Gennarina Arabia

Essential Head Tremor Is Associated with Cerebellar Vermis Atrophy: A Volumetric and Voxel-Based Morphometry MR Imaging Study

BACKGROUND AND PURPOSE: Our aim was to investigate the presence of brain gray matter (GM) abnormalities in patients with different forms of essential tremor (ET). MATERIALS AND METHODS: We used optimized voxel-based morphometry (VBM) and manually traced single region-of-interest analysis in 50 patients with familial ET and in 32 healthy subjects. Thirty patients with ET had tremor of the arms (a-ET), whereas the remaining 20 patients had both arm and head tremor (h-ET). RESULTS: VBM showed marked atrophy of the cerebellar vermis in the patients with h-ET with respect to healthy subjects (Pcorrected < .001). Patients with a-ET showed a trend toward a vermal GM volume loss that did not reach a significant difference with respect to healthy controls (Puncorrected < .01). The region-of-interest analysis showed a reduction of the cerebellar volume (CV) in the h-ET group (98.2 ± 13.6 mm3) compared with healthy controls (110.5 ± 15.5 mm3, P < .012) as well as in the entire vermal area (790.3 ± 94.5 mm2, 898.6 ± 170.6 mm2, P < .04 in h-ET and control groups, respectively). CONCLUSIONS: Atrophy of the cerebellar vermis detected in patients with h-ET strongly supports the evidence for the involvement of the cerebellum in the pathophysiology of ET. The lack of a significant CV loss observed in patients with a-ET suggests that a-ET and h-ET might represent distinct subtypes of the same disease.

Diffusion tensor MRI changes in cerebellar structures of patients with familial essential tremor

Objective: The aim of our study was to investigate the microstructural integrity of brain regions functionally involved in the tremor loop in patients with familial essential tremor (FET), using diffusion tensor imaging (DTI). Methods: Twenty-five patients with FET, 15 patients with Parkinson disease (PD), and 15 healthy subjects were studied. DTI was performed to measure fractional anisotropy (FA) and mean diffusivity (MD) in various regions of interest: red nucleus, dentate nucleus (DN), cerebellar white matter, middle (MCP) and superior cerebellar peduncle (SCP), and ventrolateral thalamus. Results: In patients with FET, FA values in the DN (median 0.19, range 0.13–0.23) were reduced (p < 0.001) compared with patients with PD (median 0.37, range 0.32–0.58) and healthy controls (median 0.36, range 0.33–0.40). In patients with FET, FA was also reduced (p = 0.003) and MD values increased (p < 0.001) in the SCP compared with patients with PD and healthy controls. Among patients with FET, those with longer disease duration showed FA values in the DN lower than those with shorter disease duration (p = 0.018). Patients with FET could be completely distinguished from both patient with PD and healthy controls using FA values of the DN alone. Conclusion: Neuroimaging evidence of microstructural changes consistent with neurodegeneration was found in the dentate nucleus (DN) and SCP of patients with familial essential tremor. This suggests that neurodegenerative pathology of cerebellar structures may play a role in essential tremor. Further studies are needed to assess the role of fractional anisotropy and mean diffusivity changes in DN and SCP in the differential diagnosis of essential tremor and Parkinson disease, which may present similar clinical signs at the onset of disease.

Patterns of brain atrophy in Parkinson’s disease, progressive supranuclear palsy and multiple system atrophy

BACKGROUND AND PURPOSE Quantitative analysis of brain atrophy may be useful in differentiating Parkinsons Disease (PD) from Progressive Supranuclear Palsy (PSP) and parkinsonian variant of Multiple System Atrophy (MSA-P); the aim of this study was to identify the volumetric differences of subcortical structures in patients with PD, PSP and MSA-P using a novel and validated fully-automated whole brain segmentation method. METHODS Volumetric MRIs were obtained in 72 patients with PD, 32 patients with PSP, 15 patients with MSA-P, and in 46 control subjects. Subcortical volume was measured automatically by FreeSurfer. Multivariate analysis of covariance, adjusted for intracranial volume (ICV), sex and age, was used to explore group differences. RESULTS No volumetric differences were found between PD and controls group; otherwise the volumes of the cerebellum, the thalamus, the putamen, the pallidum, the hippocampus, and the brainstem were significantly reduced in PSP and MSA-P compared to patients with PD and control subjects. PSP and MSA-P patients only differed in thalamus volume which was smaller in PSP group (p < 0.001). Moreover, patients with PSP and MSA-P showed a ventricular system (including lateral, third and fourth ventricles) larger than that detected in PD and controls (p < 0.001). CONCLUSIONS Volumetric data obtained with automated segmentation of cerebral regions show a significant atrophy of different brain structures in parkinsonisms rather than in PD. Our study also demonstrates that the atrophy of the thalamus only occurs in PSP while the enlargement of the whole ventricular system characterizes both PSP and MSA-P.

