000000211237
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