Atormac
brintellex
Neurology India
menu-bar5 Open access journal indexed with Index Medicus
  Users online: 1989  
 Home | Login 
About Editorial board Articlesmenu-bullet NSI Publicationsmenu-bullet Search Instructions Online Submission Subscribe Videos Etcetera Contact
  Navigate Here 
 Search
 
  
 Resource Links
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Article in PDF (871 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this Article
   References
   Article Figures

 Article Access Statistics
    Viewed92    
    Printed1    
    Emailed0    
    PDF Downloaded16    
    Comments [Add]    

Recommend this journal

 


 
Table of Contents    
LETTER TO EDITOR
Year : 2020  |  Volume : 68  |  Issue : 3  |  Page : 691-693

Pontine Tegmental Cap Dysplasia- the Role of MRI and DTI in Diagnosis


Department of Radiology, Neuroradiology Unit, KEM Hosiptal, Mumbai, Maharastra, India

Date of Web Publication6-Jul-2020

Correspondence Address:
Dr. Jenny Mukeshchandra Gandhi
Neuro and Vascular Intervention Radiologist, Shalby Group Hospital, Surat, Gujarat, India. Ex-Fellow, KEM Hospital, Mumbai Maharastra
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.289019

Rights and Permissions



How to cite this article:
Gandhi JM, Sankhe S, Udmale P. Pontine Tegmental Cap Dysplasia- the Role of MRI and DTI in Diagnosis. Neurol India 2020;68:691-3

How to cite this URL:
Gandhi JM, Sankhe S, Udmale P. Pontine Tegmental Cap Dysplasia- the Role of MRI and DTI in Diagnosis. Neurol India [serial online] 2020 [cited 2020 Aug 12];68:691-3. Available from: http://www.neurologyindia.com/text.asp?2020/68/3/691/289019


Sir,

Pontine tegmental cap dysplasia is a rare disorder of the brainstem with reduced number of axons, impaired axonal navigation, and abnormal course with ectopic track in dorsal pons ectopic track in dorsal pons.[1] The underlying cause is genetic mutation.[1] The patient presents with difficulty swallowing difficulty and cranial nerve palsies.[2] It is a radiological diagnosis and identification and classification in correct subgroup on MRI is essential.[1]

Magnetic Resonance Imaging [MRI] with Diffusion Tensor Imaging [DTI] is the investigation of choice. It pinpoints ventral pontine flattening, smaller middle cerebellar peduncles and ectopic dorsal pontine fibers causing bump on dorsal aspect of pons.[1]

A 2.5-month-old child presented with respiratory distress, hypoglycemia, difficulty in swallowing and failure to thrive. Birth history was uneventful. Chest X-ray was suggestive of bronchiolitis. We were clinically suspicious of a tracheo-oesophageal fistulata, but the barium study was conducted and proved normal. To rule out metabolic disorder, a blood investigation was performed which turned out to be normal. The child was further investigated with MRI brain to rule out any underlying causes.

MRI brain revealed normal supra-tentorial brain parenchyma with brain stem and cerebellar abnormality. On T2w sagittal image, the pons was small with flattened ventral pons and band-kike structures in the dorso-superior aspect of the pons giving cap-like appearance [Figure 1]a. Junction of midbrain and pons was short [Figure 1]a. Pons immediately caudal to band as extremely thin [Figure 1]a. Dorsal band was projecting into the fourth ventricle [Figure 1]a.
Figure 1: (a) T2w sagittal image shows flat anterior pons (orange arrow) with cap-like bump on dorsal pons (green arrow). Midbrain-pons junction appears short (red arrow). Pons immediately below the dorsal bundle is thin. (b) Sagittal DTI image shows elongated superior cerebellar peduncle in blue-pink color fibers (red arrow). (c and d) Axial DTI images show absence of ventral decussation fibers in pons (red arrow) with ectopic thick light blue transverse bundle on pons (yellow arrow). Pink color middle cerebral peduncles are hypoplastic (green arrow). Corticospinal tracts are hypoplastic (red arrow)

Click here to view


On T2w axial images, the dorsal pons was round in shape. Middle and inferior cerebellar peduncles are hypoplastic. On axial and sagittal images superior cerebellar peduncles are elongated and running laterally giving molar tooth appearance.

Cerebellar vermis was hypoplastic. Cerebellar hemispheres were normal.

Diffusion tensor imaging with color-coded fractional anisotropy maps and tractography were obtained at 3T.

