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Year : 2023  |  Volume : 26  |  Issue : 1  |  Page : 77-80

Obstructive hydrocephalus as the solitary manifestation of young onset erdheim–Chester disease

1 Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bengaluru, Karnataka, India
2 Department of Neurosurgery, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bengaluru, Karnataka, India

Date of Submission17-Jun-2022
Date of Decision29-Jul-2022
Date of Acceptance14-Apr-2022
Date of Web Publication17-Jan-2023

Correspondence Address:
Ravi Yadav
Department of Neurology, First Floor, Neurosciences Faculty Block, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bengaluru - 560 029, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aian.aian_537_22

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How to cite this article:
Jha S, Baskar D, Nandeesh B N, Vengalil S, Chaudhary R, Nalini A, Yadav R, Srinivas D. Obstructive hydrocephalus as the solitary manifestation of young onset erdheim–Chester disease. Ann Indian Acad Neurol 2023;26:77-80

How to cite this URL:
Jha S, Baskar D, Nandeesh B N, Vengalil S, Chaudhary R, Nalini A, Yadav R, Srinivas D. Obstructive hydrocephalus as the solitary manifestation of young onset erdheim–Chester disease. Ann Indian Acad Neurol [serial online] 2023 [cited 2023 Feb 1];26:77-80. Available from:


Erdheim–Chester Disease (ECD) is a rare histiocytic neoplasm affecting multiple tissues, with central nervous system (CNS) involvement in 40–50% of cases. Although known to be posterior fossa predominant, widespread neurologic involvement throughout the brain, spinal cord, meninges, orbits, and pituitary has recently been described with the involvement of other organs.[1] We present a case of young-onset, biopsy-proven ECD with solitary neurological involvement presenting as significant obstructive hydrocephalus without the involvement of other systems.

A 35-year-old gentleman, without any significant past medical illness, presented with progressive cerebellar ataxia, flaccid dysarthria, and dysphagia for 1 year. There were two episodes of left focal motor onset seizures with impaired awareness. He had a weight loss of about 15 kg over 8 months without any other systemic symptoms. On examination, the patient was conscious, obeyed commands, communicated with a few words, and opened his eyes spontaneously. Formal cognitive testing was not possible. He had mild pallor but no lymphadenopathy, organomegaly, or skin lesions. On cranial nerve examination, there was torsional down beating nystagmus, right eye hypotropia and right head tilt, bilateral facial weakness, and sluggish gag reflexes with signs suggestive of pyramidal and cerebellar involvement. Investigations showed microcytic hypochromic anemia (Hb, 10.8 g%) and neutrophilic leucocytosis. Magnetic resonance imaging (MRI) brain showed T2 hyperintense lesions in the cerebellum and pons with intense contrast enhancement and obstructive hydrocephalus [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d, [Figure 1]e. MR imaging of the spine was normal. Computed tomography (CT) of the thorax and abdomen showed cystic lesions in bilateral upper zones [Figure 1]f. X-ray of long bones and positron emission tomography (PET) CT of the whole body was normal. Stereotactic brain biopsy from the left cerebellum showed increased cellularity in the subcortical areas with a few large cell infiltrates that appeared histiocytic in morphology including a few cells with granular to foamy cytoplasm, which was positive for CD68 and negative for CD1a. These cells were also positive for BRAFV600E by immunohistochemistry, (IHC) indicating that these cells were non-Langerhans cell types and favored the diagnosis of non-histiocytic disorder compatible with ECD [Figure 2]. He underwent ventriculoperitoneal (VP) shunt for obstructive hydrocephalus with intravenous steroids, cyclophosphamide, and subcutaneous interferon with minimal improvement.
Figure 1: (a) Axial T2-weighted image shows patchy hyperintensities with expansion involving the pontomedullary junction and bilateral cerebellar hemispheres. (Solid white arrows). (b) Axial T1-weighted image shows subtle hypointensity of the lesion in the left cerebellar hemisphere (solid white arrow). (c) Axial FLAIR image shows dilated lateral and third ventricles (solid white arrows) with subependymal CSF seepage, leading to FLAIR periventricular hyperintensities. (d) Right parasagittal delayed T2 sequence showing obstructive hydrocephalus with hyperintensity in the cerebellar hemisphere with mass effect on the fourth ventricle (solid white arrow). (e) Axial 3D T1 gradient post-contrast image shows patchy, feathery enhancement in bilateral cerebellar hemispheres and pons with a homogenously enhancing rounded lesion in the left cerebellar hemisphere (solid white arrow). (f) Axial chest CT lung window shows multiple cystic lesions (solid white arrows) in the anterior segments of bilateral upper lobes

