Multiple Paraneoplastic Neurological and Rheumatological Syndromes Revealing an Ovarian Cancer

Multiple paraneoplastic syndromes are a rare clinical manifestation. We describe the case of an 82-year-old woman who presented with neurological (rapidly progressive cerebellar syndrome and combined sensory-motor neuronopathy) and rheumatological (palmar fasciitis and polyarthritis syndrome) paraneoplastic syndromes associated with two onconeural antibodies (anti-Yo and Zic4), that revealed an ovarian cancer. The involvement of multiple organ systems should be a clue to take into consideration a paraneoplastic etiology that could permit early detection of cancer. However, despite the existence of treatments, the prognosis of these conditions remains poor.

Anti-Ma2 Antibody-Associated Paraneoplastic Neurological Syndromes: A Pilot Study

Paraneoplastic neurologic syndromes (PNSs) are a heterogeneous group of disorders caused by the remote effects of cancer with immune-mediated pathogenesis. Anti-Ma2 antibody was defined as one of the well-characterized onconeural antibodies that could help establish a definite PNS diagnosis. We aimed to report and explore patients with anti-Ma2 antibody-associated paraneoplastic neurologic syndrome (Ma2-PNS) who frequently exhibit sensorimotor neuropathy (SMN) using a new method of factor analysis of mixed data (FAMD). Clinical data from a case series of eight patients with definite diagnoses were retrospectively reviewed. FAMD conducted further analyses with a comprehensive visualization in R software. Our cohort, with a predominance of females (5/8), presented more frequently with SMN (4/8), followed by limbic encephalitis (LE) (3/8). Two patients with LE were found to have a testicular germ-cell tumor and a thymoma, respectively. In addition, a patient who developed chronic SMN was diagnosed with multiple myeloma (MM) involving multiple organs. FAMD exhibited the overall features into a two-dimensional coordinate and located each individual into their corresponding position with high relevance. It provided a clue for determining their potential relationships and predictors. Our findings indicated that Ma2-PNS could frequently involve the peripheral nervous system, MM might be one of its associated cancers with a presentation of chronic SMN, and FAMD might be a clinically valuable tool.

Parkinsonism and dysautonomia with anti-CV2/CRMP5 associated paraneoplastic neurological syndromes mimicking multiple system atrophy: a case report

Background Paraneoplastic neurological syndromes (PNSs) are broad-spectrum disorders that can affect any part of the nervous system varying in core symptoms. Onconeural antibodies, including Hu, Yo, Ri, anti-CV2, amphiphysin, Ma2, and Tr are well-characterized and commonly used for the diagnosis of definite PNS. Generally, anti-CV2 antibodies have usually been associated with cerebellar ataxia, chorea, peripheral and autonomic neuropathies, myelopathy, optic neuritis, and retinitis. However, Parkinsonism has not been reported as the core symptom in patients with anti-CV2 antibodies. Case presentation We report a patient with anti-CV2 antibody manifested as Parkinsonism and autonomic dysfunction, which may lead to the diagnosis of multiple system atrophy with predominant Parkinsonism (MSA-P). A lumbar puncture examination was undergone to find a positive anti-CV2 antibody in cerebrospinal fluid. PET-CT showed no tumor. Immunotherapy was adopted and the symptoms were relieved for 5 months. However, with no evidence of tumor, he died after 8 months. Conclusions Our findings indicate that PNS with anti-CV2 antibody can be shown as MSA-P mimic. Considering that MSA is a neurodegenerative disease with a poor prognosis, screening for other treatable or controllable factors like PNS presented in this case is necessary when encountering a rapid progressive MSA-mimic patient.

Resolution of Paraneoplastic Lumbosacral Plexopathy in a Patient With Stage III Rectal Cancer after Curative Resection

Paraneoplastic syndromes are rare but possible manifestations of colorectal cancer. We present THE CASE of a 51-year-old female diagnosed with cT3N2 rectal adenocarcinoma who developed back pain and progressive muscle weakness during preoperative treatment. She had a rapid worsening in mobility and was ultimately ambulating with a wheelchair, despite physical therapy and conservative treatments. Extensive laboratory workup including onconeural antibodies was negative and her lower extremity electromyogram was suggestive of a subacute demyelinating lumbosacral plexopathy. After multidisciplinary discussion, the decision was made to proceed with curative resection. She had significant improvement in her weakness following resection, suggesting a paraneoplastic etiology. One year after resection, she remains free of disease and is ambulating comfortably. Onconeural antibodies can be a helpful diagnostic tool, but their absence does not rule out paraneoplastic disease. A high index of suspicion is necessary when assessing patients with atypical symptoms, particularly with the rise of colorectal cancer in young adults.

