Discussion
In SSPE, an altered cellular response results in virus silent persistence and later reactivation in the central nervous system. Perivascular infiltration of inflammatory cells, demyelination and oxidative damage are described in the earlier phases of the disease.4
Glutamate transport alteration and lipid peroxidation follow this stage, in which inflammation becomes less evident and cortical atrophy ensues, with neurofibrillary tangles of abnormally hyperphosphorylated tau protein accumulation and neuronal loss.1
Considering the pathogenesis of SSPE, KD utilisation could be a rational approach, given its anti-inflammatory, antioxidant and metabolic effects.10 KD also modulates glutamatergic neurotransmission.11
Two cases of SSPE treated with KD have been previously described. In the first, utilisation of a 4:1 KD regimen in a young boy resulted in the resolution of the myoclonic jerks after 2 weeks of treatment, lasting for 3 months, before loss of effect and disease progression.12
In the second, a 2:1 ketogenic diet, with an average 2.2 mmol/L blood ketone level, caused improvement in cognition and physical abilities after 1 month of diet and resolution of the myoclonic jerks after 11 months. Moreover, in this case a dramatic improvement in EEG pattern was reported.13
Neither of them has been studied with ADC ratio.
In our case, we observed global clinical improvement, stability of EEG pattern and progressive reduction of myoclonus and dystonia after the achievement of stable ketosis (June 2020).
While motor improvements could be attributed also to the other treatments, the arrest of SSPE progression is more reasonably due to the anti-inflammatory and neuroprotective action of KD.
The worsening of both motor and behavioural symptoms during the transient loss of ketosis, caused by steroids, supports the significant role of KD.
Even if 5%–6% of patients may experience spontaneous prolonged remission,6 14 we think that the use of KD may have modified the natural course of disease in this patient. Considering the complete ineffectiveness of methisoprinol and ribavirin before KD and contradictory and scarce data regarding their efficacy in literature,1 5 6 we believe that their role has been very limited.
The bilateral, asymmetrical confluent T2W and FLAIR hyperintensities involving the white matter of both parietal lobes, splenium of corpus callosum as well as the abnormalities in the basal ganglia regions are in accordance with previous observations.8 15 The NAA/Cho and NAA/Cr ratios observed in the white matter are consistent with a severe neuronal loss.8
While the new right putaminal lesion appeared before stable ketosis, the hyperintensities of the occipital bilateral white matter manifested a considerable slowing in progression in ADC ratio between the fourth (April 2020) and the fifth (September 2020) MR examination, which was the period of time when our patient achieved and maintained stable and high levels of blood ketones.