Cerebello-Thalamo-Cortical MR Spectroscopy in Patients with Essential Tremor Undergoing MRgFUS Thalamotomy: A Pilot Study.

Previous literature studies explored the association between brain neurometabolic changes detected by MR spectroscopy and symptoms in patients with tremor, as well as the outcome after deep brain stimulation (DBS) treatment. The purpose of our study was to evaluate the possible changes in cerebello-thalamo-cortical neurometabolic findings using MR spectroscopy in patients submitted to MRgFUS thalamotomy. For this pilot study, we enrolled 10 ET patients eligible for MRgFUS thalamotomy. All patients were preoperatively submitted to 3T MR spectroscopy. Single-voxel MRS measurements were performed at the level of the thalamus contralateral to the treated side and the ipsilateral cerebellar dentate nucleus. Multivoxel acquisition was used for MRS at the level of the contralateral motor cortex. At the 6-month follow-up after treatment, we found a statistically significant increase in the Cho/Cr ratio at the level of the thalamus, a significant increase of the NAA/Cr ratio at the level of the dentate nucleus and a significant decrease of the NAA/Cho ratio at the level of the motor cortex. We found a significant positive correlation between cortical NAA/Cr and clinical improvement (i.e., tremor reduction) after treatment. A significant negative correlation was found between clinical improvement and thalamic and cerebellar NAA/Cr. Confirming some previous literature observations, our preliminary results revealed neurometabolic changes and suggest a possible prognostic role of the MRS assessment in patients with ET treated by MRgFUS.

Evaluation of Cerebral Volume Changes in Patients with Tremor Treated by MRgFUS Thalamotomy.

The purpose of the study is to quantify volumetric variations of cortical and subcortical brain structures after Vim ablation using MRgFUS, and correlate them with the patients' clinical features and treatment outcomes. For this pilot retrospective study we enrolled 31 patients with a mean age of 70.86 years who were eligible for unilateral Vim thalamotomy. Clinical evaluation included tremor severity assessment using the FTM scale and cognitive assessment using the MoCA score. MRI data were acquired with a 3T scanner, using a dedicated 32-channel coil and acquiring a volumetric sequence of T1 3D IR FSPGR (BRAVO), before treatment and one year after MRgFUS thalamotomy. Image processing and volume data extraction were conducted with dedicated software. A volumetric analysis showed a significant reduction (p < 0.05) of the left thalamus 1 year after the treatment in patients with ET. Other significant results were found on the same side in the other nuclei of the basal ganglia and in the cerebellar cortex. In confronting the two groups (ET, PD), no significant differences were found in terms of age, FTM, MoCA scores, or brain volumes. Similarly, no significant correlations were found between the FTM and MoCA scores and the brain volumes before the treatment.

Comprehensive Evaluation of Factors Affecting Tremor Relapse after MRgFUS Thalamotomy: A Case-Control Study.

OBJECTIVE: To identify possible relevant factors contributing to tremor relapse after MRgFUS thalamotomy in patients with essential tremor (ET) and Parkinson's disease (PD). METHODS: We identified patients with tremor relapse from a series of 79 treatments in a single institution. The demographic and clinical characteristics of the study group patients were compared to those of patients who did not relapse in the same follow-up period. Imaging and procedural factors were compared using a control group matched for clinical and demographic characteristics. RESULTS: Concerning clinical and demographic characteristics, we did not find statistically significant differences in gender and age. Seventy-three percent of patients with tremor relapse were Parkinson's disease patients. Using MRI, we found larger thalamotomy lesions at the 1-year follow-up in the control group with stable outcomes, compared to patients with tremor relapse. In the tractography evaluation, we found a more frequent eccentric position of the DRTt in patients with tremor relapse. CONCLUSIONS: The most relevant determining factors for tremor relapse after MRgFUS thalamotomy appear to be tremor from Parkinson's disease and inaccurate thalamic targeting. Size of the thalamotomy lesion can also influence the outcome of treatment.

Comparative evaluation of tractography-based direct targeting and atlas-based indirect targeting of the ventral intermediate (Vim) nucleus in MRgFUS thalamotomy.

