Cerebral Palsy

Deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity is an inborn error of purine metabolism associated with uric acid overproduction and a continuum spectrum of neurological manifestations depending on the degree of enzyme deficiency. The complete deficiency causes Lesch-Nyhan syndrome (LNS). Partial HPRT-deficient patients can show a variable degree of neurological manifestations. Both diseases have been associated with mutations in the HPRT1 gene. Documented mutations in HPRT deficiency show a high degree of heterogeneity in type and location within the gene. In fact, more than 300 disease-associated mutations have been described. Splice mutations accounts for more that 16% of HPRT mutations and in most cases cause a complete LNS phenotype. A 16 year-old boy consulted to La Paz University Hospital because of hyperuricemia (9.4 mg/dL). At age one year he was given a diagnosis of dystonic cerebral palsy. Although he usually employs a wheelchair, under certain circumstances, he is able to stand up and walk by himself. He has never showed self injurious behavior. This patient presented a splice mutation (NM_000194.2: c.552 -2 A > G) causing exon 5 exclusion. An exon-5 specific PCR was designed, and a minor amount of normally spliced HPRT mRNA was found. Normally spliced HPRT mRNA was quantified by real-time PCR in this patient, in control subjects, and in two Lesch Nyhan patient with splice mutations excluding exon 4 (patient B) and exon 8 (patient C) who had clinically a Lesch Nyhan disease phenotype. A minor amount of normally spliced HPRT mRNA was found in all the patients. No correlation was found between the percentage of the normally spliced HPRT mRNA and the phenotype. We conclude that the partial HPRT deficient phenotype of this patient can not be explained by the finding of a minor amount of normally splice HPRT mRNA. It is possible that the amount of normally splice mRNA vary among different tissues.

OBJECTIVE: To describe the manual ability of adolescents with cerebral palsy and to investigate the relationship of manual ability with daily activities. DESIGN: Cross-sectional study. SUBJECTS: Ninety-four adolescents with cerebral palsy, aged 12-16 years. METHODS: Manual ability was assessed according to the Manual Ability Classification System (MACS) and the ABILHAND-Kids. Daily activities were assessed with the Vineland Adaptive Behavior Scales (VABS) sub-scales for (personal and domestic) daily living skills. The relationship between manual ability and daily activities was investigated with regression analysis: independent variables were manual ability, disease and personal characteristics. RESULTS: MACS and ABILHAND-Kids were both strongly associated with personal daily activities (explained variance 77% and 84%, respectively) and less strongly with domestic daily activities (explained variance 45% and 62%, respectively). Including other disease characteristics and personal characteristics in the model increased the explained variance of personal daily activities to 91% for both models and the explained variance of domestic daily activities to 68% and 73% for the MACS and ABILHAND-Kids models, respectively. CONCLUSION: Manual ability is limited in many adolescents with cerebral palsy, and limitations in manual ability are strongly related to limitations in daily activities.

BACKGROUND: Multiple differences between males and females are reported both in physiological and pathophysiological conditions. AIMS: To test the hypothesis that gender could influence the motor and cognitive development in children with cerebral palsy (CP). METHODS: Prospective, cross-sectional. One hundred seventy one children with CP (98 males and 73 females) were evaluated for motor (Gross Motor Function Measure, Gross Motor Function Classification System) and cognitive (Bayley II, Wechsler Scales) functions. Eighty-four of them were assessed before and other eighty-seven children after 4 years of age. RESULTS: No gender-related differences were observed in children with diplegia or quadriplegia, both for motor and cognitive functions. On the contrary, females with hemiplegia scored significantly better (P < 0.01) in cognitive functions and in the dimension D (standing) of the Gross Motor Function Measure, under the age of 4 years. These differences were not observed after this age. CONCLUSIONS: In this study we point out that gender might influence differently the psycho-motor development of children with hemiplegia and of those with a more severe clinical involvement as diplegia and quadriplegia. Copyright © 2010. Published by Elsevier Ltd.

