Measuring impulsivity in Parkinson's disease: a correlational and structural neuroimaging study using different tests.

BACKGROUND AND PURPOSE: Impulsivity is an aspect of personality and a major component of multiple neuropsychiatric conditions. In Parkinson's disease, it has been associated with the expression of impulse control disorders, a highly prevalent non-motor complication. Even though multiple tests of impulsivity have been used in this context, the impact of test choice has not been addressed. The aim was to evaluate whether different impulsivity measures in Parkinson's disease share substantial inter-scale and anatomical correlations or rather mirror different underlying phenomena. METHODS: In a consecutive sample of 89 Parkinson's disease patients without impulse control disorders, four common tests were evaluated assessing different aspects of impulsivity: impulsiveness trait, decisions under implicit risk with and without losses, and delay discounting. Correlations among test scores were analysed and each score was used as a regressor in a set of grey matter volume (GMV) voxel-based morphometry analyses to explore their brain structural correlates. RESULTS: No significant correlations were found between the different impulsivity tests. Furthermore, their structural brain correlates were divergent. Impulsiveness trait appeared to be associated with lower GMV in dorsal-lateral prefrontal cortices, implicit risk (with losses) with higher GMV in the left nucleus accumbens and lower left insular GMV, implicit risk (without losses) with higher GMV in the left lingual gyrus and lower GMV in the gyri recti and delay discounting with higher GMV in the left nucleus accumbens. CONCLUSIONS: In Parkinson's disease, different impulsivity measures reflect very dissimilar behavioural and brain structural correlates. Our results suggest that parkinsonian impulsivity is not a unitary phenomenon but rather a heterogeneous entity.

Visual hallucinations in patients with acute stroke: a prospective exploratory study.

BACKGROUND AND PURPOSE: The incidence, underlying physiopathology, features and association with lesion topography of visual hallucinations in acute stroke have scarcely been investigated. METHODS: Patients with a diagnosis of acute stroke (ischaemic or haemorrhagic) in any vascular territory, admitted within 24 h after the onset of symptoms, were consecutively included in the study. Patients with a previous history of psychosis or cognitive impairment were excluded. They and/or their caregivers answered a structured hallucination and sleep questionnaire at admission, within the first 15 days and at the clinical follow-up 3-6 months after discharge. Lesion location (IMAIOS online atlas) and leukoaraiosis (Wahlund scale) were determined by magnetic resonance imaging or computed tomography scan. Subsets of patients also underwent a neuropsychological evaluation (N = 50) and an electroencephalogram (N = 33) before discharge. RESULTS: In all, 77 patients with a mean age of 71 ± 12 years were included of whom 57.1% were men. The incidence of visual hallucinations was 16.7%. These hallucinations were mostly complex, in black and white and self-limited. The appearance of hallucinations was not influenced by age, sex, neuropsychological performance during admission or modified Rankin scale score at discharge. Visual hallucinations were associated with occipital cortex lesions (P = 0.04), and with sleep disturbances during and before admission (P = 0.041 and P = 0.03 respectively). CONCLUSIONS: Visual hallucinations are relatively frequent in patients with acute stroke and they are self-limited. Patients with occipital lesions and sleep disturbances are more likely to suffer them.

[Essential tremor: are we just splitting hairs? Non-motor symptoms and essential tremor-plus]. / Temblor esencial: ¿el gato tiene cinco pies? Síntomas no motores y temblor esencial plus.

INTRODUCTION: The existence of non-motor symptoms in essential tremor (ET) and the appearance of a new condition, ET-plus, are two controversial issues. AIMS: To offer a review of the current status of these two topics. DEVELOPMENT: We performed an analysis of the studies conducted on non-motor symptoms in ET and of the articles for and against the use of the term ET-plus. CONCLUSIONS: Non-motor symptoms have gained increased recognition as a feature accompanying ET. Several studies have documented its presence compared to matched controls. It is not clear, however, whether these non-motor symptoms would be part of the spectrum of ET symptoms (a primary phenomenon) or whether they would be symptoms that appear as a consequence of the physical or psychological disability produced by the clinical signs and symptoms of ET itself (a secondary phenomenon). For the time being, their evaluation and treatment are not included within the standard assessment of patients with ET. In view of the heterogeneous phenotype, the term ET-plus aims to improve phenotypic homogeneity for genetic or therapeutic studies. Yet, there is no pathological basis, and epidemiological, genetic and therapeutic research studies have numerous drawbacks. In the absence of clear objective biomarkers, distinguishing between ET and ET-plus by clinical distinction alone is very complex. We should be cautious about using new terms that are not yet backed by sound scientific evidence.

