Brain Donation by Proxy: Are There Predictors in Neurodegenerative Dementia?

OBJECTIVES: To describe the frequency and predictors of brain donation by relatives in patients with neurodegenerative dementia. DESIGN: Database review and quantitative analysis. SETTING: The Alzheimer Center Reina Sofia Foundation (ACRSF), a center devoted to the care and research of patients with neurodegenerative dementia. PARTICIPANTS: Patients with signed consent for participation in the ACRSF research program. MEASUREMENTS: A set of 38 demographic, clinical, and social variables related to patient and closest relative, which were collected by the ACRSF multidisciplinary team upon patient admission. RESULTS: Admission data were available for 198 patients who entered the ACRSF research program; 85 of them (42.9%) died during follow-up. Mean age (SD) at admission was 82.3 (6.8) years and 80.8% of the patients were female. Family link between patient and closest relative was spouse or partner (12.0%), son or daughter (74.9%), or other link (13.1%). Brain was obtained from 56 patients (65.9%). Consent by legal representative and patient's depressive symptoms were more frequent in the donors (p<0.05, corrected) and trend was observed for more aberrant motor symptoms in the donors (p<0.05, uncorrected). CONCLUSION: A high rate of brain donation was achieved, probably due to the unique characteristics of the ACRSF and consent for research policy. Wish of alleviating suffering, as well as general interest in dementia research, possibly exerted an influence in brain donation. More research is needed to ascertain the values, motivations, and circumstances that may lead to brain donation by proxy in neurodegenerative dementia.

Reduced serum progranulin level might be associated with Parkinson's disease risk.

BACKGROUND AND PURPOSE: Common genetic variants (rs5848 and rs646776) have been reported as regulators of blood progranulin (GRN) levels in healthy individuals. METHODS: To assess the influence of rs5848 and rs646776 polymorphisms in both serum GRN level and risk for common neurodegenerative diseases, we studied 304 patients with Parkinson's disease (PD), 217 individuals with Alzheimer's disease, 131 subjects with mild cognitive impairment, and 126 controls. RESULTS: The mean concentration of GRN in the serum of patients with PD (319.6 ng/ml) was significantly lower than that of controls (371.5 ng/ml; P = 0.009), whereas there were no significant differences between other groups. Rs646776 minor allele carriers had lower serum GRN levels in each of the four subgroups. There was no correlation between rs5848 genotypes and serum GRN concentrations. Genotype frequencies of both polymorphisms did not differ between groups. CONCLUSION: Reduced circulating GRN levels might be associated with PD risk by pathogenic factors different from rs5848 and rs646776 polymorphisms.

[Management and improvement of the process of outpatient treatment of transient ischemic attacks in Neurology departments]. / Gestión y mejora del proceso de tratamiento ambulatorio del accidente isquémico transitorio en consultas de Neurología.

AIMS: To describe our experience in the ambulatory treatment of transient ischemic attacks (TIA) in a second-level hospital with the implementation of an example of process management within the different services involved in attending such conditions. PATIENTS AND METHODS: The following aspects of the process--mission, limits, flowchart, eligibility criteria and performance indicators (process, sentinel and effectiveness)--were defined by multidisciplinary consensus (Emergency, Vascular Surgery, Cardiology, Neurology and Radiology departments). This process was implemented from April 2002 to May 2004, and monthly assessments were carried out to check for problems and to introduce corrective measures. After ending the process, patients with TIA were admitted as inpatients for a hospital study. RESULTS: Definition of the process: medical care (diagnosis and treatment) of TIA patients who are eligible for a complete outpatient study within seven days. Patients evaluated: 254. Indicator 1 (percentage of suitable referrals): 2002: 53%, 2003: 75%, 2004: 73%. Indicator 2 (percentage of complete studies in less than one week): 2002: 35%, 2003: 57%, 2004: 50%; hospitalised: 90%. Indicator 3 (infarcts during the study): 2002: 4.3%, 2003: 0%, 2004: 0%; hospitalised: 0%. Indicator 4 (percentage of adjustments made to treatment): 2002: 39%, 2003: 31%, 2004: 62%; hospitalised: 72%. Mean delay before visit: in February 2002: 90 days, in April 2002: 7.67 days and in April 2003: 5.37. Problems detected: delays in referrals, failure to fit hospitalisation criteria, delays in carrying out examinations not included in the protocol, unsuitable indicator design. Steps taken: redefinition of indicators, modification of the referral system, adjustments made to the circuits involved in carrying out tests, review of hospitalisation criteria. CONCLUSIONS: Process management is an ideal tool for achieving ongoing improvements in clinical praxis. Early monitoring makes it possible to detect problems and to implement corrective measures. In our area, the study of TIA must be performed in a hospital inpatient regimen in order to comply with the guidelines for clinical practice.

