Efavirenz as a cause of ataxia in children.

Acute ataxia in childhood is often caused by toxin ingestion. With the increasing number of paediatric patients on antiretroviral medication, we observe more side-effects of these drugs. Acute ataxia is defined as unsteadiness of walking or fine motor movement of <72 hours. The most common causes are postinfectious acute cerebellar ataxia, toxin ingestion and Guillain-Barré syndrome. However, the possibility of a mass lesion must always be excluded. Reported neurological abnormalities in HIV-positive children range from 10% to 68%. A South African study found the prevalence of neurological complications to be 59%, the most common of which were HIV encephalopathy and long-tract motor signs; however, no cases of cerebellar dysfunction were documented. Ataxia rarely occurs in an HIV-positive person, the chronic sequelae being neurocognitive impairment and polyneuropathy. Ataxia in the setting of HIV is generally secondary to an infectious, vascular or neoplastic cerebellar lesion. However, most infections are opportunistic and unlikely to occur when CD4 levels are adequate. The vascular or mass lesions are readily excluded with neuro-imaging. We report 2 cases of efavirenz toxicity that caused ataxia. We treated 2 children who presented in a 1-month period, which highlighted an important differential to consider in HIV-positive paediatric patients presenting with ataxia.

Severe crouch gait in spastic diplegia can be prevented: a population-based study.

We studied the prevalence of severe crouch gait over a 15-year period in a defined population of children with spastic diplegia and Gross Motor Function Classification System levels II and III, to determine if there had been a decrease following changes to the management of equinus gait. These changes were replacing observational with three-dimensional gait analysis, replacing single level with multilevel surgery, and replacing gastrocsoleus lengthening with gastrocnemius recession. Of 464 children and adolescents with spastic diplegia who underwent three-dimensional gait analysis, 27 had severe crouch gait. Seventeen of these had been managed by isolated lengthening of the gastrocsoleus. Following changes in the management of equinus gait, the prevalence of severe crouch gait decreased from 25% and stabilised at a significantly lower rate, fluctuating between 0% and 4% annually (p < 0.001). We conclude that severe crouch gait in this population was precipitated by isolated lengthening of the gastrocsoleus. These findings may be relevant to other surgical populations, as severe crouch gait may be a useful way to monitor the quality of the surgical management of abnormal gait in children with cerebral palsy and spastic diplegia.

Subjective cognitive impairment: functional MRI during a divided attention task.

BACKGROUND: Individuals with subjective cognitive impairment (SCI) have persistent memory complaints but normal neurocognitive performance. For some, this may represent a pre-mild cognitive impairment (MCI) stage of Alzheimer's disease (AD). Given that attentional deficits and associated brain activation changes are present early in the course of AD, we aimed to determine whether SCI is associated with brain activation changes during attentional processing. METHODS: Eleven SCI subjects and 10 controls completed a divided attention task during functional magnetic resonance imaging. RESULTS: SCI and control groups did not differ in sociodemographic, neurocognitive or behavioural measures. When group activation during the divided attention task was compared, the SCI group demonstrated increased activation in left medial temporal lobe, bilateral thalamus, posterior cingulate and caudate. CONCLUSION: This pattern of increased activation is similar to the pattern of decreased activation reported during divided attention in AD and may indicate compensatory changes. These findings suggest the presence of early functional changes in SCI; longitudinal studies will help to further elucidate the relationship between SCI and AD.

(11)C-PIB PET in subjective cognitive impairment.

People with Subjective Cognitive Impairment (SCI) may be at increased risk of dementia. In this study we examined amyloid load in 5 SCI subjects and 14 controls using PIB PET scanning. One SCI subject had significantly increased PIB retention in the cortical areas of interest. Larger, longitudinal studies are indicated.

The molecular basis of spinal muscular atrophy (SMA) in South African black patients.