TITLE: Temblor esencial: ¿el gato tiene cinco pies? Síntomas no motores y temblor esencial plus.Introducción. La existencia de síntomas no motores en el temblor esencial (TE) y la aparición de una nueva entidad, el TE plus, son dos temas controvertidos. Objetivos. Exponer una revisión del estado actual de estos dos temas. Desarrollo. Análisis de los estudios sobre síntomas no motores en el TE, y de los artículos favorables y contrarios al término TE plus. Conclusiones. Los síntomas no motores han aumentado su reconocimiento como un dato acompañante del TE. Varios estudios han documentado su presencia en comparación con controles pareados. Ahora bien, no está claro si estos síntomas no motores formarían parte del espectro de síntomas del TE (fenómeno primario), o si se trataría de síntomas que aparecen como consecuencia de la discapacidad física o psíquica producida por la propia sintomatología del TE (fenómeno secundario). De momento, su evaluación y su tratamiento no forman parte de la valoración estándar de los pacientes con TE. Ante el fenotipo heterogéneo, el término TE plus intenta mejorar la homogeneidad fenotípica de cara a los estudios genéticos o terapéuticos. Ahora bien, no existe una base patológica y existen numerosos inconvenientes para los estudios de investigación epidemiológicos, genéticos y terapéuticos. En ausencia de biomarcadores objetivos claros, la distinción entre TE y TE plus únicamente por distinción clínica es muy compleja. Debemos ser cautos a la hora de utilizar nuevos términos que no están todavía soportados por una base científica.

Motor changes during sertraline treatment in depressed patients with Parkinson's disease*.

BACKGROUND: Pharmacological interventions to treat depressive symptoms associated with Parkinson's disease (PD) are limited. Whether selective serotonine re-uptake inhibitors increase parkinsonism or have clinically significant interactions with antiparkinsonian drugs is unresolved. PURPOSE: We used a naturalistic approach to prospectively investigate the long-term effects on motor status of adding sertraline in a large sample of community-dwelling PD patients with depressive symptoms. METHODS: Main outcome measure was the motor part of the Unified PD Rating Scale (UPDRS) at baseline and at 1-, 3-, and 6-month follow-up. Secondary measures were the change in antiparkinsonian drugs expressed as total levodopa equivalent dose and the scores of the Hospital Anxiety and Depression Scale (HADS). Of the 374 patients included, 310 (82%) completed the study. RESULTS: Treatment with sertraline (mean dose 66.0 +/- 29.8 mg) resulted in improvement in all UPDRS domains along with a significant decrease of the HADS scores. A modest but significant increase of the total dose of levodopa, without significant change of total levodopa equivalent dose, was observed. Almost 8% of patients discontinued medication for adverse events, mainly related to the gastrointestinal system. CONCLUSIONS: Although worsening of tremor was observed in some patients, active management of depression with sertraline appears to have a positive impact on parkinsonism.

[Movement disorders units and management of motor fluctuations in advanced Parkinson's disease]. / Unidades de trastornos del movimiento y tratamiento de las fluctuaciones motoras de la enfermedad de Parkinson avanzada.

