Automatic classification of idiopathic Parkinson's disease and atypical Parkinsonian syndromes combining [11C]raclopride PET uptake and MRI grey matter morphometry.

Objective.To explore the viability of developing a computer-aided diagnostic system for Parkinsonian syndromes using dynamic [11C]raclopride positron emission tomography (PET) and T1-weighted magnetic resonance imaging (MRI) data.Approach.The biological heterogeneity of Parkinsonian syndromes renders their statistical classification a challenge. The unique combination of structural and molecular imaging data allowed different classifier designs to be tested. Datasets from dynamic [11C]raclopride PET and T1-weighted MRI scans were acquired from six groups of participants. There were healthy controls (CTRLn= 15), patients with Parkinson's disease (PDn= 27), multiple system atrophy (MSAn= 8), corticobasal degeneration (CBDn= 6), and dementia with Lewy bodies (DLBn= 5). MSA, CBD, and DLB patients were classified into one category designated as atypical Parkinsonism (AP). The distribution volume ratio (DVR) kinetic parameters obtained from the PET data were used to quantify the reversible tracer binding to D2/D3 receptors in the subcortical regions of interest (ROI). The grey matter (GM) volumes obtained from the MRI data were used to quantify GM atrophy across cortical, subcortical, and cerebellar ROI.Results.The classifiers CTRL vs PD and CTRL vs AP achieved the highest balanced accuracy combining DVR and GM (DVR-GM) features (96.7%, 92.1%, respectively), followed by the classifiers designed with DVR features (93.3%, 88.8%, respectively), and GM features (69.6%, 86.1%, respectively). In contrast, the classifier PD vs AP showed the highest balanced accuracy (78.9%) using DVR features only. The integration of DVR-GM (77.9%) and GM features (72.7%) produced inferior performances. The classifier CTRL vs PD vs AP showed high weighted balanced accuracy when DVR (80.5%) or DVR-GM features (79.9%) were integrated. GM features revealed poorer performance (59.5%).Significance.This work was unique in its combination of structural and molecular imaging features in binary and triple category classifications. We were able to demonstrate improved binary classification of healthy/diseased status (concerning both PD and AP) and equate performance to DVR features in multiclass classifications.

Translation, Adaptation and Validation of the European Portuguese Version of the NMS-Quest for Parkinson's Disease.

INTRODUCTION: Non-motor symptoms are underrecognized features of Parkinson's disease that impair quality of life and increase mortality. In this study, we aim to translate, adapt and validate the European Portuguese version of the "Non-Motor Symptoms Questionnaire", which has proven to be a valid and reliable measurement tool of non-motor symptoms in other languages. MATERIAL AND METHODS: Acceptability was evaluated regarding the range of values, ceiling and floor effects. Reliability was measured in terms of internal consistency (Cronbach's alpha) and reproducibility (intra-class correlation coefficient). For criterion validity analysis, Movement Disorders Society - Unified Parkinson's Disease Part I domains' scores were compared to those of the "Non-Motor Symptoms Questionnaire". For convergent validity, correlations between the "Non-Motor Symptoms Questionnaire" and the Movement Disorders Society - Unified Parkinson's Disease Part III, Mini-Mental State Examination score, disease duration, and severity were obtained. RESULTS: Seventy nine Parkinson's disease patients were recruited, with a mean age of 67.2 ± 10.7 years and a disease duration of 10.8 ± 8.8 years. The European Portuguese version of the "Non-Motor Symptoms Questionnaire" total score was free of significant ceiling and floor effects. With the exception of the cardiovascular domain, adequate overall internal consistency was achieved. The questionnaire domains and the corresponding Movement Disorders Society - Unified Parkinson's Disease Part I dimensions were significantly correlated, although the total questionnaire score was modestly correlated with disease duration and severity, motor and non-motor symptoms severity and cognitive dysfunction. DISCUSSION: This is the first study to translate, adapt and validate a widely used screening instrument of non-motor symptoms of European Portuguese speaking Parkinson's disease patients. CONCLUSION: The European Portuguese version of "Non-Motor Symptoms Questionnaire" is a valid and reliable tool for screening nonmotor symptoms in patients with Parkinson's disease.

