Neurocardiovascular pathology in pre-manifest and early-stage Huntington's disease.

BACKGROUND AND PURPOSE: Cardiovascular events are a major cause of early death in the Huntington's disease (HD) population. Dysautonomia as well as deterioration of circadian rhythms can be detected early in the disease progression and can have profound effects on cardiac health. The aim of the present study was to determine if patients with HD and pre-manifest mutation carriers present a higher risk of cardiovascular disease than non-mutation-carrying controls. METHODS: This was a prospective, cross-sectional, multicentre study of 38 HD mutation carriers (23 pre-manifest and 15 early-stage patients) compared with 38 age- and gender-matched healthy controls. Clinical and epidemiological variables, including the main haematological vascular risk factors, were recorded. Ambulatory blood-pressure monitoring and carotid intima-media thickness (CIMT) measurement were performed to assess autonomic function and as target-organ damage markers. RESULTS: Most (63.2%) patients with HD (86.7% and 47.8%, respectively, of the early-stage and pre-manifest patients) were non-dippers compared with 23.7% of controls (P = 0.001). CIMT values were in the 75th percentile in 46.7% and 43.5%, respectively, of the early-stage and pre-manifest patients, whereas none of the controls presented pathological values (P = 0.001 and P = 0.006, respectively). Nocturnal non-dipping was significantly associated with CIMT values in patients (P = 0.002) but not in controls. CONCLUSIONS: These results suggest that higher cardiovascular risks and target-organ damage are present even in pre-manifest patients. Although larger studies are needed to confirm these findings, clinicians should consider these results in the cardiovascular management of patients with HD.

Dopaminergic agonists in Parkinson's disease.

BACKGROUND: Non-ergoline dopamine agonists (DA) are effective treatments for Parkinson's disease (PD). This review presents the pharmacology, evidence of efficacy and safety profile of pramipexole, ropinirole, and rotigotine, and practical recommendations are given regarding their use in clinical practice. RESULTS: Extended-release formulations of pramipexole and ropinirole and transdermal continuous delivery rotigotine patches are currently available; these may contribute to stabilising of plasma levels. In early PD, the three drugs significantly improve disability scales, delay time to dyskinesia and allow a later introduction of levodopa. In late PD they reduced total 'off'-time, improved Unified Parkinson's Disease Rating Scale (UPDRS) in both 'on' and 'off' state and allowed a reduction in total levodopa dosage. A significant improvement in quality of life scales has also been demonstrated. Extended-release formulations have proved to be non-inferior to the immediate release formulations and are better tolerated (ropinirole). Despite a generally good safety profile, serious adverse events, such as impulse control disorder and sleep attacks, need to be routinely monitored. Although combination therapy has not been addressed in scientific literature, certain combinations, such as apomorphine and another DA, may be helpful. Switching from one DA to another is feasible and safe, although in the first days an overlap of dopaminergic side effects may occur. When treatment with DA is stopped abruptly, dopamine withdrawal syndrome may present. Suspending any DA, especially pramipexole, has been linked to onset of apathy, which may be severe. CONCLUSIONS: New non-ergotine DAs are a valuable option for the treatment of both early and late PD. Despite their good safety profile, serious adverse effects may appear; these effects may have a pathoplastic effect on the course of PD and need to be monitored.

[Incidence of venous system disease in pseudotumor cerebri]. / Incidencia de alteraciones del sistema venoso en pseudotumor cerebri.

OBJECTIVE: Pseudotumor cerebri (PC) is a complex syndrome characterized by increased intracranial pressure in the absence of any space occupying lesion, usually self-limiting, but often relapsing In recent years, some authors had researched the relationship between venous sinus disease and PC and they have suggested that it must be ruled out by magnetic resonance venography (MRV) before diagnosing this condition as idiopathic. Our aim is to determine the frequency of venous sinus disease and the need for MRV in these patients. METHODS: We have studied 14 patients admitted between 1998 and 2005 in the Neurology Department of the University Clinical Hospital <> (Zaragoza; Spain) who had been diagnosed of PC. We reviewed the epidemiological and clinical features. The MRVs were reviewed and their appearances rated for focal narrowing and signal gaps. RESULTS: Six patients had strong signal in both lateral and transverse sinus and their image was considered as normal. The other eight patients showed filling defects on the transverse sinus (focal unilateral narrowing in four cases, one or more signal gaps in four cases). CONCLUSIONS: The presence of signal gaps in the venous sinus (stenosis/hypoplasia or absence of signal) is a frequent finding in patients with PC. That is why we have concluded that this test is important in patients with PC in order to search for a possible etiology and treatment option.

