Huntington's chorea associated with normal pressure hydrocephalus.

Two patients with Huntington's chorea (HC) developed a gait disturbance more suggestive of normal pressure hydrocephalus (NPH) than HC. The diagnosis of NPH was confirmed by pneumoencephalography and isotope cisternography. Both patients were shunted and both showed an improvement not only in their gait but, unexpectedly, a decrease in their abnormal involuntary movements (AIMs). The association of HC with NPH is discussed.     

Treatment of hemicrania continua by occipital nerve stimulation with a bion device: long-term follow-up of a crossover study

BACKGROUND: Hemicrania continua (HC) is a primary headache that comprises persistent unilateral pain, is associated with cranial autonomic features, and is responsive to indometacin. Some patients are unable to tolerate this treatment or it is contraindicated; for these patients, the medical options for therapy are restricted. Occipital nerve stimulation (ONS) is an effective treatment for medically intractable primary headache, but only three cases of HC treated with ONS have been reported. Here, we report long-term safety and efficacy data for ONS in six patients with HC. ONS was provided by a unilateral neurostimulation device, known as a bion, which might be described as a second-generation ONS device. METHODS: Six patients aged 18 years or older who were diagnosed with HC had a suboccipital bion device implanted ipsilateral to their headache and received continuous unilateral ONS. A crossover study design was used: the bion was on for the first 3 months, off for the fourth month, and on again during long-term follow-up. Detailed prospective headache diaries were kept for 1 month before implantation and for 5 months afterwards. Long-term data were obtained from patients' estimates of their outcome. The outcome of this study was assessed by a comparison of headache pain severity before and after ONS. FINDINGS: At a median follow-up of 13.5 months (range 6-21 months), five of six patients reported sufficient benefit to recommend the device to other patients with HC. At long-term follow-up, four of six patients reported a substantial improvement (80-95%), one patient reported a 30% improvement, and one patient reported that his pain was worse by 20%. The onset of the benefit of ONS was delayed by days to weeks, and headaches did not recur for a similar period when the device was switched off. Adverse events were mild and associated with transient overstimulation. INTERPRETATION: ONS appears to be a safe and effective treatment for HC, particularly when indometacin is not tolerated or is contraindicated. The bion device was well tolerated, easily inserted without significant morbidity, and is one-twentieth of the volume of current devices. Such miniaturised devices are a potential new option for treatment of HC.     

Hydrocephalus and epileptic seizures

Is there an association between shunted hydrocephalus and the development of epileptic seizures? To answer this question a retrospective review of the medical records of 197 patients with shunted hydrocephalus was undertaken. In this series 17% of patients with hydrocephalus developed seizures. No correlation was found between the occurrence of epileptic seizures and a shunt malfunction, the number of shunts placed, the age of the patient at the initial shunt procedure or the location of the shunt. Patients with hydrocephalus who had significant cognitive delay or significant motor disability were significantly more likely to develop seizures than patients who did not. The findings of this review support the hypothesis that the occurrence of seizures in children with hydrocephalus is related to an underlying diffuse encephalopathy and not to the hydrocephalus or to procedures related to the treatment of this disorder.     

Medical complication in adults with spina bifida

Setting

Cohort study.

Introduction

Spina bifida (SB) is a congenital malformation affecting the central nervous system (CNS) and is one of the most prevalent CNS disorders in children. Hydrocephalus (HC) is present in 80% of newborns with SB. The aim of the present study was to analyze the medical complications and to relate the complications to age at examination, the level of injury, AIS grade and presence of HC in adults with SB.

Materials and methods

SB patients were recruited from the Spinalis out-patient clinic at the Karolinska University Hospital at their annual follow-up. The patients underwent a thorough general and neurological examination and background data including medical complications were retrieved from the medical files.

Results

127 of 157 (82%) SB patients (114 with MMC and 13 SB occulta) with a mean age of 34 years were included. Half of the patients had a complete SCI and a lumbar level was most common. Nearly 60% of the patients had HC. 88 patients (69%) suffered from at least one medical complication. Urinary tract infection (UTI), scoliosis and pain were the most common complications found in 46%, 30% and 28% of the patients, respectively. Less common complications were epilepsy, pressure ulcers (PU) and spasticity.

Discussion

SB gives a disability including motor, sensory dysfunctions and the patients suffer from a high frequency of medical complications like UTI, scoliosis, pain, and epilepsy. Data gives basis for adequate routines for medical examination at the follow-up.     

