The natural history of Parkinson's disease in the province of Segovia: mortality in a longitudinal study (20-year follow-up).

OBJECTIVE: We determined mortality rates and predictors of survival in 273 patients with Parkinson's disease based on a 20-year follow-up longitudinal study. MATERIAL AND METHODS: We examined 273 patients with Parkinson's disease during a 20-year follow-up, recruited between 1978 and 1998. All patients were regularly followed at the Department of Neurology until December 31, 1998, or death. RESULTS: By then, 69 patients had died, crude mortality was rate 4.43, and standardized mortality ratio for the total patient group was 1.39 (95% CI, 1.10-1.50). As Parkinson's disease is a chronic progressive disorder in adult life, disease-related mortality would be expected to increase in later stages after 15 or 20 years. Mean age at death in our cohort was 78.27 (95% CI, 76.90-79.20). Median time of death was 11 years (95% CI, 9.50-12.49). Independent predictors of mortality during the follow-up were age at onset (hazard ratio, 1.05; 95% CI, 1.01-1.09; P = 0.01), clinical form - akinesia and rigidity (hazard ratio, 2.20; 95% CI, 1.06-4.88; P = 0.03) - and treatment with dopaminergic agonist (hazard ratio, 0.49; 95% CI, 0.23-1.03; P = 0.06). Cardiovascular disease was the most frequent cause of death in 42%. CONCLUSIONS: This study suggests a link between mortality with age of onset and treatment without dopamine agonists as initial treatment. So, there is an association between decreased mortality and tremor as initial clinical forms at onset.

Penicillin transport from cerebrospinal fluid.

The passage of penicillin G from cerebrospinal fluid (CSF) was studied by continuous ventriculocisternal perfusion in conscious rabbits. The concentration of penicillin G in the perfusate, collected from the cisterna magna, was 76.5 percent +/- 1.0 (SEM) of that entering the ventricles (having adjusted for normal secretion of CSF). The mean concentration of penicillin G rose 15 percent (p less than 0.005) in the cisternal CSF after probenecid (2 mg per milliliter) was added to the perfusion fluid. We conclude that an active transport system removes penicillin G from the CSF; this mechanism can be inhibited by intraventricular probenecid. Our results are in accord with observations deriving from studies on anesthetized animals given probenecid intravenously or intraperitoneally.

Q fever mimicking herpetic encephalitis.

We describe a patient with temporal lobe encephalitis associated with primary Coxiella burnetii infection who presented with CT and MRI findings suggestive of herpes simplex encephalitis and an initial improvement during treatment with acyclovir. Q fever should be considered in the differential diagnosis of patients whose manifestations suggest herpes encephalitis.

Combined effect of HLA-DRB1*1501 and interleukin-1 receptor antagonist gene allele 2 in susceptibility to relapsing/remitting multiple sclerosis.

Susceptibility to multiple sclerosis (MS) is associated with HLA-DRB1*1501. Many reports have suggested associations with other loci but these results remain unconfirmed. We studied the IL-1 receptor antagonist (IL-1ra) gene polymorphism and the HLA-DR and DQ allele frequencies by DNA-based methods in both the primary chronic progressive form (PP MS) and the relapsing/remitting form (R/R MS). The frequency of DRB1*1501 and IL-1ra allele 2 were significantly higher in R/R MS. Association was more marked in the female sex and in patients with benign forms of R/R MS. On the other hand DR4 subtypes carrying a Val at position 86 in the DR beta chain were increased in PP MS. The present study indicates that MS is genetically heterogeneous and shows a combined effect of HLA-DR and IL-1ra genes in susceptibility to the R/R form of the disease.

Hypothermic action of bromocriptine.

The body temperature of rats has been studied in a cold environment. In this setting, bromocriptine induced hypothermia. This fall in core temperature was inhibited by pimozide. It was concluded that bromocriptine has a dopamine-like action in areas of the brain concerned with the control of body temperature, as has previously been shown for apomorphine and amphetamine.

Herpes simplex brainstem encephalitis with a relapsing course.

We report a patient with a relapsing form of acute brainstem encephalitis. Pathological examination demonstrated necrotizing encephalitis in the cerebral cortex and, more pronounced, throughout the diencephalon, as well as in the pes pontis. Neurons and glial cells in the cerebral cortex and brainstem contained herpesvirus antigens. The clinical interrelationship of brainstem encephalitis, Miller Fisher syndrome and Landry-Guillain-Barré syndrome is discussed.

Tardive dyskinesia treated with pimozide.

