Showing papers in "Lancet Neurology in 2005"

The age-dependent relation of blood pressure to cognitive function and dementia

Abstract: Summary The relation of blood pressure with cognitive function and dementia has, in recent years, received much attention from epidemiological research. Some cross-sectional studies have shown an inverse association between blood pressure and the prevalence of dementia and Alzheimer's disease, whereas longitudinal studies yield mixed results that largely depend on the age at which blood pressure is measured and the time interval between blood pressure and outcome assessments. Some studies suggest that midlife high blood pressure is a risk factor for late-life cognitive impairment and dementia, and that low diastolic pressure and very high systolic pressure in older adults may be associated with subsequent development of dementia and Alzheimer's disease. Observational studies and randomised clinical trials provide limited evidence for a protective effect of antihypertensive therapy against dementia and stroke-related cognitive decline. Atherosclerosis resulting from long-standing hypertension, and cerebral hypoperfusion secondary to severe atherosclerosis and to low blood pressure may be major biological pathways linking both high blood pressure in midlife and low blood pressure in late-life to cognitive decline and dementia.

Leisure-time physical activity at midlife and the risk of dementia and Alzheimer's disease

Abstract: Summary Background Physical activity may help maintain cognitive function and decrease dementia risk, but epidemiological findings remain controversial. The aim of our study was to investigate the association between leisure-time physical activity at midlife and the subsequent development of dementia and Alzheimer's disease (AD). Methods Participants were randomly selected from the survivors of a population-based cohort previously surveyed in 1972, 1977, 1982, or 1987. 1449 persons (72·5%) age 65–79 years participated in the re-examination in 1998 (mean follow-up, 21 years). 117 persons had dementia and 76 had AD. Multiple logistic regression methods were used to analyse the association between leisure-time physical activity and dementia or AD. Findings Leisure-time physical activity at midlife at least twice a week was associated with a reduced risk of dementia and AD (odds ratio [OR] 0·48 [95% CI 0·25–0·91] and 0·38 [0·17–0·85], respectively), even after adjustments for age, sex, education, follow-up time, locomotor disorders, APOE genotype, vascular disorders, smoking, and alcohol drinking. The associations were more pronounced among the APOE ɛ4 carriers. Interpretation Leisure-time physical activity at midlife is associated with a decreased risk of dementia and AD later in life. Regular physical activity may reduce the risk or delay the onset of dementia and AD, especially among genetically susceptible individuals.

Lessons from brain mapping in surgery for low-grade glioma: insights into associations between tumour and brain plasticity

Abstract: Summary Surgical treatment of low-grade gliomas (LGGs) aims to maximise the amount of tumour tissue resected, while minimising the risk of functional sequelae. In this review I address the issue of how to reconcile these two conflicting goals. First, I review the natural history of LGG—growth, invasion, and anaplastic transformation. Second, I discuss the contribution of new techniques, such as functional mapping, to our understanding of brain reorganisation in response to progressive growth of LGG. Third, I consider the clinical implications of interactions between tumour progression and brain plasticity. In particular, I show how longitudinal studies (preoperative, intraoperative, and postoperative) could allow us to optimise the surgical risk-to-benefit ratios. I will also discuss controversial issues such as defining surgical indications for LGGs, predicting the risk of postoperative deficit, aspects of operative surgical neuro-oncology (eg, preoperative planning and preservation of functional areas and tracts), and postoperative functional recovery.

Clinically isolated syndromes suggestive of multiple sclerosis, part I: natural history, pathogenesis, diagnosis, and prognosis

Abstract: In 85% of young adults with multiple sclerosis (MS), onset is a subacute clinically isolated syndrome (CIS) of the optic nerves, brainstem, or spinal cord. Methods of assessing the prognosis for patients who present with a CIS have been sought, because only 30-70% of patients with a CIS develop MS. When clinically silent brain lesions are seen on MRI, the likelihood of developing MS is high. MS can be diagnosed within 3 months of CIS presentation with certain MRI and CSF criteria. Disability from MS is less likely in patients with a CIS of optic neuritis or sensory symptoms only, few or no MRI lesions, a long period to the first relapse, and no disability after the first 5 years. Development of more reliable prognostic markers will enable new treatments to be targeted for those who are most likely to benefit. We encourage continued clinical and laboratory assessment of patients with a CIS.

