Progressive neuronal degeneration of childhood (Alpers syndrome) with hepatic cirrhosis

Abstract

Four children, from two families, suffered from fatal degeneration of the cerebral grey matter. Their disease was characterised by intractable epilepsy, epilepsia partialis continua, progressive deterioration, and terminal hepatic dysfunction. EEG showed marked and distinctive slow wave abnormality, visual evoked responses were diminished, and cerebral atrophy was seen on CT scan. Pathological findings were of neuronal loss and hepatic cirrhosis. The combination of cerebral degeneration, hepatic disease and familial occurrence suggests an inborn error of metabolism with autosomal recessive inheritance. The features described are those of Alpers syndrome, especially the recently delineated subgroup with progressive neuronal degeneration and liver disease.

Evidence That Alpers-Huttenlocher Syndrome Could Be a Mitochondrial Disease

“…All terminal venules had, however, a mantle of connective tissue with mature collagen, pointing to earlier damage of the centrilobular parenchyma. 3,4,11,11 Other clinical symptoms of our patient consistent with those of previously reported patients with this syndrome were the premorbid development, the intense vomiting related to the seizures, and the visual problems.1,2,1l His epileptic manifestations, except for the epilepsia partialis continua, were less aggressive than those usually described in these patients, but the EEG changes were compatible with the typical high-amplitude slow-wave activity with polyspikes seen in Alpers-Huttenlocher syndromes. DISCUSSION Before the patient developed his liver symptoms, he appeared to be a child with mild psychomotor retardation who developed epilepsy, which was initially easy to control.…”

“…DISCUSSION Before the patient developed his liver symptoms, he appeared to be a child with mild psychomotor retardation who developed epilepsy, which was initially easy to control. 2,3,8,11,14 Characteristic liver changes in this condition are subacute or chronic hepatitis or cirrhosis with bile-duct proliferation, fatty change, fibrosis, and necrosis.l,2,5,8,14 Even though microsteatosis was found in some hepatocytes in our patient, no gross steatosis was seen. 6 The epilepsia partialis continua helped us to focus the diagnostic search.…”

Developmental and Inherited Liver Disease

“…1828 They have diffuse cerebral degeneration and progressive neuromuscular deterioration, including ataxia, which leads to death, often in the first 2 years of life. 1842,1843 The initial presentation is usually neurological, with myoclonic seizures and developmental delay; hepatic involvement is variable but can progress to liver failure over months, and thus frequently heralds death. Rarely, the clinical mitochondrial translation elongation factor G1, encoded by GFM1.…”

Kozhevnikov epilepsy: The disease and its eponym

“…Nowadays the epileptic syndrome described by Kozhevnikov is reported to be associated with focal, multifocal, and diffuse brain lesions and may include numerous syndromes. In children, EPC is described in multisystem degenerative diseases, such as mitochondrial disorders (Andermann et al., 1986; Carrascosa Romero et al., 1990; Antozzi et al., 1995; Veggiotti et al., 1995), or the Alpers syndrome (Wilson et al., 1993; Worle et al., 1998; Rasmussen et al., 2000). EPC as the first clinical manifestation has been described in progressive cerebral degeneration of childhood with liver disease (Alpers Huttenlocher disease) with cytochrome oxidase deficiency (Worle et al., 1998) as well as in a patient with a missense mutation in the mitochondrial DNA CO I gene encoding the cytochrome c oxidase subunit I (Varlamov et al., 2002).…”