Mauro Dam

Effects of Fluoxetine and Maprotiline on Functional Recovery in Poststroke Hemiplegic Patients Undergoing Rehabilitation Therapy

BACKGROUND AND PURPOSE In animals, drugs that increase brain amine concentrations influence the rate and degree of recovery from cortical lesions. It is therefore conceivable that antidepressants may influence outcome after ischemic brain injury in humans. We evaluated the effects of the norepinephrine reuptake blocker maprotiline and the serotonin reuptake blocker fluoxetine on the motor/functional capacities of poststroke patients undergoing physical therapy. METHODS Fifty-two severely disabled hemiplegic subjects were randomly assigned to three treatment groups; during 3 months of physical therapy, patients were treated with placebo, maprotiline (150 mg/d), or fluoxetine (20 mg/d). Before and at the end of the observation period, we assessed activities of daily living by the Barthel Index, degree of neurological deficit by a neurological scale for hemiplegic subjects, and depressive symptomatology by the Hamilton Depression Rating Scale. RESULTS The diverse treatments ameliorated walking and activities of daily living capacities to different extents. The greatest improvements were observed in the fluoxetine-treated group and the lowest in the maprotiline-treated group. Furthermore, fluoxetine yielded a significantly larger number of patients with good recovery compared with maprotiline or placebo. These effects of the drugs were not related to their efficacy in treating depressive symptoms. CONCLUSIONS Fluoxetine may facilitate or, alternatively, maprotiline may hinder recovery in poststroke patients undergoing rehabilitation. The effects of fluoxetine as an adjunct to physical therapy warrant further investigation, since treatment with fluoxetine may result in a better functional outcome from stroke than physical therapy alone.

The discovery of central monoamine neurons gave volume transmission to the wired brain

The dawn of chemical neuroanatomy in the CNS came with the discovery and mapping of the central dopamine, noradrenaline and 5-hydroxytryptamine neurons by means of transmitter histochemistry using the Falck-Hillarp formaldehyde fluorescence technique in the early 1960s. Our mapping of the central monoamine neurons was continued and further established with tyrosine hydroxylase, dopa decarboxylase and dopamine-beta-hydroxylase immunohistochemistry in collaboration with Menek Goldstein and Tomas Hökfelt. During recent years an evolutionary constraint in the nuclear parcellation of the DA, NA and 5-HT neurons was demonstrated in the order Rodentia and other mammals. The abundant existence of global monoamine varicose nerve terminal networks synthesizing, storing and releasing monoamines in various parts of the CNS, including the release of DA by tubero-infundibular DA neurons as a prolactin inhibitory factor from the external layer of the median eminence into the portal vessels and the appearance of extraneuronal DA fluorescence after, e.g., treatment with amphetamine in nialamide pretreated rats (Falck-Hillarp technique) were also remarkable observations. These observations and others like the discovery of transmitter-receptor mismatches opened up the possibility that monoamines were modulating the wired brain, built up mainly by glutamate and GABA neurons, through diffusion and flow in the extracellular fluid of the extracellular space and in the CSF. This transmission also involved long-distance channels along myelinated fibers and blood vessels and was called volume transmission (VT). The extracellular space (ECS), filled with a 3D matrix, plays a fundamental role in this communication. Energy gradients for signal migration in the ECS are produced via concentration, temperature and pressure gradients, the latter two allowing a flow of the ECF and CSF carrying the VT signals. The differential properties of the wiring transmission (WT) and VT circuits and communication channels will be discussed as well as the role of neurosteroids and oxytocin receptors in volume transmission leading to a new understanding of the integrative actions of neuronal-glial networks. The role of tunneling nanotubes with mitochondrial transfer in CNS inter alia as part of neuron-glia interactions will also be introduced representing a novel type of wiring transmission. The impact of the technicolour approach to the connectome for the future characterization of the wired networks of the brain is emphasized.

The effects of long-term rehabilitation therapy on poststroke hemiplegic patients.

Background and Purpose Rehabilitation therapy is believed to be useful during the first few months after stroke when recovery usually takes place. However, evidence exists that this may not be the rule for all stroke victims. Therefore, we investigated, in a selected group of poststroke patients, the profile of recovery in response to long-term rehabilitation therapy. Methods Fifty-one hemiplegic subjects unable to walk 3 months after stroke were enrolled in this study. Patients underwent consecutive periods of rehabilitation up to 2 years after the cerebrovascular accident. Autonomy in daily living activities and the degree of neurological compromission were periodically assessed with the Barthel Index and a neurological scale designed for hemiplegic subjects. The main features of the patients were also evaluated as a possible predictor of outcome Results In a consistent percentage of the patients, significant gains in gait and daily living abilities were observed during the first year and, in individual cases, during the second year after stroke. At the end of the study, 74% of the patients regained their capacity to walk without assistance, and up to 79% had a Barthel Index score above 70. Sphincter function, level of neurological impairments, and capacity in daily living activities are significantly related to the outcome of the patients as a whole but were not useful to anticipate the outcome of each patient. Conclusions These results suggest that disabled poststroke subjects may attain significative functional improvements in response to prolonged restorative therapy. However, the possibility of predicting the outcome of individual patients appears the major problem to solve in order to assign to long-term rehabilitation programs only patients whowill benefit from the therapy.

