Epidemiological and clinical studies show higher prevalence of amyotrophic lateral sclerosis (ALS) in males than in females and more severe lesions in androgen receptor (AR)‐expressing tissues. The gene contains a polymorphic CAG trinucleotide repeat, whose expansion over a certain threshold is toxic to motor neurons, causing spinal and bulbar muscular atrophy (SBMA).
Management of childhood dystonia differs in certain respects from that of adult dystonia: (i) childhood dystonia is more often secondary than primary; (ii) mixed motor disorders are frequent; (iii) in children, the course of dystonia may be influenced by ongoing brain maturation and by the remarkable plasticity of the young brain; (iv) drug tolerability and effectiveness can be different in children; (v) the therapeutic strategy must be discussed with both the patient and his or her parents; and (vi) the child’s education must be taken into account. Based on a systematic review of the literature through June 2011 and on our personal experience, we propose a therapeutic approach to childhood dystonia. After a detailed clinical evaluation and a comprehensive work‐up to rule out a treatable cause of dystonia, symptomatic treatment may include various drugs, local botulinum toxin injections, and deep brain stimulation, in addition to rehabilitation.
Data on the role of endogenous sex steroids in cerebrovascular disease are sparse. Estradiol is a hormone with diverse actions on the central nervous system. Our aim was to investigate the role of circulating estradiol levels in a postmenopausal acute stroke population.
To investigate whether dopaminergic pre‐treatment alters placebo and dopamine agonist responses in restless legs syndrome (RLS).
Two large, multi‐centre trials (SP790 and SP792; registration numbers NCT00136045 and NCT00135993) on the efficacy of rotigotine in RLS reported supplemental International RLS (IRLS) sum score data for pre‐treated and drug‐naïve patients, allowing for the estimation of the regression slope of the clinical response (change in the IRLS sum score) on baseline IRLS sum score.
In both trials, patients pre‐treated with dopaminergic medications tended to have blunted responses after placebo administration compared with drug‐naïve patients. In the SP790 study, the pre‐treated group had a negative slope (i.e. the response observed after placebo administration decreased as the baseline IRLS sum score increased), whereas the slope was positive in drug‐naïve patients (slope, −0.43 vs. 0.28; = 0.027). In the SP792 study, the two slopes were parallel ( = 0.84), but the magnitude of the response after placebo administration was smaller in the pre‐treated group (6.31 vs. 10.49; = 0.0089). Pre‐treatment had no significant effect on rotigotine‐group responses in either of the two studies.
In RLS trials, dopaminergic pre‐treatment tends to increase the apparent effect of new dopaminergic drugs by decreasing the placebo effect in the placebo arm without substantially modifying the placebo effect in the active treatment arm. This observation highlights that placebo‐controlled trials are not necessarily placebo‐effect controlled trials.
Measurements of binding antibodies (BAbs), neutralizing antibodies (NAbs) and mRNA expression are used to analyse the immunological reactions in patients with MS treated with IFN‐β. The correlations between these are yet not fully understood.
We measured BAbs and NAbs to IFN‐β in 110 serum samples from 83 patients with MS treated with IFN‐β, and in a subgroup, antibody titre was compared with corresponding expressions of mRNA. The methods used were capture ELISA assay, luciferase reporter gene assay and mRNA RT‐PCR for gene expression.
There were significant correlations between binding, neutralizing and results. Cut‐off values are suggested for the definition of samples of BAbs and NAbs as negative, positive and grey zones. Naturally occurring groups of low and high antibody titres were identified by the correlation between BAbs and NAbs, probably as a result of an immunological maturation process of antibodies. The low‐titre group had lower correlations between BAbs and NAbs than the high‐titre group.
High correlation is demonstrated between the results obtained by the three methods, and we suggest the possibility of using ELISA measurements of BAbs to identify patients with high titres of anti‐IFN‐β antibodies that block the biological response to IFN‐β. Ιn patients with low titres, we suggest to supplement ELISA with measurement of mRNA to establish whether the bioavailability of IFN‐β is preserved.
Carotid atherosclerosis is a risk factor for stroke and cognitive decline, but knowledge on how progression of carotid atherosclerosis affects cognitive function in stroke‐free individuals is scarce.
