Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0848771 (neurological disability)
 928 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent effective treatments for subacute sclerosing panencephalitis (SSPE) are oral inosiplex and intrathecal interferon therapy. The former seems to be effective for life expectancy but not for neurological disability, and the latter is a debating antiviral treatment although favorable reports are increasing. A 12 year-10 month-old boy with SSPE was presented as a successful case of prolonged effectiveness in both neurological symptoms and life expectancy. There are no significant side effects by the 200 weeks treatment of intrathecal alpha-interferon of large dose (6 million unit/dose/week) and ordinary dose of inosiplex (100 mg/kg/day). Neurological disability index (Dyken) improved from 70% to 10%; speech and higher cerebral functions improved from aphasia and almost vegetative states to verbal communicable level; motor dysfunction from bedridden to wheel chair level; and myoclonic and other seizures were controlled. Laboratory data also improved; periodic synchronized discharge (PSD) and other paroxysmal discharges disappeared and alpha activity that had once disappeared in the background activity of active stages reappeared in the EEGs. Measles antibodies in serum and CSF improved, and oligoclonal bands disappeared. However diffuse brain atrophy remained on neuroimaging. Long-term intrathecal large dose treatment with alpha-interferon is effective and safe. It should be started as soon as the diagnosis is made, and a trial of large-dose and long-term therapy may be worthy even for more advanced cases irrespective of progress of neuroimages.
 ...
PMID:[Successful treatment of subacute sclerosing panencephalitis with long-term intrathecal large dose of alpha-interferon--a case report]. 754 89

The objectives of the present study was to correlate the segmented magnetic resonance imaging (MRI) volumes of intracranial cerebrospinal fluid (CSF) spaces (expressing the extent of brain atrophy) and cerebral plaques with the neurological disability in secondary progressive multiple sclerosis (MS). Earlier studies have mainly correlated MS plaques and neurological disability measured by expanded disability status scale (EDSS). The data on the association between brain atrophy and EDSS or regional functional scoring scale (RFSS) are very limited. We measured the volumes of intracranial CSF spaces in 28 patients with secondary progressive MS using MRI, and semiautomatic segmentation software. The volumes of T1-weighted hypointense and T2-weighted hyperintense MS plaques were also measured. In multiple regression analysis, increasing volumes of total (P=0.006) and relative (P=0.005) intracranial CSF spaces were significantly associated with worsening neurological disability as expressed by EDSS. No associations were found between these intracranial CSF space volumes and total RFSS scores. The mean volume of T2-weighted plaques showed a tendency to associate with total RFSS score (r=0.40, P=0.03), but no correlations were detected between T1- or T2-weighted plaque volumes and EDSS. The application of a new segmentation technique in quantifying intracranial cerebrospinal fluid spaces allowed an exact and sensitive way of assessing brain atrophy. The associations between brain atrophy and neurological disability expressed by EDSS suggests that the effect of MS therapies should be evaluated by measurement of brain atrophy.
 ...
PMID:Volumes of brain atrophy and plaques correlated with neurological disability in secondary progressive multiple sclerosis. 1042 45

In primary progressive multiple sclerosis (PPMS) abnormalities in brain magnetic resonance imaging (MRI) differ from abnormalities in other subtypes of multiple sclerosis (MS). It was investigated whether the extent of brain and spinal cord MRI abnormalities is reflected in the neurological disability in PPMS. Focal and diffuse changes and atrophy in central nervous system (CNS) in patients with PPMS (n = 28) and healthy controls (n = 20) were assessed by semi-automatic MRI segmentation and volumetric analysis. The measurements were related to neurological disability as expressed by the expanded disability status scale (EDSS), the regional functional scoring system (RFSS), the arm index and the ambulation index. Plaques in T1- and/or T2-weighted images were seen in all brains, while spinal plaques were detected in 23 of 28 patients (82%). The total volumes of brain and spinal cord were significantly smaller in patients than in controls (P = 0.001 and 0.000, respectively). The volumes of T1 or T2 lesions in the brain correlated to the ambulation index (r = 0.51, P = 0.005 and r = 0.53, P = 0.004, respectively). No correlations were detected between MRI measurements and total EDSS score, but relative brain atrophy correlated inversely with the total RFSS scores, poor arm index and higher cerebral disturbances (r = -0.53, P = 0.004; r = -0.53, P = 0.004; and r = -0.52, P = 0.005, respectively). Although the number of spinal T2 lesions correlated with sensory disturbances (r = 0.60, P = 0.001), no correlations were found between EDSS subscores and spinal cord atrophy. These findings show that marked atrophy of brain and spinal cord detected by volumetric quantitation correlates with neurological disability. This observation indicates the importance of neurodegenerative events in PPMS.
 ...
PMID:Volumetric quantitation by MRI in primary progressive multiple sclerosis: volumes of plaques and atrophy correlated with neurological disability. 1464 11

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system in which axonal damage and degeneration contribute significantly to the progressive irreversible neurological disability. Similar to pathogenic myelin autoimmunity, autoimmune responses to neuronal antigens may contribute to axonal damage and irreversible disability in MS. Auto-antibodies to the axonal cytoskeletal protein neurofilament light (NF-L) are associated with cerebral atrophy in MS and we have recently reported that NF-L autoimmunity is pathogenic in mice. However, the T-cell response to NF-L in MS patients has not been examined. Here, we identify and characterize T-cell proliferative responses to NF-L as compared with myelin oligodendrocyte glycoprotein (MOG) in MS patients and healthy controls. Using a carboxyfluorescein succinimidyl ester dilution assay, we show that while responses to MOG are dominated by CD3(+)CD4(+) T cells, responses to NF-L were observed in both CD3(+)CD4(+) and CD3(+)CD8(+) T-cell populations. Both MOG- and NF-L-reactive cells expressed CD45RO(+), indicative of a memory phenotype. Moreover, in contrast to MOG stimulation which predominantly induced IFN-gamma, both T(h)1- and T(h)2-type T-cell responses to NF-L were observed as indicated by the induction of IFN-gamma, tumor necrosis factor-alpha as well as IL-4. The finding of T-cell responses to NF-L in MS patients may reflect transient activation of pathogenic potential but their presence also in healthy controls indicates that these cells are part of the normal immune repertoire.
 ...
PMID:T-cell responses to neurofilament light protein are part of the normal immune repertoire. 1924 89

