Differential Influence of Carotid Stenosis and White Matter Disease on Motor and Cognitive Activation.

BACKGROUND: Cognitive and motor performance can be supported, especially in older subjects, by different types of brain activations, which can be accurately studied by functional magnetic resonance imaging (fMRI). Vascular risk factors (VRFs) are extremely important in the development of cognitive impairment, but few studies have focused on the fMRI cortical activation characteristics of healthy subjects with and without silent cerebrovascular disease including white matter hyperintensities (WMH) and carotid stenosis (CS) performing cognitive tasks. METHODS: Thirty-five volunteers with and without asymptomatic unilateral carotid stenosis above 70% and variable degrees of WMH underwent performance of a simple motor and cognitive task during an fMRI session. RESULTS: While the performance of the motor task resulted in a cortical activation dependent of age but not of WMH and carotid stenosis, performance of the cognitive task was accompanied by a significantly increased activation independently correlated with age, presence of WMH as well as of carotid stenosis. CONCLUSIONS: in this study, cognitive domains regulating attention and working memory appear to be activated with a pattern influenced by the presence of carotid stenosis as well as by white matter hyperintensities. The impairment of these cognitive abilities is of high relevance in Alzheimer's disease pathology. The fMRI pattern shown in patients with asymptomatic but significant carotid stenosis might be related to chronic cerebrovascular hypoperfusion, a critical pathophysiological mechanisms in AD. In these patients, carotid endoarterectomy should be considered also for AD prevention and might be recommended.

Quality of life in stroke survivors: first results from the reliability and validity of the Italian version of the Stroke Impact Scale 3.0.

The purpose of this study was to establish the reliability and validity of the Italian version of the Stroke Impact Scale 3.0 (SIS 3.0), a specific and multidimensional instrument that assesses quality of life (QOL) in stroke survivors. Forty-five patients treated in three Rehabilitation Hospitals of the Lazio Region were included in the study. Patients were assessed using the SIS 3.0, the SF-36, the Barthel Index, the Mini Mental State Examination, the Hospital Anxiety and Depression Scale, the NIH Stroke Scale, the Modified Rankin Scale, and the Instrumental Activities of Daily Living. Results showed good internal consistency of the SIS 3.0 (Cronbach's alpha 0.86-0.98), and a good test-retest reliability (r > 0.70, p < 0.000) except for the Emotion and Social Participation subscales. At the re-test, 15 days after the first administration, SIS 3.0 showed a good responsiveness to change, documenting clinical improvement in stroke survivors. Significant correlations between the other instruments and the SIS 3.0 allowed to establish the concurrent validity of the SIS 3.0. Although the small sample size the Italian version of the SIS 3.0 showed good internal consistency and test retest reliability, as well as validity and responsiveness to changes. Since the SIS 3.0 is a specific tool to measure QOL in stroke survivors, its Italian version could be successfully used also in Italian population to better identify predictors of QOL and evaluate the effectiveness of health interventions.

ESWL prediction of outcome and failure prevention.

Based on our own experiences and a review of the recent literature, this article evaluates recent developments in predicting outcomes and failures of shockwave lithotripsy when treating patients with urinary tract stones. After a detailed MEDLINE research, the authors identified several variables that influence and predict extracorporeal shockwave lithotripsy (ESWL) success. These variables may be categorized as stone variables, patient variables and operator variables. Only multivariate analysis on a large number of homogenous patients may offer an objective evaluation of the factors conditioning ESWL outcome.

Cortical hyperexcitability in post-traumatic stress disorder secondary to minor accidental head trauma: a neurophysiologic study.

