Deep Gray Matter Lesions Research Articles

Predictability of cerebral palsy in a high-risk NICU population

AimThis study aims to create a predictive model for the assessment of the individual risk of developing cerebral palsy in a large cohort of selected high-risk infants. Patients and methods1099 NICU-admitted high-risk infants were assessed up to the corrected age of at least 12months. CP was categorized relative to subtype, distribution and severity. Several perinatal characteristics (gender, gestational age, multiple gestation, small for gestational age, perinatal asphyxia and duration of mechanical ventilation), besides neonatal cerebral ultrasound data were used in the logistic regression model for the risk of CP. ResultsPerinatal asphyxia, mechanical ventilation>7days, white matter disease except for transient echodensities<7days, intraventricular haemorrhage grades III and IV, cerebral infarction and deep grey matter lesions were recognized as independent predictors for the development of CP. 95% of all children with CP were correctly identified at or above the cut-off value of 4.5% probability of CP development. Higher gestational age, perinatal asphyxia and deep grey matter lesion are independent predictors for non-spastic versus spastic CP (OR=1.1, 3.6, and 7.5, respectively). Independent risk factors for prediction of unilateral versus bilateral spastic CP are higher gestational age, cerebral infarction and parenchymal haemorrhagic infarction (OR=1.2, 31, and 17.6, respectively). Perinatal asphyxia is the only significant variable retained for the prediction of severe CP versus mild or moderate CP. ConclusionThe presented model based on perinatal characteristics and neonatal US-detected brain injuries is a useful tool in identifying specific infants at risk for developing CP.

Neuroimaging in very preterm infants

Cranial ultrasonography (cUS) and MRI are the preferred modalities used to image the neonatal brain. Both have their specific contributions and advantages. A neuroimaging study, including sequential cUS and single MRI, was performed in a cohort of very preterm infants (gestational age &lt;32 weeks). The major aims were: to study brain imaging findings and to assess the incidences of brain abnormalities and the relationship between brain abnormalities and perinatal clinical parameters; to compare cUS and MRI findings; to describe imaging findings of the thalami and basal ganglia; and to study the reliability of cUS for detection of (diffuse) white matter injury. Patients &amp; methods: Very preterm infants, born during a 1.5-year period, were eligible if there were no exclusion criteria (i.e., metabolic and genetic disorders, or infections and/or congenital malformations of the CNS). Sequential cUS was performed from admission until discharge and on the day of the MRI following a standardized protocol. MRI (3 Tesla) was performed around or shortly after term equivalent age (TEA). Results: A total of 133 infants were included. The mean number of cUS scans per infant was 8.3 (range: 2–23). MRI was performed in 113 infants at a mean postmenstrual age of 44.7 weeks (range: 40.0–55.9). During admission we found periventricular echodensities and intraventricular hemorrhage in 80 and 30% of infants, respectively – both significantly associated with male gender. The incidence of lenticulo striate vasculopathy (LSV) was 19%. Around TEA, ventricular dilatation and widening of extracerebral spaces were frequent findings. In addition, MRI showed punctate white matter lesions and diffuse excessive high-signal intensity. MRI detected subtle white matter lesions more effectively, whereas cUS was better for the detection of LSV, calcifications and germinolytic and plexus cysts. Diffuse, subtle echogenicity of the basal ganglia and thalami was observed in the majority of infants with normal MRI findings in this area. Focal deep gray matter lesions were only rarely encountered. Conclusions: In very preterm infants, frequent, sequential cUS is an excellent tool to image and follow the brain throughout the neonatal period and detects some lesions and transient changes more effectively than MRI. Single MRI provides invaluable and detailed additional information on the growth and development of, and injury to, the brain. Sequential cUS throughout the neonatal period and a single MRI around TEA are therefore warranted. Bilateral, diffuse and subtle echogenicity in the deep gray matter on cUS probably reflects (normal) maturational processes in the immature brain. With the exception of LSV, focal lesions in the deep gray matter are rare and need to be distinguished from benign phenomena in the deep gray matter. Sequential high-quality cUS during the neonatal period predicts severe white matter injury, but is less predictive of mild-to-moderate white matter injury around TEA.

