Disconnective hemispherectomy.

Hemispherectomy is a valuable procedure in the management of seizure disorders caused by unilateral hemispheric disease. Modifications to anatomical hemispherectomy have been proposed to reduce the incidence of superficial cerebral hemosiderosis and hydrocephalus while still achieving seizure control. We report on the modification of a previously described disconnective form of hemispherectomy. We used this procedure on 2 children, with the aid of stereotactic navigation in 1 of the 2 cases. This disconnection was achieved via a transventricular route with minimal cortical resection or disruption of the blood supply. Over the 20 months of follow-up, 1 patient achieved complete seizure control, and 1 patient achieved control of previously incapacitating seizures with few minor seizures persisting. Motor function and speech significantly improved in both patients. Blood loss during the two procedures was significantly less than that reported for anatomical hemispherectomy, and so far there have been no signs of postoperative complications. The hospital stay was limited to 7-14 days after surgery.

Selective posterior rhizotomy and intrathecal baclofen for the treatment of spasticity.

Spasticity occurs in children and adults due to a wide range of conditions, including cerebral palsy, head and spinal cord trauma, cerebrovascular accidents and multiple sclerosis. Multiple treatment options have been described, including medical and surgical treatments. Medical treatments include intramuscular botulinum A toxin, oral baclofen and supportive bracing. Surgical approaches include selective posterior rhizotomy, intrathecal baclofen and orthopedic procedures to address deformities. Many reports have been published on these different treatment options, but rarely has a comparison been made between them. Therefore, this review is aimed at comparing selective posterior rhizotomy and intrathecal baclofen injection for spasticity due to cerebral palsy, especially in children.

Generation of APLP2 KO mice and early postnatal lethality in APLP2/APP double KO mice.

Amyloid precursor protein (APP) is a member of a larger gene family including amyloid precursor-like proteins (APLP), APLP2 and APLP1. To examine the function of APLP2 in vivo, we generated APLP2 knockout (KO) mice. They are of normal size, fertile, and appear healthy up to 22 months of age. We observed no impaired axonal outgrowth of olfactory sensory neurons following bulbectomy, suggesting against an important role for APLP2 alone in this process. Because APLP2 and APP are highly homologous and may serve similar functions in vivo, we generated mice with targeted APLP2 and APP alleles. Approximately 80% of double KO mice die within the first week after birth, suggesting that APLP2 and APP are required for early postnatal development. The surviving approximately 20% of double KO mice are 20-30% reduced in weight and show difficulty in righting, ataxia, spinning behavior, and a head tilt, suggesting a deficit in balance and/or strength. Adult double KO mice mate poorly, despite apparent normal ovarian and testicular development. Otherwise, double KO mice appear healthy up to 13 months of age. We conclude, that APLP2 and APP can substitute for each other functionally.

Studies on the metabolism and biological function of APLP2.

Amyloid precursor proteins (APP) are a member of a larger family of proteins that include the amyloid precursor-like proteins (APLP) APLPI and APLP2. We have examined the expression and metabolism of APLP2 and document that APLP2 is expressed at high levels in the nervous system and in peripheral tissues. Furthermore, several APLP2 isoforms encoded by alternatively spliced transcripts are posttranslationally modified by a chondroitin sulfate glycosaminoglycan (CSGAG) chain. Furthermore, CSGAG modification is regulated by the insertion of sequences encoded by an alternatively spliced exon. Notably, expression of the CSGAG form of APLP2 appears restricted to embryonic neurons and mature neuronal populations that undergo regeneration, such as olfactory sensory neurons. Thus, differences in posttranslational modifications between the APLP2 isoforms and APP are likely to underlie differences in the regulation and function of these homologues. Our present efforts are directed towards using gene targeting strategies to disrupt the expression of the mouse APP/APLP2 genes to define the normative roles of the encoded molecules in development, plasticity, regeneration, and repair.

The mouse APLP2 gene. Chromosomal localization and promoter characterization.

Senile plaques are primarily comprised of deposits of the beta-amyloid precursor-like proteins APLP1 and APLP2. proteins (APPs). APP is a member of a gene family, including amyloid precursor-like proteins APLP1 and APLP2. Using interspecific mouse backcross mapping, we localized the mouse APLP2 gene to the promixmal region of mouse chromosome 9, syntenic with a region of human 11q. We cloned an approximately 1.2-kilobase mouse genomic fragment containing the APLP2 gene promoter. The APLP2 promoter lacks a typical TATA box, is GC-rich, and contains several sequences for transcription factor binding. S1 nuclease protection analysis revealed the presence of multiple transcription start sites. The lack of a TATA box, the presence of a high GC content, and multiple transcription start sites place the APLP2 promoter in the class of promoters of "housekeeping genes." Regulatory regions within the promoter were assayed by transfection of mouse N2a and Ltk- cells with constructs containing progressive 5'-deletions of the APLP2 promoter fused to the bacterial chloramphenicol acetyl transferase (CAT) reporter gene. A minimal region that includes sequences 99 bp upstream of the predominant transcription start site of the APLP2 promoter was sufficient to direct high levels of CAT expression.