Intrathecal medications
Nusinersen (Spinraza) was approved by US FDA for the treatment of SMA in December 2016, and The European Medicines Agency in June 2017, that is administered intrathecally. In 26 patients of SMA, Mousa et al. were able to successfully perform a total of 104 intrathecal nusinersen injections, even in patients with sophisticated spinal instrumentation (44 of 104). There were no immediate or long-term complications.46 In SMA type 2 and 3 patients, who constitute the adolescent and adult group and more likely to be having complex spinal anatomy and surgery and respiratory insufficiency, Wurster et al. evaluated practicability and safety of intrathecal nusinersen injection in these patients. They analyzed 93 lumbar punctures in 20 patients, surveyed the duration of the procedure, site of LP, oxygen saturation, number of attempts, need for sedation and analgesia.47 Intrathecal nusinersen was found to be safe, feasible and well tolerated(complication rate was 5% and consisted of mild PLPH) , even in adult onset SMA patients, both with standard and image guided LPs.47 Shortly, nusinersen use will be widespread and physicians will need to well be conversed with these procedures.
Many intracranial infections are smoldering infections which carry high mortality if not promptly and aggressively treated. Unfortunately, very few antibiotics cross the blood-brain barrier to reach concentrations enough to be effective. Intrathecal (ITH) and intraventricular (IVT) administration of antibiotics can be lifesaving in such situations.
Bargiacchi et al. did a systematic review of 51 case studies of Gram-negative CNS infections in adults treated with intrathecal or intraventricular colistin.12 They found that Intrathecal or intraventricular Colistin at a dose of 125,000 IU, suggested by IDSA Guidelines administered once daily for at least 14 days is safe and effective. No nephrotoxicity was reported with ITH/IVT colistin.12
However, there is no standard criterion for dosing for IVT/ITH vancomycin. Wombell et al. did the systemic review of cases reported on IVT/ITH vancomycin, and recommended that a daily dose of 10-mg, aiming for a trough level of 15 to 20 mg/L48 is safe and effective.
Various other combinations of antibiotics have been used. Zhang et al. reported 86 patients with intracranial infections with severe traumatic brain injury (STBI).49The group treated with ITH meropenem and vancomycin had better cure time compared to patients treated with intravenous meropenem and vancomycin (p- 0.004), lesser adverse reactions (p-0.035) and less severe sequelae (p-0.007).49
Intrathecal Interferon has been used since ages to treat SSPE,50 but there are still no clear-cut guidelines regarding the dosing schedule. The various reported studies with their dosing schedule are detailed in Table 151,52,53,54,55,56,13. Based on studied by Kurta et al., Steiner et al. and Thurner et al., we recommend continuous intrathecal infusion of interferon at a rate of 3 million U/week as more effective than intermittent bolus infusion.55,54,57