Neurofibromatosis type 1: pathologic substrate of high-signal-intensity foci in the brain

PURPOSE: To investigate a correlation between pathologic and radiologic findings with regard to the characteristic high-signal-intensity foci seen on long repetition time (TR) magnetic resonance (MR) images of the brain in patients with neurofibromatosis type 1 (NF-1). MATERIALS AND METHODS: Three girls with NF-1 and abnormal hyperintensities on long TR images of the brain underwent pathologic examination at autopsy. RESULTS: Two 10-year-old girls had classic, focal hyperintensities in the internal capsules and globus pallidus regions, which have been associated with NF-1. The third patient, a neonate, had diffuse hyperintensity of the supratentorial and infratentorial white matter on T2-weighted MR images. Findings at histopathologic examination revealed spongiotic change in the tissue sections that correspond to the high-signal-intensity foci demonstrated on T2-weighted images. CONCLUSION: Hyperintense foci seen on T2-weighted MR images appear to correspond to pathologic findings of areas of vacuolar or spongiotic change. The resultant fluid-filled vacuoles explain the occurrence of high signal intensity demonstrated on T2-weighted images.     

Magnetic resonance imaging demonstrates incomplete myelination in 18q- syndrome: evidence for myelin basic protein haploinsufficiency

Magnetic resonance imaging (MRI) and MRI relaxometry were used to investigate disturbed brain myelination in 18q- syndrome, a disorder characterized by mental retardation, dysmorphic features, and growth failure. T1-weighted and dual spin-echo T2-weighted MR images were obtained, and T1 and T2 parametric image maps were created for 20 patients and 12 controls. MRI demonstrated abnormal brain white matter in all patients. White matter T1 and T2 relaxation times were significantly prolonged in patients compared to controls at all ages studied, suggesting incomplete myelination. Chromosome analysis using fluorescence in situ hybridization techniques showed that all patients with abnormal MRI scans and prolonged white matter T1 and T2 relaxation times were missing one copy of the myelin basic protein (MBP) gene. The one patient with normal-appearing white matter and normal white matter T1 and T2 relaxation times possessed two copies of the MBP gene. MRI and molecular genetic data suggest that incomplete cerebral myelination in 18q- is associated with haploinsufficiency of the gene for MBP.     

Magnetic resonance imaging of the brain in systemic lupus erythematosus

Magnetic resonance imaging (MRI) of the brain is a sensitive method to detect parenchymal tissue lesions. Its value in the diagnosis of central nervous system (CNS) lupus is disputed. To address this question, we have conducted an open and prospective study in a population of 44 SLE patients. We investigated 24 patients (mean age 33 +/- 13 yr) with past or active CNS lupus (group A) that included organic brain syndrome (12), migraine (8), focal neurological signs (7), seizures (2), myelopathy (1) and narcolepsy-cataplexy (1), and 20 patients (mean age 32 +/- 12 yr) without CNS lupus (group B). Health controls comprising nine females and one male aged 31 +/- 9 yr were also studied for comparison (group C). MRI was performed using sagittal T1-weighted images, axial and coronal spin density, and T2-weighted images. All scans were read blindly. Thirteen patients in group A and 10 in group B had well-identified lesions on sequences with long repetition time. Lesions were mostly multiple, small, punctate areas of increased signal at periventricular or subcortical white matter of both cerebral hemispheres. The number and location of lesions were not significantly different in both groups. None of the group C patients had MRI lesions. The presence of lesions was significantly associated with age at study and disease duration, but not with the presence of CNS lupus. In summary, MRI abnormalities are detected in neurologically asymptomatic SLE patients. Whether this represents subclinical brain involvement remains unknown.     