[Neuroprotection in Parkinson's disease: analysis though group of experts' methodology]. / Neuroprotección en la enfermedad de Parkinson: análisis a través de la metodología de informadores clave.

INTRODUCTION: Currently used antiparkinsonian drugs neither stop nor slow-down the progressive nature of the disease. The final phase of PD is characterized by the presence of symptoms and signs resistant to dopaminergic agents, such as depression, dementia, freezing and falls. Therefore, it is urgent to develop therapies able to positively modify this outcome. Despite neuroprotection is a research priority in PD, no effective strategies have been found so far. METHOD: A key informants study was conducted. A group of experts in PD fulfilled a questionnaire of 10 questions to explore the most important topics related to neuroprotection. Afterwards a consensus about the current situation of neuroprotection in PD was established and future directions of development were suggested. RESULTS: Most of the answers emphasized the need of new concepts, the limitations of animal models and the difficulties in the difficulties in demonstrating a neuroprotective effects in humans owing to a lack of biomarkers. Some of the experts believe that we are already exerting a disease modifying effect. CONCLUSIONS: The concept of neuroprotection should be widened. Animal models should be improved. A reliable biomarker to start neuroprotective therapies long before the appearance of motor symptoms and to evaluate the neuroprotective effect of any therapy should be urgently developed.

[Acute transverse myelitis secondary to hepatitis B vaccination]. / Mielitis transversa aguda secundaria a la vacunación de la hepatitis B.

INTRODUCTION: Acute transverse myelitis is an inflammatory disorder. The pathogenesis is unclear, but the probable mechanism involves an autoimmune phenomenon. Possible causes included multiple sclerosis and parainfectious and postvaccinal events. Myelitis has rarely been reported secondary to vaccinations including hepatitis B. We present a case of acute myelitis, which seems secondary to the administration of the hepatitis B vaccine. CLINICAL CASE: A 15-years-old female presented with progressive numbness of the right arm and leg, with right leg weakness. Symptom began one week after receiving the first dose of the hepatitis B vaccine. Spinal cord magnetic resonance (MR) revealed a diffuse increased signal extending from C6 to D2. Cerebral MR and cerebrospinal fluid were normal. She was treated with high doses of methylprednisolone with a complete recovery of neurological functional. Repeat medullar cord MR was normal. There was no relapse during a four years follow up. CONCLUSIONS: Potential causal relationship between vaccination against hepatitis B and multiple sclerosis was brought to the attention and to public debate. However, no conclusive association could be made between vaccination and demyelination. In the clinical setting, the distinction between a first episode of multiple sclerosis or postvaccinal myelitis depends upon subsequent course.

[Diabetes mellitus and stroke]. / Diabetes mellitus e ictus.

INTRODUCTION: Diabetes mellitus (DM) is an important risk factor in cerebral vascular disease since it causes endothelial proliferation and thickening of the plasmatic membrane in the small blood vessels. The pathogenic mechanism is thus different from that of athero-thrombosis or emboli. Our objective was to determine whether there are differences between strokes in diabetic patients and strokes secondary to other diseases. PATIENTS AND METHODS: We made a prospective study of 415 stroke patients admitted to hospital consecutively over one year. Transient ischaemia and subarachnoid hemorrhage were excluded. We analysed age, sex, risk factors, severity (Canadian scale), mortality and functional prognosis one week later. RESULTS: Of the 415 patients, 354 were diagnosed as having cerebral infarcts and 61 parenchymatous hemorrhage. The average age was 72.2 years. The commonest risk factor was arterial hypertension (n = 241). There were 95 patients with DM. Bivariate and multivariate analysis showed independent variables associated with DM to be the onset of cerebrovascular pathology at a younger age (p = 0.009), association with arterial hypertension (p = 0.002) and poor previous quality of life (p = 0.003). We did not find a higher incidence of lacunar infarcts amongst the diabetic patients. CONCLUSIONS: The diabetic patient is younger and often also has arterial hypertension. There was no difference in mortality or type of stroke (ischemic compared with hemorrhagic). No significant relationship was found with lacunar infarcts.

[Transient global amnesia: a review of 58 cases]. / Amnesia global transitoria: revisión de 58 casos.