Hydrocephalus following aneurysmal subarachnoid haemorrhage

Ninety-four patients with hydrocephalus following subarachnoid haemorrhage were investigated. Fourteen of these patients had temporary ventricular drains inserted, 19 had drains that were later converted to ventricular-peritoneal shunts, and 61 patients had shunts only. All patients were analysed with respect to their grade on admission, the distribution of blood on CT scan, their Glasgow Coma Score, their intracranial pressure, and the presence or absence of vasospasm on angiography. Outcome was analysed by shunt procedure and time of shunt insertion. The higher the grade on admission, the more likely it was the patient would require a shunt. Fewer patients with a good outcome required shunting as compared to those whose outcome was poor. Patients having more subarachnoid blood on CT scan tended to present with a lower Glasgow Coma Score. The outcome of patients with intraventricular haemorrhage was not obviously influenced by the insertion of a ventriculostomy. Vasospasm was not more common in patients requiring a ventriculo-peritoneal shunt, nor did early shunting in patients with hydrocephalus affect the incidence of vasospasm. The majority of patients were either shunted in the first three days or after 30 days post-SAH. The outcome was better in those patients shunted at a later date.     

Cerebral processing of social rejection in patients with borderline personality disorder

An intense fear of abandonment or rejection is a central feature of social relationships for individuals with borderline personality disorder (BPD). A total of 20 unmedicated BPD patients and 20 healthy participants (HC, matched for age and education) played a virtual ball-tossing game including the three conditions: exclusion, inclusion and a control condition with predefined game rules, whereas cerebral activity was assessed using functional magnetic resonance imaging. Subjective experiences of exclusion were assessed after each blocked condition. Both groups felt similarly excluded during the exclusion condition; however, BPD subjects felt more excluded than HC during the inclusion and control conditions. In all three conditions, BPD patients showed a stronger engagement of the dorsal anterior cingulate and medial prefrontal cortex. For HC, activation in several cerebral regions such as the insula and the precuneus differed depending on the interaction situation, whereas for BPD subjects activation in these regions was not modulated by experimental conditions. Subjects with BPD differed from HC in both their subjective reactions to and their neural processing of social interaction situations. Our data suggest that individuals with BPD have difficulty in discriminating between social situations, and tend to hypermentalize during social encounters that are not determined by the intentions of others.     

Cerebrospinal fluid shunt infections in children

A total of 431 patients who underwent their first cerebrospinal fluid shunt insertion at Children's Memorial Hospital over a 10-year period were retrospectively studied with regard to the relationship between the etiology of the hydrocephalus, age at the time of shunt placement, and infection rate. Forty percent of the patients had constrictive hydrocephalus and meningomyelocele, 33% congenital communicating or obstructive hydrocephalus, and 18% tumors. Intraventricular hemorrhage and meningitis accounted for the remaining 8%. Eighty-three percent of the patients were less than 1 year old at the time of surgery; 18% were 1 week old or younger. A total of 1,485 procedures were performed with an average of 3 procedures per patient. Ninety-six patients had infections, resulting in a 22% infection rate per patient and a 6% infection rate per procedure. No significant correlation was evident between etiology of the hydrocephalus and infection rate (P>0.05), even though meningomyelocele patients seemed to be more prone to infection than congenital hydrocephalus patients (P=0.06). Age at the time of shunt placement was related to infection rate, with younger patients having more infections than older ones (P<0.01). More in-depth analysis of the relationship between age and infection rate was possible in the meningomyelocele and congenital hydrocephalus groups, owing to the significant number of these patients that fell into each one of the subdivisions chosen with respect to age at the time of shunt placement. Meningomyelocele patients shunted in the first week of life have a higher infection rate than those shunted at 2 weeks of age or older (P<0.01). The same is not true for the congenital hydrocephalus patients (P>0.5). It is suggested that, whenever feasible, meningomyelocele patients be shunted at 2 weeks of age or later.     