Neurological complications of HIV infection

Abstract: Cognitive disorders, vacuolar myelopathy, and sensory neuropathies associated with HIV are the most common disorders in patients with HIV AIDS, and are the focus of this review. These disorders are treatable and of those associated with HIV AIDS the pathogenic mechanisms are the most understood. Although triggered by productive HIV macrophage infections, aberrant immune activation plays a major role in inducing the CNS disorders. Novel therapies aimed at these inflammatory mechanisms can be effective. The sensory neuropathies associated with HIV infection are a major cause of morbidity; incidence may be increased by the toxic effects of specific antiretroviral drugs within the peripheral nervous system.

Pathogenesis, clinical features, and neurological outcome of cerebral malaria.

Abstract: Cerebral malaria is the most severe neurological complication of Plasmodium falciparum malaria. Even though this type of malaria is most common in children living in sub-Saharan Africa, it should be considered in anybody with impaired consciousness that has recently travelled in a malaria-endemic area. Cerebral malaria has few specific features, but there are differences in clinical presentation between African children and non-immune adults. Subsequent neurological impairments are also most common and severe in children. Sequestration of infected erythrocytes within cerebral blood vessels seems to be an essential component of the pathogenesis. However, other factors such as convulsions, acidosis, or hypoglycaemia can impair consciousness. In this review, we describe the clinical features and epidemiology of cerebral malaria. We highlight recent insights provided by ex-vivo work on sequestration and examination of pathological specimens. We also summarise recent studies of persisting neurocognitive impairments in children who survive cerebral malaria and suggest areas for further research.

Quality of life and its assessment in multiple sclerosis: integrating physical and psychological components of wellbeing

Abstract: Summary Health-related quality of life (HRQoL) has been more intensively studied in multiple sclerosis (MS) than in any other neurological disorder. Traditional medical models of impairment and disability are an incomplete summary of disease burden. Quality of life can be thought of as the sum of all sources of satisfaction (including anticipated sources) minus all threats (including anticipated threats). Many psychosocial factors—including coping, mood, self-efficacy, and perceived support—influence the quality of life of patients with MS more than biological variables such as weakness or extent of MRI lesions. Neuropsychiatric complications such as cognitive impairment and fatigue are also important predictors, even in those patients in the early stages of the disease. We review generic and specific HRQoL measures to help clinicians choose the most appropriate therapies. Subjective (self-report) HRQoL measures may serve to alert clinicians to areas that would otherwise be overlooked. Studies of new interventions should include an assessment of HRQoL not just impairment or disability alone.

Cerebral hyperperfusion syndrome.

Abstract: Cerebral hyperperfusion syndrome (CHS) after carotid endarterectomy is characterised by ipsilateral headache, hypertension, seizures, and focal neurological deficits. If not treated properly it can result in severe brain oedema, intracerebral or subarachnoid haemorrhage, and death. Knowledge of CHS among physicians is limited. Most studies report incidences of CHS of 0-3% after carotid endarterectomy. CHS is most common in patients with increases of more than 100% in perfusion compared with baseline after carotid endarterectomy and is rare in patients with increases in perfusion less than 100% compared with baseline. The most important risk factors in CHS are diminished cerebrovascular reserve, postoperative hypertension, and hyperperfusion lasting more than several hours after carotid endarterectomy. Impaired autoregulation as a result of endothelial dysfunction mediated by generation of free oxygen radicals is implicated in the pathogenesis of CHS. Treatment strategies are directed towards regulation of blood pressure and limitation of rises in cerebral perfusion. Complete recovery happens in mild cases, but disability and death can occur in more severe cases. More information about CHS and early institution of adequate treatment are of paramount importance in order to prevent these potentially severe complications.

Epilepsy and social identity: the stigma of a chronic neurological disorder.

