Evoked potentials in patients with Huntington's disease and their offspring. I. Somatosensory evoked potentials

Spinal and cortical somatosensory evoked potentials (SEPs) were recorded in a large sample of patients with Huntington's disease (n = 37) and subjects at risk (first order offspring, n = 43). The SEPs were elicited by stimulation of the median and tibial nerves and recorded at Erb's point, the cervical level (C2) and at the corresponding scalp areas.The most striking finding in patients with Huntington's disease was a drastic diminution of the amplitude of the early cortical components, especially N20/P25 for the median nerve and N33/P40 for the tibial nerve. The latencies (Erb's point, C2, cortical) were only slightly prolonged in comparison to the normal values.Forty-three per cent of the persons at risk exhibited pathological results with a clear reduction in amplitude of the early cortical responses or with a pathological side difference between the amplitudes. Fifty-three per cent of the persons at risk exhibited a normal result. Two persons at risk (=6%) could not be classified unambiguously. Some patients with benign and symptomatic chorea were investigated. These showed normal results with one exception.The diagnostic and predictive value of the investigation of SEPS in Huntington's disease is discussed.     

Genetic prediction and family structure in Huntington's chorea.

A deoxyribonucleic acid marker linked to the locus for Huntington''s chorea exists, but its possible use in the prediction of this disorder depends on the pedigree structure of individual families. Analysis of data from a population register for Huntington''s chorea in south Wales showed that only a minority of subjects at risk had the appropriate members of their family living to allow the presence or absence of the gene to be definitively predicted. However, the structure of the family allowed a degree of prediction (in particular, exclusion of the disorder) to be made for the fetus during pregnancies of these subjects in almost 90% of cases. Such a prediction need not alter the risk state for the parent at risk. The structure of the family will remain crucial for prediction even when current limitations of the linked marker have been overcome.     

Surveillance of AIDS in the United Kingdom.

The surveillance of cases of the acquired immune deficiency syndrome (AIDS) in the United Kingdom is described and a preliminary analysis made of the 1012 cases that were reported to the end of August 1987. Homosexuals were the largest risk group. For the first time it is possible to present cases by the date of diagnosis and by the regional health authority of residence. The rate of increase of new cases shows no sign of slowing down. One third of patients with AIDS lived in a different regional health authority from that in which their disease had been diagnosed. The geographical distribution varied with the risk group. The commonest presenting clinical feature at diagnosis was Pneumocystis carinii pneumonia. Kaposi''s sarcoma was considerably more common among homosexuals than among people in other groups at risk.     

Incidence of AIDS and excess of mortality associated with HIV in haemophiliacs in the United Kingdom: report on behalf of the directors of haemophilia centres in the United Kingdom.

OBJECTIVE--To estimate the cumulative incidence of AIDS by time since seroconversion in haemophiliacs positive for HIV and to examine the evidence for excess mortality associated with HIV in those who had not yet been diagnosed as having AIDS. DESIGN--Analysis of data from ongoing national surveys. SETTING--Haemophilia centres in the United Kingdom. PATIENTS--A total of 1201 men with haemophilia who had lived in the United Kingdom during 1980-7 and were positive for HIV. INTERVENTION--None. END POINTS--Diagnosis of AIDS; death in those not diagnosed as having AIDS. MEASUREMENTS AND MAIN RESULTS--Estimation of cumulative incidence of AIDS and number of excess deaths in seropositive patients not diagnosed with AIDS. Median follow up after seroconversion was 5 years 2 months. Eight five patients developed AIDS. Cumulative incidence of AIDS five years after seroconversion was 4% among patients aged less than 25 at first test positive for HIV, 6% among those aged 25-44, and 19% among those aged greater than or equal to 45. There was little evidence that type or severity of haemophilia or type of factor VIII or IX that had caused HIV infection affected the rate of progression to AIDS. Mortality was increased among those who had not been diagnosed as having AIDS, especially among those with "AIDS related complex." Thirteen deaths were observed among 36 patients diagnosed as having AIDS related complex against 0.65 expected, and 34 deaths in 1080 other patients against 22.77 expected; both calculations were based on mortality rates observed in haemophiliacs in the United Kingdom in the late 1970s. CONCLUSIONS--Rate of progression to AIDS depended strongly on age. There is a substantial burden of fatal disease among patients positive for HIV who have not been formally diagnosed as having AIDS.     

