Cerebellar leptomeningeal enhancement: An imaging finding of rapidly progressive Purkinje cell cytoplasmic autoantibody type 1 paraneoplastic cerebellar syndrome.

Purkinje cell cytoplasmic autoantibody type 1 (PCA1), also known as anti-Yo, is a 'high-risk' paraneoplastic antibody, associated with rapidly progressive cerebellar syndrome. In patients with this syndrome, various MRI abnormalities have been documented, including atrophy in the cerebellum and brainstem, T2 hyperintensity in the brainstem and spinal cord, and cranial nerve enhancement. This report introduces an imaging finding, cerebellar leptomeningeal enhancement, which was observed in all three cases at early stages. Despite neurological deterioration, all patients underwent immunotherapy, and subsequent follow-up MRI revealed resolution of the leptomeningeal enhancement, suggesting that this feature is distinct from meningeal carcinomatosis.

FDG PET Unveils the Course of Paraneoplastic Cerebellar Degeneration: A Semiquantitative Analysis.

ABSTRACT: In paraneoplastic cerebellar degeneration (PCD), the standard diagnostic workup might be inconclusive, especially in seronegative subtypes. Brain 18F-FDG PET is an accurate supportive diagnostic tool in immune-mediated disorders, but findings in PCD are controversial. Semiquantitative analysis of 18F-FDG PET can meaningfully assist visual assessment in different neurological conditions and has been mainly applied to disclose regional hypometabolism. We describe a seronegative PCD associated with small cell lung cancer in which 18F-FDG PET semiquantitative analysis accurately disclosed the longitudinal pathological changes of brain metabolism occurring in the acute and posttreatment remission stages and paralleling clinical impairment and response to treatment.

Acute-onset paraneoplastic cerebellar degeneration secondary to neuroendocrine carcinoma with atypical prognosis: a case report.

Paraneoplastic cerebellar degeneration (PCD) is a neurological syndrome that is likely caused by tumor-induced autoimmunity against the cerebellum. Neuroendocrine carcinoma (NEC) is a type of neoplasm with high-grade malignant histology and biological behavior. The prognosis for both PCD and NEC is typically poor. We report a case of PCD secondary to metastatic NEC in the lymph nodes, with an unknown primary origin. The case presented acute cerebellar manifestations with typical neuroimaging findings, but with atypical prognosis after lymph node dissection. Neurological symptoms can provide clues to potential tumors, and early antitumor treatment may have contributed to the positive prognosis of PCD secondary to NEC in the present case.

A Case of Paraneoplastic Cerebellar Degeneration that Preceded the Diagnosis of Classical Hodgkin's Lymphoma by 16 Months.

BACKGROUND Paraneoplastic cerebellar degeneration (PCD) is a rare condition that can present as an acute or subacute cerebellar syndrome. PCD is most commonly associated with gynecological and breast cancer, small-cell lung cancer, and classical Hodgkin's lymphoma. The symptoms of PCD can arise several months before tumor diagnosis. This report is of a case of a 44-year-old man with PCD that preceded the diagnosis of classical Hodgkin's lymphoma by 16 months. CASE REPORT A 44-year-old man was admitted to hospital with a cerebellar syndrome that was initially diagnosed as vertebrobasilar insufficiency. Eight months later, cerebral magnetic resonance imaging (MRI) findings and serum anti-Tr antibodies supported the diagnosis of PCD, but no underlying malignancy was initially found. At 16 months after the initial diagnosis of PCD, the patient developed an enlarged inguinal lymph node. Histology of the excisional lymph node biopsy confirmed the diagnosis of classic mixed cellularity Hodgkin's lymphoma, Ann Arbor stage IIA. The patient responded to four cycles of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy. CONCLUSIONS This case illustrates that in patients who present with PCD, an associated malignancy, such as classical Hodgkin's lymphoma, may emerge several months later, which supports long-term follow-up. The presence of anti-Tr antibodies may support a diagnosis of classical Hodgkin's lymphoma in a patient with a history of PCD who develops lymphadenopathy.

Stroke-Like Presentation of Paraneoplastic Cerebellar Degeneration: a Single-Center Experience and Review of the Literature.

Paraneoplastic cerebellar degeneration (PCD) is usually thought to have a subacute progression over several weeks. We report herein incidence and clinical features of hyperacute onset PCD, a vertebrobasilar stroke mimic. We performed a retrospective analysis of all suspected PCD cases referred to the Udine University Hospital between 2009 and 2017. Our center provides the only neuroimmunology laboratory for three provinces of the Friuli-Venezia Giulia region, Italy (983,190 people as of January 1, 2017). Inclusion criteria were (1) abrupt onset of neurological symptoms; (2) initial consideration of a vascular etiology; (3) final diagnosis of "definite PCD." We also carried out a systematic review of the literature in order to identify previous stroke-like PCD cases. Between 2009 and 2017, 24 patients received a final diagnosis of PCD. The age-standardized incidence rate of PCD was 0.22/100,000 person-years. Two cases (8.3%) had a stroke-like onset, with an incidence of 0.02/100,000 person-years. Additionally, 10 previously reported stroke-like PCD cases were identified. Among all cases (n = 12), 67% were female; median age was 51 years (range, 22-69). An associated cancer was discovered in all cases. Brain imaging was normal in most (75%) of the patients. Cerebrospinal fluid (CSF) analysis showed inflammatory alterations in 73% of the cases. Cancer treatment was more effective than immunotherapy in improving the neurological syndrome. Typical patients with hyperacute PCD are middle-aged women with normal brain imaging, inflammatory markers in CSF, and cancer. Surgery of the underlying cancer is probably the best treatment. PCD must be considered in the differential diagnosis of acute-onset ataxia and/or vertigo.

