Improve Motor Deficits Research Articles

Validation of a Standardized Normalization Template for Statistical Parametric Mapping Analysis of 123I-FP-CIT Images

(123)I-FP-CIT ((123)I-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl)nortropane) is a SPECT dopamine transporter (DAT) tracer that probes dopaminergic cell loss in Parkinson's disease (PD). Quantification of (123)I-FP-CIT images is performed at equilibrium using a ratio (BR) of specific (striatal) to nonspecific (occipital) uptake with values obtained from regions of interest drawn manually over these structures. Statistical parametric mapping (SPM) is a fully automated voxel-based statistical approach that has great potential in the context of DAT imaging. However, the accuracy of the spatial normalization provided by SPM has not been validated for (123)I-FP-CIT images. Our first aim was to create an (123)I-FP-CIT template that does not require the acquisition of patient-specific MRI and to validate the spatial normalization procedure. Next, we hypothesized that this customized template could be used by different SPECT centers without affecting the outcomes of imaging analyses. The spatial normalization to the customized template created with SPM (template A1) was validated using (123)I-FP-CIT images obtained from 6 subjects with essential tremor (ET) with normal DAT status and 6 PD patients. Variability in BR values due to the normalization was evaluated using striatal volume of interest (VOI). To determine whether different SPECT centers could use a unique (123)I-FP-CIT template, we generated 3 other (123)I-FP-CIT templates using different subjects and image-processing schemes. The interchangeability of these templates was assessed using (a) putamen BR values analyzed with the intraclass correlation coefficient (ICC) and the Bland-Altman graphical analysis, and (b) SPM analysis comparing the results of group comparisons-that is, ET versus PD, obtained after normalization to each of the 4 templates. There was no significant difference between pre- and post-normalization striatal BR values in our study. The mean variability calculated with putamen VOI values after normalization to each template was <10%, with the lowest ICC of 98%. Intergroup analyses performed with VOI and SPM approaches provided similar results independently of the template used. SPM normalization was accurate even in subjects with low striatal (123)I-FP-CIT uptake, making it a promising approach for automatic analysis of (123)I-FP-CIT images using a single customized template at different centers.

Nicotinic receptors as CNS targets for Parkinson's disease

Parkinson's disease is a debilitating neurodegenerative movement disorder characterized by damage to the nigrostriatal dopaminergic system. Current therapies are symptomatic only and may be accompanied by serious side effects. There is therefore a continual search for novel compounds for the treatment of Parkinson's disease symptoms, as well as to reduce or halt disease progression. Nicotine administration has been reported to improve motor deficits that arise with nigrostriatal damage in parkinsonian animals and in Parkinson's disease. In addition, nicotine protects against nigrostriatal damage in experimental models, findings that have led to the suggestion that the reduced incidence of Parkinson's disease in smokers may be due to the nicotine in tobacco. Altogether, these observations suggest that nicotine treatment may be beneficial in Parkinson's disease. Nicotine interacts with multiple nicotinic receptor (nAChR) subtypes in the peripheral and central nervous system, as well as in skeletal muscle. Work to identify the subtypes affected in Parkinson's disease is therefore critical for the development of targeted therapies. Results show that striatal α6β2-containing nAChRs are particularly susceptible to nigrostriatal damage, with a decline in receptor levels that closely parallels losses in striatal dopamine. In contrast, α4β2-containing nAChRs are decreased to a much smaller extent under the same conditions. These observations suggest that development of nAChR agonists or antagonists targeted to α6β2-containing nAChRs may represent a particularly relevant target for Parkinson's disease therapeutics.

The effect of striatal dopamine depletion and the adenosine A 2A antagonist KW-6002 on reversal learning in rats

