The International Standards for Neurological Classification of Spinal Cord Injury: relationship between S4-5 dermatome testing and anorectal testing.

STUDY DESIGN: Prospective cross-sectional multicenter study. OBJECTIVE: To evaluate the correlation, sensitivity, specificity and predictive values of S4-5 dermatome and the anorectal examination for determination of sacral sparing in the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination. SETTING: Two tertiary hospitals that specialize in pediatric spinal cord injuries. METHODS: In all, 189 patients who were at minimum 3 month after spinal cord injury participated in complete ISNCSCI examinations. All examiners completed training for the proper completion of the ISNCSCI examination. Correlations and sensitivity/specificity analyses were conducted between S4-5 dermatome testing and the anorectal examination. Results were analyzed by age of patient, examiner, tetraplegia/paraplegia classification and injury level (T10-S3, L1-S3 and S3). RESULTS: The correlation between S4-5 dermatome and anorectal sensation was moderate (0.62, P<0.001). Using the anorectal examination as the gold standard, the sensitivity of S4-5 testing was 0.60 (0.49, 70) and specificity was 0.96 (0.90, 0.99). No single age group, tester, level, or type of injury differed from the overall result. CONCLUSION: In the pediatric population, the correlation between S4-5 and anorectal sensation was lower than anticipated. The sensitivity of 0.62 for S4-5 testing and diminished sensation between T10 and S3 suggests that anorectal testing may either be a more sensitive representation of S4-5 function or activate an alternative neuronal pathway that is perceived by the patient. Further investigation into the validity of the sacral sparing components of the ISNCSCI examination is warranted.

Patient and caregiver knowledge of severity of injury among youth with spinal cord injury.

DESIGN: Multicenter cross sectional study. OBJECTIVES: Describe patient and caregiver knowledge of severity of injury and examine the relationship between AIS status and patient/caregiver report. SETTING: United States METHODS: Participants were between 1 and 21 years of age with a stable spinal cord injury (SCI). Participants underwent ISCSCI exams and were interviewed with the following questions: 1. Did the patient/caregiver know the difference between complete and incomplete spinal cord injury before participation? 2. What level of injury does the patient/caregiver report? 3. What severity of injury does the patient/caregiver report? 4. If a severity is given, who told them and how was it tested? RESULTS: Overall, 16% of patients and 20% of caregivers knew the difference between complete and incomplete SCI. Older patients were more likely to know the difference and caregivers of patients with shorter durations of injury were more likely to know the difference. Those who reported a severity of injury different from their actual severity were more likely to have a complete spinal cord injury and a higher injury severity as measured by the AIS impairment scale. Only 18% of people who were able to report a severity of injury stated that an ISCSCI exam was how the doctor gave them the diagnosis. CONCLUSION: Many patients and caregivers do not understand the difference between complete and incomplete SCI. It is vital that an AIS diagnosis only be given following the ISCSCI exam based on agreed standards.

Patient and caregiver knowledge of autonomic dysreflexia among youth with spinal cord injury.

OBJECTIVES: To describe the prevalence and knowledge of autonomic dysreflexia (AD) from patient and caregiver perspectives, and its relationship to the American Spinal Injury Association (ASIA) Impairment Scale (AIS) classification, level of injury, severity of injury, injury etiology, gender and race. METHODS: Participants were between 1 and 21 years old. Demographic information was collected from the medical records, and patients and caregivers were interviewed with the following questions: (1) Does the patient experience AD? (2) Does the patient/caregiver know what AD is? (3) Can the patient/caregiver name three signs/symptoms of an AD episode? (4) Does the patient/caregiver know how to treat AD? RESULTS: Overall, 40% of patients and 44% of caregivers said that the patient was symptomatic for AD. AD was more common in those with traumatic etiologies, in patients with injuries at or above T6 and those with greater injury severity as measured by the AIS. For patients and caregivers, AD was less common in the youngest age group (0-5 years old). Patients with greater knowledge of AD were more likely to have traumatic etiologies, have T6 or higher injuries, be in the oldest age at injury group, be older at time of examination and have had a shorter duration of injury. CONCLUSIONS: AD seems to be more common in patients with traumatic injuries, older ages at injury, greater injury severity on the AIS and level of injury at or above T6.

Intra-rater agreement of the anorectal exam and classification of injury severity in children with spinal cord injury.

STUDY DESIGN: Intra-rater reliability study, cross-sectional design. OBJECTIVES: To report on the intra-rater agreement of the anorectal examinations and classification of injury severity in children with spinal cord injury (SCI). SETTING: Two, non-profit children's hospitals specializing in pediatric SCI. METHODS: 180 subjects had at least two trials of the anorectal examinations as defined by the International Standards for Neurological Classification of Spinal Cord Injury. Intraclass correlation coefficients (ICC) and 95% confidence intervals (CI) were used to evaluate the agreement. ICC>0.90=high agreement; ICC between 0.75-0.89=moderate agreement; ICC<0.75=poor agreement. RESULTS: When evaluated for the entire sample, agreement was moderate-high for anal sensation and contraction and injury classification. When evaluated as a function of age at examination and type of injury, agreement for anal sensation was poor for subjects with tetraplegia in the 12-15-year age group (ICC=0.56) and 16-21-year age group (ICC=0.70) and for subjects with paraplegia in the 6-11-year age group (ICC=0.69). Agreement for anal contraction was moderate for subjects with tetraplegia in the 16-21-year age group (ICC=0.81) and subjects with paraplegia in the 12-15-year age group (ICC=0.78) and poor for subjects with paraplegia in the 6-11-year age group (ICC=0.67). Agreement for injury classification was poor for subjects with tetraplegia in the 12-15-year group (ICC=0.56) and 16-21-year group (ICC=0.74) and paraplegia in the 6-11-year group (ICC=0.11) and 12-15-year group (ICC=0.63). Anorectal responses had high agreement in subjects with tetraplegia in the 6-11-year group and moderate to high agreement in subjects with paraplegia in the 16-21-year group. CONCLUSION: The data do not fully support the use of anorectal examination in children. Further work is warranted to establish the validity of anorectal examination.