AIM: This study aims to create a predictive model for the assessment of the individual risk of developing cerebral palsy in a large cohort of selected high-risk infants. PATIENTS AND METHODS: 1099 NICU-admitted high-risk infants were assessed up to the corrected age of at least 12months. CP was categorized relative to subtype, distribution and severity. Several perinatal characteristics (gender, gestational age, multiple gestation, small for gestational age, perinatal asphyxia and duration of mechanical ventilation), besides neonatal cerebral ultrasound data were used in the logistic regression model for the risk of CP. RESULTS: Perinatal asphyxia, mechanical ventilation>7days, white matter disease except for transient echodensities<7days, intraventricular haemorrhage grades III and IV, cerebral infarction and deep grey matter lesions were recognized as independent predictors for the development of CP. 95% of all children with CP were correctly identified at or above the cut-off value of 4.5% probability of CP development. Higher gestational age, perinatal asphyxia and deep grey matter lesion are independent predictors for non-spastic versus spastic CP (OR=1.1, 3.6, and 7.5, respectively). Independent risk factors for prediction of unilateral versus bilateral spastic CP are higher gestational age, cerebral infarction and parenchymal haemorrhagic infarction (OR=1.2, 31, and 17.6, respectively). Perinatal asphyxia is the only significant variable retained for the prediction of severe CP versus mild or moderate CP. CONCLUSION: The presented model based on perinatal characteristics and neonatal US-detected brain injuries is a useful tool in identifying specific infants at risk for developing CP. Copyright © 2010 Elsevier Ltd. All rights reserved.

OBJECTIVE: To examine risk factors for neonatal clinical seizures and to determine the independent association with death or neurodevelopmental impairment (NDI) in extremely low birth weight (ELBW) infants. STUDY DESIGN: A total of 6499 ELBW infants (401-1000 g) surviving to 36 weeks postmenstrual age (PMA) were included in this retrospective study. Unadjusted comparisons were performed between infants with (n = 414) and without (n = 6085) clinical seizures during the initial hospitalization. Using multivariate logistic regression modeling, we examined the independent association of seizures with late death (after 36 weeks PMA) or NDI after controlling for multiple demographic, perinatal, and neonatal variables. RESULTS: Infants with clinical seizures had a greater proportion of neonatal morbidities associated with poor outcome, including severe intraventricular hemorrhage, sepsis, meningitis, and cystic periventricular leukomalacia (all P < .01). Survivors were more likely to have NDI or moderate-severe cerebral palsy at 18 to 22 months corrected age (both P < .01). After adjusting for multiple confounders, clinical seizures remained significantly associated with late death or NDI (odds ratio, 3.15; 95% CI, 2.37-4.19). CONCLUSION: ELBW infants with clinical seizures are at increased risk for adverse neurodevelopmental outcome, independent of multiple confounding factors. Copyright © 2010 Mosby, Inc. All rights reserved.

BACKGROUND: In children with spastic cerebral palsy, the range of motion of the ankle joint is often limited. Measurement of range of motion may be hampered by a non-rigid foot deformity. We constructed a hand-held instrument which allows measurements of static ankle angle and moment in children with cerebral palsy while correcting for foot deformity. This study aimed to test the reproducibility of the instrument and to use it for measuring ankle moment-angle characteristics in individual children who are typically developing and children with cerebral palsy. METHODS: Ankle angles and moments were measured at five standardized positions in ten children who are typically developing and ten children with cerebral palsy. The intraclass correlation coefficient was calculated for test-retest reliability. For precision, the standard error of measurement and smallest detectable difference were determined. The ankle range of motion and the slope of the moment-angle curve were determined, both towards plantar flexion and dorsiflexion. FINDINGS: The reproducibility study revealed a high reliability of the dynamometer at 5 repetitions (>0.97). Precision lies within 5 degrees for angle measurements and within 0.2 Nm for moment measurements. In the children with cerebral palsy, the range of motion towards dorsiflexion was 18 degrees lower and the slope of the moment-angle curve towards dorsiflexion was substantially higher. INTERPRETATION: We developed a hand-held dynamometer which allows reliable and precise measurements of static ankle angle and moment in children with cerebral palsy. The hand-held dynamometer allows corrections of foot deformities and is qualified to reproducibly evaluate moment-angle characteristics in a clinical context. Copyright © 2010 Elsevier Ltd. All rights reserved.