This study assessed whether dopamine in the dorsomedial striatum is necessary for flexible adaptation to changes in stimulus–response contingencies. As KW-6002 (Istradefylline), an adenosine A 2A antagonist, improves motor deficits resulting from striatal dopamine depletion, we also tested for potential ameliorative effects of KW-6002 on dopamine depletion-induced cognitive deficits. Male Lister hooded rats were presented with two bowls, discriminable by either a textured covering on the outer surface, their scent or the bowl contents (digging media) in which bait was buried. Once they had learned in which bowl food was buried, the stimulus–response contingencies were reversed. In both phases (acquisition and reversal), the criterion for learning was defined a priori as six consecutive correct trials. Following depletion of dopamine in the dorsomedial striatum, acquisition of the discriminations was intact but there was an increase in the number of trials to attain criterion performance in the reversal phases, indicating an impairment in reversal learning. KW-6002 (1 mg/kg bidaily for 10 days) non-specifically increased the number of trials to criterion at all stages of the test and in both controls (sham-operated) and dopamine-depleted rats. Chronic KW-6002 treatment did not improve the reversal deficits in dopamine-depleted rats. These findings suggest that dopamine transmission in the dorsomedial striatum is critical for the flexible shifting of response patterns and the ameliorative effects of KW-6002 following depletion of dopamine in the striatum may be restricted to motor functions without relieving deficits in response-shifting flexibility.

Effect of subthalamic nucleus lesions in a 6-hydroxydopamine–induced rat parkinsonian model: behavioral and biochemical studies

The purpose of this study was to determine whether subthalamic nucleus (STN) ablation caused by kainic acid can restore dopaminergic neurotransmission and improve motor deficits in a 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonian model. The authors investigated behavioral changes in rats displaying parkinsonian symptoms (6-OHDA-lesioned rats) after an STN lesion was created using kainic acid. They also measured levels of dopamine and its metabolites following tissue dissection. The results of this study showed that STN ablation led to behavioral improvement in parkinsonian motor deficits. Increased levels of dopamine were also observed in the striatum and globus pallidus externus (GPE). The results indicate that creation of an STN lesion in this hemiparkinsonian rat model may counteract some of the neurochemical changes within the striatum and GPE caused by the 6-OHDA, and influence striatal dopaminergic metabolism.

Switching from Levodopa to the Long-acting Dopamine D2/D3 Agonist Piribedil Reduces the Expression of Dyskinesia While Maintaining Effective Motor Activity in MPTP-treated Primates

The control of motor complications following dopaminergic medication in late-stage Parkinson disease remains problematic. We now investigate the potential of oral administration of the long-acting dopamine D2/D3 agonist piribedil to decrease the expression of dyskinesia induced by prior exposure to levodopa in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-treated primates. MPTP-treated common marmosets were treated with equieffective doses of levodopa (10.0-12.5 mg/kg PO, twice daily) or piribedil (3.0-4.0 mg/kg PO, once daily) for 30 days and then switched to the alternative treatment for a further 35 days. Levodopa administration markedly improved motor function, but dyskinesia rapidly appeared and intensified as treatment progressed. Administration of piribedil produced a similar reversal of MPTP-induced motor deficits but with comparatively mild dyskinesia. On switching from levodopa to piribedil, the intensity of dyskinesia decreased without altering the improvement in motor deficits. However, on switching from piribedil to levodopa, the rapid increase in dyskinesia despite the improvement in motor function being maintained suggests that piribedil also primes for but does not markedly express dyskinesia. The study confirms the low dyskinesia expression resulting from piribedil treatment compared with an equieffective dose of levodopa. Importantly, the results show that switching from levodopa to piribedil rapidly results in a sustained decrease in dyskinesia intensity.

Cystamine and cysteamine prevent 3‐NP‐induced mitochondrial depolarization of Huntington's disease knock‐in striatal cells

Abstract Cystamine significantly improved motor deficits and extended survival in mouse models of Huntington's disease (HD); however, the precise mechanism(s) by which cystamine and the related compound cysteamine are beneficial remain to be elucidated. Using clonal striatal cell lines from wild-type (STHdhQ7/HdhQ7) and mutant huntingtin knock-in (STHdhQ111/HdhQ111) mice, we have tested the hypothesis that cystamine and cysteamine could be beneficial by preventing the depolarization of mitochondria in cell cultures. Treatment with 3-nitroproprionic acid (3-NP), a mitochondrial complex II inhibitor, induces mitochondrial depolarization and cell death of mutant HD striatal cells but not of wild-type cells. The 3-NP-mediated decrease in the mitochondrial membrane potential was attenuated by 50 microm cystamine and completely inhibited by 250 microm cystamine. Similar results were obtained using cysteamine (50-500 microm). In addition, both cystamine and cysteamine significantly attenuated the 3-NP-induced cell death. Treatment of mutant HD striatal cells with 3-NP resulted in a robust decrease in the cellular and mitochondrial levels of glutathione (GSH) compared with cells exposed to the vehicle alone. Pre-treatment of the cells with cystamine and cysteamine completely prevented the 3-NP-mediated decrease in cellular and mitochondrial GSH levels. Incubation with L-buthionine (S,R) sulfoximine (BSO) 250 microm in combination with cystamine (250 microm) or cysteamine (250 microm) prior to being treated with 3-NP completely prevented the beneficial effects of cystamine and cysteamine on the 3-NP-mediated mitochondrial depolarization. These results demonstrate that cystamine and cysteamine prevent the 3-NP-induced mitochondrial depolarization of HD striatal cell cultures.

