Standardizing the intensity of upper limb treatment in rehabilitation medicine.

OBJECTIVE: To describe a treatment protocol for the upper limb that standardizes intensity of therapy input regardless of the severity of presentation. DESIGN: The protocol is described (Part 1) and feasibility and effect explored (Part 2). SUBJECTS: Participants (n = 11) had a single ischaemic stroke in the middle cerebral artery territory more than one year previously, and had residual weakness of the hand with some extension present at the wrist and the ability to grasp. INTERVENTIONS: Following two baseline assessments, participants attended therapy for 1 hour a day for 10 consecutive working days. Treatment consisted of a combination of strength and functional task training. Outcomes were measured immediately after training, at one month and three months. OUTCOME MEASURES: Intensity was measured with Borg Rating of Perceived Exertion. Secondary outcome measures included Action Research Arm Test (ARAT), nine-hole peg test, and Goal Attainment Scale. RESULTS: Borg scores indicated that the level of intensity was appropriate and similar across all participants despite individual differences in the severity of their initial presentation (median (interquartile range) = 14 (13-15)). The mean ARAT score significantly increased by 6.8 points (chi(2)(3) = 15.618, P<0.001), and was maintained at three-month follow-up (z = - 2.384, P = 0.016). The nine-hole peg test also showed a main effect of time and 88% of goals set were achieved. CONCLUSIONS: The physiotherapy protocol standardized intensity of treatment by grading exercise and task-related practice according to the person's residual ability, rather than simply standardizing treatment times. It was feasible and well tolerated in this group.

What can man do without basal ganglia motor output? The effect of combined unilateral subthalamotomy and pallidotomy in a patient with Parkinson's disease.

We have studied motor performance in a man with Parkinson's disease (PD) in whom thermolytic lesions of the left subthalamic and left globus pallidus nuclei interrupted the basal ganglia (BG)-thalamo-cortical motor circuit in the left hemisphere. This allowed us to study remaining motor capabilities in the absence of aberrant BG activity typical of PD. Movements of the left arm were slow and parkinsonian whereas movement speed and simple reaction times (RT) of the right (operated) arm were within the normal range with no obvious deficits in a range of daily life activities. Two main abnormalities were found with the right hand. (a) Implicit sequence learning in a probabilistic serial reaction time task was absent. (b) In a go/no-go task when the percent of no-go trials increased, the RT superiority with the right hand was lost. These deficits are best explained by a failure of the cortex, deprived of BG input, to facilitate responses in a probabilistic context. Our findings confirm the idea that it is better to stop BG activity than allowing faulty activity to disrupt the motor system but dispute earlier claims that interrupting BG output in PD goes without an apparent deficit. From a practical viewpoint, our observations indicate that the risk of persistent dyskinesias need not be viewed as a contraindication to subthalamotomy in PD patients since they can be eliminated if necessary by a subsequent pallidotomy without producing deficits that impair activities of daily life.

In-hospital direct cost of acute ischemic and hemorrhagic stroke in Greece.

OBJECTIVES: The geographic inequity and the wide variation in the patterns of care of stroke found across Europe together with the lack of health economics evaluation in Greece led to this prospective study, aiming to provide data on in-hospital direct cost of patients with an acute stroke in Greece, and to identify independent prognostic factors. METHODS: Demographic and clinical data were recorded on 429 consecutive patients with an acute ischemic or hemorrhagic stroke admitted to a tertiary care hospital in Greece during a period of 18 months. The costs incurred were estimated using the official financial charts listing in euro (euro), the real expenditure of all hospital departments. RESULTS: The direct in-hospital cost for all stroke cases was 1,551,445euro for a total of 4674 days (331.9euro per day in-hospital). The mean in-hospital cost per stroke patient was 3624.9euro (+/-2695.4). Hemorrhagic strokes were significantly more expensive than the ischemic strokes [mean 5305.4 (+/-4204.8)euro and 3214.5 (+/-1976.2)euro, respectively) and lacunar strokes the least expensive among ischemic stroke subtypes. The length of stay was highly correlated with in-hospital total cost. Multivariate linear regression analysis showed that admission ward, stroke severity on admission, stroke type and status discharge were independent predictors of cost. CONCLUSIONS: Purchasers in our health services should differentiate in their cost estimates and pricing schemes between types of cerebrovascular events. Future studies should focus on modifiable factors related, not only with stroke characteristics, but also with operational policies of hospitals, that may influence length of stay.

Neural correlates of age-related changes in cortical neurophysiology.

