Luiz Augusto Franco de Andrade

Chronic exposure to the fungicide maneb may produce symptoms and signs of CNS manganese intoxication.

Manganese (Mn) poisoning, a well-known hazard in miners and industrial workers, shares many features with Parkinsons disease. Two young agricultural workers with a parkinsonian syndrome, who mentioned exposure to the fungicide maneb (manganese ethylene-bis-dithiocarbamate), led us to investigate a new possible source of Mn intoxication. Fifty male rural workers with occupational exposure to maneb were compared with 19 rural workers without fungicide exposure. We noted significantly higher prevalence of plastic rigidity with cogwheel phenomenon, headache, fatigue, nervousness, memory complaints, and sleepiness in the exposed group. In addition, we saw other neurologic signs, such as postural tremor, cerebellar signs, and bradykinesia, although without statistical significance. The data suggest that occupational exposure to pesticides containing Mn is a possible source of Mn intoxication of the CNS.

Higher dopamine transporter density in Parkinson’s disease patients with depression

RationaleDepression is a frequent non-motor symptom in Parkinson’s disease (PD) with increasing rates with the progression of the disease. Molecular imaging studies have shown a reduction of dopamine transporter (DAT) density in depressed PD patients (dPD); however, DAT role in the pathophysiology of PD depression is not clear since clinical matching was inappropriate and DAT reduction could be attributed to PD severity.ObjectivesTo further examine the role of DAT in PD depression, this study compared thoroughly matched depressed vs. non-depressed PD patients (ndPD).Materials and methodsTwenty PD patients (n = 10 ndPD; n = 10 dPD) matched for age and disease severity were submitted to brain SPECT imaging with [99mTc]-TRODAT-1, a DAT radioligand. DAT-binding potential was calculated using regions of interest bilaterally drawn in the striatum, caudate, and putamen. Depression was defined according to Beck Depression Inventory (BDI; cut-off >18).ResultsMean BDI scores were higher in dPD (25.0 ± 5.6) than in ndPD patients (8.0 ± 1.9, p < 0.0001). DAT density was greater on dPD especially in the left caudate (dPD 0.87 ± 0.19 vs. ndDP 0.69 ± 0.18, p = 0.02) and right putamen (dPD 0.37 ± 0.07 vs. ndPD 0.28 ± 0.13, p = 0.03) than in ndPD patients.ConclusionOur results suggest that in vivo DAT density is increased in dPD patients as compared to ndPD, suggesting that DAT is implicated in the pathophysiology of PD depression.

Effect of voice rehabilitation on oral communication of Parkinson's disease patients

Voice and speech disorders are common in Parkinsons disease patients and may lead to social isolation. We employed routine clinical voice therapy measures to evaluate the effect of voice rehabilitation. Twenty patients with a stable drug regimen participated in this study. The patients were assessed before and after a program of voice rehabilitation consisting of 13 group therapy sessions during 1 month, with emphasis on the increase in laryngeal sphincteric activity. Voice rehabilitation produced an increase in maximal phonation times, decrease in the values of s/z ratio and air flow, increase in vocal intensity, decrease in the complaints of weak and strained‐strangled voice and monotonous and unintelligible speech and elimination of complaints of swallowing alterations. These data indicate a greater glottic efficiency after voice rehabilitation reflecting a more functional oral communication.

Parkinson's disease and dopamine transporter neuroimaging - a critical review

Parkinsons disease (PD) is a common neurodegenerative disorder that is mainly caused by dopaminergic neuron loss in the substantia nigra. Several nuclear medicine radiotracers have been developed to evaluate PD diagnoses and disease evolution in vivo in PD patients. Positron emission tomography (PET) and single photon computerized emission tomography (SPECT) radiotracers for the dopamine transporter (DAT) provide good markers for the integrity of the presynaptic dopaminergic system affected in PD. Over the last decade, radiotracers suitable for imaging the DAT have been the subject of most efforts. In this review, we provide a critical discussion on the utility of DAT imaging for Parkinsons disease diagnosis (sensitivity and specificity).

Genetic and environmental findings in early‐onset Parkinson's disease Brazilian patients

Parkinsons disease (PD) etiology has been attributed both to genetic and environmental factors. In this study, we investigated Brazilian early‐onset PD (EOPD) patients for mutations in PARK2 and PARK8, exposure to environmental factors and possible correlations between PARK2 polymorphisms, environmental exposure, and disease age of onset. We enrolled 72 EOPD index patients and 81 healthy volunteers. Both groups were investigated for environmental exposure. EOPD patients were screened for PARK2 and PARK8 mutations. PARK2 coding polymorphisms Ser167Asn and Val380Leu were investigated in both groups. Mutations were present in 18% of the patients and in 32% of those with a positive family history. PARK2 mutations represented 12.5% and PARK8 mutations accounted for 5.5% of the mutations. A novel PARK2 mutation (D53X) was identified in 2 patients. A positive correlation was found between EOPD and well water drinking. In patients exposed to well water, a later age of onset was observed for those who carried at least one PARK2 380Leu allele. PARK2 mutations have an important role in EOPD Brazilian patients and PARK8 might be the second most important disease causing gene in this group. Well water drinking exposure represents a risk factor for EOPD and the PARK2 coding polymorphism Val380Leu might be interacting with environmental factors acting as a disease modifier.