Abstract: Summary Epilepsy is the most common serious neurological disorder worldwide, affecting about 50 million people. 1 In most people with epilepsy, the disorder is clinically benign. However, because of the stigma associated with having epilepsy, which is common to many cultures, there can be a negative effect on the social identity of people with the disorder, particularly for those living in resource-poor countries. In this paper, we present general theories of stigma, as well as those specific to chronic illness. We relate these theories to the stigma associated with epilepsy throughout history and across cultures. We review research on the relation between stigma and the overall quality of life of people with epilepsy. Finally, we address reduction of the stigma.

Neurocysticercosis: updated concepts about an old disease

Abstract: Neurocysticercosis, the infection of the human brain by the larvae of Taenia solium, is a major cause of acquired epilepsy in most low-income countries. Cases of neurocysticercosis are becoming more common in high-income countries because of increased migration and travel. Diagnosis by neuroimaging and serological assessment has greatly improved over the past decade, and the natural progression of the disease and response to antiparasitic drugs is now much better understood. Neurocysticercosis is potentially eradicable, and control interventions are underway to eliminate this infection. Meanwhile, updated information on diagnosis and management of neurocysticercosis is required, especially for clinicians who are unfamiliar with its wide array of clinical presentations.

Epidemiology and aetiology of epilepsy in sub-Saharan Africa

Abstract: Summary Data on the incidence of and prognosis for epilepsy in sub-Saharan Africa are scarce, but prevalence data show that epilepsy is two or three times more common than in industrialise countries in non-tropical areas. The high prevalence of epilepsy and low life expectancy indicate that incidence is high. Relative contributions of each cause of epilepsy are difficult to determine. Only a few case-control studies have been done in sub-Saharan Africa. Infections, in particular cysticercosis in its endemic areas, cause most cases of epilepsy. The implementation of studies to accurately determine the causes of epilepsy in sub-Saharan Africa is urgently required. Such studies will help to lower the incidence of epilepsy in this region and better understand the aetiology of epilepsy in other areas.

Relation of C-reactive protein to stroke, cognitive disorders, and depression in the general population: systematic review and meta-analysis

Abstract: Summary Evidence suggests that a high concentration of C-reactive protein (CRP) is a cardiovascular risk factor and an important correlate of cognitive disorders and depression. Recently, population-based studies examining the association between CRP and stroke, cognitive impairment, or depression have been done but have not yet been systematically reviewed. Here we present a systematic review of the associations between CRP and stroke, cognitive impairment, and depression. Hospital or clinic-based studies were excluded because the inferences might not be easily applicable to the general population. 19 eligible studies of CRP were selected: seven for stroke, six for cognitive disorders, and six for depression. Raised CRP concentrations were associated with history of stroke and increased risk of incident stroke. Meta-analysis of studies with long follow-up (>8 years) showed that the risk for stroke in healthy individuals with the highest quartile of CRP concentrations increased nearly 70% compared to those with the lowest quartile. High concentrations of CRP were predictive of cognitive decline and dementia. The relations of CRP to depression were all cross-sectional and were not consistent. We conclude that high concentrations of CRP are associated with increased risk of stroke and cognitive impairment. The association between CRP and depression should be studied prospectively.

The restless legs syndrome

Abstract: The restless legs syndrome is a common disorder that encompasses an idiopathic form of genetic or unknown origin and symptomatic forms associated with many causes. Symptomatic forms occur during pregnancy and are coincident with uraemia, iron depletion, polyneuropathy, spinal disorders, and rheumatoid arthritis. For the hereditary forms, at least three gene loci, located on chromosomes 12, 14, and 9, have been traced so far. Prevalence in the general population is between 3% and 9%, increases with age, and is higher in women than in men. Treatment is needed only in the moderate to severe forms of the disorder and mostly in elderly people. Pathophysiology and treatment may be closely linked to the dopaminergic system and iron metabolism. Dopaminergic treatment with levodopa and dopamine agonists is the first choice in idiopathic restless legs syndrome, but augmentation and rebound should be monitored in long-term treatment. Various other drugs, such as opioids, gabapentin, and benzodiazepines, provide alternative treatment possibilities.

