Decreased Gray-White Matter Contrast of [11C]-PiB Uptake in Cognitively Unimpaired Subjects with Severe Obstructive Sleep Apnea.

BACKGROUND: Very recently, cognitively normal, middle-aged adults with severe obstructive sleep apnea (OSA) were shown to have regional cortical amyloid-ß deposits. In the normal brain, amyloid tracer (e.g., [11C]-PiB) uptake is observed in white matter (WM) but not in cortical gray matter (GM), resulting in clear GM-WM contrast. There are no reports on possible changes in this contrast in severe OSA. OBJECTIVES: Evaluate changes in the global [11C]-PiB GM-WM contrast and study if factors reflecting clinical and imaging characteristics are associated with them. DESIGN AND SETTING: Cross-sectional imaging study. PARTICIPANTS: 19 cognitively intact middle-aged (mean 44 years) patients with severe OSA (Apnea-Hypopnea Index >30/h), carefully selected to exclude any other possible factors that could alter brain health. MEASUREMENTS: Detailed neuroimaging (amyloid PET, MRI). Signs of possible alterations in amyloid tracer GM-WM contrast and kinetics were studied with static and dynamic [11C]-PiB PET and WM structures with detailed 3.0T MRI. RESULTS: Static [11C]-PiB PET uptake showed significantly decreased GM-WM contrast in 5 out of 19 patients. This was already clearly seen in visual evaluation and also detected quantitatively using retention indexes. Dynamic imaging revealed decreased contrast due to alterations in trace accumulation in the late phase of [11C]-PiB kinetics. Decreased GM-WM contrast in the late phase was global in nature. MRI revealed no corresponding alterations in WM structures. Importantly, decreased GM-WM contrast was associated with smoking (p = 0.007) and higher Apnea-Hypopnea Index (p = 0.001). CONCLUSIONS: Severe OSA was associated with decreased GM-WM contrast in amyloid tracer uptake, with significant correlation with clinical parameters of smoking and AHI. The results support and further extend the current understanding of the deleterious effect of severe OSA on proper amyloid clearance, possibly reflecting dysfunction of the brain glymphatic system.

Quantitative Three-Dimensional Assessment of the Pharmacokinetic Parameters of Intra- and Peri-tumoural Tissues on Breast Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

We aimed to assess the feasibility of three-dimensional (3D) segmentation and to investigate whether semi-quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters are associated with traditional prognostic factors for breast cancer. In addition, we evaluated whether both intra-tumoural and peri-tumoural DCE parameters can differentiate the breast cancers that are more aggressive from those that are less aggressive. Consecutive patients with newly diagnosed invasive breast cancer and structural breast MRI (3.0 T) were included after informed consent. Fifty-six patients (mean age, 57 years) with mass lesions of > 7 mm in diameter were included. A semi-automatic image post-processing algorithm was developed to measure 3D pharmacokinetic information from the DCE-MRI images. The kinetic parameters were extracted from time-signal curves, and the absolute tissue contrast agent concentrations were calculated with a reference tissue model. Markedly, higher intra-tumoural and peri-tumoural tissue concentrations of contrast agent were found in high-grade tumours (n = 44) compared to low-grade tumours (n = 12) at every time point (P = 0.006-0.040), providing positive predictive values of 90.6-92.6% in the classification of high-grade tumours. The intra-tumoural and peri-tumoural signal enhancement ratios correlated with tumour grade, size, and Ki67 activity. The intra-observer reproducibility was excellent. We developed a model to measure the 3D intensity data of breast cancers. Low- and high-grade tumours differed in their intra-tumoural and peri-tumoural enhancement characteristics. We anticipate that pharmacokinetic parameters will be increasingly used as imaging biomarkers to model and predict tumour behavior, prognoses, and responses to treatment.

A multiparametric classification system for lesions detected by breast magnetic resonance imaging.

