Cerebral Palsy

Aim? Children and adolescents highly value their ability to participate in relevant daily life and recreational activities. The Activities Scale for Kids-performance (ASKp) instrument measures the frequency of performance of 30 common childhood activities, and has been shown to be valid and reliable. A revised and expanded 38-item ASKp (ASKp38) version has been reported in recent literature and is currently used in clinical research. The aim of this paper is to assess the factor structure and item-level statistics of the ASKp38. Method? Our study used factor analyses and Rasch analyses to determine the item-set dimensionality and to calculate item-level statistics respectively, for existing ASKp38 data from 200 children (104 males; 96 females; mean age 12y 7mo; SD 2y 8mo; range 6-20y) with physical disabilities. The children had a variety of physical impairments including cerebral palsy (n=105; range 8-13y), limb salvage (n=18; range 11-20y), arthrogryposis (n=13; 6-17y), and other, including individuals with spina bifida and spinal cord injury (n=64; 8-19y). Results? A two-factor model, with components of activities of daily living and play, most optimally fit the data. Item-fit statistics based on this two-factor model demonstrated adequate fit and content coverage. Interpretation? The ASKp38 appears to consist of two factors, defined as (1) activities of daily living and (2) play, and may be used to measure the frequency of activity performance on two corresponding subscales.

© The Authors. Journal compilation © Mac Keith Press 2010.

Brain damage through excitotoxic mechanisms is a major cause of cerebral palsy in infants. This phenomenon usually occurs during the fetal period in human,and often leads to lifelong neurological morbidity with cognitive and sensorimotor impairment. However, there is currently no effective therapy. Significant recovery of brain function through neural stem cell implantation has been shown in several animal models of brain damage, but remains to be investigated in detail in neonates. In the present study, we evaluated the effect of cell therapy in a well-established neonatal mouse model of cerebral palsy induced by excitotoxicity (ibotenate treatment on postnatal day 5). Neurosphere-derived precursors (NDPs) or control cells (fibroblasts) were implanted into injured and control brains contralateral to the site of injury, and the fate of implanted cells was monitored by immunohistochemistry. Behavioral tests were performed in animals that received early (4 hrs after injury) or late (72 hrs after injury) cell implants. We show that NDPs implanted into the injured brains of 5 day-old pups migrated to the lesion site remained undifferentiated at day 10, differentiated into oligodendrocyte and neurons at day 42. Although grafted cells finally die there few weeks later, this procedure triggered a reduction in lesion size and an improvement in memory performance compared to untreated animals, both 2 weeks and 5 weeks after treatment. While further studies are warranted, cell therapy could be a future therapeutic strategy for neonates with acute excitotoxic brain injury.

Aim? Gastrostomy feeding children with spastic quadriplegic cerebral palsy (SQCP) improves weight gain but may cause excess deposition of body fat. This study was designed to investigate whether weight gain could be achieved without an adverse effect on body composition by using a low-energy feed in gastrostomy-fed children with SQCP. Method? Fourteen children (seven male; seven female; median age 2y; range 10mo-11y) with SQCP were studied, 13 of whom were classified as Gross Motor Function Classification Score (GMFCS) level V and one as GMFCS level IV. Children were eligible for the study if they weighed between 8 and 30kg with a diagnosis of severe SQCP and significant feeding difficulties in whom a clinical decision had been made to insert a gastrostomy feeding tube. The feed used in the study had an energy concentration of 0.75kcal/mL (Nutrini Low Energy Multi Fibre). Assessments were performed before gastrostomy insertion (baseline) and after 6?months, and included body composition, growth, nutritional intake, and gastrointestinal symptoms. Results? There was a significant increase in weight (median difference 1.9kg; 95% confidence interval [CI] 0.85-3.03kg; p=0.012), mid-upper arm circumference (median difference 1.45cm; 95% CI -0.36cm to 3.47cm; p=0.043), and lower leg length (median difference 1.62cm; 95% CI 0.44-3.95cm; p=0.012) over the 6?months. There was no significant increase in fat mass index (median diff 1.21, 95% CI -1.15 to 2.94, p=0.345) or fat free mass index (median diff -1.43, 95% CI -1.15 to 2.94, p=0.249). Micronutrient levels remained within reference ranges with the exception of elevated chromium. The median percentage intake of the estimated average requirements for energy (kcal) was 43% at the beginning of the study and 48.8% after 6?months on the low-energy feed. Interpretation? Children with SQCP who are fed a low-energy, micronutrient-complete, high-fibre feed continue to grow even with energy intakes below 75% of the estimated average requirements. This was not associated with a disproportionate rise in fat mass or fat percentage, and the majority of micronutrient levels remained within the reference range.