Paraneoplastic Cerebellar Degeneration in Nasopharyngeal Carcinoma: a Unique Association.

Paraneoplastic cerebellar degeneration (PCD) is a rare disorder that is associated with lung or gynecological malignancies and Hodgkin lymphoma. Neurologic symptoms are commonly the initial presenting sign leading to the diagnosis of an underlying malignancy. We are presenting an Asian male with progressive lower extremity weakness with EBV-positive nasopharyngeal carcinoma (NPC) and anti-Yo antibodies. Peculiarly, transient diffuse leptomeningeal enhancement is seen on MR imaging. This is the first report of PCD associated with NPC and thus illustrates that PCD embodies a boarder set of disease than previously described.

TRIM9 and TRIM67 Are New Targets in Paraneoplastic Cerebellar Degeneration.

To describe autoantibodies (Abs) against tripartite motif-containing (TRIM) protein 9 and 67 in two patients with paraneoplastic cerebellar degeneration (PCD) associated with lung adenocarcinoma. Abs were characterized using immunohistochemistry, Western blotting, cultures of murine cortical, and hippocampal neurons, immunoprecipitation, mass spectrometry, knockout mice for Trim9 and 67, and cell-based assay. Control samples included sera from 63 patients with small cell lung cancer without any paraneoplastic neurological syndrome, 36 patients with lung adenocarcinoma and PNS, CSF from 100 patients with autoimmune encephalitis, and CSF from 165 patients with neurodegenerative diseases. We found Abs targeting TRIM9 and TRIM67 at high concentration in the serum and the cerebrospinal fluid (CSF) of a 78-year-old woman and a 65-year-old man. Both developed subacute severe cerebellar ataxia. Brain magnetic resonance imaging found no abnormality and no cerebellar atrophy. Both had CSF inflammation with mild pleiocytosis and a few oligoclonal bands. We identified a pulmonary adenocarcinoma, confirming the paraneoplastic neurological syndrome in both patients. They received immunomodulatory and cancer treatments without improvement of cerebellar ataxia, even though both were in remission of their cancer (for more than 10 years in one patient). Anti-TRIM9 and anti-TRIM67 Abs were specific to these two patients. All control serum and CSF samples tested were negative for anti-TRIM9 and 67. Anti-TRIM9 and anti-TRIM67 Abs appeared to be specific biomarkers of PCD and should be added to the panel of antigens tested when this is suspected.

[A Case of Rectal Colon Cancer with Paraneoplastic Cerebellar Degeneration].

A case complicated with colorectal and prostate cancers in paraneoplastic(subacute)cerebellar degeneration(PCD)is extremely rare. We report a retrospective case of rectal carcinoma with paraneoplastic cerebellar degeneration. A 79-year-old man with Parkinson's disease was unable to walk because of paralysis. Brain MRI showed cerebellar atrophy. He was admitted to our hospital for anal bleeding and was diagnosed with colon cancer. An associated diagnosis of PCD was made. After resection, his paralysis and dysarthria were resolved to the extent of beingable to walk and speak fluently. Brain MP-RAGE showed no findings suggestive of metastasis or atrophy. He was treated surgically, which resulted in a transient improvement in PCD symptoms. Per blood testing, cytokines IL-6 and IL-10 were lower postoperatively. Immunosuppressive levels of myeloid- derived suppressor cells(MDSCs)were lower compared with the preoperative values. Thus, innate immunocompetence and resolution of paralysis followed the surgical intervention.

Paraneoplastic cerebellar syndromes associated with antibodies against Purkinje cells.

The paraneoplastic cerebellar syndrome presents as severe neuroimmunological disease associated with malignancies. Antibodies against antigens expressed by tumor cells cross-react with proteins of cerebellar Purkinje cells leading to neuroinflammation and neuronal loss. These antineuronal antibodies are preferentially investigated by serological analyses while examination of the cerebrospinal fluid is only performed infrequently. We retrospectively investigated 12 patients with antineuronal antibodies against Purkinje cells with a special focus on cerebrospinal fluid. Our results confirm a subacute disease with a severe cerebellar syndrome in 10 female patients due to anti-Yo antibodies associated mostly with gynecological malignancies. While standard cerebrospinal fluid parameters infrequently revealed pathological results, all patients presented oligoclonal bands indicating intrathecal IgG synthesis. Analyses of anti-Yo antibodies in cerebrospinal fluid by calculating the antibody specific index revealed intrathecal synthesis of anti-Yo antibodies in these patients. In analogy to anti-Yo syndrome, an intrathecal production of anti-Tr antibodies in one patient who presented with a paraneoplastic cerebellar syndrome was detected. In an additional patient, anti-Purkinje cell antibodies of unknown origin in the cerebrospinal fluid but not in serum were determined suggesting an isolated immune reaction within the central nervous system (CNS) and underlining the importance of investigating the cerebrospinal fluid. In conclusion, patients with a cerebellar syndrome display a distinct immune reaction within the cerebrospinal fluid including intrathecal synthesis of disease-specific antibodies. We emphasize the importance of a thorough immunological work up including investigations of both serum and cerebrospinal fluid.

Paraneoplastic Cerebellar Degeneration Associated with Pelvic Liposarcoma: A Rare Case Report.

Paraneoplastic cerebellar degeneration (PCD) is one of the most common paraneoplastic neurological syndromes characterized by the rapid development of severe cerebellar ataxia. In this report, a 23-year-old female with noticeable dizziness and gait instability was described. The enhanced CT scanning suggested the presence of a pelvic tumor. Then, PCD was established. Postoperative pathological result defined it as a liposarcoma (LS) with dedifferentiation. Interestingly, clinical symptoms disappeared after the surgical removal of the pelvic tumor. To our knowledge, this was the first case report with PCD due to LS.