American Journal of Neuroradiology 31:E47-E48, May 2010
© 2010 American Society of Neuroradiology

C. Amato^a, M. Elia^b and C. Schepis^c
aDepartment of Neuroradiology
^bDepartment of Neurology
^cDepartment of Dermatology “Oasi Maria SS.”–Research Institute (IRCCS) Troina, Italy

This letter focuses on Schimmelpenning syndrome (SS), a neurocutaneousdisorder related to epidermal nevus syndromes and characterized by craniofacial nevus, neurologic anomalies, and ocular pathology.

We discuss clinical and MR imaging features of a 10-year-old boy, pointing out the etiopathologic substratum of this condition and the vascular origin of brain abnormalities; in our case, there is an unusual association of hemimacrocephaly and ipsilateral cerebral hemiatrophy.

Epidermal nevus syndrome is a rare phacomatosis characterized by epidermal nevi in association with neurologic disorders and ocular or skeletal anomalies; other organ systems may be involved with hamartomas. The term “epidermal nevus syndrome” does not indicate 1 disease but rather a heterogeneous group of neurocutaneous disorders with a distinct genetic profile and a similar cutaneous phenotype.¹ These conditions may differ from one another either by type and site of nevi or by distinctive clinical correlations.

SS represents the best definition for a craniofacial sebaceus nevus associated with difficult seizures, mental retardation, and ocular lesions, such as coloboma or epibulbar lipodermoid; skull deformity is usually present. Cerebral manifestations include developmental anomalies, vascular lesions, tumors, and tumorlike conditions, which are all generally ipsilateral to the nevi.^2,3

The classic form of SS is characterized by craniofacial hemihypertrophy,hemimegalencephaly, and pachygyria-polymicrogyria. The reported case of a large epidermal nevus of the head and neck differs from the classic form and consists of cerebral hemiatrophy with normal cortical organization, vascular anomalies, and giant Virchow-Robin spaces (VRSs).

The pathogenesis and clinical expression of SS and correlate syndromes are based on genomic mosaicism, in which 2 genotypical different clones of the same specific cell line coexist in a single individual.

Epidermal and pigmentary cells originate early in the neural crest and, after proliferation, migrate to the periphery of the embryo. In neurocutaneous disorders, a somatic mutation at this time originates an altered cellular clone that will be phenotypically represented along the so-called lines of Blaschko (Fig 1). These lines indicate the pathway of embryonic ectoderm and are clinically apparent when recognizable from surrounding normal cells, thus representing the cutaneous expression of mosaicism. When genetic mutations occur early and their products do not cause the death of the embryo because of involvement of only some cell lineages, by the lethal gene theory,⁴ skin and the embryogenetically contiguous central nervous system will both be damaged.

View larger version (72K): [in this window] [in a new window] Fig 1. A, Patient at 10 years old with a large, tumefactive, and hyperkeratotic epidermal nevus involving the skull, face, and neck. B, Note lines of Blaschko on the head and neck. Modified from Moss et al.4

The neurologic abnormalities are strictly related to the timing of these events. If mutation occurs during neuronal migrationor cortical organization, there will be brain malformations; whereas if it happens later, atrophy and vascular anomalies will be more evident.

In our patient, unilateral hypoplasia of the arterial system, Sylvian stenosis, and ischemic changes in the temporal lobe(Figs 2 and 3) should refer to a malformative vasculopathy that occurred late in utero or at least after brain gyration andseriously reduced hemispheric perfusion. In fact, patients with SS are at risk of vascular anomalies, as reported in approximately one-third of published cases; among these anomalies are aortic coarctation and aneurysm, and renal artery and carotid stenosis.⁵

View larger version (121K): [in this window] [in a new window] Fig 2. MR angiography of the patient at 2 years old shows a hypoplastic right siphon and middle cerebral artery, with a stenotic Sylvian bifurcation.

View larger version (188K): [in this window] [in a new window] Fig 3. A, Coronal T2-weighted image of the patient at 20 days old shows a right cerebral hemiatrophy with cortical thinning and mild parenchymal change in the temporal lobe (arrow). On the same side, macrocrania and dilated liquoral spaces are present. B, Coronal T2-weighted image of the patient at 2 years old shows hypomyelination and an old infarct (arrow) in the right temporal lobe. Next to the ventricle, confluent and enlarged VRSs are recognizable. C, MR image of the patient at 10 years old. Coronal T2-weighted image shows, on the right side, stable cerebral hemiatrophy, a giant VRS next to the ventricle, and old ischemic changes within the hypomyelinated temporal lobe. D, High-resolution axial T2-weighted image shows a scleroatrophic right eyeball with a hypoplastic optic nerve. Lipodermoid tissue in the lacrimal fossa is present (arrow).