INTRODUCTION: Transient global amnesia (TGA) is a clinical condition in which the etiopathogenesis is still not clear. The most generally accepted theory is of a vascular origin, although epilepsy or migraine have also been considered to possibly be the cause. OBJECTIVE: To make a retrospective review of the risk factors, etiopathogenesis and clinical characteristics of 58 patients with TGA. PATIENTS AND METHODS: The variables recorded were compared with those from two control groups: one of healthy individuals and one of patients with transient ischemic attacks (TIA). RESULTS: The average age of the patients with TGA was 66.01 years. The risk factors included: arterial hypertension (58.62%), dyslipemia (15.51%) and migraine (8.62%). In three patients the EEG showed weak bilateral frontotemporal interference. Cerebral CT scans were done in all cases and were found to be pathological in 23, with lacunar multinfarct the commonest abnormality. With regard to patients with TIA, these were older (66.01 vs 72.94), smoked more (1.72% vs 12.06%) and a previous stroke was more frequent (8.62% vs 31.03%). We did not find differences regarding dyslipemia, atrial fibrillation, arterial hypertension or cardiac ischemia. However, the prevalence of vascular risk factors was significantly higher in patients with TGA as compared to healthy controls. CONCLUSION: We suggest that the etiopathogenesis of TGA is probably a transient ischemic phenomenon triggered (or not) following an attack of migraine.

[Cardioembolic infarction: clinical course and characteristics]. / Infarto cardioembólico: características clínicas y evolutivas.

INTRODUCTION: Approximately 20% of all ischemic strokes are due to cardioembolism and occur more frequently in the younger patients. Our objective was to determine the clinical characteristics and course of cardioembolic infarcts (ICCE) comparing them with infarcts due to other aetiologies (ICNCE). PATIENTS AND METHODS: We made a prospective study of 354 patients admitted to hospital over a period of one year, after excluding transient ischaemia and parenchymatous/subarachnoid hemorrhage. Two groups were established: ICCE (29.4%) and ICNCE (70.6%), comparing age, sex, risk factors and course of the illness. Subsequently a study lasing two years was done to assess the recurrence rate. RESULTS: The ICCE patients were older (75.89 compared with 72.58, p = 0.004), often know the exact time of onset of their symptoms (p = 0.015) and usually are admitted to hospital during the first six hours of their illness (p = 0.01). There was a significantly higher incidence of ischemic cardiopathy or auricular fibrillation (p = 0.0052); p = 0.005); more complications arose (p = 0.000); stay in hospital was longer (13.62 as compared to 11.8 days; p = 0.035), there was a lower weekly BI score (p = 0.0023) and higher mortality (p = 0.000). In the subgroup of 70 patients evaluated two years later 11 cases recurred, with no difference observed between the anticoagulant and anti-aggregant groups. CONCLUSION: The ICCE occurs in older patients, they develop worse neurological defects, have a worse short-term prognosis, develop more complications and have significantly greater mortality.

[Symptomatic epilepsy: review of 208 patients]. / Epilepsia sintomática: revisión de 208 pacientes.

OBJECTIVE: To determine the main etiological mechanisms of symptomatic epilepsy and its frequency according to age. PATIENTS AND METHODS: We made a retrospective analysis of 208 patients admitted during a period of four and a half years, studying the variables: age, sex and type of seizures: simple partial, secondarily generalized partial, complex partial, tonic-clonic, generalized tonic, and also EEG and neuroimaging. RESULTS: The main etiological mechanisms found were: vascular (31.25%), alcoholic (12.01%), intracranial disorders (9.61%), traumatic (5.28%), degenerative (5.28%), infectious (2.88%) and cryptogenic (33.65%). In the last group there was an outstandingly large proportion of patients with silent infarcts. When considering vascular epilepsy, those seizures occurring during the acute phase of the stroke (24/65) are differentiated from those of late onset (41/65). In the latter there was a marked predominance of ischemic etiology (48.78% corresponded to extensive infarcts in the territory of the middle cerebral artery; 36.58% were associated with partial infarcts) probably because of the greater frequency of ischemic stroke as compared with hemorrhagic stroke. After the acute phase, the latency was of 10.68 +/- 0.43 months and the most frequent seizures were tonic-clonic (48.78%). CONCLUSION: In persons under 30 years of age, etiology is multifactorial; between 30 and 50 years of age alcoholic epilepsy (39.53%) and traumatic epilepsy (11.62%) predominate; over the age of 50 years the cause was vascular in 43.5%. In the latter age group there was a high proportion of patients with heraldic seizures.

[Idiopathic hypophyseal hyperplasia: diagnosis by magnetic resonance]. / Hiperplasia hipofisaria idiopática: diagnóstico por resonancia magnética.

