An unusual case of acute encephalitic syndrome: Is it acute measles encephalitis or subacute sclerosing panencephalitis?
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.217942
Source of Support: None, Conflict of Interest: None
Subacute sclerosing panencephalitis is a late complication of measles infection and develops usually 6 to 15 years after the primary measles infection. Fulminant subacute sclerosing panencephalitis is an infrequently encountered form wherein the disease rapidly progresses to death. A six-year old male child presented with fever, abnormal movements of the left side of body followed by weakness of the left side of the body, and involuntary abnormal movements of right upper and lower limbs. On examination, he was drowsy and was unable to communicate. He had right-sided hemiballismus. He also had left-sided hemiparesis and the left plantar reflex was extensor. Cerebrospinal fluid examination revealed elevated protein and cells. In the serum and cerebrospinal fluid, anti-measles IgG antibodies were found to be positive. No other viral marker was noted in the cerebrospinal fluid. Magnetic resonance imaging of the brain showed extensive damage to the right temporal, parietal, and to a lesser extent, the frontal region as well as subcortical structures of these regions. Electroencephalography revealed generalized slowing of waves. Over a period of the next 3 days, the intensity and frequency of choreiform movements markedly reduced and the patient developed periodic generalized myoclonus, which was predominantly present on the right side. The patient succumbed to his illness and died after one month. Fulminant subacute sclerosing panencephalitis may have unusual clinical manifestations such as hemiballismus. In fulminant subacute sclerosing panencephalitis, neuroimaging may show extensive cortical damage.
Keywords: Acute encephalitic syndrome, acute encephalitic syndrome, encephalitis, hemiballismus, measles-associated encephalitis, myoclonus
Measles infection is associated with a variety of encephalitic syndromes including primary measles encephalitis, acute measles encephalomyelitis, measles inclusion body encephalitis, and subacute sclerosing panencephalitis. Subacute sclerosing panencephalitis is a late complication and usually develops 6-to–15 years after the primary measles infection. Fulminant subacute sclerosing panencephalitis is an infrequently encountered form where the disease rapidly progresses to death., We present an unusual case of fulminant subacute sclerosing panencephalitis; the clinical presentation of this case was similar to that of an acute encephalitic syndrome.
A six-year old male child had complaints of fever, abnormal movements of the left side of the body, followed by weakness of the left side of the body, and involuntary abnormal movements of the right upper and lower limbs. The fever was of moderate-to-high grade and was associated with chills. After about 3-4 days of fever, the patient developed left focal seizures. The seizure episodes lasted for 2-–3 minutes and the patient was conscious and alert during these episodes. These episodes of focal seizures occurred 5-–7 times a day. After 2 days of seizures, the patient developed left hemiparesis; and 3-–4 days thereafter, he developed involuntary movements of the right side of the body. These involuntary movements persisted throughout the day and subsided during sleep. He was brought to our hospital on the 10th day of illness. There was no past history of measles but the patient did not receive measles immunization. On examination, his pulse, blood pressure and body temperature were normal. He was drowsy and was unable to communicate. He could show his tongue after prolonged coaxing. All the cranial nerves were normal. The patient also had a right-sided hemiballismus. These movements were irregular, jerky, arrhythmic, violent, and affected the arm and shoulder muscles [Video 1]. He had left hemiparesis and the left plantar reflex was extensor. Examination of the other systems did not reveal any abnormality.
The routine haematological and biochemical profile, including renal function tests, liver enzymes, thyroid function tests, and vitamin B12 levels were normal. The testing for human immunodeficiency virus test was negative. A repeat electroencephalography again revealed generalised slowing of waves. The cerebrospinal fluid (CSF) examination revealed an elevated protein level of 100 mg/dl; the CSF sugar level was 65 mg/dl (the corresponding blood sugar was 90 mg/dl); and, the cell count was 5, with all lymphocytes. The CSF gram stain and culture were negative. Serum and cerebrospinal fluid were subjected to assessment for dengue virus, Japanese encephalitis virus, mumps, herpes simplex virus, West Nile virus, varicella zoster virus, cytomegalovirus, and Epstein Barr virus, and all these tests were found to be negative. The cerebrospinal fluid examination for polymerase chain reaction for tuberculosis was also negative. The India ink testing of cerebrospinal fluid was negative. In the serum and cerebrospinal fluid, anti-measles IgG antibodies (the cerebrospinal fluid ratio was 1.74 and the serum ratio was 2.46; the positive value for the laboratory was > 1.1; Calbiotech, USA) was found positive; however, anti-measles IgM antibodies, assessed both in the serum and cerebrospinal fluid, were not detected. Polymerase chain reaction test for measles virus RNA (ribonucleic acid) was negative. Magnetic resonance imaging of the brain showed extensive damage to the right temporal, parietal, and to a lesser extent, frontal region, and the subcortical structures of these regions. Magnetic resonance signal changes were also noted in the left temporal, parietal, frontal regions and subcortical structures. This inflammatory process also involved the medial temporal lobe, amygdala, hypothalamus, and hippocampus of both sides. The magnetic resonance angiography was normal [Figure 1]. The patient was treated with supportive care, sodium valproate, and clonazepam. Over a period of the next 3 days, the intensity and frequency of choreiform movements markedly reduced. Subsequently, the patient developed periodic generalised myoclonus, which was dominantly present on the right side but affected the left side and trunk as well. The patient succumbed to his illness and died after one month. An autopsy was not performed.
