Lhermitte-Duclos disease: a critical appraisal of different radiologic methods

EUROPEAN JOURNAL OF RADIOLOGY

ELSEVIER

European Journal of Radiology 19 (1994) 21-24

Lhermitte-Duclos disease: a critical appraisal of different radiologic methods R. Verheggen*a, H. Bruhnb’d, B.U. Schr6derc, J. Frahmd, E. Markakisa aNeurochirurgL&e Klinik. Georg-August-Universittit, Robert-Koch-%. 40. D-37075 Giittingen, Germany bRadiologisches Zentrum, Georg-August-Vniversitiit, Robert-Koch-Str. 40, D-37075 GBttingen, Germany CInstitutfur Neuropathologie. Georg-August-Universittit, Robert-Koch-Str. 40, D-37075 Giittingen, Germany dBiomedizinische NMR Forschungs GmbH, Max-Planck-Institut ftir biophysikalische Chemie, Postfach 2841, D-37078 Giittingen. Germany Received 3 March 1994; revision received 22 June 1994; accepted 6 July 1994

Keywords: Magnetic resonance (MR), brain; Magnetic resonance (MR), proton spectroscopy; Magnetic resonance (MR), tissue

characterization; Brain, MRS; Brain, neoplasms; Neoplasms, brain

1. Introduction Lhermitte-Duclos disease is an uncommon lesion of the cerebellum with signs of a posterior fossa tumor. While the etiology is not clearly defined, it presents features of a congenital malformation and hamartoma [1,2]. Histology shows regional enlargement of the cerebellar stratum granulosum, a progressive hypertrophy of granular cell neurons and an excessive myelination of their axons in the molecular layer. The transition from normal to abnormal tissue includes a localized disappearance of Purkinje cells as well as of central white matter in the axis of the hypertrophied cerebellar folia. Although some pediatric cases have been reported, the majority of patients were diagnosed in the third or fourth decade of life without a sex preference [2]. Of note, a similar dysplastic lesion of the cerebellum was described in an adult horse supporting its consideration as a developmental disorder because of abnormal neural growth [3]. While the pathogenesis is controversial, the following terms have been used synonymously: dysplastic gangliocytoma, diffuse hamartoma of the cerebellum, myelinated neurocytoma, and Purkinjeoma. Corresponding author.

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The disorder becomes clinically symptomatic when stenosis of the cerebral aqueduct due to the mass effect causes rising intracranial pressure, hydrocephalus, and cerebellar symptoms. These symptoms may last from a few months up to a number of years [2]. Preoperative radiologic investigations by computed tomography (CT) or magnetic resonance imaging (MRI) are not specific or remain ambiguous [2,4-81. Even at surgery the diagnosis of a Lhermitte-Duclos may be overlooked due to preservation of a gyral pattern [5]. Here, the addition of localized proton MRS to the preoperative workup of a case of Lhermitte-Duclos with bilateral cerebellar involvement has lead to a critical appraisal of other radiologic methods currently in use including CT, MRI, and angiography. 2. Case report 2.1. Symptoms and history On hospital admittance, a young man of 22 years complained of severe headaches, nausea, dizziness, and later of numbness within the innervation area of the second branch of the right trigeminal nerve 012). He also suffered hemihypesthesia of the right half of the body.

R. Verheggen et al. /Eur. J. Radiol. 19 (1994) 21-24

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While signs of elevated intracranial pressure including papilledema and bradycardia were noted, a thorough neurologic examination revealed a horizontal, gazeparetic nystagmus to the left, oscillopsia, and cerebellar ataxia including dysmetria, dysdiadochokinesia, pastpointing, and intention tremor. Moreover, the patient had a guttural, scanning speech with slurring of syllables. His clinical history disclosed short attacks of vertigo and hot flushes during school years as well as headaches of increasing frequency and intensity during the last 4 years. A nephew on the woman’s side had died of complications due to a hydrocephalus of unknown etiology.

2.2. Neuroradiologic investigations Cranial CT disclosed a triventricular

hydrocephalus

a

b

d

e

related to aqueductal stenosis. In addition, a hypodense lesion was noted within both cerebellar hemispheres that contained small calcifications (Fig. la) but did not show enhancement with intravenous contrast medium (Fig. lb). MRI was performed with spin-echo and gradientecho sequences in all three orientations. Tl-weighted scans disclosed a large hypointense mass within both cerebellar hemispheres compressing the fourth ventricle. The lesion itself showed small septations corresponding to thickened cerebellar folia (Fig. lc,e, 2a). No contrast enhancement was observed with intravenous paramagnetic Gd-DTPA (Dimeglumine/Magnevist, Schering AG, Berlin). T2-weighted images depicted areas of increased signal intensity within the lesion (Fig. If). Conventional angiography as well as elective MR angiography confirmed the presence of a large non-vascular growth in the posterior cranial fossa (Fig. Id).

Fig. 1. Radiologic images of Lhermitte-Duclos disease. Axial CT scan (a) without, (b) with contrast enhancement; (c) transverse MRI (SE 600/15), (d) MR angiography depicting transverse maximal intensity projection of 3DFLASH acquisitions; (e) sagittal MR images, 4 mm sections: Tl-weighted 3DFLASH (15/6/20”), (f) T2-weighted CE-FAST ( 14/-6/400).

