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Bilateral wallerian degeneration of the middle cerebellar peduncles secondary to pontine infarction: A case series
Journal of the Neurological Sciences 388 (2018) 182–185
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Bilateral wallerian degeneration of the middle cerebellar peduncles secondary to pontine infarction: A case series ⁎
Yaoyao Shena, , Wen Jianb, Juan Lic, Tingmin Daia, Bing Baoa, Hongbing Niea,
T
⁎
a Institute: Department of Neurology, The Affiliated Hospital of Jiujiang University, Address: No.57 Xunyang East Rode, Xunyang District, Jiujiang 332000, Jiangxi Province, China b Institute: Department of Neurology, The People's Hospital of Xinyu City, Address: No.369 Xinxin North Rode, Yushui District, Xinyu 338000, Jiangxi Province, China c Institute: Department of Neurology, The Second Affiliated Hospital of Nanchang University, Address: No.1 Mingde Rode, Donghu District, Nanchang 330006, Jiangxi Province, China
A R T I C LE I N FO
A B S T R A C T
Keywords: Wallerian degeneration Pontine infarction Middle cerebellar peduncle Magnetic resonance imaging
Objective: Wallerian degeneration (WD) of middle cerebellar peduncles (MCPs) secondary to pontine infarction is rarely reported in the literature. Our aim in this study is to characterize its clinical and neuroradiological features. Methods: A retrospective review of 7 patients from a single institution was conducted. Only patients with pontine infarction and subsequent degeneration of the MCPs were included in the analysis. The features of clinical presentation and neuroimaging finding were summarized by our experienced neurologists. Results: Seven patients (5 male, 2 female), ranging in age from 50 to 77 years, satisfied the inclusion criteria. All patients had cardiovascular risk factors and hypertension was the most common one. Almost all of the patients had hemiparesis and dysarthria, and could achieved good clinical outcome. On the initial scan, hyperintense on T2- and diffusion-weighted images suggested the acute pontine infarction. On the follow-up scan, however, hyperintensities of bilateral MCPs on T2-weight and FLAIR images were apparently demonstrated in all patients. The specific lesions in the MCPs were attributed to bilateral WD of the pontocerebellar fibres secondary to pontine infarction. Conclusion: WD should be taken into account when patients are initially diagnosed with paramedian pontine infarction and follow-up MRI manifest as symmetrical hyperintense in the MCPs.
1. Introduction Wallerian degeneration (WD) was first described in 1850 by Augustus Waller in the glossopharyngeal and hypoglossal nerves of frogs [1]. It is the process of progressive demyelination and disintegration of the distal axonal segment following the transection of the axon or damage to the neuron [2]. WD is most frequently observed involving the corticospinal tract, but can also be uncovered affecting other projecting systems such as corticopontocerebellar tract, dentaterubro-olivary pathway, posterior column of the spinal cord, corpus callosum, limbic circuit, and optic pathway [3]. Infarction is the most common cause resulting in WD. Also neoplasms, hemorrhage, surgery, epilepsy, white matter diseases and multiply system atrophy are reported entities that may leading to degeneration. Histopathologically, WD develops through sequential stages. Initially, it is characterized by physical disintegration of the axons and myelin sheaths. Subsequently, the myelin sheaths break down structurally into smaller particles. This
⁎
is followed by chemical decomposition of the protein components of myelin sheath. Finally, gliosis occupies the area of the degenerated axons and myelin sheaths [4]. To our knowledge, bilateral symmetrical hyperintense in the middle cerebellar peduncles (MCPs) on T2-weighted or fluid attenuation inversion recovery (FLAIR) images, which suggests WD of the corticopontocerebellar tract secondary to pontine infarction, has been rarely reported in the literature [17,18]. In this retrospective study, our aim is to characterize the clinical and neuroradiological features of WD involving bilateral MCPs. Both the clinician and radiologist must maintain a high level of suspicion for this entity in patients presenting with characteristic features. 2. Methods This retrospective study was approved by the Institutional Review Board (IRB) of The Affiliated Hospital of Jiujiang University. Those
Corresponding authors. E-mail addresses: [email protected] (Y. Shen), [email protected] (H. Nie).
https://doi.org/10.1016/j.jns.2018.03.027 Received 21 October 2017; Received in revised form 10 March 2018; Accepted 15 March 2018 Available online 20 March 2018 0022-510X/ © 2018 Elsevier B.V. All rights reserved.
