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Amyotrophic Lateral Sclerosis 09/2012; · 3.40 Impact Factor
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ABSTRACT: The CMAP (Compound Muscle Action Potential) scan is a non-invasive electrodiagnostic tool, which provides a quick and visual assessment of motor unit potentials as electrophysiological components that together constitute the CMAP. The CMAP scan records the electrical activity of the muscle (CMAP) in response to transcutaneous stimulation of the motor nerve with gradual changes in stimulus intensity. Large MUs, including those that result from collateral reinnervation, appear in the CMAP scan as so-called steps, i.e., clearly visible jumps in CMAP amplitude. The CMAP scan also provides information on nerve excitability. This study aims to evaluate the influence of the stimulation protocol used on the CMAP scan and its quantification.
The stimulus frequency (1, 2 and 3 Hz), duration (0.05, 0.1 and 0.3 ms), or number (300, 500 and 1000 stimuli) in CMAP scans of 23 subjects was systematically varied while the other two parameters were kept constant. Pain was measured by means of a visual analogue scale (VAS). Non-parametric paired tests were used to assess significant differences in excitability and step variables and VAS scores between the different stimulus parameter settings.
We found no effect of stimulus frequency on CMAP scan variables or VAS scores. Stimulus duration affected excitability variables significantly, with higher stimulus intensity values for shorter stimulus durations. Step variables showed a clear trend towards increasing values with decreasing stimulus number.
A protocol delivering 500 stimuli at a frequency of 2 Hz with a 0.1 ms pulse duration optimized CMAP scan quantification with a minimum of subject discomfort, artefact and duration of the recording. CMAP scan variables were influenced by stimulus duration and number; hence, these need to be standardized in future studies.
Journal of Brachial Plexus and Peripheral Nerve Injury 04/2012; 7(1):4.
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ABSTRACT: Cerebrovascular disease can complicate head and neck radiotherapy and result in transient ischemic attack and ischemic stroke. Although the incidence of radiation vasculopathy is predicted to rise with improvements in median cancer survival, the pathogenesis, natural history, and management of the disease are ill defined.
We examined studies on the epidemiology, imaging, pathogenesis, and management of medium- and large-artery intra- and extra-cranial disease after head and neck radiotherapy. Controlled prospective trials and larger retrospective trials from the last 30 years were prioritized.
The relative risk of transient ischemic attack or ischemic stroke is at least doubled by head and neck radiotherapy. Chronic radiation vasculopathy affecting medium and large intra- and extra-cranial arteries is characterized by increasing rates of hemodynamically significant stenosis with time from radiotherapy. Disease expression is the likely consequence of the combined radiation insult to the intima-media (accelerating atherosclerosis) and to the adventitia (injuring the vasa vasorum). Optimal medical treatment is not established. Carotid endarterectomy is confounded by the need to operate across scarred tissue planes, whereas carotid stenting procedures have resulted in high restenosis rates.
Head and neck radiotherapy significantly increases the risk of transient ischemic attack and ischemic stroke. Evidence-based guidelines for the management of asymptomatic and symptomatic (medium- and large-artery) radiation vasculopathy are lacking. Long-term prospective studies remain a priority, as the incidence of the problem is anticipated to rise with improvements in postradiotherapy patient survival.
Stroke 08/2011; 42(9):2410-8. · 5.73 Impact Factor
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International Journal of Stroke 04/2011; 6(2):176-8. · 2.38 Impact Factor
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ABSTRACT: There is evidence that amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is more common in men than in women and that gender influences the clinical features of the disease. The causes of this are unknown.
This review examines the gender differences that are found in ALS and postulates reasons for these differences.
A literature review of PubMed (with no date limits) was performed to find information about gender differences in the incidence, prevalence, and clinical features of ALS, using the search terms ALS or MND and gender or sex, ALS prevalence, and SOD1 mice and gender. Articles were reviewed for information about gender differences, together with other articles that were already known to the authors.
The incidence and prevalence of ALS are greater in men than in women. This gender difference is seen in large studies that included all ALS patients (sporadic and familial), but is not seen when familial ALS is studied independently. Men predominate in the younger age groups of patients with ALS. Sporadic ALS has different clinical features in men and women, with men having a greater likelihood of onset in the spinal regions, and women tending to have onset in the bulbar region. Gender appears to have no clear effect on survival. In animals with superoxide dismutase 1 (sod1) mutations, sex does affect the clinical course of disease, with earlier onset in males. Possible reasons for the differences in ALS between men and women include different exposures to environmental toxins, different biological responses to exogenous toxins, and possibly underlying differences between the male and female nervous systems and different abilities to repair damage.