Organochlorine pesticide residues in human fat in the United Kingdom 1976-7.

Between May 1976 and August 1977 samples of human body fat were taken during routine necropsies in the United Kingdom on 236 subjects aged over 5 years and four infants aged under 4 months. Comparison with results from earlier studies showed a further decline in residues of pp''-dichlorodiphenyltrichloroethane (pp''-DDT) and dieldrin (HEOD) and increased amounts of hexachlorobenzene residues; concentrations of other compounds were similar to those observed in the studies carried out in 1963-4, 1965-7, and 1969-71. Comparison of the data with those from other countries, showed that the concentrations of organochlorine pesticide residues and polychlorobiphenyls in human fat samples from residents of the United Kingdom remain among the lowest in Europe and, indeed, the world.     

Snoring and breathing pauses during sleep: telephone interview survey of a United Kingdom population sample.

OBJECTIVES: To determine the prevalence of snoring, breathing pauses during sleep, and obstructive sleep apnoea syndrome and determine the relation between these events and sociodemographic variables, other health problems, driving accidents, and consumption of healthcare resources. DESIGN: Telephone interview survey directed by a previously validated computerised system (Sleep-Eval). SETTING: United Kingdom. SUBJECTS: 2894 women and 2078 men aged 15-100 years who formed a representative sample of the non-institutionalised population. MAIN OUTCOME MEASURES: Interview responses. RESULTS: Forty per cent of the population reported snoring regularly and 3.8% reported breathing pauses during sleep. Regular snoring was significantly associated with male sex, age 25 or more, obesity, daytime sleepiness or naps, night time awakenings, consuming large amounts of caffeine, and smoking. Breathing pauses during sleep were significantly associated with obstructive airways or thyroid disease, male sex, age 35-44 years, consumption of anxiety reducing drugs, complaints of non-restorative sleep, and consultation with a doctor in the past year. The two breathing symptoms were also significantly associated with drowsiness while driving. Based on minimal criteria of the International classification of Sleep Disorders (1990), 1.9% of the sample had obstructive sleep apnoea syndrome. In the 35-64 year age group 1.5% of women (95% confidence interval 0.8% to 2.2%) and 3.5% of men (2.4% to 4.6%) had obstructive sleep apnoea syndrome. CONCLUSIONS: Disordered breathing during sleep is widely underdiagnosed in the United Kingdom. The condition is linked to increased use of medical resources and a greater risk of daytime sleepiness, which augments the risk of accidents. Doctors should ask patients and bed partners regularly about snoring and breathing pauses during sleep.     

Demographic and social characteristics of adults with cystic fibrosis in the United Kingdom.

OBJECTIVE--To obtain information about social and demographic characteristics and lifestyle of adult patients with cystic fibrosis, including those who do not attend major specialist clinics. DESIGN--Confidential self completion postal questionnaire to adult patients with cystic fibrosis, asking about social and demographic characteristics, social class and occupation, employment, education, insurance and social security benefits, symptom severity, and medical care. SETTING--National association for adults with cystic fibrosis. SUBJECTS--1052 adult members of the Association of Cystic Fibrosis Adults UK, accounting for 68% of those with cystic fibrosis in the United Kingdom population over 16 years of age and over 80% of those over 25 in June 1990. RESULTS--The response rate was 82% (397 women, 423 men). Most adults with cystic fibrosis were found to be living fulfilling lives into adulthood. Significantly fewer men were married or cohabiting than women (110 (26%) men, 175 (44%) women). 420 (55%) responders were working, and of these 235 (56%) had less than two weeks'' sick leave a year. Half of those not employed gave ill health as the reason. Revealing that they had cystic fibrosis at job interviews reduced likelihood of being employed for those with mild to moderate disease. People with cystic fibrosis had been less successful than the general population in achieving O level or equivalent qualifications, but more successful in achieving A level or higher qualifications. Achievement of any qualifications enhanced employment prospects irrespective of disease severity. CONCLUSION--Contrary to an image of chronic ill health and disability, a high proportion of adults with cystic fibrosis are living full and productive lives.     

Time processing in Huntington's disease: a group-control study

Background

“Timing” processes are mediated via a disturbed neuronal network including the basal ganglia. Brain structures important for “timing” are also discussed to be critical for the deterioration of movements in Huntington''s disease (HD). Changes in “timing processes” are found in HD, but no study has varied the degree of motor demands in timing functions in parallel in HD. It may be hypothesized that timing functions may be deteriorated to a different extent in motor and non-motor timing, because in motor timing the underlying brain structures may be more demanding than in non-motor timing.

