Differences Among Native Hawaiian, Asian, and White Patients with Progressive Supranuclear Palsy.

BACKGROUND: Most studies of progressive supranuclear palsy (PSP) have been conducted in White populations. OBJECTIVE: The objective of this study was to identify whether differences exist for patients with PSP among Whites, East Asians (EAs), and Native Hawaiians/Pacific Islanders (NHPIs) in Hawaii. METHODS: We conducted a single-center, retrospective study of patients meeting Movement Disorder Society probable PSP criteria (2006-2021). Data variables included age of onset and diagnosis, comorbidities, and survival rate. Variables were compared across groups using Fisher's exact test, Kruskal-Wallis rank sum test, and log-rank tests. RESULTS: A total of 94 (59 EAs, 9 NHPIs, 16 Whites, and 10 Others) patients were identified. Mean age ± standard deviation (in years) of symptom onset/diagnosis were both youngest in NHPIs (64.0 ± 7.2/66.3 ± 8.0) followed by Whites (70.8 ± 7.6/73.9 ± 7.8), then EAs (75.9 ± 8.2/79.2 ± 8.3) (P < 0.001). Median survival from diagnosis was significantly lower (P < 0.05) in NHPIs (2 years) compared with EAs (4 years) and Whites (6 years). CONCLUSIONS: There may be racial disparities for PSP, and studies are needed to identify genetic, environmental, and socioeconomic contributions. © 2023 International Parkinson and Movement Disorder Society.

Prognostic Discrepancy on Overall Survival Between Ambulatory and Nonambulatory Patients with Metastatic Spinal Cord Compression.

BACKGROUND: Contradictory results have been reported regarding the prognostic effect of ambulatory status in patients with metastatic spinal cord compression (MSCC). The aim of this study was to investigate whether ambulatory status is a significant predictor of overall survival in patients with MSCC and to distinguish the differences of predictors between patients who were ambulatory and those who were not ambulatory before operation. METHODS: Three clinical centers were retrospectively reviewed to identify patients operated on for MSCC between 2005 and 2015. Fourteen prognostic factors were analyzed using Kaplan-Meier survival curves, univariate log-rank test, and multivariate Cox hazard regression model for the whole cohort and the subgroups of ambulatory and nonambulatory patients. RESULTS: In all, 169 patients were consecutively enrolled. Their mean age was 59.6 ± 10.5 years (range, 18-84 years). The median survival time in the whole cohort was 7.0 ± 0.5 months, whereas it was 7.0 ± 0.8 months and 5.0 ± 1.3 months in ambulatory and nonambulatory patients, respectively. Multivariate Cox regression analysis showed that ambulatory status was not a significant predictor of overall survival (P = 0.266), but primary tumor type and Karnofsky performance status were independent predictors of overall survival for the whole cohort. Primary tumor and metastatic site were significantly associated with survival in ambulatory patients. Gender and Karnofsky performance status were associated with survival in nonambulatory patients. CONCLUSIONS: Ambulatory status was not shown to predict the prognosis of patients with MSCC. prognostic factors should be distinguished between ambulatory and nonambulatory patients when choosing a therapeutic modality.

Motoric cognitive risk syndrome and mortality: results from the EPIDOS cohort.

BACKGROUND AND PURPOSE: Cognitive impairment, slow walking speed and motoric cognitive risk syndrome (MCR) have separately been associated with an increased risk for mortality in the short term. The aim of the study was to examine the association of MCR and its components [i.e. subjective cognitive complaint (SCC) and slow walking speed] with short-, medium- and long-term mortality in older community-dwellers. METHODS: In all, 3778 participants from the Epidémiologie de l'Ostéoporose (EPIDOS) study were selected. MCR was defined as the combination of slow walking speed and SCC in participants without major neurocognitive disorders. Deaths were prospectively recorded using mail, phone calls, questionnaires and/or the French national death registry at 5, 10, 15 and 19 (end of follow-up period) years. RESULTS: Over the follow-up of 19 years, 80.5% (n = 3043) participants died. Slow walking speed and MCR were associated with mortality [hazard ratio (HR) 1.20 with P = 0.004 for slow walking speed and HR = 1.26 with P = 0.002 for MCR at 10 years; HR = 1.27 with P ≤ 0.001 for slow walking speed and HR = 1.22 with P = 0.001 for MCR at 15 years; HR = 1.41 with P ≤ 0.001 at 19 years for slow walking speed and MCR]. There was no association between SCC and mortality. Kaplan-Meier distributions of mortality showed that participants with MCR and slow walking speed died earlier compared to healthy participants and those with SCC (P < 0.001). CONCLUSIONS: Slow walking speed and MCR were associated with an increased risk for mortality at the medium and long term, whereas no association was found with SCC.

Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: a prospective cohort study.

BACKGROUND: Glucocorticoid treatment is recommended as a standard of care in Duchenne muscular dystrophy; however, few studies have assessed the long-term benefits of this treatment. We examined the long-term effects of glucocorticoids on milestone-related disease progression across the lifespan and survival in patients with Duchenne muscular dystrophy. METHODS: For this prospective cohort study, we enrolled male patients aged 2-28 years with Duchenne muscular dystrophy at 20 centres in nine countries. Patients were followed up for 10 years. We compared no glucocorticoid treatment or cumulative treatment duration of less than 1 month versus treatment of 1 year or longer with regard to progression of nine disease-related and clinically meaningful mobility and upper limb milestones. We used Kaplan-Meier analyses to compare glucocorticoid treatment groups for time to stand from supine of 5 s or longer and 10 s or longer, and loss of stand from supine, four-stair climb, ambulation, full overhead reach, hand-to-mouth function, and hand function. Risk of death was also assessed. This study is registered with ClinicalTrials.gov, number NCT00468832. FINDINGS: 440 patients were enrolled during two recruitment periods (2006-09 and 2012-16). Time to all disease progression milestone events was significantly longer in patients treated with glucocorticoids for 1 year or longer than in patients treated for less than 1 month or never treated (log-rank p<0·0001). Glucocorticoid treatment for 1 year or longer was associated with increased median age at loss of mobility milestones by 2·1-4·4 years and upper limb milestones by 2·8-8·0 years compared with treatment for less than 1 month. Deflazacort was associated with increased median age at loss of three milestones by 2·1-2·7 years in comparison with prednisone or prednisolone (log-rank p<0·012). 45 patients died during the 10-year follow-up. 39 (87%) of these deaths were attributable to Duchenne-related causes in patients with known duration of glucocorticoids usage. 28 (9%) deaths occurred in 311 patients treated with glucocorticoids for 1 year or longer compared with 11 (19%) deaths in 58 patients with no history of glucocorticoid use (odds ratio 0·47, 95% CI 0·22-1·00; p=0·0501). INTERPRETATION: In patients with Duchenne muscular dystrophy, glucocorticoid treatment is associated with reduced risk of losing clinically meaningful mobility and upper limb disease progression milestones across the lifespan as well as reduced risk of death. FUNDING: US Department of Education/National Institute on Disability and Rehabilitation Research; US Department of Defense; National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases; and Parent Project Muscular Dystrophy.

Long-term outcome of abusive head trauma.

Abusive head trauma is a severe inflicted traumatic brain injury, occurring under the age of 2 years, defined by an acute brain injury (mostly subdural or subarachnoidal haemorrhage), where no history or no compatible history with the clinical presentation is given. The mortality rate is estimated at 20-25% and outcome is extremely poor. High rates of impairments are reported in a number of domains, such as delayed psychomotor development; motor deficits (spastic hemiplegia or quadriplegia in 15-64%); epilepsy, often intractable (11-32%); microcephaly with corticosubcortical atrophy (61-100%); visual impairment (18-48%); language disorders (37-64%), and cognitive, behavioral and sleep disorders, including intellectual deficits, agitation, aggression, tantrums, attention deficits, memory, inhibition or initiation deficits (23-59%). Those combined deficits have obvious consequences on academic achievement, with high rates of special education in the long term. Factors associated with worse outcome include demographic factors (lower parental socioeconomic status), initial severe presentation (e.g., presence of a coma, seizures, extent of retinal hemorrhages, presence of an associated cranial fracture, extent of brain lesions, cerebral oedema and atrophy). Given the high risk of severe outcome, long-term comprehensive follow-up should be systematically performed to monitor development, detect any problem and implement timely adequate rehabilitation interventions, special education and/or support when necessary. Interventions should focus on children as well as families, providing help in dealing with the child's impairment and support with psychosocial issues. Unfortunately, follow-up of children with abusive head trauma has repeatedly been reported to be challenging, with very high attrition rates.

