Annals of Indian Academy of Neurology
  Users Online: 559 Home | About the Journal | InstructionsCurrent Issue | Back IssuesLogin      Print this page Email this page  Small font size Default font size Increase font size

Table of Contents
LETTERS TO THE EDITOR
Year : 2022  |  Volume : 25  |  Issue : 4  |  Page : 733-734
 

Encephalitis and ocular flutter due to an undifferentiated connective tissue disorder


1 Department of Neurology, Aster Medcity, Kochi, Kerala, India
2 Department of Rheumatology, Aster Medcity, Kochi, Kerala, India

Date of Submission17-Dec-2021
Date of Decision01-Jan-2022
Date of Acceptance24-Jan-2022
Date of Web Publication25-Mar-2022

Correspondence Address:
Boby Varkey Maramattom
Department of Neurology, Aster Medcity, Kochi, Kerala
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aian.aian_1079_21

Rights and Permissions

 



How to cite this article:
Maramattom BV, Thomas J. Encephalitis and ocular flutter due to an undifferentiated connective tissue disorder. Ann Indian Acad Neurol 2022;25:733-4

How to cite this URL:
Maramattom BV, Thomas J. Encephalitis and ocular flutter due to an undifferentiated connective tissue disorder. Ann Indian Acad Neurol [serial online] 2022 [cited 2022 Sep 26];25:733-4. Available from: https://www.annalsofian.org/text.asp?2022/25/4/733/340910




Sir,

A 30-year-old woman presented to us with fever, chills, and rigor and lethargy of three days duration. She had a history of polyarthritis and fatigue of three years duration. Two months earlier, she had been started on hydroxychloroquine. On examination, she was febrile, drowsy, had neck stiffness, papilloedema, and ocular flutter (OF). [Video 1] Optic nerve sheath diameters were elevated (0.65 mm) bilaterally, suggestive of raised intracranial pressure. Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) brain with contrast was normal. Her blood results showed Leukopenia (3,000/uL), thrombocytopenia 147 k/Ul, and normal C3, C4 levels. Cerebrospinal Fluid (CSF) showed mild pleocytosis (total count of 28 cells [100% lymphocytes]) and high protein 226 mg/dl with normal glucose levels and an elevated opening pressure of 27 cms H20. A Biofire meningoencephalitis panel was negative [E. coli, H. influenzae, L. monocytogenes, N. meningitidis, S.agalactiae, S. pneumoniae, CMV, Enterovirus, HSV 1 and 2, HHV-6, human parechovirus, Varicella zoster virus, and C.neoformans/gattii]. Work up for Dengue, Malaria, Scrub Typhus, Leptospira, HIV, and Lyme disease were negative. Rheumatoid Factor (30 IU/mL) and Antinuclear Antibody (ANA) were positive. ANA profile showed very strong bands for nRNP/SM and Ro-52. Anti CCP [<7 U/mL], anti-Beta 2 glycoprotein IGG, IGM, Lupus anticoagulant-DRVVT, Anti-Ds DNA and anti-Cardiolipin antibodies (IgG and IgM) reports were negative. Autoimmune neuronal antibodies [GABA B receptor, Glutamate receptor antibody NMDA (Anti NR-1), Contactin-associated protein 2 (CASPR2), Leucine-rich glioma inactivated protein 1 (LGI1), AMPA 1, and AMPA 2 antibodies], MOG IgG, and NMO IgG were negative. Paraneoplastic antibody panel [ANNA-1, 2, 3, PCA 1, 2, Tr, AGNA-1, Amphiphysin, CRMP-5, Ma/Ta] were also negative. She was started on Inj Dexamethasone 4 mg IV BD × 5 days and made an uneventful recovery within a week. Subsequently, Mycophenolate mofetil 1 gm/day was added to hydroxychloroquine at discharge.

Our patient fulfilled the criteria for undifferentiated connective tissue disease (UCTD) [Arthralgia, arthritis, a positive ANA result, and a disease duration of three years]. She presented with a short-lasting steroid-responsive encephalitis, specifically a rhombencephalitis with OF. [Table 1]. Rhombencephalitis refers to inflammatory conditions affecting the hindbrain (brainstem and cerebellum) and is associated with a wide variety of etiologies including infections (predominantly Listeriosis), autoimmune disease, and paraneoplastic syndromes. The detection of OF in our patient localized the condition to the ponto-cerebellar area. We present an unusual case UCTD with OF.
Table 1: Conditions associated with Opsoclonus-myoclonus syndrome and ocular flutter

Click here to view


There are five major diffuse connective tissue diseases (DCTD) according to the conventional classification schema: Systemic lupus erythematosus; Systemic sclerosis (scleroderma); Myositis, Rheumatoid arthritis, and Sjögren's syndrome. Apart from these classic five, there are patients who meet the criteria for more than one DCTD, while others exhibit only some of the symptoms characteristic of different DCTD and cannot be definitively classified. These are also known as undifferentiated systemic rheumatic diseases (USRD). The concept of an entity called UCTD was first established in 1980.[7] Subsequently mixed connective tissue disease (MCTD), and other overlap syndromes were also described.

