Responses to and Outcomes of Treatment of Autoimmune Cerebellar Ataxia in Adults

Jones, Amy Little; Flanagan, Eoin P.; Pittock, Sean J.; Mandrekar, Jay; Eggers, Scott D.Z.; Ahlskog, J. Eric; McKeon, Andrew

doi:10.1001/jamaneurol.2015.2378

Cited by 89 publications

(75 citation statements)

References 43 publications

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“…One‐third of patients with autoimmune epilepsy responded to immunotherapy in 1 series . Fifty‐two percent of patients with GAD65 antibody‐associated ataxia improved with immunotherapy in another series, usually robustly, with more than half of the subjects in 1 series wheelchair free at both 5 and 10 years postsymptom onset . Ambulatory outcomes among those patients were similar to ataxic patients harboring antibodies targeting cell surface antigens, such as P/Q‐type calcium channel antibodies.…”

Section: Treatmentmentioning

confidence: 93%

GAD65 neurological autoimmunity

2017

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The glutamic acid decarboxylase 65-kilodalton isoform (GAD65) antibody is a biomarker of autoimmune central nervous system (CNS) disorders and, more commonly, nonneurological autoimmune diseases. Type 1 diabetes, autoimmune thyroid disease, and pernicious anemia are the most frequent GAD65 autoimmune associations. One or more of these disorders coexists in approximately 70% of patients with GAD65 neurological autoimmunity. Neurological phenotypes have CNS localization and include limbic encephalitis, epilepsy, cerebellar ataxia, and stiff-person syndrome (SPS), among others. Classic SPS is a disorder on the spectrum of CNS hyperexcitability which also includes phenotypes that are either more restricted (stiff-limb syndrome) or more widespread (progressive encephalomyelitis with rigidity and myoclonus). GAD65 antibody is not highly predictive of a paraneoplastic cause for neurological disorders, but diverse cancer types have been occasionally reported. For all phenotypes, responses to immunotherapy are variable (approximately 50% improve). GAD65 autoimmunity is important to recognize for both coexisting nonneurological autoimmune associations and potential immunotherapy-response. Muscle Nerve 56: 15-27, 2017.

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Section: Treatmentmentioning

confidence: 93%

GAD65 neurological autoimmunity

2017

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“…In a recent analysis of 313 patients with SCLC in the United Kingdom, longer survival was demonstrated for patients with SCLC and LES than for patients with SCLC without LES, even after accounting for lead‐time bias (18 months vs. 9.5 months) . Survival in a large series of patients with autoimmune ataxia was 76% at last follow‐up (median 25 months, range, 2–223), but 75% of deaths occurred in the paraneoplastic group . In a previously published series of SCLC patients with paraneoplastic cerebellar ataxia and LES, survival was worse for SCLC patients with accompanying cerebellar ataxia (1‐year survival 46%) compared with SCLC patients without ataxia (1‐year survival 76%) .…”

Section: Discussionmentioning

confidence: 99%

Calcium channel autoimmunity: Cerebellar ataxia and lambert‐eaton syndrome coexisting

et al. 2018

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“…The clinical picture is dominated by progressive cerebellar ataxia, reaching a plateau within the first weeks to months in the majority of patients, with 50-70 % of patients becoming wheelchair-bound during this time [24]. In most cases, irreversible loss of Purkinje cells is the underlying cause of this condition.…”

Section: Paraneoplastic Cerebellar Degeneration (Pcd)mentioning

confidence: 99%

Management of Immune-Mediated Paraneoplastic Neurological Disorders

Ayzenberg

Gold

Kleiter

2017

Neurology International Open

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AbsTR Ac TParaneoplastic neurological disorders are rare and clinically heterogeneous diseases. They can affect both the central and peripheral nervous system as well as the neuromuscular junction and muscle. Neurological deficits develop in 2/3 of cases prior to cancer diagnosis. The diagnostic approach includes screening for antineuronal antibodies and a search for the underlying tumor. A prompt tumor therapy in combination with immunotherapy is the cornerstone in the management of these diseases. Due to lack of clinical trials, treatment recommendations are based on case series and expert opinions. Highdose corticosteroids, intravenous immunoglobulins and apheresis therapies are often used in the acute stage of the disease. These therapies should be started as early as possible, e. g., during tumor screening, in order to prevent irreversible damage. Long-term treatment is mostly immunosuppressive and depends on the specific paraneoplastic syndrome. Outcomes vary depending upon the prognosis of the underlying cancer and the nature of the antineuronal antibodies. Disorders with antibodies directed against antigens on the neuronal cell surface are highly sensitive to B cell-directed therapies and mostly associated with a favorable outcome. A thorough review of published data on actual treatment recommendation is provided along with discussion of currently not validated, but potentially effective new therapies. E264Ayzenberg I et al. Management of Immune-mediated Paraneoplastic … Neurology International Open 2017; 1: E264-E274 course, treatment response and prognosis of PNS [2,3]. Depending on tumor association, obligate and facultative paraneoplastic Abs are differentiated (Tab. 1).Clinically, the following PNS exist [3,4]: A. In the central nervous system: ▪ Encephalomyelitis (incl. brainstem encephalitis) ▪ Limbic encephalitis ▪ Subacute cerebellar degeneration ▪ Opsoclonus-myoclonus syndrome ▪ Optic neuritis/neuromyelitis optica ▪ Myelopathy/myelitis ▪ Stiff person syndrome ▶Table 1 Paraneoplastic antibodies: associated neurological syndromes and tumors. Target antigen clinical presentation# Association with tumorObligate paraneoplastic Abs (directed against intracellular antigens; tumor association > 95 %) In this review we discuss the diagnosis and management of PNS. With regard to facultative paraneoplastic syndromes which are more frequently of autoimmune origin, such as neuromyelitis optica or myasthenia gravis, the reader should refer to pertinent reviews [5,6]. Diagnostic and Pathogenetic Significance of Antibodies to Intracellular and Surface AntigensAntibodies (Abs) to intracellular antigens or so-called "classical" Abs are almost always tumor-associated (exception: GAD-Abs). They can be associated with various tumors and a variety of neurological conditions [7]. However, a direct pathogenetic significance of these Abs has not yet been demonstrated. Abs to intracellular antigens serve as useful diagnostic markers in the targeted tumor search in PNS. Here, cell-mediated immune responses play a major p...

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Responses to and Outcomes of Treatment of Autoimmune Cerebellar Ataxia in Adults

Cited by 89 publications

References 43 publications

GAD65 neurological autoimmunity

GAD65 neurological autoimmunity

Calcium channel autoimmunity: Cerebellar ataxia and lambert‐eaton syndrome coexisting

Management of Immune-Mediated Paraneoplastic Neurological Disorders

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