Putaminal T1/T2-weighted ratio is increased in PSP compared to PD and healthy controls, a multi-cohort study.

INTRODUCTION: Differentiating Parkinson's disease (PD) from progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) is a common clinical problem. We aimed to apply the T1-/T2-weighted ratio imaging technique, based on standard clinical MRI, to reveal differences in neurodegeneration in three large cohorts. METHODS: Three cohorts, with a total of 405 participants (269 PD, 44 PSP, 38 MSA, 54 controls), were combined and T1/T2-weighted ratio image analyses were carried out. A combination of automatic segmentation and atlas-based ROI were used in this study. The cohorts were combined using the ComBat batch correction procedure. RESULTS: Group differences were found in the putamen (p = 0.040), with higher T1/T2-weighted ratio in this region in PSP compared to PD and healthy controls (p-values 0.010 and 0.007 respectively). Using putaminal T1/T2-weighted ratio for diagnostic separation, a fair performance was found in separating PSP from healthy controls, with an area under the receiver operating characteristic curve of 0.701. CONCLUSION: Different patterns of T1/T2-weighted ratio, reflecting differences in underlying pathophysiology, were found between the groups. Since T1/T2-weighted ratio can be applied to standard clinical MRI sequences to allow more quantitative analyses, this seems to be a promising biomarker for diagnostics and treatment evaluation of parkinsonian disorders for clinical trials.

MRI detection of brain gadolinium retention in multiple sclerosis: Magnetization transfer vs. T1-weighted imaging.

BACKGROUND AND PURPOSE: Evidence of brain gadolinium retention has affected gadolinium-based contrast agent usage. It is, however, unclear to what extent macrocyclic agents are retained and whether their in vivo detection may necessitate nonconventional MRI. Magnetization transfer (MT) could prove suitable to detect gadolinium-related signal changes since dechelated gadolinium ions bind to macromolecules. Therefore, this study aimed to investigate associations of prior gadolinium administrations with MT and T1 signal abnormalities. METHODS: A cohort of 23 persons with multiple sclerosis (MS) (18 females, 5 males, 57 ± 8.0 years) with multiple past gadolinium administrations (median 6, range 3-12) and 23 age- and sex-matched healthy controls underwent 1.5 Tesla MRI with MT, T1-weighted 2-dimensional spin echo, and T1-weighted 3-dimensional gradient echo. The signal intensity index was assessed by MRI in gadolinium retention predilection sites. RESULTS: There were dose-dependent associations of the globus pallidus signal on gradient echo (r = .55, p < .001) and spin echo (r = .38, p = .013) T1-weighted imaging, but not on MT. Relative to controls, MS patients had higher signal intensity index in the dentate nucleus on T1-weighted gradient echo (1.037 ± 0.040 vs. 1.016 ± 0.023, p = .04) with a similar trend in the globus pallidus on T1-weighted spin echo (1.091 ± 0.034 vs. 1.076 ± 0.014, p = .06). MT detected no group differences. CONCLUSIONS: Conventional T1-weighted imaging provided dose-dependent associations with gadolinium administrations in MS, while these could not be detected with 2-dimensional MT. Future studies could explore newer MT techniques like 3D and inhomogenous MT. Notably, these associations were identified with conventional MRI even though most patients had not received gadolinium administrations in the preceding 9 years, suggestive of long-term retention.

Hyperprolactinemia in Adults with Prader-Willi Syndrome.

Prader-Willi syndrome (PWS) is a rare neurodevelopmental genetic disorder typically characterized by body composition abnormalities, hyperphagia, behavioural challenges, cognitive dysfunction, and hypogonadism. Psychotic illness is common, particularly in patients with maternal uniparental disomy (mUPD), and antipsychotic medications can result in hyperprolactinemia. Information about hyperprolactinemia and its potential clinical consequences in PWS is sparse. Here, we present data from an international, observational study of 45 adults with PWS and hyperprolactinemia. Estimated prevalence of hyperprolactinemia in a subset of centres with available data was 22%, with 66% of those related to medication and 55% due to antipsychotics. Thirty-three patients were men, 12 women. Median age was 29 years, median BMI 29.8 kg/m2, 13 had mUPD. Median prolactin was 680 mIU/L (range 329-5702). Prolactin levels were higher in women and patients with mUPD, with only 3 patients having severe hyperprolactinemia. Thyroid function tests were normal, 24 were treated with growth hormone, 29 with sex steroids, and 20 with antipsychotic medications. One patient had kidney insufficiency, and one a microprolactinoma. In conclusion, severe hyperprolactinemia was rare, and the most common aetiology of hyperprolactinemia was treatment with antipsychotic medications. Although significant clinical consequences could not be determined, potential negative long-term effects of moderate or severe hyperprolactinemia cannot be excluded. Our results suggest including measurements of prolactin in the follow-up of adults with PWS, especially in those on treatment with antipsychotics.

