Paulo Bugalho

Autosomal dominant cerebellar ataxia: frequency analysis and clinical characterization of 45 families from Portugal

Background and purpose:  The relative frequency of the different autosomal dominant cerebellar ataxia (ADCA) varies widely amongst different geographic locations. Here we describe a series of 45 ADCA families from Portugal.

Clinical features associated with REM sleep behavior disorder symptoms in the early stages of Parkinson’s disease

We aimed to characterize the clinical features associated with REM sleep behaviour disorder (RBD) in early stage Parkinson’s disease (PD). Presence of clinical RBD was determined according to ICSD minimal clinical criteria and a validated RBD questionnaire. We registered time of appearance of RBD symptoms in relation to PD onset and the occurrence of RBD symptoms in the past in non-RBD patients. RBD and non-RBD groups were compared in terms of motor and cognitive dysfunction. The same comparisons were made between patients who reported RBD symptoms at some point in time (including those non-RBD patients that reported occurrence of RBD symptoms in the past) and those who did not (RBDS and non-RBDS, respectively). We assessed 75 patients. Forty-one (55%) patients presented with RBD, 19 beginning before PD onset. Five non-RBD patients reported having had RBD symptoms in the past. There were no significant differences between RBD and non-RBD patients. RBDS group presented a significantly higher proportion of non-tremor motor sub-type compared to non-RBDS patients. Our results suggest that RBD is very frequent in the early stages of PD. In some patients, RBD symptoms could have disappeared before or in the first years after motor disturbance onset. Non-tremor motor sub-type was related to RBD symptoms history, rather than to the presence of RBD clinical criteria at time of evaluation, suggesting that the physiopathological changes that cause the association with motor status could remain, in spite of symptom fluctuation.

Cognitive function correlates with frontal white matter apparent diffusion coefficients in patients with leukoaraiosis.

Background and aimsDiffusion weighted imaging (DWI) displays a high sensitivity to white matter changes, even in areas where no lesions are visible. Correlation with vascular risk factors and cognitive dysfunction seems to be feasible using this technique. We aimed to test relations between age, blood pressure and cognitive function,with lesion load and average Apparent Diffusion Coefficient (ADC) values in lesioned (LWM) and in normal appearing white matter (NAWM), in patients with age related white matter lesions (ARWML).MethodsSubjects were 29 patients (mean age 72.6 ± 5.2 years) with different severity of ARWML on MRI and no (or mild) disability assessed by the Instrumental Activities of Daily Living Scale. Imaging lesion load was quantified in bilateral frontal, temporal, parieto-occipital, basal ganglia and infratentorial regions, using a simple visual rating scale; ADC was measured bilaterally in Regions of Interest in parieto-occipital and frontal NAWM, and in frontal periventricular LWM. Neuropsychological examination consisted of Raven Colored Progressive Matrices, Rey’s Complex Figure, Digit Canceling. Symbol digit Substitution, Inverse Digit Repetition and Verbal Fluency tests.ResultsVisual scales scores and ADC were significantly higher in frontal and parieto-occipital regions. Both were significantly correlated to age and blood pressure, in frontal (visual scale scores and ADC) and parieto-occipital regions (ADC). Attention skills were negatively correlated to ADC in LWM and NAWM in frontal regions and with frontal region visual scale scores.ConclusionOur findings suggest that severity of white matter ischemic changes is correlated with worse cognitive function, as well as advanced age and higher blood pressure.A higher vulnerability of frontal white matter to vascular disease seems to play an important role in executive dysfunction, mainly determined by impairment of attentional skills.DWI results suggest this could be true even for NAWM.

Alzheimer's disease: a clinical practice-oriented review

Investigation in the field of Alzheimer’s disease (AD), the commonest cause of dementia, has been very active in recent years and it may be difficult for the clinician to keep up with all the innovations and to be aware of the implications they have in clinical practice. The authors, thus, reviewed recent literature on the theme in order to provide the clinician with an updated overview, intended to support decision-making on aspects of diagnosis and management. This article begins to focus on the concept of AD and on its pathogenesis. Afterward, epidemiology and non-genetic risk factors are approached. Genetics, including genetic risk factors and guidelines for genetic testing, are mentioned next. Recommendations for diagnosis of AD, including recently proposed criteria, are then reviewed. Data on the variants of AD is presented. First approach to the patient is dealt with next, followed by neuropsychological evaluation. Biomarkers, namely magnetic resonance imaging, single photon emission tomography, FDG PET, PiB PET, CSF tau, and Aβ analysis, as well as available data on their diagnostic accuracy, are also discussed. Factors predicting rate of disease progression are briefly mentioned. Finally, non-pharmacological and pharmacological treatments, including established and emerging drugs, are addressed.

