The neurologic sequelae post-measles are less common than other complications measles-related and can lead to severe disability or death: primary measles encephalitis (PME), acute post-infectious measles encephalomyelitis (APME), Measles Inclusion Body Encephalitis (MIBE), and Subacute Sclerosing Panencephalitis (SSPE). SSPE syndrome can affect people years from the acute measles virus infection, as result of the persistence of defective viral particles in brain cells. Clinical onset typically manifests with progressive intellectual deterioration, behavioral changes, and myoclonic jerks. The course of SSPE in the majority of affected children is that of a progressive worsening with fatal outcome within 2 years. This report described an Italian case of fulminant SSPE syndrome that led to death within few months from the initial onset

Magurano, Fabio

Annali dell'Istituto Superiore di Sanità

B
r
ie
f
 n
o
t
e
s
167
Key words
• SSPE
• measles
• vaccination
• death
• virus
A case of fulminant subacute sclerosing 
panencephalitis presenting with acute 
myoclonic-astatic epilepsy
Fabio Magurano1, Gian Luca Marella2, Antonella Marchi1, Antonietta Filia3,  
Luigi Tonino Marsella2, Saverio Potenza2, Roberto Massa4, Paola Bucci1, Melissa Baggieri1 
and Loredana Nicoletti1
1Laboratorio Nazionale di Riferimento per il Morbillo e la Rosolia, Dipartimento di Malattie Infettive, Istituto 
Superiore di Sanità, Rome, Italy 
2Dipartimento di Sanità Pubblica, Sezione Medicina Legale, Università degli Studi di Roma “Tor Vergata”, 
Rome, Italy  
3Dipartimento di Malattie Infettive, Istituto Superiore di Sanità, Rome, Italy 
4Dipartimento di Neuroscienze, UOC Neurologia, Università degli Studi di Roma “Tor Vergata”, Rome, Italy
Ann Ist Super Sanità 2017 | Vol. 53, No. 2: 167-169
DOI: 10.4415/ANN_17_02_15
Abstract
The neurologic sequelae post-measles are less common than other complications mea-
sles-related and can lead to severe disability or death: primary measles encephalitis 
(PME), acute post-infectious measles encephalomyelitis (APME), measles inclusion 
body encephalitis (MIBE), and subacute sclerosing panencephalitis (SSPE). SSPE syn-
drome can affect people years from the acute measles virus infection, as result of the 
persistence of defective viral particles in brain cells. Clinical onset typically manifests 
with progressive intellectual deterioration, behavioral changes, and myoclonic jerks. The 
course of SSPE in the majority of affected children is that of a progressive worsening 
with fatal outcome within two years. This report described an Italian case of fulminant 
SSPE syndrome that led to death within few months from the initial onset.
INTRODUCTION
Measles virus (MV) can affect the CNS inducing 
encephalitis in at least 4 different paradigms that can 
cause serious and permanent brain dysfunction or 
death [1]: primary measles encephalitis (PME), acute 
postinfectious measles encephalomyelitis (APME), 
measles inclusion body encephalitis (MIBE), and sub-
acute sclerosing panencephalitis (SSPE). 
Most patients with SSPE have a history of primary 
measles infection at an early age: children who contract 
measles before the age of 2 years are at great risk for 
subsequent development of SSPE [2]. Even, children 
who contract measles before the age of 1 year carry a 
risk of 16 times greater than infected after the age of 5 
years [3]. This suggests that the pathogenesis of SSPE 
involves an immature immune system [4]. Although the 
usual age of onset between 5 and 15 years, with males 
affected more than females [5], cases have been report-
ed as young as 22 months [6] and 4 months [7], and as 
old as 30 years [8].
SSPE disease results difficult to be diagnosed in its 
earliest stage since initial symptoms manifest by de-
crease in school performance, irritability, and emotional 
lability. Weeks to months later, decline in intellectual 
functioning becomes more obvious, and motor dys-
function develops with myoclonic jerks tending to be 
