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.

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.

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.

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.

[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.

[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.

Serum endothelial adhesion molecules levels correlate with lesion burden in multiple sclerosis patients treated with interferon beta-1b.

The levels of serum-soluble intracellular adhesion molecule-1 and soluble endothelial-leukocyte adhesion molecule-1, and the Gadolinium-enhanced T1-weighted MRI were studied in a group of patients with relapsing-remitting multiple sclerosis treated with interferon beta-1b and compared to a non-treated control group. The levels of serum-soluble intracellular adhesion molecule-1 and soluble endothelial-leukocyte adhesion molecule-1 increased, after three months treatment, as compared to baseline and the non-treated MS patients. A significant correlation was found in the treated group between serum-soluble endothelial-leukocyte adhesion molecule-1 and the lesion area in the Gadolinium-enhancing (T2 weighted scan) MRI.

[Benign atheroembolic syndrome secondary to systemic fibrinolysis with streptokinase]. / Síndrome ateroembólico de curso benigno secundario a fibrinólisis sistémica con estreptoquinasa.

We present the case of an 60-year-old male patient that after a acute myocardial infarction inferior diagnostic was subjected to a fibrinolysis with streptokinase. The evolution from the cardiologic point of view was favourable, but at fourth day postacute myocardial infartion he starts with peripherics vasculars symptoms, pain and livedo reticularis in lower part of the body. A symptomatic treatment was made requiring amputation of his fifth right toe. The evolution was towards healing without any organic afectation at another level.

[Scleroderma with traces of disseminated lupus erythematosus associated with Hashimoto's thyroiditis and papillary carcinoma of the thyroid gland (author's transl)]. / Esclerodermia con rasgos de lupus eritematoso diseminado (conectivopatía de superposición), asociada a tiroiditis de Hashimoto y carcinoma papilar de tiroides.

The coexistence of organ-specific and nonorgan-specific autoimmune diseases is an interesting phenomenon. A 52-year-old woman was admitted with fever, general discomfort, polyarthritis, and Raynaud's phenomenon. Physical examination revealed a goiter of stony consistency, hardening, paleness, and atrophy of the skin on the face and upper limbs, and blood hypertension (180/110 mmHg). The biological data included leukopenia, moderate anemia, and a very high sedimentation rate. The latex test was positive (+++); LE cells positive (+); hypergammaglobulinemia (3.5 g); antinuclear antibodies, 1/1280 with an immunofluorescence granular pattern; antithyroid antibodies, 1/160. There was pulmonary, renal, and gastrointestinal involvement compatible with scleroderma, which was confirmed by skin biopsy. A thyroidectomy revealed the existence of a papillary carcinoma with thyroiditis. Responde to treatment with immunosuppressive agents, hypotensive drugs, and thyroid substitution therapy was initially good. The patient was readmitted 8 months later with general discomfort and a severe hyperproteinemia (10 g/100 ml), including 65 percent gammaglobulin and requiring various sessions of plasmapheresis. The patient was discharged, but died suddenly 4 months later. The association of lupus and scleroderma in this patient is discussed and the possibility of its being a mixed connective tissue disease is discarded. The association of this condition with Hashimoto's thyroiditis, and the latter with papillary carcinoma of the thyroid are analyzed. The peculiar features of this case are pointed out. The authors postulate that the cause of the sudden death was a vascular cerebral complication induced by the extreme hyperproteinemia.

Tamponade as the clinical onset of a cardiac angiosarcoma.

Primary tumors of the heart are usually benign, with the malignant forms being rare. In this article we report the case of an angiosarcoma with the only manifestation being a cardiac tamponade. When the patient being admitted to the hospital, an important differential diagnosis was pulmonary tumor. A mass in the right atrium was later detected in the echocardiogram. Further image studies, such as MRI, showed spectacular images of this mass suggestive of neoplasm. An intra-operatory biopsy diagnosed the mass as an angiosarcoma. Since there was no evidence of primary neoplasm in other studies carried out, the neoformation was diagnosed as a primary angiosarcoma. Surgery was carried out with a survival of only 13 months after the procedure. We also use this case to make a brief review of the primary tumors of the heart, especially angiosarcomas.

[Hypothyroidism concealed by Parkinson's disease]. / Hipotiroidismo enmascarado por enfermedad de Parkinson.