In the population‐based Tromsø study, we calculated the change in ultrasound‐assessed carotid plaque number and total plaque area from baseline (survey 4) to follow‐up 7 years later (survey 5) in 4274 middle‐aged stroke‐free subjects. Cognitive function was assessed at follow‐up by the verbal memory test, the digit‐symbol coding test, and the tapping test and repeated after an additional 6 years in a subgroup of 2042 subjects (survey 6). Associations between the average of survey 4 and survey 5 plaque scores and the progression of plaque scores and cognitive test scores were assessed in regression analyses adjusted for baseline age, sex, education, depression, and cardiovascular risk factors.
Progression of total plaque area was associated with lower scores in the digit‐symbol coding test (multivariable adjusted standardized β, −0.03; 95% CI, −0.05 to −0.00; = 0.04) and the tapping test (β, −0.03; 95% CI, −0.06 to −0.00; = 0.03). Similar results were seen for progression of plaque number. The average plaque scores were associated with lower scores in all cognitive tests (‐values ≤ 0.01). No association was found between plaque scores and cognitive decline.
The average plaque scores were associated with lower scores in all cognitive tests. Progression of plaque scores was associated with lower scores in the digit‐symbol coding test and the tapping test, but not with the verbal memory test or with cognitive decline.
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A general hypothesis is that pain following stroke (PFS) causes disabilities. However, the clinical implication of PFS on other disabilities after stroke and has not been fully investigated. The aims of this observational study were to analyze the correlation between PFS and other disabilities at different time points after stroke, whether PFS can be a predictor of coming disabilities and whether other disabilities can be predictors of coming PFS.
Patients with a first‐ever stroke were assessed initially ( = 109), and at 3 ( = 95) and 18 months ( = 66) after stroke for PFS, mobility, self‐care as well as touch, proprioceptive, muscle tone, and movement functions.
PFS was correlated to impaired upper extremity movement function on all occasions, while the correlations between PFS and other disabilities varied across the three occasions. Initial PFS and PFS at 3 months did not independently predict coming disabilities. Initial mobility limitation independently predicted PFS at 3 months and impaired touch function, initially and at 3 months, independently predicted PFS at 18 months. No other disabilities independently predicted coming PFS.
The present results do not support the hypothesis that PFS causes other disabilities. Our results indicate that PFS is correlated to other disabilities; however, no ultimate conclusions can be drawn on causality. PFS was not a predictor of coming disabilities, while some disabilities were predictors of coming PFS.
Rectal biopsy is usually performed for diagnosis of Kufs disease (KD). We evaluated the usefulness of rectal biopsy in the diagnosis of such condition by comparing ultrastructural data of patients with suspicion of KD with those of control subjects. Furthermore, we reviewed literature data concerning the value of such a diagnostic procedure in the diagnosis of KD.
Sixty‐five subjects were enrolled and underwent rectal biopsy. Of these, 13 had a clinical picture in keeping with KD, whereas 52, affected by Irritable Bowel Syndrome, constituted the control group.
Ultrastructural analysis evidenced fingerprint (FP) inclusions in 12 subjects, 4/13 with suspicion of KD and 8/52 controls. In patients, FPs were mainly located in vascular smooth muscle cells (VSMC) while in controls they were mostly found in pericytes and VSMC. No FPs were found in one patient with genetically confirmed KD. In literature, we identified 14 KD patients who underwent rectal biopsy. In most reports, ultrastructural features were not systematically analyzed or described.
Fingerprints are the most common ultrastructural finding in rectal biopsy in patients with suspicion of KD. However, their presence in pericytes and VSMC is not specific for KD because they may be found in controls subjects. Our literature review revealed that data on the value of rectal biopsy in the diagnosis of KD are scarce. In light of these findings, the relevance of rectal biopsy in such condition should be re‐evaluated.
The standard of care in patients with glioblastoma (GBM) relies on surgical resection, radiation therapy (RT), and temozolomide. Steroids are required in almost all patients to reduce peritumoral edema, but are associated with numerous side effects. Vascular endothelial growth factor (VEGF) is a key driver of peritumoral edema and angiogenesis in human GBM. Recently, angiotensin‐II inhibitors were reported to reduce VEGF secretion and tumor growth in some animal models.
To investigate whether angiotensin‐II inhibitors might have a similar effect in humans and before undertaking a prospective study, we retrospectively investigated a series of 87 consecutive, newly diagnosed GBM patients, treated in a single center. Amongst these patients, 29 (33%) were already treated before RT for high blood pressure (HBP), 18 of them (21%) with an angiotensin‐II inhibitor. In all patients, performance status, surgical procedures, and steroid dosages were documented.
