RESUMO
OBJECTIVES: In Parkinson's disease (PD), Parkinson's disease dementia (PDD) and Parkinson's disease-mild cognitive impairment (PD-MCI) are common. PD-MCI is a risk factor for developing PDD. Knowledge of cognition in early-stages PD is essential in understanding and predicting the dementia process. MATERIALS AND METHODS: We describe the cognitive profile in early-stage PD patients with no prior clinical suspicion of cognitive impairment, depression or psychiatric disturbances, and investigate possible features distinguishing patients with cognitive deficits, defining a PD-MCI risk-profile. Single Photon Emission Computerized Tomography (SPECT) DaT-scan and neurological examination confirmed the diagnosis. Mini-mental state examination-, Addenbrooke's Cognitive Examination, Unified Parkinson's Disease Rating Scale scoring, Hoehn &Yahr/Activity of Daily Living staging and a neuropsychological test battery were applied. Mild cognitive impairment patients were identified according to modified criteria by Troster necessarily omitting subjective cognitive complaints. 80 patients, mean age 61.0 years (SD 6.6), mean duration of disease 3.4 years (SD 1.2) were included. 76 patients were neuropsychologically tested. RESULTS: 26 (34%) patients fulfilled modified PD-MCI criteria, 18 (69%) of these showed episodic memory deficits, 14 (54%) executive dysfunction, 13 (50%) language/praxis deficits, 12 (46%) visuospatial/constructional deficits and 9 (35%) attention/working memory deficits. Cognitive impairment was associated with higher Unified Parkinson's Disease Rating scale (UPDRS)-, bradykinesia- and rigidity scores and more symmetric distribution of symptoms, but not tremor scores. Patients with cognitive impairment were less educated. Other demographic and clinical variables were comparable. CONCLUSIONS: 34% of early-stage PD patients without prior clinical suspicion of cognitive impairment exhibit cognitive impairment, which is associated to disease severity, especially bradykinesia, rigidity, axial symptoms and less asymmetry of motor symptoms, even at early disease stages and when cognitive symptoms are mild.
Assuntos
Transtornos Cognitivos/etiologia , Doença de Parkinson/psicologia , Transtornos Cognitivos/epidemiologia , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Feminino , Humanos , Hipocinesia/epidemiologia , Hipocinesia/etiologia , Masculino , Pessoa de Meia-Idade , Rigidez Muscular/epidemiologia , Rigidez Muscular/etiologia , Testes Neuropsicológicos , Doença de Parkinson/epidemiologia , Índice de Gravidade de DoençaRESUMO
A classic question in evolutionary biology concerns the tempo and mode of lineage evolution. Considered variously in relation to resource utilization, intrinsic constraints or hierarchic level, the question of how evolutionary change occurs in general has continued to draw the attention of the field for over a century and a half. Here we use the largest species-level phylogeny of Coenozoic fossil mammals (1031 species) ever assembled and their body size estimates, to show that body size and taxonomic diversification rates declined from the origin of placentals towards the present, and very probably correlate to each other. These findings suggest that morphological and taxic diversifications of mammals occurred hierarchically, with major shifts in body size coinciding with the birth of large clades, followed by taxonomic diversification within these newly formed clades. As the clades expanded, rates of taxonomic diversification proceeded independently of phenotypic evolution. Such a dynamic is consistent with the idea, central to the Modern Synthesis, that mammals radiated adaptively, with the filling of adaptive zones following the radiation.