Incidence of unprovoked seizures and epilepsy in Iceland and assessment of the epilepsy syndrome classification: a prospective study

Abstract: Summary Background No population-based incidence studies of epilepsy have studied syndrome classification from the outset. We prospectively studied the incidence of a single unprovoked seizure and epilepsy in the population of Iceland, and applied the syndrome classification endorsed by the International League Against Epilepsy to this population. Methods We used a nationwide surveillance system to prospectively identify all residents of Iceland who presented with a first diagnosis of a single unprovoked seizure or epilepsy between December 1995 and February 1999. All cases were classified by seizure type, cause or risk factors, and epilepsy syndrome. Results The mean annual incidence of first unprovoked seizures was 56·8 per 100 000 person-years, 23·5 per 100 000 person-years for single unprovoked seizures, and 33·3 per 100 000 person-years for epilepsy (recurrent unprovoked seizures). Incidence was similar in males and females. Partial seizures occurred in 40% and a putative cause was identified in 33%. Age-specific incidence was highest in the first year of life (130 per 100 000 person-years) and in those 65 years and older (110·5 per 100 000 person-years). Using strict diagnostic criteria for epilepsy syndromes, 58% of cases fell into non-informative categories. Idiopathic epilepsy syndromes were identified in 14% of all cases. Interpretation Findings are consistent with incidence studies from developed countries. Although the epilepsy syndrome classification might be useful in tertiary epilepsy centers, it has limited practicality in population studies and for use by general neurologists.

Cholesterol in Alzheimer's disease.

Abstract: Summary Alzheimer's disease (AD) is the most common form of neurodegenerative dementia and affects up to 15 million people worldwide. Although no single cause of AD has been identified, recent research has suggested that several pathogenetic factors influence risk and expression. A growing amount of evidence underscores a mechanistic link between cholesterol metabolism in the brain and the formation of amyloid plaques. Excess brain cholesterol has been associated with increased formation and deposition of amyloid-β peptide from amyloid precursor protein. Cholesterol-lowering statins have become a focus of research in AD. Genetic polymorphisms associated with pivotal points in cholesterol metabolism in brain tissues may contribute to the risk and pathogenesis of AD. In this review, we summarise current knowledge of the role of cholesterol metabolism in the pathogenesis of AD and examine the potential of statins in the prevention and treatment of AD.

The United Kingdom Infantile Spasms Study (UKISS) comparing hormone treatment with vigabatrin on developmental and epilepsy outcomes to age 14 months: a multicentre randomised trial

Abstract: Summary Background Infantile spasms is a severe infantile seizure disorder that is difficult to treat and has a high morbidity. Absence of spasms on days 13 and 14 after randomisation is more common in infants allocated hormone treatments than in those allocated vigabatrin. We sought to assess whether early control of spasms is associated with improved developmental or epilepsy outcomes. Methods Infants enrolled in the United Kingdom Infantile Spasms Study (UKISS) were randomly assigned hormone treatment (n=55) or vigabatrin (n=52) and were followed up until clinical assessment at 12–14 months of age. We assessed neurodevelopment with the Vineland adaptive behaviour scales (VABS) at 14 months of age on an intention to treat basis. Findings Of 107 infants enrolled, five died and 101 survivors reached both follow-up assessments. Absence of spasms at final clinical assessment (hormone 41/55 [75%] vs vigabatrin 39/51 [76%]) was similar in each treatment group (difference 1·9%, 95% CI −18·3% to 14·4%; χ 2 =0·05; p=0·82). Mean VABS score did not differ significantly (hormone 78·6 [SD 16·8] vs vigabatrin 77·5 [SD 12·7]; difference 1·0, 95% CI −4·9 to 7·0; t 99 =0·35, p=0·73). In infants with no identified underlying aetiology, the mean VABS score was higher in those allocated hormone treatment than in those allocated vigabatrin (88·2 [17·3] vs 78·9 [14·3]; difference 9·3, 95% CI 1·2 to 17·3; t 95 =2·28, p=0·025). Interpretation Hormone treatment controls spasms better than does vigabatrin initially, but not at 12–14 months of age. Better initial control of spasms by hormone treatment in those with no identified underlying aetiology may lead to improved developmental outcome.