AIM: The aim of this study was to develop a tool to identify paediatric hypertonia subtypes. METHOD: Items generated by experts were subscaled (spasticity, dystonia, rigidity). The tool was administered to 34 children (19 males, 15 females, mean age 8y 2mo, range 2y 5mo-18y 7mo) with hypertonia and cerebral palsy (CP) in Gross Motor Function Classification System (GMFCS) levels: I, n=7; II, n=5; III, n=7 level IV, n=7; and level V, n=8 level. Kuder-Richardson Formula 20 determined internal consistency. To assess reliability, two physicians administered the tool to 25 additional children with CP (15 males, 10 females; mean age 10y 8 mo; GMFCS levels I, n=4; II, n=3; III, n=7; IV, n=4; and V, n=7) on two occasions, 2 weeks apart. To evaluate validity, a third physician diagnosed the hypertonia by neurological examination. RESULTS: The internal consistency of the spasticity items was moderate (alpha = 0.58), and dystonia was high (a=0.79). Item reduction eliminated seven of the 14 original items. The agreement of the spasticity and rigidity subscales was adequate (prevalence-adjusted bias-adjusted kappa [PABAK] ranging from moderate [0.57] to excellent [1.0]) for validity, test-retest reliability, and interrater reliability. For dystonia agreement was lower, with PABAK ranging from fair (0.30) to good (0.65). Eighty-seven per cent had spasticity and 78% had dystonia. INTERPRETATION: The Hypertonia Assessment Tool has good reliability and validity for identifying spasticity and the absence of rigidity, and moderate findings for dystonia.

Trochlear nerve palsy associated with spontaneous subarachnoid hemorrhage (SAH) is known to be a rare malady. We report here on a patient who suffered with left trochlear nerve palsy following rupture of a right posterior communicating artery aneurysm. A 56-year-woman visited our emergency department with stuporous mental change. Her Hunt-and-Hess grade was 3 and the Fisher grade was 4. Cerebral angiography revealed a ruptured aneurysm of the right posterior communicating artery. The aneurysm was clipped via a right pterional approach on the day of admission. The patient complained of diplopia when she gazed to the left side, and the ophthalmologist found limited left inferolateral side gazing due to left superior oblique muscle palsy on day 3. Elevated intracranial pressure, intraventricular hemorrhage or a dense clot in the basal cisterns might have caused this trochlear nerve palsy.

This report is a case of slipped capital femoral epiphysis in a nonambulatory patient with spastic quadriplegic type of cerebral palsy. Such a case is unusual as no weight-bearing forces were acting on the hip; however, spasticity may have played a role. To the best of our knowledge no earlier cases have been reported in the literature.

Whipple’s disease is a rare multisystemic infection caused by the intracellular bacteria Thropheryma whippelii. Central nervous system (CNS) involvement is not rare. The most frequent CNS manifestations are cognitive and behavioural changes, sopranuclear ophtalmoplegia, myoclonus, epilepsy, ataxia, meningitis and focal cerebral palsy. We report one case of cerebral localization of Whipple’s disease with a clinical presentation of recurrent endocranic hypertension and hydrocephalus, and uncommon neurological symptoms, successfully treated by endoscopic third ventriculostomy and antibiotic therapy with ceftriaxone and Trimethoprim-Sulfamethoxazole. Copyright © 2010 Elsevier B.V. All rights reserved.