A case of diffuse fasciitis and its MRI findings

A 36-year-old woman with diffuse fasciitis and her MRI findings are reported. The patient developed pain and swelling in the calves, right forearm, and left arm, predominantly in the right calf muscle. Her body temperature was 38.4 degrees C, the ESR 104 mm/2 hours and white blood cell count 8,000/microliter without eosinophilia. The fascia and muscle were biopsied from her right calf. The light microscopy showed that the fascia was thickened and infiltrated with mononuclear cells with no eosinophils, mostly in perivascular areas. The muscle fibers were spared. MRI of legs revealed marked hyperintensities on T2 and mild hyperintensities on T1-weighted images in the fascia, superficial flexor muscles, especially soleus muscle, and Achilles tendons. Moderate dose of prednisolone was very effective and the abnormal signals on MRI almost disappeared within a month. T2 weighted MRI was very useful to detect the lesions and to evaluate the course of diffuse fasciitis.     

Changes in cerebral blood flow and oxygen metabolism related to magnetic resonance imaging white matter hyperintensities in Alzheimer's disease

We studied changes in cerebral perfusion and oxygen metabolism to elucidate the pathophysiological nature and clinical significance of white matter hyperintensities in Alzheimer's disease (AD). METHODS: Sixteen AD patients (age 71.6 +/- 3.1 yr) whose T2-weighted MR images showed white matter hyperintensities, and 16 age-matched AD patients (age 71.0 +/- 4.3 yr) without white matter hyperintensities were compared. Regional cerebral blood flow (CBF), oxygen metabolism (CMRO2) and oxygen extraction fraction (OEF) were measured by using (15)O steady-state method and PET. RESULTS: There was no significant difference in cognitive impairment between the two groups. Compared to the patients without white matter hyperintensities, those with them had significantly low CBF values and significantly high OEF values in all cortical and white matter regions. However, there were no significant differences in CMRO2 values between the two groups. Severity of white matter hyperintensities correlated with the mean cortical and mean white matter OEF. CONCLUSION: In AD patients, white matter hyperintensities on T2-weighted MR images represent ischemic changes in which oxygen metabolism and function are fairly compensated. These changes are not disease-specific but are age-associated coincidences, as in normal aging with or without vascular risk factors.     

MR imaging in solvent-induced chronic toxic encephalopathy

PURPOSE: To use MR to examine patients with CNS symptoms indicating +chronic intoxication. MATERIAL AND METHODS: Thirty-two subjects exposed to industrial solvents for 5 to 28 years and 40 age-matched, healthy controls were examined. RESULTS: All patients showed decreased signal in the basal ganglia on T2-weighted images. In 11 of the patients the white matter showed diffuse hyperintensity with loss of the grey-white matter discrimination and with distinct periventricular hyperintensities in 5 of the patients. The controls had no pathological changes in the brain. CONCLUSION: Although the relatively small number of patients may obscure the significance, findings observed on T2-weighted images were patchy periventricular hyperintensities and hypointensities in the basal ganglia. Fast spin-echo is a good technique with fast acquisition of images with true spin-echo contrast features.     

1997 IPA/Bayer Research Awards in Psychogeriatrics. Subcortical hyperintensities in late-life depression: acute response to treatment and neuropsychological impairment

