Prevalence and determinants of hip pain in non-ambulatory cerebral palsy children: a retrospective cohort study.

BACKGROUND: Hip pain is common in cerebral palsy children, particularly at Gross-Motor Function Classification System level IV-V. It is associated to hip displacement and relates to the migration percentage. Recent literature suggested early reconstructive bone surgery, as the best approach to prevent hip luxation, then hip pain. Still, high rates of hip pain are reported. AIM: To investigate prevalence and determinants of hip pain in an Italian cerebral palsy sample. DESIGN: Single-center retrospective cohort study. SETTING: Inpatient and outpatient. POPULATION: Patients with spastic or dyskinetic cerebral palsy, Gross-Motor Function Classification System level IV or V, age 0-18. METHODS: A chart review was implemented to report hip pain, as a dichotomous variable (pain/no pain), age, sex, cerebral palsy subtype, Gross-Motor Function level, lumbar scoliosis, migration percentage, previous orthopedic surgery, or botulinum injections, oral or intrathecal baclofen, drug-resistant epilepsy, assistive devices for standing or walking. Descriptive statistics and a multivariate logistic stepwise regression were performed. RESULTS: A total of 504 subjects were included: 302 level V, 209 females, 432 spastics. The mean length of follow-up was 6 years. The overall prevalence of hip pain was 8.9% (6.3% were at level V) and of hip dislocation was 19% (15.9% were at level V). Just 39% of dislocated hips were painful. Children at spastic subtype and level V were predominantly affected. Botulinum and soft tissue surgery related to lower rates of hip pain, without statistical significance. Age (OR 1.19, 95%CI 1.14-1.25, P value 0.000), sex (OR 1.72, 95%CI 1.18-2.52, P value 0.005), migration percentage (OR 1.02, 95%CI 1.02-1.03, P value 0.000) and lumbar scoliosis (OR 1.32, 95%CI 0.86-2.01, P value 0.200) resulted significant independent determinants of hip pain. CONCLUSIONS: Hip pain relates with the migration percentage, but not all dislocated hips become painful. Hip pain may be transient and requires a targeted and individualized approach. Children at spastic subtype and level V were predominantly affected. Age and sex are confirmed as determinants. Specific validated measures are to be implemented to assess hip pain. CLINICAL REHABILITATION IMPACT: Considering severe non-ambulatory cerebral palsy patients, pain and quality of life should be considered as outcomes, in the management of hip luxation.

Treatment of spasticity in children and adolescents with cerebral palsy in Northern Europe: a CP-North registry study.

BACKGROUND: Spasticity is present in more than 80% of the population with cerebral palsy (CP). The aim of this study was to describe and compare the use of three spasticity reducing methods; Botulinum toxin-A therapy (BTX-A), Selective dorsal rhizotomy (SDR) and Intrathecal baclofen therapy (ITB) among children and adolescents with CP in six northern European countries. METHODS: This registry-based study included population-based data in children and adolescents with CP born 2002 to 2017 and recorded in the follow-up programs for CP in Sweden, Norway, Denmark, Iceland and Scotland, and a defined cohort in Finland. RESULTS: A total of 8,817 individuals were included. The proportion of individuals treated with SDR and ITB was significantly different between the countries. SDR treatment ranged from 0% ( Finland and Iceland) to 3.4% (Scotland) and ITB treatment from 2.2% (Sweden) to 3.7% (Denmark and Scotland). BTX-A treatment in the lower extremities reported 2017-2018 ranged from 8.6% in Denmark to 20% in Norway (p < 0.01). Mean age for undergoing SDR ranged from 4.5 years in Norway to 7.3 years in Denmark (p < 0.01). Mean age at ITB surgery ranged from 6.3 years in Norway to 10.1 years in Finland (p < 0.01). Mean age for BTX-A treatment ranged from 7.1 years in Denmark to 10.3 years in Iceland (p < 0.01). Treatment with SDR was most common in Gross Motor Function Classification System (GMFCS) level III, ITB in level V, and BTX-A in level I. The most common muscle treated with BTX-A was the calf muscle, with the highest proportion in GMFCS level I. BTX-A treatment of hamstring and hip muscles was most common in GMFCS levels IV-V in all countries. CONCLUSION: There were statistically significant differences between countries regarding the proportion of children and adolescents with CP treated with the three spasticity reducing methods, mean age for treatment and treatment related to GMFCS level. This is likely due to differences in the availability of these treatment methods and/or differences in preferences of treatment methods among professionals and possibly patients across countries.

