Substantia nigra hyperechogenicity in essential tremor and Parkinson's disease: a longitudinal study.

BACKGROUND AND PURPOSE: Essential tremor (ET) and Parkinson's disease (PD) sometimes overlap in their clinical expression with ET preceding PD onset, often leading to misdiagnosis. Transcranial sonography (TCS) has been shown to be a valid and non-invasive diagnostic tool to identify early idiopathic PD and to differentiate it from ET. The purpose of this study was to investigate the relevance of substantia nigra hyperechogenicity in patients with ET. METHODS: A total of 138 patients (79 with PD, 59 with ET) and 50 matched controls underwent TCS examination at baseline. All patients were followed in a 3-year longitudinal assessment. RESULTS: A total of 10 subjects were excluded from the analysis due to the bilateral absence of a temporal acoustic window. During the follow-up period, 11 of the patients with ET developed new-onset parkinsonian features, without fulfilling criteria for PD diagnosis (ET+). Nine patients developed clinical features meeting diagnostic criteria for probable PD (ET-PD). Patients with ET- did not develop parkinsonian features. For each group, the maximum size of the substantia nigra hyperechogenicity was as follows: 5.62 ± 5.40 mm2 in the control group, 19.02 ± 14.27 mm2 in patients with PD, 9.15 ± 11.26 mm2 in patients with ET-, 20.05 ± 13.78 mm2 in patients with ET+ and 20.13 ± 13.51 mm2 in patients with ET-PD. ET-PD maximum values were significantly different from controls. Maximum values in patients with ET+ were different from both controls and patients with ET-. CONCLUSION: Substantia nigra hyperechogenicity in ET seems to represent a risk marker for developing early parkinsonian symptoms or signs in the 3 years following TCS assessment.

Correction to: The Italian Dystonia Registry: rationale, design and preliminary findings.

In the original article, Gina Ferrazzano was affiliated to Department of Neurology and Psychiatry, Neuromed Institute IRCCS, Sapienza University of Rome, Pozzilli, Italy.The corrected affiliation should be: Neuromed Institute IRCCS, Pozzilli, IS, Italy.

The Italian Dystonia Registry: rationale, design and preliminary findings.

The Italian Dystonia Registry is a multicenter data collection system that will prospectively assess the phenomenology and natural history of adult-onset dystonia and will serve as a basis for future etiological, pathophysiological and therapeutic studies. In the first 6 months of activity, 20 movement disorders Italian centres have adhered to the registry and 664 patients have been recruited. Baseline historical information from this cohort provides the first general overview of adult-onset dystonia in Italy. The cohort was characterized by a lower education level than the Italian population, and most patients were employed as artisans, builders, farmers, or unskilled workers. The clinical features of our sample confirmed the peculiar characteristics of adult-onset dystonia, i.e. gender preference, peak age at onset in the sixth decade, predominance of cervical dystonia and blepharospasm over the other focal dystonias, and a tendency to spread to adjacent body parts, The sample also confirmed the association between eye symptoms and blepharospasm, whereas no clear association emerged between extracranial injury and dystonia in a body site. Adult-onset dystonia patients and the Italian population shared similar burden of arterial hypertension, type 2 diabetes, coronary heart disease, dyslipidemia, and hypothyroidism, while hyperthyroidism was more frequent in the dystonia population. Geographic stratification of the study population yielded no major difference in the most clinical and phenomenological features of dystonia. Analysis of baseline information from recruited patients indicates that the Italian Dystonia Registry may be a useful tool to capture the real world clinical practice of physicians that visit dystonia patients.

Right putamen and age are the most discriminant features to diagnose Parkinson's disease by using 123I-FP-CIT brain SPET data by using an artificial neural network classifier, a classification tree (ClT).

