White Matter Hyperintensities in Parkinson’s Disease: Do They Explain the Disparity between the Postural Instability Gait Difficulty and Tremor Dominant Subtypes?

Background: Brain white matter hyperintensities (WMHs) commonly observed on brain imaging of older adults are associated with balance and gait impairment and have also been linked to cognitive deficits. Parkinson’s disease (PD) is traditionally sub-classified into the postural instability gait difficulty (PIGD) sub-type, and the tremor dominant (TD) sub-type. Considering the known association between WMHs and axial symptoms like gait disturbances and postural instability, one can hypothesize that WMHs might contribute to the disparate clinical sub-types of patients with PD. Methods: 110 patients with PD underwent a clinical evaluation and a 3T MRI exam. Based on the Unified Parkinson Disease Rating Scale, the patients were classified into motor sub-types, i.e., TD or PIGD, and scores reflecting PIGD and TD symptoms were computed. We compared white matter burden using three previously validated methods: one using a semi-quantitative visual rating scale in specific brain regions and two automated methods. Results: Overall, MRI data were obtained in 104 patients. The mean WMHs scores and the percent of subjects with lesions in specific brain regions were similar in the two subtypes, p = 0.678. The PIGD and the TD scores did not differ even when comparing patients with a relatively high burden of WMHs to patients with a relatively low burden. Across most of the brain regions, mild to moderate correlations between WMHs and age were found (r = 0.23 to 0.41; p<0.021). Conversely, no significant correlations were found between WMHs and the PIGD score or disease duration. In addition, depressive symptoms and cerebro-vascular risk factors were similar among the two subtypes. Conclusions: In contrast to what has been reported previously among older adults, the present study could not demonstrate any association between WMHs and the PIGD or TD motor sub-types in patients with PD

Idiopathic pyostomatitis-pyodermatitis vegetans with nasal obstruction: A case report

Pyostomatitis-pyodermatitis vegetans is an uncommon mucocutaneous dermatosis of unknown etiology. It presents as erythematous pustules that coalesce to form exudative vegetating plaques on the oral mucosa and/or skin. Diagnosis is largely based on clinical assessment, although histopathology should be used as supporting evidence. Pyostomatitis-pyodermatitis vegetans is associated with inflammatory bowel disease, liver dysfunction, and others. We report a case of a 48-year-old man who presented with erythematous eroded plaques involving his nares and upper lip. Investigations revealed a dense mixed inflammatory infiltrate and pronounced peripheral eosinophilia. Uniquely, the patient did not have inflammatory bowel disease or any other systemic condition. Systemic corticosteroids were helpful in clearing mucocutaneous lesions; however, this effect was only sustained at high doses. There are few reports of pyostomatitis-pyodermatitis vegetans in the medical literature. This case highlights key aspects of this extremely rare dermatosis, especially in otherwise healthy patients without inflammatory bowel disease

Real‐world treatment escalation from metformin monotherapy in youth‐onset Type 2 diabetes mellitus: A retrospective cohort study

BackgroundDue to high rates of comorbidities and rapid progression, youth with Type 2 diabetes may benefit from early and aggressive treatment. However, until 2019, the only approved medications for this population were metformin and insulin.ObjectiveTo investigate patterns and predictors of treatment escalation within 5 years of metformin monotherapy initiation for youth with Type 2 diabetes in clinical practice.SubjectsCommercially‐insured patients with incident youth‐onset (10–18 years) Type 2 diabetes initially treated with metformin only.MethodsRetrospective cohort study using a patient‐level medical claims database with data from 2000 to 2020. Frequency and order of treatment escalation to insulin and non‐insulin antihyperglycemics were determined and categorized by age at diagnosis. Cox proportional hazards regression was used to evaluate potential predictors of treatment escalation, including age, sex, race/ethnicity, comorbidities, complications, and metformin adherence (medication possession ratio ≥ 0.8).ResultsThe cohort included 829 (66% female; median age at diagnosis 15 years; 19% Hispanic, 17% Black) patients, with median 2.9 year follow‐up after metformin initiation. One‐quarter underwent treatment escalation (n = 207; 88 to insulin, 164 to non‐insulin antihyperglycemic). Younger patients were more likely to have insulin prescribed prior to other antihyperglycemics. Age at diagnosis (HR 1.14, 95% CI 1.07–1.21), medication adherence (HR 4.10, 95% CI 2.96–5.67), Hispanic ethnicity (HR 1.83, 95% CI 1.28–2.61), and diabetes‐related complications (HR 1.78, 95% CI 1.15–2.74) were positively associated with treatment escalation.ConclusionsIn clinical practice, treatment escalation for pediatric Type 2 diabetes differs with age. Off‐label use of non‐insulin antihyperglycemics occurs, most commonly among older adolescents.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/169332/1/pedi13232_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/169332/2/pedi13232.pd

Subcortical volumes differ in Parkinson&#39;s disease motor subtypes: New insights into the pathophysiology of disparate symptoms

Objectives: Patients with Parkinson’s disease (PD) can be classified, based on their motor symptoms, into the Postural Instability Gait Difficulty (PIGD) subtype or the Tremor Dominant (TD) subtype. Gray matter changes between the subtypes have been reported using whole brain Voxel-Based Morphometry, however, the evaluation of subcortical gray matter volumetric differences between these subtypes using automated volumetric analysis has only been studied in relatively small sample sizes and needs further study to confirm that the negative findings were not due to the sample size. Therefore, we aim to evaluate volumetric changes in subcortical regions and their association with PD motor subtypes. Methods: Automated volumetric MRI analysis quantified the subcortical gray matter volumes of patients with PD in the PIGD subtype (n=30), in the TD subtype (n=30), and in 28 healthy controls. Results: Significantly lower amygdala and globus pallidus gray matter volume was detected in the PIGD, as compared to the TD subtype, with a trend for an association between globus pallidus degeneration and higher (worse) PIGD scores. Furthermore, among all the patients with PD, higher hippocampal volumes were correlated with a higher (better) dual tasking gait speed (r=0.30, p<0.002) and with a higher global cognitive score (r=0.36, p<0.0001). Lower putamen volume was correlated (r=-0.28, p<0.004) with higher (worse) freezing of gait score, an episodic symptom which is common among the PIGD subtype. As expected, differences detected between healthy controls and patients in the PD subgroups included regions within the amygdala and the dorsal striatum but not the ventral striatum, a brain region that is generally considered to be more preserved in PD.Conclusions: The disparate patterns of subcortical degeneration can explain some of the differences in symptoms between the PD subtypes such as gait disturbances and cognitive functions. These findings may, in the future, help to inform a personalized therapeutic approach

Visual rating of White Matter Hyperintensities according to Schelten et al.

<p>Deep White Matter Hyperintensities (DWM); Periventricular Hyperintensities (PVH).</p

An example of periventricular WMHs in two patients with the PIGD subtype and two patients with the TD subtype.

<p>As shown, a subject with PIGD had a low score on the Scheltens scale, while another had a relatively high score (5 out of max. possible 6). Similarly, one patient in the TD group had a low score, while another had a relatively high score. These examples are consistent with the lack of an association between the Scheltens’ scoring and PIGD and TD subtypes that was seen in general.</p

Cerebro-vascular risk factors.

*<p>Entries are % of subjects or mean±SD.</p

Demographics and basic disease characteristics.

<p>Demographics and basic disease characteristics.</p

Correlations between Schelten’s scoring of WMHs and PIGD and TD symptom.

*<p>Entries are Pearson’s correlation coefficient and the associated p-value. Deep White Matter Hyperintensities (DWM); Periventricular Hyperintensities (PVH).</p