Predicting Hip Dysplasia in Teenagers with Cerebral Palsy in order to Optimize Prevention and Rehabilitation. A Longitudinal Descriptive Study.

OBJECTIVE: To develop a predictive model of neuromuscular hip dysplasia (NHD) in teenagers with cerebral palsy (CP) to optimize rehabilitation. DESIGN: A longitudinal, multicenter, double-blinded, descriptive study of one hundred and two teenagers with CP (age 16.5 ± 1.2 years, range 12-18 years). Data on etiology, diagnosis, spasticity, epilepsy, clinical history, and functional assessments were collected from 2005 to 2017 and entered in the prediction model "PredictMed." RESULTS: Poor walking abilities [p < .001; Odd Ratio (OR) Infinity], scoliosis (p 0.01; OR 3.22), trunk muscles' tone disorder (p 0.002; OR 4.81), spasticity (p 0.006; OR 6.6), poor motor function (p 0.02; OR 5.5), and epilepsy (p 0.03; OR 2.6) were predictors of NHD development. The accuracy of the model was 77%. CONCLUSION: Trunk muscles' tone disorder, severe scoliosis, epilepsy, and spasticity were predictors of NHD in teenagers with CP. Based on the results we have developed appropriate preventative rehabilitation interventions.

Associations between Folate Metabolism Enzyme Polymorphisms and Lung Cancer: A Meta-Analysis.

Some previous studies already investigated potential associations between folate metabolism enzyme polymorphisms and lung cancer (LC). However, the results of these studies were inconsistent. Thus, we performed this meta-analysis to explore associations between folate metabolism enzyme polymorphisms and LC in a larger pooled population. Systematic literature research of PubMed, WOS, Embase and CNKI was performed to identify eligible studies. Review Manager Version 5.3.3 was used to conduct statistical analyses. Totally 37 genetic association studies were included for analyses. The pooled analyses showed that MTRR rs1801394 (dominant model: p = 0.01; recessive model: p = 0.04; allele model: p = 0.005) and MTHFR rs1801133 (dominant model: p = 0.008; recessive model: p = 0.0003; allele model: p = 0.0002) polymorphisms were both significantly associated with susceptibility to LC in overall population. Subgroup analyses revealed similar significant findings for MTHFR rs1801133 polymorphism in East Asians. Significant associations with LC were also observed for MTRR rs1801394 and MTHFR rs1801133 polymorphisms in smokers. In conclusion, this meta-analysis indicated that MTRR rs1801394 was significantly associated with LC in smokers, and MTHFR rs1801133 polymorphisms was also significantly associated with LC in smokers and East Asians. These results suggested that these two polymorphisms could be used to identify individuals at high risk of developing LC in certain populations.

Clinical, ophthalmological, imaging and genetic features in Brazilian patients with ARSACS.

BACKGROUND: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an important form of inherited ataxia with a varied clinical spectrum. Detailed studies of phenotype and genotype are necessary to improve diagnosis and elucidate this disorder pathogenesis. OBJECTIVE AND METHODS: To investigate the clinical phenotype, retinal architecture, neuroimaging features and genetic profile of Brazilian patients with ARSACS, we performed neurological and ophthalmological evaluation in thirteen Brazilian patients with molecularly confirmed ARSACS, and examined their mutation profiles. Optical coherence tomography protocol (OCT) consisted in peripapillary retinal nerve fiber layer (RNFL) measurement and qualitative analysis of perifoveal scans. Neuroimaging protocol accessed the frequency of atrophy in cerebellum, corpus callosum and parietal lobe, brainstem signal abnormalities, and posterior fossa arachnoid cysts. We reviewed the literature to delineate the ARSACS phenotype in the largest series worldwide. RESULTS: All patients had ataxia and spasticity, and 11/13 had peripheral neuropathy. Macular microcysts were present in two patients. Peripapillary striations, dentate appearance of inner retina and papillomacular fold were found in eleven cases. All individuals exhibited thickening of RNFL in OCT. The most frequent radiological signs were cerebellar atrophy (13/13), biparietal atrophy (12/13), and linear pontine hypointensities (13/13). Genetic analysis revealed 14 different SACS variants, of which two are novel. CONCLUSION: Macular microcysts, inner retina dentate appearance and papillomacular fold are novel retinal imaging signs of ARSACS. Ophthalmological and neuroimaging changes are common findings in Brazilian patients. The core clinical features of ARSACS are ataxia, spasticity and peripheral neuropathy with onset predominantly in the first decade of life.

