[Are mental and neurological disorders related?] / Zijn zenuw- en zielsziekten familie van elkaar?

A recent article in Science reported the results of a genome-wide analysis of a variety of psychiatric and neurological conditions, conducted by an international consortium. Psychiatric disorders showed some degree of genetic risk sharing; conversely, the genetic risk profiles of neurological disorders lacked virtually any resemblance to each other as well as to mental diseases. Even though the spectrum of studied diseases was incomplete, the findings are unsurprising. Of course, neurological disorders and mental disorders share a common substrate in the brain, which has led to different methods attempting to discover the material basis of mental disorders. Yet, there is and continues to be an important difference regarding the causal role of the environment, viz. psychological and social factors. However, in terms of the way diseases manifest themselves, i.e. the symptoms experienced by patients, there is considerable overlap between psychological and somatic factors. Body and mind may be separated in medical textbooks, but not in the waiting room.

Transient monocular blindness and the risk of vascular complications according to subtype: a prospective cohort study.

Patients with transient monocular blindness (TMB) can present with many different symptoms, and diagnosis is usually based on the history alone. In this study, we assessed the risk of vascular complications according to different characteristics of TMB. We prospectively studied 341 consecutive patients with TMB. All patients were interviewed by a single investigator with a standardized questionnaire; reported symptoms were classified into predefined categories. We performed Cox regression analyses with adjustment for baseline vascular risk factors. During a mean follow-up of 4.0 years, the primary outcome event of vascular death, stroke, myocardial infarction, or retinal infarction occurred in 60 patients (annual incidence 4.4 %, 95 % confidence interval (CI) 3.4-5.7). An ipsilateral ischemic stroke occurred in 14 patients; an ipsilateral retinal infarct in six. Characteristics of TMB independently associated with subsequent vascular events were: involvement of only the peripheral part of the visual field (hazard ratio (HR) 6.5, 95 % CI 3.0-14.1), constricting onset of loss of vision (HR 3.5, 95 % CI 1.0-12.1), downward onset of loss of vision (HR 1.9, 95 % CI 1.0-3.5), upward resolution of loss of vision (HR 2.0, 95 % CI 1.0-4.0), and the occurrence of more than three attacks (HR 1.7, 95 % CI 1.0-2.9). We could not identify characteristics of TMB that predicted a low risk of vascular complications. In conclusion, careful recording the features of the attack in patients with TMB can provide important information about the risk of future vascular events.

A Patient With Word Blindness in the Seventeenth Century.

Johann Jakob Wepfer (1620-1695), city physician in Schaffhausen, Switzerland, published two books on "apoplexy." He proposed new ideas about the events in the brain during such attacks, based on Harvey's theory of the circulation of the blood. Wepfer postulated extravasation of whole blood or serum in the brain, in opposition to the Galenic notion of blocked ventricles. His case histories are remarkably precise and untainted by interpretation. This allows the recognition of a patient with word blindness, who was also unable to read words written by himself. Unlike patients with pure "alexia without agraphia," he could not write complete sentences because of additional language defects, especially speech comprehension. Jules Dejerine (1849-1917) would, in 1892, not only describe a patient with the pure form of this syndrome (cécité verbale avec intégrité de l'écriture spontanée et sous dictée) but also provide an explanation of its anatomical basis.

End-of-life decisions in patients with severe acute brain injury.

Most in-hospital deaths of patients with stroke, traumatic brain injury, or postanoxic encephalopathy after cardiac arrest occur after a decision to withhold or withdraw life-sustaining treatments. Decisions on treatment restrictions in these patients are generally complex and are based only in part on evidence from published work. Prognostic models to be used in this decision-making process should have a strong discriminative power. However, for most causes of acute brain injury, prognostic models are not sufficiently accurate to serve as the sole basis of decisions to limit treatment. These decisions are also complicated because patients often do not have the capacity to communicate their preferences. Additionally, surrogate decision makers might not accurately represent the patient's preferences. Finally, in the acute stage, prediction of how a patient would adapt to a life with major disability is difficult.

Is the long-term prognosis of transient ischemic attack or minor ischemic stroke affected by the occurrence of nonfocal symptoms?