New therapies for the treatment of Parkinson's disease: Adenosine A2A receptor antagonists

The development of non-dopaminergic therapies for the treatment of Parkinson's disease (PD) has attracted much interest in recent years. Among new different classes of drugs, adenosine A2A receptor antagonists have emerged as best candidates. The present review will provide an updated summary of the results reported in literature concerning the effects of adenosine A2A antagonists in rodent and primate models of PD. These results show that A2A receptor antagonists improve motor deficits without inducing dyskinesia and counteract parkinsonian tremor. In progress clinical trials have shown that a low dose of l-DOPA plus KW-6002 produced symptomatic relief no different from that produced by an optimal dose of l-DOPA alone, whereas dyskinesias were reduced rendering this class of compounds particularly attractive.

Ballism After Stroke Responds to Standard Physical Therapeutic Interventions

Mark VW, Oberheu AM, Henderson C, Woods AJ. Ballism after stroke responds to standard physical therapeutic interventions. Arch Phys Med Rehabil 2005;86: 1226–33. Objective To report the effects of noninvasive standard physical therapy (PT) interventions on an involuntary movement disorder after stroke. Design Single case with clinical follow-up over 2 years. Setting Inpatient stroke and rehabilitation services and outpatient clinic. Participant A man with acute bilateral ballism after unilateral subthalamic infarction. Interventions Rhythmic coordinated bilateral limb movements and firm tactile stimulation to the hand. Main Outcome Measures We had not anticipated that dyskinesia itself would specifically improve during treatment. Consequently, we used qualitative clinical observations, including review of videotaped performance, and self-reported limb control. Hypotheses concerning treatment effects were developed after data collection. Results Involuntary movements recurrently improved within treatment sessions. Conclusions PT may improve dyskinesia after stroke. The benefit may be adjunctive or alternative to current invasive treatments of movement disorders after brain injury and merits confirmation. The improvements are consistent with current research indicating that (1) intact cortical, subcortical, cerebellar, and spinal areas interact to generate bilateral rhythmic limb movements that can overcome dyskinesia and (2) tactile stimulation can improve motor deficits associated with basal ganglia disorders. Finally, because functional activities assessments improved our evaluation of ballism, these should be routinely used along with conventional neurologic examination to assess involuntary movement disorders.

New adenosine A 2A receptor antagonists: Actions on Parkinson's disease models

The 8-substituted 9-ethyladenine derivatives: 8-bromo-9-ethyladenine (ANR 82), 8-ethoxy- 9-ethyladenine (ANR 94), and 8-furyl-9-ethyladenine (ANR 152) have been characterized in vitro as adenosine receptor antagonists. Adenosine is deeply involved in the control of motor behaviour and substantial evidences indicate that adenosine A 2A receptor antagonists improve motor deficits in animal models of Parkinson's disease. On this basis, the efficacy of ANR 82, ANR 94, and ANR 152 in rat models of Parkinson's disease was evaluated. All compounds tested reversed the catalepsy induced by haloperidol. However, in unilaterally 6-hydroxydopamine-lesioned rats, only ANR 94 and ANR 152 potentiated l-dihydroxy-phenylalanine ( l-DOPA) effect on turning behaviour and induced contralateral turning behaviour in rats sensitised to l-DOPA. Taken together the results of this study indicate that some 8-substituted 9-ethyladenine derivatives ameliorate motor deficits in rat models of Parkinson's disease, suggesting a potential therapeutic role of these compounds.