Coronal FA image shows light blue-colored transverse bundle in the dorsal pons with the absence of ventral and middle transverse fibers [Figure 1]b, [Figure 1]c, [Figure 1]d. These ectopic light blue-colored bundles are not connecting with middle cerebellar peduncles. There were elongated blue- and pink-colored superior cerebellar peduncles and hypoplastic middle cerebellar peduncles [Figure 1]b, [Figure 1]c, [Figure 1]d. Dark blue-colored cortico-cerebral fibers in ventral pons also appeared hypoplastic [Figure 1]b, [Figure 1]c, [Figure 1]d.

Malformation of the brainstem is poorly understood both radiologically and pathologically hence it is not well described in medical literature.[1] Barth et al. first named the disease as PTCD.[1],[3] The exact genetic mutation is not understood but autosomal recessive and dominant inheritance both have been described.[1],[4] It is detected sporadically in males and females without any affected siblings and consanguinity as in our case.[4]

Patients with this disorder present with pyramidal and cerebellar signs. There will be multiple cranial nerve palsies especially V, VI, VII and VIII nerves in affected child which leads to neuro-sensorial hearing loss, swallowing impairment and oculomotor palsy.[2] Our patient presented with swallowing difficulty, which leads to reflux, aspiration pneumonitis and failure to thrive. Ataxia, speech disorder, developmental delay and other neurological investigation could not be investigated because due to the early age of presentation.

The molecular basis is responsible for this disease.[5],[6],[7],[8] Etiology underlying this disease is abnormality of the HOX gene, loss of Unc5h3 receptor functions and/or abnormality in ciliary protein function. This causes reduced numbers of axons with impaired navigation and migration. Moreover, developing neurons undergo apoptosis if synaptic connections are not established.

Abnormal axonal navigation and migration causes misorientation of descending pathway of the dorsal long tracks, that is, medial lemniscus, lateral lemniscus, medial longitudinal fasciculus, posterior longitudinal fasciculus, central tegmental, trigeminothalamic, spinothalamic, and tectospinal tracts and ectopic fibers on dorsal aspect of pons.[1],[9] On morphological MRI study, this ectopic track appears to be continuous with the MCPs but color FA map of DTI study reveals this track does not join MCP.

Reduced number of axons, their abnormal migration and subsequent apoptosis leads to a smaller size of cortico-spinal and cortico-pontine tracts in the ventral pons, which are smaller as compared to normal patients.[10],[11],[12],[13],[14],[15],[16],[17],[18] The smaller size of these tracts explains the motor problems observed in our patient.[10],[11],[12],[13],[14],[15],[16],[17],[18] Three other major findings were identified on the color FA map of our patient: absence of the SCP decussation, markedly diminished size of the MCPs, and poor or non-visualization of the ICPs.

Abnormality in ciliary protein function causes abnormality in decussation of both the SCPs. The cortico-spinal tracts are also affect, giving the appearance of molar tooth like midbrain like in Joubert syndrome.[19],[20],[21],[22],[23],[24],[25]

Prognosis of PTCD appears to be very variable. Language disorders are a constant feature in PTCD and may result in complete absence of verbal language, sign language only, understandable speech with moderate to severe problems in both being able to understand and to express one-self. The neurological outcome of PTCD patients is also variable, ranging from severe intellectual disability up to normal intelligence.

Thus, PTCD is a newly characterized entity of brain-stem and cerebellar malformation. The exact etiology is still under research but likely to be genetic cause. However, MRI findings are fairly diagnostic of disorder.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Jissendi-Tchofo P, Doherty D, McGillvray G, Hevner R, Shaw D, Ishak G, et al. Pontine tegmental cap dysplasia: MR imaging and diffusion tensor imaging features suggestive of impaired axonal navigation. AJNR 2009;30:113-9.  Back to cited text no. 1
    
2.
Maeoka Y, Yamamoto T, Ohtani K, Takeshita K. Pontine hypoplasia in child with sensorineural deafness. Brain Dev 1997;19:436-9.  Back to cited text no. 2
    
3.
Barth PG, Majoie CB, Caan MW, Weterman MAJ, Kyllerman M, Smit LME, et al. Pontine tegmental cap dysplasia: A novel brain malformation with a defect in axonal guidance. Brain 2007;130:2258-66.  Back to cited text no. 3
    
4.
Stankiewicz P, Lupski JR. Genome architecture, rearrangements and genomic disorders. Trends Gener 2002;18:74-82.  Back to cited text no. 4
    
5.
Altman J, Bayer SA. Development of the Cerebellar System. Boca Raton, FL: CRC Press; 1997.  Back to cited text no. 5
    
6.
Marillat V, Sabatier C, Failli V, Matsunaga E, Sotelo C, Tessier-Lavigne M, et al. The slit receptor Rig-1/Robo3 controls midline crossing by hindbrain precerebellar neurons and axons. Neuron 2004;43:69-79.  Back to cited text no. 6
    