INTRODUCTION: Advanced Parkinson's disease (PD) entails complications, such as motor fluctuations. In Spain, medical attention for such cases is often provided in movement disorder units (MDU). AIM: To gain further knowledge of the diagnostic resources and therapeutic approach of MDU. SUBJECTS AND METHODS: A descriptive cross-sectional study was conducted. The researchers designed an on-line questionnaire, addressed to neurologists from MDUs, containing 48 questions about the resources they have available, the number of patients with PD and motor fluctuations that have been attended to, as well as the therapeutic approach, according to the Hoehn and Yahr (HY) scale. RESULTS: Fifty-five neurologists participated. Structural neuroimaging is available to 100% of them; 89% have access to functional neuroimaging; 89% have acute pharmacological tests available for use; 78% have access to genetic tests; and 53% have transcranial ultrasound at their disposal. There are 2.5 neurologists and 1.2 nurses per unit. Of the patients with PD that they see, 19% of them are in HY stage 1, 59% are in HY stage 2-3 and 22% are in HY stage 4-5. Treatment consists, first of all, in monoamine oxidase type B inhibitors in HY stages 1 and 2, and levodopa in HY stages 3, 4 and 5. Twenty-four per cent of the patients have motor fluctuations, with 5.5 off episodes per day, lasting 44 minutes, with a total of seven off hours per day. Fourteen per cent of the patients under 70 years of age with more than three long-term off episodes per day are receiving invasive treatment for motor fluctuations. CONCLUSIONS: MDUs are well equipped with diagnostic and pharmacological resources. Pharmacological treatments are tailored to each patient with a wide range of combinations. Despite this optimisation, the prevalence of motor fluctuations is still high in advanced patients, and invasive therapies may be underused.

TITLE: Unidades de trastornos del movimiento y tratamiento de las fluctuaciones motoras de la enfermedad de Parkinson avanzada.Introduccion. La enfermedad de Parkinson (EP) avanzada conlleva complicaciones, como fluctuaciones motoras. Su atencion sanitaria en España se realiza frecuentemente en unidades de trastornos del movimiento (UTM). Objetivo. Conocer los recursos diagnosticos y el abordaje terapeutico de las UTM. Sujetos y metodos. Estudio descriptivo, transversal. Se diseño un cuestionario en linea, dirigido a neurologos de UTM, de 48 preguntas sobre recursos disponibles, numero de pacientes atendidos con EP y con fluctuaciones motoras, y abordaje terapeutico segun el estadio de Hoehn y Yahr (HY). Resultados. Participaron 55 neurologos. Disponen de neuroimagen estructural el 100%; neuroimagen funcional, el 89%; tests agudos farmacologicos, el 89%; tests geneticos, el 78%, y ecografia transcraneal, el 53%. Hay 2,5 neurologos y 1,2 enfermeras por unidad. Atienden a un 19% de pacientes con EP en estadio de HY 1, un 59% en estadio de HY 2-3 y un 22% en estadio de HY 4-5. Utilizan en primer lugar los inhibidores de la monoaminooxidasa B en los estadios de HY 1 y 2, y levodopa en los estadios de HY 3, 4 y 5. Un 24% de los pacientes tiene fluctuaciones motoras, con 5,5 episodios off diarios, de 44 minutos, con un total de siete horas off diarias. Un 14% de los pacientes de hasta 70 años con mas de tres episodios off diarios de larga duracion recibe tratamiento invasivo para las fluctuaciones motoras. Conclusiones. Las UTM estan bien dotadas de recursos diagnosticos y farmacologicos. Los tratamientos farmacologicos se individualizan con gran variedad de combinaciones. A pesar de esta optimizacion, la prevalencia de fluctuaciones motoras es todavia alta en pacientes avanzados, y las terapias invasivas pueden infrautilizarse.

Bilateral deep brain stimulation in Parkinson's disease: a multicentre study with 4 years follow-up.

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.

[The essence of essential tremor: neurochemical bases]. / La esencia del temblor esencial: bases neuroquimicas.