Subcortical hyperintensities are easily visualized areas of signal abnormality that are seen on T2-weighted magnetic resonance imaging (MRI). Characteristically they occur in the white matter of the brain and are more common in elderly people. In depression, little is known of the clinical significance of subcortical hyperintensities or their contribution to the prognosis. Fifty-eight consecutive patients with DSM-III-R depression and an age range of 65 to 85 years were prospectively collected from an old-age psychiatry service. Response to treatment was assessed with a clinical global outcome measure. A neuropsychology battery was completed on all patients after treatment. Forty-four patients completed MRI scanning. The scans were scored using a regional rating system for hyperintensities. Forty-eight percent of patients had a favorable response to treatment on the clinical global outcome scale. Poor outcome was associated with female sex (p = .07), poor physical health (p = .040), diabetes (p = .018), psychosis (p = .026), and an early age at onset of first episode of depression (p = .036). Even after adjustment for confounding effects, there were significant neuropsychological associations with the regional hyperintensities. Distribution in the periventricular area correlated with delayed recall after distraction (p = .025), and punctate lesions in the basal ganglia correlated with impaired category production (p = .020). Pontine reticular formation hyperintensities were related to impaired psychomotor speed (p = .04). Location in the frontal deep-white matter (p = .024), basal ganglia (p = .03), and pontine reticular formation (p = .02) was associated with a poor acute response to treatment. However, the response to treatment was not related to total cerebral white-matter hyperintensity load. A logistic regression equation included all the significant prognostic features and found four independent predictors of poor outcome: More than five punctate lesions of the basal ganglia, diabetes, lower mean arterial pressure, and hyperintensity of the pontine reticular formation significantly predicted outcome. These four factors correctly predicted 95.6% of patients with a poor outcome and 85.7% with a favorable outcome. In late-life depression, subcortical hyperintensities are common. Lesions in the cerebral white matter are predominantly associated with memory disturbance, and those in deeper infratentorial areas, with psychomotor slowing and executive deficits. Total white-matter load has no prognostic value, and although some subcortical regions are associated with poor response, individually they have little specificity. However, a combination of involvement in three areas (basal ganglia, pons, and frontal lobe) is clinically relevant and predicts outcome with great accuracy (91%). Patients with lesions in the basal ganglia and deep white matter had an especially poor response to pharmacotherapy.     

Congenital muscular dystrophy with merosin deficiency: MRI findings in five patients

We present the MRI findings in five patients with congenital muscular dystrophy (CMD) and merosin (laminin alpha2) deficiency, which was total in one and partial in four. In one patient with partial merosin deficiency, MRI was normal. The other four patients had supratentorial white matter abnormalities. In three, T2-weighted images revealed subcortical, deep lobar and periventricular high signal in white matter, while in the other there were only small peritrigonal areas of increased signal. On T1-weighted images, there was slightly low signal. Cortical abnormalities were absent. None of these changes were accompanied by symptoms or signs of central nervous system involvement. White matter abnormalities in a patient with CMD should prompt investigation of merosin.     

Pre-and post-mortem MR imaging of unsuspected multiple sclerosis in a patient with Alzheimer's disease

A patient with the clinical diagnosis of Alzheimer's disease is presented in whom pre-mortem T2-weighted MRI revealed a periventricular white matter lesion. Postmortem T2 weighted MRIs of the formalin fixed brain revealed the same white matter lesion. Microscopically, classical Alzheimer changes were found and, unsuspectedly, the histopathological correlate of the white matter lesion proved to be an old, inactive, MS plaque. A similar lesion was discovered in the cervical myelum. These findings illustrate that T2-weighted post-mortem MRIs are highly comparable to pre-mortem images and that MRI is sensitive in detecting clinically silent white matter lesions. The histopathology of such lesions may also include MS plaques.     

Clinical, neurodiagnostic, and MR findings in children with spinal and brain stem multiple sclerosis

PURPOSE: To describe the clinical, neurodiagnostic, and MR findings in seven children with brain stem and spinal multiple sclerosis. METHODS: Spinal or brain stem multiple sclerosis was diagnosed in seven children between 1986 and 1992. All patients had neurologic and MR examinations as well as neurodiagnostic testing, including spinal fluid analysis and brain stem and auditory evoked potentials. RESULTS: Three children had clinical findings and masslike lesions in the brain stem (two) or spinal cord (one) suggestive of neoplasm, which prompted biopsy (two) or radiation therapy (one). Five of six patients with spinal involvement had cord swelling with increased signal on T2-weighted images over at least three cord segments, and two children had essentially holocord involvement. Three children had normal cranial MR at presentation. CONCLUSIONS: Multiple sclerosis involvement of the brain stem and spinal cord may be associated with extensive swelling and MR signal changes suggestive of neoplasm without typical cerebral white matter abnormalities. Serial clinical and neuroimaging examinations may be necessary to make a definitive diagnosis of multiple sclerosis in children.     