High Rates of Psychiatric Disorders and Below Normal Mental Capacity Associated With Spastic Peroneal Flatfoot: A New Relationship.

Spastic peroneal flatfoot (SPFF) is a rare hindfoot pathology usually seen in the adolescent age group that is characterized by painful spasms in the peroneal muscles. We have clinically observed that patients with SPFF also have some behavioral and emotional difficulties and problems in their academic achievements. Because of these observations, we investigated the prevalence and patterns of psychiatric disorders and intellectual disability among young subjects with SPFF. Our cohort consisted of 16 patients with SPFF. Their mean age at presentation was 21 (range 13 to 31) years. Only 6 patients had a tarsal coalition as an underlying condition. The psychometric evaluation was conducted using validated instruments (Wechsler Intelligence Scale for Children-revised form, Stanford Binet intelligence quotient [IQ] test, and Cattell IQ test). Psychiatric disorders were assessed using a semistructured diagnostic instrument (Schedule for Affective Disorders and Schizophrenia for School Age Children Present and Lifetime Version). The testers and psychiatrists were unaware of the orthopedic condition and the preliminary psychiatric diagnoses. The ethical committee approved the study protocol. The mean follow-up period was 41 (range 12 to 97) months. The mean IQ score of the patients was 75.1 ± 17.9 (range 52 to 107). Compared with the general population, the rate of intellectual disability was significantly greater (p = .0001) and the rate of normal intelligence significantly lower (p = .0015) in our patient group. Furthermore, according to the community schooling ratio, our cohort also had lower junior high and secondary education rates compared with the general population. The rate of most psychiatric disorders diagnosed in the SPFF patients was greater than that in the normal population. The most commonly identified psychiatric disorders were social phobia and attention deficit and hyperactivity disorder (75%). Timely interventions of the psychosocial and academic problems of patients with SPFF might increase their compliance with orthopedic treatment and help with their psychological well-being and academic achievement. In addition, this relationship might be a clue for uncovering the etiology of this disease, which has not yet been clarified.

Medical use of cannabis: Italian and European legislation.

This review illustrates some brief considerations of the medical use of cannabis recently issued in Italy. History and uses of cannabis throughout centuries and different countries are illustrated together with a description of botany and active phytocannabinoids. Then, medical use of cannabis anti-pain treatment for patients resistant to conventional therapies is described in case of chronic neuropathic pain, spasticity, for anticinetosic and antiemetic effect in nausea and vomiting caused by chemotherapy, for appetite stimulating effect in cachexia, anorexia, loss of appetite in cancer patients or patients with AIDS and in anorexia nervosa, hypotensive effect in glaucoma resistant to conventional therapies and for reduction of involuntary body and facial movements in Gilles de la Tourette syndrome. Italian most recent legislation on medical cannabis is detailed with some law proposals, also showing the inconsistent legislation within European Union. Some final considerations of future studies are also reported.

Long-term effects of intrathecal baclofen in multiple sclerosis.

OBJECTIVES: Spasticity is associated with various neurological conditions. In this study the authors analyzed the long term effects of intrathecal baclofen therapy in multiple sclerosis and evalued the benefits of the treatment on spasticity, disability, pain, spasm frequency and rated the incidence of side effects. PATIENTS AND METHODS: A records of 123 patients, with a severe, progressive and refractory to medical therapy spasticity from different causes, underwent baclofen pump placement, after a bolus test, from 2000 to 2012,under Department of Neurosurgery at the Second University of Naples/Italy. We present our experience in treating 28 subjects that was affected by multiple sclerosis. For all patients we reviewed long-term response to therapy, surgical technique, surgery- and pump-related complications. Every patients were evaluated by means of the Modified Ashworth Scale (MAS), Penn Spasm Frequency Scale (SFS), Visual analogue Scale For Pain (VAS), Barthel index (BI) and Self Rating Depression Scale (SDS) RESULTS: During follow up the mean MAS score for upper and lower extremities decrease significantly. Also SFS's decrease was statistically significant. This resulted in a dramatic improvement of BI. Furthermore, we observed a marked improvement in VAS and SDS. CONCLUSIONS: Intrathecal baclofen provides effective long-term treatment of spasticity multiple sclerosis related. ITB therapy increases the quality of lifestyle and functional independence in appropriately selected cases.