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Figure 2: (a-d) Microphotograph showing neuroparenchyma with stromal rarefaction, scattered histiocytic infiltration (arrows) along with a few lymphocytes. (H & E stain; A, B – ×100; C, D – ×200). (e and f) Microphotograph showing histiocytes (arrows) stained by CD68 (CD68, IHC ×200). (g) Microphotograph showing the absence of staining for CD1a. (CD1a, IHCX 100). (H and I) Microphotograph showing histiocytes stained with BRAFV600E IHC; (H – ×100, I – ×200)

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With greater knowledge about the disease and heightened capacity for its diagnosis, there has been an increase in the detection of ECD although it remains a rare disease commonly affecting males in the fifth to seventh decades.[2] Although the clinical and radiological features were consistent with ECD in our case, the neurological impairment was isolated, without evidence of any other system involvement upon extensive evaluation. The age of our patient was also uncommon, given that the prevalence of ECD is the highest among male patients between the fifth and the seventh decades of life.[3],[4],[5] Diabetes insipidus (DI) and bone pains that predate neurological symptoms often direct the physician to the diagnosis of ECD,[5] especially in young patients,[6] both of which were conspicuously absent in our case. The other few cases reported in the literature to be “isolated” CNS involvement have had associated diabetes insipidus or bone lesions detected on functional imaging.[7],[8] Moreover, these cases of isolated neurological involvement have been intracranial mass lesions, unlike our case, which is a novel presentation of obstructive hydrocephalus secondary to cerebellar–brainstem lesions. Furthermore, obstructive hydrocephalus has been reported to be in ECD secondary to dural involvement,[2] whereas in our case, extensive posterior fossa involvement causing direct mass effect appears to be the cause of hydrocephalus in contrast to a systematic review that reports cerebellar lesions to less likely produce mass effect unlike other intracranial lesions in ECD.[5] However, there was no supratentorial involvement, in this case, to account for the seizures, which could be best explained by the obstructive hydrocephalus.

The MRI abnormalities of ECD could follow infiltrative or meningeal patterns. As seen in this case, the infiltrative pattern includes areas of hyperintense signal in the cerebellum and brainstem with spotted enhancement without any involvement of meninges, hypothalamic–pituitary axis, orbit, bones, or the supratentorial compartment.[9]

Histiocytic neoplasms include ECD, Langerhans cell histiocytosis (LCH), and Rosai–Dorfman disease (RDD) along with several other disorders. Brainstem and cerebellar involvement are known in ECD and LCH, whereas RDD only manifests with dural and skull-based lesions [Table 1]. Orbital masses are majorly seen with ECD. Radiologically, LCH can have T1 hyperintensity of the dentate nucleus apart from overlapping features with ECD as described previously. Although cardiac, respiratory, retroperitoneal involvement, and DI are prevalent with ECD and LCH, subcutaneous nodules and lymphadenopathy are more common in RDD. Compared with ECD and LCH, RDD infiltrates often show a more inflammatory background. Although ECD is CD68 positive and CD1a negative, LCH is CD1a positive and RDD retains S100 expression. In addition, for ECD and LCH, IHC analysis of paraffin sections using the BRAF V600Ee mutant-specific antibody has high specificity.[10]
Table 1: Differentiating features of common histiocytic neoplasms

