Letter to the Editor. Clinical manifestations of Erdheim-Chester disease besides epilepsy

TO THE EDITOR: We read with interest the article by Stuebe et al.¹ (Stuebe CM, Jenson AV, Lines TW, et al. Recurrent petit mal seizures in Erdheim-Chester disease mimicking an intraaxial brain tumor: illustrative case. J Neurosurg Case Lessons. 2023;6[16]:CASE23248). We disagree that Erdheim-Chester disease (ECD) manifested only through seizures. The patient had retroperitoneal fibrosis, which caused ureteral obstruction and is a common feature of ECD.² The patient also had diabetes.¹ Because diabetes can be a complication of pancreatitis and pancreatitis is a manifestation of ECD, it is conceivable that diabetes was a third ECD manifestation in addition to epilepsy and retroperitoneal fibrosis.

A limitation of the authors’ study is that alternative triggers of seizures were not sufficiently ruled out. The most common cause of focal seizures is temporal lobe epilepsy, which usually begins in childhood with febrile seizures, followed by a seizure-free interval during adolescence.³ A second cause of focal epilepsy not adequately ruled out is genetic epilepsy. No family history was provided, and no panel for the most commonly mutated genes in genetic epilepsy was performed. We should also know whether the patient’s history was positive for seizures before age 55, particularly in childhood, and whether there was a history of traumatic brain injury or birth trauma, meningitis/encephalitis, a family history of epilepsy, or a metabolic defect.

A second limitation is that no results from electroencephalography (EEG) recordings were provided. To assess whether the amygdala lesions were truly the origin of seizure activity, the recording of standard or video EEG signals would have been mandatory. A cerebral lesion in a patient with seizures does not necessarily mean that this lesion is the origin of seizure activity.

A third limitation is that a long-term follow-up was not provided. We should know whether the patient remained seizure-free, whether antiseizure drugs (lamotrigine, levetiracetam) could be discontinued after surgery, whether the right temporal lesion regressed or progressed, and whether the patient tolerated the immunosuppressive therapy (dabrafenib, trametinib) without side effects. Because ECD is a progressive, multisystem disease,² we should know whether organs other than the brain, bones, and retroperitoneum were affected as the disease progressed.

A fourth limitation is that no information about the cerebral arteries was provided. ECD is a disorder that commonly affects arteries through sheathing and leads to focal stenosis or occlusion, especially of large but also of medium-sized arteries, and then to ischemia in the corresponding vascular bed.² The aorta and its major branches are most commonly affected, although there are also reports about the involvement of carotid, vertebral, and intracranial arteries.⁴

Often, ECD also affects the pituitary gland and manifests clinically as diabetes insipidus, polydipsia, and electrolyte disturbances.⁵ Was there evidence of pituitary involvement, such as diabetes insipidus?

The patient was initially diagnosed with immune encephalitis.¹ What diagnostic criteria were used to diagnose immune encephalitis? We should know whether autoimmune encephalitis-associated antibodies were elevated, whether there was an enhancing magnetic resonance imaging lesion, and whether other immunological parameters in the cerebrospinal fluid were abnormal.

In summary, ECD is a progressive, multisystem disease, which is why it is inconceivable that only the brain is affected and why these patients require systematic, prospective screening for multisystem involvement. Symptomatic treatment of organ involvement in addition to immunosuppression can greatly determine the outcome of these patients.