Slow oscillatory activity and levodopa-induced dyskinesias in Parkinson's disease.

The pathophysiology of levodopa-induced dyskinesias (LID) in Parkinson's disease is not well understood. We have recorded local field potentials (LFP) from macroelectrodes implanted in the subthalamic nucleus (STN) of 14 patients with Parkinson's disease following surgical treatment with deep brain stimulation. Patients were studied in the 'Off' medication state and in the 'On' motor state after administration of levodopa-carbidopa (po) or apomorphine (sc) that elicited dyskinesias in 11 patients. The logarithm of the power spectrum of the LFP in selected frequency bands (4-10, 11-30 and 60-80 Hz) was compared between the 'Off' and 'On' medication states. A peak in the 11-30 Hz band was recorded in the 'Off' medication state and reduced by 45.2% (P < 0.001) in the 'On' state. The 'On' was also associated with an increment of 77. 6% (P < 0.001) in the 4-10 Hz band in all patients who showed dyskinesias and of 17.8% (P < 0.001) in the 60-80 Hz band in the majority of patients. When dyskinesias were only present in one limb (n = 2), the 4-10 Hz peak was only recorded in the contralateral STN. These findings suggest that the 4-10 Hz oscillation is associated with the expression of LID in Parkinson's disease.

Movement-related changes in oscillatory activity in the human subthalamic nucleus: ipsilateral vs. contralateral movements.

A voluntary movement is accompanied by a series of changes in neuronal oscillatory activity in the subthalamic nucleus (STN). These changes can be recorded through electrodes implanted for deep brain stimulation to treat Parkinson's disease in the time interval between the surgery and the internalization of the connections to the batteries. Both baseline activity and movement-related changes are different in the 'on' and 'off' medication motor states. In the 'off' state a low frequency activity in the alpha-beta range (8-25 Hz) that dominates the spectrum is interrupted during the movement, while in the 'on' state baseline frequencies are higher and a peri-movement gamma increase (70-80 Hz) is usually observed. Similar changes have been described with electrocorticographic recordings over the primary motor cortex but the gamma increase was only present during contralateral movements. We compared ipsi- and contralateral movement-related changes in STN activity, using a time-frequency analysis of the recordings obtained simultaneously in both STN and the scalp (electroencephalography) during right and left hand movements. The movement-related changes observed in the STN in the 'on' and the 'off' states were similar to those described previously in terms of predominant frequency bands, but we found bilateral changes in the STN during movements of either hand. A contralateral earlier start of the beta STN changes was mostly observed when the moving hand corresponded to the less-affected side, irrespective of hand dominance. These results suggest that movement-related activity in the STN has, by and large, a bilateral representation and probably reflects cortical input.

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.

Quality of life of caregivers in Parkinson's disease.

OBJECTIVE: To assess the impact of PD on informal caregivers of patients and identify the main factors related to caregiver strain. PATIENTS AND METHODS: Pairs of PD patients and their caregivers. Evaluation by neurologists included the Hoehn and Yahr, Schwab and England, UPDRS (parts 1-3), ISAPD, and Pfeiffer's SPMSQ rating scales. Patients completed the Euro-QoL 5D, PDQ-8, and Hospital Anxiety and Depression Scale. The SQLC was used to assess caregivers' quality of life (QoL), with caregivers, in turn, applying the Euro-QoL and PDQ-8 to assess patients' health-related quality of life (HRQoL). Multiple linear regression models were fitted to ascertain factors linked to the SQLC. RESULTS: Significant correlations were in evidence between the following scores: SQLC and clinical rating scales and SQLC and patients' HRQoL. Based on multiple regression analysis, patients' functional state (ADL) proved to be the main predictor of caregivers' QoL. Self- and caregiver-assessed patients' HRQoL also proved to be a relevant factor. CONCLUSIONS: (1) Patients' functional state was significantly related to caregivers' psychosocial burden; (2) patients' HRQoL proved to be an additional factor linked to caregiver QoL; (3) improvement of patient disability and HRQoL might alleviate caregiver strain.

Efficacy of deep brain stimulation of the subthalamic nucleus in Parkinson's disease 4 years after surgery: double blind and open label evaluation.

