Spanish Case of Acute Encephalopathy With Biphasic Seizures and Late Reduced Diffusion: Are We Only Seeing the Tip of the Iceberg?

Abstract

To the Editors: We read with interest the recent paper of Syridou et al1 about the first case of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) in a Caucasian child. Only one more European case of AESD recently reported by our study group is known so far.2 A few months later, a new case of AESD has come to our attention. A 3-year-old boy of Caucasian origin with spinal muscular atrophy type 1, under treatment with nusinersen and receiving chronic invasive mechanical ventilation, presented with a generalized tonic-clonic seizure which lasted approximately 35–45 minutes and ceased after administration of 3 doses of benzodiazepines. On admission, he showed disturbed consciousness (Glasgow Coma Scale at 8) that partially recovered after 12 hours. He had a fever for 24 hours and nasal discharge. Laboratory studies showed white blood cells count of 6010/mm3 with a differential of 4590 neutrophils, procalcitonin (PCT) 2.34 ng/mL, and C-reactive protein (CRP) 0.7 mg/dL; the following day, PCT reached a maximum of 46.35 ng/mL while CRP was 3.2 mg/dL. The cytological and biochemical parameters of the cerebrospinal fluid (CSF) were normal. The initial cerebral magnetic resonance imaging (MRI) was normal. An initial interictal electroencephalogram was compatible with diffuse encephalopathy and did not show epileptiform activity. Nasopharyngeal PCR for influenza B was positive; therefore, oseltamivir was prescribed. PCR in CSF for most common viral causes of encephalitis and CSF, tracheal aspirate and blood cultures were negative. On the fifth day, the patient had a cluster of myoclonic seizures of the right limbs and deterioration of consciousness. A new electroencephalogram showed epileptiform activity over the posterior quadrant of the left hemisphere and slowing of background activity. MRI on day 7 demonstrated bilateral, symmetric reduced diffusion throughout the supratentorial white matter on diffusion-weighted imaging (Fig. 1). Five-day methylprednisolone pulse therapy and 5-day intravenous immunoglobulin course were started on day 8. Seizures were controlled on day 9, after treatment with levetiracetam, valproic acid, clonazepam and a continuous perfusion of propofol; in parallel, deterioration of consciousness progressively disappeared.FIGURE 1.: DWI at day 7 showed restricted diffusion in the white matter of the parietal and occipital lobes and, to a lesser extent, of the frontal lobe and loss of cortical/subcortical differentiation (A and B). Repeat MRI of brain at 3 months follow-up demonstrated marked generalized cortical-subcortical atrophy (C).Follow-up MRI at 3 months showed marked generalized cortical-subcortical atrophy (Fig. 1C). From a clinical point of view, he was under antiepileptic medication and had not experienced any further seizures. AESD is the most common acute encephalopathy syndrome in children in Japan.3 This recently described illness is hardly known outside Asia, which probably contributes to underdiagnosis in low prevalent areas, as is suggested by the fact that 2 of the 3 European cases of AESD notified so far have been diagnosed in our institution, where index of suspicion has been obviously higher since the first case was diagnosed. Although spinal muscular atrophy does not seem to be a predisposing factor for excitotoxic neuronal damage, which is thought to play the most important role in the pathogenesis of AESD,3 this is the second reported case of AESD in a child with this underlying disorder.4 Finally, as we previously described,2 PCT and PCT/CRP were markedly elevated during the first days of AESD and appear to be useful for early diagnosis.