Development and Optimization of A High-Throughput 3D Rat Purkinje Neuron Culture to Study Paraneoplastic Cerebellar Degeneration

Improved understanding of the mechanisms involved in neurodegenerative disease has been hampered by the lack of robust cellular models that faithfully replicate in vivo features. Here, we present a refined protocol for generating age-dependent, well-developed and synaptically active rat Purkinje neurons in a 3D cell network culture which are responsive to a disease inducer. Using our model, we found that the application of autoantibody Yo, a paraneoplastic cerebellar degeneration (PCD) inducer, alters the structure of the dendritic arbour of cultured Purkinje neurons. The numbers of dendrites per branch-order, the branch-order in itself and the dendritic length were reduced by anti-Yo, proving a functional role for anti-Yo in the pathogenesis of PCD. Our new ex-vivo model is flexible and can be used to investigate disease mechanisms that disturb Purkinje neuron function and communication in 3D. Since it is possible to use the approach in a multi-well format, this method also has high-throughput screening potential.

Anti-Tr/DNER antibody paraneoplastic cerebellar degeneration preceding a very late relapse of Hodgkin Lymphoma after 12 years

Background Paraneoplastic cerebellar degeneration (PCD) is a classic neurological syndrome where the presence of Anti-Tr/DNER antibodies is strongly associated with Hodgkin Lymphoma (HL). Awareness of the syndrome is important because with prompt treatment the prognosis of HL is good. The diagnosis can be a challenge in some patients. The importance of PCD in the detection of a cancer relapse is not clarified. We report the case of a 76-year-old man where a PCD, initially misdiagnosed as a stroke led to a diagnosis of a very late relapse of HL after 12 years. Case presentation A 76-year-old male with a 3-week history of unstable walking, slow speech and dizziness was admitted to our stroke unit apparently because the symptoms started acutely. With a diagnostic delay of 3–4 weeks a correct diagnosis of relapse HL was made based on cerebrospinal fluid changes with a strong positive reaction to anti-Tr/DNER antibodies, FDG-PET/CT scan, and biopsy findings. The medical history revealed that the patient had been diagnosed with HL previously, but has been in complete remission for 12 years. The patient was treated with intravenous immunoglobulin, chemo- and radiation therapy. Over the following 6–8 weeks he improved. Conclusions Late relapse in HL is very rare. If it occurs it presents as a symptomatic lymphadenopathy. Our case shows, that PCD can be the only presenting symptom of a very late relapse of HL. Paraneoplastic neurological syndromes (PNS) should be considered even in patients with very long cancer remission. PCD can in rare cases mimic a stroke within the posterior circulation. If MR imaging in severe acute/subacute cerebellar syndrome is normal further investigation is mandatory to rule out a PNS, particular in patients with a previous cancer.