Historical setting and neuropathology of lathyrism: Insights from the neglected 1944 report by Oliveras de la Riva.

Lathyrism is a central motor system disorder recognized since antiquity resulting from prolonged dietary dependence on the grasspea (Lathyrus sativus). The neuropathology underlying the characteristic spastic paraparesis of lathyrism is sketchy. Described here is a landmark but little-known Spanish-language neuropathological study of two patients with lathyrism of recent onset. Due to erroneous interpretations of Filimonov's influential work in 1926, it was assumed that spastic paraparesis of lathyrism was explained by destruction of Betz's pyramidal cells in the motor cortex. Contrary to present understanding, Betz cells and anterior horn cells were preserved, and pathological findings dominated by myelin loss were largely limited to pyramidal tracts in the lumbar cord. Thickening of the adventitia of capillaries and arterioles, together with proliferation of perivascular astrocytes, was found along the length of the spinal cord. Oliveras de la Riva proposed that the segmental spinal pathology arose because distal regions of elongate pyramidal tract axons are distant from their trophic center in the motor cortex, a view not far from the current distal axonopathy concept of lathyrism. In addition, we review the historical circumstances of Filimonov's work in Russia, a summary of the epidemic of lathyrism in Spain following its Civil War (1936-1939), and some historical aspects of the Cajal Institute in Madrid, where Oliveras de la Riva's work was carried out under the supervision of Fernando de Castro, one of Cajal's favorite students.

[Pharmacological treatment of Korsakoff's psychosis: a review of the literature and experience in two cases]. / Tratamiento farmacológico de la psicosis de Korsakoff: revisión de la bibliografía y experiencia en dos casos.

INTRODUCTION: Korsakoff s psychosis (KP) is a relatively frequent pathological condition in our community that has been infradiagnosed. The most common cause is chronic alcohol consumption, although it can be brought about by other aetiologies accompanied by vitamin deficiencies. The lack of thiamine entails an alteration in the synthesis of neurotransmitters, which provides the neurochemical foundation for the specific cognitive impairment that defines the syndrome. AIMS: To evaluate the application of pharmacological treatments, in accordance with the neurochemical disorders described in the literature, and report our experience in two cases treated with anticholinesterases. CASE REPORTS: 1) Female aged 47, with a history of addiction to alcohol. Following Wernicke s encephalopathy, which improved with parenteral thiamine, she presented a memory disorder compatible with KP. After two months treatment with donepezil, a cognitive improvement was observed in the neuropsychological tests. 2) Male aged 77, who presented KP a month after being diagnosed and treated for a post encephalitic vasculitis caused be varicella zoster virus. His cognitive and functional condition improved after 3 months treatment with donepezil. DISCUSSION AND CONCLUSIONS: There are not enough studies in the literature with representative samples that consider the effects of thiamine or of other forms of treatment on cognitive impairment in KP. Noradrenaline, serotonin, glutamate and acetylcholine have been proposed in the pathogeny of the syndrome. Based on experiences gained in cholinergic disorders, two cases responded to treatment with donepezil. Effective treatment must be based on a combination of aetiological and pharmacological treatment, and cognitive rehabilitation.

[Neuropsychological changes in epilepsy]. / Alteraciones neuropsicológicas en epilepsia.

OBJECTIVE: The neuropsychological assessment of the epileptic patient is a very important aspect of diagnosis and treatment. It may be used to contribute to localization of the hemisphere involved in the seizures, differentiate situations of anxiety or depression or when planning treatment for rehabilitation. We review the different aspects of neuropsychological changes in patients with epilepsy. DEVELOPMENT: Firstly we review the different tests used in the neuropsychological assessment of epilepsy. Dodrill's neuropsychological battery of tests, in which the patients score less than the controls, is the most commonly used. We then evaluate and study the so-called 'transient cognitive disorder'. We also study memory problems in epilepsy. There may be episodes of seizures with amnesic features ('amnesic epileptic seizures'). Finally, the possibility of neuropsychological dysfunction secondary to antiepileptic drugs should always be considered. CONCLUSIONS: Epileptic patients have lower scores than persons taken as controls for the results of various neuropsychological tests, although there is less difference between the two groups when the patient group is made up of persons with a normal intelligence quotient. Transient cognitive involvement is common in epileptics and may cause underachievement at school or psychological problems. Memory disorders, particularly subjective, are common in epileptics, although neuropsychological tests other than those generally used may be necessary to evaluate this. It is possible that such memory disorders, if occurring as seizures, may be due to amnesic partial crises, which should always be differentiated from the diagnosis of transient global amnesia. Almost all antiepileptic drugs can cause negative neuropsychological effects, especially the benzodiazepines and barbiturates.

