Patients with advanced Parkinson's disease with and without freezing of gait: a comparative analysis of vascular lesions using brain MRI.

INTRODUCTION: Freezing of gait (FOG) is one of the most disabling and enigmatic symptoms in Parkinson's disease. Vascular lesions, observed in magnetic resonance imaging (MRI) scans, may produce or exacerbate this symptom. PATIENTS AND METHODS: The study includes 22 patients with Parkinson's disease subjects, 12 with freezing of gait and 10 without. All patients underwent an MRI scan and any vascular lesions were analysed using the modified Fazekas scale. RESULTS: Patients with FOG scored higher on the modified Fazekas scale than the rest of the group. Although the two groups contained the same percentage of patients with vascular lesions (50% in both groups), lesion load was higher in the group of patients with FOG. Vascular lesions in the periventricular area and deep white matter seem to be the most involved in the development of FOG. DISCUSSION: Vascular lesions may contribute to the onset or worsening of FOG in patients with PD. This study suggests that cerebral vascular disease should be considered in patients with FOG.

Tratamiento específico del infarto cerebral agudo. Presente y futuro / Specific treatment of acute cerebral infarction. Present and future

Las estrategias farmacológicas específicas en el tratamiento de la fase aguda del infarto cerebral se orientan a potenciar la reperfusión (antitrombóticos o trombolíticos) y la neuroprotección lo más precozmente posible. Desarrollo: los antitrombóticos son anticoagulantes, hipofibrinogemiantes (Ancrod) y antiagregantes. Con anticoagulantes se realizó el IST, empleando heparinas que causó un aumento de hemorragias sin beneficio neto evidente. Otros usaron heparinoides (TOAST) o heparinas de bajo peso molecular (FISS y FISS bis) y tampoco demostraron ningún beneficio y si un exceso de hemorragia en el primerio. En cuanto a Ancrod, acaba de concluir en ensayo en Norteamérica (STAT) con administración en < 3 horas que ha indicado beneficio significativo a los tres meses. Continúa otro europeo (ESTAT). Respecto a los antiagregantes, con ácido acetilsalicílico se realizaron el IST y el CAST en los que ha aprecido una reducción de recurrencias precoces y un aumento de las repercusiones, por lo que se ha recomendado su uso en las primeras 48 horas. Existen estudios con abcximab, un antagonista de receptores glicoproteína IIb-IIIa, uno en fase II en AVC ha demostrado que es seguro y que los paceintes tratados tienden a evolucionar mejor. Está en desarrollo otro fase III. Los trombolíticos han sido evaluados en diversos ensayos. Por vía IA el estudio PROACT valoró por-UK frente a placebo y demostró repermeabilización significativa en oclusiones de la arteria cerebral media, pero con mayor númer de hemorragias y sin una reducción de mortalidad. En PROACT II aparece mejor evolución en los pacientes tratados. Por vía IV, el ensayo NINDS con rt-PA (0.9 mg/kg en <3h) demostró una mejoría a los tres meses que se contrarrestó con un aumento de hemorragias cerebrales y mortalidad. El ECASS-II, con dosis similares al NINDS e idéntica ventaja que el ECASS, demostró un tendencia favorable en la evolución del grupo tratado sin aumento de las hemorragias intracraneales sintomáticas.

Tratamiento específico del infarto cerebral agudo. Presente y futuro / Specific treatment of the acute cerebral infarct. Present and future

