Ana Lúcia Zuma de Rosso

A study of LRRK2 mutations and Parkinson's disease in Brazil

Mutations in the Leucine-rich repeat kinase 2 (LRRK2) gene are known as a common cause of Parkinsons disease (PD) among patients from different geographic origins. In this study, we evaluated the prevalence of LRRK2 mutations in exons 31 and 41 in a cohort of 154 consecutive, unrelated Brazilian patients with familial or sporadic PD, including early and late onset patients. The LRRK2 p.G2019S mutation was present in heterozygous state in three index cases (approximately 2%), and in three additional relatives. No carriers of this mutation were found among 250 control chromosomes. Clinically, all mutation-positive patients presented a typical PD phenotype and a good response to levodopa. Mutation segregation analysis in a large sibling showed incomplete penetrance of the p.G2019S. Our findings suggest that the LRRK2 p.G2019S mutation has a substantial contribution to PD susceptibility among Brazilian population and add new clues to current research of this disease.

Depression in Parkinson's disease: diagnosis and treatment

The prevalence of non-motor symptoms in Parkinsons disease (PD) is high. Depression varies from 20 to 50% of the PD patients, and is associated with increasing disability. The key characteristics of depression are anhedonia and low mood. The recommended scales for screening purposes are: HAM-D, BDI, HADS, MADRS and GDS. As for measurement of severity: HAM-D, MADRS, BDI and SDS. In cases with mild depression, non-pharmacological intervention is the treatment of choice. In moderate depression, antidepressants are required. The choice of an antidepressant should be based mainly on the comorbidities and unique features of the patient. Evidence for antidepressant effectiveness is seen mostly with amitriptyline and nortriptyline, but one should be cautious in elderly patients. Other antidepressants that can be prescribed are: citalopram, escitalopram, sertraline, bupropion, trazodone, venlafaxine, mirtazapine and duloxetin. The dopaminergic agonist pramipexole is a treatment option.

Involuntary movements and AIDS: report of seven cases and review of the literature

We studied 1086 AIDS patients in the last six years. Of these 389 (35.82%) had neurological manifestation and 7 (1.8%) male patients had abnormal involuntary movements (parkinsonism in 3, hemichorea-hemiballism in 2, spinal myoclonus in 1 and rubral tremor in another). All patients were men, 5 white and 2 black. Four were homosexual, 2 drug-users and 1 bisexual. The mean age was 33.14 years. The time between AIDS diagnosis and the onset of movement disorders was 23.8 months in 5 patients and in 2 it was the first symptom. The parkinsonian patients did not show any opportunistic infection in connection with the neurological symptoms but in the remaining four cases this relationship was suggested. The data showed that not only the opportunistic infection but also the AIDS virus may play an important role on the development of involuntary movements.

Transcranial sonography as a diagnostic tool for Parkinson’s disease a pilot study in the city of Rio de Janeiro, Brazil

UNLABELLED In Brazil there is no systematic study on Transcranial Sonography (TCS), a neuroimaging method that depicts echogenic deep brain structures using ultrasound. OBJECTIVE To establish the percentage of subjects with permissive temporal windows and to address the ability of TCS of the substantia nigra (SN) to distinguish parkinsonian patients in a Brazilian sample. METHOD We performed TCS using the Acuson X300 (Siemens, Germany) in 37 individuals: 23 with Parkinsons disease (PD) and 14 healthy controls. RESULTS 10.8% of subjects had insufficient temporal acoustic bone windows. SN echogenic areas were larger in patients (mean ± SD, 0.31 ± 0.08 cm(2)) compared to controls (mean ± SD, 0.17 ± 0.02 cm(2)). TCS accurately identified 88.2% of PD patients. CONCLUSION A large proportion of Brazilians seem to be eligible for TCS. An expressive number of PD patients could be diagnosed by TCS based on an expanded SN echogenic area. However, the current data is preliminary and must be corroborated by larger studies.

Bedside Assessment of Swallowing in Stroke: Water Tests Are Not Enough

Abstract Objective: The clinical functional evaluation is the usual method for dysphagia screening in patients with acute stroke. This study compared two methods of evaluation — with liquid and semisolid viscosities. Method: Twenty-six patients with stroke onset within 7 days — with a mean age of 63.5 ± 12.4 years — were prospectively evaluated for deficit severity, swallowing mechanisms, chest X-ray studies, and late (30 days after discharge) assessment of disability with the modified Rankin Scale. Results: Tests using water and pudding correlated poorly (p < .001). The water test exhibited higher sensitivity for detection of problems in laryngeal protection, and the test with pudding was more sensitive for the functional analysis of dysphagia itself. Abnormalities in the water test were associated with weak spontaneous cough, while a normal pudding test correlated well with oral feeding 30 days after hospital discharge. The initial neurological severity correlated with results from both tests. No patient had pulmonary infiltrates 72 hours after testing or pneumonia up to 30 days after hospital discharge. Conclusion: The two evaluation methods should be used to both decrease the risk of aspiration and increase the likelihood of a safe and early reintroduction of oral feeding.