© The Authors. Journal compilation © Mac Keith Press 2010.

ABSTRACT A multivariate model of determinants of change in gross-motor ability and engagement in self-care and play provides physical and occupational therapists a framework for decisions on interventions and supports for young children with cerebral palsy and their families. Aspects of the child, family ecology, and rehabilitation and community services may influence children’s activity and participation. Aspects of the child include primary and secondary impairments, associated and comorbid health conditions, and adaptive behaviors. Literature support for the model is reviewed. A clinical scenario illustrates the use of the model as a framework for practice. The model encourages therapists to broaden the focus of rehabilitation services for young children with CP to include not only development of motor abilities but also comprehensive interventions and supports to enhance participation in daily activities and routines. Therapists are encouraged to consider how child, family, and service factors interact when planning interventions and evaluating outcomes.

Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) have been suggested as being associated with cerebral palsy (CP) but the evidence is uncertain. The purpose of this study was to investigate whether MTHFR gene polymorphisms contribute to the development of CP in Chinese infants. For this study, 169 health controls and 159 infants with CP including 43 cases also suffering from mental retardation (MR) were recruited. Genomic DNA was prepared from venous blood and all five single nucleotide polymorphisms in MTHFR (rs4846049, rs1476413, rs1801131, rs1801133 and rs9651118) were genotyped using TaqMan technology. There were no significant differences in allele or genotype frequencies between the CP patients and controls at any of the five genetic polymorphisms. Subgroup analysis found statistically significant difference in allele and genotype frequencies between cases with both CP and MR (CP + MR) compared with both CP-only cases and controls at rs4846049, rs1476413 and rs1801131. The frequencies of the T alleles of rs4846049, rs1476413 and the G allele of rs1801131 were greater in the CP + MR patients than in the CP-only patients and controls. This study provides the first evidence pointing to a MTHFR gene polymorphism as a potential risk factor for CP combined with MR.Journal of Human Genetics advance online publication, 21 October 2010; doi:10.1038/jhg.2010.127.

A 63-year-old man with hypercholesterolemia developed sensory and motor disturbances in the ulnar side of the right hand, and over three days the weakness evolved to entire right arm. Examination on the 6th day after onset showed mild lower facial palsy in addition to the upper limb weakness on the right. The weakness involved entire right arm sparing shoulder girdle muscles, which was worse in the 4th and 5th digits with claw hand deformity of the hand. Magnetic resonance imaging showed multiple small infracts in the centrum semiovale as well as in the medial side of the precentral knob on the left. Magnetic resonance angiography, ultrasonography, and 3D-CT angiography of the neck showed severe stenosis associated with unstable plaque of the left internal carotid artery. Hemodynamic mechanisms including microemboli and hypoperfusion associated with severe internal carotid artery stenosis are likely to cause stroke in evolution after initial presentation of pseudo-ulnar palsy in the present case.