[Use of lamotrigine in the treatment of absence epilepsy crises]. / Utilidad de la lamotrigina en el tratamiento de las crisis epilépticas de ausencia.

OBJECTIVE: To review the current treatment and usefulness of lamotrigine in absence seizures. DEVELOPMENT: Absence seizures are classified amongst the generalized epilepsies. They are defined as a transient loss of consciousness of sudden onset and recovery characteristically associated with generalized spike-and-wave discharges on the EEG. In recent years, the epileptic syndromes associated with this type of seizure have been better defined, basically by means of video-EEG studies. The International League Against Epilepsy has recognized four epileptic syndromes with typical absences: absence-epilepsy of childhood, juvenile absence-epilepsy, juvenile myoclonic epilepsy and epilepsy with myoclonic absences. The classical treatment for this type of seizure was based on ethosuximide, or more often, sodium valproate. Sometimes both drugs together were necessary. Other useful drugs are the benzodiazepines such as clobazam. CONCLUSIONS: We review studies of the efficacy and tolerance of lamotrigine in the treatment of absence seizures, one of the groups of seizures in which this drug has been shown to be most effective. Although studies comparing lamotrigine, valproate and ethosuximide are necessary, we emphasize the possibility that lamotrigine may be a drug of choice in absence seizures.

[Acute symptomatic epilepsies]. / Epilepsias agudas sintomáticas.

OBJECTIVES: To review the differentiating characteristics of symptomatic acute epilepsies, epidemiology, aetiology and controversies over treatment, and describe our experience with symptomatic acute epilepsy in cerebrovascular disorders. DEVELOPMENT AND CONCLUSIONS: The so-called symptomatic acute epilepsies show clearly differentiated characteristics with regard to true epileptic disorders: 1. A clearly identified causal association; 2. Generally tend not to recur; 3. Usually long-term anti-epileptic treatment is not necessary. Therefore the most suitable term for them is symptomatic acute seizures. They make up a large proportion of all newly-diagnosed epilepsies around 40%. The highest incidence occurs during the first year of life (probably because of the high incidence of seizures due to encephalopathies, metabolic disorders and infections) and in elderly patients (especially in relations to cerebrovascular disorders). The commonest causes are: cerebrovascular disorders, head injury, infections of the central nervous system, alcohol and drugs. The risk of subsequent epilepsy is increased in a subgroup of these patients, especially in cases with associated cerebrovascular disorders, head injuries and central nervous system infection. Long-term preventive treatment is rarely indicated in these patients.

[Peripheral facial paralysis: etiology, diagnosis and treatment]. / Parálisis facial periférica: etiología, diagnóstico y tratamiento.

OBJECTIVE: Peripheral facial paralysis is one of the commonest mononeuropathies. The frequency of idiopathic peripheral paralysis or Bell's palsy varies between 62% and 93% of all cases, with an incidence of between 14 and 25 cases per 100,000 inhabitants per year. However, in spite of its relative frequency in the population, there is still no definite unanimously agreed strategy currently used by neurologists. Although its course is relatively benign, up to 16% of the patients show moderate or severe sequelae according to follow-up data in 1,011 untreated patients. In this article we review the aetiology, diagnostic methods and therapeutical strategies at the present time. DEVELOPMENT: The topographic diagnosis of the lesion is based on the symptoms associated with the paralysis. The neurophysiological studies (trigeminofacial reflection and electroneurogram), usually done after the first week are prognoses that permit differentiation of the degree of the lesion (neuropraxis, axonotmesis or neurotmesis). In spite of recent trials with combined therapy (acyclovir and steroids) the most generally accepted treatment at present is still prednisose at a dose of 1 mg/kg/day. CONCLUSIONS: Peripheral facial paralysis is a common condition, usually with no apparent cause and an eminently clinical diagnosis. The electrophysiological studies determine the prognosis. Currently the standard treatment is still oral prednisone.