Assuntos
Evolução Biológica , Tamanho Corporal , Fósseis , Mamíferos/anatomia & histologia , Paleontologia/métodos , Animais , Mamíferos/genética , Fenótipo , Filogenia , Análise de RegressãoRESUMO
BACKGROUND: The role of electromyography (EMG) recorded from the external anal sphincter (EAS) in the diagnosis of atypical parkinsonian syndromes is a matter for continuous debate. Most studies addressing this issue are retrospective. METHODS: In this study, we prospectively investigated six patients with Parkinson's Disease (IPD), 14 patients with multiple system atrophy (MSA) and eight with progressive supranuclear palsy (PSP) using EMG of the EAS, motor-evoked potential (MEP) to the EAS and EMG of m. gastrocnemius and nerve conduction velocity measured at the sural nerve. Patients were followed up for 2 years to secure correct diagnosis. RESULTS: The mean duration of motor unit potentials (MUPs) recorded from the EAS was significantly longer in patients with MSA and PSP compared with MUPs recorded from patients with PD (P < 0.005 for both). There were no signs of diffuse loss of motor neurons or peripheral neuropathy. MEP revealed signs of supranuclear affection in patients with MSA, whereas in patients with PSP the mechanism is a focal loss of motor neurons in Onuf's nucleus. CONCLUSION: Abnormal EMG of the EAS is strongly suggestive of atypical parkinsonism and the pathophysiology may be different in patients with MSA and PSP.
Assuntos
Canal Anal/fisiopatologia , Eletromiografia/métodos , Transtornos Parkinsonianos/diagnóstico , Transtornos Parkinsonianos/fisiopatologia , Idoso , Potenciais Evocados/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atrofia de Múltiplos Sistemas/diagnóstico , Atrofia de Múltiplos Sistemas/fisiopatologia , Estudos Prospectivos , Paralisia Supranuclear Progressiva/diagnóstico , Paralisia Supranuclear Progressiva/fisiopatologiaRESUMO
Patients with hereditary spastic paraplegia (HSP) are often treated with antispastic drugs to relieve symptoms but documentation is lacking. In this study, gabapentin was tested in a double-blind crossover trial on a group of patients with HSP and linkage to the SPG4 locus. There was no difference between periods with gabapentin and placebo treatment in clinical assessment, self-reported parameters or paired transcranial magnetic stimulation evaluation of motor cortical excitability.
Assuntos
Adenosina Trifosfatases/genética , Aminas/uso terapêutico , Anticonvulsivantes/uso terapêutico , Ácidos Cicloexanocarboxílicos/uso terapêutico , Paraplegia Espástica Hereditária/tratamento farmacológico , Paraplegia Espástica Hereditária/genética , Ácido gama-Aminobutírico/uso terapêutico , Adulto , Idoso , Estudos Cross-Over , Método Duplo-Cego , Feminino , Gabapentina , Humanos , Masculino , Pessoa de Meia-Idade , Espastina , Estatísticas não ParamétricasRESUMO
Dobrynin et al. (Genome Biol 16:277, 2015) recently published the complete genome of the cheetah (Acinonyx jubatus) and provided an exhaustive set of analyses supporting the famously low genetic variation in the species, known for several decades. Their genetic analyses represent state-of-the-art and we do not criticize them. However, their interpretation of the results is inconsistent with current knowledge of cheetah evolution. Dobrynin et al. suggest that the causes of the two inferred bottlenecks at â¼ 100,000 and 10,000 years ago were immigration by cheetahs from North America and end-Pleistocene megafauna extinction, respectively, but the first explanation is impossible and the second implausible.
Assuntos
Acinonyx/genética , Genoma , Animais , MasculinoRESUMO
Seventy-eight patients admitted with their first cerebrovascular episode of presumed ischemic origin were evaluated during the first 24 hours to decide whether the differential diagnosis of stroke versus transient ischemic attacks (TIAs) could be made earlier than after 24 hours, if the initial degree of neurologic deficit and the persistence of symptoms beyond a certain limit of time were taken into account. Within 1 hour, 50% of TIA cases had recovered, and 90% had recovered within 4 hours. Neurologic deficit graded by a score at onset was significantly less in TIA patients than in stroke patients. We concluded that persistence of symptoms beyond a few hours and to a lesser extent the severity of symptoms at onset or at admission give a reliable indication of the diagnosis.