Aberrant expression of neuropeptide Y in hippocampal mossy fibers in the absence of local cell injury following the onset of spike-wave synchronization.

Stargazer mutant mice inherit a recessive neuronal excitability phenotype featuring frequent non-convulsive spike-wave seizures that arise from synchronous bursting in neocortical, thalamic and hippocampal networks. Immunocytochemistry reveals that granule cells in the mutant dentate gyrus aberrantly express neuropeptide Y (NPY) at multiple ages following the developmental onset of seizures. The ectopic NPY is selectively concentrated in the mossy fibers, co-localizing with the releasable dense core vesicle pool. The NPY content of native NPY+local circuit neurons is also elevated in the mutant CNS. There is no concurrent elevation of hippocampal 72 kDa heat shock protein (HSP72), glial fibrillary acidic protein (GFAP) or NADPH-diaphorase, three markers that are induced during cellular injury, and no evidence of granule cell loss. Since mossy fiber NPY expression appears after the developmental onset of spike-wave discharges and can be induced in wild type granule cells by electrical stimulation, the altered peptide phenotype is likely to reflect transynaptic gene induction triggered by synchronous bursting. These results link a specific pattern of repetitive synaptic input with selective molecular plasticity in dentate granule cells that may contribute to dynamic modifications in hippocampal network excitability.

Ionization and adsorption of a series of local anesthetics in detergent micelles: studies of drug fluorescence.

The goal of this study was to compare the behavior of structurally homologous local anesthetics (LAs) adsorbed to a simplified membrane model. Interactions of LAs with micelles made from negative and neutral detergents were assayed by drug fluorescence. Micellar:drug affinity, equivalent dielectric constant and pKa of bound LAs were assessed for procaine, tetracaine, procainamide, benzocaine and aminoparabenzyldiethylamine, a procaine homologue containing an alkyl chain instead of an ester bond. Shifts in maximum emission wavelength and changes in fluorescence intensity showed that 1) increased LA hydrophobicity (expressed as octanol:buffer partition coefficient) corresponded to increased affinity for all micelles; 2) protonated species of LA were bound more tightly than neutral species to negative micelles, but less tightly to unchanged micelles; 3) drugs with larger dipole moments (amide < ester < alkyl) bind less tightly to micelles than those with smaller dipoles; 4) Larger dipole moments of LAs also result in a larger equivalent dielectric constant around the micellar-bound LAs, meaning that the LA binds at a shallower depth from the micelle surface; and 5) binding the neutral micelles lowers the pKa but binding to negatively charged micelles raises the pKa (due to the concentrating effects of surface charge on H+). The results provide a picture of interfacial adsorption of LAs in a relatively simple system that should allow interrelation of the dipole field contributions to LA behavior in phospholipid bilayers.

Fundamental properties of local anesthetics. II. Measured octanol:buffer partition coefficients and pKa values of clinically used drugs.

Because local anesthetic molecules interact with ion channel proteins embedded in membranes to effect impulse blockade, and because their clinical potency often depends on both vascular absorption and distribution into the tissue surrounding the site of deposition, the ability to partition into these various compartments is an important determinant of local anesthetic action. Therefore, the hydrophobic nature of local anesthetics used clinically was characterized by the octanol:buffer partition coefficients of their charged (P+) and neutral (Po) species. This was accomplished by previously described optical methods in which direct spectrophotometric measurement of both the pH-dependent distribution coefficient (Q) and of the ionization permit calculation of the pKa and partition coefficients. The rates of alkaline hydrolysis of ester-linked molecules also were measured to assess potential interference of such hydrolysis with the physicochemical assays. Results indicate that the hydrophobicity of a local anesthetic is increased by manipulation of the molecular structure at three sites: (a) the aromatic ring; (b) the intermediate linking group; and (c) the tertiary amine. Po for the agents studied was 10(3)-10(5) times greater than P+. Although there is no systematic relationship between hydrophobicity and pKa, the latter is greater with ester-linked (pKa = 8.59-9.30) than with amide-linked (pKa = 7.92-8.21) local anesthetics. All of the charged species, with the exception of bupivacaine, selectively partition into the aqueous environment (P+ less than 1.0). The temperature dependence of partitioning of the local anesthetics, measured at 25 and 36 degrees C, indicates an entropy-driven hydrophobic uptake. Solutions buffered with bicarbonate and including 5% CO2 showed the same local anesthetic partitioning as that of CO2-free solutions, suggesting that potentiation of impulse blockade by CO2 is not due to increased membrane uptake. Correlations of physicochemical properties of local anesthetics with potencies on isolated nerve confirm that the more potent local anesthetics have greater octanol:buffer partition coefficients, and that the ester-linked local anesthetics are more potent than their amide-linked counterparts having the same hydrophobicities. The correlations of structure with potency also suggest that the extracellular protonated species may contribute to impulse blockade.