Total Macular Atrophy in Subacute Sclerosing Panencephalitis

 

 Buy Article Permissions and Reprints

Measles is a highly contagious viral infection producing flu-like symptoms, conjunctivitis, and both an enanthem and exanthem. When contracted before the age of 2 years, measles can manifest several years later as Subacute Sclerosing Panencephalitis (SSPE) [1]. SSPE is a devastating progressive neurodegenerative disorder, frequently lethal within 24 months. It results from a chronic infection of the brain by a defective measles virus and manifests initially as behavioral changes followed by myoclonus, dystonia and rigidity, evolving to a vegetative state. Visual loss can occur in about 50 % of SSPE patients, at any stage of the disease, and can even precede SSPE [2]. Visual impairment results mostly from a maculopathy, usually bilaterally. Other rarer ocular manifestations of SSPE have been described (optic neuropathy, peripheral retinochoroiditis) [2] [3] [4] [5] [6] [7].

A previously healthy 13-year-old girl born in Kosovo presented with a two weeks history of right-sided myoclonus and nocturnal incontinence. School performance had been poor for several months. She had no history of measles and benefited from a late vaccination at 3 years of age. On examination, dysarthria, slow mentation and suddenbouts of crying were observed. She had spontaneous myoclonic jerks of the right side of her body every 20 – 30 seconds, causing falls. Fine motor tasks were impaired on her right side with micrographia. Increased measles IgG were found on CSF studies and a diagnosis of SSPE was made two months after the onset of neurologic symptoms. MRI revealed bilateral hippocampal and subcortical atrophy.

One year after the onset of neurologic symptoms, she complained of visual loss of her left eye. One month later, visual acuity was 8/10 RE and 1/50 LE. Left vitritis was present and fundus showed a well defined atrophy of the left macula and temporal pallor of the left optic disc ([Fig. 1]). Optical Coherence Tomography (OCT) demonstrated a complete disappearance of all retinal layers of the central 10 – 15° in the left eye ([Fig. 1]). Measurement of the retinal nerve fiber layer thickness by OCT was normal in the RE (82 µm) but decreased in the LE (72 µm), related only to a sectorial temporal atrophy of the left optic disc (temporal quadrant thickness: 64 µm RE versus 27 µm LE; results from all other quadrants were normal in both eyes without interocular asymmetry). Such a degree of sectorial temporal atrophy resulted from the maculopathy Kinetic manual perimetry showed a deep central scotoma in the left eye with a normal peripheral field of vision ([Fig. 2]). Multifocal electroretinography revealed a corresponding depression of electrical activity within the central 10 – 15° ([Fig. 2]). Examination of the right eye was normal.

From the moment of the diagnosis, a combined therapy associating oral Isoprinosine and amantadine with subcutaneous interferon-beta led to a significant motor improvement. However, over the next twelve months her cognitive functions progressively declined. Follow-up of her visual function showed no progression over the next 6 months.

In more than 50 % of cases, visual loss in SSPE results from a fulminant retinitis localized to the macula. It resolves in about 2 weeks, leaving irregular areas of retinal pigment epithelial atrophy, gliotic scar and even epiretinal membrane formation. Vitreous inflammation and choroidal involvement are usually minimal. The majority of cases present with bilateral involvement but monocular cases are possible in up to 17 % [4]. The onset of such a maculopathy without any associated neurological and behavioural disturbances might cause a diagnostic problem to the ophthalmologist. The differential diagnosis includes mostly toxoplasmosis chorioretinopathy, other possibilities including vitelliform maculopathy (Best’s disease), Stargardt’s disease, and acute posterior multifocal placoid pigment epitheliopathy [4] [5].