In conclusion, our patient exhibited typical features of SS with craniofacial epidermal nevus, ipsilateral cerebral abnormalities, difficult epilepsy, mental retardation, and ocular pathology; such characteristics give us the possibility of distinguishing this condition from the other related disorders. The relevance of this case is in the unusual association of hemimacrocrania and ipsilateral cerebral atrophy; moreover, brain abnormalities are the result of an in utero vasculopathy and do not include cortical dysplasia as in most of the previous reports.

References

1. Happle R. Epidermal nevus syndrome. Semin Dermatol 1995;14:111–21[CrossRef][Medline]
2. Sugarman JL. Epidermal nevus syndrome. Semin Cutan Med Surg 2007;26:221–30[CrossRef][Medline]
3. Zhang W, Simos PG, Ishibashi I, et al. Neuroimaging features of epidermal nevus syndrome. AJNR Am J Neuroradiol 2003;24:1468–70[Abstract/Free Full Text]
4. Moss C, Larkins S, Stacey M, et al. Epidermal mosaicism and Blaschko’s lines. J Med Genet 1993;30:752–55[Abstract/Free Full Text]
5. Greene AK, Rogers GF, Mulliken JB. Schimmelpenning syndrome: an association with vascular anomalies. Cleft Palate Craniofac J 2007;44:208–15[CrossRef][Medline]

American Journal of Neuroradiology 31:E45, May 2010
© 2010 American Society of Neuroradiology

K. Bendfeldt^a, L. Kappos^a, E.W. Radue^a and S. Borgwardt^a
aMedical Image Analysis Centre University Hospital Basel Basel, Switzerland

We read with great interest the article by Filippi and Rocca entitled “MR Imaging of Gray Matter Involvement in Multiple Sclerosis: Implications for Understanding Disease Pathophysiology and Monitoring Treatment Efficacy.”¹The authors reported on how advances in MR imaging technology and methods of analysis are contributing to the detection of focal lesions and occult pathology and atrophy in multiple sclerosis (MS). They concluded that the application of quantitative MR imaging–based techniques has shown consistently that gray matter (GM) is not spared by MS and that GM damage is present in all MS phenotypes since the earliest clinical stages of the disease, affects various GM compartments, and is associated with the main clinical manifestations of MS. They discussed several aspects of GM pathology, including focal macroscopic lesions, intrinsic diffuse changes, and irreversibletissue loss.

To date, relatively little is known about the spatiotemporal relationship of regional white matter (WM) and GM changes. A recent cross-sectional study using MR imaging–based lesion probability maps (LPMs) showed that retrograde damage of the perikarya from axonal injury within MS plaques might be crucial to the genesis of GM atrophy.² In this study, an association of focal WM damage in the optic radiations with upstream GM atrophy of the lateral geniculate nucleus and visual cortex in the calcarine sulcus of the occipital lobe was found. To develop a better understanding of the longitudinal spatiotemporal relations between regional GM and WM changes in patients with MS, our group studied the associations of regional WM lesion changes and regional GM volume reductions in patient groups with either “progressive” or “nonprogressive” WM lesion load. Voxel-wise regional brain volume changes were assessed by using voxel-based morphometry (VBM), a structural image analysis method that avoids an a priori knowledge about the relationship among these anatomic structures and queries the entire brain.³ We also used LPMs, obtained from T2-weighted or T1-weighted structural MR imaging of a large sample of patients with MS and applied “optimized” VBM to compare WM and GM changes.⁴

By using LPMs, we demonstrated a more widespread regional distribution pattern of WM lesions in the progressive group compared with the nonprogressive group of patients with relapsing-remitting MS.⁴ This might be a central issue predicting further lesion development as well as development of GM atrophy in patients with MS. Furthermore, the longitudinal VBM analysis revealed spatial T2 lesion changes in parts of the cerebral projection, commissural, and association fiber systems only in the progressive group. These changes were accompanied by GM volume reductions in specific cortical regions predilected for atrophy. Multiple disconnections between different areas of cortical networks could relate to widespread cortical atrophy and cognitive impairment, commonly observed in MS. A small number of nonprogressive lesions located in WM tracts (ie, of the associative cortex) might have interrupted relatively few connections with little or no effect on regional GM volumes in the nonprogressive group. A larger number of progressive lesions, however, accompanied by a widespreadspatial distribution, could have interrupted a higher number of associative connections, thereby contributing to the progression of GM atrophy in the progressive group. Further large-scale studies using VBM or other measures for estimation of regional brain volumes may help to disentangle the spatiotemporal relations between regional GM and WM pathology and could impact current views on MS pathogenesis.