Assuntos
Ataque Isquêmico Transitório/fisiopatologia , Arteriopatias Oclusivas/complicações , Angiografia Cerebral , Artérias Cerebrais , Transtornos Cerebrovasculares/classificação , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/fisiopatologia , Constrição Patológica , Avaliação da Deficiência , Feminino , Humanos , Ataque Isquêmico Transitório/classificação , Ataque Isquêmico Transitório/complicações , Ataque Isquêmico Transitório/diagnóstico por imagem , Masculino , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
The present study evaluates an assay of cytotoxic effect of plasma from patients with amyotrophic lateral sclerosis. Plasma from 20 recently diagnosed ALS patients induced hemolysis of normal red blood cells with a significantly greater intensity than that of normal controls. After at least 1 month of treatment with prednisone and azathioprine, the hemolytic activity of ALS plasma was reduced but was still higher than that of control plasma.
Assuntos
Esclerose Lateral Amiotrófica/sangue , Hemólise , Idoso , Idoso de 80 Anos ou mais , Esclerose Lateral Amiotrófica/tratamento farmacológico , Azatioprina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêuticoRESUMO
We performed proton magnetic resonance spectroscopy (1H-MRS) in patients with motor neuron disease (MND) to determine the absolute in vivo concentrations in the brain of the metabolites N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr/PCr). We examined the spectra acquired from a 20 x 20 x 20-mm3 voxel placed in the motor cortex and in the cerebellum from seven patients with clinically probable or definite amyotrophic lateral sclerosis (ALS) according to the El Escorial criteria, from three patients with suspected ALS (progressive muscular atrophy), and from eight normal control subjects. We estimated the concentrations of the metabolites using the water signal as an internal standard. The concentrations of Cho and Cr/PCr in both brain regions, as well as the concentration of NAA in the cerebellum, were unaltered in the MND patients compared with the controls. Only MND patients with both upper and lower motor neuron signs had a significantly decreased concentration of NAA (9.13 +/- 0.28 mM, mean +/- SEM) in the primary motor cortex when compared with healthy controls (10.03 +/- 0.22 mM). In conclusion, the slightly decreased concentration of NAA in the primary motor cortex from ALS patients may represent a loss of neurons in this region.
Assuntos
Esclerose Lateral Amiotrófica/diagnóstico , Esclerose Lateral Amiotrófica/metabolismo , Cerebelo/metabolismo , Espectroscopia de Ressonância Magnética , Córtex Motor/metabolismo , Adulto , Idoso , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Colina/metabolismo , Creatina/metabolismo , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/metabolismo , Prótons , Valores de ReferênciaRESUMO
This study was initiated to elucidate the mechanisms behind valproate-induced weight gain. Eight patients with epilepsy were studied with identical examination programs before and during the end of the first month of treatment with sodium valproate (VPA). The measurements included registration of food intake, indirect calorimetry, and determination of pancreatic and thyroid hormones, catecholamines, albumin, electrolytes, glycerol, and free fatty acids. Measurements were performed both at the basal condition and during a 3-hour oral glucose tolerance test (OGTT). After the start of VPA treatment, the mean levels during the OGTT of plasma glucose and catecholamines were significantly decreased by 7% and 25%, respectively (P less than .05). The mean ratio of insulin to glucagon decreased by 37% (P less than .01). During the glucose load, the decreases in free fatty acids were less pronounced after the start of VPA treatment, whereas the mean levels of glycerol were found to be unchanged. We detected no differences between the two periods with regard to total energy intake or macronutrient selection, energy expenditure, or thyroid hormones. As VPA is known to affect the concentration of carnitine in humans, it is hypothesized that a possible VPA-induced deficiency of the beta-oxidation of fatty acids is important for the development of obesity in epileptic patients in long-term treatment with VPA, but changes in catecholamines or other hormones might also be of importance.