The value of temporary external lumbar CSF drainage in predicting the outcome of shunting on normal pressure hydrocephalus

OBJECTIVE: It has been reported that temporary external lumbar CSF drainage (ELD) is a very accurate test for predicting the outcome after ventricular shunting in patients with normal pressure hydrocephalus (NPH). However, only a limited number of patients have been studied for assessing the predictive accuracy of ELD. Therefore, the value of ELD in predicting the outcome after a ventriculoperitoneal shunt in patients with presumed NPH was assessed. METHODS: All patients with presumed NPH were invited to participate in this study. Clinical assessment, MRI, and neuropsychological evaluation were followed by a lumbar CSF tap test consisting of removing 40 ml CSF. When this test resulted in marked clinical improvement of gait impairment, mental disturbances, or both, the patient was shunted without further tests. In patients with either questionable or no improvement after the CSF tap test, ELD was carried out. The value of ELD for predicting the outcome after shunting was calculated by correlating the results of ELD with that of ventriculoperitoneal shunting. RESULTS: Between January 1994 and December 2000, 49 presumed NPH patients from three institutes were included. Forty three had idiopathic, and the remaining six had secondary NPH. Forty eight patients were shunted; 39 had an ELD of whom 38 completed the test. After 2 months 35 of the 48 (73%) shunted patients had improved. The predictive value of a positive ELD was 87% (95% confidence interval (95% CI) 62-98) and that of a negative ELD 36% (95% CI 17-59). In two patients serious test related complications (meningitis) occurred without residual deficit. CONCLUSION: The study suggests that although the predictive value of a positive ELD is high, that of a negative ELD is deceptively low because of the high rate of false negative results. The costs and invasiveness of the test and the possibility of serious test related complications further limits its usefulness in managing patients with presumed NPH.     

Medical, functional, and social determinants of health-related quality of life in individuals with myelomeningocele

The purpose of this study was to identify factors associated with health-related quality of life (HRQOL) in individuals with myelomeningocele. Eighteen female and 16 male patients with myelomeningocele (mean age 13y, SD 6y; range 4 to 27y) were prospectively enrolled. Twenty-four of the patients had lesions at or above the L4 level, and 11 were wheelchair dependent. Twenty-five patients had shunted hydrocephalus; mean IQ of the cohort on testing was 85 (SD 18; range 36 to 111). Functional independence was measured in three areas (self-care, mobility, and social cognition) using the Functional Independence Measure for Children (WeeFIM). The Support Function Scale (social supports available to the family), the Amount of Assistance Questionnaire (assistance required for activities of daily living), and the Health Utilities Index II (HUI-II; perceived health status measure) were completed by participants or their parents. Each patient's HRQOL was quantified using a 'feeling thermometer', which is a plastic 'thermometer' scaled from 0 (least desirable health state) to 100 (perfect health). Results of multiple regression analysis using HRQOL as the dependent variable revealed that the Amount of Assistance Questionnaire, WeeFIM self-care, and HUI-II were significantly correlated with quality of life ratings (p < 0.025). Maximizing functional independence should be a priority in improving HRQOL in individuals with myelomeningocele.     

Hydrodynamics in vein of Galen malformations

Forty-three patients with vein of Galen aneurysmal malformations (VGAM) referred to us for endovascular treatment between 1985 and 1990 and 335 additional cases published in the literature were reviewed with particular attention to the presence of ventricular enlargement and outcome after shunting. Hydrocephalus was the second most frequent symptom (46.8%); it is more frequent in infants (73%) than in children, adults (30%) or neonates (15%). Of the patients reported in the literature, 17.9% had undergone shunting. Within the shunted population there was an overall morbidity of 41% and a mortality of 10% (especially in the infant group). In our series 17 patients (39.5%) were shunted and a significant difference in the clinical outcome was noted between the shunted and the nonshunted group. Of the nonshunted patients, 66.6% were free of any neurological deficit or mental retardation and fewer than 5% presented with significant mental retardation. On the other hand, only 33.3% of the shunted patients had a favorable outcome and more than 15% developed significant mental retardation. Among the various causes of hydrocephalus in patients with VGAMs, such as obstruction of the aqueduct, subarachnoid hemorrhage, or ex vacuo hydrocephalus, high venous pressure may be of particular importance. In this article a physiopathological interpretation of the hydrodynamics in VGAMs is developed and a speculative explanation for CSF disorders related to ventricular shunting proposed. Treatment of hydrocephalus in VGAMs can be achieved through obliteration of the malformation or at least diminishing the venous pressure; surgical ventricular shunting does not have to be the first treatment of hydrodynamic disorders associated with VGAMs, especially in infants.     