generalized with prominent axial musculature involve-
ment [9]. Individuals may develop seizures, and ocular 
involvement occurs in at least 50% of SSPE cases [10]. 
Loss of swallowing, and bladder/bowel dysfunction be-
come obvious along the course of illness. Latest, the 
patient becomes stuporous, with decorticated rigidity 
ultimately progressing to vegetative state and death. In 
the majority of patients, the interval between the on-
set of symptoms and death is between 1 and 2 years 
[11, 12]. Diagnosis of SSPE measles-related is based on 
the characteristic symptomatology, specific electroen-
cephalographic changes, and elevated titers of measles 
antibodies in serum and cerebrospinal fluid (CSF). A 
definitive confirm of the diagnosis can be obtained by 
the detection of measles virus antigen by brain biopsy 
using reverse-transcriptase polymerase chain reaction 
for measles virus RNA [13].
We describe a fulminant SSPE case whose initial 
clinical and neuroradiological picture was suggestive of 
myoclonic-astatic epilepsy (MAE).
Address for correspondence: Fabio Magurano, Laboratorio Nazionale di Riferimento per il Morbillo e la Rosolia, Dipartimento di Malattie Infettive, 
Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. E-mail: fabio.magurano@iss.it.
Fabio Magurano, Gian Luca Marella, Antonella Marchi et al.
B
r
ie
f
 n
o
t
e
s
168
CASE REPORT
A 5-year-old, previously healthy, girl with 7 weeks his-
tory of poor balance and frequent episodes of muscle 
weakness was admitted to an emergency department 
with a first diagnosis of myoclonic-astatic epilepsy 
(MAE) suggested by a electroencephalogram (EEG) 
showing several epileptiform abnormalities such as 
widespread paroxysmal spikes short in duration during 
sleep, and episodes of atonies of the axial muscles asso-
ciated to a widespread slow paroxysmal. After a period 
of hospitalization lasted almost four months she died. 
By the first physical examinations the child was inter-
ested by episodes of sudden falls during walking with-
out loss of consciousness, head drop attacks of short 
duration (1-2 episodes/day) and sporadic loss of trunk 
control, prior to the appearance of episodes of seizure. 
The patient had been under a not effective therapy of 
sodium valproate and ethosuximide for controlling my-
oclonus, presenting a marked increase of episodes of 
seizure (50 episodes/day). 
The EEG after admission documented the presence 
of widespread paroxysmal polyphasic slow waves dur-
ing sleep ranging from 3 to 4 s in duration associated to 
axial atonies and massive myoclonus, with no improve-
ment under administration of Frisium 7.5 mg during 
EEG recording. Following the first investigations, a 
presumptive diagnosis of “status epilepticus” was estab-
lished and benzodiazepine (Midazolam) 2 g/kg/min was 
added to the current therapy. 
Sudden the child felt in a sleepy and drowsy state with 
persistence of critical episodes characterized by myoc-
lonus segmental distal of upper limbs and face, and 
atonies of head and trunk. Because of the increasing of 
episodes of myoclonus, the therapy was supported with 
rufinamide (100 mg x 2/day).
To investigate the causes of neurological symptoms, 
a cerebrospinal fluid (CSF) sample was collected. Mo-
lecular tests for Cytomegalovirus, EBV, Herpes Simplex 
and Enterovirus were negative; albumin was 129 mg/
dL (normal: 140-200 mg/dL) and immunoglobulin G 
(IgG) was 150 mg/L (normal: 20-40 mg/L), no oligoclo-
nal bands were identified and protein electrophoresis 
showed an increase of monoclonal components of the 
immunoglobulins IgG Lambda and Kappa. The patient 
underwent a therapy with immunoglobulins (0.4 g/kg/
die) but without any neurological improvement.
Despite several changes and adjustments in the 
therapy, after a month of hospitalization a particularly 
marked deterioration of overall clinical condition oc-
curred together with a progressive reduction in the level 
of consciousness and response to external stimuli to 