Tuberculous meningitis: many questions, too few answers

Abstract: Summary Tuberculous meningitis (TM) is difficult to diagnose and treat; clinical features are non-specific, conventional bacteriology is widely regarded as insensitive, and assessment of newer diagnostic methods is not complete. Treatment includes four drugs, which were developed more than 30 years ago, and prevents death or disability in less than half of patients. Mycobacterium tuberculosis resistant to these drugs threatens a return to the prechemotherapeutic era in which all patients with TM died. Research findings suggest that adjunctive treatment with corticosteroids improve survival but probably do not prevent severe disability, although how or why is not known. There are many important unanswered questions about the pathophysiology, diagnosis, and treatment of TM. Here we review the available evidence to answer some of these questions, particularly those on the diagnosis and treatment of TM.

The Recognition of Stroke in the Emergency Room (ROSIER) scale: development and validation of a stroke recognition instrument.

Abstract: Summary Background In patients with acute stroke, rapid intervention is crucial to maximise early treatment benefits. Stroke patients commonly have their first contact with medical staff in the emergency room (ER). We designed and validated a stroke recognition tool—the Recognition of Stroke in the Emergency Room (ROSIER) scale—for use by ER physicians. Methods We prospectively collected data for 1 year (development phase) on the clinical characteristics of patients with suspected acute stroke who were admitted to hospital from the ER. We used logistic regression analysis and clinical reasoning to develop a stroke recognition instrument for application in this setting. Patients with suspected transient ischaemic attack (TIA) with no symptoms or signs when assessed in the ER were excluded from the analysis. The instrument was assessed using the baseline 1-year dataset and then prospectively validated in a new cohort of ER patients admitted over a 9-month period. Findings In the development phase, 343 suspected stroke patients were assessed (159 stroke, 167 non-stroke, 32 with TIA [17 with symptoms when seen in ER]). Common stroke mimics were seizures (23%), syncope (23%), and sepsis (10%). A seven-item (total score from −2 to +5) stroke recognition instrument was constructed on the basis of clinical history (loss of consciousness, convulsive fits) and neurological signs (face, arm, or leg weakness, speech disturbance, visual field defect). When internally validated at a cut-off score greater than zero, the instrument showed a diagnostic sensitivity of 92%, specificity of 86%, positive predictive value (PPV) of 88%, and negative predictive value (NPV) of 91%. Prospective validation in 173 consecutive suspected stroke referrals (88 stroke, 59 non-stroke, 26 with TIA [13 with symptoms]) showed sensitivity of 93% (95% CI 89–97), specificity 83% (77–89), PPV 90% (85–95), and NPV 88% (83–93). The ROSIER scale had greater sensitivity than existing stroke recognition instruments in this population. Interpretation The ROSIER scale was effective in the initial differentiation of acute stroke from stroke mimics in the ER. Introduction of the instrument improved the appropriateness of referrals to the stroke team.

Visual hallucinations in the diagnosis of idiopathic Parkinson's disease: a retrospective autopsy study

Abstract: Summary: Background: For many years, visual hallucinations (VH) in idiopathic Parkinson's disease (PD) were thought to be a complication of antiparkinsonian treatment. The cause of VH is now thought to be nerve-cell loss and Lewy-body pathology in the ventral-temporal regions of the brain. However, the use of VH as a clinical sign of PD has not been investigated. Methods: 788 cases with parkinsonism archived at the Queen Square Brain Bank for Neurological Diseases were identified for study. Patients had not been given standardised antemortem assessments. Clinical records were assessed for reports of VH. The incidence of VH in pathologically diagnosed cases was calculated, and factors affecting onset of VH were investigated. Findings: VH occurred in 50% (221/445) of patients with PD, in 73% (32/44) with dementia with Lewy bodies (DLB), and in only 7% (18/255) of patients with non-Lewy-body parkinsonism. The specificity of VH for Lewy-body parkinsonism (PD and DLB combined) was 92·9% (95% CI 89·1–95·8) and the positive predictive value was 93·4% (89·7–95·8). VH were associated with cognitive dysfunction (hazard ratio 5·62, 3·37–9·35), autonomic dysfunction (3·13, 1·77–5·52), axial rigidity (2·22, 1·26–3·85) within the first 2 years of disease onset and also age of onset (1·05, 1·03–1·07). In PD, the onset of VH typically occurred in the second half of the disease course, and time to onset of VH was only weakly correlated with use of selegiline (Spearman's rho 0·22, p=0·005) and ergot dopamine agonists (0·24, p=0·006) but not correlated with use of levodopa, amantadine, or anticholinergic drugs. Interpretation: The presence of VH is helpful in the differentiation of PD from other non-Lewy-body causes of parkinsonism. We propose that VH be added, as a supportive criterion, to the operational clinical criteria for the diagnosis of PD.