BACKGROUND: To validate a new categorisation scheme for suspicious breast lesions according to the well-defined Breast Imaging Reporting and Data System (BI-RADS) magnetic resonance imaging (MRI) lexicon descriptors, apparent diffusion coefficients (ADC), T2-weighted signal intensity (SI), and kinetic curve assessment categories. METHODS: The MRI descriptors and ADC were analysed in 697 lesions detected in 499 subjects. The descriptors were classified into Minor, Intermediate, and Major findings, and were divided into the BI-RADS subcategories 3, 4A, 4B, 4C, and 5 according to the number of descriptors. Positive predictive values (PPV) were calculated for each descriptor. The descriptors were then fitted into a multinomial logistic regression model to determine the odds ratio for a malignant diagnosis. The PPV were measured for the new categories and compared with the assigned PPV of the BI-RADS descriptors. RESULTS: The PPV for MRI descriptors ranged from 17.9%-100%. Of the 697 lesions assessed, 19 (2.7 %) were categorized as BI-RADS 3, 27 (3.9 %) as 4A, 53 (7.6 %) as 4B, 174 (25.0 %) as 4C, and 424 (60.8 %) as 5. None of the subjects in BI-RADS category 3 had a malignant diagnosis. The PPV for malignancy increased progressively with increasing BI-RADS category (4A, 11.1 %; 4B, 28.3 %; 4C, 64.4 %; 5, 94.8 %). All descriptor groups were significant in the logistic regression model. CONCLUSIONS: This study shows that using BI-RADS MRI descriptors together with ADC and T2-weighted SI in a multiparametric classification system can yield an applicable categorisation of lesions with PPV values within the recommended ranges for BI-RADS categories.

Feasibility of mapping breast cancer with supine breast MRI in patients scheduled for oncoplastic surgery.

OBJECTIVES: To prospectively determine the feasibility of preoperative supine breast MRI in breast cancer patients scheduled for oncoplastic breast-conserving surgery. METHODS: In addition to a diagnostic prone breast MRI, a supplementary supine MRI was performed with the patient in the surgical position including skin markers. Tumours' locations were ink-marked on the skin according to findings obtained from supine MRI. Changes in tumours' largest diameter and locations between prone and supine MRI were measured and compared to histology. Nipple-to-tumour and tumour-to-chest wall distances were also measured. Tumours and suspicious areas were surgically removed according to skin ink-markings. The differences between MRI measurements with reference to histopathology were evaluated with the paired-sample t test. RESULTS: Fourteen consecutive patients, 15 breasts and 27 lesions were analysed. Compared to histology, prone MRI overestimated tumour size by 47.1% (p = 0.01) and supine MRI by 14.5% (p = 0.259). In supine MRI, lesions' mean diameters and areas were smaller compared to prone MRI (- 20.9%, p = 0.009 and - 38.3%, p = 0.016, respectively). This difference in diameter was more pronounced in non-mass lesions (- 31.2%, p = 0.031) compared to mass lesions (- 9.2%, p = 0.009). Tumours' mean distance from chest wall diminished by 69.4% (p < 0.001) and from nipple by 18.2% (p < 0.001). Free microscopic margins were achieved in first operation in all patients. CONCLUSIONS: Supine MRI in the surgical position is feasible and useful in the precise localisation of prone MRI-detected lesions and provides a helpful tool to implement in surgery. Supine MRI more accurately determines tumours' size and location and might have an important role to diminish overestimations. KEY POINTS: • Breath-hold supine breast MRI is feasible using commercially available coils and sequences. • Size and area of lesions on MRI were consistently smaller when measured from the supine position as compared to the prone position. • Supine breast MRI is useful in the precise preoperative localisation of prone MRI-detected lesions. •.

Left atrial appendage morphology and relative contrast agent concentration in patients undergoing coronary artery CTA.

