Paraneoplastic Diseases of the Central Nervous System

Galli, Jonathan; Greenlee, John

doi:10.12688/f1000research.21309.1

Cited by 23 publications

(18 citation statements)

References 107 publications

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“…The pathophysiology of PNS is not entirely understood; autoantibodies and T-cell-mediated immunity against onconeuronal antigens are widely accepted hypotheses [9, 10]. These syndromes can involve the central and peripheral nervous systems, neuromuscular junctions, and muscles [1, 9, 10]. Amongst PNS, sensory neuropathy is the most common manifestation, accounting for approximately 50% of cases [2].…”

Section: Discussionmentioning

confidence: 99%

“…Paraneoplastic neurological syndromes (PNS) are immune-mediated nervous system disorders with diverse clinical manifestations [1]. Anti-neuronal nuclear antibody (ANNA-1) is among the most common autoantibody associated with PNS.…”

Section: Introductionmentioning

confidence: 99%

“…Anti-neuronal nuclear antibody (ANNA-1) is among the most common autoantibody associated with PNS. ANNA-1, also known as the anti-Hu antibody, is a polyclonal IgG antibody directed against intracellular antigens of both tumor and neural cells [1]. Anti-Hu autoantibody-associated PNS can manifest as sensory neuropathy, sensory neuronopathy, autonomic neuropathy, cerebellar ataxia, and limbic encephalitis [2-4].…”

Section: Introductionmentioning

confidence: 99%

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A Rare Case of Sensory Neuropathy Associated with Transitional Cell Carcinoma of the Bladder

Ketineni¹,

Kodali²,

Gorantla³

2020

Case Rep Oncol

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Malignancies can trigger an autoimmune response against the nervous system and manifest as paraneoplastic neurological syndromes (PNS). Initial symptoms of PNS may develop up to 5 years prior to the diagnosis of the underlying malignancy. We report a rare case of PNS associated with transitional cell carcinoma of the bladder in a 70-year-old male with a 6-month history of rapidly progressive symmetric sensory neuropathy. Peripheral neuropathy serological workup was unremarkable. A paraneoplastic neuropathy panel revealed anti-Hu autoantibodies. Further evaluation with a whole-body PET scan could not identify the primary malignancy, but it showed hypermetabolic hilar lymph nodes. An endobronchial ultrasound biopsy of the hilar lymph nodes was negative for cancer. The patient developed painless hematuria 2.5 years after the onset of the sensory neuropathy. Cystoscopy with biopsy revealed non-muscle-invasive transitional cell carcinoma of the bladder. Progression of the sensory neuropathy stopped after tumor resection. This case highlights the importance of a diligent and systematic approach to diagnose PNS. A relentless search is often required to detect PNS-associated occult malignancies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Rare Case of Sensory Neuropathy Associated with Transitional Cell Carcinoma of the Bladder

Ketineni¹,

Kodali²,

Gorantla³

2020

Case Rep Oncol

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“…As already discussed, antibodies against neuronal autoantigens such as anti-Yo antibodies are extremely useful diagnostic biomarkers. Their direct pathogenic potential documented in in vitro models is still unproven in vivo (5,13,149,153,171). However, autoreactive B cells could participate in the development of the disease.…”

Section: Overall Immunological Scenario For the Initiation And Develomentioning

confidence: 99%

Immunological Bases of Paraneoplastic Cerebellar Degeneration and Therapeutic Implications

