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Subacute sclerosing panencephalitis (SSPE) is a rare delayed complication of measles virus infection in infancy. It is characterised by behavioural changes, myoclonus, cognitive impairment, visual disturbance, pyramidal and extrapyramidal signs, and ultimately coma leading to death.1 Typically, SSPE presents in childhood or early adolescence, but adult onset cases are recognised. Widespread measles immunisation in the UK has led to a dramatic fall in the incidence of SSPE in children, leading to the disease almost becoming extinct.2 However, a latent disease pool remains and cases may still come to the attention of adult neurologists, as borne out by our recent experience in West Yorkshire.
An 18 year old man gave a three week history of blinking episodes lasting approximately one second, associated with a brief head jerk. These were not present in sleep. Examination revealed myoclonic jerks involving the neck associated with blinking. Initial electroencephalograms (EEGs), blood tests, and a magnetic resonance imaging scan were normal. Several anticonvulsant medications failed to suppress the jerks, which by four weeks had spread to the legs, causing unsteadiness. The mini mental test examination score at this stage was 26 of 30. He began to deteriorate rapidly, with disorientation, blunted affect, dystonic posturing of the left arm, bradykinesia, and rigidity. Cerebrospinal fluid (CSF) was sent for analysis of 14-3-3 and S-100 proteins, which were negative. A further EEG, nine weeks after onset, demonstrated high voltage periodic complexes occurring every 10 seconds, consistent with SSPE. CSF and serum measles titres were raised at 35110 mIU/ml and 152930 mIU/ml, respectively. The CSF to serum albumen ratio was 1:300, consistent with intrathecal antibody synthesis. There was no past history of measles, although he had received MMR (measles mumps rubella) immunisation at age 9. Oral inosiplex (isoprinosine) and subcutaneous interferon α2b were started and an Ommaya reservoir was inserted to administer intraventricular interferon α2b. By this stage, the myoclonus had subsided but he had gaze paresis, mutism, widespread spasticity, and required gastrostomy feeding. He received intraventricular treatment for six weeks before reservoir infection necessitated its removal. His condition plateaued and he was maintained on inosiplex alone. Eventually, he was discharged home in a dependent state.
A 25 year old woman presented to her general practitioner complaining of impaired concentration, mood swings, disturbed sleep, and memory loss. One month later, she had noticed a fine tremor in both hands and occasional spasms affecting her right foot. Her concentration was worse and she mentioned word finding difficulties. She also had a tendency to stagger and fall. She was seen by a psychiatrist and somatisation was initially suspected. Later, she was referred to a neurologist. He noted that she had been acting oddly—for example, being found by her mother in a bath of cold water. Neurological examination was normal except for a mini mental test examination score of 20 of 30 with a child-like effect and stilted speech. A magnetic resonance imaging scan was unremarkable. She continued to deteriorate, developing right sided myoclonus. By this stage, she was unable to perform simple tasks, such as washing, and was aware of crawling sensations all over her body. Six months after her first presentation she had an EEG. This revealed repetitive complexes occurring every four to six seconds, often associated with a myoclonic jerk and consistent with SSPE. CSF analysis confirmed oligoclonal bands not present in the serum, which were positive for measles antibody antigen by immunoblotting. She had contracted measles at age 11 months. She was started on oral piracetam and inosiplex, along with subcutaneous interferon β1a, but she became bed bound with quadriparesis, dysarthria, and diffuse hyperalgesia. Her treatment was changed to intraventricular interferon α2a administered via an Ommaya reservoir. She required subcutaneous infusions of midazolam and diamorphine for symptom control, and nasogastric feeding was started. Her condition subsequently stabilised and she was discharged to a children’s hospice.
The estimated incidence of SSPE each year in developed nations is < 1/10 million of the population under the age of 20. The occurrence of two adult cases in the small region of West Yorkshire (population two million) within a few months of one another is remarkable. Although probably a chance finding, our experience emphasises the need for continued surveillance in populations where measles is no longer endemic. In theory more adult onset SSPE cases could present to neurologists in the future. This is because slow central nervous system spread of the virus over many years leaves open the potential for SSPE to present in later life, decades after population eradication of measles. In addition, routine immunisation has led to a shift in the incidence of measles towards unprotected children age < 1, who are at a higher relative risk of developing SSPE in later life after a longer incubation period.2 Recently, there has been an increase in the number of measles outbreaks after a decline in the uptake of the combined MMR immunisation because of safety fears.3
In our patients, SSPE was not initially suspected, leading to diagnostic delay. Enquiring about measles in childhood may have been helpful in case 2, but not case 1, because infection in infancy was probably subclinical. In this patient the lack of typical findings on initial EEGs led to further delay, and instead we considered variant Creutzfeltd Jakob disease as a possibility. Patient 2 presented with early cognitive and behavioural changes. Initially, patients may come to the attention of other specialties with non-specific or psychiatric symptoms.4 It was only subsequent worsening of the patient’s mental state associated with the development of unilateral myoclonic jerks that prompted further investigation, including EEG.
There is no curative treatment for SSPE. Trials have been complicated by variable natural history and spontaneous long remissions of the disease, although it is eventually fatal (median survival, three years). One study demonstrated similar response rates among patients randomised to inosiplex, with or without intraventricular interferon α2b treatment for six months (35% v 34%).5 However, these figures were substantially higher than historical remission rates of between 5% and 10%. In our hands, intraventricular interferon was associated with initial worsening of encephalopathy and pronounced hyperpyrexia, possibly the result of chemically induced meningitis, and reservoir infection was a further complication. In both patients, disease appeared eventually to stabilise after antiviral treatment, particularly in patient 1, in whom rapid progression at onset was suggestive of fulminant SSPE, usually fatal within three months.
Prevention seems to be the best approach, with mass immunisation leading to a drastic reduction in reported cases of measles and associated complications. However, our experience suggests that SSPE in adults should not be forgotten. Clinicians should remain vigilant for this devastating disease.
Competing interests: none declared