Studies on the eosinophilic granule cells in the gills of the rainbow trout, Oncorhynchus mykiss

Hypoxic-ischemic changes in brain are detected earlier with diffusion-weighted (DW) than with T2-weighted magnetic resonance (MR) imaging techniques in adults, whereas the response in immature brain is not known. We investigated MR imaging changes prior to, during, and/or after 2 h of hypoxia-ischemia (right carotid artery occlusion + 2 h of hypoxia) in 7-day-old rats anesthetized with isoflurane. In general, within the first 45 min of hypoxia-ischemia there were no changes in the DW or T2-weighted images. By the second hour of hypoxia-ischemia there were marked areas of increased intensity in both the T2 and the DW images, with cortex and striatum being affected prior to thalamus and hippocampus. The area of DW exceeded that of T2 hyperintensities. In the first hour after hypoxia-ischemia there was a transient recovery of hyperintensities on both T2 and DW images. Between 24 and 72 h the hyperintense area on DW images decreased, whereas that on T2-weighted images increased. The distribution of pathological damage assessed histologically correlated with the areas of hyperintensity on the MR images. In contrast to adult brain, early hypoxic-ischemic injury in immature brain is detected as an increase in intensity in both diffusion- and T2-weighted images, indicating a unique alteration in brain water dynamics in this neonatal model of hypoxia-ischemia. These imaging changes and alterations in brain water can rapidly but transiently reverse upon the start of normoxia and reperfusion, suggestive of secondary energy failure or delayed neuronal death.     

MRI of focal cortical dysplasia

We studied nine cases of focal cortical dysplasia (FCD) by MRI, with surface-rendered 3D reconstructions. One case was also examined using single-voxel proton MR spectroscopy (MRS). The histological features were reviewed and correlated with the MRI findings. The gyri affected by FCD were enlarged and the signal of the cortex was slightly increased on T1-weighted images. The gray-white junction was indistinct. Signal from the subcortical white matter was decreased on T1- and increased on T2-weighted images in most cases. Contrast enhancement was seen in two cases. Proton MRS showed a spectrum identical to that of normal brain.     

Use of fluorescent in situ hybridization to detect aneuploidy in cervical dysplasia

An 8 year old girl with acute disseminated encephalomyelitis (ADEM) is described. Elevated serum antibody titers suggested recent Mycoplasma pneumoniae infection. T2-weighted image of magnetic resonance imaging (MRI) disclosed multiple lesions of high signal intensity in bilateral basal ganglia and thalami as well as in the white matter. Postcontrast T1-weighted image revealed an enhanced lesion in the deep white matter. She showed rapid clinical improvement in response to corticosteroid therapy. The lesions had disappeared completely on MRI performed 10 weeks after the onset. ADEM is believed to be a demyelinating disorder of probable autoimmune etiology. MRI findings in this case may support the hypothesis that the primary pathological event is vascular injury and demyelination occurs only as a secondary phenomenon.     

Fetal intracranial hemorrhage. Imaging by ultrasound and magnetic resonance imaging

OBJECTIVE: To describe the magnetic resonance imaging (MRI) findings associated with fetal intracranial hemorrhage and to compare them with ultrasound findings. STUDY DESIGN: In four pregnancies complicated by fetal intracranial hemorrhage, fetal imaging was carried out using T2-weighted fast spin echo sequences and T1-weighted fast low angle shot imaging sequences and by transabdominal ultrasonography. RESULTS: An antepartum diagnosis of hemorrhage was made by ultrasound in one case and by MRI in two. Retrospectively, the hemorrhagic area could be identified from the MRI images in an additional two cases and from the ultrasound images in one case. In the cases of intraventricular hemorrhage, the MRI signal intensity in the T1-weighted images was increased in the hemorrhagic area as compared to the contralateral ventricle and brain parenchyma. In a case with subdural hemorrhage, T2-weighted MRI signals from the hemorrhagic area changed from low-to high-intensity signals during four weeks of follow-up. Better imaging of the intracranial anatomy was possible by MRI than by transabdominal ultrasonography. CONCLUSION: MRI can be used for imaging and dating fetal intracranial hemorrhages. Variable ultrasound and MRI findings are associated with this complication, depending on the age and location of the hemorrhage.     

