André Carvalho Felício

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.

Cerebellar Cognitive Affective Syndrome in Machado Joseph Disease: Core Clinical Features

The cerebellum is no longer considered a purely motor control device, and convincing evidence has demonstrated its relationship to cognitive and emotional neural circuits. The aims of the present study were to establish the core cognitive features in our patient population and to determine the presence of Cerebellar Cognitive Affective Syndrome (CCAS) in this group. We recruited 38 patients with spinocerebellar ataxia type 3 (SCA3) or Machado–Joseph disease (MJD)-SCA3/MJD and 31 controls. Data on disease status were recorded (disease duration, age, age at onset, ataxia severity, and CAG repeat length). The severity of cerebellar symptoms was measured using the International Cooperative Ataxia Rating Scale and the Scale for the Assessment and Rating of Ataxia. The neuropsychological assessment consisted of the Mini-Mental State Examination, Clock Drawing Test, Wechsler Adult Intelligence Scale, Rey–Osterrieth Complex Figure, Wisconsin Card Sorting Test, Stroop Color–Word Test, Trail-Making Test, Verbal Paired Associates, and verbal fluency tests. All subjects were also submitted to the Hamilton Anxiety Scale and Beck Depression Inventory. After controlling for multiple comparisons, spatial span, picture completion, symbol search, Stroop Color–Word Test, phonemic verbal fluency, and Trail-Making Tests A and B were significantly more impaired in patients with SCA3/MJD than in controls. Executive and visuospatial functions are impaired in patients with SCA3/MJD, consistent with the symptoms reported in the CCAS. We speculate on a possible role in visual cortical processing degeneration and executive dysfunction in our patients as a model to explain their main cognitive deficit.

Molecular imaging studies in Parkinson disease: reducing diagnostic uncertainty.

Background:The diagnosis of Parkinson disease (PD) is based on clinical criteria but misdiagnosis is as high as 25% of cases as confirmed by anatomic-pathologic studies. Since the introduction of in vivo molecular imaging techniques using Single-Photon Emission Computed Tomography and Positron Emission Tomography, the diagnosis of PD became more reliable by assessing dopaminergic and even nondopaminergic systems. Review Summary:The purpose of this article is to critically review the current data on molecular neuroimaging focusing on the nigrostriatal circuitry and providing useful information on the role of these new imaging techniques in the management of clinically unclear cases of PD. Conclusions:Patients with essential tremor, psychogenic Parkinsonism or drug-induced Parkinsonism can be differentiated from PD in doubtful situations using molecular imaging techniques evaluating striatal dopamine transporters (DAT). However, in patients with vascular Parkinsonism, atypical Parkinsonism and Parkinsonism associated with dementia DAT scans have less diagnostic usefulness. Scans with non-DAT tracers (ie, D2 dopamine receptors) are necessary together with long-term clinical follow-up, and rescans to improve diagnostic accuracy.

Sleep disorders in cerebellar ataxias

Cerebellar ataxias comprise a wide range of etiologies leading to central nervous system-related motor and non-motor symptoms. Recently, a large body of evidence has demonstrated a high frequency of non-motor manifestations in cerebellar ataxias, specially in autosomal dominant spinocerebellar ataxias (SCA). Among these non-motor dysfunctions, sleep disorders have been recognized, although still under or even misdiagnosed. In this review, we highlight the main sleep disorders related to cerebellar ataxias focusing on REM sleep behavior disorder (RBD), restless legs syndrome (RLS), periodic limb movement in sleep (PLMS), excessive daytime sleepiness (EDS), insomnia and sleep apnea.

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.

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.

Fetal toxicity of Solanum lycocarpum (Solanaceae) in rats.

Lobeira (Solanum lycocarpum) is a Brazilian plant used as a hypoglycemic agent. In this study, the toxic effects of lobeira were evaluated during the fetogenesis period. Twenty pregnant Wistar rats were randomly allocated into two groups: control and treated, which received, via oral gavage, 0.5 ml of distilled water or 100 mg of the lobeira powder/kg of body weight, respectively, during days 17-20 of pregnancy. Maternal toxicity was evaluated by body weight, food intake, piloerection, locomotor activity, diarrhoea and vaginal bleeding. Euthanasia was done on 21st day, when ovaries, fetuses and their respective placentas were removed. Resorptions, live and dead fetuses were recorded. External malformations and fetal body, brain, liver, lung and kidneys were also weighed. No clinical signs of maternal toxicity were observed. The placenta weights of the treated rats were lower than those of the control (P<0.01). Lungs (P<0.01) and kidneys (P<0.02) of the fetuses treated with lobeira were also significantly reduced, suggesting a fetotoxic effect of this plant.