Methodology/Principle Findings

We assessed timing in two different experiments: a time-estimation (TE) and a time-discrimination (TD) task. The demand on motor functions is high in the TE-task and low in the TD-task. Furthermore, general motor ability was assessed at different complexity levels. A presymptomatic (pHD), a symptomatic (HD) and a control group were investigated. We found a decline in timing functions when demands on the motor system were high (TE-task), in HD and even in pHD, compared to controls. In non-motor timing (TD task) and in the assessment of general motor ability, performance in the pHD-group was comparable to the controls and better than in the symptomatic group. Performance in both timing tasks was related to the duration until the estimated age of onset in pHDs.

Conclusions/Significance

The study shows a selective deterioration of time-estimation processes in symptomatic and even presymptomatic Huntington''s disease. Time-discrimination processes were not affected in both patient groups. The relation of timing performance to the duration until the estimated age of onset in pHD is of clinical importance.     

Sporadic Creutzfeldt-Jakob disease in the United Kingdom: analysis of epidemiological surveillance data for 1970-96.

OBJECTIVE: To identify changes in the occurrence of Creutzfeldt-Jakob disease that might be related to the epidemic of bovine spongiform encephalopathy. DESIGN: Epidemiological surveillance of the United Kingdom population for Creutzfeldt-Jakob disease based on (a) referral of suspected cases by neurologists, neuropathologists, and neurophysiologists and (b) death certificates. SETTING: England and Wales during 1970-84, and whole of the United Kingdom during 1985-96. SUBJECTS: All 662 patients identified as sporadic cases of Creutzfeldt-Jakob disease. MAIN OUTCOME MEASURES: Age distribution of patients, age specific time trends of disease, occupational exposure to cattle, potential exposure to causative agent of bovine spongiform encephalopathy. RESULTS: During 1970-96 there was an increase in the number of sporadic cases of Creutzfeldt-Jakob disease recorded yearly in England and Wales. The greatest increase was among people aged over 70. There was a statistically significant excess of cases among dairy farm workers and their spouses and among people at increased risk of contact with live cattle infected with bovine spongiform encephalopathy. During 1994-6 there were six deaths from sporadic Creutzfeldt-Jakob disease in the United Kingdom in patients aged under 30. CONCLUSIONS: The increase in the incidence of sporadic Creutzfeldt-Jakob disease and the high incidence in dairy farmers in the United Kingdom may be unrelated to bovine spongiform encephalopathy. The most striking change in the pattern of Creutzfeldt-Jakob disease in the United Kingdom after the epidemic of bovine spongiform encephalopathy is provided by the incidence in a group of exceptionally young patients with a consistent and unusual neuropathological profile. The outcome of mouse transmission studies and the future incidence of the disease in the United Kingdom and elsewhere, will be important in judging whether the agent causing bovine spongiform encephalopathy has infected humans.     

Fingerprint Patterns in Huntington's Chorea and Parkinson's Disease

In the course of a continuing search for means of predicting Huntington''s chorea before the onset of neurological symptoms, a study of fingerprint patterns was undertaken, using the technique employed by Hodges and Simon in the investigation of patients with Wilson''s disease. Fingerprint patterns of 61 patients with Huntington''s chorea and 50 with Parkinson''s disease were compared with norms established by Scotland Yard. Although an increased incidence of the “whorl” pattern was seen in the left second and third fingers in patients with Huntington''s chorea, this finding could not be interpreted as having diagnostic or prognostic value as it was found also in some normal subjects and in occasional cases of Parkinson''s disease. The pattern supposedly characteristic of Wilson''s disease was also seen in persons with Huntington''s chorea.     

Audit of prenatal diagnosis for haemoglobin disorders in the United Kingdom: the first 20 years.