Tourette's syndrome: from behaviour to biology.

Abstract: Summary Tourette's syndrome (TS) is a chronic neuropsychiatric disorder characterised by motor and vocal tics. Diagnosis is based solely on clinical criteria. The prevalence of this syndrome is estimated to be between one and ten per 1000 children and adolescents and the outcome is generally favourable; most patients improve by their late teens or early adulthood. Affected individuals are at increased risk of various comorbid neurobehavioural problems, the negative effects of which commonly exceed those of tics. Despite evidence that TS is an inherited disorder, the exact genetic abnormality is unknown. Environmental factors might have an important role in the expression of tics, and a poststreptococcal autoimmune cause has been proposed but is unproven. Brain imaging, neurophysiological, and post-mortem studies support involvement of cortical–striatal–thalamocortical pathways, but the definitive pathophysiological mechanism or neurotransmitter abnormality is unknown. Recent evidence, however, suggests a prefrontal dopaminergic abnormality. Traditional neuroleptics are the standard treatment for TS, but there is increasing interest in non-neuroleptic drugs, behavioural therapies, and surgical approaches.

Treatment of intracerebral haemorrhage

Abstract: Apart from management in a specialised stroke or neurological intensive care unit, until very recently no specific therapies improved outcome after intracerebral haemorrhage (ICH). In a recent phase II trial, recombinant activated factor VII (eptacog alfa) reduced haematoma expansion, mortality, and disability when given within 4 h of ICH onset; a phase III trial (the FAST trial) is now in progress. Ventilatory support, blood-pressure reduction, intracranial-pressure monitoring, osmotherapy, fever control, seizure prophylaxis, and nutritional supplementation are the cornerstones of supportive care in intensive care units. Ventricular drainage should be considered in all stuporous or comatose patients with intraventricular haemorrhage and acute hydrocephalus. Given the lack of benefit seen in a the recent STICH trial, emergency surgical evacuation within 72 h of onset should be reserved for patients with large (>3 cm) cerebellar haemorrhages, or those with large lobar haemorrhages, substantial mass effect, and rapidly deteriorating condition.

Prevalence of movement disorders in men and women aged 50–89 years (Bruneck Study cohort): a population-based study

Abstract: Summary Background There is emerging awareness that movement disorders rank among the most common neurological diseases. However, the overall burden of these disorders in the general community is not well defined. We sought to assess the prevalence of all common categories of movement disorders in a population, accounting for sex differences and age trends. Methods As part of an ongoing prospective population-based study of carotid atherosclerosis and stroke risk (the Bruneck Study), a total of 706 men and women aged 50–89 years underwent a thorough neurological assessment. The diagnosis of movement disorders and ratings for disease severity were based on standard criteria and scales. Prevalences were estimated from logistic regression models (regression-smoothed rates) and standardised to the age and sex structure of the general community. Findings The prevalence of all common categories of movement disorders was 28·0% (95% CI 25·9–30·1). Proportions in men (27·6% [95% CI 24·5–30·7]) and women (28·3% [25·5–31·2]) were closely similar and sharply increased with age (from 18·5% [15·0–22·0] in 50–59-year olds to 51·3% [44·9–57·7] in 80–89-year olds). Almost half of all patients (90/214) had moderate-to-severe disease expression, but only 7·0% (15/214) received standard drug treatment. Prevalence of tremor was 14·5%, followed by restless legs syndrome (10·8%), parkinsonism (7%), primary dystonia and secondary dystonia (1·8%), and chorea and tics ( Interpretation There is a high prevalence of and substantial under-recognition and under-treatment of movement disorders in the general community.