Epidemiology of primary and secondary headaches in a Brazilian tertiary-care center

OBJECTIVE To analyze the demographic features of the population sample, the time of headache complaint until first consultation and the diagnosis of primary and secondary headaches. METHOD 3328 patients were analyzed retrospectively and divided according to gender, age, race, school instruction, onset of headache until first consultation and diagnosis(ICHD-II, 2004). RESULTS Sex ratio (Female/Male) was 4:1, and the mean age was 40.7+/-15 years, without statistical differences between sexes. Approximately 65% of the patients were white and 55% had less than eight years of school instruction. Headache complaint until first consultation ranged from 1 to 5 years in 32.99% patients. The most prevalent diagnosis were migraine (37.98%), tension-type headache-TTH (22.65%) and cluster headache (2.73%). CONCLUSION There are few data on epidemiological features of headache clinic populations, mainly in developing countries. According to the literature, migraine was more frequent than TTH. It is noteworthy the low school instruction of this sample and time patient spent to seek for specialized attention. Hypnic headache syndrome was seen with an unusual frequency.

Higher striatal dopamine transporter density in PTSD: an in vivo SPECT study with [ 99m Tc]TRODAT-1

RationaleSome evidence suggests a hyperdopaminergic state in posttraumatic stress disorder (PTSD). The 9-repetition allele (9R) located in the 3′ untranslated region of the dopamine transporter (DAT) gene (SLC6A3) is more frequent among PTSD patients. In vivo molecular imaging studies have shown that healthy 9R carriers have increased striatal DAT binding. However, no prior study evaluated in vivo striatal DAT density in PTSD.ObjectivesThe objective of this study was to evaluate in vivo striatal DAT density in PTSD.MethodsTwenty-one PTSD subjects and 21 control subjects, who were traumatized but asymptomatic, closely matched comparison subjects evaluated with the Clinician-Administered PTSD Scale underwent a single-photon emission computed tomography scan with [99mTC]-TRODAT-1. DAT binding potential (DAT-BP) was calculated using the striatum as the region of the interest and the occipital cortex as a reference region.ResultsPTSD patients had greater bilateral striatal DAT-BP (mean ± SD; left, 1.80 ± 0.42; right, 1.78 ± 0.40) than traumatized control subjects (left, 1.62 ± 0.32; right, 1.61 ± 0.31; p = 0.039 for the left striatum and p = 0.032 for the right striatum).ConclusionsThese results provide the first in vivo evidence for increased DAT density in PTSD. Increases in DAT density may reflect higher dopamine turnover in PTSD, which could contribute to the perpetuation and potentiation of exaggerated fear responses to a given event associated with the traumatic experience. Situations that resemble the traumatic event turn to be interpreted as highly salient (driving attention, arousal, and motivation) in detriment of other daily situations.

Sleep Disorders in Machado–Joseph Disease: Frequency, Discriminative Thresholds, Predictive Values, and Correlation with Ataxia-Related Motor and Non-Motor Features

Sleep disorders are common complaints in patients with neurodegenerative diseases such as spinocerebellar ataxia type 3 (SCA3) or Machado–Joseph disease (MJD)—SCA3/MJD. We evaluated the frequency of sleep disorders in SCA3/MJD patients against controls matched by age and gender, and correlated data with demographic and clinical variables. The main sleep disorders evaluated were rapid eye movement (REM) sleep behavior disorder (RBD), restless leg syndrome (RLS), and excessive daytime sleepiness (EDS). We recruited 40 patients with clinical and molecular-proven SCA3/MJD and 38 controls. We used the following clinical scales to evaluate our primary outcome measures: RBD Screening Questionnaire, International RLS Rating Scale, and Epworth Sleepiness Scale. To evaluate ataxia-related motor and non-motor features, we applied the International Cooperative Ataxia Rating Scale, the Scale for the Assessment and Rating of Ataxia, and the Unified Parkinson’s Disease Rating Scale part III. Psychiatric manifestations were tested with the Hamilton Anxiety Scale, and Beck Depression Inventory. The frequency of RBD and RLS were significantly higher in the SCA3/MJD group than in the control group (p < 0.001). There was no difference between both groups with regard to EDS. The accuracy of RDBSQ to discriminate between cases and controls was considered the best area under the ROC curve (0.86). Within-SCA3/MJD group analysis showed that anxiety and depression were significantly correlated with RDB, but not with RLS. Additionally, depression was considered the best predictive clinical feature for RDB and EDS.