Juan C. Giugni

Holmes tremor: Clinical description, lesion localization, and treatment in a series of 29 cases.

Objective: To describe the clinical features, etiology, findings from neuroimaging, and treatment results in a series of 29 patients with Holmes tremor (HT). Methods: A retrospective study was performed based on review of medical records and videos of patients with HT diagnosis. Results: A total of 16 women and 13 men were included. The mean age at the moment of CNS insult was 33.9 ± 20.1 years (range 8–76 years). The most common causes were vascular (48.3%), ischemic, or hemorrhagic. Traumatic brain injury only represented 17.24%; other causes represented 34.5%. The median latency from lesion to tremor onset was 2 months (range 7 days–228 months). The most common symptoms/signs associated with HT were hemiparesis (62%), ataxia (51.7%), hypoesthesia (27.58%), dystonia (24.1%), cranial nerve involvement (24.1%), and dysarthria (24.1%). Other symptoms/signs were vertical gaze disorders (6.8%), bradykinesia/rigidity (6.8%), myoclonus (3.4%), and seizures (3.4%). Most of the patients had lesions involving more than one area. MRI showed lesions in thalamus or midbrain or cerebellum in 82.7% of the patients. Levodopa treatment was effective in 13 out of 24 treated patients (54.16%) and in 3 patients unilateral thalamotomy provided excellent results. Conclusions: The most common causes of HT in our series were vascular lesions. The most common lesion topography was mesencephalic, thalamic, or both. Treatment with levodopa and thalamic stereotactic lesional surgery seems to be effective.

Treatment of advanced Parkinson’s disease

PURPOSE OF REVIEW Later stage Parkinsons disease, sometimes referred to as advanced disease, has been characterized by motor complication, as well as by the potential emergence of nonlevodopa responsive motor and nonmotor symptoms. The management of advanced stage Parkinsons disease can be complex. This review summarizes the currently available treatment strategies for addressing advanced Parkinsons disease. RECENT FINDINGS We will discuss the latest pharmacological strategies (e.g., inhibitors of dopamine-metabolizing enzymes, dopamine agonists, and extended release dopamine formulations) for addressing motor dysfunction. We will summarize the risks and benefits of current invasive treatments. Finally, we will address the current evidence supporting the treatment of nonmotor symptoms in the advanced Parkinsons disease patient. We will conclude by detailing the potential nonpharmacological and multidisciplinary approaches for advanced stage Parkinsons disease. SUMMARY The optimization of levodopa is, in most cases, the most powerful therapeutic option available; however, medication optimization requires an advanced understanding of Parkinsons disease. Failure of conventional pharmacotherapy should precipitate a discussion of the potential risks and benefits of more invasive treatments. Currently, there are no comparative studies of invasive treatment. Among the invasive treatments, deep brain stimulation has the largest amount of existing evidence, but also has the highest individual per patient risk. Nonmotor symptoms will affect quality of life more than the motor Parkinsons disease symptoms, and these nonmotor symptoms should be aggressively treated. Many advanced Parkinsons disease patients will likely benefit from multi and interdisciplinary Parkinsons disease teams with multiple professionals collaborating to develop a collective and tailored strategy for an individual patient.

The "brittle response" to Parkinson's disease medications: characterization and response to deep brain stimulation.

Objective Formulate a definition and describe the clinical characteristics of PD patients with a “brittle response” (BR) to medications versus a “non-brittle response” (NBR), and characterize the use of DBS for this population. Methods An UF IRB approved protocol used a retrospective chart review of 400 consecutive PD patients presenting to the UF Center for Movement Disorders and Neurorestoration. Patient records were anonymized and de-identified prior to analysis. SPSS statistics were used to analyze data. Results Of 345 included patients, 19 (5.5%) met criteria for BR PD. The BR group was comprised of 58% females, compared to 29% in the NBR group (P = .008). The former had a mean age of 63.4 compared to 68.1 in the latter. BR patients had lower mean weight (63.5 vs. 79.6, P = <.001), longer mean disease duration (12.6 vs. 8.9 years, P = .003), and had been on LD for more years compared to NBR patients (9.8 vs. 5.9, P = .001). UPDRS motor scores were higher (40.4 vs. 30.0, P = .001) in BR patients. No differences were observed regarding the Schwab and England scale, PDQ-39, and BDI-II. Sixty-three percent of the BR group had undergone DBS surgery compared to 18% (P = .001). Dyskinesias were more common, severe, and more often painful (P = <.001) in the BR group. There was an overall positive benefit from DBS. Conclusion BR PD occurred more commonly in female patients with a low body weight. Patients with longer disease duration and longer duration of LD therapy were also at risk. The BR group responded well to DBS.

Deep Brain Stimulation in a Case of Mitochondrial Disease

DBS has proven to be an effective therapy for Parkinsons disease, essential tremor, and primary dystonia. Mixed results have been reported in case series for other hyperkinetic disorders, and sparse data are available regarding secondary movement disorders. We report on the clinical effects of bilateral globus pallidus internus (GPi) DBS, a progressive mitochondrial cytopathy.

Comparable Botulinum Toxin Outcomes between Primary and Secondary Blepharospasm: A Retrospective Analysis

Background Blepharospasm is a focal cranial dystonia, which could be idiopathic in origin or secondary to an underlying disorder that commonly impairs quality of life. Botulinum toxin (BoNT) injections have become the treatment of choice; however, a less favorable response to BoNT is expected in secondary blepharospasm. No studies have been conducted comparing outcomes between blepharospasm cohorts. We therefore aim to compare BoNT outcomes in primary and secondary blepharospasm subjects. Methods A retrospective review of 64 blepharospasm subjects receiving BoNT therapy was conducted. Demographics, BoNT treatment schedules, duration of BoNT therapy, and side effects were recorded. Outcome measures were duration of benefit, peak-dose benefit recorded with the Clinical Global Impressions Scale (CGIS), and related side effects. Results No difference was found between the two cohorts regarding duration of benefit from treatment (primary 9.47 weeks vs. secondary 9.63 weeks, p = 0.88). Perceived peak-dose benefit was more commonly reported as “very much improved” in secondary patients, but this was not significant (p = 0.13). Higher BoNT dosages were required in both groups over time, with a mean increase of 20.5% in primary and 26.5% in secondary blepharospasm. Ptosis (8%) and diplopia (6%) were the most common reported side effects. Mean follow-up in years was similar between groups, 3.6 years for primary vs. 2.4 years for secondary blepharospasm (p = 0.17). Discussion BoNT injections were effective with comparable benefits seen in both primary and secondary blepharospasm populations. Clinicians should be aware of the similar benefit from BoNT reported in secondary blepharospasm patients. The average duration of benefit in this cohort was comparable with previous reports.

Ventral Intermediate Nucleus Versus Zona Incerta Region Deep Brain Stimulation in Essential Tremor

The ventral intermediate nucleus (VIM) is the target of choice for Essential Tremor (ET) deep brain stimulation (DBS). Renewed interest in caudal zona incerta (cZI) stimulation for tremor control has recently emerged and some groups believe this approach may address long‐term reduction of benefit seen with VIM‐DBS.