There is a complex interaction between gender and clinical phenotypes in ALS. Understanding the causes of the gender differences could give clues to processes that modify the disease.
Gender Medicine 12/2010; 7(6):557-70. · 2.10 Impact Factor
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ABSTRACT: ALS is a fatal disease with variable clinical course. There is no single reliable marker of disease progression. Sufficient records were available to study the case history of four family members with the uncommon G93V SOD1 mutation. Distal lower motor neuron (LMN) involvement occurred in all family members with onset from 30 to 51 years of age, with progression over more than six years. Between 2002 and 2009, we used electrophysiology as a biomarker to study disease progression in one patient, assessing the number of motor units in three nerves from different limbs. The loss of motor units showed an exponential decline with different half-lives in different nerves. Diffusion tractography was compared with a control to assess upper motor neuron (UMN) involvement and showed asymmetric evidence of abnormalities of the corticospinal tracts, providing evidence of central involvement despite the absence of UMN signs.
Amyotrophic Lateral Sclerosis 10/2010; 11(5):486-9. · 3.40 Impact Factor
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ABSTRACT: We aimed to derive normative data for cardiovascular autonomic function tests (AFT) in an older population using new measures. The AFT were performed in 48 healthy control subjects. The average heart rate (HR) response to deep breathing (DB) (HR(DB)), Valsalva ratio (VR), magnitude of the HR and blood pressure (BP) response of different phases of the Valsalva maneuver, BP recovery times (PRT 100 and PRT 50) and HR and BP changes on head-up tilting were calculated. The mean age (+/-standard deviation) of study participants was 58+/-14.5 years (range 20-82 years), of whom 29 (60%) were men. The systolic blood pressure (SBP) early phase 2 amplitude showed an inverse relationship with age (p=0.03). There was a trend for progressive attenuation of SBP late phase 2 amplitude with age (p=0.09). The systolic BP recovery time was not affected by age, gender or body mass index. We concluded that age has a significant effect on most AFT variables. Age and gender did not influence the systolic BP recovery time; hence, systolic BP recovery time could be useful in the evaluation of adrenergic failure.
Journal of Clinical Neuroscience 03/2010; 17(6):731-5. · 1.25 Impact Factor
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The Medical journal of Australia 02/2010; 192(4):232. · 2.81 Impact Factor
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ABSTRACT: It is important to know the effects of prolonged repetitive nerve stimulation (RNS) when it is used in neurophysiological studies. RNS with up to 100 supramaximal stimuli was given to the median, ulnar, and peroneal nerves of normal subjects and the ulnar nerves of subjects with early amyotrophic lateral sclerosis (ALS), recording evoked compound muscle action potentials (CMAPs). In all nerves, there was a decline in the CMAP area and a decrease in CMAP duration. For the peroneal nerve there was a decline in the CMAP amplitude, but a similar decline was not seen in the median or ulnar nerves. Cooling of the muscles resulted in decrement of both the amplitude and area with RNS. In ALS subjects, CMAP amplitude and area both declined after RNS of the ulnar nerve. In this study we describe the changes in CMAP with prolonged RNS among commonly tested normal nerves. Our findings have important implications with regard to RNS.
Muscle & Nerve 02/2010; 41(6):785-93. · 2.37 Impact Factor
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ABSTRACT: Lymphocytes, neutrophils and macrophages are found in the brain in areas of acute ischaemic stroke. There is also evidence of modulation of systemic immune function after stroke, with post-stroke immunosuppression being observed. Because lymphocytes are activated in the peripheral immune compartment, before entry to the target organ, we reasoned that activated lymphocytes would be present in the circulation, prior to entering the brain, in patients after stroke. Because immune responses are controlled by regulatory mechanisms, we also reasoned that the post-stroke immunosuppression would involve T regulatory cells. The aim of the study was to look for evidence of immune activation and alterations in regulatory T cells in the peripheral blood of patients after acute ischaemic stroke, in comparison to age-matched healthy controls and patients with other neurological diseases (OND), and to determine the phenotype of the activated cells. The percentages of total and activated T cells, B cells, monocyte/ macrophages, and NK/NK-T cells were determined by labelling peripheral blood leukocytes with specific cell surface markers and analysis with 4-colour flow cytometry. The percentages of activated T cells and regulatory T cells were significantly increased in patients with ischemic stroke compared to healthy subjects and patients with OND. There was also an increase in the percentage of CCR7+ T cells. There were no significant differences in the activation of other cell types. In conclusion, there is evidence of immune activation and Treg cells in acute ischaemic stroke.