Assuntos
Ácido Valproico/efeitos adversos , Aumento de Peso/efeitos dos fármacos , Adulto , Catecolaminas/sangue , Eletrólitos/sangue , Ácidos Graxos não Esterificados/sangue , Feminino , Glucose/metabolismo , Humanos , Masculino , Hormônios Tireóideos/sangueRESUMO
Eleven percent of the 272 women aged 25-45 years admitted consecutively to a neurologic department in 1980-1984 had undergone hysterectomy. The population was divided into two groups according to the discharge diagnoses. Among women with discharge diagnoses usually associated with no objective neurologic findings, the frequency of hysterectomy was 14%, compared with 5.4% in women discharged with diagnoses indicating organic neurologic disease. Gynecologic and psychiatric admissions were more frequent in the former than in the latter group. Of the 30 hysterectomized women, only six had had malignant or premalignant changes in the uterus, whereas in 22 cases the removed organs had been normal. These results suggest that a somatization disorder might have been the underlying cause for the hysterectomy as well as for the symptoms and complaints leading to referral to the neurologic service. Awareness of this problem is important in order to avoid unjustified surgery.
Assuntos
Histerectomia/estatística & dados numéricos , Doenças do Sistema Nervoso/epidemiologia , Transtornos Somatoformes/epidemiologia , Adulto , Estudos Transversais , Diagnóstico Diferencial , Feminino , Humanos , Histerectomia/psicologia , Exame Neurológico , Encaminhamento e Consulta , Estudos RetrospectivosRESUMO
The sulfated N-terminus and the carboxyamidated C-terminus of cholecystokinin octapeptide (CCK-8) were radioimmunoassayed in cerebrospinal fluid from 19 patients with multiple sclerosis (MS) and 17 control subjects. While the N-terminal immunoreactivity was normal in all phases of MS, the concentration of C-terminal CCK immunoreactivity was significantly increased from 3.7 +/- 0.3 to 7.9 +/- 1.0 pmol/l (mean +/- S.E.M.) in both progressive and stable phases. The results indicate that C-terminal forms of CCK are released at an increased rate or that increased amounts of CCK-8 are released together with enhanced aminopeptidase activity in MS.
Assuntos
Esclerose Múltipla/líquido cefalorraquidiano , Fragmentos de Peptídeos/líquido cefalorraquidiano , Sincalida/líquido cefalorraquidiano , Humanos , Radioimunoensaio/métodosRESUMO
OBJECTIVE: To evaluate changes in quantitative EMG of injected and noninjected sternocleidomastoid muscles following long-term unilateral botulinum toxin treatment of cervical dystonia. METHODS: We investigated 27 patients with cervical dystonia, who received repeated unilateral botulinum toxin injections of the sternocleidomastoid muscle, with quantitative EMG at rest and at maximal voluntary contraction. The patients had on the average 7.1 botulinum toxin treatments and the follow-up period was on the average 31 months (SD 16). RESULTS: After the first treatment, the injected sternocleidomastoid muscles showed a significant decrease in turns/s (mean 45%) and amplitude (mean 52%) at rest, and in amplitude at maximal flexion (mean 24%) and rotation (mean 39%). Except for a reduction in turns/s at rotation (mean 19%) no further reductions in EMG parameters were seen after long-term treatment. The contralateral noninjected sternocleidomastoid muscles showed no significant change in EMG activity after the first BT treatment, but after long-term treatment a significant reduction in turns/s and amplitude at both maximal flexion (turns: mean 28%; amplitude: mean 25%) and rotation (turns/s: mean 32%; amplitude: mean 25%) were seen as compared to pretreatment values. CONCLUSION: The results indicate that there seems to be no cumulative chemodenervation by repeated botulinum toxin injections of sternocleidomastoid muscles measured by quantitative EMG. Contralateral noninjected sternocleidomastoid muscles however, seem to be affected following long-term treatment. The mechanism behind this finding is unknown.
Assuntos
Toxinas Botulínicas Tipo A/uso terapêutico , Distonia/tratamento farmacológico , Distonia/fisiopatologia , Músculos do Pescoço/efeitos dos fármacos , Músculos do Pescoço/fisiopatologia , Adolescente , Adulto , Idoso , Criança , Eletromiografia , Humanos , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Machado-Joseph disease (MJD) is an autosomal dominantly inherited neurodegenerative disorder characterized by varying age of onset and pronounced phenotypic heterogeneity. The clinical core features include gait ataxia, external ophthalmoplegia, nystagmus, and bulging eyes. Recently, Kawagushi et al. (1994) cloned the MJD1 gene on chromosome 14 and MJD turned out to be the fifth neurodegenerative disease caused by an unstable CAG repeat expansion. We have studied two large Danish families and one Norwegian family with MJD. Three features not previously associated with MJD are reported: dementia, generalized muscle and joint pain, and in one case neuropathological examination revealed atrophy of the inferior olives. We found a significant inverse correlation between age of onset and the length of the CAG repeat expansion, and anticipation is described through four succeeding generations. Instability of the CAG repeat expansion was most pronounced at paternal transmission.
