White matter abnormalities in the brain

Etiology
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By Cory Toth MD BSc

Normal subjects. A matched co-twin analysis of elderly monozygotic twins examined the relationship between midlife cardiovascular risk factors and MRI-based measures of brain atrophy (Carmelli et al 1999). Data regarding cardiovascular risk factors were recorded over 25 years of adult life. Differences within pairs in midlife glucose levels, high-density lipoprotein cholesterol, and systolic blood pressure were significantly associated with differences in white matter hyperintensities. In addition, within-pair differences in volumes of white matter abnormalities were significantly associated with differences in performance on cognitive and physical function tests. Furthermore, the co-occurrence of cerebrovascular disease and the ApoE4 subtype was associated with significantly greater brain atrophy and white matter abnormalities than either ApoE4 or cerebrovascular disease alone (DeCarli et al 1999).

When both dizygotic and monozygotic male twins were subjected to MRI and neuropsychological testing, genetic influences appeared to play a role in the development of white matter abnormalities and impaired performance in cognitive function (Carmelli et al 2002). Genetic influences appeared to explain about two thirds of the variability in cognitive functioning; neurologic co-variation in presence of white matter abnormalities and cognition could be explained by genetic effect in more than 70% of cases.

Advanced-age subjects. Aging has a large effect on both the frequency and the severity of CT- and MRI-identifiable leukoaraiosis (George et al 1986a; 1986b; Matsubayashi et al 1992; Ylikoski et al 1993; Breteler et al 1994b). Although other risk factors play a role in the development of white matter abnormalities, aging is certainly an independent risk factor on its own (Fukui et al 1994; Lindgren et al 1994; Meyer et al 1994; Wahlund et al 1994; Hickie et al 1995; Streifler et al 1995). Additional risk factors identified in various multivariate analytical studies have included a history of stroke (Awad et al 1986; Inzitari et al 1987; Sullivan et al 1990; Cadelo et al 1991; Breteler et al 1994b; Streifler et al 1995), male sex (Inzitari et al 1987), hypertension (Awad et al 1986; Cadelo et al 1991; Breteler et al 1994b; Erkinjuntti et al 1994), diabetes mellitus (Schmidt et al 1992; Erkinjuntti et al 1994), and heart disease (Erkinjuntti et al 1994; Lindgren et al 1994). Prospective studies in non-disabled elderly subjects have determined that severe white matter hyperintensities identified with MRI, when occurring in the presence of medial temporal lobe atrophy, have a 4-fold associated increase in mild cognitive deficits (van der Flier et al 2005).

When the presence of white matter abnormalities is examined in normal elderly people, 3 distinct patterns of spatial localization within the brain can be observed. Presence of white matter abnormalities in temporal and occipital areas was associated with greater age, hypertension, late onset depressive disorder, and perhaps poor global cognitive function (Artero et al 2004). Even in high-functioning older adults without evidence of stroke or dementia, abnormalities in gait such as slower speed, shorter stride, and greater support time have a positive association with presence of white matter hyperintensities on MRI (Rosano et al 2006). Sequential MRI scans 20 months apart in elderly subjects with or without mobility impairment have demonstrated a 5-fold acceleration in the accumulative volume of white matter lesions in mobility impaired subjects (Wolfson et al 2005). In addition to the presence of white matter lesions, longitudinal analysis in elderly subjects without dementia has determined that other brain MRI abnormalities such as ventricular enlargement, and subclinical and basal ganglia small brain infarcts contribute to poor motor performance and faster gait speed decline over time (Rosano et al 2005).

Alzheimer disease. Between 19% and 78% of patients, have identifiable white matter abnormalities using CT studies (Erkinjuntti et al 1987; Kobari et al 1990; Blennow et al 1991; Diaz et al 1991; Lopez et al 1992; Raiha et al 1993) and 7.5% to 100% using MRI studies (Erkinjuntti et al 1987; Bondareff et al 1988; Wilson et al 1988; McDonald et al 1991a). It has been speculated that the presence of white matter abnormalities in patients with Alzheimer disease may be associated with presence of cerebral congophilic angiopathy (Gray et al 1985; Janota et al 1989).

