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Gaucher’s disease with Parkinson’s disease Clinical and pathological aspects

The association between type 1 Gaucher disease and PD has been reported in the literature. The clinical picture is characterized by the predominance of bilateral akinetic-rigid signs and poor response to levodopa therapy. The authors describe four patients (two siblings) with type 1 Gaucher disease presenting with the following signs of typical PD: asymmetric onset of rigidity, resting tremor, bradykinesia, and a favorable response to Parkinson therapies.

Familial and environmental risk factors in Parkinson's disease: a case-control study in north-east Italy.

Background and objective– The aetiology of Parkinsons disease remains unknown, although both genetic susceptibility and environmental factors are considered putative contributors to its origin. We performed a case–control study to investigate the association of familial and environmental risk factors with Parkinsons disease (PD). Methods– We studied 136 patients with neurologist confirmed PD and 272 age‐ and sex‐matched controls, affected by neurological diseases not related to PD. The risk of developing idiopathic PD associated with the following familial and environmental factors: positive family history of PD, positive family history of essential tremor (ET), age of mother at subjects birth, rural birth, rural living, well water use, farming as an occupation, exposure to pesticides, head tremor, exposure to general anaesthesia and to ionizing radiations, food restriction, concentration camp imprisonment and smoking has been assessed by using univariate and multivariate statistical techniques. Results– In the conditional multiple logistic regression analysis, positive family history of PD (OR 41.7, 95% CI 12.2–142.5, P < 0.0001), positive family history of ET (OR 10.8, 95% CI 2.6–43.7, P < 0.0001), age of mother at subjects birth (OR 2.6, 95% CI 1.4–3.7, P=0.0013), exposure to general anaesthesia (OR 2.2, 95% CI 1.3–3.8, P=0.0024), farming as an occupation (OR 7.7, 95% CI 1.4–44.1, P=0.0212) and well water use (OR 2.0, 95% CI 1.1–3.6, P=0.0308) exhibited a significant positive association with PD, whereas smoking showed a trend toward an inverse relationship with PD (OR 0.7, 95% CI 0.4–1.1, P < 0.06). Conclusions– We conclude that both familial and environmental factors may contribute to PD aetiology.

Possible risk factors for primary adult onset dystonia: a case-control investigation by the Italian Movement Disorders Study Group

OBJECTIVES Little is known about the aetiology of idiopathic adult onset dystonia. The Italian Movement Disorders Study Group promoted a case-control study on some hypothetical risk factors including past medical events, life events, life habits, occupational hazards, and family hystory of dystonia, parkinsonism, and tremor. METHODS Cases affected by idiopathic adult onset dystonia (age at symptom onset >20 years, duration of disease >one year and <five years) were selected among consecutive outpatients attending 14 Italian centres. Control outpatients matched for age (±5 years), sex, and referral centre were identified among diagnostic categories thought to be unassociated with study exposures. Information was obtained by a standardised questionnaire administered by medical interviewers. Conditional logistic univariate and multivariate regression analyses were performed by a standard statistical package. RESULTS Multivariate analysis on 202 cases and 202 age and sex matched control outpatients indicated that head or facial trauma with loss of consciousness, family history of dystonia, and family history of postural tremor independently increased the risk of developing adult onset dystonia, whereas hypertension and cigarette smoking exerted a protective effect. The findings also suggested a positive association between local body injury—for example, previous ocular diseases and neck or trunk trauma—and dystonia of the same body part. CONCLUSIONS The results support the idea that environmental and genetic factors may both be important in the aetiology of adult onset dystonia, and suggest aetiological clues worthy of further analytical investigation.

The relationship between cerebral vascular disease and parkinsonism: The VADO study.

BACKGROUND The observation of gait abnormalities, parkinsonism and vascular lesions in elderly patients is often reported as vascular parkinsonism (VP). However the status of striatal dopamine transporter (DAT) and the effects of brain vascular lesions on motor features and levodopa responsiveness are poorly defined. METHODS We recorded clinical features, chronic response to levodopa and vascular risk factors in a cross-sectional cohort of consecutive elderly patients with possible Parkinsons disease (PD) or VP recruited in 20 centers in Italy. RESULTS We included a total of 158 patients. Onset of motor symptoms was asymmetric in 93 (59%) and symmetric in 65 patients (41%). Symmetric motor onset was associated with greater disease severity. Chronic levodopa response was positive in 75 (47.8%) and negative in 82 patients (52.2%). A negative response to levodopa was associated with greater frequency of symmetric onset of motor symptoms, worst disease severity, absence of dyskinesia and greater number of vascular risk factors. Frontal lobe showed largest vascular load. Striatal DAT was normal in 48 (30.4%) and abnormal in 110 (69.6%) patients. Patients with normal DAT binding showed higher vascular load at MRI. Significant predictive factors of worst disease severity and negative response to levodopa were hypertension, vascular lesions in basal ganglia/periventricular regions, and normal DAT uptake. CONCLUSIONS Multiple cerebral vascular lesions modify clinical presentation and severity in patients with parkinsonism and this is underlined by specific risk factors primarily hypertension. Striatal DAT assessment is helpful in identifying patients where therapy benefit is less likely.

The parkin gene and its phenotype

Abstract Mutations of the parkin gene on chromosome 6 cause autosomal recessive, early onset parkinsonism. This is the most frequent form of monogenic parkinsonism so far identified. The associated phenotypical spectrum encompasses early onset, levodopa-responsive parkinsonism (average onset in the early 30s in Europe), and it overlaps with dopa-responsive dystonia in cases with the earliest onset, and with clinically typical Parkinsons disease in cases with later onset. Despite clinical features, Lewy bodies are not found at autopsy in brains of patients with parkin mutations. The parkin protein possesses ubiquitin ligase activity, which is abolished by the pathogenic mutations.

