Table 1.

Representative intrathecal steroid trials 1953–1992 [21, 22].

	Design	Patients included, MS type	Dosage and duration	Primary outcome	Results	Evidence
Kamen and Erdman, 1953 [23]	Case report	1; RR	Intrathecal HC and intramuscular ACTH; no specific data available	Recovery	Patient recovered	IV
Boines, 1961 and 1963 [24, 25]	Open-label, uncontrolled, retrospective, unblinded follow up of 12–52 weeks	42; no specific data available	40–100 mg intrathecal MPA every 2-3 weeks for a total of 6 injections, then “follow-up booster injections”	“recovery, particular of spasticity”; no specific outcome data available	“80% of patients improved/showed excellent or good results”	IV
Van Buskirk et al., 1964 [26]	Open-label, uncontrolled, prospective, unblinded	20; no specific data available	Weekly increasing doses intrathecal MPA (20–80 mg), then booster injection monthly (80–100 mg MPA); follow up 1 week-16–months	“clinical improvement”	“no effect on frequency of exacerbations, but improvement in spasticity in 14 patients”	IV
Goldstein et al., 1970 [27]	Open-label, uncontrolled, retrospective, unblinded	38; no specific data available	40–80 mg intrathecal MPA/4–8 times within 1-2 weeks; follow up 2–8 years	“improvement”	“79% improvement”	IV
Nelson et al., 1973 [28]	Open-label, uncontrolled, prospective, unblinded	23; RR, SP	40–120 mg intrathecal MPA/1–23 times within 2 months; follow up 1–84 months	EDSS CSF changes	EDSS: 4 patients (17%) improved; significant increase of CSF protein	IV
Rohrbach et al., 1988 [29]	double-blind, randomized, prospective	42, “mainly chronic progressive”	Intrathecal TCA: 80 mg/3-4 times within 14 days Oral TCA: 48 mg/d, tapering off	“spinal score”	Intrathecal TCA: “better improvement in the spinal score”	II
Heun et al., 1992 [18]	open-label, prospective, randomized, unblinded, follow up of 21 days	Intrathecal TCA: 25 Systemic MPA: 25	TCA: 40 mg on days 1, 8, and 15 MPA: 100 mg for 5 days, tapering off	EDSS AI SSEP	EDSS improved in both groups (P < .01); EDSS changes between both groups n.s.; AI n.s.	III

TCA: triamcinolone-acetonide acid; HC: hydrocortisone; ACTH: adrenocorticotropic hormone; MPA: methylprednisolone acetate; RR: relapsing-remitting MS; PP: primary chronic progressive MS; SP: secondary chronic progressive MS; MIX: mitoxantrone, EDSS: expanded disability status scale; WD: maximum walking distance; WT: maximum walking time; SSEP: somatosensory evoked potentials; AI: ambulation index; CSF: cerebrospinal fluid; n.s: non significant.