Paroxysmal dystonia and neuromyelitis optica

Paroxysmal dyskinesias (PD) are thought to be rare movement disorders. The overwhelming majority of reported cases are primary. Secondary PD has seen reported to occur in some conditions, mainly in multiple sclerosis and head trauma. The anatomic origin of the lesion is also rarely seen at the spinal cord. Our objective was to describe four patients with paroxysmal dystonia secondary to spinal lesions during the recovering phase of a neuromyelitis optica (NMO) bout. In the reviewed literature, we do not find any report of PD related to NMO.

Treatment of juvenile parkinson disease and the recurrent emergence of pathologic gambling

ObjectiveTo describe the recurrent emergence of pathologic gambling (PG) during the sequential treatment of a patient with Juvenile Parkinson disease (PD) with different dopamine agonists. MethodSingle case report. ResultsA patient with Juvenile PD developed PG soon after beginning treatment with pergolide, a mixed D1/D2 dopamine agonist that is also supposed to exhibit D3 activity. This behavior remitted upon the discontinuation of the drug. A subsequent therapeutic trial with pramipexole, a dopamine agonist with preferential D3 dopamine receptor activity, resulted in the recurrence of PG. Remarkably, previous treatment with levodopa was not associated with this side effect. ConclusionsThese findings seem to confirm previous suggestions that dopaminergic hyperactivity plays an important role in the pathogenesis of PG. They further indicate that patients with PD may develop PG as a side effect of more than one dopamine agonist. There is still no consensus regarding the best strategy to deal with this potentially disturbing phenomenon.

Mutational analysis of GIGYF2, ATP13A2 and GBA genes in Brazilian patients with early-onset Parkinson's disease

In the last decade, several genes have been linked to Parkinsons disease (PD), including GIGYF2, ATP13A2 and GBA. To explore whether mutations in these genes contribute to development of PD in the Brazilian population, we screened 110 patients with early-onset PD. No clearly pathogenic mutations were identified in ATP13A2 and GIGYF2. In contrast, we identified a significantly higher frequency of known pathogenic mutations in GBA gene among the PD cases (6/110=5.4%) when compared to the control group (0/155) (P=0.0047). Our results strongly support an association between GBA gene mutations and an increased risk of PD. Mutations in GIGYF2 and ATP13A2 do not seem to represent a risk factor to the development of PD in the Brazilian population. Considering the scarcity of studies on GIGYF2, ATP13A2 and GBA mutation frequency in Latin American countries, we present significant data about the contribution of these genes to PD susceptibility.

Exon dosage variations in Brazilian patients with Parkinson's disease: Analysis of SNCA, PARKIN, PINK1 and DJ-1 genes

Parkinson’s disease is one of the most common neurodegenerative disorders associated with aging, reaching ∼ 2% of individuals over 65 years. Knowledge achieved in the last decade about the genetic basis of Parkinson’s disease clearly shows that genetic factors play an important role in the etiology of this disorder. Exon dosage variations account for a high proportion of Parkinson’s disease mutations, mainly for PARKIN gene. In the present study, we screened genomic rearrangements in SNCA, PARKIN, PINK1 and DJ-1 genes in 102 Brazilian Parkinson’s disease patients with early onset (age of onset ≤ 50 years), using the multiplex ligation-dependent probe amplification method. Family history was reported by 24 patients, while 78 were sporadic cases. Screening of exon dosage revealed PARKIN and PINK1 copy number variations, but no dosage alteration was found in SNCA and DJ-1 genes. Most of the carriers harbor heterozygous deletions or duplications in the PARKIN gene and only one patient was found to have a deletion in PINK1 exon 1. Data about dosage changes are scarce in the Brazilian population, which stresses the importance of including exon dosage analysis in Parkinson’s disease genetic studies.

Holmes tremor in an HIV positive patient worsened by immune recovery inflammatory syndrome (IRIS).

IRIS is characterized by a paradoxical deterioration of clinical status after initiation of Anti-Retroviral Therapy (ART), despite improved immune function. It is caused by inflammatory response against the infectious antigen [1]. IRIS typically occurs in patients with a low initial CD4 (usually <50) and a rapid decline in viral load [2]. It is seen within a broad spectrum of HIV-related opportunistic infectious diseases and autoimmune disorders in patients who had been given Highly Active Anti-Retroviral Therapy (HAART) [3]. Our objective is to describe an HIV positive patient with Holmes ́ tremor worsened by IRIS, with marked recovery after therapy with steroids.