Efficacy and Safety of Thalidomide in Patients with Complicated Central Nervous System Tuberculosis: A Systematic Review and Meta-Analysis.

Thalidomide, an anti-inflammatory and immunomodulatory agent, has a potential role in cases with central nervous system tuberculosis (CNS-TB) with paradoxical reactions. Although several articles have described the use of thalidomide in CNS-TB, no systematic review has been performed in this regard. Different electronic databases were searched for articles describing the use of thalidomide in patients with CNS-TB. For determining pooled estimates in the quantitative review, studies with a minimum sample size of 5 were only considered, whereas for qualitative synthesis even single case reports were included. Fixed or random effect models were used suitably depending on the degree of heterogeneity. Fourteen articles describing a total of 107 patients (98 children and 9 adults) were selected from 156 records. A favorable clinical response was observed in 89% of patients with CNS-TB who had paradoxical reactions refractory to corticosteroids. Majority of the studies used a dose of 2-6 mg/kg/day and around 24% suffered from at least one adverse effect, with a mortality of 5%. Predominant adverse effects were rash (9.5%), neuropathy (6%), and elevated liver transaminases (9.5%). Only one placebo-controlled trial has been performed till now, which showed that high-dose thalidomide has numerous adverse effects, without any clinically significant improvement as compared with placebo. While in HIV-positive patients with TB-immune reconstitution inflammatory syndrome thalidomide was helpful in around 82% of cases. Low-dose thalidomide is helpful in patients with CNS-TB who had a paradoxical reaction and unresponsive to corticosteroids. Large, randomized trials are needed to provide more concrete information regarding the safety and efficacy of thalidomide.

Efficacy and safety of corpus callosotomy and ketogenic diet in children with Lennox Gastaut syndrome: a systematic review and meta-analysis.

BACKGROUND: Both corpus callosotomy (CC) and the ketogenic diet (KD) are commonly used in patients with Lennox Gastaut syndrome (LGS), as a significant proportion of these patients develop pharmacoresistant epilepsy. But no systematic review has yet compared the efficacy and safety of these two measures. METHODS: We conducted a systematic search on various databases to collating all available literature until 30th November 2020 with a primary objective to compare the efficacy of KD and CC in terms of the proportion of patients with complete seizure freedom, at least 75% and 50% reduction in seizure frequency at various time points after the institution of these modalities. We also attempted to compare the proportion and nature of adverse effects, impact on EEG, cognition, and behavior with these modalities. We only included original articles enrolling at least 10 patients with CC or KD for quantitative synthesis to determine a pooled estimate. We used a fixed or random effects model, depending on the degree of heterogeneity. RESULTS: We selected 23 and 7 articles describing the efficacy of CC and KD in 436 and 185 LGS patients out of 217 search items, but none of the studies compared directly these two entities. The indirect comparison between the pooled estimate of all patients with individual modalities revealed more patients with CC had seizure freedom, at least 75% and 50% reduction in seizure frequency (p=0.0001, 0.01, and 0.04 respectively). The proportion of patients with adverse effects was also higher for CC patients (p=0.01), although the proportion with serious adverse effects was not significantly different between the two modalities. Patients selected for CC were older, had higher seizure burden, more lag time after the onset of seizures, and received more number of antiseizure medications previously. Due to the availability of limited data, a firm conclusion could not be determined regarding the effect on EEG, cognition, and behavior with CC and KD. CONCLUSION: CC is more efficacious than KD in reducing seizure frequency in patients with LGS, although it has relatively more adverse effects during the immediate perioperative period.