To analyze and compare direct and indirect targeting of the Vim for MRgFUS thalamotomy. We retrospectively evaluated 21 patients who underwent unilateral MRgFUS Vim ablation and required targeting repositioning during the procedures. For each patient, in the three spatial coordinates, we recorded: (i) indirect coordinates; (ii) the coordinates where we clinically observed tremor reduction during the verification stage sonications; (iii) direct coordinates, measured on the dentatorubrothalamic tract (DRTT) at the after postprocessing of DTI data. The agreement between direct and indirect coordinates compared to clinically effective coordinates was evaluated through the Bland-Altman test and intraclass correlation coefficient. The median absolute percentage error was also calculated. Compared to indirect targeting, direct targeting showed inferior error values on the RL and AP coordinates (0.019 vs. 0.079 and 0.207 vs. 0.221, respectively) and higher error values on the SI coordinates (0.263 vs. 0.021). The agreement between measurements was higher for tractography along the AP and SI planes and lower along the RL planes. Indirect atlas-based targeting represents a valid approach for MRgFUS thalamotomy. The direct tractography approach is a valuable aid in assessing the possible deviation of the error in cases where no immediate clinical response is achieved.

Seizure burden and neurodevelopmental outcome in newborns with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia: A single center observational study.

OBJECTIVE: To examine the relationship between electrographic seizures and developmental outcome at 18 and 24 months in neonates with moderate and severe hypoxic-ischemic encephalopathy [HIE] treated with therapeutic hypothermia [TH]. STUDY DESIGN: 30 term infants with moderate-severe HIE treated with TH were enrolled prospectively from June 2012 to May 2018. All had continuous single channel amplitude integrated EEG (aEEG) monitoring for a minimum of 72 h and brain MR within 4 weeks. The aEEG was classified by severity of background and seizure burden. MR images were graded by the severity of injury. Outcome (defined abnormal in case of death, dyskinetic or spastic quadriplegic cerebral palsy, epilepsy, or Bayley III score < 85 in all three subscales or < 70 in any individual subscale) was assessed at 18 and 24 months. RESULTS: Seizures were recorded in 24 out of 30 [80 %] neonates and an abnormal outcome was observed in 7 [23 %] of infants. Patients with poor outcome had a statistically significant correlation with: high seizure burden (p = 0.0004), need for more than one antiepileptic drugs (p = 0.006), a persistent abnormal aEEG trace at 48 h (p = 0.0001) and moderate-severe brain injury at MRI (p = 0.0001). Moreover, infants with status epilepticus or frequent seizures reported a significantly association with abnormal MR imaging and poor outcome than patients with sporadic seizures (p = 0.0009). CONCLUSION: The role of seizures in the pathogenesis of brain injury remains controversial. In our cohort the presence of seizures, per se, was not associated with abnormal outcome; however a high seizure burden as well as a persistent abnormal aEEG background pattern and MR lesions resulted significantly associated with poor prognosis.

An experience-based review of HIFU in functional interventional neuroradiology: transcranial MRgFUS thalamotomy for treatment of tremor.

Tremor is a common and very disabling symptom in patients with essential tremor and Parkinson's disease. In the recent years, transcranial ablation of thalamic nuclei using magnetic resonance guided high-intensity focused ultrasound has emerged as a minimally invasive treatment for tremor. The aim of this review is to discuss, in the light of our single-center experience, the technique, current applications, results, and future perspectives of this novel technology.

Severe neurologic and hepatic toxicity in a newborn prenatally exposed to methamphetamine. A case report.