OBJECTIVE: The differential diagnosis of Parkinson's disease (PD) and other conditions, such as essential tremor and drug-induced parkinsonian syndrome or normal aging brain, represents a diagnostic challenge. 123I-FP-CIT brain SPET is able to contribute to the differential diagnosis. Semiquantitative analysis of radiopharmaceutical uptake in basal ganglia (caudate nuclei and putamina) is very useful to support the diagnostic process. An artificial neural network classifier using 123I-FP-CIT brain SPET data, a classification tree (CIT), was applied. CIT is an automatic classifier composed of a set of logical rules, organized as a decision tree to produce an optimised threshold based classification of data to provide discriminative cut-off values. We applied a CIT to 123I-FP-CIT brain SPET semiquantitave data, to obtain cut-off values of radiopharmaceutical uptake ratios in caudate nuclei and putamina with the aim to diagnose PD versus other conditions. SUBJECTS AND METHOD: We retrospectively investigated 187 patients undergoing 123I-FP-CIT brain SPET (Millenium VG, G.E.M.S.) with semiquantitative analysis performed with Basal Ganglia (BasGan) V2 software according to EANM guidelines; among them 113 resulted affected by PD (PD group) and 74 (N group) by other non parkinsonian conditions, such as Essential Tremor and drug-induced PD. PD group included 113 subjects (60M and 53F of age: 60-81yrs) having Hoehn and Yahr score (HY): 0.5-1.5; Unified Parkinson Disease Rating Scale (UPDRS) score: 6-38; N group included 74 subjects (36M and 38 F range of age 60-80 yrs). All subjects were clinically followed for at least 6-18 months to confirm the diagnosis. To examinate data obtained by using CIT, for each of the 1,000 experiments carried out, 10% of patients were randomly selected as the CIT training set, while the remaining 90% validated the trained CIT, and the percentage of the validation data correctly classified in the two groups of patients was computed. The expected performance of an "average performance CIT" was evaluated. RESULTS: For CIT, the probability of correct classification in patients with PD was 84.19±11.67% (mean±SD) and in N patients 93.48±6.95%. For CIT, the first decision rule provided a value for the right putamen of 2.32±0.16. This means that patients with right putamen values <2.32 were classified as having PD. Patients with putamen values ≥2.32 underwent further analysis. They were classified as N if the right putamen uptake value was ≥3.02 or if the value for the right putamen was <3.02 and the age was ≥67.5 years. Otherwise the patients were classified as having PD. Other similar rules on the values of both caudate nuclei and left putamen could be used to refine the classification, but in our data analysis of these data did not significantly contribute to the differential diagnosis. This could be due to an increased number of more severe patients with initial prevalence of left clinical symptoms having a worsening in right putamen uptake distribution. CONCLUSION: These results show that CIT was able to accurately classify PD and non-PD patients by means of 123I-FP-CIT brain SPET data and provided also cut-off values able to differentially diagnose these groups of patients. Right putamen uptake values resulted as the most discriminant to correctly classify our patients, probably due to a certain number of subjects with initial prevalence of left clinical symptoms. Finally, the selective evaluation of the group of subjects having putamen values ≥2.32 disclosed that age was a further important feature to classify patients for certain right putamen values.

Prognostic factors in children with PRES and hematologic diseases.

OBJECTIVES: Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological entity characterized by focal neurological signs, headache, confusion, and seizure, associated with transitory lesions in the posterior areas of the brain detectable with neuroimaging. Among children, one of the most common causes of PRES is cancer. MATERIALS AND METHODS: In this review, we present the cases of 5 children developing PRES after stem cell transplantation for hematological disease and review all the cases reported in English literature to investigate outcomes and associated risk factors. RESULTS: One hundred and eleven cases were reported. Hypertension was very frequent (80%). Clinical features included seizures (80.1%), headache (44.1%), visual disturbance (26.1%), and mental change (48.6%). EEG was abnormal in 27 of 32 patients. MRI revealed characteristic lesions in all patients even in early stages. Abnormal MRI findings in late stages were associated with neurological sequelae. Nineteen patients died (17.1%) of which 2 of PRES. Among alive patients, 17 had neurological sequelae. Four cases of PRES relapse were described. CONCLUSIONS: Thus, all transplant recipients with symptoms consistent with PRES should be promptly recognized to avoid long-term complications or even death.

A novel spinocerebellar ataxia type 15 family with involuntary movements and cognitive decline.

BACKGROUND AND PURPOSE: SCA15 is a recently identified spinocerebellar ataxia with pure cerebellar involvement. Here, we report a novel SCA15 Italian family with atypical clinical features. METHODS: Three affected members from a three-generation family segregating an autosomal dominant cerebellar ataxia underwent clinical examination and genetic tests for hereditary ataxia. RESULTS: All affected members present with cognitive impairment and two of them with mild intermittent involuntary movements in association with the clinical hallmarks of SCA15 (gait ataxia, balance impairment, and dysarthria). Genetic tests detected a large deletion spanning ITPR1 and SUMF1 genes in affected members. CONCLUSION: Our findings help enlarging the clinical spectrum of SCA15.

A magnetization transfer study of mild and advanced Parkinson's disease.