Transcranial brain sonography findings predict disease progression in multiple sclerosis

In multiple sclerosis (MS), an early neurodegenerative affection of subcortical gray matter has been suggested. Transcranial sonography (TCS) shows hyperechogenic lesions of substantia nigra (SN) and basal ganglia, thought to reflect iron accumulation, in a number of primary neurodegenerative diseases. The present study deals with the question of whether TCS can also display deep gray matter lesions in patients with MS and whether sonographic findings relate to severity and progression of MS. We prospectively studied 75 patients with different courses of MS and 55 age-matched healthy subjects clinically and with TCS. Twenty-three patients additionally had 1.5-T MRI at the time of TCS. Disease progression was assessed clinically 2 years after TCS. Abnormal hyperechogenicity of SN, lenticular nucleus (LN), caudate nucleus, and thalamus was found in 41%, 54%, 40%, and 8% of the patients with MS, with similar frequency in patients with relapsing-remitting and primary or secondary progressive MS if corrected for disease duration, but only in 13%, 13%, 5% (each, p < 0.001), and none (p = 0.028) of the control subjects. Hyperechogenicity of SN and LN correlated with more pronounced MRI T2 hypointensity, thought to reflect iron deposition. Larger bilateral SN echogenic area was related to higher rate of disease progression, whereas small SN echogenic area (SN hypoechogenicity) predicted a disease course without further progression within 2 years. Neurodegenerative disease-like deep gray matter lesions can be frequently detected by transcranial sonography (TCS) in patients with multiple sclerosis (MS). Findings suggest that TCS shows changes of brain iron metabolism which correlate with future progress of MS.

Demyelination, Inflammation, and Neurodegeneration in Multiple Sclerosis Deep Gray Matter

Gray matter (GM) lesions are recognized as important components of the pathology of multiple sclerosis (MS), and involvement of the deep gray matter (DGM) is suggested by magnetic resonance imaging. The aims of this study were to determine the frequency and distribution of lesions and characterize the inflammatory and neurodegenerative changes in DGM of MS patients. Histochemistry, immunohistochemistry, and morphometry were performed on whole coronal sections of 14 MS and 12 control (6 normal, 6 from amyotrophic lateral sclerosis patients) brains. Demyelinating lesions were frequent in MS DGM; most often in the thalamus and caudate, but they were also seen in the putamen, pallidum, claustrum, amygdala, hypothalamus, and substantia nigra. Most DGM lesions involved both GM and white matter. Inflammation in active DGM lesions was similar to that in lesions only in white matter but was less intense, and there was a preponderance of activated microglia, scarce myelin-laden macrophages, and a lesser extent of axonal damage. Neuronal loss was observed both in DGM lesions and nondemyelinated DGM with neuron atrophy in nondemyelinated DGM. In conclusion, demyelination and neurodegenerative changes are common in MS DGM and may contribute to clinical impairment. Inflammation in DGM lesions is intermediate between the destructive inflammation of white matter lesions and the minimal inflammation of cortical lesions. We hypothesize that alterations of glutamate reuptake mechanisms may contribute to these differences.

Progressive Multifocal Leukoencephalopathy and Relapsing-Remitting Multiple Sclerosis

To identify clinical and magnetic resonance imaging (MRI) features that distinguish progressive multifocal leukoencephalopathy (PML) from relapsing-remitting multiple sclerosis (RRMS). Retrospective medical record review. Two urban teaching hospitals in Detroit, Michigan. Patients Forty-five confirmed PML cases and 100 patients with RRMS. Clinical and MRI features distinguishing PML from RRMS. Overall, monosymptomatic presentations were more common in multiple sclerosis (MS) than PML (85% vs 47%; P < .01). However, patients with PML presented more often with hemiparesis (24% vs 5%; P = .001) and altered mentation (19% vs 0%; P < .0001), whereas brainstem (2% vs 18%; P = .007) presentations were more common in patients with RRMS. Spinal cord and optic neuritis presentations were seen in 18% and 33% of patients with RRMS, respectively, but not in patients with PML (m < .0001). Brain MRI scans, available in 35 (78%) PML cases, revealed 7 lesion types. Large, confluent T2-weighted lesions (74% vs 2%; P < .0001) and deep gray matter lesions (31% vs 7%; P < .001) were more frequent in patients with PML than patients with RRMS. Crescentic cerebellar lesions (23% vs 0%; P < .001) were seen only in patients with PML. Gadolinium-enhancing (23%), transcallosal (9%), and periventricular (9%) lesions were noted in patients with PML. Brain magnetization transfer ratio (MTR) was low in both PML and MS lesions. However, normal-appearing brain tissue MTR in PML was higher than normal-appearing brain tissue MTR in RRMS (44.15% vs 41.04%; P = .002), suggesting that PML may be relatively more focal than MS. There appear to be differences between the clinical and MRI characteristics of PML and RRMS, which may help distinguish new MS activity from PML. Magnetization transfer ratio studies may provide additional clues in improving early detection of PML in patients with preexisting MS and warrant further investigation.