Comparison of 1 x 8 Gy and 10 x 3 Gy for functional outcome in patients with metastatic spinal cord compression

Since life expectancy is markedly reduced in patients with metastatic spinal cord compression (MSCC), a short and effective radiation schedule is desired. This study investigates a reduction of the overall treatment time to only one day by comparing 1 x 8 Gy to the multi-fractionated 10 x 3 Gy for functional outcome. Data of 204 patients, treated for MSCC with either 1 x 8 Gy (n = 96) or 10 x 3 Gy (n = 108), were analyzed retrospectively. Motor function and ambulatory status were evaluated before and up to 24 weeks after RT. A multivariate analysis (nominal regression) was performed including radiation schedule, performance status, age, irradiated vertebra, and relevant prognostic factors (histology, ambulatory status, time of developing motor deficits). Improvement of motor deficits was selected as basic category and compared with no change and deterioration. Univariate analysis showed no significant difference between the schedules for post-treatment motor function and ambulatory rates. Multivariate analysis demonstrated a significant effect on functional outcome for the prognostic factors, but not for the radiation schedule (p = 0.853 for no change, p = 0.237 for deterioration). Our data suggest the two fractionation schedules to be comparably effective for functional outcome. Thus, 1 x 8 Gy should be considered for patients with a poor survival prognosis.

The neuroprotective effect of glial cell line-derived neurotrophic factor in fibrin glue against chronic focal cerebral ischemia in conscious rats

Glial cell line-derived neurotrophic factor (GDNF) is a transforming growth factor-β which has shown beneficial effects in rats after acute focal cerebral ischemia (FCI). To study the effects of GDNF on chronic FCI injury in conscious rats, we used fibrin glue (GDNF-fibrin glue) and fibrin glue free (GDNF-only)-GDNF topically applied to the ischemic brain after right middle cerebral artery (MCA) ligation. Infarct brain volume and functional motor deficits were measured before and after FCI injury. After FCI injury induced by right MCA ligation, rats were randomly assigned to one of four treatment groups: (a) sham, (b) control, (c) topically applied GDNF (1 μg)-only, and (d) topically applied GDNF (1 μg)-fibrin glue. The degree of ischemic brain injury was estimated by infarct volume of right MCA territory at 4 weeks after occlusion. The functional motor deficits were quantified with rotarod test and grasping power test once a week. Topically applied GDNF-fibrin glue at infarct brain tissue after 4 weeks FCI injury significantly reduced the total infarct volume by 44.3% and 36%, respectively, compared to that of control group and GDNF-only group. The mean latencies for rats to stay on the rotarod were 55.0%, 50.3%, and 92.2% ( P < 0.05 vs. control group and GDNF-only group) of baseline, respectively, in the control, GDNF-only, and GDNF-fibrin glue groups at the end of the 1st week after FCI injury but 75.3%, 67.3%, and 106.6% ( P < 0.05 vs. control group and GDNF-only group) of baseline at the end of the 4th week after FCI injury. The mean values of grasping power were 78.7%, 71.7%, and 101.2% ( P < 0.05 vs. control group and GDNF-only group) of baseline, respectively, in the control, GDNF-only, and GDNF-fibrin glue groups at the end of 1st week after FCI injury but 89.6%, 97.6%, and 120.7% ( P < 0.05 vs. control group) of baseline at the end of 4th week after FCI injury. These results indicate that GDNF-fibrin glue not only reduced the total infarct volume after FCI injury but can also improve motor deficits after FCI injury. We concluded GDNF-fibrin glue could facilitate delivery of GDNF to the damaged brain tissue with subsequent reduction of ischemic brain injury accompanied by enhancing functional recovery in rats with chronic FCI injury.

Riluzole improves motor deficits and attenuates loss of striatal neurons in a sequential double lesion rat model of striatonigral degeneration (parkinson variant of multiple system atrophy)

We investigated neuroprotective effects of riluzole, an anti-glutamatergic agent that is FDA approved for disease-modifying therapy in amyotrophic lateral sclerosis (ALS), in an established double lesion rat model of striatonigral degeneration (SND), the neuropathological substrate of parkinsonism associated with MSA (MSA-P). Riluzole was administered prior to and consecutively for ten days following double lesion placement in the left-sided medial forebrain bundle and ipsilateral striatum. Assessment of motor behaviour using a flex field system showed a significant reduction of motor disturbance in animals with striatonigral lesions treated with riluzole compared to lesioned but untreated animals (P<0.001). DARPP-32 immunohistochemistry revealed a significant reduction of absolute striatal lesion volume in riluzole treated animals compared to lesioned but untreated animals (P<0.01). No significant difference in counts of nigral dopaminergic neurons was found in treated versus untreated double-lesioned animals. The results of our study indicate that riluzole mediates neuroprotective effects in the double lesion rat model of MSA-P. Whether riluzole also protects autonomic and cerebellar pathways that are frequently affected in MSA remains to be determined. Nonetheless, our study is the first to provide an experimental rationale for exploring possible neuroprotective effects of riluzole in MSA.

