Monuments to Cajal in Madrid, Spain: Rejection of public tributes.

During Santiago Ramón y Cajal's lifetime, two monuments to him were erected in Madrid. However, Cajal excused himself from attending their inaugurations for reasons that have so far remained unexplained. The present report has therefore investigated the political context and personal circumstances that might account for his behavior. The first monument is a fountain in El Retiro Park, the work of sculptor Victorio Macho, inaugurated in 1926 during a major confrontation between progressive intellectuals and physicians against the dictatorship of Miguel Primo de Rivera. An official press release warned of a prison sentence for those who attempted a second (illegal) inauguration. The second monument appeared in 1931, barely a month after the establishment of the Second Spanish Republic. This full-body statue, standing>3m (around 10ft) high on a narrow pedestal, was financed by medical students and sculpted by Lorenzo Domínguez, a Chilean medical student. Its unlikely height and thinness earned it the nickname 'The Pencil'. At present, it flanks the entrance to Cajal's old classroom at the Madrid College of Physicians. Closer inspection reveals fractures as evidence of its having been broken into pieces at some point, presumably during bombings that took place in 1936. The calcareous Novelda stone used in its construction and its exposure to the elements may also partly explain its deterioration. A few metres away, a second sculpture, apparently a replica of the original, was inaugurated in 1998. Cajal's excuses for not attending the inaugurations of both his monuments may have different explanations. Regarding the fountain, it was probably a gesture of solidarity against those (many of whom were doctors) opposing the dictatorship whereas, when The Pencil was inaugurated, Cajal was 79 years old, and his physical limitations might have accounted for his inability to attend the ceremony. Thus, given the different political context in which each inauguration took place, Cajal's attitude was presumably in line with his politics, but also the result of his age-related infirmities.

Cajal's unbearable cephalalgias: The consequences of a misdiagnosis.

Around the age of 66 Cajal consulted neurologist Nicolas Achúcarro complaining of "unbearable cephalalgias". He had not ever suffered from headaches. The diagnosis of early arteriosclerosis that was considered at the time a physiological, irreversible ailment of ageing had a strong emotional impact on Cajal. Comorbid depression, insomnia and self-treatment with escalating doses of Veronal® (barbital), a short-acting barbiturate, presumably aggravated the situation. Exposure to warm environments and being involved in tense discussions were identified as triggering factors of the headaches. Achúcarro and Cajal were probably assuming scientific concepts at the time, such as cerebral congestion, increased temperature at the cerebral cortex during mental activity and vasoconstriction and vasodilatation phenomena. Up to his death aged 82, no evidence was discovered of any organic nervous system disorder. Cajal remained anxious up to the end of his life fearing an impending cerebral haemorrhage. The diagnosis was followed by profound lifestyle changes such as social isolation, which forced him to leave his laboratory. Cajal's cephalalgias marked in some way the end of the Spanish school of neurohistology.

Azañón's disease. A 19th century epidemic of neurolathyrism in Spain.

The cultivation and consumption of grasspea (Lathyrus sativus) in Spain probably dates back centuries, especially during times of famine when the neurotoxic potential of this legume was expressed in the form of a spastic paraparesis known as neurolathyrism. Little known outside the country, the epidemic of neurolathyrism in the years following the Spanish Civil War (1936-1939) came to affect more than a thousand people. In late 1872, during the Six Years Revolutionary Term, young Alejandro San Martín Satrústegui (1847-1908), then editor of the popular weekly El Siglo Médico, travelled to Azañón, a remote village in the province of Guadalajara, to clarify a so-far unknown disease. We analysed the original article published in 1873 by San Martin, as well as communications sent by El Siglo Médico readers reporting similar cases in many other Castilian provinces. San Martín's neurological findings in seven personally examined cases were astonishingly accurate; he concluded the subjects' neurological deficits resulted from injury to the lateral columns in the lower portion of the spinal cord. Description of the clinical findings provided both by San Martín, and by the readers of El Siglo Médico, leave no doubt as to the diagnosis of neurolathyrism. However, none suspected the patient's staple food was the determinant cause of the disease. San Martín proposed the eponym Azañón's disease for lack of a better name the same year (1873) in which Cantani in Italy introduced the term lathyrism. The epidemic of neurolathyrism that affected many Castilian towns represents one of the best-documented in Europe during the last third of the 19th century.