[Is progressive anarthria a clinical form of Pick complex?]. / Anartria progresiva: forma clínica del complejo Pick?

INTRODUCTION: Progressive anarthria is defined as a clinical entity with a degenerative origin consisting in progressive difficulty in articulating while grammatical, semantic and graphic aspects of language are preserved. It is included within the group of processes affecting restricted areas of the brain although its exact nosological location is not clear. We report two cases that progressed clinically towards frontotemporal dementia and corticobasal degeneration, respectively. CASE REPORTS: Case 1: a male who, at the age of 72, began with speech difficulties while comprehension and reading/writing skills were preserved. Three years later he developed apathy, bulimia, sexual indiscretions and aggressiveness, with preservation of visual memory, visual-constructional capacity and elementary writing skills. Case 2: a male who, at the age of 70, began with speech disorders, which were associated two years later to generalised slowness with Hoehn and Yahr stage II akinetic-rigid symptoms; another two years later, he developed a dystonic attitude and melokinetic apraxia in the left upper limb. CONCLUSIONS: The two cases, which were initially compatible with progressive anarthria, progressed clinically towards frontotemporal dementia and corticobasal degeneration, which are entities that are included in 'Pick complex'. This is a concept that we believe to be useful from a clinical point of view, given the variability that exists in the histology of the entities that have been proposed as members of this syndrome group, together with the progression of the cases described in the literature and the ones we have reported in this work.

Cluster headache: interictal asymmetric increment in intraocular pressure elicited by Valsalva manoeuvre.

Changes in intraocular pressure (IOP) elicited by a Valsalva manoeuvre were studied in 11 male patients (mean age 39.8 years) suffering from episodic cluster headache (CH), and 12 healthy male controls (mean age 39.9 years). The tests were performed at rest and while exhaling hard through a mouthpiece connected to a mercury manometer. In the CH group, during symptomatic periods, between attacks, Valsalva manoeuvre elicited an asymmetric increase in IOP with significantly higher values on the symptomatic side (P = 0011), whereas no asymmetric increments in IOP were found during asymptomatic periods. Outside the cluster period the IOP values both baseline and with Valsalva manoeuvre did not differ from controls. The increment in IOP took place within a few seconds, as in spontaneous CH attacks, thus pointing to a rapid increase in intraocular blood volume or vasodilatation. These findings may reflect a latent increased vascular reactivity of the symptomatic orbit during CH period.

Objective assessment of autonomic signs during triggered first division trigeminal neuralgia.

A total of 26 episodes of V-1 trigeminal neuralgia attacks have been recorded in two female patients. Autonomic phenomena were assessed according to a semiquantitative scale. Attacks lasted 17 +/- 5 s. Mild lacrimation without conjunctival hyperaemia, rhinorrhea or ptosis was observed, even in relatively long lasting episodes. This is in clear contradiction with SUNCT (shortlasting, unilateral, neuralgiform headache with conjunctival injection, tearing and rhinorrhea) attacks that are always dramatically accompanied by both lacrimation and conjunctival injection of the symptomatic side from the very onset of symptoms. Carbamazepine provided complete and sustained relief of symptoms in both patients. Herein we will show differential autonomic features of V-1 trigeminal neuralgia vs. SUNCT that will both aid the clinician to distinguish both syndromes and stress that both entities are nosologicaly different.

Numular headache: a coin-shaped cephalgia.