Patients treated with angiotensin‐II inhibitors, but not other antihypertensive drugs, required half of the steroids of the other patients during radiotherapy ( = 0.005 in multivariate analysis, considering other antihypertensive treatments, surgical resection, and performance status). This effect of angiotensin‐II inhibitors was also significant at the beginning of radiotherapy ( = 0.03 in multivariate analysis). Treatment with angiotensin‐II inhibitors had no effect on survival (16.2 vs. 17.9 months for the treated and the non‐treated group, respectively, = 0.77).
Angiotensin‐II inhibitors might display significant steroid‐sparing effects in brain tumor patients. Given the morbidity associated with steroids, this finding might have important practical consequences in these patients and warrants a randomized study.
It remains unclear what role environmental toxins play in sporadic motor neuron disease (SMND) and its most common subtype, amyotrophic lateral sclerosis (SALS). Most previous studies of this issue have contained only small numbers of SMND cases. We sought to re‐examine possible associations between toxins and SMND in a large Australian case–control study.
Questionnaire data were available from 787 patients with SMND (614 with SALS) and 778 non‐related controls. Individuals were asked whether they had been exposed to metals or chemicals/solvents at work or to herbicides/pesticides. Chi‐square tests with odds ratios and 95% confidence intervals were calculated for responses, and significance levels were corrected for multiple testing.
Men were more likely to acquire SALS if they worked with metals (OR = 1.95, 95% CI = 1.24–3.07) or chemicals/solvents (OR = 1.96, 95% CI = 1.46–2.61) or if they had been exposed to herbicides or pesticides (OR = 1.77, 95% CI = 1.30–2.39). Women who had worked with chemicals or solvents also appeared to be at increased risk of acquiring SALS (OR = 1.71, 95% CI = 1.22–2.40).
These results support previous reports that exposures to metals or chemicals are associated with SMND. A suggested protocol for future multinational studies of environmental toxins and SMND is presented.
There is growing study of the psychiatric features of essential tremor. Depressive symptoms occur in a considerable number of patients. Yet their impact, as a primary factor, has received almost no attention. We assessed whether, independent of tremor severity, patients with more depressive symptoms have more perceived tremor‐related disability, lower tremor‐related quality of life, and poorer compliance with tremor medication.
On the basis of their Center for Epidemiological Studies Depression Scale score, we stratified 70 essential tremor patients into three groups: 41 with minimal depressive symptoms, 24 with moderate depressive symptoms, and five with severe depressive symptoms. Importantly, the three groups had similar tremor severity on neurological examination. We assessed self‐reported tremor‐related disability, tremor‐related quality of life (Quality of Life in Essential Tremor) (QUEST) score, and medication compliance.
Cases with minimal depressive symptoms had the lowest QUEST scores (i.e., highest quality of life), cases with moderate depressive symptoms had intermediate scores, and those with severe depressive symptoms had the highest QUEST scores (i.e., lowest quality of life) ( < 0.001). Depressive symptoms were a stronger predictor of tremor‐related quality of life than was the main motor feature of essential tremor (ET) itself (tremor). Self‐reported medication compliance was lowest in cases with severe depressive symptoms and highest in cases with minimal depressive symptoms.
The physical disability caused by the tremor of ET has traditionally been regarded as the most important feature of the disease that causes distress, and it has received the most attention in the management of patients with this disease. Our data indicate that this may not be the case.
Microbleeds (MBs) are frequently detected in brains of patients with Alzheimer dementia and rare in those with frontotemporal lobar degeneration (FTLD). This study investigates for the first time the topographic distribution of MBs on a T2*‐weighted gradient‐echo 7.0‐T magnetic resonance imaging (MRI) in post‐mortem FTLD brains.
The neuropathological and MRI findings in 12 FTLD brains were compared with eight age‐matched controls. The presence of cerebrovascular lesions was evaluated on a coronal section of a cerebral hemisphere at the level of the mamillary body and on a horizontal section through pons and cerebellum. On MRI, the distribution and the number of cortical focal signal intensity losses, representing MBs, were assessed on coronal sections at the frontal, the central and the occipital level of a cerebral hemisphere.
Overall, cerebrovascular lesions were rare. Only white matter damage was significantly more severe in FTLD brains compared with controls ( = 0.03). On MRI, MBs were only significantly prevalent in the deep cortical layers ( < 0.01) and borderline increased in the middle cortical layers ( = 0.07) of the frontal section.
