Long-term follow-up in diabetic Charcot feet with spontaneous onset. (1/731)

OBJECTIVE: To assess the long-term results after Charcot breakdown with spontaneous onset in diabetic feet. RESEARCH DESIGN AND METHODS: This study was retrospective. A total of 115 patients (140 feet), 107 with acute deformity and 8 with chronic Charcot deformity, were followed for a median of 48 months (range 6-114). The routine treatment for acute cases was a weight-off regimen with crutches and foot protection with therapeutic shoes until skin temperature had normalized followed by increased weightbearing and the use of bespoke shoes or modification of conventional shoes. RESULTS: The incidence of Charcot deformity was 0.3%/year in the diabetic population investigated. About half of the patients were active in their jobs. Major complications were encountered in 5 (4%) of the patients that required surgical intervention: arthrodesis for unstable malaligned ankles in 3 subjects (1 bilaterally) and major amputation in 2 subjects for unstable ankle and pressure sores. Minor complications were recorded in 43% of subjects: new attacks of Charcot breakdown in 41 patients (36%) and/or foot ulceration in 43 patients (37%) that required minor surgical procedures for 11 patients. All healed except in 2 patients: 1 patient died before the Charcot fractures had healed, and 1 patient died with an unhealed ulcer. No patient lost the ability to walk independently. CONCLUSIONS: Major surgical procedures in only 4% were particularly related to patients with Charcot deformities in the ankle. Minor complications were recorded in about half of the patients. Lifelong foot care is required for diabetic patients with Charcot feet.  (+info)

Conventional physiotherapy and treadmill re-training for higher-level gait disorders in cerebrovascular disease. (2/731)

OBJECTIVES: to compare the therapeutic effects of two approaches to gait re-training--a schedule of conventional physiotherapy and treadmill re-training--in patients with higher-level gait disorders associated with cerebral multiinfarct states. DESIGN: single-blind crossover study involving a 4-week baseline period, 4 weeks of treadmill re-training and 4 weeks of conventional physiotherapy. SETTING: a large teaching hospital. SUBJECTS: patients with cerebral multi-infarct states who met the criteria for higher-level gait disorders. Computed tomographic brain scans showed at least one large vessel infarct, basal ganglia and white matter lacunes or extensive leukoaraiosis. INTERVENTIONS: a schedule of treadmill re-training and a specific schedule of physiotherapy containing 31 interventions in three treatment modules: (i) for gait ignition failure and turning; (ii) to improve postural alignment and enhance balance reactions; and (iii) for other components of cerebral multi-infarct state disordered gait. MAIN OUTCOME MEASURES: spatial and temporal gait measures and activity of daily living assessments. RESULTS: we recruited 18 patients, mean (SD) age 79.1 (6.8) years. Patients walked an average of 7.9 (5.5) km on the treadmill and had an average of 6.7 (3.2) h of physiotherapy. There were clinically moderate but highly statistically significant (P < 0.001) improvements in the following indices: time taken to complete the sit-to-stand test; time taken to walk 10 m; number of steps over 10 m; walking velocity; right and left step lengths; and time taken to complete the 'S' test. There were no differences in the results obtained in each limb of the study. CONCLUSION: there is no difference between the effects of conventional physiotherapy and treadmill re-training on the gait of patients with higher-level gait disorders associated with cerebral multi-infarct states. However, the improvements seen during the treatment period suggest that there is scope to improve the gait of this group of frail, elderly patients.  (+info)

Abnormal GABAA receptor-mediated currents in dorsal root ganglion neurons isolated from Na-K-2Cl cotransporter null mice. (3/731)

