Life events and the onset of motor symptoms in Parkinson's disease.

BACKGROUND: Whether there may be any relationship between stressful or traumatic life events (LE) and the subsequent motor symptoms onset in Parkinson's disease (PD) is still controversial. OBJECTIVES: To explore whether a subjectively perceived as stressful or traumatic LE were more frequently present in a group of recent motor onset parkinsonian patients (Recent Onset Parkinsonism - ROP) compared with healthy controls (HC) and a group of patients already diagnosed as PD. METHODS: A consecutive series of 139 ROP patients, 138 matched PD patients and 138 HC were pooled through a validated LE exposure questionnaire evaluating the number of patients affected by LE and the amount of LE per group occurred in the last year, segregating by subjective severity in total and severe LE. RESULTS: There was no significant difference in the percentage of patients affected by total (p = 0.134) nor by severe (p = 0.133) LE within the 3 groups. No significant difference was observed in the number of total LE between ROP and HC (p = 0.063), ROP and PD (p = 0.688), nor in severe LE (ROP vs. HC, p = 0.637. ROP vs. PD, p = 0.500). CONCLUSIONS: During the year of parkinsonian motor symptoms onset, the number of ROP patients exposed to total or severe LE or the amount of total or severe LE suffered by ROP were not significantly different to the group of PD patients or HC. A casual relationship between LE and the onset of motor symptoms in parkinsonian patients may be suggested.

Validation of an events exposure questionnaire for individuals living in major cities of Argentina.

Most of the validated 'events exposure' questionnaires are focused on lifetime burden and are hardly applicable to Argentina owing to its sociocultural and natural conditions, where corruption and economic crises have been hitting middle-class people's lives in a cyclic manner. This prompted us to develop a new questionnaire, validated in Argentina, to assess the occurrence of exposure to events and their severity over a limited period. Deductive (bibliographic search) and inductive (by a Delphi group) selection was used to create an initial group of 24 questions, which were condensed into a final 14-item questionnaire. After administration to 512 inhabitants of the metropolitan area of Buenos Aires and other major cities in Argentina, the questionnaire was shown to have an intraclass correlation coefficient of 0.996 and an internal consistency, measured by the omega coefficient, of 0.86. Because this study was conducted during the coronavirus disease 2019 (COVID-19) pandemic, an additional question on how this situation affected individuals was included. The time span used to measure event exposure was 1 year prior to the study. In the case of an affirmative event exposure, the responder selected the severity of the stress perception generated on a Likert-like scale, ranging from 0 (nothing) to 5 (severe). Fifty-eight per cent of the responders were women, and the mean age was 47.14 years (SD: 13.97). The average annual event incidence per person was 2.5 events (SD: 1.88). Thirty-two per cent (164/512) reported at least one 5-point event on the severity scale. Ten per cent (51/512) responded that the COVID-19 pandemic affected them in a different manner than events related to personal or family disease, or the death of a close family member or friend.

La mayoría de los cuestionarios validados de 'exposición a eventos' se centran en la carga durante la vida y son difícilmente aplicables a la Argentina debido a las diferentes condiciones socioculturales y naturales, donde la corrupción y la crisis económica han estado golpeando la vida de las personas de clase media de una manera cíclica. Esto nos impulsó a desarrollar un nuevo cuestionario, validado en Argentina para evaluar la ocurrencia de exposición a eventos y su severidad en un período de tiempo determinado. Se utilizó selección deductiva (búsqueda bibliográfica) e inductiva (por un grupo Delphi) para crear un grupo inicial de 24 preguntas, que se condensaron en un cuestionario final de 14 ítemes con un coeficiente de correlación intraclase de 0.996 y una consistencia interna medida por el coeficiente Omega de 0.86, luego de la administración a 512 habitantes del área metropolitana de Buenos Aires y otras ciudades importantes de Argentina. Teniendo en cuenta que este estudio se realizó durante la situación de pandemia de COVID-19, se incluyó una pregunta adicional sobre cómo esta situación afectó a las personas. El intervalo de tiempo utilizado para medir la exposición a eventos fue el último año. En caso de una exposición de evento afirmativa, el respondedor tenía que seleccionar la severidad de la percepción del estrés generado en una escala tipo Likert, que va de 0 (nada) a 5 (grave). Cincuenta y ocho por ciento de los que respondieron eran mujeres, y la edad promedio fue de 47,14 años (DE = 13,97). La incidencia anual promedio de 'eventos' por persona fue de 2.5 eventos (DE = 1.88). Treinta y dos por ciento (164/512) informaron al menos un evento de 5 puntos en la escala de severidad. Diez por ciento (51/512) respondió que la pandemia de COVID-19 los afectó de manera diferente que la relacionada con la enfermedad personal o familiar o la muerte de un familiar cercano o amigo.