Journal of the Neurological Sciences 388 (2018) 182–185
Y. Shen et al.
follow-up MRI, no alterated diffusion could be seen in the pons. However, bilateral and symmetrical hyperintensities along the MCPs on T2weighted and FLAIR images were apparently showed in all patients (Fig. 1)). Furthermore, subtle hyperintense in the MCPs on DWI could also be showed in two patients. The lesions of the MCPs were attributed to bilateral WD of the crossing pontocerebellar fibres.
patients with foregoing pontine infarction and subsequent hyperintense in the MCPs on brain magnetic resonance imaging (MRI) satisfied the inclusion criteria. A total of 7 patients were selected from our electronic case database between January 2014 and September 2017. As this was a retrospective study, ethics committee approval was not required. Clinical data, such as demographics (gender and onset age), cardiovascular risk factors, symptoms, radiological findings, National Institute of Health Stroke Scale (NIHSS) score, follow-up time and outcome, were independently collected by two of our authors (YS and WJ). The magnetic resonance (MR) studies, performed on a 1.5-T MR clinical system (Signa GE, Milwaukee, USA), were detailedly scanned by experienced radiologist. T1-weighted, T2-weighted, FLAIR and diffusionweighted images were available in our cases at baseline and follow-up. Symptoms and the NIHSS scoring were documented at the time of the first admission. Functional outcome was measured by modified Rankin scale (mRS) on follow-up (an mRS score from 0 to 2 was considered as a good clinical outcome).
4. Discussion WD refers to the progressive anterograde disintegration of axons and accompanying demyelination, which occurs after injury to the proximal axon or cell body. It is most commonly seen following cerebral infarction but can also be secondary to a variety of disease processes, such as neoplasms, hemorrhage, surgery, epilepsy, and white matter diseases [3]. Presently, few case reports have depicted the MR findings of WD in the MCPs following pontine infarction [15–18]. Conventional MR sequences have been utilized to describe changes of WD in different phases. Moreover, histologic and metabolic features on different stages of WD are correlated to specific findings on MR imaging. The first stage is characterized by disintegration of the axons and myelin sheaths within 20 days after injury. But no signal intensity abnormalities are usually recognizable. The second stage is characterized by the rapid destruction of the myelin sheath from 20 days to 2–4 months after stroke. As the tissue becomes more hydrophobic accompanying by myelin-protein breakdown, the high lipid-protein ratio results in hypointense on T2-weighted image. In the third stage, with gliosis and changes in water content and structure, the hydrophilic tissue shows hyperintense on T2-weighted and FLAIR images and hypointense on T1weighted image. The terminal stage is characterized by volume loss of degenerated tissue and signal intensity abnormalities may be persistent existence for several years after infarct [2]. Anatomically, the MCPs are mainly composed of pontocerebellar tracts that connect the basal portion of the pons with the cerebellum. The middle cerebellar peduncle (MCP) is vulnerable to WD because it is the largest and the the main path for pontocerebellar tracts [13]. Pontocerebellar tracts arise from the controlateral pontine nuclei which receive cortico-pontine tracts. They cross the midline at an upper pontine level and pass through the MCP to reach the cerebellar cortex. When damage (such as ischemic insult) occurs in one side of the pons, homolateral pontine nuclei as well as the contralateral pontocerebellar tracts are simultaneously affected (Fig. 2. Therefore, the specific neuroimaging finding of symmetrical hyperintese in the MCPs can be interpreted as WD of pontocerebellar tracts following pontine infarct. In this study, we present a case series to highlight the clinical presentation and radiological finding of WD in both MCPs secondary to pontine infarction. Patients with pontine infarction may present with a variety of symptoms. Hemiparesis and dysarthria are the most common symptoms among the 7 patients. When WD of the MCPs was revealed on follow-up MR examination, MRS score was not increased in all but
3. Results 3.1. Clinical presentation The clinical summary of included cases was demonstrated in Table 1. This retrospective case series included seven patients (5 male, 2 female; age range: 50–77 years; mean age: 68 years). All patients had cardiovascular risk factors, including hypertension, diabetes mellitus, hyperlipidemia, smoking and drinking. Hypertension (n = 7) was the most common cardiovascular risk factor. On the first admission, almost all of the patients had sudden onset of hemiparesis (n = 6) and dysarthria (n = 7). Other symptoms included, vertigo (n = 3), gait ataxia (n = 2), headache (n = 2) and confusion (n = 1). The mean scores of NHISS on admission was 7.14 (range: 4–8 scores). At the time of followup (time range: 3–7 months), only one patient complained of gradually worsening dysarthria and ataxia of four limbs, while the other 6 patients achieved good clinical outcome. During the time between baseline and follow-up cranial MR examinations, however, all 7 patients did not report sudden-onset neurological symptoms. 3.2. Radiological findings All 7 patients underwent cranial MR examinations at baseline and follow-up. On the initial scan, hyperintense in paramedian pontine on T2-weighted and diffusion-weighted images was recognized in all patients. The acute onset of neurological deficits together with the accordance of the lesion on diffusion-weighted image (DWI) indicated the acute pontine infarction. Among these patients, the lesions were located in different parts of the pons, including left sided (n = 3), right sided (n = 3) and bilateral (n = 1) (Table 1). At that time, however, the MCPs were normal and did not display any signal changes. On the
Table 1 Summary of the clinical presentation and radiological finding results of 7 cases. Case No.
