Age-related decrease in paired-pulse intracortical inhibition in the human primary motor cortex.

Using biphasic magnetic stimuli, paired-pulse transcranial magnetic stimulation (TMS) at short interstimulus intervals (ISIs) was employed to investigate age-related changes in the balance between intracortical inhibition and facilitation. In 26 right-handed healthy individuals, motor evoked potentials were recorded from the relaxed right first dorsal interosseus muscle after paired-pulse TMS of the left primary motor hand area. The magnitude of intracortical paired-pulse inhibition at ISIs of 1-5 ms was markedly reduced in elderly individuals, whereas no age effect was observed for intracortical paired-pulse facilitation at ISIs of 11-15 ms. This finding demonstrates that normal aging is associated with a relative decrease in the excitability of intracortical inhibitory circuits. In conclusion, paired-pulse TMS provides a non-invasive means of studying age-related functional changes in the motor cortex.

Subthreshold 5-Hz repetitive transcranial magnetic stimulation of the human primary motor cortex reduces intracortical paired-pulse inhibition.

Paired-pulse transcranial magnetic stimulation (TMS) at short interstimulus intervals was employed to investigate short-term effects of 5-Hz repetitive TMS (rTMS) over the primary motor hand area (M1(HAND)) on intracortical excitability. In ten healthy individuals, 1250 pulses of 5-Hz rTMS were applied at 90% of motor resting threshold over the left M1(HAND). Ten minutes after 5-Hz rTMS, paired-pulse inhibition was significantly reduced, whereas paired-pulse facilitation was not modified. Sham-rTMS had no lasting effect on intracortical excitability. These findings suggest that subthreshold 5-Hz rTMS causes a short-term modulation of the excitability of intracortical circuitry in the stimulated M1(HAND). The lasting effect of subthreshold 5-Hz rTMS on intracortical inhibition provides a useful probe for studying short-term plasticity of the human M1(HAND).

Decreased fibrinolytic stimulation by a short-term venous occlusion test in patients with cerebrovascular disease.

The aim of the present study was to determine whether patients with previous cerebrovascular disease have abnormalities in hemostatic functions stimulated by a 5-min venous-occlusion-test. Twenty-two patients with brain ischaemia 3-6 months previously were compared to a control group of twenty patients with non-vascular neurological diseases. Cases showed less increase in tissue plasminogen activator and fibrin degradation products than controls. There were no differences in baseline and stimulated levels of plasminogen activator inhibitor, fibrinogen degradation products, thrombin-antithrombin complex or global lysis assay (Fibriscreen). Since patients with acute cerebrovascular disease were not included, the present findings may represent either preexisting or longterm reactive fibrinolytic deficiencies, possibly predisposing to further thrombotic disease.

Short-term motor improvement after sub-threshold 5-Hz repetitive transcranial magnetic stimulation of the primary motor hand area in Parkinson's disease.

Ten unmedicated patients with Parkinson's disease received sub-threshold 5-Hz repetitive transcranial magnetic stimulation (rTMS) over the primary motor hand area (M1(HAND)) contralaterally to the more affected upper limb. Compared to a midfrontal sham-rTMS, real-rTMS over M1(HAND) was associated with a significant decrease in the global motor UPDRS score 1 h after the cessation of rTMS. This was mainly due to a clinical improvement in the arm contralaterally to the stimulated M1(HAND). These preliminary data suggest that focal rTMS of M1(HAND) may have a therapeutic potential in PD.

Voxel-based morphometry in individual patients: a pilot study in early Huntington disease.

BACKGROUND AND PURPOSE: Voxel-based morphometry (VBM) has proved a powerful method to detect subtle changes of gray matter (GM) at the group level but the role of VBM for the detection of GM changes in single subjects, especially in those with suspected neurodegenerative disorder, remains uncertain. Here, we performed single subject analyses in 22 patients in early stages of Huntington disease (HD), a neurodegenerative disorder with a well-known and characteristic pattern of GM loss. MATERIALS AND METHODS: We applied an ANCOVA with age and gender as covariates and corrected for multiple statistical tests by false discovery rate (P < 0.05). Each patient was compared to 133 healthy controls. The same procedure was applied to 22 of the controls matched for age and gender in a pair-wise manner. RESULTS: Our analyses yielded biologically plausible results in HD patients in which GM decrease within the caudate nucleus could be identified in 15 of the 16 most affected patients while GM decrease was found in only 1 control subject. Lowering the size of the control group yielded comparable results with 99 and 66 control subjects whereas sensitivity decreased with 33 control subjects. CONCLUSIONS: Our pilot study demonstrates a potential role of VBM for the detection of cerebral GM changes in single subjects with suspected neurodegenerative disorder.