The Madrid School of Neurology (1885-1939).

The emergence of neurology in Madrid between 1885 and 1939 had well-defined characteristics. On foundations laid by Cajal and Río-Hortega, pioneers combined clinical practice with cutting-edge neurohistology and neuropathology research. Luis Simarro, trained in Paris, taught many talented students including Gayarre, Achúcarro and Lafora. The untimely death of Nicolás Achúcarro curtailed his promising career, but he still completed the clinicopathological study of the first American case of Alzheimer's disease. On returning to Spain, he studied glial cells, including rod cells. Rodríguez Lafora described progressive myoclonus epilepsy and completed experimental studies of corpus callosum lesions and clinical and neuropathology studies of senile dementia. He fled to Mexico at the end of the Spanish Civil War (1936-1939). Sanchís Banús, a sterling clinical neurologist, described the first cluster of Huntington's disease in Spain, and he and Río-Hortega joined efforts to determine that pallidal degeneration underlies rigidity in advanced stages of the disease. Just after the war, Alberca Llorente eruditely described inflammatory diseases of the neuraxis. Manuel Peraita studied "the neurology of hunger" with data collected during the siege of Madrid. Dionisio Nieto, like many exiled intellectuals, settled in Mexico DF, where he taught neurohistological methods and neuropsychiatry in the tradition of the Madrid School of Neurology.

La Salpêtrière Hospital before Charcot: a visit described by Pedro González Velasco.

INTRODUCTION: Under Charcot's leadership, La Salpêtrière was transformed into one of the world's top neurology centres. However, there is little information regarding the patient care facilities which Charcot would have encountered upon his arrival in 1862. DEVELOPMENT: A paper published in 1860 by Spanish physician Pedro González Velasco following a visit to that famous hospital is a valuable testimony to the quality of patient care just prior to Charcot's arrival. Although it essentially praises the institution, the article also describes the largely unsatisfactory conditions endured by patients with severe mental disorders, epilepsy and paralysis, who were locked inside cages with simple straw pallets on the floor for beds and open holes for toilets. Rather than an alienist, Velasco was a well-known surgeon and passionate advocate of positivism. As a personal friend and hospital fellow of Jose Maria Esquerdo's, with similar political affiliations, he had first-hand knowledge of the struggle to improve neuropsychiatric care in Madrid. CONCLUSIONS: Publishing his paper ultimately provided Velasco with a pretext for denouncing the deplorable care conditions endured by similar patients in Hospital General de Madrid. Meanwhile, Charcot would go on to improve the living conditions of inpatients at La Salpêtrière and found the specialty of neurology.

[When should a patient be referred to the pediatric surgeon?]. / Cuándo derivar un paciente al cirujano pediátrico?

INTRODUCTION: An incorrect transfer of patients to paediatric surgery clinic results in clinic saturation and both patient and medical staff discomfort. As a consequence the quality of medical care is deteriorated. AIM: 1) To evaluate the transfer of new patients to paediatric surgery clinic from primary paediatric care considering the medical diagnosis and the surgical calendar, looking for the most common mistakes. 2) To analyze the inconvenience of a wrong indication for both our patients and the medical staff. 3) To propose new measures to decrease the rate of patients incorrectly transferred. MATERIAL AND METHOD: An observational retrospective study was performed based on medical records of new patients evaluated in paediatric surgery clinic between september 2010 and january 2012. Age, address, diagnosis, transfer indication and referring centre were collected. RESULTS: Two thousand four hundred thirty medical records were reviewed from new patients finding an incorrect transfer in 44.28% of them (2.37 children/day). From these cases wrong transfer was related to surgical calendar in 18.59% and wrong diagnosis in 81.41% of them. Most common mistakes due to wrong diagnosis were Phimosis (91.45% n= 113) and Cryptorquidism (85.29% n = 122); mistakes related to surgical calendar were Umbilical Hernia (88.46%), Hypospadias (72.22% n= 31) and Hydrocele (70.83% n = 12). Mean distance of transfer for patients wrongly referred outside the metropolitan area was 35.92 km (Range: 7.1-129). CONCLUSIONS: We have detected major mistakes in patient transfer from primary paediatric care. The knowledge of surgical calendar and accurate diagnosis should avoid these problems. These mistakes result in deterioration of medical care quality, patient discomfort and clinic saturation. It is necessary to propose and develop measures that improve the knowledge of surgical calendar and to make more accurate surgical diagnosis in primary paediatric care.

