Table 1.

Recommended evaluation of suspected LM to establish the level of evidence for the diagnosis

	Recommended protocols of evaluation	Results
Clinical evaluation	Thorough neurological examination focused on abnormalities typically seen in patients with LM	Presence of typical clinical signs of LMa Any other neurological abnormalityb Normal neurological evaluation
Neuroimaging	Field strength of 1.5 or preferably 3 T Gadolinium should be injected 10 min before data acquisition at a dose of 0.1 mmol/kg. The slice thickness should be ≤1 mm at the brain level and ≤3 mm at the spinal level Brain: 3D pre-contrast T1-weighted, 2D or 3D FLAIR, 2D diffusion-weighted imaging, 2D pre-contrast T2-weighted, post-gadolinium 3D T1-weighted. Post-gadolinium 3D FLAIR sequences should be considered Spinal axis: sagittal fat-suppression T2-weighted sequences, sagittal pre-contrast T1-weighted sequences, T1-weighted post-gadolinium sagittal fat-suppressed sequence	Typical MRI findings of linear LM (type A)c Typical MRI findings of nodular LMD (type B) Both (type C) Hydrocephalus only (type D–hydrocephalus) Equivocal leptomeningeal findings or absence of leptomeningeal MRI findings (type D–normal)
CSF cytology	Fresh CSF samples should ideally be processed within 30 min after sampling CSF volume is ideally >10 ml but at least 5 ml After centrifugation, cytospins can be air-dried and subsequently May-Grünwald-Giemsa (MGG = Pappenheim) stained Alternatively, fresh CSF samples can be fixed with Ethanol-Carbowax (CSF–fixative ratio 1:1) to reduce time pressure, followed by Papanicolaou staining of the cytospins Upon indication and availability of material, additional immunocytochemical stainings for epithelial and melanocytic markers should be considered A second CSF sample should be analysed if the initial CSF sample is negative	Positive: presence of tumour cells Equivocal: suspicious or atypical cells Negative: absence of tumour cells

Adapted from Le Rhun et al.¹

2D, two-dimensional; 3D, three-dimensional; CSF, cerebrospinal fluid; CNS, central nervous system; FLAIR, fluid-attenuated inversion recovery; LM, leptomeningeal metastasis; LMD, leptomeningeal disease; MRI, magnetic resonance imaging.

^aTypical clinical signs of LM include headache, nausea and vomiting, mental changes, gait difficulties, cranial nerve palsies with diplopia, visual disturbances, hearing loss, radicular signs including weakness, voiding and cauda equina problems and focal or radiating (radicular) neck and back pain.

^bNeurological sequelae from previous brain metastases or extra-CNS metastases, treatment, comorbidities or any other medical event, but also comedication should be considered during the clinical assessment.

^cSee Table 2 and text.