Staging Parkinson's Disease Combining Motor and Nonmotor Symptoms Correlates with Disability and Quality of Life.

INTRODUCTION: In a degenerative disorder such as Parkinson's disease (PD), it is important to establish clinical stages that allow to know the course of the disease. Our aim was to analyze whether a scale combining Hoehn and Yahr's motor stage (H&Y) and the nonmotor symptoms burden (NMSB) (assessed by the nonmotor symptoms scale (NMSS)) provides information about the disability and the patient's quality of life (QoL) with regard to a defined clinical stage. MATERIALS AND METHODS: Cross-sectional study in which 603 PD patients from the COPPADIS cohort were classified according to H&Y (1, stage I; 2, stage II; 3, stage III; 4, stage IV/V) and NMSB (A: NMSS = 0-20; B: NMSS = 21-40; C: NMSS = 41-70; D: NMSS ≥ 71) in 16 stages (HY.NMSB, from 1A to 4D). QoL was assessed with the PDQ-39SI, PQ-10, and EUROHIS-QOL8 and disability with the Schwab&England ADL (Activities of Daily Living) scale. RESULTS: A worse QoL and greater disability were observed at a higher stage of H&Y and NMSB (p < 0.0001). Combining both (HY.NMSB), patients in stages 1C and 1D and 2C and 2D had significantly worse QoL and/or less autonomy for ADL than those in stages 2A and 2B and 3A and 3B, respectively (p < 0.005; e.g., PDQ-39SI in 1D [n = 15] vs 2A [n = 101]: 28.6 ± 17.1 vs 7.9 ± 5.8; p < 0.0001). CONCLUSION: The HY.NMSB scale is simple and reflects the degree of patient involvement more accurately than the H&Y. Patients with a lower H&Y stage may be more affected if they have a greater NMS burden.

Mood in Parkinson's disease: From early- to late-stage disease.

BACKGROUND: Although depression is known to be frequent in Parkinson's disease (PD), it is unclear how mood can change and/or impact on patient's quality of life (QoL) over time. Our aim was to analyze the frequency of depression, mood related factors and the contribution of mood to a patient's QoL perception in regard to disease duration. METHODS: PD patients recruited from the COPPADIS cohort from January 2016 to November 2017 were included in this cross-sectional study. Three groups were defined: <5 years (Group A); from 5 to <10 years (Group B); ≥10 years (Group C). Analysis with well-planned linear regression models was conducted to determine how different factors contribute to mood (Beck Depression Inventory-II [BDI-II] as dependent variable), to health-related QoL (39-item Parkinson's Disease Questionnaire [PDQ-39SI] as dependent variable) and to global QoL (European Health Interview Survey - Quality of Life Eight-Item Index [EUROHIS-QOL8] as dependent variable). RESULTS: Six hundred and sixty-three PD patients (62.6 ± 8.9 years old, 59.6% males) were included: Group A, 50.1% (n = 332); Group B, 33.3% (n = 221) and Group C, 16.6% (n = 110). There were no differences between the three groups in terms of the frequency of depressive symptoms nor the frequency of depression type (major vs. minor vs. subthreshold) (p = 0.729). However, the unique percent variance of PDQ-39SI and EUROHIS-QOL8 explained by BDI-II total score was 2 (23.7%) and threefold (26.9%), respectively, in Group C compared to the other two groups. EUROHIS-QOL8 total score provided the highest unique contribution to mood (16.8%). CONCLUSIONS: Although depression-type frequency does not appear to change over time in PD; the contribution of mood on QoL perception is greater in patients with longer disease duration.

Quality of life and non-motor symptoms in Parkinson's disease patients with subthreshold depression.

