Search

The Likert-type format is one of the most widely used in all types of scales in the field of social sciences. Nevertheless, there is no definitive agreement on the number of response categories that optimizes the psychometric properties of the scales. The aim of the present work is to determine in a systematic fashion the number of response alternatives that maximizes the fundamental psychometric properties of a scale: reliability and validity. The study is carried out with data simulated using the Monte Carlo method. We simulate responses to 30 items with correlations between them ranging from 0.2 to 0.9. We also manipulate sample size, analyzing four different sizes: 50, 100, 200, and 500 cases. The number of response options employed ranges from two to nine. The results show that as the number of response alternatives increases, both reliability and validity improve. The optimum number of alternatives is between four and seven. With fewer than four alternatives the reliability and validity decrease, and from seven alternatives onwards psychometric properties of the scale scarcely increase further. Some applied implications of the results are discussed.

Ponto-geniculo-occipital (PGO) waves are phasic pontine, lateral geniculate, and cortical field potentials occurring during and before REM sleep that are proposed to mediate a wide variety of sleep related neural processes. We sought to identify and characterize human PGO waves.

Peripheral sensory stimulation at the wrist inhibits the motor cortex as measured by transcranial magnetic stimulation at interstimulus intervals of approximately 20 ms (short latency afferent inhibition SAI) and 200 ms (long latency afferent inhibition LAI). Previous studies suggested that reduced SAI in Parkinson disease (PD) reflects adverse effect of dopaminergic medications and reduced LAI may be related to nondopaminergic manifestations of PD. We hypothesize that subthalamic nucleus (STN) deep brain stimulation (DBS) may correct these deficiencies.

Copyright of Neurologia (Grupo ARS XXI de Comunicacion, S.A.) is the property of Grupo ARS XXI de Comunicacion, S.A. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BACKGROUND Deep brain stimulation (DBS) is currently the most effective surgical treatment for advanced Parkinson disease (PD). Even when the electrode is well positioned in the target, the optimization of clinical results depends on careful programming of electrical parameters and changes in antiparkinsonian drug dosages. OBJECTIVE To determine whether stable outcomes from subthalamic nucleus DBS for PD can be improved by revising stimulation parameters and drug dosages through “hands-on” involvement of a neurologist expert in both movement disorders and DBS programming. METHODS In 44 consecutive patients with PD with long-term stable response to subthalamic nucleus DBS (mean ± SD, 3.5 ± 1.7 years), we compared scores from the Unified Parkinson's Disease Rating Scale parts II through IV obtained immediately before and following a formal reprogramming of their stimulation. The reprogramming was performed by a neurologist expert in both PD and DBS and accompanied by further medication adjustments. The patients were subsequently followed up for as long as 14 months. RESULTS In 24 patients (54.6%), the scores on the Unified Parkinson's Disease Rating Scale parts II and III significantly improved by 15.0% and 25.9%, respectively. Anti-PD drugs were significantly reduced (by 25.9%). No improvement was observed in 16 patients (36.4%), and the conditions of 4 patients (9.1%) worsened. CONCLUSIONS Further improvement of parkinsonian signs can be achieved in the majority of patients even after long-term stable stimulation. Improved patient outcomes from subthalamic nucleus DBS are obtained when postoperative care is personally managed by a neurologist expert in movement disorders and DBS who is directly responsible for stimulation programming and simultaneous drug adjustments based on observed clinical responses to changing stimulation parameters.Arch Neurol. 2006;63(9):1266-1272--

In spite of the controversy regarding sugar and amino acid mirror-image symmetry and nature, it has been demonstrated that an intrinsic preference for left-handedness or right-handedness would depend on weak energy responsible for stabilising L-amino acids. A weak neutral current interaction involves an enantiomeric energy difference for L-amino acids to have sufficient magnitude to break open, non-equilibrium, racemic systems' chiral symmetry. L-amino acid can form complex structural atom arrangements when building proteins to allow specific chemical and molecular interactions such as enzyme-substrate and antigen-antibody complexes. Thus, pathogens can take advantage of higher vertebrates' molecular immune system's extremely well organised molecular L-amino acid composition to establish efficient evasion mechanisms. Plasmodium falciparum (the most lethal form of malaria) clearly employs its protein ligands' non-polymorphic regions when binding to specific receptors on its target cells. These sequences are normally poorly immunogenic and nonprotection inducing when used as immunogens. It has been shown that these ligands' native L-amino acid composition and their secondary structure play a vital role in maintaining a code of silence to avoid a host immune response. Our institute has established two strategies for overcoming this problem; one consists of replacing critical ligand-derived peptide binding residues by others having similar side chain mass but opposite polarity and the other consists of altering the peptide bond and the nature of α-carbon asymmetry. This review summarises the most widely used pseudopeptide approaches for novel immunogen synthesis, emphasising their potential in peptide-based vaccines and as therapeutical agents for infectious diseases such as malaria.

Deep brain stimulation (DBS) is an effective treatment for movement disorders and pain. Recently, bilateral DBS of the anterior nucleus of thalamus (AN) was performed for the treatment of intractable epilepsy. This surgery reduced seizure frequency in an initial group of patients. However, its physiologic effects on the cortex and mechanisms of action remain poorly understood. Different classes of antiepileptic drugs (AEDs) have distinct effects on the excitatory and inhibitory circuits in the motor cortex, which can be studied noninvasively by transcranial magnetic stimulation (TMS).