References

1. Filippi M, Rocca MA. MR imaging of gray matter involvement in multiple sclerosis: implications for understanding disease pathophysiology and monitoring treatment efficacy. AJNR Am J Neuroradiol 2009 Dec 31. [Epub ahead of print]
2. Sepulcre J, Goni J, Masdeu JC, et al.Contribution of white matter lesions to gray matter atrophy in multiple sclerosis: evidence from voxel-based analysis of T1 lesions in the visual pathway. Arch Neurol 2009;66:173–79[Abstract/Free Full Text]
3. Bendfeldt K, Kuster P, Traud S, et al. Association of regional gray matter volume loss and progression of white matter lesions in multiple sclerosis: a longitudinal voxel-based morphometry study. Neuroimage 2009;45:60–67[CrossRef][Medline]
4. Bendfeldt K, Blumhagen JO, Egger H, et al. Spatiotemporal distribution pattern of white matter lesion volumes and their association with regional gray matter volume reductions in relapsing-remitting multiple sclerosis.Human Brain Mapping. 2010 Jan 27 [Epub ahead of print]

Reply

Published ahead of print on March 11, 2010
doi: 10.3174/ajnr.A2047

American Journal of Neuroradiology 31:E46, May 2010
© 2010 American Society of Neuroradiology

M. Filippi^a and M.A. Rocca^a
aNeuroimaging Research Unit Institute of Experimental Neurology Division of Neuroscience Scientific Institute and University Hospital San Raffaele Milan, Italy

We read with interest the comments from Drs Bendfeldt, Radue, Borgwardt, and Kappos to our recently published review.(1) Our scope was to summarize the most promising results obtained from the use of MR imaging for the assessment of gray matter (GM) pathology and dysfunction in patients with multiple sclerosis (MS) and to envisage the possible implications of such findings in the monitoring of new experimental treatments. As we discussed,the topic is extremely broad and includes not only our improved ability to detect macroscopic lesions in the GM(2) but also an urgent need to apply, in a systematic way, MR imaging techniques with the potential of quantifying occult damage in the GM, GM tissue volume loss, and topographic distribution of GM abnormalities and of establishing the role of brain plasticity in limiting the clinical consequences of tissue injury.

As pointed out by Bendfeldt and coworkers in their letter, the core part of which is strikingly similar to another letter they published previously,(3) and by ourselves in the review article, one of the results of this research was the demonstration of an association between T2 lesions in the white matter (WM) and GM abnormalities. Such an association has been demonstrated by many studies(1) in patients with MS by using different techniques and is supported by pathologic findings,(4) which showed that WM changes are accompanied by a significant burden of demyelination in the GM. Among these many studies, we also quoted the one that Bendfeldt et al published last year inNeuroimage,(5) and we are grateful to these authors for pointing out that an additional article dealing with the same issue is “in press,” which, for obvious reasons, we could not quote. Unfortunately, however, the biologic meaning of such a relationship and its timing are poorly known issues, which require further research. Voxel-wise methods for defining the regional distribution of lesions in the WM, combined with a regional assessment of GM atrophy distribution and progression, are certainly promising, especially in the context of longitudinal studies.

Nevertheless, as we discussed in our article,(1) there are many aspects of GM pathology in MS that have emerged during the past few years that also need to be considered. One of the most important is the presence of GM macroscopic lesions, which, as is the case of WM plaques, accumulate with time and are related to the progression of brain atrophy and disability.(6,7) How these GM lesions evolve with respect to WM ones is yet unclear. Another important aspect is the damage to “critical” WM fiber bundles, which might also be responsible for selective GM atrophy and disconnection syndromes in MS. As a consequence, we believe that the idea of responding in a clear-cut manner to such an important research question by applying voxel-based morphometry and lesion probability maps in isolation reflects a rather simplisticview of MS pathobiology and is likely to be insufficient.