OBJECTIVE: In the recent years the increase of methamphetamines (MTA) abusers women has become an emerging problem. Very little data has been published regarding the effects of prenatal MTA exposure. We describe a case of MTA related toxicity in a term newborn which have early onset of neonatal encephalopathy and liver failure. CASE REPORT: A term infant born to a MTA abuser mother developed seizures and severe neurological symptoms shortly after birth. Methamphetamine was detected both in maternal and in neonatal urine. The laboratoristic tests revealed severe hepatic insufficiency, coagulopathy and thrombocytopenia. Due to neonatal encephalopathy the newborn underwent hypothermia. Phenobarbital, fresh frozen plasma, platelet transfusions and vitamin K were administered. Cranial ultrasonography and magnetic resonance imaging (MRI) showed diffuse white matter damage and two ischemic-hemorrhagic cerebral lesions. Gradually the clinical conditions improved, at 1 month MRI showed a stabilization of cerebral lesions with residual diffuse leukomalacia. Physiotherapy and neurological follow up is ongoing to evaluate the long term effects. CONCLUSIONS: although infrequent, MTA-related toxicity should be suspected in infants with neurologic and hepatic symptoms. Further studies are warranted to confirm our findings in order to identify newborns at high risk of acute MTA toxicity in time to provide them the appropriate support.

Diagnostic accuracy of proton magnetic resonance spectroscopy and perfusion-weighted imaging in brain gliomas follow-up: a single institutional experience.

Objectives The objective of this study was to evaluate whether proton magnetic resonance spectroscopy and perfusion magnetic resonance imaging (MRI) are able to increase diagnostic accuracy in the follow-up of brain gliomas, identifying the progression of disease before it becomes evident in the standard MRI; also to evaluate which of the two techniques has the best diagnostic accuracy. Methods Eighty-three patients with cerebral glioma (50 high-grade gliomas (HGGs), 33 low-grade gliomas (LGGs)) were retrospectively enrolled. All patients underwent standard MRI, H spectroscopic and perfusion echo-planar imaging MRI. For spectroscopy variations of choline/creatine, choline/N-acetyl-aspartate ratio, and lipids and lactates peak were considered. For perfusion 2.0 was considered the cerebral blood volume cut-off for progression. The combination of functional parameters gave a multiparametric score (0-2) to predict outcome. Diagnostic performance was determined by the receiver operating characteristic curve, with sensitivity, specificity, positive predictive and negative predictive values. Results In patients with LGGs a combined score of at least 1 was the best predictor for progression (odds ratio (OR) 3.91) with 8.4 months median anticipation of diagnosis compared to standard MRI. The individual advanced magnetic resonance technique did not show a diagnostic accuracy comparable to the combination of the two. Overall diagnostic accuracy area under the curve (AUC) was 0.881. In patients with HGGs the multiparametric score did not improve diagnostic accuracy significantly. Perfusion MRI was the best predictor of progression (OR 3.65), with 6.7 months median anticipation of diagnosis. Overall diagnostic accuracy AUC was 0.897. Then spectroscopy and perfusion MRI are able to identify tumour progression during follow-up earlier than standard MRI. Conclusion In patients with LGGs the combination of the functional parameters seems to be the best method for diagnosis of progression. In patients with HGGs perfusion is the best diagnostic method.

[Neural activity related to emotional and empathic deficits in subjects with post-traumatic stress disorder who survived the L'Aquila (Central Italy) 2009 earthquake]. / Attività neurale correlata alle difficoltà emozionali ed empatiche in soggetti con disturbo post-traumatico da stress sopravvissuti al terremoto dell'Aquila del 2009.

Post-Traumatic Stress Disorder (PTSD) is a chronic anxiety disorder. The continued efforts to control the distressing memories by traumatized individuals, together with the reduction of responsiveness to the outside world, are called Emotional Numbing (EN). The EN is one of the central symptoms in PTSD and it plays an integral role not only in the development and maintenance of post-traumatic symptomatology, but also in the disability of emotional regulation. This disorder shows an abnormal response of cortical and limbic regions which are normally involved in understanding emotions since the very earliest stages of the development of processing ability. Patients with PTSD exhibit exaggerated brain responses to emotionally negative stimuli. Identifying the neural correlates of emotion regulation in these subjects is important for elucidating the neural circuitry involved in emotional and empathic dysfunction. We showed that PTSD patients, all survivors of the L'Aquila 2009 earthquake, have a higher sensitivity to negative emotion and lower empathy levels. These emotional and empathic deficits are accompanied by neural brain functional correlates. Indeed PTSD subjects exhibit functional abnormalities in brain regions that are involved in stress regulation and emotional responses. The reduced activation of the frontal areas and a stronger activation of the limbic areas when responding to emotional stimuli could lead the subjects to enact coping strategies aimed at protecting themselves from the re-experience of pain related to traumatic events. This would result in a dysfunctional hyperactivation of subcortical areas, which may cause emotional distress and, consequently, impaired social relationships often reported by PTSD patients.