Neural stimulation has rapidly become an integral tool in the treatment of Parkinsons disease and other movement disorders. Today it serves as an important adjunct to medical therapy that continues to gain applicability to patients in whom the disease has progressed significantly. Studies have demonstrated efficacy in several deep-brain targets, with prolonged benefit exceeding 5-year follow-up times. Continuing study is teaching us more about the mechanism of deep-brain stimulation effect. New targets, which may treat the disease more successfully, are being examined. In this review, the history of deep-brain stimulation, the rationale for the known targets of stimulation; the clinical evidence demonstrating their benefit and, finally, future perspectives on new treatments that are being investigated and may have an impact on the field are discussed.

Deep brain stimulation (DBS) is associated with significant improvement of motor complications in patients with severe Parkinson's disease after some 6–12 months of treatment. Long-term results in a large number of patients have been reported only from a single study centre. We report 69 Parkinson's disease patients treated with bilateral DBS of the subthalamic nucleus (STN, n = 49) or globus pallidus internus (GPi, n = 20) included in a multicentre study. Patients were assessed preoperatively and at 1 year and 3–4 years after surgery. The primary outcome measure was the change in the ‘off’ medication score of the Unified Parkinson's Disease Rating Scale motor part (UPDRS-III) at 3–4 years. Stimulation of the STN or GPi induced a significant improvement (50 and 39%; P < 0.0001) of the ‘off’ medication UPDRS-III score at 3–4 years with respect to baseline. Stimulation improved cardinal features and activities of daily living (ADL) (P < 0.0001 and P < 0.02 for STN and GPi, respectively) and prolonged the ‘on’ time spent with good mobility without dyskinesias (P < 0.00001). Daily dosage of levodopa was significantly reduced (35%) in the STN-treated group only (P < 0.001). Comparison of the improvement induced by stimulation at 1 year with 3–4 years showed a significant worsening in the ‘on’ medication motor states of the UPDRS-III, ADL and gait in both STN and GPi groups, and speech and postural stability in the STN-treated group. Adverse events (AEs) included cognitive decline, speech difficulty, instability, gait disorders and depression. These were more common in patients treated with DBS of the STN. No patient abandoned treatment as a result of these side effects. This experience, which represents the first multicentre study assessing the long-term efficacy of either STN or GPi stimulation, shows a significant and substantial clinically important therapeutic benefit for at least 3–4 years in a large cohort of patients with severe Parkinson's disease.

Deep brain stimulation (DBS) is an effective treatment for several movement disorders. However, its mechanism of action is largely unknown. Both lesioning and DBS of the ventralis intermedius (VIM) nucleus of thalamus improve essential tremor. Although DBS was initially thought to inhibit the target neurons, recent studies suggest that DBS activates neurons.

La disfunción ventricular izquierda ocasionada por arritmias ventriculares es una entidad poco conocida. Para contribuir a su difusión presentamos los casos de 5 pacientes en los que se pudo establecer de forma inequívoca la conexión arritmia-disfunción ventricular. Todos tenían arritmias ventriculares monomórficas repetitivas y disfunción ventricular izquierda (fracción de eyección ≤ 40% y dimensión telediastólica ≥55 mm). En el estudio electrofisiológico se detectó un foco arritmogénico intraventricular localizado en el ventrículo derecho en 2 casos, en el ventrículo izquierdo en otros 2 y en el seno de Valsalva izquierdo en el quinto; en todos fue suprimido mediante ablación con catéter. A los 7 ± 2 meses postablación se observó una gran mejoría de la función sistólica y el remodelado ventricular izquierdo (fracción de eyección ≥50% y dimensión telediastólica ≤51 mm en los 5 enfermos), sin recurrencia de la arritmia durante el seguimiento (10-69 meses). Estos hallazgos confirman que las arritmias ventriculares repetitivas pueden causar disfunción ventricular, reversible tras ablación con radiofrecuencia.

Cortical areas participating in the preparation of voluntary movements have been studied extensively. There is emerging evidence that subcortical structures, particularly the basal ganglia, also contribute to movement preparation. The thalamus is connected to both the basal ganglia and the cerebellar pathways, but its role in movement preparation has not been studied extensively in humans. We studied seven patients who underwent deep brain stimulation (DBS) electrode implantation in the thalamus for treatment of tremor (six patients) and myoclonus–dystonia (one patient). We recorded from the DBS contacts and scalp simultaneously, while patients performed self-paced wrist extension movements. Post-surgical MRI was used for precise localization of the DBS contacts in six patients. Back-averaging of the scalp recordings showed a slow negative movement-related potential (MRP) in all patients (onset 1846 ± 189 ms prior to electromyography onset), whereas DBS electrode recordings showed pre-movement MRP in five out of seven patients. The thalamic MRP preceded both contralateral and ipsilateral wrist movements. There was no significant difference between the onset time of thalamic MRP (−2116 ± 607 ms) and cortical MRP. Neither the scalp nor the thalamus showed pre-movement potentials with passive wrist extensions in two patients. In four patients with postoperative MRI who had thalamic MRP, the maximum amplitude or phase reversal occurred at contacts located in the ventral lateral nucleus. Frequency analysis was performed in the five patients with thalamic MRP. The medial frontocentral scalp contacts and the thalamic contacts with maximum MRP amplitude showed two discrete frequency bands in the α (mean peak 9 Hz) and β (mean peak 17 Hz) range. Both frequency bands showed pre-movement event-related desynchronization (ERD). In the grand average, α and β ERD in the scalp and β ERD in the thalamus began 2.5–2.8 s prior to the onset of movement. However, the thalamic α ERD began considerably later, at 1.2 s before EMG onset. The β band showed cortico-thalamic coherence from the beginning of the baseline period until ∼0.5 s before the onset of movement. There was no cortico-thalamic coherence in the α band. Our findings suggest that the cerebellar thalamus is involved early in the process of movement preparation. Different cortico-subcortical circuits may mediate α and β oscillations. During movement preparation, the motor thalamus and the supplementary motor area predominantly interact in the β band.

Bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) was performed in a patient with Huntington's disease (HD) with severe chorea. Stimulation at 40 and 130Hz improved chorea. Stimulation at 130Hz slightly worsened bradykinesia overall, whereas 40Hz had little effect. A [15O] H2O positron emission tomography showed increased regional cerebral blood flow in motor decision making and execution areas more evident at 40Hz. Adjustment of stimulation parameters in GPi DBS may have the potential to optimize the motor response in HD, improving chorea without aggravating bradykinesia. Ann Neurol 2004

Objective: To investigate the potential correlation between the use of extended-spectrum cephalosporins (ESCs) and resistance to this antibiotic class among clinical isolates of Enterobacter cloacae in a university-affiliated hospital. Materials and methods: Data on antimicrobial resistance and antimicrobial use concerning E. cloacae and ESCs were collected over a 4 year period. Various statistical tools were used to explore the potential relationship. Results: From 1999 to 2002, the proportion of E. cloacae isolates resistant to ESCs increased from 24.3% to 29.6%. (P=0.04), and the quantity of ESCs prescribed and given did not change. Within the subclass constituted by first-line ESCs, the proportion of ceftriaxone increased from 64.3% to 77.6% and the proportion of cefotaxime decreased accordingly, from 35.7% to 22.4%. Statistical analyses showed that E. cloacae resistance to ESCs correlated with ceftriaxone use regardless of the other ESCs. For every defined daily dose of ceftriaxone per 1000 patient days used in our hospital, resistance of E. cloacae isolates to ESCs increased by 1.36%. Conclusion: This study demonstrates a specific correlation between ceftriaxone use and the development of resistance in E. cloacae clinical isolates. The high biliary elimination of ceftriaxone compared with other ESCs may be responsible for a greater impact of this antibiotic on the digestive flora.

The subthalamic nucleus (STN) has been regarded as an important modulator of basal ganglia output. It receives its major afferents from the cerebral cortex, thalamus, globus pallidus externus and brainstem, and projects mainly to both segments of the globus pallidus, substantia nigra, striatum and brainstem. The STN is essentially composed of projection glutamatergic neurons. Lesions of the STN induce choreiform abnormal movements and ballism on the contralateral side of the body. In animal models of Parkinson’s disease this nucleus may be dysfunctional and neurons may fire in oscillatory patterns that can be closely related to tremor. Both STN lesions and high frequency stimulation ameliorate the major motor symptoms of parkinsonism in humans and animal models of Parkinson’s disease and reverse certain electrophysiological and metabolic consequences of dopamine depletion. These new findings have led to a renewed interest in the STN. The aim of the present article is to review briefly the major anatomical, pharmacological and physiological aspects of the STN, as well as its involvement in the pathophysiology and treatment of Parkinson’s disease.

Thirteen consecutive patients with thalamic deep brain stimulation (DBS) were examined serially for 3 to 5 years. Initially, all demonstrated at least 50 improvement in contralateral tremor. At last follow-up, three of eight patients with Parkinson disease no longer used DBS because tremor had markedly improved, and for two, motor fluctuations and levodopa-induced dyskinesias became the major disability, with tremor less troublesome. Two of five patients with essential tremor had contralateral tremor improvement after ongoing stimulation for 2 years; two developed marked tolerance to DBS.

Although it has long been recognized that the basal ganglia play a major role in motor control, their precise functions remain unclear. As patients with Parkinson’s disease (PD) have difficulties initiating movement, the basal ganglia may be involved in movement preparation. The subthalamic nucleus (STN) is particularly suited to play a role in movement preparation because it receives direct input from the supplementary motor area through the corticosubthalamic pathway.

The behavior of neurons in the basal ganglia is severely disrupted in Parkinson's disease (PD). In nonhuman parkinsonian primate models, the disturbance in neurons in basal ganglia output structures include increased firing, bursting, an augmented synchrony, correlated activity, and a tendency towards loss of specificity in their receptive fields. This abnormal neuronal behavior, transmitted to the thalamus, cortex and brainstem, is thought to disrupt the functioning of the motor system and underlie the major motor manifestations of PD-tremor, rigidity, akinesia, gait, and postural disturbances. The mainstay of treatment has been to replace the missing dopamine with medication. With time and disease progression, however, dopamine replacement becomes less efficacious and new adverse effects, including the development of motor fluctuations and drug-induced involuntary movements or dyskinesias, emerge. When the patients reach this stage, surgical therapy becomes an option. Most surgical interventions are performed at the level of the thalamus, globus pallidus, and subthalamic nucleus, aiming at the disruption of the pathological activity that accompanies the Parkinson's deficiency state. With this abnormal neuronal activity neutralized, normal movements can in many cases be restored.