Functional imaging studies of cortical motor systems in humans have demonstrated age-related reorganisation often attributed to anatomical and physiological changes. In this study we investigated whether aspects of brain activity during a motor task were influenced not only by age, but also by neurophysiological parameters of the motor cortex contralateral to the moving hand. Twenty seven right-handed volunteers underwent functional magnetic resonance imaging whilst performing repetitive isometric right hand grips in which the target force was parametrically varied between 15 and 55% of each subject's own maximum grip force. For each subject we characterised two orthogonal parameters, B(G) (average task-related activity for all hand grips) and B(F) (the degree to which task-related activity co-varied with peak grip force). We used transcranial magnetic stimulation (TMS) to assess task-related changes in interhemispheric inhibition from left to right motor cortex (IHIc) and to perform measures relating to left motor cortex excitability during activation of the right hand. Firstly, we found that B(G) in right (ipsilateral) motor cortex was greater with increasing values of age(2) and IHIc. Secondly, B(F) in left ventral premotor cortex was greater in older subjects and in those in whom contralateral M1 was less responsive to TMS stimulation. In both cases, neurophysiological parameters accounted for variability in brain responses over and above that explained by ageing. These results indicate that neurophysiological markers may be better indicators of biological ageing than chronological age and point towards the mechanisms by which reconfiguration of distributed brain networks occurs in the face of degenerative changes.

The effect of age on task-related modulation of interhemispheric balance.

Normal aging is associated with less lateralised task-related activation of the primary motor cortices. It has been hypothesized, but not tested, that this phenomenon is mediated transcallosaly. We have used Transcranial Magnetic Stimulation to look for age-related changes in interhemispheric inhibition (IHI). Thirty healthy individuals (aged 19-78 years) were studied using a paired-pulse protocol at rest and during a low-strength isometric contraction with the right hand. The IHI targeting the right motor cortex was assessed at two intervals, 10 ms (IHI10) and 40 ms (IHI40). The corticospinal excitability of the left hemisphere was assessed by means of input-output curves constructed during voluntary construction. Age was not correlated with IHI10 or IHI40 at rest. During muscle contraction IHI tended to increase at both intervals. However, this increase in IHI during the active condition (changeIHI) was less evident with advancing age for the 40 ms interval (r = 0.444, P = 0.02); in fact a degree of disinhibition was often present. There was no correlation between age and changeIHI10. Age was negatively correlated with the area under the recruitment curve (r = -0.585, P = 0.001) and the size of the maximum MEP collected (r = -0.485, P = 0.007). ChangeIHI and measures of corticospinal excitability were not intercorrelated. In conclusion, task-related increases in interhemispheric inhibition seem to diminish with advancing age. This phenomenon is specific for long-latency IHI and may underlie the age-related bihemispheric activation seen in functional imaging studies. The mechanism underlying changes in IHI with advancing age and the association with changes in corticospinal excitability need further investigation.

Pattern-specific role of the current orientation used to deliver Theta Burst Stimulation.

OBJECTIVE: To evaluate the role of current direction on the after-effects of Theta Burst Stimulation (TBS) delivered with a biphasic Magstim 200(2) stimulator. METHODS: Inhibitory (cTBS) and excitatory TBS (iTBS) were delivered over the motor cortex of healthy individuals using reversed and standard current orientations (initial current in the antero-posterior direction) at 80% and 100% of their respective active motor thresholds (AMT). The after-effects on the MEP amplitude were measured for 25 min. The effects of the most effective reversed cTBS paradigm on intracortical inhibition (SICI) and facilitation (ICF) were also tested. RESULTS: Reversing the current direction reduced AMT by 26%+/-2%. Compared to standard cTBS, reversed cTBS induced stronger and longer-lasting inhibition of corticospinal excitability when delivered at 100% AMTrev. SICI was reduced after cTBS100%revAMT while ICF was unchanged. The after-effects of reversed iTBS were quite variable regardless of the intensity. CONCLUSIONS: cTBS applied with antero-posterior current is more effective in suppressing subsequent MEPs than conventionally orientated cTBS when the absolute stimulation intensity is similar. On the contrary, posterior current orientation reduces the efficacy of iTBS. SIGNIFICANCE: The current direction may affect the power of inhibitory and excitatory TBS in opposite ways; this should be considered in order to optimise the after-effects of biphasic RTMS.

Exploring Theta Burst Stimulation as an intervention to improve motor recovery in chronic stroke.

OBJECTIVE: To explore the effects of a single session of repetitive Transcranial Magnetic Stimulation, given as Theta Burst Stimulation, on behavioural and physiological measures of hand function in chronic stroke patients. METHODS: Six chronic stroke patients with incomplete recovery of the hand were tested under three conditions: excitatory TBS over the stroke hemisphere (iTBS(SH)), inhibitory TBS (cTBS(IH)) over the intact hemisphere and sham stimulation. Behavioural outcomes included simple and choice reaction time paradigms. Physiological effects were assessed using single pulse TMS on both sides. Changes were sought for up to 40min after TBS. RESULTS: Immediately after iTBS(SH) simple reaction times in the paretic hands were decreased and, compared to sham stimulation, remained significantly shorter throughout the testing period. The amplitude of the MEPs at rest and during background contraction and the area under the Input-Output curves were also increased on the stroke side after iTBS(SH). cTBS(IH) suppressed the MEPs evoked in the healthy hands but did not change motor behaviour or the electrophysiology of the paretic hands. No side effects were encountered. CONCLUSIONS: TBS seems safe in chronic stroke patients. iTBS over the stroke hemisphere transiently improved motor behaviour and corticospinal output in the paretic hands. SIGNIFICANCE: Excitatory TBS may represent a useful rTMS protocol to apply to the stroke hemisphere in future longer term therapy trials.

