Cognitive and behavioral assessment in the early stages of neurodegenerative extrapyramidal syndromes.

Parkinson's disease (PD), Dementia with Lewy Bodies (DLB), Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration Syndrome (CBDS) are the most common neurodegenerative extrapyramidal syndromes. Beyond motor symptoms, cognitive dysfunctions and behavioral disturbances are reported. Neuropsychological and neuropsychiatry features in the early stages, however, are under-investigated, and few comparison studies are available yet. The aim of the present study was to evaluate the cognitive and behavioral profile in the early stages of neurodegenerative extrapyramidal syndromes. Thirty-nine PD, 27 DLB, 16 CBDS, and 24 PSP were recruited. Groups were matched for global cognitive and motor impairment. The overall sample showed a common neuropsychological core characterized by visuospatial deficits. Although in the early stage of the disease, a high presence of behavioral disturbances was detected, depression and anxiety were the most common disorders, followed by apathy and sleep disturbances. The observation of overlapping clinical entities points the attention on the need of adjunctive diagnostic markers for early differential diagnosis.

Paired transcranial magnetic stimulation for the early diagnosis of corticobasal degeneration.

OBJECTIVE: To investigate cortical excitability in patients with corticobasal degeneration (CBD) and to find a reliable diagnostic technique for differentiating CBD from Parkinson's disease (PD). METHODS: Using a paired transcranial magnetic stimulation technique, we studied motor cortex excitability at rest in 6 patients with clinically probable CBD, 10 patients with PD, and 10 normal subjects. The recovery cycle of the motor evoked potentials was tested by delivering paired magnetic stimulation over the hand area of the motor cortex at interstimulus intervals (ISIs) from 1 to 17ms. RESULTS: In patients with CBD, paired magnetic stimuli delivered at short ISIs invariably elicited enlarged test MEPs. At ISIs of 1-10ms, the conditioned test MEPs were significantly larger in patients with CBD than in control subjects; and at ISIs of 1, 2, 4, and 6ms,they were also larger in patients with CBD than in patients with PD. At the other ISIs tested, patients and control subjects had similar amplitude conditioned test responses. CONCLUSIONS: Our findings suggest that the unusual clinical manifestations of CBD might arise partly from motor cortex disinhibition. Paired magnetic stimulation could be a useful diagnostic test particularly in the early stages of the disease.

The excitability of human cortical inhibitory circuits responsible for the muscle silent period after transcranial brain stimulation.

The silent period after transcranial magnetic brain stimulation mainly reflects the activity of inhibitory circuits in the human motor cortex. To assess the excitability of the cortical inhibitory mechanisms responsible for the silent period after transcranial stimulation, we studied, in 15 healthy human subjects, the recovery cycle of the silent period evoked by transcranial and mixed nerve stimulation delivered with a paired stimulation technique. The recovery cycle is defined as the time course of the changes in the size or duration of a conditioned test response when pairs of stimuli (conditioning and test) are used at different conditioning-test intervals. The recovery cycle of the duration of the silent period in the first dorsal interosseous (FDI) muscle during maximum voluntary contraction after transcranial magnetic stimulation was studied by delivering paired magnetic shocks (a conditioning shock and a test shock) at 120% motor-threshold intensity. Conditioning-test intervals ranged from 20-550 ms. The recovery cycle of the silent period in the FDI muscle during maximum voluntary contraction after nerve stimulation was evaluated by paired, supramaximum bipolar electrical stimulation of the ulnar nerve at the wrist (conditioning-test intervals ranging from 20 to 550 ms). Electromyographic activity was recorded by a pair of surface-disk electrodes over the FDI muscle. The recovery cycle of the silent period after transcranial magnetic stimulation delivered through the large round coil showed two phases of facilitation (lengthening of the silent period), one at 20-40 ms and the other at 180-350 ms conditioning-test intervals, with an interposed phase of inhibition (shortening of the silent period) at 80-160 ms. The conditioning magnetic shock left the size of the test motor-evoked potentials statistically unchanged during maximum voluntary contraction. Paired transcranial stimulation with a figure-of-eight coil increased the duration of the test silent period only at short conditioning-test intervals. Conditioning nerve stimulation left the silent period produced by test nerve stimulation unchanged. In conclusion, after a single transcranial magnetic shock, inhibitory circuits in the human motor cortex undergo distinctive short-term changes in their excitability, probably involving different mechanisms.