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R. Verheggen et al. /Eur. J. Radiol. 19 (1994) 21-24

I NAA

NAA Cr Cr

3.6

3.2

2.6

24

2.0

I.6

Chemical

b

3.6

shift / Dam

3.2

216

2.4

2.0

1.6

C

Fig. 2. (a) Coronal FLASH MR image indicating the location of the 2 x 2 x 2 cm3 VOI selected for proton MRS within the mass in the right cerebellar hemisphere; (b) localized proton MR spectrum (STEAM 3000/20, I28 acquisitions) from the VOI indicated and (c) from a similar VOI of the cerebellar hemisphere of an age-matched control. Metabolite signals include N-acetylaspartate (NAA), creatine and phosphocreatine (Cr), choline-containing compounds (Cho), and myo-inositol (Ins). Chemical shifts are given in parts per million (ppm) referenced to 2.01 ppm for the CH3 group of NAA. The spectra are scaled to allow for direct comparison of peak intensities with (b) multiplied by a factor of two relative to (c).

Proton MRS was performed at 2.0 T (Siemens Magnetom SP) using a stimulated echo acquisition mode (STEAM) sequence with a short echo time of 20 ms and a repetition time of 3000 ms as described previously [9]. The examination comprised fast-scan MRI in three orientations to define the lesion and to select localized volumesof-interest (VOI) of 2 x 2 x 2 cm3 (Fig. 2a). We used Tl-weighted radiofrequency-spoiled fast low angle shot imaging (3D-FLASH: 15/6/20”) and TZweighted singleslice contrast-enhanced Fourier acquisition in the steady state (CE-FAST: 13.6/-6/40”) [lo]. Cerebellum spectra of normal age-matched controls were available from a large data base acquired for other purposes [l 11. Proton MR spectra of the lesion (Fig. 2b) showed a notable overall decrease of resonance signals from all metabolites relative to controls (Fig. 2~). Detected metabolites include iV-acetylaspartate (NAA), creatine and phosphocreatine (Cr), choline-containing compounds (Cho), and myo-inositol (Ins). Table 1 summarizes the results of a fully automated quantitative analysis based on LCModel [ 121. The data reveal a decrease of NAA by 62%, Cr by 56%, Cho by 68%, and Ins by 92%. Moreover, concentration ratios relative to Cr decreased for NAAKr by 12%, Cho/Cr by 25%, and Ins/Cr by 83%.

Lactate levels were not elevated relative to controls (about 0.5 mM). 2.3. Surgery The triventricular hydrocephalus with threatening signs of raised intracranial pressure required the implantation of a ventriculo-peritoneal shunt. Because of the patient’s complaints of a blurred vision and based on the results of proton MRS, we decided to perform a direct surgical exploration via a suboccipital craniectomy. Upon opening the dura, a spared foliated pattern of the upper left and right cerebellar surface was observed. The different consistency and the pearl-gray color of the growth facilitated its separation from normal cerebellum. Subtotal decompression and an incomplete tonsillar resection were performed. The diagnosis of a Lhermitte-Duclos was confirmed pathologically. The patient recovered uneventfully with an amelioration of his neurologic deficits.

3. Discussion The clinical presentation of our case of LhermitteDuclos disease resembled a posterior fossa tumor with

Table I Metabolic alterations in the right cerebellar hemisphere of a patient with Lhermitte-Duclos disease versus age-matched controls (n = 8, mean age 27 years) as detected by quantitative evaluations of localized proton MR spectra

Patient Controls

NAA

Cr

Cho

Ins

NAA/Cr

Cho/Cr

In&r

3.1 f 0.2 8.2 zt I.1

2.9 zt 0.2 6.6 ?? 1.4

0.6 f 0.08 1.9 f 0.5

0.4 f 0.2 5.2 f 2.0

1.1 1.25 * 0.1

0.21 0.28 * 0.04

0.14 0.8 zt 0.2

The values are proportional to absolute concentration levels (in mM f SD.) without corrections for a mild Tl saturation (repetition time 3000 ms) and for minor differential T2 losses (echo time 20 ms, in vivo versus in vitro reference measurements).

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R. Verheggen et al. /Eur. J. Radiol. 19 (1994) 21-24

signs of cerebellar dysfunction and elevated intracranial pressure due to a hydrocephalus as described by others [2,4-61. Although palliative shunting for chronic hydrocephalus may lead to a temporary relief of symptoms, only surgical resection is considered the treatment of choice [2,4]. In the past, radiologic findings were nonspecific. Angiography demonstrated a non-vascular space-occupying lesion in the cerebellum, and CT scans showed an infratentorial cerebellar mass with small calcifications and ill-defined borders eventually extending to the midline with distortions of the fourth ventricle [4,7]. Among the few MRI studies of Lhermitte-Duclos disease [2,4-81 only one case exhibited a bihemispheric cerebellar lesion [6]. Thus, our preoperative CT and MR images did not unequivocally point to the diagnosis of Lhermitte-Duclos disease and cavernous malformation was considered for differential diagnosis. Since localized proton MRS has been demonstrated to noninvasively assess tissue metabolites in vivo in a variety of disease states of the brain, its inclusion as a complementing modality was expected to provide additional clues about the nature of the lesion. In fact, while the overall signal decrease most likely reflects a loss of cerebellar tissue by partial volume averaging within the selected VOIs, decreased Cho/Cr (and In&r) ratios are in strict contrast to observations in cerebral tumors, where frequent increases of Cho (and Ins) levels are associated with enhanced membrane turnover and demyelination [13-161. In addition, the high level of NAA and the only slightly reduced NAA/Cr ratio clearly indicate the presence of neuroaxonal tissue as NAA has been demonstrated to be exclusively located in neurons [ 171. Together with a Cho/Cr ratio resembling the pattern found in normal gray matter (0.19 f 0.03 for a repetition time of 3000 ms), the spectroscopic alterations were in line with a gangliocytoma and promoted our decision to operate. Within the radiologic armentarium preoperative proton MRS in combination with MRI lead to the correct diagnosis. Clearly, more spectroscopic examinations are warranted to clarify whether the metabolic characteristics found in our case represent a general feature in LhermitteDuclos disease.

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