We have recently disrupted Slc12a2, the gene encoding the secretory Na-K-2Cl cotransporter in mice (NKCC1) (Delpire et al., 1999). Gramicidin perforated-patch and whole-cell recordings were performed to study GABA-induced currents in dorsal root ganglion (DRG) neurons isolated from wild-type and homozygote NKCC1 knock-out mice. In wild-type DRG neurons, strong GABA-evoked inward current was observed at the resting membrane potential, suggesting active accumulation of Cl(-) in these cells. This GABA-induced current was blocked by picrotoxin, a GABA(A) receptor blocker. The strong Cl(-) accumulation that gives rise to depolarizing GABA responses is caused by Na-K-2Cl cotransport because reduction of external Cl(-) or application of bumetanide induced a decrease in [Cl(-)](i), whereas an increase in external K(+) caused an apparent [Cl(-)](i) accumulation. In contrast to control neurons, little or no net current was observed at the resting membrane potential in homozygote NKCC1 mutant DRG neurons. E(GABA) was significantly more negative, demonstrating the absence of Cl(-) accumulation in these cells. Application of bumetanide induced a positive shift of E(GABA), suggesting the presence of an outward Cl(-) transport mechanism. In agreement with an absence of GABA depolarization in DRG neurons, behavioral analysis revealed significant alterations in locomotion and pain perception in the knock-out mouse. Our results clearly demonstrate that the Na-K-2Cl cotransporter is responsible for [Cl(-)](i) accumulation in DRG neurons and that via regulation of intracellular Cl(-), the Na-K-2Cl cotransporter participates in the modulation of GABA neurotransmission and sensory perception.  (+info)

Dopamine D2 long receptor-deficient mice display alterations in striatum-dependent functions. (4/731)

The dopamine D2 receptor (D2) system has been implicated in several neurological and psychiatric disorders, such as schizophrenia and Parkinson's disease. There are two isoforms of the D2 receptor: the long form (D2L) and the short form (D2S). The two isoforms are generated by alternative splicing of the same gene and differ only by 29 amino acids in their protein structures. Little is known about the distinct functions of either D2 isoform, primarily because selective pharmacological agents are not available. We generated D2L receptor-deficient (D2L-/-) mice by making a subtle mutation in the D2 gene. D2L-/- mice (which still express functional D2S) displayed reduced levels of locomotion and rearing behavior. Interestingly, haloperidol produced significantly less catalepsy and inhibition of locomotor activity in D2L-/- mice. These findings suggest that D2L and D2S may contribute differentially to the regulation of certain motor functions and to the induction of the extrapyramidal side effects associated with the use of typical antipsychotic drugs (e.g., haloperidol). Quinpirole induced a similar initial suppression of locomotor activity in both D2L-/- and wild-type mice. In addition, the D2S receptor in the mutant mice functioned approximately equally well as did D2L as an impulse-modulating autoreceptor. This suggests that the functions of these two isoforms are not dependent on the formation of receptor heterodimers. Our findings may provide novel information for potentially developing improved antipsychotic drugs.  (+info)

Coordination of the bladder detrusor and the external urethral sphincter in a rat model of spinal cord injury: effect of injury severity. (5/731)

Recovery of urinary tract function after spinal cord injury (SCI) is important in its own right and may also serve as a model for studying mechanisms of functional recovery after injury in the CNS. Normal micturition requires coordinated activation of smooth muscle of the bladder (detrusor) and striated muscle of the external urethral sphincter (EUS) that is controlled by spinal and supraspinal circuitry. We used a clinically relevant rat model of thoracic spinal cord contusion injury to examine the effect of varying the degree of residual supraspinal connections on chronic detrusor-EUS coordination. Urodynamic evaluation at 8 weeks after SCI showed that detrusor contractions of the bladder recovered similarly in groups of rats injured with a 10 gm weight dropped 12.5, 25, or 50 mm onto the spinal cord. In contrast, the degree of coordinated activation of the EUS varied with the severity of initial injury and the degree of preservation of white matter at the injury site. The 12.5 mm SCI resulted in the sparing of 20% of the white matter at the injury site and complete recovery of detrusor-EUS coordination. In more severely injured rats, the chronic recovery of detrusor-EUS coordination was very incomplete and correlated to decreased innervation of lower motoneurons by descending control pathways and their increased levels of mRNA for glutamate receptor subunits NR2A and GluR2. These results show that the extent of recovery of detrusor-EUS coordination depends on injury severity and the degree of residual connections with brainstem control centers.  (+info)

Comparative analysis of the gait disorder of normal pressure hydrocephalus and Parkinson's disease. (6/731)

