Cerebellar Volume and Disease Staging in Parkinson's Disease: An ENIGMA-PD Study.

peer reviewed[en] BACKGROUND: Increasing evidence points to a pathophysiological role for the cerebellum in Parkinson's disease (PD). However, regional cerebellar changes associated with motor and non-motor functioning remain to be elucidated. OBJECTIVE: To quantify cross-sectional regional cerebellar lobule volumes using three dimensional T1-weighted anatomical brain magnetic resonance imaging from the global ENIGMA-PD working group. METHODS: Cerebellar parcellation was performed using a deep learning-based approach from 2487 people with PD and 1212 age and sex-matched controls across 22 sites. Linear mixed effects models compared total and regional cerebellar volume in people with PD at each Hoehn and Yahr (HY) disease stage, to an age- and sex- matched control group. Associations with motor symptom severity and Montreal Cognitive Assessment scores were investigated. RESULTS: Overall, people with PD had a regionally smaller posterior lobe (dmax  = -0.15). HY stage-specific analyses revealed a larger anterior lobule V bilaterally (dmax  = 0.28) in people with PD in HY stage 1 compared to controls. In contrast, smaller bilateral lobule VII volume in the posterior lobe was observed in HY stages 3, 4, and 5 (dmax  = -0.76), which was incrementally lower with higher disease stage. Within PD, cognitively impaired individuals had lower total cerebellar volume compared to cognitively normal individuals (d = -0.17). CONCLUSIONS: We provide evidence of a dissociation between anterior "motor" lobe and posterior "non-motor" lobe cerebellar regions in PD. Whereas less severe stages of the disease are associated with larger motor lobe regions, more severe stages of the disease are marked by smaller non-motor regions

Parkinson's disease and brain mitochondrial dysfunction: a functional phosphorus magnetic resonance spectroscopy study

In spite of several evidences for a mitochondrial impairment in Parkinson's disease (PD), so far it has not been possible to show in vivo mitochondrial dysfunction in the human brain of PD patients. The authors used the high temporal and spatial resoln. 31 phosphorus magnetic resonance spectroscopy (31P MRS) technique, which they have previously developed in normal subjects and in patients with mitochondrial diseases to study mitochondrial function by observing high-energy phosphates (HEPs) and intracellular pH (pH) in the visual cortex of 20 patients with PD and 20 normal subjects at rest, during, and after visual activation. In normal subjects, HEPs remained unchanged during activation, but rose significantly (by 16%) during recovery, and pH increased during visual activation with a slow return to rest values. In PD patients, HEPs were within the normal range at rest and did not change during activation, but fell significantly (by 36%) in the recovery period; pH did not reveal a homogeneous pattern with a wide spread of values. Energy unbalance under increased oxidative metab. requirements, i.e., the postactivation phase, discloses a mitochondrial dysfunction that is present in the brain of patients with PD even in the absence of overt clin. manifestations, as in the visual cortex. This is in agreement with our previous findings in patients with mitochondrial disease without clin. central nervous system (CNS) involvement. The heterogeneity of the physicochem. environment (i.e., pH) suggests various degrees of subclin. brain involvement in PD. The combined use of MRS and brain activation is fundamental for the study of brain energetics in patients with PD and may prove an important tool for diagnostic purposes and, possibly, to monitor therapeutic interventions. [on SciFinder (R)

Visual cortex spectrum and brain temperature measurement.

<p>Voxel of 20x20x10 mm centred on the calcarine sulcus of a subject (A) from which a 1H MR unfitted spectrum (B) is obtained. Spectra acquisition parameters: PRESS sequence, TR 2000 ms, TE 270 ms. The MR signals corresponding to water and N-Acetyl-Aspartate are identified (respectively H2O and NAA). The chemical shift used for temperature calculations is shown by arrows. (C) shows the centrum semiovale voxel of 20x20x10 mm.</p

MR brain spectra acquisition for temperature measurement.

<p>On the x axis time is represented (minutes). The bars show the time during which each spectrum is acquired, at rest, during visual stimulation and recovery. Each bar corresponds to one spectrum and to one temperature measurement. The entire study takes 18.5 minutes for each subject.</p

Comparison between fiber optic thermometry and MRS thermometry in a brain-like phantom.

<p>The first row reports fiber optic measured phantom <u>temperatures,</u> the second row reports MRS measured phantom temperatures. Temperatures are reported in °C.</p><p>Comparison between fiber optic thermometry and MRS thermometry in a brain-like phantom.</p

Visual cortex brain temperature single values.

<p>Each of the 20 rows corresponds to a different subject: for each patient brain temperature in the visual cortex is reported through the five different states (rest, first part of visual stimulation, second part of visual stimulation, first part of recovery, second part of recovery).</p><p>Visual cortex brain temperature single values.</p

Brain temperature mean values

<p>Values are reported as °C (group mean), in parentheses SD.</p><p>Values are rounded at 0.20 °C steps.</p><p>Brain temperature mean values</p

Central nervous system trans-synaptic effects of acute axonal injury : a 1-H magnetic resonance spectroscopy study

N-acetylaspartate (NAA) has previously been proposed as a neuronal marker. 1H magnetic resonance spectroscopy (MRS) is able to detect NAA in brain, and decreases of NAA have been documented after brain injury. The reason for this decrease is not fully understood and neuron loss damage and "dysfunction" have all been proposed. It is hypothesized that acute central nervous system (CNS) deafferentation causes a trans-synaptic NAA decrease and that high resolution 1H MRS is able to detect such a decrease. To test this hypothesis, an experimental model was used in which axonal lesions were obtained by stretch injury in guinea pig right optic nerve (95-99% crossed fibers). The trans-synaptic concentration of NAA, total creatine (Cr), and the NAA/Cr ratio in lateral geniculate bodies (LGB) and superior colliculi (SC) sample extracts were measured 72 h later by high resolution 1H MRS. In the left LGB/SC, which is where right optic nerve fibers project, reductions of NAA and NAA/Cr were found whereas Cr levels were normal. NAA, NAA/Cr, and Cr values were all normal in the right LGB/SC. Histology and EM findings revealed no abnormalities. At 7 days, left LGB/SC NAA and NAA/Cr values were in the normal range. It was concluded that 1) acute deafferentation in the CNS causes a trans-synaptic decrease of NAA levels that can be detected by 1H MRS and 2) NAA decrease may be due to changes of NAA metabolism caused by functional neuronal inactivity rather than neuronal loss, injury or "dysfunction." 1H MRS is a potential tool for the study of functional effect of CNS lesions in vivo

Magnetic resonance spectroscopy in Parkinson's disease and parkinsonian syndromes

This paper looks at the use of magnetic resonance spectroscopy (MRS) for diagnostic and research purposes in Parkinson’s disease and parkinsonian syndromes. The review considers both proton MRS (1H MRS) and phosphorus MRS (31 P MRS) studies. MRS is useful for diagnostic purposes, helping to differentiate Parkinson’s disease from other parkinsonian syndromes. Even more usefully, MRS can be used for non invasive in vivo human researc

VBM analysis: PCA patients compared to healthy controls showed a widespread pattern of bilateral grey matter loss, predominantly affecting the posterior areas of the brain.

<p>The opposite contrast (PCA patients more than controls) did not reveal any significant difference. Statistical threshold: p<0.05 Family Wise Error (FWE) corrected at cluster level. See text for further details.</p