Patients with acenocoumarol treatment and migraine.

OBJECTIVE: The aim of our study was to investigate the possible effect of acenocoumarol, which is indicated for nonneurological disease, on headache. BACKGROUND: It has been suggested that anticoagulation can have beneficial effects in the control of migraine attacks. METHODS: Four hundred randomized patients on oral anticoagulant therapy were asked to complete a questionnaire regarding their headaches. RESULTS: Headache was present before or during oral anticoagulation in 166 (66 migraineurs and 100 nonmigraineurs) of 326 respondents. The major finding was that oral anticoagulation produced improvement in 63% of patients with migraine versus 38% of patients with nonmigranous headache. Improvement was related to the severity of migraine but not to age. CONCLUSIONS: Oral anticoagulant therapy can improve migraine. The way in which anticoagulant therapy acts on migraine is unknown, but potential mechanisms include its effect on platelet aggregability and pharmacological effects such as suppression of enhanced nitric oxide.

[Visual field changes secondary to vigabatrin treatment]. / Alteraciones de los campos visuales secundarias al tratamiento con vigabatrina.

INTRODUCTION: Vigabatrin is an effective antiepileptic drug for treatment of partial crises with or without generalization. It acts by increasing GABA levels by irreversible inhibition of the enzyme GABA-transaminase. In recent years there have been several reports published on the appearance of alterations of the visual fields of patients treated with this drug. OBJECTIVE: To study the prevalence and characteristics of the visual field changes associated with vigabatrin treatment in an adult epilepsy clinic. PATIENTS AND METHODS: Ophthalmological examination, consisting of questions about eye symptoms, study of the fundus oculi, Humphrey-type campimetry, protocol 30-2, visual evoked potentials and electroretinogram were done on a group of 10 patients on long-term vigabatrin treatment. RESULTS: Six of the ten patients (60%) had campimetric alterations, which were serious in two cases (20%). Only the two patients with severe field defects complained of sight changes when questioned and their complaints were mainly of repeatedly bumping into things. In two patients (20%) there was pallor of the optic nerve. In both cases, the patients with severe field defects showed alterations on the electroretinogram. Visual evoked potentials were normal in all cases. CONCLUSIONS: There is a very high prevalence of visual field defects in patients on long-term treatment with vigabatrin. Clinical ophthalmological signs are not usually seen until advanced stages. Pallor of the optic nerve was seen in a group of patients. It is very important that serial campimetric studies are done for early detection of such alterations.

[Revalidation and standardization of the cognition mini-exam (first Spanish version of the Mini-Mental Status Examination) in the general geriatric population]. / Revalidación y normalización del Mini-Examen Cognoscitivo (primera versión en castellano del Mini-Mental Status Examination) en la población general geriátrica.

BACKGROUND: The revalidation of the Mini Examen Cognoscitivo (MEC), first Spanish version (1978) of the Mini-Mental Status Examination (MMSE) and documentation of "population-based norms" should clarify the potential confusion induced by later versions of MMSE. CONTEXT: The Zaragoza Study on the prevalence of dementia and depression in a representative sample of the elderly community (N = 1,080). INSTRUMENTS: MEC-35 and MEC-30 points, and validated, Spanish versions of Geriatric Mental State (GMS), History and Aetiology Schedule (HAS) and Social Status Schedule (SSS). PROCEDURE: a) validation of MEC (standardized lay interviewers) against the gold standard of psychiatric diagnosis (DSM-III-R), two months later; b) "population-based norms" in the "healthy" population, and c) comparison with other MMSE versions. RESULTS: The instrument fulfills criteria of "feasibility", "content", "procedural" and "construct validity". Test-retest reliability: weighted kappa = 0.637. MEC-30 (cut-off point 23/24), sensitivity = 89.8%, specificity = 75.1% (80.8% with the cut-off at 22/23), and ROC curve, AUC = 0.920. The coefficients of individual items were satisfactory and the specificity increases in MEC-35 (83.9%). Other MMSE Spanish versions have not improved these coefficients. "Population-based norms" confirm the hypothesized influence of age and education level. MEC-30 is the version with most comparable results with the MMSE in USA. CONCLUSIONS: The validity of MEC is confirmed in the elderly population, with the same cut-off points recommended in the original standardization. MEC-30 is the best version for international comparisons.