Clinical and social determinants of a longer duration of untreated psychosis of schizophrenia in a Japanese population

Aim: To measure the duration of untreated psychosis (DUP) among patients with schizophrenia in a Japanese population and to investigate clinical and social determinants of the DUP. Methods: A multicentre, retrospective study at seven medical centres in three cities (Tokyo, Toyama and Kochi) was performed. In total, 150 consecutive patients (78 men) with neuroleptic-naïve first-episode schizophrenia were investigated; their DUP and demographic, clinical and social variables were obtained from their medical charts and analysed. Results: The intraclass correlation coefficient for the DUP was quite good (ICC = 0.849). The mean DUP of all the subjects attending the seven psychiatric services was 20.3 months, and the median DUP was 6.0 months. Fourteen patients (9.3%) had a DUP of more than 60 months, and 47 patients, or about one-third, had a DUP of more than 24 months. No significant differences in the mean DUPs were observed among the three cities. Patients who were employed or who were students had a significantly shorter DUP (14.3 months). The median DUP for those with an insidious onset of psychosis (n = 85) was 18.0 months, compared with a median of 2.0 months for those with a sudden and acute onset (n = 61). However, no other clinical or social variables examined in this study were associated with differences in the DUP. Conclusions: The DUP of patients with schizophrenia is relatively long in Japan. The provision and modification of psychiatric services for easy access and a system for the early recognition and detection of mental illness are needed.     

Plasma homocysteine in vascular disease and in nonvascular dementia of depressed elderly people.

Depression among elderly people with reversible cognitive loss often manifests with concomitant vascular disease and can also precede the development of nonvascular degenerative dementia. Little is known about etiological factors for reversible or irreversible dementias in older depressed people. The amino acid homocysteine (HC), which is both a vascular disease risk factor and a precursor of the excitotoxic amino acids cysteine and homocysteic acid, could play a role in the pathophysiology of such individuals. Twenty-seven depressed elderly acute inpatients by DSM-III-R criteria had significantly higher plasma homocysteine levels and lower cognitive screening test scores than did 15 depressed young adult inpatients. HC was highest in the older patients who had concomitant vascular diseases (n = 14). HC was lowest in the older depressives who had neither vascular illnesses nor dementia (n = 8), comparable to the young adult depressives. Higher HC correlated significantly with poorer cognition only in the nonvascular geriatric patients (rs = -0.53). The findings extend earlier work showing higher HC in vascular patients from general medical populations, and also suggest a possible metabolic factor in certain dementias associated with late-life depression.     

Continuous intraoperative electroencephalographic monitoring in carotid endarterectomy

Continuous electroencephalographic (EEG) monitoring was done during 143 consecutive carotid endarterectomies in 130 patients to detect intolerance to cross-clamping. An intraluminal shunt was inserted when EEG changes appeared (in the first 100 procedures) or when EEG changes appeared and a long clamping time was supposed (in the last 43 cases). 121 patients had no EEG changes at clamping time and only 1 had a postoperative deficit due to embolization, which occurred before clamping and was revealed by a decrease of voltage on tracing. 15 patients showed early (within 4 min after clamping) changes and in 11 patients shunting led to the reversal of EEG anomalies in all cases but 2. The state of these 2 patients was worse after surgery, in one because of embolic problems, in the other (shunted 30 min after clamping) probably for hemodynamic reasons. 4 patients with early EEG changes, not shunted because of the short clamping time, had no neurological deficit. 7 patients, 2 of which were shunted, showed late (after 4 min) EEG changes. Only 1 nonshunted patient in this group awoke with a minor, transitory neurological complication. Moreover, EEG changes have been correlated with the preoperative clinical condition and with the presence, on angiography, of contralateral carotid lesions. Also, EEG findings have been correlated with the computed tomography data (in 71 cases) and with the values of interior carotid artery (ICA) back pressure (in 58 cases). No possibility to predict the tolerance to clamping appeared from these correlations. However, a relatively higher risk of intolerance to clamping in patients with contralateral ICA occlusion was noted.(ABSTRACT TRUNCATED AT 250 WORDS)     

