MR Imaging of the Cauda Equina in Charcot-Marie-Tooth disease

Transcription

1 MR Imaging of the Cauda Equina in Charcot-Marie-Tooth disease Poster No.: C-0741 Congress: ECR 2015 Type: Scientific Exhibit Authors: Y. Tatewaki, S. Nishiyama, Y. Kato, T. Murata, S. Mugikura, L. Li, D. Mata Mbemba, S. Takahashi; Sendai/JP Keywords: Neuroradiology spine, Musculoskeletal spine, MR, Audit and standards, Tissue characterisation DOI: /ecr2015/C-0741 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 20

2 Aims and objectives Charcot-Marie Tooth disease (CMT) Definition: Heterogeneous group of hereditary motor-sensory peripheral neuropathies characterized by symmetrical and predominately distal motor and sensory disturbances. Electrophysiologically, CMT is subdivided into demyelinating (CMT1) or axonal (CMT2) types. Morbidity: 1/2500 individuals Causal gene: PMP22, MPZ, connexin 32, neurofilament light gene Onset Age: -CMT1: in 1st decade typical, often delayed until early or mid-adulthood -CMT2: Often later in life; symptoms commonly begin during 2nd decade Clinical manifestation: Muscle weakness/atrophy (motor > sensory) at the distal extremity ( Fig. 1 on page 4 ), steppage gait, a pes cavum deformity Clinical phenotypes of Charcot-Marie-Tooth disease ( Fig. 2 on page 4 ) a. Electrophysiological subtypes of CMT: -CMT1 (demyelinating type): severe diffuse motor nerve conducting velocity (NCV) slowing which represents an impairment of salutatory conduction due to demyelination of peripheral nerve -CMT2 (axonal type): relatively normal motor NCV which represents a preserved salutatory conduction due to absence of demyelination. b. Genetic subtypes of CMT: Page 2 of 20

3 CMTs are subdivided according to causal genes. There are 50 genes associated with different subtypes of CMT [2]( Fig. 2 on page 4 ). Pathological findings of CMTs CMT1 (demyelinating type)( Fig. 3 on page 5 ): -Repeated cycles of demyelination and remyelination produce concentric myelin layers around axons, the so-called "onion bulb formation". -The axons located at the central part of "onion-bulb "are spared. CMT2 (axonal type) ( Fig. 4 on page 6 ): -Primary axonal loss which leads to Wallerian degeneration without remyelination/ demyelination cycles -Absence of "onion-bulb formation" Background -CMT is the most common inherited neurologic disorder with slow progressing manifestations. -CMT1 usually leads to enlargement of peripheral nerves whereas CMT2 does not. -With recent improvements in MR imaging, detailed assessment of spinal nerve roots has been achieved. -Delineation of peripheral nerve enlargement corresponding with onion-bulbs with MRI was reported for clinical use to characterize CMT subtypes [6]. -The importance of evaluating the cauda equina nerve roots with MRI in the purpose of diagnosis of CMT has received little interest in the literature. Study purpose We investigated MR imaging of cauda equina nerve roots as a possible method to characterize CMT subtypes. Page 3 of 20

4 Images for this section: Fig. 1: Clinical features of Charcot-Marie-Tooth disease. A patient with CMT1A shows a pes cavus (left row), wasting and weakness of distal limb muscles (showing the so-called " inverted champagne bottle appearance of the legs"), involving especially the peroneal compartment (right row), usually associated with distal sensory loss, skeletal deformities, and decrease or absence of deep tendon reflexes. Modified from Pareyson D et.al [1]. Page 4 of 20

5 Fig. 2: Charcot-Marie-Tooth disease is electrophysiologically subdivided into demyelinating (CMT1) or axonal type (CMT2) by nerve conduction velocities (NCVs); CMT1 demonstrates severe diffuse motor NCV slowing and CMT2 demonstrates relatively normal motor NCV. Slowing NCV with CMT1 represents impairment of salutatory conduction due to demyelination of peripheral nerve. The relatively normal NCV noted in CMT2 represents preserving salutatory conduction. Within each group of CMT1 or CMT2, molecular genetics further subdivides according to causal genes. Page 5 of 20

6 Fig. 3: Pathological findings of CMT1 (demyelinating type) is repeated cycles of demyelination and remyelination which produces concentric myelin layers around axons, the so-called "onion-bulb formation" (A). Axons located at the central part of "onion-bulb "are comparatively spared (B). (A) is modified from Disorders of peripheral nerves, 1974 [3] and (B) Cellerini [4]. (C) and (D) are modified from Escourolle and Poirier's Manual of Basic Neuropathology [5]. Page 6 of 20

7 Fig. 4: Figure 4 cited from Escourolle and Poirier's Manual of Basic Neuropathology [5]. Pathological findings of CMT2 (axonal type) is primary axonal loss without "onion-bub formation". Page 7 of 20