A 62-year-old immunocompetent woman presented with 11 days of headache, 2 days of right eye ache and 1 day of fever and lethargy. Neurological examination revealed nuchal stiffness, right proptosis, bilateral ptosis, and right abducens palsy. Cerebrospinal fluid (CSF) examination revealed elevated white cell count (164 /microl) and protein level (115 mg/dl). Cranial MRI showed sphenoid sinusitis, thromboses of the right superior ophthalmic vein, bilateral cavernous sinuses, left sphenoparietal sinus and left sigmoid sinus, and enhanced meninges. Purulent meningitis and multiple mycotic cerebral venous sinus thromboses were diagnosed. After empirical therapy with meropenem, fever persisted and CSF cell count further elevated (668/microl on day 3). Additional treatment with liposomal amphotericin B (L-AMB) and low-dose heparin from day 3 ameliorated her symptoms and lowered her CSF cell count. Laboratory test on admission later revealed elevated serum aspergillus antigen (index = 3.6) and positive blood culture for streptococcus viridans. L-AMB was replaced by voriconazole due to skin rash, and the latter was changed to itraconazole due to drug-induced hepatitis. She was discharged without complication and has been free of recurrence for 7 months. Aspergillus has a propensity to invade cerebral vessels and meninges, causing local thrombosis and meningitis with high mortality and morbidity. Direct penetration from adjacent sphenoid sinus can be a cause of cavernous sinus thrombosis, due to extreme thinness of the wall of sphenoid sinus. Cerebral venous sinuses lack valves, and this may facilitate the spread of mycotic thrombus to the other sinuses. Early preemptive treatment with antimycotic agents brought a favorable outcome to our patient.

Tauopathies represent a class of neurodegenerative disorders characterized by abnormal tau phosphorylation and aggregation into neuronal paired helical filaments (PHFs) and neurofibrillary tangles. AMP-activated protein kinase (AMPK) is a metabolic sensor expressed in most mammalian cell types. In the brain, AMPK controls neuronal maintenance and is overactivated during metabolic stress. Here, we show that activated AMPK (p-AMPK) is abnormally accumulated in cerebral neurons in 3R+4R and 3R tauopathies, such as Alzheimer’s disease (AD), tangle-predominant dementia, Guam Parkinson dementia complex, Pick’s disease, and frontotemporal dementia with parkinsonism linked to chromosome 17, and to a lesser extent in some neuronal and glial populations in the 4R tauopathies, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and argyrophilic grain disease. In AD brains, p-AMPK accumulation decorated neuropil threads and dystrophic neurites surrounding amyloid plaques, and appeared in more than 90% of neurons bearing pre-tangles and tangles. Granular p-AMPK immunoreactivity was also observed in several tauopathies in apparently unaffected neurons devoid of tau inclusion, suggesting that AMPK activation preceded tau accumulation. Less p-AMPK pathology was observed in PSP and CBD, where minimal p-AMPK accumulation was also found in tangle-positive glial cells. p-AMPK was not found in purified PHFs, indicating that p-AMPK did not co-aggregate with tau in tangles. Finally, in vitro assays showed that AMPK can directly phosphorylate tau at Thr-231 and Ser-396/404. Thus, activated AMPK abnormally accumulated in tangle- and pre-tangle-bearing neurons in all major tauopathies. By controlling tau phosphorylation, AMPK might regulate neurodegeneration and therefore could represent a novel common determinant in tauopathies.

This prospective study was conducted in the department of orthopedic surgery in Bangabandhu Sheikh Mujib Medical University (BSMMU) Dhaka, Bangladesh, from January 2005 to December 2007. Total number of 20 patients with 37 feet of equinus deformity due to cerebral palsy was managed by Baker's method. Equinus deformity in cerebral palsy is not uncommon in our outpatient department. Before operation patient walks on tip toes and after operation by Baker's method by apponeurotic lengthening of gastrocnemius muscle, with extensive physiotherapy, patients can able to walk normally in plantigrade feet. Among 20 patients only the spastic diplegic or hemiplegic equinus deformity in cerebral palsy was between 3 years to 12 years with a mean age of 5 years 9.6 months (SD+/-2 years 4.97 months). There were 3(15%) unilateral and 17(85%) bilateral cases. Among 20 cases, 13(65%) were male and 7(35%) were female. All cases were followed up for period ranging from 4 month to 28 months. Final clinical outcome was satisfactory (excellent and good) in 34(92%) feet and unsatisfactory (fair plus poor) in 3(8%) feet (p<0.001).