The levels of evidence (class I-IV) supporting the recommendations and ratings of recommendations (A-C, Good Practice Points) are defined at the end of the "Major Recommendations" field.
Good Practice Points
- Patients with paraneoplastic neurological syndrome (PNS) most often present with neurological symptoms before an underlying tumour is detected. Onconeural antibodies should be sought in sera from patients with suspected PNS. The antibodies are important for diagnosis and tumour search.
- Radiological investigations for tumours, such as high resolution CT for the detection of small cell lung cancer (SCLC), are important, but should be followed by fluorodeoxyglucose positron-emission tomography (FDG PET) if no tumour is found.
- Patients should also be followed at regular intervals, for example every 6 months for up to 4 years, to search for tumour in cases where the initial tumour screen was negative.
- Early detection and treatment of the tumour is the approach that seems to offer the greatest chance for PNS stabilization. This is carried out in cooperation with the oncologist, pulmonologist, gynaecologist or paediatrician depending on the associated tumour.
- Immune therapy (steroids, plasma exchange or intravenous immunoglobulin) usually has no or modest effect on paraneoplastic limbic encephalitis (PLE), subacute sensory neuropathy (SSN) or paraneoplastic cerebellar degeneration (PCD).
- Children with paraneoplastic opsoclonus-myoclonus (POM) may respond to immune therapy, whereas no clear evidence of such therapy has been shown in adults with POM.
- Patients with Lambert-Eaton myasthenic syndrome (LEMS) or paraneoplastic peripheral nerve hyperexcitability (PPNH) usually improve with immune therapy.
- Symptomatic therapy should be offered to all patients with PNS.
Definitions:
Evidence Classification Scheme for a Diagnostic Measure
Class I: A prospective study in a broad spectrum of persons with the suspected condition, using a "gold standard" for case definition, where the test is applied in a blinded evaluation, and enabling the assessment of appropriate tests of diagnostic accuracy
Class II: A prospective study of a narrow spectrum of persons with the suspected condition, or a well-designed retrospective study of a broad spectrum of persons with an established condition (by "gold standard") compared to a broad spectrum of controls, where test is applied in a blinded evaluation, and enabling the assessment of appropriate tests of diagnostic accuracy
Class III: Evidence provided by a retrospective study where either persons with the established condition or controls are of a narrow spectrum, and where test is applied in a blinded evaluation
Class IV: Any design where test is not applied in blinded evaluation OR evidence provided by expert opinion alone or in descriptive case series (without controls)
Evidence Classification Scheme for a Therapeutic Intervention
Class I: An adequately powered prospective, randomized, controlled clinical trial with masked outcome assessment in a representative population or an adequately powered systematic review of prospective randomized controlled clinical trials with masked outcome assessment in representative populations. The following are required:
- Randomization concealment
- Primary outcome(s) is/are clearly defined
- Exclusion/inclusion criteria are clearly defined
- Adequate accounting for dropouts and crossovers with numbers sufficiently low to have minimal potential for bias
- Relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences
Class II: Prospective matched-group cohort study in a representative population with masked outcome assessment that meets a–e above or a randomized, controlled trial in a representative population that lacks one criteria a–e
Class III: All other controlled trials (including well-defined natural history controls or patients serving as own controls) in a representative population, where outcome assessment is independent of patient treatment
Class IV: Evidence from uncontrolled studies, case series, case reports, or expert opinion
Rating of Recommendations for a Diagnostic Measure
Level A rating (established as useful/predictive or not useful/predictive) requires at least one convincing class I study or at least two consistent, convincing class II studies.
Level B rating (established as probably useful/predictive or not useful/predictive) requires at least one convincing class II study or overwhelming class III evidence.
Level C rating (established as possibly useful/predictive or not useful/predictive) requires at least two convincing class III studies.
Rating of Recommendations for a Therapeutic Intervention
Level A rating (established as effective, ineffective, or harmful) requires at least one convincing class I study or at least two consistent, convincing class II studies.
Level B rating (probably effective, ineffective, or harmful) requires at least one convincing class II study or overwhelming class III evidence.
Level C rating (possibly effective, ineffective, or harmful) requires at least two convincing class III studies.
Good Practice Points Where there was lack of evidence but consensus was clear the Task Force members have stated their opinion as good practice points.
