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Table of Contents    
Year : 2022  |  Volume : 70  |  Issue : 2  |  Page : 744-748

Adult-Onset Subacute Sclerosing Panencephalitis: Exploring A Potential Cure

Department of Neurology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India

Date of Submission20-Jan-2021
Date of Decision18-Feb-2021
Date of Acceptance29-Mar-2021
Date of Web Publication3-May-2022

Correspondence Address:
Dr. Samhita Panda
Department of Neurology, All India Institute of Medical Sciences, Jodhpur, Rajasthan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.344671

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 » Abstract 

Subacute sclerosing panencephalitis (SSPE), an insidiously progressive slow viral infection of the central nervous system caused by the mutated measles virus, is invariably fatal. Various medications have been tried unsuccessfully till date with rare remissions. A case of 21-year woman with adult-onset SSPE who improved after treatment is reported. She had seizures, psychosis, and extrapyramidal symptoms and was on multiple anti-seizure medications without response. She was given a trial of levamisole with gradual escalation and achieved complete clinical remission by 21 months. This case demonstrates the curative potential of levamisole in adult-onset SSPE. A review of previous treatments attempted in cases who underwent remission of SSPE is also presented.

Keywords: Adult-onset, immunomodulation, levamisole, remission, subacute sclerosing panencephalitis
Key Message: This case demonstrates complete clinical remission of SSPE after treatment with levamisole and is to be seen in the light of the high mortality and poor response to most treatment regimens currently available.

How to cite this article:
Panda S. Adult-Onset Subacute Sclerosing Panencephalitis: Exploring A Potential Cure. Neurol India 2022;70:744-8

How to cite this URL:
Panda S. Adult-Onset Subacute Sclerosing Panencephalitis: Exploring A Potential Cure. Neurol India [serial online] 2022 [cited 2022 Jun 25];70:744-8. Available from: https://www.neurologyindia.com/text.asp?2022/70/2/744/344671

Subacute sclerosing panencephalitis (SSPE) or Dawson's disease, a devastating slow viral infection of the central nervous system caused by mutated measles virus, is still quite prevalent in developing nations such as India and Pakistan despite worldwide decline in prevalence to one per 100,000 cases of measles due to better immunization coverage in developed countries.[1],[2] As per WHO surveillance data, India had 10761 and 3178 cases in 2019 and 2020, respectively [Figure 1]. However, updated data on current incidence and prevalence of SSPE is not available. As per the last available literature, reported incidence rates were 21 cases per million population in India, 11 per million in Japan, and 0.06 per million in Canada.[3] Further, the true magnitude of the existing problem may be underestimated due to variability in physician seeking practices, misdiagnosis, inadequate follow-up, and premature death.[4]
Figure 1: (a) World distribution of measles in December 2019; (b and c) Surveillance data of Measles from India from 2014 to 2020 as per World Health Organization

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SSPE, manifested by diffuse chronic encephalopathy with a progressive stereotypic decline in cognitive function, quasiperiodic myoclonus, psychiatric, visual, and gait abnormalities culminating in a quadriparetic vegetative state, and premature death, has again been generating interest recently.[1] Pathogenesis of SSPE and its predisposing factors are under rigorous evaluation with genetic studies demonstrating point mutations in matrix (M) and fusion (F) protein genes. Unfortunately, therapeutics have been dismal and various medications tried such as isoprinosine, interferons, and ribavirin have been unsuccessful till date.[5],[6] With this background of apparent hopelessness, a case of adult-onset SSPE, who is in complete remission after treatment, is highlighted with a brief review of previous therapeutic attempts at cure.

 » Case Report Top

A 21-year-old woman presented with recurrent myoclonic jerks and generalized tonic clonic seizures for 6 months with one episode of convulsive status epilepticus with cardiorespiratory arrest. She was on anti-seizure medications in addition to aripiprazole for psychosis. Cognitive decline and slowness of gait requiring two-person support for activities of daily living were noted. She was cachexic, drooling saliva, and irritable with low volume and dysarthric speech, generalized lead-pipe rigidity, and bradykinesia. Quasiperiodic negative myoclonus was noted every 10–14 s, persisting throughout the day which would subside during sleep with frequent major jerks causing her to fall. She had contracted measles between 6 and 8 years of age.