a level of Glasgow Coma Scale of 3-4, which reached 
level 1 the following month. Repeat lumbar puncture 
was performed and high level of anti-measles IgG, not 
tested in the first CSF sample, was measured in the sec-
ond CSF. Then, also high level of neutralizing antibod-
ies (titer 1:2560) to measles virus were also detected in 
serum, even if the patient had no a documented history 
of measles.
Brain magnetic resonance imaging (MRI) examina-
tion of the skull and spinal in T2-weighetd and FLAIR 
images performed after the admission showed tenuous 
hyperintensity of the white matter bilaterally with non-
specific meaning, probably referring to areas of termi-
nal myelination. It revealed a small amount of spilling 
in the right mastoid and the thickening of soft-tissue 
of the nasopharynx. An additional MRI was performed 
twenty days after the first.
The radiological pattern was indicative of a suffering 
and bilateral diffuse parenchymal abnormalities and the 
hippocampal alterations. These alterations caused neu-
ronal hyperactivation phenomena which were expres-
sion of epileptic status.
On the basis of clinic, instrumental and laboratory 
data a diagnosis of SSPE post-measles was established 
and an antiviral therapy included isoprinosine (100 mg/
kg/day) and lamivudine (10 mg/kg/day) and subcutane-
ous interferon alpha-2a (10 mU/m2/three times a week) 
was added to the symptomatic supportive care but soon 
suspended because the onset of thrombocytopenia.
The evolving EEG pattern revealed widespread slow 
activity and appearing of polyphasic slow-waves fol-
lowed by brain electrical activity depression with a pseu-
do periodic trend, associated to blinking and spams.
Neurological and systemic state worsened with fre-
quent vomiting, fever and electrolyte disorders and the 
patient showed a progressively worsening, until the pa-
tient presented hypotension, a severe metabolic acido-
sis, hypothermia (34 °C), anuria and bradycardia that 
led to the death.
A postmortem examination was performed. Brain 
biopsy of white and gray matter preserved in formalin 
were specifically threated and total RNA was extracted. 
Specific PCR assay was performed to detect measles 
genome but no RNA was detected.
DISCUSSION
Measles is a highly contagious infectious disease 
whose complications account for nearly half of the 1.6 
million deaths caused by vaccine-preventable diseases 
every year worldwide [14]. The incidence of SSPE 
has been calculated to be between 4 and 11 cases per 
100 000 cases of measles but reported rates of SSPE 
tend to be much lower [15, 16].
Cases of SSPE similar to that described above have 
been reported: such cases are likely to be associated 
with the delay in diagnosis, resulting in unnecessary di-
agnostic and therapeutic interventions [17].
In the case described above symptoms were of rapid 
progression. In the early stage of the disease the pa-
tient manifested progressive balance deterioration, 
axial atonies and massive myoclonus. The EEG pattern 
was characterized by epileptiform abnormalities such 
as generalized slow paroxysmal activity with polyphasic 
spike-wave complexes during sleep. Myoclonous and 
atonies were further recorded in association to slow 
wave polyphasic complexes.
During few weeks the general picture worsened, lead-
ing the child to death after 4 months. The patient had 
no history of measles-like illness, actually it remain un-
known how much time has elapsed from the infection 
to the onset of neurologic disease. Moreover, no vacci-
nation anti-measles had be administered to the child in 
infancy or early childhood. Although, serological profile 
Subacute ScleroSing panencephalitiS
B
r
ie
f
 n
o
t
e
s
169
shows a previous measles infection in absence of vac-
cination, and the high measles IgG titer is suggesting of 
reinfection or reactivation of the virus. Moreover, MRI 
scans show data compatible with a SSPE disease. The 
characteristic symptomatology, the specific MRI pat-
terns, and elevated titers of measles antibodies in the 