Dystonia is a neurological syndrome involving sustained contractions of opposing muscles leading to abnormal movements and postures. Recent studies report abnormally low pallidal neuronal activity in patients with generalized dystonia, suggesting hyperkinetic disorders result from underactive basal ganglia output. We examined this hypothesis in 11 patients with segmental and generalized dystonia undergoing microelectrode exploration of the internal globus pallidus (GPi) before pallidotomy or deep brain stimulation (DBS) implantation. The mean firing rates and firing patterns were compared with those in six patients with Parkinson's disease (PD). In seven patients who underwent surgery under local anesthesia, the mean GPi firing rate was 77Hz, similar to the 74Hz observed in the PD patients. However, in three dystonic patients under propofol anesthesia, GPi mean firing rate was much reduced (31Hz), and the firing pattern was distinguished by long pauses in activity, as reported by others. Low‐dose propofol in one other dystonia patient also seemed to suppress GPi firing. These results indicate that an abnormally low basal ganglia output is not the sine qua non of dystonia. The widely accepted pathophysiological models of dystonia that propose global decreases in basal ganglia output need to be viewed with caution in light of these findings. Ann Neurol 2003

Local field potentials and pairs of neurones in the subthalamic nucleus (STN) of patients with Parkinson’s disease show high‐frequency oscillations (HFOs) at 15–30 Hz. This study explores how these HFOs are modulated by voluntary movements and by dopaminergic medication. We examined 15 patients undergoing implantation of bilateral deep brain stimulating electrodes using microelectrode recordings of pairs of STN neurones (eight patients) and macroelectrode recordings of local field potentials from the STN (14 patients). Synchronized HFOs between STN neurones were observed in 28 out of 37 pairs in five patients who had tremor in the operating room and none of 45 pairs in three patients who did not. In two of the three non‐tremulous patients, HFOs in the frequency spectra of local field potentials were detected but were weaker than in those patients with tremor. Active movement suppressed synchronized HFOs in three out of five pairs of neurones, independent of changes in firing rate. HFOs observed in the local field potentials in nine out of 14 patients were reduced with voluntary movement in six of the eight patients tested. Dopaminergic medication decreased the incidence of synchronized HFOs in STN neurone pairs, reduced HFO synchrony in a pair of tremor cells concurrent with a reduction in firing rate and limb tremor, and decreased HFOs of local field potentials in the STN. These results demonstrate that HFO synchronization in the STN is reduced by voluntary movements and by exogenous dopaminergic medication. A mechanism for neuronal oscillatory synchronization in basal ganglia is proposed. It is suggested that the firing of STN neurones can be synchronized by 15–30 Hz cortical beta oscillatory activity, particularly when dopamine deficiency results in a higher background firing rate of STN neurones, and that this synchronization contributes to parkinsonian pathophysiology.

Transcranial magnetic stimulation (TMS) studies have found abnormalities in several excitatory and inhibitory circuits in the motor cortex in PD. These include motor evoked potential (MEP) recruitment curve, silent period duration (SP), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), and long-interval intracortical inhibition (LICI).

High frequency electrical stimulation by means of electrodes implanted into the brain (deep brain stimulation; DBS) recently has become an accepted technique for the treatment of several movement disorders and in particular for Parkinson's disease. Because the effects produced by DBS are similar to those produced by making a lesion in the same region, it has been proposed that the overall effect of DBS is to inhibit the neural activity in the region stimulated. However, whether this is actually the case is presently not known, but various mechanisms have been proposed in an attempt to explain how DBS could mimic the effects of a lesion. We describe the various mechanisms that have been proposed to account for the inhibition or disruption of the pathologic outflow by high‐frequency DBS, ranging from depolarisation block to stimulation‐evoked release of γ‐aminobutyric acid and describes preliminary findings that show that stimulation within these structures can result in inhibition. © 2002 Movement Disorder Society

The internal segment of the globus pallidus (GPi) is being targeted in neurosurgical procedures to treat Parkinson's disease and dystonia. Precise targeting of the pallidal complex is important in determining the efficacy of the surgical intervention and for the avoidance of adverse effects. Intraoperative microelectrode recording can be used to characterize the patterns of activity and receptive field properties of single pallidal neurons and to identify important bordering structures, including the optic tract and internal capsule. Because the clinical features of movement disorders can be differentially affected as a function of location within the pallidal complex, further refinements in intraoperative targeting may become important. © 2002 Movement Disorder Society

The purpose of the present study was to assess the effects on reproductive activity of melatonin implants inserted immediately after the winter solstice compared with the classical implantation around the spring equinox. The experiment was conducted at latitude 41˚ N in the absence of rams. Twenty-one ovariectomised, oestradioltreated Rasa Aragonesa ewes received (M1, n = 7, 15 January; M2, n = 7, 15 March) or not (C, n = 7) a single implant containing 18 mg melatonin. Blood samples were collected twice weekly from 15 January (M1) and from 15 March (M2, C), and assayed for luteinizing hormone. Six M1 ewes resumed their reproductive activity by 20 April, 95 days after implant insertion, although the reproductive season induced only lasted for 45 days. Melatonin implants inserted on 15 March did not induce a resumption of reproductive activity (0 ewes; P &lt; 0.05). It is concluded that, in the absence of males, the response of Mediterranean ewes to melatonin implants is better when implantation takes place immediately after the winter solstice than around the spring equinox. Two subsequent field experiments with the same breed and year were carried out. Animals were implanted (M) or not (C) with melatonin on 29 December (M, n = 156; C, n = 159) and on 20 March (M, n = 150; C, n = 128). Results confirmed the efficacy of the treatment with melatonin immediately after the winter solstice in ewes with a short seasonal anoestrous period. Implants induced a mean productivity increase of 0.30 (December) and 0.36 (March) lambs per treated ewe compared with those in the control groups. LH, photoperiod, melatonin, sheep.