Cerebral Amyloid Angiopathy-Related Inflammation: Report of a Case with Very Difficult Therapeutic Management.

Background. Cerebral amyloid angiopathy-related inflammation (CAA-ri) results from autoimmune response to beta-amyloid deposits in cerebral vessels. Its clinical course and complications have seldom been described in literature. Case Report. In a patient presenting with delirium and left hemiparesis the diagnosis of CAA-ri was supported by the finding of elevated anti-amyloid autoantibodies in the cerebrospinal fluid (CSF). Steroid therapy produced significant improvements in clinical and investigational assessments, but after two months, it caused Acute Respiratory Distress Syndrome. After steroid therapy discontinuation the patient presented a rapidly progressive dementia, Guillain-Barré syndrome, new cerebral ischemic lesions, and thrombosis of the right cephalic and subclavian veins that were treated with subcutaneous heparin. After a week the patient died because of brain hemorrhage. Conclusion. This case suggests caution in steroid therapy discontinuation and antithrombotic therapy administration in patients with CAA-ri. The CSF search of anti-amyloid autoantibodies could be helpful to support the diagnosis.

Neuromyelitis optica: atypical clinical and neuroradiological presentation.

The extreme variability of clinical and MRI findings in the suspicion of Devic's disease always requires the detection of specific antibodies (AQP4). MRI scans were performed with a high-field MRI scanner (1.5T General Electric Signa Horizon): the MRI protocol of the brain employed axial DP, T2, T1, FLAIR and DWI weighted images (wi) and coronal T2-wi. After intravenous administration of contrast medium axial and sagittal T1-weighted images of the brain were repeated. The spine protocol employed after contrast medium included sagittal T2-wi, T2-wi with fat suppression and T1-wi. In May 2004, a 64-year-old healthy Caucasian woman began to suffer loss of motor and thermal sensitivity in the left lower limb. MRI showed non-specific areas of abnormal signal intensity on the deep left frontal and right frontoparietal white matter with no pathological enhancement after contrast medium and a small intramedullary area of altered signal at metameric level C2-C4 with a diagnosis of post-viral transverse myelitis. The patient had two similar episodes years later so the neurologist decided to search for circulating IgG AQP4 with the definitive diagnosis of neuromyelitis optica. In this case, compared to a clinical presentation of atypical deficit neurological involvement, the neuroradiological results of a progressive diffuse involvement of the white matter were atypical.

Neural activity related to cognitive and emotional empathy in post-traumatic stress disorder.

The aim of this study is to evaluate the empathic ability and its functional brain correlates in post-traumatic stress disorder subjects (PTSD). Seven PTSD subjects and ten healthy controls, all present in the L'Aquila area during the earthquake of the April 2009, underwent fMRI during which they performed a modified version of the Multifaceted Empathy Test. PTSD patients showed impairments in implicit and explicit emotional empathy, but not in cognitive empathy. Brain responses during cognitive empathy showed an increased activation in patients compared to controls in the right medial frontal gyrus and the left inferior frontal gyrus. During implicit emotional empathy responses patients with PTSD, compared to controls, exhibited greater neural activity in the left pallidum and right insula; instead the control group showed an increased activation in right inferior frontal gyrus. Finally, in the explicit emotional empathy responses the PTSD group showed a reduced neural activity in the left insula and the left inferior frontal gyrus. The behavioral deficit limited to the emotional empathy dimension, accompanied by different patterns of activation in empathy related brain structures, represent a first piece of evidence of a dissociation between emotional and cognitive empathy in PTSD patients. The present findings support the idea that empathy is a multidimensional process, with different facets depending on distinct anatomical substrates.