[Epidemiology of various types of vascular epilepsy in adults]. / Epidemiología de los distintos tipos de epilepsia vascular en adultos.

From studies of the incidence of epilepsy, figures of between 40 and 70 per 100,000 inhabitants are obtained whilst in studies of prevalence, 5 to 7 cases per 1,000 are found. Cerebrovascular disease is the commonest cause of epileptic crises in the developed world, being more frequent in patients aged over 60, who make up 50% of all cases. Depending on the moment of presentation of crises in relation to the cerebrovascular disease, these may be classified as herald crises or precursors of vascular epilepsy, early crises if they occur during the first week and late crises if they occur after. Whilst early crises are usually due to metabolic or cytotoxic factors, the late crises occur in true vascular epilepsy. When these patients are assessed it is also important to consider increased hospital mortality in those with early crises and possible deterioration of neurological deficit as sequelae following late epileptic crises.

[Safety profile of 311C90 (zolmitriptan)]. / Perfil de seguridad del 311C90 (zolmitriptán).

A bibliographic review of the safety profile of 311C90 or zolmitriptan is performed in the present study showing the large number of clinical trials carried out in both healthy volunteers and patients with migraine. The molecule, a potent, selective agonist for the 5HT1B/1D receptors with central and peripheral activity does not appear to have significant influence on arterial pressure. ECG and Holter ECG studies did not show any alterations in healthy volunteers. In migraine patients, the ECG did not demonstrate ischemic alterations at any of the dosages of zolmitriptan used. In patients who had undertaken treatment for months, the hemogram and biochemical follow up did not show any changes. This new triptan was well tolerated in a wide spectrum of patients and healthy volunteers. Complaints of subjective side effects usually increase according to an increase in dosage. The most frequent adverse effects were nausea and dizziness. Other discomforts are: dryness of the mouth, sensation of heat, paresthesia, asthenia, drowsiness, and dizziness. The sensation of heaviness, tightness or pressure of the throat and chest have also been reported. The adverse effects reported with 5 mg of zolmitriptan are similar to those found with 100 mg of sumatriptan. The adverse side effects are usually mild, last a short time and remit without therapy. Zolmitriptan used together with the other most often used drugs in migraine patients did not show any important clinical interactions. However, it seems reasonable to limit the daily administration of zolmitriptan with monoaminoxidase inhibitors (MAOI-A) since a possible increase of the levels of zolmitriptan and its metabolites may be detected in the presence of one (moclobemide). At a dose of 2.5 mg, zolmitriptan appears to provide the best relationship between benefits and risk.

The hypnic headache syndrome: report of three new cases.

Three new cases compatible with hypnic headache syndrome (HHS) are presented. The patients were 70, 77, and 79 years of age (2F, 1M). They described a history of nocturnal headache ranging from 5 months to 7 years. One patient was afflicted with diffuse pain but the other two had unilateral pain. In one patient headache was clearly related with dreams, but in the other two this point could not be confirmed. Except for headache being unilateral in two cases, the remaining HHS criteria were present. It is noteworthy that pain responded to flunarizine in two patients.

Long-term evolution of a laughing headache associated with Chiari type 1 malformation.

We describe an acute-onset, sharp, short-lasting (few seconds) headache at the vertex, that first occurred 10 years ago in a 44-year-old woman. Attacks were triggered by vigorous laughing. A magnetic resonance imaging study showed a Chiari type 1 malformation. To our knowledge, laugh-induced headache with long-term evolution in association with Chiari type 1 malformation has not been previously reported.

[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.