OBJECTIVES: Comparative gait analyses in neurological diseases interfering with locomotion are of particular interest, as many hypokinetic gait disorders have the same main features. The aim of the present study was (1) to compare the gait disturbance in normal pressure hydrocephalus and Parkinson's disease; (2) to evaluate which variables of the disturbed gait pattern respond to specific treatment in both diseases; and (3) to assess the responsiveness to visual and acoustic cues for gait improvement. METHODS: In study 1 gait analysis was carried out on 11 patients with normal pressure hydrocephalus, 10 patients with Parkinson's disease, and 12 age matched healthy control subjects, on a walkway and on a treadmill. In study 2, patients with normal pressure hydrocephalus were reinvestigated after removal of 30 ml CSF, and patients with Parkinson's disease after administration of 150 mg levodopa. In part 3 visual cues were provided as stripes fixed on the walkway and acoustic cues as beats of a metronome. RESULTS: The gait disorder in both diseases shared the feature of a reduced gait velocity, due to a diminished and highly variable stride length. Specific features of the gait disturbance in normal pressure hydrocephalus were a broad based gait pattern with outward rotated feet and a diminished height of the steps. After treatment in both diseases, the speed increased, due to an enlarged stride length, now presenting a lower variability. All other gait variables remained unaffected. External cues only mildly improved gait in normal pressure hydrocephalus, whereas they were highly effective in raising the stride length and cadence in Parkinson's disease. CONCLUSION: The gait pattern in normal pressure hydrocephalus is clearly distinguishable from the gait of Parkinson's disease. As well as the basal ganglia output connections, other pathways and structures most likely in the frontal lobes are responsible for the gait pattern and especially the disturbed dynamic equilibrium in normal pressure hydrocephalus. Hypokinesia and its responsiveness to external cues in both diseases are assumed to be an expression of a disturbed motor planning.  (+info)

Forward signaling mediated by ephrin-B3 prevents contralateral corticospinal axons from recrossing the spinal cord midline. (7/731)

To investigate Eph-ephrin bidirectional signaling, a series of mutations were generated in the ephrin-B3 locus. The absence of both forward and reverse signaling resulted in mice with mirror movements as typified by a hopping locomotion. The corticospinal tract was defective as axons failed to respect the midline boundary of the spinal cord and bilaterally innervated both contralateral and ipsilateral motor neuron populations. A second mutation that expresses a truncated ephrin-B3 protein lacking its cytoplasmic domain did not lead to hopping, indicating that reverse signaling is not required for corticospinal innervation. Ephrin-B3 is concentrated at the spinal cord midline, while one of its receptors, EphA4, is expressed in postnatal corticospinal neurons as their fibers pathfind down the contralateral spinal cord. Our data indicate ephrin-B3 functions as a midline-anchored repellent to stimulate forward signaling in EphA4-expressing axons.  (+info)

Modified emory functional ambulation profile: an outcome measure for the rehabilitation of poststroke gait dysfunction. (8/731)

BACKGROUND AND PURPOSE: The modified Emory Functional Ambulation Profile (mEFAP) is an easily administered test that measures the time to ambulate through 5 common environmental terrains with or without an assistive device or manual assistance. The mEFAP was evaluated for its interrater reliability, test-retest reliability, concurrent validity, and sensitivity to change during outpatient rehabilitation for poststroke gait dysfunction. METHODS: Twenty-six poststroke patients were followed up prospectively in a rehabilitation day-treatment program. The mEFAP, Berg Balance Test (BBT), and 7-item mobility subsection of the Functional Independence Measure + Functional Assessment Measure (FAMm) were completed at admission and discharge. RESULTS: mEFAP interrater reliability (intraclass coefficient [ICC] 0.999) and test-retest reliability (ICC 0.998) were high. The BBT demonstrated high interrater (ICC 0.992) but poor test-retest (ICC 0.605) reliability. Initial and final scores comparing the mEFAP with the BBT (r=-0.735, r=-0.703) and the mEFAP with the FAMm (r=0.685, r=-0.775) were strongly correlated. Improvement on the mEFAP correlated with improved BBT performance (r=-0.524). There was no correlation between overall change observed on the FAMm and change on the mEFAP (r=-0.145). Total mEFAP and all mEFAP subtask scores improved over time (P:<0.0001). CONCLUSIONS: The mEFAP is a reliable gait-assessment tool for patients with stroke and is sensitive to change in ambulation speed.  (+info)