Numular headache is a chronic, mild to moderate, pressurelike pain in a circumscribed cranial area of approximately 2 to 6 cm in diameter. Pain usually is limited to the parietal region, although it may appear in any cranial site. It is a benign process of usually unknown origin.

[Crossed apraxia secondary to a right parietal infarct]. / Apraxia cruzada secundaria a infarto parietal derecho.

INTRODUCTION: Crossed apraxia is an unusual alteration in praxic function due to a cerebral lesion which is contralateral to that which would be expected. We report a case of crossed apraxia due to a right parietal lesion in a left handed patient who had been obliged to be right handed. We discuss the peculiar neuropsychological profile and possible relation of this to left handedness. CLINICAL CASE: A 75 year old man, left handed but obliged to use the right hand, suffered an acute episode of alteration in the management of utensils (lids, taps, medicine containers), although he maintained his usual social behaviour and orientation. On neurosomatic examination no focal deficits were observed. On MMST he scored 29/30, on the Edinburgh questionnaire he scored 35 (left handed dominance). On a Barcelona PIENC battery his scores were in the pathological range for subtests on understanding orders, carrying out symbolic gestures and imitating gestures, in perceiving super imposed images and visual memory. MRI showed a right parietal laminar infarct. CONCLUSIONS: The patient showed clear bilateral ideo motor apraxia, which could not be justified/explained by visuo spatial agnosia secondary to a right parietal ischaemic lesion. It is usually considered that ideatory and ideomotor apraxias are due to left hemisphere lesions, whilst contsructive apraxia and apraxia related to dress are due to right hemisphere lesions. In this case, there was ideomotor apraxia secondary to a right parietal lesion, that is to say a crossed ideomotor apraxia, without crossing of other neuropsychological functions. This supports the theory of independence of hemisphere dominance for different cognitive functions. The frustrated left handedness of the patient might be related to the greater probability of unusual hemisphere dominance for ideomotor praxis function in this particular case.

[Acalculia. Neurological bases, evaluation and disorders]. / Acalculia. Bases neurológicas, evaluación y trastornos.

OBJECTIVE: To make a review of the literature on alterations in mathematical ability secondary to structural cerebral lesions. DEVELOPMENT AND CONCLUSIONS: We refer to the initial classification of acalculia of Berger (secondary acalculia when this is due to broader neuropsychological deficits and primary acalculia when it occurs alone) to the classical division of Hecaen (alexia and numerical agraphia with or without alterations in reading and writing of letters and words, visuo-spatial acalculia due to alterations in the spatial organization of multi-digit figures and the partial results of arithmetical operations, anarithmetia or primary failure in mathematical ability) and the most recent classifications based on neurocognitive models, which subdivide the acalculias into those secondary to changes in the system for processing numbers and those due to changes in the cognitive system for mathematics (McCloskey and Caramazza). Similarly, we review the correlations between the clinical changes in mathematics and the cerebral localization of the causative lesions (left parieto-temporal, right and including frontal and subcortical associative areas) together with the association of acalculia and other neuropsychological deficits. Finally we review the neuropsychological instruments available for the evaluation of acalculias, with particular reference to the tools validated and scaled for our language and sociocultural setting.

[Extrapontine myelinolyses caused by iatrogenic hypernatremia following rupture of a hydatid cyst of the liver with an amnesic syndrome as sequela]. / Mielinólisis extrapontina causada por hipernatremia yatrogénica tras rotura de un quiste hidatídico hepático con síndrome amnésico secuelar.