AIMS: Although it is commonly recognised that diseases of the thyroids can simulate extrapyramidal disorders, a review of the causes of Parkinsonism in the neurology literature shows that they are not usually mentioned or, if so, only very briefly. The development of hypothyroidism in a patient with Parkinson s disease can go undetected, since the course of both diseases can involve similar clinical features. Generally speaking there is always an insistence on the need to conduct a thyroidal hormone study in any patient with symptoms of Parkinson, but no emphasis is put on the need to continue to rule out dysthyroidism throughout the natural course of the disease, in spite of the fact that the concurrence of both pathological conditions can be high and that, in the same way hypothyroidism can simulate Parkinson s disease, the latter can also conceal hypothyroidism. CASE REPORT: We report the case of a female patient who had been suffering from Parkinson s disease for 17 years and started to present on off fluctuations that did not respond to therapy. Hypothyroidism was observed and the hormone replacement therapy used to resolve the problem allowed the Parkinsonian fluctuations to be controlled. CONCLUSIONS: We believe that it is very wise to suspect hypothyroidism in patients known to be suffering from Parkinson s disease, and especially so in cases where the clinical condition worsens and symptoms no longer respond properly to antiparkinsonian treatment. These observations stress the possible role played by thyroid hormones in dopaminergic metabolism and vice versa.

[Neuropsychiatric disorders in multiple sclerosis]. / Trastornos neuropsiquiátricos en la esclerosis múltiple.

OBJECTIVE: Neuropsychological investigations over the past 20 years have shown the high prevalence of cognitive dysfunction in multiple sclerosis, although there are still large gaps. In this article we review current concepts regarding the different types of neuropsychiatric disorders, their physiopathology, diagnosis and treatment. DEVELOPMENT: We present a classification of the most important types of cognitive and psychiatric alterations in multiple sclerosis, and their physiopathology. We review the methods used in diagnosis, follow up and assessment of these patients. Finally, we analyze the current treatment available for each of these disorders. CONCLUSIONS: Although considerable advances have been made in understanding the neuropsychological disorders occurring in multiple sclerosis, there are still many questions to be answered. There is a need for a unified, agreed, validated battery of neuropsychological tests for the study of specific cognitive deficits in multiple sclerosis so that results may be compared. There is also a lack of biological markers which would help in diagnosis and prognosis. Finally the design and carrying out of clinical trials in the search for specific, effective drugs for the treatment of neuroconductual disorders of multiple sclerosis is necessary.

[Myelographic diagnosis of an epidural arterio-venous fistula]. / Diagnóstico mielográfico de una fistula arteriovenosa epidural.

INTRODUCTION: Epidural arterio-venous fistulae are a little known clinical condition. They are probably commoner than is thought, since diagnosis and angiographic demonstration are difficult. CLINICAL CASE: We present the case of a 49 year old man with the clinical features of chronic myelo-radiculopathy with episodes of intermittent medullary claudication. This shows the use of myelography, which in certain cases allows clear detection of vascular structures which might otherwise pass unnoticed. CONCLUSIONS: One should think of this condition when compatible features are found and there is no other diagnosis, since if confirmed by myelography and/or magnetic resonance prior to angiographic study, it may benefit from embolization, which is an effective treatment for this.

[Intrathecal perfusion pump with baclofen in generalized dystonia]. / Bomba de perfusión intratecal de baclofén en la distonía generalizada.

OBJECTIVES: We show the effectiveness of treatment with continuous intrathecal baclofen infusion in a case of hereditary generalized dystonia refractory to anticholinergics, tetrabenazine, pimozide, L-dopa, benzodiazepines and thalamotomy. CLINICAL CASE: A 26 years old female patient, when she was 11 years old began with torsion dystonia in her left feet, that progressively worsened to involve her entire body. She had painful spasms. She had four brothers, three of them with dystonia and one healthy. Her uncle grandfather had similar symptoms. Complementary explorations to reject secondary origin was negatives. She was treated with high and progressive dosages of anticholinergics, pimozide, tetrabenazine, benzodiazepines, L-dopa and thalamotomy without improvement. Underwent intrathecal baclofen test dosing, we used 25, 50, 100 micrograms/day, the last one with improvement during 10 hours. A pump was inserted with an initial dose of 220 micrograms/day. After pump insertion, baclofen dosage was gradually increased to 450 micrograms/day. She had a great improvement in right part of her body and less in her left body. Painful spasms had disappeared. CONCLUSION: We propose continuous baclofen intrathecal infusion pump for patients with severe torsion dystonia that not response to ordinal treatment.