BACKGROUND AND PURPOSE: In patients with a transient ischemic attack or ischemic stroke, nonfocal neurological symptoms, such as confusion and nonrotatory dizziness, may be associated with a higher risk of vascular events. We assessed the relationship between nonfocal symptoms and the long-term risk of vascular events or death in patients with a transient ischemic attack or minor ischemic stroke. METHODS: We related initial symptoms with outcome events in 2409 patients with a transient ischemic attack (n=723) or minor ischemic stroke (n=1686), included in the Life Long After Cerebral ischemia cohort. All patients underwent a standardized interview on the occurrence of focal and nonfocal neurological symptoms during the qualifying event. The primary outcome was the composite of any stroke, myocardial infarction, or vascular death. Secondary outcomes were all-cause death, vascular death, cardiac death, myocardial infarction, and stroke. Hazard ratios were calculated with Cox regression. RESULTS: Focal symptoms were accompanied by nonfocal symptoms in 739 (31%) patients. During a mean follow-up of 10.1 years, the primary outcome occurred in 1313 (55%) patients. There was no difference in the risk of the primary outcome between patients with both focal and nonfocal symptoms and patients with focal symptoms alone (adjusted hazard ratio, 0.97; 95% confidence interval, 0.86-1.09; P=0.60). The risk of each of the secondary outcomes was also similar in both groups. CONCLUSIONS: About one third of the patients with a transient ischemic attack or minor ischemic stroke has both focal and nonfocal neurological symptoms. Nonfocal symptoms are not associated with an increased long-term risk of vascular events or death. CLINICAL TRIAL REGISTRATION: This trial was not registered because enrollment began before July 1, 2005.

Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage.

BACKGROUND: Rebleeding is an important cause of death and disability in people with aneurysmal subarachnoid haemorrhage. Rebleeding is probably related to dissolution of the blood clot at the site of aneurysm rupture by natural fibrinolytic activity. This review is an update of a previously published Cochrane review. OBJECTIVES: To assess the effects of antifibrinolytic treatment in people with aneurysmal subarachnoid haemorrhage. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (February 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 1), MEDLINE (1948 to December 2012), and EMBASE (1947 to December 2012). In an effort to identify further published, unpublished, and ongoing studies we searched reference lists and trial registers, performed forward tracking of relevant references and contacted drug companies. SELECTION CRITERIA: Randomised trials comparing oral or intravenous antifibrinolytic drugs (tranexamic acid, epsilon amino-caproic acid, or an equivalent) with control in people with subarachnoid haemorrhage of suspected or proven aneurysmal cause. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted the data. Three review authors assessed trial quality. For the primary outcome we converted the outcome scales between good and poor outcome for the analysis. We scored death from any cause and rates of rebleeding, cerebral ischaemia, and hydrocephalus per treatment group. We expressed effects as risk ratios (RR) with 95% confidence intervals (CI). We used random-effects models for all analyses. MAIN RESULTS: We included 10 trials involving 1904 participants. The risk of bias was low in six studies. Four studies were open label and were rated as high risk of performance bias. One of these studies was also rated as high risk for attrition bias. Four trials reported on poor outcome (death, vegetative state, or severe disability) with a pooled risk ratio (RR) of 1.02 (95% confidence interval (CI) 0.91 to 1.15). All trials reported on death from all causes with a pooled RR of 1.00 (95% CI 0.85 to 1.18). In a trial that combined short-term antifibrinolytic treatment (< 72 hours) with preventative measures for cerebral ischaemia the RR for poor outcome was 0.85 (95% CI 0.64 to 1.14). Antifibrinolytic treatment reduced the risk of re-bleeding reported at the end of follow-up (RR 0.65, 95% CI 0.44 to 0.97; 78 per 1000 participants), but there was heterogeneity (I² = 62%) between the trials. The pooled RR for reported cerebral ischaemia was 1.41 (95% CI 1.04 to 1.91, 83 per 1000 participants), again with heterogeneity between the trials (I² = 52%). Antifibrinolytic treatment showed no effect on the reported rate of hydrocephalus in five trials (RR 1.11, 95% CI 0.90 to 1.36). AUTHORS' CONCLUSIONS: The current evidence does not support the use of antifibrinolytic drugs in the treatment of people with aneurysmal subarachnoid haemorrhage, even in those who have concomitant treatment strategies to prevent cerebral ischaemia. Results on short-term treatment are promising, but not conclusive. Further randomised trials evaluating short-term antifibrinolytic treatment are needed to evaluate its effectiveness.