INTRODUCTION: Essential tremor is the most frequent movement disorder in adults. It has been considered a benign disease, but can result in significant physical and psychosocial disability. Pharmacological treatment is still not very satisfactory. Its causation, pathophysiology and anatomy remain only partially understood. AIMS: An understanding of its neurochemical basis is essential to be able to develop more efficient therapies. We review what is currently known in this field in order to motivate further research and ideas that allow an enhanced understanding of the disease and which foster the development of new pharmacological therapies. DEVELOPMENT: We review the studies conducted to date in humans and in animal models of neurotransmitters (gamma-aminobutyric acid, glutamate, noradrenalin, serotonin, adenosine), proteins and other neurochemical phenomena, such as T-type calcium channels, in essential tremor. CONCLUSIONS: Four neurochemical dysfunctions have been described that basically occur in the cerebellum and the inferior olivary nucleus: alteration of the GABAergic system, increased post-inhibitory rebound via T-type calcium currents, decreased neuronal inhibition mechanisms and an increase in excitatory neurotransmitter activity. These neurochemical dysfunctions would involve an increase in the activity of the deep neurons of the cerebellum with an oscillatory activity that would shift to the thalamic nucleus and the motor cortex, which in turn would lead to the appearance of tremor. Further research is needed to be able to confirm these hypotheses and to continue to advance towards achieving more efficient pharmacological treatments for patients with essential tremor.

TITLE: La esencia del temblor esencial: bases neuroquimicas.Introduccion. El temblor esencial es el trastorno del movimiento mas frecuente en el adulto. Se ha considerado una enfermedad benigna, pero puede ocasionar una importante discapacidad fisica y psicosocial. El tratamiento farmacologico sigue siendo poco satisfactorio. Su etiologia, fisiopatologia y anatomia siguen sin conocerse del todo. Objetivo. El conocimiento de las bases neuroquimicas es fundamental para el desarrollo de terapias mas eficaces. Se revisan los conocimientos actuales en este campo a fin de incentivar nuevas investigaciones e ideas que permitan mejorar la comprension de la enfermedad y que fomenten el desarrollo de nuevas terapias farmacologicas. Desarrollo. Se revisan los trabajos realizados hasta la fecha en humanos y en modelos animales de neurotransmisores (acido gamma-aminobutirico, glutamato, noradrenalina, serotonina, adenosina), proteinas y otros fenomenos neuroquimicos, como los canales de calcio de tipo T en el temblor esencial. Conclusiones. Se han descrito cuatro disfunciones neuroquimicas que acontecerian basicamente en el cerebelo y el nucleo olivar inferior: alteracion del sistema gabergico, aumento del rebote postinhibitorio mediante corrientes de calcio de tipo T, disminucion de los mecanismos de inhibicion neuronal y aumento de la actividad de los neurotransmisores excitatorios. Estas disfunciones neuroquimicas comportarian un aumento de la actividad de las neuronas profundas cerebelosas con actividad oscilatoria, que se trasladaria al nucleo del talamo y a la corteza motora, y comportarian la aparicion del temblor. Son necesarios nuevos estudios para poder confirmar estas hipotesis y seguir avanzando para conseguir tratamientos farmacologicos mas eficaces para los pacientes con temblor esencial.

A randomized placebo-controlled comparative trial of gabapentin and propranolol in essential tremor.

BACKGROUND: New medication is needed to treat essential tremor. Preliminary evidence suggests that gabapentin may be effective in the treatment of this disorder. OBJECTIVE: To study the effects of gabapentin in a comparative, double-blind, crossover, placebo-controlled trial of patients who have essential tremor. PATIENTS AND METHODS: 16 patients with essential tremor (6 with a new onset and 10 with a 2-week washout period of previous treatment with propranolol hydrochloride) received gabapentin (Neurontin), 400 mg 3 times daily; propranolol hydrochloride, 40 mg 3 times daily; and placebo for 15 days with a 1-week washout period between treatments. MAJOR OUTCOME MEASURES: Major outcome evaluations consisted of a Tremor Clinical Rating Scale, accelerometric recordings, and a self-reported disability scale obtained before drug intake on study days 1 and 15 of each treatment period. In addition, the initial (day 1) and superimposed (day 15) drug effects were studied before and 2, 4, 6, and 8 hours after drug intake. RESULTS: At day 15, both gabapentin and propranolol demonstrated significant and comparable efficacy in reducing tremor from baseline in all tremor measures. The initial drug effects evaluated through accelerometry revealed no significant changes with the use of a placebo, but gabapentin and propranolol use significantly reduced tremor power. CONCLUSION: Gabapentin may be useful for the treatment of essential tremor.