AIM: To evaluate whether certain morphological features of the left atrial appendage (LAA) would influence the LAA/ascending aorta (AA) radiodensity ratio, as a reflection of the blood flow conditions in the LAA. MATERIALS AND METHODS: Eight-hundred and eight consecutive patients undergoing computed tomography angiography (CCTA) were evaluated. Of these, 749 had no history of atrial fibrillation and none had suffered acute stroke. The LAA/AA radiodensity ratio, and the length, lobe number, and morphological classification of LAAs were assessed. RESULTS: The distribution of morphological classes for LAAs were: windsock 62.3%, cactus 18.6%, chicken wing 10.0%, and cauliflower 9.2%. The mean LAA/AA radiodensity ratio was 0.87±0.14 (range 0.22-1.44). Female gender (p=0.001), elevated body mass index (BMI; r=-0.129; p=0.003), and diabetes (p=0.03) were associated with lower LAA/AA radiodensity ratios, while heart failure (p=0.017), significant coronary artery stenosis (p=0.010), and LAAs with multiple lobes (p=0.018), exhibited higher LAA/AA radiodensity ratios. Multiple regression analysis revealed that a short one-lobed cauliflower morphology was an independent predictor (p=0.007) of a decreased LAA/AA radiodensity ratio. CONCLUSION: A decline in the LAA/AA radiodensity ratio may reflect decreased blood flow in the LAA, paralleling spontaneous echo contrast in transoesophageal echocardiography. Thus, CCTA might be of value in recognising LAA structures that predispose to decreased blood flow.

Preoperative sentinel lymph node localization in vulvar cancer: preliminary experience with inguinal intradermal contrast-enhanced ultrasound.

OBJECTIVE: To evaluate the feasibility and diagnostic performance of intradermal contrast-enhanced ultrasound (CEUS) sentinel lymph node (SLN) procedure in vulvar cancer. METHODS: Twelve consecutive patients with vulvar cancer underwent preoperatively inguinal CEUS SLN examination and guide wire marking of the enhanced lymph nodes. Altogether, 20 groins were examined with CEUS contrast agent injections including 8 bilateral groins due to midline tumours. One groin was excluded due to previous inguinal surgery. The results of the CEUS examinations were compared to conventional SLN biopsy using radiocolloid scintigraphy and/or methylene blue dye and final postoperative histopathology. RESULTS: The inguinal sentinel CEUS procedure had a technical success rate of 94.7% (18/19 injections) for identifying a potential inguinal SLN. Conventional SLN biopsy using lymphoscintigraphy and/or methylene blue dye was successfully performed in 16 groins. Compared to conventional SLN biopsy, the overall sensitivity was 81.2% (13/16 injections). Additionally, CEUS detected enhancing SLNs in two cases when traditional SLN procedure failed to do so. All metastatic SLNs (n = 5) were correctly identified by CEUS procedure. CONCLUSIONS: Intradermal CEUS SLN localization can be applied in the inguinal lymphatic region in patients with vulvar cancer. Further studies are needed to verify the clinical value of this method. KEY POINTS: • CEUS is a feasible method for inguinal SLN detection in vulvar cancer • All metastatic inguinal SLNs were identified by CEUS procedure • Further studies are needed to verify the clinical value of this method.

Frontotemporal dementia as a comorbidity to idiopathic normal pressure hydrocephalus (iNPH): a short review of literature and an unusual case.

Behavioural variant frontotemporal dementia (bvFTD) and idiopathic normal pressure hydrocephalus (iNPH) are neurodegenerative diseases that can present with similar symptoms. These include decline in executive functions, psychomotor slowness, and behavioural and personality changes. Ventricular enlargement is a key radiological finding in iNPH that may also be present in bvFTD caused by the C9ORF72 expansion mutation. Due to this, bvFTD has been hypothesized as a potential comorbidity to iNPH but bvFTD patients have never been identified in studies focusing in clinical comorbidities with iNPH. Here we describe a patient with the C9ORF72 expansion-associated bvFTD who also showed enlarged ventricles on brain imaging. The main clinical symptoms were severe gait disturbances and psychiatric problems with mild cognitive decline. Cerebrospinal fluid removal increased the patient's walking speed, so a ventriculoperitoneal shunt was placed. After insertion of the shunt, there was a significant improvement in walking speed as well as mild improvement in cognitive function but not in neuropsychiatric symptoms relating to bvFTD. Comorbid iNPH should be considered in bvFTD patients who have enlarged ventricles and severely impaired gait.