UCTD is a distinct clinical entity among USRD and its characteristics include: (a) clinical manifestation of at least one of the CTDs, (b) a positive ANA result, and (c) a disease duration of > one year.[8] Most patients with UCTD are young women who remain in the same category as UCTD throughout their lifetime, although a third can evolved into other well-defined CTDs. Like the DCTD, UCTD is associated with neurological complications such as myositis, inflammatory demyelinating disease, hypertrophic pachymeningitis, and reversible posterior leuko-encephalopathy, among others.[9] Meningitis, encephalitis, or OF have not yet been described with UCTD.

OF is an abnormal involuntary eye movement that consists of repetitive, irregular, bursts of horizontal saccades without an intersaccadic interval.[10] It results primarily from an abnormality in the saccadic generation pathway (the saccadic premotor neurons) that consists of the excitatory burst neurons (EBN), inhibitory burst neurons (IBN), and omnipause neurons (OPN). The OPN lies in the paramedian pontine reticular formation. It functions to silence the EBN and IBN in the inter-saccade interval and prevent unwanted movements in between. Increased GABAA receptor sensitivity in the Olivary-cerebellar-brainstem premotor neuron circuit may also be responsible. Thus, OF occurs when there is mistiming of neuronal activity between the cerebellar nuclei (vermis and fastigial nuclei) and the brainstem premotor neurons.[11] OF and opsoclonus share a similar pathophysiological mechanism. However, unlike opsoclonus, which can occur in any plane, OF is restricted to the horizontal plane. OF is associated with a wide variety of aetiologies including paraneoplastic syndromes, cerebellar/brainstem encephalitis, metabolic-toxic disturbance, demyelinating disease, viral infections, post-infectious syndrome, or as “isolated OF” when it cannot be attributed to any identifiable cause.[12] [Table 1] In our case, a transient autoimmune response directed against the OPN neurons due to UCTD, probably caused OF.

Thus, among patients who present with a meningo-encephalitis and OF, a DTCD or a USRD should be in the differential diagnosis. Such patients may respond to IV steroids. Long-term disease-modifying antirheumatic drugs will also need to be considered. Our case adds to the spectrum of neurological involvement in UCTD or USRD.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Breza M, Smyrni N, Koutsis G, Anagnostou E, Tzartos J, Velonakis G, et al. Ocular flutter as presenting manifestation of pediatric MOG antibody-associated demyelination: A case report. Mult Scler 2019;25:122-5.  Back to cited text no. 1
    
2.
Sim S-S, Sun J-T. Ocular flutter in the serotonin syndrome. N Engl J Med 2016;375:e38.  Back to cited text no. 2
    
3.
Apsner R, Schulenburg A, Steinhoff N, Keil F, Janata K, Kalhs P, et al. Cyclosporin A-induced ocular flutter after marrow transplantation. Bone Marrow Transplant 1997;20:255-6.  Back to cited text no. 3
    
4.
Ploner CJ, Kupsch A. Ocular flutter in a patient with intracranial hypertension following cerebral venous thrombosis. Neurology 2002;59:959.  Back to cited text no. 4
    
5.
Manta A, Ugradar S, Theodorou M. Ocular flutter after mild head trauma. J Neuro-Ophthalmology 2018;38:476-8.  Back to cited text no. 5
    
6.
Blumkin L, Kivity S, Lev D, Cohen S, Shomrat R, Lerman-Sagie T, et al. A compound heterozygous missense mutation and a large deletion in the KCTD7 gene presenting as an opsoclonus-myoclonus ataxia-like syndrome. J Neurol 2012;259:2590-8.  Back to cited text no. 6
    
7.
Leroy EC, Maricq HR, Bashar Kahaleh M. Undifferentiated connective tissue syndromes. Arthritis Rheum 1980;23:341-3.  Back to cited text no. 7
    
8.
Mosca M, Tani C, Talarico R, Bombardieri S. Undifferentiated connective tissue diseases (UCTD): Simplified systemic autoimmune diseases. Autoimmun Rev 2011;10:256-8.  Back to cited text no. 8
    
9.
Maramattom B. Facial myokymia due to a pontine inflammatory demyelinating disorder associated with Mixed connective tissue disorder [MCTD]. Ann Indian Acad Neurol 2020;23:355.  Back to cited text no. 9
    
10.
Leigh J, Zee DS. The Neurology of Eye Movements. 4th ed. O. Oxford University Press; New York, NY, USA. 2006. p. 475-558; 2015.  Back to cited text no. 10
    
11.
Optican LM, Pretegiani E. A GABAergic dysfunction in the olivary-cerebellar-brainstem network may cause eye oscillations and body tremor. II. Model simulations of saccadic eye oscillations. Front Neurol 2017;8:372.  Back to cited text no. 11
    
12.
Vavougios GD, Pelidou S-H, Mavromatis T, Mandras D, Ntoskas T. Spontaneous, isolated, and gaze-evoked ocular flutter: A rare case report. Clin Case Rep 2020;8:955-7.  Back to cited text no. 12
    



 
 
    Tables

  [Table 1]



 

Top
Print this article  Email this article

    

 
   Search
 
  
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Article in PDF (327 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  


    References
    Article Tables

 Article Access Statistics
    Viewed278    
    Printed18    
    Emailed0    
    PDF Downloaded19    
    Comments [Add]    

Recommend this journal