Assessment of T2- and T1-weighted MRI brain lesion load in patients with subcortical vascular encephalopathy

Previous cross-sectional studies in patients with subcortical vascular encephalopathy (SVE) have shown little or no correlation between brain lesion load and clinical disability, which could be due to the low specificity of T2-weighted MRI. Recent studies have indicated that T1-weighted MRI may be more specific than T2-weighted MRI for severe tissue destruction. We studied 37 patients with a diagnosis of SVE and 11 normal controls with standardised T1- and T2-weighted MRI. All patients underwent detailed clinical assessment including a neuropsychological test battery and computerised gait analysis. Both the T2- and T1-weighted total MRI lesion loads different between patients and controls different, particularly T1. The ratio of T2-/T1-weighted lesion load was lower in controls than in patients. There was no overall correlation of T1- or T2-weighted lesion load with clinical disability, but group comparison of patients with severe and mild clinical deficits showed different lesion loads. We suggest that T1- and T2-weighted MRI lesion loads demonstrate relevant structural abnormality in patients with SVE.     

Familial leukoencephalopathy in bipolar disorder

OBJECTIVE: Imaging studies of patients with bipolar disorder demonstrate changes in deep white matter and subcortical gray nuclei that are seen as focal hyperintensities on T2-weighted magnetic resonance imaging (MRI). The objective of this study was to examine MRIs in a family with a strong history of bipolar disorder to look for possible MRI abnormalities in members with and without affective illness. METHOD: The authors obtained MRIs of 21 members of a family with a strong history of bipolar disorder. Eight of the family members studied had bipolar illness, one had symptoms of bipolar disorder but did not meet full DSM-III-R criteria, two had unipolar disorder, and 10 did not have bipolar disorder. RESULTS: Fifteen of the 21 family members had MRI findings, including six of 10 family members who had no affective disorder and all of those with bipolar disorder. Lesions of both white matter and subcortical gray nuclei were found. CONCLUSIONS: Although the clinical significance of these MRI findings is unknown, the high prevalence of MRI findings in both affected and unaffected family members suggests that MRI findings may potentially serve as a biological marker for bipolar disorder. Recent genetic studies have established a link between familial leukoencephalopathy and chromosome 19. If leukoencephalopathy appears to be related to bipolar disorder, it may allow clearer characterization of the genetics of the disorder.     

MRI and clinical features in amyotrophic lateral sclerosis

MRI of the brain and spinal cord was performed in 21 patients with amyotrophic lateral sclerosis (ALS), 8 normal volunteers and 16 neurological disease controls. High signal was seen in the intracranial corticospinal tract in 16 of the 21 patients on T2-weighted and in 10 on proton density (PD)-weighted images. In one patient, the high signal on T2-weighted images became less marked with progression of the disease. Low signal intensity was seen in the motor cortex in 12 of the 21 patients. High signal in the anterolateral column of the spinal cord on T1 weighted images was seen in 14, and high signal in the lateral corticospinal tract on T2 weighted images was seen in 7 of the 21 patients. The relationship between the abnormal images and upper motor neurone signs remained unclear. High signal intensity was seen in the corticospinal tract in the brain on T2-weighted images in two normal volunteers and four disease controls, and on PD weighted images in three disease controls. Low signal intensity in the motor cortex on T2 weighted images was seen in three normal volunteers and four disease controls. However, high signal intensity was seen in the intracranial corticospinal tract on T1 weighted images in five patients with ALS who showed pronounced upper motor neurone signs including spastic paraparesis, but not in controls. Thus, abnormalities on MRI in the brain and spinal cord should be considered in the diagnosis of ALS, and high signal intensity of the intracranial corticospinal tract on T1-weighted images may reflect the severe pathological changes of the upper motor neurones in ALS.     