[Neisser and the clap]. / Neisser en de druiper.

In 1879, during his specialization in dermatology, Albert Ludwig Sigesmund Neisser (1855-1916) discovered the bacterial cause of gonorrhoea. The gonococcus - Neisseria gonorrhoea - would, however, not bear his name until 1933. Neisser's early research focused primarily on venereal diseases, syphilis in particular, and on leprosy. Later, as a hygienist, he became a passionate advocate of public clinics for venereal diseases, regulated prostitution, and health education. In 1916, Neisser died of sepsis after lithotripsy for nephrolithiasis. His scientific inheritance includes many publications on a variety of venereal and skin diseases and public health-related topics, and textbooks such as Ikonographia dermatologica and Stereoskopischer Medizinischer Atlas.

[Kolff and the artificial kidney]. / Kolff en de kunstnier.

Willem Kolff (1911-2009), son of a physician, studied medicine in Leiden and specialised in internal medicine in Groningen. It was there that he started attempts to apply the phenomenon of dialysis in patients suffering from renal failure. He built the first prototypes of dialysis machines after his appointment as an internist in the municipal hospital in Kampen, during the Second World War. Indeed, in the first 15 patients he managed to decrease urea levels, resulting in temporary clinical improvement, but eventually they all died. It was not until after the war that dialysis helped a patient survive an episode of acute glomerulonephritis. After 1950 he continued his work on artificial organs in the United States (first in Cleveland and later, after 1967, in Salt Lake City). Although most of his work from then on revolved around the development of an artificial heart, he also contributed to the design of a compact, disposable apparatus for dialysis, the 'twin coil'. Haemodialysis also became feasible for patients with chronic renal failure after the 'Scribner shunt' (1960) provided easy access to the circulation. Peritoneal dialysis is another option. Excess mortality, mainly from cardiovascular disease, is still a largely unsolved problem.

[Collaboration in the first-line setting in medically unexplained symptoms: from powerlessness to coordination]. / Samenwerken rond onverklaarde klachten: van machteloosheid naar regie.

Two women aged 19 and 37 consulted their general practitioners (GPs) for medically unexplained symptoms (MUS). Patient A suffered sudden pain in her legs. She needed crutches, but no somatic explanation could be found. After systematically exploring the history (somatic, emotional and social aspects, thoughts, conduct), the GP initiated a proactive, multidisciplinary treatment regimen. He worked with a mental health nurse practitioner and focused the treatment regimen on the effects of the symptoms. The patient's pain gradually decreased. Patient B had multiple functional complaints. She had little trust in her GP which resulted in inefficient care. The GP explored her history systematically. Together with the nurse practitioner, he initiated a multidisciplinary collaboration and coordinated all the other professionals involved. The patient, now more trusting, visits her GP regularly. Her symptoms still exist.

[Boerhaave and his syndrome]. / Boerhaave en zijn syndroom.

Herman Boerhaave (1668-1738), professor of botany, medicine and chemistry at the University of Leyden, attracted students from across Europe, thanks to his didactic qualities, reinforced by bedside teaching. His published writings, often unauthorised, were mainly theoretical and systematic. The more remarkable is the extensive and 'atrocious' case history he published about the 51-year-old nobleman Jan Gerrit van Wassenaer. As courtier and admiral of the Dutch fleet Van Wassenaer was a regular attendant at copious banquets, but at home he used to eat sparingly and sometimes he resorted to emetics. One day, having taken several bowls with an extract of Blessed Thistle (Carduus benedictus) and trying to vomit, he was seized by excruciating pain in the chest. The pain continued unabated until his death, the next day. Boerhaave, called to his bedside in the middle of the night, was unable to make a diagnosis from the history and physical examination. Post mortem examination showed the oesophagus had been torn off in the chest. Later generations have linked Boerhaave's name with spontaneous rupture of the oesophagus.

[Riva-Rocci and blood pressure]. / Riva-Rocci en de bloeddruk.