Clinical experience with miglustat therapy in pediatric patients with Niemann-Pick disease type C: a case series.

Niemann-Pick disease type C (NP-C) is an inherited neurovisceral lysosomal lipid storage disease characterized by progressive neurological deterioration. Different clinical forms have been defined based on patient age at onset: perinatal, early-infantile (EI), late-infantile (Li), juvenile and adult. We evaluated the efficacy and tolerability of miglustat in 16 symptomatic NP-C patients, with comparative reference to one neurologically asymptomatic, untreated patient. All patients were categorized according to age at neurological disease onset, and were assessed using a standardized clinical assessment protocol: disability and cognitive function scales, positron emission tomography (PET), and biochemical markers. PET and disability scale evaluations indicated that cerebral hypometabolism and neurological symptoms were stabilized during treatment in juvenile-onset NP-C patients. EI and Li NP-C patients, who had higher disease severity at baseline (treatment start), showed increased disability scores and progressive cerebral hypometabolism during follow up. Similarly, while cognitive scale scores remained relatively stable in patients with juvenile NP-C, cognition deteriorated in EI and Li patients. Plasma chitotriosidase (ChT) activity was lower in the juvenile NP-C subgroup than in EI and Li patients, and generally increased in patients who discontinued treatment. Plasma CCL18/PARC and ChT activities indicated greater macrophagic activity in EI and Li patients versus juveniles. Miglustat was generally well tolerated; frequent adverse events included diarrhea and flatulence, which were managed effectively by dietary modification and loperamide. Overall, miglustat appeared to stabilize neurological status in juvenile-onset NP-C patients, but therapeutic benefits appeared smaller among younger patients who were at a more advanced stage of disease at baseline.

Reliability of maximum bite force measurements in age-varying populations.

In order for bite forces to be used clinically, they must be reliable. While bite force transducers are accurate and precise during bench tests, widely varying reliabilities of intra-oral bite forces have been reported when measured in human subjects. Because few studies have reported total reliability, the clinical use of intra-oral bite forces measurements remains questionable. The purposes of this study were to (i) estimate total reliability, including both within- and between-session reliabilities, of repeated maximum incisor and molar bite force measurements and (ii) demonstrate how extraneous variation affects reliability by comparing estimates for which the effects of age have and have not been controlled. A sample of 28 healthy subjects with Class I normal occlusion (seven subjects in each of four age groups: 5, 8, 11 and 14 years) performed two sessions approximately 90 min apart. Each session consisted of three maximum voluntary bites at three bite positions (incisor and right and left molars). For each bite position, between-subject variance (true variance), between-session variance and within-session variance were calculated using Multilevel modelling procedures. The variances were used to estimate between-session reliabilities, within-session reliabilities and total reliabilities. Within-session reliabilities were substantially higher than between-session reliabilities, which in turn was higher than total reliabilities at all bite positions. Reliabilities were highest at the incisor bite position. Not controlling for age effects substantially overestimated total reliability at all bite positions. After controlling for age effects, total reliabilities of repeated maximum bite forces were low to moderate.

Reduced reciprocal inhibition is seen only in spastic limbs in patients with neurolathyrism.

If reduced reciprocal inhibition plays a causal role in the pathophysiology of spasticity as has been suggested in several studies, the inhibition is expected to be impaired in spastic, but not in normal muscles. Patients with neurolathyrism offer a possibility of testing this prediction since the spastic symptoms in these patients are restricted to the lower extremities only. Three patients with neurolathyrism were tested. Their data were compared with 15 age-matched healthy subjects. All patients showed signs of spasticity in the legs. Two patients had normal voluntary muscle force in the lower extremities and one had decreased force. No clinical abnormalities were found in the upper extremities. Reciprocal inhibition between ankle dorsiflexor and plantarflexor muscles was absent in all patients, whereas the inhibition between wrist extensor and flexor muscles was present and of normal size and latency. These findings are consistent with the hypothesis that reduced reciprocal inhibition plays a causal role in the pathophysiology of spasticity.