OBJECTIVE: To evaluate the long term (4 years) efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in advanced Parkinson's disease. METHODS: We performed a double blind crossover evaluation of the efficacy of DBS of the STN in the "off" medication condition in 10 patients with Parkinson's disease. Assessments included the Unified Parkinson's Disease Rating Scale (UPDRS) part III (motor) and two timed tests (arm tapping and walking). Open evaluation of the effect of stimulation in the off and on drug states preoperatively and at 1 and 4 years postoperatively was also conducted. The latter assessment included the UPDRS parts II (activities of daily living) and III (dyskinesia scale and global assessment) as judged by the patient and examiner. The mean amount of levodopa daily dose at base line, 1 year, and 4 years after surgery was compared. RESULTS: A significant (p<0.04) effect of stimulation was observed in the overall group regarding both the UPDRS motor and the timed tests. Open evaluation also showed a significant benefit of STN DBS with respect to preoperative assessment in both the motor and activities of daily living scales, dyskinesia scale, and in global assessment. Levodopa daily dose was reduced by 48% and 50% at 1 and 4 years, respectively. There was no difference between the 1 and 4 years evaluations in any of the parameters evaluated. Complications due to stimulation were minor. CONCLUSIONS: DBS of the STN provides a significant and persistent anti-parkinsonian effect in advanced Parkinson's disease 4 years after surgery.

The origin of motor fluctuations in Parkinson's disease: importance of dopaminergic innervation and basal ganglia circuits.

The severity of dopamine depletion and the consequent pathophysiologic changes that occur in basal ganglia circuits determine the severity of parkinsonian signs. Restoring the dopamine deficit or the downstream physiologic abnormalities improves Parkinson's Disease (PD) main motor features and as a result, attenuates the short-duration response (SDR). Therefore, both the magnitude and duration of the motor response are a function of the degree of motor severity, which is primarily governed by the loss of tonic dopaminergic activity and disruption of basal ganglia homeostatic mechanisms among which the STN-GPe/GPi circuits play a fundamental role. As neurodegeneration advances, standard levodopa administration give rises to wider oscillations in striatal dopamine availability and "pulsatile" stimulation of striatal dopamine receptors becomes predominant. This induces molecular and physiologic changes that further accentuate and aggravate the SDR that sustains motor fluctuations. Treatments capable of providing and restoring more tonic and physiologic dopaminergic stimulation may avoid many of these abnormalities and lead to better clinical outcomes.

[A study of the incidence and a descriptive analysis of adult non-tuberculous primary bacterial meningitis in a population in Argentina]. / Estudio de incidencia y análisis descriptivo de la meningitis bacteriana primaria no tuberculosa del adulto en una población argentina.

INTRODUCTION: Adult non tuberculous primary bacterial meningitis (PBM) represents an important cause of morbidity and mortality in hospitals. The shortage of studies based on the population in Latin America provided the motivation for this work. AIMS: To determine the incidence of PBM in the captive population of our hospital and carry out a descriptive analysis of the cases detected. PATIENTS AND METHODS: We performed an epidemiological study of the captive population (CP) of the hospital (an average of 85,200 patients in 11 years) and a retrospective descriptive examination of patients who had been admitted. The clinical histories of all patients over the age of 18 who had been admitted with PBM between 1 January 1988 and 31 December 1998 were studied. RESULTS AND CONCLUSIONS: A total number of 87 cases of primary bacterial meningitis were registered, of which 70 belonged to the CP. The overall gross rate of PBM incidence in the CP was 8.6/100,000 per year. The annual incidence rate, adjusted to the 1991 National Census on the Argentinean Population, was 5.4/100,000 per year, with a greater frequency between the ages of 70 and 79: 21/100,000 per year. Median age: 73 (lower quartile, 66; upper quartile, 78). Clinical manifestations included high temperatures (90%), consciousness disorders (87%), and a stiff neck (81%). The frequency with which it appeared remained constant over the 11 year period, without showing any seasonal variations. The most frequent etiological agent was pneumococcus (50%). No cases of PBM by Listeria were reported. Overall fatality during the stay in hospital was 23%, without any type of modification over the period we studied.