Hematological and biochemical investigations were unremarkable. MRI brain showed mild diffuse cerebral and cerebellar atrophy [Figure 2]a,[Figure 2]b,[Figure 2]c. EEG showed generalized slowing of background activity with quasiperiodic long duration long interval generalized sharp and slow wave Radermecker complexes [Figure 3]a. Cerebrospinal fluid (CSF) was clear, under normal pressure, and paucicellular with normal protein and sugar. IgG antibody by ELISA was positive for measles in the CSF (>250 U/mL; ref: <8 U/mL) while IgM was 2.05 U/mL. Based on Dyken's criteria, diagnosis of SSPE (modified Risk and Haddad Stage 2c) was made.[1]
Figure 2: Axial 3D FLAIR images (a-c) acquired 1 year after onset of SSPE show faint FLAIR hyperintensity along bilateral peri-trigonal white matter (white arrow) with mild diffuse cerebral atrophy. Follow-up corresponding images (d-f) done after 2 years show similar peri-trigonal hyperintensities and mild cerebral atrophy without significant interval change

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Figure 3: Serial EEGs of the patient with adult-onset SSPE in awake state showing (a) classical generalized long duration long interval Radermecker complexes at baseline; (b) increase in inter-complex interval to 15-20 s after 6 months; (c) normal background with no epileptiform activity at 18 months and (d) 29 months

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As the patient was resistant to multiple anti-seizure medications (levetiracetam, clobazam, and sodium valproate) and unable to afford immunomodulatory medications generally recommended for SSPE, a trial of levamisole was given with gradual dose escalation (cost of 150 mg tablet being INR 15.70). No adverse hematological or biochemical effects were noted after initiation. Though there was no immediate clinical change, a subtle decrease in frequency of major jerks was noted after 2 months. By 3–6 months of therapy, major jerks had reduced to once in 4–5 h and periodic myoclonus to once in 20 s. After 8 months, EEG showed periodic complexes at intervals of 15–20 s [Figure 3]b. At this time, levamisole was stopped due to transient thrombocytopenia which recovered [platelet count: 64000/mm3 (before) and 1.97 lac/mm3 (after stopping)]. However, the patient continued to improve and at 18 months, jerk frequency had reduced to once in 5–10 min. Gait and speech had improved. By 20 months, rare myoclonus in 8–10 h and progressive gain of weight and independent functions were observed. The jerks completely subsided by 21 months and at 2 years after starting treatment with levamisole, she was able to walk unsupported and erect, talked more fluently while making eye contact. EEG was normal [Figure 3]c with later persistence of normalcy [Figure 3]d. MRI brain after 24 months of remission showed no new lesions or progression of cortical atrophy [Figure 2]d,[Figure 2]e,[Figure 2]f. CSF examination at 24 months was unremarkable. IgG antibody by ELISA was positive for measles in serum (28251.5 U/mL; ref: <8 U/mL) while it was 635.2 U/mL in CSF and CSF/serum quotient was 0.05 (<1.3 normal). At 36 months, patient was normally conversant, interactive, and expressed her desire to continue improving and come off medications entirely (modified Risk and Haddad Stage 4c).

 » Discussion Top

Currently, there is no cure for SSPE, and eradication by an effective vaccination program is considered to be more beneficial and cost-effective than any other form of control. Despite measles vaccine being part of childhood national vaccination schedules world over and measles elimination goal for year 2020 in six WHO regions, an almost constant number of new patients are diagnosed every year and none of these milestones have been met.[2],[3],[4] SSPE is probably a highly preventable illness possible by preventing the inciting measles disease. However, it must be recognized that the translation of good measles control to decline in new SSPE cases occurs only years after decline in incident measles cases. Therefore, a period of at least 5–10 years has to elapse before an impact on SSPE incidence and major decline in SSPE, respectively, is observed after measles control. The further daunting goal is the eradication of SSPE as cases may keep occurring up to 20 to 30 years after elimination of measles due to wide latency period.