Introducción. Las estrategias farmacológicas específicas en el tratamiento de la fase aguda del infarto cerebral se orientan a potenciar la reperfusión (antitrombóticos o trombolíticos) y la neuroprotección lo más precozmente posible. Desarrollo. Los antitrombóticos son anticoagulantes, hipofibrinogemiantes (Ancrod) y antiagregantes. Con anticoagulantes se realizó el IST, empleando heparina sc que causó un aumento de hemorragias sin beneficio neto evidente. Otros usaron heparinoides (TOAST) o heparinas de bajo peso molecular (FISS y FISS bis) y tampoco demostraron ningún beneficio y sí un exceso de hemorragia en el primero. En cuanto a Ancrod, acaba de concluir un ensayo en norteamérica (STAT) con administración en <3 horas que ha indicado beneficio significativo a los tres meses. Continúa otro europeo (ESTAT). Respecto a los antiagregantes, con Aspirina se realizaron el IST y el CAST en los que ha aparecido una reducción de recurrencias precoces y un aumento de las recuperaciones, por lo que se ha recomendado su uso en las primeras 48 horas. Existen estudios con abciximab (Reopro), un bloqueante de receptores glicoproteína IIb-IIIa, uno en fase II en ictus ha demostrado que es seguro y con tendencia a mejor evolución en pacientes tratados. Está en desarrollo otro en fase III. Los trombolíticos han sido evaluados en diversos ensayos.Por vía ia el estudio PROACT valoró pro-UK frente a placebo y demostró repermeabilización significativa en oclusiones de arteria cerebral media, pero con mayor número de hemorragias y sin una reducción de la mortalidad. En PROACT II aparece mejor evolución en los pacientes tratados. Por vía iv, el ensayo NINDS con rt-PA (0,9 mg/kg en <3 h) demostró una mejoría del estado funcional a los tres meses. El ECASS empleó dosis de 1,1 mg/kg de rt-PA en <6 horas, apareciendo una mejoría a los tres meses que se contrarrestó con un aumento de hemorragias cerebrales y mortalidad. El ECASS-II, con dosis similares al NINDS e idéntica ventana que el ECASS, demostró una tendencia favorable en la evolución del grupo tratado sin aumento de las hemorragias intracraneales sintomáticas. Conclusiones. Los neuroprotectores han mostrado eficacia en modelos de isquemia experimental, pero por el momento no existen evidencias definitivas de su beneficio en los numerosos ensayos realizados en humanos, aunque algunos subgrupos de pacientes parecen beneficiarse con alguno de ellos, por lo que continúan en desarrollo otros estudios. En un futuro podría plantearse su combinación con trombólisis (AU)

[Specific treatment of the acute cerebral infarct. Present and future]. / Tratamiento específico del infarto cerebral agudo. Presente y futuro.

INTRODUCTION: Specific pharmacological strategies in the treatment of the acute phase of a cerebral infarct are directed towards potentiating reperfusion (antithrombotic or thrombolytic drugs) and neuroprotection as early on as possible. DEVELOPMENT: The antithrombotic agents are anticoagulants, hypofibrinogemiant agents (Ancrod) and antiaggregants. The IST was done with anticoagulants, using heparin subcutaneously which causes increased bleeding without any obvious benefit. Others have used heparinoids (TOAST) or low molecular weight heparins (FISS or FISS bis) with no benefit either but with excessive bleeding with the former. Regarding Ancrod, a recent North American study (STAT) with administration of it within three hours showed significant benefit three months later. Another European study is still underway (ESTAT). With regard to antiaggregants, IST and CAST were done using Aspirin, showing a drop in early recurrences and increase in recoveries, so that aspirin has been recommended for use during the first 48 hours. There are studies using abciximab (Reopro), a blocker of the IIb-IIIa glycoprotein receptors, in which phase II data have shown that it is safe and tends to improve the outcome. A study on phase III is currently ongoing. The thrombolytic drugs have been evaluated in various trials. The PROACT study evaluated intraarterial pro-UK and showed significant recanalization of middle cerebral artery occlusions, but with a larger number of hemorrhages and no reduction in mortality and besides, in PROACT II the outcome of treated patients was better. The NINDS trial using intravenous rt-PA (0.9 mg/kg in < 3 hours) showed an improved functional state 3 months later. In the ECASS doses of 1.1 mg/kg of rt-PA in < 6 hours were used and improvement was seen after three months which was countered by an increase in cerebral hemorrhage and mortality. The ECASS II, with similar dosage to NINDS and an identical window to ECASS, showed a favorable tendency in the evolution of the treated group, with no increase in symptomatic intracranial hemorrhages. Neuroprotectors have shown to be effective in experimental models of ischaemia but at the moment there is no definite evidence of their benefit in the numerous trials carried out on humans, although some subgroups of patients seem to benefit from some of them. Studies therefore are still being done. In future their use in combination with thrombolysis may be considered.

[Anticoagulation and antiaggregation: implication in the acute phase of stroke following IST, CAST, TOAST, FISS and FISS bis]. / Anticoagulación y antiagregación: implicaciones en la fase aguda del ictus después del IST, CAST, TOAST, FISS y FISS bis.

