Jacob Valk

Magnetic resonance of myelin, myelination, and myelin disorders

This edition has been revised to include new data on genetics, molecular biology, and the role of cellular structures on one side and the growing experience with MR patterns of less common myelin disorders on the other. In addition, chapters have been added on disorders of which the white matter involvement was previously unclear.

Histopathology of an infantile-onset spongiform leukoencephalopathy with a discrepantly mild clinical course

Abstract Recently, we described an as yet unidentified white matter disorder in eight patients which probably has an autosomal recessive mode of inheritance. The disease was characterized by megalencephaly and leukoencephalopathy with onset during the 1st year of life and a delayed onset of slowly progressive neurological dysfunction. No basic biochemical defect could be identified. Brain biopsy was performed in one of the patients and the histopathological findings are described in the present report. A spongiform leukoencephalopathy was revealed, without cortical involvement. Most vacuoles were covered by single five-layered membranes, representing single myelin lamellae. Some vacuoles were partially covered by multilamellar myelin sheaths or oligodendroglial cell extensions. The vacuoles were never found in the middle or inner parts of myelin sheaths, but involved the outermost lamellae of myelin sheaths only, whereas the remainder of the myelin sheats remained undisturbed. The histopathological findings place the disease among the vacuolating myelinopathies, although it is distinct from the well-known forms. Possible pathophysiological mechanisms are splitting of the outermost myelin lamellae at the intraperiod line or a disturbance of compaction of the outermost myelin lamellae at the intraperiod line.

Subcortical Arteriosclerotic Encephalopathy

In 1894, Binswanger was the first to describe subcortical arteriosclerotic encephalopathy (SAE), distinguishing it from the progressive paralysis of syphilis. SAE is frequently called Binswanger’s disease, recently also designated Binswanger’s microangiopathic leukoencephalopathy. The age at onset is usually between 50 and 70 years, but sometimes earlier or later on in life. SAE is a relatively common affliction of elderly patients, most of whom have risk factors for arteriosclerosis. It is clearly associated with a history of hypertension, although there are also reports of patients whose necropsy examinations reveal SAE but who did not have hypertension during life.

Myelination and Retarded Myelination

Flechsig (1920) was the originator of the view that the degree of myelination of the central nervous system might be correlated with functional capacity. In his theory he stated that myelination started in projection pathways before association pathways, in peripheral nerves before central pathways, and in sensory areas before motor ones. Although he did modify his theory slightly because of his critics, he maintained that fibers always myelinated in the same order: first the afferent (sensory), then the efferent (motor), then the association fibers. The histological study of fetal development has confirmed that myelination proceeds systemetically and, in nerve pathways with several neurons, in the order of conduction of the impulse. The first signs of myelination appear in the column of Burdach at the gestational age of 16 weeks, growing stronger from the 24th week. The column of Goll starts to myelinate at 23 weeks gestation. Cerebellar tracts start to myelinate at about 20 weeks gestation and the amount of myelin at birth is considerable. Pyramidal tracts start to myelinate at 36 weeks at the level of the pons, but at birth the amount of myelin is still scanty. In other tracts, for example, the rubrospinal tracts, the pattern of the pyramidal tract is followed. The olive and cerebellar connections begin to myelinate by 22 weeks gestation with rapid progression thereafter. In the pons some myelination is present at 36 weeks, but is still slight at birth. The corticopontine-cerebellar tracts are relatively late in myelination and show hardly any myelination at birth. In a full-term neonate of 40 weeks gestation, myelin stains reveal myelin in the medulla oblongata, in the central fibers of the cerebellum, in some fiber tracts in the pons and mesencephalon, in the posterior limb of the internal capsule, and some in the basal nuclei, spreading from there to the central parts of the centrum semiovale into the postcentral gyms. For further details see chapter 3.4.

