Cerebral Palsy. A Clinical and Neuropathological Study

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Figure 3 A shows 2 images through the levels of the lateral ventricles in a child with mild WMDI and a diagnosis of mild PVL who clinically has mild diplegia. In contrast, Figure 3 A also shows an image obtained at a level through the lateral ventricles of a child with severe WMDI and a diagnosis of severe PVL who has quadriplegia. When the location of the white-matter loss was investigated in the children with bilateral spastic CP, in general, those with posterior only or posterior and middle WMDI were found to have spastic diplegia.

These children were often able to walk and had some communication skills. The spastic quadriplegia group, however, mostly had damage across all areas, and virtually all could not walk and often had very limited communication skills Figure 4. Basal ganglia and thalamic damage was mainly associated with dystonic CP, which accounted for There were no children with hemiplegia. Figure 3 B shows an image at the level of thalamus and basal ganglia in a child with dyskinetic CP. Figure 3 B also shows an image of the same child at the level of the parietal lobes.

Among children with hemiplegia, Figure 3 C shows an example of a child with hand-dominated left hemiplegia who probably had an embolus in the right middle cerebral artery. This group included children with multicystic encephalomalacia and other cortical lesions. All CP types apart from ataxia were represented in this group. Thirty-two children were found to have malformations. Six of the malformations were thought to be a result of specific in utero infections, such as cytomegalovirus, which can be identified on MRI by the specific distribution of calcifications. Figure 3 D shows an image of a child with cytomegalovirus infection who clinically has spastic quadriplegia and extensive dysplasia involving large parts of both parietal lobes.

Twenty-five children 7. Some of these children may have unidentified genetic abnormalities. Forty-one of the children There may be genetic defects among this group.

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Figure 5 indicates the distribution of pathologic MRI findings in 2 groups, those born before 34 weeks of gestational age and those born at or after 34 weeks. In summary, the MRI findings relate both to the clinical description of the child and the severity of the condition. The timing of the lesion might help to define which events might have caused the CP. Not only do MRI scans help reveal the pathologic basis of the condition, but also, the findings have strong correlations with clinical findings.

This may be useful in helping parents, clinicians, and others involved in the care of children with CP to understand the nature of the children's condition and to predict their needs in the future. Our study has some important implications in relationship to possible malpractice suits. The scans can be reviewed in relationship to the pathologic findings to determine which might have been caused by some event during the delivery. Among infants born before 34 weeks, the great majority had white-matter damage.

This is often thought to be caused by obstetric malpractice, but there is little evidence for this. As pointed out by Nelson, 14 changes in obstetric practice over the last 20 years and the development of overall neonatal care during the same period have had little effect on the rate of CP. Rather, predisposing factors that include genetic factors, nutritional factors, and infections during pregnancy and before the onset of premature labor lead to placental damage developing throughout the pregnancy.

By the time this occurs, the event has reached a stage at which it cannot be affected by interventions. This may lead to premature birth and concerns about the infant. In other instances, no event is noted by the mother or her attendants, and the child is born at term with established white-matter damage. Interventions around the time of either of these events will not affect the outcome.

In our study, 54 children with white-matter damage were born after 34 weeks. These, together with the 32 children with malformations, again indicative of earlier cerebral damage, would not have been affected by perinatal processes. Of the other groups, focal infarcts are clearly not caused by obstetric events, and the 25 infants in the miscellaneous group included some infections. In the 41 children with normal MRI results, some infants probably had genetic causes for their CP, but when there is no evident lesion in the cerebral cortex, it is hard to conceive of an obstetric cause.

Thus, in our study, only Although a proportion of these may have had difficulties due to some obstetric inattention, many would not, and it seems likely that the proportion of infants who might have had damage because of obstetric malpractice within the CP population is therefore low. This study has once again emphasized the great importance of infections occurring in mothers during pregnancy. Most study centers had no access to normative data on this topic. The closest comparable population data on the incidence of urinary tract infection during pregnancy that we were able to access were through the St Mary's Maternity Information System.