Emotional functioning in adolescent anorexia nervosa patients

OBJECTIVE: In this study, emotional functioning of adolescent anorexia nervosa patients was compared with two control groups; another internalizing psychiatric outpatient group and a healthy control group. METHODS: Forty-eight anorexia nervosa patients (AN), 21 other psychiatric outpatients with depressive and/or anxiety disorders (PSYCH) and 48 healthy controls (HC) completed a battery of tasks and questionnaires designed to measure different aspects of emotional functioning. Cognitive (parallel) tasks were administered to control for differences of a cognitive nature. RESULTS: The AN and the PSYCH groups had clear deficits in emotional functioning compared to the HC group. Considering the data from the alexithymia questionnaire, it was the AN group who scored significantly worse on emotional functioning when compared to the HC group. Considering the data from the emotional tasks, both psychiatric groups performed worse than the HC group in their processing of visual emotional information and the PSYCH group had more difficulty in memorizing responses to auditory emotional stimuli than the AN and HC group. Furthermore, the PSYCH group processed auditory emotional information more slowly than the HC group. No differences between the three groups were found on the non-emotional, cognitive tasks. CONCLUSION: Both the AN and PSYCH patients show deficits in their processing of emotional information and details are discussed.     

Facial emotion recognition in euthymic patients with bipolar disorder and their unaffected first-degree relatives

BackgroundFacial emotion recognition (FER) is an important task associated with social cognition because facial expression is a significant source of non-verbal information that guides interpersonal relationships. Increasing evidence suggests that bipolar disorder (BD) patients present deficits in FER and these deficits may be present in individuals at high genetic risk for BD. The aim of this study was to evaluate the occurrence of FER deficits in euthymic BD patients, their first-degree relatives, and healthy controls (HC) and to consider if these deficits might be regarded as an endophenotype candidate for BD.MethodsWe studied 23 patients with DSM-IV BD type I, 22 first-degree relatives of these patients, and 27 HC. We used the Penn Emotion Recognition Tests to evaluate tasks of FER, emotion discrimination, and emotional acuity. Patients were recruited from outpatient facilities at the Institute of Psychiatry of the University of Sao Paulo Medical School, or from the community through media advertisements, had to be euthymic, with age above 18 years old and a diagnosis of DSM-IV BD type I.ResultsEuthymic BD patients presented significantly fewer correct responses for fear, and significantly increased time to response to recognize happy faces when compared with HC, but not when compared with first-degree relatives. First-degree relatives did not significantly differ from HC on any of the emotion recognition tasks.ConclusionOur results suggest that deficits in FER are present in euthymic patients, but not in subjects at high genetic risk for BD. Thus, we have not found evidence to consider FER as an endophenotype candidate for BD.     

The socio-familial background and prevalence of medical aetiological factors in children attending ESN/M schools

ABSTRACT. A study of 169 mildly mentally retarded children included consideration of social class, medical risk factors, sibship position, family size and parental education. Ninety-four (56%) children were from social class IV or V. Medical risk factors were identified in 71 (42%) children overall: the prevalence fell from 55% in social class II to 30% in social class V. Prenatal factors were identified in 22 children of whom 14 were third or later born in their sibship: this may reflect increased maternal age at birth. Perinatal events had been reported in 41 children, 20 of whom were in social class III; there was no clear relationship to sibship position. Seven of eight postnatal events had occurred in children in social class II or III. Children in social class IV or V did not appear to be at increased risk of retardation from environmental medical events. First born children were over-represented in the survey, with a minor shift towards fourth or later-born children. Average family size was 3.25 children (general population 2.0 children). The prevalence of medical risk factors was lowest (18%) in children from large sibships in social class V. Both parents of 86 children had had educational problems: this included 13 children in social class III. Thirty-eight (33%) of these children had medical risk factors, compared with 43/83 (51%) in children where at least one patient had achieved average education. Thirty children had no medical risk factor, nor any history of parental learning difficulty.     

Psychometric intelligence after infantile hydrocephalus

Methodological issues in research concerning intellectual sequelae of infantile hydrocephalus are reviewed, and a multivariate statistical approach to this problem is proposed and exemplified. The significance of a variety of medical history variables with regard to psychometric intelligence was assessed in a sample of 5- to 8-year-old children who had been shunted in the 1st year of life. Stepwise discriminant analyses revealed that many medical history variables were neutral with regard to intellectual outcome (as assessed by performance on psychometric tests). The presence of additional medical problems in infancy, as well as current ocular defects, were the most significant variables that were associated with a high likelihood of mental retardation. Implications for further research are discussed.     

