Association study between four polymorphisms in the HFE, TF and TFR genes and Parkinson's disease in southern Italy.

Iron overload may lead to neurodegenerative disorders such as Parkinson's disease (PD) and alterations of iron-related genes might be involved in the pathogenesis of this disease. The gene of haemochromatosis (HFE) encodes the HFE protein which interacts with the transferrin receptor (TFR), lowering its affinity for iron-bound transferrin (TF). We examined four known polymorphisms, C282Y and H63D in the HFE gene, G258S in the TF gene and S82G in the TFR gene, in 181 sporadic PD patients and 180 controls from Southern Italy to investigate their possible role in susceptibility to PD. No significant differences were found in genotype and allele frequencies between PD and controls for all the polymorphisms studied, suggesting that these variants do not contribute significantly to the risk of PD.

An magnetic resonance imaging T2*-weighted sequence at short echo time to detect putaminal hypointensity in Parkinsonisms.

At 1.5 T, T2*-weighted gradient echo (GE) sequences are more sensitive in revealing mineral deposition in the basal ganglia than standard T2 weighted sequences. T2*-weighted GE sequences, however, may detect putaminal hypointensities either in patients affected by parkinsonian syndromes or in healthy subjects. The aim of this study was to identify the magnetic resonance imaging (MRI) T2*-weighted sequence which more specifically detected putaminal hypointensities differentiating atypical parkinsonian syndromes from Parkinson's disease (PD) and control subjects. In a sample of 38 healthy subjects, we performed three T2*-weighted GE sequences at increasing time echo (TE; TE = 15 millisecond, TE = 25 millisecond, and echoplanar at TE = 40 millisecond; T2* sequences study). The sequence not showing any putaminal abnormality in the healthy subjects was then used to assess putaminal signal intensity in 189 patients with PD, 20 patients with multiple system atrophy (MSA), 41 patients with progressive supranuclear palsy (PSP), and in 150 age and sex-matched control subjects. In the T2* sequences study, the T2*-weighted TE = 15 (T2*/15) did not show any putaminal abnormalities in the healthy subjects. This sequence detected putaminal hypointensities in a significantly higher proportion of patients with MSA (35%, P < 0.05) and PSP (24.4%, P < 0.05) than in patients with PD (5.3%), but in none of the controls. The sensitivity of putaminal hypointensity in T2*/15 sequence was 25.4% for PD, 43.9% for PSP, and 55% for MSA versus controls whereas the specificity was 93.2% for all groups. Despite the suboptimal sensitivity, the high specificity of the T2*/15 sequence performed on routine MRI suggests its usefulness in clinical practice for identifying putaminal hypointensities associated with parkinsonian disorders.

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.

Myocardial (123)I-MIBG scintigraphy for differentiation of Lewy bodies disease from FTD.

Clinical distinction between Lewy bodies disease (LBD) and frontotemporal dementia (FTD) is sometimes difficult. Nigrostriatal dopaminergic degeneration occurs in both LBD and FTD, limiting helpfulness of DAT imaging to differentiate these forms of dementia. Several studies have emphasized the usefulness of myocardial scintigraphy with (123)Metaiodobenzylguanidine ((123)I-MIGB) in assessing the sympathetic nerve terminals in LBD demonstrating that cardiac (123)I-MIGB uptake is decreased in patients with this disease. We investigated the role of cardiac (123)I-MIBG scintigraphy in differentiating patients with LBD from those with FTD. Clinical diagnosis of LBD and FTD was determined according to established consensus criteria. Nine patients with LBD (1 possible and 8 probable), 6 patients with FTD, and 16 control subjects were involved in the study. The heart to mediastinum ratio (H/M) of (123)I-MIBG uptake was markedly reduced in all patients with LBD (H/M early: 1.25±0.12; delayed: 1.14±0.13) whereas it was normal in patients with FTD (H/M early: 1.86±0.20; delayed: 1.80±0.23) and in controls (H/M early: 1.91±0.17; delayed: 1.99±0.19), suggesting that cardiac (123)I-MIBG scintigraphy can help distinguish patients with LBD from those with FTD.

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 Parkinson's 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 (123)I-FP-CIT-single-photon emission tomography (DAT-SPECT) and cardiac (123)metaiodobenzylguanidine (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.

Cardiac MIBG scintigraphy in Primary Progressive Freezing Gait.

Freezing of gait (FOG) generally occurs as a late manifestation of Parkinson's Disease (PD). FOG, however, can present in isolation, constituting the so-called "Primary Progressive Freezing Gait"(PPFG). Myocardial (123)Metaiodiobenzylguanidine (MIBG) enables the assessment of postganglionic sympathetic cardiac nerve terminals. MIBG uptake reflects sympathetic system integrity, and reduced myocardial uptake of the tracer has been observed in nearly all patients with PD. We investigated MIBG uptake in 7 patients with PPFG, 14 patients with mild PD, and 6 patients with advanced PD and FOG (PD-FOG), and 18 control subjects. Our study shows that myocardial MIBG uptake was normal in all patients with PPFG (H/M ratio: mean+/-SD, 1.85+/-0.11 early; 1.71+/-0.15 delayed) and in the controls (H/M ratio: mean+/-SD, 1.94+/-0.18 early; 2.02+/-0.19 delayed) whereas it was markedly decreased in the patients with mild and advanced PD (H/M ratio: mean+/-SD, PD: 1.17+/-0.02 early; 1.16+/-0.02 delayed; PD-FOG: 1.22+/-0.10 early; 1.08+/-0.06 delayed). Our findings demonstrate that cardiac sympathetic denervation did not occur in patients with PPFG, confirming that PPFG and PD are distinct diseases.

Apparent diffusion coefficient of the superior cerebellar peduncle differentiates progressive supranuclear palsy from Parkinson's disease.

The early diagnosis of progressive supranuclear palsy (PSP) may be challenging, because of clinical overlapping features with Parkinson's disease (PD) and other parkinsonian syndromes such as the Parkinsonian variant of multiple system atrophy (MSA-P). Conventional MRI can help in differentiating parkinsonian disorders but its diagnostic accuracy is still unsatisfactory. On the basis of the pathological demonstration of superior cerebellar peduncle (SCP) atrophy in patients with PSP, we assessed the SCP apparent diffusion coefficient (ADC) values in patients with PSP, PD, and MSA-P in order to evaluate its differential diagnostic value in vivo. Twenty-eight patients with PSP (14 with possible-PSP and 14 with probable-PSP), 15 PD, 15 MSA-P, and 16 healthy subjects were studied by using diffusion weighted imaging (DWI). ADC was calculated in regions of interest defined in the left and right SCP by two clinically blinded operators. Intrarater (r = 0.98, P < 0.001) and interrater reliability (r = 0.97; P < 0.001) for SCP measurements were high. Patients with PSP had higher SCP rADC values (median 0.98 x 10(-3)mm(2)/s) than patients with PD (median 0.79 x 10(-3) mm(2)/s, P < 0.001), MSA-P (median 0.79 x 10(-3) mm(2)/s, P < 0.001), and healthy controls (median 0.80 x 10(-3) mm(2)/s, P < 0.001). DWI discriminated patients with PSP from PD and healthy subjects on the basis of SCP rADC individual values (100% sensitivity and specificity) and from patients with MSA-P (96.4% sensitivity and 93.3% specificity). The higher values of rADC in SCP of patients with PSP correspond with the in vivo microstructural feature of atrophy detected postmortem and provide an additional support for early discrimination between PSP and other neurodegenerative parkinsonisms.