Genotype-Phenotype Relations in Primary Familial Brain Calcification: Systematic MDSGene Review.

This systematic MDSGene review covers individuals with confirmed genetic forms of primary familial brain calcification (PFBC) available in the literature. Data on 516 (47% men) individuals, carrying heterozygous variants in SLC20A2 (solute carrier family 20 member 2, 61%), PDGFB (platelet-derived growth factor subunit B, 12%), XPR1 (xenotropic and polytropic retrovirus receptor, 16%), or PDGFRB (platelet-derived growth factor receptor beta, 5%) or biallelic variants in MYORG (myogenesis-regulating glycosidase, 13%) or JAM2 (junctional adhesion molecule 2, 2%), were extracted from 93 articles. Nearly one-third of the mutation carriers were clinically unaffected. Carriers of PDGFRB variants were more likely to be clinically unaffected (~54%), and the penetrance of SLC20A2 and XPR1 variants (<70%) was lower in comparison to the remaining three genes (>85%). Among the 349 clinically affected patients, 27% showed only motor and 31% only nonmotor symptoms/signs, whereas the remaining 42% had a combination thereof. While parkinsonism and speech disturbance were the most frequently reported motor manifestations, cognitive deficits, headache, and depression were the major nonmotor symptoms/signs. The basal ganglia were always calcified, and the cerebellum, thalamus, and white matter contained calcifications in 58%, 53%, and 43%, respectively, of individuals. In autosomal-dominant PFBC, mutation severity influenced the number of calcified brain areas, which in turn correlated with the clinical status, whereby the risk of developing symptoms/signs more than doubled for each additional region with calcifications. Our systematic analysis provides the most comprehensive insight into genetic, clinical, and neuroimaging features of known PFBC forms, to date. In addition, it puts forth the penetrance estimates and newly discovered genotype-phenotype relations that will improve counseling of individuals with mutations in PFBC genes. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Trends of inpatient palliative care use among hospitalized patients with Parkinson's disease.

INTRODUCTION: Palliative care in Parkinson's Disease (PD) is an effective intervention to improve quality of life, although historically, access and availability have been very restricted. METHODS: We performed a retrospective cohort study using the National Inpatient Sample (NIS) data from 2007 to 2014. Diagnostic codes were used to identify patients with PD and palliative care referral. Trends were calculated and logistic analysis performed to identify predictors of palliative care use. RESULTS: We identified 397,963 hospitalizations from 2007 to 2014 for patients with PD. Of these, 10,639 (2.67%) were referred to palliative care. The rate of consultation increased from 0.85% in 2007 to 4.49% in 2014. For 1 unit in year increase, there was 1.23 time the odds of receiving palliative consultation (OR 1.23, CI 1.21-1.25, p < 0.0001). Hispanics (OR 0.90, CI 0.81-1.01, p = 0.0550), Black (OR 0.90, CI 0.81-1.01, p = 0.0747) and White patients had similar rates of referral after adjustment. Women were less likely to be referred to palliative care (OR 0.90, CI 0.87-0.94, p < 0.0001). Other factors strongly associated with a higher rate of referrals included private insurance when compared to Medicare (OR 2.14, CI 1.89-2.41, p < 0.0001) and higher income (OR 1.41, CI 1.30-1.53, p < 0.0001). CONCLUSION: There has been a significant increase in palliative care referrals among hospitalized patients with PD in the US, although the overall rate remains low. After controlling for confounders, racial and ethnic disparities were not found. Women, patients with Medicare/Medicaid, and those with lower income were less likely to be referred to palliative care.

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.

Severe tooth loss secondary to orofacial dyskinesias in anti-NMDA receptor encephalitis.

A 24-year-old woman with no significant medical or psychiatric history was brought to the emergency department due to altered mental status and bizarre behaviour. Physical examination was remarkable for decreased speech output and orofacial dyskinesia. Upon further evaluation, electroencephalogram showed extreme delta brush waves and cerebrospinal fluid was positive for anti-NMDA receptor antibodies. Despite aggressive treatment with steroids and immunosuppressive therapy, her dyskinesia was severe enough to cause tooth loss, tongue and lip laceration.

Revisiting eligibility for deep brain stimulation: Do preoperative mood symptoms predict outcomes in Parkinson's disease patients?

INTRODUCTION: Anxiety and depression are common in PD, occurring in an estimated 30%-40% of PD patients. However, the extent to which these emotional symptoms interfere with Deep Brain Stimulation (DBS) outcomes is not well established. This study examined the association between pre-operative emotional well-being and postsurgical cognitive, emotional, and motor performance in PD. METHODS: Forty-nine PD patients underwent neurological, neuropsychological (global cognition, processing speed, language, visuospatial, memory), and emotional assessments pre- and post-DBS. Fifteen patients were administered the UPDRS. Patients were divided into Anxious (Anx; n = 21), Comorbid Anxious and Depressed (Anx + Dep; n = 15), and Emotionally Asymptomatic (EA; n = 13) based on BAI and BDI-II cutoffs, and compared on pre-post changes in neurocognitive, mood, and motor scores using analyses of covariance (ANCOVA), controlling for education, ethnicity, and disease duration. RESULTS: Pre-DBS, there were no significant differences between the three groups on any neuropsychological measure. Overall change from pre-to post-DBS revealed declines on multiple cognitive measures and lower symptom endorsement on the BAI among all participants. No group differences were observed on neurocognitive measures, mood, or UPDRS. CONCLUSIONS: PD patients with mild-moderate anxiety or comorbid anxiety/depression pre-DBS do not show greater cognitive, emotional, and motor changes post-DBS compared to emotionally asymptomatic patients. These data emphasize the importance of discussing potential DBS outcomes, while keeping in mind that psychiatric comorbidity should not necessarily exclude patients from DBS. The notion that premorbid mood symptoms could disqualify a candidate for surgery would be a disservice, as this group performs comparably to asymptomatic peers.