Marcelo Merello

THE NATURE OF APRAXIA IN CORTICOBASAL DEGENERATION

Although apraxia is one of the most frequent signs in corticobasal degeneration, the phenomenology of this disorder has not been formally examined. Hence 10 patients with corticobasal degeneration were studied with a standardised evaluation for different types of apraxia. To minimise the confounding effects of the primary motor disorder, apraxia was assessed in the least affected limb. Whereas none of the patients showed buccofacial apraxia, seven showed deficits on tests of ideomotor apraxia and movement imitation, four on tests of sequential arm movements (all of whom had ideomotor apraxia), and three on tests of ideational apraxia (all of whom had ideomotor apraxia). Ideomotor apraxia significantly correlated with deficit in both the mini mental state examination and in a task sensitive to frontal lobe dysfunction (picture arrangement). Two of the three patients with ideomotor apraxia and ideational apraxia showed severe cognitive impairments. The alien limb behaviour was present only in patients with ideomotor apraxia. In conclusion, ideomotor apraxia is the most frequent type of apraxia in corticobasal degeneration, and may be due to dysfunction of the supplementary motor area. There is a subgroup of patients with corticobasal degeneration who have a severe apraxia (ideomotor and ideational apraxia), which correlates with global cognitive impairment, and may result from additional parietal or diffuse cortical damage.

Apomorphine responses in parkinson's disease and the pathogenesis of motor complications

Article abstract-We studied the contribution of basal ganglia circuitry downstream from the nigrostriatal dopaminergic system to the pathogenesis of levodopa associated motor complications by means of an apomorphine dose-response paradigm in 28 parkinsonian patients grouped according to their clinical response to levodopa therapy. With progression from the dopa-naive to the severely fluctuating dyskinetic state, apomorphine response duration shortened, the dose-response slope steepened, and the therapeutic window narrowed. Because apomorphine acts independently of the integrity of presynaptic dopaminergic neurons, our results suggest that postsynaptic alterations account mainly for the appearance of response complications. The present findings support the possibility, raised by animal model studies, that motor response complications arise as a consequence of altered signal transduction mechanisms in striatal medium-sized neurons. NEUROLOGY 1997;48: 369-372

The syndromal validity and nosological position of apathy in Parkinson's disease†

Although apathy is among the most frequent behavioral changes in Parkinsons disease (PD), its diagnosis is still problematic, and the overlap with depression and dementia poorly studied. Aim of the study was validate specific criteria to diagnose apathy in PD, and to examine its association with subsyndromes of depression and dementia. A series of 164 patients with PD, 44 patients with “primary” depression and no PD, 23 patients with Alzheimers disease, and 26 age‐comparable healthy controls underwent a comprehensive psychiatric assessment that included a structured psychiatric interview and the Apathy Scale. A set of seven diagnostic criteria showed high sensitivity and specificity for clinically diagnosed apathy. Fifty‐two of the 164 patients with PD (32%) met diagnostic criteria for apathy. Eighty‐three percent of patients with apathy had comorbid depression and 56% had dementia. Only 5 of the 40 PD patients (13%) with neither depression nor dementia had apathy. We validated a set of standardized criteria for the diagnosis of apathy in PD. About one third of a series of patients attending a Movement Disorders Clinic showed apathy. Both depression and dementia were the most frequent comorbid conditions of apathy in PD.

Apomorphine induces changes in GPi spontaneous outflow in patients with Parkinson's disease

To determine the effect of a single dose of apomorphine on internal globus pallidus (GPi) neuronal discharge in patients with Parkinsons disease (PD).

Unilateral radiofrequency lesion versus electrostimulation of posteroventral pallidum: A prospective randomized comparison

Microelectrode‐guided posteroventral pallidotomy (PVP) has shown to be an effective method in the treatment of a group of patients with advanced Parkinsons disease. A nonlesioning approach by means of deep brain electrodes connected to a programmable neuropacemaker has also been used to inhibit the internal segment of globus pallidus (posteroventral stimulation [PVS]) reporting comparable clinical efficacy to the one obtained with the ablative method. Nevertheless, no controlled studies have been performed to compare the efficacy of both procedures. A prospective series of 13 patients with a clinical indication for globus pallidus surgery was randomized either to a pallidotomy or stimulator implantation, and comparisons on motor and neuropsychologic measurements were made on a 3‐month follow‐up basis. Primary measurements of efficacy showed a comparable effect on Unified Parkinsons Disease Rating Scale and activities of daily living score after both procedures. Secondary measurements of efficacy showed that although both techniques improve hand tapping score and dyskinesia score, the bilateral improvement in the former was greater after PVS whereas the latter improved more significantly after PVP. No significant changes in neuropsychologic parameters were observed after either PVP or PVS. Side effects and surgery complications occurred in six of 13 patients (three after PVP and three after PVS): they were mild, transient, and unrelated to optic tract injury. In conclusion, the short‐time effect and safety of both procedures is comparable.

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.

