Proton magnetic resonance spectroscopic imaging in patients with cerebellar degeneration

Using proton magnetic resonance spectroscopic imaging, we studied the cerebellum of 9 patients with cerebellar degeneration and of 9 age-matched normal control subjects. This technique permits the simultaneous measurement of N- acetylaspartate, choline-containing compounds, creatine/phosphocreatine, and lactate signal intensities from four 15-mm slices divided into 0.84-ml single-volume elements. Because patients with cerebellar degeneration often show substan- tial atrophy on magnetic resonance imaging (MRI), we specifically chose to analyze the spectroscopic signals only from tissue that did not have an atrophic appearance on the MRI. The spectroscopic findings showed a significant reduction of N-acetylaspartate in all parts of the cerebellum, a significant correlation with MRI scores of cerebellar atrophy, and a significant correlation with clinical rating scores of cerebellar disturbance. Our method of analysis suggests the presence of a neurodegenerative process in cerebellar areas that do not appear to be atrophic on the MRI. Some limitations of proton magnetic resonance spectroscopic imaging in the present study were related to the partial field inhomogeneity characteristics of the posterior fossa, the anatomical location of the cerebellum, and the particularly severe cerebellar atrophy in some of the patients.     

Cardiac assessment of limb-girdle muscular dystrophy 2I patients: an echography, Holter ECG and magnetic resonance imaging study

Mutations in the FKRP gene may be associated with cardiac involvement. The aim of our study was to assess myocardial involvement in patients with LGMD2I, using physical examination, echocardiography, resting and 24-h ambulatory electrocardiogram and cardiac magnetic resonance imaging, with particular attention to the detection of myocardial morphologic abnormalities. Patients were compared to matched controls. Twenty-three patients were enrolled (men 10 - women 13; 32.3+/-9.5 years). Twenty-two had the C826A gene mutation (homozygous 12, heterozygous 10). Nine patients had severe muscle alterations, 10 had milder muscle involvement and 4 had isolated exertional myoglobinuria. When compared to controls, LGMD2I patients had reduced left ventricular ejection fraction (50.8+/-13.9 versus 66.6+/-3.8%, p<0.0001). Sixty percent of patients had reduced left ventricular ejection fraction, including 8% with severe reduced left ventricular ejection fraction <30%. None had significant arrhythmia. Gene mutation and the severity of the muscle disease were not predictive of cardiac involvement. Cardiac magnetic resonance imaging displayed a high prevalence of myocardial functional abnormalities, fatty replacement and fibrosis, among the 13 patients investigated. Reduced contractility and cardiac magnetic resonance imaging morphological abnormalities are highly prevalent in LGMD2I patients suggesting that all patients should be referred for cardiac evaluation.     

Diffusion-weighted images in neonatal cerebral hypoxic-ischemic injury

Diffusion-weighted images of magnetic resonance imaging, obtained by mapping apparent diffusion coefficients, are more sensitive than other magnetic resonance imaging sequences in the earliest detection of acute cytotoxic injury. The usefulness of diffusion-weighted images in focal ischemic brain injury has been documented in children and adults. We report eight full-term neonates with global cerebral hypoxic-ischemic injury and abnormalities on diffusion-weighted images. Distribution of diffusion-weighted imaging abnormalities in the eight neonates was consistent with global hypoxic-ischemic injury in full-term neonates, with diffuse cortical necrosis, border-zone infarcts, or basal ganglia/thalamic injury. Magnetic resonance imaging scans with diffusion-weighted images were obtained within the first 4 days of age in all eight neonates. In each patient, standard magnetic resonance imaging sequences substantially underestimated the extent of injury when compared with diffusion-weighted images in unmyelinated neonatal brains. Extensive injury bilaterally with basal ganglia and thalamic and widespread multifocal cortical injury correlated with a severe neurologic outcome. Lesser degrees of injury, limited to smaller sectors of cortical or border zone involvement, were associated with better neurologic outcome. The high sensitivity of diffusion-weighted images to map the extent of hypoxic-ischemic injury in neonates makes it a potentially useful tool for assessing future neuroprotective strategies for neonatal hypoxic-ischemic injury.     