Understanding causation of cerebral palsy by using magnetic resonance imaging

Magnetic resonance imaging (MRI) plays an important role in elucidating aetiology, or at least pathogenesis of cerebral palsy (CP). When systematically analyzing studies using MRI in children with CP, MRI proves to be abnormal in around 85% of cases and gives a clear pathogenetic pattern in more than 80%. White matter lesions, predominantly in the periventricular area, are most frequent (more than 50%), followed by cortical and deep grey matter lesions (around 20%). Brain maldevelopments are rather rare, described in less than 10%. Brain maldevelopments and grey matter lesions are more often seen in term than in preterm children with CP (16% vs 2.5% and 33% vs 3.5%), whereas periventricular white matter lesions occur significantly more often in preterm than in term children (90% vs 20%). Thus, CP is mainly characterized by brain lesions which can be identified by MRI. This supports a mainly acquired, e.g. lesional origin in the majority of children. This is especially true for children with spastic and dyskinetic CP subtypes, which account for 94% of CP. Ataxic CP is different; abnormal MRI-findings are reported in less than 40% and in at least 50% of cases are clearly not lesional.

The place of conventional MRI and newly emerging MRI techniques in monitoring different aspects of treatment outcome

Magnetic resonance imaging (MRI) is the most important paraclinical measure for assessing and monitoring the pathologic changes implicated in the onset and progression of multiple sclerosis (MS). Conventional MRI sequences, such as T1-weighted gadolinium (Gd) enhanced and spin-echo T2-weighted imaging, only provide an incomplete picture of the degree of inflammation and underlying neurodegenerative changes in this disease. Two- and three-dimensional fluid-attenuated inversion recovery and double inversion recovery sequences allow better identification of cortical, periventricular and infratentorial lesions. Ultra-high field strength MRI has the potential to detect subpial cortical and deep gray matter lesions. Unenhanced T1-weighted imaging can reveal hypointense black holes, a measure of chronic neurodegeneration. Magnetization transfer imaging (MTI) is increasingly used to characterize the evolution of MS lesions and normal-appearing brain tissue. Evidence suggests that the dynamics of magnetization transfer changes correlate with the extent of demyelination and remyelination. Magnetic resonance spectroscopy, which provides details on tissue biochemistry, metabolism, and function, also has the capacity to reveal neuroprotective mechanisms. By measuring the motion of water, diffusion imaging can provide information about the orientation, size, and geometry of tissue damage in white and gray matter. These advanced non-conventional MRI techniques relate better to clinical impairment, disease progression, accumulation of disability, and have the potential to detect neuroprotective effects of treatment. Although detecting the status of neuronal integrity using MRI techniques continues to improve, a "gold standard" model remains to be established.

Can imaging techniques measure neuroprotection and remyelination in multiple sclerosis?