In Vivo MRI Measurement of Spinal Cord Displacement in the Thoracolumbar Region of Asymptomatic Subjects with Unilateral and Sham Straight Leg Raise Tests.

BACKGROUND: Normal displacement of the conus medullaris with unilateral and bilateral SLR has been quantified and the "principle of linear dependence" has been described. PURPOSE: Explore whether previously recorded movements of conus medullaris with SLRs are i) primarily due to transmission of tensile forces transmitted through the neural tissues during SLR or ii) the result of reciprocal movements between vertebrae and nerves. STUDY DESIGN: Controlled radiologic study. METHODS: Ten asymptomatic volunteers were scanned with a 1.5T magnetic resonance (MR) scanner using T2 weighted spc 3D scanning sequences and a device that permits greater ranges of SLR. Displacement of the conus medullaris during the unilateral and sham SLR was quantified reliably with a randomized procedure. Conus displacement in response to unilateral and sham SLRs was quantified and the results compared. RESULTS: The conus displaced caudally in the spinal canal by 3.54±0.87 mm (mean±SD) with unilateral (p≤.001) and proximally by 0.32±1.6 mm with sham SLR (p≤.542). Pearson correlations were higher than 0.99 for both intra- and inter-observer reliability and the observed power was 1 for unilateral SLRs and 0.054 and 0.149 for left and right sham SLR respectively. CONCLUSIONS: Four relevant points emerge from the presented data: i) reciprocal movements between the spinal cord and the surrounding vertebrae are likely to occur during SLR in asymptomatic subjects, ii) conus medullaris displacement in the vertebral canal with SLR is primarily due to transmission of tensile forces through the neural tissues, iii) when tensile forces are transmitted through the neural system as in the clinical SLR, the magnitude of conus medullaris displacement prevails over the amount of bone adjustment.

Sensorimotor, visual, and auditory cortical atrophy in Unverricht-Lundborg disease mapped with cortical thickness analysis.

BACKGROUND AND PURPOSE: EPM1, caused by mutations in the CSTB gene, is the most common form of PME. The most incapacitating symptom of EPM1 is action-activated and stimulus-sensitive myoclonus. The clinical severity of the disease varies considerably among patients, but so far, no correlations have been observed between quantitative structural changes in the brain and clinical parameters such as duration of the disease, age at onset, or myoclonus severity. The aim of this study was to evaluate possible changes in CTH of patients with EPM1 compared with healthy controls and to correlate those changes with clinical parameters. MATERIALS AND METHODS: Fifty-three genetically verified patients with EPM1 and 70 healthy volunteers matched for age and sex underwent 1.5T MR imaging. T1-weighted 3D images were analyzed with CTH analysis to detect alterations. The patients were clinically evaluated for myoclonus severity by using the UMRS. Higher UMRS scores indicate more severe myoclonus. RESULTS: CTH analysis revealed significant thinning of the sensorimotor and visual and auditory cortices of patients with EPM1 compared with healthy controls. CTH was reduced with increasing age in both groups, but in patients, the changes were confined specifically to the aforementioned areas, while in controls, the changes were more diffuse. Duration of the disease and the severity of myoclonus correlated negatively with CTH. CONCLUSIONS: Cortical thinning in the sensorimotor areas in EPM1 correlated significantly with the degree of the severity of the myoclonus and is most likely related to the widespread stimulus sensitivity in EPM1.

