Digital movement analysis,a new objective method of measuring tardive dyskinesia and drug-induced parkinsonian tremor: acceptability,reliability and validity

Digital movment analysis (DMA) is a new instrumental approach to assessing oral tardive dyskinesia (TD) by means of digital image processing of a video signal, tracking five paper dots placed around the patient's mouth. A total of 40 schizophrenic patients, 30 with and 10 without TD, were examined twice (with a 3-month interval) with this new device. The patients were further examined with two TD rating scales: the St. Hans Rating Scale for extrapyramidal syndromes (SHRS) and the Abnormal Involuntary Movement Scale (AIMS).The schizophrenic patients accepted the instrumental assessment without any anxiety or resistance. The internal relibility of the apparatus was high, with correlation coefficients of 0.80–0.99. The DMA TD values correlated with the SHRS and AIMS scores with correlation coefficients of 0.48–0.73 indicating an acceptable, although not strong, concurrent validity. Fluctuations occurred from the first to the second examination independent of medication. For these fluctuations no correlation was found between DMA values and rating scores. Finally, the DMA device was able to detect perioral tremor as a sign of parkinsonism.It has been concluded that DMA is a useful supplement to classical TD rating, although further validity evaluation is warranted.     

Flunarizine induces a transient loss of tyrosine hydroxylase immunoreactivity in nigrostriatal neurons

Neurotoxic effects of flunarizine (Fz), a selective calcium channel blocker, on the nigrostriatal dopamine system was investigated. Systemic injections of Fz to mice resulted in a transient loss of tyrosine hydroxylase (TH) immunoreactive nigrostriatal neurons without cell loss. TH immunoreactivity in these neurons was greatly reduced as rapidly as one day after drug administration (regardless of dosage used) and thereafter recovered in both dose- and time-dependent manners. Such a novel neurotoxic action of Fz may constitute a morphological substrate for reversible drug-induced parkinsonian signs described in recent clinical case reports.     

Central Nervous System Lymphomatoid Granulomatosis Presenting with Parkinsonism

Lymphomatoid granulomatosis (LG) is a potentially malignant lymphoproliferative disorder. The lung is the most common involved site, followed by the skin and nervous system. However, LG of the central nervous system presenting with Parkinsonism is very rare. We report a patient with LG who presented with parkinsonian features such as bilateral rigidity, bradykinesia, and agitation. Brain magnetic resonance imaging showed multifocal punctuate enhanced lesions in both supra- and infratentorial areas. Steroid pulse therapy resulted in a dramatical improvement in the symptoms and MRI abnormalities.     

Parkinson's disease in Africa: A systematic review of epidemiologic and genetic studies.

Parkinson's disease (PD) occurs worldwide, but little is known about PD in Africa. We systematically reviewed publications on PD in Africa, with emphasis on epidemiologic and genetic studies. Articles published between 1944 and December 2004 were identified using several strategies. The studies emanated from 13 African countries (Kenya, Uganda, Tanzania, Ethiopia, Nigeria, Senegal, Ghana, Togo, Libya, Tunisia, Algeria, Zimbabwe, and South Africa). The publications fell into four categories: clinical series (n = 17), prevalence studies (n = 7), incidence studies (n = 1), and genetic studies (n = 3). The clinical series documented the occurrence of PD in Africa and described its clinical characteristics. The prevalence studies suggested some intracontinental geographic variation in PD prevalence. Overall, the prevalence figures and the incidence rates of PD in Africa appeared lower than those reported for European and North American populations. Few genetic studies of PD have been reported from Africa, and none in blacks. There are no case-control or cohort studies of PD reported from Africa. This review provides a summary of PD research in Africa over the past 60 years and highlights the information gaps and potential areas for future research.     

Progressive motor syndrome in a welder with pallidal T1 hyperintensity on MRI: A two-year follow-up.

Chronic exposure to manganese (Mn) fume during welding may lead to mainly extrapyramidal syndrome that is resistant to treatment. We present a 32-year-old patient who developed severe postural instability, Parkinsonism, dystonia, and pyramidal signs in the 10th year of welding. The neurological condition of the patient worsened markedly in the following 3 years, resulting in severe disability rendering him to be assisted in all his daily activities and he did not benefit from any dopaminergic agent. T1 sequences of the MRI of the brain showed pallidal hyperintensity symmetrically. Welders in our country often protect their eyes but ignore to use tools that protect them from inhalation of the fume. Since chronic Mn toxicity may cause serious disability and irreversible neurological disturbances, we strongly believe that it is necessary to inform welders and their employers about this potential hazard.     

Cholinergic balance in dementia with Lewy bodies: reversible worsening of Parkinsonism at rivastigmine dosage modulation

We describe a patient with probable dementia with Lewy bodies (DLB) whose Parkinsonism worsened after administration of rivastigmine within the therapeutic dose range. Some extrapyramidal signs (EPS) then reversed to pre-treatment level after rivastigmine dose reduction. We draw attention to the need of EPS monitoring during titration of cholinesterase inhibitors in patients with DLB. This is the first report to our knowledge of iatrogenic worsening of Parkinsonism which was successfully managed by dose reduction.