INTRODUCTION: Extrapontine myelinolisis is a rare condition caused by severe hydroelectrolytic disorders. Following an initial stage of diffuse encephalopathy, the neurological sequelae are usually of diffuse cognitive deficits and extrapyramidal or cortico-bulbo-spinal disorders. We report a case of extrapontine myelinolisis following hypertonic peritoneal lavage due to rupture of a hydatid cyst of the liver (HCL), which was followed by a syndrome of isolated amnesia due to bilateral hippocampal lesions. CLINICAL CASE: Following rupture of a HCL a 37 year old man was treated by peritoneal lavage with hypertonic saline solution. In the immediate postoperative period he had a prolonged confusion state associated with natremia of 176 mg/dl, which was corrected in less than 24 hours. Seven days later the patient had an apathy-inattention frontal syndrome. Six weeks later, and lasting until three months after operation, he had a selective memory deficit in learning tests (of the Barcelona-PIENC series of tests) with normality (29/30) in the MMST. On magnetic resonance there were hyperintense images in T2 in both hippocampus, insulas and corpus callosum. CONCLUSIONS: Generally caused by rapidly corrected hyponatremia, isolated hyponatremia or hypernatremia may also lead to extrapontine myelinolisis. However, we have found no report of extrapontine myelinolisis due to rupture of HCL and treatment with hypertonic peritoneal lavage. The neurological sequelae of extrapontine myelinolisis are usually global cognitive deficits, extra-pyramidal or cortico-bulbo-spinal disorders. Lesions seen on MR are usually found in the basal ganglia, thalamus or corpus callosum (with or without involvement of the pons). We have found no descriptions of bilateral hippocampal lesions causing selective memory deficits in this condition. Treatment by hypertonic peritoneal lavage for ruptured HCL may cause severe hydro-electrolytic alterations which may lead to myelinolisis of the CNS. We report of a case with bilateral hippocampal lesions and selective memory deficit, not previously described within the clinical spectrum of extrapontine myelinolisis.

Native language shifts across sleep-wake states in bilingual sleeptalkers.

STUDY OBJECTIVES: To assess language used during episodes of sleeptalking in bilingual children. DESIGN: The investigation was accomplished through the parents who, after having received appropriate information, participated by filling out a survey on sleeptalking. SETTINGS: The study was performed in three bilingual schools of the Basque country, a region in northern Spain in which two completely different official languages are spoken. PATIENTS: A total of 1000 parents agreed to participate, and 681 children were studied. MEASUREMENTS AND RESULTS: Sleeptalking was reported by 383 (56.3%) of children (mean age 9 years; range: 3-17). Most individuals used their dominant (i.e., native) language during sleep. However, a minority (< 4%) were found to use their non-dominant language persistently during episodes of sleeptalking. CONCLUSIONS: Balanced bilinguals (those who have equal proficiency in both languages) may sleeptalk in either of the two languages. Dominant bilinguals (i.e., having greater proficiency in one language) may preferentially sleeptalk in their dominant language, with immediate past events probably influencing language use in individual subjects on particular nights. Several considerations are postulated as an explanation for the group who systematically exhibited a dominance shift during sleep.

Chronic paroxysmal hemicrania-tic syndrome.

We report the coexistence of both chronic paroxysmal hemicrania (CPH) and trigeminal neuralgia (tic douloureux) in a female patient. The clinical features combined to make a configuration of CPH-tic syndrome. The two components of the syndrome appeared synchronously in the same orbital region--first branch of the trigeminal nerve--with a latency of several years after the onset of isolated tic attacks of the second and third trigeminal divisions. The concurrence of both types of pain in the same symptomatic area may have some significance for pathogenic, clinical, and pharmacological aspects of such a syndrome. We discuss all these and postulate a provisional distinction between CPH-V2,3 tic and CPH-V1 tic.

[Vehicle drivers with Parkinson disease: behavior schedules of a patient sample from the Community of Madrid]. / Conductores de vehículos con enfermedad de Parkinson: pautas de comportamiento en una muestra de pacientes de la Comunidad de Madrid.