Congenital cerebral palsy and prenatal exposure to self-reported maternal infections, fever, or smoking.

OBJECTIVE: The objective of the study was to investigate the association between maternal self-reported infections, fever, and smoking in the prenatal period and the subsequent risk for congenital cerebral palsy (CP). STUDY DESIGN: We included the 81,066 mothers of singletons born between 1996 and 2003 who participated in the Danish National Birth Cohort. Children were followed up through December 2008. Information on maternal infections, fever, smoking, and other demographic and lifestyle factors during pregnancy were reported by mothers in computer-assisted telephone interviews in early and midgestation. We identified 139 CP cases including 121 cases of spastic CP (sCP) as confirmed by the Danish National Cerebral Palsy Register. Cox proportional hazards regression models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). RESULTS: Self-reported vaginal infections were associated with an increased risk of CP and sCP (aHR, 1.52; 95% CI, 1.04-2.24; and aHR, 1.73; 95% CI, 1.16-2.60, respectively) and particularly untreated vaginal infections were associated with an increased risk of sCP (aHR, 1.95; 95% CI, 1.16-3.26). Fever was associated with the risk of CP (aHR, 1.53; 95% CI, 1.06-2.21). Smoking 10 or more cigarettes per day during pregnancy was also associated with sCP (aHR, 1.80; 95% CI, 1.10-2.94). There was a modest excess in risk for children exposed to both heavy smoking and vaginal infections. No other self-reported infections were significantly associated with CP. CONCLUSION: Self-reported vaginal infections, fever, and smoking 10 or more cigarettes per day during pregnancy were associated with a higher risk of overall CP and/or sCP.

Oxidative stress and platelet activation in subjects with moderate hyperhomocysteinaemia due to MTHFR 677 C→T polymorphism.

The methylenetetrahydrofolate reductase (MTHFR) 677 C→T polymorphism may be associated with elevated total homocysteine (tHcy) levels, an independent risk factor for cardiovascular disease. It was the study objective to evaluate in vivo lipid peroxidation and platelet activation in carriers of the MTHFR 677 C→T polymorphism and in non-carriers, in relation to tHcy and folate levels. A cross-sectional comparison of urinary 8-iso-prostaglandin (PG)F(2α) and 11-dehydro-thromboxane (TX)B(2) (markers of in vivo lipid peroxidation and platelet activation, respectively) was performed in 100 carriers and 100 non-carriers of the polymorphism. A methionine-loading test and folic acid supplementation were performed to investigate the causal relationship of the observed associations. Urinary 8-iso-PGF(2α) and 11-dehydro-TXB(2) were higher in carriers with hyperhomocysteinaemia than in those without hyperhomocysteinaemia (p<0.0001). Hyperhomocysteinaemic carriers had lower folate levels (p=0.0006), higher urinary 8-iso-PGF(2α) (p<0.0001) and 11-dehydro-TXB(2) (p<0.0001) than hyperhomocysteinaemic non-carriers. On multiple regression analysis, high tHcy (p<0.0001), low folate (p<0.04) and MTHFR 677 C→T polymorphism (p<0.001) independently predicted high rates of 8-iso-PGF(2α) excretion. Methionine loading increased plasma tHcy (p=0.002), and both urinary prostanoid metabolites (p=0.002). Folic acid supplementation was associated with decreased urinary 8-iso-PGF(2α) and 11-dehydro-TXB2 excretion (p<0.0003) in the hyperhomocysteinaemic group, but not in the control group, with substantial inter-individual variability related to baseline tHcy level and the extent of its reduction. In conclusion, hyperhomocysteinaemia due to the MTHFR 677 C→T polymorphism is associated with enhanced in vivo lipid peroxidation and platelet activation that are reversible, at least in part, following folic acid supplementation. An integrated biomarker approach may help identifying appropriate candidates for effective folate supplementation.

Spasticity improvement in patients with relapsing-remitting multiple sclerosis switching from interferon-ß to glatiramer acetate: the Escala Study.