Total sleep deprivation and Parkinson disease

Twelve Parkinson disease (PD) patients were submitted to a single night of total sleep deprivation (SD). Disease duration had a median of 5.1 years and all were using either anticholinergic or L-Dopa or the combination of both drugs. After SD there was an improvement of rigidity, bradykinesia, gait and posture disturbances and functional disability that remained significant for 2 weeks. No effect was observed on tremor. Concerning depressive symptoms, a significant difference was noted, that remained for one week. These results suggest that SD may be an useful procedure to improve PD symptomatology. It is discussed a possible change of dopaminergic receptors, induced by SD, to explain the improvement.

Higher nigrostriatal dopamine neuron loss in early than late onset Parkinson's disease?-A [99mTc]-TRODAT-1 SPECT study

Early‐onset Parkinsons disease (EOPD) is distinct from the classic late‐onset PD (LOPD) because of its slower disease progression. The aim of this study was to compare dopamine neuronal loss in EOPD with that of LOPD with the same disease duration, through dopamine transporter (DAT) estimation. Fourteen patients, seven EOPD (<50 years) and seven LOPD, matched for disease duration were scanned with [99mTc]‐TRODAT‐1‐SPECT (INER‐Taiwan), and were assessed with standard PD scales. EOPD patients had 34% lower striatal DAT binding potential (BP) compared with that of LOPD patients (BP = 0.29 ± 0.12, BP = 0.44 ± 0.12, P < 0.02) with similar PD severity. These results suggest that EOPD patients have greater dopamine density loss than LOPD patients without motor‐symptom worsening.

Increased dopamine transporter density in Parkinson's disease patients with social anxiety disorder☆

Social Anxiety Disorder (SAD) is more common among PD patients than in the general population. This association may be explained by psychosocial mechanisms but it is also possible that neurobiological mechanism underlying PD can predispose to SAD. The aim of this study was to investigate a possible dopaminergic mechanism involved in PD patients with SAD, by correlating striatal dopamine transporter binding potential (DAT-BP) with intensity of social anxiety symptoms in PD patients using SPECT with TRODAT-1 as the radiopharmaceutical. Eleven PD patients with generalized SAD and 21 PD patients without SAD were included in this study; groups were matched for age, gender, disease duration and disease severity. SAD diagnosis was determined according to DSM IV criteria assessed with SCID-I and social anxiety symptom severity with the Brief Social Phobia Scale (BSPS). Demographic and clinical data were also collected. DAT-BP was significantly correlated to scores on BSPS for right putamen (r=0.37, p=0.04), left putamen (r=0.43, p=0.02) and left caudate (r=0.39, p=0.03). No significant correlation was found for the right caudate (r=0.23, p=0.21). This finding may reinforce the hypothesis that dopaminergic dysfunction might be implicated in the pathogenesis of social anxiety in PD.

Huntington disease: DNA analysis in brazilian population

Huntington disease (HD) is associated with expansions of a CAG trinucleotide repeat in the HD gene. Accurate measurement of a specific CAG repeat sequence in the HD gene in 92 Brazilian controls without HD, 44 Brazilian subjects with clinical findings suggestive of HD and 40 individuals from 6 putative HD families, showed a range from 7 to 33 repeats in normal subjects and 39 to 88 repeats in affected subjects. A trend between early age at onset of first symptoms and increasing number of repeats was seen. Major increase of repeat size through paternal inheritance than through maternal inheritance was observed. Data generated from this study may have significant implications for the etiology, knowledge of the incidence, diagnosis, prognosis, genetic counseling and treatment of HD Brazilian patients.

Botulinum toxin A for trismus in cephalic tetanus

Cephalic tetanus is a localized form of tetanus. As in generalized forms, trismus is a prominent feature of the disease, leading to considerable difficulty in feeding, swallowing of the saliva and mouth hygiene. These difficulties often precede respiratory problems and aspiration bronchopneumonia is a frequent life-threatening complication. Muscle relaxants other than curare drugs may show a limited benefit for relieving trismus. Tetanospasmin, the tetanic neurotoxin, and botulinum toxin share many similarities, having a closely related chemical structure, an origin from related microorganisms (Clostridium tetani and Clostridium botulinum, respectively), and presumably, the same mechanisms of action in the neuron. The difference between the two lies in their peculiar neurospecificity, acting in different neurons. Injection of minute doses of botulinum toxin in the muscles involved in focal dystonias or other localized spastic disorders have proved to be very effective in these conditions. We describe the use of botulinum toxin A in the successful treatment of trismus in a patient suffering from cephalic tetanus. We believe that this form of treatment may be of value in lowering the risk of pulmonary complications in tetanic patients.