Post-mortem findings in 10 patients with presumed normal-pressure hydrocephalus and review of the literature.

AIMS: Neuropathological features of idiopathic normal-pressure hydrocephalus (iNPH) are poorly characterized. Brain biopsy during life may help in the differential diagnosis of dementia, but post-mortem validation of biopsy findings is scarce. Here we review and report brain biopsy and post-mortem neuropathological findings in patients with presumed NPH. METHODS: We evaluated 10 patients initially investigated by intraventricular pressure monitoring and a frontal cortical biopsy for histological and immunohistochemical assessment as a diagnostic procedure for presumed NPH. RESULTS: Out of the 10 patients, eight were shunted and seven benefited. Until death, six had developed severe and two mild cognitive impairment. One was cognitively unimpaired, and one was mentally retarded. Three subjects displayed amyloid-ß (Aß) aggregates in their frontal cortical biopsy obtained at the initial procedure. One of these patients developed Alzheimer's disease during a follow-up time of nearly 10 years. One patient with cognitive impairment and NPH suffered from corticobasal degeneration. In six patients various vascular lesions were seen at the final neuropathological investigation. Five of them were cognitively impaired, and in four vascular lesions were seen sufficient in extent to be considered as causative regarding their symptoms. CONCLUSIONS: The frequent finding of vascular pathology in NPH is intriguing, suggesting that vascular alterations might be causative of cognitive impairment in a notable number of patients with NPH and dementia. Brain biopsy can be used to detect Aß aggregates, but neuropathological characteristics of iNPH as a distinct disease still need to be discovered.

Functional MRI and motor behavioral changes obtained with constraint-induced movement therapy in chronic stroke.

BACKGROUND: The clinical benefits of intensive stroke rehabilitation vary individually. We used multimodal functional imaging to assess the relationship of clinical gain and imaging changes in patients with chronic stroke whose voluntary motor control improved after constraint-induced movement therapy (CIMT). METHODS: Eleven patients (37.6 ± 36.8 months from stroke) were studied by functional MRI (fMRI), transcranial magnetic stimulation (TMS), and behavioral assessment of hand motor control (Wolf Motor Function Test) before and after 2 weeks of CIMT. Individual and group-level changes in imaging and behavioral parameters were investigated. RESULTS: Increase in fMRI activation in the sensorimotor areas was greater amongst those subjects who had poor hand motor behavior before therapy and/or whose motor behavior improved notably because of therapy than amongst subjects with relatively good motor behavior already before therapy. The magnitude of CIMT-induced changes in task-related fMRI activation differed between lesioned and non-lesioned hemispheres, and the fMRI laterality index was different for paretic and non-paretic hand tasks. The corticospinal conduction time in TMS was significantly decreased after CIM therapy. CONCLUSIONS: Alterations in sensorimotor cortical activations (fMRI) and corticospinal conductivity (TMS) were observed after intensive rehabilitation in patients with chronic stroke. Activation and functional changes in fMRI and TMS correlated significantly with the degree of clinical improvement in hand motor behavior. The present data advance the understanding of the functional underpinnings of motor recovery, which may be obtained even years after the stroke.

Cerebellar apparent diffusion coefficient changes in patients with supratentorial ischemic stroke.

OBJECTIVES: To evaluate apparent diffusion coefficient (ADC) in cerebellar subregions in patients with stroke. MATERIALS AND METHODS: The total counts and ADCs were bilaterally measured on cerebellar white matter, gray matters of medial (G1), intermediate (G2), and lateral zones (G3) on SPECT and ADC maps from 20 patients with supratentorial ischemic stroke within the first 48 h and on day 8 after onset. ADCs were also obtained from 15 age-matched controls. RESULTS: Within 48 h, the ADCs were significantly increased bilaterally in the G3, and tended to be increased bilaterally in the white matter and G1, and contralateral G2 compared with controls. On day 8, the ADCs were significantly increased in all contralateral cerebellar subregions and in ipsilateral G1 and G2, and tended to be increased in ipsilateral G3. The ADC value was significantly higher in contralateral than in ipsilateral white matter on day 8. The interhemispheric asymmetry indices (AIs) of ADC and SPECT were significantly associated with each other in G2 and G3 within 48 h, but not on day 8. The AIs of ADC and SPECT were significantly related to each other in the G3 within 48 h and on day 8. CONCLUSIONS: Supratentorial ischemic stroke may cause mild cerebellar vasogenic edema.