SMA is an autosomal recessive disorder that results in symmetrical muscle weakness and wasting due to degeneration of the anterior horns of the spinal cord. The gene for SMA, the survival motor neuron (SMN) gene is found on chromosome 5q13, in a region harbouring a 500kb duplication, resulting in two copies (a telomeric and a centromeric) of each of the genes found within the duplication. SMN1 is homozygously deleted in approximately 95% of patients worldwide. Results of the current study show that only 51% (42/92) of South African black SMA patients have homozygous deletions of the SMN1 gene. This frequency is significantly lower than observed in the South African white patient group and in other international populations. The pattern of deletions in the South African black patients is also significantly different. In order to elucidate the molecular basis of SMA in the black population, a dosage assay enabling the detection of SMN1 deletion heterozygotes was independently developed. This assay confirmed SMN1 heterozygosity in at least 70% of black non-deletion SMA patients. However, no second disease-causing mutation or a common chromosomal background for this mutation could be identified in these patients. The frequency of SMA in both the black and white population was also determined using the SMN1 gene dosage assay. Results showed that SMA is more common than previously thought with carrier rates of 1 in 50 and 1 in 23 and a predicted birth incidence of 1 in 3574 and 1 in 1945 in the black population and the white population, respectively. Development and incorporation of the SMN1 dosage assay into the molecular diagnostic service will increase the percentage of cases in which the diagnosis of SMA can be confirmed and allow preclinical and prenatal diagnosis. Further gene characterisation and functional studies would need to be performed in order to further define the molecular basis of SMA in the South African black population.

Correction of severe crouch gait in patients with spastic diplegia with use of multilevel orthopaedic surgery.

BACKGROUND: Severe crouch gait in patients with spastic diplegia causes excessive loading of the patellofemoral joint and may result in anterior knee pain, gait deterioration, and progressive loss of function. Multilevel orthopaedic surgery has been used to correct severe crouch gait, but no cohort studies or long-term results have been reported, to our knowledge. METHODS: In order to be eligible for the present retrospective cohort study, a patient had to have a severe crouch gait, as defined by sagittal plane kinematic data, that had been treated with multilevel orthopaedic surgery as well as a complete clinical, radiographic, and instrumented gait analysis assessment. The surgical intervention consisted of lengthening of contracted muscle-tendon units and correction of osseous deformities, followed by the use of ground-reaction ankle-foot orthoses until stable biomechanical realignment of the lower limbs during gait was achieved. Outcome at one and five years after surgery was determined with use of selected sagittal plane kinematic and kinetic parameters and valid and reliable scales of functional mobility. Knee pain was recorded with use of a Likert scale, and all patients had radiographic examination of the knees. RESULTS: Ten subjects with severe crouch gait and a mean age of 12.0 years at the time of surgery were studied. After surgery, the patients walked in a more extended posture, with increased extension at the hip and knee and reduced dorsiflexion at the ankle. Pelvic tilt increased, and normalized walking speed was unaltered. Knee pain was diminished, and patellar fractures and avulsion injuries healed. Improvements in functional mobility were found, and, at the time of the five-year follow-up, fewer patients required the use of wheelchairs or crutches in the community than had been the case prior to intervention. CONCLUSIONS: Multilevel orthopaedic surgery for older children and adolescents with severe crouch gait is effective for relieving stress on the knee extensor mechanism, reducing knee pain, and improving function and independence.

Cardiac tamponade presenting to the emergency department after sternal wire disruption.

An unusual case of cardiac tamponade presenting to the emergency department is reported in a patient with sternal wire disruption after a pectus excavatum repair two years previously. The complication, although rare may have potentially life threatening sequelae and therefore consideration of sternal wire disruption in all patients presenting with chest pain after a previous sternotomy should be made.

Sagittal gait patterns in spastic diplegia.

Classifications of gait patterns in spastic diplegia have been either qualitative, based on clinical recognition, or quantitative, based on cluster analysis of kinematic data. Qualitative classifications have been much more widely used but concerns have been raised about the validity of classifications, which are not based on quantitative data. We have carried out a cross-sectional study of 187 children with spastic diplegia who attended our gait laboratory and devised a simple classification of sagittal gait patterns based on a combination of pattern recognition and kinematic data. We then studied the evolution of gait patterns in a longitudinal study of 34 children who were followed for more than one year and demonstrated the reliability of our classification.

Walking speed in children and young adults with neuromuscular disease: comparison between two assessment methods.