BACKGROUND: The role of subthreshold depression (subD) in Parkinson's Disease (PD) is not clear. The present study aimed to compare the quality of life (QoL) in PD patients with subD vs patients with no depressive disorder (nonD). Factors related to subD were identified. MATERIAL AND METHODS: PD patients and controls recruited from the COPPADIS cohort were included. SubD was defined as Judd criteria. The 39-item Parkinson's disease Questionnaire (PDQ-39) and the EUROHIS-QOL 8-item index (EUROHIS-QOL8) were used to assess QoL. RESULTS: The frequency of depressive symptoms was higher in PD patients (n = 694) than in controls (n = 207) (p < 0.0001): major depression, 16.1% vs 7.8%; minor depression, 16.7% vs 7.3%; subD, 17.4% vs 5.8%. Both health-related QoL (PDQ-39; 18.1 ±â€¯12.8 vs 11.6 ±â€¯10; p < 0.0001) and global QoL (EUROHIS-QOL8; 3.7 ±â€¯0.5 vs 4 ±â€¯0.5; p < 0.0001) were significantly worse in subD (n = 120) than nonD (n = 348) PD patients. Non-motor Symptoms Scale (NMSS) total score was higher in subD patients (45.9 ±â€¯32 vs 29.1 ±â€¯25.8;p < 0.0001). Non-motor symptoms burden (NMSS;OR = 1.019;95%CI 1.011-1.028; p < 0.0001), neuropsychiatric symptoms (NPI; OR = 1.091; 95%CI 1.045-1.139; p < 0.0001), impulse control behaviors (QUIP-RS; OR = 1.035; 95%CI 1.007-1063; p = 0.013), quality of sleep (PDSS; OR = 0.991; 95%CI 0.983-0.999; p = 0.042), and fatigue (VAFS-physical; OR = 1.185; 95%CI 1.086-1.293; p < 0.0001; VAFS-mental; OR = 1.164; 95%CI 1.058-1.280; p = 0.0001) were related to subD after adjustment to age, disease duration, daily equivalent levodopa dose, motor status (UPDRS-III), and living alone. CONCLUSIONS: SubD is a frequent problem in patients with PD and is more prevalent in these patients than in controls. QoL is worse and non-motor symptoms burden is greater in subD PD patients.

COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015): an ongoing global Parkinson's disease project about disease progression with more than 1000 subjects included. Results from the baseline evaluation.

BACKGROUND AND PURPOSE: In Parkinson's disease (PD), the course of the disorder is highly variable between patients. Well-designed, prospective studies for identifying PD progression biomarkers are necessary. Our aim was to show the results of baseline evaluations of an ongoing global PD project, COPPADIS-2015 (Cohort of Patients with PArkinson's DIsease in Spain, 2015). METHODS: This was an observational, descriptive, nationwide study (Spain). The recruitment period ended in October 2017. Baseline evaluation included more than 15 validated scales and complementary studies in a subgroup of participants. RESULTS: In total, 1174 subjects from 35 centres were considered valid for baseline analysis: 694 patients (62.6 ± 8.9 years old, 60.3% males), 273 caregivers (58.5 ± 11.9 years old, 31.8% males) and 207 controls (61 ± 8.3 years old, 49.5% males). The mean disease duration was 5.5 ± 4.4 years. Hoehn and Yahr stage was 1 or 2 in 90.7% of the patients whilst 33.9% and 18.1% of them presented motor fluctuations and dyskinesias, respectively. The mean Non-Motor Symptoms Scale total score was 45.4 ± 38.1, and 30.4% of the patients presented cognitive impairment, 16.1% major depression, 12.7% impulse control disorder, 7.2% compulsive behaviour, 57.2% pain and 13.2% falls. Compared to the control group, PD patients presented a significantly higher burden of non-motor symptoms and a worse quality of life. More than 300 subjects conducted complementary studies (serum biomarkers, genetic and neuroimaging). CONCLUSIONS: Parkinson's disease is a complex disorder and different non-motor symptoms are frequently present and are more prevalent than in controls. In real clinical practice it is important to ask for them.

[Ziprasidone in Parkinsonian dopamine psychosis]. / Ziprasidona en la psicosis dopaminérgica parkinsoniana.

INTRODUCTION: The dopamine psychosis that appears in Parkinson's disease (PDP) is a complication that is often related with frequent intake of antiparkinsonian agents, especially levodopa and dopamine agonists. Morbidity and the risk of being institutionalised are increased in such patients and therapeutic management is difficult. Its treatment is based on reducing the intake of antiparkinsonian drugs or the use of atypical antipsychotics, due to the fact that they have scarce or no motor effects (at least in theory). In this work, we examine the role that ziprasidone (ZPS) can play in PDP. DEVELOPMENT: We reviewed the studies in which ZPS was used to treat PDP that have appeared in the literature. To date, very few studies have been conducted and only a small number of patients were included in each case. Nevertheless, it seems that, at doses below those used in schizophrenia (20-80 mg/day), ZPS is an effective antipsychotic. In general, the extrapyramidal side effects that do appear are infrequent and mild. Pathological laughter was detected in some patients. The drug was well tolerated and safe. CONCLUSIONS: ZPS seems to be an effective antipsychotic for PDP, with scarce or no extrapyramidal side effects; it is also safe and well tolerated. In view of the scarcity of studies and patients, however, further research is needed (if possible, by means of double-blind randomised trials) to be able to assess the true role of ZPS in PDP.

