Irra Tariq

Background Pseudobulbar affect (PBA) is a disabling neuropsychiatric condition characterized by sudden, involuntary episodes of crying or laughing incongruent with mood. It occurs in several neurological disorders, including amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, and traumatic brain injury (TBI). Dextromethorphan/quinidine (DM/Q) is the only Food and Drug Administration (FDA)-approved therapy for PBA, but optimal dosing and safety profiles remain uncertain. Objective To evaluate the efficacy and safety of different DM/Q dosing regimens for treating PBA through a systematic review and network meta-analysis. Methods A comprehensive search of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov was conducted through March 2025. Randomized controlled trials reporting outcomes on the Center for Neurologic Study–Lability Scale (CNS-LS), Visual Analog Scale–Quality of Life (VAS-QOL), Visual Analog Scale–Quality of Recovery (VAS-QOR), and adverse events were included. Analyses were performed using R (netmeta package), and bias was assessed with the Cochrane RoB 2.0 tool. Results Five randomized controlled trials comprising 605 participants were analyzed. DM/Q 20/10 mg and 30/10 mg significantly improved CNS-LS scores (mean difference [MD] − 2.52 and − 2.45, respectively), while DM/Q 30/30 mg produced greater gains in VAS-QOL (MD 17.20) and VAS-QOR (MD 14.90). Dizziness was the only statistically significant, dose-related adverse event. Conclusion DM/Q combination therapy provides effective symptom control for PBA, with favorable tolerability. Both 20/10 mg and 30/10 mg doses improve emotional lability, while 30/30 mg yields additional quality-of-life benefits. Further studies should assess long-term safety and disorder-specific dosing optimization.

In recent decades, deep brain stimulation (DBS) has been extensively studied due to its reversibility and significantly fewer side effects. DBS is mainly a symptomatic therapy, but the stimulation of subcortical areas by DBS is believed to affect the cytoarchitecture of the brain, leading to adaptability and neurogenesis. The neurological disorders most commonly studied with DBS were Parkinson’s disease, essential tremor, obsessive-compulsive disorder, and major depressive disorder. The most precise approach to evaluating the location of the leads still relies on the stimulus-induced side effects reported by the patients. Moreover, the adequate voltage and DBS current field could correlate with the patient’s symptoms. Implantable pulse generators are the main parts of the DBS, and their main characteristics, such as rechargeable capability, magnetic resonance imaging (MRI) safety, and device size, should always be discussed with patients. The safety of MRI will depend on several parameters: the part of the body where the device is implanted, the part of the body scanned, and the MRI-tesla magnetic field. It is worth mentioning that drug-resistant individuals may have different pathophysiological explanations for their resistance to medications, which could affect the efficacy of DBS therapy. Therefore, this could explain the significant difference in the outcomes of studies with DBS in individuals with drug-resistant neurological conditions.