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Sommario Si descrive il caso di un paziente affetto da Demenza a corpi di Lewy (Dementia with Lewy Bodies, DLB) probabile, in cui si è assistito ad un peggioramento del parkinsonismo dopo somministrazione di rivastigmina a dosi terapeutiche. Alcuni segni extrapiramidali sono regrediti al livello pre-trattamento con una riduzione posologica di rivastigmina. Si sottolinea la necessità di un monitoraggio dei segni extrapiramidali durante la titolazione della terapia con inibitori dell’acetilcolinesterasi cerebrale in pazienti con DLB. Questo è il primo caso descritto, a nostra conoscenza, di un peggioramento iatrogeno di parkinsonismo efficacemente gestito con una riduzione posologica della terapia con rivastigmina.

     

Neurochemical Findings in the Cerebrospinal Fluid of Schizophrenic Patients with Tardive Dyskinesia and Neuroleptic-Induced Parkinsonism

Abstract: Monoamine and their acid metabolites were determined in the CSF of 18 drug-treated chronic schizophrenic patients with the symptoms of tardive dyskinesia and neuroleptic-induced Parkinsonism (Parkinsonism). Six healthy volunteers were used as the control group.
The norepinephrine (NE) levels were found to be significantly higher in the patients with tardive dyskinesia than in the controls. Furthermore, elevated CSF NE levels were also observed in the patients with Parkinsonism. Epinephrine (E) and Dopamine (DA) were not present in the CSF of the control group, whereas measurable levels of DA could be detected in 4 out of 9 and E was found in 8 out of 9 patients with tardive dyskinesia. The mean concentration of HVA was slightly but not significantly elevated in the patients with tardive dyskinesia and Parkinsonism. The mean values of CSF 5-HIAA were all within the normal range in both patient groups. From the above results, it was suggested that abnormal adrenergic activity rather than abnormal dopaminergic activity may play an important role as a mechanism in the etiopathogenesis of extrapyramidal disorders. Furthermore, in the patients with Parkinsonism, CSF neurochemical observations were similar to those of the patients with tardive dyskinesia in this study. It may help to explain the clinical coexistence of tardive dyskinesia and neuroleptic-induced Parkinsonism.     

Role of ubiquitin-mediated proteolysis in the pathogenesis of neurodegenerative disorders

Intraneuronal inclusions containing ubiquitylated filamentous protein aggregates are a common feature of many of the major human neurodegenerative disorders, including Alzheimer's and Parkinson's disease. Loss of function mutations in enzymes of the ubiquitin conjugation/deconjugation pathway are sufficient to cause familial forms of neurodegenerative diseases, suggesting that failure of ubiquitin-mediated proteolysis could also be central to inclusion formation in the more common sporadic cases. Examination of ubiquitin-positive inclusions at the protein level provides evidence of attempted proteasomal proteolysis, however close inspection of the temporal aspects of inclusion formation indicates that ubiquitylation is probably a late event. In this regard, the presence of ubiquitin within inclusions of idiopathic neurodegenerative disorders may indicate not a primary dysfunction of ubiquitin-mediated proteolysis, but rather a secondary, presumably protective cellular response. Within this model, other factors are likely to be initiating in inclusion biogenesis. Consistent with these proposals, non-ubiquitylated forms of the principal ubiquitylated components of Alzheimer's disease neurofibrillary tangles and Parkinson's disease Lewy bodies, tau and alpha-synuclein proteins, respectively, can be degraded by proteasomes in a pathway which does not have an absolute requirement for ubiquitylation. Inhibition of proteasome function in the pathological state, as has been reported in both Alzheimer's and Parkinson's disease, could therefore contribute both to accumulation of non-ubiquitylated forms of aggregation-prone neuronal proteins, as well as impaired clearance of ubiquitylated aggregates.     

Neurochemical correlates of sparing from motor deficits in rats depleted of striatal dopamine as weanlings

The behavioral and neurochemical effects of striatal DA depletions were investigated in rats lesioned as weanlings (Day 27) or as adults (250-300 g). Administration of 6-OHDA into the medial forebrain bundle resulted in comparably large (> or = 95%) depletions of tissue levels of DA in both age groups. As expected, rats depleted of DA as adults exhibited marked deficits in motoric behavior and body weight regulation that persisted for the 8 days of postsurgical observation. In contrast, rats depleted of DA as weanlings were spared from such deficits, and their behavior closely resembled that of age-matched controls. Microdialysis studies revealed dialysate levels of striatal DA that paralleled these age-dependent behavioral differences. At a time when age-related behavioral differences were still quite pronounced (5-6 days postsurgery), basal DA levels were reduced by 80% of control values in rats lesioned as adults whereas basal DA levels in rats lesioned as weanlings were unchanged relative to their controls. Finally, adults depleted of striatal DA as weanlings were no more sensitive to the movement-impairing effects of intrastriatal sulpiride (3.0 or 10.0 micrograms/hemisphere) infusions than were control rats. These data suggest that weanlings compensate for large, but incomplete, denervation of striatal DA with markedly enhanced release and turnover from residual terminals. This developmental plasticity may prevent the occurrence of behavioral deficits soon after the lesion and also the supersensitivity to the challenging effects of DA antagonists as animals grow into adulthood.