Motor and non-motor symptoms of Parkinson's disease and their impact on quality of life and on different clinical subgroups. / Síntomas no motores y motores en la enfermedad de Parkinson y su relación con la calidad de vida y los distintos subgrupos clínicos.

INTRODUCTION: The aim of the present study is to analyse the influence that motor and non-motor symptoms have on the quality of life (QoL) of patients with Parkinson's disease (PD), and to study the relationship between the two types of symptoms. MATERIAL AND METHODS: This cross-sectional study included 103 patients with PD (55 men and 48 women). Quality of life was measured on the PDQ-39 scale. The UPDRS scale (I-IV) was also used, and different items were grouped to analyse the presence of tremor, rigidity, bradykinesia, and axial symptoms. The non-motor symptoms scale (NMSS) was administered to assess non-motor symptoms. We performed correlation analyses between different scales to analyse the influence of motor and non-motor symptoms on QoL. RESULTS: Correlations were observed between the PDQ-39 summary index (PDQ39_SI) and the NMSS (correlation coefficient [cc], 0.56; p<.001), UPDRS III (cc, 0.44; p< .001) and UPDRS IV (cc, 0.37; p<.001) scores. The strongest correlation was between cognitive symptoms and mood. The analysis pointed to a direct relationship between the NMSS score and axial symptoms (cc, 0.384; p<.01), bradykinesia (cc, 0.299; p<.01), and to a lesser extent, rigidity (cc, 0.194; p<.05). No relationship was observed between presence of tremor and the NMSS score. CONCLUSION: Cognitive symptoms and mood exert the most influence on QoL of patients with PD. We found at least two phenotypes; one with predominantly axial symptoms, with significant involvement of non-motor symptoms, and a tremor-associated phenotype in which these symptoms are less prevalent.

Cardiocirculatory manifestations in Parkinson's disease patients without orthostatic hypotension.

The objective of this study was to characterize cardiac sympathetic denervation in Parkinson's disease (PD) patients without neurogenic orthostatic hypotension (NOH), both in terms of hemodynamics and in its relation with vascular denervation. We studied 20 PD patients without NOH. We analyzed the heart rate and blood pressure variability during various physical maneuvers. The following parameters were calculated: expiratory-inspiratory ratio, stroke volume, cardiac output, cardiac index, left ventricular ejection time, left ventricular work index, thoracic fluid content, total peripheral resistance and baroreflex sensitivity (BRS). We also measured direct and spectral derivatives of cardiac (cardiovagal) parasympathetic function. Myocardial I-123 metaiodobenzylguanidine (MIBG) scintigraphy was performed and early and late heart/mediastinum uptake ratios were analyzed. We observed that the late heart/mediastinum uptake ratio was 1.33±0.21. This parameter was correlated with years since diagnosis (correlation coefficient:-0.485; P=0.05), Unified Parkinson's Disease Rating Scale (UPDRS) III score (cc:-0.564; P=0.02) and pressure recovery time in the Valsalva maneuver (cc: 0.61; P<0.001). At rest, it was correlated with BRS (cc:0.75; P=0.003) and low-frequency diastolic blood pressure (LFDBP; cc: 0.58;P=0.017). We found no correlations with any of the cardiography impedance variables. In linear regression models, the variable that best correlated with MIBG results was LFDBP. Our results support that in absence of NOH the degree of denervation of the heart does not produce any effect on its inotropic function. Moreover, BRS and LFDBP can be used as an indirect measure of cardiac sympathetic denervation at rest.

Hirayama disease: Is surgery an option?

INTRODUCTION: Hirayama disease is a rare cervical myelopathy, predominantly affecting young males, which presents with distal atrophy of the upper limbs as its first and main symptom. It must be differentiated from motor neuron diseases because its natural history is different and because HD tends to stabilise in less than 5 years. Diagnosis is based on clinical findings and dynamic flexion MRI showing segmental spinal muscular atrophy, detachment of the posterior dura mater and venous congestion in the epidural space. The tendency is to indicate conservative treatment and no indications for surgery have been established. PATIENTS: We present 4 cases meeting both clinical criteria and dynamic MRI imaging criteria for a diagnosis of Hirayama disease. Two have stabilised spontaneously over the course of many years, and MRI scans show that typical changes have disappeared. Another case also remains stable following a shorter observation time. The fourth case is a young man who developed severe myelopathy in just over a year, and therefore underwent surgery. While his follow-up time is still short, his condition remains stable. CONCLUSIONS: Our 4 cases suggest that the condition of most patients with Hirayama stabilises naturally; patients should be evaluated for surgery on an individual basis, and surgery should probably be limited to the most severe cases that have progressed quickly.

Cardiac sympathetic denervation precedes nigrostriatal loss in the E46K mutation of the alpha-synuclein gene (SNCA).