OBJECTIVE: We applied paired transcranial magnetic stimulation (pTMS) to patients with post-traumatic stress disorder (PTSD) secondary to minor accidental head trauma. Our purpose was to determine the potential abnormality of motor cortex excitability in this pathologic condition. METHODS: pTMS stimulation, according to the conditioning-test paradigm employing interstimulus intervals (ISIs) of 1-6 ms, was used to investigate intracortical inhibition in control subjects and patients with PTSD. The study population consisted of 14 patients who had developed PTSD following minor head trauma, 12 healthy volunteers without a clinical history of head trauma and 11 healthy subjects who had reported accidental minor head trauma 1-4 months before the study. This clinical electrophysiologic study was performed at the Department of Neuroscience, University of Rome "Tor Vergata." RESULTS: All patients with PTSD exhibited a significantly lower motor evoked potential (MEP) inhibition than controls at 2 ms, 3 ms and 4 ms ISI. The statistical analysis of the pTMS protocol showed a significant effect (F2,36 = 25.63, p < 0.001) of the factor "group," because patients with PTSD showed a mean conditioned MEP amplitude higher than that observed in both control groups for all 6 ISIs analyzed. The "ISI" factor was also significant (F5,180 = 89.85, Greenhouse-Geisser epsilon = 0.35; p < 0.001), with the mean conditioned MEP amplitude increasing from 22.5% to 127.8% as the ISI increased from 1 ms to 6 ms. Finally, the interaction of group with ISI was also significant (F10,180 = 8.97, p < 0.001), showing that the condition of PTSD secondary to head trauma was able to affect the MEP amplitude at different ISIs. CONCLUSIONS: Our results demonstrate that PTSD can give rise to abnormalities in intracortical inhibition. Our results provide further evidence that alterations in cortical inhibitory circuits may underlie specific forms of neuroticism in humans.

CSF from MS patients can induce acute conduction block in the isolated optic nerve.

In the present in vitro electrophysiological study, the acute effects of the cerebrospinal fluid (CSF) from multiple sclerosis (MS) and control subjects were measured on the axonal conduction of rat optic nerve, a central tract that is commonly affected in MS. Optic nerve compound action potential (CAP) amplitude was insensitive to the application of CSF obtained from the whole population of non-MS patients and from seven of 15 MS CSF. In the remaining eight MS cases, conversely, a time-dependent depression of CAP amplitude was observed. The reversible blockade of ion channels by soluble substances might account, at least in part, for the transient symptoms often seen in MS patients.

Uric acid, phosphate and oxalate stones: treatment and prophylaxis.

Medical treatment for the most commonly encountered types of renal stones is described. Nowadays treatment for uric acid stones is well-defined: alkalinizing urine is easy with drugs that are sufficiently active and well enough managed. Relapse is avoided in a high percentage of patients. Medical treatment of phosphate or calcium stones is a more open question as results are far from satisfactory compared with intra- and extra-corporeal approaches which are often minimally invasive and well accepted by both patient and urologist. Relapses are not easy to control because prophylactic measures such as changes in lifestyle and diet are never activated or because they are adopted for a brief period of time. Water therapy is examined, with the choice of water depending on the type of stone, together with drug therapy. Drugs such as citrate, with or without magnesium, and thiazides are considered excellent for curing renal stones and relapses. Although medical therapy has a limited role in many types of stones, its use is decisive in some others.

Lithiasic obstructive uropathy. Hydronephrosis characterization by magnetic resonance pyelography.

OBJECTIVES: The purpose of this study was to evaluate the role of magnetic resonance (MR) pyelography in patients affected by hydronephrosis due to ureteric stones, in order to identify a pyonephrotic condition. MATERIALS AND METHODS: In the last 3 years, 315 patients, who had originally been investigated by ultrasonography, were evaluated with MR pyelography in order to define the etiology of obstruction. In 67 patients hydronephrosis was referred as caused by lithiasis. RESULTS: MR pyelography not only confirmed urinary tract dilatation in all patients, but also identified grade and site of obstruction, both in acute dilatation (25 patients) and in chronic obstructions (42 patients). In 7 patients, MR pyelography documented pyonephrosis that was obviously confirmed by nephrostomic drainage. CONCLUSION: MR pyelography, made with ultrafast breath-hold sequences, has a great value in identifying hydronephrosis in patients with ureteric stones. Furthermore, it provides the chance to identify pyonephrosis requiring an immediate drainage of the kidney before major complications develop.

Brain excitability changes in the relapsing and remitting phases of multiple sclerosis: a study with transcranial magnetic stimulation.