A validation study of depressive syndromes in Parkinson's disease

The validity, sensitivity, and specificity of depressive symptoms for the diagnosis of major depression, minor depression, dysthymic disorder, and subsyndromal depression in Parkinsons disease (PD) were examined. A consecutive series of 173 patients with PD attending a Movement Disorders Clinic underwent a comprehensive psychiatric and neurological assessment. The symptoms of loss of interest/pleasure, changes in appetite or weight, changes in sleep, low energy, worthlessness or inappropriate guilt, psychomotor retardation/agitation, concentration deficits, and suicide ideation were all significantly associated with the presence of the DSM‐IV depressed mood criterion for major depression. The symptoms of changes in appetite, changes in sleep, low energy, low self‐esteem, poor concentration, and hopelessness were all significantly associated with the presence of the DSM‐IV criterion of sad mood for dysthymic disorder. Thirty percent of our sample met DSM‐IV diagnostic criteria for major depression, 20% met diagnostic criteria for dysthymic disorder, 10% met diagnostic criteria for minor depression, and 8% met clinical criteria for subsyndromal depression. Patients with either major or minor depression had significantly more severe deficits in activities of daily living, more severe cognitive impairments, and more severe Parkinsonism than patients with either dysthymic disorder or no depression. This study provides validation to the DSM‐IV diagnostic criteria for major depression and dysthymic disorder for use in PD. The categories of minor and subsyndromal depression may need further validation.

Catatonia in depression: prevalence, clinical correlates, and validation of a scale.

OBJECTIVES--To examine the clinical correlates of catatonia in depression, to validate a scale for catatonia, and to assess the validity of the DSM-IV criteria of the catatonic features specifier for mood disorders. METHODS--A series of 79 consecutive patients with depression and 41 patients with Parkinsons disease without depression were examined using the modified Rogers scale (MRS), the unified Parkinsons disease rating scale (UPDRS), and the structured clinical interview for DSM-III-R (SCID). RESULTS--Sixteen of the 79 depressed patients (20%) had catatonia. Depressed patients with catatonia had significantly higher scores on the MRS than non-catatonic depressed patients matched for severity of depression, or non-depressed patients with Parkinsons disease matched for severity of motor impairment. Depressed patients with catatonia were older, had a significantly higher frequency of major depression, more severe cognitive impairments, and more severe deficits in activities of daily living than depressed non-catatonic patients. The DSM-IV criteria of catatonia separated depressed catatonic patients from patients with Parkinsons disease matched for motor impairment, with a specificity of 100%. Catatonic signs did not improve after apomorphine. CONCLUSIONS--catatonia is most prevalent among elderly patients with severe depression. The study showed the validity of the MRS for the diagnosis of catatonia in depressed patients, as well as the specificity of the DSM-IV criteria of the catatonic features specifier.

Motor response to acute dopaminergic challenge with apomorphine and levodopa in Parkinson's disease: implications for the pathogenesis of the on-off phenomenon.

OBJECTIVES--To evaluate the contribution of postsynaptic changes to motor fluctuations, three groups of parkinsonian patients with differing responses to treatment were acutely challenged with two dopaminergic drugs-apomorphine and levodopa-having different mechanisms of action. METHODS--Forty two patients with Parkinsons disease (14 untreated, eight with a stable response to levodopa, and 20 with levodopa induced motor fluctuations) were challenged on two consecutive days with apomorphine and levodopa. The latency, duration, and magnitude of motor response was measured. RESULTS--A progressive shortening of mean latency after levodopa challenge was found passing from the untreated to the stable and fluctuating groups; the difference between untreated and fluctuating patients was statistically significant (P < 0.01). Response duration after levodopa challenge was similar in untreated and stable patients, whereas it showed a significant shortening in patients with motor fluctuations (P < 0.05 v both untreated and stable patients). When subcutaneous apomorphine was given, untreated patients had a longer response duration than those who had developed motor fluctuations (P < 0.05). Although baseline disability was significantly greater in the fluctuating patients than in the untreated and stable patients, the severity of residual parkinsonian signs after both apomorphine and levodopa challenge was similar for all three groups; as a result, the degree of improvement in parkinsonian signs after dopaminergic stimulation was substantially greater in more advanced than in early cases. Linear regression analysis also indicated that latency and duration after apomorphine challenge did not significantly correlate with those after levodopa challenge, whereas magnitude of response to apomorphine showed a strong positive correlation with that after levodopa challenge (r = 0.9, P < 0.001). CONCLUSION--The progressive shortening of motor response after both apomorphine and levodopa suggests that pharmacodynamic factors play an important part in determining the duration of motor response and argue against altered central pharmacokinetics of levodopa being principally responsible for the on-off effect. The widening response amplitude and increasing off phase disability occurring during disease progression are also critical factors in determining the appearance of motor fluctuations.

Neuropsychological and psychiatric differences between Alzheimer's disease and Parkinson's disease with dementia.

OBJECTIVE: To examine neuropsychological and neuropsychiatric differences between patients with probable Alzheimers disease and patients with Parkinsons disease and dementia. METHODS: Thirty three patients with probable Alzheimers disease and 33 patients with Parkinsons disease and dementia were matched for age, sex, and mini mental state examination scores and given a battery of neuropsychological and neuropsychiatric tests. RESULTS: Patients with Parkinsons disease with dementia had a significantly higher prevalence of major depression than patients with Alzheimers disease; patients with Alzheimers disease showed more severe anosognosia and disinhibition than patients with Parkinsons disease. Whereas no significant between group differences were found on tests of memory and language, demented patients with Parkinsons disease had a significantly greater impairment on a test of visual reasoning than patients with Alzheimers disease. CONCLUSION: There were significant psychiatric differences between patients with Alzheimers disease and demented patients with Parkinsons disease, but neuropsychological differences were restricted to a single cognitive domain.