Posterior leukoencephalopathy without severe hypertension: utility of diffusion-weighted MRI

OBJECTIVE: Standard MRI confirms the diagnosis of posterior leukoencephalopathy syndrome (PLES), recently associated with an increasing number of medical conditions. In PLES, T2-weighted MRI demonstrates hyperintensity spreading out from posterior brain regions; the pathophysiology remains mysterious. In the acute setting, diffusion-weighted imaging (DWI), but not standard MR imaging, can distinguish ischemic injury from those conditions known to cause vasogenic brain edema. DWI is potentially valuable in understanding the pathophysiology of PLES and in diagnosing patients who do not have previously known risk factors. METHODS: Serial CT and MRI studies (including DWI, apparent diffusion coefficient [ADC] maps, and, in one instance, perfusion-weighted imaging) were performed in three female patients with a neurologic syndrome consistent with PLES while hospitalized for treatment of other conditions. RESULTS: None of the patients had previously described risk factors for PLES; all had only mild elevations in blood pressure. MRI showed large, abnormal, T2 hyperintense regions in the posterior cerebrum with corresponding hyperintensity on ADC maps-signal characteristics predominantly consistent with vasogenic edema. There were also smaller patchy posterior cortical regions with decreased ADC and bright DWI consistent with infarction in one, and dramatic conversion of a large region to an ischemic pattern in another. CONCLUSIONS: ADC maps and DWI can successfully differentiate PLES from early cerebral ischemia, thus playing a pivotal role in treatment decisions. PLES is associated with a wider variety of conditions than has been previously reported and is not always reversible. Hyperintense DWI signal in patients with the syndrome likely marks a tissue stage of permanent brain injury.     

von Willebrand factor, tissue plasminogen activator, and dehydroepiandrosterone sulphate predict cardiovascular death in a 10 year follow up of survivors of acute myocardial infarction

Earlier reports on T2-weighted magnetic resonance imaging (MRI) in the classical form of Pelizaeus-Merzbacher disease seemed to divide the patterns of the high-intensity lesions in the white matter into three subtypes: type I, diffusely hemispheric and corticospinal; type II, diffusely hemispheric without brainstem lesions; and type III, patchy in the hemispheres. The four boys presented in our study, between 10 and 17 years of age, with classical Pelizaeus-Merzbacher disease, who all had a duplicated proteolipid protein gene, invariably manifested type I despite their various clinical severities. Follow-up MRI after an interval of 5 years and proton magnetic resonance spectroscopy was performed in three of the patients. The white matter on the last MRI was unchanged in volume and the distribution of high-intense areas. Proton magnetic resonance spectroscopy revealed no abnormal peaks. These results were consistent with the lack of definite neurologic regression in the last 5 years and with the pathologic characteristics of well-preserved axons and the absence of sclerosis. Further study is required to precisely determine whether the patterns of MRI findings can be divided into subtypes corresponding to those of proteolipid protein gene abnormalities.     

Anterior temporal white matter lesions in myotonic dystrophy with intellectual impairment: an MRI and neuropathological study

We studied 12 patients with myotonic dystrophy using MRI and the Mini-mental state examination (MMSE), to see it specific MRI findings were associated with intellectual impairment. We also compared them with the neuropathological findings in an autopsy case of MD with intellectual impairment. Mild intellectual impairment was found in 8 of the 12 patients. On T2-weighted and proton density-weighted images, high-intensity areas were seen in cerebral white matter in 10 of the 12 patients. In seven of these, anterior temporal white-matter lesions (ATWML) were found; all seven had mild intellectual impairment (MMSE 22-26), whereas none of the four patients with normal mentation had ATWML. In only one of the eight patients with intellectual impairment were white-matter lesions not found. Pathological findings were severe loss and disordered arrangement of myelin sheaths and axons in addition to heterotopic neurons within anterior temporal white matter. Bilateral ATWML might be a factor for intellectual impairment in MD. The retrospective pathological study raised the possibility that the ATWML are compatible with focal dysplasia of white matter.