Concomitant rheumatoid arthritis and amyotrophic lateral sclerosis: report of two new cases and review of literature

Padovan, Melissa; Caniatti, Luisa; Trotta, Francesco; Govoni, Marcello

doi:10.1007/s00296-010-1760-3

Cited by 10 publications

(6 citation statements)

References 45 publications

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“…There have been 3 prior studies of ALS developing in patients treated with TNF-inhibitors. 130 , 132 , 133 Nevertheless, cardinal and unique features in our case—including CSF abnormalities and the presence of antineuronal antibodies—were not described in these 3 other patients. We therefore believe that our patient represents the first case in the literature which provides the most convincing evidence for a TNF-inhibitor-induced ALS-plus syndrome, with several collective features suggestive that the TNF-inhibitors were causative and associated with an immune-mediated syndrome.…”

Section: Discussioncontrasting

confidence: 47%

“…Table 2 D describes that there were 7 reports of ALS in 14 rheumatic disease patients, including 2 patients with SLE, 127 , 128 5 patients with Behcet's syndrome, 129 4 patients with RA who were not on TNF-inhibitor therapy, 130 , 131 and 3 patients (1 with ankylosing spondylitis and 2 with RA) with ALS developing in the context of TNF-inhibitor therapy. 130 , 132 , 133 Three patients presented with abnormal MRI findings, 128 – 130 but with lesions which were not spatially disseminated, and therefore could not account for a diffuse ALS-plus presentation. Although 2 patients with foot drop were categorized as having atypical clinical findings, 128 , 129 , 131 the initial clinical presentation of ALS is heterogeneous, and can encompass clinical findings such as an early foot drop.…”

Section: Literature Reviewmentioning

confidence: 99%

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Movement and Other Neurodegenerative Syndromes in Patients with Systemic Rheumatic Diseases

et al. 2015

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Patients with rheumatic diseases can present with movement and other neurodegenerative disorders. It may be underappreciated that movement and other neurodegenerative disorders can encompass a wide variety of disease entities. Such disorders are strikingly heterogeneous and lead to a wider spectrum of clinical injury than seen in Parkinson's disease. Therefore, we sought to stringently phenotype movement and other neurodegenerative disorders presenting in a case series of rheumatic disease patients. We integrated our findings with a review of the literature to understand mechanisms which may account for such a ubiquitous pattern of clinical injury.Seven rheumatic disease patients (5 Sjögren's syndrome patients, 2 undifferentiated connective tissue disease patients) were referred and could be misdiagnosed as having Parkinson's disease. However, all of these patients were ultimately diagnosed as having other movement or neurodegenerative disorders. Findings inconsistent with and more expansive than Parkinson's disease included cerebellar degeneration, dystonia with an alien-limb phenomenon, and nonfluent aphasias.A notable finding was that individual patients could be affected by cooccurring movement and other neurodegenerative disorders, each of which could be exceptionally rare (ie, prevalence of ∼1:1000), and therefore with the collective probability that such disorders were merely coincidental and causally unrelated being as low as ∼1-per-billion. Whereas our review of the literature revealed that ubiquitous patterns of clinical injury were frequently associated with magnetic resonance imaging (MRI) findings suggestive of a widespread vasculopathy, our patients did not have such neuroimaging findings. Instead, our patients could have syndromes which phenotypically resembled paraneoplastic and other inflammatory disorders which are known to be associated with antineuronal antibodies. We similarly identified immune-mediated and inflammatory markers of injury in a psoriatic arthritis patient who developed an amyotrophic lateral sclerosis (ALS)-plus syndrome after tumor necrosis factor (TNF)-inhibitor therapy.We have described a diverse spectrum of movement and other neurodegenerative disorders in our rheumatic disease patients. The widespread pattern of clinical injury, the propensity of our patients to present with co-occurring movement disorders, and the lack of MRI neuroimaging findings suggestive of a vasculopathy collectively suggest unique patterns of immune-mediated injury.

