wolfram (didmoad) syndrome with ventral central pontine...

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1310 Neurology India / November 2016 / Volume 64 / Issue 6 Letters to Editor endings. Neurotoxic paralysis may begin within the first hour of snake bites and is seen first as ptosis and then as blurred vision and diplopia. This is followed by facial weakness, dysphagia, and dysarthria. The postsynaptic toxicity may be reversed by antivenom that may facilitate the dissociation of toxin from the receptor and accelerate recovery or facilitate a response to anticholinesterase therapy. Our case is an atypical presentation of acquired strabismus fixus following a neurotoxic snake bite. This occurrence could be as a result of unresolved prolonged oculomotor paresis or due to a prolonged up rolling of eyes due to Bell’s phenomenon in an unconscious state during the ICU stay. 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 The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.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. Kasturi Nirupama, Srinivasan Renuka Department of Ophthalmology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India E‑mail: [email protected] References 1. Von Noorden GK, editor. Strabismus fixus, clinical findings and etiology. In: Binocular Vision and Ocular Motility. 5 th ed. St. Louis: Mosby; 1996. p. 443-4. 2. Rao KV. Optic neuritis and ophthalmoplegia caused by snake bite. Indian Figure 1: (a) Clinical photograph showing bilateral ptosis with hypertropia and exotropia. (b) Postoperave photograph showing improvement in the ptosis, hypertropia, and exotropia b a This is an open access article distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as the author is credited and the new creations are licensed under the identical terms. How to cite this article: Nirupama K, Renuka S. Hypertropic and exotropic strabismus fixus following neurotoxic snake bite. Neurol India 2016;64:1309‑10. Access this article online Website: www.neurologyindia.com Quick Response Code DOI: 10.4103/0028-3886.193831 PMID: xxxxx J Ophthalmol 1981;29:243-5. 3. Lee SW, Jung IC, Yoon YH, Hong SH, Han KS, Choi SH, et al. Anticholinesterase therapy for patients with ophthalmoplegia following snake bites: Report of two cases. J Korean Med Sci 2004;19:631-3. 4. John J, Gane BD, Plakkal N, Aghoram R, Sampath S. Snake bite mimicking brain death. Cases J 2008;1:16. Wolfram (DIDMOAD) syndrome with ventral central pontine hyperintensity without brainstem atrophy Sir, A 27‑year‑old male, diagnosed to be having a juvenile‑onset diabetes mellitus and bilateral sensory neural hearing loss, presented with an 8‑year history of gradually progressive visual loss. The history was suggestive of the typical Wolfram (DIDMOAD, Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness) syndrome. He had features of hypogonadism, and no other neurological symptoms or signs were noted. His best corrected visual acuity was 3/60 N36 in the right eye and 6/60 N18 in the left eye. Fundus examination showed temporal disc pallor with moderate non‑proliferative diabetic retinopathic changes in both eyes. Visual evoked potential (VEP) was not elicitable in both the eyes. His visual field charting revealed severe visual field defects with macular sparing [Figure 1]. He underwent a magnetic resonance imaging (MRI), which showed T2/fluid‑attenuated inversion recovery (FLAIR) hyperintensity in the anterior half of lower pons [Figures 2a‑c]. High signal intensity was seen in the ventral and central pons, with subtle hyperintensity in the ventral paramedian position [Figures 2b and c]. No atrophy of the pons, [Downloaded free from http://www.neurologyindia.com on Saturday, July 22, 2017, IP: 202.88.253.66]

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1310 Neurology India / November 2016 / Volume 64 / Issue 6

Letters to Editor

endings. Neurotoxic paralysis may begin within the first hour of snake bites and is seen first as ptosis and then as blurred vision and diplopia. This is followed by facial weakness, dysphagia, and dysarthria. The postsynaptic toxicity may be reversed by antivenom that may facilitate the dissociation of toxin from the receptor and accelerate recovery or facilitate a response to anticholinesterase therapy.

Our case is an atypical presentation of acquired strabismus fixus following a neurotoxic snake bite. This occurrence could be as a result of unresolved prolonged oculomotor paresis or due to a prolonged up rolling of eyes due to Bell’s phenomenon in an unconscious state during the ICU stay.

Declaration of patient consentThe 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 sponsorshipNil.

Conflicts of interestThere are no conflicts of interest.

Kasturi Nirupama, Srinivasan RenukaDepartment of Ophthalmology, Jawaharlal Institute of

Postgraduate Medical Education and Research, Puducherry, India

E‑mail: [email protected]

References

1. VonNoordenGK,editor.Strabismusfixus,clinicalfindingsandetiology.In: Binocular Vision and Ocular Motility. 5th ed. St. Louis: Mosby; 1996. p. 443-4.

2. Rao KV. Optic neuritis and ophthalmoplegia caused by snake bite. Indian

Figure 1: (a) Clinical photograph showing bilateral ptosis with hypertropia and exotropia. (b) Postoperative photograph showing improvement in the ptosis, hypertropia, and exotropia

baThis is an open access article distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Nirupama K, Renuka S. Hypertropic and exotropic strabismus fixus following neurotoxic snake bite. Neurol India 2016;64:1309‑10.