SSPE has a high mortality (about 95%) with average life span of 3.8 years (45 days–12 years). Prolonged survival was documented for 3 to 13.8 years from India.[4] While a brief plateau phase or slight improvement may be noted in some patients, long-term stabilization or remission is exceptional. It is clinically difficult to predict which patient will have a substantial remission and “why.” The role of immunological status of host, infection by a wild strain, and altered virulence of measles virus in pathogenesis and outcome of SSPE requires exploration as 5% have substantial spontaneous remissions defined as a bedridden patient, incapable of self-care who becomes ambulatory and able to attend to ones needs.[7] Age of onset of SSPE may prognosticate spontaneous favorable outcome.[7] Adult-onset SSPE appears to have higher rate of spontaneous remission compared to childhood-onset SSPE.[4] Stage of SSPE also contributes as in our case who did not progress beyond modified Risk and Haddad Stage 2c. Similarly, long-term improvement was associated with disappearance of EEG periodic complexes and emergence of normal background activity.[7] However, despite being in remission, they continue to have elevated CSF IgG and measles antibody titers.

While supportive treatment is the mainstay, no standard successful therapeutic protocols have yet evolved. Antiviral drugs and immunomodulators are used in SSPE, specifically isoprinosine, interferon-alfa, ribavirin, and lamivudine.[1],[5] Occasionally amantadine, an anti-RNA agent that retards maturation of viruses by not allowing them to replicate, has been tried.[8],[9] Ketogenic diet, antiapoptotic agents, and RNA inhibitors are also potential candidates. Hence, the search for cure of SSPE is still on.

A review of literature exploring remission-inducing potential of various treatment regimen shows that no drug independently or in combination consistently achieved substantial remission [Table 1]. Of these, isoprinosine alone or in combination with intraventricular interferon has shown greater chance of remissions than spontaneously.[5],[10],[11],[12],[13] In another series of long-term survival in SSPE, 8 of 19 patients achieved substantial improvement from being bedridden to community ambulant stage, but details of specific treatment had not been documented.[4] Complete clinical, radiological, electrographic, and immunological parameters as well as dynamics of changes in these features during period of remission and degree of clinical recovery have not been consistently documented across all these reports [Table 1]. Some patients have also remained in dependent, vegetative states with persistent features of SSPE. As such, whether these instances may be considered as a legitimate complete remission in SSPE may be debatable.
Table 1: Review of literature illustrating the patients with documented clinical remission of SSPE in relation to specific medications

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Levamisole, the levo-isomer of tetramisole, is primarily an immunopotentiating anticarcinogenic agent also used in dermatological disorders. It may stimulate recovery of defective cell-mediated immunity by stimulating lymphocytes, granulocytes, and macrophages.[15] In a series of autoimmune disorders including SSPE, a marked increase in the number of E-rosettes was noted in patients with SSPE suggesting effect on T-cell mediated immunity though it did not clinically translate to improvement in a short period of 4–6 months.[15] Though seldom used in SSPE, our index case demonstrates the potential curative potential of levamisole in SSPE with no major side effects.[4] Addition of levamisole seems to have triggered the positive turn of events leading to clinical, radiological, and electrographic remission which has lasted till time of publication (42 months from treatment and 54 months after onset of SSPE). It will be difficult to postulate a definite cause and effect relationship though a temporal association between initiation of treatment and progressive improvement may suggest a possible effect. The author accepts that a small number of patients may defy the natural course and have variable stabilization and substantial spontaneous remission lasting many years.

 » Conclusions Top

As a global community and a relatively resource-poor nation like India, where we are still struggling to eradicate measles and reduce the incidence of SSPE, definitive and effective therapeutic options are still at large. Yet among the dismal performance of other regimes, levamisole may be a potential low-cost candidate demonstrating a curative potential in SSPE.