Age (yrs), Sex
Cardiovascular risk factor
Symptom on admission
Infarction location in the pons
NIHSS score
Follow-up time (months)
Outcome mRS
1
73, M
Hypertension, diabetes mellitus
Bilateral
12
5
4
2 3 4 5 6 7
77, 77, 68, 60, 72, 50,
Hypertension, Hypertension, Hypertension Hypertension, Hypertension, Hypertension, smoking
Hemiparesis, confusion, vertigo, headache, dysarthria Hemiparesis, vertigo, dysarthria Hemiparesis, gait ataxia, dysarthria Gait ataxia, dysarthria Hemiparesis, dysarthria Hemiparesis, vertigo, dysarthria Hemiparesis, headache, dysarthria
Left Left Right Right Right Left
7 8 4 6 7 6
4 3 7 5 4 6
2 2 1 2 2 2
M M F M F M
hyperlipidemia smoking, drinking diabetes mellitus hyperlipidemia Hyperlipidemia,
Abbreviations: F female, M male, yrs years, NIHSS National Institute of Health Stroke Scale, mRS modified Rankin Scale.
183
Journal of the Neurological Sciences 388 (2018) 182–185
Y. Shen et al.
Fig. 1. Initial brain MRI demonstrates restricted diffusion (A) in left paramedian pontine and normal signal intensity in bilateral middle cerebellar peduncles (MCPs) on T2weighted and Flair imagings (B, C). On the follow-up MRI, hypointense in the pons on T1-weighted image (D) and symmetrical hyperintensity in the MCPs on T2-weighted and FLAIR images (E, F) suggest previous pontine infarction and following Wallerian degeneration of the MCPs, respectively.
follow-up (mean time: 3.5 months). Whereas, no evidence of restricted diffusion is showed in five others on follow-up (mean time: 5.4 months). It may be concluded that any diffusion abnormality of the degenerating fibres may be subsided over time. Previously, Okamoto et al. retrospectively reviewed the MR features of 27 patients with bilateral MCPs involvement. They reported symmetrical MCP lesions in neurodegenerative diseases and metabolic diseases, including olivopontocerebellar atrophy (OPCA), spinocerebellar ataxia (SCA), adrenoleukodystrophy (ALD), Wilson disease and hypoglycemic coma. After systematically reviewed of relevant publications, a wide spectrum of diseases need to be differentiated. Classification of diseases that manifest as symmetrical lesions on the MCPs includes neurodegenerative diseases: multiply system atrophy (MSA) [5], SCA [6] and Creutzfeldt-Jakob disease [7]; toxic or metabolic diseases: ALD [6], Wilson's Disease [8], heroin inhalation toxicity [9], toluene abuse [14] and hypoglycemic encephalopathy [6,10]; cerebrovascular diseases: bilateral MCPs infarction [11,12] and Wallerian degeneration [13]; demyelinating diseases: demyelinating diseases and acute disseminated encephalomyelitis [14]. MSA is a progressive and fatal neurodegenerative disorder characterized by variable combination of parkinsonism, cerebellar ataxia and autonomic dysfunction. Hyperintensity of the MCP on T2-weighted image has been suggested to be more frequent in patients with MSA, especially the cerebellar dominant type of multiple system atrophy (MSA-c) [19]. Differentiating imaging features are hot cross bun sign, volume loss in the pons and cerebellum, and T2 signal loss in the dorsolateral putamen with hyperintense rim on FLAIR sequence [20]. SCAs are a heterogeneous group of neurodegenerative disorders inherited in an autosomal dominant fashion with symptoms caused by dysfunction of the cerebellum and brainstem, along with their associated pathways and connections [21]. Positive family history and gene detection help us to distinguish it from WD of the MCPs. As symmetrical hyperintensities in the MCPs obviously demonstrated on T2WI and FLAIR images, bilateral MCPs infarction may be mainly taken into account for differential diagnosis. But, ischemic damage cannot explain this specific MR findings for the following reasons. Firstly, the symmetrical nature of the lesions is not consistent with a single arterial territory and the neighbouring structures within the same vascular territory are not involved. In addition, these patients do not report sudden-onset symptoms during the time between the two radiological examinations. Moreover, toxicant exposure, careful examination and specific neuroimaging sign will provide some guidance for differentiating most of these conditions.