The Impact of Deep Brain Stimulation on the Sexual Function of Patients With Parkinson's Disease.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is used in the treatment of advanced Parkinson's disease (PD) with well-established benefits over motor complications. However, few studies addressing the impact of DBS on nonmotor dimensions such as sexual function have been conducted. This study aims to determine the effect of DBS-STN on the sexual activity of patients with PD and to establish predictive factors for sexual function decline after surgery. MATERIALS AND METHODS: Twenty-one patients with PD submitted to DBS-STN were compared with 19 eligible surgery candidates. Clinical measures included disease progression (Hoehn and Yahr scale), sexual function evaluation (Female Sexual Function Index and International Index of Erectile Function), severity of depressive symptoms (Beck Depressive Inventory-II), motor symptoms (Movement Disorders Society-Unified Parkinson's Disease Rating Scale Part III), and quality of life (39-item Parkinson's Disease Questionnaire). The primary outcomes were the development of sexual dysfunction in women and erectile dysfunction in men. Regression analysis was performed to outline risk factors for developing sexual function deterioration. RESULTS: Erectile dysfunction was present in 83.3% of men and sexual dysfunction in 77.8% of women treated with DBS-STN. Women with sexual dysfunction had higher emotional well-being 39-item Parkinson's Disease Questionnaire scores (P=0.017) and a higher prevalence of cardiovascular diseases (P=0.012) comparing with women without sexual dysfunction. Age was an independent predictive factor for developing erectile dysfunction in men (relative risk=1.26; P=0.033) and sexual dysfunction in women (relative risk =1.30; P=0.039), regardless of DBS-STN submission. CONCLUSIONS: Sexual function in both sexes of patients with PD does not seem to be influenced by DBS-STN itself, but by psychological and clinical features.

Freezing of gait and postural instability: the unpredictable response to levodopa in Parkinson's disease.

Freezing of gait (FOG) and postural instability are challenging motor symptoms that present a serious therapeutic dilemma in Parkinson's disease. Appropriate distinction between FOG subtypes may be difficult during routine clinical visits, as shown in the case we present. The patient was examined in three different states in relation to levodopa (L-DOPA) and apomorphine subcutaneous (sc) tests with video documentation: (1) 'overnight-off', after 12 hours without medication; (2)'on', 60 min after intake of regular levodopa dose (200 mg) and 20 min after 2 mg of apomorphine sc; and (3) 'supra-on', after 350 mg of L-DOPA and 3 mg of apomorphine sc. The patient clearly showed a dose-dependent paradoxical response to L-DOPA treatment with the emergence of severe FOG and postural instability. The tendency to develop these axial symptoms was less pronounced with apomorphine at doses that achieved similar improvements of other Parkinsonian features.

[Acute Generalized Chorea, Dystonia and Brain Calcifications: A Case Report]. / Coreia Aguda Generalizada, Distonia e Calcificações Cerebrais: A Propósito de um Caso Clínico.

Pathological basal ganglia calcification, or Fahr's Syndrome, can be secondary to a variety of diseases, namely parathyroid disturbances. Movement disorders are common clinical features, in which chorea is seen in less than 20% of cases and dystonia just in 8%. We report the clinical case of a 49-year-old male with a history of thyroidectomy, who was admitted in Emergency Service with acute generalized chorea and focal painful feet dystonia. Laboratory analysis showed hypocalcemia and rhabdomyolysis, and computed tomography scan revealed parenchymal calcification with basal ganglia involvement. After complementary studies we established a Fahr's Syndrome diagnosis secondary to an iatrogenic hypoparathyroidism. Clinical management has been successful with stabilized calcium levels, with no more neurologic symptoms. Hypocalcemia should be readily investigated and treated after a thyroidectomy, given the irreversibility of intracerebral calcifications and potential neurological or systemic consequences.

A calcificação dos núcleos da base, ou síndrome de Fahr, pode ser secundária a variadas doenças, nomeadamente as que cursam com envolvimento da paratiróide. Distúrbios do movimento são achados clínicos comuns, mas a coreia é observada em menos de 20% dos casos e a distonia apenas em 8%. Apresentamos o caso de um homem de 49 anos com antecedentes de tiroidectomia, admitido no serviço de urgência com coreia aguda generalizada e distonia focal dolorosa dos pés, cujo estudo laboratorial revelava hipocalcémia e rabdomiólise e a tomografia computorizada crânio-encefálica mostrava calcificações parenquimatosas extensas com envolvimento dos núcleos da base. A alargada investigação complementar permitiu fazer o diagnóstico de síndrome de Fahr secundária a hipoparatiroidismo iatrogénico. Após estabilização da calcémia, a evolução clínica foi favorável com resolução dos sintomasneurológicos. A hipocalcémia deve ser investigada e corrigida depois de tiroidectomias, dada a irreversibilidade das calcificações intracerebrais e as potenciais consequências neurológicas e sistémicas.

