To the Editors
Paraneoplastic neurological syndromes are caused by hormones and cytokines synthesised by tumours, and occur in 1–3% of all cancer patients. They can have impacts on both the central and peripheral nervous systems [1].
We present a case report of a 68-year-old postmenopausal woman who was admitted to our hospital’s Accident & Emergency with a 7-day history of unsteadiness of gait, ataxia and speech disorder. Similar, transient symptoms were observed in 2022 when the patient was discharged from hospital with a TIA diagnosis.
In neurological examination, lower limbs ataxia, slurred speech, and bilateral positive Babinski sign were observed. Brain CT and MRI scan were normal. Basic laboratory tests revealed slightly elevated TSH levels. Tumour biomarkers were negative in serum. A general cerebrospinal fluid (CSF) examination showed normal results. However, a paraneoplastic antibody screening detected anti-Yo antibodies in both CSF and blood serum.
To identify an underlying neoplasm, we conducted a whole-body CT scan and PET-CT scan (Fig. 1). The whole-body CT revealed a tumour in the right ovary. In the PET-CT, an increased metabolism of fludeoxyglucose (FDG) in the right ovary was observed and the patient was qualified to laparoscopy followed by laparotomy. A histopathological evaluation showed G3 adenocarcinoma of the right fallopian tube. IVIG treatment was implemented, with no improvement of neurological symptoms. Due to her poor neurological and general condition, chemotherapy was not implemented and palliative care was recommended. Six months later, she has stable neurological symptoms with limbs ataxia and slurred speech.
Paraneoplastic cerebellar degeneration (PCD) is a very rare condition occurring in less than 1% of cancer cases. It is usually associated with breast and gynaecological malignancies, but can also occur in small-cell carcinoma and Hodgkin’s lymphoma. The neurological symptoms include subacute cerebellar ataxia, dysarthria, kinetic tremor, diplopia and/or oscillopsia. Specific antibodies are reported in both serum and CSF (Tab. 1).
|
Antibody (alternative name) |
Frequency of cancer [%] |
Usual tumours |
|
Yo (PCA-1) |
> 90 |
Ovarian cancer, breast cancer |
|
Anti CRMP5(CV2) |
> 80 |
SCLC, thymoma |
|
Anti-mGLuR1 |
30 |
Mostly haematological |
|
Anti Ri (ANNA2) |
> 70 |
Breast > lung (SCLC and NSCLC) |
|
PCA-2 |
80 |
SCLC, NCLC, breast cancer |
|
P/Q VGCC |
50 (LEMS, nearly 90 for rapidly progressive cerebellar syndrome) |
SCLC |
|
SOX1 |
> 90 |
SCLC |
|
Tr (DNER) |
90 |
Hodgkin’s lymphoma |
The Anti-Yo antineuronal antibody against Purkinje cells is the most commonly detected antibody in connection with PCD [2, 3]. They affect the vermis and midline cerebellum. Anti-Hu, anti-Tr, anti-Ri and anti-mGluR1 have also been identified in PCD patients [2]. The antibodies could be specific for different kind of tumours. Therefore, it helps in directing cancer diagnosis, even several months to years before local mass effect [4, 5].
Outcomes of PCD are typically poor, and treatment is limited, including tumour resection, chemotherapy, and immunosuppressive treatment [5]. Early treatment initiation provides better prognosis.
PCD poses a significant challenge both in diagnosis and treatment. Due to its unspecific nature, it is under-recognised. Moreover, because of its rarity, no randomised controlled trials have been conducted to establish the optimal treatment approach.
This letter highlights the critical need to address the under-recognition of PCD by neurologists and oncologists. An early diagnosis significantly improves patient outcomes and reduces the risk of severe, irreversible complications. By incorporating targeted PCD-associated antibody screening into routine workups, we can ensure timely diagnosis and improve patient outcomes.
Article information
Conflicts of interest: None.
Funding: None.