Our finding that The results appear to show a raised rate of infection. This finding is also supported by the case-control study of Neufeld et al, 18 in which maternal infection was a risk factor for CP in both term and preterm infants. While there is a legitimate concern about overprescription of antibiotics, there should be no question that treating infections during pregnancy is a potential area for prevention.

A systematic approach to identifying and treating maternal infections needs to be developed, as emphasized by Nelson. Twin pregnancies are another potential area for prevention of CP. Multiple pregnancies, including pregnancies after infertility treatment, should be monitored closely, especially when other risk factors are present. Because of the lack of warning to parents at discharge from special care infant units about the risks of potential problems, delay in diagnosis and referral to an appropriate service was common.

These findings suggest that at discharge from the hospital, better arrangements should be made for the follow-up of these children, particularly as there is a possibility that further brain damage might occur after birth from, for example, nutritional effects. We think it is not unreasonable to assume that with increased awareness of possible preventive measures, over the next decade the rate of CP could be reduced substantially, thus reducing the burden on families and saving tremendous sums of money for health services.

Author Contributions: Dr Bax had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Critical revision of the manuscript for important intellectual content : Bax, Tydeman, Flodmark. Role of the Sponsor: The funders had no role in the design, collection, analysis, and interpretation of data; in the writing of the report; or in the preparation, review, or decision to submit the manuscript for publication.

Acknowledgment: We thank all those who have helped to make this research possible, especially the children, the parents, and the families who allowed their information to be used. We also thank the numerous clinicians and staff involved in the care of these children who generously gave their time and efforts to help with the study.

All Rights Reserved. Figure 1. Figure 2. Figure 3. Figure 4. WMDI indicates white-matter damage of immaturity. Figure 5. MRI indicates magnetic resonance imaging. Table 1. Several hundred contributions related to these fields and other aspects of paediatric neurology and paediatrics have been published.

They include a series of books written by Victor or by Victor and Lilly Dubowitz. Victor Dubowitz has communicated his knowledge not only in written text but also in oral communications. Victor Dubowitz not only has excellent ideas but he also put them into practice: he did not just talk about the future of the European Federation of Paediatric Neurology Societies, he also became the first president of the new European Paediatric Neurology Society and the founding editor of the European Journal of Paediatric Neurology.

Thesis: The development of the electroencephalogram in normal children and adolescents from the age of 1 through 21 years. Supervisor for PhD students in Uppsala 3 , and Oslo 1. Main interests: epilepsy, general paediatric neurology, clinical neurophysiology, genetics, headache, neurometabolic disorders, neuromuscular disorders. Born , Japan Undergraduate and postgraduate training University of Tokyo Major contributions to Paediatric Neurology Several hundred publications and a series of books have been published by professor Fukuyama, mainly in the field epilepsy and paediatric neuromuscular disorders.

It is exceptionally rare for everybody to agree that one person has had such a major impact on enhancing international collaboration in the field of paediatric neurology. Yukio Fukuyama really has built a bridge between Japanese, Asian-Ocean and European Paediatric Neurology: He has not only opened up the European and American progress in paediatric neurology to Japan but he has also opened up paediatric neurology in Japan and the Asian-Oceanic region to Europe.

Many of us have enjoyed the charming hospitality of Yukio and Mrs. Fukuyama between the books and journals in their house in Tokyo. Received her Medical Degree at University of Debrecen. Training in pediatrics, neurology and pediatric neurology at University Debrecen and at Semmelweis University , Budapest. Doctoral thesis on neonatal neurology: Budapest. Retired but still active as honorary consultant and lecturer in the Pediatric Institute of the University of Debrecen.

She has published over a hundred papers, two books and numerous book chapters, mainly in Hungarian. Main interest: neonatal neurology and epilepsy. Neil Gordon has written several hundred contributions, many relating to cortical functioning and dysfunction, for example in childhood epilepsy, and to learning and behavioural disorders. Both during scientific and clinical meetings and in his correspondence with journals, and in his superb reviews, Neil Gordon has manifested his vast knowledge of the field of paediatric neurology.

In his very gentle way, both in his oral communications and in his written comments, he has successfully put great energy into improving the quality of communicated facts and interpretations in the field of paediatric neurology.