Impulsivity across reactive, proactive and cognitive domains in Parkinson's disease on dopaminergic medication: Evidence for multiple domain impairment.

Impulse control disorders (ICD) may occur in Parkinson's disease (PD) although it remains to be understood if such deficits may occur even in the absence of a formal ICD diagnosis. Moreover, studies addressing simultaneously distinct neurobehavioral domains, such as cognitive, proactive and reactive motor impulsivity, are still lacking. Here, we aimed to investigate if reactive, proactive and cognitive impulsivity involving risk taking are concomitantly affected in medicated PD patients, and whether deficits were dependent on response strategies, such as speed accuracy tradeoffs, or the proportion of omission vs. commission errors. We assessed three different impulsivity domains in a sample of 21 PD patients and 13 matched controls. We found impaired impulsivity in both reactive (p = 0.042) and cognitive domains (p = 0.015) for the PD patients, irrespective of response strategy. For the latter, effect sizes were larger for the actions related with reward processing (p = 0.017, dCohen = 0.9). In the proactive impulsivity task, PD patients showed significantly increased number of omissions (p = 0.041), a response strategy which was associated with preserved number of commission errors. Moreover, the number of premature and proactive response errors were correlated with disease stage. Our findings suggest that PD ON medication is characterized compared to healthy controls by impairment across several impulsivity domains, which is moderated in the proactive domain by the response strategy.

Parkinson's disease with hypocalcaemia: adult presentation of 22q11.2 deletion syndrome.

A growing amount of evidence indicates that 22q11.2 deletion syndrome (22q11.2DS) increases the risk of early-onset Parkinson's disease (EOPD). Here, we describe a 36-year-old patient with EOPD. The patient presented with 22q11.2DS features, including associated cognitive disabilities, hypocalcaemia and facial dysmorphia that led us to screen for and confirm this deletion. In addition, hypocalcaemia and vitamin D deficiency were the main factors responsible for severe, painful muscle spasms that were non-levodopa (L-Dopa) responsive and remitted after calcium and vitamin D replacement therapy. Many patients with this deletion remain undiagnosed until adulthood due to the absence of 'major' phenotypic hallmarks, which usually present during early childhood. Later onset problems involving various medical subspecialties are increasingly recognised as important components of 22q11.2DS. Therefore, the multisystem nature and associated burden of morbidities demand a high degree of suspicion for this entity from all clinicians regardless of their medical subspecialty.

Apathy Profile in Parkinson's and Huntington's Disease: A Comparative Cross-Sectional Study.

BACKGROUND/AIMS: Apathy is one of the most frequent, disabling and difficult-to-treat symptoms that show up in many neurodegenerative disorders. The aim of this study was to assess and compare apathy profile in Parkinson's and Huntington's patients using the same comprehensive instruments to measure apathy, cognition and depressive symptoms. MATERIALS AND METHODS: We consecutively assessed Parkinson's disease (PD) and Huntington's disease (HD) patients recruited from a Movement Disorders Unit. In all patients, information related to demographics, clinical data, motor score (Movement Disorders Society-Unified Parkinson Disease Rating Scale; Unified Huntington Disease Rating Scale), cognition (Montreal Cognitive Assessment scale), depressive symptoms (Beck Depression Inventory II) and apathy (Apathy Evaluation Scale - clinical version) was collected. Patients with dementia or major depression according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revised criteria were excluded from the study. RESULTS: Seventy-five patients were enrolled, 45 with PD and 30 with HD. Apathy was present in 42.5% of PD patients and 51.7% of HD patients. In PD patients, apathy was associated with motor score, shorter duration of disease, lower dose of levodopa equivalent daily dose and depressive symptomatology, whereas in HD patients, apathy was related to disease duration, motor score and cognitive impairment. CONCLUSIONS: We found a similar prevalence of apathy in PD and HD patients but with different clinical correlations and different apathy domains involved, and this may warrant the development of different therapeutic approaches.

Clinical rating scale for pantothenate kinase-associated neurodegeneration: A pilot study.