8 Methods and materials Subjects recruitment Study population -A consecutive 14 patients who were diagnosed with CMT at Tohoku University Hospital from January 2007 to March 2014 were included. -Clinical diagnosis of CMT1 or CMT2 were confirmed with electrophysiological examination and/or genetic test. Exclusion criteria -Coexisting CIDP (chronic inflammatory demyelinating disease) -Severe degenerative change and canal stenosis of lumbosacral spine -Significant imaging artifact due to CSF flow in spinal canal Final study groups: -CMT1: 7 individuals (5 men and 2 women) mean age of 46.1 years (18-78 years) -CMT2: 2 individuals (all men) mean age of 61.5 years (57 and 66 years) -Control: one healthy man age of 40 years Imaging procedure -All 10 subjects underwent Lumbosacral MR imaging, -Protocol of MR imaging: axial and sagittal sections of conventional T1WI, T2WI and GdT1WI using 3-tesla MRI scanner Evaluation of Image features -One experienced (8 years) neuroradiologists -Degree of imaging abnormality: comparison to the healthy control Page 8 of 20

9 Items evaluated: -Location of thickening cauda equina: nerve root (focal or diffuse), epidural nerve -Degree of thickening: mild(+), intermediate(++) or prominent(+++) -Degree of T2 brightness: hyper-, iso- or hypo-intense -Degree of enhancement: strong or subtle -Pattern of T2 abnormality and enhancement: (long axis): diffuse or partial (cross section): rim, central, entire of section Results Cases presentation Representative MR imaging of a patient with CMT1 (Case 4) whose complaint was slowprogressing gait disturbance and sensory disturbance of lower extremities are shown in Fig. 5 on page 10 and Fig. 6 on page 11. Result Comparison of MRI features of cauda equina nerve roots in patients with CMT1 and those with CMT2 are summarized in Table 1 on page 12. Morphology Partial or diffuse thickening of cauda equina nerve roots was observed in 5 of 7 (85.7%) patients with CMT1 and none of 2 patients with CMT2. Location of thickening cauda equina -Intradural nerve roots (diffuse): 5/7 cases with CMT1 (71.4%) -Intradural nerve roots (localized to distal part): 1/7 case with CMT1 (14.3%) -Epidural peripheral nerves: 1/7 cases with CMT1 (14.3%) Page 9 of 20

10 Degree of thickening of cauda equina ( Fig. 7 on page 13 ) -Thickening of cauda equina nerve roots were observed in 6/7 cases with CMT1 (85.7%) (mild: 1 case; intermediate: 3 cases; prominent: 2 cases) -No abnormality of cauda equina nerve root was noted in patient with CMT2 Degree and pattern of T2 brightness ( Fig. 8 on page 15 ) -Iso- or hypo-intensities of thickened nerve roots in patients with CMT1: (isointense: 1 case (14.2%); hypointense: 6 cases (85.7%)) -No patient with CMT1 showed marked homogenous hyperintensity in thickened nerve roots. -Focal hyperintensity, "central high" signal located at central axis areas of thickening nerve roots were observed in 3/ 7 patients with CMT1 (42.8%). -No signal abnormality of cauda equina was seen in patients with CMT2 Degree of enhancement strength ( Fig. 9 on page 15 ) -Diffuse faint heterogeneous enhancement of nerve roots in patients with CMT1 -Patchy enhancement corresponding to the T2-"central high" regions in patients with CMT1 -No case demonstrated strong enhancement along thickened nerve roots -No abnormal enhancement of cauda equina was noted in patients with CMT2 Images for this section: Page 10 of 20

11 Fig. 5: Sagittal MR imaging of the patient with CMT1 (Case 4). On T2WI, the nerve roots of the cauda equina appeared diffuse thickened, packing the space within the lumbar vertebral canal. On postcontrast-t1wi, heterogeneous faint enhancements were seen along cauda equina nerve roots. Page 11 of 20

12 Fig. 6: Axial MR imaging of the same patient (Case 4). On T2WI, nerve roots appeared diffusely thickened. Most of the thickened nerve roots appeared slightly hypointense mainly at their rim. Additionally, some of them showed focal hyperintensities at their central axis which is called "central high". On postcontrast-t1wi, mild heterogeneous enhancement was observed in the nerve roots including the regions corresponding to the "central high" noted on T2WI. Page 12 of 20

13 Table 1: Comparison of MRI features of cauda equina nerve roots in patients with CMT1 and those with CMT2 Page 13 of 20