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Intellectual disability ID is defined as impairment of general mental abilities that impacts on adaptive functioning [ 21 ]. Children mark a box when they are finished. Assessment of verbal comprehension and non-verbal reasoning when standard response mode is challenging: A comparison of different response modes and an exploration of their clinical usefulness. Audiovisual, cognitive compromise and behavioral disorders can occur. Join Our Mailing List Sign up to receive helpful resources, breaking news, and special updates from Holland Bloorview. However, the validity of these novel measures is unclear. Pediatr Neurol.

The detailed attention Neil Gordon gives to his correspondence is an example to all of us. Major contributions to Paediatric Neurology Several hundreds of papers have been published related to the topics cerebral palsy, e. The careful clinical and epidemiological study of cerebral palsy allowed Bengt Hagberg to define a population of children with typical cerebral palsy and a population of children with atypical, obviously non-cerebral palsy types of developmental disorder.

After the original publication by Rett, the first international publication on Rett syndrome was published by Hagberg in together with Jean Aicardi Paris and Karin Dias Lisbon. This was the start of a still continuing flow of clinical and scientific progress on Rett syndrome. Bengt Hagberg built a Swedish network with P.

Sourander neuropathology , the late L. Svennerholm neurochemistry and A. Erlandsson clinical genetics. Skiljedal Norway and Jean Aicardi France. His studies in acute encephalitis in childhood showed that a high proportion of encephalopathies meeting carefully applied criteria for that diagnosis were of viral origin and defined age and clinical evidence of cerebral hemisphere involvement as powerful predictors of clinical outcome.

He conceived and led a novel international multicentre randomized controlled drug trial that led to discontinuation of the use of diuretics for post-haemorrhagic ventricular dilatation PHVD in premature infants: our reports and related Cochrane review, showed that the treatment was ineffective and harmful. He played a major role in the largest published study of pseudotumour cerebri syndrome in childhood that established its epidemiology, clinical features and associated risk factors with unprecedented precision.

A treatment trial may yet follow. These showed that UNHS was an effective screen and was associated with superior language and reading skills, benefits that remained demonstrable at the age of 17 years. Many other countries have followed suit and PCHL is now by far the commonest health condition detected by newborn screening — an unusual coincidence of paediatric neurological disorder and public health issue.

Second, he led a concerted long-term effort to make measurement of quality of survival QoS a central feature of European treatment trials for childhood brain tumours. The challenge was to arrive at a single robust dataset of neuro-developmental outcome over a wide age range of children and young people. This was achieved with a framework that depended on patient-reported outcomes in multiple European languages.

Its creation, which took decades of discussion and consensus-building across Europe, was finally published in Its application has shown important differences between treatment regimens with respect to subsequent QoS. Families now provide these data on-line via their own laptops and tablets. We found several associations between demographics and clinical variables and cognitive impairment.

Older age, being a woman, lower educational attainment, and a previous diagnosis of stroke were associated with dementia status in our study and are in line with results from other studies [ 61 , 90 , 91 ]. Hypertension, coronary artery disease, higher body mass index, currently smoking, and alcohol use were more common among participants without dementia. Although paradoxal, the inverse associations between some risk factors and dementia in late life has been described before [ 92 , 93 ] and may reflect a secondary effect associated with dementia e. Our study has several advantages.

We presented clinical and neuropathological data from a large sample of individuals who had a low educational level mean education of 4 y and were of admixed race. Previous large studies included mainly white or Asian participants with high education attainment mean education of 16 y in most studies [ 9 , 78 ]. We also collected comprehensive clinical and neuropathological data that allowed us to develop the NPC score and investigate its association with cognitive and neuropsychiatric scales.

Moreover, we investigated the association between clinical symptoms and AGD, which has not been fully explored in other series [ 44 ]. In addition, the BBBABSG is a community-based autopsy study, which allows for the collection of a large number of brains from individuals with normal cognition and also an opportunity to study participants with dementia of unknown etiology. However, our results should be examined considering the study limitations. We did not follow participants during life, and clinical variables were evaluated postmortem through an interview with an informant.