Obsessive-compulsive symptoms in primary focal dystonia: A controlled study†‡§

Primary focal dystonia is an idiopathic neurological disorder causing involuntary muscle contraction. Its pathophysiology probably involves the basal ganglia and cortical‐basal pathways. Primary dystonia appears to be associated with significant obsessive‐compulsive symptoms, but evidence remains scarce and contradictory. We addressed the following research questions: (1) Do primary dystonia patients have high obsessive‐compulsive symptom scores? (2) Are these symptoms more severe in dystonia than in controls with equivalent peripheral neurological disorders? and (3) Is psychopathology different in botulinum toxin‐treated and ‐untreated dystonia patients? This work was a cross‐sectional, descriptive, controlled study comprising 45 consecutive patients with primary focal dystonia (i.e., blepharospasm, spasmodic torticollis, or writers cramp) 46 consecutive patients with hemifacial spasm, cervical spondylarthropathy, or carpal tunnel syndrome, and 30 healthy volunteers. Assessment included the DSM‐IV based psychiatric interview, Symptom Checklist 90R, Yale‐Brown Obsessive‐Compulsive Scale and Checklist, and the Unified Dystonia Rating Scale. Dystonia patients had higher Yale‐Brown Obsessive‐Compulsive Symptom scores than both control groups. Dystonia patients with obsessive‐compulsive symptom scores above cut‐off for clinical significance predominantly developed hygiene‐related symptoms. Major depression and generalized anxiety disorder were the most frequent psychiatric diagnoses in primary focal dystonia. Obsessive‐compulsive disorder frequency was 6.7%. Primary focal dystonia patients have higher obsessive‐compulsive symptom scores than individuals with similar functional disabilities resulting from other neurological disorders, suggesting that obsessive‐compulsive symptoms in dystonia are not reactive to chronic disability. Dystonic muscle contractions and obsessive‐compulsive symptoms may share a common neurobiological basis related to cortical‐basal dysfunction. Psychopathology, especially obsessive‐compulsive symptoms, should be actively explored and treated in primary focal dystonia.

Set-shifting and behavioral dysfunction in primary focal dystonia.

The occurrence of cognitive and behavioral symptoms in patients with primary dystonia remains a matter of debate. We compared 45 patients with primary dystonia with 27 control subjects for performance on neuropsychological tasks with a load on executive‐Wisconsin Card Sorting Test (WCST) and Stroop test, and visuospatial‐Bentons visual retention test (BVRT) and Block assembly test from Wechsler Adult Intelligence Scale BAT‐functions, as well as for intensity of obsessive‐compulsive symptoms (Yale Brown Obsessive Compulsive Scale, Y‐BOCS). Correlation analysis was performed between neuropsychological performance, dystonia characteristics (duration, age of onset) and severity (Unified Dystonia Rating Scale, UDRS), and Y‐BOCS. Patients made more perseverative errors on the WCST (P = 0.042) and had a higher mean Y‐BOCS (P = 0.003) score than controls. Timed tests (BVRT, BAT, Stroop test) correlated with UDRS. Y‐BOCS, WCST, and UDRS scores were not significantly correlated with one another.These results suggest that patients with primary dystonia may have set‐shifting deficits and a higher intensity of obsessive compulsive symptoms when compared to healthy subjects. This may reflect a pattern of complex neurophysiological dysfunction involving dorsolateral, orbitofrontal, and motor frontostriatal circuits.

Dream features in the early stages of Parkinson’s Disease

Few studies have investigated the relation between dream features and cognition in Parkinson’s disease (PD), although vivid dreams, hallucinations and cognitive decline have been proposed as successive steps of a pathological continuum. Our objectives were therefore to characterize the dreams of early stage PD and to study the relation between dream characteristics, cognitive function, motor status, depression, dopaminergic treatment, and the presence of REM sleep behaviour disorder (RBD) and hallucinations. Dreams of 19 male PD patients and 21 matched control subjects were classified according to Hall and van de Castle system. h statistics was used to compare the dream content between patients and controls. We tested the relation between patients’ dreams characteristics and cognitive function (Frontal assessment battery (FAB) and Mini-Mental State Examination tests) depression (Beck depression inventory), motor function (UPDRS), dopaminergic treatment, the presence of RBD (according to clinical criteria) and hallucinations, using general linear model statistics. Patients and controls differed only on FAB scores. Relevant differences in the Hall and van de Castle scale were found between patient’s dreams and those of the control group, regarding animals, aggression/friendliness, physical aggression, befriender (higher in the patient group) and aggressor and bodily misfortunes (lower in the patient group) features. Cognitive and particularly frontal dysfunction had a significant influence on the frequency of physical aggression and animal related features, while dopaminergic doses, depressive symptoms, hallucinations and RBD did not. We found a pattern of dream alteration characterized by heightened aggressiveness and the presence of animals. These were related to more severe frontal dysfunction, which could be the origin of such changes.

