Neurogenic orthostatic hypotension in Parkinson's disease: is there a role for locus coeruleus magnetic resonance imaging?

Locus coeruleus (LC) is the main noradrenergic nucleus of the brain, and degenerates early in Parkinson's disease (PD). The objective of this study is to test whether degeneration of the LC is associated with orthostatic hypotension (OH) in PD. A total of 22 cognitively intact PD patients and 52 age-matched healthy volunteers underwent 3 T magnetic resonance (MRI) with neuromelanin-sensitive T1-weighted sequences (LC-MRI). For each subject, a template space-based LC-MRI was used to calculate LC signal intensity (LC contrast ratio-LCCR) and the estimated number of voxels (LCVOX) belonging to LC. Then, we compared the LC-MRI parameters in PD patients with OH (PDOH+) versus without OH (PDOH-) (matched for sex, age, and disease duration) using one-way analysis of variance followed by multiple comparison tests. We also tested for correlations between subject's LC-MRI features and orthostatic drop in systolic blood pressure (SBP). PDOH- and PDOH+ did not differ significantly (p > 0.05) based on demographics and clinical characteristics, except for blood pressure measurements and SCOPA-AUT cardiovascular domain (p < 0.05). LCCR and LCVOX measures were significantly lower in PD compared to HC, while no differences were observed between PDOH- and PDOH+. Additionally, no correlation was found between the LC-MRI parameters and the orthostatic drop in SBP or the clinical severity of autonomic symptoms (p > 0.05). Conversely, RBD symptom severity negatively correlated with several LC-MRI parameters. Our results failed to indicate a link between the LC-MRI features and the presence of OH in PD but confirmed a marked alteration of LC signal in PD patients.

Alzheimer's Disease and Neurosyphilis: Meaningful Commonalities and Differences of Clinical Phenotype and Pathophysiological Biomarkers.

BACKGROUND: Neurosyphilis-associated cognitive and behavioral impairment- historically coined as "general paralysis of the insane"- share clinical and neuroradiological features with the neurodegenerative disease spectrum, in particular Alzheimer's disease (AD). Anatomopathological similarities have been extensively documented, i.e., neuronal loss, fibrillary alterations, and local amyloid-ß deposition. Consequently, accurate classification and timely differential diagnosis may be challenging. OBJECTIVE: To describe clinical, bio-humoral, brain MRI, FDG-PET, and amyloid-PET features in cases of neurosyphilis with an AD-like phenotypical presentation, as well as clinical outcome in terms of response to antibiotic therapy. METHODS: We selected the studies comparing patients with AD and with neurosyphilis associated cognitive impairment, to investigate candidate biomarkers classifying the two neurological diseases. RESULTS: The neuropsychological phenotype of general paralysis, characterized by episodic memory impairment and executive disfunction, substantially mimics clinical AD features. Neuroimaging often shows diffuse or medial temporal cortical atrophy, thus contributing to a high rate of misdiagnosis. Cerebrospinal fluid (CSF)-based analysis may provide supportive diagnostic value, since increased proteins or cells are often found in neurosyphilis, while published data on pathophysiological AD candidate biomarkers are controversial. Finally, psychometric testing using cross-domain cognitive tests, may highlight a wider range of compromised functions in neurosyphilis, involving language, attention, executive function, and spatial ability, which are atypical for AD. CONCLUSION: Neurosyphilis should be considered a potential etiological differential diagnosis of cognitive impairment whenever imaging, neuropsychological or CSF features are atypical for AD, in order to promptly start antibiotic therapy and delay or halt cognitive decline and disease progression.

DBS in tremor with dystonia: VIM, GPi or both? A review of the literature and considerations from a single-center experience.

BACKGROUND: Deep brain stimulation (DBS) is an established treatment for dystonia and tremor. However, there is no consensus about the best surgical targeting strategy in patients with concomitant tremor and dystonia. Both the thalamic ventral intermediate nucleus (VIM) and the globus pallidus pars interna (GPi) have been proposed as targets. Few cases using them together in a double-target approach have also been reported. METHODS: We reviewed the literature on this topic, summarizing results of different target choices. Additionally, we retrospectively report a case series of nine patients with sporadic dystonia and severe tremor treated with a double-target strategy at our center. Outcome measures were the Burke-Fahn-Marsden Dystonia Rating Scale (BFM) and Eq-5d scale. RESULTS: In published studies of patients with dystonia and tremor, VIM-DBS is highly effective on tremor but raise some concerns about dystonia's control, while GPi-DBS is more effective on dystonia but does not always relieve tremor. GPi + VIM-DBS shows good efficacy but is rarely reported and reserved for selected patients. In our patients, the double-target strategy obtained a significant and durable improvement in tremor, dystonia, and quality of life. Additionally, compared with a cohort of patients with tremor treated with VIM-DBS only, significantly lower frequency and intensity of VIM stimulation were required to control tremor. CONCLUSION: Our findings and published evidence seem to support the double-targeting approach as a safe and effective option in selected patients with tremor-dominant dystonia. This strategy appears to provide a more extensive control of either dystonia or tremor and may have a potential for limiting stimulation-related side effects.

Morphometric imaging and quantitative susceptibility mapping as complementary tools in the diagnosis of parkinsonisms.

BACKGROUND AND PURPOSE: In the quest for in vivo diagnostic biomarkers to discriminate Parkinson's disease (PD) from progressive supranuclear palsy (PSP) and multiple system atrophy (MSA, mainly p phenotype), many advanced magnetic resonance imaging (MRI) techniques have been studied. Morphometric indices, such as the Magnetic Resonance Parkinsonism Index (MRPI), demonstrated high diagnostic value in the comparison between PD and PSP. The potential of quantitative susceptibility mapping (QSM) was hypothesized, as increased magnetic susceptibility (Δχ) was reported in the red nucleus (RN) and medial part of the substantia nigra (SNImed) of PSP patients and in the putamen of MSA patients. However, disease-specific susceptibility values for relevant regions of interest are yet to be identified. The aims of the study were to evaluate the diagnostic potential of a multimodal MRI protocol combining morphometric and QSM imaging in patients with determined parkinsonisms and to explore its value in a population of undetermined cases. METHOD: Patients with suspected degenerative parkinsonism underwent clinical evaluation, 3 T brain MRI and clinical follow-up. The MRPI was manually calculated on T1-weighted images. QSM maps were generated from 3D multi-echo T2*-weighted sequences. RESULTS: In determined cases the morphometric evaluation confirmed optimal diagnostic accuracy in the comparison between PD and PSP but failed to discriminate PD from MSA-p. Significant nigral and extranigral differences were found with QSM. RN Δχ showed excellent diagnostic accuracy in the comparison between PD and PSP and good accuracy in the comparison of PD and MSA-p. Optimal susceptibility cut-off values of RN and SNImed were tested in undetermined cases in addition to MRPI. CONCLUSIONS: A combined use of morphometric imaging and QSM could improve the diagnostic phase of degenerative parkinsonisms.