OBJECTIVE: Recent functional and imaging studies have substantially contributed to extend the concept of multiple sclerosis (MS), classically regarded as a disease limited to the myelin axonal sheath. Several findings, in fact, point to a parallel involvement of neuronal components of the central nervous system (CNS) in the course of MS. In the present study, therefore, we explored, in MS patients, some characteristics of central motor pathways related to changes of neuronal excitability as measured using transcranial magnetic stimulation (TMS). METHODS: Seventy-nine patients affected by relapsing-remitting (RR) MS were examined using single and paired TMS in order to assess excitability changes in the hand motor cortex occurring during relapse and/or remission of the disease. The analyzed parameters were: motor-evoked potential (MEP) threshold, silent period (SP), intracortical inhibition (ICI) with paired pulses from 1 to 6 ms interstimulus intervals (ISIs), and central motor conduction time (CMCT). RESULTS: The analysis of variance exhibited a strong correlation (P<0.001) between the clinical phase and the type of excitability changes: 'relapsing' patients showed increased threshold and reduced SP duration. 'Relapsing' patients also displayed a significant lack of normal intracortical inhibition (ICI). By contrast, 'remitting' patients showed a significant SP prolongation with normal motor thresholds. CONCLUSIONS: The present findings reveal changes in cortical excitability that might play a role in the pathophysiology of MS symptoms. In particular, the relapsing phase of MS has been found to be associated with cortical hyperexcitability irrespective of the site of clinical manifestation or new plaque formation. These results might help to explain the puzzling picture of neurological symptoms observed in MS patients during different phases of the disease. SIGNIFICANCE: Alterations of neuronal components of the CNS play a role in MS.

Pramipexole in comparison to l-dopa: a neuropsychological study.

Twenty right-handed patients affected by early/mild Parkinson's disease were evaluated in a randomised study using neuropsychological and clinical assessements during three treatment modalities: when in the off treatment condition, when on pramipexole, and when on l-dopa. In comparison to the off treatment condition, the DA-agonist pramipexole produced a significant impairment of short term verbal memory, attentional-executive functions and verbal fluency, while l-dopa did not. Moreover, pramipexole opposite to l-dopa, failed to improve FAS and Stroop tests. Present findings indicate that pramipexole may worsen cognitive functions although not exceeding normative values.

Ipsilateral activation of the unaffected motor cortex in patients with hemiparetic stroke.

BACKGROUND AND PURPOSE: Recent research has shown that following stroke patients can display ipsilateral activity reflecting a functional link between the undamaged hemisphere and the affected upper limb on the same side of the body. In the present study the capacity for ipsilateral activation is documented during recovery by using transcranial magnetic stimulation (TMS) and transcranial Doppler (TCD). METHODS: Fourteen patients affected by hemispheric stroke were examined with TMS and TCD within 48 h of onset, and again 6 months later. Neurological signs were scored with reference to the NIHSS, and patients executed a thumb to finger opposition task so as to further estimate the motor deficit. Twenty healthy volunteers represented the control population. RESULTS: (1) Both TMS and TCD yielded homogeneous results showing ipsilateral activity between affected hands and undamaged hemispheres. On stimulating the motor cortex 3 cm anterior and 3 cm lateral to Cz, a scalp site remote from the primary motor area, ipsilateral motor evoked potentials (iMEPs) from hand muscles were found in recovered patients. (2) In 8 controls iMEPs with smaller amplitudes than patients could be obtained by stimulating only the left hemisphere. (3) TCD revealed increased blood flow velocity in the ipsilateral MCA by activating the recovering hand (10.5+/-3.3%; P<0.001). CONCLUSION: TMS reveals a specific area in the motor cortex from which ipsilateral MEPs can be elicited and both TMS and TCD indicate that an ipsilateral corticospinal tract can be accessible in some adult controls or becomes unmasked after cerebral damage.

Motor cortex excitability in chronic fatigue syndrome.

