Diagnostic accuracy of imaging brain vesicular monoamine transporter type 2 (VMAT2) in clinically uncertain parkinsonian syndrome (CUPS): a 3-year follow-up study in community patients

ObjectivesTo further validate the diagnostic utility of 18F-AV-133 vesicular monoamine transporter type 2 (VMAT2) positron emission tomography (PET) in patients with clinically uncertain parkinsonian syndromes (CUPS) by comparison to clinical diagnosis at 3 years follow-up.Design, setting and participantsIn a previous study, we reported that 18F-AV-133 PET in community patients with CUPS changed diagnosis and management and increased diagnostic confidence. The current diagnosis of this cohort was obtained from the patient and treating specialist and compared with the diagnosis suggested 3 years earlier by the 18F-AV-133 PET. A second 18F-AV-133 PET was available in those with a discordant or inconclusive final diagnosis.Study outcome measuresThe primary end point was the proportion of patients who had a follow-up clinical diagnosis, which was concordant with their initial 18F-AV-133 PET scan. Secondary end points were the proportion of patients who had the same diagnosis at follow-up as that reached after the initial scan and the stability of diagnostic changes made after the first scan.Results81 of the 85 patients previously recruited to the CUPS study had follow-up of which 79 had a clinical diagnosis and 2 remained CUPS. The diagnosis was in agreement with the initial 18F-AV-133 PET scan result in 74 cases. Five patients had a discordant diagnosis; one patient with rubral tremor had a severely abnormal scan that had worsened when rescanned; four cases with normal initial and repeat scans had a clinical diagnosis of Parkinson’s disease. Two patients with suspected genetic disorders remained classified as CUPS and both had normal scans. In the 24 CUPS cohort patients where 18F-AV-133 PET initially changed diagnosis, this change was supported by follow-up diagnosis in all but the one rubral tremor case.Conclusion18F-AV-133 PET is a useful tool in improving diagnostic accuracy in CUPS providing results and diagnostic changes that remain robust after 3 years follow-up.

Vim stimulation as a predictor of response to deep brain stimulation in patients of severe tremor undergoing dual stimulation

Deep brain stimulation, targeting the ventral intermediate nucleus of the thalamus (Vim), has been shown to be an effective management tool for tremors refractory to other therapies. There is some variance in response to Vim stimulation for severe essential and rubral tremors. This study looked at dual stimulations (addition, in which the Vim is stimulated along with an additional nucleus or augmentation, in which a second lead is placed within the Vim itself) for these types of tremors. A total of eight patients, four with rubral and four with severe essential tremors, were treated with deep brain stimulation. The responses of the patients were characterized on a scale from excellent improvement to worsening of condition. Two of the four patients with rubral tremor had an excellent response to Vim stimulation. These patients showed additional benefits when the prelemniscal radiation (Raprl) was stimulated, in addition to the Vim. Three of the four patients with severe essential tremor reported either a good or excellent response to Vim stimulation. One of these patients had the Raprl stimulated in addition to the Vim while another had an augmentation of the Vim, with ventralis oralis posterior (Vop) stimulation. Both showed additional benefits with the addition or augmentation performed. We conclude that if a patient with severe medically refractory tremor (essential or rubral tremor) responds to Vim stimulation but is still disabled he will likely also have a response to dual stimulation with an additional lead in the Raprl or an augmentation with an additional lead in the Vop. Patients who did not initially respond to Vim stimulation did not respond to the placement of a second lead. We also conclude that for severe essential tremor, Raprl stimulation showed a better response than Vim stimulation.

Functional lesional neurosurgery for tremor: a systematic review and meta-analysis

BackgroundThis work evaluates the consistency, effect size and incidence of persistent side effects of lesional neurosurgical interventions in the treatment of tremor due to Parkinson’s disease (PD), essential tremor (ET), multiple sclerosis (MS) and midbrain lesions.MethodsSystematic review and meta-analysis according to PRISMA-P guidelines. Random effects meta-analysis of standardised mean difference based on a peer-reviewed protocol (PROSPERO no. CRD42016048049).ResultsFrom 1249 abstracts screened, 86 peer-reviewed studies reporting 102 cohorts homogeneous for tremor aetiology, surgical target and technique were included.Effect on PD tremor was better when targeted at the ventral intermediate nucleus (V.im.) by radiofrequency ablation (RF) (Hedge’s g: −4.15;) over V.im. by Gamma Knife (GK) (−2.2), subthalamic nucleus (STN) by RF (−1.12) and globus pallidus internus (GPi) by RF (−0.89). For ET MRI-guided focused ultrasound (MRIgFUS) ablation of the cerebellothalamic tract (CTT) (−2.35) and V.im. (−2.08) showed similar mean tremor reductions to V.im. ablation by RF (−2.42) or GK (−2.13). In MS V.im. ablation by GK (−1.96) and RF (−1.63) were similarly effective.Mean rates of persistent side effects after unilateral lesions in PD were 12.8% (RF V.im.), 13.6% (RF STN), 9.2% (RF GPi), 0.7% (GK V.im.) and 7.0% (MRIgFUS V.im.). For ET, rates were 9.3% (RF V.im.), 1.8% (GK V.im.), 18.7% (MRIgFUS V.im.) and 0.0% (MRIgFUS CTT), for MS 37.7% (RF V.im.) and for rubral tremor 30.3% (RF V.im.).ConclusionThis meta-analysis quantifies safety, consistency and efficacy of lesional neurosurgical interventions for tremor by target, technique and aetiology.

Mesencephalotomy, How I Do It: Analysis of 34 Cases

The present paper aims to demystify the use of rostral mesencephalic reticulotomy (mesencephalotomy) in the treatment of chronic pain in cancer patients. A retrospective review of the medical records from the Central Pain and Stereotaxy Department of the A. C. Camargo Cancer Center, São Paulo, state of São Paulo, Brazil, between 2005 and 2012, was performed. Surgical indication was restricted to patients with cancer pain refractory to etiological and symptomatic treatments, > 2 months of expected survival, preserved cognition, and absence of coagulation disorders, of systemic infection, and of intracranial hypertension. We have selected 34 patients, with an average follow-up of 9.4 months, an average age of 54.3 years-old, and an average follow-up time until death of 6.4 months. Lung cancer was the most frequent diagnosis. Satisfactory and immediate pain relief was achieved in 91% of the cases, and 83% of these patients had no relapses. Among the complications, ocular movement disorder was the most frequent, but often transient. Permanent disturbances occurred in 8.8% of the cases (diplopia, rubral tremor, and paresthesia). Compared to the pharmacological treatment, mesencephalotomy was economically feasible, more effective, and improved quality of life. According to the data presented, it can be concluded that mesencephalotomy is a viable procedure for cancer pain control in selected cases.