Scipione Riva-Rocci (1863-1937) was educated in Turin as a physician and later as a doctor of internal medicine. In 1896 and 1897 he published a series of four articles (in Italian) on a new method for measuring blood pressure. Previous non-invasive methods were all based on compression of the radial pulse, in keeping with centuries of medical tradition, but they were cumbersome and unreliable. Riva-Rocci's innovation consisted in compressing the brachial artery instead, at the level of the upper arm. For this purpose he devised an inflatable rubber tube, which was rigid on the outside. Disappearance of the radial pulse on palpation indicated the systolic arterial pressure, as Riva-Rocci confirmed by calibration experiments in animals and with human cadavers. His instrument was introduced world-wide after a chance visit by the American neurosurgeon Harvey Cushing (1869-1939). The Russian surgeon Nikolai Korotkoff (1874-1920) was the first to apply auscultation of the artery below the cuff (in 1905), a method that allowed determination of diastolic arterial pressure. Riva-Rocci was Chief of Medicine at the municipal hospital in Varese from 1900 to 1928, where he developed a special interest in paediatrics.

[Ranke and modern surgery in Groningen]. / Ranke en de moderne heelkunde in Groningen.

Hans Rudolph Ranke (1849-1887) studied medicine in Halle, located in the eastern part of Germany, where he also trained as a surgeon under Richard von Volkmann (1830-1889), during which time he became familiar with the new antiseptic technique that had been introduced by Joseph Lister (1827-1912). In 1878 he was appointed head of the department of surgery in Groningen, the Netherlands, where his predecessor had been chronically indisposed and developments were flagging. Within a few months, Ranke had introduced disinfection by using carbolic acid both before and during operations. For the disinfection of wound dressings, he replaced carbolic acid with thymol as this was less pungent and foul-smelling. The rate of postoperative infections dropped to a minimum despite the inadequate housing and living conditions of the patients with infectious diseases. In 1887, at the age of 37, Ranke died after a brief illness - possibly glomerulonephritis - only eight years after he had assumed office. A street in the city of Groningen near its present-day University Medical Centre has been named after him.

[Papanicolaou and the cervical smear]. / Papanicolaou en het uitstrijkje.

George N. Papanicolaou (1883-1962) was born in Kymi (on the island of Euboea, Greece). He studied medicine in Athens but chose not to join his father's practice in Kymi. Instead, he obtained his doctoral degree at the Zoological Institute in Munich (1910) and - after a brief return and marriage in Greece - went to work at the Oceanographic Institute in Monaco. Recalled in 1912 by the death of his mother and the Balkan Wars, he and his wife emigrated a year later to New York. After some difficulty, he found work as a research biologist at the Cornell University Department of Anatomy. Papanicolaou concentrated on vaginal cells right from the start, initially from guinea pigs. His real goal was to harvest egg cells for the study of sex differentiation; he succeeded in finding the right time by recording the cyclic changes in genital epithelium. These same changes appeared to occur during the human menstrual cycle. It was by chance that he encountered cancer cells in a human specimen in 1928. More than 10 years would pass before he took up the subject of cancer again, in collaboration with the gynaecologist Herbert F. Traut (1894-1963). After their first publication in 1941, Papanicolaou gradually fine-tuned the technique of cytological diagnostics in a variety of organs. In 1961, he moved to Miami Beach as head of a new cancer centre, but suddenly died a few months later.

[Behçet and his triad]. / Behçet en zijn trias.

Hulusi Behçet (1889-1948) was an internationally oriented Turkish dermatologist. He was closely involved in establishing the Istanbul Faculty of Medicine, where he later became a professor. In addition, Behçet was a scientist and an editor of the German professional journal, Dermatologische Wochenschrift. In articles published in this journal, he had written about 3 patients who suffered from an inexplicable triad of symptoms: eye problems, oral en genital ulcers. This oculo-urogenital syndrome now bears his name: 'Behçet's disease'.

[Hoogendoorn and the medical registry]. / Hoogendoorn en de medische registratie.