OBJECTIVE: To use transcranial magnetic stimulation (TMS) to define motor cortical excitability in chronic fatigue syndrome (CFS) subjects during a repetitive, bilateral finger movement task. METHODS: A total of 14 CFS patients were tested and compared with 14 age-matched healthy control subjects. TMS of the motor cortex (5% above threshold) was used to elicit motor evoked potentials (MEPs). Subjects performed regular (3-4/s) repetitive bilateral opening-closing movements of the index finger onto the thumb. MEPs of the first dorsal interosseus (FDI) were measured before, immediately following exercise periods of 30, 60 and 90 s, and after 15 min of rest. RESULTS: Performance, defined by rate of movement, was significantly slower in CFS subjects (3.5/s) than in controls (4. 0/s) independent of the hand measured. The rate, however, was not significantly affected by the exercise duration for either group. The threshold of TMS to evoke MEPs from the FDI muscle was significantly higher in CFS than in control subjects, independent of the hemisphere tested. A transient post-exercise facilitation of MEP amplitudes immediately after the exercise periods was present in controls independent of the hemisphere tested, but was absent in CFS subjects. A delayed facilitation of MEPs after 15-30 min of rest was restricted to the non-dominant hemisphere in controls; delayed facilitation was absent in CFS subjects. CONCLUSIONS: Individuals with CFS do not show the normal fluctuations of motor cortical excitability that accompany and follow non-fatiguing repetitive bimanual finger movements.

Delayed facilitation of motor cortical excitability following repetitive finger movements.

OBJECTIVES: To define motor cortical excitability changes occurring at various times after non-fatiguing bimanual exercise of the index fingers. METHODS: Twenty healthy right-handed subjects were studied with transcranial magnetic stimulation (TMS) of the right non-dominant hemisphere. They performed regular (3-4/s) repetitive opening-closing bilateral movements of the index finger onto the thumb. Motor evoked potentials (MEPs) of the left first dorsal interosseus (FDI) and rate of the repetitive finger movements were determined (1) before exercise, (2) immediately following 3 exercise periods of 30, 60 and 90 s, and (3) over a subsequent 30 min rest period. RESULTS: Rate of movement did not show significant change during any of the exercise periods but did increase significantly when tested after 15 min of rest. MEPs immediately after 30 and 60 s of exercise were facilitated whereas MEPs after 90 s of exercise did not differ from baseline measures. MEP amplitudes were significantly increased after rest of approximately 15 min compared to the baseline MEPs. In contrast, motor potentials evoked by peripheral nerve stimulation were unchanged throughout the experimental test periods. CONCLUSIONS: Motor cortical excitability relating to an intrinsic finger muscle (FDI) was facilitated beginning 15 min after a brief period of non-forceful, repetitive activity of that muscle. This delayed facilitation of motor cortex after exercise may represent a form of short-term potentiation of motor cortical excitability.

Pharmacologic reversal of cortical hyperexcitability in patients with ALS.

OBJECTIVE: To reverse the profile of abnormal intracortical excitability in patients with ALS by administering drugs that promote GABAergic transmission. BACKGROUND: Transcranial magnetic stimulation (TMS) has revealed abnormalities of cortical inhibition in ALS, a reduction of the silent period, and the absence of intracortical inhibition normally occurring in response to paired TMS. Impaired inhibitory transmission could play a role in the physiopathology of this illness. METHODS: Using paired TMS with conditioning stimuli from 1-to-6-msec-interstimulus intervals, we investigated 16 patients with ALS. The protocol included: (1) the "drug-free" profile of paired TMS; (2) paired TMS 30 minutes after the intake of diazepam (3.5 mg); (3) paired TMS after 3 weeks' treatment with gabapentin (GBP) (600 mg/day) or riluzole (50 mg/twice a day). RESULTS: Intracortical inhibition is lost in patients with ALS, and this abnormal profile is reversed by diazepam or sustained treatment with GBP. We also noted that motor-evoked potential amplitudes to single stimuli increased (p<0.01) after diazepam and GBP. CONCLUSIONS: The demonstration of pharmacologic reversal of hyperexcitability in patients with ALS makes a potentially significant contribution toward understanding the pathophysiology of a disease that has so far eluded an effective cure.

The effect of riluzole in amyotrophic lateral sclerosis: a study with cortical stimulation.

