Parkinsonism in a pair of monozygotic CADASIL twins sharing the R1006C mutation: a transcranial sonography study.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common hereditary cerebral small vessel disease, is caused by mutations in the NOTCH3 gene on chromosome 19. Clinical manifestations of CADASIL include recurrent transient ischemic attacks, strokes, cognitive defects, epilepsy, migraine and psychiatric symptoms. Parkinsonian features have variably been reported in CADASIL patients, but only a few patients showed a clear parkinsonian syndrome. We studied two patients, a pair of monozygotic twins, carrying the R1006C mutation of the NOTCH3 gene and affected by a parkinsonian syndrome. For the first time in CADASIL patients, we used transcranial sonography (TCS) to assess basal ganglia abnormalities. TCS showed a bilateral hyperechogenic pattern of substantia nigra in one twin, and a right hyperechogenic pattern in the other. In both patients, lenticular nuclei showed a bilateral hyperechogenic pattern, and the width of the third ventricle was slightly increased. The TCS pattern found in our CADASIL patients is characteristic neither for Parkinson's disease, nor for vascular parkinsonism and seems to be specific and related to the disease-specific pathological features.

Parkinsonism is a late, not rare, feature of CADASIL: a study on Italian patients carrying the R1006C mutation.

BACKGROUND AND PURPOSE: To describe parkinsonism as a clinical manifestation of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. METHODS: We report 5 patients carrying the R1006C mutation in the exon 19 of NOTCH3 gene. All cases presented late onset, slowly progressive parkinsonism, not responsive to l-dopa. We performed brain MRI and (123)I-FP-CIT SPECT in all and in 3 additional patients carrying the same mutation but without parkinsonism. Four patients with parkinsonism underwent myocardial (123)I-meta-iodobenzylguanidine scintigraphy. RESULTS: In all patients, brain MRI showed widespread ischemic lesions in the periventricular white matter, the internal and external capsules, the basal ganglia, and thalami. (123)I-FP-CIT SPECT showed symmetrical or asymmetrical reduction of tracer uptake in the putamen, with inconstant caudate involvement. Myocardial (123)I-meta-iodobenzylguanidine scintigraphy resulted normal. Nigrostriatal denervation was also demonstrated in 2 patients without parkinsonism. CONCLUSIONS: In cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, parkinsonism may be a not rare, late onset manifestation. The clinical picture, the lack of response to dopaminergic treatment, and MRI findings suggest a vascular parkinsonism, which may be preceded by a protracted presymptomatic phase.

Rapid genetic analysis, imaging with 18F-DOPA-PET/CT scan and laparoscopic surgery in congenital hyperinsulinism.

Congenital hyperinsulinism (CHI) is responsible for profound hypoglycaemia which needs aggressive treatment in order to prevent neurological damage. Mutations in seven different genes have been held responsible for the inappropriate insulin secretion, typical of this condition. The most common cause of CHI is autosomal recessive mutations in the ABCC8 and KCNJ11 genes which encode for two subunits (SUR 1 and Kir6.2, respectively) of the pancreatic B-cell ATP-sensitive potassium channel. Furthermore, histopathological lesions, diffuse and focal, have been associated with different genetic alterations. [18F]Fluorodopa PET/CT imaging, in most cases, differentiates focal from diffuse disease and is 100% accurate in localizing the focal lesion. Recently laparoscopic pancreatectomy has been performed and is curative in the focal form. We report a case in which clinical experience together with rapid genetic analysis, imaging with 18F-DOPA-PET/CT and laparoscopic surgery, were able to guide the correct clinical management of this condition.

Technetium-99m sestamibi scintigraphy is sensitive and specific for the staging and the follow-up of patients with multiple myeloma: a multicentre study on 397 scans.

We evaluated the additional benefit of Technetium(99)-sestamibi (99mTc-MIBI) scanning in comparison with standard X-ray techniques for multiple myeloma patients either at diagnosis or during follow-up. Between February 2001 and January 2005, 397 whole body scans were acquired. On 229 scans performed at diagnosis, 146 (64%) were positive and 81 cases have discordant X-ray results. The sensitivity of 99mTc-MIBI and X-ray were 77% and 45% respectively. As a result of 99mTc-MIBI, 40% of asymptomatic myeloma patients were up-staged. The positivity of 99mTc-MIBI correlated significantly with all of the most relevant clinical and biological parameters. Multivariate analysis selected only high reactive C protein (P = 0.0005), bone marrow infiltration (P = 0.02) and bone pain (P = 0.002) as factors affecting 99mTc-MIBI pattern. In 22 patients with solitary myeloma, 99mTc-MIBI was positive in 86% of cases and detected more disease sites than X-ray. Among 168 scans performed during follow-up, 99mTc-MIBI presented high specificity in patients showing a complete response (CR; 86%), and correlated with myeloma activity and with response to therapy. At multivariate analysis, a positive pattern correlated with bone marrow infiltration (P = 0.002) and disease status other than CR (P = 0.03). We conclude that 99mTc-MIBI scanning is an additional diagnostic tool with a high specificity for the staging and the follow-up of multiple myeloma patients.

Radiotherapy planning: PET/CT scanner performances in the definition of gross tumour volume and clinical target volume.

PURPOSE: Positron emission tomography is the most advanced scintigraphic imaging technology and can be employed in the planning of radiation therapy (RT). The aim of this study was to evaluate the possible role of fused images (anatomical CT and functional FDG-PET), acquired with a dedicated PET/CT scanner, in delineating gross tumour volume (GTV) and clinical target volume (CTV) in selected patients and thus in facilitating RT planning. METHODS: Twenty-eight patients were examined, 24 with lung cancer (17 non-small cell and seven small cell) and four with non-Hodgkin's lymphoma in the head and neck region. All patients underwent a whole-body PET scan after a CT scan. The CT images provided morphological volumetric information, and in a second step, the corresponding PET images were overlaid to define the effective target volume. The images were exported off-line via an internal network to an RT simulator. RESULTS: Three patient were excluded from the study owing to change in the disease stage subsequent to the PET/CT study. Among the remaining 25 patients, PET significantly altered the GTV or CTV in 11 (44%) . In five of these 11 cases there was a reduction in GTV or CTV, while in six there was an increase in GTV or CTV. CONCLUSION: FDG-PET is a highly sensitive imaging modality that offers better visualisation of local and locoregional tumour extension. This study confirmed that co-registration of CT data and FDG-PET images may lead to significant modifications of RT planning and patient management.