Progressive Multifocal Leukoencephalopathy Following Treatment with Rituximab in an HIV-Negative Patient with Non-Hodgkin Lymphoma. A Case Report and Literature Review.

Progressive multifocal leukoencephalopathy (PML) is a rare rapidly progressive demyelinating disease of the central nervous system caused by reactivation of latent John Cunningham (JC) polyomavirus (JCV) infection. We describe an unusual case of PML in a 54-year-old patient with follicular non-Hodgkin lymphoma who received rituximab plus cyclophosphamide, hydroxydaunorubicin, oncovicin and prednisolone (R-CHOP) therapy. She started to notice gradual progressive neurological symptoms about two months after completion of rituximab treatment and was therefore admitted to hospital. On admission, brain CT and MRI showed widespread lesions consistent with a demyelinating process involving the subcortical and deep white matter of the cerebral and cerebellar hemispheres. CT and MRI findings were suggestive of PML, and JC virus DNA was detected by polymerase chain reaction assay of the cerebrospinal fluid and serum. The patient was treated supportively but reported a progressive worsening of the clinical and radiological findings. Our report emphasizes the role of CT and MRI findings in the diagnosis of PML and suggests that PML should be considered in patients with progressive neurological disorders involving the entire nervous system and mainly the white matter, especially in the presence of previous immunomodulatory treatment or immunosuppression.

Dysfunctional neural networks associated with impaired social interactions in early psychosis: an ICA analysis.

The "default mode", or baseline of brain function is a topic of great interest in schizophrenia research. Recent neuroimaging studies report that the symptoms of chronic schizophrenia subjects are associated with temporal frequency alterations as well as with the disruption of local spatial patterns in the default mode network (DMN). Previous studies both on chronic and medicated subjects with psychosis suffered from limitations; on this basis, it was hypothesized that the default mode network showed abnormal activation and connectivity in young and neuroleptic-naïve patients with first-episode psychosis. This study investigated emotional responses to pleasant and unpleasant/disgusting visual stimuli by a resting-state analysis of fMRI-data from 12 untreated first-episode psychosis patients with prevalently negative symptomatology versus 12 healthy subjects. We chose this experimental task to explore the functional link between default mode network and hedonic processing which has been proposed as a marker of cerebral dysfunction in psychotic disorder and implicated in its pathophysiology. Independent Component Analysis (ICA) was used to identify the default mode component. Both healthy and first-episode subjects showed significant spatial differences in the default mode network. In first-episode subjects, medial frontal hypoactivity and cerebellar hyperactivity were correlated with the severity of negative symptoms.

Regional cerebral changes and functional connectivity during the observation of negative emotional stimuli in subjects with post-traumatic stress disorder.

Patients with post-traumatic stress disorder (PTSD) exhibit exaggerated brain responses to emotionally negative stimuli. Identifying the neural correlates of emotion regulation in these subjects is important for elucidating the neural circuitry involved in emotional dysfunction. The aim of this study was to investigate the functional connectivity between the areas activated during emotional processing of negative stimuli in a sample of individuals affected by PTSD compared to a group of healthy subjects. Ten subjects with PTSD (who survived the L'Aquila 2009 earthquake) and ten healthy controls underwent fMRI during which the participants observed 80 images: 40 pictures with negative emotional valence and 40 neutral (scrambled) stimuli. A higher activation was found in the left posterior (LP) insula for PTSD group and in the ventromedial prefrontal cortex (vmPFC) for the healthy group. Two sets of Granger causality modeling analyses were performed to examine the directed influence from LP-insula and vmPFC to other brain regions. Activity in the vmPFC in the healthy group while observing negative stimuli predicted activity in several subcortical regions and insula, while in the PTSD group the LP-insula exerted a positive directed influence on several cortical regions. The hyperactivation in PTSD subjects of subcortical areas such as the insula would underlie the emotional, social, and relational difficulties of PTSD patients.