Influence of white matter MRI hyper-intensities on acute l-dopa response in patients with Parkinson's disease.

OBJECTIVE: To determine whether brain white matter hyperintensities (WMH) influence l-dopa response in Parkinson's disease (PD) patients. METHODS: We prospectively evaluated 60 PD patients with an acute l-dopa challenge test, and assessed motor performance with the Movement Disorders Society revised Unified Parkinson's Disease Rating Scale (MDS-UPDRS) during "ON" and "OFF" medication states. Magnetic resonance images were examined using a visual semi-quantitative rating scale for quantification and distribution analysis of WMH. l-dopa challenge test response was correlated to extent and location of WMH, to determine a potential association between them. RESULTS: Subjects with greater deep WMH burden, showed less response to l-dopa on axial motor symptoms (R = -0.35; p < 0.027), when tested with Part III of the MDS-UPDRS before and after acute levodopa challenge. CONCLUSIONS: Results suggest WMH may affect response to l-dopa on axial function of PD patients, which could be due to either non-dopaminergic (cortico-basal ganglia) motor pathway disruption, or postsynaptic nigrostriatal pathway involvement.

Autosomal dominant cerebellar ataxias: a systematic review of clinical features.

BACKGROUND AND PURPOSE: To assess, through systematic review, distinctive or common clinical signs of autosomal dominant cerebellar ataxias (ADCAs), also referred to as spinocerebellar ataxias (SCAs) in genetic nomenclature. METHODS: This was a structured search of electronic databases up to September 2012 conducted by two independent reviewers. Publications containing proportions or descriptions of ADCA clinical features written in several languages were selected. Gray literature was included and a back-search was conducted of retrieved publication reference lists. Initial selection was based on title and abstract screening, followed by full-text reading of potentially relevant publications. Clinical findings and demographic data from genetically confirmed patients were extracted. Data were analyzed using the chi-squared test and controlled for alpha-error inflation by applying the Holms step-down procedure. RESULTS: In all, 1062 publications reviewing 12 141 patients (52% male) from 30 SCAs were analyzed. Mean age at onset was 35 ± 11 years. Onset symptoms in 3945 patients revealed gait ataxia as the most frequent sign (68%), whereas overall non-ataxia symptom frequency was 50%. Some ADCAs often presented non-ataxia symptoms at onset, such as SCA7 (visual impairment), SCA14 (myoclonus) and SCA17 (parkinsonism). Therefore a categorization into two groups was established: pure ataxia and mainly non-ataxia forms. During overall disease course, dysarthria (90%) and saccadic eye movement alterations (69%) were the most prevalent non-ataxia findings. Some ADCAs were clinically restricted to cerebellar dysfunction, whilst others presented additional features. CONCLUSIONS: Autosomal dominant cerebellar ataxias encompass a broad spectrum of clinical features with high prevalence of non-ataxia symptoms. Certain features distinguish different genetic subtypes. A new algorithm for ADCA classification at disease onset is proposed.

Multiple-time-scale framework for understanding the progression of Parkinson's disease.