Normal-pressure hydrocephalus: White matter lesions correlate negatively with gait improvement after lumbar puncture

OBJECTIVES To test relations between white matter lesions (WML) load in Normal Pressure Hydrocephalus (NPH) patients and gait characteristics at baseline, duration of symptoms, gait improvement after lumbar puncture (LP), vascular risk factors. PATIENTS Fifteen idiopathic NPH patients. METHODS Patients underwent a timed walking test, before and after LP. Five gait variables were assessed and improvement percentages were calculated. WML load was rated regionally and globally in T2 weighted MRI images, using a simple visual scale. Spearman or Pearson correlation coefficients were used to test relations between variables. RESULTS Significant negative correlations were found between WML scores and gait improvement after CSF removal but not with duration of symptoms or gait variables before LP. CONCLUSIONS WML seem to contribute to the irreversibility of symptoms in NPH but not to the pathophysiological mechanisms that lead to them.

Psychiatric symptoms screening in the early stages of Parkinson’s disease

Psychiatric complaints are common in Parkinson’s disease (PD), and have a significant influence in disease outcome and quality of life. Little attention has been paid to psychiatric symptoms at early stage disease. We aimed to screen a population of early stage PD patients for psychiatric symptoms and to study the relation with motor and cognitive function. Thirty-six early stage PD patients underwent motor [Hoehn and Yahr (HY), Unified Parkinson’s Disease Rating Scale] and cognitive [Frontal Assessment Battery, Mini-Mental State Examination (MMSE)] assessment as well as general psychiatric [Symptom Check-List 90 (SCL-90-R)] and psychosis [Brief Psychiatric Rating Scale (BPRS)] screening. Relation between psychiatric domains scores was studied with principal component analysis. Relation between psychiatric, disease related, cognitive and motor function was assessed with bivariate correlation (Pearson). SCL-90-R scores were higher for somatization (significant scores in 66.7% of patients), depression (36.1%), anxiety (27%) and obsessive—compulsive symptoms (OCS) (52.8%). Scores were highly correlated, except for psychosis and phobia. Depression and anxiety were negatively correlated to MMSE score and dopaminergic doses, respectively. BPRS scores were higher for somatic concern, depression, anxiety and hallucinations. There was segregation between depression, anxiety, hallucinations, other positive psychotic symptoms and negative psychotic symptoms. Depression was related to MMSE score. We found a high prevalence of psychiatric complaints in PD patients, mostly related to depression, anxiety, somatization and OCS. Hallucinations were also frequent, but not associated to cognitive function or dopaminergic doses, suggesting a different physiopathological background.

Brief cognitive assessment in the early stages of Parkinson disease.

Introduction:Cognitive dysfunction is an integral part of the Parkinson disease (PD) symptom spectrum. Early detection of cognitive dysfunction could help to delineate prevention strategies. Our main objective was to study the validity of brief cognitive tests, the Frontal Assessment Battery (FAB) and Mini-Mental State Examination (MMSE), as cognitive screening tools for detecting global and executive cognitive deficits in early stages of PD, as compared to a healthy control population. Methods:We evaluated 75 early-stage PD patients and 45 healthy age-matched and education-matched controls with the MMSE (global test) and FAB (frontal test), and compared total and subtest scores. We evaluated PD motor function with the Unified Parkinson Disease Rating Scale Part III. We assessed the relationship between cognitive and motor variables. Results:Frontal and global cognitive dysfunction was significantly more frequent in PD patients. PD patients scored significantly lower on FAB total and similarities, motor series, and conflicting instructions scores, and on the MMSE total, visuoconstructive, and memory scores. MMSE scores correlated significantly with Unified Parkinson Disease Rating Scale part III total score, speech, and bradykinesia scores. Conclusions:Early-stage PD patients present with frontal, memory, and visuoconstructive deficits in brief cognitive tests. Our results suggest that these brief bedside tests are useful for cognitive deficit screening in the early stages of PD. Our study did not account for the influence of depression in cognition. This constitutes a limitation, because many PD patients have depressive symptoms, which some studies have shown can be related to cognitive dysfunction.