BACKGROUND: A recent pilot study suggested spasticity improvement during glatiramer acetate (GA) treatment in multiple sclerosis (MS) patients who previously received interferon-ß (IFN-ß). OBJECTIVE: To evaluate changes in spasticity in MS patients switching from IFN-ß to GA. METHODS: Observational, multicentre study in patients with relapsing-remitting MS (RRMS) and spasticity switching from IFN-ß to GA. The primary endpoint comprised changes on Penn Spasm Frequency Scale (PSFS), Modified Ashworth Scale (MAS), Adductor Tone Rating Scale (ATRS), and Global Pain Score (GPS) at months 3 and 6 after starting GA. RESULTS: Sixty-eight evaluable patients were included (mean age,41.7±9.5 years; female,70.6%; mean time from MS diagnosis to starting GA,7.6±5.7 years). Previous treatments were subcutaneous IFN-ß1a in 42.6% patients, intramuscular IFN-ß1a in 41.2% and IFN-ß1b in 32.4%, whose mean durations were 3.5±3.3, 2.7±2.5 and 4.4±3.6 years, respectively. Statistically significant reductions in mean scores on all spasticity measurements were observed from baseline to month 3 (PSFS, 1.7±0.9 vs 1.4±0.6, p<0.01; MAS, 0.7±0.5 vs 0.6±0.5, p<0.01; highest MAS score, 1.9±0.8 vs 1.7±0.8, p<0.01; ATRS, 1.6±0.6 vs 1.4±0.6, p<0.01; GPS, 29.4±22.1 vs 24.7±19.4, p<0.01) and from baseline to month 6 (PSFS, 1.7±0.9 vs 1.3±0.6, p<0.01; MAS, 0.7±0.5 vs 0.5±0.5, p<0.01; highest MAS score, 1.9±0.8 vs 1.5±0.9, p<0.01; ATRS, 1.6±0.6 vs 1.3±0.6, p<0.01; GPS, 29.4±22.1 vs 19.1±14.8, p<0.01). CONCLUSION: Spasticity improvement in terms of spasm frequency, muscle tone and pain can be noted after three months and prolonged for six months of GA treatment.

[Fumonisin intake and human health]. / Consumo de fumonisinas y daños a la salud humana.

Fumonisins are mycotoxins that contaminate maize, disrupt the folate and sphingolipid metabolism, are associated with neural tube defects, and are considered by the International Agency for Research on Cancer (IARC) as possible human carcinogens. Since maize-based foods are significant components of the Mexican diet and there is a high prevalence of genetic susceptibility for folate deficiency among Mexicans, this essay presents international and national evidence of fumonisin exposure and the relevance that such exposure represents for Mexico.

Consumo de fumonisinas y daños a la salud humana / Fumonisin intake and human health

Las fumonisinas son una familia de micotoxinas que contaminan al maíz, alteran el metabolismo de los esfingolípidos y del folato, se asocian con defectos del tubo neural y están catalogadas por la Agencia Internacional de Investigación en Cáncer (IARC por sus siglas en inglés) como posibles carcinógenos humanos. Debido a que en México los derivados de maíz constituyen una parte importante de la dieta y existe alta prevalencia de población genéticamente susceptible a la deficiencia de folato, en este ensayo se presentan las evidencias mundiales y nacionales de la exposición a fumonisinas y la relevancia que para México representa la evaluación de esta exposición.

Fumonisins are mycotoxins that contaminate maize, disrupt the folate and sphingolipid metabolism, are associated with neural tube defects, and are considered by the International Agency for Research on Cancer (IARC) as possible human carcinogens. Since maize-based foods are significant components of the Mexican diet and there is a high prevalence of genetic susceptibility for folate deficiency among Mexicans, this essay presents international and national evidence of fumonisin exposure and the relevance that such exposure represents for Mexico.

Clinical correlates of fatigue in spinal cord injury.

STUDY DESIGN: Retrospective chart review. OBJECTIVES: To determine the prevalence of fatigue in an outpatient spinal cord injury population and to examine the clinical variables contributing to that fatigue. SETTING: GF Strong Rehabilitation Centre, Vancouver, British Columbia, Canada. METHODS: Medical charts of 76 individuals admitted to the GF Strong Outpatient SCI Program between December 2004 and December 2005 were reviewed. Data collected included information on clinical characteristics, demographics and Fatigue Severity Scale (FSS) scores. Multivariable analysis was completed to determine the independent association between these variables and fatigue severity. RESULTS: A total of 57% (95% confidence interval (CI)=45-67%) of the sample were found to have fatigue severe enough to interfere with function. People that were admitted for medical reasons; had pain, spasticity, incomplete injuries, and/or were on more that one medication with a known side effect of fatigue had significantly higher FSS scores. Multivariable analysis indicated incomplete injury was the only statistically significant predictor of a higher FSS scores; pain approached significance (P=0.07, CI=-0.09, 2.06). Together these variables account for 18% of the variance in FSS scores in this sample. CONCLUSION: Fatigue among individuals with spinal cord injury who are seeking outpatient rehabilitation is very common. The severity of fatigue was greater for individuals with incomplete lesions. Pain was also a potentially important covariate of fatigue. Further research is required to determine what else contributes to fatigue severity beyond these clinical variables as only minimal variance was accounted for in our model.

