Deep Brain Stimulation for an Unusual Presentation of Myoclonus Dystonia Associated with Russell-Silver Syndrome.

Background: Myoclonus dystonia syndrome typically results from autosomal dominant mutations in the epsilon-sarcoglycan gene (SGCE) via the paternally expressed allele on chromosome 7q21. There is evidence that deep brain stimulation (DBS) is beneficial for this genotype, however, there are few prior case reports on DBS for myoclonus dystonia syndrome secondary to other confirmed genetic etiologies. Case Report: A 20-year-old female with concomitant Russell-Silver syndrome and myoclonus dystonia syndrome secondary to maternal uniparental disomy of chromosome 7 (mUPD7) presented for medically refractory symptoms. She underwent DBS surgery targeting the bilateral globus pallidus interna with positive effects that persisted 16 months post-procedure. Discussion: We present a patient with the mUPD7 genotype for myoclonus dystonia syndrome who exhibited a similar, if not superior, response to DBS when compared to patients with other genotypes. Highlights: This report outlines the first described case of successful deep brain stimulation treatment for a rare genetic variant of myoclonus dystonia syndrome caused by uniparental disomy at chromosome 7. These findings may expand treatment options for patients with similar conditions.

Individualized Anatomy-Based Targeting for VIM-cZI DBS in Essential Tremor.

BACKGROUND: Deep brain stimulation of the ventral intermediate nucleus (VIM) or caudal zona incerta (cZI) is effective for refractory essential tremor (ET). To refine stereotactic planning for lead placement, we developed a unique individualized anatomy-based planning protocol that targets both the VIM and the cZI in patients with ET. METHODS: 33 patients with ET underwent VIM-cZI lead implantation with targeting based on our protocol. Indirect targeting was adjusted based on anatomic landmarks as reference lines bisecting the red nuclei and ipsilateral subthalamus. Outcomes were evaluated through the follow-up of 31.1 ± 18.4 months. Active contact coordinates were obtained from reconstructed electrodes in the Montreal Neurological Institute space using the MATLAB Lead-DBS toolbox. RESULTS: Mean tremor improvement was 79.7% ± 22.4% and remained stable throughout the follow-up period. Active contacts at last postoperative visit had mean Montreal Neurological Institute coordinates of 15.5 ± 1.6 mm lateral to the intercommissural line, 15.3 ± 1.8 mm posterior to the anterior commissure, and 1.4 ± 2.9 mm below the intercommissural plane. No hemorrhagic complications were observed in the analyzed group. CONCLUSIONS: Individualized anatomy-based VIM-cZI targeting is feasible and safe and is associated with favorable tremor outcomes.

Safety of Noncontrast Imaging-Guided Deep Brain Stimulation Electrode Placement in Parkinson Disease.

BACKGROUND: Deep brain stimulation (DBS) is considered standard of care for the treatment of medically refractory Parkinson disease (PD). The placement of brain electrodes is performed using contrast imaging to enhance blood vessel identification during stereotactic planning. We present our experience with a series of patients implanted using noncontrast imaging. METHODS: All cases of DBS surgery for PD performed between 2012 and 2018 with noncontrast imaging were retrospectively reviewed. Clinical features, postoperative imaging, and complications were analyzed. RESULTS: A total of 287 deep-seated electrodes were implanted in 152 patients. Leads were placed at the subthalamic nucleus and globus pallidus internus in 258 and 29 hemispheres, respectively. We identified 2 cases of intracranial hemorrhage (0.7%). CONCLUSIONS: DBS lead placement can be performed without the use of intravenous contrast with a postoperative intracranial hemorrhage rate comparable with other reported series.

Gender Disparities in Deep Brain Stimulation for Parkinson's Disease.

OBJECTIVES: This study sought to determine whether there is a gender disparity in patients undergoing deep brain stimulation (DBS) surgery for Parkinson's disease (PD) at a single health system, and better understand the reasons for this discrepancy. MATERIALS AND METHODS: We analyzed data from the University of Miami DBS Database, which included 3251 PD patients, using chi-square, repeated measures ANOVA, and t tests to examine gender differences in the number of patients referred for surgery, reasons for referral, number receiving/not receiving surgery, reasons for not receiving surgery, and postsurgical outcomes. RESULTS: During the study period, 207 PD patients were referred for DBS (75.8% male), and 100 underwent surgery (77.0% male). Of those who did not receive surgery, the most common reasons were need for further medical optimization (26.2%), suboptimal performance on neuropsychological evaluation (22.4%), other reason (20.6%), lost to follow-up (18.7%), or patient preference (12.2%). However, in women one of the most common reasons was patient preference (28.0%), and this was significant compared to men (p < 0.001). Men were more likely to be lost to follow-up (p = 0.046). There was no statistically significant difference in postsurgical outcomes. CONCLUSIONS: Despite similar postsurgical improvements, women were less likely to undergo DBS surgery due to their own preference, while men were more likely to be lost to follow-up. These data underscore the need for increased education and awareness of DBS so that all patients with PD who qualify for surgery can benefit from this procedure.