Electrolyte and acid-base imbalance in severe COVID-19.

Acute systemic diseases, such as severe infections, can lead to electrolyte and acid-base alterations. To study the presence of electrolyte imbalance in severe COVID-19, we investigated the frequency and consequences of changes in electrolyte and acid-base patterns over time. We performed a retrospective cohort study including 406 patients with severe COVID-19. Levels of electrolytes, base excess, pH, serum osmolality, and hematocrit, the first 2 weeks of hospitalization, were collected daily from the laboratory database and clinical data from patients' medical records. We found that hyponatremia was present in 57% of the patients at admission and 2% in hypernatremia. However, within 2 weeks of hospitalization 42% of the patients developed hypernatremia, more frequently in critically ill patients. Lower levels of sodium and potassium during admission were associated with the need for mechanical ventilation. Decreased pH at admission was associated with both death and the need for mechanical ventilation. Hypernatremia in the ICU was combined with rising base excess and a higher pH. In the group without intensive care, potassium levels were significantly lower in the patients with severe hypernatremia. Presence of hypernatremia during the first 2 weeks of hospitalization was associated with 3.942 (95% CI 2.269-6.851) times higher odds of death. In summary, hypernatremia was common and associated with longer hospital stay and a higher risk of death, suggesting that the dynamics of sodium are an important indicator of severity in COVID-19.

Automated brainstem volumetry can aid in the diagnostics of parkinsonian disorders.

INTRODUCTION: Separating progressive supranuclear palsy (PSP) from Parkinson's disease (PD) and multiple system atrophy (MSA) is often challenging in early disease but is important for appropriate management. Magnetic resonance imaging (MRI) can aid the diagnostics and manual 2D measurements are often used. However, new fully automatic brainstem volumetry could potentially be more accurate and increase availability of brainstem metrics. METHODS: Clinical 3D T1-weighted MRI were obtained from 196 consecutive patients; 29 PSP, 27 MSA, 140 PD. Midbrain-pons ratio and magnetic resonance parkinsonism index (MRPI) 1.0 and 2.0 were manually calculated, and intra-rater and inter-rater reliability was assessed. FreeSurfer was used to automatically segment brainstem substructures, normalized to the intracranial volume. The robustness of the automated analysis was evaluated in 3 healthy controls. The diagnostic accuracy of the brainstem biomarkers was assessed using receiver operating characteristic curves. RESULTS: Automatic brainstem volumetry had good repeatability/reproducibility with intra-scanner coefficient of variation 0.3-5.5% and inter-scanner coefficient of variation 0.9-8.4% in the different brainstem regions. Midbrain volume performs better than planimetric measurements in separating PSP from PD (Area under the curve (AUC) 0.90 compared with 0.81 for midbrain-pons ratio (p = 0.019), 0.77 for MRPI 1.0 (p = 0.007) and 0.81 for MRPI 2.0 (p = 0.021)). Midbrain volume performed on par with planimetry for separation between PSP and MSA. CONCLUSION: Automatic brainstem segmentation is robust and shows promising diagnostic performance in separating PSP from PD and MSA. If further developed, it could play a role in diagnosing PSP and could potentially be used as an outcome in clinical trials.

Mapping of apparent susceptibility yields promising diagnostic separation of progressive supranuclear palsy from other causes of parkinsonism.

