The motor prodromes of parkinson's disease: from bedside observation to large-scale application.

There is sufficient evidence that the pathological process that causes Parkinson's disease begins years before the clinical diagnosis is made. Over the last 15 years, there has been much interest in the existence of a prodrome in some patients, with a particular focus on non-motor symptoms such as reduced sense of smell, REM-sleep disorder, depression, and constipation. Given that the diagnostic criteria for Parkinson's disease depends on the presence of bradykinesia, it is somewhat surprising that there has been much less research into the possibility of subtle motor dysfunction as a pre-diagnostic pointer. This review will focus on early motor features and provide some advice on how to detect and measure them.

Neuralgia del trigémino clásica familiar / Familial classic trigeminal neuralgia

Introducción: La neuralgia del trigémino clásica es un cuadro habitualmente esporádico, sin asociación familiar. Pero se estima que hasta un 2% de las neuralgias del trigémino podrían ser de tipo familiar. La caracterización de esta entidad es de utilidad para su identificación e incluso podría ser clave para definir las causas subyacentes en la neuralgia del trigémino clásica esporádica. Por esta razón, se aporta una serie de 5 familias en las que al menos existen 2 familiares con este cuadro, constituyendo un total de 11 casos. Material y métodos: Se recogieron casos familiares entre marzo del 2014 y marzo del 2015, interrogando sistemáticamente a los pacientes que acudían a la consulta de Neurología general con el diagnóstico de neuralgia del trigémino. Resultados: La neuralgia del trigémino clásica familiar afecta predominantemente a mujeres, la edad media de inicio es de 62,9 ± 13,93 años, es más frecuente la afectación de V2 y la edad de presentación es más temprana en la siguiente generación. La mayoría responde al tratamiento farmacológico. La respuesta al tratamiento neuroquirúrgico no es efectiva en todos los casos. Conclusiones: Estas agrupaciones familiares apoyan la idea de probables implicaciones genéticas en el desarrollo de este cuadro. Se postulan como posibles causas: conformaciones anatómicas heredadas en la estructura de la base del cráneo que facilitarían la compresión del trigémino por estructuras vasculares; HTA familiar responsable de formar vasos tortuosos que comprimirían el nervio trigémino; o alteraciones genéticas en la codificación de canales de calcio que provocarían su hiperexcitabilidad. Se sugiere una forma de herencia autosómica dominante con fenómeno de anticipación

Introduction: The classic form of trigeminal neuralgia is usually sporadic (no familial clustering). However, around 2% of all cases of trigeminal neuralgia may be familial. Describing this entity may be useful for diagnosing this process and may also be key to determining the underlying causes of sporadic classical trigeminal neuralgia. We report on cases in a series of 5 families with at least 2 members with classic trigeminal neuralgia, amounting to a total of 11 cases. Material and methods: We recorded cases of familial classical trigeminal neuralgia between March 2014 and March 2015 by systematically interviewing all patients with a diagnosis of trigeminal neuralgia who visited the neurology department on an outpatient basis. Results: In our sample, most patients with familial classic trigeminal neuralgia were women. Mean age at onset was 62.9 ± 13.93 years, decreasing in subsequent generations. V2 was the most frequently affected branch. Most of our patients responded well to medical treatment, and surgery was not effective in all cases. Conclusions: These family clusters support the hypothesis that classic trigeminal neuralgia may have a genetic origin. Several causes have been suggested, including inherited anatomical changes affecting the base of the skull which would promote compression of the trigeminal nerve by vascular structures, familial AHT (resulting in tortuous vessels that would compress the trigeminal nerve), and mutations in the gene coding for calcium channels leading to hyperexcitability. Classic trigeminal neuralgia may be an autosomal dominant disorder displaying genetic anticipation

Familial classic trigeminal neuralgia. / Neuralgia del trigémino clásica familiar.

INTRODUCTION: The classic form of trigeminal neuralgia is usually sporadic (no familial clustering). However, around 2% of all cases of trigeminal neuralgia may be familial. Describing this entity may be useful for diagnosing this process and may also be key to determining the underlying causes of sporadic classical trigeminal neuralgia. We report on cases in a series of 5 families with at least 2 members with classic trigeminal neuralgia, amounting to a total of 11 cases. MATERIAL AND METHODS: We recorded cases of familial classical trigeminal neuralgia between March 2014 and March 2015 by systematically interviewing all patients with a diagnosis of trigeminal neuralgia who visited the neurology department on an outpatient basis. RESULTS: In our sample, most patients with familial classic trigeminal neuralgia were women. Mean age at onset was 62.9±13.93 years, decreasing in subsequent generations. V2 was the most frequently affected branch. Most of our patients responded well to medical treatment, and surgery was not effective in all cases. CONCLUSIONS: These family clusters support the hypothesis that classic trigeminal neuralgia may have a genetic origin. Several causes have been suggested, including inherited anatomical changes affecting the base of the skull which would promote compression of the trigeminal nerve by vascular structures, familial AHT (resulting in tortuous vessels that would compress the trigeminal nerve), and mutations in the gene coding for calcium channels leading to hyperexcitability. Classic trigeminal neuralgia may be an autosomal dominant disorder displaying genetic anticipation.

Robustness of the approximate likelihood of the protracted speciation model.