Self-selected walking speed is being increasingly used as a primary outcome measure in the management of neuromuscular disease. It would be useful if the speed recorded in the gait laboratory represented the child's walking speed in the community. This study investigated the difference in self-selected walking speeds between a 10-meter walk, as measured during instrumented gait analysis, and a 10-minute walk. The authors found that self-selected walking speed during the 10-minute walk was slower than the self-selected walking speed recorded during the 10-meter walk. The former may be more representative of walking speed in the community setting. Walking speed measured during walks of 10 minutes or more should become an integral part of gait laboratory evaluation.

Femoral derotation osteotomy in spastic diplegia. Proximal or distal?

We describe the results of a prospective study of 28 children with spastic diplegia and in-toed gait, who had bilateral femoral derotation osteotomies undertaken at either the proximal intertrochanteric or the distal supracondylar level of the femur. Preoperative clinical evaluation and three-dimensional movement analysis determined any additional soft-tissue surgery. Distal osteotomy was faster with significantly lower blood loss than proximal osteotomy. The children in the distal group achieved independent walking earlier than those in the proximal group (6.9 +/- 1.3 v 10.7 +/- 1.7 weeks; p < 0.001). Transverse plane kinematics demonstrated clinically significant improvements in rotation of the hip and the foot progression angle in both groups. Correction of rotation of the hip was from 17 +/- 11 degrees internal to 3 +/- 9.5 degrees external in the proximal group and from 9 +/- 14 degrees internal to 4 +/- 12.4 degrees external in the distal group. Correction of the foot progression angle was from a mean of 10.0 +/- 17.3 degrees internal to 13.0 +/- 11.8 degrees external in the proximal group (p < 0.001) compared with a mean of 7.0 +/- 19.4 degrees internal to 10.0 +/- 12.2 degrees external in the distal group (p < 0.001). Femoral derotation osteotomy at both levels gives comparable excellent correction of rotation of the hip and foot progression angles in children with spastic diplegia.

Classification of gait patterns in spastic hemiplegia and spastic diplegia: a basis for a management algorithm.

Classifications of gait and postural patterns in spastic hemiplegia and spastic diplegiía are presented, based on the work of previous authors. The classifications are used as a biomechanical basis, linking spasticity, musculoskeletal pathology in the lower limbs, and the appropriate intervention strategies. The choice of target muscles for spasticity management, the muscle contractures requiring lengthening and the choice of orthotics are then linked to the underlying gait pattern.

Corticotropin-releasing factor increases in vitro firing rates of serotonergic neurons in the rat dorsal raphe nucleus: evidence for activation of a topographically organized mesolimbocortical serotonergic system.

In vivo studies suggest that the stress-related neuropeptide corticotropin-releasing factor (CRF) modulates serotonergic neurotransmission. To investigate the underlying mechanisms for this interaction, the present study examined the effects of CRF in vitro on dorsal raphe neurons that displayed electrophysiological and pharmacological properties consistent with a serotonergic phenotype. In the presence of either 1 or 2 mm Ca(2+), perfusion of ovine CRF or rat/human CRF rapidly and reversibly increased firing rates of a subpopulation (19 of 70, 27%) of serotonergic neurons predominantly located in the ventral portion of the dorsal raphe nucleus. For a given responsive neuron, the excitatory effects of CRF were reproducible, and there was no tachyphylaxis. Excitatory effects were dose-dependent (over the range of 0.1-1.6 micrometer) and were completely absent after exposure to the competitive CRF receptor antagonists alpha-helical CRF(9-41) or rat/human [d-Phe(12), Nle(21, 38), alpha-Me-Leu(37)]-CRF(12-41). Both the proportion of responsive neurons and the magnitude of excitatory responses to CRF in the ventral portion of the caudal dorsal raphe nucleus were markedly potentiated in slices prepared from animals previously exposed to isolation and daily restraint stress for 5 d. Immunohistochemical staining of the recorded slices revealed close associations between CRF-immunoreactive varicose axons and tryptophan hydroxylase-immunoreactive neurons in the area of the recordings, providing anatomical evidence for potential direct actions of CRF on serotonergic neurons. The electrophysiological properties and the distribution of responsive neurons within the dorsal raphe nucleus are consistent with the hypothesis that endogenous CRF activates a topographically organized mesolimbocortical serotonergic system.

Examination of intrafascicular muscle fiber terminations: implications for tension delivery in series-fibered muscles.