Intake of vitamin E, vitamin C, and carotenoids and the risk of Parkinson's disease: a meta-analysis

Abstract: Summary We studied the effect of vitamin C, vitamin E, and β carotene intake on the risk of Parkinson's disease (PD). We did a systematic review and meta-analysis of observational studies published between 1966 and March 2005 searching MEDLINE, EMBASE, and the Cochrane Library. Eight studies were identified (six case-control, one cohort, and one cross-sectional). We found that dietary intake of vitamin E protects against PD. This protective influence was seen with both moderate intake (relative risk 0·81, 95% CI 0·67–0·98) and high intake (0·78, 0·57–1·06) of vitamin E, although the possible benefit associated with high intake of vitamin E was not significant. The studies did not suggest any protective effects associated with vitamin C or β carotene. We conclude that dietary vitamin E may have a neuroprotective effect attenuating the risk of PD. These results require confirmation in randomised controlled trials.

Symptomatic therapy and neurorehabilitation in multiple sclerosis.

Abstract: Multiple sclerosis (MS) is associated with a variety of symptoms and functional deficits that result in a range of progressive impairments and handicap. Symptoms that contribute to loss of independence and restrictions in social activities lead to continuing decline in quality of life. Our aim is to give an updated overview on the management of symptoms and rehabilitation measures in MS. Appropriate use of these treatment options might help to reduce long-term consequences of MS in daily life. First, we review treatment of the main symptoms of MS: fatigue, bladder and bowel disturbances, sexual dysfunction, cognitive and affective disorders, and spasticity. Even though these symptomatic therapies have benefits, their use is limited by possible side-effects. Moreover, many common disabling symptoms, such as weakness, are not amenable to drug treatment. However, neurorehabilitation has been shown to ease the burden of these symptoms by improving self-performance and independence. Second, we discuss comprehensive multidisciplinary rehabilitation and specific treatment options. Even though rehabilitation has no direct influence on disease progression, studies to date have shown that this type of intervention improves personal activities and ability to participate in social activities, thereby improving quality of life. Treatment should be adapted depending on: the individual patient's needs, demands of their surrounding environment, type and degree of disability, and treatment goals. Improvement commonly persists for several months beyond the treatment period, mostly as a result of reconditioning and adaptation and appropriate use of medical and social support at home. These findings suggest that quality of life is determined by disability and handicap more than by functional deficits and disease progression.

Cortical adaptation in patients with MS: a cross-sectional functional MRI study of disease phenotypes

Abstract: Summary Background Movement-associated cortical reorganisation is known to occur in multiple sclerosis (MS). We aimed to define the development of such cortical reorganisation by comparing data from patients with different disease phenotypes. Methods We studied patients with different phenotypes of MS: 16 patients with a clinically isolated syndrome (CIS), 14 patients with relapsing-remitting MS (RRMS) and no disability, 15 patients with RRMS and mild clinical disability, and 12 patients with secondary progressive MS (SPMS). Patients did a simple motor task with their unimpaired dominant hand during MRI, which was compared across the phenotype groups. Findings Patients with a CIS activated more of the contralateral primary sensorimotor cortex than those with RRMS and no disability, whereas patients with RRMS and no disability activated more of the supplementary motor area than those with a CIS. Patients with RRMS and no disability activated more of the primary sensorimotor cortex, bilaterally, and more of the ipsilateral supplementary motor area than patients with RRMS and mild clinical disability. Conversely, patients with RRMS and mild clinical disability activated more of the contralateral secondary somatosensory cortex and inferior frontal gyrus, and the ipsilateral precuneus. Patients with RRMS and mild clinical disability activated more of the contralateral thalamus and of the ipsilateral secondary somatosensory cortex than those with SPMS. However, patients with SPMS activated more of the inferior frontal gyrus, bilaterally, the middle frontal gyrus, bilaterally, the contralateral precuneus, and the ipsilateral cingulate motor area and inferior parietal lobule. Interpretation Movement-associated cortical reorganisation in patients with MS seems to vary across individuals at different stages of disease. Our study suggests that early in the disease course more areas typically devoted to motor tasks are recruited. Then bilateral activation of these regions is seen, and late in the disease course, areas that healthy people recruit to do novel or complex tasks are activated.