Cerebellar Atrophy in Essential Tremor Using an Automated Segmentation Method

BACKGROUND AND PURPOSE: Essential tremor (ET) is a slowly progressive disorder characterized by postural and kinetic tremors most commonly affecting the forearms and hands. Several lines of evidence from physiologic and neuroimaging studies point toward a major role of the cerebellum in this disease. Recently, voxel-based morphometry (VBM) has been proposed to quantify cerebellar atrophy in ET. However, VBM was not originally designed to study subcortical structures, and the complicated anatomy of the cerebellum may hamper the automatic processing of VBM. The aim of this study was to determine the efficacy and utility of using automated subcortical segmentation to identify atrophy of the cerebellum and other subcortical structures in patients with ET. MATERIALS AND METHODS: We used a recently developed automated volumetric method (FreeSurfer) to quantify subcortical atrophy in ET by comparing results obtained with this method with those provided by previous evidence. The study included T1-weighted MR images of 46 patients with ET grouped into those having arm ET (n = 27, a-ET) or head ET (n = 19, h-ET) and 28 healthy controls. RESULTS: Results revealed the expected reduction of cerebellar volume in patients with h-ET with respect to healthy controls after controlling for intracranial volume. No significant difference was detected in any other subcortical area. CONCLUSIONS: Volumetric data obtained with automated segmentation of subcortical and cerebellar structures approximate data from a previous study based on VBM. The current findings extend the literature by providing initial validation for using fully automated segmentation to derive cerebellar volumetric information from patients with ET.

Accuracy of magnetic resonance parkinsonism index for differentiation of progressive supranuclear palsy from probable or possible Parkinson disease.

Combined measurements on conventional magnetic resonance imaging (MRI), such as midbrain area/pons area or magnetic resonance parkinsonism index (MRPI) (pons area/midbrain area × middle cerebellar peduncle width/superior cerebellar peduncle width), have been proposed as powerful tools in the differential diagnosis between progressive supranuclear palsy (PSP) and Parkinson disease (PD). In this study, we evaluated the accuracy of MRPI, compared with midbrain/pons ratio, in distinguishing PSP from probable and possible PD.

Prefrontal alterations in Parkinson's disease with levodopa-induced dyskinesia during fMRI motor task.

Levodopa‐induced dyskinesia represents disabling complication of long‐term therapy with dopaminergic drugs in treating Parkinsons disease (PD). Recently, our group demonstrated that PD patients with levodopa‐induced dyskinesia were characterized by abnormal volumetric changes in the inferior prefrontal gyrus. In this study, the functional relevance of this structural abnormality was explored using functional magnetic resonance imaging. Ten dyskinetic PD patients and 10 nondyskinetic PD patients were studied in the OFF phase with functional magnetic resonance imaging while performing externally and internally triggered visuomotor tasks. Although neither group demonstrated behavioral differences during execution of motor tasks, magnetic resonance imaging analysis detected significant changes in target cortical regions. In particular, PD patients with levodopa‐induced dyskinesia showed significant overactivity in the supplementary motor area and underactivity in the right inferior prefrontal gyrus during execution of both tasks when compared with PD patients without levodopa‐induced dyskinesia. Moreover, these prefrontal functional alterations were significantly correlated with Abnormal Involuntary Movement Scale scores. This functional magnetic resonance imaging study together with our previous volumetric findings highlights the role of the prefrontal cortex in the neuronal mechanisms of dyskinesia.