Inactivation of neurones in the subthalamic nucleus (STN) of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treated monkey model of Parkinson's disease has been shown to relieve parkinsonian motor symptoms. In patients with Parkinson's disease, neurones in the STN display hyperactive firing rates and rhythmic discharge activity such as tremor-related oscillations (3–8 Hz) and synchronous high-frequency oscillations (15–30 Hz). In this study, microinjections of lidocaine (n = 4) and muscimol, a GABAA receptor agonist (n = 2), were performed in the STN of six patients with Parkinson's disease to determine whether the focal suppression of STN neuronal activity can lead to an improvement in tremor, bradykinesia and rigidity. We also report the first use of microelectrode recording of the effects of microinjections on neuronal activity in the human brain (n = 2). Microinjections of 10–23 μl of lidocaine produced striking improvements in bradykinesia, limb tremor and rigidity in three out of three patients. These improvements were correlated with good therapeutic effects of subsequent STN deep brain stimulation performed in the same microelectrode trajectories as these injections. The most dramatic observation following lidocaine injections was the appearance of dyskinetic limb movements. In one patient, simultaneous microelectrode recording during an injection of 3.5 μl of lidocaine demonstrated a suppression of neuronal activity at distances of <0.9 mm from the injection site, but no suppression was observed at ≥1.2 mm from the injection site. Microinjections of 5–10 μl of muscimol in a region with tremor-related activity resulted in suppression of limb tremor in two out of two patients. Interestingly, in one of these patients, 4 Hz oscillatory activity was diminished in a neurone recorded 1.3 mm from the injection site, but there was no reduction in the mean firing rate or 20 Hz oscillatory activity. These results demonstrate that inactivation of neuronal activity in the STN of patients with Parkinson's disease improves motor symptoms. These findings also suggest that a focal block of the STN might alter the oscillatory activity of neurones located beyond the inhibited region.

Platelet factor-4 is a protein belonging to the family of ELR-negative CXC chemokines which binds to fibroblast growth factor and inhibits its mitogenic activity. Platelet factor-4 also inhibits tumor growth by mechanisms involving antiangiogenesis. Antiangiogenic activity in vitrohas also been shown for the 24-residue C-terminal fragment of the protein, which decreases the affinity between basic fibroblast growth factor and its cell-surface receptor. In this study, the preferential conformation of this fragment in solution has been determined and has been found to be composed of two helical subdomains. In addition, we show that the fragment forms a specific 1:1 complex with acidic and basic fibroblast growth factors and that both subdomains are probably required for inhibition of fibroblast growth factor-driven mitogenesis. Finally, we show that the binding of the fragment alters the structure of the fibroblast growth factors, although some of such alterations do not seem related with the inhibition of mitogenic activity. Since this fragment has recently been shown to inhibit fibroblast growth factor-induced angiogenesis in vivowhen injected intraperitoneally, these results are relevant for developing new antiangiogenic treatments.

Employing [(18)F]fluorodeoxyglucose (FDG) and PET, we have found previously that stereotaxic ablation of the internal globus pallidus (GPi) for Parkinson's disease causes resting metabolic changes in brain regions remote from the lesion site. In this study we determined whether similar metabolic changes occur in Parkinson's disease patients treated with deep brain stimulation (DBS) of the GPi. We studied seven Parkinson's disease patients with FDG-PET to measure resting regional cerebral glucose utilization on and off GPi stimulation. We used statistical parametric mapping to identify significant changes in regional brain metabolism that occurred with this intervention. We also quantified stimulation-related changes in the expression of a specific abnormal Parkinson's disease-related pattern of metabolic covariation (PDRP) that had been identified in earlier FDG-PET studies. Metabolic changes with DBS were correlated with clinical improvement as measured by changes in Unified Parkinson's Disease Rating Scale (UPDRS) motor ratings off medication. GPi DBS improved UPDRS motor ratings (36%, P < 0.001) and significantly increased regional glucose metabolism in the premotor cortex ipsilateral to stimulation and in the cerebellum bilaterally. GPi DBS also resulted in a significant (P < 0.01) decline in PDRP activity ipsilateral to stimulation, which correlated significantly with clinical improvement in UPDRS motor ratings (P < 0.03). Clinical improvement with GPi DBS is associated with reduced expression of an abnormal Parkinson's disease-related metabolic network involving elements of the cortico-striato-pallido-thalamocortical and the cerebello-cortical motor loops.

This study examines the effect of apomorphine (APO), a nonselective D1- and D2-dopamine receptor agonist, on the firing activity of neurons in the subthalamic nucleus (STN) and internal segment of the globus pallidus (GPi) in patients with Parkinson's disease (PD). Single-unit microelectrode recordings were conducted in 13 patients undergoing implantation of deep brain stimulation electrodes in STN and 6 patients undergoing a pallidotomy. Doses of APO (2.5–8 mg) were sufficient to produce anonstate, but not intended to induce dyskinetic movements. Following baseline recordings from a single neuron, APO was administered and the activity of the neuron followed for an average of 15 min. The spontaneous discharge of neurons encountered before (n= 309), during (n= 146, 10–60 min), and after the effect of APO had waned (n= 127, >60 min) was also sampled, and the response to passive joint movements was noted. In both nuclei, APO increased the overall proportion of spikes in burst discharges (as detected with Poisson “surprise” analysis), and a greater proportion of cells with an irregular discharge pattern was observed. APO significantly decreased the overall firing rates of GPi neurons (P< 0.01), but there was no change in the overall firing rate of neurons in the STN (P= 0.68). However, the mean firing rates of STN neurons during APO-induced movements (choreic or dystonic dyskinesias) that occurred in four patients were significantly lower thanoff-period baseline values (P< 0.05). Concurrent with a reduction in limb tremor, the percentage of cells with tremor-related activity (TCs) was found to be significantly reduced from 19 to 6% in the STN and 14 to 0% in the GPi following APO administration. APO also decreased the firing rate of STN TCs (P< 0.05). During the offstate, more than 15% of neurons tested (STN = 93, GPi = 63) responded to passive movement of two or more joints. After APO, this proportion decreased significantly to 7% of STN cells and 4% of GPi cells (STN = 28, GPi = 26). These findings suggest that the APO-induced amelioration of parkinsonian symptoms is not solely due to a decrease in overall activity in the GPi or STN as predicted by the current model of basal ganglia function in PD.