[Pseudotumour cerebri in a patient with Lyme disease and hypothyroidism]. / Pseudotumor cerebri en un paciente con enfermedad de Lyme e hipotiroidismo.

INTRODUCTION: Lyme disease is a complex infectious disease affecting multiple organic systems. The most frequent complications are of a dermatological, rheumatological, ophthalmological, cardiac and neurological nature. Among the neurological complications, pseudotumour cerebri is considered to be a rare manifestation of the disease. Hypothyroidism, however, is known to be only infrequently associated to pseudotumour cerebri. Paparone recently reported a case in which Lyme disease and primary hypothyroidism were concurrent, and Becker and Trock described the case of three patients with concurrent thyrotoxicosis and Lyme disease. CASE REPORT: We present the case of a 19 year old female with pseudotumour cerebri and hypothyroidism secondary to autoimmune thyroiditis, which improved after treating her for concomitant Lyme. CONCLUSIONS: We suggest there is a common aetiopathogenic connection between the three processes through autoimmune thyroiditis triggered by Borrelia burgdorferi. Thus, in this patient, the pseudotumour cerebri could be due to either a direct mechanism, triggered by B. burgdorferi, or indirectly, through hypothyroidism secondary to thyroiditis induced by B. burgdorferi, or perhaps to both mechanisms. It might be wise to consider infection by B. burgdorferi in patients with pseudotumour cerebri or thyroiditis coming from areas in which Lyme disease is endemic

[Neuroborreliosis in a patient with progressive supranuclear paralysis. An association or the cause?]. / Neuroborreliosis en un paciente con parálisis supranuclear progresiva: asociación o causa?

INTRODUCTION: Many different neurological conditions may be seen in the later stages of Lyme's Disease, such as blindness, epileptic crises, CVA, extrapyramidal disorders, amyotrophic lateral sclerosis, and dementia may be yet another form of presentation of chronic infection due to Borrelia burgdorferi (Bb). Progressive Supranuclear Paralysis (PSP), a disorder of unknown aetiology, considered to be the commonest cause of Parkinsonism-plus, one of the symptoms of which is dementia, has never been mentioned in this type of differential diagnosis. CLINICAL CASE: We present the case of a 78 year old man with sub-acute mental deterioration, Bb positive serology in both plasma and CSF, and with clinical and epidemiological features compatible with Lyme's Disease. Complementary tests were negative. The syndrome corresponded to Lyme's Disease and improved after treatment with ceftriaxona. CONCLUSIONS: We consider aspects of the aetiology of PSP which are still not clear. In our patient, the aetiology seemed to be Bb infection, according to the criteria of the original description of the disease and in view of the neuropathological findings which have shown Bb in the substancia nigra of the mid-brain and the existence of an animal model in which Bb shows a particular tendency to colonize infratentorial structures.

[Familial cerebral cavernomatosis associated with cutaneous angiomas]. / Cavernomatosis cerebral familiar asociada a angiomas cutáneos.

UNLABELLED: OBJECTIVE, PATIENTS AND METHOD: We present a genealogical study of a person with familial cerebral cavernomatosis (CCF) discovered following study of a man who presented with status epilepticus at the age of 35 years. This had also affected another three members of the family consisting of a total of 43 persons, studied over six generations. RESULTS: In the family members studied we did not find cavernomas at other sites but there were dermatological lesions whose relation to cerebral cavernomas (CC) is discussed. CCs are the second commonest type of cerebral vascular malformations. Their major clinical features are epilepsy and cerebral haemorrhage. There are two forms of CC: a sporadic form with single lesions and a familial form with multiple lesions. Although the condition has been recognized since 1854, very little is known about it. Recently a gene causing the familial form has been found on chromasome 7. CONCLUSIONS: We discuss the clinical findings in this family with relation to descriptions in the literature. We emphasize the importance of MR in diagnosis of the condition and for detection of asumptomatic carriers. We consider a possible relationship between these findings and genes which have been mapped, and in view of recent genetic data, the hypothesis of a possible Spanish ancestor with the condition.