Mammalian skeletal muscles with long fascicle lengths are predominantly composed of short muscle fibers that terminate midbelly with no direct connection to the muscle origin or insertion. The manner in which these short fibers terminate and transmit tension through the muscle to their tendons is poorly understood. We made an extensive morphological study of a series-fibered muscle, the guinea pig sternomastoid, in order to define the full range of structural specializations for tension transmission from short fibers within this muscle. Terminations were examined in single fibers, teased small bundles of fibers, and in sections at both the light and electron microscopic level. In many cases, sites of fiber termination were defined by reactivity for the enzyme acetylcholinesterase, which also marks myotendinous junctions. Additionally, transport of the lipophilic fluorescent dye, DiI, or injection of Lucifer Yellow were used to visualize undisturbed fiber terminations in whole muscles using confocal and fluorescence microscopy. At the light microscopic level, we find that intrafascicularly terminating fibers end about equally often in either a long progressive taper, or in a series of small or larger blunt steps. Combinations of these two morphologies are also seen. However, when analyzed at higher resolution with confocal or electron microscopy, the apparently smooth progressive tapers appear also to be predominantly composed of a series of fine stepped terminations. Stepwise terminations in most cases join face-to-face with complementary endings of neighboring muscle fibers, some via an extended collagenous bridge and others at close interdigitating myomyonal junctions. These muscle-to-muscle junctions show many of the features of myotendinous junctions, including dense subsarcolemmal plaques in regions of myofibrillar termination and we suggest that they serve to pass tension from fiber to fiber along the longitudinal axis of the muscle. In addition, we observe regions of apparent side-to-side adhesion between neighboring fibers at sites where there is no apparent fiber tapering or structural specialization typical of myofibril termination. These sites show acetylcholinesterase reactivity, and large numbers of collagen fibers passing laterally from fiber to fiber. These latter connections seem most likely to be involved in lateral transmission of tension, either from fiber to fiber, or from fiber to endomysium. Overall, our results suggest that tension from intrafascicularly terminating fibers is likely to be passed along the muscle to the tendon using both in-series and in-parallel arrangements. The results are discussed in light of current theories of tension delivery within the series-fibered muscles typical of large, nonprimate mammals.

The clinical and genetic characteristics of spinocerebellar ataxia type 7 (SCA 7) in three Black South African families.

OBJECTIVES: Spinocerebellar ataxia type 7 is a rare autosomal dominant neurodegenerative disorder characterized by progressive cerebellar and retinal degeneration, described in various population groups in the literature. This is the first description from South Africa. The objective was to document the clinical and genetic characteristics of our patients and to determine concordance with other described cases. PATIENTS AND METHODS: The index cases were identified clinically on the basis of the typically described features of progressive ataxia with visual failure due to progressive cerebellar and retinal/macular degeneration. Associated neurological disturbances were documented. Where possible, and available, family members were assessed and pedigrees were delineated. Molecular tests for SCA expansions were determined in the index cases. RESULTS: Three pedigrees of SCA 7 were identified. The patients were all Black South Africans. The genetic and clinical characteristics are typical for SCA 7. CONCLUSION: SCA 7 is a rare distinct neurodegenerative disorder characterized by trinucleotide expansion.

High- or low- technology measurements of energy expenditure in clinical gait analysis?

The repeatability of energy-expenditure measurements were studied in five children and four adults without disabilities using the Cosmed K4 (high technology). The ability to detect change in measurements was compared between this instrument and the Physiological Cost Index (PCI; low technology). The results of repeatability (95% range) for oxygen cost were 13.1% in children and 13% in adults. In contrast, the SD of PCI was 6 to 72% of the mean in adults and wider in children (91%; 95% range). The validity of PCI as an outcome measure was questioned. In addition, 177 children with motor disability were prospectively studied using the Cosmed K4. Previous experience with the Cosmed K2 (intermediate technology) helped to develop a practical and repeatable protocol for testing children with disability using the Cosmed K4. The protocol commenced with 5 minutes of rest to achieve baseline values of heart rate and oxygen consumption, followed by 10 minutes of continuous walking at a self-selected speed on a 10-metre level oval walking track. The test concluded with 5 minutes of rest to monitor the return to baseline values. Ninety-one percent of the children with disability quickly reached a steady-state of oxygen consumption and carbon-dioxide production. The carbon-dioxide sensor in the Cosmed K4 has enabled a new group of severely involved children with cerebral palsy (9%) to be defined. These children have been termed 'physiologically marginal ambulators'.