Fig. 2. Schematic drawing illustrating the Wallerian degeneration (WD) of bilateral middle cerebellar peduncles (MCPs) following pontine infarction.
one subject who complained of worsening dysarthria and ataxia. WD in the MCPs, therefore, does not seem to be a predictor for a bad outcome. The MCPs are mainly composed of pontocerebellar tracts, which are responsible for coordinating movement. Abnormal signal intensities of the MCPs in patients with different causes may share common clinical manifestations, such as ataxia of trunk and limbs, dysarthria, vertigo, and hearing impairment. Nevertheless, not all patients present with new symptoms as above-mentioned when WD happens. Two reasons have been speculated to explain this mismatch between MCP presentation on MRI and clinical feature. First of all, it is a consecutively pathophysiological process from initial pontine infarction to secondary WD of the MCPs. Symptoms such as ataxia, and dysarthria, had been presented in some of our patients when they developed to pontine infarction. In addition, at the time of follow-up, those symptoms had been partially or completely compensated by rehabilitative treatment and daily activities. Hence, when WD is presented, new-onset neurological symptoms and MRS score on follow-up might not always be occurred and increased, respectively. In our patients, bilateral MCPs show hyperintense on T2- weighted and FLAIR images on follow-up, which are correlated to histologic and metabolic features of the third stage of WD. There is also case reports that increased signal intensities in the MCPs on DWI can persist for 4 months later after stroke [16]. In our study, a slightly restricted diffusion in the MCPs is revealed in two patients on 184
Journal of the Neurological Sciences 388 (2018) 182–185
Y. Shen et al.
Some limitations need to be noted in our case series study. The most important one is low number of cases due to the retrospective nature of our study. The other limitation is no use of DTI sequence to provide information on the structural integrity of axonal white matter by being a measure of local diffusion characteristics of water. Therefore, further case-control studies with larger sample sizes and advanced MRI techniques may help to strengthen the association between bilateral WD of the MCPs and paramedian pontine infarction. In conclusions, our study summarizes the features of clinical presentation and neuroradiological finding of WD involving bilateral MCPs. When patients are initially diagnosed with paramedian pontine infarction and follow-up MRI manifest as symmetrical hyperintense lesions on the MCPs, WD should be taken into account. Furthermore, This specific neuroimaging sign should be differentiated from other diseases, especially neurodegenerative diseases, toxic or metabolic diseases and cerebrovascular diseases. Both clinician and radiologist ought to deepen the awareness of this entity in patients presenting with characteristic features.
spinal cord of the baboon, Papio papio, Acta Neuropathol. 12 (1969) 314–328. [5] E.A. Lee, H.I. Cho, S.S. Kim, W.Y. Lee, Comparison of magnetic resonance imaging in subtypes of multiple system atrophy, Parkinsonism Relat. Disord. 10 (2004) 363–368. [6] K. Okamoto, S. Tokiguchi, T. Furusawa, K. Ishikawa, et al., MR features of diseases involving bilateral middle cerebellar peduncles, AJNR 24 (10) (2003) 1946–1954. [7] T. Nishida, A.M. Tokumaru, K. Doh-Ura, A. Hirata, et al., Probable sporadic Creutzfeldt-Jakob disease with valine homozygosity at codon 129 and bilateral middle cerebellar peduncle lesions, Intern. Med. 42 (2) (2003) 199–202. [8] S. Sinha, A.B. Taly, S. Ravishankar, L.K. Prashanth, et al., Wilson's disease: cranial MRI observations and clinical correlation, Neuroradiology 48 (9) (2006) 613–621. [9] C.F. Keogh, G.T. Andrews, S.D. Spacey, K.E. Forkheim, et al., Neuroimaging features of heroin inhalation toxicity: "chasing the dragon", Am. J. Roentgenol. 180 (3) (2003) 847–850. [10] C. Yamashita, H. Shigeto, N. Maeda, M. Kawaquchi, et al., Transient interhemispheric disconnection in a case of insulinoma-induced hypoglycemic encephalopathy, J. Neurol. Sci. 335 (1–2) (2013) 233–237. [11] H. Kataoka, T. Izumi, S. Kinoshita, M. Kawahara, et al., Infarction limited to both middle cerebellar peduncles, J. Neuroimaging 21 (2) (2011) e171–172. [12] K. Akiyama, S. Takizawa, K. Tokuoka, Y. Ohnuki, et al., Bilateral middle cerebellar peduncle infarction caused by traumatic vertebral artery dissection, Neurology 56 (5) (2001) 693–694. [13] M. Mejdoubi, I. Catalaa, C. Cognard, C. Manelfe, Bilateral wallerian degeneration of the middle cerebellar peduncles due to unilateral pontineinfarction, J. Neuroradiol. 