Early hyperglycemia is associated with poor gross motor outcome in asphyxiated term newborns.

BACKGROUND: Hyperglycemia after ischemic stroke in adults and after near-drowning in children is associated with a poor neurological outcome. Anaerobic metabolism of glucose leads to buildup of lactic acid, free radical production, mitochondrial failure, and ultimately an increase in neurological injury. In asphyxiated infants, high lactate peaks are seen in the basal ganglia with magnetic resonance spectroscopy. Because motor disability in asphyxiated full-term newborns often relates to injury in the basal ganglia, we hypothesized that hyperglycemia and associated buildup of lactic acid may lead to worse gross motor outcome. METHODS: Glucose, blood gas values, and demographic data were abstracted from the medical records of 41 term infants with asphyxia and without confounding diagnoses. Their Gross Motor Function Classification System scores were determined from the medical record or by structured telephone interviews. RESULTS: The outcomes of 14 infants were considered poor on the basis of death within the first 6 months or moderate-to-severe cerebral palsy (Gross Motor Function Classification System score 1-5). The other 27 infants had no gross motor disability (Gross Motor Function Classification System score 0). The highest recorded blood glucose correlated with poor outcome (P = 0.046 by logistic regression). Infants with hyperglycemia (blood glucose > 150 mg/dL) were more likely to have poor outcome (P = 0.017; odds ratio: 5.9; 95% confidence interval: 1.4-24.7). CONCLUSIONS: High blood glucose in the first 12 hours is associated with poor gross motor outcome in this cohort of asphyxiated term infants. Clinicians should avoid hyperglycemia in managing term infants with asphyxia.

Evaluation of destructive effects of exposure to cisplatin during developmental stage: no profound evidence for sex differences in impaired motor and memory performance.

We have elucidated the alteration in hippocampal and cerebellum function following chronic cisplatin treatment in male and female rats. Hippocampus and cerebellum related behavioral dysfunction in cisplatin-treated [intraperitoneally, 5 mg/(kg/week) for 5 weeks from 23-day-old] rats were analyzed using explorative, motor function, learning, and memory tasks (grasping, rotarod, open field, and Morris water maze tests). Exposure to cisplatin impaired the motor coordination in male and female rats. Exposure to cisplatin was reflected by a decrease in grasping time compared to vehicle-treated controls (saline) only in male rat while there were not any differences in female rats. When the rearing frequency, total distance moved and velocity of their recorded in open fieldtest, both males and females were dramatically affected by exposure to cisplatin. Compared to the saline, male and female rats trained 5 weeks after cisplatin injection showed significant memory deficits in the Morris water maze test. However, hippocampal and cerebellum functions of male and female rats were profoundly affected by exposure to cisplatin while no sex differences in the most variable were evident.

Prevalencia de enfermedades que afectan las potencialidades del movimiento y el desempeño funcional en adultos mayores institucionalizados / Prevalence of diseases affecting movement and functional performance in elderly institutionalized

Introducción. El proceso de envejecimiento genera en su presentación cambios fisiológicos que pueden favorecer la ocurrencia de enfermedades que dentro de sus características van a repercutir en mayor o menor medida sobre las capacidades funcionales y desempeños. Objetivo. Establecer la prevalencia con la que se dan enfermedades que afectan las potencialidades del movimiento y el desempeño funcional en adultos mayores institucionalizados. Método. Se desarrolló un estudio transversal tomando de un censo la totalidad de adultos mayores que aparecían en los registros estadísticos de atención de Fisioterapia de las prácticas del Programa de Fisioterapia de la Universidad Manuela Beltrán en el mes de febrero de 2011, y a partir de lo anterior se calcularon las prevalencias de las entidades. Resultados. Un 41,3% (n=50, error estándar=0,04) de las afecciones atendidas que repercuten en las potencialidades del movimiento comprometían al sistema musculoesquelético, un 30,57% (n=37, error estándar=0,05) afectaban el sistema nervioso, y un 18,18% (n=22, error estándar=0,07) al sistema cardiopulmonar. Conclusiones. Las principales entidades atendidas en Fisioterapia que limitan las potencialidades del movimiento en el adulto mayor institucionalizado son las que afectan elementos del sistema musculoesquelético (AU)