Estudio de incidencia y análisis descriptivode la meningitis bacteriana primaria no tuberculosadel adulto en una población argentina / A study of the incidence and a descriptive analysis of adult non-tuberculous primary bacterial meningitis in a population in argentina

Introducción. La meningitis bacteriana primaria no tuberculosa del adulto (MBP) representa una causa importante de morbimortalidad hospitalaria. La escasez de trabajos basados en la población en Latinoamérica motivó el presente estudio. Objetivos. Establecer la incidencia de MBP en la población `cautiva' de nuestro hospital y hacer un análisis descriptivo de los casos detectados. Paciente y métodos. Se realizó un estudio epidemiológico basado en la población cautiva (PC) del hospital (promedio de 85.200 pacientes en 11 años) y una investigación descriptiva, retrospectiva de pacientes internados. Se estudiaron todas las historias clínicas de pacientes mayores de 18 años internados entre el 1 de enero de 1988 y el 31 de diciembre de 1998 con MBP. Resultados y conclusiones. Se registraron 87 meningitis bacterianas primarias, 70 pertenecían a la PC. La tasa bruta global de incidencia de MBP en la PC fue de 8,6/100.000/año. La tasa de incidencia anual ajustada al Censo Nacional de Población Argentina de 1991 fue de 5,4/100.000/año, con mayor frecuencia entre los 70 y 79 años (21/100.000/año). Edad mediana: 73 (cuartil inferior, 66; cuartil superior, 78). Las manifestaciones clínicas incluyeron fiebre (90 por ciento), trastorno de conciencia (87 por ciento) y rigidez de nuca (81 por ciento). La frecuencia de aparición se mantuvo constante durante los 11 años, sin variaciones estacionales. El agente etiológico más frecuente fue el neumococo (50 por ciento). No se registraron MBP por Listeria. La letalidad global durante la hospitalización fue de un 23 por ciento, sin modificarse en el tiempo de estudio (AU)

[Fisher's one and half syndrome with facial palsy as clinical presentation of giant cell temporal arteritis]. / Síndrome del uno y medio de Fisher y parálisis facial periférica como forma de presentación de la arteritis de células gigantes.

An ischemic stroke in an old patient is commonly due to thrombosis or embolism. A restriction in the differential diagnosis and not considering another etiology could occasion the loss of effective therapy and prevent major complications. We report the case of a patient who suffering from systemic symptoms for a few months, was admitted to the hospital with the one and a half syndrome described by Fisher, together with right facial palsy, both products of an ischemic pontine lesion. Bilateral biopsies of the temporal arteries were diagnostic of temporal arteritis and MRN of the cranium confirmed multiple ischemic lesions involving the pons. In conclusion, the diverse clinical presentations of temporal arteritis oblige us to consider it among the etiological options in older patients with neurological signs affecting the vertebral-basilar system, accompanied by systemic signs and symptoms and a high VSG. To avoid anterior ischemic optic neuropathy and other complications a quick diagnosis and treatment are necessary.

Síndrome del uno y medio de Fisher y parálisis facial periférica como forma de presentación de la arteritis de células gigantes. / [Fishers one and half syndrome with facial palsy as clinical presentation of giant cell temporal arteritis]

An ischemic stroke in an old patient is commonly due to thrombosis or embolism. A restriction in the differential diagnosis and not considering another etiology could occasion the loss of effective therapy and prevent major complications. We report the case of a patient who suffering from systemic symptoms for a few months, was admitted to the hospital with the one and a half syndrome described by Fisher, together with right facial palsy, both products of an ischemic pontine lesion. Bilateral biopsies of the temporal arteries were diagnostic of temporal arteritis and MRN of the cranium confirmed multiple ischemic lesions involving the pons. In conclusion, the diverse clinical presentations of temporal arteritis oblige us to consider it among the etiological options in older patients with neurological signs affecting the vertebral-basilar system, accompanied by systemic signs and symptoms and a high VSG. To avoid anterior ischemic optic neuropathy and other complications a quick diagnosis and treatment are necessary.