Improvement of Kinaesthetic Deficits by Subthalamic Nucleus Stimulation in Parkinson's Disease

Recent studies have revealed that patients with Parkinson's disease (PD) exhibit kinaesthesic deficits. For example, they have higher perceptual thresholds in detecting passive elbow movements. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor deficits in PD, but its effect on kinaesthesia is unknown. We have now examined how STN DBS affects the perception of limb position. 9 PD patients with bilateral chronic STN DBS and 7 controls were tested. The subject's forearm was moved passively (˜ 0.5 deg/s) while resting on a splint. A torque motor was mechanically connected to the splint, moving it at a constant speed causing either forearm flexion or extension. For each condition (ON or OFF stimulation), 40 flexion and 40 extension movements were recorded with elbow joint angular displacements of 0.2, 0.6, 1 up to 8. To account for order effects, a subset of the PD patients (n=5) was tested in the ON-stimulation state first, while the remaining patients were first examined during the OFF-stimulation state (n=4). A 1° displacement was detected in 78% of the trials and a 2° displacement in over 91% of the trials by the control subjects. In contrast, PD patients were clearly impaired in the correct detection of movement direction. During ON-stimulation they showed correct responses in 74% for 2° displacements. Deficits worsened when the DBS device was OFF with PD patients correctly detecting 2° displacements in only 60% of the trials. Thresholds for 75% correct responses were 0.9° for controls, 2.5° for PD patients when stimulation was OFF and 2.0° when stimulation was ON. We conclude that STN DBS may improve kinaesthesic deficits in PD, but does not lead to a full recovery of proprioceptive function. (Work supported by a grant from the DFG (MA 2209/3–1.)

Dopamine, but not norepinephrine or serotonin, reuptake inhibition reverses motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primates.

Monoamine reuptake inhibitors that do not discriminate between the transporters for dopamine (DA), norepinephrine (NE), or 5-hydroxytryptamine (5-HT, serotonin) can reverse locomotor deficits and motor disability in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmosets. DA reuptake inhibition is presumed to be primarily responsible, but the role played by inhibition of NE and 5-HT reuptake is unknown. We now evaluate the efficacy of a range of monoamine reuptake inhibitors either alone or in combination in MPTP-treated common marmosets to determine the actions required for effective antiparkinsonian activity. Monoamine reuptake inhibitors not discriminating between the DA, NE, and 5-HT transporters [1-[1-(3,4-dichlororphenyl)cyclobutyl]-2-(3-diaminethylaminopropylthio)ethanone monocitrate (BTS 74 398) and nomifensine] reversed locomotor deficits and motor disability in MPTP-treated marmosets but bupropion was without effect. The selective DA reuptake inhibitor 1-(2-(bis-(4-fluorophenyl)-methoxy)ethyl)-4-(3-phenylpropyl) piperazine) dihydrochloride (GBR 12909) also reversed these motor deficits. The relative efficacy of the compounds (BTS 74 398 > GBR 12909 > nomifensine >> bupropion) paralleled their potency in inhibiting DA uptake in vitro and in vivo. In contrast, the selective NE reuptake inhibitor nisoxetine and the 5-HT reuptake inhibitor sertraline administered alone failed to improve motor function and tended to worsen the deficits. Coadministration of nisoxetine attenuated the improvement in motor deficits produced by GBR 12909. Coadministration of sertraline also abolished the reversal of motor deficits produced by GBR 12909. Coadministration of both sertraline and nisoxetine similarly abolished the improvement of motor deficits produced by GBR 12909. Molecules possessing potent DA reuptake inhibitory activity may be useful in the treatment of the motor symptoms of Parkinson's disease. In contrast, there seems to be no role for NE or 5-HT reuptake inhibitors, and they may impair antiparkinsonian activity mediated through dopaminergic mechanisms.