Assuntos
Doença de Machado-Joseph/diagnóstico , Adulto , Idoso , Ataxina-3 , Demência/genética , Feminino , Humanos , Doença de Machado-Joseph/genética , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Proteínas Nucleares , Linhagem , Fenótipo , Proteínas Repressoras , Países Escandinavos e Nórdicos , Repetições de TrinucleotídeosRESUMO
CSF 5-HT and 5-HIAA were measured in endogenously depressed patients (ICD-9) (n = 23) and controls (n = 11). Distribution of sex, age and body height was similar in the two groups. Non-parametric statistics were used. In depressed patients CSF 5-HT concentrations were found to be higher (P less than or equal to 0.01) than in controls. A further classification of the depressed patients by the Newcastle Scale showed that the highest values were found in the endogenous group compared to the non-endogenous group (P less than or equal to 0.02). CSF 5-HIAA was found to be equal in the two groups, even when pairs matched for height were compared. No relation between clinical recovery due to drug treatment and changes in CSF 5-HT was seen. Our data support a possible involvement of 5-HT in the biology of depression, but the anatomical and functional levels of a serotonin derangement are still unknown.
Assuntos
Transtorno Depressivo/líquido cefalorraquidiano , Ácido Hidroxi-Indolacético/líquido cefalorraquidiano , Serotonina/líquido cefalorraquidiano , Amitriptilina/uso terapêutico , Citalopram , Transtorno Depressivo/terapia , Eletroconvulsoterapia , Humanos , Isocarboxazida/uso terapêutico , Propilaminas/uso terapêutico , SuicídioRESUMO
Some studies report reduced levels of the dopamine metabolite HVA in CSF in depression. In the present study including 24 depressed patients and 10 controls, we found significantly increased concentrations of total CSF dopamine in depressed patients. This finding suggests a dysfunction in central dopamine turnover in depression. No differences in CSF levels of noradrenaline or the amine metabolites homovanillic acid and 3-methoxy-4-hydroxy-phenylglycol were seen when comparing depressed patients with controls.
Assuntos
Transtorno Depressivo/líquido cefalorraquidiano , Dopamina/líquido cefalorraquidiano , Norepinefrina/líquido cefalorraquidiano , Adulto , Idoso , Transtorno Depressivo/psicologia , Feminino , Ácido Homovanílico/líquido cefalorraquidiano , Humanos , Masculino , Metoxi-Hidroxifenilglicol/líquido cefalorraquidiano , Pessoa de Meia-Idade , Escalas de Graduação PsiquiátricaRESUMO
Within the latest years botulinum toxin A (BT) applied locally in affected muscles has gained a superior position in the treatment of cervical dystonia. EMG is often used as a guidance for the injections, which has caused a need for better knowledge about the electromyographic changes in the muscles involved. In the present study we used the turns-amplitude analysis for the quantitative evaluation of the EMG of the sternocleidomastoid muscles and posterior neck muscles in 44 patients with cervical dystonia, not previously treated with BT. Twelve healthy subjects were examined for comparison. At rest 13 patients showed abnormal activity (defined as > 100 turns/s) in the sternocleidomastoid muscle contralateral to the involuntary head rotation (CS) and the ipsi- and contralateral posterior neck muscles (IPN and CPN): 12 patients had abnormal activity in CS and IPN, and seven patients had abnormal activity in all muscles, including the ipsilateral sternocleidomastoid muscle (IS). Other combinations were seen less often. The distribution of muscles with abnormal activity was not always obvious from the clinical examination. CPN and IS, i.e., apparently unaffected muscles, showed reduced EMG activity during attempted maximal voluntary contraction, indicating difficulties in activating all motor units.
