Titulaer MJ, Soffietti R, Dalmau J, Gilhus NE, Giometto B, Graus F, Grisold W, Honnorat J, Sillevis Smitt PAE, Tanasescu R, Vedeler CA, Voltz R, Verschuuren JJGM
EUROPEAN JOURNAL OF NEUROLOGY Volume: 18 Issue: 1 Pages: 19-e3 Published: January 2011
Background: Paraneoplastic neurological syndromes (PNS) almost invariably predate detection of the malignancy. Screening for tumours is important in PNS as the tumour directly affects prognosis and treatment and should be performed as soon as possible.
Objectives: An overview of the screening of tumours related to classical PNS is given. Small cell lung cancer, thymoma, breast cancer, ovarian carcinoma and teratoma and testicular tumours are described in relation to paraneoplastic limbic encephalitis, subacute sensory neuronopathy, subacute autonomic neuropathy, paraneoplastic cerebellar degeneration, paraneoplastic opsoclonus-myoclonus, Lambert-Eaton myasthenic syndrome (LEMS), myasthenia gravis and paraneoplastic peripheral nerve hyperexcitability.
Methods: Many studies with class IV evidence were available; one study reached level III evidence. No evidence-based recommendations grade A–C were possible, but good practice points were agreed by consensus.
Recommendations: The nature of antibody, and to a lesser extent the clinical syndrome, determines the risk and type of an underlying malignancy. For screening of the thoracic region, a CT-thorax is recommended, which if negative is followed by fluorodeoxyglucose-positron emission tomography (FDG-PET). Breast cancer is screened for by mammography, followed by MRI. For the pelvic region, ultrasound (US) is the investigation of first choice followed by CT. Dermatomyositis patients should have CT-thorax/abdomen, US of the pelvic region and mammography in women, US of testes in men under 50 years and colonoscopy in men and women over 50. If primary screening is negative, repeat screening after 3–6 months and screen every 6 months up till 4 years. In LEMS, screening for 2 years is sufficient. In syndromes where only a subgroup of patients have a malignancy, tumour markers have additional value to predict a probable malignancy.
Comment by Lucia Muntean
In January 2011 the report of the EFNS Task Force regarding the screening for tumours in paraneoplastic neurological syndromes (PNS) was published. This followed the previously published data concerning the diagnosis and management of PNS developed by PNS Euronetwork and by the EFNS Task Force.
PNS represent a remote effect of a tumour, not directly caused by mass lesions, metastases, infections, nutritional factors or anti-tumour treatment.
This paper focuses on screening for tumours in patients with the classical PNS: Lambert-Eaton myasthenic syndrome (LEMS), paraneoplastic limbic encephalitis (PLE), subacute sensory neuronopathy (SSN), subacute autonomic neuropathy (SAN), paraneoplastic cerebellar degeneration (PCD), paraneoplastic opsoclonus-myoclonus (POM), paraneoplastic peripheral nerve hyperexcitability (PPNH), myasthenia gravis (MG) and paraneoplastic retinopathy (CAR). Dermatomyositis is only briefly mentioned.
The nature of the antibodies seems to be the most important factor in determining the type of the underlying tumour. Therefore the authors provide recommendations for two different situations.
First of all PNS with detectable antibodies are taken into consideration. The most frequent cancer types associated with PNS are: small cell lung cancer (SCLC), thymoma, breast cancer, ovarian carcinoma and teratoma and testicular tumours. Screening for tumours requires a multidisciplinary approach, starting with a thorough medical examination and continuing with imaging procedures: computed tomography (CT), ultrasound (US) and sometimes even fluorodeoxyglucose-positron emission tomography (FDG- PET).
The second situation is the case of PNS without detectable antibodies. The data available is less clear in this case, because most studies have only searched for a few antibodies. The authors recommend as good clinical practice point screening for tumours in the most likely site given by the clinical PNS with conventional methods and if necessary with whole-body FDG-PET.
Dermatomyositis was approached separately due to the high rate of malignancy that it associates. It is recommended that all adult patients with dermatomyositis should be tested by CT-thorax/abdomen. Women should be tested by US of the pelvic region and mammography. Males under 50 years old should have US of the testes. Patients over 50 years old should have a colonoscopy.
In many cases the initial screening for tumours in patients with PNS and detectable antibodies can be negative. The current guidelines recommend rescreening after 3–6 months, followed by regular screening every 6 months for 4 years. In patients with LEMS, 2 years is sufficient.
To sum up, these recommendations focusing on the screening methods for tumours in patients with PNS are very concise and thorough up-to-date. Diagnosing and treating the underlying malignancy insures a better outcome of the PNS, as most of them are severe and debilitating conditions.
Lucia Muntean is neurologist and works at the University of Medicine and Pharmacy Cluj-Napoca, Romania and Paracelsus Elena Klinik, Kassel, Germany. She is the EAYNT Representative of the EFNS Scientist Panel on Neuro-oncology.