The aim of this study was to evaluate features of the disease, habits patterns at the wheel, and reasons to give up driving motor vehicles in subjects with Parkinson's disease (PD). Prospective study using a semistructured questionnaire comparing current or former drivers with PD patients and a control group matched for age, sex and social background. In a PD and movement disorders clinic in an university hospital. Sixty-two out of 166 PD subjects interviewed owned a driving licence. Only 19.2% of PD subjects were currently active drivers. Compared to parkinsonian ex-drivers, they were 6 years younger on average, most were in disease stage II, and were less often under antidepressant medication. Nevertheless, disabling motor fluctuations and dyskinesias were present in 19% of the patients. A 47% of the active drivers reported no difficulty at the wheel; the remaining declared to experience a wide range of difficulties, particularly to manage pedals or to assess distances properly. PD itself lead to driving withdrawal in 80% of ex-drivers in contrast to 6% of controls who stop driving due to other illness. Only 40% of PD subjects were driving 5 years after diagnosis. Medical advice was influential in deciding to stop driving in a single patient. Disease onset in early adulthood often allowed to keep driving for 10 years or longer. Most subjects with PD give up driving during the first 5 years following disease onset, most due to the disease itself. Most active drivers adapt themselves to their physical circumstances, either by reducing the number of hours at the wheel or reducing speed. They are usually in early stages of the disease, despite which many experience subjective motor and visuospatial difficulties during driving. A minority keep on driving despite disabling fluctuations. This subset presumably represent a group at risk to suffer an increased rate of traffic accidents and in whom medical advice would be desirable.

[Mini-mental state examination: proposal of protocol to be used]. / Examen del estado Mini-Mental: propuesta de una normativa para su aplicación.

The Mini-Mental State Examination (MMSE) is currently one of the most widely used tools for the assessment and screening of cognitive impairment despite a number of issues raised regarding the sensitivity of some subtests and the negative impact of advanced age and poor education. The informal use of invalidated and poor quality translations of the MMSE into Spanish language is widespread, and presumably this further increases some of the uncertainties linked to this test. The result may be misleading, not only as it may overestimate the prevalence of dementia but because it decreases interrater consistency with a view to epidemiological projects. A validated translation of the MMSE into Spanish is therefore much needed. Such a version would not only pay attention to educational and age issues but it would also take into account potential cultural and linguistics inter-community difference of some subtests when specifically applied in Spain which may represent another potential source of inconsistency throughout the country. Furthermore, subtle inhomogeneities in the way the test is administered may result in gross intra-rater and inter-rater variability, hence further decreasing reliability. On the basis of experience gained from a large hospital-based experience in administering the traditional MMSE to neurological patients we propose a standardized version to apply MMSE in Spanish with the alm to improve reliability. This is a preliminary step toward developing a reliable and sensitive Spanish version of the MMSE.

[Depressive pseudodementia in early Parkinson's disease: lessons from a case with long-term follow-up]. / Seudodemencia depresiva en enfermedad de Parkinson incipiente: lecciones a partir de un caso con seguimiento prolongado.

A common observation in neurological practice is parkinsonism with concomitant cognitive decline, an association that usually arises from various underlying degenerative or vascular conditions, most of which are untreatable. An elderly woman with no history of psychiatric disease presented complaining of memory and cognitive impairment serious enough to interfere with daily life activities over the preceding year. She soon developed a predominantly left-sided tremor, rigidity and bradykinesia. She had had only 2 years of formal education. Neuropsychological assessment showed poor performance on Wechsler memory scale sub-items, as well as constructional apraxia, dyscalculia, reasoning difficulties and gross information deficits. A 3-month trial course of levodopa was followed by dramatic improvement in both parkinsonian symptoms and cognitive performance, including a 7-point gain in the Mini-Mental Status Examination score. At the same time, the Beck Depression Inventory score fell from 27 (baseline) to 18. Over the 10-year follow-up period the patient developed late levodopa syndrome and a persistent but mild dysthymic disorder, but never manifested dementia as defined by DSM-III-R criteria. This patient's case illustrates three important principles. First, although parkinsonism is known to be preceded by depressive episodes, particularly in a subgroup of younger patients, the symptoms of the elderly patient whose Parkinson's disease is foreshadowed by depression can mimic depressive pseudodementia, potentially leading to diagnostic confusion. Second, impaired motivation and disturbances in cognitive function are different from mood disorders, as the former involve the mesolimbic/mesocortical dopamine system, explaining the beneficial effect of levodopa on motivation and cognition in this patient even as mood was unaffected. Finally, depressive pseudodementia in Parkinson's disease does not necessarily herald the development of organic dementia in the long term.