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Regarding the treatment, there are only a few prospective therapeutic studies for ECD. Corticosteroids, cytotoxic and immunosuppressive agents, and interferon-α-based therapy (IFN-α) have been the mainstay. Targeted therapies that show promise include selective BRAFV600 kinase inhibitor vemurafenib, which can cross the blood–brain barrier.[2] CNS involvement has been shown to reduce survival and induce non-responsiveness to conventional treatments in ECD, which could account for the poor outcome of our patient.

To conclude, CNS involvement in ECD needs to be detected early because it is associated with a poor prognosis. Isolated CNS involvement with posterior fossa involvement and obstructive hydrocephalus presenting in the third decade is unusual, and a high index of suspicion is required to diagnose and treat early to avoid the usual dismal outcomes.

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There are no conflicts of interest.

   References Top

Boyd LC, O'Brien KJ, Ozkaya N, Lehky T, Meoded A, Gochico BR, et al. Neurological manifestations of Erdheim–Chester Disease. Ann Clin Transl Neurol 2020;7:497-506.  Back to cited text no. 1
De Macêdo LP, Ferreira US, Ferreira YD, de Carvalho Júnior EV, Faquini IV, Almeida NS, et al. Erdheim-Chester disease with intracranial involvement causing hydrocephalus: Case report. Interdiscip Neurosur 2020;21:100722.  Back to cited text no. 2
Cohen Aubart F, Idbaih A, Galanaud D, Law-Ye B, Emile J-F, Charlotte F, et al. Central nervous system involvement in Erdheim-Chester disease: An observational cohort study. Neurology 2020;95:e2746-54.  Back to cited text no. 3
Lachenal F, Cotton F, Desmurs-Clavel H, Haroche J, Taillia H, Magy N, et al. Neurological manifestations and neuroradiological presentation of Erdheim-Chester disease: Report of 6 cases and systematic review of the literature. J Neurol 2006;253:1267-77.  Back to cited text no. 4
Mazor RD, Manevich-Mazor M, Shoenfeld Y. Erdheim-Chester disease: A comprehensive review of the literature. Orphanet J Rare Dis 2013;8:1-3.  Back to cited text no. 5
Abdellateef EE, Abdelhai AR, Gawish HH, Abdulmonaem GA, Abdelbary EH, Ahmed AI. The first reported case of Erdheim-Chester disease in Egypt with bilateral exophthalmos, loss of vision, and multi-organ involvement in a young woman. Am J Case Rep 2016;17:360-70.  Back to cited text no. 6
Conley A, Manjila S, Guan H, Guthikonda M, Kupsky WJ, Mittal S. Non-langerhans cell histiocytosis with isolated CNS involvement: An unusual variant of Erdheim-Chester disease. Neuropathology 2010;30:634-47.  Back to cited text no. 7
Jain RS, Sannegowda RB, Jain R, Mathur T. Erdheim-Chester disease with isolated craniocerebral involvement. BMJ Case Rep 2013;2013:bcr2012006823.  Back to cited text no. 8
Bianco F, Iacovelli E, Tinelli E, Locuratolo N, Pauri F, Fattapposta F. Characteristic brain MRI appearance of Erdheim-Chester disease. Neurology 2009;73:2120-2.  Back to cited text no. 9
Goyal G, Young JR, Koster MJ, Tobin WO, Vassallo R, Ryu JH, et al. The Mayo Clinic histiocytosis working group consensus statement for the diagnosis and evaluation of adult patients with histiocytic neoplasms: Erdheim-Chester disease, Langerhans cell histiocytosis, and Rosai-Dorfman disease. Mayo Clin Proc 2019;94:2054-71.  Back to cited text no. 10


  [Figure 1], [Figure 2]

  [Table 1]


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