Introduction: The presence of the aging process generates physiological changes. These changes may favor the occurrence of diseases whose characteristics will have a repercussion, to a greater or lesser extent, on the subject’s functional capabilities and performance. Objective: To determine the prevalence of diseases that affect the motion potential and functional performance in the elderly institutionalized subjects. Method: A cross-sectional study was carried out through a census of all elderly adults who were included in the statistical records of Physiotherapy care practices of the Physiotherapy Program at the University Manuela Beltrán in the month February 2011. Based on the above, prevalence was calculated. Results: A total of 41.3% (n = 50, standard error = 0.04) of the conditions seen that have a repercussion on the motion potentialities affect the musculoskeletal system, 30.57% (n = 37, standard error = 0.05) affect the nervous system and 18.18% (n = 22, standard error = 0.07) the cardiopulmonary system. Conclusions: The main conditions treated in physiotherapy that limit potential movement in the institutionalized elderly subject are those that affect the musculoskeletal system(AU)

Movement disorder emergencies in childhood.

The literature on paediatric acute-onset movement disorders is scattered. In a prospective cohort of 52 children (21 male; age range 2mo-15y), the commonest were chorea, dystonia, tremor, myoclonus, and Parkinsonism in descending order of frequency. In this series of mainly previously well children with cryptogenic acute movement disorders, three groups were recognised: (1) Psychogenic disorders (n = 12), typically >10 years of age, more likely to be female and to have tremor and myoclonus (2) Inflammatory or autoimmune disorders (n = 22), including N-methyl-d-aspartate receptor encephalitis, opsoclonus-myoclonus, Sydenham chorea, systemic lupus erythematosus, acute necrotizing encephalopathy (which may be autosomal dominant), and other encephalitides and (3) Non-inflammatory disorders (n = 18), including drug-induced movement disorder, post-pump chorea, metabolic, e.g. glutaric aciduria, and vascular disease, e.g. moyamoya. Other important non-inflammatory movement disorders, typically seen in symptomatic children with underlying aetiologies such as trauma, severe cerebral palsy, epileptic encephalopathy, Down syndrome and Rett syndrome, include dystonic posturing secondary to gastro-oesophageal reflux (Sandifer syndrome) and Paroxysmal Autonomic Instability with Dystonia (PAID) or autonomic 'storming'. Status dystonicus may present in children with known extrapyramidal disorders, such as cerebral palsy or during changes in management e.g. introduction or withdrawal of neuroleptic drugs or failure of intrathecal baclofen infusion; the main risk in terms of mortality is renal failure from rhabdomyolysis. Although the evidence base is weak, as many of the inflammatory/autoimmune conditions are treatable with steroids, immunoglobulin, plasmapheresis, or cyclophosphamide, it is important to make an early diagnosis where possible. Outcome in survivors is variable. Using illustrative case histories, this review draws attention to the practical difficulties in diagnosis and management of this important group of patients.

The natural course of gross motor deterioration in metachromatic leukodystrophy.

AIM: Motor deterioration is a key feature in metachromatic leukodystrophy (MLD). The lack of data about its natural course impedes evaluation of therapeutic interventions. This study aimed to provide data about motor decline in MLD. METHOD: Fifty-nine patients (27 males, 32 females) with MLD (21 with late-infantile MLD and 38 with juvenile MLD) were recruited within a nationwide survey (the German LEUKONET). Median (range) age at onset was 17 months (9-27) for the group with late-infantile MLD and 6 years 2 months (2y 11mo-14y) for the group with juvenile MLD. Gross motor function was assessed using the Gross Motor Function Classification for MLD. RESULTS: In late-infantile MLD, all patients showed loss of all gross motor function until 3 years 4 months of age. Patients with juvenile MLD showed a more variable and significantly longer motor decline (p<0.001). For a patient with the juvenile form showing first gait disturbances, the probability of remaining stable for more than 1 year was 84%, and 51% for more than 2 years. Having lost independent walking, subsequent motor decline was as steep as in the late-infantile form (median 5 mo, interquartile range 3-22). INTERPRETATION: The course of motor disease was more variable in juvenile MLD with respect to onset and dynamics. However, the motor decline after the loss of independent walking was similarly steep in both forms. These data can serve as a reference for clinical studies that are topics of current research and allow definition of inclusion/exclusion criteria.