33 (4) (2006) 263–265. [14] A. Uchino, A. Sawada, Y. Takase, S. Kudo, Symmetrical lesions of the middle cerebellar peduncle: MR imaging and differential diagnosis, Magn. Reson. Med. Sci. 3 (3) (2004) 133–140. [15] W. Küker, F. Schmidt, S. Hcekl, T. Nägele, et al., Bilateral Wallerian degeneration of the middle cerebellar peduncles due to paramedian pontineinfarction: MRI findings, Neuroradiology 46 (11) (2004) 896–899. [16] C. Fitzek, S. Fitzek, P. Stoeter, Bilateral Wallerian degeneration of the medial cerebellar peduncles after ponto-mesencephalicinfarction, Eur. J. Radiol. 49 (3) (2004) 198–203. [17] Y. Shen, H. Nie, Wallerian degeneration of the bilateral middle cerebellar peduncles secondary to pontine infarction, Neurol. Sci. (2017) (online). [18] S.A. Nabavizadeh, A. Mowla, A.C. Mamourian, Wallerian degeneration of the bilateral middle cerebellar peduncles, J. Neurol. Sci. 349 (1–2) (2015) 256–257. [19] S. Ngai, Y.M. Tang, L. Du, S. Stuckey, Hyperintensity of the middle cerebellar peduncles on fluid-attenuated inversion recovery imaging: variation with age and implications for the diagnosis of multiple system atrophy, AJNR 27 (10) (2006) 2146–2148. [20] T. Peeraully, Multiple system atrophy, Semin. Neurol. 34 (2) (2014) 174–181. [21] M. Coutelier, G. Coarelli, M.L. Monin, J. Konop, et al., A panel study on patients with dominant cerebellar ataxia highlights the frequency of channelopathies, Brain 140 (6) (2017) 1579–1594.
Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. References [1] A. Waller, Experiments on the section of the glossopharyngeal and hypoglossal nerves of the frog, and observations of the alterations produced thereby in the structure of their primitive fibres, Philos. Trans. R. Soc. Lond. 140 (1850) 423–429. [2] T. De Simone, C. Regna-Gladin, M.R. Carriero, L. Farina, et al., Wallerian degeneration of the pontocerebellar fibers, AJNR 26 (2005) 1062–1065. [3] Y.J. Chen, S.A. Nabavizadeh, A. Vossough, S. Kumar, et al., Wallerian degeneration beyond the corticospinal tracts: conventional and advanced MRI findings, J. Neuroimaging 27 (3) (2017) 272–280. [4] P.M. Daniel, S.J. Strich, Histological observations on Wallerian degeneration in the
185
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Bilateral wallerian degeneration of the middle cerebellar peduncles secondary to pontine infarction: A case series ⁎
Yaoyao Shena, , Wen Jianb, Juan Lic, Tingmin Daia, Bing Baoa, Hongbing Niea,
T
⁎
a Institute: Department of Neurology, The Affiliated Hospital of Jiujiang University, Address: No.57 Xunyang East Rode, Xunyang District, Jiujiang 332000, Jiangxi Province, China b Institute: Department of Neurology, The People's Hospital of Xinyu City, Address: No.369 Xinxin North Rode, Yushui District, Xinyu 338000, Jiangxi Province, China c Institute: Department of Neurology, The Second Affiliated Hospital of Nanchang University, Address: No.1 Mingde Rode, Donghu District, Nanchang 330006, Jiangxi Province, China
A R T I C LE I N FO
A B S T R A C T
Keywords: Wallerian degeneration Pontine infarction Middle cerebellar peduncle Magnetic resonance imaging
Objective: Wallerian degeneration (WD) of middle cerebellar peduncles (MCPs) secondary to pontine infarction is rarely reported in the literature. Our aim in this study is to characterize its clinical and neuroradiological features. Methods: A retrospective review of 7 patients from a single institution was conducted. Only patients with pontine infarction and subsequent degeneration of the MCPs were included in the analysis. The features of clinical presentation and neuroimaging finding were summarized by our experienced neurologists. Results: Seven patients (5 male, 2 female), ranging in age from 50 to 77 years, satisfied the inclusion criteria. All patients had cardiovascular risk factors and hypertension was the most common one. Almost all of the patients had hemiparesis and dysarthria, and could achieved good clinical outcome. On the initial scan, hyperintense on T2- and diffusion-weighted images suggested the acute pontine infarction. On the follow-up scan, however, hyperintensities of bilateral MCPs on T2-weight and FLAIR images were apparently demonstrated in all patients. The specific lesions in the MCPs were attributed to bilateral WD of the pontocerebellar fibres secondary to pontine infarction. Conclusion: WD should be taken into account when patients are initially diagnosed with paramedian pontine infarction and follow-up MRI manifest as symmetrical hyperintense in the MCPs.
