Use of carbidopa levodopa in a patient with hydrocephalus and frozen movement

While movement disorders are frequently encountered after brain injuries, and may create a host of complicated problems for the clinician, only a few cases of Parkinsonism associated with hydrocephalus have ever been described in the literature. Parkinsonism like syndrome complicating hydrocephalus is a rare disorder, especially when associated with nontumoral aqueductal stenosis. Yet as this case report discusses, hdyrocephalus induced Parkinsonism may be responsive to levodopa-carbidopa administra tion. This report describes a perplexing case of persistent akinesis following corrective surgery for aqueductal stenosis and the subsequent response to levodopa carbidopa administration. We present the case of a 28 year old male with a history of non tumoral aqueductal stenosis diagnosed at age 12. As a child, he underwent a ventriculo peritoneal shunt placement for obstructive hydrocephalus followed by multiple shunt revisions over the next several years. Sixteen years after his initial shunt placement, the patient presented with a decline in mental status. A third ventriculocisternostomy was performed rather than another shunt revision. Following surgery, the patient remained obtunded, and displayed profound hypokinesis, best described as freezing in movement. Upon admission to a rehabiliation unit 2 weeks later, he had made only minimal progress. A SPECT single photon emission computed tomography brain scan revealed decreased basal ganglia perfusion. Levodopa carbidopa therapy was initiated and within 2 weeks, the patient showed improvement in speed of movement, facial expres sion and verbal output. Eight weeks later, the patient could independently complete his basic activities of daily living and demonstrated little, if any, disordered movement. This report illustrates how dopaminergic agents may be useful in cases of hypokinesis following corrective surgery for aqueductal stenosis. SPECT may further aid in the diagnosis and management of Parkinsonism like syndromes in brain injuries.     

Psychomotor agitation following gabapentin use in brain injury

Gabapentin, an anticonvulsant structurally related to gamma aminobutyric acid GABA was recently reported to be effective in pain associated with reflex sympathetic dystrophy RSD and in pain associated with neuropathy. Yet, to our knowledge, the use of gabapentin for neuropathic pain in the presence of cognitive impairment has not been reported. In this report, we describe two patients one with a traumatic brain injury, one with a putative acquired brain injury who presented to a neurorehabilitation unit complaining of pain that was diagnosed as neurologically mediated. Within one week of receiving a daily 900mg dose of gabapentin, both patients complained of heightened anxiety and restlessness. Correspondingly, each reported a diminution of psychological symptoms within 48 hours of gabapentin cessation. These two cases suggest that gabapentin may cause agitation in cognitive impaired patients. Physicians treating brain injured patients and prescribing gabapentin for neuropathic pain may wish to closely monitor patients for similar signs of restlessness or anxiety.     

Modification of guanine nucleotide-regulatory components in brain membranes. I. Changes in guanosine 5'-triphosphate regulation of opiate receptor-binding sites

Guanine nucleotides regulate binding of opiate agonists to membrane receptors by increasing agonist dissociation rates. The current study demonstrates that the ability of guanosine 5'-triphosphate (GTP) and its nonhydrolyzable analogue guanylyl-5'-imidodiphosphate (Gpp(NH)p) to inhibit opiate agonist binding to rat brain membranes can be altered by two methods: by preincubating with EDTA, and by preincubating at pH 4.5. EDTA pretreatment increased the potency of Gpp(NH)p in inhibiting [3H]morphine binding by 4-fold, with little apparent change in the maximum effect of Gpp(NH)p or on levels of binding itself. The effect of EDTA pretreatment was blocked by prior incubation of membranes with excess calcium or manganese but could not be reversed by any divalent cation if the EDTA incubation was longer than 10 min. EDTA pretreatment increased the effects of GTP on dissociation rates of agonists. Pretreatment of membranes at pH 4.5 increased the ability of guanine nucleotides to regulate agonist binding by increasing the maximum effect of Gpp(NH)p from 50% to 80% inhibition of [3H]morphine binding with minor increase in potency of Gpp(NH)p. The actions of EDTA and low pH pretreatments were additive when both were conducted on the same membranes. These results suggest that modification of brain membranes can alter the interaction of receptors with guanine nucleotide-regulatory components which may lead to changes in post-receptor membrane events.     

Estimating changes in river faecal coliform loading using nonparametric multiplicative regression

Faecal coliform (FC) concentration was monitored weekly in the Tangipahoa River over an eight year period. Available USGS discharge and precipitation data were used to construct a nonparametric multiplicative regression (NPMR) model for both forecasting and backcasting of FC density. NPMR backcasting and forecasting of FC allowed for estimation of concentration for any flow regime. During this study a remediation effort was undertaken to improve disinfection systems of contributing municipal waste water treatment plants in the watershed. Time-series analysis of FC concentrations demonstrated a drop in FC levels coinciding with remediation efforts. The NPMR model suggested the reduction in FC levels was not due to climate variance (i.e. discharge and precipitation changes) alone. Use of the NPMR method circumvented the need for construction of a more complex physical watershed model to estimate FC loading in the river. This method can be used to detect and estimate new discharge impacts, or forecast daily FC estimates.     

New alginate microcapsule system for angiogenic protein delivery and immunoisolation of islets for transplantation in the rat omentum pouch

Severe hypoxia caused by a lack of vascular supply and an inability to retrieve encapsulated islets transplanted in the peritoneal cavity for biopsy and subsequent evaluation are obstacles to clinical application of encapsulation strategies for islet transplantation. We recently proposed an omentum pouch model as an alternative site of encapsulated islet transplantation and have also described a multi-layer microcapsule system suitable for coencapsulation of islets with angiogenic protein in which the latter could be encapsulated in an external layer to induce vascularization of the encapsulated islet graft. The purpose of the present study was to determine the angiogenic efficacy of fibroblast growth factor (FGF-1) released from the external layer of the new capsule system in the omentum pouch graft. We prepared 2 groups of alginate microspheres, each measuring ∼600 μm in diameter with a semipermeable poly-L-ornithine (PLO) membrane separating 2 alginate layers. While one group of microcapsules contained no protein (control), FGF-1 (1.794 μg/100 microcapsules) was encapsulated in the external layer of the other (test) group. From each of the 2 groups, 100 microcapsules were transplanted separately in an omentum pouch created in each normal Lewis rat and were retrieved after 14 days for analysis of vessel density using the technique of serial sample sections stained for CD31 with quantitative three-dimensional imaging. We found that FGF-1 released from the external layer of the test microcapsules induced a mean ± SD vessel density (mm²) of 198.8 ± 59.2 compared with a density of 128.9 ± 10.9 in pouches measured in control capsule implants (P = .03; n = 5 animals/group). We concluded that the external layer of our new alginate microcapsule system is an effective drug delivery device for enhancement of graft neovascularization in a retrievable omentum pouch.