Patients with obstructive jaundice (OJ) that requires surgery often have malnutrition associated with increased perioperative morbidity. This study investigated the factors influencing nutritional derangements in these patients. A series of 46 OJ patients were investigated prospectively (28 malignant tumors, 18 benign obstructions). A nutritional risk index of < 83.5 was used to define protein-calorie malnutrition. Liver function, cholecystokinin (CCK), tumor necrosis factor-a (TNFa), and endotoxin levels were determined. A multivariate analysis was performed, and an obstructive jaundice malnutrition index (OJMI) was obtained. Altogether, 22 (48%) OJ patients had malnutrition (33% with benign obstructions, 57% with malignant disease). Malnourished patients had higher serum bilirubin levels (258 ± 120 vs. 154 ± 62 mmol/L; p= 0.005), longer duration of jaundice (16 ± 9 vs. 9 ± 5 days; p= 0.03), and higher plasma levels of CCK (4.0 ± 1.3 vs. 1.7 ± 1.0 pmol/L; p= 0.005), alanine aminotransferase (ALT) (226 ± 209 vs. 187 ± 161 UI/L; p= 0.01), endotoxin (15 ± 10 vs. 6.5 ± 7.0 EU/L; p= 0.007), and TNFa (69 ± 82 vs. 23 ± 15 pg/ml; p= 0.008) than those without malnutrition. However, only serum bilirubin, CCK, ALT, and patient age were predictors for malnutrition by multivariate analysis. Malnutrition might be expected (95% confidence interval) in patients older than 68 years with increased bilirubin (> 290 mmol/L) and ALT (> 210 UI/L) levels that corresponded with an OJMI > 55. It was concluded that nutritional alterations in patients with obstructive jaundice were determined by the intensity of the biliary obstruction correlated with increased plasma CCK levels as well as with liver dysfunction and patient age.

Deep brain stimulation is a promising treatment for PD, but its physiologic effects and mechanisms of action remain poorly understood. Magnetic stimulation studies have revealed abnormalities in several different excitatory and inhibitory circuits in the motor cortex in PD.

The 4-methylated fatty acids 4,9-dimethyldecanoic, 4,11-dimethyldodecanoic, 4,10-dimethyldodecanoic, and 4,13-dimethyltetradecanoic acid as well as the 2-methylated fatty acids 2,13-dimethyltetradecanoic and 2,12-dimethyltetradecanoic acid were identified for the first time in nature in the halophilic bacterium Bacillus sp. isolated from the salt pans of Burgas in Bulgaria. The principal fatty acids in this bacterium were a series of iso-anteiso fatty acids with chain lengths between C11 and C19, but an interesting series of linear alkylbenzene fatty acids with chain lengths between C10 and C14, such as 12-phenyldodecanoic acid, were also identified. The novel 4-methylated fatty acids were characterized using a combination of GC−MS and chemical transformations such as N-acylpyrrolidide derivatization. The 2-methylated fatty acids were also identified by GC−MS and gas chromatographic coelution with synthetic samples. The novel methyl-branched fatty acids probably originated from the selective incorporation of methylmalonyl-CoA by one of the fatty acid-synthesizing enzymes of the bacterium.

We measured regional cerebral blood flow with H215O and positron emission tomography (PET) scanning at rest and during a motor task to study the mechanism of motor improvement induced by deep brain stimulation of the internal globus pallidus in Parkinson's disease. Six right‐handed patients with Parkinson's disease were scanned while performing a predictable paced sequence of reaching movements and while observing the same screen displays and tones. PET studies were performed ON and OFF stimulation in a medication‐free state. Internal globus pallidus deep brain stimulation improved off‐state United Parkinson's Disease Rating Scale motor ratings (37%, p< 0.002) and reduced timing errors (movement onset time, 55%, p< 0.01) as well as spatial errors (10%, p< 0.02). Concurrent regional cerebral blood flow recordings revealed a significant enhancement of motor activation responses in the left sensorimotor cortex (Brodmann area [BA] 4), bilaterally in the supplementary motor area (BA 6), and in the right anterior cingulate cortex (BA 24/32). Significant correlations were evident between the improvement in motor performance and the regional cerebral blood flow changes mediated by stimulation. With internal globus pallidus deep brain stimulation, improved movement initiation correlated with regional cerebral blood flow increases in the left sensorimotor cortex and ventrolateral thalamus and in the contralateral cerebellum. By contrast, improved spatial accuracy correlated with regional cerebral blood flow increases in both cerebellar hemispheres and in the left sensorimotor cortex. These results suggest that internal globus pallidus deep brain stimulation may selectively improve different aspects of motor performance. Multiple, overlapping neural pathways may be modulated by this intervention. Ann Neurol 2001:49:155–164

