A novel presenilin 1 mutation (L174 M) in a large Cuban family with early onset Alzheimer disease.

We studied a Cuban family with presenile dementia (autosomal dominant) consisting of 281 members within six generations, the proband descended from a Spanish founder. Mean age at onset was 59 years of age. Memory impairment was the main symptom in all patients, additionally, ischemic episodes were described in 4 (n = 18) patients. Neuropathological examination of brain material (1 patient) revealed neuronal loss, amyloid plaques, and neurofibrillary tangles. Thirty DNA samples were genotyped (regions on chromosome 1, 3, 10, 12, 14, 17, 19, 20, and 21). A maximum Lod score of 3.79 at theta = 0 was obtained for marker D14S43, located in a 9-cM interval in which all patients shared the same haplotype. Sequencing of the PSEN1 gene revealed a heterozygous base substitution, C520A (exon 6), which is predicted to cause an amino acid change from leucine to methionine in the TMIII of the presenilin 1 protein. The mutation was found to co-segregate with the disease phenotype and the associated disease haplotype. The C --> A change was not observed in 80 control chromosomes from the Cuban population. Leucine at position 174 is highly conserved among species and is identical in presenilin 1 and presenilin 2 proteins. We propose the L174 M mutation might lead to an abnormal N-terminal and probably C-terminal fragments and malfunction of the protein complex. In conclusion, we found a novel PSEN1 mutation in a large family with clinical and pathological diagnosis of early onset familial Alzheimer disease, which may be relevant for other Hispanic populations.

Factores pronosticos de deterioro cognitivo en pacientes con infarto cerebral / Prognostic factors of cognitive deterioration in patients with cerebral infarctus

Introducción. El deterioro cognitivo es una manifestación frecuente en pacientes que han presentado un infarto cerebral, que afecta su calidad de vida, y los factores pronósticos asociados al mismo no se esclarecen completamente. Objetivos. determinar la frecuencia de deterioro cognitivo después del infarto cerebral y los factores pronósticos asociados a su aparición. Pacientes y métodos. Se efectuó un estudio de cohorte prospectivo en el Hospital Clínico Quirúrgico Hermanos Ameijeiras, de Ciudad de La Habana, Cuba, en 401 pacientes con diagnóstico confirmado de infarto cerebral, en el período comprendido de marzo de 1997 a febrero del año 2000. A todos los pacientes se les llenó un formulario que contenía lasposibles variables pronosticas y se les realizaron las pruebas neuropsicológicas a los tres y seis meses de evolución del infarto cerebral, para determinar la aparición del deterioro cognitivo. El análisis estadístico incluyó test de chi al cuadrado (x2), estimación del riesgo relativo y análisis de regresión logística múltiple. Resultados. La frecuencia de deterioro cognitivo a los tres y seis meses de evolución del infarto cerebral fue de 22,2 y 6,9 por ciento, respectivamente. El análisis de regresión logística múltiple mostró como variables pronosticas del deterioro cognitivo a la hipertensión arterial (p= 0,001, RR: 2,0) y el número de infartos cerebrales actuales visualizados en la tomografía axial computadorizada (p= 0,000, RR: 5,2). Conclusiones. El deterioro cognitivo fue una complicación frecuente después del infarto cerebral y varios factores pronósticos se asociaron a su aparición

[Prognostic factors of cognitive deterioration in patients with cerebral infarcts]. / Factores pron sticos de deterioro cognitivo en pacientes con infarto cerebral.

INTRODUCTION: Cognitive deterioration is a frequent finding in patients who have had a cerebral infarct which affected their quality of life. The prognostic factors associated with this are still not completely clear. OBJECTIVES: To determine the frequency of cognitive deterioration following cerebral infarct and the prognostic factors associated with its appearance. PATIENTS AND METHODS: We made a study of a prospective pohort in the Hospital Clínico Quirúrgico Hermanos Ameijeiras de Ciudad de La Habana, Cuba, in 401 patients with the confirmed diagnosis of cerebral infarct during the period March 1997 February 2000. A questionnaire was completed for all patients. This contained the possible variables for prognosis. The neuropsychological tests were done 3 and 6 months after the cerebral infarct occurred to determine the appearance of cognitive deterioration. Statistical analysis included the c2 test, relative risk estimation, and multiple logistic regression analysis. RESULTS: The frequency of cognitive deterioration 3 and 6 months after the cerebral infarct occurred was 22.2% and 6.9% respectively. Multiple logistic regression analysis showed prognostic variables of cognitive deterioration to be arterial hypertension (p=0.001, RR:2.0) and the number of current cerebral infarcts shown on computerized axial tomography (p=0.000, RR:5.2). CONCLUSIONS: Cognitive deterioration was a frequent complication after a cerebral infarct and several prognostic factors were associated with its appearance.

