Physiological responses during clinical spasticity evaluation in elbow flexors in children with cerebral palsy.

BACKGROUND: The Tardieu test is often used to identify and evaluate the severity of spasticity for clinical decision-making and treatment evaluation in cerebral palsy (CP). Objective: The study's objective was to gain further insight into the construct validity of clinical spasticity evaluation in children with CP. Methods: The kinematics and neuromuscular response of the biceps brachii (BB) during passive elbow extension were studied when performing the Tardieu test with its corresponding clinical interpretation. Fifteen children with unilateral spastic CP and 15 typically developing (TD) peers 15 (median/interquartile range age; 13/4 and 12/5 years, respectively) participated. Results: A clinical catch was detected in 9 of the 15 children with CP. During fast passive elbow extension, the CP group had higher BB activation (p = 0.041), lower fast maximal angular velocity (p = 0.001), and decelerated earlier in the extension movement (p = 0.001). Discussion: On average, the CP group without a clinical detected catch were closer to TD for all those variables, but this only reached statistical 20 significance in the latter variable (p = 0.018). This inconsistency also shows in possibly one false positive and three false negative catch observations. Conclusion: The Tardieu test should be carried out with caution on individual level and more studies including kinematic and neuromuscular measures are necessary.

Ataxia with vitamin e deficiency in norway.

OBJECTIVE: Ataxia with vitamin E deficiency (AVED) is a rare autosomal recessive neurological disorder which usually starts in childhood. The clinical presentation is very similar to Friedreich ataxia, most patients have progressive truncal and extremity ataxia, areflexia, positive Babinski sign, dysarthria and sensory neuropathy. METHODS: We made an inquiry to our colleagues in Norway, we included information from a prevalence study published southern Norway and added data from our own known case. RESULTS: A newly published prevalence study of hereditary ataxias (total of 171 subjects) found only one subject with AVED in Southeast Norway. We describe two more patients, one from the Central part and one from the Northern part of Norway. All 3 cases had age of onset in early childhood (age of 4-5 years) and all experienced gait ataxia and dysarthria. The genetic testing confirmed that they had pathogenic mutations in the α-tocopherol transfer protein gene (TTPA). All were carriers of the non-sense c.400C > T mutation, one was homozygous for that mutation and the others were compound heterozygous, either with c.358G > A or c.513_514insTT. The homozygous carrier was by far the most severely affected case. CONCLUSIONS: We estimate the occurrence of AVED in Norway to be at least 0.6 per million inhabitants. We emphasize that all patients who develop ataxia in childhood should be routinely tested for AVED to make an early diagnosis for initiating treatment with high dose vitamin E to avoid severe neurological deficits.

A mutation in the human CBP4 ortholog UQCC3 impairs complex III assembly, activity and cytochrome b stability.

Complex III (cytochrome bc1) is a protein complex of the mitochondrial inner membrane that transfers electrons from ubiquinol to cytochrome c. Its assembly requires the coordinated expression of mitochondrial-encoded cytochrome b and nuclear-encoded subunits and assembly factors. Complex III deficiency is a severe multisystem disorder caused by mutations in subunit genes or assembly factors. Sequence-profile-based orthology predicts C11orf83, hereafter named UQCC3, to be the ortholog of the fungal complex III assembly factor CBP4. We describe a homozygous c.59T>A missense mutation in UQCC3 from a consanguineous patient diagnosed with isolated complex III deficiency, displaying lactic acidosis, hypoglycemia, hypotonia and delayed development without dysmorphic features. Patient fibroblasts have reduced complex III activity and lower levels of the holocomplex and its subunits than controls. They have no detectable UQCC3 protein and have lower levels of cytochrome b protein. Furthermore, in patient cells, cytochrome b is absent from a high-molecular-weight complex III. UQCC3 is reduced in cells depleted for the complex III assembly factors UQCC1 and UQCC2. Conversely, absence of UQCC3 in patient cells does not affect UQCC1 and UQCC2. This suggests that UQCC3 functions in the complex III assembly pathway downstream of UQCC1 and UQCC2 and is consistent with what is known about the function of Cbp4 and of the fungal orthologs of UQCC1 and UQCC2, Cbp3 and Cbp6. We conclude that UQCC3 functions in complex III assembly and that the c.59T>A mutation has a causal role in complex III deficiency.

Botulinum neurotoxin treatment in children with cerebral palsy: a population-based study in Norway.

BACKGROUND/AIM: To study proportions and characteristics of children treated and un-treated with Botulinum neurotoxin (BoNT) in a population-based cohort of children with cerebral palsy (CP). METHODS: All children with CP born during 1999-2003, recorded in the Norwegian CP Register were included (N=411). Gross motor function was assessed using the gross motor classification system (GMFCS). RESULTS: Sixty-eight percent of children with bilateral spastic, 63% with unilateral spastic and 41% with dyskinetic CP had received BoNT. The percentage of children treated increased from 62% at GMFCS level I to 88% at level IV, but was only 38% among children at level V. A similar trend was seen for fine motor function. Ninety-four percent of the children received BoNT in their lower limbs. Children without significant cognitive impairment were more often treated than children with such impairment (OR: 2.61; 95% CI: 1.49-4.58). INTERPRETATION: In this first population-based study, approximately 2/3 of all children with spastic CP were treated with BoNT. The results suggest preference for treatment of children with potential for functional improvement, while treatment to relieve pain and facilitate care, and of children with cognitive impairment appeared to be less common. Whether the latter groups are treated appropriately requires further studies.