Atrophic enlargement of CSF volume after subarachnoid hemorrhage: correlation with neuropsychological outcome.

BACKGROUND AND PURPOSE: Ventricular dilation and sulcal enlargement are common sequelae after aSAH. Our aim was to quantify the late ventricular dilation and volumes of the CSF spaces after aSAH and to determine if they correlate with neurologic and cognitive impairments frequently detected in these patients. MATERIALS AND METHODS: 3D T1-weighted images needed for volumetry were available in 76 patients 1 year after aSAH, along with 75 neuropsychological assessments. Volumes of CSF segments and ICV were quantified by SPM in 76 patients and 30 control subjects to determine CSF/ICV ratios. The mCMI was calculated to roughly evaluate the ventricular dilation. The contributing factors for enlarged ventricles and CSF volumes were reviewed from radiologic, clinical, and neuropsychological perspectives. RESULTS: The mCMI was higher in patients with aSAH (0.23 +/- 0.06) compared with control subjects (0.20 +/- 0.04; P = .020). In line with these planimetric measurements, the SPM-based CSF/ICV ratios were higher in patients with aSAH (35.58 +/- 7.0) than in control subjects (30.36 +/- 6.25; P = .001). Preoperative hydrocephalus, higher HH and Fisher grades, and focal parenchymal lesions on brain MR imaging, but not the treatment technique, were associated with ventricular enlargement. The clinical outcome and presence of neuropsychological deficits correlated significantly with CSF enlargement. CONCLUSIONS: Ventricular and sulcal enlargement, together with reduced GM volumes, after aSAH may indicate general atrophy rather than hydrocephalus. Enlarged CSF spaces correlate with cognitive deficits after aSAH. A simple measure, mCMI proved to be a feasible tool to assess the diffuse atrophic brain damage after aSAH.

Motor cortex and thalamic atrophy in Unverricht-Lundborg disease: voxel-based morphometric study.

OBJECTIVE: To evaluate possible changes in the gray matter volume of patients with Unverricht-Lundborg disease (EPM1) compared with healthy controls. METHODS: Thirty-four genetically verified patients with EPM1 and 30 healthy controls matched for age and sex underwent MRI (T1-, T2-, fluid-attenuated inversion recovery-, and T1-weighted 3-dimensional images). T1-weighted 3-dimensional images were analyzed with voxel-based morphometry (VBM) to compare the regional differences in gray matter volumes between patients and controls. The patients with EPM1 were also clinically evaluated for myoclonus severity using the Unified Myoclonus Rating Scale. RESULTS: VBM analysis revealed atrophy in the bilateral primary, premotor, and supplementary motor cortex. The thalamus and precuneus were also bilaterally affected. No infratentorial changes were detected in the group analysis. CONCLUSION: The cortical motor areas of the brain are particularly affected in EPM1, correlating with the motor symptoms of this disease. The combination of detailed imaging with neurophysiologic evaluation may help to reveal the pathogenesis of Unverricht-Lundborg disease.

Heterogeneity of cerebral perfusion 1 week after haemorrhage is an independent predictor of clinical outcome in patients with aneurysmal subarachnoid haemorrhage.