Unrecognized Tourette syndrome in adult patients referred for psychogenic tremor.

BACKGROUND: The diagnosis of Tourette syndrome may be overlooked in patients with severe psychopathologic disorder but mild motor manifestations of Tourette syndrome. OBJECTIVE: To describe 4 patients with long-lasting general psychopathologic disorder and previously unrecognized mild motor and phonic tics exacerbated during adulthood by the onset of tremor; all of the patients had been referred for the evaluation of psychogenic tremor. SUBJECTS: Four adult patients, with previous psychiatric diagnoses of depression (2 cases), generalized anxiety disorder (3 cases), malingering (1 case), and conversion disorder (3 cases). METHODS: Single case studies. RESULTS: Clinical interviews disclosed that the 4 patients had positive family histories of Tourette syndrome, and all had mild motor and phonic tics that had started before the age of 18 years. On neurologic examination, 2 patients had bilateral postural tremor of the hands that varied in frequency, rhythmicity, and amplitude, and the other 2 had resting tremor mimicking parkinsonism. All 4 patients described involuntary somatic sensations of the affected limbs, which they attempted to alleviate by executing movements. No consistent positive placebo response was observed, but in all patients tremoric movements improved with haloperidol. CONCLUSIONS: These cases illustrate an unusual movement disorder (tremor as a "tic equivalent") in adults with Tourette syndrome and emphasize that cases of the syndrome with mild tics often go unrecognized, precluding adequate treatment.

Obsessive-compulsive disorder associated with brain lesions: clinical phenomenology, cognitive function, and anatomic correlates.

We studied the behavioral, cognitive, and neuroimaging characteristics of obsessive-compulsive disorder (OCD) in 13 patients with focal brain lesions (acquired OCD) and compared their clinical features and the severity of obsessive and compulsive (OC) symptoms with patients with idiopathic OCD. Both OCD groups were further compared with matched normal controls on a series of neuropsychological tests. Patients with acquired OCD had a negative familial history and later age at onset of OCD symptoms than patients with idiopathic OCD. The two OCD groups showed relatively similar clinical phenomenology, severity of OC symptoms, and profile of neuropsychological deficits. Compared with normal control subjects, both OCD groups showed cognitive deficits affecting attention, intellectual function, memory, word retrieval, and motor and executive functions. Eight of the 13 patients with acquired OCD had abnormal neurologic examinations, whereas only 3 of the 13 patients with idiopathic OCD had abnormal neurologic examinations. Neuroimaging in the acquired OCD group disclosed a variety of lesions involving exclusively the cerebral cortex (frontal, temporal, or cingulate regions), the basal ganglia, or both. These results suggest that acquired and idiopathic OCDs may share a common pathophysiologic mechanism, and that structural damage to specific frontal-limbic-subcortical circuits plays an important role in the pathogenesis of acquired OCD.

Mania following deep brain stimulation for Parkinson's disease.

Three patients with PD developed manic behavior after bilateral implantation of electrodes for deep-brain stimulation (DBS). Common to all three patients were manic symptoms unremitting after levodopa reduction or stimulation "off," lower electrodes positioning caudal to the subthalamic nucleus area, postoperative DBS with the lower contacts (0) of the quadripolar electrodes, and resolution of the manic episodes coinciding with stimulation through higher contacts.

Effects of repetitive transcranial magnetic stimulation on memory subtypes: a controlled study.

Repetitive transcranial magnetic stimulation (rTMS) of human cortex may disrupt or facilitate cortical activity. The aim of the present study was to investigate the consequences of rTMS applied over different cortical areas during various memory tasks, measuring immediate, working and episodic verbal memory. The study was performed in 16 right-handed healthy men. A double-blind, cross-over, within-subject repeated measures design was used. There were five rTMS conditions: baseline without stimulation, high frequency (HF) rTMS over right and left dorsolateral prefrontal cortex (DLPFC) and over right cerebellum, and low frequency (LF) parameters over left DLPFC. Digits forwards and backwards and letter-number sequencing of the Wechsler Adults Intelligence Scale (WAIS) were used to assess immediate and working verbal memory, and logical memory of the Rivermead Behavioural Memory Test was used to assess episodic memory encoding. An analysis of variance (ANOVA) for repeated measures in the scores of each memory task according to rTMS conditions was used. Significantly lower scores in the number of memory units of the episodic memory task were observed when rTMS high frequency parameters were applied over left DLPFC (P=0.009). No significant differences were found in the other memory subtype tasks analysed during the different rTMS conditions. These findings provide evidence for the significant role of the left DLPFC in episodic verbal memory processes.

