Recovery of chronic motor neuropathy due to acute intermittent porphyria after givosiran treatment in a young boy: a case report.

BACKGROUND: We describe the first case of a pediatric patient with acute intermittent porphyria and severe chronic porphyric neuropathy treated with givosiran, a small-interfering RNA that drastically decreases delta-aminolevulinic acid production and reduces porphyric attacks' recurrence. CASE REPORT: A 12-year-old male patient with refractory acute intermittent porphyria and severe porphyric neuropathy was followed prospectively for 12 months after givosiran initiation (subcutaneous, 2.5 mg/kg monthly). Serial neurological, structural, and resting-state functional magnetic resonance imaging (MRI) evaluations were performed, including clinical scales and neurophysiological tests. Delta-aminolevulinic acid urinary levels dropped drastically during treatment. In parallel, all the administered neurological rating scales and neurophysiological assessments showed improvement in all domains. Moreover, an improvement in central motor conduction parameters and resting-state functional connectivity in the sensory-motor network was noticed. At the end of the follow-up, the patient could walk unaided after using a wheelchair for 5 years. CONCLUSIONS: A clear beneficial effect of givosiran was demonstrated in our patient with both clinical and peripheral nerve neurophysiologic outcome measures. Moreover, we first reported a potential role of givosiran in recovering central motor network impairment in acute intermittent porphyria (AIP), which was previously unknown. This study provides Class IV evidence that givosiran improves chronic porphyric neuropathy.

Megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus (MPPH): report of a new case.

Megalencephaly (MEG), or enlargement of the brain, can either represent a familial variant with normal cerebral structure, or a rare brain malformation associated with developmental delay and neurological problems. MEG has been split into two subtypes: anatomical and metabolic. The latter features a build-up inside the cells owing to metabolic causes. Anatomical MEG has been detected in many different conditions, including many overgrowth syndromes. In 2004 Mirzaa et al. reported five non-consanguineous patients with a new MCA/MR syndrome characterized by severe congenital MEG with polymicrogyria (PMG), postaxial polydactyly (POLY) and hydrocephalus (HYD). The authors argued that these findings identified a new and distinct malformation syndrome, which they named MPPH. We report on a new case of MPPH, the first to be described after the original series (Mirzaa et al., 2004).

Severe encephalopathy associated with reactivated human herpesvirus 6 in a six year-old immunocompetent child.

When a six year-old immunocompetent child affected by encephalitis was subjected to virological studies, human herpesvirus 6 variant B2 resulted to be the cause of illness. Laboratory diagnosis based on the finding of human herpesvirus 6 genome in the cerebrospinal fluid of the patient both at the beginning of the disease and on the occasion of a relapse which occurred forty days after the patient's hospital discharge. The presence of high-avidity IgG to human herpesvirus 6 detected in the patient's serum at the time of the first hospital admission proved that he had suffered from a past infection by human herpesvirus 6. In the consequence of this, the human herpesvirus 6 DNA finding in the patient's cerebrospinal fluid was to ascribed to virus reactivation. In the light of virological and serological results, the clinical case described underlines the ability of human herpesvirus 6 to cause neurological disorders not only during primary infections but also during infections supported by rescued virus.

A study on the characteristics of La Sota strain of Newcastle disease virus adapted to grow in a cell line from bovine embryo kidney (BS/BEK).

The lentogenic La Sota strain of Newcastle disease virus (NDV) was adapted to grow in the BS/BEK cell line of bovine embryo kidney origin with a infectious titre similar to that in chicken embryos. No modification in the biological properties was detected after serial passages in the cell line, as indicated by CPE and by size and shape of the plaques. By contrast, the intracerebral pathogenicity index test, determined in 1-day-old chicks, was lower than for La Sota grown in chicken embryos. However, the immunogenicity of the cell culture adapted virus did not show any variation as demonstrated by serological response and by protection following challenge with virulent NDV. Accordingly, it appears that La Sota grown in cell cultures has retained its biological and immunological characteristics and if these results are confirmed by field trials and long term protection tests, the use of the BS/BEK cell line could be an alternative to chicken embryos for the cultivation of NDV.

A study of two mutant strains of pseudorabies virus (PRV) unable to express thymidine kinase (TK) function.

Two mutant strains of pseudorabies virus (PRV) were selected from the virulent 86/27V virus treated with chemical drugs. The viruses, named 6A1 and 6C2, respectively, appeared to be unable to express thymidine kinase function, as demonstrated by the autoradiography test. They showed a reduced virulence for some susceptible animal species (chickens, mice, rabbits, calves, lambs and piglets) and virus was isolated sporadically. The mutant viruses appeared to be able to protect animals against infection with the virulent strain of PRV. At gross, as well as at histological examination, no lesions in apparatus, system and tissues were detected in pigs inoculated with 6A1 and 6C2 viruses. By contrast, rabbits treated with 6C2 mutant strain presented lymphomononucleated cuffs, microgliosis, and neuronophagia in some areas of the brain. This focal spreading, together with the absence of neuronal necrosis and intranuclear inclusions, suggest an infection induced by a modified strain of PRV.