Assuntos
Eletromiografia , Músculos do Pescoço/inervação , Torcicolo/fisiopatologia , Adulto , Idoso , Feminino , Lateralidade Funcional/fisiologia , Humanos , Contração Isométrica/fisiologia , Masculino , Pessoa de Meia-Idade , Neurônios Motores/fisiologia , Valores de Referência , Processamento de Sinais Assistido por ComputadorRESUMO
Injection of botulinum toxin (BT) into affected neck muscles gives symptomatic relief to patients with cervical dystonia by causing a presynaptic block of acetylcholine release. In a retrospective study of 19 patients, we used the turns-amplitude analysis of the EMG interference pattern for the evaluation of electrophysiological changes as a function of time after BT treatment. EMG was performed immediately before and during injection, and muscles showing abnormally increased activity (> 100 turns/s at rest) were given botulinum toxin A (Oculinum (= Botox)) 40-120 units. A second EMG was done 6-30 weeks later. At attempted rest, the sternocleidomastoid muscle contralateral to the involuntary head rotation showed the most pronounced changes, possibly due to relatively large doses of BT, and the EMG changes were related to the time after BT treatment. Six weeks after treatment the muscle showed decreased turns/s, mean amplitude and ratio (turns/amplitude) at rest. At 30 weeks, turns and mean amplitude reached values as before treatment, while ratio was increased to 175% of the pre-treatment value. This pattern may reflect a reversible and random loss of muscles fibres, due to presynaptic denervation. At maximal voluntary contractions, no correlation was seen between time after BT treatment and quantitative EMG.
Assuntos
Toxinas Botulínicas/uso terapêutico , Distonia/tratamento farmacológico , Músculos do Pescoço/efeitos dos fármacos , Adulto , Idoso , Toxinas Botulínicas/administração & dosagem , Distonia/fisiopatologia , Eletromiografia , Feminino , Humanos , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Músculos do Pescoço/fisiopatologia , Fatores de TempoRESUMO
Dyskinetic syndromes are conditions with involuntary movements. They can have different causes, but are often due to dysfunction of the basal ganglias. The clinical picture varies but all show spontaneous alterations in intensity as well as deterioration with stress. This often leads to misjudgment of cases of dyskinesia. It is however important to be aware of these syndromes as medical treatment is effective in many cases. The treatment of tremor, tics, chorea, myoclonus, dystonia and medically induced dyskinesia is reviewed and the clinical pictures are briefly described.
Assuntos
Transtornos dos Movimentos/tratamento farmacológico , Humanos , Transtornos dos Movimentos/diagnóstico , Transtornos dos Movimentos/fisiopatologiaRESUMO
Amyotrophic lateral sclerosis is characterized by degeneration of the motor neurones in the central nervous system and, as a rule, the condition results in rapid incapacity and death. The etiology is unknown but experimental results from recent years suggest that immunological mechanisms are of pathophysiological significance. Gangliosides constitute an important membrane component in nerve tissue and the majority of patients probably have high titres of circulation polyclonal IgM-antibodies to these compounds, particularly gangliosides GM1 and GD1a. The antibody titre appears to be correlated with the clinical condition and selective immune suppression (e.g. with cyclophosphamide) may possibly be of therapeutic value.
Assuntos
Esclerose Lateral Amiotrófica/imunologia , Doenças Autoimunes/imunologia , Esclerose Lateral Amiotrófica/tratamento farmacológico , Anticorpos Monoclonais/análise , Gangliosídeos/imunologia , Humanos , Imunoglobulina M/análise , Imunossupressores/administração & dosagemRESUMO
Knowledge of the neurophysiology of bladder control is growing, as better diagnostic methods are developed and because clinical interest in the field is greater and treatments are better. It is problematic that the symptoms are very few and do not provide much information about the lesions in the nervous system. We describe the bladder symptoms in most neurological diseases, and the neurophysiology of normal voiding is described. A strategy for handling neurological bladder symptoms is outlined.