Myelin and White Matter

Myelin makes up most of the substance of white matter in the central nervous system (CNS). It is also present in large quantities in the peripheral nervous system (PNS). In both the CNS and the PNS, myelin is essential for normal functioning of the nerve fibers.

Globoid Cell Leukodystrophy: Krabbe’s Disease

Globoid cell leukodystrophy (GLD), also known as Krabbe’s disease, is a disorder of myelin metabolism with autosomal recessive inheritance. A number of clinical types can be distinguished, which differ in age of onset and in the more or less rapid course of symptomatology. The early-infantile type or classical type is most well known. The other types are: congenital, lateinfantile, juvenile and adolescent-adult. Early and late onset forms of GLD may occur within the same family.

partially saturated fluid attenuated inversion recovery (FLAIR) sequences in multiple sclerosis: Comparison with fully relaxed FLAIR and conventional spin-echo

Fluid attenuated inversion recovery (FLAIR) sequences produce selective cerebrospinal fluid (CSF) suppression by employing a very long inversion time (TI). We used the FLAIR sequence to study patients with multiple sclerosis (MS) at 0.6 T. So far, a very long TR (and long acquisition time) has been used in a fully relaxed (FR-FLAIR) system. To speed up the FLAIR sequences, we used a shorter TR, and demonstrated that complete CSF suppression can be maintained with partial saturation (PS-FLAIR) by reducing TI at the same time. The introduction of partial saturation, however, reduced the contrast between lesions and normal appearing white matter (NAWM). Suboptimal CSF suppression therefore had to be accepted to maintain sufficient lesion to NAWM contrast. Using a TE of 60 ms, the PS-FLAIR and FR-FLAIR performed equally well in the detection of MS-lesions, although the former provided poorer CSF suppression. Both FLAIR sequences, however, provided poorer constrast between lesions and NAWM compared to conventional spin-echo sequences. Although the long acquisition time of the FLAIR sequence can be reduced by using partial saturation, complete CSF suppression and good lesion to NAWM contrast are incompatible at short TRs. Using a TE of 60 ms, conventional spin-echo sequences detect more lesions and provide better contrast between lesions and NAWM than FLAIR sequences in MS patients.

Canavan’s Disease

Canavan’s disease (CD) is a rare hereditary neurological disorder affecting children. The disease is also called spongy degeneration of the CNS of the van Bogaert-Bertrand type. Similar to Tay-Sachs disease and Niemann-Pick disease, CD is most frequently found in children of Jewish Ashkenazi origin. An autosomal recessive mode of inheritance is evident: the disease appears in children of apparently normal parents, the siblings of patients are also frequently affected, there is an equal sex ratio, and there is high consanguinity in the parents of affected children.

Rhizomelic Chondrodysplasia Punctata

The rhizomelic form of chondrodysplasia punctata (RCP) is a rare autosomal recessive disorder. Clinical signs are present from birth onwards and consist of proximal shortening of the limbs (rhizomelia), microcephaly and in some of the neonates also a low weight and/or height. Contractures of large joints are often present and feet may show equinovarus or calcaneovalgus deformities. Some patients have a characteristic facies with flat nasal bridge, hypertelorism, anteverted nares and a long philtrum. Respiratory distress is occasionally present in the neonatal period. Feeding is usually poor due to poor sucking and swallowing. Erythematous and scaling skin lesions (ichthyosiform erythroderma) are observed in 25% of the patients. In 75% cataracts are found, but optic fundi are normal.

Pattern Recognition in White Matter Disorders

MR imaging is highly sensitive in the detection of white matter lesions. A close association has been demonstrated between the occurrence of white matter abnormalities observed with MRI and those found at autopsy. It has been generally assumed that the specificity of MRI is much lower than its sensitivity. However, the specificity of MRI depends not only on the potential and limitations of the method, but also on the capabilities of the person interpreting the MR images (Fig. 70.1). Hence, optimization of the specificity of MRI for white matter disorders is achieved by optimizing the quality of both MR images and MRI interpretation.