Year : 2002 | Volume
: 12 | Issue : 1 | Page : 43--50
MRI in white matter diseases - clinico radiological correlation
BN Lakhkar, M Aggarwal, JR John
Department of Radio Diagnosis and Imaging, Kasturba Medical College, Manipal, Karnataka, India
B N Lakhkar
Department of Radio Diagnosis and Imaging, Kasturba Medical College, Manipal, Karnataka
Objectives: The purpose of this study is to evaluate the role of MRI as an investigative modality in white matter diseases and to document its value in early diagnosis and management. This was done by studying the MR appearances of various white matter diseases encountered in our hospital with special reference to multiple sclerosis and correlating it with the clinical presentation. In addition, the most common diseases among them were identified. Materials and Methods: Forty patients with a strong clinical suspicion of demyelinating disorder were evaluated by MRI using 0.5 Tesla (Signa Contour, GE) scanner in a prospective study period of 2 years. Images were obtained in sagittal, axial and coronal planes using SE T1, PD and T2 and FLAIR sequences. Slice thickness of 5mm, FOV of 24 x 24 and 256 x 192 matrix were used. Results: Demyelinating foci were demonstrated with a high degree of accuracy on MR as prolonged T1 and T2 relaxation times, the site of the lesion varying in different disorders. Multiple sclerosis accounted for the majority of cases (37.5 percent) followed by acute disseminated encephalomyelitis (15 percent). Other causes like infections, toxic causes, periventricular leukomalacia and leukodystrophies comprised the remainder of the cases. In multiple sclerosis, majority of the patients presented in the third decade of life with a definite female preponderance (M:F-1:2). The most common symptom and site of involvement were visual impairment (73.3 percent) and periventricular area (80 percent) respectively. Conclusion: MRI due to its excellent gray-white matter resolution is very sensitive in detecting subtle demyelination, the sensitivity being still further enhanced by FLAIR sequences. The present study concludes that MRI, in correlation with the clinical signs and symptoms is an ideal modality in early diagnosis of white matter diseases and aids in the early institution of therapy so that the curable conditions among them can be treated.
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Lakhkar B N, Aggarwal M, John J R. MRI in white matter diseases - clinico radiological correlation.Indian J Radiol Imaging 2002;12:43-50
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Lakhkar B N, Aggarwal M, John J R. MRI in white matter diseases - clinico radiological correlation. Indian J Radiol Imaging [serial online] 2002 [cited 2020 Aug 8 ];12:43-50
Available from: http://www.ijri.org/text.asp?2002/12/1/43/28416
Only very few studies on white matter diseases have been done in India. However, with the introduction of MRI and increasing awareness of the disease, more and more cases of multiple sclerosis and other demyelinating diseases are being diagnosed. Many of these diseases if detected early can be cured and MRI plays a vital role in its early diagnosis. MRI has virtually replaced all other imaging modalities including CT in the evaluation of white matter diseases due to its excellent gray-white matter resolution and multiplanar imaging capability. The inherent sensitivity of MRI to altered water content enables the earlier detection of demyelination compared to CT. Simultaneous imaging of spinal cord and orbits can also be done by MRI.
In this article, we report our experience with MR in 40 patients with a clinical diagnosis of demyelination and evaluate its role in the diagnosis of these diseases. In addition, pertinent literature regarding these diseases has also been reviewed.
Materials and Methods
Forty clinically suspected patients with demyelination during a period of two years (January 1999 to February 2001) formed the basis of the present study. The patient population consisted of 22 men and 18 women. All the patients with age related vascular causes of demyelination were excluded from the study group.