7.
Kawauchi D, Taniguchi H, Watanabe H, Saito T, Murakami F. Direct visualization of nucleogenesis by precerebellar neurons: Involvement of ventricle-directed, radial fibre associated migration. Development 2006;133:1113-23.  Back to cited text no. 7
    
8.
Wellik DM. Hox patterning of the vertebrate axial skeleton. Dev Dyn 2007;236:2454-63.  Back to cited text no. 8
    
9.
Fitzgerald MJT. Neuro-anatomy Basic and Applied. Oxford, UK: Balliere Tindall; 1985. p. 84-93.  Back to cited text no. 9
    
10.
Barallobre MJ, Pascual M, Del Río JA, Soriano E. The netrin family of guidance factors: Emphasis on netrin-1 signalling. Brain Res Brain Res Rev 2005;49:22-47.  Back to cited text no. 10
    
11.
Serafini T, Colamarino SA, Leonardo ED, Wang H, Beddington R, Skarnes WC, et al. Netrin1 is required for commissural axon guidance in the developing vertebrate nervous system. Cell 1996;87:1001-14.  Back to cited text no. 11
    
12.
Deiner MS. Netrin-1 and DCC mediate axon guidance locally at the optic disc: Loss of function leads to optic nerve hypoplasia. Neuron 1997;19:575-89.  Back to cited text no. 12
    
13.
Astic L, Pellier-Monnin V, Saucier D, Charrier C, Mehlen P. Expression of netrin-1 and netrin-1 receptor, DCC, in the rat olfactory nerve pathway during development and axonal regeneration. Neuroscience 2002;109:643-56.  Back to cited text no. 13
    
14.
Finger JH, Bronson RT, Harris B, Johnson K, Przyborski SA, Ackerman SL. The netrin 1 receptors Unc5h3 and Dcc are necessary at multiple choice points for the guidance of corticospinal tract axons. J Neurosci 2002;22:10346-56.  Back to cited text no. 14
    
15.
Inatani M. Molecular mechanisms of optic axon guidance. Naturwissenschaften 2005;92:549-61.  Back to cited text no. 15
    
16.
Bhat KM, Gaziova I, Krishnan S. Regulation of axon guidance by slit and netrin signaling in the Drosophila ventral nerve cord. Genetics 2007;176:2235-46.  Back to cited text no. 16
    
17.
Sibbe M, Taniguchi M, Schachner M, Bartsch U. Development of the corticospinal tract in semaphoring 3a- and CD24-deficient mice. Neuroscience 2007;150:898-904.  Back to cited text no. 17
    
18.
Mann F, Rougo G. Mechanisms of axon guidance: Membrane dynamics and axonal transport in semaphorin signaling. J Neurochem 2007;102:316-23.  Back to cited text no. 18
    
19.
Mykytyn K. Clinical variability in ciliary disorders. Nat Genet 2007;39:818-19.  Back to cited text no. 19
    
20.
Yachnis AT, Rorke LB. Cerebellar and brainstem development: An overview in relation to Joubert syndrome. J Child Neurol 1999;14:570-73.  Back to cited text no. 20
    
21.
Parisi MA, Doherty D, Chance PF, Glass IA. Joubert syndrome (and related disorders) (OMIM 213300). Eur J Hum Genet 2007;15:511-21.  Back to cited text no. 21
    
22.
Gleeson JG, Keeler LC, Parisi MA, Marsh SE, Chance PF, Glass IA, et al. Molar tooth sign of the midbrain-hindbrain junction: Occurrence in multiple distinct syndromes. Am J Med Genet A 2004;125:125-34.  Back to cited text no. 22
    
23.
Tournier JD, Calamante F, Gadian DG, Connelly A. Direct estimation of the fibre orientation density function from diffusion weighted MRI data using spherical deconvolution. Neuroimage 2004;23:1176-85.  Back to cited text no. 23
    
24.
Fitzgerald MJT. Neuroanatomy Basic and Applied. Oxford, UK: Ballière Tindall; 1985. p. 84-93.  Back to cited text no. 24
    
25.
Briguglio M, Pinelli L, Giordano L, Ferraris A, Germanò E, Micheletti S, et al. Pontine tegmental cap dysplasia: Developmental and cognitive outcome in three adolescent patients. Orphanet J Rare Dis 2011;6:36.  Back to cited text no. 25
    


    Figures

  [Figure 1]



 

Top
Print this article  Email this article
   
Online since 20th March '04
Published by Wolters Kluwer - Medknow