MRI is the most important paraclinical measure for assessing and monitoring the pathologic changes implicated in the onset and progression of multiple sclerosis (MS). Conventional MRI sequences, such as T1-weighted gadolinium-enhanced and spin-echo T2-weighted imaging, are unable to provide full details about the degree of inflammation and underlying neurodegenerative changes. Newer nonconventional MRI techniques have the potential to detect clinical impairment, disease progression, accumulation of disability, and the neuroprotective effects of treatment. Unenhanced T1-weighted imaging can reveal hypointense black holes, a measure of chronic neurodegeneration. Two- and three-dimensional fluid-attenuated inversion recovery sequences allow better identification of cortical lesions. Ultrahigh-field strength MRI has the potential to detect subpial cortical and deep gray matter lesions. Magnetization transfer imaging is increasingly used to characterize the evolution of MS lesions and normal-appearing brain tissue. Evidence suggests that the dynamics of magnetization transfer changes correlate with the extent of demyelination and remyelination. Magnetic resonance spectroscopy, which provides details on tissue biochemistry, metabolism, and function, also has the capacity to reveal neuroprotective mechanisms. By measuring the motion of water, diffusion imaging can provide information about the orientation, size, and geometry of tissue damage in white and gray matter. Functional MRI may help clarify the brain's plasticity-dependent compensatory mechanisms in patients with MS. High-resolution microautoradiography and new contrast agents are proving to be sensitive means for characterizing molecular markers of disease activity, such as activated microglia and macrophages. Optical coherence tomography, a new research technique, makes it possible to investigate relevant physiologic systems that provide accurate measures of tissue changes secondary to the MS disease process. Although detecting the status of neuronal integrity using MRI techniques continues to improve, a "gold standard" model remains to be established.

The role of magnetic resonance imaging in elucidating the pathogenesis of cerebral palsy: a systematic review

The aim of this study was to show the role of magnetic resonance imaging (MRI) in elucidating the aetiology, or at least pathogenesis, of cerebral palsy (CP). A systematic review of studies using MRI in children with CP was performed according to pathogenetic patterns characterizing different timing periods of occurence of the lesions, and with respect to gestational age (term vs preterm) and CP subtypes. Out of the studies published since 1990 in English, six met all the inclusion criteria; they involved children with spastic and dyskinetic CP. Abnormal MRI was reported in 334 out of 388 (86%) patients and gave clues to pathogenesis in 83%. Fourteen studies met only part of the inclusion criteria and abnormal MRIs were reported even more frequently in these (91%; 930/1022). Periventricular white matter lesions were most frequent (56%) followed by cortical and deep grey matter lesions (18%); brain maldevelopments were rather rare, described in 9%. Brain maldevelopments and grey matter lesions were more often seen in term than in preterm-born children with CP (brain maldevelopments: 16% vs 2.5%; grey matter lesions: 33% vs 3.5%); periventricular white matter lesions occurred significantly more often in preterm than in term-born children (90% vs 20%). CP is mainly characterized by brain lesions which can be identified by MRI in around 75% of preterm infants; brain maldevelopments occur in around 10%.

The Current Etiologic Profile and Neurodevelopmental Outcome of Seizures in Term Newborn Infants

The objectives of this study were to delineate the etiologic profile and neurodevelopmental outcome of neonatal seizures in the current era of neonatal intensive care and to identify predictors of neurodevelopmental outcome in survivors. Eighty-nine term infants with clinical neonatal seizures underwent neurologic examination, electroencephalography (EEG), neuroimaging, and extensive diagnostic tests in the newborn period. After discharge, all infants underwent regular neurologic evaluations and, at 12 to 18 months, formal neurodevelopmental testing. We tested the prognostic value of seizure etiology, neurologic examination, EEG, and neuroimaging. Etiology was found in 77 infants. Global cerebral hypoxia-ischemia, focal cerebral hypoxia-ischemia, and intracranial hemorrhage were most common. Neonatal mortality was 7%; 28% of the survivors had poor long-term outcome. Association between seizure etiology and outcome was strong, with cerebral dysgenesis and global hypoxia-ischemia associated with poor outcome. Normal neonatal period/early infancy neurologic examination was associated with uniformly favorable outcome at 12 to 18 months; abnormal examination lacked specificity. Normal/mildly abnormal neonatal EEG had favorable outcome, particularly if neonatal neuroimaging was normal. Moderate/severely abnormal EEG, and multifocal/diffuse cortical or primarily deep gray matter lesions, had a worse outcome. Mortality associated with neonatal seizures has declined although long-term neurodevelopmental morbidity remains unchanged. Seizure etiology and background EEG patterns remain powerful prognostic factors. Diagnostic advances have changed the etiologic distribution for neonatal seizures and improved accuracy of outcome prediction. Global cerebral hypoxia-ischemia, the most common etiology, is responsible for the large majority of infants with poor long-term outcome.