Journal of Neuroimmunology 01/2009; 206(1-2):112-7. · 2.96 Impact Factor
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Journal of Clinical Neuroscience 05/2008; 15(4):456, 487. · 1.25 Impact Factor
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ABSTRACT: There is limited evidence for the treatment of orthostatic hypotension in idiopathic Parkinson's disease. The objective of this study was to determine the efficacy of three treatments (nonpharmacological therapy, fludrocortisone, and domperidone). Phase I assessed the compliance, safety, and efficacy of nonpharmacological measures. Phase II was a double-blind randomized controlled crossover trial of the two medications. Primary outcome measures consisted of the orthostatic domain of the Composite Autonomic Symptom Scale (COMPASS-OD), a clinical global impression of change (CGI), and postural blood pressure testing via bedside sphygmomanometry (Phase I) or tilt table testing (Phase II). For the 17 patients studied, nonpharmacological therapy did not significantly alter any outcome measure. Both medications improved the CGI and COMPASS-OD scores. There was a trend towards reduced blood pressure drop on tilt table testing, with domperidone having a greater effect.
Movement Disorders 09/2007; 22(11):1543-9. · 4.51 Impact Factor
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ABSTRACT: We describe three young patients who had strokes in an unusual setting; two patients during coitus and 1 patient after a bout of laughter. Two patients had a patent foramen ovale and one patient developed vertebral artery dissection during coitus. The underlying stroke mechanisms in the three patients are discussed. These cases highlight the importance of questioning the events preceding stroke onset.
Journal of Clinical Neuroscience 09/2007; 14(8):786-7. · 1.25 Impact Factor
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ABSTRACT: We have developed a new method of motor unit number estimation (MUNE) for assessing diseases such as amyotrophic lateral sclerosis (ALS). We used data from the whole stimulus-response curve and then performed a Bayesian statistical analysis. The Bayesian method uses mathematical equations that express the basic elements of motor unit activation after electrical stimulation and allows for the sources of variability and uncertainty in this formulation. The Bayesian MUNE method was used to determine the most probable number of motor units in 8 normal subjects, 49 ALS subjects, and 3 subjects with progressive lower motor neuron (LMN) weakness. In normals the number of motor units was calculated to be 75-85 in hand and 40-58 in foot muscles. In ALS subjects the number of motor units per muscle was less than in normal subjects. In 17 ALS subjects and 3 subjects with LMN weakness the median, ulnar, or peroneal nerve was studied on repeated occasions over an average of 189 days (range 63-1,071) and the number of motor units progressively declined, with a half-life ranging from 62-834 days. The results of our MUNE technique were reproducible on replicate studies. A Bayesian statistical MUNE method is a new approach that can be used to study ALS patients serially for assessment and treatment trials.
Muscle & Nerve 09/2007; 36(2):206-13. · 2.37 Impact Factor
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Archives of Neurology 02/2007; 64(1):134-5. · 7.58 Impact Factor
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ABSTRACT: Previous research has attempted to analyze the relationship between post-stroke hyperthermia and prognosis. These analyses have been hindered by a lack of information about the time course and determinants of temperature change after stroke.
Serial temperatures were measured until 48 h after ischaemic stroke in a prospectively recruited cohort. Potential determinants of temperature, including stroke severity [measured using the National Institutes of Health Stroke Scale (NIHSS)], infection and paracetamol use were recorded. Mixed-effects models were used to model serial temperature measurements over time, adjusted for significant determinants.
In 155 patients the mean temperature rose from 36.5 degrees C at the time of stroke to 36.7 degrees C approximately 36 h later. The factors with significant multivariable associations with serial temperatures were: first- and second-order time components, infection, paracetamol administration and the interaction between stroke severity (NIHSS > or =6) and time (all p < 0.1). Patients with admission NIHSS > or =6 had a mean temperature rise of 0.35 degrees C during the first 36 h after stroke, compared with a rise of 0.17 degrees C in those with NIHSS < or =5.
Temperature spontaneously rises during the first 36 h after stroke, particularly after severer stroke and in the presence of infection.
Cerebrovascular Diseases 02/2007; 24(1):104-10. · 2.72 Impact Factor
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ABSTRACT: Previous research suggests that blood pressure falls acutely after ischemic stroke. We aimed to further characterize this fall with a statistical technique that allows the application of regression techniques to serial blood pressure outcome data.