Magnetic resonance imaging and brain-stem auditory evoked potentials in neuro-Behcet's disease

We studied central nervous system lesions in patients with neuro-Behcet's disease using magnetic resonance imaging (MRI) of the brain and recording of brain-stem auditory evoked potentials (BAEPs). MRI revealed abnormal findings in seven of eight patients. MRI studies demonstrated extensive regions with high intensity signal in the brain stem and/or basal ganglia on T2-weighted images obtained during the acute stage of the disease in three patients. One of these patients had a strongly gadolinum-enhanced round lesion in the lower pons. In four of the other five patients with chronic disease, brain-stem atrophy was observed on T1-weighted images. Atrophic changes were more severe in the brain stem than in the cerebellum. Abnormal BAEPs were observed in three patients and consisted of prolongation of interpeak latency of waves III-V and defects of wave III or V. Abnormal BAEPs were recorded in patients with severe inflammatory changes or progression of atrophic changes in the brain stem. Our findings show that MRI and BAEPs are useful in detecting the presence and assessing the degree of neurological involvement in patients with neuro-Behcet's disease.     

Grey matter abnormalities in multiple sclerosis: proton magnetic resonance spectroscopic imaging

Pathologically defined abnormalities in the cortical gray matter (GM) are well described in multiple sclerosis (MS) but are infrequently seen by conventional magnetic resonance imaging (MRI). We systematically evaluated 52 relapsing-remitting MS patients and 20 normal volunteers with high resolution MRI and short echo proton magnetic resonance spectroscopic imaging (MRSI). Individual tissue contributions to the spectroscopic voxels were estimated based on MRI that incorporated both CSF suppression and magnetization transfer, or double inversion images in which both CSF and GM were suppressed. Strong resonances in the 0.8 to 1.5 p.p.m. spectral region were observed in 13 MS patients. Image segmentation based on the MRI characteristics of tissues contributing to the spectroscopic voxels showed that these additional peaks originated mainly from GM. The presence of these additional peaks suggests that the normal appearance GM on MRI, is biochemically abnormal in a substantial proportion of relapsing-remitting MS patients.     

New insights in mucopolysaccharidosis type VI: Neurological perspective

Objective: Mucopolysaccharidosis type VI is a rare autosomal recessive storage disorder, caused by deficiency of arylsulfatase B. Data on neurological involvement in mucopolysaccharidosis type VI patients under enzyme-replacement therapy are limited. This study explores the neurological and magnetic resonance imaging findings in a sample of mucopolysaccharidosis type VI patients receiving enzyme-replacement therapy. Methods: We performed a cross-sectional study including six patients with biochemical confirmation of mucopolysaccharidosis type VI and at least 105 consecutive weeks (two years) receiving intravenous enzyme-replacement therapy. The protocol included a comprehensive clinical examination, brain and spinal cord magnetic resonance imaging for all subjects. Results: Overall, cognition was spared, while we found presence of hearing impairment, increasing in deep tendon reflexes and deep sensation reduction in three patients. In addition to the classical abnormalities related to other types of mucopolysaccharidosis, imaging studies demonstrated morphological changes in anatomy of middle cranial fossa and sella shape. Even in asymptomatic or mild compromised patients, spinal cord compression was found. In four patients we noticed atlantoaxial joint subluxation and three had cervical spinal stenosis. Degenerative processes involving vertebral column, including discal protrusion and axis abnormalities, were present in all patients. Conclusions: Neuroaxis involvement was a universal finding and neurological examination might not predict the severity of the disease in course. Image studies should not be performed according exclusively clinical parameters for these patients, once we have demonstrated that neurological involvement may be silent in these patients.     

The Use of Susceptibility-Weighted Imaging for Epileptic Focus Localization in Acute-Stage Pediatric Encephalopathy: A Case Report

BackgroundSusceptibility-weighted imaging is a novel high-spatial-resolution three-dimensional gradient-echo magnetic resonance imaging technique with phase postprocessing that accentuates the paramagnetic properties of blood products. The use of susceptibility-weighted imaging for epileptic focus localization in the acute stage of encephalopathy in a child has not been documented.PatientsWe report three pediatric patients with status epilepticus in the setting of fever, in whom susceptibility-weighted imaging showed transient prominence of the focal venous vasculature.ResultsConventional cranial T1- and T2-weighted images and diffusion-weighted images showed no abnormalities. The prominence of the focal venous vasculature in these patients, as demonstrated by susceptibility-weighted imaging, was consistent with the epileptic focuses suggested by both clinical symptoms and electroencephalograph findings and resolved completely without neurological sequelae in all patients.ConclusionsSusceptibility-weighted imaging may facilitate assessing epileptic focus localization in the acute stage of encephalopathy in children.     

Cerebral circulation and oxygen metabolism associated with subclinical periventricular hyperintensity as shown by magnetic resonance imaging

A combined magnetic resonance imaging and positron emission tomography study was performed on 21 patients with cerebrovascular risk factors but without neurological abnormalities. Our purpose was to investigate the hypothesis that periventricular hyperintensity (PVH) reflects ischemia. Periventricular hyperintensity was evaluated with a method we devised, and cerebral circulation and oxygen metabolism were evaluated with the oxygen-15 steady-state technique. We concluded that the brain with severe periventricular hyperintensity had abnormal circulation, although oxygen metabolism was not measurably affected. The role of a compensation mechanism under conditions of decreased oxygen supply was considered.     