Wild-type human TDP-43 expression causes TDP-43 phosphorylation, mitochondrial aggregation, motor deficits, and early mortality in transgenic mice.

Transactivation response DNA-binding protein 43 (TDP-43) is a principal component of ubiquitinated inclusions in frontotemporal lobar degeneration with ubiquitin-positive inclusions and in amyotrophic lateral sclerosis (ALS). Mutations in TARDBP, the gene encoding TDP-43, are associated with sporadic and familial ALS, yet multiple neurodegenerative diseases exhibit TDP-43 pathology without known TARDBP mutations. While TDP-43 has been ascribed a number of roles in normal biology, including mRNA splicing and transcription regulation, elucidating disease mechanisms associated with this protein is hindered by the lack of models to dissect such functions. We have generated transgenic (TDP-43PrP) mice expressing full-length human TDP-43 (hTDP-43) driven by the mouse prion promoter to provide a tool to analyze the role of wild-type hTDP-43 in the brain and spinal cord. Expression of hTDP-43 caused a dose-dependent downregulation of mouse TDP-43 RNA and protein. Moderate overexpression of hTDP-43 resulted in TDP-43 truncation, increased cytoplasmic and nuclear ubiquitin levels, and intranuclear and cytoplasmic aggregates that were immunopositive for phosphorylated TDP-43. Of note, abnormal juxtanuclear aggregates of mitochondria were observed, accompanied by enhanced levels of Fis1 and phosphorylated DLP1, key components of the mitochondrial fission machinery. Conversely, a marked reduction in mitofusin 1 expression, which plays an essential role in mitochondrial fusion, was observed in TDP-43PrP mice. Finally, TDP-43PrP mice showed reactive gliosis, axonal and myelin degeneration, gait abnormalities, and early lethality. This TDP-43 transgenic line provides a valuable tool for identifying potential roles of wild-type TDP-43 within the CNS and for studying TDP-43-associated neurotoxicity.

Survival prognosis of Japanese with severe motor and intellectual disabilities living in public and private institutions between 1961 and 2003.

BACKGROUND: Although the prognosis for survival in people with severe functional disabilities is a serious concern for their families and health care practitioners, there have been few reports on survival rates for this population. Every year, the Japanese Association of Welfare for Persons with Severe Motor and Intellectual Disability collects anonymous records of individual registrations and deaths from all private and public institutions, excepting national institutions. We used these data to estimate the prognosis for survival. METHODS: We reviewed the records of 3221 people with severe motor and intellectual disabilities (SMID); all subjects had lived in one of 119 public or private institutions in Japan between 1961 and 2003. Kaplan-Meier survival estimates were calculated according to disability type and birth year range. RESULTS: Of the 3221 persons, 2645 were alive and 576 had died. The survival rate at the age of 20 for all subjects was 79% (95% confidence interval, 78%-81%). Among people who were unable to sit, those with lower intelligence quotients had lower survival rates. CONCLUSIONS: The survival rate among people with SMID housed in public and private institutions in Japan was much worse than that of the general population, and has not improved since the 1960s.

Clinical evaluation and follow-up outcome of diffusion tensor imaging-based functional neuronavigation: a prospective, controlled study in patients with gliomas involving pyramidal tracts.