The MRI scan was performed using a 0.5 Tesla (Signa Contour, GE) scanner using standard head coil for the acquisition of images. Axial and sagittal scans were obtained using multislice multiecho sequences with a slice thickness of 5mm and an interslice gap of 3mm. The data acquisition was done using a matrix of 256 x 192. For T1W images, pulse sequences used were TR/TE of 440/10 msecs, for proton density images, TR/TE of 2240/30 msecs and for T2WI, TR/TE of 2240/90 msecs. Special sequence like FLAIR (Fluid attenuated inversion recovery sequence) were obtained in all cases (TR/TE 10,000/94 msecs). Contrast (Gadolinium - DTPA) at dose of 0.1 mmol/kg body weight was given wherever necessary. All patients were followed up to reach a therapeutic/biopsy diagnosis. The symptomatic response of the patient to medical therapy was noted which helped in the retrospective confirmation of the diagnosis. Brain biopsy was not done in any of the cases.
Multiple sclerosis (MS) was the most common white matter disease encountered in our study. [Table 1] shows the distribution of the various diseases we encountered in our hospital. In MS, majority of the patients were in the third decade of life with a definite female preponderance (M:F - 1:2). The mean age of onset was 27.6 years. The average age of onset in females was found to be 23.9 years and 35.2 years in males.
The most common symptom noted was visual impairment (73.3%). [Table 2] summaries the main presenting complaints of the 15 patients with MS.
MR revealed multiple lesions confined to the white matter, appearing hypointense on T1W and hyperintense on T2W images. In all patients, more than three lesions were seen. The lesions varied in size with most of the lesions being less than 1 cm. The commonest site of involvement in MS was found to be the periventricular area (80%) with the perivenular extension (Dawson's fingers) being specific for the disease [Figure 1]. Lesions at the calloso-septal interface are also characteristic with atrophy of the corpus callosum. We had only one patient with callosal atrophy [Figure 2]. Brain stem and cerebellar involvement were seen in 40% and 6.6% respectively. Spinal cord and optic nerve involvement were noted in 20% each. None of the lesions exhibited mass effect or perifocal edema. Contrast administration showed enhancement in only four cases which was of both solid and ring type of enhancement [Figure 3] and [Figure 4].
Six patients of acute disseminated encephalomyelitis (ADEM) were evaluated by MRI, all having a history of fever prior to the onset of clinical symptoms. The age group varied through a wide range of 6 to 55 years, of which four were adults and two children. The most common clinical symptoms were altered consciousness (50%) followed by motor symptoms and urinary retention (33.3% each). Majority of the lesions in our study were located in the cerebral white matter (83.3%) with asymmetric and patchy involvement [Figure 5], followed by brain stem involvement (50%). Spinal cord and cerebellar involvement were noted in one patient each. Thalamic involvement was seen in two cases and added to the specificity of diagnosis [Figure 6]. On steroid therapy, majority showed clinical improvement.
Herpes simplex encephalitis (HSE) accounted for five cases, all of which were females and three patients coming under 20-30 years age group. The commonest symptoms were altered sensorium and fever (80%) followed by seizures (40%). On MR, hypointense lesions on T1WI and hyperintense on T2WI and FLAIR characteristically involving the temporal lobes were seen in all cases extending into the basifrontal areas in 60% [Figure 7] and [Figure 8]. Contrast enhancement was seen in only one of the patients being patchy in appearance and hemorrhage was not noted in any of them. Four cases showed bilateral asymmetric involvement, the left temporal lobe being affected more than the right in 60% while unilateral involvement was seen in only one case. All cases showed prompt recovery with acyclovir therapy.
Our study included two patients with progressive multifocal leukoencephalopathy (PML). Both were HIV positive males with a mean age of onset of 29 yrs. The mean age of onset in HIV positive cases is significantly lower than HIV Sero negative PML. Both our patients presented with motor symptoms in the form of hemiparesis and one patient had cerebellar signs in addition. On MR, well defined non enhancing hypointense lesions on T1WI were seen in both patients with one showing supratentorial (frontal white matter) and the other posterior fossa (pons and cerebellum) involvement [Figure 9]. The lesions were focal with no mass effect or cortical atrophy.
There were four patients of central pontine myelinolysis (CPM) (10%) in our study. All the patients were males with the age group ranging from 24 to 60 years. Three of them had definite predisposing factors like hyponatremia in two patients and alcoholism in one patient. All the four patients showed extra pontine involvement in addition to the characteristic involvement of central pons [Figure 10] and [Figure 11].