Manganese intoxication and chronic liver failure

Manganese intoxication and chronic liver failure are associated with strikingly similar clinical, imaging, and pathological abnormalities. As manganese is primarily cleared by the liver, inadequate elimination of manganese absorbed from the normal diet may lead to manganese overload in patients with liver disease. We report a significant elevation of blood manganese concentration in 3 patients with biopsy-proved hepatic cirrhosis who exhibited neurological dysfunction and characterstic abnormal signal hyperintensity in the globi pallidi and substantia nigra on T1-weighted magnetic resonance imaging. We speculate that manganese accumulation in the brain accounts for the magnetic resonance imaging abnormalities and contributes to neurological dysfunction in patients with liver disease.     

1H-MR Spectroscopy in Traumatic Brain Injury

Traumatic brain injury (TBI) is a common cause of neurological damage and disability. Conventional imaging (CT scan or MRI) is highly sensitive in detecting lesions and provides important clinical information regarding the need for acute intervention. However, abnormalities detected by CT scan or conventional MRI have limited importance in the classification of the degree of clinical severity and in predicting patients’ outcome. This can be explained by the widespread microscopic tissue damage occurring after trauma, which is not observable with the conventional structural imaging methods. Advances in neuroimaging over the past two decades have greatly helped in the clinical care and management of patients with TBI. The advent of newer and more sensitive imaging techniques is now being used to better characterize the nature and evolution of injury and the underlying mechanisms that lead to progressive neurodegeneration, recovery or subsequent plasticity. This review will describe the role of proton magnetic resonance spectroscopic (MRS), an advanced MRI technique as related to its use in TBI. Proton MRS is a noninvasive approach that acquires metabolite information reflecting neuronal integrity and function from multiple brain regions and allows to assess clinical severity and to predict disease outcome.     

MR evidence of structural and metabolic changes in brains of patients with Werner’s syndrome

Abstract. Objective: To assess CNS abnormalities in patients with Werners syndrome (WS) using MR metrics specific for tissue damage. Background: WS is a rare autosomal recessive disorder that causes premature aging. The CNS involvement in this disease is still debated. Methods: Two siblings who showed signs of neurological involvement underwent MR spectroscopic imaging (MRSI) and magnetization transfer (MT) imaging. Also, on conventional T₁-weighted MR images, measurements of total brain volume were performed. Results: Conventional MR images of both WS patients did not show abnormalities on visual inspection. However, both WS patients showed significantly lower values of normalized total brain volume and MT ratio in the white matter than agematched normal controls. Also, proton MRSI showed significantly lower values of central brain NAA/Cr in WS patients than in normal controls. Conclusions: Our findings suggest that, despite normal appearance on conventional MRI, diffuse structural and metabolic tissue damage can be demonstrated in WS brains by means of sensitive MR methods even in patients with moderate or subclinical CNS involvement.     

Chemical pathology of acute demyelinating lesions and its correlation with disability

We report the chemical pathological changes on magnetic resonance spectroscopic images of 4 patients, each of whom had a single large demyelinating plaque. The patients were followed from soon after the onset of the symptoms for a minimum of 7 months to a maximum of 3 1/2 years. We observed increases in the relative resonance intensities of choline-containing compounds, lactate, and myo-inositol inside the lesion acutely. Decreases in relative resonance intensities of N-acetylaspartate and creatine were seen both in and around the magnetic resonance imaging—detected lesions. In all patients neurological deficits improved and creatine, lactate, and myo-inositol resonance intensities normalized during the follow-up. Choline compounds recovered more slowly and were still abnormally high in 1 patient after 7 months. Partial recovery of the N-acetylaspartate resonance was seen for all patients. Evaluation of the relationships between indices of cerebral chemical pathology, brain lesion volumes, and functional disability showed highly significant negative correlations between N-acetylaspartate resonance intensities and both brain lesion volumes (r = ?0.80, p < 0.0001) and clinical disability (r = ?0.73, p < 0.0001). As N-acetylaspartate is localized solely in neurons in the adult central nervous system, our results suggest that neuronal dysfunction may be a proximate mechanism of disability even in inflammatory disorders primarily affecting myelin and oligodendroglial cells.     

