Progressive multifocal leukoencephalopathy secondary to idiopathic CD4 lymphocytopenia treated with pembrolizumab.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease due to a lytic infection of oligodendrocytes caused by John Cunningham polyoma virus (JCV) infection. Idiopathic CD4+ T-cell lymphocytopenia (ICL) is a very rare cause of PML. METHODS: We present an individual with PML secondary to ICL treated with 3 doses of pembrolizumab, a Programmed-Death-1 Immune Checkpoint Inhibitor following with complete resolution of symptoms and conduct a review of the literature. CONCLUSION: This report illustrates the objective clinical and radiological improvement in a patient with PML due to ICL and suggests further study of immune checkpoint inhibitors as potential treatment for patients with PML.

Assessment of Risk Factors and Early Presentations of Parkinson Disease in Primary Care in a Diverse UK Population.

IMPORTANCE: Early features of Parkinson disease (PD) have been described through population-based studies that overrepresent White, affluent groups and may not be generalizable. OBJECTIVE: To investigate the association between risk factors and prediagnostic presentations of PD in an ethnically diverse UK population with high socioeconomic deprivation but universal access to health care. DESIGN, SETTING, AND PARTICIPANTS: A nested case-control study was conducted using electronic health care records on 1 016 277 individuals from primary care practices in East London to extract clinical information recorded between 1990 and February 6, 2018. The data were analyzed between September 3, 2020, and September 3, 2021. Individuals with a diagnosis of PD were compared with controls without PD or other major neurological conditions. MAIN OUTCOMES AND MEASURES: A matched analysis (10 controls matched for each patient with PD according to age and sex) and an unmatched analysis (adjusted for age and sex) were undertaken using multivariable logistic regression to determine associations between risk factors and prediagnostic presentations to primary care with subsequent diagnosis of PD. Three time periods (<2, 2-<5, and 5-10 years before diagnosis) were analyzed separately and together. RESULTS: Of 1 016 277 individuals included in the data set, 5699 were excluded and 1055 patients with PD and 1 009 523 controls were included in the analysis. Patients with PD were older than controls (mean [SD], 72.9 [11.3] vs 40.3 [15.2] years), and more were male (632 [59.9%] vs 516 862 [51.2%]). In the matched analysis (1055 individuals with PD and 10 550 controls), associations were found for tremor (odds ratio [OR], 145.96; 95% CI, 90.55-235.28) and memory symptoms (OR, 8.60; 95% CI, 5.91-12.49) less than 2 years before the PD diagnosis. The associations were also found up to 10 years before PD diagnosis for tremor and 5 years for memory symptoms. Among midlife risk factors, hypertension (OR, 1.36; 95% CI, 1.19-1.55) and type 2 diabetes (OR, 1.39; 95% CI, 1.19-1.62) were associated with subsequent diagnosis of PD. Associations with early nonmotor features, including hypotension (OR, 6.84; 95% CI, 3.38-13.85), constipation (OR, 3.29; 95% CI, 2.32-4.66), and depression (OR, 4.69; 95% CI, 2.88-7.63), were also noted. Associations were found for epilepsy (OR, 2.5; 95% CI, 1.63-3.83) and hearing loss (OR, 1.66; 95% CI, 1.06-2.58), which have not previously been well reported. These findings were replicated using data from the UK Biobank. No association with future PD diagnosis was found for ethnicity or deprivation index level. CONCLUSIONS AND RELEVANCE: This study provides data suggesting that a range of comorbidities and symptoms are encountered in primary care settings before PD diagnosis in an ethnically diverse and deprived population. Novel temporal associations were observed for epilepsy and hearing loss with subsequent development of PD. The prominence of memory symptoms suggests an excess of cognitive dysfunction in early PD in this population or difficulty in correctly ascertaining symptoms in traditionally underrepresented groups.

Developing and assessing a new web-based tapping test for measuring distal movement in Parkinson's disease: a Distal Finger Tapping test.