2020

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Paraneoplastic cerebellar degeneration (PCD) is a rare immune-mediated disease that develops mostly in the setting of neoplasia and offers a unique prospect to explore the interplay between tumor immunity and autoimmunity. In PCD, the deleterious adaptive immune response targets self-antigens aberrantly expressed by tumor cells, mostly gynecological cancers, and physiologically expressed by the Purkinje neurons of the cerebellum. Highly specific anti-neuronal antibodies in the serum and cerebrospinal fluid represent key diagnostic biomarkers of PCD. Some anti-neuronal antibodies such as anti-Yo autoantibodies (recognizing the CDR2/CDR2L proteins) are only associated with PCD. Other anti-neuronal antibodies, such as anti-Hu, anti-Ri, and anti-Ma2, are detected in patients with PCD or other types of paraneoplastic neurological manifestations. Importantly, these autoantibodies cannot transfer disease and evidence for a pathogenic role of autoreactive T cells is accumulating. However, the precise mechanisms responsible for disruption of self-tolerance to neuronal self-antigens in the cancer setting and the pathways involved in pathogenesis within the cerebellum remain to be fully deciphered. Although the occurrence of PCD is rare, the risk for such severe complication may increase with wider use of cancer immunotherapy, notably immune checkpoint blockade. Here, we review recent literature pertaining to the pathophysiology of PCD and propose an immune scheme underlying this disabling disease. Additionally, based on observations from patients' samples and on the pre-clinical model we recently developed, we discuss potential therapeutic strategies that could blunt this cerebellum-specific autoimmune disease.

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“…The first autoantibodies to be identified against neuronal targets include anti-neuronal nuclear antibody type 1 (Anti-Hu) in 1965 ( 2 ) and Purkinje cell cytoplasmic antibody (anti-Yo) in 1983 ( 3 ) which both represent classic paraneoplastic neurological syndromes. It is hypothesized that cross-reactivity between proteins expressed on the tumor and neuronal antigens is responsible for the development of neurologic symptoms, of which cerebellar ataxia is one of the most common manifestations ( 4 ). Since those two autoantibodies were described, the rate of discovery of new autoantibodies to other neuronal targets has been rapidly increasing and there are now several antibodies known to cause cerebellar ataxia both in the setting of malignancy (i.e.…”

Section: Introductionmentioning

confidence: 99%

Update in Autoimmune Movement Disorders: Newly Described Antigen Targets in Autoimmune and Paraneoplastic Cerebellar Ataxia

Garza¹,

Piquet²

2021

Front. Neurol.

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Movement disorders are a common feature of many antibody-associated neurological disorders. In fact, cerebellar ataxia is one of the most common manifestations of autoimmune neurological diseases. Some of the first autoantibodies identified against antigen targets include anti-neuronal nuclear antibody type 1 (ANNA-1 or anti-Hu) and Purkinje cell cytoplasmic antibody (PCA-1) also known as anti-Yo have been identified in paraneoplastic cerebellar degeneration. Historically these antibodies have been associated with an underlying malignancy; however, recently discovered antibodies can occur in the absence of cancer as well, resulting in the clinical syndrome of autoimmune cerebellar ataxia. The pace of discovery of new antibodies associated with autoimmune or paraneoplastic cerebellar ataxia has increased rapidly over the last few years, and pathogenesis and potential treatment options remains to be explored. Here we will review the literature on recently discovered antibodies associated with autoimmune and paraneoplastic cerebellar ataxia including adaptor protein-3B2 (AP3B2); inositol 1,4,5-trisphophate receptor type 1 (ITPR1); tripartite motif-containing (TRIM) proteins 9, 67, and 46; neurochondrin; neuronal intermediate filament light chain (NIF); septin 5; metabotropic glutamate receptor 2 (mGluR2); seizure-related 6 homolog like 2 (SEZ6L2) and homer-3 antibodies. We will review their clinical characteristics, imaging and CSF findings and treatment response. In addition, we will discuss two clinical case examples of autoimmune cerebellar ataxia.

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Paraneoplastic Diseases of the Central Nervous System

Cited by 23 publications

References 107 publications

A Rare Case of Sensory Neuropathy Associated with Transitional Cell Carcinoma of the Bladder

A Rare Case of Sensory Neuropathy Associated with Transitional Cell Carcinoma of the Bladder

Immunological Bases of Paraneoplastic Cerebellar Degeneration and Therapeutic Implications

Update in Autoimmune Movement Disorders: Newly Described Antigen Targets in Autoimmune and Paraneoplastic Cerebellar Ataxia

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