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).

ABSTRACT:

BACKGROUND: Long waiting times and large caseloads are a challenge to children’s therapy services internationally. Research in hospital-based healthcare indicates that waiting times are a function of throughput, and that length of care episode is related to clinicians’ caseload management behaviour (i.e. actions at assessment, treatment, post-treatment, and discharge). There have been few attempts to study this in community health services. The present study investigated whether community occupational therapists’ behaviour predicts children’s length of time (LoT) on caseloads.

METHODS: Retrospective survey of case notes of children recently discharged from occupational therapy services. Using cluster random sampling, case notes were drawn from therapy records in six NHSScotland Health Boards. Data about therapists’ behaviours of assessing, treating, reviewing and discharging, together with child characteristics, were used to construct regression models of factors related to LoT.

RESULTS: Twenty-six therapists [median(IQR) time in paediatrics 8(6-13) years] and 154 of their cases [mean(SD) age 7(3) years; median(IQR) LoT 10(3-21)] were included. A multi-level model, adjusting for clustering, for therapists’ actions of communicating assessment outcomes to parents, providing treatment, and placing the child on review, and for a diagnosis of cerebral palsy, explained 44% of variation in LoT.

CONCLUSIONS: Occupational therapists’ caseload management behaviours are associated with children’s LoT on caseloads. Further research is required to investigate the direction of relationships between therapists’ behaviours and LoT; and the relationships between contextual factors, therapists’ caseload management behaviours and LoT. Further exploration of therapists’ beliefs about caseload management could also be useful in identifying possible factors contributing to variation between therapists.

This work was undertaken to assess the usefulness of magnetic resonance imaging (MRI) of the brain for early prognosis of cerebral palsy. The study group included 47 neonates (24 term and 23 preterm) with symptoms of perinatal asphyxia. MRI examinations in term neonates were performed during the first month of life but not before the second week of life, while in preterm neonates MRI data were acquired between 38 and 40 weeks from conception. MRI of the brain demonstrated hypoxic-ischemic findings in all neonates born with perinatal asphyxia who later progressed to cerebral palsy. These results support the hypothesis that MRI performed in the neonatal period plays an essential role in predicting cerebral palsy in both term and preterm neonates, regardless of their gestational age.

Objective Poor condition at birth may impact on IQ, although its effect on other measures of neurodevelopment is unclear. The authors’ aim was to determine whether infants receiving resuscitation after birth have reduced scores in measures of attention, memory and language skills or the need for educational support at school even in the absence of clinical encephalopathy. Methods Three groups of term infants were identified from the Avon longitudinal study of parents and children: infants resuscitated at birth but asymptomatic for encephalopathy (n=612), infants resuscitated who developed symptoms of encephalopathy (n=40) and the reference infants who were not resuscitated and had no further neonatal care (n=8080). Measures of attention, language, memory and the need for educational support were obtained for children between 8 years and 11 years. Test results (standardised to a mean of 100 and SD of 15) were adjusted for clinical and social covariates. Missing covariate data were imputed using chained equations. Results Infants asymptomatic after resuscitation had similar scores to those not requiring resuscitation for all measures while infants who developed encephalopathy had lower working memory (-6.65 (-12.34 to -0.96)), reading accuracy (-7.95 (-13.28 to -2.63)) and comprehension (-9.32 (-14.47 to -4.17) scores and increased risk of receiving educational support (OR 6.24 (1.52 to 26.43)) than infants thought to be well at birth, although there was little evidence for an association after excluding infants who developed cerebral palsy. Conclusions The authors found no evidence that infants who were resuscitated but remained well afterwards differed from those not requiring resuscitation in the aspects of neuropsychological functioning assessed in this study. Infants who developed neonatal encephalopathy had evidence of worse functioning, particularly in language skills and were more likely to receive educational support at school.

PURPOSE: We sought to identify measures of variability from sitting postural sway that are significantly different among infants who were developing typically, those who were developmentally delayed or hypotonic, and those who later on had a diagnosis of spastic or athetoid cerebral palsy.

METHODS: Sixty-five infants were evaluated when they were just developing the ability to sit upright by assessing center of pressure (COP) data, using measures of both amount and temporal organization of COP variability.

RESULTS: The results indicated that measures of variability of COP could discriminate between infants with developmental delay and infants with cerebral palsy and add to the description of sitting postural behavior.

CONCLUSIONS: Our method of evaluating sitting postural control could be an objective tool to help describe distinctive features of motor delay in an individual infant and could lead in the design of selective therapeutic interventions for improving postural control of infants with motor delays.