Bower, James H.

Background: Parkinson’s disease (PD) most commonly surfaces at middle age. An earlier onset is named early-onset Parkinson’s disease (EOPD), but the exact definition is a matter of ongoing scientific debate. Objective: To investigate 40-year EOPD incidence trends in a population-based cohort of parkinsonism in Olmsted County, Minnesota. Methods: We used the Rochester Epidemiology Project (REP) to identify all incident EOPD cases in Olmsted County, 1976–2015. A movement-disorder specialist reviewed all cases to confirm the EOPD diagnosis. For EOPD definition, we used two age cut-offs: motor-symptom onset at or before 50 and 55 years. Results: EOPD incidence was 1.43/100,000 person-years for ≤55 and 0.55/100,000 for ≤50 years. Men had a higher incidence in both groups [1.84 vs. 1.03 ( p = 0.04); and 0.70 vs. 0.40 ( p = 0.24), respectively]. EOPD incidence of patients with motor-symptom onset before age 55 increased from 1.02/100.000 person-year 1976–1985, to 1.32/100.000 person-year 2006–2015. A similar trend was observed when ≤50 years cut-off was used (0.28/100,000 person-years 1976–1985, to 0.59/100,000 person-year 2006–2015). However, negative binomial regression found no significant change in incidence per 10 years (RR = 1.04 and 1.24 in the two groups). Incidence was consistently higher in men than women. Median time from EOPD-symptom onset to death was shorter in the EOPD ≤55 group (21.9 years) compared to the EOPD ≤50 group (25.6 years). Conclusion: We observed an increased trend in the incidence of EOPD with both cut-off ages. Overall, incidence of EOPD was 1.43 (≤55) and 0.55 (≤50) cases per 100,000 person-years, higher in men.

AbstractBackgroundStiff person spectrum disorder (SPSD) is heterogeneous, and accurate diagnosis can be challenging.MethodsPatients referred for diagnosis/suspicion of SPSD at the Mayo Autoimmune Neurology Clinic from July 01, 2016, to June 30, 2021, were retrospectively identified. SPSD diagnosis was defined as clinical SPSD manifestations confirmed by an autoimmune neurologist and seropositivity for high‐titer GAD65‐IgG (>20.0 nmol/L), glycine‐receptor‐IgG or amphiphysin‐IgG, and/or confirmatory electrodiagnostic studies (essential if seronegative). Clinical presentation, examination, and ancillary testing were compared to differentiate SPSD from non‐SPSD.ResultsOf 173 cases, 48 (28%) were diagnosed with SPSD and 125 (72%) with non‐SPSD. Most SPSD were seropositive (41/48: GAD65‐IgG 28/41, glycine‐receptor‐IgG 12/41, amphiphysin‐IgG 2/41). Pain syndromes or functional neurologic disorder were the most common non‐SPSD diagnoses (81/125, 65%). SPSD patients more commonly reported exaggerated startle (81% vs. 56%, p = 0.02), unexplained falls (76% vs. 46%, p = 0.001), and other associated autoimmunity (50% vs. 27%, p = 0.005). SPSD more often had hypertonia (60% vs. 24%, p < 0.001), hyperreflexia (71% vs. 43%, p = 0.001), and lumbar hyperlordosis (67% vs. 9%, p < 0.001) and less likely functional neurologic signs (6% vs. 33%, p = 0.001). SPSD patients more frequently had electrodiagnostic abnormalities (74% vs. 17%, p < 0.001), and at least moderate symptomatic improvement with benzodiazepines (51% vs. 16%, p < 0.001) or immunotherapy (45% vs. 13% p < 0.001). Only 4/78 non‐SPSD patients who received immunotherapy had alternative neurologic autoimmunity.InterpretationMisdiagnosis was threefold more common than confirmed SPSD. Functional or non‐neurologic disorders accounted for most misdiagnoses. Clinical and ancillary testing factors can reduce misdiagnosis and exposure to unnecessary treatments. SPSD diagnostic criteria are suggested.

Background: The diagnostic issue of paroxysmal spells, including epileptic seizure (ES) mimics, is one that neurologists frequently encounter. This review provides an up-to-date overview of the most common causes of ES mimics encountered in the outpatient setting. Review Summary: Paroxysmal spells are characterized by changes in awareness, attention, perception, or abnormal movements. These can be broadly classified as ES and nonepileptic spells (NES). NES mimics ES but are distinguished by their symptomatology and lack of epileptiform activity on electroencephalography. NES may have psychological or physiological underpinnings. Psychogenic non-ES are the most common mimics of ES. Physiological causes of NES include syncope, cerebrovascular, movement, and sleep-related disorders. Conclusions: Distinguishing NES from ES at times may be challenging even to the most experienced clinicians. However, detailed history with an emphasis on the clinical clues, including taking a moment-by-moment history of the event from the patient and observers and physical examination, helps create an appropriate differential diagnosis to guide further diagnostic testing. An accurate diagnosis of NES prevents iatrogenic harm, including unnecessary exposure to antiseizure medications and overuse of health care resources. It also allows for the correct specialist referral and appropriate treatment.