OBJECTIVES: To audit services for prenatal diagnosis for haemoglobin disorders in the United Kingdom. DESIGN: Comparison of the annual number of cases recorded in a United Kingdom register of prenatal diagnoses for haemoglobin disorders, with the annual number of pregnancies at risk of these disorders, by ethnic group and regional health authority. The number of pregnancies at risk was estimated using data on ethnic group from the 1991 census and data from the United Kingdom thalassaemia register, which records the number of babies born with thalassaemia. SETTING: The three national prenatal diagnosis centres for haemoglobin disorders. SUBJECTS: 2068 cases of prenatal diagnosis for haemoglobin disorders in the United Kingdom from 1974 to 1994. MAIN OUTCOME MEASURES: Utilisation of prenatal diagnosis by risk, ethnic group, and regional health authority. Proportion of referrals in the first trimester and before the birth of any affected child. RESULTS: National utilisation of prenatal diagnosis for haemoglobin disorders was around 20%. During the past 10 years it has remained steady at about 50% for thalassaemias and risen from 7% to 13% for sickle cell disorders. Utilisation for sickle cell disorders varies regionally from 2% to 20%. Utilisation for thalassaemias varies by ethnic group. It is almost 90% for Cypriots and ranges regionally for British Pakistanis from 0% to over 60%. About 60% of first prenatal diagnoses are done for couples without an affected child. Less than 50% of first referrals are in the first trimester. CONCLUSIONS: National utilisation of prenatal diagnosis for haemoglobin disorders is far lower than expected, and there are wide regional variations. A high proportion of referrals are still in the second trimester and after the birth of an affected child. The findings point to serious shortcomings in present antenatal screening practice and in local screening policies and to inadequate counselling resources, especially for British Pakistanis.     

Haemophilia A home therapy in the United Kingdom 1975-6.

Data on home treatment for patients with haemophilia A (factor VIII deficient haemophilia) were compiled for 1975 and 1976 from questionnaires answered by directors of haemophilia centres throughout the United Kingdom. There were 48 haemophilia centres in 1975 and 71 in 1976. The number of patients on or in training for home treatment increased from 267 to 488 in the two years, and a further 241 haemophiliacs were considered suitable for home therapy by the end of 1976. Apart from a small (but increasing) number of haemophiliacs on prophylactic treatment, most patients were on low-dose (250-500 units) on-demand regimens, using a mean of 20 000 factor VIII units per patient per year in 1976. An estimated 55% of the blood product used for home therapy in the UK in 1976 was imported from commercial sources. Despite the fact that the numbers of patients on home treatment have increased, so that about 60% of the potential population were receiving or being considered for home treatment in 1976, inadequacies in the service still remain. In some centres follow-up is clearly inadequate; about 15% of patients still rely on cryoprecipitate; and too little money has been invested in making the NHS self-sufficient in factor VIII production.     

Homologous blood use and conservation techniques for cardiac surgery in the United Kingdom.

The transfusion laboratories of 32 cardiothoracic surgical centres for adults were surveyed to determine the donor blood requirement for open heart surgery in the United Kingdom. Details of the transfusion practice and the use of blood conservation techniques were sought from a representative senior cardiac anaesthetist at each centre. Suitable data were received from 24 transfusion laboratories (75%) and 29 anaesthetists (90%). The mean (SD) blood use was 5.07 (1.53) units per operation. Seven centres routinely transfused fresh frozen plasma to all patients postoperatively. Experience with autologous deposit (three centres), "cell separators" (four centres), and the reinfusion of shed mediastinal blood (four centres) was limited. Prebypass phlebotomy for postbypass reinfusion (14 centres) and the infusion of residual oxygenator blood (27 centres) were the conservation techniques most commonly applied. In only nine centres was a postoperative normovolaemic anaemia to a haemoglobin concentration of less than 100 g/l accepted. Applying blood conservation techniques more widely would help to maintain blood supplies and reduce morbidity and mortality related to transfusion.     

Is risk of Kaposi's sarcoma in AIDS patients in Britain increased if sexual partners came from United States or Africa?

OBJECTIVE--To determine whether the risk of Kaposi''s sarcoma in patients with AIDS is increased by sexual contact with groups from abroad with a high incidence of Kaposi''s sarcoma. DESIGN--Analysis of risk of Kaposi''s sarcoma in patients with AIDS, according to country of origin of their sexual partners. SETTING--United Kingdom. PATIENTS--2830 patients with AIDS reported to the Communicable Disease Surveillance Centre and the Communicable Disease (Scotland) Unit up to March 1990, of whom 566 had Kaposi''s sarcoma. MAIN OUTCOME MEASURES--Percentage of patients with AIDS who had Kaposi''s sarcoma. RESULTS--537 of 2291 homosexual or bisexual men (23%) with AIDS had Kaposi''s sarcoma; 10% (14/135) of the men and women who acquired HIV by heterosexual contact had Kaposi''s sarcoma. None of the 316 subjects who acquired HIV through non-sexual routes had Kaposi''s sarcoma. Kaposi''s sarcoma was more common among homosexual men whose likely source of infection included the United States (171/551, 31%) or Africa (9/34, 26%) than among those infected in the United Kingdom (119/625, 19%) (p less than 0.05). CONCLUSION--The data suggest that Kaposi''s sarcoma is caused by a sexually transmissible agent which was introduced into the British homosexual population mainly from the United States [corrected].     