Successful stent-grafting for iatrogenic aortic rupture and life-threatening hemoptysis.

Bronchiectasis presenting as massive hemoptysis and iatrogenic lesions of the thoracic aorta are life-threatening processes with very difficult management. We report a case of massive hemoptysis from bronchiectasis complicated with contained rupture of the descending thoracic aorta during bronchial artery embolization. Both lesions were confirmed by angiography and successfully treated by implantation of an endovascular stent-graft in the thoracic aorta. As far as we know, there are no previous reports of successful management of massive hemoptysis from bronchiectasis with an endovascular covered stent-graft prosthesis.

[Epileptic encephalopathies in infancy. How do we treat them? Does the aetiology influence the response to treatment?] / Encefalopatias epilepticas del lactante. Como las tratamos? Influye la etiologia en la respuesta al tratamiento?

INTRODUCTION: Resistance to treatments is a common feature of Ohtahara, Aicardi, West and Dravet syndromes, as well as malignant migrating epilepsy in infancy. AIMS: To update the therapeutic management and to analyse whether the aetiology somehow determines the treatment. DEVELOPMENT: Convulsive seizures in the first year of life may be due to a potentially treatable aetiology, which makes it essential to carry out a complete evaluation so as to be able to begin, as early as possible, the most suitable and the non-specific symptomatic treatments to control the seizures, which prevents or minimises their deleterious effects. Metabolic disease must be ruled out and it is also essential to try a therapeutic regimen of vitamins and cofactors, as well as antiepileptic drugs. In Ohtahara and Aicardi syndromes, the first-order treatment is phenobarbital and phenytoin, and the most commonly used second-order drugs are midazolam, levetiracetam, lidocaine and valproate. In West's syndrome, the first-order treatment consists of adrenocorticotropic hormone and vigabatrine for the case of tuberous sclerosis; if there is no response, other pharmaceuticals, a ketogenic diet and surgery must be considered. For Dravet's syndrome, the main treatment consists in valproate with clobazam and stiripentol, and as the second order, other drugs and a ketogenic diet should be considered. In epilepsy with migrating seizures, the most effective treatment is with bromides, stiripentol, clonazepam and levetiracetam. CONCLUSIONS: Today there is little consensus on the therapeutic approach to be able to establish specific indications. The aetiology has an influence on the treatment, both in cases in which a curative treatment exists (metabolic diseases) and in the symptomatic management with antiepileptic drugs or other treatments (ketogenic diet or surgery).

TITLE: Encefalopatias epilepticas del lactante. Como las tratamos? Influye la etiologia en la respuesta al tratamiento?Introduccion. La refractariedad es una caracteristica comun del tratamiento de los sindromes de Ohtahara, Aicardi, West, Dravet y epilepsia maligna del lactante con crisis migrantes. Objetivo. Actualizar el manejo terapeutico y analizar si la etiologia determina de alguna manera el tratamiento. Desarrollo. Las crisis convulsivas en el primer año de vida pueden deberse a una etiologia potencialmente tratable, por lo que es imperativo una completa evaluacion para instaurar de manera precoz el tratamiento adecuado y el sintomatico no especifico para el control de las crisis, que evite o minimice el efecto deletereo de estas. Es obligado hasta descartar metabolopatia y ensayar pauta de vitaminas y cofactores, ademas de antiepilepticos. En los sindromes de Ohtahara y Aicardi, la primera linea es fenobarbital y fenitoina, y en segunda linea, los mas habituales son midazolam, levetiracetam, lidocaina y valproato. En el sindrome de West, la primera linea la constituye la hormona adrenocorticotropa y la vigabatrina para el caso de esclerosis tuberosa; si no hay respuesta, considerar otros farmacos, dieta cetogenica y cirugia. Para el sindrome de Dravet, los principales son valproato con clobazam y estiripentol, y de segunda linea, considerar otros farmacos y dieta cetogenica. En la epilepsia con crisis migrantes, los mas eficaces son bromuros, estiripentol, clonacepam y levetiracetam. Conclusiones. Actualmente existe poco consenso en el abordaje terapeutico para establecer indicaciones taxativas. La etiologia influye en el tratamiento, tanto en el caso de disponer de tratamiento curativo (metabolopatias) como en el abordaje sintomatico con antiepilepticos u otros tratamientos (dieta cetogenica o cirugia).