Radiation induced white matter demyelination can also be clearly demonstrated by MRI. We had one such patient with optico-chiasmatic glioma post op and post radiotherapy. On MR, extensive demyelination of the cerebral white matter with scalloped edges was noted which was not enhancing on the contrast study [Figure 12]. An enhancing tumour at the optico-chiasmatic area was also noted suggestive of recurrence [Figure 13].
Four cases of periventricular leucomalacia (PVL) were studied in our series. All were children within the age group 3 to 9 years with a 3:1 male predominance. Two had a history of preterm delivery & asphyxia while the remaining two were full term infants with insult in the prenatal life. The most common clinical presentation was spastic diplegia (cerebral palsy) followed by seizures. MRI showed loss of white matter volume and bilateral symmetrical hyperintensity of the periventricular white matter especially of the periatrial region in all patients [Figure 14]. Ventriculomegaly and scalloping of ventricular margins were seen in two patients [Figure 15].
In our study, leukodystrophies constituted only 7.5% of total demyelinating diseases. Two boys with metachromatic leukodystrophy (MLD) were evaluated who presented clinically with pyramidal dysfunction and developmental regression. MRI revealed bilateral symmetrical diffuse periventricular hyperintensity [Figure 16]. Thalamic hypointensity on T2-weighted images and cerebral atrophy were noted in both cases suggesting long standing disease [Figure 17].
One classical case of adrenoleukodystrophy (ALD) was studied, the child being a 4 year old boy with progressive visual loss and neuro regression. On MR, there was hyperintensity on T2-weighted images in the periatrial region spanning the corpus callosum and thus explaining the symptoms [Figure 18] and [Figure 19].
The advent of MR has revolutionized the concept of understanding of white matter diseases. MRI is considered far superior to CT and the imaging modality of choice in white matter diseases. Though CT was used previously for cranial imaging in these conditions, it was not able to detect subtle lesions especially in stages of clinical inactivity and not ideal in posterior fossa imaging due to the beam hardening artifacts produced. MR scores over CT in all the above aspects. It is a noninvasive modality with multiplanar imaging capability and has a very high sensitivity for demyelinating foci due to its excellent gray-white matter resolution.
In our study, we found that FLAIR sequences had a better sensitivity for subtle demyelinating foci especially those with periventricular locations thus correlating with the study done by Ashikaqa R et al.
MS is an inflammatory demyelinating disease of the central nervous system (CNS) due to autoimmune demyelination in genetically susceptible individuals. Prior to the advent of CT, the role of the radiologist in the diagnosis of MS was mainly of exclusion. However, with the advent of multiecho sequences of MR, even subtle lesions of demyelination can be detected.
MS commonly occurs in the third and fourth decades of life with a definite female preponderance. We also got similar observations and these were consistent with the studies done by Kuroiwa et al  in the Western population and Mani J  et al in the Indian population. However, most of the other Indian series have reported a male preponderance in India. The only significant difference in clinical symptoms between Indian and Western MS was the higher frequency of visual involvement in Indian cases and low yield of oligoclonal bands in CSF.
The most common site of lesion in our study was the periventricular area. Fazekas et al and Jena AN et al have also noted the periventricular area as the commonest location. Gean-Marton et al in a prospective study found that 93% of MS patients demonstrated confluent / focal lesions involving the calloso-septal interface and concluded that callosal involvement was specific for MS. Kurtze K et al  reported a higher percentage of brainstem and cerebellar involvement (85&77%) in US veterans suggesting that cerebellar involvement is more commonly seen in Caucasians than in Orientals. All active lesions in the study showed contrast enhancement and treatment with steroids was associated with a marked reduction of lesion morphology and enhancement.
