Luisa Chiapparini

Age-related Iron Deposition in the Basal Ganglia: Quantitative Analysis in Healthy Subjects

PURPOSE To determine the values of iron accumulation in the basal ganglia of healthy volunteers of different ages with R2* and raw signal intensity measurements from T1-weighted magnetic resonance (MR) images, supported by voxel-based relaxometry (VBR), and to compare them with previously reported iron concentrations found in autopsy material. MATERIALS AND METHODS The ethics committee approved the study, and the participants or their parents gave written informed consent. Eighty subjects (41 female and 39 male subjects; age range, 1-80 years) were examined at 1.5 T. For each subject, R2* values were calculated. Curves for R2* versus age were obtained for globus pallidus (GP), putamen, caudate nucleus, substantia nigra (SN), and frontal white matter (FWM). To highlight possible differences in iron concentration among the age decades, VBR was applied. Signal intensity values were estimated on T1-weighted fast low-angle shot images, and regions of interest were drawn in each nucleus. R2* values were also compared with iron concentrations reported in a postmortem study. Statistical analysis was performed (t test), and a difference with P < .05 (FDR corrected) was significant. RESULTS The curves for R2* versus age showed an exponential increase with increasing age in all the basal ganglia. VBR demonstrated significant differences (P < .05, corrected) in the comparison between the 2nd and the following decades for lenticular nuclei. Good correlation coefficients were found for GP (R(2) = 0.64), putamen (R(2) = 0.51), and SN (R(2) = 0.53) when compared with findings in the postmortem study. Signal intensity curves were similar to the R2* curves. CONCLUSION R2* measurements can be used to quantify brain iron accumulation and thus may allow better evaluation of neurodegenerative diseases associated with iron deposition.

Stimulation of the globus pallidus internus for childhood-onset dystonia

We report the results of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in 12 patients with childhood‐onset generalized dystonia refractory to medication, including 3 patients with status dystonicus. There were 8 patients who had DYT1‐negative primary dystonia, 1 had DYT1‐positive dystonia, and 3 had symptomatic dystonia. Stimulation was effective in all but 1 patient. Dystonic postures and movements of the axis and limbs responded to DBS to a greater extent than oromandibular dystonia and fixed dystonic postures. These findings provide further evidence that pallidal stimulation is an effective treatment for intractable childhood‐onset dystonia, including status dystonicus, and together with previous findings, suggest that it should be considered the treatment of choice for these conditions.

Spinal radiological findings in nine patients with spontaneous intracranial hypotension.

Abstract. Cranial magnetic resonance imaging (MRI) findings in spontaneous intracranial hypotension (SIH) are well known, while spinal studies have received less attention. Radiological spinal findings in nine patients with SIH are presented, looking for possible characteristic features. Five of the nine patients had histories of previous minor trauma, one of previous surgery; in three patients possible relevant preceding events were completely absent. All nine patients had cervical, seven thoracic, and four lumbar spine MRI studies; post-contrast studies were obtained in seven cases, MRI myelograms in five. Radioisotope myelocisternography was performed in four patients and myelo-CT in four. Epidural fluid collections were found in seven patients. In six cases the dural sac had collapsed, with a festooned appearance; intense epidural enhancement on post-contrast studies demonstrated marked dilatation of the epidural venous plexus. In three cases an irregular root sleeve suggested a possible point of cerebrospinal fluid (CSF) leakage. Myelo-CT demonstrated the CSF fistula in two cases, radioisotope myelocisternography in three. The pattern of spinal abnormalities is different from that seen in cranial MRI for anatomical reasons: in the spinal canal the dura is not adherent to the bone; therefore, collapse of the dural sac and dilatation of epidural venous plexus occur, rather than subdural hematomas. In most cases the search for the dural tear is difficult. Radioisotope cisternography is probably the most sensitive examination for documenting the leakage of CSF out of the subarachnoid space; myelo-CT may precisely demonstrate the point of the CSF fistula, whereas MRI may only suggest it.

Rasmussen's encephalitis: Early characteristics allow diagnosis

Objective: To identify early manifestations of Rasmussen encephalitis (RE) that can prompt early and reasonably secure diagnosis, allowing medical or surgical therapies at an early stage when they may be more effective in slowing the disease. Methods: The authors studied 12 patients with clinical and neuropathologic diagnosis of RE, followed from disease onset, assessing clinical history, imaging, and EEG and focusing on early characteristics. Anti-GluR3 antibody assays were also considered in 11 patients. Results: By 4 months from first symptoms, all cases had 1) refractory focal seizures with a predominant motor component, 2) slow focal activity on EEG contralateral to the motor manifestations, and 3) focal contralateral white matter hyperintensity with insular cortical atrophy on neuroimaging. Less constant or later findings were epilepsia partialis continua, oligoclonal bands, and serum anti-GluR3 antibodies. Conclusions: The association of partial seizures with focal EEG and neuroimaging changes allows a tentative diagnosis of RE 4 to 6 months after first symptoms.