In a prospectively recruited ischemic stroke cohort, systolic (SBP) and diastolic (DBP) blood pressure was recorded every 4 h until 48 h after stroke. Potential determinants of blood pressure, including stroke severity and acute infection, were also recorded. Mixed effects models were used to model serial blood pressure measurements over time, adjusted for significant determinants.
In 156 patients, SBP and DBP fell by 14.9 mm Hg (95% CI 6.2-22.6 mm Hg) and 6.2 mm Hg (95% CI 1.4-10.6 mm Hg), respectively, over the first 48 h after stroke. SBP was higher in patients with premorbid hypertension, a previous history of stroke or TIA, current alcohol use, increasing age, stroke of mild to moderate severity (NIHSS 3-13) and in patients treated with antihypertensives. SBP was lower in smokers. There was a progressive rise in SBP in patients with acute infection. No factors other than time were associated with DBP.
The use of mixed effects models has identified a linear SBP and DBP fall over the first 48 h after stroke. The timing and magnitude of this fall should be accounted for in the design of future prognostic and intervention studies.
Cerebrovascular Diseases 02/2007; 24(5):426-33. · 2.72 Impact Factor
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ABSTRACT: All muscle contractions are dependent on the functioning of motor units. In diseases such as amyotrophic lateral sclerosis (ALS), progressive loss of motor units leads to gradual paralysis. A major difficulty in the search for a treatment for these diseases has been the lack of a reliable measure of disease progression. One possible measure would be an estimate of the number of surviving motor units. Despite over 30 years of motor unit number estimation (MUNE), all proposed methods have been met with practical and theoretical objections. Our aim is to develop a method of MUNE that overcomes these objections. We record the compound muscle action potential (CMAP) from a selected muscle in response to a graded electrical stimulation applied to the nerve. As the stimulus increases, the threshold of each motor unit is exceeded, and the size of the CMAP increases until a maximum response is obtained. However, the threshold potential required to excite an axon is not a precise value but fluctuates over a small range leading to probabilistic activation of motor units in response to a given stimulus. When the threshold ranges of motor units overlap, there may be alternation where the number of motor units that fire in response to the stimulus is variable. This means that increments in the value of the CMAP correspond to the firing of different combinations of motor units. At a fixed stimulus, variability in the CMAP, measured as variance, can be used to conduct MUNE using the "statistical" or the "Poisson" method. However, this method relies on the assumptions that the numbers of motor units that are firing probabilistically have the Poisson distribution and that all single motor unit action potentials (MUAP) have a fixed and identical size. These assumptions are not necessarily correct. We propose to develop a Bayesian statistical methodology to analyze electrophysiological data to provide an estimate of motor unit numbers. Our method of MUNE incorporates the variability of the threshold, the variability between and within single MUAPs, and baseline variability. Our model not only gives the most probable number of motor units but also provides information about both the population of units and individual units. We use Markov chain Monte Carlo to obtain information about the characteristics of individual motor units and about the population of motor units and the Bayesian information criterion for MUNE. We test our method of MUNE on three subjects. Our method provides a reproducible estimate for a patient with stable but severe ALS. In a serial study, we demonstrate a decline in the number of motor unit numbers with a patient with rapidly advancing disease. Finally, with our last patient, we show that our method has the capacity to estimate a larger number of motor units.
Biometrics 01/2007; 62(4):1235-50. · 1.83 Impact Factor
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Archives of Neurology 06/2006; 63(5):780. · 7.58 Impact Factor
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ABSTRACT: We aimed to characterise the patterns of circadian blood pressure (BP) variation after acute stroke and determine whether any relationship exists between these patterns and stroke outcome. BP was recorded manually every 4 h for 48 h following acute stroke. Patients were classified according to the percentage fall in mean systolic BP (SBP) at night compared to during the day as: dippers (fall > or = 10-<20%); extreme dippers (> or = 20%); non-dippers (> or = 0-<10%); and reverse dippers (<0%, that is, a rise in mean nocturnal SBP compared to mean daytime SBP). One hundred and seventy-three stroke patients were included in the study (83 men, 90 women; mean age 74.3 years). Four patients (2.3%) were extreme dippers, 25 (14.5%) dippers, 80 (46.2%) non-dippers and 64 (36.9%) reverse dippers. There was a non-significant trend in the proportion of patients who were dead or dependent at 3 months in the extreme dipper (p=0.59) and reverse dipper (p=0.35) groups. Non-dipping and reverse-dipping were relatively common patterns of circadian BP variation seen in acute stroke patients. These patterns were not clearly associated with outcome.
Journal of Clinical Neuroscience 06/2006; 13(5):558-62. · 1.25 Impact Factor