INTRODUCTION: Here we report the case of an asymptomatic carrier of the E46K substitution in alpha-synuclein gene where we have documented that cardiac sympathetic denervation precedes nigrostriatal dopaminergic loss. MATERIAL AND METHODS: She has been followed up regularly with standard neurological examination, UPDRS, neuropsychological formal testing, parkinson disease sleep scale-PDSS, Epworth scale, Hamilton-D scale, SCOPA Aut, orthostatic hypotension test, brief smell identification test, polysomnography, cerebral 123-I-FP-CIT SPECT, and, 123I-MIBG cardiac scintigraphy. RESULTS: She shows no presence of orthostatic hypotension. Olfactory test results demonstrate normal limits. In the PSG the nocturnal sleep shows mild abnormalities although the sleep efficiency and stage proportion remain under normal limits. The 123-I-FP-CIT SPECT is normal; in contrast, the 123I-MIBG cardiac scintigraphy shows a complete lack of isotopic uptake compatible with a severe sympathetic myocardial denervation. CONCLUSION: This example of monogenic autosomal dominant parkinsonism due to an alpha-synuclein mutation favours the hypothesis that peripheral autonomous nervous system involvement occurs earlier than the CNS degeneration.

Prevalence of neuropsychiatric symptoms in mild cognitive impairment and Alzheimer's disease, and its relationship with cognitive impairment.

OBJECTIVE: The study aimed to describe the prevalence of Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD), amnestic mild cognitive impairment (MCI) and controls using the 12-item Neuropsychiatric Inventory (NPI) and to analyze the relationships between neuropsychiatric symptoms with specific neuropsychological tests. PATIENTS AND METHODS: We prospectively studied 485 patients from the Memory Unit in Cruces Hospital (Spain), 344 met the criteria of NINCDS-ADRDA for probable AD (99 were classified as mild and 245 as moderate-severe), 91 for MCI and 50 were controls. Mini-mental State Examination (MMSE) and CDR (Clinical Dementia Rating) were used to evaluate global cognitive function and to classify the severity of cognitive impairment. The neuropsychological test battery included memory test, verbal fluency, visuoespatial skills and daily living scales. The 12-items Neuropsychiatric Inventory (NPI) version was used to assess neuropsychiatric symptoms. All patients underwent a neuroimaging study (CT scan and/or MRI). Patients were not treated with antidementia or psychotropic drugs. RESULTS: Apathy and depression were more prevalent NPS in moderate-severe AD (78.4% and 44.1%, respectively), mild AD (64.6% and 41.4%, respectively) and MCI (50.5% and 33%, respectively) patients than in controls (6% and 8%, respectively). The prevalence and the mean scores of all symptoms increased along the severity of the disease, except for sleep and appetite disorders. In patients with mild AD a relationship was found between the presence of NPS and RDRS-2 scale (p = 0.003); and between NPS and RDRS-2 (p = 0.029) and SS-IQCODE scales (p = 0.039) in moderate-severe patients. CONCLUSIONS: NPS were more prevalent in AD and MCI patients than in controls. In AD and MCI patients apathy and depression were the most prevalent NPS. The prevalence and the mean scores of all symptoms gradually increased along the severity of the disease, except for sleep and appetite disorders. We have no found a relationship between neuropsycological test and the presence of NPS, but in patients with mild and moderate-severe AD there is a relationship with daily living scales.

[Sleep disorders in Parkinson's disease: REM sleep behaviour disorder and restless legs syndrome]. / Trastornos del sueño en la enfermedad de Parkinson: trastorno de conducta del sueño REM y síndrome de piernas inquietas.

INTRODUCTION: It is well known that patients with Parkinson's disease (PD) and other neurodegenerative diseases very commonly present sleep disorders, and that they possibly share common pathophysiological mechanisms with motor signs. DEVELOPMENT: In the case of REM sleep behaviour disorder, a number of studies have shown that it may appear more than ten years before the motor signs. Although there is no evidence to prove that patients with restless legs syndrome have an increased risk of suffering from PD, the high prevalence of this symptom in PD and the good response to dopamine agonists suggest the existence of a relation between the two conditions. CONCLUSIONS: The impact that these conditions have on patients' quality of life makes it very important to know how to diagnose and treat them.

Application of depression criteria (DSM-IV) in patients with Parkinson's disease.

INTRODUCTION: The aim of this study is to analyze the clinical differences between Parkinson's disease patients with major (MD) and minor depression (md) and to see how both affect the quality of life. MATERIAL AND METHODS: 118 patients diagnosed with Parkinson's disease. The mean age of onset was 60.4+/-11.2 years with a mean duration of 8.5+/-6.2 years. Depression was diagnosed according to DSM-IV-TR criteria. Scores on the Hamilton depression inventory, MMSE, PDQ-39, NPI-10, UPDRS III, and UPDRS IV were recorded. RESULTS: Twenty-one patients (17.8%) met the criteria of major depression (MD) and 33 (28.0%) those of minor depression (md). The scores on the PDQ-39 and NPI-10 of patients with MD were higher than in patients with md, and control group. The MMSE scores were lower in patients with MD. In 52.2% of the patients with MD, the diagnosis of depression was made prior to that of PD, this occurred only in 24.2% of the patients with md (p<0.001). The presence of anhedonia was related to cognitive impairment and the presence of neuropsychiatric symptoms. DISCUSSION: MD is probably a part of the disease process of PD; it is associated with cognitive impairment and may precede motor symptoms.

