Neurometabolic changes in patients with subacute sclerosing panencephalitis

Aims: Subacute sclerosing panencephalitis (SSPE) is a progressive neurodegenerative disease caused by a mutated measles virus. Cerebral damage may not only be caused by the infective agent but also by secondary inflammatory mechanisms. The impact of secondary metabolic changes such as disturbed neurotransmitter synthesis or tetrahydrobiopterin (BH4) deficiency remains unclear.

Methods: Retrospective analysis of homovanillic acid (HVA), 5-hydroxyindolacetic acid (5HIAA), 5-methyltetrahydrofolate (5MTHF), neopterin and BH4 in CSF, as well as of MRI and MR spectroscopy (MRS) results from seven patients (four boys, three girls; age 10 to 16 years).

Results: Thirteen CSF analyses could be evaluated. Elevated neopterin was found in 12/13 samples (mean 141 [range 36 to 310 nmol/L]). Six children showed a decrease of HVA (87 [14 to 167 nmol/L]), three of 5HIAA (48 [33 to 72 nmol/L]), five of 5MTHF (12 [3.5 to 23 nmol/L]), and seven of BH4 (5 [2 to 15 nmol/L]). Follow-up studies performed in four children showed a rapid decrease of HVA, 5HIAA, 5MTHF, and BH4. During antiviral therapy, HVA, 5HIAA, and 5MTHF partially increased. One boy with persistently low BH4 concentrations was treated with BH4, leading to improved concentration and memory functions. In one girl, dystonic movements responded to L-dopa/carbidopa.

MRS performed in all children showed increased lactate (n = 3) and choline peaks (n = 4, demyelinization), and decreased N-acetylaspartate peaks (n = 5, neuronal degeneration).

Conclusion: Children with SSPE have noticeable CSF changes of neurotransmitters, pterins, and folates. In contrast to inborn errors of metabolism, no specific metabolic pattern was found pointing to secondary changes. The most prominent findings were low HVA and BH4 levels. These might contribute to the disease course and offer new treatment options, such as supplementation of L-dopa and/or BH4.