Dirk Hoogendoorn (1914-1990) was a solo general practitioner in the village of Wijhe (eastern part of the Netherlands) from 1941, during the time of the German occupation, until 1971. From the very beginning, he combined his practice with the recording of disease patterns. He first concentrated on infectious diseases, especially whooping cough, which was the subject of his doctoral thesis. He later set up registries in two regional hospitals. When his initiative expanded to a national organisation, he became its advisor. He nonetheless continued to produce statistics on a variety of disorders as well as on surgical procedures, even more so after his retirement. The subjects ranged from traffic accidents and tonsillectomies to the discrepancy between increased body height and the unchanging height of the tennis net, but he had the most affinity with the practice of obstetrics. He stirred up much emotion by showing that a decrease in perinatal mortality was proceeding slower in the Netherlands than in other European countries, especially by suggesting a causal relationship between this lag and the high rate of Dutch home deliveries. This debate has continued to this day.

[Quincke and his oedema]. / Quincke en zijn oedeem.

Heinrich Irenaeus Quincke (1842-1922), the son of a physician, was born in Frankfurt but was educated in Berlin where he also completed his medical studies in 1864. After a 'grand tour' that took him to Paris, Vienna and London, he was trained in Berlin, first in surgery and later in internal medicine, under Von Frerichs (1819-1885). In 1878, he became a professor of internal medicine in Berne; from 1883 he held the chair of medicine in Kiel, which he would hold for the next 30 years. In 1882, he published a synthesis of several observations of 'acute, circumscribed oedema of the skin'. Quincke accurately described the clinical features and distinguished the familial from the sporadic forms. He was correct in attributing the condition to increased vascular permeability, but he surmised the causal factors were neurogenic rather than humoral, according to current insights (excess of bradykinin due to external factors or hereditary deficiency of C1-esterase inhibitor). Quincke not only contributed to several other clinical observations, but also pioneered the lumbar puncture, initially not for diagnostic purposes, but to relieve headache in hydrocephalic children.

Vitamin K antagonists versus antiplatelet therapy after transient ischaemic attack or minor ischaemic stroke of presumed arterial origin.

BACKGROUND: People who have had a transient ischaemic attack (TIA) or non-disabling ischaemic stroke have an annual risk of major vascular events of between 4% and 11%. Aspirin reduces this risk by 20% at most. Secondary prevention trials after myocardial infarction indicate that treatment with vitamin K antagonists is associated with a risk reduction approximately twice that of treatment with antiplatelet therapy. OBJECTIVES: To compare the efficacy and safety of vitamin K antagonists and antiplatelet therapy in the secondary prevention of vascular events after cerebral ischaemia of presumed arterial origin. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last searched 15 September 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3), MEDLINE (2008 to September 2011) and EMBASE (2008 to September 2011). In an effort to identify further relevant trials we searched ongoing trials registers and reference lists. We also contacted authors of published trials for further information and unpublished data. SELECTION CRITERIA: Randomised trials of oral anticoagulant therapy with vitamin K antagonists (warfarin, phenprocoumon or acenocoumarol) versus antiplatelet therapy for long-term secondary prevention after recent transient ischaemic attack or minor ischaemic stroke of presumed arterial origin. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed trial quality and extracted data. MAIN RESULTS: We included eight trials with a total of 5762 participants. The data showed that anticoagulants (in any intensity) are not more efficacious in the prevention of vascular events than antiplatelet therapy (medium intensity anticoagulation: relative risk (RR) 0.80, 95% confidence interval (CI) 0.56 to 1.14; high intensity anticoagulation: RR 1.02, 95% CI 0.49 to 2.13). There is no evidence that treatment with low intensity anticoagulation gives a higher bleeding risk than treatment with antiplatelet agents: RR 1.27 (95% CI 0.79 to 2.03). However, it was clear that medium and high intensity anticoagulation with vitamin K antagonists, with an INR of 2.0 to 4.5, were not safe because they yielded a higher risk of major bleeding complications (medium intensity anticoagulation: RR 1.93, 95% CI 1.27 to 2.94; high intensity anticoagulation: RR 9.0, 95% CI 3.9 to 21). AUTHORS' CONCLUSIONS: For the secondary prevention of further vascular events after TIA or minor stroke of presumed arterial origin, there is sufficient evidence to conclude that vitamin K antagonists in any dose are not more efficacious than antiplatelet therapy and that medium and high intensity anticoagulation leads to a significant increase in major bleeding complications.