Sacsinopathies: sacsin-related ataxia.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) was originally found among inhabitants of the Charlevoix-Saguenay region of northeastern Quebec in Canada. This disease is a neurodegenerative disorder characterized by early-onset spastic ataxia, dysarthria, nystagmus, distal muscle wasting, finger and foot deformities, and retinal hypermyelination. The principal neuropathology comprises atrophy of the upper vermis and the loss of Purkinje cells in the cerebellum. The SACS gene was originally reported to consist of a single gigantic exon spanning 12.8 kb with an 11.5-kb open reading frame (ORF), and to encode the protein sacsin. Recently, eight exons upstream from the original gigantic one, however, have been found, and the new ORF has elongated to 13.7 kb. To date, at least 28 mutations have been found in Quebec and non-Quebec patients including ones in Italy, Japan, Spain, Tunisia, and Turkey, and ARSACS thus shows a worldwide occurrence. Although most of the mutations reported have been in the gigantic exon, the genotype is now expanding upstream from this gigantic exon. Therefore, the new exons upstream of the gigantic one should be analyzed when a case is clinically compatible with ARSACS, even without any mutation in the gigantic exon. Although Quebec patients show a homogeneous phenotype, non-Quebec patients exhibit some atypical clinical features, as follows: slightly later onset than that in Quebec patients, absence of retinal hypermyelination, intellectual impairment, and lack of spasticity. Thus, since ARSACS shows the clinical diversity, the SACS gene should be analyzed not only in typical cases as Quebec patients but also in atypical cases as non-Quebec patients. As more SACS mutations are identified worldwide, the clinical spectrum of 'sacsinopathies' will expand, and a finer genotype-phenotype correlation study will become possible and shed light on the molecular mechanism underlying ARSACS.

[Guide to the comprehensive treatment of spasticity]. / Guia del tratamiento integral de la espasticidad.

AIMS AND DEVELOPMENT: Spasticity is an important medical problem with a high rate of incidence both in childhood, mainly as a result of cerebral palsy, and in adults, which is frequently brought about by traumatic brain injuries, strokes and spinal cord injuries. Spasticity is part of upper motoneuron syndrome, which gives rise to important problems, such as limited joint movement, abnormal postures that can produce pain, impaired functional capacity, aesthetic or hygiene disorders, among others. It progresses naturally towards chronicity, accompanied by static phenomena due to alterations affecting the properties of soft tissues (elasticity, plasticity and viscosity). Numerous therapeutic options are available for the treatment of spasticity, including medication, physiotherapy, orthopaedic aid, surgery, and so forth. Moreover, treatment should be individualised and realistic, with goals that have been agreed between the patient or caregiver and the medical team. The aim of the following guide is to further our knowledge of this condition, its causes, epidemiology and progression, as well as to outline an approach that is both rational and global from the point of view of pharmacological, rehabilitation and surgical treatment. CONCLUSIONS: Spasticity is a complex problem that requires specialists (neurologist, rehabilitation doctor, occupational therapist, orthopaedic surgeon, general practitioner, etc.) to work as a team in order to achieve the goals set out when treatment is begun. Early treatment is important to avoid or reduce, as far as possible, the severe complications stemming from this condition.

Indian Agarwal megalencephalic leukodystrophy with cysts is caused by a common MLC1 mutation.

