Histiocytosis-related cerebellar leukoencephalopathy

Dear Sir,

A 7-year-old boy was diagnosed as histiocytosis after a peripheral tissue biopsy when he was 2 years old and completed the course of chemotherapy with vinblastin and prednol. Four years after the diagnosis he presented with subacute onset of truncal ataxia, diplopia, and mild appendicular ataxia especially while reaching for objects. He also exhibited dysarthria and tremulousness. Fundoscopic examination was normal and telangiectasis was not confirmed in the conjunctiva or skin. No neurological sign was noted in the cranial or peripheral nerves. Cranial MRI performed for cerebellar signs, revealed bilateral symmetric lesions on the cerebellar dentate nucleus, middle cerebellar peduncle, and dorsal pons defined as hyperintensities on T2 and FLAIR, which are referred to be neurodegeneration [Figures 1 and 2]. His ataxia gradually improved during follow-up but lesions remained stable in control MRIs performed 3 and 9 months later.

Figure 1.

FLAIR MR sequence, hyperintensities at dentate nucleus and middle cerebellar peduncle

Figure 2.

T2 MR sequence, hyperintensities at posterior pons and middle cerebellar peduncle

CNS involvement of histiocytosis may vary from space occupying lesions – like granulomas in peripheral tissues - to neurodegenerative changes.[1] Neurodegenerative lesions in histiocytosis are a less frequent and well-known complication than the classical histiocytic granuloma-like lesions and these degenerative lesions do not occupy space, do not exert mass effect, and do not show contrast enhancement.[2] Lesions usually involve cerebellar white matter areas and dentate nuclei symmetrically with basal ganglia and brain stem.[3] Reported pathological examinations revealed focal areas of demyelination with gliosis, loss of neuronal cells in the granular, and Purkinje layers of the cerebellar cortex, with no evidence of typical CD1a+ histiocytic infiltration. Latest studies indicate that neurodegeneration can be caused by a profound inflammatory process, dominated by CD8+ lymphocytes.[4] MRI findings do not correlate with neurologic deterioration. Patients can stay free of neurologic symptoms for years but can present with a spectrum of clinical signs ranging from subtle tremor or mild abnormalities of the reflexes, discrete gait disturbance, dysarthria, dysphagia, and motor spasticity to pronounced ataxia, behavioral disturbances, learning difficulties, or even severe psychiatric disease.[5]