Multiple sclerosis is a chronic, demyelinating disorder of the central nervous system. It is characterised by progressive neurological disability, which is likely to occur as a result of permanent axonal damage. Such damage may be reflected by brain atrophy, which can be identified early in the course of the disease. Patients who present with an initial episode of inflammatory demyelination, commonly referred to as a clinically isolated syndrome, are at high risk of developing clinically definite multiple sclerosis, especially if their magnetic resonance imaging studies suggest the presence of multi-focal disease. Treatment with disease-modifying therapies at the initial episode of demyelination may postpone this development. In this review we present an overview of evidence supporting early treatment initiation. We focus on three large placebo-controlled trials of interferon beta therapy: Controlled High-Risk Avonex Multiple Sclerosis Prevention Study, Early Treatment of Multiple Sclerosis and Betaferon in Newly Emerging Multiple Sclerosis for Initial Treatment. Results from these early treatment studies are presented, and the impact of using interferon beta treatment in the early stages of disease is discussed with the aim of considering optimal therapeutic strategies to improve long-term patient outcome.
 ...
PMID:Treatment of early multiple sclerosis: the value of treatment initiation after a first clinical episode. 1980 40

Most patients contract hypoxic encephalopathy after suffering a cardiac arrest. They usually endure severe neurological sequelae and the temporal profile of the disease progression remains unclear. This case study shows how the effects of hypoxic encephalopathy continue to progress for several years after the initial event. Up to eight years after the hypoxic insult, the patient's intellect steadily deteriorated, and brain atrophy progressed. As the hypoxic insult on the brain is only transient, the neurological disability seems not to be exacerbated for years. However, our case indicates that this disorder may have a long progression.
 ...
PMID:A case of hypoxic encephalopathy with delayed exacerbation. 2042 10

The long-term neuroimaging correlates of clinical recovery have not been described in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. The aim of the study is to evaluate the long-term outcome of brain atrophy in anti-NMDAR encephalitis. Patients were two women (ages 17 and 33 years) with severe anti-NMDAR encephalitis resulting in decreased level of consciousness, autonomic instability, hypoventilation, and dyskinesias requiring continuous infusion of anesthetic agents for 6-7 months. Brain MRI and cerebral blood flow SPECT obtained at the time of maximal neurological disability were compared with similar studies obtained 5-7 years later. Both patients were hospitalized for 9-14 months and developed frontotemporal atrophy and hypoperfusion 7-12 months after symptom presentation. In both patients, cognitive functions gradually improved over the next 4-5 years. Comparative neuroimaging studies obtained 5-7 years after symptom presentation showed dramatic improvement of the atrophy and frontotemporal hypoperfusion. The severe and protracted deficits and the frontotemporal atrophy that occur in some patients with anti-NMDAR encephalitis are potentially reversible. This suggests that a functional rather than a structural neuronal damage underlies the pathogenesis of this disorder.
 ...
PMID:Reversible brain atrophy in anti-NMDA receptor encephalitis: a long-term observational study. 2051 15

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) that involves myelin, oligodendrocytes and axons and culminates in consecutive neuronal death and progressive neurologic disability. Based on magnetic resonance imaging (MRI), neuroaxonal loss in MS results in brain atrophy and has a strong correlation with neurological disability. The newer MR imaging tools seem to be sensitive biomarkers for measuring the pathogenetic processes associated with disease activity and progression. However, they are unable to detect apoptosis in neurodegenerative diseases. Annexin V has a high affinity for phosphatidylserine (PS) that presents on the outer surface of the plasma membrane early on during the onset of apoptosis. Radiolabeled annexin V imaging may reveal the initiation and degree of neuronal apoptosis. We propose that radiolabeled annexin V imaging is a useful modality in determining apoptosis in MS and can assess and monitor the effectiveness of neuroprotective and immunomodulatory therapies on the clinical course of MS.
 ...
PMID:Radiolabeled annexin V imaging: a useful technique for determining apoptosis in multiple sclerosis. 2144 Mar 74

Optical coherence tomography (OCT) is a non-invasive imaging technique that allows the different layers of the retina to be visualised in vivo. One of them is the so-called retinal nervous fibre layer (RNFL), which is made up of amyelinic axons from the ganglionic cells, and therefore part of the central nervous system. Recent studies have begun to examine possible applications of OCT in the field of neurology and, more specifically, the usefulness of measuring the thickness of the RNFL in multiple sclerosis (MS). In both cross-sectional and longitudinal studies it has been shown that a decrease in the RNFL is produced in eyes that are affected and unaffected by optic neuritis in MS patients, compared with controls. Several studies have found evidence of an inverse relation between the thickness of the nerve fibre layer and the neurological disability or cerebral atrophy parameters in magnetic resonance imaging of the brain in these same patients. The correlations are, however, weak and sometimes contradictory. Although there are still many doubts that need settling, the role OCT may play in gaining a better understanding of the disease and its follow-up and monitoring seems promising. A review of the different studies published on the thickness of the RNFL in patients with MS will also be conducted.
 ...
PMID:[Optical coherence tomography in multiple sclerosis]. 2253 20