Access this article onlineWebsite:

www.neurologyindia.com

Quick Response Code

DOI:

10.4103/0028-3886.193831

PMID:

xxxxx

J Ophthalmol 1981;29:243-5.3. Lee SW, Jung IC, Yoon YH, Hong SH, Han KS, Choi SH, et al.

Anticholinesterase therapy for patients with ophthalmoplegia following snake bites: Report of two cases. J Korean Med Sci 2004;19:631-3.

4. John J, Gane BD, Plakkal N, Aghoram R, Sampath S. Snake bite mimicking brain death. Cases J 2008;1:16.

Wolfram (DIDMOAD) syndrome with ventral central pontine hyperintensity without brainstem atrophy

Sir,A 27‑year‑old male, diagnosed to be having a juvenile‑onset diabetes mellitus and bilateral sensory neural hearing loss, presented with an 8‑year history of gradually progressive visual loss. The history was suggestive of the typical Wolfram (DIDMOAD, Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness) syndrome. He had features of hypogonadism, and no other neurological symptoms or signs were noted. His best corrected visual acuity was 3/60 N36 in the right eye and 6/60 N18 in the left eye. Fundus examination showed temporal disc pallor with moderate non‑proliferative diabetic retinopathic changes in both eyes. Visual evoked potential (VEP) was not elicitable in both the eyes. His visual field charting revealed severe visual field defects with macular sparing [Figure 1]. He underwent a magnetic resonance imaging (MRI), which showed T2/fluid‑attenuated inversion recovery (FLAIR) hyperintensity in the anterior half of lower pons [Figures 2a‑c]. High signal intensity was seen in the ventral and central pons, with subtle hyperintensity in the ventral paramedian position [Figures 2b and c]. No atrophy of the pons,

[Downloaded free from http://www.neurologyindia.com on Saturday, July 22, 2017, IP: 202.88.253.66]

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1311Neurology India / November 2016 / Volume 64 / Issue 6

Letters to Editor

cerebellum, or cerebellar peduncles was seen. Although subtle FLAIR hyperintensity was seen in the optic radiation, it was not entirely convincing [Figure 2d]. The posterior pituitary T1 hyperintense bright spot was seen, albeit small in size[Figure 2e]. Bilateral optic nerves were small with prominence of perioptic cerebrospinal fluid spaces[Figures 2f‑h]. Mild T1 hyperintensity was seen in both the globus pallidi.

Wolfram syndrome 1 (WFS1) is a rare autosomal recessive genetic disorder, in which optic atrophy, diabetes mellitus, and hearing loss are associated with diabetes insipidus, commonly due to the mutation of the WFS1 gene on chromosome 4p16.1. Wolfram syndrome 2, in which optic atrophy, diabetes mellitus, and hearing loss are seen, but not diabetes insipidus, is caused by CISD2 gene mutation.[1]Juvenile‑onset diabetes mellitus and optic atrophy are minimal requirements for the diagnosis of both the varieties of WS, whereas sensorineural hearing loss, ataxia, and urinary tract problems are the other major symptoms,[2]with or without diabetes insipidus. Juvenile diabetes mellitus is probably the first clinical manifestation

of the syndrome, whereas visual deterioration and hearing loss present during the second or third decade of life. Ataxia or imbalance is one of the common neurological problems seen in up to 60% of patients;[2] psychiatric symptoms[3,4] and cognitive impairment are the other less common neurological presentations.

MRI findings previously described in this syndrome are brainstem atrophy,[5]optic tract atrophy, absent posterior pituitary T1 bright spot, cerebellar atrophy, and third ventricular atrophy.[6]Although optic tract atrophy was reported in 100% of cases in larger series,[6] in our case, there was no evidence of optic tract atrophy; however, the visual evoked potential (VEP) was inelicitable. This was attributed to sparing of some proportion of optic tract fibres sufficient enough to preserve his macular vision and give a normal MRI appearance but inadequate to give a positive response on VEP testing. Mild T1 hyperintensities in bilateral globus pallidi were probably suggestive of a more widespread degenerative process even in the absence of gross cerebral parenchymal atrophy. This finding is in accordance with a previous study, in which multimodal imaging demonstrated brain abnormalities even in the early stage of the syndrome.[7] Previously reported cases showed either normal or absent posterior pituitary signal intensity on T1 weighted images; however, in our case, the posterior pituitary T1 bright spot was small but discernable. Due to progressive degeneration of supraoptic and paravertentricular nuclei, posterior pituitary atrophy may occur. This may lead to the absence of the posterior pituitary bright spot in the late stages, as well as its its presence in the early stages of the disease. Probably, our case is representative of an intermediate stage of degeneration in the spectrum. Moderate atrophy of

Figure 1: Visual field chart showing macular sparing visual field defect in both eyes