BACKGROUND AND PURPOSE: Aneurysmal subarachnoid haemorrhage (aSAH) can be associated with acute global and regional decrease in cerebral perfusion. Furthermore, cerebral vasospasm may lead to development of delayed ischaemic deficits. The aim of the study was to find out whether cerebral perfusion heterogeneity, an indicator of cerebral microvascular function and autoregulation, measured by single-photon emission tomography (SPET), is able to predict the long-term clinical outcome of aSAH. METHODS: The perfusion SPET data of 55 patients with aSAH were analysed by dividing the brain into 384 regions of interest. Spatial perfusion heterogeneity was assessed by calculating the relative dispersions (RD, coefficient of variation) from the SPETs performed before treatment (RD1) and 1 week after early surgical or endovascular treatment of the ruptured aneurysm (RD2). Both RDs were compared to the clinical outcome (Glasgow Outcome Scale, GOS), neuropsychological test scores and late ischaemic findings in MRI 1 year after SAH. RESULTS: High RD2 (OR 1.96; 95% CI 1.18-3.26; p = 0.009) and poor clinical condition (Hunt and Hess grade) on admission (OR 6.60; 95% CI 1.78-24.52; p = 0.005) proved to be independent predictors of poor or moderate clinical outcome (GOS 1-4). RD2 was higher in patients with ischaemic findings in 12-month MRI than in those without ischaemic findings (p = 0.008). RD2 also correlated with neuropsychological outcome 1 year after aSAH. CONCLUSIONS: Perfusion heterogeneity is an independent predictor of the clinical outcome of aSAH and may thus be a valuable measure in the assessment of the disease.

Apolipoprotein E epsilon 4 allele is associated with increased atrophy in progressive mild cognitive impairment: a voxel-based morphometric study.

BACKGROUND: The apolipoprotein E (APOE) epsilon4 allele is a risk factor for Alzheimer's disease. Earlier studies have shown differences in brain structure according to the APOE epsilon4 status. OBJECTIVE: To assess possible differences in brain structure according to the APOE epsilon4 status in mild cognitive impairment (MCI) subjects in relation to conversion to dementia. METHODS: In a follow-up study of 56 MCI subjects, 13 MCI subjects progressed to dementia (PMCI) during a mean follow-up time of 31 months. Brain structure differences in both stable MCI (SMCI) and PMCI epsilon4 carriers and noncarriers in the baseline MRI scan were assessed with voxel-based morphometry. RESULTS: The SMCI epsilon4 carriers had atrophy in the amygdala and hippocampus compared to the SMCI noncarriers. The PMCI epsilon4 carriers revealed atrophy of the left inferior frontal gyrus and parietal cortex compared to the PMCI noncarriers. CONCLUSION: The rate of brain atrophy in certain brain areas may be increased in epsilon4-positive MCI subjects progressing to dementia.

Non-primary motor areas in the human frontal lobe are connected directly to hand muscles.

Structural studies in primates have shown that, in addition to the primary motor cortex (M1), premotor areas are a source of corticospinal tracts. The function of these putative corticospinal neuronal tracts in humans is still unclear. We found frontal non-primary motor areas (NPMAs), which react to targeted non-invasive magnetic pulses and activate peripheral muscles as fast as or even faster than those in M1. Hand muscle movements were observed in all our subjects about 20 ms after transcranial stimulation of the superior frontal gyrus (Brodmann areas 6 and 8). Stimulation of NPMA could activate both proximal and distal upper limb muscles with the same delay as a stimulation of the M1, indicating converging motor representations with direct functional connections to the hand. We suggest that these non-primary cortical motor representations provide additional capacity for the fast execution of movements. Such a capacity may play a role in motor learning and in recovery from motor deficits.

Juvenile-onset neuronal ceroid lipofuscinosis with infantile CLN1 mutation and palmitoyl-protein thioesterase deficiency.