BACKGROUND AND PURPOSE: Magnetization transfer ratio (MTR) technique has identified brain changes in grey and white matter in Parkinson's disease (PD), even in the early phase. However, how these tissue changes differ along the course of the illness is still unclear. This study was aimed at investigating how MTR values change from mild PD (PD1) to patients with advanced PD (PD2). METHODS: We measured MTR values by region of interest, in 11 PD1, 11 PD2 and 10 healthy age-matched subjects. RESULTS: Compared with controls, patients with PD1 exhibited a significant MTR reduction in substantia nigra pars compacta, substantia nigra pars reticulata, putamen, periventricular white matter and parietal white matter. In addition to the changes observed in PD1, the PD2 group exhibited a significant MTR reduction in caudate, pons, frontal white matter and lateral thalamus. CONCLUSION: These results suggest that MTR might reflect morphological changes induced by the disease in distinct brain areas at different stages.

Hyperhomocysteinemia recurrence in levodopa-treated Parkinson's disease patients.

BACKGROUND: Patients with Parkinson's disease (PD) and chronically treated with L-DOPA exhibit, in a percentage of 10-30%, supra-physiological levels of plasma total homocysteinemia (tHcy). In this study, we have investigated, in a group of hyper-homocysteinemic PD patients, the time of hyper-tHcy recurrence after discontinuation of 1-month folate supplementation given to normalize plasma tHcy levels. METHODS: Plasma tHcy, cobalamin and folate were assayed before and after 1-month folate supplementation (5 mg/day), and after 2 and 4 months after folate discontinuation in 29 PD patients (16M/13F, mean age 69.4 +/- 6.9 years) stabilized on a mean L-DOPA dose of 509.4 +/- 312.1 mg/day. RESULTS: After folate supplementation, plasma tHcy levels fell within the normal range in all patients. At the 2-month control after folate discontinuation, plasma tHcy remained within physiological values in 25 out of 29 patients. Conversely, 4 months after folate discontinuation, all patients exhibited hyper-tHcy. CONCLUSIONS: One-month intake of 5 mg/day folate normalizes plasma tHcy levels in all hyper-homocysteinemic PD patients. Following folate discontinuation, hyper-tHcy recurs in all patients within 4 months. Knowledge of this time interval is useful to optimize pulses of folate therapy in hyper-homocysteinemic patients with PD.

Cerebrospinal fluid beta-glucocerebrosidase activity is reduced in Dementia with Lewy Bodies.

The autophagy-lysosomal degradation pathway plays a role in the onset and progression of neurodegenerative diseases. Clinical and genetic studies indicate that mutations of beta-glucocerebrosidase represent genetic risk factors for synucleinopathies, including Parkinson's Disease (PD) and Dementia with Lewy Bodies (DLB). We recently found a decreased activity of lysosomal hydrolases, namely beta-glucocerebrosidase, in cerebrospinal fluid of PD patients. We have thus measured the activity of these enzymes - alpha-mannosidase (EC 3.2.1.24), beta-mannosidase (EC 3.2.1.25), beta-glucocerebrosidase (EC 3.2.1.45), beta-galactosidase (EC 3.2.1.23) and beta-hexosaminidase (EC 3.2.1.52) - in cerebrospinal fluid of patients suffering from DLB, Alzheimer's Disease (AD), Fronto-Temporal Dementia (FTD) and controls. Alpha-mannosidase activity showed a marked decrease across all the pathological groups as compared to controls. Conversely, beta-glucocerebrosidase activity was selectively reduced in DLB, further suggesting that this enzyme might specifically be impaired in synucleinopathies.

CT angiography versus colour-Doppler US in acute dissection of the vertebral artery.

PURPOSE: Conventional digital subtraction angiography (DSA) still represents the criterion standard for the diagnosis of vertebral artery dissection (VAD), but the main drawbacks of this technique include invasiveness, patient discomfort and risk of complications. We evaluated the potential of multidetector computed tomography angiography (CTA) as a noninvasive tool providing high-resolution images of the arterial lumen and wall by comparing the diagnostic accuracy of CTA and colour-Doppler ultrasonography (CDUS) in detecting acute VAD. MATERIALS AND METHODS: We retrospectively reviewed 15 cases of VAD in 15 patients (five men and ten women, age range 28-58 years) who came to our attention between August 2001 and September 2005. The diagnosis was made on the basis of appropriate clinical presentation, absence of atherosclerotic disease in the cerebrovascular circulation and evidence of distinctive CT features, which were subsequently confirmed by conventional angiography used as reference standard. All patients with a clinical suspicion of VAD underwent CDUS of the neck vessels prior to CTA. Accuracy, sensitivity and specificity of CDUS and CTA were expressed as percentages of agreement with the reference angiographic procedure. Interreader concordance for detection of VAD by CTA was calculated with the Cohen K value. RESULTS: The CDUS examinations revealed ten out of 15 VAD, with a sensitivity of 66%, a specificity of 60%, a positive predictive value of 55.5% and a negative predictive value of 70.5%. In five cases, CDUS revealed nonspecific wall and flow alterations; in eight patients, high resistance obstructive flow; and in two patients, intimal flap with demonstration of the true and false lumen. CTA enabled the correct identification of all 15 VAD. The reported sensitivity, specificity, positive predictive value and negative predictive value were 100%, 95%, 93.7% and 100%, respectively. With regard to localisation of VAD, CTA showed 100% correlation with DSA. The differences in CTA and CDUS sensitivity (100% vs 66%), specificity (95% vs 60%), and overall diagnostic accuracy (97% vs 62.8%), assessed by cross tabulations and compared by using the McNemar's two-sided test, were significant (p<0.05). CONCLUSIONS: Multidetector CTA is a sensitive technique for the diagnosis of VAD. Used as a complement to unenhanced brain CT, it has the advantage of being readily available and easy to perform.