Disability in Parkinson's disease (PD) is measured by standardised scales including the MDS-UPDRS, which are subject to high inter and intra-rater variability and fail to capture subtle motor impairment. The BRadykinesia Akinesia INcoordination (BRAIN) test is a validated keyboard tapping test, evaluating proximal upper-limb motor impairment. Here, a new Distal Finger Tapping (DFT) test was developed to assess distal upper-limb function. Kinetic parameters of the test include kinesia score (KS20, key taps over 20 s), akinesia time (AT20, mean dwell-time on each key) and incoordination score (IS20, variance of travelling time between key taps). To develop and evaluate a new keyboard-tapping test for objective and remote distal motor function in PD patients. The DFT and BRAIN tests were assessed in 55 PD patients and 65 controls. Test scores were compared between groups and correlated with the MDS-UPDRS-III finger tapping sub-scores. Nine additional PD patients were recruited for monitoring motor fluctuations. All three parameters discriminated effectively between PD patients and controls, with KS20 performing best, yielding 79% sensitivity for 85% specificity; area under the receiver operating characteristic curve (AUC) = 0.90. A combination of DFT and BRAIN tests improved discrimination (AUC = 0.95). Among three parameters, KS20 showed a moderate correlation with the MDS-UPDRS finger-tapping sub-score (Pearson's r = - 0.40, p = 0.002). Further, the DFT test detected subtle changes in motor fluctuation states which were not reflected clearly by the MDS-UPDRS-III finger tapping sub-scores. The DFT test is an online tool for assessing distal movements in PD, with future scope for longitudinal monitoring of motor complications.

Magnetic Resonance Imaging in Stable Mild Cognitive Impairment, Prodromal Alzheimer's Disease, and Prodromal Dementia with Lewy Bodies.

INTRODUCTION: Fifteen percent of people with mild cognitive impairment (MCI) will progress to dementia within 2 years. There is increasing focus on the evaluation of biomarkers which point towards the underlying pathology. This enables better prediction of clinical outcomes. Early diagnosis of the dementia subtype is crucial for appropriate management and accurate prognosis. The aim of this study was to compare MRI measures in stable mild cognitive impairment patients (stable-MCI), prodromal Alzheimer's disease (pro-AD), and prodromal dementia with Lewy bodies (pro-DLB). METHODS: Out of 1,814 patients assessed in Essex memory clinic between 2002 and 2017, 424 had MCI at baseline with follow-up data. All patients underwent comprehensive clinical and cognitive assessment at each assessment. MRI scans were acquired at patients' baseline assessment, corresponding to the time of initial MCI clinical diagnosis. Patients were grouped according to their diagnosis at the end of follow-up. All baseline scans were visually rated according to established rating scales for medial temporal atrophy (MTA), global cortical atrophy (GCA), and white matter lesions (WMLs). RESULTS: MRI scans were available for 28 pro-DLB patients and were matched against 27 pro-AD and 28 stable-MCI patients for age, sex, and education. The mean follow-up duration was 34 months for the pro-AD group, 27 months for the pro-DLB group, and 21 months for the stable-MCI group. MTA scores were significantly greater in pro-AD patients compared to pro-DLB (p = 0.047) and stable-MCI patients (p = 0.012). There was no difference on GCA or WMLs between pro-AD, pro-DLB, and stable-MCI. CONCLUSIONS: This study indicates that a simple visual rating of MTA at the stage of MCI already differs at a group level between patients that progress to AD, DLB, or continue to be stable-MCI. This could aid clinicians to differentiate between MCI patients who are likely to develop AD, versus those who might progress to DLB or remain stable.

Ethnic Variation in the Manifestation of Parkinson's Disease: A Narrative Review.

The global prevalence of Parkinson's disease is increasing, yet the characteristics, risk factors and genetics of PD in Black, Asian and Hispanic populations is little understood. In this paper we review the published literature on clinical variation in the symptoms and signs of Parkinson's disease in different ethnic groups and responses to treatment. We included any study that sampled patients with Parkinson's disease from distinct ethnic backgrounds. We conclude that whilst there is little published evidence for ethnic variation in the clinical features of Parkinson's disease, there are substantial limitations and gaps in the current literature, which mean that the evidence does necessarily not fit with clinical observation. Possible explanations for expected differences in manifestation include genetic determinants, the co-existence of cerebrovascular disease and/or Alzheimer's disease pathology, healthcare inequalities and socio-cultural factors.