Paraneoplastic neurological syndromes

Leypoldt, Frank; Wandinger, Klaus Peter

doi:10.1111/cei.12185

Cited by 133 publications

(129 citation statements)

References 87 publications

(151 reference statements)

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“…Ayzenberg 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.…”

Section: E264mentioning

confidence: 99%

“…Clinically, the following PNS exist [3,4]: A. In the central nervous system: ▪ Encephalomyelitis (incl.…”

Section: E264mentioning

confidence: 99%

“…Ayzenberg I et al Management of Immune-mediated Paraneoplastic … Neurology International Open 2017; 1: E264-E274 tracellular antigens with mainly T cell-mediated immune responses [3,16,19,20]. If the patient does no improve with acute treatment, an early (typically up to 2 weeks after the above-mentioned primary treatment) escalation to cyclophosphamide (as a shortterm high-dose treatment with 750-1000 mg/m 2 IV) or rituximab (e. g., 500 mg IV on days 1 and 15) can be undertaken [16,21,22].…”

Section: E266mentioning

confidence: 99%

“…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.…”

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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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Section: E264mentioning

confidence: 99%

“…Clinically, the following PNS exist [3,4]: A. In the central nervous system: ▪ Encephalomyelitis (incl.…”

Section: E264mentioning

confidence: 99%

Section: E266mentioning

confidence: 99%

mentioning

confidence: 99%

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Management of Immune-Mediated Paraneoplastic Neurological Disorders

Ayzenberg

Gold

Kleiter

2017

Neurology International Open

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“…Neurologists should have a high index of suspicion for paraneoplastic syndromes when evaluating a patient with known or suspected malignancy, even though only up to 1% of patients with cancer have an obvious paraneoplastic disorder. 8 Moreover, meningeal disease, coagulopathy, metastasis, toxic, metabolic, and chemotherapy-induced causes should be ruled out before attributing a paraneoplastic diagnosis. 8,9 While positive antibodies in patients with a suspected paraneoplastic syndrome are generally diagnostic, undetected antibodies occur in approximately 20% of patients with paraneoplastic syndromes of the CNS and most of the patients with paraneoplastic syndromes of the peripheral nervous system.…”

Section: Figurementioning

confidence: 99%

Clinical Reasoning: Stepwise paralysis in a patient with adenocarcinoma of lung

2016

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A 54-year-old man presented with pain in the left chest for 3 days. His medical history was remarkable for hyperlipidemia managed with diet and statin. He denied tobacco smoking and consumption of alcohol. Physical examination was unrevealing. The patient was diagnosed with an adenocarcinoma of the lung harboring an epidermal growth factor receptor (EGFR) mutation that metastasized to T2-T4 levels. He was treated with radiotherapy and dexamethasone followed by Gefitinib.In Approximately 2 weeks after his surgery, the patient developed rapidly progressive, severe weakness affecting lower and upper limbs with increasing respiratory discomfort over a 3-day period. The patient was intubated and transferred to the intensive care unit due to respiratory distress. He was alert without obvious cranial nerve dysfunction. Neurologic examination was remarkable for a severe, flaccid tetraparesis (MRC of 1/5 at most in all tested muscles in the lower limbs and MRC of 2/5 at most in all tested muscles in the upper limbs) in addition to diffuse areflexia and neutral plantar responses.Questions for consideration:

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Cell‐surface central nervous system autoantibodies: Clinical relevance and emerging paradigms

Irani

Gelfand

Al-Diwani

et al. 2014

Annals of Neurology

167

149

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The recent discovery of several potentially pathogenic autoantibodies has helped identify patients with clinically distinctive central nervous system diseases that appear to benefit from immunotherapy. The associated autoantibodies are directed against the extracellular domains of cell-surface–expressed neuronal or glial proteins such as LGI1, N-methyl-D-aspartate receptor, and aquaporin-4. The original descriptions of the associated clinical syndromes were phenotypically well circumscribed. However, as availability of antibody testing has increased, the range of associated patient phenotypes and demographics has expanded. This in turn has led to the recognition of more immunotherapy-responsive syndromes in patients presenting with cognitive and behavioral problems, seizures, movement disorders, psychiatric features, and demyelinating disease. Although antibody detection remains diagnostically important, clinical recognition of these distinctive syndromes should ensure early and appropriate immunotherapy administration. We review the emerging paradigm of cell-surface–directed antibody–mediated neurological diseases, describe how the associated disease spectrums have broadened since the original descriptions, discuss some of the methodological issues regarding techniques for antibody detection and emphasize considerations surrounding immunotherapy administration. As these disorders continue to reach mainstream neurology and even psychiatry, more cell-surface–directed antibodies will be discovered, and their possible relevance to other more common disease presentations should become more clearly defined.

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Paraneoplastic neurological syndromes

Cited by 133 publications

References 87 publications

Management of Immune-Mediated Paraneoplastic Neurological Disorders

Management of Immune-Mediated Paraneoplastic Neurological Disorders

Clinical Reasoning: Stepwise paralysis in a patient with adenocarcinoma of lung

Cell‐surface central nervous system autoantibodies: Clinical relevance and emerging paradigms

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