A population of 31 patients with sporadic amyotrophic lateral sclerosis (ALS) was selected for a prospective open study based on treatment with riluzole. A neurophysiological evaluation was performed by means of single and paired transcranial magnetic stimulation (TMS). The examined parameters, excitability threshold, motor evoked potential (MEP) duration, silent period (SP) duration and time course of intracortical inhibition to paired TMS after 6 months treatment, were matched against those recorded from the patients themselves before the beginning of treatment and from 20 (single TMS) or 10 (paired TMS) age-matched control subjects. Normal behaviour of the SP in response to increasing TMS was found in the treated patients; they showed a significant linear correlation between these two parameters (r=0.96) comparable to that calculated for controls (r=0.98), and significantly different with respect to drug-free patients (r=0.8, P=0.014). A significant reduced size of the 'conditioned' MEPs to paired stimulation was documented in the treated patients compared with the untreated patients (P=0.002). Our neurophysiological contribution to the assessment of the effect of riluzole on the motor cortical inhibitory property in ALS may be considered a setting for controlled trials in extended patient series, even in a pre-clinical phase.

The effect of benzodiazepines and flumazenil on motor cortical excitability in the human brain.

In the present study, the effects of benzodiazepines (diazepam) were evaluated in terms of cortical excitability changes, as tested with transcranial magnetic simulation (TMS). In particular, analyzed were drug-induced changes regarding two selected parameters of TMS: (1) the cortical excitability threshold and (2) the silent period duration (SP). For this purpose, we evaluated the effects of long-term therapy with diazepam in the patients affected by anxiety disorders and the changes induced by single oral doses of diazepam in both healthy controls and patients. In addition, we tested cortical excitability changes in two 'extreme conditions' where a considerable concentration of serum benzodiazepine-like activity was reached, as represented by diazepam overdose and idiopathic recurrent stupor (IRS). In both groups of patients, a significant increment of motor threshold was found, while in the overdose patients, the SP was also increased. The administration of flumazenil in these two conditions was followed by a prompt reversal effect, consisting of a return to normal cortical excitability parameters. The long-term usage of diazepam in patients with anxiety disorders is associated with significantly increased threshold; the increased value of these parameters was temporarily further enhanced by the administration of a single oral dose of diazepam, which, in normal control subjects, is not associated with changes of cortical excitability. The results of this study reveal that different physio-pathological conditions induced by the influence of benzodiazepine and its antagonist are reflected in excitability changes which attest to the involvement and modification of cortical GABAergic activity.

The treatment of severe forms of myasthenia gravis.

In this study we introduced and tested the clinical efficacy of a combined treatment based on the association of plasma exchange (PE) with high daily doses of prednisone in 18 patients with severe forms of myasthenia gravis (MG). A myasthenic score based on strength and resistance was evaluated in each patient in basal condition and during the treatment. The study design included 5 sessions of PE, performed within a period of 15 days, 1 session every 3 days, associated with administration of oral prednisone (1 mg/kg of body weight), which began at the same time as the first session and was continued following a daily schedule for at least three months. A significant improvement was obtained from the start of the therapy, with a reduction of the myasthenic score from 26.56 to 11.44 by day 10 and with further reduction after PE interruption. An early improvement, recorded within 24-48 hours of the beginning of the study design, was observed in 11/18. The administration of steroid therapy was never followed by a worsening of myasthenic symptoms (as reported when it is administered in the absence of concomitant PE). No recurrence of symptoms was reported after 29 months' follow-up. This type of therapeutic association was generally well tolerated and no unwanted side effects were observed. According to our results we can conclude that medium-high doses of oral prednisone in simultaneous association with PE lead to a successful control of severe forms of MG and may be considered a valid therapeutic strategy.

Ipsilateral motor activation in patients with cerebral gliomas.