1. Introduction Wallerian degeneration (WD) was first described in 1850 by Augustus Waller in the glossopharyngeal and hypoglossal nerves of frogs [1]. It is the process of progressive demyelination and disintegration of the distal axonal segment following the transection of the axon or damage to the neuron [2]. WD is most frequently observed involving the corticospinal tract, but can also be uncovered affecting other projecting systems such as corticopontocerebellar tract, dentaterubro-olivary pathway, posterior column of the spinal cord, corpus callosum, limbic circuit, and optic pathway [3]. Infarction is the most common cause resulting in WD. Also neoplasms, hemorrhage, surgery, epilepsy, white matter diseases and multiply system atrophy are reported entities that may leading to degeneration. Histopathologically, WD develops through sequential stages. Initially, it is characterized by physical disintegration of the axons and myelin sheaths. Subsequently, the myelin sheaths break down structurally into smaller particles. This
⁎
is followed by chemical decomposition of the protein components of myelin sheath. Finally, gliosis occupies the area of the degenerated axons and myelin sheaths [4]. To our knowledge, bilateral symmetrical hyperintense in the middle cerebellar peduncles (MCPs) on T2-weighted or fluid attenuation inversion recovery (FLAIR) images, which suggests WD of the corticopontocerebellar tract secondary to pontine infarction, has been rarely reported in the literature [17,18]. In this retrospective study, our aim is to characterize the clinical and neuroradiological features of WD involving bilateral MCPs. Both the clinician and radiologist must maintain a high level of suspicion for this entity in patients presenting with characteristic features. 2. Methods This retrospective study was approved by the Institutional Review Board (IRB) of The Affiliated Hospital of Jiujiang University. Those
Corresponding authors. E-mail addresses: [email protected] (Y. Shen), [email protected] (H. Nie).
https://doi.org/10.1016/j.jns.2018.03.027 Received 21 October 2017; Received in revised form 10 March 2018; Accepted 15 March 2018 Available online 20 March 2018 0022-510X/ © 2018 Elsevier B.V. All rights reserved.
Journal of the Neurological Sciences 388 (2018) 182–185
Y. Shen et al.
follow-up MRI, no alterated diffusion could be seen in the pons. However, bilateral and symmetrical hyperintensities along the MCPs on T2weighted and FLAIR images were apparently showed in all patients (Fig. 1)). Furthermore, subtle hyperintense in the MCPs on DWI could also be showed in two patients. The lesions of the MCPs were attributed to bilateral WD of the crossing pontocerebellar fibres.
patients with foregoing pontine infarction and subsequent hyperintense in the MCPs on brain magnetic resonance imaging (MRI) satisfied the inclusion criteria. A total of 7 patients were selected from our electronic case database between January 2014 and September 2017. As this was a retrospective study, ethics committee approval was not required. Clinical data, such as demographics (gender and onset age), cardiovascular risk factors, symptoms, radiological findings, National Institute of Health Stroke Scale (NIHSS) score, follow-up time and outcome, were independently collected by two of our authors (YS and WJ). The magnetic resonance (MR) studies, performed on a 1.5-T MR clinical system (Signa GE, Milwaukee, USA), were detailedly scanned by experienced radiologist. T1-weighted, T2-weighted, FLAIR and diffusionweighted images were available in our cases at baseline and follow-up. Symptoms and the NIHSS scoring were documented at the time of the first admission. Functional outcome was measured by modified Rankin scale (mRS) on follow-up (an mRS score from 0 to 2 was considered as a good clinical outcome).