HNT neurons delay onset of motor deficits in a model of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease that manifests as a progressive muscular weakness leading to paralysis and death. Because of the diffuse nature of the motor neuron death, this disease is not considered a good candidate for treatment through neural transplantation. The purpose of this study was to show that transplantation of human neuron-like cells (hNT neurons) into the spinal cord of a transgenic ALS mouse model would improve motor deficits. The hNT neurons were transplanted bilaterally into L4-L5 spinal cord of the transgenic mice (∼8 weeks of age), and the animals were evaluated on health and behavioral measures. The animals were perfused, and immunohistochemistry was performed to identify the transplanted cells. Transplantation of the hNT neurons into the spinal cord delayed the onset of motor behavioral symptoms. This was the first demonstration that even localized transplantation of neural cells directly into the parenchyma could improve motor function in an ALS model. Further study is needed to delineate the mechanism underlying these effects. This therapeutic approach has the potential to restore neural transmission, thereby improving quality of life for the ALS patient and possibly extend life expectancy.

(−)-1-(Benzofuran-2-yl)-2-propylaminopentane enhances locomotor activity in rats due to its ability to induce dopamine release

“Catecholaminergic and serotoninergic activity enhancer” effects are newly found mechanisms of action of a class of compound that enhance impulse propagation-mediated release of catecholamines and serotonin in the brain. In the present study, (−)-1-(benzofuran-2-yl)-2-propylaminopentane hydrochloride [(−)-BPAP HCl], a compound with selective and potent “catecholaminergic and serotoninergic activity enhancer” effects, was tested for its efficacy to potentiate locomotor activity in normal rats and to attenuate hypolocomotion in reserpine-treated rats. (−)-BPAP HCl potentiated locomotor activity in non-habituated rats during a 2-h observation period dose-dependently (0.3–10 mg/kg). (−)-BPAP HCl (1–3 mg/kg) was also effective to reverse reserpine-induced hypolocomotion. The effects of (−)-BPAP HCl in normal and reserpine-treated rats were attenuated by the dopamine D1 receptor antagonist, R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine (SCH 23390), suggesting that the effects of (−)-BPAP HCl were mediated by activation of the dopaminergic system. In addition, the administration of (−)-BPAP HCl increased ipsilateral turning in unilaterally 6-hydroxydopamine-lesioned rats, implying presynaptic activation of nigrostriatal dopaminergic terminals by (−)-BPAP HCl. Furthermore, although antiparkinsonian agents, such as apomorphine and amantadine, failed to improve reserpine-induced ptosis, (−)-BPAP HCl significantly improved ptosis. These findings suggested that a “catecholaminergic and serotoninergic activity enhancer” compound, (−)-BPAP, stimulates motor function in rats and improves motor deficits in animal models of Parkinson's disease due to its ability to induce dopamine release.

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) In Diabetes: Two Different Patterns Of Response To IV IG

OBJECTIVE: The finding of predominantly demyelinating polyneuropathies has been considered unusual in diabetic patients, however recent studies reported polyneuropathies satisfying electrophysiological criteria for diagnosis of CIDP (Gorson et al., 2000; Rotta et al., 2000) can be detected in diabetic patients. It is uncertain if this type of PN shows similar response to immunomodulating treatment as compared to other CIDP. In this study we evaluated response to IV IG in 10 diabetic patients with predominantly demyelinating polyneuropathy. PATIENTS AND METHODS: We included all diabetic patients with CIDP evaluated in our department from July 1999 to November 2000. 13 patients were found to be affected with predominantly demyelinating polyneuropathy; 3 of them refused IV IG. Sensory and motor disturbances according to Van Dijk et al. (1999) and nerve conduction studies (NCS) according to standard techniques were performed before IV IG treatment (T0) and 1 month (T1) and 6 months (T2) after IV IG. All patients underwent CSF examination and anti‐MAG, anti‐sulphatide and anti‐GM1 antibody assay. RESULTS: Increased CSF protein levels were found in 6 patients. No patients were positive for anti‐MAG, anti‐sulphatide or anti‐GM1 antibody assay. We did not detect significant clinical improvement after IV IG treatment, however there was improvement of motor deficit in 2 patients and of sensory score in 3. Six patients, 3 with increased CSF proteins level, had improvement on NCS, however there was not overall significant improvement of NCS abnormalities at T1. Patients with normal CSF protein levels had greater, although not significant, improvement on NCS than patients with increased protein levels. All patients with increased CSF protein levels deteriorated clinically or on NCS before T2. All patients with normal CSF protein levels remained stable on both items at T2. DISCUSSION: Our results confirmed low response of diabetic patients with demyelinating polyneuropathy to immunomodulating treatment, outlined by Gorson et al. (2000). In our study patients with normal CSF protein levels seem to have a better response to IV IG treatment probably reflecting a different pathogenesis as compared to patients with increased CSF protein levels. On the other hand, the high rate of relapse after IV IG treatment in patients with increased CSF protein levels seems to confirm the association of diabetes mellitus and CIDP in some patients.