GABA content and glutamic acid decarboxylase activity in brain of Huntington's chorea patients and control subjects.

—GABA contents are significantly decreased in the caudate nucleus, putamen-globus pallidus, substantia nigra, and occipital cortex in autopsied brain from Huntington's chorea patients, as compared to values in the same regions from control subjects who have died without neurological disease. Homocarnosine levels are lower in choreic than in control brain, but only in the putamen-globus pallidus and the cerebellar cortex are the differences significant. Activity of the enzyme which synthesizes GABA, glutamic acid decarboxylase, is reduced in the brains of some choreic patients, but may be equally low in brain of control subjects, even though the latter exhibit normal brain GABA content. Low glutamic acid decarboxylase activity in autopsied human brain is not uniquely characteristic of Huntington's chorea. No evidence was found in this study for an inhibitor of glutamic acid decarboxylase in choreic brain, nor for the presence of an isoenzyme with decreased affinity for glutamate. GABA aminotransferase, the enzyme which degrades GABA, was equally active in control and choreic brain; therefore, increased activity of this enzyme cannot account for the low brain GABA levels in Huntington's chorea.     

Comparisons of therapeutic effects of levodopa,levodopa and selegiline,and bromocriptine in patients with early,mild Parkinson's disease: three year interim report. Parkinson's Disease Research Group in the United Kingdom.

OBJECTIVE--To determine the optimum treatment for early Parkinson''s disease. DESIGN--An open, long term, prospective randomised trial conducted by the Parkinson''s Disease Research Group of the United Kingdom. SETTING--93 hospitals throughout the United Kingdom. SUBJECTS--782 patients with early Parkinson''s disease who were not receiving dopaminergic treatment. INTERVENTIONS--Patients allocated to treatment with levodopa/dopa decarboxylase inhibitor alone (arm 1), levodopa/decarboxylase inhibitor/selegiline in combination (arm 2), or bromocriptine (arm 3). MAIN OUTCOME MEASURES--Disability assessment as judged by improvement on Hoehn and Yahr, modified Webster, and North Western University disability scales. Adverse event profile and mortality ratios. RESULTS--Interim results indicate that all three treatment regimens led to improvement in baseline disabilities after 12 months'' treatment and that deterioration in control was apparent by three years. No significant differences were found between the results of treatment in arm 1 and arm 2, but both were significantly more effective than bromocriptine (arm 3) and had fewer early adverse reactions. The adjusted difference (95% confidence interval) in Webster rating for arm 3 v 1 was 0.93 points (0.27 to 1.50; p = 0.0058) and for arm 3 v 2 was 1.25 points (0.61 to 1.89; p = 0.0002). The incidence of dyskinesias and motor oscillations, however, was significantly lower in arm 3 (2% and 5%, respectively) than in arm 1 (27% and 33%, respectively) and arm 2 (34% and 35%, respectively). CONCLUSIONS--As there were no marked differences in functional improvement between the three groups the choice of treatment in the early stages of Parkinson''s disease may not be critical.     

Obstetric Anaesthesia Services in the United Kingdom

In a survey of obstetric anaesthetic services in the United Kingdom questionnaires were sent to 398 hospital maternity units and 347 general-practitioner maternity units, of which 344 and 272 respectively were returned. Many hospitals were unable to provide an anaesthetist for obstetric surgery only, and few consultant anaesthetist sessions were allocated to obstetric surgery, particularly in regional hospitals in England and Wales. Constant supervision of junior anaesthetic staff with under 12 months'' experience was lacking in several hospitals. Endotracheal intubation is widely used throughout the United Kingdom. Though regional analgesic techniques are used by most anaesthetists it is impossible to provide a 24-hour regional analgesic service in all but a few hospitals.