Inhibitory action of forearm flexor muscle afferents on corticospinal outputs to antagonist muscles in humans.

1. To find out whether muscle afferents influence the excitability of corticospinal projections to antagonist muscles, we studied sixteen healthy subjects and one patient with a focal brain lesion. 2. Using transcranial magnetic and electrical brain stimulation we tested the excitability of corticomotoneuronal connections to right forearm muscles at rest after conditioning stimulation of the median nerve at the elbow. Somatosensory potentials evoked by median nerve stimulation were also recorded in each subject. 3. Test stimuli delivered at 13-19 ms after median nerve stimulation significantly inhibited EMG responses elicited in forearm extensor muscles by transcranial magnetic stimulation, but did not inhibit responses to electrical stimulation. In contrast, magnetically and electrically elicited responses in forearm flexor muscles were suppressed to the same extent. 4. The higher the intensity of the test shocks, the smaller was the amount of median nerve-elicited inhibition. Inhibition in extensor muscles was also smaller during tonic wrist extension, or if the induced electrical stimulating current in the brain flowed from posterior to anterior over the motor strip rather than vice versa. Test responses evoked by magnetic transcranial stimulation in the first dorsal interosseous and in brachioradialis muscles were not inhibited after median nerve stimulation at the elbow. Stimulation of digital nerves failed to inhibit motor potentials in extensor muscles. 5. Test stimuli delivered at 15 and 17 ms after radial nerve stimulation significantly inhibited EMG responses elicited in forearm flexor muscles by magnetic transcranial stimulation. 6. In the patient with a focal thalamic lesion, who had dystonic postures and an absent N20 component of the somatosensory-evoked potentials but normal strength, median nerve stimulation failed to inhibit magnetically evoked responses in forearm extensor muscles. 7. We propose that activation of median nerve muscle afferents can suppress the excitability of cortical areas controlling the antagonist forearm extensor muscles acting on the hand. The inhibitory effect occurs at short latency and might assist spinal pathways mediating reciprocal inhibition by contrasting the co-activation of antagonistic pools of corticospinal cells.

Indomethacin loaded chitosan microspheres. Correlation between the erosion process and release kinetics.

The preparation of chitosan microspheres covalently linked with citric acid and loaded with indomethacin is described. The release kinetics correlated with the concentration of chitosan in the microsphere preparative mixture and the pH of the release medium. Deviations from Fickian to zero order kinetics were observed at higher concentrations of chitosan and at pH 7.4. The variations induced by these parameters on drug diffusion and solubility in the matrix undergoing erosion were analyzed.

Influence of physico-chemical parameters on the release kinetics of ketoprofen from Poly(HEMA) crosslinked microspheres.

This report analyses the release of Ketoprofen from Poly(HEMA) microspheres crosslinked with EGDMA at different crosslinking ratios and loaded by soaking in saturated solutions of the drug. Release appears to be influenced by the dissolution of Ketoprofen in the hydrogel and it is strictly correlated with the diffusibility of the drug in the gelled matrix. The release rate of the drug in the hydrogel rises with the increase in the diffusional conductance and the release kinetics approaches zero order particularly at the higher values of the diffusional conductance.

Release of ketoprofen from dermal bases in presence of cyclodextrins: effect of the affinity constant determined in semisolid vehicles.

We describe a method to determine the affinity constant values between Ketoprofen and beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin in semisolid vehicles. The method is based on the diffusion of the drug, released from semisolid vehicles, through a lipidic non porous membrane. The affinity constants of Ketoprofen towards cyclodextrins as determined in semisolid media better represent the release of the drug from dermal bases than the corresponding values in aqueous systems.