To increase the reliability of these data, we included only participants who had at least weekly contact with the informant and excluded individuals when the informant provided conflicting information during the clinical interview. Second, the neuropathological criteria for the diagnosis of VaD have not been standardized through different research centers [ 47 ]. We used a conservative neuropathological criterion for VaD. In addition, some recent neuropathological diagnoses, such as chronic traumatic encephalopathy or TDP deposition [ 95 ], were not systematically investigated in our sample.

Although we assessed all individuals with an undetermined neuropathological diagnosis or a clinical diagnosis of frontotemporal dementia or primary progressive aphasia to rule out the possibility of FTLD-TDP, we only completed TDP assessment for participants. Despite the fact that TDP inclusions are found in a considerable percentage of brains of cognitively normal elderly, evidence shows that TDP inclusions in limbic structures may worsen the cognition in the context of AD [ 95 , 96 ].

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SPAS receives people who die from natural causes, and cardiac arrests are common in this population; therefore, we might have over-represented individuals with cardiovascular disease and that might have increased the frequency of cerebrovascular lesions in our sample participants with and without dementia , but it should be emphasized that cerebrovascular lesions were much more frequent in the group with dementia.

On the other hand, individuals with macroscopically detectable acute brain infarctions, hemorrhages, or trauma were underrepresented in the BBBABSG, as an immediate examination was required for the completion of the death certificate, and this fact might have decreased the frequency of cerebrovascular lesions in our sample. Unfortunately, selection bias has been found in most population-based studies on dementia. Almost half of the first individuals submitted to autopsy in the CFAS study had dementia, a much higher proportion than the one found in the general population [ 74 ], whereas the Honolulu-Asia Aging study only recruited Americans with Japanese ethnicity [ 97 ] and the Nun study only included white women [ 98 ].

The Religious Order study mainly included individuals who identified as white, and the mean age of death was higher than that of the general population [ 77 , 99 ]. Average older age at death was also present in other studies [ 20 , — ]. In conclusion, we described the association of neuropathological lesions and cognitive and neuropsychiatric outcomes in a unique sample of Brazilian individuals with low education attainment and admixed race. In concordance with previous studies, NFT deposition and high comorbidity neuropathological scores were highly associated with dementia status.

We also found a higher frequency of cerebrovascular lesions than previously described. Future clinicopathological studies with populations in LMICs are important to confirm our findings. Abstract Background Clinicopathological studies are important in determining the brain lesions underlying dementia. Conclusions NFT deposition, vascular lesions, and high NPC scorewere associated with cognitive impairment in a unique Brazilian sample with low education. Author summary Why was this study done? Definitive diagnosis of dementia etiology requires a neuropathological exam.

In high-income countries HICs , Alzheimer disease AD is the most common cause of dementia, usually coexisting with other neurodegenerative and vascular lesions. Almost no neuropathological information is available for LMICs; therefore, we investigated the frequency of neurodegenerative and cerebrovascular lesions and their correlation with cognitive and neuropsychiatric symptoms in a clinicopathological study with 1, admixed older participants from Brazil.

What did the researchers do and find? In a cross-sectional study, we described the frequency of the most common causes of dementia, as well as the correspondence between clinical and neuropathological diagnosis, in a large population-based series with 1, older adults from a LMIC. We developed a comorbidity neuropathological score to account for the association between the coexistence of cerebral lesions and cognitive and neuropsychiatric symptoms.

Forty-four percent of participants had enough neuropathological lesions to fulfill the criteria for at least one neuropathological diagnosis. Higher neuropathological comorbidity associated with worse cognition and a higher burden of neuropsychiatric symptoms. What do these findings mean? Although vascular dementia was not as frequent as AD, its frequency was relatively higher than in HIC series. Introduction In , Methods Participants Autopsy verification is mandatory in Brazil to define the cause of death for most individuals who die of natural causes. Clinicofunctional assessments and definitions Trained gerontologists supervised by a registered nurse with expertise in dementia performed the clinicofunctional assessments.