INTRODUCTION: Hypophyseal hyperplasia is an uncommon disorder in which the gland increase in size due to excessive proliferation of strings of normal cells, which usually secrete prolactin. Different aetiologies may cause this disorder of the hypophyseal gland. However, in a small number of cases the hyperplasia is not due to any of these aetiologies and is therefore known as idiopathic hypophyseal hyperplasia. There are few references in the literature to idiopathic hypophyseal hyperplasia with hyperprolactinaemia. Usually diagnosis is reached after treatment for a hypophyseal adenoma, since the clinical features are similar. CLINICAL CASES: We present three cases seen in our department, in which hormone and endocrine studies were done to exclude known causes of hyperplasia, together with CT and MR scans. We analyzed the behaviour of hypophyseal hyperplasia by using imaging techniques, and the differential aspects with regard to hypophyseal adenomas. Firm diagnosis is only made on anatomopathological study of the hypophysis. However, we consider that sound knowledge of the characteristics of this condition may help to establish the correct diagnosis and thus avoid unnecessary surgery. CONCLUSIONS: We review the information published in the literature on this subject, emphasizing the importance of differential diagnosis by means of imaging techniques.

[Mitochondrial respiratory chain deficiency may present as multiple sclerosis]. / El déficit en la cadena respiratoria mitocondrial se puede presentar como una esclerosis múltiple.

Defects of the mitochondrial respiratory chain are associated with a great variety of clinical disorders. In addition to the well recognized syndromes, a significant number of patients present non-specific encephalopathic disorders. In consequence these types of mitochondrial disorder are very difficult to diagnose on clinical features alone. In this paper, we describe the clinical and the magnetic resonance findings of 2 patients with a neurological syndrome indistinguishable from multiple sclerosis (Poser). Muscle biochemistry revealed defect of complex IV of the respiratory chain. We think that these patients have a mitochondrial encephalomyopathy. We suggest that in patients presenting as atypical multiple sclerosis it could be necessary investigating mitocondrial encephalopathy.

[Evaluation study of the chronic headache questionnaire]. / Estudio de validación de un cuestionario para cefaleas crónicas.

INTRODUCTION: Semi-structured questionnaires, based on clinical criteria are used in the diagnosis of headache, but none has been used to study the two commonest types of chronic headache. The first step, before clinical application, is to carry out a study of the questionnaire's validity and predictive value. OBJECTIVE: The objectives of our study were to evaluate the validity and determine the effectiveness of the ZZA questionnaire in the differential diagnosis between transformed migraine (TM) and chronic tension headache (CTH), in a specialist Neurology Clinic. MATERIAL AND METHODS: The ZZA questionnaire, elaborated by one of the investigators, was made up of 20 questions aimed at TM, CTH or the chronicity of the headache. An observer, who did not know the diagnosis, gave the questionnaire to patients who had previously been diagnosed by the head of the Headache Clinic as having TM or CTH. The process of validation of the questionnaire consisted in showing that it was reliable, with valid contents and valid criteria. RESULTS: On analysis of reliability, the items ZZA1, ZZA15, ZZA16 and ZZA18 gave the highest indices. The Cochran Q test showed lack of uniformity of replies. Only ZZA1, ZZA15 and ZZA18 were predictive items showing MT. None of the questions to show CTH were predictive. After final adjustment the definitive model was made up of ZZA1, ZZA15 and ZZA18. CONCLUSIONS: The proposed questionnaire was not found to be useful for differential diagnosis between TM and CTH. Only 3 of the 20 questions were accepted as having some degree of validity and effectiveness. Two of these 3 questions, based on clinical impressions of the author, might well be included in the diagnostic criteria of TM.

[Hormonal response to stress after cerebrovascular accident: relation to type, size and site of the lesion]. / Respuesta hormonal de estrés tras un accidente cerebrovascular. Relación con el tipo, tamaño y localización de la lesión.

OBJECTIVE: To study the relationship between the hormone response to stress seen after ACV (CVA) and the type, size and site of the lesion. MATERIAL AND METHODS: We made a prospective study of the relationship between stress hormones and the radiological characteristics of the lesion in 82 patients admitted to hospital for non AIT ACV (CVA). We assessed the 24 hour urine catecholamines (total catecholamines, adrenaline, noradrenaline, vanillylmandelic acid, metanephrines and dopamine) and the 24 hour urine cortisol, collected on the second and third day after admission respectively. The type, size and site of the lesions were studies on CT scans done between 3 and 7 days after admission. RESULTS: We studied 82 patients, 43 men and 39 women with an average age of 71.7. In 7 patients the lesion was parenchymatous haemorrhage; in 75 it was an infarct, which was small (< 6 cm3) in 30.5%, moderate sized (6-60 cm3) in 38.6% and large in 30.6%. In the cases of infarct, only the cortisol was significantly different in the three groups (average (DE) standard deviation, respectively: 80.6 (50), 114 (124) and 246 (207); p = 0.0014). This relationship persisted when the cortisol level was compared with the volume in cm3 (p = 0.0028). The cortical infarcts had significantly higher levels of cortisol than the more deeply situated infarcts (83.2 (55) as compared to 174 (184); p = 0.0321), but the latter were smaller and no difference was seen when size was taken into account. All findings were similar in haemorrhages and infarcts of equal size. CONCLUSIONS: There was no relationship between the catecholamines and the type or size of the lesion. In our series, the site of the lesion did not appear to have any effect on the characteristics or intensity of the hormone response.