Different molecular basis for spinal muscular atrophy in South African black patients.

Spinal muscular atrophy (SMA) is an autosomal recessive disorder occurring at a rate of between 1/5,000 and 1/10,000 births in most European countries. The phenotype results from the degeneration of the anterior horn cells of the spinal cord, resulting in symmetrical muscle weakness and wasting. The disorder can be classified according to the severity of the disease and the age of onset into three major types. Two candidate SMA genes, NAIP and SMN, isolated from the 5q13 region, have been reported to be homozygously deleted in approximately 30% and >95% of SMA patients, respectively. Black SMA patients have been reported to have facial muscle weakness more commonly. This study aimed to determine the molecular basis of SMA in South African black SMA patients. The SMN gene was found to be homozygously deleted in 65.5% (19/29) of patients, significantly less frequently than in previous studies. Similarly, the NAIP gene was homozygously deleted in a smaller number, 14% (4/29) of patients; 47% (9/19) of SMN deletion patients appeared to have deletions of telomeric exon 7, but not exon 8. In at least six of these patients a gene conversion event has occurred. No detectable deletions were found in 35% (10/29) of patients. Haplotype analysis in the nondeletion patients, using six closely linked markers, provided no evidence for a founder mutation. No mutations were found in exons 3 and intron 6 through exon 8 by sequence analysis of these nondeletion patients. It is proposed that the differences in the SMA phenotype observed in black patients may in part be explained by a different molecular basis.

Barodontalgia: a review, and the influence of simulated diving on microleakage and on the retention of full cast crowns.

This paper reviews the causes of barodontalgia and reports on a study that indicates a possible cause of barodontalgia in the diver. In the study, extracted teeth had full cast crowns cemented with either a zinc phosphate, a glass ionomer, or a resin cement, and simulated diving to 30 m (3.0 atmospheres) was performed. During simulated diving, the teeth were pressure cycled 15 times to 3 atmospheres and microleakage was monitored. The force required to dislodge the crown was then tested; a significant difference was found between the zinc phosphate and the glass ionomer cement groups (p < 0.01). No difference was found between the resin cement groups. Microleakage was also detected in the zinc phosphate and glass ionomer cement groups and was found to occur sooner, and to a greater extent with zinc phosphate. No microleakage was detected in the resin cement experimental group. This study showed that the retention of full cast crowns to extracted teeth is reduced after pressure cycling and that microleakage does occur if the crowns are cemented with either zinc phosphate cement or glass ionomer cement.

The effect of environmental pressure changes during diving on the retentive strength of different luting agents for full cast crowns.

STATEMENT OF PROBLEM: The effect of pressure cycling on the bond strength of cement luting agents is largely unknown. PURPOSE: This study investigated the effect of pressure cycling on the retention of full cast crowns to extracted teeth. MATERIAL AND METHODS: Sixty extracted single-rooted premolar teeth had full cast crowns cemented, 20 with a zinc phosphate cement, 20 with a glass ionomer, and 20 with a resin cement. After 7 days of storage, each of the teeth in the experimental groups was pressure cycled 15 times from 0 to 3 atmospheres (304 KPa), after which the force required to dislodge the crowns was tested in an Instron testing machine. RESULTS: A significant difference was found (Students t test; p > 0.01) between the force required to remove the crowns in the zinc phosphate control (142.10 +/- 36.42 N) and experimental (15.93 +/- 11.13 N) groups and the glass ionomer cemented control (186.33 +/- 24.33 N) and experimental (91.50 +/- 33.07 N) groups; no difference was found between the resin cemented control (291.15 +/- 78.48 N) and experimental (281.32 +/- 85.43 N) groups. CONCLUSION: This study showed that the retention of full cast crowns to extracted teeth is reduced after pressure cycling if the crowns are cemented with either zinc phosphate cement or glass ionomer cement. Dentists should consider using a resin cement when cementing crowns and fixed partial dentures for patients, such as divers, who are likely to be exposed to pressure cycling.