BACKGROUND: Parkinson’s disease (PD)-associated psychosis is a well-known non-motor complication, occurring years after diagnosis of PD. Incidence data vary across different studies highlighting a need for long-term observation and clinical definition. OBJECTIVE: To determine the incidence of psychosis in patients with PD and to investigate their survival in an incident cohort study from 1991–2010 in Olmsted County, MN. METHODS: We used the Rochester Epidemiology Project to define an incident-cohort study of parkinsonism (1991–2010) in Olmsted County, MN. A movement-disorder specialist reviewed the electronic medical records and applied diagnosis criteria to PD. Psychosis was diagnosed using of NINDS/NIMH unified criteria. RESULTS: We identified 669 cases of parkinsonism; 297 patients were clinically diagnosed with PD. 114/297 (38.4%) patients had evidence of psychosis (60% male); the median onset age of psychosis was 79.4 years. The incidence of Parkinson’s disease psychosis (PDP) was 4.28/100 person-years. PDP patients had a 71% increased risk of death compared to PD patients. In PD patients without psychosis, men had 73.4% increased risk of death compared to women, whereas no significant sex difference was observed among PDP men vs. women. Of 114 patients diagnosed with psychosis, 59 were treated with antipsychotics. There was no significant difference in survival between treated and untreated patients. CONCLUSION: PDP increased the odds of death compared to PD patients. Men with PD without psychosis had greater odds of death compared to women; however, in PD with psychosis the odds of death were comparable among sexes. Lastly, treatment with anti-psychotics did not significantly affect survival.

ObjectiveThe aim was to analyze the timeline, prevalence, and survival of rapid eye movement (REM) sleep behavior disorder (RBD) in patients who developed alpha‐synucleinopathies (Parkinson disease, dementia with Lewy bodies, and Parkinson disease dementia) compared with age‐ and sex‐matched controls in a population‐based incident‐cohort study.MethodsWe used a population‐based, 1991 to 2010 incident‐cohort study of alpha‐synucleinopathies. A movement‐disorder specialist reviewed medical records to confirm diagnoses. RBD was diagnosed by reported dream‐enactment symptoms or polysomnography. Probable RBD and polysomnographically confirmed RBD were analyzed separately and combined.ResultsAmong the 444 incident cases of alpha‐synucleinopathy, 86 were clinically diagnosed with RBD (19.8%), including 30 (35%) by polysomnography and 56 (65%) as probable. The prevalence of idiopathic RBD at alpha‐synucleinopathy diagnosis was 3.4%, increasing to 23.8% after 15 years. Cumulative lifetime incidence was 53 times greater in alpha‐synucleinopathy patients than in controls (odds ratio [OR] = 53.1, 95% confidence interval [CI]: 13.0–217.2, p < 0.0001), higher in dementia with Lewy bodies than in Parkinson disease (OR = 2.57, 95% CI: 1.50–4.40, p = 0.0004), and higher in men than in women with Parkinson disease, dementia with Lewy bodies, or Parkinson disease dementia (OR = 3.70, 95% CI: 2.07–6.62, p < 0.0001), but did not increase mortality risk.InterpretationOur cohort had RBD incidence of 3.4%. Overall RBD increased to 23.8% after 15 years, with an overall incidence of 2.5 cases per 100 person‐years. With 53 times greater lifetime incidence in alpha‐synucleinopathy patients than in controls, RBD was more likely to develop in dementia with Lewy bodies than in Parkinson disease or Parkinson disease dementia, and in men than in women, but did not increase mortality risk within our cohort. ANN NEUROL 2021;89:293–303

AbstractBackgroundSeveral studies have proposed a role for infections to induce an inflammatory response triggering Parkinson's disease. This remains controversial and the influence of severe infections on other α‐synucleinopathies (Dementia with Lewy Bodies, Parkinson's disease dementia, and Multiple System Atrophy) has not been adequately investigated.ObjectivesTo assess the association between hospitalization‐required infections or sepsis and risk of clinically diagnosed α‐synucleinopathies.MethodsUsing the medical records‐linkage system (Rochester Epidemiology Project), we identified all α‐synucleinopathy cases of in Olmsted County (1991–2010). Cases were matched by symptom‐onset age and sex to controls. We reviewed complete medical records to detect hospital‐required infections or sepsis preceding clinical‐motor onset of α‐synucleinopathies. We used conditional logistic regression to calculate the odds ratio of all α‐synucleinopathies, adjusting for medications, coffee, and smoking.ResultsThere was no association between infection‐related hospitalization (odds ratio: 1.05; 95% confidence interval: 0.78–1.40; P = 0.76) or sepsis (odds ratio: 0.86; 95% confidence interval: 0.40–1.85; P = 0.70) and all α‐synucleinopathies in multivariable analyses. We did not identify any associations after stratifying for type of α‐synucleinopathy, sex, and age at clinical‐motor onset. We analyzed sepsis separately with similar results.ConclusionWe did not observe any associations between infections leading to hospitalization or sepsis and development of any α‐synucleinopathies. © 2020 International Parkinson and Movement Disorder Society

Abstract Background Multiple system atrophy (MSA) is a neurodegenerative disorder from α‐synuclein aggregation. in vitro studies suggest vitamin B12 may interrupt α‐synuclein‐mediated neurodegeneration. The objective of this study was to determine whether serum vitamin B12 level at MSA diagnosis is associated with survival. Methods One hundred eighty‐two MSA patients evaluated at Mayo Clinic with vitamin B12 testing were studied. We determined the risk of death in relationship to serum vitamin B12 levels at MSA diagnosis, adjusting for predictors of poor survival. Results Predictors of shorter survival included vitamin B12 < 367 ng/L (HR, 1.8; 95% CI, 1.3–2.7), falls within 3 years of MSA diagnosis (HR, 1.6; 95% CI, 1.1–2.3), bladder symptoms (HR, 1.6; 95% CI, 1.0–2.6), urinary catheter requirement (HR, 1.7; 95% CI, 1.0–2.8), male sex (HR, 1.4; 95% CI, 1.0–2.0), and MSA‐P subtype (HR, 1.5; 95% CI, 1.0–2.0). Conclusions Low vitamin B12 levels are associated with shorter survival in MSA. Additional studies to explore this observation and assess the potential role of vitamin B12 as a modifiable survival factor are needed. © 2020 International Parkinson and Movement Disorder Society