[Epilepsy as the first sign of multiple sclerosis]. / Epilepsia como primera manifestación de esclerosis múltiple.

INTRODUCTION: Epileptic crises are uncommon in patients with multiple sclerosis. However, epilepsy is commoner in these patients than in the general population. An epileptic crisis as the presenting feature of multiple sclerosis is even rarer. The lesions involved in the pathogenesis of these crises are plaques of demyelinization which affect the cortical or subcortical areas. Other factors, some of which are still not clearly understood, such as the fibre, electrolytic changes, size of the plaque, reactive gliosis and the enzyme (Na(+)-K+)ATPase, seem also to play a part in the production mechanism. Magnetic resonance is a very sensitive technique used in the detection of demyelinating lesions during the acute phase. The sensitivity is further increased by the use of gadolinium. CLINICAL CASES AND CONCLUSIONS: We present two cases of multiple sclerosis which presented as epileptic crises. In one there were generalized tonic-clonic crises and in the other partial sensitive crises. We mention the EEG findings, CSF analysis and neuroimaging diagnostic techniques.

[Epilepsy with normal CT: the MR contribution]. / Epilepsia con TC normal: aportaciones de la RM.

We present a study of 165 patients with fits with normal brain computerized tomography (CT) scan or else who showed no evidence as to the etiology of such attacks. We analyzed the magnetic resonance (MR) results obtained. In 36.6% of cases MR was pathological, the most frequent finding in our series being cerebral atrophy (12.8%). We comment on the most important pathology groups, highlighting the contribution MR made in our patients.

[Principal components analysis]. / Análisis de componentes principales.

OBJECTIVE: This study wants to identify factors or components latent besides health indicators from Spanish regions, and its graphic output. DESIGN: Observational study. SETTING: Twenty eight indicators from regions were used: mortality, morbidity, communicable and no-communicable diseases, diet, dwelling and sanitary resources. Measurement was made between 1980-1988. INTERVENTIONS: Principal component analysis has been applied to the indicators, reducing data dimension. MEASUREMENT AND MAIN RESULTS: Eight factors have been extracted, which explain 90% of the original information. This analysis, as can be seen from communnalities, represents correctly the set of original variables. The factors with more easily interpretation were: shortage sanitary resources, develop diet, mortality, chronic diseases and accidental. CONCLUSIONS: Only reduction data dimension could be justify the use of principal component analysis. Behind the agrupation of variables is mostly the socioeconomic background.

[Giant aneurysms of the basilar artery. Six cases]. / Aneurismas gigantes del tronco basilar. A propósito de 6 casos.

The authors describe 6 cases of giant aneurysm of the basilar artery diagnosed in the Neurology Department of the Hospital Clínico Universitario of Zaragoza over the last 8 years by cerebral CT, arteriography and NMR with the clinical, diagnostic, and evolutive features of the same being reported. In 2 cases the clinical manifestations initiated as subarachnoid hemorrhage, in another two as AIT, in the fifth case as cerebral infarction and in the sixth case with pseudotumoral clinical manifestations with a necropsy study being available in the latter case. Three of the 6 patients died and of the remaining three only one was, successfully operated on. Anatomopathologic, clinical, therapeutic and diagnostic aspects of giant aneurysms of the basilar trunk are also reviewed with NMR being recommended as the technique of choice in diagnosis.

[Magnetic resonance in Hallevorden-Spatz disease]. / Resonancia magnética en la enfermedad de Hallevorden-Spatz.

The Hallevorden-Spatz disease should be suspected in children or young people with motor, pyramidal or extrapyramidal symptomatology and deterioration of superior functions specially upon the existence of family history. Pathognomonic diagnosis may only be obtained by necropsy but magnetic resonance images, although not pathognomic, are sufficiently characteristics to strongly support the diagnosis. Four cases of Hallevorden-Spatz disease are presented with special emphasis on the MR images characteristic of this disease.