INTRODUCTION: One of the therapeutic strategies in the acute phase of cerebral ischaemia is the use of antiaggregants and anticoagulants. DEVELOPMENT: Until recently, their clinical use was empirical. It was based on the favourable results of clinical trials using these drugs in acute coronary ischaemia and the results of some preliminary clinical trials (although not the definitive trials) in the acute phase of cerebral infarct. These involved a small number of patients and randomization errors which did not definitely show the benefit/risk ratio, particularly in cases of bleeding of any origin. However, they served as a basis for further studies. Therefore, IST was done using anticoagulants in a large number of patients. It was randomized and open, using subcutaneous non-fractionated heparin without a TPT control. Use of heparin was associated with a significant number of haemorrhages without obvious net benefit, so should not be used in these conditions. Other trials used heparinoids (TOAST) or low molecular weight heparin (FISS and repeat FISS) and showed no benefit either. IST and CAST are trials involving antiaggregants. They included larger numbers of patients using an open, randomized design. The results showed benefit, with reduction in the early recurrence of ischemia, death and dependence. There was also a significant, but not very relevant, increase in recovery. CONCLUSION: In view of this data Aspirin in doses of 160-300 mg/d during the first 48 hours after onset of the cerebral infarct has been recommended.

[Epileptic seizures as the first sign of fibrous bone dysplasia]. / Crisis epilépticas como primera manifestación de displasia ósea fibrosa.

INTRODUCTION: Fibrous bone dysplasia is an unusual disorder of the maturation of bone, seen as hyperostosis of the craniofacial bones and the diaphyses of long bones. Monostotic and polyostotic forms occur, depending on whether one or more bones are affected. The diagnosis is radiological (cranial CT or MR) or on morbid anatomy. The etiopathogenesis is not known. The association of epilepsy and monostotic fibrous bone dysplasia is rare. We present a case of monostotic fibrous bone dysplasia which presented with epileptic seizures. CLINICAL CASE: A 28 year-old-woman had had undiagnosed epilepsy for 12 years. Neurological examination was normal and EEG findings non-specific. Cranial CT and MR suggested fibrous bone dysplasia. Since there was bilateral reduction of the visual fields, due to compression of both optic nerves, the affected bones were removed surgically. Anatomopathological study confirmed the diagnosis of fibrous bone dysplasia. CONCLUSIONS: The association between epilepsy and monostotic fibrous bone dysplasia is unusual. Epilepsy may be an initial symptom in asymptomatic fibrous bone dysplasia. The mechanism for the production of epileptic seizures may not be related to compression phenomena or local ischemia, but be secondary to alteration in the mechanism of cAMP as the second messenger of the cerebral cortex. Patients with fibrous bone dysplasia should undergo neurological examination to rule out local compression with minimal clinical findings.

[Analysis of the echocardiographic findings in young patients with cerebral ischemia]. / Análisis de los resultados ecocardiográficos en pacientes jóvenes con isquemia cerebral.

INTRODUCTION: When we consider the importance of cardioembolism in the aetiology of cerebral ischaemia in young adults, echocardiography, both transthoracic and transesophageal, becomes of increasing diagnosis importance. We analyze its usefulness and contribution to the reduction in the number of cerebral ischemias of unknown origin. PATIENTS AND METHODS: We selected persons aged between 14 and 45 years who had had cerebral ischaemia during the period between January 1991 and April 1998. The protocol for the diagnosis of stroke in young persons was applied to all of them together with transthoracic echocardiography whenever there was the possibility of embologenous cardiopathy followed by transesophageal echocardiography when the transthoracic echocardiography was not diagnostic. RESULTS: In 114 identified cases, 98 transthoracic echocardiographs were done, of which 14 were diagnostic, together with 32 transesophagic echocardiograms, which showed nine cases of embologenous cardiopathy not detected on transthoracic echography. The most frequent diagnoses were: prolapsed mitral valve (14); patent foramen ovale (8); mitral stenosis (5) and interauricular septal aneurysm (4). A total of 31 patients were diagnosed as having a previously unrecognized cardioembolic origin of their illness. CONCLUSIONS: The diagnostic usefulness of transthoracic echography was 22.45% (9.18% were false negatives), and 28.12% for transesophagic echocardiography. These reduced the diagnosis of ischaemia of unknown origin by 32.69% and 20% respectively. Besides, in 75% of the patients with a patent foramen ovale and 100% of those with interauricular septal aneurysms, no other possible cause for their condition was found. Transthoracic echocardiography is a technique to be recommended in all cases of cerebral ischaemia of unknown origin in young adults. Its usefulness may be enhanced by transesophagic ultrasonography when diagnosis cannot be definitely made on transthoracic echosonography alone.