CSF and the serum samples were strong for the conclu-
sive diagnosis of SSPE syndrome. 
The clinical case described highlights the importance 
of measles vaccination: despite the development of an 
effective vaccination, measles continues to take the 
lives of hundreds of thousands of children worldwide 
each year.
Conflict of interest statement
There are no potential conflicts of interest or any fi-
nancial or personal relationships with other people or 
organizations that could inappropriately bias conduct 
and findings of this study.
Received on 3 October 2016.
Accepted on 21 March 2017.
REFERENCES
1. Klein de Licona H, Bonthius DJ. Measles. In: Biller J 
(Ed). Interface of neurology and internal medicine. Philadel-
phia, PA: Lippincott, Williams &Wilkins; 2007. p 877-83.
2. Bonthius DJ, Stanek N, Grose C. Subacute sclerosing 
panencephalitis, a measles complication, in an interna-
tionally adopted child. Emerging Infect Dis 2000:6:377-81. 
DOI: 10.3201/eid0604.000409
3. Garg RK. Subacute sclerosing panencephalitis. J Neurol 
2008;255(12):1861-71. DOI: 10.1007/s00415-008-0032-6
4. Gershon AA. Chickenpox, measles and mumps. In: 
Remington JS, Klein JO (Eds). Infectious diseases of the 
fetus and newborn infant. Philadelphia, PA: WB Saunders; 
1995. p. 565-618.
5. Modlin JF, Halsey NA, Eddins DL, Conrad JL, Jabbour 
JT, Chien L, Robinson H. Epidemiology of subacute scle-
rosing panencephalitis. J Pediatr 1979;94:231-6.
6. Barram TZ, Gonzalez-Gomez I, Xie ZD, et al. Subacute 
sclerosing panencephalitis in an infant: diagnostic role of 
viral genome analysis. Ann Neurol 1994;36:103-8. 
7. Zwiauer K, Forstenpointner E, Popow-Kraupp T, Hauser 
E, Jellinger KA. Rapid progressive subacute sclerosing 
panencephalitis after perinatally acquired measles virus 
infection. Lancet 1995;345:1124.
8. Cape CA, Martinez AJ, Robertson JT, Hamilton R, Jab-
bour JT. Adult onset of subacute sclerosing panencepha-
litis. Arch Neurol 1973;28:124-7.
9. Bonthius DJ, Stanek N, Grose C. Subacute sclerosing 
panencephalitis, a measles complication, in an interna-
tionally adopted child. Emerging Infect Dis 2000:6:377-81. 
DOI:10.3201/eid0604.000409
10. Babu RB, Biswas J. Bilateral macular retinitis as the 
presenting feature of subacute sclerosing pan encepha-
litis. J Neuroophthalmol 2007;27:288-91. DOI: 10.1097/
WNO.0b013e31815b98e6
11. Dyken PR. Subacute sclerosing panencephalitis: current 
status. Neurol Clin 1985;3:179-96. 
12. Gascon GG. Subacute sclerosing panencephalitis. Semin 
Pediatr Neurol 1996;3:260-9.
13. Mustafa MM, Weitman SD, Winick NJ, Bellini, WJ, 
Timmons CF, Siegel JD. Subacute measles encephalitis 
in the young immunocompromised host. Report of two 
cases measles virus and associated central nervous system 
113 diagnosed by polymerase chain reaction and treated 
with ribavirin and review of the literature. Clin Infect Dis 
1993;16:654-60. 
14. Katz SL. A vaccine-preventable infectious disease kills half 
a million children annually. J Infect Dis 2005;192:1679-80. 
DOI: https://doi.org/10.1086/497172
15. 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. DOI: 10.1093/
ije/dym207
16. Bellini WJ, Rota JS, Lowe LE, Katz RS, Dyken PR, Zaki 
SR, Shieh WJ, Rota PA. Subacute sclerosing panenceph-
alitis. More cases of this fatal disease are prevented by 
measles immunization than was previously recognized. J 
Infect Dis 2005;192:1686-93. DOI: 10.1086/497169
17. Goraya J, Marks H, Khurana D, Legido A, Melvin 
J. Subacute sclerosing panencephalitis (SSPE) ore-
senting as acute disseminated encephalomyelitis in 
a child. J Child Neurol 2009;24(7):899-903. DOI: 
10.1177/0883073808330184


A case of fulminant subacute sclerosing panencephalitis presenting with acute myoclonic-astatic epilepsy

http://www.annali-iss.eu/article/download/464/348

A case of fulminant subacute sclerosing panencephalitis presenting with acute myoclonic-astatic epilepsy

Abstract

Similar works

Full text

Available Versions

Annali dell'Istituto Superiore di Sanità