Primary Intramedullary Spinal Cord Lymphoma Presenting as a Cervical Ring-Enhancing Lesion in an AIDS Patient.

Primary intramedullary spinal cord lymphoma (PISCL) is rare and constitutes only 1% of central nervous system lymphomas. We report a case of PISCL in a 37-year-old man with advanced AIDS. To our knowledge, only 4 cases of PISCL in the setting of HIV/AIDS have been reported in the literature. Despite treatment, prognosis remains dismal.

Acute symptomatic peri-lead edema 33 hours after deep brain stimulation surgery: a case report.

BACKGROUND: Symptomatic peri-lead edema is a rare complication of deep brain stimulation that has been reported to develop 4 to 120 days postoperatively. CASE PRESENTATION: Here we report the case of a 63-year-old Hispanic man with an 8-year history of Parkinson's disease who underwent bilateral placement of subthalamic nucleus deep brain stimulation leads and presented with acute, symptomatic, unilateral, peri-lead edema just 33 hours after surgery. CONCLUSIONS: We document a thorough radiographic time course showing the evolution of these peri-lead changes and their regression with steroid therapy, and discuss the therapeutic implications of these findings. We propose that the unilateral peri-lead edema after bilateral deep brain stimulation is the result of severe microtrauma with blood-brain barrier disruption. Knowledge of such early manifestation of peri-lead edema after deep brain stimulation is critical for ruling out stroke and infection and preventing unnecessary diagnostic testing or hardware removal in this rare patient population.

Association of the sirtuin and mitochondrial uncoupling protein genes with carotid plaque.

OBJECTIVE: Sirtuins (SIRTs) and mitochondrial uncoupling proteins (UCPs) have been implicated in cardiovascular diseases through the control of reactive oxygen species production. This study sought to investigate the association between genetic variants in the SIRT and UCP genes and carotid plaque. METHODS: In a group of 1018 stroke-free subjects from the Northern Manhattan Study with high-definition carotid ultrasonography and genotyping, we investigated the associations of 85 single nucleotide polymorphisms (SNPs) in the 11 SIRT and UCP genes with the presence and number of carotid plaques, and evaluated interactions of SNPs with sex, smoking, diabetes and hypertension as well as interactions between SNPs significantly associated with carotid plaque. RESULTS: Overall, 60% of subjects had carotid plaques. After adjustment for demographic and vascular risk factors, T-carriers of the SIRT6 SNP rs107251 had an increased risk for carotid plaque (odds ratio, OR = 1.71, 95% CI = 1.23-2.37, Bonferroni-corrected p = 0.03) and for a number of plaques (rate ratio, RR = 1.31, 1.18-1.45, Bonferroni-corrected p = 1.4×10(-5)), whereas T-carriers of the UCP5 SNP rs5977238 had an decreased risk for carotid plaque (OR = 0.49, 95% CI = 0.32-0.74, Bonferroni-corrected p = 0.02) and plaque number (RR = 0.64, 95% CI = 0.52-0.78, Bonferroni-corrected p = 4.9×10(-4)). Some interactions with a nominal p≤0.01 were found between sex and SNPs in the UCP1 and UCP3 gene; between smoking, diabetes, hypertension and SNPs in UCP5 and SIRT5; and between SNPs in the UCP5 gene and the UCP1, SIRT1, SIRT3, SIRT5, and SIRT6 genes in association with plaque phenotypes. CONCLUSION: We observed significant associations between genetic variants in the SIRT6 and UCP5 genes and atherosclerotic plaque. We also found potential effect modifications by sex, smoking and vascular risk factors of the SIRT/UCP genes in the associations with atherosclerotic plaque. Further studies are needed to validate our observations.

Erythromycin as a potential precipitating agent in the onset of Leber's hereditary optic neuropathy.

A 23-years-old male entered a safety clinical trial for cetirizine (a selective histamine H(1)-receptor antagonist) in combination with the antibiotic erythromycin. Within a few weeks of finishing the trial, the patient reported bilateral vision loss with optic nerve atrophy. Genetic studies showed that he had a mitochondrial DNA (mtDNA) mutation at position 11778 (within the gene for subunit 4 of NADH-coenzyme Q oxidoreductase), commonly associated with Leber's hereditary optic neuropathy. To test if erythromycin could worsen the mitochondrial respiratory chain defect associated with the 11778 mtDNA mutation, we transferred the patient's mtDNA to cultured mtDNA-less osteosarcoma cells. Erythromycin inhibited proliferation of the patient's transmitochondrial cybrids in conditions that required mitochondrial respiration for growth. We confirmed that erythromycin is a potent inhibitor of mitochondrial translation in these cells. Taken together, these results suggest that erythromycin may have hastened a bioenergetics crisis in the optic nerve of this patient. This association underscores the importance of being cautious with the use of drugs that interfere with cellular respiration in individuals with an underlying mitochondrial dysfunction.