OBJECTIVE: The aim of this study is to provide neurophysiologic evidence of ipsilateral hemispheric activation in patients affected by intracerebral gliomas via the use of transcranial magnetic stimulation. BACKGROUND: The mechanisms involved in such ipsilateral activation have yet to be established, but they may involve preexisting routes that either are suppressed or undetected in the normal brain. Ipsilateral pathways may act in reserve, activated by the impairment of contralateral control. This hypothesis is suggested by the fact that the considerable size of the tumors in our patients is not matched by a proportionate loss of motor performance in the limbs contralateral to the affected hemisphere. However, it remains possible that ipsilateral motor-evoked potentials (iMEPs) may reflect reorganizational changes without significant functional effects. METHODS: The effects of such activation were investigated using both focal and nonfocal coils stimulating cortical motor areas, with MEPs recorded from both left and right thenar muscles. Fifteen healthy control subjects and seven patients were examined. RESULTS: iMEPs were generally absent in normal subjects, but in contrast they were obtained in the patients by stimulating the healthy hemisphere using both round and figure-of-eight coils. Distinct from contralateral MEPs, iMEPs are obtained with higher thresholds (range, 60 to 80% of stimulator output) and display longer latencies (20.9 msec versus 19.4 msec). CONCLUSIONS: Taken in conjunction with recent research using functional imaging brain exploration and a variety of clinical, anatomic, and neurophysiologic studies, our results reflect a growing awareness of ipsilateral motor control and its potential compensatory role when contralateral routes are damaged.

Plasmapheresis in severe forms of myasthenia gravis.

In this study we introduce a new combination treatment of plasma exchange (PE) and high daily doses of prednisone for severe forms of myasthenia gravis (MG). The clinical efficacy of the combined therapy has been tested in 18 patients suffering from severe forms of MG. The protocol included 5 sessions of PE, performed in a range of 15 days, 1 session every 3 days, with concurrent administration of oral prednisone (1 mg/kg of body weight), starting at the first session of PE and given daily for at least 3 months. At the end of the entire cycle of PE, almost complete recovery (more than 90% of the initial clinical score) was obtained in 8 of 18 patients while an improvement between 60 and 90% of the initial score was achieved in 9 of 18 patients. An early improvement was noted 24 h after the beginning of plasmapheresis in 11 of 18 patients. No recurrence of symptoms was reported after 36 months of follow-up for 17 patients. The administration of steroid therapy was never followed by an early exacerbation of myasthenic symptoms as reported when it is administered in the absence of concomitant PE. According to our results, we can conclude that high doses of oral prednisone therapy in simultaneous association with PE lead to successful control of severe forms of MG, significantly superior to the therapeutic strategies until now adopted and reported in literature.

Towards a neurophysiological marker of amyotrophic lateral sclerosis as revealed by changes in cortical excitability.

Motor evoked potentials (MEPs) to magnetic trans cranial stimulation (TCS) were recorded in 47 patients with amyotrophic lateral sclerosis (ALS) in order to evaluate both excitability and conductivity changes relating to central motor pathways. The results were compared with those obtained from a control population of 43 subjects, 34 patients with definite multiple sclerosis (MS) and 15 patients with a rigid early from of Parkinson's disease (PD). The excitability threshold to TCS was higher in ALS patients for both upper and lower limbs compared with both controls and PD patients, but lower than that of MS patients. The Silent Period duration (SP (hand recordings): 80.1 ms, SD: 38.5) was significantly shorter in ALS patients than in all the other examined subjects (P < 0.001), nor did it increase proportionally to TCS intensity as with control subjects. The abnormal behavior of the SP appears to be specifically linked to the ALS disease, since it was neither observed in PD patients, nor in those with multiple sclerosis, who, on the contrary, displayed a prolonged mean duration of the SP (161.6 ms, SD 77 vs. 115.7 ms, SD 62 for the control group). Due to the neuronal loss of the largest neurons in ALS, MEP latency, amplitude, duration and the motor central conduction time (CCT) were in different proportion found abnormal. Our study shows how different neurological diseases with central motor involvement share broadly similar MEP abnormalities, but a different involvement of the silent period. We suggest that in ALS patients there may be abnormalities of motor cortical inhibitory mechanisms which are detected with the measurement of the SP. The distinctive 'depression' of this parameter in the case of ALS could be a significant marker for diagnosing this disease.

General cognitive abilities and patterns of adaptation: for Serial Color-Word Test norms based on reading times.

In a pool of 859 clinical and nonclinical Serial Color-Word Test protocols, significant positive correlations were observed between reading times on the Stroop task and measures of linear and nonlinear change. Especially nonlinear change, both within and between the five subtests, showed high correlations with reading times. To derive new time-related norms, the sample was divided into five time groups of the same size and stratified medians were calculated for each of the variables of the test. The new classification procedure should permit an assessment of patterns of adaptation less dependent on the general level of perceptual-cognitive functioning.