Abstract:  The purpose of this study was to compare the effect of salinity on the symbiotic efficiencies and mycelial infectivity of two arbuscular mycorrhizal fungi (AMF), one isolated from saline soils (Glomus sp.) and the other (Glomus deserticola) from nonsaline soils (belonging to the Estación Experimental del Zaidín collection). Lettuce plants inoculated with either of these two fungi or maintained as uninoculated controls were grown in soil with three salt concentrations (0.25, 0.50 or 0.75 g NaCl kg–1 dry soil). Both AMF protected host plants against salinity. However, when the results of shoot dry weight and nutrient contents were expressed relative to the total length of mycorrhiza formed, it was found that both AMF differed in their symbiotic efficiencies. These differences were more evident at the two highest salt levels. Glomus sp.-colonized plants grew less and accumulated less N and P, whereas they formed a higher amount of mycorrhiza. The mechanism by which Glomus sp. protected plants from the detrimental effects of salt was based on the stimulation of root development, while the effects of G. deserticola were based on improved plant nutrition. The increase in salinity of soil decreased the hyphal growth and/or viability of Glomus sp. to a higher extent than those of G. deserticola since the mycelial network generated by G. deserticola was more infective than that of Glomus sp.

Seven patients with Parkinson's disease were implanted with deep brain stimulators to provide chronic electrical stimulation to the subthalamic nucleus bilaterally. Acoustic recordings and neurologic assessments were undertaken before surgery in the medication‐off and medication‐on conditions and after surgery with and without electrical stimulation in the medication‐off and medication‐on conditions. The data showed significant improvements in limb motor performance in response to medication before surgery and when the subthalamic nucleus was stimulated after surgery. Six months after surgery, there were small but statistically significant increases in sound pressure level and fundamental frequency variability in response to stimulation in the medication‐on condition. No other statistically significant speech changes were measured. These findings are consistent with several other studies that have reported disparity between limb and speech improvements after neurosurgical intervention for Parkinson's disease.

The aim of this study was to examine possible neuropsychological changes in patients with advanced idiopathic Parkinson's disease treated with bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN). Eleven patients (age = 67 ± 8 years, years with Parkinson's disease = 15 ± 3, verbal IQ = 114 ± 12) were evaluated (in their best `on state') with tests assessing processes reliant on the functional integrity of frontal striatal circuitry, prior to the procedure (n = 11), at 3–6 months (n = 11) and at 9–12 months (n =10) post-operatively. Six of these patients were older than 69 years. Despite clinical motor benefits at 3–6 months post-operative, significant declines were noted in working memory, speed of mental processing, bimanual motor speed and co-ordination, set switching, phonemic fluency, long-term consolidation of verbal material and the encoding of visuospatial material. Declines were more consistently observed in patients who were older than 69 years, leading to a mental state comparable with progressive supranuclear palsy. `Frontal' behavioural dyscontrol without the benefit of insight was also reported by half (three of six) of the caregivers of the elderly subgroup. At 9–12 months postoperative, only learning based on multiple trials had recovered. Tasks reliant on the integrity of frontal striatal circuitry either did not recover or gradually worsened over time. Bilateral STN DBS can have a negative impact on various aspects of frontal executive functioning, especially in patients older than 69 years. Future studies will evaluate a larger group of patients and examine the possible reversibility of these effects by turning the DBS off.

Akinesia and gait disturbances are particularly incapacitating for patients with Parkinson's disease. The anatomical and physiological substrates for these disturbances are poorly understood. The pedunculopontine nucleus (PPN) is thought to be involved in the initiation and modulation of gait and other stereotyped movements, because electrical stimulation and the application of neuroactive substances in the PPN can elicit locomotor activity in experimental animals. Glutamatergic neurones of the PPNd (pars dissipatus) are thought to be important regulators of the basal ganglia and spinal cord. The other component of the PPN, the cholinergic pars compacta (PPNc), is a principal component in a feedback loop from the spinal cord and limbic system back into the basal ganglia and thalamus. Electrophysiological studies suggest that `bursting' glutamatergic PPNd neurones are related to the initiation of programmed movements while non-bursting cholinergic PPNc neurones are related to the maintenance of steady-state locomotion. Furthermore, since patients with Parkinson's disease have significant loss of PPN neurones and experimental lesions in the PPN of normal monkeys result in akinesia, the degeneration of PPN neurones or their dysfunction may be important in the pathophysiology of locomotor and postural disturbances of parkinsonism. The goal of this review is (i) to highlight the anatomical connections and physiological attributes of the PPN, (ii) to discuss how the function of these connections may be altered in the parkinsonian state, and (iii) to speculate how present and potential future therapy directed to the PPN might improve akinesia and gait difficulties in parkinsonian patients.

Neurosurgical treatment of Parkinson's disease (PD) frequently employs chronic high-frequency deep brain stimulation (DBS) within the internal segment of globus pallidus (GPi) and can very effectively reduce L-dopa–induced dyskinesias and bradykinesia, but the mechanisms are unknown. The present study examined the effects of microstimulation in GPi on the activity of neurons close to the stimulation site. Recordings were made from GPi using two fixed or independently controlled microelectrodes, with the electrode tips usually ∼250 or >600 μm apart in PD patients undergoing stereotactic exploration to localize the optimal site for placement of a lesion or DBS electrode. The spontaneous activity of nearly all of the cells (22/23) recorded in GPi in three patients was inhibited by microstimulation at currents typically <10 μA (0.15-ms pulses at 5 Hz). The inhibition had a duration of 10–25 ms at threshold. These findings suggest that microstimulation within GPi preferentially excites the axon terminals of striatal and/or external pallidal neurons causing release of GABA and inhibition of GPi neurons.