Secondary prevention of cardioembolic stroke: oldest and newest promises.

Atrial fibrillation (AF) is the most common cause of cardioembolism. An update on secondary prevention strategies used to protect from the risk of stroke AF patients is presented. The main line of actions of stroke prevention in AF are antithrombotics (anticoagulant or antiplatelet), antiarrhythmics (for rate control and sinus rhythm restore), mechanical means (for occlusion of the left atrial appendage or protection of the internal carotid artery from emboli). Classic pharmacological prevention with K vitamin Kantagonists such as warfarin may be overcome by direct thrombin inhibitors like ximelagatran and melagatran. New ablation technologies promise to cure, at least a part of Nonvalvolae AF in the community, restoring sinus rhythm. Recent achievements on endovascular procedures deploying carotid artery implants provide an opportunity to divert emboli to nonhazardous locations, whereas cardiac devices can seal left atrial appendages and avoid risk of clot migration in the blood stream. In the next decade, the challenge will be to understand competitiveness between old and new drugs with endovascular implants.

Multimodal use of computed tomography in early acute stroke, part 2.

Computed tomography (CT) scan remains the most widely technique in the cerebrovascular emergency, as it is largely available, minimally invasive, fast, cheap and reliable. Noncontrast enhanced CT (NeCT) imaging can show early signs of infarction in ischemic stroke; however, it could not show if the ischemic tissue is irreversibly damaged. CT perfusion (CTP) imaging has been shown to predict stroke location and size and can provide information about ischemic cerebral parenchyma not definitively compromised. CT angiography (CTA) could highlight stenosis or occlusion both in intracranial and extracranial vessels. By combining NeCT, CTP, and CTA the entire cerebrovascular axis can be imaged during acute stroke. Currently, the term "multimodal CT" indicates the combined use of these three techniques in order to obtain a complete picture of the extension of ischemic damage in acute stroke patients.

Educational approach on stroke training in Europe.

According to the European Stroke Initiative (EUSI), stroke care is best delivered within a stroke unit by a specialized multidisciplinary stroke team led by stroke specialists. At present, there is no guideline or consensus regarding training requirements or clinical standards that stroke specialists should achieve. It is envisaged that stroke specialists in training would need to acquire adequate knowledge and competency across three major areas of stroke care: acute stroke, stroke rehabilitation, and stroke prevention. With an EUSI document, the European Association of Young Neurologists and Trainees Stroke Subspeciality Group aims to promote discussion on the many aspects of stroke training and the requirements to be a stroke specialist in the European community. The ultimate purpose is to agree on common standards to promote good clinical care and effective stroke prevention across Europe. In the future, this may be translated into better patient outcome and a reduction in the global burden of this condition.

Assessment of tremor: a new computerised tool for clinical practice.

The quantitative assessment of tremor represents the main difficulty in clinical evaluation. We developed a software package - T-Lab - for the biomechanical analysis of hyperkinetic movement disorders. This software can receive and elaborate data from an electronic device interfaced with a personal computer. The aim of our study was to verify the validity of the PC-aided method proposed in the routine assessment of tremor. We did this by a correlation (regression) analysis between the scores obtained by Webster's Amplitude Clinical Scale and the amplitude data by T-Lab and between EMG data and frequency measures of T-Lab. Forty-seven patients presenting with upper limb tremor were enrolled. Four series of data were obtained: two series for frequency and two for amplitude. A significant correlation between all sets of data compared was found. T-Lab represents a valid, objective and useful device of quantifying tremors in clinical practice.