Voxel-based morphometry indicates relative preservation of the limbic prefrontal cortex in early Huntington disease.

In Huntington disease (HD), both the genetic defect and mutant gene product huntington are known but the exact mechanisms that lead to neuronal loss are poorly understood. Until now, the distribution of tissue loss throughout the brain has been investigated intensively. Here we searched for areas that, antipodal to the striatum, display grey-matter (GM) preservation. We performed high resolution T1-weighted magnetic resonance imaging and voxel-based morphometry in 46 patients in early HD and 46 healthy controls. We applied an analysis of covariance (ANCOVA) model with the total GM volume of each participant as covariate. In accordance with earlier reports, group comparisons revealed GM decrease in the striatum, insula, and thalamus as well as in dorsolateral frontal and occipital areas. In contrast, the limbic prefrontal cortex displayed GM preservation. Our findings support hypotheses that postulate differential involvement of frontosubcortical circuits in the pathophysiology of HD.

[Epilepsy in the elderly]. / Altersepilepsie.

The new occurrence of epileptic disorders increases continuously above the age of 60 years. The most frequent etiology of epilepsy in the elderly is vascular (32-54%). Tumors are the cause of epilepsy in the elderly in 11 to 33 per cent of cases, with a peak around the age of 60. The etiology of about one third of the cases of epilepsy newly diagnosed in old age cannot be clarified. The risks of inducing epileptic disorders are: after cerebral ischemia 4-9%, intracerebral hemorrhage 3%, and subarachnoidal hemorrhage 4-12%. It is important to recognize confusional states, for they may be symptoms of a psychomotor status or a prolonged postical phase. Occasional seizures occur more often in the elderly. Due to altered pharmacokinetics and problems of compliance in old age, the titration period of antiepileptic drugs should be planned with particular care and patients given simple drug regimens.

Clonidine- and methohexital-induced epileptiform discharges detected by magnetoencephalography (MEG) in patients with localization-related epilepsies.

PURPOSE: During presurgical evaluation, 14 patients with medically intractable focal epilepsies underwent magnetoencephalographic (MEG) recordings to localize the epileptogenic focus. To increase the number of epileptiform discharges required for MEG analysis, methohexital a short-acting barbiturate that is known to activate epileptiform activity, was used. Additionally, we investigated the spike-provoking properties of clonidine in comparison to methohexital. METHODS: After oral premedication with clonidine, short-lasting anesthesia was provided by intravenously administered methohexital. The number and location of epileptiform MEG discharges were assessed after clonidine premedication and during methohexital anesthesia. Results were compared with baseline MEG recordings. RESULTS: Methohexital increased the frequency of focal epileptiform discharges in eight of 13 patients (one of the 14 patients did not receive methohexital after premedication with clonidine). Additionally, premedication with clonidine was found to increase focal epileptiform discharges in nine of 14 patients. When compared with baseline MEG recordings, recordings after treatment with both clonidine premedication and methohexital anesthesia showed a significant increase in the total number of epileptiform signals and the number of spikes contributing to MEG source localizations. CONCLUSIONS: This study confirms the selective proconvulsant effects of methohexital on the epileptogenic focus as suggested previously by EEG and electrocorticogram (ECoG) investigations. Additionally, our data establish for the first time that clonidine increases epileptiform activity in patients with seizure disorders. These results indicate that clonidine is suited as an activating agent for the localization of epileptogenic foci by means of MEG. This effect of clonidine on specific epileptic activity also indicates that clonidine should be used with caution as an antihypertensive drug in patients with seizure disorders.

Clonidine and methohexital-induced epileptic magnetoencephalographic discharges in patients with focal epilepsies.