Increased prefrontal volume in PD with levodopa‐induced dyskinesias: A voxel‐based morphometry study

Levodopa‐induced dyskinesias represent disabling complications from long‐term therapy with dopaminergic drugs for treating Parkinsons disease (PD). Although several neuroimaging studies have reported altered striatofrontal function that contributes to the emergence of these motor complications, the neuroanatomical correlates of this disorder are still unknown. Optimized voxel‐based morphometry (VBM) was applied to the MRI brain images of 36 PD patients with levodopa‐induced dyskinesias, 36 PD patients without levodopa‐induced dyskinesias, and 32 age‐ and sex‐matched controls. The VBM analysis comparing dyskinetic and nondyskinetic groups provided evidence of increased gray matter volume of the bilateral inferior frontal gyrus in dyskinetic patients, a finding that was more evident in patients with early‐onset PD. No significant differences were detected in the dyskinetic and nondyskinetic groups when compared with the controls. Our findings suggest that the presence of dyskinesias in patients with PD is characterized by an aberrant neural plasticity that could play a role in the pathophysiology of these motor complications.

Combined use of DAT-SPECT and cardiac MIBG scintigraphy in mixed tremors

The cooccurrence of rest and postural tremor (mixed tremor) as the predominant clinical manifestation in patients who do not fulfill diagnostic established criteria for essential tremor (ET) or Parkinsons disease (PD) poses a clinical diagnostic challenge. Twenty‐two patients with mixed tremor and additional mild extrapyramidal features, such as bradykinesia and rigidity, 20 patients with probable PD, 10 patients with probable ET, and 18 controls were investigated through the combined use of dopamine transporter 123I‐FP‐CIT‐single‐photon emission tomography (DAT‐SPECT) and cardiac 123metaiodobenzylguanidine (MIGB) scintigraphy. Six of the 22 mixed‐tremor patients had normal DAT‐SPECT, a condition usually found in patients with ET, whereas 16 patients showed damage to the nigrostriatal system. Cardiac MIBG allowed further differentiation between these 16 patients because eight of them had decreased tracer uptakes (heart/mediastinum [H/M] ratio in delayed image, H/M ratio delayed: 1.16 ± 0.11, P < 0.001 vs controls), indicating a PD, whereas the remaining eight had normal cardiac tracer uptakes, a finding suggestive of a parkinsonian syndrome (H/M ratio delayed: 1.90 ± 0.13). Both DAT‐SPECT and cardiac MIBG scintigraphies were abnormal in the 20 patients with probable PD, whereas these were normal in both the patients with probable ET as well as in the controls. Our study suggests that the combined use of both DAT‐SPECT and MIBG scintigraphy in mixed tremors with additional extrapyramidal features can help distinguish patients with ET from those with PD and parkinsonism.

Fronto-parietal overactivation in patients with essential tremor during Stroop task.

Neuropsychological dysfunctions have been consistently reported in essential tremor but the underlying neurobiological mechanisms are unknown. We explored potential abnormalities in the neural network involved in cognitive functions in patients with essential tremor by using functional magnetic resonance imaging. The functional response of 12 patients with essential tremor and 12 matched controls was studied while performing a functional magnetic resonance imaging Stroop task aimed to assess attentional control and evaluating executive functions. Despite similar performances during this task, patients with essential tremor showed greater magnitude of brain response in the dorsolateral prefrontal cortex and in the inferior parietal cortex with respect to controls. Our study shows that patients with essential tremor require additional cognitive effort to achieve comparable performance levels on test of attentional control.

Prefrontal thickening in PD with levodopa-induced dyskinesias: New evidence from cortical thickness measurement

PURPOSE Neurodegenerative processes in Parkinsons disease (PD) patients with levodopa-induced dyskinesias (LID) are still a matter of debate. Recently, we demonstrated that this clinical phenotype is associated with an abnormal gray matter increase in the prefrontal cortex when compared to PD without LID. This evidence was found by using voxel-based morphometry (VBM). However, VBM may not be the most appropriate procedure to assess cortical pathology, since its normalization/smoothing steps reduce the ability to anatomically characterize sulci and gyri. The aim of this study is to better delineate the LID-related anatomical abnormalities by using an advanced neuroimaging method that provides a direct and objective measure of the cortical morphology. METHODS Surface-based investigation of cortical mantle (cortical thickness) was carried out by using Freesurfer in two groups of treated PD patients with LID (no 29) and without LID (no 30), and one group of age- and sex-matched controls (no 24). RESULTS Cortical thickness analysis revealed a pronounced increase of thickness in the right inferior frontal sulcus in PD patients with LID with respect to PD patients without LID. DISCUSSION The current study confirms our previous morphological findings on the role of the prefrontal cortex in the pathophysiology of LID and delineates with more precision the anatomical abnormalities characterizing this clinical phenotype.