The protracted speciation model presents a realistic and parsimonious explanation for the observed slowdown in lineage accumulation through time, by accounting for the fact that speciation takes time. A method to compute the likelihood for this model given a phylogeny is available and allows estimation of its parameters (rate of initiation of speciation, rate of completion of speciation and extinction rate) and statistical comparison of this model to other proposed models of diversification. However, this likelihood computation method makes an approximation of the protracted speciation model to be mathematically tractable: it sometimes counts fewer species than one would do from a biological perspective. This approximation may have large consequences for likelihood-based inferences: it may render any conclusions based on this method completely irrelevant. Here, we study to what extent this approximation affects parameter estimations. We simulated phylogenies from which we reconstructed the tree of extant species according to the original, biologically meaningful protracted speciation model and according to the approximation. We then compared the resulting parameter estimates. We found that the differences were larger for high values of extinction rates and small values of speciation-completion rates. Indeed, a long speciation-completion time and a high extinction rate promote the appearance of cases to which the approximation applies. However, surprisingly, the deviation introduced is largely negligible over the parameter space explored, suggesting that this approximate likelihood can be applied reliably in practice to estimate biologically relevant parameters under the original protracted speciation model.

Measuring vibration sensations with graduated tuning fork. Simple and reliable means to detect diabetic patients at risk of neuropathic foot ulceration.

To find a simple and reliable means to measure vibration sensations, 189 diabetic patients and 88 control subjects were tested at different sites with a graduated tuning fork. Within-test variation at big toes reached 8.4% in diabetic patients vs. 2.2% in control subjects. Mean contralateral variation was 7.5% in diabetic patients vs. 2.5% in control subjects. Tuning-fork sensations were inversely correlated with duration of diabetes, whereas no correlation was found with HBA1c levels or the severity of retinopathy. Ninety-nine (52%) patients had vibratory sensation at big toes of less than 99th percentile of normal values for age. In addition, 51% of the patients with clinical symptoms at extremities (n = 67), 70% of the patients without tendon reflexes (n = 50), and 75% of the patients with abnormal nerve conduction velocities (n = 60) also had low vibration sensations. All patients with lower-limb injuries (n = 7) had values at big toes of less than 2. Altogether, the graduated tuning fork represents a simple and reliable alternative to quantitate vibration sensations. Long-term follow-up of asymptomatic patients will indicate whether these abnormalities reflect underlying neuropathy. Patients with abnormal values at screening will necessitate additional investigations and special foot-care education programs.

[Microalbuminuria and diabetic nephropathy. Detection and correlation with other degenerative complications]. / Microalbuminurie et néphropathie diabétique. Dépistage et corrélations avec les autres complications dégénératives.

The prevalence of microalbuminuria and persistent proteinuria was studied in a population of 801 diabetic patients (535 with type II and 266 with type I diabetes). Urinary albumin excretion rate (AER) was measured on morning samples by laser nephelometry. Normoalbuminuria, as defined, in the absence of contaminated urine, by an albumin: creatinine (A/C) ratio below 2, was found in 551 patients, microalbuminuria (NC greater than or equal to 2 with AER below 200 mg/l) in 190 patients and persistent proteinuria (AER greater than or equal to 200 mg/l) in 60 patients. Microalbuminuria was present in 48 (18 p. 100) IDDM patients and 142 NIDDM patients. In IDDM patients, AER increased with the duration of the disease with no apparent influence of age at the onset. The prevalence of hypertension was 25 p. 100 and 61 p. 100 in IDDM patients with microalbuminuria and macroproteinuria respectively versus 10 p. 100 in patients with normoalbuminuria. This prevalence increased in NIDDM patients from 39.3 p. 100 with normoalbuminuria to 40.8 p. 100 and 76.2 p. 100 with microalbuminuria or macroproteinuria respectively. Proliferative retinopathy in type I and type II patients with normal AER was 7.4 p. 100 and 1.2 p. 100 respectively increasing to 15.2 p. 100 and 8.9 p. 100 with microalbuminuria and 27.8 p. 100 and 23.1 p. 100 with macroproteinuria. The prevalence of coronary disease increased from 4 to 10.4 p. 100 in patients with type I diabetes and microalbuminuria. The prevalence of cardiac failure increased from 1.5 to 2.1 p. 100 in type I diabetics and from 3.2 to 7.8 p. 100 in type II diabetics in the presence of microalbuminuria. Patients with microalbuminuria had increased levels of glycosylated hemoglobin A 1C but statistical difference was only obtained for patients with type II diabetes. Routine analysis of AER in diabetics allows early detection of diabetic nephropathy and emphasizes the need for tight metabolic and blood pressure control. Hypertension can be detrimental to nephropathy but might also initiate renal lesions in NIDDM patients.

Reduction of exogenous oxalate in urine of rats by binding with aluminium-oxyhydrate (Andursil) and an anion-exchanger (Colestid) in the intestinal tract.

The influence of calcium carbonate, aluminium oxyhydrate (Andursil) and an anion exchanger (Colestid) on the absorption of oxalate from the intestine in rats was investigated. The animals were administered daily doses of 15mg oxalate as a 14C-sodium-oxalate solution by means of a throat probe, and the substances of interest were mixed with the food. The intake of food and the 14C-activity in the urine were measured during four urine-collecting periods of 3 days each. The quantity of the enterally administered oxalate excreted with urine has a negative correlation to the amount of the investigated test substances ingested with food.