Paraneoplastic Neuropathies: What's New Since the 2004 Recommended Diagnostic Criteria

The diagnostic criteria published by the PNS (Paraneoplastic Neurological Syndromes) Euronetwork in 2004 provided a useful classification of PNS, including paraneoplastic neuropathies. Subacute sensory neuronopathy (SSN) was the most frequently observed peripheral PNS, whereas other forms of neuropathy, as sensory polyneuropathy, sensorimotor polyneuropathy, demyelinating neuropathies, autonomic neuropathies, and focal nerve or plexus lesions, were less frequent. At the time of publication, the main focus was on onconeural antibodies, but knowledge regarding the mechanisms has since expanded. The antibodies associated with PNS are commonly classified as onconeural (intracellular) and neuronal surface antibodies (NSAbs). Since 2004, the number of antibodies and the associated tumors has increased. Knowledge has grown on the mechanisms underlying the neuropathies observed in lymphoma, paraproteinemia, and multiple myeloma. Moreover, other unrevealed mechanisms underpin sensorimotor neuropathies and late-stage neuropathies, where patients in advanced stages of cancer—often associated with weight loss—experience some mild sensorimotor neuropathy, without concomitant use of neurotoxic drugs. The spectrum of paraneoplastic neuropathies has increased to encompass motor neuropathies, small fiber neuropathies, and autonomic and nerve hyperexcitability syndromes. In addition, also focal neuropathies, as cranial nerves, plexopathies, and mononeuropathies, are considered in some cases to be of paraneoplastic origin. A key differential diagnosis for paraneoplastic neuropathy, during the course of cancer disease (the rare occurrence of a PNS), is chemotherapy-induced peripheral neuropathy (CIPN). Today, novel complications that also involve the peripheral nervous system are emerging from novel anti-cancer therapies, as targeted and immune checkpoint inhibitor (ICH) treatment. Therapeutic options are categorized into causal and symptomatic. Causal treatments anecdotally mention tumor removal. Immunomodulation is sometimes performed for immune-mediated conditions but is still far from constituting evidence. Symptomatic treatment must always be considered, consisting of both drug therapy (e.g., pain) and attempts to treat disability and neuropathic pain.

Paraneoplastic neurological syndrome: an evolving story

Paraneoplastic neurological syndrome (PNS) comprises a group of neurological disorders that result from a misguided immune response to the nervous system triggered by a distant tumor. These disorders frequently manifest before the diagnosis of the underlying neoplasm. Since the first reported case in 1888 by Oppenheim, the knowledge in this area has evolved rapidly. Several classic PNS have been described, such as limbic encephalitis, paraneoplastic cerebellar degeneration, encephalomyelitis, opsoclonus-myoclonus, sensory neuronopathy, Lambert-Eaton Myasthenic syndrome, and chronic gastrointestinal dysmotility. It is now recognized that PNS can have varied nonclassical manifestations that extend beyond the traditional syndromic descriptions. Multiple onconeural antibodies with high specificity for certain tumor types and neurological phenotypes have been discovered over the past 3 decades. Increasing use of immune checkpoint inhibitors (ICIs) has led to increased recognition of neurologic ICI-related adverse events. Some of these resemble PNS. In this article, we review the clinical, oncologic, and immunopathogenic associations of PNS.

Serum Tumor Markers in Paraneoplastic Neurologic Syndromes: A Systematic Review of Guidelines

Purpose: Algorithms for the detection of a malignancy in patients with unclear neurologic symptoms of suspicious paraneoplastic origins are not universally applied. Frequently, circulating tumor markers (TMs) are considered a valuable tool for cancer diagnosis in patients with paraneoplastic neurologic syndromes (PNS). Our aim was to extract the recommendations on the use of TMs and onconeural antibodies (Abs) for the diagnosis of malignancies in PNS from clinical practice guidelines and put them forward as evidence in a common framework to facilitate diffusion, dissemination, and implementation.Methods: Systematic literature searches were performed for guidelines on both oncology and PNS published since 2007. Guidelines containing information and recommendations for clinical practice pertaining to the screening and diagnosis of PNS were selected. Information on circulating TMs and onconeural Abs was extracted and synthesized in consecutive steps of increasing simplification.Results: We retrieved 799 eligible guidelines on oncology for the potential presence of information on PNS but only six covered treated diagnosis or the screening of cancer in PNS, which were then selected. Seventy-nine potentially relevant guidelines on PNS were identified as eligible and 15 were selected. Synoptic tables were prepared showing that classical TMs are not recommended for the screening or the diagnosis of a malignancy in patients with a suspected PNS. Neither should onconeural Abs be considered to screen for the presence of a malignancy, although they could be helpful to define the probability of the paraneoplastic origin of a neurologic disorder.Conclusion: The present work of synthesis may be a useful tool in the diffusion, dissemination, and implementation of guideline recommendations, potentially facilitating the decrease of the inappropriate use of circulating biomarkers for cancer screening in the presence of PNS.

Paraneoplastic neurological syndromes: clinical presentations and management

We provide an overview of the varied presentations of paraneoplastic neurological syndromes. We also review the onconeural antibodies and their particular oncological and neurological associations. Recognition of these syndromes and their oncological associations is crucial, as early diagnosis and management has been associated with better patient outcomes. Specific management strategies and prognosis vary widely depending on the underlying etiology. An understanding of the relevant clinical details, imaging findings, and other diagnostic information can help tailor treatment approaches. We provide an outline of the diagnostic evaluation and treatment of various paraneoplastic neurological disorders, presenting with central and/or peripheral nervous system involvement. We briefly discuss neurologic immune checkpoint inhibitor-related adverse events, which can occasionally present with paraneoplastic neurological syndrome phenotypes.