Fixed dystonia unresponsive to pallidal stimulation improved by motor cortex stimulation

into the healthy hemispheric field, vision improved or normalized. Finally, the possibility of changes in the modality-specific attention, a special type of attention that is not necessarily spatially distributed, was raised. Changes in this subtype of attention on lateral gazing may therefore help in overcoming visual field deficit as a compensatory mechanism. 5 We would like to comment upon the tendency of our patient to bisect a horizontal line ipsilaterally to the side of hemianopia, that is, contralaterally to the side of occipital lesion. Patients with complete hemianopia can see only the line on the side of the normal hemifield and would thus be expected to bisect the line ipsilaterally to the brain lesion. However, this is true only in patients with hemianopia and hemispatial neglect, whereas patients with pure hemianopia, as in our case, show a tendency to bisect the line contralaterally to the side of the lesion, toward the hemianopic visual field. 6,7 This is explained by a change in atten-tional distribution when a patient with hemianopia tends to search for the end of the line in the direction of the blind hemis-pace as an adaptive mechanism. 7,8 However, this adaptation may occur on cost of accuracy in perception, as the erroneous bisection shows. The onset of ocular lateropulsion in the direction opposite to the direction of adaptation would therefore possibly temper this attentional redistribution and lead to a greater ease in accurately perceiving the visual world. Neck–proprioceptive and caloric–vestibular stimulation have been shown to improve visual neglect. 9 It seems possible that even though our patient had no neglect, the acute onset of vestibular imbalance due to infarction of the left vestibular nucleus could have contributed to the reset of his attentional distribution and to the pronounced left ocular lateropulsion as well. The skew deviation resolved earlier than the ocular lateropul-sion. This might be due to differences in the neural substrates underlying skew deviation and ocular lateropulsion. Whereas skew deviation in lateral medullary infarcts is related to damage to the otolith pathways at the level of the medial vestibular nucleus , ocular lateropulsion is the result of involvement of the olivo-cerebellar fibers in the inferior cerebellar peduncle, as described above. A different impact of the ischemia on these two, although anatomically proximate, neural structures might explain the different speed of recovery. Despite the fact that the mechanism responsible for improvement of vision is unknown, it seems that …

Chronic bilateral electrical stimulation of the subthalamic nucleus for the treatment of advanced Parkinson's disease.

Abstract Preliminary reports in patients with Parkinsons disease (PD) showed that subthalamic nucleus (STN) stimulation was able to reverse parkinsoniam state. Since 1998 we evaluated the safety and the efficacy of STN stimulation in 7 patients affected by advanced PD. All patients were included using CAPIT protocol. Motor functions and quality of life were evaluated, before and after surgery, with UPDRS and PDQ38, respectively. At the 6-month follow-up, the off medication/on stimulation UPDRS motor score improved by 50.6% and the on medication/on stimulation by 20.3%. Motor fluctuations were reduced by 57.2% and dyskinesias by 73.5%. The total D-dopa equivalent daily dose was reduced by 40.7%. PDQ38 ameliorated by 49.9%. We did not observe any perioperatory complication and only mild and tolerable side effects after stimulation.

‘Speech Initiation Hesitation’ following Subthalamic Nucleus Stimulation in a Patient with Parkinson’s Disease

‘Speech Initiation Hesitation’ following Subthalamic Nucleus Stimulation in a Patient with Parkinson’s Disease R. Moretti a–c, P. Torre b, c, R.M. Antonellob, c, L. Capusb, M. Gioulisb, S. Zambito Marsalab, G. Cazzatob, A. Bava a aDipartimento di Fisiologia e Patologia, bDipartimento di Medicina Clinica e Neurologia, UCO di Clinica Neurologica, and cDipartimento di Medicina Clinica e Neurologia, UCO di Clinica Neurologica, Sezione Disturbi Cognitivi, Università degli Studi di Trieste, Trieste, Italy

Cognitive changes following subthalamic nucleus stimulation in two patients with Parkinson disease

The limits of a drug therapy in severe forms of Parkinson disease have led to refining neurosurgery on the basal ganglia. Deep brain stimulation of the subthalamic nucleus has been recognized as one of the most promising techniques to decrease “off” motor symptoms and motor fluctuations, allowing a reduction of drug therapy and limiting side effects of the drugs. There is still open debate on the possible consequences of chronic subthalamic stimulation in other ways, apart from motor symptoms, of general cognitive performance. We examined and followed two patients with Parkinson disease for 9 mo. after surgery for deep stimulation, studying their cognitive performances. There is a general amelioration of cognitive performances, in particular as far as linguistic capabilities is concerned. We discuss the possible significance of these results, reminding strenuously that only two patients were involved, so the potential for generalization is seriously limited.

Peculiar aspects of reading and writing performances in patients with olivopontocerebellar atrophy.

Olivopontocerebellar atrophy (OPCA) is a still debated condition, of which motor disruption is the most common feature. A high incidence of associated mood disorders may exist, but there are few studies on concomitant cognitive impairment. Our aim was to assess whether there is reading and writing disruption in olivopontocerebellar atrophy (OPCA). 6 patients were administered different reading and writing tasks. Scores were then compared to those obtained by healthy volunteers. There was an evident impairment in reading and writing execution in out patients compared to those of the control group. On the contrary, no difference could be found in abstraction, problem-solving, and memory tasks. We discuss the results, debating the role of the cerebellum in the conscious process of cognition or in ocular movement control (necessary for reading and writing fluidity and effective execution) and in the dynamic activation of all the cerebral cortex mediated by the diffuse projection to the reticular system.