The effects of multiple pre- and perinatal risk factors on the occurrence of cerebral palsy. A Norwegian register based study.

AIMS: To examine the effects of multiple risk factors on cerebral palsy (CP). MATERIALS/METHODS: For 176,591 Norwegian infants born 1996-98 and surviving the early neonatal period, data on a number of potential pre- and perinatal risk factors (RFs) for CP were available in the Medical Birth Registry of Norway. For 241 children with CP detailed clinical data were available in the Norwegian CP registry. RESULTS: In children born at term, 31% had no RF, and none had five or more, while in children born preterm, 9% had no RF in addition to prematurity (p < 0.001 vs. term), and 5% had five or more (p < 0.02 vs. term). In both groups, few children shared the same combination of RFs. Interdependent sequences were more often observed among children born preterm than at term (p < 0.001 vs. term). The most detrimental effect was observed for the combination of maternal disease and low 5-min Apgar score, registered in 11.2% of children with CP. The combination of maternal disease and premature birth had an interaction contrast ratio of 9.25 (CI: 3.56; 14.94), which may be consistent with biological interaction. CONCLUSIONS: The majority of children with CP born at term most likely had an antenatal or single cause, suggesting individual susceptibility to an injury. The majority of children born preterm, had combinations or sequences of antenatal and perinatal risk factors as the most likely cause of CP.

Prevalence of hip dislocation among children with cerebral palsy in regions with and without a surveillance programme: a cross sectional study in Sweden and Norway.

BACKGROUND: Hip dislocation is a serious complication among children with cerebral palsy (CP). The aim of this study was to compare the prevalence of hip dislocation among children with CP in an area providing regular care with an area providing hip surveillance services. METHODS: This is a cross-sectional study in seven Norwegian counties providing regular care and one Swedish healthcare region where a hip surveillance programme was introduced in 1994. Data were provided by the Norwegian Cerebral Palsy Register and the CP Register in Southern Sweden. Children born 1996 - 2003 with moderate to severe CP, defined as Gross Motor Classification System (GMFCS) levels III - V, were included. In all, 119 Norwegian and 136 Swedish children fulfilled the criteria. In Norway, data on hip operations and radiographs of the hips were collected from medical records, while these data are collected routinely in the Swedish register. The hip migration percentage was measured on the recent radiographs. Hip dislocation was defined as a migration percent of 100%. RESULTS: The proportion of children at GMFCS levels III - V was 34% in the Norwegian and 38% in the Swedish population. In the Norwegian population, hip dislocation was diagnosed in 18 children (15.1%; CI: 9.8 - 22.6) compared with only one child (0.7%; 95% CI: 0.01 - 4.0) in Southern Sweden (p = < 0.001). Hip surgery was performed in 53 (44.5%) of the Norwegian children and in 43 (32%) of the Swedish children (p = 0.03). The total number of hip operations was 65 in Norway and 63 in Sweden. Norwegian children were first operated at a mean age of 7.6 years (SD: 2.9) compared with 5.7 years (SD: 2.3) in Sweden (p = 0.001). CONCLUSIONS: The surveillance programme reduced the number of hip dislocations and the proportion of children undergoing hip surgery was lower. However, with the surveillance programme the first operation was performed at a younger age. Our results strongly support the effectiveness of a specifically designed follow-up programme for the prevention of hip dislocation in children with CP.

Induction of labor and cerebral palsy: a population-based study in Norway.

OBJECTIVE: To investigate the association between labor induction and later development of cerebral palsy (CP). DESIGN: Registry-based cohort study. SETTING: Perinatal data on all children born in Norway 1996-1998 were obtained from the Medical Birth Registry of Norway (MBRN). Neurodevelopmental data were collected from the Norwegian Cerebral Palsy Registry (CPRN). POPULATION: A total of 176,591 children surviving the neonatal period. Of 373 children with CP, detailed data were available on 241. METHODS: Unadjusted and adjusted odds ratios (OR) with 95% confidence intervals (CI) were calculated as estimates of the relative risk that a child with CP was born after labor induction. MAIN OUTCOME MEASURES: Total CP and spastic CP subtypes. RESULTS: Bilateral cerebral palsy was more frequently observed after induced labor (OR: 3.1; 95% CI 2.1-4.5). For children born at term the association between bilateral CP and labor induction was stronger (OR: 4.4; 95% CI 2.3-8.6). The association persisted after adjustment for maternal disease, gestational age, standard deviation score for birthweight (z-score) and prelabor rupture of membranes (PROM) (adjusted OR: 3.7; 95%CI 1.8-7.5). Among children with CP born at term, four-limb involvement (quadriplegia) was significantly more frequent after induced (45.5%) compared with non-induced labor (8.0%). There was no significant association between labor induction and unilateral CP subtype or CP in preterm born children. CONCLUSIONS: In this study population, we found that labor induction at term was associated with excess risk of bilateral spastic CP and in particular CP with four-limb involvement.