Accurate diagnosis, especially in progressive hereditary diseases, is essential for the treatment and genetic counseling of the patient and the family. Neuronal ceroid lipofuscinoses (NCL) are amongst the most common groups of neurodegenerative diseases. Infantile, juvenile, and adult-onset types with multiple genotype-phenotype associations have been described. A fluorimetric enzyme assay for palmitoyl protein thioesterase (PPT) from leukocytes and fibroblasts has been previously developed to confirm the diagnosis of infantile NCL. We describe a patient with juvenile-onset NCL phenotype with a new CLN1 mutation and deficient PPT activity. Over 40 different mutations have been found in patients with PPT deficiency, indicating that screening for known mutations is not an efficient way to diagnose this disorder. Therefore, PPT enzyme analysis should precede mutation analysis in suspected PPT deficiency, particularly in patients with granular osmiophilic deposits (GROD) or in patients who have negative ultrastructural data. The use of enzyme assay led to the diagnosis of this patient with juvenile-onset Finnish variant NCL with PPT deficiency, and we expect that greater awareness of the utility of the enzymatic assay may lead to identification of other similar cases awaiting a definitive diagnosis.

ApoE polymorphism and acute stroke: a study with diffusion- and perfusion-weighted MRI and MR angiography.

OBJECTIVES: We examined whether the apolipoprotein E (ApoE) allele epsilon4 influences imaging findings in stroke as assessed by diffusion- (DWI) and perfusion-weighted (PWI) magnetic resonance imaging, and MR angiography (MRA). METHODS: Eight ApoE epsilon4 carriers and 15 non-carriers with acute ischemic stroke in the anterior circulation underwent DWI, PWI, and MRA within 24 h of stroke. DWI and PWI were repeated a week later. The apparent diffusion coefficient, relative cerebral volume (rCBV), relative cerebral blood flow (rCBF) and relative mean transit time were measured in three subregions on day one. RESULTS: In the ischemic core and the area of infarct growth, rCBV values were significantly higher in the epsilon4 carriers compared with the non-carriers. Based on the MRA findings, collateral blood flow was better in the epsilon4 carriers than in the non-carriers. Under the comparable severity of hypoperfusion, the hypoperfused area proceeded to infarction later or did not proceed to infarction at all in the non-carriers. CONCLUSION: These preliminary data suggest that in the ApoE allele epsilon4 carriers the threshold for the brain tissue to survive hypoperfusion versus to proceed to infarction seems to be different from that of the non-carriers.

Cerebroretinal microangiopathy with calcifications and cysts.

BACKGROUND: Extensive cerebral calcifications and leukoencephalopathy have been reported in two rare disorders Coats plus and leukoencephalopathy with calcifications and cysts. In the latter, a progressive formation of parenchymal brain cysts is a special feature, whereas Coats plus is characterized by intrauterine growth retardation, bilateral retinal telangiectasias and exudations (Coats disease), sparse hair, and dysplastic nails without cyst formation. METHODS: We identified 13 patients, including two pairs of siblings, with extensive cerebral calcifications and leukoencephalopathy. We reviewed clinical, ophthalmologic, radiologic and neuropathologic data of seven deceased patients and studied five patients prospectively. RESULTS: Eleven patients were small for gestational age; the other symptoms emerged from infancy to adolescence. All patients had neurologic symptoms including seizures, spasticity, dystonia, ataxia, and cognitive decline. Progressive intracerebral calcifications involved deep gray nuclei, brainstem, cerebral and cerebellar white matter, and dentate nuclei and were accompanied by diffuse white matter signal changes and, in five patients, cerebral cysts. Eleven patients had retinal telangiectasias or angiomas. Additional features were skeletal and hematologic abnormalities, intestinal bleeding, and poor growth. Neuropathologic examination showed extensive calcinosis and abnormal small vessels with thickened, hyalinized wall and reduced lumen. CONCLUSIONS: Our data suggest that Coats plus syndrome and leukoencephalopathy with calcifications and cysts belong to the same spectrum. The primary abnormality seems to be an obliterative cerebral angiopathy involving small vessels, leading to dystrophic calcifications via slow necrosis and finally to formation of cysts and secondary white matter abnormalities.