BACKGROUND: A distinct clinical syndrome characterized by megalencephaly, mild to moderate cognitive decline, slowly progressive spasticity, ataxia, occasional seizures, and extensive white matter changes with temporal cysts by imaging studies has been described in a particular ethnic group (Agarwals) in India. This disorder is very similar to megalencephalic leukoencephalopathy with subcortical cysts (MLC), a newly characterized leukodystrophy whose molecular basis was recently shown to be mutations in a gene (KIAA0027) that has been renamed MLC1. OBJECTIVE: To determine if this disorder among the Agarwals is due to mutations in MLC1 by a mutation screening study conducted on affected Agarwal patients. METHODS: Genomic DNA from these Indian leukodystrophy patients was screened for mutations in the entire coding region, including the exon-intron boundaries, of the MLC1 gene. RESULTS: Thirty-three affected individuals whose clinical and imaging presentations were consistent with MLC were screened. All were from northern India and included 31 known Agarwals, 1 non-Agarwal, and 1 adopted patient whose ethnicity is unknown. All 31 Agarwal patients tested positive for a homozygous insertion of a cytosine in exon 2. The adopted patient was homozygous for A157E. No mutation in the coding region was found in the non-Agarwal patient. CONCLUSIONS: Indian patients with megalencephaly and MRI changes that show extensive white matter changes with temporal cysts should raise suspicion for MLC. Members of the Agarwal ethnic group affected with the disorder present with a mildly progressive course and show a common mutation (320insC) in the MLC1 gene, suggesting a founder effect.

Spasticity in adults living in a developmental center.

OBJECTIVES: To ascertain the prevalence of spasticity among adults living in a developmental center and to document the development of spasticity treatment plans for this population. DESIGN: Descriptions of the clinical features of medical disorders and a prevalence survey. SETTING: Residential developmental center. PARTICIPANTS: One hundred three adults. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Characteristics described included the prevalence of spasticity in this population, the specific spasticity diagnosis, functional goals for spasticity treatment identified by the participants' multidisciplinary teams, and the specific treatment indicated by the neurologist. RESULTS: Of the 103 people diagnosed by the neurologist, 24 had diplegic spasticity, 4 had hemiplegic spasticity, 44 had quadriplegic spasticity, and 31 had no spasticity. Functional goals identified by multidisciplinary teams were undergarment change (46.3% of the persons for whom goals were identified), splinting hands (11%), dressing (57.4%), hygiene (20.4%), wheelchair positioning (25.9%), ambulation improvement (14.8%), and transfers (9.3%). After physical and occupational therapy, the first invasive treatments indicated for people with spasticity included botulinum toxin injections (60%), intrathecal baclofen (26.4%), orthopedic surgery (5.6%), and medication (1.4%). No treatment was recommended for 25% of the spasticity patients. CONCLUSIONS: The prevalence of spasticity was 35% in this developmental center population of 205 individuals. A multidisciplinary team approach to the evaluation of adults with spasticity who live in a developmental center makes it possible to identify functional goals that are amenable to spasticity treatment and minimizes treatment that does not target specific functional goals.

Manejo de la espasticidad con toxina botulínica en población pediátrica

La toxina botulinica A (TBA), es la más potente de las toxinas, producidas por el Clostridium Botulinium; ejerce su acción a nivel de la unión neuromuscularpor inhibición de la liberación de acetilcolina, ocacionando parálisis flácida reversible. Inicialmente se utilizó en blefaroespasmo y estrabismo, posteriormente se extendio su uso a distonias y espasticidad. la aplicación en niños se ha limitado a paralisis cerebral espastica. La dosis usada es de 6 a 8 unidades por Kg. Se realizo un estudio prospectivo, incluyendo 70 pacientes (42 de sexo masculinino), con edades entre los 6 meses y los 18 años (51 menores de 10 años). La etiología más frecuente de la espasticidad, fue perinatal (76 porciento) secundaria a hipoxia perinatal en 36 pacientes, eventos isquemicos transitorios perinatales en 13 y hemorragia intraventricular del prematuro en 6. Los musculos inyectados con más frecuencia fueron los gastrocnemios, aductores de la cadera y flexores de la rodilla. se aplicó TBA en musculos para espinales, trapecio y abductor del pulgar poco mencionados en otros trabajos. El grado de espasticidad de los musculos fue determinado mediante la escala de Asworth. En todos los pacientes se observo disminución de la puntuación luego de la aplicación de la TBA, con mejoria clinica a las 4.5 dias en promedio, 4 pacientes lograron marcha independiente y se evidencio mejoria en la función motora, higiene y calidad de vida de los pacientes. La aplicacion de Tba es un método seguro y una buena alternativa en el manejo conservador de la espasticidad de diferente etiologia en pacientes pediatricos, recomendandose su uso previo a cirugía ortopédica