OBJECTIVE: To evaluate diffusion tensor imaging (DTI)-based functional neuronavigation in surgery of cerebral gliomas with pyramidal tract (PT) involvement with respect to both perioperative assessment and follow-up outcome. METHODS: A prospective, randomized controlled study was conducted between 2001 and 2005. A consecutive series of 238 eligible patients with initial imaging diagnosis of cerebral gliomas involving PTs were randomized into study (n = 118) and control (n = 120) groups. The study cases underwent DTI and three-dimensional magnetic resonance imaging scans. The maps of fractional anisotropy were calculated for PT mapping. Both three-dimensional magnetic resonance imaging data sets and fractional anisotropy maps were integrated by rigid registration, after which the tumor and adjacent PT were segmented and reconstructed for presurgical planning and intraoperative guidance. The control cases were operated on using routine neuronavigation. RESULTS: There was a trend for high-grade gliomas (HGGs) in the study group to be more likely to achieve gross total resection (74.4 versus 33.3%, P < 0.001). There was no significant difference of low-grade gliomas resection between the two groups. Postoperative motor deterioration occurred in 32.8% of control cases, whereas it occurred in only 15.3% of the study cases (P < 0.001). The 6-month Karnofsky Performance Scale score of study cases was significantly higher than that of control cases (86 +/- 20 versus 74 +/- 28 overall, P < 0.001; 93 +/- 10 versus 86 +/- 17 for low-grade gliomas, P = 0.013; and 77 +/- 27 versus 53 +/- 32 for HGGs, P = 0.001). For 81 HGGs, the median survival of study cases was 21.2 months (95% confidence interval, 14.1-28.3 mo) compared with 14.0 months (95% confidence interval, 10.2-17.8 mo) of control cases (P = 0.048). The estimated hazard ratio for the effect of DTI-based functional neuronavigation was 0.570, representing a 43.0% reduction in the risk of death. CONCLUSION: DTI-based functional neuronavigation contributes to maximal safe resection of cerebral gliomas with PT involvement, thereby decreasing postoperative motor deficits for both HGGs and low-grade gliomas while increasing high-quality survival for HGGs.

The HD mutation causes progressive lethal neurological disease in mice expressing reduced levels of huntingtin.

Huntingtin is an essential protein that with mutant polyglutamine tracts initiates dominant striatal neurodegeneration in Huntington's disease (HD). To assess the consequences of mutant protein when huntingtin is limiting, we have studied three lines of compound heterozygous mice in which both copies of the HD gene homolog (Hdh) were altered, resulting in greatly reduced levels of huntingtin with a normal human polyglutamine length (Q20) and/or an expanded disease-associated segment (Q111): Hdh(neoQ20)/Hdh(neoQ20), Hdh(neoQ20)/Hdh(null) and Hdh(neoQ20)/Hdh(neoQ111). All surviving mice in each of the three lines were small from birth, and had variable movement abnormalities. Magnetic resonance micro-imaging and histological evaluation showed enlarged ventricles in approximately 50% of the Hdh(neoQ20)/Hdh(neoQ111) and Hdh(neoQ20)/Hdh(null) mice, revealing a developmental defect that does not worsen with age. Only Hdh(neoQ20)/Hdh(neoQ111) mice exhibited a rapidly progressive movement disorder that, in the absence of striatal pathology, begins with hind-limb clasping during tail suspension and tail stiffness during walking by 3-4 months of age, and then progresses to paralysis of the limbs and tail, hypokinesis and premature death, usually by 12 months of age. Thus, dramatically reduced huntingtin levels fail to support normal development in mice, resulting in reduced body size, movement abnormalities and a variable increase in ventricle volume. On this sensitized background, mutant huntingtin causes a rapid neurological disease, distinct from the HD-pathogenic process. These results raise the possibility that therapeutic elimination of huntingtin in HD patients could lead to unintended neurological, as well as developmental side-effects.

Progressive versus catastrophic loss of the ability to walk: implications for the prevention of mobility loss.

OBJECTIVES: Loss of mobility is an important functional outcome that can have devastating effects on quality of life and the ability of older persons to remain independent in the community. Although a large amount of research has been done on risk factors for disability onset, little work has focused on the pace of disability progression. This study characterizes the development of severe walking disability over time and evaluates risk factors and subsequent mortality as they relate to mobility disability with progressive or catastrophic onset. DESIGN: Population-based prospective cohort study with annual follow-up assessments for up to 7 years SETTING: Three communities of the Established Populations for Epidemiologic Studies of the Elderly. PARTICIPANTS: There were 5,355 persons not disabled at baseline and the first follow-up who had adequate data available to classify mobility disability during subsequent follow-ups. MEASUREMENTS: Severe mobility disability was defined as the need for help from a person to walk across a room or inability to walk across a room. Those developing severe mobility disability were classified as having progressive mobility disability if they had been unable to walk half a mile in either of the prior 2 years. They were classified as having catastrophic mobility disability if they reported having been able to walk half a mile in two previous annual interviews. RESULTS: The overall incidence of severe mobility disability was 11.6 cases/1,000 person years. Those age 85 and older or having three or more chronic conditions at baseline were significantly more likely to develop progressive disability than catastrophic disability. Stroke, hip fracture, and cancer occurring during follow-up were associated with very high risk of severe mobility disability. For stroke and hip fracture, the risk was twice as high for catastrophic disability as for progressive disability, but this difference did not reach statistical significance. Risk for catastrophic disability from cancer was significantly greater than for progressive disability. Half of catastrophic disability subjects had stroke, hip fracture, or cancer in the year immediately preceding this disability. Incident heart attack did not predict severe mobility disability. Among those who developed severe mobility disability, type of disability did not influence subsequent survival for the first 3 years, but beyond 3 years those with catastrophic disability had a relative risk of death of 0.4 (95% confidence interval 0.2-0.9) compared with those with progressive disability. CONCLUSION: The observation that risk factors and mortality outcomes were both different for progressive and catastrophic mobility disability supports the value of ascertaining the pace of disability development as a useful characterization of disability. Further progress in developing prevention and treatment strategies may be made by taking the pace of disability development into account.