A case report of recurrent adult-onset xanthogranuloma: is the radiotherapy a treatment option?

Adult-onset xanthogranuloma (AOX) is one of the four uncommon syndromes called adult xanthogranulomatous disease (AXD), which is diagnosed by characteristic histopathology. AXD is rare and heterogeneous group of entities that can affect multiple organ systems. Orbital involvement is included in the xanthogranulomatous disease although less prevalent. This work focuses on the use of external beam radiotherapy in the control of local symptoms of periocular manifestation of AOX as case report and literature review.

Organ contouring for prostate cancer: interobserver and internal organ motion variability.

The purpose of this study is to assess the uncertainties that arise in locating the boundaries of anatomical structures, such as the prostate and the bladder, due to interobserver variability in the delineation of the structures and to internal organ motion. The variabilities are computed in all the radial directions and this information is used to obtain the margins, following the techniques and limitations imposed by medical practice. The margins obtained from the organ motions are significantly greater than those arising from interobserver variability. The developed tools, allow us to obtain the required margins in an efficient way.

Prognosis in hereditary amyotrophic lateral sclerosis.

Two different forms of hereditary amyotrophic lateral sclerosis (ALS) has been separated according to duration of illness. A rapid course with short survival as seen in sporadic ALS is usual, but a comparatively benign type with a mean survival of 12 years has been reported in some families. Four patients from an ALS-afflicted family with five affected members in three generations were examined and then followed up. A conspicuous variability in progression among the patients was observed, with death occurring from 26 months to 12 years after onset; one patient is alive 13 years after onset. Wide differences were also found with respect to initial site of involvement and pyramidal tract signs. Three other families with this mixed pattern of prognosis have been reported previously. Affected individuals within involved families had either short or long duration of the disease, rather than displaying a continuum. However, in view of the existence of a type of hereditary ALS with marked intrafamilial variability, prognosis, even in the presence of previous benign cases, should be cautiously given.

Preclinical EEG abnormalities in subacute sclerosing panencephalitis.

Persistent electroencephalographic (EEG) abnormalities were observed for 4 years before the clinical onset of subacute sclerosing panencephalitis (SSPE) in a girl initially chosen as a "normal" control subject. Neurologic or mental changes were not observed during this period. Initially, there were focal paroxysmal discharges with shifting characteristics. Nonrepetitive generalized slow-wave complexes during wakefulness appeared later and persisted 3 weeks after onset of clinical manifestations. SSPE repetitive complexes were observed 1 month later. Multifocal paroxysmal EEG discharges during the presymptomatic stage of SSPE probably arise from restricted cortical areas containing persistently infected neurons and indicate that despite relative tolerance, the brain is not completely unresponsive to the presence of the virus.

Treatment of cutaneous leishmaniasis with localized current field (radio frequency) in Tabasco, Mexico.

In Mexico cutaneous leishmaniasis (CL) occurs in 17 of 32 States, and is a serious public health problem. This is a report of treatment of CL patients in the State of Tabasco, Mexico with a localized current field-radio frequency (LCF-RF) device to generate precisely controlled heat as an alternative to prohibitively expensive drug treatment. It was not a controlled clinical trial, but rather an evaluation of the feasibility of this form of treatment for all CL patients encountered in the endemic area. A total of 201 previously diagnosed patients with CL caused by Leishmania mexicana were treated with a portable Thermosurgery LCF-RF generator powered by rechargeable batteries. The ages of the patients ranged from two to 75 years; the sex distribution was 63% males and 37% females. A single device was used in five different municipalities. Lesions were first anesthetized with 1% lidocaine HCl and moistened with normal saline solution. Treatment consisted of a single application that produced 50 degrees C for 30 sec. After four weeks, 122 patients were available for evaluation, of which 95% were totally cured; (even those involving ear cartilage, which respond poorly to antimonials). At eight weeks post-treatment, 191 patients were evaluated, with a total cure rate of 90%. This form of treatment proved to be effective and convenient for use in primary health care facilities in Mexico and has many advantages over traditional forms of therapy.