More elderly patients diagnosed with Alzheimer disease have greater levels of periventricular, lobar white matter and basal ganglia white matter hyperintensities on MRI when compared to a control group. Younger onset Alzheimer disease patients did not have similar white matter abnormalities demonstrable. Despite this difference in the presence of white matter abnormalities, cortical atrophy did not differ significantly between presenile onset and senile onset Alzheimer disease patients. This may suggest that more elderly patients with Alzheimer disease may be subject to greater cerebrovascular risk factors that may play a role in the formation of their dementia (Scheltens et al 1992).

In another imaging-based study, Alzheimer disease patients were found to have significantly more white matter abnormalities than controls, with preferential involvement of the frontal lobes (70%). This study also identified an inverse correlation with grey matter cortical volume. Presence of white matter abnormalities was significantly associated with vascular risk factors and with poorer performances on memory testing (Capizzano et al 2004). In a controlled study, the combination of deep white matter lesion burden and periventricular white matter lesion burden were associated with reduced global cognition in Alzheimer disease patients but not in non-demented elderly patients (Burns et al 2005). However, another study examining Alzheimer disease patients with and without white matter abnormalities did not demonstrate an association of white matter abnormality volume with more severe cognitive dysfunction, but did find association with urinary bladder incontinence, presence of grasp reflex, and abnormal motor examinations (Hirono et al 2000a).

In patients with Alzheimer disease and presence of white matter abnormalities, psychiatric evaluation may identify greater apathy, and neurologic examination may demonstrate greater extrapyramidal signs than in Alzheimer disease patients without white matter abnormalities (Starkstein et al 1997). SPECT scans in patients with Alzheimer disease and MRI-identified white matter abnormalities may indicate significant deficits in perfusion over basal ganglia, thalamic, and frontal regions (Starkstein et al 1997).

Elevated homocysteine levels in Alzheimer disease patients have been positively associated with the presence of leukoaraiosis on CT scanning (Hogervorst et al 2002). Leukoaraiosis was more noticeable over deep white matter regions than within periventricular regions in this population (Hogervorst et al 2002). Hypertension is an oft-cited association with white matter lesions, or leukoaraiosis, and a controlled study has suggested that elevations in pulse pressure correlate with presence of leukoaraiosis in Alzheimer disease patients (Lee et al 2006).

An Irish family with familial Alzheimer disease due to an E280G mutation in exon 8 of presenilin-1 has been demonstrated to have spastic changes along with white matter abnormalities identifiable on MRI (O'Riordan et al 2002).

White matter abnormalities do not appear to be unique to dementia patients diagnosed with Alzheimer disease, as patients with Lewy body disease also have higher than normal numbers of white matter abnormalities (Barber et al 1999). Patients with clinical and radiological patterns of vascular dementia, as could be expected, have higher numbers of white matter abnormalities than either Lewy body disease or Alzheimer disease patients (Barber et al 1999). The presence of white matter abnormalities in demented patients may contribute to an increased risk for depressive symptoms (Barber et al 1999).

Psychiatric disorders. Although any association remains uncertain due to methodological problems, including lack of a suitable control group, psychiatric disorders have been described as having excessive numbers of leukoaraiosis using MRI for detection (Breitner et al 1990; Coffey et al 1990; Swayze et al 1990; Deicken et al 1991; McDonald et al 1991b; Aylward et al 1994; Hickie et al 1995). A small study examined the frequency of MRI hyperintensities in patients with bipolar disorder and a matched control group, with hyperintensities found within the right frontoparietal subcortical white matter in patients only. No periventricular white matter lesions were demonstrated in any group (Gulseren et al 2006). Although substantiation is required, a small study of patients with major depressive disorder has suggested the presence of a greater number of subcortical white matter lesions, particularly in those patients with depressed folate levels or hypertension (Iosifescu et al 2005).

The brains of patients with schizophrenia may be subject to abnormalities in white matter without a loss of white matter volume. Relative to control subjects, males with schizophrenia who were subjected to MRI diffusion tensor imaging demonstrate lower anisotropy, without changes in grey matter. The abnormal white matter anisotropy is present throughout—from frontal to occipital white matter (Lim et al 1999). Brain anisotropy relates to proton movement, which is a reflection of physically restricted water movement; in white matter, brain anisotropy is related to the presence of myelin. When T2 and proton density maps for gray matter and white matter are examined in schizophrenic males and controls, longer T2 values are found within both white and grey matter within the brains afflicted with schizophrenia. It does not appear that whatever process is producing prolonged T2 values fully accounts for the abnormally low anisotropy observed selectively in white matter in schizophrenia (Pfefferbaum et al 1999).

