Central Nervous System Disease in Langerhans Cell Histiocytosis

Abstract

Diabetes insipidus and anterior pituitary dysfunction, are familiar central nervous system (CNS) complications of Langerhans cell histiocytosis (LCH) but the pathophysiology and biological behaviour of other forms of CNS involvement in LCH are poorly understood. In an attempt to improve our understanding of these rare complications, we studied 23 patients with LCH in whom neuroradiological abnormalities, with or without neurological dysfunction other than diabetes insipidus, developed during the course of disease. Neuroradiological abnormalities were of three basic types (a) poorly-defined changes in white matter, (b) well-defined changes in white and grey matter and (c) extra-parenchymal "tumoural" masses. There was a profusion of associated neurological signs and symptoms in most cases but some patients were asymptomatic. The neuropathological features were complex but infiltration of the CNS by histiocytes with xanthomatous change, particularly prominent in mass lesions, was common in the 13 cases in which biopsies were done. Patients with lytic lesions of the skull and diabetes insipidus are evidently most at risk of developing these rare manifestations of LCH. Therapeutic questions could not be answered from this study because no standard treatment had been given and outcome varied widely.

Langerhans Cell Histiocytosis in Children: A Single Center Experience from Turkey.

“…13 The most common clinical manifestation is CDI. It occurs more frequently in patients with craniofacial bone lesions, ear, eye and/or oral lesions 14 and thus these lesions are known as CNS-risk lesions.…”

An Unusual Intracranial Inflammatory Process of Unknown Origin

“…MRI can show bilateral signal changes and non-enhancing lesions in the dentate nucleus, often extending to the surrounding white matter involving the midbrain, pons, globus pallidus and cerebellar peduncle or presenting with cerebellar atrophy. [8][9][10][11][12] There are varying opinions on the indication for HPA biopsy in terms of the size of the lesion or severity of symptoms. 13 Studies by Jian et al 13 , Leger et al 14 and Adani et al 15 all propose different cut-offs for biopsy, such as presence of an endocrinopathy, radiological changes (e.g., when the stalk is >7 mm) and/or clinical deterioration.…”

Histiocytosis: a review focusing on neuroimaging findings

“…Intracranial lesions have been observed during the course of disease in patients with a history of proved LCH and also as the first and presenting LCH manifestations, in which case they can cause considerable diagnostic challenge 3 . Four groups of patients can be clinically distinguished: 1) those with a disorder of the hypothalamic-pituitary system; 2) patients presenting with site-dependent symptoms from space-occupying lesions, such as seizures; 3) those who exhibit a neurologic dysfunction mostly following a cerebellar-pontine pathway involvement, including reflex abnormalities, ataxia, intellectual impairment, tremor, or dysarthria with variable progression to severe CNS deterioration; and 4) patients who present with an overlap of the symptoms mentioned previously 6 .…”

“…Differential diagnosis includes acute disseminated encephalomyelitis, acute multiphasic disseminated encephalitis, metabolic and degenerative disorders, or chemo-/radiation therapy sequelae 7 . Atrophic changes may be limited to the cerebellar hemispheres but may also be global, usually in patients with a progressive symptomatic course 11 .…”