PURPOSE: During presurgical evaluation, 14 patients with medically intractable focal epilepsies underwent magnetoencephalographic (MEG) recordings for focus localization. To increase the number of epileptic discharges required for MEG analysis, we administered methohexital (MHT), a short-acting barbiturate known to provoke epileptic activity. We also investigated the spike-provoking properties of clonidine in comparison with MHT. METHODS: Patients were briefly anesthetized with intravenously administered MHT after being premedicated orally with clonidine. Numbers and locations of epileptic MEG discharges were assessed after clonidine premedication as well as during MHT anesthesia. Results were compared with baseline MEG recordings. RESULTS: MHT increased the frequency of focal epileptic discharges in 8 of 13 patients ( of the 14 patients did not receive MHT after premedication with clonidine). Premedication with clonidine also increased focal epileptic discharges in 9 of 14 patients. The numbers of epileptic signals and numbers of spikes contributing to MEG source localizations were significantly increased in MEG recordings under both treatment conditions (clonidine premedication and MHT anesthesia) as compared with baseline MEG recordings. CONCLUSIONS: Our results confirmed the selective proconvulsive effects of MHT on the epileptic focus, as previously suggested by EEG and electrocorticographic (ECoG) investigations. However, our present data establish for the first time that clonidine increases epileptic activity in patients with seizure disorders and indicate that clonidine is suitable as an activating agent for localization of epileptogenic foci by MEG. This effect of clonidine on specific epileptic activity also indicates that specific care must be taken when clonidine is used as an antihypertensive drug in patients with seizure disorders.

Continuous transcranial magnetic stimulation during positron emission tomography: a suitable tool for imaging regional excitability of the human cortex.

In six healthy volunteers, H(2)(15)O positron emission tomography (PET) was employed to evaluate rate-dependent functional activation of the left primary sensorimotor hand area (SM1(HAND)) during subthreshold repetitive transcranial magnetic stimulation (rTMS). Using an eight-shaped coil, continuous trains of rTMS were delivered during nine 50-s H(2)(15)O PET scans. Nine different stimulation frequencies were used, ranging from 1 to 5 Hz. Stimulus intensity was set at 10% below active motor threshold. During three additional PET scans, an ineffective rTMS was applied via another eight-shaped coil, which was held 10 cm above the vertex. Statistical parametric mapping was employed to assess relative differences in normalized regional cerebral blood flow (rCBF) across conditions. Compared with ineffective rTMS, subthreshold rTMS increased normalized rCBF in the stimulated SM1(HAND). Moreover, the increase in rCBF in the left SM1(HAND) showed a linear positive relationship with the rate of rTMS, indicating a rate-dependent functional activation of the stimulated SM1(HAND). These data demonstrate that, by varying the variables of rTMS across scans, continuous rTMS during H(2)(15)O PET provides a noninvasive tool to study the regional excitability profile of a distinct cortical area.

Brain correlates of fast and slow handwriting in humans: a PET-performance correlation analysis.

The present study examined the cerebral control of velocity during handwriting. We employed H215O positron emission tomography (PET) to measure the regional cerebral blood flow (rCBF) in 10 healthy subjects. Participants were required to write the German verb 'bellen' ('to bark') either at their normal speed (i.e. fast open-loop handwriting) or to write at approximately half of their normal speed without visual feedback. The second task required a continuous modification of the motor output according to the kinaesthetic feedback from the hand (i.e. slow closed-loop handwriting). Pencil movements were recorded during PET scanning and analysed off-line using a stroke-based analysing program. The mean number of inversions in velocity (NIV) per stroke was used to quantify the mode of motor control during each PET scan. A NIV of 1 indicates fast open-loop processing, whereas an increase in NIV reflects a shift towards slow closed-loop processing of handwriting. Foci in the left primary sensorimotor cortex, the right lateral premotor cortex, the left anterior parietal cortex, the left anterior putamen, the left rostral supplementary motor area and the right precuneus showed a graded increase in functional activation with the mean NIV per stroke, suggesting that this set of brain regions is particularly involved in the processing of slow closed-loop writing movements. No area showed a negative relationship between rCBF and the mean NIV per stroke, suggesting that fast open-loop handwriting is achieved by an optimized cooperation of the manual sensorimotor network rather than by a selective activation of a distinct network component.