The entity of an occult tight filum terminale syndrome, characterized by clinical findings consistent with a tethered cord syndrome, but with the conus ending in a normal position, has been recognized recently. The indications for sectioning the filum terminale in this situation are not well characterized and are controversial. We report a retrospective review of a consecutive series of 60 children (ages 3–18 years) with a diagnosis of occult tight filum terminale syndrome who underwent section of the filum and were followed for more than 6 months (mean 13.9 months). The criteria for surgical intervention were (1) spina bifida occulta, (2) progressive bladder instability unresponsive to conservative measures, (3) urological/nephrological evaluation to confirm or rule out nonneurogenic etiology, and (4) two or more of the following: (a) bowel involvement (fecal incontinence or chronic constipation), (b) lower extremity weakness, (c) gait changes, (d) reflex/tone abnormalities, (e) sensory disturbances, (f) back/leg pain, (g) orthopedic abnormalities/limb length discrepancy, (h) scoliosis/lordosis, (i) recurrent urinary tract infections, (j) abnormal voiding cystourethrogram/ultrasound, (k) syringomyelia, and (l) neurocutaneous stigmata. Postoperatively, urinary incontinence/retention showed complete resolution in 52%, marked improvement (>95% resolution) in 35%, moderate improvement (>75%) in 6%, minimal improvement (> 50%) in 6%, and no improvement (<50%) in 2%. Fecal incontinence completely resolved in 56%, improved in 41%, and was unchanged in 3%. Weakness, sensory abnormalities, and pain improved or resolved in all patients.

Central to malaria pathogenesis is the invasion of human red blood cells by Plasmodium falciparum parasites. Following each cycle of intracellular development and replication, parasites activate a cellular program to egress from their current host cell and invade a new one. The orchestration of this process critically relies upon numerous organised phospho-signaling cascades, which are mediated by a number of central kinases. Parasite kinases are emerging as novel antimalarial targets as they have diverged sufficiently from their mammalian counterparts to allow selectable therapeutic action. Parasite protein kinase A (PfPKA) is highly expressed late in the cell cycle of the parasite blood stage and has been shown to phosphorylate a critical invasion protein, Apical Membrane Antigen 1. This enzyme could therefore be a valuable drug target so we have repurposed a substituted 4-cyano-3-methylisoquinoline that has been shown to inhibit rat PKA with the goal of targeting PfPKA. We synthesised a novel series of compounds and, although many potently inhibit the growth of chloroquine sensitive and resistant strains of P. falciparum, they were found to have minimal activity against PfPKA, indicating that they likely have another target important to parasite cytokinesis and invasion.

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