Parkinson's disease is marked by neurodegenerative processes that affect the pattern of discharge of basal ganglia neurons. The main features observed in the parkinsonian globus pallidus pars interna (GPi), a subdomain of the basal ganglia that is involved in the regulation of voluntary movement, are pathologically increased and synchronized neuronal activity. How these changes affect the implemented neuronal code is not well understood. Our experimental temporal structure-function analysis shows that in parkinsonian animals the rate-coding window of GPi neurons needed for the proper performance of voluntary actions is reduced. The model of the GPi network that we develop and discuss here reveals indeed that the size of the rate-coding window shrinks as the network activity increases and is expanded if the coupling strength among the neurons is increased. This leads to the novel interpretation that the pathological neuronal synchronization in Parkinson's disease in the GPi is the result of a collective attempt to counterbalance the shrinking of the rate-coding window due to increased activity in GPi neurons.

Oro-buccal symptoms (dysphagia, dysarthria, and sialorrhea) in patients with Parkinson's disease: preliminary analysis from the French COPARK cohort.

INTRODUCTION: Abnormal oro-buccal functions including dysarthria, sialorrhea and dysphagia commonly affect patients with Parkinson's disease (PD). OBJECTIVES: To estimate the prevalence of such oro-buccal symptoms at baseline in the first 419 patients with PD included in the COPARK cohort and to analyze their correlations with patients' demographics, clinical characteristics, and drugs consumption. METHODS: Patients were assessed using the Unified PD Rating Scale, the Hospital Anxiety and Depression Scale, and the PDQ-39. Dysarthria, sialorrhea, and dysphagia were defined as UPDRS items 5, 6, or 7 ≥ 1. RESULTS: Dysarthria, sialorrhea, or dysphagia were present in 51%, 37%, or 18% out of the 419 patients, respectively. At least one of these symptom was present in 267/419 patients (65%), whilst a combination of symptoms was present in 136/419 (33%). Logistic regression showed that the presence of each of the three oro-buccal symptoms was significantly correlated with that of the two others. Other correlations included male gender, hallucinations, disease severity, levodopa use and lack of opiates consumption for dysarthria; disease severity, orthostatic hypotension and absence of antidepressants consumption for sialorrhea; female gender, motor fluctuations, and depressive symptoms for dysphagia. None of the three oro-buccal symptoms were associated with a reduced PDQ-39 score. CONCLUSION: Oro-buccal symptoms were present in two of three patients with moderate PD, the presence of each symptoms being significantly correlated with that of the two others.

Decision-making in Parkinson's disease patients with and without pathological gambling.

BACKGROUND AND PURPOSE: Pathological gambling (PG) in Parkinson's disease (PD) is a frequent impulse control disorder associated mainly with dopamine replacement therapy. As impairments in decision-making were described independently in PG and PD, the objective of this study was to assess decision-making processes in PD patients with and without PG. METHODS: Seven PD patients with PG and 13 age, sex, education and disease severity matched PD patients without gambling behavior were enrolled in the study. All patients were assessed with a comprehensive neuropsychiatric and cognitive evaluation, including tasks used to assess decision-making abilities under ambiguous or risky situations, like the Iowa Gambling Task (IGT), the Game of Dice Task and the Investment Task. RESULTS: Compared to PD patients without gambling behavior, those with PG obtained poorer scores in the IGT and in a rating scale of social behavior, but not in other decision-making and cognitive tasks. CONCLUSIONS: Low performance in decision-making under ambiguity and abnormal social behavior distinguished PD patients with PG from those without this disorder. Dopamine replacement therapy may induce dysfunction of the ventromedial prefrontal cortex and amygdala-ventral striatum system, thus increasing the risk for developing PG.

Addenbrooke's Cognitive Examination validation in Parkinson's disease.