This child posed many diagnostic challenges. He presented with a clinical picture consistent with an acute encephalitic syndrome. He had partial seizures, altered sensorium, and right-sided hemiballismus. Neuroimaging revealed extensive damage to the right cerebral cortex and right basal ganglion. The involvement of the left temporal lobe, inferior frontal lobe, insula, and cingulate gyrus were also seen. Acute encephalitic syndrome is defined as the acute onset of fever and an altered mental state and/or new-onset seizures. We performed a battery of tests needed for the diagnosis of common central nervous system viral infections, in particular Japanese encephalitis.,, This is because an epidemic of Japanese encephalitis is currently prevalent in this region., A variety of movement disorders and imaging abnormalities of the thalamus, basal ganglia, and substantia nigra are characteristically seen in Japanese encephalitis., In our patient, all common virological markers in the cerebrospinal fluid were absent, except for an increase in the level of anti-measles IgG titres. Anti-measles IgG titres were raised both in serum as well as in cerebrospinal fluid. Measles-specific antibodies, in particular IgG and IgM, if detected in serum, suggests a systemic measles infection. Their detection in cerebrospinal fluid indicates an intrathecal immune response against the central nervous system measles infection. Hence, we considered the possibility of measles-associated encephalitis in our patient.
Encephalitis is a serious neurological complication of measles virus infection. Usually, systemic measles infection recovers within 2–3 weeks. However, in children with impaired immunity, measles can affect the brain., Measles infection is associated with the four kinds of encephalitic syndromes that include primary measles encephalitis, acute post-measles encephalitis, measles inclusion body encephalitis, and subacute sclerosing panencephalitis. Our patient presented acutely, without any preceding illness and rash, with encephalitis manifesting as altered sensorium, motor deficits, and movement disorder. Initially, the patient had a right-sided hemiballismus, which later evolved to a generalized periodic myoclonus with dominant right-sided involvement. An altered mental state, extensive parenchymal brain damage, periodic myoclonus, generalized slowing of waves on electroencephalogram, and elevated IgG anti-measles antibodies in cerebrospinal fluid, led us towards making a diagnosis of subacute sclerosing panencephalitis [Table 1].
Subacute sclerosing panencephalitis, a fatal complication of measles infection, develops in a proportion of children who encounter measles at a young age. The incubation and disease periods of measles infection are in the range of years.
Autoimmune encephalitis is a closely resembling diagnosis in such patients. Autoimmune encephalitis often manifests with subacute memory and cognitive decline, altered consciousness, or coma. A variety of movement disorders, such as dyskinesias and/or rigidity/abnormal posturing, are an integral feature of anti- N-methyl-D-aspartate receptor encephalitis. The presence of elevated titers of anti-measles antibody in the cerebrospinal fluid has recently been demonstrated in four patients with autoimmune encephalitis, adding to the diagnostic and therapeutic dilemma.
Our patient with subacute sclerosing panencephalitis had an unusually ultra-fulminant course and died within a month. Fulminant subacute sclerosing panencephalitis is an infrequently encountered form of subacute sclerosing panencephalitis wherein the disease rapidly progresses to death (within 6 months of the disease onset). Fulminant subacute sclerosing panencephalitis accounts for approximately 10% of the cases with a measles infection. The clinical features of fulminant subacute sclerosing panencephalitis are often atypical and can pose a diagnostic challenge., Exactly what triggers a fulminant course in a patient with subacute sclerosing panencephalitis is not known. An acute change in the host immune status or an altered virulence of the mutated measles virus may be responsible. An early onset of measles infection (occurring at less than 2 years of age) and lack of a proper immunization protocol have been associated with fulminant subacute sclerosing panencephalitis [Table 2].
An unusual feature in our case was that, initially, the patient had hemiballismus, and within a week, the movement disorder evolved into generalized periodic myoclonus. In subacute sclerosing panencephalitis, in addition to myoclonus, dystonia, tics, and hemichorea are other types of movement disorders that have also been described. In subacute sclerosing panencephalitis, hemiballismus has not yet been seen; however, it has been reported in subacute measles encephalitis.
Neuroimaging in our patient revealed an unusually extensive cortical and subcortical damage on the right side. Neuroimaging abnormalities were seen on the left side as well. On the left side, there was involvement of the temporal lobe, inferior frontal lobe, insula, and cingulate gyrus. There is no specific neuroimaging abnormality in early subacute sclerosing panencephalitis. In fulminant cases, demyelinating white matter lesions are seen in the periventricular or subcortical regions with predominant involvement of the parieto-occipital lobe. At times, this involvement is asymmetric and extensive. The fulminant disease may involve the thalamus, basal ganglia, corpus callosum, and parts of the limbic system as well. In the usual course of subacute sclerosing panencephalitis, after 1–2 years, diffuse cerebral atrophy invariably occurs. Pons or bilateral pontocerebellar peduncular lesions may also be the only abnormality. Lesions have also been noted in the corpus callosum, thalamus, cerebellum, and spinal cord.
Meningeal and parenchymal contrast enhancement and tumor-like lesions in the brain parenchyma may also be observed. Diffusion-weighted magnetic resonance imaging shows restricted diffusion within the white matter lesions. Magnetic resonance spectroscopy can show decreased N-acetylaspartate peaks indicating neuronal loss. Increased choline and myoinositol levels indicates glial proliferation and inflammation before the neuronal loss occurs.
Brain tissue biopsy/autopsy in subacute sclerosing panencephalitis is confirmatory. Histopathological examination of the brain tissue shows inflammatory changes with numerous eosinophilic intranuclear and intracytoplasmic inclusion bodies, perivascular lymphocytic infiltration, and astrocytic gliosis. Unfortunately, we were not able to perform an autopsy study in our patient.
In conclusion, subacute sclerosing panencephalitis, at times, evolves quite rapidly and presents with unusual clinical features. Asymmetric extensive cortical damage and hemiballismus were unusual features in our patient.
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[Table 1], [Table 2]