CADASIL. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy is characterized by multiple subcortical infarcts and leukoencephalopathy with an autosomal dominant pattern of inheritance related to a genetic defect on chromosome 19q12 (Tournier-Lasserve et al 1993). Patients with CADASIL also experience migraine, mood disturbances, and recurrent strokes, often with progression to subcortical dementia and premature death. White matter abnormalities in CADASIL may be more likely to occur in insular regions and temporal lobes as compared to white matter abnormalities in hypertensive patients. In addition, involvement of the external capsule and corpus callosum may be more specific for CADASIL patient brains (O'Sullivan et al 2001). Pathologically, CADASIL is characterized by small deep strokes and leukoencephalopathy. Small vessels in the brain have a concentric thickening of tunica media secondary to granular eosinophilic infiltration (Baudrimont et al 1993; Gray et al 1994).

As patients with CADASIL age, MRI signal abnormalities increase (Chabriat et al 1999). Besides the subcortical and periventricular regions, the brainstem can also be subject to T2 signal hyperintensities, most frequently within the pons, in the brains of CADASIL patients.

Miscellaneous disorders. Wilson disease (hepatolenticular degeneration) is an autosomal recessive disorder of copper metabolism. MRI has demonstrated abnormally increased T2 signal within the putamen and caudate, but also in the thalamus, dentate nuclei, midbrain, and subcortical white matter (Prayer et al 1990).

Hallervorden-Spatz disease is a progressive movement disorder with abnormal iron deposition in the globus pallidus, substantia nigra, and red nucleus. MRI may reveal decreased T2 signal in the lentiform nuclei and perilentiform white matter but increased T2 signal within the periventricular white matter (Gallucci et al 1990).

Neuroacanthocytosis is an uncommon neurodegenerative disorder associated with a movement disorder, dementia, and acanthocytosis. T2-weighted MRI may identify regions with increased signal within the white matter of the periventricular regions, as well as within the corpus callosum (Nicholl et al 2004).

Dystonia has not been associated with traditional MRI changes, but the new technique of diffusion tensor imaging may be sensititve enough to detect subcortical white matter asymmetry in dystonia patients (Blood et al 2006). Although the reason for this diffusion tensor imaging association is not clear, it may relate to activity-dependent microstructural changes in abnormally firing neuronal projection fibers, as patients receiving botulinum toxin for dystonia have at least partial and transient reversal of these diffusion tensor imaging changes (Blood et al 2006).

Fragile X-associated tremor and ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder mainly seen in carriers, usually males, of premutation alleles (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene. Clinically, FXTAS may present with progressive intention tremor and gait ataxia, and MRI demonstrates characteristic white matter abnormalities, particularly within cerebral and cerebellar locations (Greco et al 2006). The neuropathological hallmark of FXTAS is an intranuclear inclusion found in both neurons and astrocytes throughout the CNS (Greco et al 2002).

Children with cerebral palsy have frequent abnormalities identified using MRI. Eighty-eight percent of children have abnormal findings on MRI, including frequent changes of white matter disease of immaturity. Although focal infarcts are identified in 7% of children with cerebral palsy, periventricular leukomalacia is identified in 43%, and lesions within the basal ganglia and cortical/subcortical regions are also commonly seen (Bax et al 2006). Such changes were reported in 71% of children with diplegia and could also be found in cerebral palsy patients with hemiplegia (34%) and quadriplegia (35%). The location of such white matter lesions in diplegic patients was posterior dominant, whereas patients with quadriplegia had evidence of diffuse white matter changes. Those cerebral palsy patients with basal ganglia or thalamic changes tended to have a dystonic form of cerebral palsy (76%) (Bax et al 2006).

Susac syndrome is clinically composed of the triad of encephalopathy, retinopathy, and hearing loss. This disease of recurrent flares is a microvasculopathy secondary to thrombosis for unclear reasons (Gordon et al 1991; Xu et al 2004).

Although their significance is uncertain in myopathic disorders, both myotonic dystrophy type 1 and type 2 patients have white matter abnormalities demonstrable using MRI (Kornblum et al 2004). Of these disorders, intellectual dysfunction, possibly related to presence of cerebral atrophy and white matter abnormalities, has been demonstrated in patients with myotonic dystrophy type 2.