Effects of ropinirole on motor behavior in MPTP-treated common marmosets

The effects of ropinirole (4-[2-(dipropylamino)ethyl]-2-indolinone monohydrochloride), a nonergoline dopamine receptor agonist with a high affinity for native dopamine D 2-like receptors, on Parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 2.5 mg/animal in common marmosets were examined and compared to the effects of bromocriptine. Ropinirole (0.1–3 mg/kg, PO) increased motor activity dose dependently and reversed akinesia or uncoordinated movement in MPTP-treated marmosets. The activities for ropinirole were very similar to those of bromocriptine. Ropinirole had, however, several properties that differed from those of bromocriptine. Ropinirole caused a more rapid onset of anti-Parkinsonian activity compared to bromocriptine, and had a potency more than five times greater than that of bromocriptine in the improvement of motor deficits. The combination of ropinirole and l-DOPA increased the effectiveness of ropinirole or l-DOPA alone, and produced a more marked additive effect on motor activity than did bromocriptine and l-DOPA. Chronic administration of ropinirole for 21 days produced a statistically significant increase in motor activity compared to the initial administration, and akinesia scores, measured through rating the quality of movements, were also improved without obvious dyskinesia. This study suggests that ropinirole is a dopamine D 2-like receptor agonistic drug of potential use in the treatment of Parkinson's disease.

Cerebral Palsy.

The neurorehabilitation program for cerebral palsy changes over time. During the first 2 years of life, an infant stimulation program with an emphasis on more than just improving motor deficits is emphasized. The importance of involvement of a knowledgeable therapist cannot be overemphasized. Realistic expectations must be articulated firmly. Rather then cautiously attempting to correct a dysfunction that cannot be corrected, the therapist should help the patient develop compensation techniques; the severity of the disability frequently militates against the development of "normal" motor control. Educating the parents about cerebral palsy, showing how positioning can be an effective way of helping the child be mobile, and encouraging parent-child interaction are aspects of an infant stimulation program. The therapist should serve as a coach to the parents, who implement much of the actual treatment on a daily basis at home. From 2 to 5 years of age, rapid growth occurs, and muscle tone will either develop or worsen--the latter leading not only to the development of contracture but also to a decrease in mobility. In developing a program to control this muscle tone, the most important question to be answered is, Can I improve the patient's function and decrease the patient's disability by altering muscle tone? It is not uncommon for the real problem preventing the patient from performing certain functions to be lack of motor control or lack of sensation and not the abnormal muscle tone. Between 5 and 10 years of age, the child begins to approach adult height. At this time, definitive orthopedic intervention can be considered; as already noted, contracture development occurs as a result of abnormal muscle tone in combination with growth. Finally, as the child approaches the teen years, issues of sitting and hygiene are important considerations, especially in the nonambulatory patient. The problem of pain secondary to spasticity or dystonia must be addressed.

The effect of sleep deprivation on motor impairment and retinal adaptation in Parkinson's disease

1. 1. Sleep deprivation has previously been reported to result in a temporary improvement of motor deficits in Parkinson's disease patients. 2. 2. The mechanism of this action is unclear but may involve an activation of dopamine pathways. 3. 3. Other studies suggest that light adaptive changes in the retinal pigment epithelium may serve as a model of dopamine sensitivity. 4. 4. The present study examined the effects of one night of total sleep deprivation on RPE potentials and motor abnormalities in Parkinson's patients. 5. 5. Sleep deprivation significantly improved motor deficits and these changes were strongly correlated with increases in light adaptive RPE potentials.