Periventricular Nodular Heterotopia: Classification, Epileptic History, and Genesis of Epileptic Discharges

Summary:  Purpose. Periventricular nodular heterotopia (PNH) is among the most common malformations of cortical development, and affected patients are frequently characterized by focal drug‐resistant epilepsy. Here we analyzed clinical, MRI, and electrophysiologic findings in 54 PNH patients to reevaluate the classification of PNH, relate the anatomic features to epileptic outcome, and ascertain the contribution of PNH nodules to the onset of epileptic discharges.

Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation

Neurodegeneration with brain iron accumulation (NBIA) comprises a clinically and genetically heterogeneous group of disorders with progressive extrapyramidal signs and neurological deterioration, characterized by iron accumulation in the basal ganglia. Exome sequencing revealed the presence of recessive missense mutations in COASY, encoding coenzyme A (CoA) synthase in one NBIA-affected subject. A second unrelated individual carrying mutations in COASY was identified by Sanger sequence analysis. CoA synthase is a bifunctional enzyme catalyzing the final steps of CoA biosynthesis by coupling phosphopantetheine with ATP to form dephospho-CoA and its subsequent phosphorylation to generate CoA. We demonstrate alterations in RNA and protein expression levels of CoA synthase, as well as CoA amount, in fibroblasts derived from the two clinical cases and in yeast. This is the second inborn error of coenzyme A biosynthesis to be implicated in NBIA.

Iron-related MRI images in patients with pantothenate kinase-associated neurodegeneration (PKAN) treated with deferiprone: Results of a phase II pilot trial

The safety and efficacy of the oral iron‐chelating agent deferiprone on magnetic resonance pallida iron concentration and on clinical status were investigated in 10 patients affected by pantothenate kinase–associated neurodegeneration.

Anti–amyloid β autoantibodies in cerebral amyloid angiopathy–related inflammation: Implications for amyloid-modifying therapies

Cerebral amyloid angiopathy–related inflammation (CAA‐ri) is characterized by vasogenic edema and multiple cortical/subcortical microbleeds, sharing several aspects with the recently defined amyloid‐related imaging abnormalities (ARIA) reported in Alzheimers disease (AD) passive immunization therapies. Herein, we investigated the role of anti–amyloid β (Aβ) autoantibodies in the acute and remission phases of CAA‐ri.

Diffusion Tensor Imaging Shows Different Topographic Involvement of the Thalamus in Progressive Supranuclear Palsy and Corticobasal Degeneration

BACKGROUND AND PURPOSE: In progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), postmortem studies show different topographic involvement of the thalamus, basal ganglia, and their cortical connections. Diffusion tensor imaging (DTI) is an MR imaging technique sensitive to gray and white matter microstructure integrity. This study was performed to determine whether DTI may demonstrate microstructural differences between PSP and CBD, particularly within the thalamus and its cortical connections. MATERIALS AND METHODS: Nine patients with probable PSP, 11 with probable CBD, and 7 controls formed the study group. Apparent diffusion coefficient average (ADCave) and fractional anisotropy (FA) values were measured in regions of interest positioned in the ventrolateral (motor), medial, anterior, and posterior regions of the thalami, basal ganglia, fronto-orbital white matter, cingulum, supplementary motor area (SMA), and precentral and postcentral gyri in patients and controls. RESULTS: In PSP, ADCave values were increased in several areas: the thalamus, particularly in its anterior and medial nuclei; cingulum; motor area; and SMA. FA values were particularly decreased in the fronto-orbital white matter, anterior cingulum, and motor area. In CBD, ADCave was increased in the motor thalamus, in the precentral and postcentral gyri, ipsilateral to the affected frontoparietal cortex, and in the bilateral SMA. FA was mainly decreased in the precentral gyrus and SMA, followed by the postcentral gyrus and cingulum. CONCLUSIONS: In patients with PSP, thalamic involvement was diffuse and prevalent in its anterior part, whereas in CBD involvement was asymmetric and confined to the motor thalamus. DTI may be useful in the differential diagnosis of these 2 parkinsonian disorders.

Can MR Imaging Diagnose Adult-Onset Alexander Disease?

BACKGROUND AND PURPOSE: In recent years, the discovery that mutations in the glial fibrillary acidic protein gene (GFAP) were responsible for Alexander disease (AD) brought recognition of adult cases. The purpose of this study was to demonstrate that MR imaging allows identification of cases of AD with adult onset (AOAD), which are remarkably different from infantile cases. MATERIALS AND METHODS: In this retrospective study, brain and spinal cord MR imaging studies of 11 patients with AOAD (7 men, 4 women; age range, 26–64 years; mean age, 43.6 years), all but 1 genetically confirmed, were reviewed. Diffusion and spectroscopic investigations were available in 6 patients each. RESULTS: Atrophy and changes in signal intensity in the medulla oblongata and upper cervical spinal cord were present in 11 of 11 cases and were the diagnostic features of AOAD. Minimal to moderate supratentorial periventricular abnormalities were seen in 8 patients but were absent in the 3 oldest patients. In these patients, postcontrast enhancement was also absent. Mean diffusivity was not altered except in abnormal white matter (WM). Increase in myo-inositol (mIns) was also restricted to abnormal periventricular WM. CONCLUSIONS: Awareness of the MR pattern described allows an effective selection of the patients who need genetic investigations for the GFAP gene. This MR pattern even led to identification of asymptomatic cases and should be regarded as highly characteristic of AOAD.