Apparent diffusion coefficient restriction in the white matter: going beyond acute brain territorial ischemia.

BACKGROUND: Reduction of apparent diffusion coefficient (ADC) values in white matter is not always ischaemic in nature. METHODS: We retrospectively analysed our MRI records featuring reduced ADC values in the centrum semiovale without grey matter involvement or significant vasogenic oedema. RESULTS: Several conditions showed the aforementioned MR findings: moose-horn lesions on coronal images in X-linked Charcot-Marie-Tooth disease; small fronto-parietal lesions in Menkes disease; marked signal abnormalities in the myelinised regions in the acute neonatal form of maple syrup urine disease; strip-like involvement of the corpus callosum in glutaric aciduria type 1; persistent periventricular parieto-occipital abnormalities in phenylketonuria; diffuse signal abnormalities with necrotic evolution in global cerebral anoxia or after heroin vapour inhalation; almost completely reversible symmetric fronto-parietal lesions in methotrexate neurotoxicity; chain-like lesions in watershed ischaemia; splenium involvement that normalises in reversible splenial lesions or leads to gliosis in diffuse axonal injury. CONCLUSION: Neuroradiologists must be familiar with these features, thereby preventing misdiagnosis and inappropriate management.

Neural correlates of automatic perceptual sensitivity to facial affect in posttraumatic stress disorder subjects who survived L'Aquila eartquake of April 6, 2009.

The "Emotional Numbing" (EN) constitutes one of the core symptoms in PTSD although its exact nature remains elusive. This disorder shows an abnormal response of cortical and limbic regions which are normally involved in understanding emotions since the very earliest stages of the development of processing ability. The aim of our study, which included ten physically healthy subjects with PTSD, diagnosed according to DSM-IV-TR, who survived L'Aquila earthquake of April 6, 2009, and 10 healthy controls matching for age, sex and education, was to examine automatic perceptual sensitivity to facial affect in PTSD, through an affective priming task that was administered during functional magnetic resonance (fMRI). Behavioural data revealed in the PTSD group a higher sensitivity to negative facial affect on an automatic processing level. FMRI data analysis revealed that PTSD subjects showed a significantly higher activation in right insula and left amygdala that we did not observe in healthy subjects; on the contrary, healthy controls showed a greater activation of left lingual gyrus. Our data support the hypothesis that PTSD appears to be sensitive to negative affect on an automatic processing level and correlates with the activation of specific areas involved in processing emotions. An elevated activation of these areas may underlie the emotion dysregulation in PTSD and could explain the Emotional Numbing symptom associated with this disorder. The present study suffers of a number of limitations, for instance, the relatively small sample size did not allow the application of alternative statistical models.

Pediatric stroke: clinical findings and radiological approach.

This paper focuses on radiological approach in pediatric stroke including both ischemic stroke (Arterial Ischemic Stroke and Cerebral Sinovenous Thrombosis) and hemorrhagic stroke. Etiopathology and main clinical findings are examined as well. Magnetic Resonance Imaging could be considered as the first-choice diagnostic exam, offering a complete diagnostic set of information both in the discrimination between ischemic/hemorrhagic stroke and in the identification of underlying causes. In addition, Magnetic Resonance vascular techniques supply further information about cerebral arterial and venous circulation. Computed Tomography, for its limits and radiation exposure, should be used only when Magnetic Resonance is not available and on unstable patients.

Primary myxopapillary ependymoma of the cerebellopontine angle: report of a case.

Myxopapillary ependymoma is a rare variant of ependymoma, almost exclusively occurring in the region of the cauda equina and filum terminale. We describe a myxopapillary ependymoma located in the left cerebellopontine angle of a young man suffering from peripheral vertigo and left sensorineural hearing loss for years. The patient underwent surgical removal of the tumour. Microscopic examination showed histological and immunohistochemical features consistent with a diagnosis of myxopapillary ependymoma. Imaging studies of the spine yielded normal findings, confirming the lesion's primary nature. To the best of our knowledge, this is the first case of primary intracranial myxopapillary ependymoma described in this location.