[Risk factors involved in symmetrical distal diabetic neuropathy]. / Factores de riesgo de la neuropatía diabética simétrica distal.

INTRODUCTION: Diabetic neuropathy is a common neurological complication in patients with diabetes mellitus which affects their quality of life. The risk factors involved in this are not completely clear. OBJECTIVE: To determine the frequency of symmetrical distal diabetic neuropathy and the risk factors associated with its occurrence in the group studied. PATIENTS AND METHODS: A transversal study was made in the Hospital Clinico Quirurgico Hermanos Ameijeiras of Ciudad de la Habana (Cuba), in 200 patients diagnosed as having type 1 or type 2 diabetes mellitus, between January 1997 and December 1999. A clinical neurological examination and neurophysiological investigations were done on all patients to make a diagnosis of diabetic neuropathy. Subsequently, we compared those with diabetic neuropathy and those without in relation to the risk factors. Statistical analysis included the chi squared test and estimation of the relative risk. RESULTS. The frequency of symmetrical distal diabetic neuropathy was 30.0%. Related risk factors were: smoking (p= 0.00, RR= 2.59), raised serum cholesterol (p= 0.00, RR= 4.12), poor metabolic control of diabetes mellitus (p= 0.00, RR= 4.13), associated disorders (p= 0.00, RR= 5.31) including arterial hypertension (p= 0.03, RR= 1.90) and duration of diabetes mellitus (p= 0.00, RR= 2.01). CONCLUSIONS: In our study symmetrical distal diabetic neuropathy was a common complication of diabetes mellitus associated with various risk factors.

[Neurological complications of patients with lymphomas]. / Complicaciones neurológicas en pacientes con linfomas.

INTRODUCTION: The lymphomas are neoplasias which may affect the nervous system at any stage of development, and affect the quality of life and survival time of these patients. OBJECTIVES: To identify the neurological complications of patients with lymphomas, determine the survival time and the cause of death in these patients. PATIENTS AND METHODS: We made a prospective study in 270 patients with the diagnosis of lymphoma who were admitted to the Hospital Clinico Hermanos Ameijeiras Ciudad de la Habana (Cuba). The complications were classified as direct or indirect, the average survival time was determined according to the Kaplan-Meier curve and the cause of death was established with anatomopathological confirmation. RESULTS: We found 26 patients to have neurological complications. Of 188 patients with non-Hodgkin lymphomas, 12.2% had neurological disorders and in these patients leptomeningeal infiltration was the main neurological complication. In the 82 patients with Hodgkin's disease, 3.6% had neurological disorders of which herpes zoster infection was the commonest. The average survival time following diagnosis and the neurological features was 9.7 months. The neurological complication was the cause of death in 57.1% of those who died. CONCLUSIONS: The patients with lymphomas had direct and indirect complications, with an average survival time of less than one year, and most died of a nervous system complication.

[Clinical course of post-laminectomy cervical spondylitic myelopathy]. / Curso clínico de la mielopatía espondilótica cervical poslaminectomía.

INTRODUCTION AND OBJECTIVE: To study the postsurgical clinical course of spondylitic myelopathy. PATIENTS AND METHODS: We assessed 39 patients admitted to the Departments of Neurology and Neurosurgery of the Hospital Clinico Quirúrgico Hermanos Ameijeiras, Cuba, with a confirmed diagnosis of spondylitic myelopathy who had decompressing laminectomies during the period between January 1996 and December 1997. RESULTS: Of the predicted variables, there was predominance of an age under 60 years (51.3%); male sex (71.8%); a history of cervical trauma and habitual dangerous physical activity in 38.5% and 41% respectively. The duration of preoperative symptoms was less than one year in 46.2%. The vertebral level most often involved was C5-C6 (97.4%). In 51.3% three levels were affected: 100% of the patients had stenosis in the zone of maximum compression; 28.2% had congenital stenosis of the canal and 66.7% had partial block shown on myelography or magnetic resonance studies of the cervical spine. There was clinical improvement in 78.4% after one month, in 91.9% after 3 months and in 94.6% after 6 months; only 2 patients had not improved on completion of the study. Motor and sensory function of the legs improved more than motor function of the arms and sphincter. CONCLUSIONS: The variables which influenced the degree of improvement were: age, duration of the symptoms, number of vertebral levels affected, presence of blockage and functional state. After application of the multiple regression model, it was seen that the duration of preoperative symptoms is an important predictor of the postoperative clinical course.

[A longitudinal study of the course of Alzheimer type dementia]. / Estudio longitudinal sobre el curso de la demencia tipo Alzheimer.