Figure 2: (a) Midsagittal T2‑weighted, (b) axial T2, (c) axial FLAIR MR images showing ventral lower pontine hyperintensity without volume loss, with normal cerebellum. (d) Axial FLAIR image showing normal optic radiation. (e) Midsagittal T1‑weighted image showing small posterior pituitary bright spot. (f‑h) Coronal and axial T2‑weighted images showing bilateral optic nerve atrophy

a b c d

e f g h

[Downloaded free from http://www.neurologyindia.com on Saturday, July 22, 2017, IP: 202.88.253.66]

1312 Neurology India / November 2016 / Volume 64 / Issue 6

Letters to Editor

This is an open access article distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Harsha KJ, Parameswaran K. Wolfram (DIDMOAD) syndrome with ventral central pontine hyperintensity without brainstem atrophy. Neurol India 2016;64:1310‑2.

Access this article onlineWebsite:

www.neurologyindia.com

Quick Response Code

DOI:

10.4103/0028-3886.193793

PMID:

xxxxx

the brainstem and cerebellum was described as the first sign even in patients without clinical evidence of neurological problems;[3]however, the first sign in our case was T2/FLAIR hyperintensity in the central and ventral pons without atrophy. The possible etiology of this hyperintensity is the degeneration of the ventral nucleus of trapezoid body, that represents the major decussation of the central auditory pathway. As the patient had residual hearing for low frequencies, he did not have the advanced stage of the disease. Probably, only patients in an advanced stage produce the typical central and bilateral paramedian T2/FLAIR hyperintensities of ventral lower pons with associated atrophy.[8]

In conclusion, we report a case of WS with T2/FLAIR hyperintensity in the ventral midline pons in the absence of brain atrophy. The presence of T2/FLAIR hyperintensity in anterior central pons could be one of the initial MRI abnormalities of the brain. In addition, our case describes the additional MRI findings associated with the syndrome, that is, bilateral globus pallidi T1 hyperintensities, and a small posterior pituitary T1 bright spot.

Financial support and sponsorshipNil.

Conflicts of interestThere are no conflicts of interest.

Kamble J. Harsha, K. Parameswaran1

Departments of Neuroimaging and Endovascular Neurosurgery and 1Neurology, Indo‑American Hospital,Brain and Spine

Centre, Vaikom, Kerala, IndiaE‑mail: [email protected]

References

1. Rigoli L, Di Bella C.Wolfram syndrome1 and Wolfram syndrome2. Curr Opin Pediatr2012;24:512-7.

2. Urano F. Wolfram Syndrome: Diagnosis, management, and treatment. Curr Diab Rep 2016;16:6.

3. Swift RG, Sadler DB, Swift M. Psychiatric findings in Wolfram syndrome homozygotes. Lancet 1990;336:667-9.

4. Swift RG, Perkins DO, Chase CL, Sadler DB, Swift M. Psychiatric disorders in 36 families with Wolfram syndrome. Am J Psychiatry 1991;148: 775-9.

5. Barrett TG, Bundey SE, Macleod AF. Neurodegeneration and diabetes: UK nationwide study of Wolfram (DIDMOAD) syndrome. Lancet 1995;346:1458-63.

6. Medlej R, Wasson J, Baz P, Azar S, Salti I, Loiselet J, et al. Diabetes mellitus and optic atrophy: A study of Wolfram syndrome in the Lebanese population. J Clin Endocrinol Metab2004;89:1656-61.

7. Hershey T, Lugar HM, Shimony JS, Rutlin J, Koller JM, Perantie DC, et al. Early brain vulnerability in Wolfram syndrome. PLoS One 2012;7:e40604.

8. GocmenR,GulerE.TeachingNeuroImages:MRIofbrainfindingsofWolfram (DIDMOAD) syndrome. Neurology 2014;83:e213-4.

Commentary: Wolfram (DIDMOAD) syndrome: A progressive disorder with nonsynchronized clinical and imaging features

The authors report the case of a 27‑year‑old male patient who presented with progressive visual diminution, bilateral sensorineural hearing impairment, and history of juvenile‑onset diabetes mellitus; however, cranial magnetic resonance imaging (MRI) revealed paucity of neuroimaging abnormality, which was only limited to the ventral pons and optic radiation showing a hyperintense signal, despite marked endocrinal and neurological deficit. In Wolfram syndrome, the clinical and imaging findings may not always appear in synchrony, with either radiological features preceding the onset of clinical features or vice versa.[1]

Wolfram syndrome is a rare, autosomal recessive genetic disease with an estimated prevalence of approximately 1 in 770,000 people.[2] It is characterized by the presence of juvenile‑onset insulin‑dependent diabetes mellitus, bilateral optic nerve atrophy, diabetes insipidus, along with hearing impairment and symptoms related to the dysfunction of various regions of brain caused by degeneration.[2] Wolfram syndrome is caused by mutation of Wolfram syndrome type 1 (WSF1) gene, which is responsible for coding wolframin and maps to chromosome 4p.[3] The WSF1 gene loss causes chronic endoplasmic reticulum stress‑mediated apoptosis of cells

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