Biological markers in CSF and blood for axonal degeneration in multiple sclerosis

Abstract: Biomarkers in body fluids could help to predict and monitor neurological decline in people with multiple sclerosis (MS). We discuss markers for axonal damage in body fluids in people with MS. The most promising axonal marker for discriminating patients with MS from those with other neurological diseases is the neurofilament light chain in CSF. Antibodies against the heavy-chain isoform are associated with disease progression. Other studies have shown altered CSF concentrations of tau proteins, actin, tubulin, and 14-3-3 protein. Interestingly, the concentration of 24S-hydroxycholesterol was decreased in serum of patients with MS. No clear changes have been shown for the markers apolipoprotein E and neurospecific enolase. We describe three types of markers for axonal damage: markers that reflect processes in the CNS, those that reflect extraneural processes, and those that reflect whole-body changes. These concepts may be helpful for biomarker research in various neurodegenerative diseases.

Infectious causes of multiple sclerosis

Abstract: Summary Multiple sclerosis (MS) is a serious chronic neurological disorder in which demyelination and inflammation occur in the white matter of the CNS. The findings of many epidemiological studies and a discordance of MS in monozygotic twins suggest that the disorder is acquired. The most likely cause is a virus because more than 90% of patients with MS have high concentrations of IgG, manifest as oligoclonal bands, in the brain and CSF. Most chronic inflammatory CNS disorders are infectious. More indirect evidence that MS is caused by a virus is the association of several viruses with demyelinating encephalomyelitis in human beings, and the induction of demyelination in animals infected with viruses in research. Nevertheless, no virus has been isolated from the brains of patients who had MS. Molecular analysis of IgG gene specificity in the brain and CSF of those with MS has shown features of an antigen-driven response: clonal amplification and extensive somatic mutations. A viral antigen against which the IgG in MS brain and CSF is directed might be identified.

The neuro-ophthalmology of multiple sclerosis

Abstract: Multiple sclerosis (MS) is the most common disabling neurological disease in young people. Most CNS lesions involve neuroanatomically non-eloquent zones that often do not result in symptomatic complaints. By contrast, tissue-injury mechanisms involving inflammatory demyelination can involve more eloquent sites, such as the optic nerve and brainstem, which can correspondingly produce the development of well recognised syndromes such as optic neuritis and internuclear ophthalmoplegia, respectively. In this review we discuss the broad landscape of abnormalities that affect the afferent visual system and the ocular motor apparatus, and emphasise relevant features, the recognition and treatment of which are of importance to general neurological practice. The commonness of visual sensory and eye movement abnormalities in MS highlights the importance of understanding the principles addressed in this review.

Relation between migraine and stroke

Abstract: A complex bidirectional relation between migraine, mostly migraine with aura (MA), and ischaemic stroke is known. A cerebral infarction can occur during a MA, and MA is a risk factor for ischaemic stroke, particularly in young women. Conversely, cerebral ischaemia can induce MA. Both ischaemic stroke and MA might be consequences of many underlying vascular disorders. Despite the relation between migraine and stroke, migraine as a primary headache disorder is mostly benign.

Progressive myoclonic epilepsies: a review of genetic and therapeutic aspects.

Abstract: The progressive myoclonic epilepsies (PMEs) are a group of symptomatic generalised epilepsies caused by rare disorders, most of which have a genetic component, a debilitating course, and a poor outcome. Challenges with PME arise from difficulty with diagnosis, especially in the early stages of the illness, and further problems of management and drug treatment. Recent advances in molecular genetics have helped achieve better understanding of the different disorders that cause PME. We review the PMEs with emphasis on updated genetics, diagnosis, and therapeutic options.