Prolonged hypoglycemic encephalopathy can lead to chronic encephalopathic changes and prolonged coma. In addition to acute MRI changes similar to that of ischemia, such as hyperintensity in the cerebral white matter and in the boundary zones between vascular territories, as well as superficial laminar necrosis, later assessments can demonstrate white matter changes consistent with pathologically identified severe myelin loss with astrocytosis (Mori et al 2006).

Trauma. The occurrence of closed-head injury in patients subjected to trauma may also be associated with presence of white matter changes. Of those patients found with white matter abnormalities (which may be less than 10%), the co-occurrence of SPECT abnormalities with abnormal perfusion to frontal, temporal, or parietal lobes performed 6 months after injury may suggest a poorer outcome 2 years after head injury. Patients with both white matter abnormalities and SPECT scan abnormalities were found to have poor function within rehabilitation programs and with activity of daily living scores (Vinjamuri and O’Driscoll 2000).

Patients suffering from electrical injury can be subject to both brain atrophy, sometimes progressive, and supratentorial white matter lesions (Milton et al 1996). Electrical injury may result in various acute neurologic complications such as coma, amnesia, seizures, and such delayed complications such as choreoathetosis, cerebellar ataxia, and parkinsonism (Kalita et al 2002). MRI performed in the acute stages after electrocution may demonstrate discrete hyperintense signal changes in the subcortical regions and basal ganglia. Several weeks after electrocution, white matter changes may still be present, or other findings such as cerebellar and cerebral atrophy may be identified (Kalita et al 2002).

Migraine. MRI evaluations of migraineurs have demonstrated a high incidence of increased signal intensity in the white matter on T2-weighted scans (Kaplan et al 1987; Soges et al 1988; Jacome and Leborgne 1990). In particular, these white matter abnormalities have been identified in patients under 40 years of age, which is unusual for an entity expected in an elderly population (Osborn et al 1991). When compared to an age- and sex-controlled population without headache, 14% of migraineurs have demonstrable white matter abnormalities seen usually in the periventricular white matter or near grey-white matter junctional areas, as compared to 4% of control subjects. In migraineurs, these lesions were usually in the parietal regions (Robbins and Friedman 1992). Another older study reported a 40% incidence of white matter abnormalities in patients with migraine, more commonly found in patients with migraine with aura or complicated migraine (Igarashi et al 1989). No pathological studies of white matter abnormalities in migraineurs exist, but it may be possible that white matter abnormalities in this patient group may represent an immune-mediated demyelination, which may explain the peculiar distribution of the migraine-associated lesions. Alternatively, ischemia or other forms of demyelination may be responsible (Robbins and Friedman 1992).

AIDS dementia. Patients with acquired immunodeficiency syndrome dementia complex can have associated deep white matter changes and cerebral atrophy identified on MRI. The presence of white matter abnormalities in deep white matter was associated with a trend to having an increased risk for AIDS dementia complex in patients with defined AIDS. However, higher grades of deep white matter abnormalities were more likely to be associated with AIDS dementia complex, and presence of white matter signal intensities in the splenium was associated with AIDS dementia complex. Conversely, diffuse cerebral atrophy was significantly associated with AIDS dementia complex (p = .001) (Broderick et al 1993).

Apolipoprotein E epsilon 4 status. Carriers for ApoE4 have a significantly higher subcortical white matter abnormalities volume burden than ApoE33 carriers independent of hypertension. Subjects with the combination of hypertension and at least 1 ApoE4 allele have the highest amounts for both subcortical and periventricular white matter abnormalities (De Leeuw et al 2004b). Yet in another study controlling for confounding cerebrovascular risk factors, the number of ApoE4 alleles was not associated with presence of white matter abnormalities, which were only found to be associated positively with age and hypertension (Hirono et al 2000b).

Cardiovascular risk factors. Patients with atrial fibrillation detected by electrocardiography (De Leeuw et al 2000) are more likely to have severe number and volume of periventricular white matter abnormalities when compared to control subjects (relative risk of 6.3). However, atrial fibrillation did not appear to be a risk factor for subcortical white matter abnormalities.