The authors would like to thank the Departments of Diagnostic and Interventional Radiology and Microbiology, All India Institute of Medical Sciences, Jodhpur for the neuroimaging and serological evaluation of the patient, respectively.

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


Conflicts of interest

There are no conflicts of interest.

 » References Top

Garg RK, Mahadevan A, Malhotra HS, Rizvi I, Kumar N, Uniyal R. Subacute sclerosing panencephalitis. Rev Med Virol 2019;29:e2058.  Back to cited text no. 1
World Health Organization. Progress towards regional measles elimination – Worldwide, 2000–2018. Reform of the International Coordinating Group for vaccine provision: A new framework for coordination, accountability and transparency. Wkly Epidemiol Rec 2019;94:581-600.  Back to cited text no. 2
Campbell H, Andrews N, Brown KE, Miller E. Review of the effect of measles vaccination on the epidemiology of SSPE. Int J Epidemiol 2007;36:1334-48.  Back to cited text no. 3
Prashanth LK, Taly AB, Ravi V, Sinha S, Rao S. Long term survival in subacute sclerosing panencephalitis: An enigma. Brain Dev 2006;28:447-52.  Back to cited text no. 4
Aydin OF, Senbil N, Kuyucu N, Gürer YK. Combined treatment with subcutaneous interferon-alpha, oral isoprinosine, and lamivudine for subacute sclerosing panencephalitis. J Child Neurol 2003;18:104-8.  Back to cited text no. 5
Di Trapani G, Mazza S, Tomassetti P, Pentimalli LCR, Macchi G. Clinical-electrophysiological correlations in a long-term case of subacute sclerosing panencephalitis with partial clinical improvement. Eur Neurol 1991;31:23-9.  Back to cited text no. 6
Santoshkumar B, Radhakrishnan K. Substantial spontaneous long-term remission in subacute sclerosing panencephalitis (SSPE). J Neurol Sci 1998;154:83-8.  Back to cited text no. 7
Robertson WC Jr, Clark DB, Markesbery WR. Review of 38 cases of subacute sclerosing panencephalitis: Effect of amantadine on the natural course of the disease. Ann Neurol 1980;8:422-5.  Back to cited text no. 8
Gokoglu A, Gozdas HT. Adult-onset subacute sclerosing panencephalitis presented with neuropsychiatric symptoms. J Coll Physicians Surg Pak 2019;29:S29-30.  Back to cited text no. 9
Gokcil Z, Odabasi Z, Demirkaya S, Eroglu E, Vural O. Alpha-interferon and isoprinosine in adult-onset subacute sclerosing panencephalitis. J Neurol Sci 1999;162:62-4.  Back to cited text no. 10
Gascon G, Yamani S, Crowell J, Stigsby B, Nester M, Kanaan I, et al. Combined oral isoprinosine-intraventricular alpha-interferon therapy for subacute sclerosing panencephalitis. Brain Dev 1993;15:346-55.  Back to cited text no. 11
Huttenlocher PR, Mattson RH. Isoprinosine in subacute sclerosing panencephalitis. Neurology 1979;29:763-71.  Back to cited text no. 12
Kwak M, Yeh H-R, Yum M-S, Kim H-J, You SJ, Ko T-S. A long-term subacute sclerosing panencephalitis survivor treated with intraventricular interferon-alpha for 13 years. Korean J Pediatr 2019;62:108-12.  Back to cited text no. 13
Serdaroğlu A, Gücüyener K, Dursun I, Aydin K, Okuyaz C, Subaşi M, et al. Macular retinitis as a first sign of subacute sclerosing panencephalitis: The importance of early diagnosis. Ocul Immunol Inflamm 2005;13:405-10.  Back to cited text no. 14
Verhaegen H, De Cree J, De Cock W, Verbruggen F. Restoration by levamisole of low E-rosette forming cells in patients suffering from various diseases. Clin Exp Immunol 1977;27:313-8.  Back to cited text no. 15


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1]


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