Effects of alprazolam on the acoustic startle response in humans.

In the present study, we assessed the effects of the potent benzodiazepine alprazolam on the human acoustic startle response in healthy volunteers. Eight undergraduate students received single oral doses of placebo and alprazolam 2 mg on 2 separate days, according to a double-blind balanced crossover design. Electromyographic activity of the orbicularis oculi muscle was recorded 5, 7 and 11 h after drug administration. At each recording time, subjects received 21 acoustic stimuli (1 KHz, 116 dB, 50 ms duration) separated by variable intervals (8-30 s, mean 16.5 s). Consistent with previous results obtained for diazepam in humans, alprazolam significantly reduced the amplitude of the startle reflex. A patent increase in onset latency was also observed, this being a novel effect not previously described for benzodiazepines in human studies. Both effects were maximum at 5 h after dosing, the startle response experiencing a recovery as the drug disappeared from systemic circulation. These results indicate a potent inhibitory effect of alprazolam on baseline startle at the dose used, with a robust time-dependent recovery of initial values effectively counteracting between-session habituation.

Abnormalities of the acoustic startle reflex and reaction time in gilles de la tourette syndrome.

OBJECTIVE: To study the startle reflex and the effect of the startle reflex stimulus over reaction time (start-react effect) in Gilles de la Tourette syndrome (GTS). METHOD: Ten GTS patients and ten matched healthy volunteers underwent a simple RT paradigm (4 blocks of 50 trials). Forty acoustic startle reflex stimuli (110 dB) were randomly delivered with a 20% occurrence probability and presented unexpectedly at the same time as the imperative stimuli of the RT. Variables of interest were: amplitude, onset latency, degree of spread and rate of habituation of the startle response, and RT and the start-react effect caused by the startle stimuli. RESULTS: GTS patients showed a significantly higher amplitude, a major degree of spread and fewer habituation phenomena of the startle reflex. GTS patients showed poorer non statistically significant RT performance compared to controls, with a significant correlation between RT and severity of the disease. The start-react effect was significantly less pronounced in GTS patients. CONCLUSIONS: The present study confirms that GTS has an exaggerated startle reflex response and extend the spectrum of abnormalities to the start-react effect. A state of dopaminergic hyperactivity may have contributed to these results.

Motor circuitry re-organization after pallidotomy in Parkinson disease: a neurophysiological study of the bereitschaftspotential, contingent negative variation, and N30.

The aim of the study was to evaluate the reorganization changes in the motor circuitry of the basal ganglia following unilateral posteroventral pallidotomy in Parkinson disease (PD) patients using neurophysiological paradigms. Eight advanced PD patients received a neurophysiological battery 2 months prior and 6 months after unilateral pallidotomy. Examinations were all performed in the practically defined "off" situation. Bereitschaftspotential (BP) and N30 were recorded for each hand alternately. Contingent negative variation (CNV) was obtained using a visual Go/no-Go paradigm. ANOVAs (electrode position; surgery) were applied for BP and CNV results. N30 data were analyzed using Wilcoxon matched-pair tests. A significant increase in amplitude of the late component (NS') of the BP was evidenced with patient performing with the hand contralateral to pallidotomy. No significant amplitude differences were found in CNV after surgery in any lead, or in any of the time windows tested. A trend toward significance was observed corresponding to a postsurgical numerical increase in amplitude of the N30 peak in the hand contralateral to pallidotomy. These results suggest that neurophysiological changes after pallidotomy are mainly in the last stages of movement preparation and execution.

A six-month study of pergolide and levodopa in de novo Parkinson's disease patients.