There is a need for methods that distinguish Parkinson's disease (PD) from progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), which have similar characteristics in the early stages of the disease. In this prospective study, we evaluate mapping of apparent susceptibility based on susceptibility weighted imaging (SWI) for differential diagnosis. We included 134 patients with PD, 11 with PSP, 10 with MSA and 44 healthy controls. SWI data were processed into maps of apparent susceptibility. In PSP, apparent susceptibility was increased in the red nucleus compared to all other groups, and in globus pallidus, putamen, substantia nigra and the dentate nucleus compared to PD and controls. In MSA, putaminal susceptibility was increased compared to PD and controls. Including all studied regions and using discriminant analysis between PSP and PD, 100% sensitivity and 97% specificity was achieved, and 91% sensitivity and 90% specificity in separating PSP from MSA. Correlations between putaminal susceptibility and disease severity in PD could warrant further research into using susceptibility mapping for monitoring disease progression and in clinical trials. Our study indicates that susceptibility in deep nuclei could play a role in the diagnosis of atypical parkinsonism, especially in PSP.

Quantitative susceptibility mapping differentiates between parkinsonian disorders.

INTRODUCTION: It is often challenging to clinically distinguish between Parkinson's disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Quantitative susceptibility mapping (QSM) is an accurate indirect method for estimating brain iron levels in vivo. This method has yet to be applied in atypical parkinsonism. We aimed to investigate differences in brain iron accumulation parkinsonian disorders and healthy controls using QSM. METHODS: 15 patients with PSP, 11 patients with MSA, 62 patients with PD and 14 healthy controls were included in the study and their phase and magnitude data from susceptibility-weighted magnetic resonance imaging were retrospectively analyzed with an in-house pipeline to create susceptibility maps. Two-way ANCOVA were used to assess group differences. Pairwise comparisons within the ANCOVA were corrected for multiple comparisons. RESULTS: Red nucleus susceptibility was higher in PSP compared with PD (p < 0.001), MSA (p < 0.001) and controls (p < 0.001), which separated PSP from these groups with areas under receiver operating characteristic curve of 0.97, 0.75 and 0.98 respectively. PSP showed higher globus pallidus susceptibility compared with PD (p < 0.001), MSA (p = 0.006) and controls (p < 0.001). Putamen susceptibility was higher in MSA than in PD (p = 0.022) and controls (p = 0.026). Substantia nigra susceptibility was increased in PD compared to controls (p = 0.030). CONCLUSION: We show that all studied parkinsonian disorders have increased susceptibility subcortically, reflecting distinct topographical patterns of abnormal brain iron accumulation. QSM, particularly of the red nucleus, is a promising biomarker in differentiating parkinsonian disorders, and would be interesting to study longitudinally for monitoring disease progression and treatment effects.

Trunk sway measures of postural stability during clinical balance tests in patients with chronic whiplash injury symptoms.

STUDY DESIGN: Trunk sway occurring during clinical stance and gait tasks was compared between a group of subjects with a chronic whiplash injury, resulting from an automobile collision, and a normal collective. OBJECTIVES: To examine if population specific trunk sway patterns for stance and gait could be identified for chronic whiplash injury patients. SUMMARY OF BACKGROUND DATA: Our previous work has established that it is possible to identify specific patterns of stance and gait deficits for vestibular loss (both acute and compensated) patients and those with Parkinson's disease. Our question was whether it was possible to use the same stance and gait tasks to identify patterns of trunk sway differences with respect to those of healthy subjects and individuals with a chronic whiplash injury. METHODS: Twenty-five subjects with history of whiplash injury and 170 healthy age-matched control subjects participated in the study. Trunk sway angular displacements in chronic whiplash patients were assessed for a number of stance and gait tasks similar to those of the Tinetti and Clinical Test of Sensory Interaction and Balance (CTSIB) protocols. We used a lightweight, easy-to-attach, body-worn apparatus to measure trunk angular displacements and velocities in the roll (lateral) and the pitch (forward-backward) planes. RESULTS: Data analysis revealed several significant differences between the two groups. A pattern could be identified, showing greater trunk sway for stance tasks and for complex gait tasks that required task-specific gaze control such as walking up and down stairs. Trunk sway was less, however, for simple gait tasks that demanded large head movements but no task-specific gaze control, such as walking while rotating the head. CONCLUSIONS: Subjects who have a chronic whiplash injury show a characteristic pattern of trunk sway that is different from that of other patient groups with balance disorders. Balance was most unstable during gait involving task-specific head movements which possibly enhance a pathologic vestibulo-cervical interaction.