Yavuz S. Silay

Emerging drugs in Tourette syndrome.

Proper education of the patient is the first step in the treatment of Tourette syndrome (TS). Before deciding how to treat the patient, it is important to decide whether to treat the TS-related symptoms. Counselling and behavioural modification may be sufficient for those with mild symptoms. Medications, however, may be considered when symptoms begin to interfere with peer relationships, social interactions, academic or job performance, or with activities of daily living. Therapy must be individualised and the most troublesome symptoms should be targeted first. Antidopaminergic agents are clearly the most effective drugs in the treatment of tics. Although haloperidol and pimozide are the only drugs currently approved by the FDA for the treatment of TS, other dopamine receptor-blocking drugs and tetrabenazine, a dopamine depleting drug, as well as botulinum toxin injections, have been used to treat tics associated with TS. Carefully designed, comparative, longitudinal trials assessing the efficacy and adverse-effect profiles of these drugs, including tardive dyskinesia, are lacking. Selective serotonin reuptake inhibitors are recommended for the treatment of obsessive-compulsive behaviour: a common comorbidity. Psychostimulants, such as methylphenidate, are the treatment of choice for attention deficit hyperactivity disorder. Even though these drugs may transiently increase tics, this does not necessarily constitute a definite contraindication to the use of these drugs in patients with TS. Here, existing and emerging medical treatments in patients with tics and comorbid behavioural disorders associated with TS are reviewed.

Subthalamic deep brain stimulation in patients with a previous pallidotomy

The safety and efficacy of subthalamic nucleus (STN) deep brain stimulation (DBS) in patients who have had a previous unilateral pallidotomy is not clear. We identified 10 patients (9 male) at the Baylor College of Medicine Parkinsons Disease Center who underwent STN DBS after prior unilateral pallidotomy. Demographics, efficacy as determined by off Unified Parkinsons Disease Rating Scale (UPDRS) part III scores, and levodopa equivalent dosing were analyzed. We then compared these to an age‐ and sex‐matched group of 25 DBS patients who had no prior pallidotomy. After their initial pallidotomy (mean age, 51.8 ± 10.8 years), the mean UPDRS motor off medicine scores improved from 51.3 ± 14.3 to 34.9 ± 12.8, and the UPDRS dyskinesia score improved from 1.8 ± 1.0 to 0.8 ± 0.7. Their STN DBS off UPDRS motor scores (mean age, 56.0 ± 10.2 years) improved by 16.0% from 53.1 ± 9.7 (range, 42–68) to 44.6 ± 11.1 (range, 25–67). In contrast, the UPDRS off motor scores in a control group of 25 DBS patients improved by 49.9%, from 49.7 ± 11.1 to 25.7 ± 18.9, (16.0% vs. 49.9%; P < 0.001). Changes in UPDRS dyskinesia scores were similar in both groups. AE thought to be related to the STN DBS following pallidotomy included worse dysarthria (three) and worse balance (two). STN DBS patients with prior pallidotomy had less improvement in UPDRS off motor score compared to other STN DBS patients, despite relatively good outcomes immediately after their pallidotomy. This may be partially due to a selection bias, but it may also indicate that prior pallidotomy is a negative predictor of outcome of STN DBS and should be considered in patient selection.

Intravenous flumazenil for Parkinson's disease: A single dose, double blind, placebo controlled, cross-over trial

Flumazenil is a short‐acting intravenously administered γ‐aminobutyric acid (GABA) antagonist used to reverse the effects of benzodiazepines. Based upon current basal ganglion models in Parkinsons disease (PD), flumazenil could normalize neuronal signaling at several different locations. We conducted a double‐blind, placebo controlled, single dose, cross‐over trial of flumazenil and placebo in 16 subjects with PD. Subjects were primarily assessed with serial tapping tests (1 minute for each hand) at 15‐minute intervals for 90 minutes after infusion. Secondary assessments included the Unified Parkinsons Disease Rating Scale (UPDRS) Motor part at baseline and 45 minutes after infusion, and global impressions. Subjects then underwent a 90‐minute washout and entered the opposite arm of the cross‐over. Change in tapping speed compared to baseline improved throughout the 90‐minute period (P < 0.0001) and at each individual time (P < 0.01), except for 15 minutes status after infusion, with flumazenil compared to placebo. UPDRS scores tended to improve more on drug, but this finding was not significant. The medication was well tolerated. The most common adverse event on drug was a sense of “light‐headedness” or “dizziness.” GABA antagonists represent a novel potential treatment class for PD.

Emerging drugs in lung transplantation.

The balance between immunosuppression to ensure graft tolerance while preventing emergence of infectious complications is key in lung transplantation. Although opportunistic infection may appear to be the most important of these complications, malignancies and severe drug toxicities significantly affect the short- and long-term outcomes of the patients. The present practice is combination therapy using drugs with complementary immunosuppressive action, to achieve synergistic immunosuppression with the lowest possible toxicity. Components of immunosuppression include induction and maintenance regimens. Primary graft failure remains an important cause of mortality and morbidity in the immediate post-transplant period. Acute rejection is a common complication after lung transplant, but responds well to augmented immunosuppression and immunomodulation. Chronic rejection still is the major cause of mortality in patients who survive the initial year post-transplantation. Several new drugs have shown promise in decreasing the rate of loss of graft function. This review discusses the current and emerging therapeutic regimens.