Diabetes mellitus has been associated with the presence of cerebral atrophy and white matter abnormalities. Even in patients not specifically diagnosed with diabetes mellitus, elevated glycated hemoglobin levels can be found in non-demented elderly patients with MRI-identified white matter lesions (Murray et al 2005). There are significantly more deep WMA found in patients with diabetes, with or without hypertension, when compared to control subjects undergoing MRI. One cross-sectional study has suggested that type 2 diabetes is an independent risk factor for deep WML in living elderly patients (van Harten et al 2006). Not only is type 2 diabetes associated with deep WMAs, but it is also associated with both cortical and subcortical atrophy and impaired cognitive performance (attention and executive function, information-processing speed, and memory) (Manschot et al 2006). The most common locations for diabetes-associated white matter abnormalities are in the caudate and putaminal nuclei, internal capsule, thalamus, dentate nucleus, supratentorial white matter, and brainstem (Schmidt et al 2004). Diabetic-associated white matter abnormalities, in themselves, are a risk factor for stroke (Fushimi et al 1996), as well as for cognitive deficits such as memory and executive functioning and abnormalities in gait and balance dysfunction (Awad et al 2004; Korf et al 2006). In the diabetic brain, periventricular brain regions are predominantly affected with increased T2-weighted MRI signals (Tornheim 1981), possibly due to changes in periventricular fluid dynamics with a disrupted subependymal lining (Harris et al 1993). Other previously speculated mechanisms in the development of white matter abnormalities in the diabetic brain include vascular border zone hypoperfusion, subclinical ischemia (Yoshiura et al 2000), neuronal loss and axonal degeneration (Ball 1989), and abnormalities in the blood-brain barrier and cerebrospinal fluid dynamics (Yoshiura et al 2000). In older patients with long-standing type I diabetes, informational processing speed is compromised when compared to controls, but several other measures are only mildly affected in older type I diabetes patients. In this type I diabetes patient population, there were no definite WMA detected when compared to patients without diabetes, and brains exposed to long-term type I diabetes showed a trend toward brain atrophy only. Among patients with diabetes, age, hypertension, hemoglobin A1C levels, and retrograde hemoglobin A1C levels were related to significant slowing of information processing. The duration of diabetes was also inversely related to memory, attention and executive functioning, with disease onset before age 18 showing greatest relationship. Onset of diabetes prior to age 18 in combination with known atherosclerotic disease were also related to the presence of WMA.

Pathologically, areas of white matter abnormalities in diabetic and other brains relate to presence of regions of myelin pallor with relative loss of axons, myelinated fibers, and oligodendrocytes over affected regions, which may demonstrate spongiosis and extracellular space expansion (Braffman et al 1988a; Schmidt et al 1992; Fazekas et al 1998). The most common locations for white matter abnormalities in human brain are in the caudate and putaminal nuclei, internal capsule, thalamus, dentate nucleus, supratentorial white matter, and brainstem (Munoz et al 1993).

Hypertension is commonly associated with presence of white matter abnormalities, whether in patients with co-existing stroke, transient ischemic attack, or vascular dementia (Bogousslavsky et al 1987; Rezek et al 1987; Wallin et al 1989; van Swieten et al 1992) as well as in asymptomatic control subjects (George et al 1986b). In addition, the presence of leukoaraiosis on CT is strongly associated with presence of lacunar infarcts and intracerebral hemorrhage (Inzitari and Mascalchi 1990; Cadelo et al 1991), both of which occur in the presence of hypertension. Although not demonstrated, the co-occurrence of cerebrovascular risk factors may be associated with an even higher white matter lesion load.

When patients with Alzheimer disease with or without presence of white matter abnormalities on MRI are examined for hypertension, those patients with white matter abnormalities are more likely to have presence of hypertension. However, the degree of atrophy did not depend on the presence or absence of hypertension in this population (De Leeuw et al 2004a). Although some authors claim that the risk of Alzheimer disease is increased in patients with type 2 diabetes, it is not clear that the cognitive decline in such patients is clearly related to accentuated Alzheimer disease pathology. However, patients with diagnoses of both type 2 diabetes and Alzheimer disease have greater cortical atrophy identified on MRI when compared to patients with Alzheimer Disease without diabetes. Even though infarcts are more common in patients with Alzheimer disease and type 2 diabetes, these did not explain the increased atrophy identified, suggesting that non-vascular mechanisms are contributing to increased cortical atrophy associated with diabetes (Biessels et al 2006).

