Diagnosis of ALS remains primarily a clinical diagnosis based on the number of affected body parts (bulbar, cervical, thoracic and lumbosacral) with simultaneous upper motor neuron and lower motor neuron signs [6]. Riluzole is the sole approved medication that has demonstrated in clinical trials its ability to slow ALS progression. However, Riluzole is not a cure and its impact is limited. In clinical trials, patients treated with Riluzole lived about 3 months longer at the 18-month mark set by the researchers compared to those who received a placebo [7]. ALS remains an incurable progressive disease. It is important that physicians to look for treatable pathology that can mimic the presentation of ALS.
Idiopathic and paraneoplastic association between malignancies and ALS has been previously reported [8]. Gordon et al reviewed 56 cases of concomitant ALS and lymphoproliferative disorder observed at their centre and reported in the literature [1]. The authors concluded that more than half of the patients with lymphoproliferative disorders including lymphoma, multiple myeloma, chronic lymphocytic leukaemia and macroglobulinemia and ALS had both upper and lower motor neuron signs while the remaining had lower motor neuron signs only. Based on circulating paraproteins and bone marrow biopsies of ALS, the authors suggested that the frequency of lymphoproliferative disorders in ALS patients was around 2–5% [8].
Sarcoidosis and ALS occurring comorbidly or as a manifestation of neurosarcoidosis is not common. However, a recent retrospective study revealed that likelihood of both those diseases coinciding might be underestimated. A diagnosis of sarcoid was reported in 6 per 1000 patients with ALS[5]. A literature search yielded twelve cases of ALS and sarcoid. Nine of these twelve cases had a spinal onset ALS, while three had a bulbar onset [6]. Sarcoid and ALS were simultaneously diagnosed in three patients. Sarcoid was diagnosed prior to ALS in two patients and at autopsy of the lymph nodes in one [6]. Four of these cases reported that sarcoid treatment did not change the ALS course, whereas one author reported improvement of symptoms [6].
Sarcoid-like reactions are characterized by the development of a granulomatous disease on histopathology with or without clinical features of sarcoidosis. Sarcoid- like reactions may affect a single organ such as the skin, spleen, kidneys, and lungs [7]. Reported medications that have been linked to a sarcoid -like reaction include antiretroviral therapies, tumour necrosis factor-α antagonists, interferons, and immune checkpoint inhibitors [7]. In a study looking at the association of sarcoidosis and lymphoma, the authors described the development of sarcoidosis in 39 patients treated for lymphoma. About one-third of these patients had received rituximab [7]., whereas patients receiving chemotherapy alone without rituximab for haematological malignancy did not report sarcoid like reaction as a side effect of treatment [7].
This case demonstrates an extremely rare combination of three pathologies: CLL, sarcoid like reaction and ALS. It also highlights both the potential difficulty in diagnosis and treatment of these conditions. The initial clinical presentation of the patient, together with the results of the neurophysiology, lumbar puncture results and radiological investigations, were consistent with a ALS presentation and subsequently neurosarcoid. However, despite treatment for neurosarcoidosis, the symptoms did not improve., The subsequent clinical course has remained consistent with ALS.