A boy with a severe phenotype of succinic semialdehyde dehydrogenase deficiency

Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder affecting γ-aminobutyric acid degradation. We describe here a boy with a severe phenotype of SSADH deficiency. He was referred because of a developmental delay at 4 months of age. At the age of 8 months, severe seizures developed. The diagnosis of SSADH deficiency was confirmed by an increase in 4-hydroxybutyric acid and heteroallelic mutation in the ALDH5A1 gene. His seizures were successfully treated with high-dose phenobarbital, and the electroencephalogram (EEG) abnormalities were ameliorated. However, the patient showed a degenerative clinical course with severe neurological deficits. A magnetic resonance imaging (MRI) scan revealed abnormal high intensities in the putamina and caudate nuclei on T2-weighted images, followed by marked atrophic changes. The clinical manifestation of our patient indicates the wide variety of SSADH deficiency phenotypes.     

Combined diffusion- and perfusion-weighted imaging: a new way for the assessment of hemispheric transient ischemic attack patients

Abnormalities in diffusion-weighted and perfusion-weighted magnetic resonance images not only occur in stroke patients but also in transient ischemic attack patients. We found magnetic resonance images were abnormal in 28 patients (68%): 15 had diffusion-weighted imaging abnormalities, 7 had both diffusion-weighted imaging and perfusion-weighted imaging defects and 6 had an isolated perfusion-weighted imaging abnormality. Patients with shorter onset to magnetic resonance imaging, large artery atherothrombosis, coronary artery disease, hyperlipidemia and hemiparesis were more likely to show perfusion-weighted imaging abnormalities. Compared with patients who had a good prognosis, in poor prognosis patients, the relative cerebral blood flow and relative cerebral blood volume was significantly higher. The data suggest that transient ischemic attack patients are more likely to have a poor prognosis when white matter of the symptomatic side shows hyperperfusion within 24 h of symptom onset; however, patients are more likely to have a good prognosis when white matter of the symptomatic side shows hypoperfusion.     

Imaging of axonal damage in multiple sclerosis: Spatial distribution of magnetic resonance imaging lesions

We performed magnetic resonance imaging and magnetic resonance spectroscopic imaging on 28 patients with multiple sclerosis stratified for disability and clinical course (relapsing with at least partial remissions or secondary progressive disease). Lesions were segmented on the conventional proton density and T2-weighted magnetic resonance images, and lesion distribution images were generated for each patient. The conventional magnetic resonance and spectroscopic images were transformed into a standard brain-based stereotaxic coordinate space, allowing comparison of images from different patients on a voxel-by-voxel basis. The spatial distribution of lesions in the transformed magnetic resonance images did not differ significantly between the relapsing and the progressive disease groups. We then generated from the individual data sets, group lesion probability distribution images for the relapsing and the progressive disease groups. The spatial distribution of metabolites was characterized with respect to lesion distribution using the magnetic resonance spectroscopic images transformed into stereotaxic space and averaged. The neuronal marker N-acetylaspartate was diffusely lower in the multiple sclerosis patients than in normal control subjects. Comparison of the averaged metabolite and T2-weighted lesion probability images confirmed loss of N-acetylaspartate in regions of both high and low lesion probability. This suggests that diffuse axonal volume loss or dysfunction extends beyond the inflammatory lesions of multiple sclerosis, perhaps due to microscopic disease or wallerian degeneration along projection pathways of axons traversing the lesions.     

Clinical application of brain perfusion imaging in detecting stroke mimics: A review

Stroke mimics constitute a significant proportion of patients with suspected acute ischemic stroke. These conditions may resemble acute ischemic stroke and demonstrate abnormalities on perfusion imaging sequences. The most common stroke mimics include seizure/epilepsy, migraine with aura, brain tumors, functional disorders, infectious encephalopathies, Wernicke's encephalopathy, and metabolic abnormalities. Brain perfusion imaging techniques, particularly computed tomography perfusion and magnetic resonance perfusion, are being widely used in routine clinical practice for treatment selection in patients presenting with large vessel occlusion. At the same time, the utilization of these imaging modalities enables the opportunity to better diagnose patients with stroke mimics in a time-sensitive setting, leading to appropriate management, decision-making, and resource allocation. In this review, we describe patterns of perfusion abnormalities that could discriminate patients with stroke mimics from those with acute ischemic stroke and provide specific case examples to illustrate these perfusion abnormalities. In addition, we discuss the challenges associated with interpretation of perfusion images in stroke-related pathologies. In general, perfusion imaging can provide additional information in some cases—when used in combination with conventional magnetic resonance imaging and computed tomography—and might help in detecting stroke mimics among patients who present with acute onset focal neurological symptoms.     