The clinicofunctional assessment lasts for about 40 min and consists of three parts: Sociodemographics age at death, sex, years of formal education, race, and the frequency of contact with the informant. Race was reported by the next-of-kin during the clinical interview, according to the following categories: white, black, brown, and other races i. Other demographic data were confirmed on government-issued documents; Past medical history hypertension, diabetes, coronary artery disease, heart failure, arrhythmia, and stroke , family history, and lifestyle data smoking habits, alcohol use, and physical activity ; Clinicofunctional and neuropsychiatric assessment.

The CDR is a five-point scale used to stage dementia severity by assessing six domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Because of the nature of this study, only the informant section of the CDR was applied. A score of 3 means no change, and a 5 means that an individual declined considerably in all items evaluated. Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory NPI [ 28 ], which evaluates frequency and severity of a wide range of neuropsychiatric symptoms delusions, hallucinations, dysphoria, anxiety, agitation, aggression, euphoria, disinhibition, irritability, lability, apathy, and aberrant motor activity.

Scores vary from 0 to points, and higher scores are associated with higher frequency and severity of symptoms. Body mass index was calculated by dividing the weight in kilos by the square of the height in meters. Dementia diagnosis followed the definitions from the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders [ 29 ].

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Neuropathological assessment and definitions Brain tissue was obtained within 24 h of death. Statistical analysis Study design and statistical analyses for this study were planned 2 y after obtaining the data. Download: PPT. Table 1. Fig 1. Table 2. Table 3. Fig 2. Fig 3. Table 4. Discussion Here we described neuropathological findings and clinical and neuropathological variables associated with cognitive impairment in a community-based sample of 1, older adults from a LMIC with broad educational attainment and admixed race background, a population profile much different compared to the samples enrolled in other neuropathologic studies conducted in developed countries.

The main findings of this study were as follows: Neurodegenerative and cerebrovascular lesions are common in older adults from a LMIC, similar to data from HICs.

Furthermore, almost one-fourth of cognitively normal individuals met the criteria for a neuropathological diagnosis, and these numbers increase progressively in participants with questionable dementia and dementia, respectively. Finally, a small fraction of individuals lack a neuropathological diagnosis to explain the cognitive impairment. NFT burden, hippocampal sclerosis, lacunar infarcts, hyaline atherosclerosis, siderocalcinosis, and LBD were independently associated with cognitive impairment.

NFT burden was the main driver of the association between higher NPC scores and worse cognitive and neuropsychiatric outcomes.

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Overlapping neuropathological lesions had an additive rather than a multiplicative impact on cognition. The clinical criteria for LBD presented the highest specificity and accuracy, although the sensibility was very poor. Both clinical criteria for AD and VaD showed a moderate accuracy. Strengths and limitations of the study Our study has several advantages. Supporting information.

S1 Checklist. S1 Fig. S1 Table. S2 Table. S3 Table. S4 Table. References 1. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement. Alzheimer's disease and vascular dementia in developing countries: prevalence, management, and risk factors. Lancet Neurology. Prevalence of dementia in Latin America: a collaborative study of population-based cohorts. International Psychogeriatrics. Classification and basic pathology of Alzheimer disease. Acta Neuropathol. Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration.

Vascular pathology in the aged human brain. Post-mortem assessment in vascular dementia: advances and aspirations.

Symptoms of Cerebral Palsy

BMC Med. Epidemiological pathology of dementia: attributable-risks at death in the Medical Research Council Cognitive Function and Ageing Study. PLoS Med. Mixed brain pathologies account for most dementia cases in community-dwelling older persons. The burden and costs of chronic diseases in low-income and middle-income countries. Prevalence of dementia subtypes in a developing country: a clinicopathological study. Clinics Sao Paulo. View Article Google Scholar Very low levels of education and cognitive reserve: a clinicopathologic study.

African ancestry protects against Alzheimer's disease-related neuropathology. Mol Psychiatry. Chronic non-communicable diseases in Brazil: burden and current challenges. Hippocampal sclerosis in advanced age: clinical and pathological features. Neuropathological correlates of dementia in overyear-old brain donors from the population-based Cambridge city overs cohort CC75C study. J Alzheimers Dis. Frequency of dementia etiologies in four ethnic groups.