Formal studies examining the antiparkinsonian efficacy of levodopa and pergolide monotherapy in de novo Parkinson's disease (PD) are lacking. The authors conducted a preliminary, 6-month, open-label parallel experimental study with de novo consecutive PD patients who were randomly assigned to three daily doses of pergolide (n = 10; mean age, 63.7 years; mean Hohen & Yahr score, 1.5; mean final dose, 2.8 mg daily) or levodopa (n = 10; mean age, 67.3 years; mean Hohen & Yahr score, 1.8; mean final dose, 435 mg daily). Doses were titrated individually according to patients' evaluation of their own functional ability, known side-effects, and a monthly administration of the Unified Parkinson's Disease Rating Scale (UPDRS) by a clinician blind to the treatment regime. All patients completed the study. There were no significant basal differences between groups and no significant treatment ortreatment-by-time effects in UPDRS scores (according to two-way ANOVA). A clear time effect was observed for most of the functional and motor variables (p < 0.001), with significant improvement during the first month that was maintained for the duration of the study in both groups. Side effects were mild, transient, and comparable. In this preliminary study, pergolide and levodopa exhibited similar symptomatic efficacy and incidence of side effects in the short-term treatment of de novo PD patients at their usual age of clinical manifestation.

SPECT mapping of cerebral activity changes induced by repetitive transcranial magnetic stimulation in depressed patients. A pilot study.

Repetitive transcranial magnetic stimulation (rTMS) is being investigated as an alternative treatment for depression. However, little is known about the clinical role and the neurophysiological mechanisms of the action of rTMS in these patients. In this study, 99mTc-HMPAO single photon emission computed tomography (SPECT) was used to map the effects of left dorsolateral prefrontal rTMS on prefrontal activity in seven patients who met DSM-IV criteria for major depression resistant to pharmacological treatment. rTMS consisted of 30 trains of 2-s duration stimuli (20 Hz, 90% of motor threshold), separated by 30-s pauses. Each patient underwent three SPECTs: at baseline; during the first rTMS; and 1 week after 10 daily sessions of rTMS. Regional cerebral blood flow (rCBF) of each cerebral region was normalized to the rCBF value in the cerebellum and relative changes in normalized rCBF were addressed using a region-of-interest analysis. The Hamilton Depression Rating Scale (HDRS) was used for clinical evaluation before and after rTMS. A significant rCBF increase after the 10 sessions of rTMS was found in the left prefrontal region (MANOVA F=5.29, d.f.=2,10, P=0.027), but no significant rCBF changes were found during the first rTMS session. The remaining cerebral regions showed no significant rCBF changes at any time. Only two patients showed a clinical improvement after rTMS, with 50% reduction of the initial HDRS score. The study was repeated under placebo conditions (identical design but addressing coil discharges to the air) in these two patients, who failed to show any rCBF increase during sham-rTMS. No relationship was found between the percentage of left prefrontal rCBF change and the clinical findings. In conclusion, rTMS of the left prefrontal cortex induces a significant rCBF increase in this region, despite the limited clinical effect in our sample of depressed patients. Cerebral perfusion SPECT is a useful tool to map cerebral activity changes induced by rTMS.

Transcranial magnetic stimulation for treating depression.