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Section: Discussioncontrasting

confidence: 47%

Section: Literature Reviewmentioning

confidence: 99%

Movement and Other Neurodegenerative Syndromes in Patients with Systemic Rheumatic Diseases

et al. 2015

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“…ALS is rarely concomitant with polyglutamine diseases, including Huntington's disease, spinocerebellar ataxia type 2 (SAC2) and SCA6 . On the other hand, ALS may be concurrent with several autoimmune or inflammatory disorders, including rheumatoid arthritis, systemic lupus erythematosus, scleroderma and neurosarcoidosis . Thus, the variety and rarity of such an association may not represent evidence in favor of shared pathomechanisms and may simply be an example of random co‐occurrence.…”

Section: Discussionmentioning

confidence: 99%

Coexistence of amyotrophic lateral sclerosis with neuro‐Behçet's disease presenting as a longitudinally extensive spinal cord lesion: clinicopathologic features of an autopsied patient

et al. 2013

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We report the clinical and autopsy features of a 65-year-old Japanese man who clinically exhibited overlap of both neuro-Behçet's disease (NBD) and amyotrophic lateral sclerosis (ALS). The patient had a HLA-B51 serotype, a recent history of uveitis and had suffered paraparesis, sensory and autonomic disturbance, frontal signs and tremor. A brain and spine MRI study revealed a longitudinally extensive thoracic cord (Th) lesion, but no apparent intracranial abnormalities. The lesion extended ventrally from Th4 to Th9, exhibiting low intensity on T1-weighted images, high intensity on T2-weighted and fluid-attenuated inversion recovery images and gadolinium enhancement. The patient's upper and lower motor neuron signs and sensory disturbance worsened and he died 16 months after admission. At autopsy, the spinal cord and brain exhibited characteristic histopathological features of both NBD and ALS, including chronic destruction of the ventral thoracic white and gray matter, perivascular lymphocytic infiltration, binucleated neurons, lower and upper motor neuron degeneration, Bunina bodies and skein-like inclusions. Although incidental coexistence of these rare disorders could occur in an individual, this case raises the possibility of a pathomechanistic association between NBD and ALS.

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“…Notably, as reported by Padovan et al, in two patients with RA, ALS developed rapidly after the introduction of or increase in dose of infliximab, a TNFA antagonist ( 24 ). While these authors acknowledge the limitations of such anecdotal observations, this finding would fit with an upregulation of the antiapoptotic TNFRSF1B in chronic RA, thereby masking a tendency toward ALS in the cases they report.…”

Section: Drugs Used For Rheumatoid Arthritismentioning

confidence: 85%

Immune Modulation in the Treatment of Amyotrophic Lateral Sclerosis: A Review of Clinical Trials

et al. 2017

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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the degeneration of motor neurons. Though many molecular and genetic causes are thought to serve as predisposing or disease propagating factors, the underlying pathogenesis of the disease is not known. Recent discoveries have demonstrated the presence of inflammation propagating substrates in the central nervous system of patients afflicted with ALS. Over the past decade, this hypothesis has incited an effort to better understand the role of the immune system in ALS and has led to the trial of several potential immune-modulating therapies. Here, we briefly review advances in the role of such therapies. The clinical trials discussed here are currently ongoing or have been concluded at the time of writing.

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Concomitant rheumatoid arthritis and amyotrophic lateral sclerosis: report of two new cases and review of literature

Cited by 10 publications

References 45 publications

Movement and Other Neurodegenerative Syndromes in Patients with Systemic Rheumatic Diseases

Movement and Other Neurodegenerative Syndromes in Patients with Systemic Rheumatic Diseases

Coexistence of amyotrophic lateral sclerosis with neuro‐Behçet's disease presenting as a longitudinally extensive spinal cord lesion: clinicopathologic features of an autopsied patient

Immune Modulation in the Treatment of Amyotrophic Lateral Sclerosis: A Review of Clinical Trials

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