4. Discussion WD refers to the progressive anterograde disintegration of axons and accompanying demyelination, which occurs after injury to the proximal axon or cell body. It is most commonly seen following cerebral infarction but can also be secondary to a variety of disease processes, such as neoplasms, hemorrhage, surgery, epilepsy, and white matter diseases [3]. Presently, few case reports have depicted the MR findings of WD in the MCPs following pontine infarction [15–18]. Conventional MR sequences have been utilized to describe changes of WD in different phases. Moreover, histologic and metabolic features on different stages of WD are correlated to specific findings on MR imaging. The first stage is characterized by disintegration of the axons and myelin sheaths within 20 days after injury. But no signal intensity abnormalities are usually recognizable. The second stage is characterized by the rapid destruction of the myelin sheath from 20 days to 2–4 months after stroke. As the tissue becomes more hydrophobic accompanying by myelin-protein breakdown, the high lipid-protein ratio results in hypointense on T2-weighted image. In the third stage, with gliosis and changes in water content and structure, the hydrophilic tissue shows hyperintense on T2-weighted and FLAIR images and hypointense on T1weighted image. The terminal stage is characterized by volume loss of degenerated tissue and signal intensity abnormalities may be persistent existence for several years after infarct [2]. Anatomically, the MCPs are mainly composed of pontocerebellar tracts that connect the basal portion of the pons with the cerebellum. The middle cerebellar peduncle (MCP) is vulnerable to WD because it is the largest and the the main path for pontocerebellar tracts [13]. Pontocerebellar tracts arise from the controlateral pontine nuclei which receive cortico-pontine tracts. They cross the midline at an upper pontine level and pass through the MCP to reach the cerebellar cortex. When damage (such as ischemic insult) occurs in one side of the pons, homolateral pontine nuclei as well as the contralateral pontocerebellar tracts are simultaneously affected (Fig. 2. Therefore, the specific neuroimaging finding of symmetrical hyperintese in the MCPs can be interpreted as WD of pontocerebellar tracts following pontine infarct. In this study, we present a case series to highlight the clinical presentation and radiological finding of WD in both MCPs secondary to pontine infarction. Patients with pontine infarction may present with a variety of symptoms. Hemiparesis and dysarthria are the most common symptoms among the 7 patients. When WD of the MCPs was revealed on follow-up MR examination, MRS score was not increased in all but
3. Results 3.1. Clinical presentation The clinical summary of included cases was demonstrated in Table 1. This retrospective case series included seven patients (5 male, 2 female; age range: 50–77 years; mean age: 68 years). All patients had cardiovascular risk factors, including hypertension, diabetes mellitus, hyperlipidemia, smoking and drinking. Hypertension (n = 7) was the most common cardiovascular risk factor. On the first admission, almost all of the patients had sudden onset of hemiparesis (n = 6) and dysarthria (n = 7). Other symptoms included, vertigo (n = 3), gait ataxia (n = 2), headache (n = 2) and confusion (n = 1). The mean scores of NHISS on admission was 7.14 (range: 4–8 scores). At the time of followup (time range: 3–7 months), only one patient complained of gradually worsening dysarthria and ataxia of four limbs, while the other 6 patients achieved good clinical outcome. During the time between baseline and follow-up cranial MR examinations, however, all 7 patients did not report sudden-onset neurological symptoms. 3.2. Radiological findings All 7 patients underwent cranial MR examinations at baseline and follow-up. On the initial scan, hyperintense in paramedian pontine on T2-weighted and diffusion-weighted images was recognized in all patients. The acute onset of neurological deficits together with the accordance of the lesion on diffusion-weighted image (DWI) indicated the acute pontine infarction. Among these patients, the lesions were located in different parts of the pons, including left sided (n = 3), right sided (n = 3) and bilateral (n = 1) (Table 1). At that time, however, the MCPs were normal and did not display any signal changes. On the
Table 1 Summary of the clinical presentation and radiological finding results of 7 cases. Case No.
Age (yrs), Sex
Cardiovascular risk factor
Symptom on admission
Infarction location in the pons
NIHSS score
Follow-up time (months)
Outcome mRS
1
73, M
Hypertension, diabetes mellitus
Bilateral
12
5
4
2 3 4 5 6 7
77, 77, 68, 60, 72, 50,
Hypertension, Hypertension, Hypertension Hypertension, Hypertension, Hypertension, smoking
Hemiparesis, confusion, vertigo, headache, dysarthria Hemiparesis, vertigo, dysarthria Hemiparesis, gait ataxia, dysarthria Gait ataxia, dysarthria Hemiparesis, dysarthria Hemiparesis, vertigo, dysarthria Hemiparesis, headache, dysarthria
Left Left Right Right Right Left
7 8 4 6 7 6
4 3 7 5 4 6
2 2 1 2 2 2
M M F M F M
hyperlipidemia smoking, drinking diabetes mellitus hyperlipidemia Hyperlipidemia,
Abbreviations: F female, M male, yrs years, NIHSS National Institute of Health Stroke Scale, mRS modified Rankin Scale.
183
Journal of the Neurological Sciences 388 (2018) 182–185
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Fig. 1. Initial brain MRI demonstrates restricted diffusion (A) in left paramedian pontine and normal signal intensity in bilateral middle cerebellar peduncles (MCPs) on T2weighted and Flair imagings (B, C). On the follow-up MRI, hypointense in the pons on T1-weighted image (D) and symmetrical hyperintensity in the MCPs on T2-weighted and FLAIR images (E, F) suggest previous pontine infarction and following Wallerian degeneration of the MCPs, respectively.