BACKGROUND: There is a clear need for brief, sensitive and specific cognitive screening instruments in Parkinson's disease (PD). OBJECTIVES: To study Addenbrooke's Cognitive Examination (ACE) validity for cognitive assessment of PD patient's using the Mattis Dementia Rating Scale (MDRS) as reference method. A specific scale for cognitive evaluation in PD, in this instance the Scales for Outcomes of Parkinson's disease-Cognition (SCOPA-COG), as well as a general use scale the Mini-mental state examination (MMSE) were also studied for further correlation. METHODS: Forty-four PD patients were studied, of these 27 were males (61%), with a mean (SD) age of 69.5 (11.8) years, mean (SD) disease duration of 7.6 (6.4) years (range 1-25), mean (SD) total Unified Parkinson's Disease Rating Scale (UPDRS) score 37 (24) points, UPDRS III 16.5 (11.3) points. MDRS, ACE and SCOPA-COG scales were administered in random order. All patients remained in on-state during the study. RESULTS: Addenbrooke's Cognitive Examination correlated with SCOPA-COG (r = 0.93, P < 0.0001), and MDRS (r = 0.91 P < 0.0001) and also with MMSE (r = 0.84, P < 0.001). Area under the receiver-operating curve, taking MDRS as the reference test, was 0.97 [95% confidence interval (CI): 0.92-1.00] for ACE, 0.92 (95% CI: 0.83-1.00) for SCOPA-COG and 0.91 (95% CI: 0.83-1.00) for MMSE. Best cut-off value for ACE was 83 points [Sensitivity (Se) = 92%; Specificity (Sp) = 91%; Kappa concordance (K) = 0.79], 20 points for the SCOPA-COG (Se = 92%; Sp = 87%; K = 0.74) and 26 points for MMSE (Se = 61%; Sp = 100%; K = 0.69). CONCLUSION: Addenbrooke's Cognitive Examination appears to be a valid tool for dementia evaluation in PD, with a cut-off point which should probably be set at 83 points, displaying good correlation with both the scale specifically designed for cognitive deficits in PD namely SCOPA-COG, as well as with less specific tests such as MMSE.

[Non-motor disorders in Parkinson's disease]. / Trastornos no motores en la enfermedad de Parkinson.

INTRODUCTION: Parkinson's disease (PD) is a progressive disorder that is strongly linked to non-motor symptoms (NMS). Unfortunately, these symptoms have been almost neglected for many years and only recently have researchers begun to assess how they affect the quality of life in patients with PD. AIMS: To review our current understanding of the subject and to highlight the importance of NMS in PD. DEVELOPMENT: Recent studies have emphasised the fact that the basal ganglia play an important role in a number of non-motor functions. At the same time, the exclusive involvement of the substantia nigra in PD is being reviewed and the development of PD has been defined as a continuum that covers a range of different stages, including non-dopaminergic systems and nuclei. This would account for the constellation of non-motor symptoms that do not respond to dopamine replacement therapy and which affect patients with PD, such as depression, apathy, sialorrhea and urinary incontinence, among others. CONCLUSIONS: NMS make a significant contribution to the morbidity and mortality rates of PD and are often the main cause of hospitalisation of patients with PD. Current evidence suggests that some NMS, such as constipation, hyposmia and REM sleep disorders, could even be preclinical markers of PD. Both of these reasons stress the importance of reaching a diagnosis faster and earlier.

Trastornos no motores en la enfermedad de Parkinson / Non-motor disorders in Parkinson’s disease

La enfermedad de Parkinson (EP) es un trastorno progresivo que se encuentra fuertemente asociadoa síntomas no motores (SNM). Lamentablemente, éstos han recibido muy poca atención durante muchos años, y sólo recientemente se ha comenzado a valorar su implicación sobre la calidad de vida de los pacientes con EP. Objetivos. Revisar el conocimiento actual y resaltar la importancia de los SNM en la EP. Desarrollo. Estudios recientes han enfatizado el hecho deque los ganglios basales desempeñan un papel importante en diversas funciones no motoras. Simultáneamente, la exclusiva afectación de la sustancia negra en la EP se ha puesto en revisión, y se ha definido el desarrollo de la EP como un continuo a través de diferentes estadios, incluyendo núcleos y sistemas no dopaminérgicos. Esto explicaría la constelación de síntomas de características no motoras que no responden a la terapia de reemplazo dopaminérgica y que afectan a los pacientes con EP, como depresión, apatía, sialorrea e incontinencia urinaria, entre otros. Conclusiones. Los SNM contribuyen significativamentea la morbimortalidad de la EP, y son, en muchos casos, la principal causa de hospitalización de los pacientes con EP. La evidencia actual sugiere que algunos SNM, como estreñimiento, hiposmia y trastornos del sueño REM, podrían incluso ser marcadores preclínicos de la EP. Ambos motivos refuerzan la imperiosa necesidad de incrementar su diagnostico rápido y temprano