BACKGROUND: Pantothenate kinase-associated neurodegeneration is a progressive neurological disorder occurring in both childhood and adulthood. The objective of this study was to design and pilot-test a disease-specific clinical rating scale for the assessment of patients with pantothenate kinase-associated neurodegeneration. METHODS: In this international cross-sectional study, patients were examined at the referral centers following a standardized protocol. The motor examination was filmed, allowing 3 independent specialists in movement disorders to analyze 28 patients for interrater reliability assessment. The scale included 34 items (maximal score, 135) encompassing 6 subscales for cognition, behavior, disability, parkinsonism, dystonia, and other neurological signs. RESULTS: Forty-seven genetically confirmed patients (30 ± 17 years; range, 6-77 years) were examined with the scale (mean score, 62 ± 21; range, 20-106). Dystonia with prominent cranial involvement and atypical parkinsonian features were present in all patients. Other common signs were cognitive impairment, psychiatric features, and slow and hypometric saccades. Dystonia, parkinsonism, and other neurological features had a moderate to strong correlation with disability. The scale showed good internal consistency for the total scale (Cronbach's α = 0.87). On interrater analysis, weighted kappa values (0.30-0.93) showed substantial or excellent agreement in 85% of the items. The scale also discriminated a subgroup of homozygous c.1583C>T patients with lower scores, supporting construct validity for the scale. CONCLUSIONS: The proposed scale seems to be a reliable and valid instrument for the assessment of pediatric and adult patients with pantothenate kinase-associated neurodegeneration. Additional validation studies with a larger sample size will be required to confirm the present results and to complete the scale validation testing. © 2017 International Parkinson and Movement Disorder Society.

Transcranial Sonography and DaTSCAN in Early Stage Parkinson's Disease and Essential Tremor.

BACKGROUND: The diagnosis of Parkinson's disease (PD) can sometimes be a challenge in the early stages of the disease. Both transcranial sonography (TCS) and DaTSCAN are recommended as auxiliary examinations for the differential diagnosis of PD; however, only few data exist regarding their diagnostic accuracy in the early stage of PD and essential tremor (ET). METHODS: We evaluated patients with clinically suspected diagnosis of PD at early stages (Hoehn and Yahr ≤2) or ET. All patients underwent DaTSCAN and TCS with a maximum interval of 6 months. Final diagnosis was established after 1-year follow-up. RESULTS: From the 63 patients recruited, 3 were excluded due to transcranial insonability and 2 for uncertain clinical diagnosis. The final clinical diagnosis was ET in 44.8% and PD in 55.2%. Compared to clinical diagnosis of PD, TCS had a sensitivity of 87.5% and specificity of 96.2%; DaTSCAN sensitivity was 84.4% and specificity was 96.2%. Both diagnostic tests demonstrated a substantial level of agreement (Cohen's kappa coefficient: 0.83, 95% CI 0.68-0.97, p < 0.001). CONCLUSION: TCS and DaTSCAN have similar diagnostic accuracy for the diagnosis of early stage PD versus ET.

[Extensive Myelitis as a Manifestation of Neuroborreliosis]. / Mielite Extensa como Manifestação de Neuroborreliose.

Neurological manifestations of Lyme disease are reported in 3% - 12% of patients, with the most common form of presentation being meningoradiculitis. Other symptoms involving the central nervous system, such as myelitis or encephalitis, are rare (< 5 %). We report a case of a 66-year-old male, with a subacute extensive transverse myelitis, secondary to Borrelia burgdorferi infection. The patient underwent antibiotic therapy filed for neuroborreliosis with a good clinical outcome. The rareness in clinical symptoms and imaging presentation, based on a treatable infectious disease, highlights the importance of the inclusion of neuroborreliosis in the differential diagnosis of longitudinally extensive transverse myelitis.

As manifestações neurológicas na doença de Lyme ocorrem em 3% - 12% dos doentes, sendo a forma de apresentação mais comum a meningorradiculite. Outros sintomas de envolvimento do sistema nervoso central, como encefalomielite ou mielite são raros (< 5%). Descreve-se um caso clínico de um homem de 66 anos com uma mielite transversa extensa, de instalação subaguda, secundária a infeção por Borrelia burgdorferi. O doente foi submetido a terapêutica antibiótica dirigida, com uma boa evolução clínica. A raridade na forma de apresentação clínica e imagiológica deste caso, tendo como base uma doença infecciosa tratável, destaca a importância da sua inclusão no diagnóstico diferencial da mielite transversa longitudinalmente extensa.