14 Page 14 of 20

15 Fig. 7: Comparison of degree of thickening of cauda equina nerve roots between CMT1 and CMT2. Marked thickening of nerve roots were depicted on T2WI in patients with CMT1. No abnormality of cauda equina was noted in patients with CMT2. Fig. 8: Comparison of T2-brightness of cauda equina nerve roots in patients with CMT1 and those with CMT2. As compared to the normal patient, the thickened nerve roots in patient with CMT1 consistently demonstrated mild-hypointensity on T2WI. Three of 7 patients with CMT1 showed a coexistence of the focal hyperintense area ("central high") in the central part and the hypointense areas at the peripheral part of the nerve. Page 15 of 20

16 Fig. 9: Comparison of enhancing pattern in patients with CMT1 and CMT2. Thickened nerve roots demonstrated faint heterogeneous enhancement. No diffuse strong Page 16 of 20

17 enhancement was seen in patients with CMT1. Patchy mild enhancement was observed in the region corresponding to the "central high" areas noted on T2WI in the thickened nerve roots. Neither signal abnormality nor pathological enhancement of cauda equina was noted in patients with CMT2. Page 17 of 20

18 Conclusion Discussion Correlation between the swelling of the cauda equina and the "onion-bulb" formation Our result showing high prevalence of the thickening of the nerve roots in patients with CMT1 and no thickening of nerve roots in patients with CMT2 was consistent with the literature. Cellerini and colleagues reported that two of their 5 patients with CMT1 showed enlargement of their nerve roots on MRI, whereas none of those of CMT2 showed such enlargement. Furthermore, they reported that the MR imaging spectrum of lumbosacral spinal nerve root abnormalities were correlated to the extremely high number of onion bulbs at sural nerve biopsy [4]. Therefore, the thickening of the cauda equina nerve roots delineated by lumbosacral MRI in the present study could also represent an increased amount of onion bulbs associated with CMT1. T2-brightness of thickened nerve roots Several studies reported enlargement of cauda equina nerve roots associated with CMT [4, 7]. With regards to the T2-brightness of thickened nerve roots, our result showing iso or mild hypointensity opposes some previous reports which indicated "hyperintensity". On the other hand, Ellegala and colleagues who investigated peripheral nerve in patients with CMT using MR neurography reported that T2-signal brightness of the peripheral nerve affected with CMT1 showed iso or hypointensity [6], which was similar to T2-signal brightness of thickened nerve roots observed in our study. Although the true reason of dissociation noted in the degree of T2-brightness of thickened nerve roots between the previous reports and our study is not clearly understood, we speculated that thickened nerve roots with lower intensity on T2WI might indicate "onion-bulb"-like hypertrophic myelin. T2-"central high" Characteristic finding of focal hyperintensity at central axis area ("central high") of thickened nerve roots was observed in almost half of the patients with CMT1. The pathological background of "central high" was unclear but we believe that this imaging feature could represent a subtle diagnostic clue for CMT1. Further study to investigate the clinical significance of "central high" is needed. Page 18 of 20

19 Limitations -The number of participants with CMT2 was too small to perform statistical comparisons. -Correlation between MR imaging spectrum of cauda equina nerve root abnormalities and disease severity and/or duration has not been evaluated. Conclusion MR imaging finding of cauda equina nerve roots was useful for characterization CMT subtypes. Patients with CMT1 showed marked thickening of cauda equina nerve roots representing "onion bulb", while those with CMT2 did not show swelling of the cauda equina nerve roots. In addition, the T2- brightness of thickened nerve roots noted in patients with CMT1 was iso or mild hypointense occasionally accompanied by "central high". Personal information References 1. Pareyson D, Scaiolo V, Laura M. Clinical and electrophysiological aspects of CharcotMarie-Tooth disease. Neuromol Med 2006;8: Bergamin G.Mutation Analysis of MFN2, GJB1, MPZ and PMP22 in Italian Patients with Axonal Charcot-Marie-Tooth disease. Neuromol Med 2014;16: Bradley WG:Disorders of peripheral nerves. Oxford, Blackwell, 1974, p Cellerini M, Salti S, Desideri V, Marconi G. MR imaging of the cauda equina in hereditary motor sensory neuropathies: correlations with sural nerve biopsy. AJNR 2000; 21: Gray F, Duyckaerts D, Girolami U: Escourolle and Poirier's Manual of Basic Neuropathology. Oxford, New York, 2014 Page 19 of 20

20 6. Ellegala D. B, Monteith S. J, Haynor D, Bird T.D, Goodkin R, Kliot M. Characterization of genetically defined types of Charcot-Marie-Tooth neuropathies by using magnetic resonance neurography. J Neurosurg 2005;102: Pareyson D,Testa D,Morbin M, Erbrtta A, Cinano C, Lauria G, Nilani M, Taroni F. Does CMT1A homozygosity cause more severe disease with root hypertrophy and higher CSF proteins? Neurology 2003;60: Page 20 of 20