Our patient presented with a monocular maculopathy, one year after the onset of behavioral and neurological symptoms of SSPE, despite the systemic therapy. Funduscopy showed a well circumscribed area of macular atrophy and OCT confirmed the lesion to be confined to the central 10 – 15° of the left retina ([Fig. 1]). Pathologic examinations of patients with SSPE maculopathy have demonstrated the presence of inclusion bodies (presumed to be viral particles) within the retinal ganglion and bipolar cells. Histopathologically, SSPE maculopathy is characterized by a diffuse retinal thinning involving the RPE (limited to the macular area) with a minimal choroidal involvement [3]. Our patient demonstrated similar findings by OCT, all the macular retinal layers were markedly involved, including the retinal pigment epithelium (RPE) ([Fig. 1]). No choroidal abnormalities were found on OCT. Fundus examination also revealed a moderate sectorial atrophy of the left optic disc. Some patients with SSPE can present a combination of maculopathy and optic neuropathy or even an isolated optic neuropathy [2] [4]. We believe that the left optic disc atrophy exhibited by our patient was not primary, but secondary to the severe maculopathy for two reasons: first, it was sectorial and moderate; second, the size of the left central scotoma corresponded exactly to the size of the macular lesion and mERG abnormalities.

SSPE is a rare but dreadful complication of measles. Both visual and vital prognoses are very poor as 10 % of patients progress rapidly in just a few months, only 20 % live up to 4 years and less than 7 % live more than 6 years [1]. A spontaneous remission rate of only 5 % has been detected, and it might be temporary [6] [7]. Before systematic immunization, the incidence of SSPE was 1 per million in North America. Most cases of SSPE develop in children who contracted measles before the age of two. With the advent of widespread routine immunization programs in the 60’s and 70’s, the incidence of measles, hence of SSPE also, has been drastically reduced.

Ophthalmologists need to be aware of this entity as two factors might cause a resurgence of SSPE in western countries. First, the global rate of vaccination against measles in western countries has a general tendency to decrease. Second, there is an increased rate of immigration from countries where vaccination programs are less well developed. Early recognition of SSPE is also mandatory for the general prognosis/survival of the patient. Promising results from recent attempts to treat SSPE patients with interferon, ribavirin and isoprinosine have brought some hope for these patients [6] [8] [9] [10].

The possibility of SSPE maculopathy should be entertained in a child/teenager presenting with an acute rapidly progressing maculopathy even in the absence of neurological symptoms.

Conflict of Interest: None

• References

• 1 Garg RK. Subacute sclerosing panencephalitis. J Neurol 2008; 255: 1861-1871
  CrossrefPubMedGoogle Scholar
• 2 Berker N, Batman C, Guven A et al. Optic atrophy and macular degeneration as initial presentations of subacute sclerosing panencephalitis. Am J Ophthalmol 2004; 138: 879-881
  CrossrefPubMedGoogle Scholar
• 3 Nelson DA, Weiner A, Yanoff M et al. Retinal lesions in subacute sclerosing panencephalitis. Arch Ophthamol 1970; 84: 613-621
  CrossrefPubMedGoogle Scholar
• 4 Cochereau-Massin I, Gaudric A, Reinert P et al. Altérations du fond d’œil au cours de la panencéphalite sclérosante subaiguë. J Fr Ophtalmol 1992; 15: 255-226
  PubMedGoogle Scholar
• 5 Green SH, Wirtschafter JD. Ophthalmoscopic findings in subacute sclerosing panencephalitis. Br J Ophthalmol 1973; 57: 780-788
  CrossrefPubMedGoogle Scholar
• 6 Gutierrez J, Issacson RS, Koppel BS. Subacute sclerosing panencephalitis: an update. Dev Med Child Neurol 2010; 52: 901-907
  CrossrefPubMedGoogle Scholar
• 7 Serdaroglu A et al. Macular retinitis as a first sign of acute sclerosing panencephalitis: the importance of early diagnosis. Ocul Immunol Inflamm 2005; 13: 405-410
  CrossrefPubMedGoogle Scholar
• 8 Anlar B, Yalaz K, Öktem F et al. Long-term follow-up of patients with subacute sclerosing panencephalitis treated with intraventricular alpha-interferon. Neurology 1997; 48: 526-528
  CrossrefPubMedGoogle Scholar
• 9 Tomada A, Nomura K, Shiraishi S et al. Trial of intraventricular ribavarin therapy for subacute sclerosing panencephalitis in Japan. Brain Dev 2003; 27: 514-517
  PubMedGoogle Scholar
• 10 Gascon GG. Randomized study of isoniplexversus combined isoniplex and intraventricular interferon alpha in subacute sclerosing panencephalitis (SSPE): international multicenter study. J Child Neurol 2003; 18: 819-827
  CrossrefPubMedGoogle Scholar