eXeRCISeS FOR PAReTIC UPPeR LIMb AFTeR STROKe: A COMbINeD VIRTUAL-ReALITY AND TeLeMeDICINe APPROACH

OBJECTIVE Telerehabilitation enables a remotely controlled programme to be used to treat motor deficits in post-stroke patients. The effects of this telerehabilitation approach were compared with traditional motor rehabilitation methods. DESIGN Randomized single-blind controlled trial. PATIENTS A total of 36 patients with mild arm motor impairments due to ischaemic stroke in the region of the middle cerebral artery. METHODS The experimental treatment was a virtual reality-based system delivered via the Internet, which provided motor tasks to the patients from a remote rehabilitation facility. The control group underwent traditional physical therapy for the upper limb. Both treatments were of 4 weeks duration. All patients were assessed one month prior to therapy, at the commencement and termination of therapies and one month post-therapy, with the Fugl-Meyer Upper Extremity, the ABILHAND and the Ashworth scales. RESULTS Both rehabilitative therapies significantly improved all outcome scores after treatment, but only the Fugl-Meyer Upper Extremity scale showed differences in the comparison between groups. CONCLUSION Both strategies were effective, but the experimental approach induced better outcomes in motor performance. These results may favour early discharge from hospital sustained by a telerehabilitation programme, with potential beneficial effects on the use of available resources.

Virtual reality for the rehabilitation of the upper limb motor function after stroke: a prospective controlled trial

BackgroundRecent evidence has demonstrated the efficacy of Virtual Reality (VR) for stroke rehabilitation nonetheless its benefits and limitations in large population of patients have not yet been studied.ObjectivesTo evaluate the effectiveness of non-immersive VR treatment for the restoration of the upper limb motor function and its impact on the activities of daily living capacities in post-stroke patients.MethodsA pragmatic clinical trial was conducted among post-stroke patients admitted to our rehabilitation hospital. We enrolled 376 subjects who had a motor arm subscore on the Italian version of the National Institutes of Health Stroke Scale (It-NIHSS) between 1 and 3 and without severe neuropsychological impairments interfering with recovery. Patients were allocated to two treatments groups, receiving combined VR and upper limb conventional (ULC) therapy or ULC therapy alone. The treatment programs consisted of 2 hours of daily therapy, delivered 5 days per week, for 4 weeks. The outcome measures were the Fugl-Meyer Upper Extremity (F-M UE) and Functional Independence Measure (FIM) scales.ResultsBoth treatments significantly improved F-M UE and FIM scores, but the improvement obtained with VR rehabilitation was significantly greater than that achieved with ULC therapy alone. The estimated effect size of the minimal difference between groups in F-M UE and FIM scores was 2.5 ± 0.5 (P < 0.001) pts and 3.2 ± 1.2 (P = 0.007) pts, respectively.ConclusionsVR rehabilitation in post-stroke patients seems more effective than conventional interventions in restoring upper limb motor impairments and motor related functional abilities.Trial registrationItalian Ministry of Health IRCCS Research Programme 2590412

Virtual environment training therapy for arm motor rehabilitation

Enhanced feedback provided by a virtual reality system has been shown to promote motor learning in normal subjects. We evaluated whether this approach could be useful for treating patients with motor deficits following brain lesions. Fifty subjects with mild to intermediate arm impairments due to stroke were selected for the study. The patients received treatment daily for one month, consisting of an hour of virtual-environment therapy with enhanced feedback. Before and after the therapy, we assessed the degree of motor impairment and autonomy in daily living activities using the Fugl-Meyer scale for the upper extremities and Functional Independence Measure, respectively. We also analyzed the velocity, duration, and morphology of a sequence of reaching movements, finally comparing the kinematic measures with the scores obtained on the clinical scales. The rehabilitation therapy yielded significant improvements over baseline values in the mean scores on the Fugl-Meyer and Functional Independence Measure scales. The mean Fugl-Meyer score correlated significantly with the duration and velocity of reaching movements. The collated data indicate that motor recovery in post-stroke patients may be promoted by the enhanced feedback provided in a virtual environment and that kinematic analysis of their movements provides reliable measures of motor function changes in response to treatment.