follow-up (mean time: 3.5 months). Whereas, no evidence of restricted diffusion is showed in five others on follow-up (mean time: 5.4 months). It may be concluded that any diffusion abnormality of the degenerating fibres may be subsided over time. Previously, Okamoto et al. retrospectively reviewed the MR features of 27 patients with bilateral MCPs involvement. They reported symmetrical MCP lesions in neurodegenerative diseases and metabolic diseases, including olivopontocerebellar atrophy (OPCA), spinocerebellar ataxia (SCA), adrenoleukodystrophy (ALD), Wilson disease and hypoglycemic coma. After systematically reviewed of relevant publications, a wide spectrum of diseases need to be differentiated. Classification of diseases that manifest as symmetrical lesions on the MCPs includes neurodegenerative diseases: multiply system atrophy (MSA) [5], SCA [6] and Creutzfeldt-Jakob disease [7]; toxic or metabolic diseases: ALD [6], Wilson's Disease [8], heroin inhalation toxicity [9], toluene abuse [14] and hypoglycemic encephalopathy [6,10]; cerebrovascular diseases: bilateral MCPs infarction [11,12] and Wallerian degeneration [13]; demyelinating diseases: demyelinating diseases and acute disseminated encephalomyelitis [14]. MSA is a progressive and fatal neurodegenerative disorder characterized by variable combination of parkinsonism, cerebellar ataxia and autonomic dysfunction. Hyperintensity of the MCP on T2-weighted image has been suggested to be more frequent in patients with MSA, especially the cerebellar dominant type of multiple system atrophy (MSA-c) [19]. Differentiating imaging features are hot cross bun sign, volume loss in the pons and cerebellum, and T2 signal loss in the dorsolateral putamen with hyperintense rim on FLAIR sequence [20]. SCAs are a heterogeneous group of neurodegenerative disorders inherited in an autosomal dominant fashion with symptoms caused by dysfunction of the cerebellum and brainstem, along with their associated pathways and connections [21]. Positive family history and gene detection help us to distinguish it from WD of the MCPs. As symmetrical hyperintensities in the MCPs obviously demonstrated on T2WI and FLAIR images, bilateral MCPs infarction may be mainly taken into account for differential diagnosis. But, ischemic damage cannot explain this specific MR findings for the following reasons. Firstly, the symmetrical nature of the lesions is not consistent with a single arterial territory and the neighbouring structures within the same vascular territory are not involved. In addition, these patients do not report sudden-onset symptoms during the time between the two radiological examinations. Moreover, toxicant exposure, careful examination and specific neuroimaging sign will provide some guidance for differentiating most of these conditions.
Fig. 2. Schematic drawing illustrating the Wallerian degeneration (WD) of bilateral middle cerebellar peduncles (MCPs) following pontine infarction.
one subject who complained of worsening dysarthria and ataxia. WD in the MCPs, therefore, does not seem to be a predictor for a bad outcome. The MCPs are mainly composed of pontocerebellar tracts, which are responsible for coordinating movement. Abnormal signal intensities of the MCPs in patients with different causes may share common clinical manifestations, such as ataxia of trunk and limbs, dysarthria, vertigo, and hearing impairment. Nevertheless, not all patients present with new symptoms as above-mentioned when WD happens. Two reasons have been speculated to explain this mismatch between MCP presentation on MRI and clinical feature. First of all, it is a consecutively pathophysiological process from initial pontine infarction to secondary WD of the MCPs. Symptoms such as ataxia, and dysarthria, had been presented in some of our patients when they developed to pontine infarction. In addition, at the time of follow-up, those symptoms had been partially or completely compensated by rehabilitative treatment and daily activities. Hence, when WD is presented, new-onset neurological symptoms and MRS score on follow-up might not always be occurred and increased, respectively. In our patients, bilateral MCPs show hyperintense on T2- weighted and FLAIR images on follow-up, which are correlated to histologic and metabolic features of the third stage of WD. There is also case reports that increased signal intensities in the MCPs on DWI can persist for 4 months later after stroke [16]. In our study, a slightly restricted diffusion in the MCPs is revealed in two patients on 184
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Some limitations need to be noted in our case series study. The most important one is low number of cases due to the retrospective nature of our study. The other limitation is no use of DTI sequence to provide information on the structural integrity of axonal white matter by being a measure of local diffusion characteristics of water. Therefore, further case-control studies with larger sample sizes and advanced MRI techniques may help to strengthen the association between bilateral WD of the MCPs and paramedian pontine infarction. In conclusions, our study summarizes the features of clinical presentation and neuroradiological finding of WD involving bilateral MCPs. When patients are initially diagnosed with paramedian pontine infarction and follow-up MRI manifest as symmetrical hyperintense lesions on the MCPs, WD should be taken into account. Furthermore, This specific neuroimaging sign should be differentiated from other diseases, especially neurodegenerative diseases, toxic or metabolic diseases and cerebrovascular diseases. Both clinician and radiologist ought to deepen the awareness of this entity in patients presenting with characteristic features.
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