Chronic stimulation of the ventral intermediate nucleus (Vim) of the thalamus is highly effective for the treatment of tremor. Patients with tremor associated with Parkinson's disease and essential tremor appear to respond best. Patients with cerebellar tremors may also respond but to a lesser extent. Although tremor is improved, Vim DBS does not substantially improve the daily living activities of patients with Parkinson's disease. This is related to the lack of effect on rigidity, bradykinesia, and gait and postural disturbances associated with Parkinson's. For this reason, the majority of patients with Parkinson's disease who require surgery are better treated with interventions in the globus pallidusor subthalamic nucleus, targets that allow improvement in all cardinal features of Parkinson's disease. In contrast, Vim DBS has unequivocal functional benefit in patients with essential tremor, this is likely to remain the major indication of this form of therapy. The mechanism of action of thalamic DBS is not understood and remains a research priority.

Current models of basal ganglia anatomy posit the existence of multiple parallel, anatomically segregated circuits. Anatomical data from non-human primates suggest that the circuits subserving motor functions are segregated from those subserving cognitive functions. Here we present data that demonstrate that, in humans, motor and cognitive frontosubcortical circuits are segregated. We studied a group of patients with Parkinson's disease undergoing surgical lesioning of the globus pallidus internus for relief of their symptoms. Lesion location along an anteromedial-to-posterolateral axis was found to be related to postsurgical outcome on both cognitive and motor measures. Performance on several neuropsychological measures, including the generation of category exemplars and continuous mental addition, was linearly related to distance along this axis, with anteromedial lesions leading to postsurgical impairment, intermediate lesions having little effect and posterolateral lesions leading to an improvement on several measures. The same relationship was found between memory performance under conditions of proactive interference and lesion location within the globus pallidus internus. In contrast, bradykinesia, assessed as the speed of finger-tapping, had a non-linear relationship to lesion location, intermediate lesions leading to greater postsurgical improvement than lesions in more extreme anteromedial or posterolateral locations. These data demonstrate that the cognitive effects of pallidotomy can be dissociated from the motor effects. These effects depend upon the placement of the lesions within the globus pallidus internus, supporting the segregation of functionally distinct circuits in the human pallidum.

This paper highlights the neuropsychological sequelae of posteroventral pallidotomy (PVP) and deep brain stimulation (DBS) of the subthalamic nucleus (STN) and the internal segment of the globus pallidus (GPi) at 3/6 months postoperatively. Results are based on our extensive experience with PVP and our preliminary observations with DBS. Patients with borderline cognitive or psychiatric functioning risk postoperative decompensation. Nonlateralizing attentional and hemisphere-specific impairments of frontostriatal cognitive functions followed unilateral PVP. “Frontal” behavioral dyscontrol was observed in approximately 25% of patients. Three cases of staged bilateral PVP suggest that premorbid factors may predict outcome, although lesion size and location are also critical. Older patients are at risk for significant cognitive and behavioral decline after bilateral STN DBS, while GPi DBS may be safer.

AbstractIn just 12 years since its introduction, deep brain stimulation (OBS) has become well established as a safe - and effective therapy in the treatment of medically refractory movement disorders. Ventralis intermedius (Vim) OBS has virtually replaced thalamotomy in the routine clinical treatment ofessential tremor, affording relief to thousands of patients who previously would not have undergone surgery, and there is increasing usage of Vim DBS in other tremors of intention (e.g., multiple sclerosis). Subthalamic nucleus (STN) and globus pallidus internus (GPO DBS have revolutionized the treatment of advanced stage Parkinsonls disease, improving all cardinal disease features and increasing lon l time without dyskinesias. Finally, DBS of various sub-cortical structures is being developed and tested in other less prevalent movement disorders such as dystonia. Future developments in this rapidly advancing area will no doubt include widening indications for this relatively safe surgical procedure, elucidation of the mechanisms of action of electrical stimulation, and technological advancements improving effectiveness and convenience. [Neural Res 2000; 22:247-258]

Hamstring extensibility is a crucial component of athletic performance and spinal health. In this regard, hip range of motion analysis through standardized clinical tests has been used as a valid and reliable method for measuring hamstring extensibility. Consequently, new inertial devices have been designed for this purpose. The aims of this study were to: (i) analyze the concurrent validity of inertial sensors for measuring hamstring extensibility through the Active Straight Leg Raise (ASLR) and Passive Straight Leg Raise (PSLR) tests; and (ii) analyze the test-retest reliability of inertial sensors for measuring hamstring extensibility through the ASLR and PSLR tests. A total of 18 healthy participants took part in this cross-sectional study. The hamstring extensibility was measured through the range of motion of the left and right hip in the Active Straight Leg Raise (ASLR) and Passive Straight Leg Raise (PSLR) tests. Data were collected by inertial sensors (WIMU Pro) and an ISOMED bi-level inclinometer, which was used as the reference instrument. The inertial sensors reported a standard error of the measurement (SEM) below 0.6° in all measurements. The R2correlation and the intraclass correlation coefficient (ICC) were very close to 1 in all measurements. Regarding the reliability analysis, there were no significant differences (p> 0.05) between test and retest measures, and the SEM were below 0.8° in both instruments. The ICC were close to 1 in all cases as well. The coefficients of variation (CV) were below 2.7% in the inertial device and 2.2% in the inclinometer. This study showed that using microtechnology through WIMU Pro may be a valid and reliable method for measuring hip range of motion during the ASLR and PSLR tests.