A short review of cognitive and functional neuroimaging studies of cholinergic drugs: implications for therapeutic potentials

Summary. In the last 20 years a cholinergic dysfunction has been the major working hypothesis for the pharmachology of memory disorders. Cholinergic antagonists and lesions impair and different classes of cholinomimetics (i.e. acetylcholine precursors, cholinergic agonists and acetylcholinesterase inhibitors) enhance attention and memory in experiment animals, healthy human subjects and Alzheimer disease patients. In addition, acetylcholinesterase inhibitors improve different cognitive (i.e. visuospatial and verbal) functions in a variety of unrelated disorders such as dementia with Lewy bodies, Parkinson disease, multiple sclerosis, schizoaffective disorders, iatrogenic memory loss, traumatic brain injury, hyperactivity attention disorder and, as we recently reported, vascular dementia and mild cognitive impairment. In animals, different cholinomimetics dose-dependently increased regional cerebral metabolic rates for glucose (rCMRglc) and regional blood flow (rCBF), two indices of neuronal function, more markedly in subcortical regions (i.e. thalamus, hippocampus and visual system nuclei). In both healthy human subjects and Alzheimer disease patients acetylcholinesterase inhibitors increased rCMRglc and rCBF in subcortical and cortical brain regions at rest but attenuated rCBF increases during cognitive performances. Hence, acetylcholinesterase inhibitors may enhance cognition and rCMRglc by acting primarily on subcortical regions that are involved in attentional (i.e. thalamus) and memory (i.e. hippocampus) processes; such an effect probably is not specific for Alzheimer disease and can be beneficial in patients suffering from a wide array of neuropsychiatric disorders.

The effects of propofol anesthesia on local cerebral glucose utilization in the rat.

The autoradiographic 14C-2-deoxy-D-glucose method was used to determine local cerebral glucose utilization (LCGU) during propofol anesthesia and recovery in 52 regions of the rat brain. Control rats intravenously received 5 ml.kg-1.h-1 of the egg-oil-glycerol emulsion that constitutes the vehicle for propofol. Anesthetized animals received an iv bolus of propofol (20 mg/kg) followed by continuous infusion of the anesthetic at 12.5, 25, or 50 mg.kg-1.h-1 for 1 h prior to injection of 14C-2-deoxy-D-glucose and for the following 45 min. In addition, a fifth group of animals were studied immediately after awakening from a 20 mg/kg bolus of propofol as indicated by the first reappearance of head lift. All rats were spontaneously breathing room air throughout the experimental procedure. The general pattern of the cerebral metabolic response to propofol anesthesia was a dose-related, widespread depression of LCGU. At the three infusion rates of propofol tested, overall mean LCGU was reduced by 33%, 49%, and 55%, respectively, and significant decreases were observed in 60%, 85%, and 90% of the regions assayed. These effects were rapidly reversible, since in the recovery group, LCGU returned to near control values in the majority of the brain areas. Although all of the anatomofunctional systems (sensorimotor, extrapyramidal, limbic, and reticular) were involved, forebrain structures showed a greater sensitivity to the depressant action of propofol than did hindbrain regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Satisfaction with care in post-stroke patients undergoing a telerehabilitation programme at home

We conducted a pilot telerehabilitation study with post-stroke patients with arm motor impairment. We compared the degree of satisfaction of patients undergoing a virtual reality (VR) therapy programme at home (Tele-VR group) to satisfaction experienced by those undergoing the same VR therapy in a hospital setting (VR-group). The rehabilitation equipment used a 3D motion tracking system to create a virtual environment in which the patients movement was represented. In tele-therapy, the patient equipment was installed in their homes, connected to the hospital by four ISDN lines at a total bandwidth of 512 kbit/s. Rehabilitation data were transmitted via one line and videoconferencing via the other three. Ten patients with mild to intermediate arm motor impairment due to an ischaemic stroke, were randomized into VR or Tele-VR groups. A questionnaire was used at the end of treatment to measure each patients degree of satisfaction. Tele-VR treated patients showed median values equal to or higher than the VR group patients in all 12 items investigated, except one. In motor performance, the Tele-VR group improved significantly (P ≤ 0.05), while the VR group showed no significant change. Patients assigned to the Tele-VR group were able to engage in therapy at home and the videoconferencing system ensured a good relationship between the patient and the physical therapist whose physical proximity was not required.

Motor tele-rehabilitation in post-stroke patients

Primary objective: The advanced communication technology may allow rehabilitative interventions to patients living at home from a remote provider. We evaluated the effects of a tele-rehabilitation system for the therapy of arm motor impairments due to a stroke. Research design: Experimental observational study. Methods and procedures: We selected five patients suffering from mild/intermediate arm motor impairments due to a long-lasting ischaemic stroke. Two workstations were utilized, one in the patients house and the other in the rehabilitation hospital, connected through the phone lines. A virtual reality based software allowed the patient to perform adequate motor tasks created by the physiotherapist. During performance, the patient could see not only their movement but also the correct trajectory that they had to accomplish. The feedback derived from the patients action, its outcome, and feedback from the supervision of the physiotherapist may favour the acquisition of new motor abilities. Main outcome measures: The arm motor performance and the activities of daily living were evaluated using the Fugl-Meyer and Functional Independence Measure scale, together with the determination of the velocity and duration of 10 representative reaching movements. Results: Subjects underwent the tele-rehabilitation programme for 4 weeks. The therapy significantly improved the Fugl-Meyer mean score, the mean duration and the velocity of the movements, but not the Functional Independence Measure scale score. Conclusions: These results indicated that this tele-rehabilitation system did not appear to adversely affect rehabilitation; rather it may improve arm motor deficits due to a stroke. If these evidences are further confirmed, tele-rehabilitation may represent a new home-based therapy to treat disabled people.