Introduction. Parkinson’s disease (PD) is a progressive disorder that is strongly linked to non-motor symptoms(NMS). Unfortunately, these symptoms have been almost neglected for many years and only recently have researchers begun to assess how they affect the quality of life in patients with PD. Aims. To review our current understanding of the subject and to highlight the importance of NMS in PD. Development. Recent studies have emphasised the fact that the basal ganglia play an important role in a number of non-motor functions. At the same time, the exclusive involvement of the substantia nigra inPD is being reviewed and the development of PD has been defined as a continuum that covers a range of different stages, including non-dopaminergic systems and nuclei. This would account for the constellation of non-motor symptoms that do not respond to dopamine replacement therapy and which affect patients with PD, such as depression, apathy, sialorrhea and urinary incontinence, among others. Conclusions. NMS make a significant contribution to the morbidity and mortality rates of PD and are often the main cause of hospitalisation of patients with PD. Current evidence suggests that some NMS, such asconstipation, hyposmia and REM sleep disorders, could even be preclinical markers of PD. Both of these reasons stress the importance of reaching a diagnosis faster and earlier

Prospective randomized 1-year follow-up comparison of bilateral subthalamotomy versus bilateral subthalamic stimulation and the combination of both in Parkinson's disease patients: a pilot study.

It has been suggested that potential risk of hemiballismus after subthalamotomy makes DBS preferable to ablation for IPD treatment; however, cost and the need for regular electrode control have also been observed as disadvantages to stimulation. The objective was to compare efficacy and safety of different surgical approaches to STN, in a prospective randomized pilot study. Sixteen consecutive IPD patients randomized to receive either: bilateral STN-DBS, bilateral subthalamotomy or unilateral subthalamotomy plus contralateral STN-DBS implantation, and followed for 12 months after surgery. One patient died and was excluded from the analysis. Total and motor UPDRS scores, as well as drug-induced dyskinesias improved significantly at 1 year follow-up, regardless of the procedure administered and without statistically significant differences between treatment modalities. Discrete changes were observed on ACE and MMSE scores. Psychiatric examination of patients subjected to bilateral stimulation and lesion, revealed slight increment in apathy and irritability scores, coinciding with significant deterioration of mentation, behaviour and mood as measured using the UPDRS. One patient presented persistent hemiballismus and required ulterior posteroventral pallidotomy. In this small group of patients, overall motor performance significantly improved after all three procedures, without major differences in outcome. Adverse events were, nevertheless, observed after both ablation and stimulation. The role of bilateral subthalamotomy in patients unable to receive a DBS electrode-implant merits further exploration in a larger series of patients with longer follow-up.

Kinematic evaluation of gestural and repetitive single joint movements of the arm after posteroventral pallidotomy, subthalamotomy or both procedures combined in two Parkinson's disease patients: two case studies.

Two patients with severe Parkinson's disease undergoing partial or complete ablative interruption of basal ganglia (BG) output are presented. One patient who underwent bilateral subthalamotomy, and a second who underwent unilateral posteroventral pallidotomy, followed 7 years later by a bilateral subthalamotomy because of contralateral disease progression, were studied. In addition to the usual clinical evaluation, changes in joint kinematics observed during unconstrained, skilled multi-joint movement and repetitive single joint (RSJ) movement of the wrist were studied. Clinical UPDRS items referred to hand movements contralateral to the procedure, and instrumental measurement of RSJ improved in both patients after either pallidotomy or subthalamotomy. When both BG outflow paths were interrupted as was the case in the second patient (bilateral subthalamotomy after the initial pallidotomy), no added clinical improvement was observed, RSJ even deteriorated slightly. Instrument-based studies for movement alteration detection after simultaneous ablation of the globus pallidus and the subthalamic nucleus of these two patients showed greater sensitivity than clinical evaluation alone. Complex gestural movement performance remained unaffected after partial (subthalamotomy or pallidotomy) or complete interruption of BG outflow (case 2), indicating BG compensatory capacity after total outflow interruption remained intact.