References

1. Filippi M, Rocca MA. MR imaging of gray matter involvement in multiple sclerosis: implications for understanding disease pathophysiology and monitoring treatment efficacy. AJNR Am J Neuroradiol 2009 Dec 31 [Epub ahead of print]
2. Geurts JJ, Bo L, Pouwels PJ, et al.Cortical lesions in multiple sclerosis: combined postmortem MR imaging and histopathology. AJNR Am J Neuroradiol 2005;26:572–77[Abstract/Free Full Text]
3. Bendfeldt K, Radue EW, Borgwardt SJ, et al. Progression of gray matter atrophy and its association with white matter lesions in relapsing-remitting multiple sclerosis. J Neurol Sci 2009;285:268–69, author reply 69[CrossRef][Medline]
4. Kutzelnigg A, Lucchinetti CF, Stadelmann C, et al. Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 2005;128:2705–12[Abstract/Free Full Text]
5. Bendfeldt K, Kuster P, Traud S, et al. Association of regional gray matter volume loss and progression of white matter lesions in multiple sclerosis: a longitudinal voxel-based morphometry study. Neuroimage 2009;45:60–67[CrossRef][Medline]
6. Calabrese M, Rocca M, Atzori M, et al. A 3-year magnetic resonance imaging study of cortical lesions in relapse-onset multiple sclerosis. Ann Neurol 2010;67:376–83[Medline]
7. Calabrese M, Rocca MA, Atzori M, et al. Cortical lesions in primary progressive multiple sclerosis: a 2-year longitudinal MR study. Neurology 2009;72:1330–36[Abstract/Free Full Text]

American Journal of Neuroradiology 31:E33, March 2010
© 2010 American Society of Neuroradiology

P. Lalitha^a and B. Reddy^a
aDepartment of Radiology Focus Diagnostics Hyderabad, India

Neurocysticercosis (NCC) is a common cause of morbidity in manydeveloping countries and a common cause of seizure disorder in children and adults. The 4 stages of NCC are vesicular, vesicular colloidal, granular nodular, and nodular calcified.¹ The appearance on MR imaging would depend on the stage of the disease. Most commonly, NCC presents as isohypointense lesions on T1-weighted MR imaging. To our knowledge, extensive hyperintense signals on T1-weighted images have not been described for NCC.

A young man 22 years of age presented with headache on and off for 5–6 months. There was no history of seizures, which was also very unusual in his case. Plain and contrast MR imaging of the brain was performed. T1-weighted images revealed multiple hyperintense foci of varying sizes, in bilateral cerebral, cerebellar hemispheres and the brain stem (Fig 1). The T1 hyperintense signals were thicker in the right cerebellar hemisphere (Fig 2). Multiple other lesions were revealed on gradient images, which were not demonstrated on routine MR images. These multiple extensive T1 hyperintense signals were confirmed to be calcifications on CT, which was performed subsequent to the MR imaging. Few of the T1 hyperintense lesions showed mild enhancement on contrast administration.

View larger version (112K): [in this window] [in a new window] Fig 1. Plain T1-weighted image reveals small hyperintense foci in the bilateral cerebral hemispheres.

View larger version (121K): [in this window] [in a new window] Fig 2. Plain T1-weighted image reveals hyperintense signals in both cerebellar hemispheres, thicker on the right side.

The MR imaging appearance and contrast characteristics would depend on the stage of the parasitic cyst. The unusual appearance of such extensive T1 hyperintense signals, as seen in our patient, has not been described earlier and is probably due to calcifications, which are known to appear hyperintense on T1-weighted MR imaging.^2,3 The reason for calcifications demonstrating T1 hyperintense signals has not been clearly elucidated.² These signals in calcifications are probably due to shortening of the T1 relaxation time, due to the paramagnetic effect of calcium on adjacent water.² Thedegree of T1 shortening is larger with a larger area of calcification. Calcifications may also appear hyperintense on the T1-weighted images if they contain other paramagnetic elements like manganese or iron.² Such extensive T1 hyperintense calcifications with blooming on gradient images must not be mistaken for multiple bleeds.

