A young man who kept falling over

Abstract

In January, 2005, an 18-year-old student was referred to us, by a private neurologist, for investigation of a movement disorder. 4 months previously, the patient had begun to have episodic, involuntary, single “jerks” of the trunk and limbs; after each jerk, he had to support himself with his hands, to avoid falling. Since the jerks began, his academic performance had deteriorated. His medical and family histories were unremarkable. We observed sudden, stereotyped, involuntary movements, consisting of truncal myoclonus and limb extension, accompanied by tongue protrusion and momentary speech arrest. Each episode lasted 1 s, and was succeeded by a loss of muscle tone of about 0∙5 s, which caused the patient to fall. Blood tests showed no abnormalities: notably, concentrations of caeruloplasmin, creatine kinase, thyroid hormones, and autoantibodies were normal. MRI of the brain showed nothing of note. Cerebrospinal fl uid (CSF) concentrations of protein and glucose were normal; microscopy and culture of CSF gave negative results. Video-electroencephalography (EEG) showed periodic discharges of generalised, large-amplitude, slow-wave complexes, coinciding with myoclonus (fi gure). Measles antibody titres, measured by complement fi xation assay, were high in CSF and serum, at 1:64 and 1:320 respectively. We identifi ed a positive IgG oligoclonal band, consistent with infl ammation, in the CSF. The parents revealed that the patient had had measles in 1988, before scheduled immunisation at 12 months. We diagnosed subacute sclerosing panencephalitis (SSPE). We prescribed inosine pranobex to treat the infection, and clonazepam and levetiracetam to counteract myoclonus. However, 3 months later, the CSF measles antibody titre had not decreased, and myoclonus persisted. Intraventricular inter feron was declined by the patient and his parents, because they felt that the risks of implanting an Ommaya reservoir outweighed the likely benefi ts. A trial of subcutaneous interferon β was initiated, but stopped owing to intolerable adverse eff ects. Despite continuing treatment with inosine pranobex, clonazepam, and levetiracetam, the patient’s condition continued to deteriorate. When last seen, in December, 2005, he was heavily dependent on his parents, and had frequent, violent myoclonus. 1 week later, he was found unconscious in bed by his parents, and was certifi ed dead on arrival at hospital. SSPE is a neurodegenerative disorder, caused by measles virus infection persisting in the CNS. The diagnostic criteria of SSPE are clinical presentation, EEG changes, positive CSF oligoclonal bands, high measles antibody titres in CSF or serum, and positive fi ndings on biopsy of the brain; biopsy is rarely needed when the clinical picture supports the diagnosis. The median incubation period is 6–8 years. Although observational studies suggest that treatment with inosine pranobex, an immunomodulating agent, combined with intra ventri cular interferon, might temporarily delay progress of the disease, such treatment does not improve prognosis, which is uniformly poor: the patient is expected to survive 1–3 years after diagnosis. The risk of developing SSPE after childhood measles is estimated to be 1 in 25 000, but only 1 in 5500 if infection occurs before the patient is 1 year old. SSPE, like other complications of measles, is rare in affl uent societies— including Hong Kong, where a measles vaccination programme began in 1967. World wide, numbers of deaths from measles fell by more than half between 2000 and 2005; the decline is attributed to vaccination. In the UK, a decreased rate of MMR vaccination, in recent years, has coincided with an increased rate of infection; it has become a challenge for health profes sionals to clarify parental beliefs about vaccine safety. Of the seven cases of SSPE reported in Hong Kong between 1988 and 2002, fi ve were attributed to a measles outbreak in 1988; our patient’s history indicates that his SSPE was also caused by this outbreak—with an incubation period of nearly 17 years.