Neurovascular territory involved in different etiological subtypes of ischemic stroke in the Perugia Stroke Registry.

UNLABELLED: We studied the correlation between the potential causes of stroke (TOAST etiological groups) and the involvement of different vascular territories seen on computed tomography (CT) scans in patients with ischemic stroke. Information from consecutive patients with a first-ever stroke have been prospectively coded and entered into a computerized data bank (Perugia Stroke Registry). A population of 1,719 patients were evaluated: 1,284 patients (74.7%) had ischemic stroke. Large artery disease was the main cause of entire middle cerebral artery (MCA) territory infarcts (40.9%), superficial MCA territory infarcts (35.7%), and watershed infarcts (68.2%). The highest presence of emboligenic heart disease was found in the entire MCA territory infarcts (28.8%) or superficial (29.4%) supratentorial infarcts and in cerebellar infarcts (36.8%). Small artery disease was the most common presumed cause of deep MCA infarcts (75.0%) and posterior cerebral artery (PCA) territory infarcts (52.1%). IN CONCLUSION: stroke location could depend on its etiology. Lacunar infarcts are the most prevalent (36.7%), being mostly localized in the deep MCA territory; large artery disease includes more than two-thirds of watershed infarcts; the most prevalent territories involved in cardioembolic stroke are the entire MCA and posterior fossa.

Magnetization transfer changes of grey and white matter in Parkinson's disease.

Since the attempt to evidence structural brain damage in Parkinson's disease (PD) by conventional magnetic resonance imaging (MRI) is usually disappointing, we have investigated whether the magnetization transfer ratio (MTR) can reflect changes in grey and white matter of PD patients. MTR was quantified in 44 regions of interest (ROIs) in both grey and white matter of 11 non-demented PD patients, ranging from 2 to 4 on the Hoehn and Yahr Scale, and eight age-matched healthy subjects. MTR differences between patients and controls were found in the supratentorial white matter and in the brainstem. In particular, lower MTR values were found in the paraventricular white matter of PD patients (p<0.05) while no differences were observed in corpus callosum, frontal, parietal, occipital lobes or centrum semiovalis. Lower MTR values were found in substantia nigra (p<0.001), red nucleus (p<0.05) and pons (p<0.05) of the patient group. No differences were discovered in basal ganglia and thalamus. These findings suggest that MTR measurements in the paraventricular white matter and brainstem may help to recognize a marker for probable PD.

Risk factors for spread of primary adult onset blepharospasm: a multicentre investigation of the Italian movement disorders study group.

OBJECTIVES: Little is known about factors influencing the spread of blepharospasm to other body parts. An investigation was carried out to deterrmine whether demographic features (sex, age at blepharospasm onset), putative risk, or protective factors for blepharospasm (family history of dystonia or tremor, previous head or face trauma with loss of consciousness, ocular diseases, and cigarette smoking), age related diseases (diabetes, hypertension), edentulousness, and neck or trunk trauma preceding the onset of blepharospasm could distinguish patients with blepharospasm who had spread of dystonia from those who did not. METHODS: 159 outpatients presenting initially with blepharospasm were selected in 16 Italian Institutions. There were 104 patients with focal blepharospasm (mean duration of disease 5.3 (SD 1.9) years) and 55 patients in whom segmental or multifocal dystonia developed (mainly in the cranial cervical area) 1.5 (1.2) years after the onset of blepharospasm. Information was obtained from a standardised questionnaire administered by medical interviewers. A Cox regression model was used to examine the relation between the investigated variables and spread. RESULTS: Previous head or face trauma with loss of consciousness, age at the onset of blepharospasm, and female sex were independently associated with an increased risk of spread. A significant association was not found between spread of dystonia and previous ocular diseases, hypertension, diabetes, neck or trunk trauma, edentulousness, cigarette smoking, and family history of dystonia or tremor. An unsatisfactory study power negatively influenced the validity and accuracy of the negative findings relative to diabetes, neck or trunk trauma, and cigarette smoking. CONCLUSIONS: The results of this exploratory study confirm that patients presenting initially with blepharospasm are most likely to experience some spread of dystonia within a few years of the onset of blepharospasm and suggest that head or face trauma with loss of consciousness preceding the onset, age at onset, and female sex may be relevant to spread. The suggested association between edentulousness and cranial cervical dystonia may be apparent because of the confounding effect of both age at onset and head or face trauma with loss of consciousness. The lack of influence of family history of dystonia on spread is consistent with previous findings indicating that the inheritance pattern is the same for focal and segmental blepharospasm.