Ictal non-forced grasping behaviour.

Our aim was to investigate whether patients with epileptiform foci in the frontal lobe, as revealed by video EEG (VEEG) analysis, exhibit non-forced grasping behaviour and manipulatory movements during seizures. We retrospectively reviewed ictal videotapes of 30 consecutive patients with frontal and 30 with temporal lobe epilepsy undergoing VEEG for the presence and type of grasping and manipulatory movements. Four of the 30 patients with frontal lobe epilepsy (13%) showed unilateral grasping behaviour, three of whom had whole hand prehension (one with manipulation movements as well) and one pinching movements. In all patients, arm abduction and elevation resembling reaching invariably preceded grasping hand movements. The epileptogenic focus was located in the contralateral and ipsilateral frontocentral region in two and one patient, respectively, and in the ipsilateral orbitofrontal region in another. However, none of the patients with temporal lobe epilepsy showed grasping behaviour. Patients with frontal lobe epilepsy may show non-forced grasping with or without manipulatory finger movements as part of ictal phenomena.

Dyskinesias induced by subthalamotomy in Parkinson's disease are unresponsive to amantadine.

BACKGROUND: Dyskinesias are a transient but severe complication of subthalamotomy in some patients. PATIENTS AND METHODS: Three patients with Parkinson's disease undergoing bilateral micro-recording guided surgery of the subthalamic nucleus (STN) are described; deep brain stimulation (DBS) was used in one case, and subthalamotomy in the other two. Prior to surgery, levodopa induced dyskinesia had improved (< or = 50%) under treatment with amantadine (400 mg/day, po) in all three patients. The patient treated with DBS developed severe dyskinesia a few days after discharge and began self medication with amantadine but showed no improvement. This suggested a possible lack of response to amantadine for treatment of dyskinesias induced by surgery of the STN. RESULTS: Both patients treated with bilateral subthalamotomy developed unilateral choreoballistic movements immediately after surgery, despite not taking levodopa (L-dopa). Patients were scored using the dyskinesia scale and started treatment with 400 mg amantadine (po) for 4 days within the first postoperative week with no effect on dyskinesia score or its phenomenology. Amantadine was therefore discontinued. One month after surgery both patients were free of involuntary movements with an improvement of about 60% in the "off" state UPDRS motor score. Six month follow up showed maintained antiparkinsonian benefit, without need for levodopa treatment and complete absence of dyskinesia. CONCLUSION: The present findings suggest that: (i) amantadine probably exerts its anti-dyskinetic effect by acting on the "indirect" pathway; (ii) the pathophysiological mechanisms of subthalamotomy induced dyskinesias may differ from those involved in L-dopa induced dyskinesias; (iii) dyskinesias induced by STN surgery resolve spontaneously as compensatory mechanisms develop.

Functional surgery for Parkinson's disease treatment: a structured analysis of a decade of published literature.

The aim of this study was to analyse and compare published data during the last decade on the different approaches to Parkinson's disease surgery. Eighty-eight papers published between 1990 and 2001 fulfilled the inclusion criteria. Full-text and prospective papers on lesion and stimulation of GPi or STN were assessed. Descriptive analysis of surgery procedure and population under study was performed, as well as a meta-analysis of the most consistently reported variables. A total of 1702 patients underwent surgery with a mean age of 58.75 years (range 46.5 - 72.5), mean duration of illness 13.6 years (8.1 - 18.1) and a male:female ratio 1.5:1. Mean postoperative follow-up was 9 months (1 - 52). Single blind assessment was performed in two papers, while double blind evaluation was used in 6. In the GPi group, no difference was found between the pre- and postoperative levodopa equivalent daily dose (960.39 v. 943.13; p > 0.05), while the STN group showed a marked reduction (1104.8 v. 483.04; p < 0.05) of this dosage. Meta-analysis of the most consistently reported variables (UPDRS total score, UPDRS motor score, UPDRS ADL score and Schwab & England score showed that Nucleus, Bilaterality of Approach and Surgical Procedure were the best moderators for defining outcome. Bilateral DBS STN procedures proved to be associated with better outcome. Microelectrode recording was not found to be a moderator that influenced outcome. Although there was a significant improvement of dyskinesias among the different approaches described in the papers, the heterogeneity of data makes it impossible to perform a structured analysis on this item.