Cerebrovascular lesions are rare in FTLD. The white matter damage has to be considered as part of the neurodegenerative process. MBs prevail in the frontal regions with the most severe neuronal damage and probably represent associated disruption of the blood–brain barrier.
Stroke‐associated early seizures (ES) often complicate the initial course of acute stroke. This study intended to estimate the rate of and the predictive factors for ES and the impact of ES on the clinical outcome in patients with first‐ever acute stroke.
Consecutive patients with first‐ever acute stroke admitted in the Department of Medicine from June 2010 to December 2011 were prospectively included. ES were defined as seizures occurring within 7 days from acute stroke. Patients with history of epilepsy, transient ischaemic attack, subarachnoid haemorrhage and cerebral venous thrombosis were excluded. Clinical outcomes were measured under the subheadings of mortality and disability at discharge, according to modified Rankin score.
Of the 441 (56.92% male patients, median age 55 years, 49.43% had haemorrhagic stroke) patients, 79 (17.91%, 95% confidence interval (CI): 14.61–21.78%) suffered from ES. At discharge, 37.64% were disabled, and 19.5% were dead. In multivariate analysis, alcoholism, NIHSS at admission, haemorrhagic stroke and cortical location were significant predictors of ES. Thirty‐day mortality was predicted by NIHSS at admission [hazard ratio (HR): 1.14, 95% CI: 1.11–1.18, < 0.001], history of hypertension (HR: 3.79, 95% CI: 2.1–6.85, < 0.001), history of alcoholism (HR: 2.43, 95% CI: 1.49–3.95, < 0.001) and early seizure (HR: 2.58, 95% CI: 1.54–4.34, = 0.001).
Early seizures occurred in about 18% acute stroke patients. Alcoholism, haemorrhagic stroke, cortical and severe strokes predict development of ES. ES are an independent important risk factor for early mortality.
Recently, contrast‐enhanced transcranial Doppler (cTCD) studies have shown that right‐to‐left shunt (RLS) may be a risk factor for migraine in Westerners; however, limited data in the literature describes the prevalence of RLS in Chinese patients with migraine.
To assess the prevalence of RLS in patients with migraine in China and to evaluate the relationship between the extent of RLS and migraine.
A total of 217 consecutive patients with a diagnosis of migraine and 100 volunteers were recruited. cTCD was used to assess the prevalence and the extent of RLS in all subjects.
In the migraine group, the rate of positive RLS was 44.2% (96/217), with 23.5% (51/217) of these being large. In the healthy group, 28.0% (28/100) were positive for RLS overall, and 5.0% (5/100) were large (=0.006; <0.001). In patients having migraines with aura (MwA), 66.1% (39/59) were positive for RLS overall, and 37.3% (22/59) were large, which was significantly higher when compared with the healthy group (<0.001; <0.001); in patients having migraines without aura (MwoA), 36.1% (57/158) were positive for RLS overall, and 18.4% (29/158) were large, which was against significantly higher (<0.001; =0.003). In the MwoA group, the large RLS rate was also higher than in the healthy group (=0.002).
A close correlation has been documented between RLS and migraine, especially MwA, but these relationships exist only when the shunts were large.
Polymerase chain reaction (PCR) as a means to amplify nucleic acids has become an essential element in diagnosis of infections. It has evolved into a simple and rapid, easy‐ to‐ use approach. At present there are no published guidelines for the usage of PCR technology for the diagnosis of infections of the nervous system.
We reviewed the advantages and pitfalls of PCR in order to guide neurologists and infectious diseases experts in its application for the diagnosis of infections of the nervous system. Medical reference systems were searched, and original papers, meta‐analyses, review papers, book chapters and guidelines recommendations were reviewed. The final literature search was performed in May 2012. Recommendations were reached by consensus.
The reliability of PCR technology for the diagnosis of neurological infections is currently based on the pathogens. The main contribution of PCR is to the diagnosis of viral infections followed by bacterial CNS infections with the notable exception of tuberculous meningitis. Efficacy for the diagnosis of protozoal infections and helminthic infestations has also been established in many instances. Unfortunately, current molecular PCR technology is far from becoming routine in resource‐poor countries where such infections are prevalent. Despite the importance of fungal infections in the context of the immune‐compromised host, there is not enough data to recommend the routine use of PCR.
PCR technology is currently a reliable method for the diagnosis of viral and bacterial (except tuberculosis) infections, and only for some protozoal infections and helminthic infestations.