OBJECTIVE: We carried out a prospective longitudinal study of 41 patients diagnosed as probably having a mild form of Alzheimer's disease according to the data of an investigation of prevalence done in 1991 in the municipality of Habana Vieja. MATERIAL AND METHODS: The research covered two phases, with an interval of one year between them. During both phases the patients were interviewed by the same neurology resident in a door-to-door survey using the Mini-Mental State, Hughes scale (CDR) and Blessed scale, to evaluate higher mental functions. We determined the progress of the disease over the course of two years (1991-1992 and 1992-1993) and the frequency and degree of deterioration of cognitive functions during a period of one year. RESULTS AND CONCLUSIONS: There was evidence of progressive worsening of the illness in 46.4% of the patients. In 34.2% this was to a moderate form and in 12.2% to a severe form. There was no progression in 46.3%. In this group 17.0% continued with a diagnosis of doubtful dementia and 29.3% as having slight dementia. The other 7.3% of the total number of patients (n = 41) were reclassified as normal. Cognitive functions almost always showed a tendency to deteriorate over time, but in a small percentage of patients they did not deteriorate and some even improved. The cognitive functions which deteriorated most were those of orientation, language and copying, with an average deterioration of 28% and 24% respectively with regard to their initial values.

[Primary diffuse leptomeningeal gliomatosis. Presentation of one case]. / Gliomatosis leptomeníngea difusa primaria: presentación de un caso.

A twenty-four-year-old woman presented with asthenia, anorexia and weight los associated with headache, neck ache, lumbo-sacral pain, flaccid quadriparous, bilaterally diminished vision and sphincter disorders. On computerized axial tomography of the skull, only slight signs of ventricular dilatation were seen. Cytochemical study of the cerebro-spinal fluid showed a marked increase in protein and there was a raised erythrocyte sedimentation rate. The patient was treated with steroids in view of the possibility of vasculitis or a demyelinating disorder. However the disease worsened and she died four months after onset of the disorder. Neuro-pathological study showed tumour infiltration of the leptomeninges of the base of both cerebral hemispheres, cerebellum and spinal medulla. The optic nerves, chiasma and spinal nerve roots were also infiltrated with neoplastic cells. No intraparenchymatous tumour was found. The neuropathological findings were compatible with primary diffuse leptomeningeal gliomatosis.

[Treatment of acute attack of migraine with sumatriptan]. / Tratamiento del ataque agudo de la cefalea migrañosa con sumatriptán.

INTRODUCTION AND MATERIAL: In the Hospital Clínico Quirúrgico Hermanos Almeijeiras a randomized double blind clinical trial was carried out involving 52 patients who presented with painful migraine crises with or without prodromes. A group of 27 patients were given 6 mg of sumatriptan subcutaneously. Another group of 25 patients were given 1 mg of dihydroergotamine intramuscularly. It was seen that both drugs relieved the migrainous pain. However, sumatriptan did so in a greater percentage of patients. RESULTS AND CONCLUSIONS: There was earlier, and also more complete, relief of pain in those patients receiving sumatriptan. With regard to side-effects of sumatriptan were pain at the back of the site of injection, sensation of pressure at the back of the neck, facial flushing and asthenia.

[Clinical characteristics of Cuban epidemic neuropathy]. / Caracterización clínica de la neuropatía epidémica cubana.

INTRODUCTION: At the beginning of 1992 an epidemic neuropathy was seen in Cuba. MATERIAL AND METHODS: To determine the clinical characteristics we studied the clinical and neurological features, cerebrospinal fluid, and did neurophysiological investigations and sural nerve biopsies. RESULTS: Sixty patients were studied. Of these, 42 (70%) had polyneuropathy which was predominantly peripheral and 18 (30%) had combined forms. Most patients had asthenia and weight loss. The polyneuropathic effects were mainly in the legs. In 33.3% of the patients there were distal autonomic effects and sphincter disorders. Only 7 patients had hypoacusia. However, subclinical neurosensorial hypoacusia was seen in 33.3%. Optic neuropathy affected central vision bilaterally and symmetrically with temporal pallor of the papilla in half the cases. In 3 patients there was loss of ganglionar nerve fibres of the papillo-macula bundle. The contrast sensitivity visual test was abnormal in some patients with peripheral polyneuropathy, showing subclinical optic neuropathy in these cases. Sensory neuroconduction suggested axonal neuropathy in 30 patients, demyelinating neuropathy in 5 patients, while the remainder were normal. Motor neuroconduction was normal in most patients. Sural nerve biopsy of 27 patients showed axon damage in 96.2% of cases. CONCLUSIONS: The clinical picture is similar to that seen in nutritional deficiencies and toxic processes.