References

1. Osborne AG. Diagnostic Neuroradiology: The Requisites. St Louis: Mosby; 2003:709–12
2. Tawil MI, Wilson JP, Wright NB. Intracranial lithography? Br J Radiol 2002:75:563–64[Free Full Text]
3. Dell LA, Brown MS, Orrison WW, et al. Physiologic intracranial calcification with hyperintensity on MR imaging: case report and experimental model. AJNR Am J Neuroradiol 1988;9:1145–48[Abstract]

American Journal of Neuroradiology 31:E29, February 2010
© 2010 American Society of Neuroradiology

J. Linn^a and H. Brückmann^a
aDepartment of Neuroradiology University Hospital Munich Munich, Germany

With great interest, we read the recent review article by Kumar entitled “Neuroimaging in Superficial Siderosis: An In-Depth Look,” published on-line ahead of print in the American Journal of Neuroradiology in September 2009.¹The author provides a thorough review of neuroimaging in superficial siderosis (SS) of the central nervous system and details important underlyingcauses of this phenomenon. Besides the common mechanisms (eg, history of trauma or intradural surgery), the author lists cerebral amyloid angiopathy (CAA) as a potential pathomechanism for SS.¹ We want to underline the role of this microangiopathic disease as an important cause of SS.

Most interesting, the published CAA cases with SS lack the typical clinical findings of “classic” SS, which are progressive gait ataxia with cerebellar dysarthria and sensorineural hearing loss, but patients often present with headache, seizures, and cognitive impairment.^2–4 This is most probably due to the characteristic localization of SS in patients with CAA: While the “classic” SS mainly affects brain stem and posterior fossa,¹ SS in CAA is typically found in a supratentorial distribution over the cerebral convexities.^2–4

In our opinion, CAA should be thoroughly considered as a cause of SS, especially in older patients with isolated supratentorial SS and an atypical clinical presentation. Further studies on the sensitivity and specificity of SS as a noninvasive diagnostic MR imaging sign of CAA are necessary.

References

1. Kumar N. Neuroimaging in superficial siderosis: an in-depth look.AJNR Am J Neuroradiol 2010;31:5–14[Abstract/Free Full Text]
2. Linn J, Herms J, Dichgans M, et al. Subarachnoid hemosiderosis and superficial cortical hemosiderosis in cerebral amyloid angiopathy. AJNR Am J Neuroradiol 2008;29:184–86[Abstract/Free Full Text]
3. Roch JA, Nighoghossian N, Hermier M, et al. Transient neurologic symptoms related to cerebral amyloid angiopathy: usefulness of T2*-weighted imaging. Cerebrovasc Dis 2005;20:412–14[CrossRef][Medline]
4. Feldman HH, Maia LF, Mackenzie IR, et al. Superficial siderosis: a potential diagnostic marker of cerebral amyloid angiopathy in Alzheimer disease. Stroke 2008;39:2894–97[Abstract/Free Full Text]

Fall is upon us and so is the lecturing season! Like years before, this Fall I will be giving my brachial plexus lecture several times and the most commonly asked question by the audience is: “where can I get your MRI protocol?” For this reason I am posting it here.  Posting of protocols seems to gather considerable attention; Dr. Wiggins post on MRI and CT protocols has been viewed over 1900 times!  Caveats regarding this post: our BP protocol was designed to satisfy the needs of our clinicians here at UNC, your referring physicians may be expecting different information and you will have to adjust it to meet their needs.  There is more “than one way to skin a cat”: I suggest looking at the way others image the BP.  Dr. Ken Maravilla and his group at the University of Washington use MR neurography, a technique that we do not have but produces lovely images of the peripheral nerves.  They have published extensively about it.  Brian Bowen from the University of Miami has also written several articles on imaging of the BP and uses a very nice protocol which is different than ours.

September 24 – 25, 2010 in Leipzig, Germany.

Chairman:
Thomas Kahn, M.D., Leipzig, Germany

Co-Chairs:
Jonathan S. Lewin, M.D., Baltimore, U.S.A.
Ferenc A. Jolesz, M.D., Boston, U.S.A.

Venue:
The Westin Hotel Leipzig

Topics:
MR-guided Cryotherapy and RF Ablation
MR-guided molecular imaging
High Intensity Focused Ultrasound
MR-guided Biopsies
Robotics
Navigation
Intraoperative MRI
MR-guided Cardiovascular Procedures

Further information:
www.uni-leipzig.de/radiologie

Email:
interventional.mri@medizin.uni-leipzig.de

Description of the Symposium: [PDF]

This event note was sent to the AJNR by Jochen Fuchs at the Department of Diagnostic and Interventional Radiology, University Hospital Leipzig.