BACKGROUND: Transcranial magnetic stimulation can either excite or inhibit cortical areas of the brain, depending on whether the speed of the repetitive stimulation is applied at high or low frequencies. It has been used for physiological studies and it has also been proposed as a treatment for depression. OBJECTIVES: To assess the clinical efficacy and safety of transcranial magnetic stimulation for treating depression. SEARCH STRATEGY: An electronic search was performed including the Cochrane Collaboration Depression, Neurosis and Anxiety Review Group trials register (last searched June, 2001), the Cochrane Controlled Trials Register (Issue 2, 2001), MEDLINE (1966-2001), EMBASE (1974-2001), PsycLIT (1980-2001), and bibliographies from reviewed articles. Unpublished data and grey literature were searched through personal communications with researchers. SELECTION CRITERIA: Randomised controlled trials assessing the therapeutic efficacy and safety of transcranial magnetic stimulation for depression. DATA COLLECTION AND ANALYSIS: All reviewers independently extracted the information and verified it by cross-checking. Disagreements were resolved through discussion. Continuous data: When similar studies were grouped, the overall standardised mean difference was calculated under a fixed effect model weighted by the inverse variance method with 95% confidence intervals. (In the presence of statistical heterogeneity, a random effects model was to be used.) MAIN RESULTS: Sixteen trials were included in the review and fourteen contained data in a suitable form for quantitative analysis. Most comparisons did not show differences between rTMS and other interventions. No difference was seen between rTMS and sham TMS using the Beck Depression Inventory or the Hamilton Depression Rating Scale, except for one time period (after two weeks of treatment) for left dorsolateral prefrontal cortex and high frequency; and also for right dorsolateral prefrontal cortex and low frequency, both in favour of rTMS and both using the Hamilton scale. Comparison of rTMS (left dorsolateral prefrontal cortex and high frequency) with electroconvulsive therapy showed no difference except for psychotic patients after two weeks treatment, using the Hamilton scale, which indicated that electroconvulsive therapy was more effective than rTMS. REVIEWER'S CONCLUSIONS: The information in this review suggests that there is no strong evidence for benefit from using transcranial magnetic stimulation to treat depression, although the small sample sizes do not exclude the possibility of benefit.

[Postural tremor: clinical and neurophysiological study in a consecutive series of 300 patients]. / Temblor postural: estudio clínico y neurofisiológico en una serie consecutiva de 300 pacientes.

BACKGROUND: There are few studies analysing the clinical and neurophysiological characteristics of postural tremor in Spain. PATIENTS AND METHOD: We studied prospectively 300 consecutive patients referred to a Movement Disorders Section because of postural tremor of the upper limbs. Syndromic diagnosis of postural tremor was made according to clinical criteria with the aid of neurophysiological criteria (accelerometric and EMG data). In patients diagnosed with essential tremor (ET), diagnostic sensitivity studies, correlation studies of clinical and neurophysiological data and multivariate analysis were performed. RESULTS: Most frequent syndromic diagnoses were ET (77%), parkinsonian postural tremor (10%) and exaggerated physiological tremor (6%). Fifty percent of ET patients reported having affected relatives, and 7% reported that their tremor improved with alcohol. Mostly specific variables for the diagnosis of ET were: affected relatives (77%), cephalic tremor (80%), alcohol improvement (100%), and synchronous EMG pattern (79%). The presence of affected relatives and a synchronous EMG pattern were significant predictive variables on a multivariate analysis. We found a significant correlation between age at time of consulting and frequency (rs = 0.561; p < 0.0005) and amplitude (rs = 0.470; p < 0.0005) of tremor. CONCLUSIONS: In the present study, ET was the most common cause of reference for postural tremor. Selective clinical data and neurophysiological evaluation are useful for the diagnosis of postural tremor.

[A retrospective study of potential benefits of thrombolytic drugs in a stroke]. / Beneficio potencial de los fármacos trombolíticos en patología vascular cerebral. Estudio retrospectivo.

We carried out a retrospective analysis into the possible uses of thrombotic drugs on 190 consecutive patients with ischaemic stroke who had been admitted to the Neurological Service of the Barcelona 'Hospital de la Santa Creu i Sant Pau' in accordance with exclusion criteria commonly accepted for the use of this type of medication. We thus analyzed the initial symptoms, type of instauration, etiological diagnosis and topographical diagnosis. In those patients who could be possible candidates for such treatment with these drugs we assessed their disability variations (on the Rankin scale) at the end of two weeks using currently available therapeutic means. 70% of patients would subsequently be excluded from our study. Among reasons for exclusion were especially minor neurological deficiencies, age and latency time. As for patients included, most predominant factors were immediate instauration, cardioembolic etiological mechanism and severe onset symptomatology (motor disorder, awareness and language abnormalities). We observed a substantial spontaneous improvement in 7% of patients. This fact is especially clear in cardioemboligenic etiology patients. Bearing the spontaneous improvement cases in mind, we concluded that some 23% of patients with ischaemic cerebrovascular pathology could benefit from thrombotic drugs in our milieu.