Arm function after stroke: neurophysiological correlates and recovery mechanisms assessed by transcranial magnetic stimulation.

Transcranial Magnetic Stimulation has been used for over 20 years to investigate recovery of motor function in stroke patients. In particular, it has been used to quantify the extent of damage to the corticospinal output, reorganisation of the cortical representation of the affected body parts and excitability of intracortical and cortico-cortical circuitries in both hemispheres. In this review, we provide a detailed account of most of the published data with particular reference to methodological issues that affect their interpretation.

Common carotid artery intima media thickness and post-stroke cognitive impairment.

BACKGROUND AND PURPOSE: Acute stroke and other forms of cerebrovascular disease are well-recognized causes of cognitive impairment. Common carotid artery intima media thickness (CCA-IMT) has been associated with certain forms of cerebrovascular disease, but its association with cognitive impairment of vascular origin has not been elucidated. The purpose of this study was to investigate whether CCA-IMT is associated with cognitive impairment 1 year after an acute ischemic stroke. METHODS: A total of 171 consecutive patients with the first ever stroke (mean age 66+/-11.5, 41% female) underwent carotid ultrasonography during hospitalization. Demographic data, vascular risk factors and presenting stroke features were also recorded. One year later, patients' cognitive performance and depression were assessed using the Mini-Mental State Examination (MMSE), and the Montgomery Asberg Depression Rating Scale (MADRS). RESULTS: Cognitive impairment (MMSE score<24) was found in 67 (39%) of the 171 patients. CCA-IMT was significantly associated with cognitive impairment, and this association remained unchanged (OR 1.94; 95% CI 1.19-3.18) after adjustment for demographic data, vascular risk factors, stroke features, other carotid ultrasonography measurements and depression. Older age, low education level, large hemispheric lesions, hyperdense carotid plaques and depression were also independently associated with post-stroke cognitive impairment. CONCLUSIONS: In this study, CCA-IMT was independently associated with cognitive impairment 1 year after an acute ischemic stroke, and thus, it might help with the screening of stroke patients at risk of cognitive impairment.

Is the common carotid artery intima-media thickness associated with functional outcome after acute ischaemic stroke?

BACKGROUND: Common carotid artery intima-media thickness (CCA-IMT) is an independent and early marker of generalised atherosclerosis. Brain affected by atherosclerosis may be more vulnerable to an ischaemic insult. OBJECTIVE: To investigate the association between CCA-IMT and functional outcome after an acute ischaemic stroke. DESIGN: Prospective cohort analysis. METHODS: 284 consecutive patients (mean (SD) age, 68.7 (12.7) years, 126 (44%) female) with an acute ischaemic stroke had carotid ultrasonography, carried out by a single operator. Demographic data, vascular risk factors, initial stroke severity, and brain imaging findings were recorded. Outcome was assessed at seven days from stroke onset, at discharge from hospital, and at one year post-stroke. RESULTS: CCA-IMT was not significantly associated with adverse short or long term functional outcome in univariate analysis, or after adjustment in a multivariate logistic regression analysis for demographic data, initial stroke severity, conventional vascular risk factors, and the characteristics of the ischaemic lesion. Age and initial stroke severity were the only independent predictors of outcome. CONCLUSIONS: CCA-IMT was not associated with adverse functional outcome after an ischaemic stroke. Adding CCA-IMT in a prediction model for stroke outcome would probably not improve the power of the model.

The effect of vascular disease on late onset Parkinson's disease.

The clinical severity of late onset Parkinson's disease (PD) varies from patient to patient and it is further complicated by the increasing prevalence of accompanying disorders in the elderly. We set out to study the impact of ischemic heart disease, minor stroke, hypertension and diabetes mellitus in a group of late onset PD patients (age >or=70 years). Consecutive late onset PD patients seen in the Department of Neurology, Medical School of Patras, Greece were included in this study. We used very strict criteria to eliminate the possibility of including patients with vascular parkinsonism. Comparisons were made between groups of patients suffering with idiopathic Parkinson's disease (IPD) and the above-mentioned diseases. One hundred and sixty-seven consecutive late onset PD patients were included in this study. The most common accompanying disorders in our group were hypertension in 31 (18%) of the patients and minor stroke in 20 (12%). The Hoen and Yahr score in late onset IPD patients who suffered from minor stroke, ischemic heart disease or diabetes mellitus was significantly higher when compared with patients without the above disorders. The results clearly suggest that the presence of vascular disease on an IPD patient may aggravate PD severity. In clinical grounds, these findings can be proved significant since early and aggressive prevention of vascular disease and treatment of vascular risk may contribute in controlling symptom severity in PD.