[Tics and Gilles de la Tourette syndrome]. / Tics y síndrome de Gilles de la Tourette.

INTRODUCTION: Tourette syndrome is a neurologic disorder characterized by involuntary vocal and motor tics. It affects around 1 to 2% of school-age children and is the most common movement disorder in paediatric age. Tics are involuntary or semivoluntary, sudden, brief, intermittent, repetitive movements (motor tics) or sounds (phonic tics). It is often associated with psychiatric comorbidities, mainly attention-deficit/hyperactivity disorder and obsessive-compulsive disorder. Given its diverse presentation, Tourette's syndrome can almost mimic many hyperkinetic disorders, making the diagnosis challenging at times. DEVELOPMENT: The etiology of this syndrome is thought to be related to basal ganglia dysfunction and many clues have been pursued, both genetic and environmental factors, but no compelling major contribution to the pathogenesis of the disease has yet emerged. Treatment can be behavioural, pharmacologic, or surgical, and is dictated by the most incapacitating symptoms. Alpha-2-adrenergic agonists are the first line of pharmacologic therapy, but dopamine-receptor-blocking drugs are required for multiple, complex tics. Dopamine-receptor-blocking drugs are associated with potential side effects. CONCLUSION: Appropriate diagnosis and treatment can substantially improve quality of life and psychosocial functioning in affected patients.

[Motor fluctuations and dyskinesias in Parkinson's disease: variables that discriminate both complications in a sample of 285 patients]. / Fluctuaciones motoras y discinesias en la enfermedad de Parkinson: variables que discriminan ambas complicaciones en una muestra de 285 pacientes.

INTRODUCTION: A large proportion of patients with Parkinson's disease suffer fluctuations and dyskinesias in the course of the disease. The present study explores the variables that predict the appearance of these complications. PATIENTS AND METHODS: This is a cross-sectional study that studies 285 patients with Parkinson's disease. Patient's age, date of diagnosis and of treatment with levodopa and motor situation (UPDRS III) were recorded. Drugs and doses were documented. Finally, levodopa equivalent dose in those patients using agonists or prolonged release formulations was calculated. RESULTS: Mean age of the patients was 71.1 years (+/-9.1). Disease duration was 8.7 years (+/-11.8). A total of 118 patients (41.4%) presented motor fluctuations, and 61 patients (21.4 %) had dyskinesias. Two discriminant analytical models were established. In the first model, the dependent variable was the presence of fluctuations, and three variables significantly discriminated between the two groups: the levodopa equivalent dose, the duration of treatment with levodopa and the motor situation. In the second model the presence of dyskinesias constituted the dependent variable. The only variable selected by this model was the levodopa equivalent dose. DISCUSSION: The duration of treatment with levodopa, the doses of agonists and levodopa and the motor situation differentiate patients with fluctuations from those without them. In the case of dyskinesias, only the agonists and levodopa doses were selected by the analytical model.

Influence of motor symptoms upon the quality of life of patients with Parkinson's disease.

We studied the impact of various motor and nonmotor symptoms upon quality of life in patients with Parkinson's disease (PD). The study comprised 110 patients with PD (age: 68.6 years, course of the disease: 7.6 years). The Unified Parkinson Disease Rating Scale (UPDRS; I-IV) and Parkinson's Disease Questionnaire (PDQ-39) were recorded. We recorded the correlations between years of disease and UPDRS IV, as well as PDQ-39 and UPDRS I, II, III and IV. Introduction of all variables into a linear regression model showed that 3 variables accounted for 51% of the variance in PDQ-39. Mental condition, gait disorders and complications of dopaminergic drugs are the variables that most affect the quality of life of patients with PD.

Monozygotic twins suffering from Huntington's disease show different cognitive and behavioural symptoms.

Monozygotic male twins, carrying the same number of trinucleotide repeats in the IT 15 Huntington disease (HD) gene, showed a different clinical course. Patient 1 presented with anxiety and chorea at the age of 40. Patient 2 showed persecution paranoia and motor impersistence at the age of 42. Both patients were monitored for 30 months using currently recommended motor and behaviour scales. No differences were observed in motor scoring besides small interevaluation fluctuations. However, on the cognitive and behaviour scales, patient 1 showed a significant worsening when compared with patient 2. Our cases support the belief that the motor symptoms and signs in HD are highly dependent on the trinucleotide expansion. However, the differences in the evolution of mental status in our patients suggest that other still unknown environmental factors are important in the phenotypic expression of Huntington's disease.

[Prion diseases]. / Enfermedades priónicas o prionpatías.

Prion diseases are one of the paradigms of modern neurological nosology founded on molecular grounds. Their incidence is low, however the public health challenges derived from their transmissibility, especially due to the appearance of a variant of Creutzfeldt-Jakob disease (vCJD) confers them a preferential place among health care authority concerns. The evolution of data from the European surveillance systems suggests a generalized underdiagnosis of prion diseases and casts doubts about their ability to detect a possible second wave of atypical vCJD, especially if their clinical-pathological characteristics change. Recent data also challenge the feasibility of a subclassification of prion diseases according to their genetic-molecular features