[Photic sneeze reflex or autosomal dominant compelling helio-ophthalmic outburst syndrome]. / Reflejo fótico de estornudo o síndrome de estornudos heliooftálmicos incoercibles autosómico dominante.

Sneeze is an ubiquitous phenomenon that happens to everyone. In spite of this, little attention has been paid to it, among medical literature in general, and even less in neurologic texts. A curious entity, called photic sneeze reflex, solar sneeze reflex, light sneeze reflex or autosomal dominant compelling helio-ophthalmic outburst syndrome, known perhaps since ancient Greek, has been scarcely described in the scientific literature, mainly as clinical notes and letters to the editor, but in a detailed way, we can find just a few reports. This reflex appears when subjects are exposed suddenly to intense sunlight and it consists of long incoercible sneeze bursts. It is usually ignored by its sufferers, who report it as a curiosity or a minor complaint, and its importance has been neglected in spite of its hereditary nature and its apparently high prevalence. We review the history, epidemiology, genetics, neuroanatomy, neurophysiology and physiopathology of this reflex hereditary response.

[Sneezing. A review of its causation and pathophysiology]. / El estornudo. Revisión de su etiología y fisiopatología.

AIMS: To review some of the lesser known aspects of sneezing, which is a universal phenomenon suffered the world over but which has received little attention in the medical literature and especially by that dealing with neurology. DEVELOPMENT: Here we consider the causation, neurophysiology, pathophysiology, diagnosis and treatment of this reflex action, which sometimes goes beyond being just a simple ailment of little importance and becomes a sign associated to a series of different medical conditions. CONCLUSIONS: Despite its being such a commonplace occurrence, little is known about sneezing and few studies have been conducted to further our knowledge on the subject. Today there are still reports of cases of pathological sneezers, who often respond poorly to different treatments and for whom this reflex paroxysm becomes both a social and a health problem. Moreover, sneezing is sometimes associated with severe secondary medical sequelae. In contrast, there have also been reports of conditions in which the first symptom was an inability to sneeze. A thorough knowledge of this reflex, its causes and associated phenomena can be a valuable aid in the diagnosis of other concomitant diseases.

[Autosomal dominant compelling helio-ophthalmic outburst syndrome (photic sneeze reflex). Clinical study of six Spanish families]. / Síndrome de estornudos heliooftálmicos compulsivos autosómico dominante (reflejo fótico de estornudo). Estudio clínico de seis familias españolas.

INTRODUCTION: Sneeze is an ubiquitous phenomenon that happens to everyone. In spite of this, little attention has been paid to it, among medical literature in general, and even less in neurologic texts. A curious entity, called autosomal dominant compelling helio-ophthalmic outburst syndrome, has been scarcely described in the scientific literature. This reflex appears when subjects are exposed suddenly to intense sunlight and it consists of long incoercible sneeze bursts. There are no publications on this subject among the spanish literature.and intensity increase with time. OBJECTIVE: To study the clinical and physiological features of the reflex in Spanish families. PATIENTS AND METHOD: Affected subjects were identified by personal interview and given a questionnaire drawn up for this study. Besides, they were instructed to give the questionnaire to their relatives.and intensity increase with time. RESULTS: All the six families showed a high-penetrance, autosomal dominant inheritance. The reflex had a high consistency, a latency about 3 seconds, an intersneeze interval of 2 seconds and a frequency of 2-3 sneezes/ burst. Refractory period was long.and intensity increase with time. DISCUSSION: Our study suggest a higher consistency, shorter latency and lower age of onset of the reflex in our patients than general population, and that frequency and intensity increase with time.

[The intrathecal baclofen pump in the long-term treatment of generalised dystonias]. / Bomba de baclofén intratecal en el tratamiento a largo plazo de las distonías generalizadas.

INTRODUCTION: Much has been written in the literature about the use of intrathecal baclofen in an infusion pump in spasticity, but it has only recently been applied to cases of dystonia. AIMS: The purpose of this study was to determine whether intrathecal baclofen is a therapeutic option in patients with a long history of generalised dystonias who have failed to respond to conventional treatment. CASE REPORTS: We conducted a prospective study involving five patients from whom the following data were collected: age, sex, time since the onset of dystonia and the type of dystonia. They were also chosen because they had failed to respond to any kind of treatment, including oral baclofen, but had experienced a clinical improvement following the administration of baclofen by means of a spinal tap in progressive 25, 50, 75 and 100 mg boluses. The Burke-Fahn-Marsden scale was used before and after implanting the pump to evaluate functional capacity. Of the five patients, one improved remarkably to the point of being able to lead a normal life; three others showed marked improvements, although they are still to some extent limited when it comes to carrying out certain basic activities; and in the case of the third female patient the pump had to be withdrawn due to the absence of any kind of response. CONCLUSIONS: Intrathecal baclofen is a therapy that has only recently been introduced but these results allow us to state that it does bring about an improvement in the symptoms of patients with a long history of dystonia in whom conventional treatment has failed.