Persistent mobility deficit in the absence of deficits in activities of daily living: a risk factor for mortality.

OBJECTIVES: To investigate the extent to which self-reported mobility deficit in the absence of impairment in activities of daily living (ADL) is associated with elevated mortality risk. DESIGN: Prospective cohort study, with annual assessments of mobility and ADL status and ongoing monitoring of vital status. SETTING: Population-based cohort drawn from Medicare enrollees in New York City. PARTICIPANTS: One thousand two hundred ninety-eight older adults reporting functional status at baseline (1992-1994) and 2 years later. MEASUREMENTS: Subjects reported mobility (e.g., walking, climbing stairs, and rising from a chair) and ADL (e.g., bathing, toilet use, dressing, grooming, and feeding) limitations. Two-year functional status trajectories were noted. We used two additional follow-up periods, at 2 and 4 years, to examine the likelihood that older people with mobility deficit may face an increased risk of death without first passing through a state of enduring ADL disability. RESULTS: At 2 years, 12.7% had incident mobility deficit without ADL disability, and 21.3% were persistently disabled in mobility without ADL disability. Relative to subjects free of disability at baseline and follow-up, risk of mortality in the incident mobility deficit group was elevated at 2 and 4 years but did not achieve statistical significance. By contrast, for subjects with persistent mobility impairment who did not report ADL impairment, the mortality risk was significantly elevated both at 2 years (relative risk (RR) = 2.5; 95% confidence interval (CI) = 1.1-5.7)) and 4 years (RR = 2.9; 95% CI = 1.7-4.9)) of follow-up. Mortality was significantly elevated in this group in analyses restricted to respondents with no or only one comorbid condition. CONCLUSION: Continuing, self-reported mobility impairment in the absence of ADL deficit is a risk factor for mortality. Older people with self-reported mobility deficit face an increased risk of mortality without first passing through enduring states of ADL disability.

Predictors of survival among elders suffering strokes in Taiwan: observation from a nationally representative sample.

BACKGROUND AND PURPOSE: Cerebrovascular disease was the leading cause of death in Taiwan from 1963 to 1982. Deaths due to stroke now rank second only to cancer, with more deaths resulting from strokes than from any other single pathology. It is important to understand stroke prognosis among elderly stroke survivors, with respect to survival and attendant predictive factors, because aged population in Taiwan is growing rapidly. The aim of the present study was to discern factors affecting survival in stroke patients from a nationally representative elderly sample. METHODS: A total of 99 stroke survivors, from a representative national sample of elders aged >/=65 years on December 31, 1988, whose strokes occurred in the period 1989-1993, were followed for mortality until July 1, 1995. Personal data were gathered through home interviews conducted by well-trained community nurses, and mortality data were obtained from the national census office by using identification card numbers. Cox proportional hazards regression analysis and the stepwise technique were used to search for important prognostic factors of survival. RESULTS: Women experienced a higher mortality rate (139.8 per 1000 person-years) than men (126.4 per 1000 person-years), as age-adjusted for World Health Organization world-population figures. Stroke patients who received continuous treatment for diabetes experienced mortality risks similar to those of patients without diabetes and much lower risks than those with discontinuous diabetes treatment. Cognitive impairment was also an independent predictor of survival (relative risk 2.69, P<0.05). In addition, patients with both cognitive and mobility impairments had a 2- to 3-fold greater risk of mortality than those with only a single abnormality. CONCLUSIONS: This first report on the various prognostic factors related to survival of elderly stroke patients in Taiwan's Chinese population emphasized the benefit of continuous diabetes treatment in improving survival chances. These stroke patients should also be monitored for cognitive and mobility impairments and undergo rehabilitation.