The presence of a positive family history of stroke or hypertension in first degree relatives is significantly associated with the presence of white matter abnormalities (Reed et al 2000) and may be one of the best predictors for the existence of white matter abnormalities.

Patients with hypertension have more white matter abnormalities than controls or patients in whom blood pressure was controlled with antihypertensives (Dufouil et al 2001).

White matter abnormalities, in themselves, are a risk factor for stroke (Braffman et al 1988b) and cognitive deficits in functions such as memory and executive functioning as well as abnormalities in gait and balance dysfunction (de Groot et al 2000; Gunning-Dixon and Raz 2000; Vermeer et al 2003). White matter abnormalities disrupt prefrontal-subcortical loops involved in frontal lobe executive control (Whitman et al 2001).

Pediatric diseases. A variety of white matter diseases, particularly pediatric in onset, can be associated with white matter disease identifiable on MRI. Although some of these disorders may have imaging findings that can appear similar to white matter abnormalities; the nature of the white matter changes is generally dissimilar. Some of these disorders also affect the grey matter and peripheral nervous system. The classic forms of leukodystrophies include adrenoleukodystrophy, Krabbe globoid cell, and metachromatic leukodystrophy, as well as less common entities. These are genetic in origin and are caused by a specific inherited biochemical defect important in the metabolism of myelin proteolipids that results in abnormal accumulation of a metabolite in brain tissue.

Adrenoleukodystrophy is a peroxisomal disorder that leads to abnormal accumulation of very long chain fatty acids. Adrenoleukodystrophy is both a demyelinating and dysmyelinating disorder. Initially, it involves predominantly the parietal-occipital lobes but then progresses forward into the frontotemporal regions over time. Both periventricular and subcortical white matter are affected, and in advanced disease the internal capsule, corpus callosum, corticospinal tracts and other white matter fiber tracts in the brainstem can be involved. The white matter disease tends to be contiguous within fiber tracts and confluent within large white matter regions (Kumar et al 1987). Typical MR findings include large, symmetric, hyperintense lesions on T2-weighted MRI.

Krabbe disease (globoid cell leukodystrophy) is an autosomal recessive disorder that presents shortly after birth and progresses rapidly. This is due to a deficiency of the enzyme galactocerebroside beta-galactosidase, leading to abnormal production and maintenance of myelin. MRI reveals bilateral, confluent changes within cerebral and cerebellar white matter (Demaerel et al 1990).

Metachromatic leukodystrophy is a lysosomal disorder with autosomal recessive inheritance due to deficiency of arylsulfatase A. This is primarily a dysmyelinating disorder. T2 signal shortening may be seen in the thalamus, the posterior limb of the internal capsule, the cerebellum, and the quadrigeminal plate (Kim et al 1997).

Other leukodystrophies that may demonstrate evidence of white matter disease include Alexander disease, Canavan disease, Pelizaeus-Merzbacher disease, Cockayne syndrome, Hurler disease, and Lowe syndrome.

Mitochondrial diseases may also present with evidence of white matter changes. Leigh disease (subacute necrotizing encephalomyelopathy) is a familial disorder with autosomal recessive inheritance, usually with onset in infancy or childhood. MRI may reveal symmetric areas of increased T2 signal within the basal ganglia, brainstem, and cerebellum (Medina et al 1990).

Kearns-Sayre syndrome in children may have T2 hyperintensities of the basal ganglia and brainstem (Valanne et al 1998). Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes may have infarct-like lesions within subcortical white matter that does not correspond to vascular territories due to metabolic ischemia (Valanne et al 1998). Children with combined complex I and IV deficiency can have extensive white matter changes (Valanne et al 1998; de Lonlay-Debeney et al 2000).

Another pediatric cause for white matter abnormalities is the presence of pyridoxine deficiency and associated epilepsy (Jardim et al 1994). These infants may have presence of frontal or occipital white matter lesions.

Another cause of pediatric white matter changes is infection. Cytomegalovirus infection can present with white matter changes on MRI (van der Knaap et al 2004), including multifocal lesions with deep parietal white matter.

In This Article

Introduction
Historical note and nomenclature
Clinical manifestations
Clinical vignette
Etiology
Pathogenesis and pathophysiology
Epidemiology
Prevention
Differential diagnosis
Diagnostic workup
Prognosis and complications
Management
References cited
Contributors