ADEM is an immune mediated demyelination which is typically seen five days to two weeks following a viral illness or immunization. On MR, lesions are located in the subcortical white mater with asymmetric involvement of both hemispheres with or without brainstem involvement. Though it predominantly involves the white matter, it can involve the gray matter as well. Menor F et al  opined that T2 prolongation in deep gray matter, specially thalamic involvement is a useful distinguishing feature of ADEM over MS. Involvement of spinal cord is very common.
HSE is the most common cause of fatal sporadic encephalitis. The early changes are detected as increased signal intensity in the temporal and inferior frontal lobes on T2-weighted scans involving the gray and white matter as early as 48 hours following the onset of symptoms. Enhancement is absent in the early stages but as disease progresses, bilateral and asymmetric involvement with gyriform enhancement pattern is noted. Associated mass effect is also seen. Early MRI diagnosis is essential as antiviral therapy can significantly reduce the mortality.
PML is probably the best known virally induced demyelinating disease. Krupp LB et al reported that PML has a stronger association with AIDS than with any immunosuppressive disease and 55% to 85% of recent PML cases are attributable to AIDS and correlated with our study. On MRI, bilateral and asymmetric hyperintensities are seen in the subcortical or periventricular white matter of the parieto-occipital region. There is absence of mass effect and enhancement due to the paucity of perivenous inflammation. PML is commonly seen to involve the posterior fossa also.
CPM is a demyelinating disease found commonly in alcoholics and in systemic disorders with electrolyte abnormalities. MR findings are of high signal intensity on T2WI in the upper and middle central pons and characteristically spares the peripheral pial and ventricular surface. Gadolinium contrast enhancement is occasionally seen at the periphery of the lesion early in the course of the disease. In addition to the pons, extra pontine sites like the deep white matter particularly external capsules as well as deep gray matter can get involved. Though MR is a decisive diagnostic modality, the size of the pontine lesion was not found to correlate with the clinical severity as supported by Laubenberger et al .
Radiation and chemotherapy causes leukoencephalopathy, the degree of damage depending on several factors. Focal necrosis resemble a mass lesion while diffuse radiation injury is characterized by periventricular increased signal on PD and T2WI. The lesions are extensive, confluent and scalloped laterally adjacent to the cortical gray matter due to arcuate fibre damage with variable gadolinium enhancement on T1. Mass effect and edema are common findings in the acute phase. Later in the course of the disease, ventricular enlargement and atrophic changes predominate.
PVL is due to the ischaemic infarction of the periventricular white matter, the vascular watershed zone in the developing fetus. It is particularly seen in preterm infants and in perinatal asphyxia. The most characteristic presentation is spastic diplegia, a form of cerebral palsy. Typical imaging findings include peritrigonal hyperintensities on T2WI, focal ventricular enlargement and irregular, scalloped ventricular contours. White matter volume is reduced and the posterior corpus callosum appears moderately atrophic.
Metachromatic leukodystrophy is a demyelinating disorder with extensive symmetrical demyelination of the periventricular and subcortical white matter resulting in a butterfly configuration. The demyelination initially spares the subcortical U fibres and the basal ganglia. Cortical atrophy occurs later in the course of the disease with involvement of the arcuate fibres and the cerebellar white matter. The basal ganglia will appear hypointense on T2-weighted images in the later stages due to the accumulation of hemosiderin. Both the cases in our study also showed hypo intensities in the basal ganglia suggesting long standing disease.
Adrenoleukodystrophy appears in boys between 4 and 8 years of age in the form of behavioural disorders, dementia and visual/auditory impairment. Symptoms of Addison's disease may accompany. The classic MR appearance is the bilateral and symmetrical demyelination of the occipital lobes and the splenium of the corpus callosum. Enhancement of the inflammatory leading edge of demyelination is noted when contrast is administered. Calcification can be seen in the parieto-occipital region.
In our study, we observed that a correct diagnosis could be made in majority of the patients based on MR findings and clinical history alone. Confirmation by brain biopsy thus is not essential in all patients except in indeterminate conditions. We thus conclude that MR, in conjunction with clinical findings, plays a significant role in establishing the diagnosis and in the further follow up of patients with white matter diseases.
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