We have investigated the action of pimozide in tardive dyskinesia induced by prolonged administration of phenothiazines. Improvement was recorded in a double blind study of 18 patients treated with maximum tolerated dosage (mean 18.8 mg/day) for 6 weeks. There was no deterioration in the therapeutic action of pimozide over this time. Parkinsonism and sedation were the main adverse effects. They were corrected by reduction of the dose of pimozide, but often recurred so that further adjustments of dosage were necessary. Our findings support the view that tardive dyskinesia is produced by a disturbance in the balance of central transmitters such that dopaminergic transmission is increased.

Postural myoclonus induced by phenytoin.

Involuntary movements are an infrequent complication of treatment with phenytoin and include tremor, asterixis, myoclonus, parkinsonism, and dyskinesias. The mechanism by which phenytoin exerts its actions is unclear. Phenytoin has been observed to exert variable effects on dopamine metabolites and also may induce changes in serotonergic activity. In this report, we discuss the available experimental evidence concerning the possible mechanisms of involuntary movements induced by phenytoin. We describe a case of postural myoclonus during treatment with phenytoin.

Aggravation of parkinsonian tremor by cisapride.

Cisapride, a substituted piperidinyl benzamide that is chemically related to metoclopramide, is a prokinetic agent that facilitates motility of the gastrointestinal tract (1). The mechanism by which cisapride exerts its actions is not clear. It enhances acetylcholine release in the myenteric plexus of the gut, and evidence exists that it has an agonistic action on a serotonin receptor, probably the 5-HT4 receptor (2). The drug is well tolerated, and no central nervous system side effects have been reported. We describe two patients with parkinsonism who experienced aggravation of tremor while on therapy with cisapride.

Ipsilateral symptomatology in left temporal lobe lesions.

Two cases of ipsilateral symptomatology related to left temporal lobe lesions are presented. The possibility of ipsilateral symptoms after temporal lobe lesions has to be considered, mainly when they occur in the dominant hemisphere. Direct or indirect damage to the insula of Reil's sensory-motor secondary area seems to be the motive of these ipsilateral symptoms.

[Side effects of antithrombotic treatment in the secondary prevention of cerebrovascular disease]. / Efectos secundarios del tratamiento antitrombótico en la prevención secundaria de la enfermedad cerebrovascular.

OBJECTIVE: To determine the incidence of adverse effects of antithrombotic drugs (platelet anti-aggregants and anticoagulants) in patients with transient ischemic attacks (TIA) and mild ischemic strokes (IL). PATIENTS AND METHODS: Clinical follow-up data on the patients with TIA and IL included in a community-based observational study undertaken in the province of Segovia. Adverse effects which led to suspension of treatment or were a potential danger for the patient's life were recorded. RESULTS: The groups studied included 235 patients and the average initial age was 70.8 years. The average follow-up time was 3.6 years. The treatment initially given included: aspirin (75.7%), ticlopidine (12.8%) and acenocumarol (9.4%). Adverse effects led to suspension of treatment in 6% (5% with aspirin and acenocumarol, 17% with ticlopidine). The adverse effects of ticlopidine were mild and patients did not need admission to hospital (cutaneous exanthema, diarrhoea and reversible leucopenia). Aspirin was associated with digestive tract bleeding (2.8%) and cerebral hemorrhage (1.7%) which required hospital admission in most cases. One patient treated with acenocumarol presented with a retroperitoneal hematoma. CONCLUSIONS: In general antithrombotic drugs are well-tolerated by patients with TIA and LI. Hemorrhagic complications, particularly of the digestive tract, associated with aspirin limit tolerance to it.

[Clinico-epidemiological study of neurolisteriosis in the province of Segovia]. / Estudio clinicoepidemiológico de la neurolisteriosis en la provincia de Segovia.

INTRODUCTION: Listeria monocytogenes is a microorganism with marked tropism towards the central nervous system. One of the commonest forms of presentation is as a meningeal infection. The objective of this study is to describe the epidemiological, clinical and laboratory characteristics and therapeutic implications. PATIENTS AND METHODS: We made a retrospective analysis of four patients, admitted to hospital with the diagnosis of meningeal infection and positive culture for L. monocytogenes in the cerebrospinal fluid (CSF), who were admitted to our centre between 1 January 1996 and 31 December 2000. The overall rate of meningitis due to L. monocytogenes in the province of Segovia is similar to that reported from the USA and Europe (six cases per million inhabitants per year). All the patients were male, aged between 19 and 79 years. The commonest form of presentation was a meningeal syndrome. Analysis of the CSF showed pleocytosis with high protein and low glucose levels. Gram staining was negative in all cases. Initial empirical treatment proved to be correct in two of the four patients. The only predisposing factors observed were alcoholism and diabetes mellitus. All four cases recovered. CONCLUSION: We emphasize the difficulty in diagnosing meningitis due to L. monocytogenes, since the presenting symptoms are relatively non specific, CSF analysis gives variable results and Gram staining is of little use. Clinical suspicion is important so that specific antibiotic treatment may be given to improve the prognosis.