White matter and subcortical gray matter lesion volume changes and late-life depression outcome: a 4-year magnetic resonance imaging study

Cross-sectional studies have shown that late-onset depression is associated with larger deep white matter lesions (WMLs) and subcortical gray matter lesions (GMLs). In a longitudinal analysis, we examined changes in deep WMLs and subcortical GMLs in older depressed and nondepressed subjects over a 4-year period. Brain magnetic resonance imaging (MRI) scans were obtained on 164 depressed and 126 healthy subjects aged 60 years or older at baseline, and 2 and 4 years after recruitment. WMLs and GMLs were measured using a semiautomated technique. We used repeated-measures analysis of covariance to determine cross-sectional lesion volume differences, whether lesion volume changes differed between patients and controls, and the effect of lesion volume changes on outcome in late-life depression. Mean volumes of lesions for the depressive group were 6.51, 8.18 and 7.75 cm2 for WMLs and 0.23, 0.30 and 0.34 cm2 for GMLs at baseline, 2-year and 4-year follow-up, respectively. Mean volumes of lesions for the control group were 4.83, 6.22 and 6.45 cm2 for WMLs and 0.17, 0.25 and 0.23 cm2 for GMLs at baseline, 2-year and 4-year follow-up, respectively. Cross-sectional between-group mean lesion volumes were significantly different for each measure. However, the pattern of WML and GML volume changes over time was not significantly different between groups. Treatment outcome was associated with changes in total and white matter lesion volume over time. Lesion volume progression is associated with aging and the pathological condition of late-life depression. The mechanisms that produce these progressive lesion changes remain unclear. Treatments aimed at arresting lesion progression may play a role in the management of late-life depression.

The Value of Morphological Neuroimaging after Acute Exposure to Toxic Substances

Many toxic agents induce brain dysfunction and/or lesions. Modern neuroimaging techniques, such as CT and more recently magnetic resonance imaging (MRI), are able to demonstrate toxic brain lesions at both early and delayed phases of disease progression. In the early phase, neuroimaging enables the detection of acutely injured brain areas responsible for sudden onset of neurological dysfunction, but the severity and the extension of brain lesions on neuroimages do not necessarily parallel the severity of the clinical status. In the chronic phase, when neurological dysfunction has become permanent, neuroimaging allows precise identification of neuroanatomical sequelae that do not necessarily match the severity of the chronic neurological impairment. Papers in the medical imaging literature have dealt mainly with the brain changes induced by 'chronic exposure' to toxic substances such as solvents or heavy metals. This article selectively reviews the main radiological changes observed on CT/magnetic resonance (MR) neuroimages after 'acute exposure' to industrial products (methanol [methyl alcohol], ethylene glycol), environmental agents (cyanide, carbon monoxide), pharmaceuticals (insulin, valproic acid) and illicit substances (heroin, cocaine). Different kinds of lesions, which lack specificity for toxic injury, can be observed on radiological images, but deep grey matter lesions with symmetrical distribution throughout basal ganglia are most often seen. However, such findings have also been reported after anoxic-ischaemic insults or during severe metabolic disturbances. Lesions in the white matter may also be present in the case of acute exposure to toxic agents. The true prognostic value of toxic-induced brain changes in the acute phase in CT or MR studies is unclear, although serial MRI may add new information as may quantitative or molecular imaging techniques such as the MR diffusion-weighted imaging or MR spectroscopy.

Which vascular lesions are of importance in vascular dementia?

Most necropsy surveys of dementia have found that vascular disease is second only to Alzheimer's disease as a cause of dementia. Alzheimer's disease and cerebrovascular disease also often coexist. The purpose of the present study was to determine the nature of the cerebrovascular lesions that are most significant in producing dementia. These were analyzed in a group of cases of dementia in which only vascular pathology was present and, in particular, no more than trivial amounts of Alzheimer-type pathology were present. The cerebrovascular lesions in this group of cases were compared with those in a group of stroke cases who were nondemented and a group of elderly cases without stroke or dementia. Severe cribriform change and deep white/grey matter micro-infarcts were significantly more common in the test group than in either of the control groups, whereas single macroscopic infarcts were more common in the stroke control group than either of the other two groups. Thus, microvascular deep white and grey matter lesions, but not macroscopic infarction, were significant in vascular dementia. The results of this study will be discussed in relation to the view that microvascular lesions may also contribute to dementia in subjects with more extensive Alzheimer-type pathology and thus lower the threshold at which Alzheimer-type pathology becomes clinically manifest.