Involuntary closure of eyelids in parkinsonism. Electrophysiological evidence for prolonged inhibition of the levator palpebrae muscles.

Involuntary closure of eyelids (ICE), a phenomenon variously interpreted as blepharospasm and apraxia of lid opening, is occasionally observed in parkinsonism. Nine patients (4 with Parkinson's disease, 2 with post-encephalitic parkinsonism, and 3 with supranuclear palsy) with prominent ICE, were studied by electromyographic recording of the eye muscles. ICE episodes were shown to be dependent upon prolonged, irregular inhibition of the normal tonic activity of the levator palpebrae superioris (LPS) muscle causing drooping of the upper eyelid without any corresponding activation of the orbicularis oculi (OO) muscle. Nevertheless, some degree of excessive, widely fluctuating OO activity was present in seven of the patients. Blepharocolysis (from Gr. blepharon, eyelid, and kolysis inhibition) is put forward as the term to designate ICE episodes resulting from abnormally long inhibition of the LPS muscles and should be differentiated electrophysiologically from blepharospasm, excessive OO muscles activity. Abnormal influences from basal ganglia acting on brainstem structures that regulate blinking may falicitate either of the two components of normal blinking resulting in ICE due to the predominance of LPS inhibition (blepharocolysis), the predominance of OO activation (blepharospasm) or a combination of the two.

Familial communicating syringomyelia.

Calssical cervical syringomyelia was found in 3 members of one family. All 3 underwent air myelogram, and a Chiari malformation type I and postural collapse of the spinal cord was found in each case. An affected 7-year-old boy was discovered after a clinical and radiological survey of 8 first-degree relatives on the basis of mild scoliosis, pyramidal tract signs in the lower limbs and enlarged sagittal diameter of the cervical canal. One other member had basilar impression of the skull but no neurological abnormalities. No positive correlation was found between either the size of the cystic cord enlargement or descent of the ectopic tonsils with the duration or severity of the neurological findings. Suboccipital decompressive craniotomy and upper cervical laminectomy in one case was followed by improvement in strength and sensation 1 year later. Progression in familial syringomyelia appears to occur through a mechanism identical to that in the sporadic form and surgery is therefore also indicated. In affected families, routine survey of close relatives for abnormal neurological signs, and radiological evidence of scoliotic deformity of the spine, enlarged cervical canal and bone abnormalities at the craniovertebral junction may prove valuable for early detection. A dominantly inherited, genetically determined malformation seems to be the probable mechanism of inheritance in this family.

Progressive supranuclear palsy and corticobasal ganglionic degeneration: differentiation by clinical features and neuroimaging techniques.

To assess the extent of overlap between clinically diagnosed patients with progressive supranuclear palsy (PSP) and corticobasal ganglionic degeneration (CBGD) we compared clinical scores for rigidity, bradykinesia, supranuclear gaze abnormalities, hemineglect and limb apraxia, postural instability, neck rigidity, and limb dystonia in 15 patients with a degenerative rigid-akinetic syndrome at presentation and at follow-up 3 to 120 months later. Only the presence of hemineglect, usually in combination with limb apraxia, was a reliable and early clinical factor for discriminating between these two conditions. These symptoms were present at admission in all 4 CBGD patients but not in any of the 11 PSP patients either at presentation or later during serial examinations. Though supranuclear ophthalmoplegia, neck rigidity, and postural instability were already observed in most CBGD patients at presentation, their scores remained low compared to those for PSP patients over the longterm. CT-scans and MRI were helpful in supporting clinically-based diagnoses made at presentation in that the vast majority of the PSP patients exhibited various degrees of midbrain atrophy and 50 percent of the CBGD patients exhibited asymmetric pericentral cortical atrophy.