[The efficiency and cost-utility ratio of interferon beta in the treatment of multiple sclerosis in Andalusia]. / Eficiencia y relación coste-utilidad del interferón beta en la esclerosis múltiple en Andalucía.

INTRODUCTION: The availability of the interferon beta in its three forms at the moment available in our country and of glatiramer acetate has marked a point of flexion in the natural history of multiple sclerosis (MS), but the high cost of these treatments cause that its use is questioned. In this work we have studied the effectiveness and efficiency of the processing with interferon beta, and the cost-utility of these treatments in MS in Spain has been also analyzed. PATIENTS AND METHODS: For this work we studied 102 patients affected of RR MS, treated with the three interferons beta which we have available in our country. We used as control 330 patients who had participated in the pivotal clinical interferon trials with both interferon beta 1a. In these patients in addition to effectiveness data, we have studied the disability measured as area below curve and the quality of life (AVACs). We also calculated the economical costs, considering the relation cost-utility in our country. RESULTS: Besides to confirm the data of effectiveness of three interferons, in this study a saving of 23 days/year is demonstrated what corresponds to 0.063 AVACs. The additional cost of interferons is greater than the avoided cost until the fifth year of treatment in which the tendency is reversed in favor of the group of treated patients, if we assume that the same effectiveness that we found in the first years is maintained in the long term. CONCLUSION: The use of the treatment with interferon beta is justified by its effectiveness, efficacy and efficiency. The additional cost of the treatment will be compensated in the long term if the effectiveness of the interferon beta is maintained.

[Multifocal motor neuropathy with conduction blocks and prurigo nodularis. A paraneoplastic syndrome in a patient with non-Hodgkin B-cell lymphoma?]. / Neuropatía multifocal motora con bloqueos de conducción y prurigo nodular. ¿Un síndrome paraneoplásico en un paciente con un linfoma no Hodgkin de tipo B?

Multifocal motor neuropathy with conduction blocks (MMNCB) is a peripheral demyelinating neuropathy. The etiology of this disease is unknown, but an autoimmune origin is postulated. Prurigo nodularis (PN), a chronic dermatosis also having an unknown etiology and many peripheral neuropathies of different nature are associated to hematological tumors. We have found no cases in the literature in which MMNCB was presented as a paraneoplastic syndrome of a non-Hodgkin B-cell type lymphoma (NHL-B). We present the case of a 67 year old man who simultaneously developed PN and MMNCB in upper limbs and who was diagnosed of a NHL-B 19 months later. We raise the hypothesis that both prurigo and neuropathy are a paraneoplastic syndrome for lymphoma with a possible common autoimmune pathogenic mechanism.

[The use of magnetic resonance imaging in the study of asymptomatic familial multiple sclerosis patients]. / Estudio de pacientes asintomáticos de esclerosis múltiple familiar mediante resonancia magnética.

INTRODUCTION: Multiple sclerosis (MS) is the neurological non-traumatic disease that produces permanent incapacity in the young people with the greatest frequency. An almost total consensus exists on the implication of environmental and genetic factors in the pathogenesis of the disease. In a considerable percentage of patients, antecedent relatives of other cases of MS exist, who are separated by other healthy relatives sometimes. AIMS: We try to study the familial antecedents of the MS patients, to locate to the healthy members of the family including in the forced line of the possible genetic transmission of the disease and ruling out subclinical involvement by the use of magnetic resonance imaging (MRI). PATIENTS AND METHODS: We reviewed the familial antecedents of the MS patients followed by the MS Unit of the Service of Neurology of the Hospital Virgen Macarena of Seville. After the accomplishment of their genealogical trees, we identified the cases of familial MS. We locate and practice MRI on the healthy subjects of the family, who are in the genetic line of communication of the disease (obligate carriers). RESULTS AND CONCLUSIONS: We were able to identify 14 obligate carriers of the gene in 12 of the families. In the MRIs that were done, we found MS-compatible lesions in 10 subjects. These findings confirm the existence of silent forms of the disease, that make difficult the knowledge of the genetic implications in the pathogenesis of the disease.