Sex differences in the prevalence of mobility disability in old age: the dynamics of incidence, recovery, and mortality.

OBJECTIVES: This study examined sex differences in the prevalence of mobility disability in older adults according to the influences of three components of prevalence: disability incidence, recovery from disability, and mortality. METHODS: Participants in a population-based study of older adults from three communities in the United States (N = 10,263) were studied for up to 7 years. Life table methods were used to estimate the influence of each of the three components of disability prevalence in women and men. Sex differences in probabilities for transition states were measured by relative risks derived from a single model using a Markov chain approach. RESULTS: The proportion of disabled women increased from 22% of women aged 70 years to 81% of those aged 90 years. In men, comparable figures were 15% and 57%. Incidence had the greatest impact on the sex differences in disability prevalence until age 90 and older when recovery rates had a greater impact on differences in prevalence. Mortality differences in men and women had only a modest impact on sex differences in disability prevalence. These findings initially seemed to contradict striking sex differences observed in the relative risks for mortality in men compared with women. Subsequent graphical analyses showed that incidence rather than recovery or mortality largely accounted for sex differences in disability prevalence in old age. CONCLUSION: Disability incidence, recovery from disability, and mortality dynamically influence the sex differences in the prevalence of mobility disability. However, incidence has the greatest impact overall on the higher prevalence of disability in women compared with men.

Riluzole protects from motor deficits and striatal degeneration produced by systemic 3-nitropropionic acid intoxication in rats.

The putative neuroprotective effect of riluzole was investigated in a rat model of progressive striatal neurodegeneration induced by prolonged treatment (three weeks, intraperitoneal) with 3-nitropropionic acid, an irreversible inhibitor of succinate dehydrogenase. Quantitative analysis of motor behaviour indicated a significant protective effect (60%) of riluzole (8 mg/kg/day) on 3-nitropropionic acid-induced motor deficits as assessed using two independent motor tests. Furthermore, quantitative analysis of 3-nitropropionic acid-induced lesions indicated a significant 84% decrease in the volume of striatal damage produced by 3-nitropropionic acid, the neuroprotective effect apparently being more pronounced in the posterior striatum and pallidum. In addition, it was checked that this neuroprotective effect of riluzole against systemic 3-nitropropionic acid did not result from a decreased bioavailability of the neurotoxin or a direct action of riluzole on 3-nitropropionic acid-induced inhibition of succinate dehydrogenase. We found that riluzole significantly decreased by 48% the size of striatal lesions produced by stereotaxic intrastriatal injection of malonate, a reversible succinate dehydrogenase inhibitor. Furthermore, the inhibition of cortical and striatal succinate dehydrogenase activity induced by systemic 3-nitropropionic acid was left unchanged by riluzole administration. The present results, consistent with a beneficial effect of riluzole in amyotrophic lateral sclerosis, suggest that this compound may be useful in the treatment of chronic neurodegenerative diseases.

[A clinical study of death in profound mental retardation with motor disturbance].

Among 848 cases of profound mental retardation with motor disturbance admitted to Metropolitan Medical Center of Severely Handicapped in the last 20 years, 98 died. The 94 cases whose cause of death was determined were clinically investigated. There was no difference in sex, and 72% of the patients died before the age of 15 years. Half of the patients died of pneumonia; sudden death occurred in 9, and ileus in 8. These three were thought to be the most important and characteristic causes of death in severely handicapped patients. In recent years, deaths due to pneumonia have decreased and those due to ileus have disappeared, but deaths due to malignant neoplasm have begun to be recognized. There were also some deaths from intracranial hemorrhage in young children, and some deaths from tracheal bleeding in those who had tracheal tubes. These two were also important causes of death in the patients. Sudden death had certain characteristics: most cases were adolescent or young patients with mixed quadriplegia who were sensitive to environmental changes and often showed marked hypertonia by athetosis, and in addition, all of their acute changes occurred between 5 and 8 a.m. or between 6 and 9 p.m.