Bilateral pallidotomy for treatment of Parkinson's disease induced corticobulbar syndrome and psychic akinesia avoidable by globus pallidus lesion combined with contralateral stimulation.

OBJECTIVE: Posteroventral pallidotomy (PVP) has proved to be an effective method for the treatment of Parkinson's disease. However, data on bilateral procedures are still limited. To assess the effects of bilateral globus pallidus (GPi) lesion and to compare it with a combination of unilateral GPi lesion plus contralateral GPi stimulation (PVP+PVS), an open blind randomised trial was designed. METHODS: A prospective series of patients with severe Parkinson's disease refractory to medical treatment, and severe drug induced dyskinesias, were randomised either to simultaneous bilateral PVP or simultaneous PVP+PVS. All patients were assessed with the core assessment programme for intracerebral transplantation (CAPIT), and a comprehensive neuropsychological and neuropsychiatric battery both before surgery and 3 months later. RESULTS: The severe adverse effects found in the first three patients subjected to bilateral PVP led to discontinuation of the protocol. All three patients developed depression and apathy. Speech, salivation, and swallowing, as well as freezing, walking, and falling, dramatically worsened. By contrast, all three patients undergoing PVP+PVS had a significant motor improvement. CONCLUSION: Bilateral simultaneous lesions within the GPi may produce severe motor and psychiatric complications. On the other hand, a combination of PVP+ PVS significantly improves parkinsonian symptoms not associated with the side effects elicited by bilateral lesions.

Prevalence and correlates of parkinsonism in patients with primary depression.

The authors examined the prevalence, clinical correlates, and longitudinal changes of parkinsonism in 94 patients with primary depression and 20 healthy control subjects. Parkinsonism was present in 20% of patients with primary depression. This syndrome was significantly associated with older age, more severe depression, and more severe cognitive impairment. In a subgroup of depressed patients, parkinsonism was reversible upon recovery from the mood disorder.

Mismatch between electrophysiologically defined and ventriculography based theoretical targets for posteroventral pallidotomy in Parkinson's disease.

OBJECTIVES: Over the past few years many reports have shown that posteroventral pallidotomy is an effective method for treating advanced cases of Parkinson's disease. The main differences with earlier descriptions were the use of standardised evaluation with new high resolution MRI studies and of single cell microrecording which can electrophysiologically define the sensorimotor portion of the internal globus pallidus (GPi). The present study was performed on a consecutive series of 40 patients with Parkinson's disease who underwent posteroventral pallidotomy to determine localisation discrepancies between the ventriculography based theoretical and the electrophysiologically defined target for posteroventral pallidotomy. METHODS: The tentative location of the posteroventral GPi portion was defined according to the proportional Talairach system. Single cell recording was performed in all patients. The definitive target was chosen according to the feasibility of recording single cells with GPi cell features, including the presence of motor drive and correct identification of the internal capsule and of the optic tract by activity recording and microstimulation. RESULTS: In all 40 patients the electrophysiologically defined sensorimotor portion of the GPi was lesioned, with significantly improved cardinal Parkinson's disease symptoms as well as levodopa induced dyskinesias, without damage to the internal capsule or optic tract. Significant differences between the localisation of the ventriculography based theoretical versus electrophysiological target were found in depth (p<0.0008) and posteriority (p<0.04). No significant differences were found in laterality between both approaches. Difference ranges were 8 mm for laterality, 6.5 mm for depth, and 10 mm for posteriority. CONCLUSIONS: Electrophysiologically defined lesion of GPi for posteroventral pallidotomy, shown to be effective for treating Parkinson's disease, is located at a significantly different site from the ventriculography based theoretical target.