"Tell me how do I feel"--emotion recognition and theory of mind in symptomatic mesial temporal lobe epilepsy

Specific interictal personality characteristics in epilepsy, sometimes referred to as "Waxman-Geschwind Syndrome", have been recognized for centuries and extensively described. Despite the persevering clinical impression that patients with mesial temporal lobe epilepsies (MTLE) suffer from problems in communication and interpersonal relations, uncertainties and controversies remain as to the precise origin of these psychosocial difficulties. Here, we investigated social-cognitive and decision-making abilities using a set of tasks that combine behavioural and psychological measures of social and emotional variables to answer the question of whether patients with MTLE are specifically impaired in social cognition compared to both an epilepsy and a healthy control group. MTLE patients, an epilepsy control group (extra-MTLE; patients with epilepsy, not originating within the frontal or mesial temporal lobe) and healthy controls (HC) were assessed according to their general cognitive status as well as with our Social Cognition Battery, which included tests of basic processes of social cognition, theory of mind, decision making, and various aspects of psychopathology and quality of life. MTLE patients were significantly impaired compared to HC on most measures of the Social Cognition Battery. MTLE patients were predominantly impaired in general emotion recognition compared to extra-MTLE patients. Performance in the epilepsy control group, although not significantly differing from performance in either the MTLE or the healthy control group, lay between these two groups. MTLE can be considered a significant risk factor for the development of deficits in social cognition beyond weaknesses that might be associated with epilepsy as a stigmatized chronic neurological disorder. The presence of deficits in social cognition may explain various behavioural symptoms that have historically driven concepts such as "epileptic personality" or "interictal personality disorder" and may indicate new routes for therapeutic interventions.     

Functioning and utility for current health of patients with depression or chronic medical conditions in managed, primary care practices.

BACKGROUND: Health utility is the recommended outcome metric for medical cost-effectiveness studies. We compared health utility and quality of life for primary care patients with depression or chronic medical conditions. METHODS: Respondents were outpatients (N = 17 558) of primary care clinicians (N = 181) in 7 managed care organizations. Utility was assessed by time tradeoff, or the years of life that patients would exchange for perfect health, and standard gamble, or the required chance of success to accept a treatment that can cause immediate death or survival in perfect health. Probable 12-month depressive disorder and affective syndromes were assessed through self-report items from a diagnostic interview. Medical conditions were assessed with self-report. Quality of life was assessed by the 12-Item Short-Form Health Survey. Regression models were used to compare quality of life and utility for patients with depression vs chronic medical conditions. RESULTS: Patients with probable 12-month depressive disorder had worse mental health and role-emotional and social functioning and lower utility for their current health than patients with each chronic medical condition (for most comparisons, P<.001). Depressed patients had worse physical functioning than patients with 4 common chronic conditions but better physical functioning than patients with 4 other conditions (each P<.001). Patients with lifetime bipolar illness and 12-month double depression had the poorest quality of life and lowest utility. CONCLUSIONS: Primary care patients with depressive conditions have poorer mental, role-emotional, and social functioning than patients with common chronic medical conditions, and physical functioning in the midrange. The low utility of depressed patients relative to patients with chronic medical conditions suggests that recovery from depression should be a high practice priority.     

Hereditary heparin cofactor II deficiency and the risk of development of thrombosis

Heparin cofactor II (HC II) levels were measured by electro-immunoassay in healthy volunteers, and patients with liver disease, DIC, proteinuria or a history of venous thrombosis. Analysis of the data in 107 healthy volunteers revealed that plasma HC II increases with age (at least between 20 and 50 years). HC II was found to be decreased in most patients with liver disease (mean value: 43%) and only in some patients with DIC. Elevated levels were found in patients with proteinuria (mean value 145%). In 277 patients with a history of unexplained venous thrombosis three patients were identified with a HC II below the lower limit of the normal range (60%). Family studies demonstrated hereditary HC II deficiency in two cases. Among the 9 heterozygotes for HC II deficiency only one patient had a well documented history of unexplained thrombosis. Therefore the question was raised whether heterozygotes for HC II deficiency can also be found among healthy volunteers. When defining a group of individuals suspected of HC II deficiency as those who have a 90% probability that their plasma HC II is below the 95% tolerance limits of the normal distribution in the relevant age group, 2 suspected HC II deficiencies were identified among the healthy volunteers. In one case the hereditary nature of the defect could be established. It is concluded that hereditary HC II deficiency is as prevalent among healthy volunteers as in patients with thrombotic disease. Further it is unlikely that heterozygosity for HC II deficiency in itself is a risk factor for the development of venous thrombosis.