Subclinical neurological involvement in Behçet's disease

CONTEXT: Beh?et's disease (BD) is a multisystem inflammatory disorder with unknown etiology characterized by recurrent oral and genital aphthous ulcers and uveitis. Beh?et's disease can affect the central nervous system. AIMS: We aimed to investigate subclinical neurological involvement in patients who were suffering from BD and who had no neurological symptoms. SETTINGS AND DESIGN: A total of 49 patients were included in the study. For the investigation of subclinical neurological involvement, the patients received imaging and/or neurophysiologic evaluations. MATERIALS AND METHODS: The evaluation techniques were as follows: single photon emission computed tomography, 33 patients; cranial magnetic resonance imaging (MRI), 25 patients; brainstem auditory evoked potential examination, 36 patients; and electroencephalography (EEG), 30 patients. STATISTICAL ANALYSIS USED: The Mann-Whitney U test and Wilcoxon Rank-Sum W test were used. RESULTS: Patients in the MRI and EEG groups showed significantly more abnormalities than did age- and gender-matched controls. CONCLUSIONS: Early diagnosis of neurological involvement in BD is important in reducing or preventing complications. Cranial MRI and EEG were found to be useful for detecting subclinical neurological abnormalities in patients with Beh?et's disease.     

Pregabalin‐withdrawal encephalopathy and splenial edema: A link to high‐altitude illness?

A postherpetic-neuralgia patient abruptly discontinued pregabalin. Thirty hours later, unexplained nausea, headache, and ataxia developed, progressing to delirium 8 days later. Magnetic resonance imaging indicated T2-hyperintense lesions of her splenium. Similar magnetic resonance imaging abnormalities, interpreted as focal vasogenic edema, develop in some epileptic patients after rapid anticonvulsant withdrawal. Patients with high-altitude cerebral edema have similar splenial-predominant magnetic resonance imaging abnormalities that accompany these same neurological symptoms. This case is the first to associate anticonvulsant-withdrawal splenial abnormalities with neurological symptoms, with gabapentin-type anticonvulsants, and is among the first in nonepileptic patients, suggesting that sudden anticonvulsant withdrawal alone, unaccompanied by seizures, can initiate symptomatic focal brain edema. The similarity of this syndrome to high-altitude cerebral edema suggests a possible common pathophysiology and offers potential therapies.     

Conventional MRI and MR spectroscopy in nonclassical mitochondrial disease: report of three patients with mitochondrial DNA deletion

Objects The objectives were to present magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) findings in three patients with deletion on mitochondrial DNA (mtDNA) and nonclassical mitochondrial disorders (NCMD), correlating these findings with the percentage of deleted mtDNA.Results Our study confirms the high prevalence of white matter (WM), basal ganglia, and posterior fossa lesions in NCMD, ranging from mild to severe involvement. The subcortical WM, caudate, thalamus, globus pallidus, and dorsal brain stem were more frequently affected. A lactate peak was the most frequent finding at the MRS. We found a correlation between the percentage of mtDNA deletion and degree of MRS abnormalities.Conclusions Our findings showed that MRS is a useful investigational tool in patients with NCMD. Supplementary studies are necessary to elucidate the correlation of quantitative mtDNA deletion and neuroimaging phenotype.     

Pattern of Cortex and White Matter Involvement in Severe Middle Cerebral Artery Ischemia

BACKGROUND AND PURPOSE: In middle cerebral artery (MCA) stroke, ischemia usually is unevenly distributed within the MCA territory. We sought to investigate which brain structures are critical for the acute neurological deficit in severe MCA stroke. METHODS: We used magnetic resonance (MR) imaging and statistical parametric mapping in 64 consecutive stroke patients (64 +/-13 years) to study the pattern of the initial perfusion abnormality. RESULTS: Patients with lesion progression had more severe time-to-peak (TTP) abnormalities (P < .0001) in the inferior frontal gyrus, superior temporal gyrus, insula, and underlying hemispheric white matter than those with lesion regression. Also, patients with lesion progression had more severe T2 abnormalities on day 8 than those with lesion regression. In contrast, the changes of water diffusion were similar among the two groups resulting in a perfusion-diffusion mismatch in lesion progression. TTP-lesions were related to the neurological deficit score (r(s)=-0.563, P < .0001), T2-lesions (r= 0.686, P < .0001), and cerebral artery abnormalities assessed on MR-angiography (r(s)= 0.399, P < .01). CONCLUSIONS: In major MCA, stroke ischemia was most severe in the central portion of the MCA territory. It is suggested that involvement of hemispheric white matter accentuated the neurological deficit probably by affecting cortico-cortical and cortico-subcortical fibers.