Intraventricular pentosan polysulphate in human prion diseases: an observational study in the UK.

UNLABELLED: BACKGROUND, PURPOSE AND METHODS: This observational study assessed the effect of continuous intraventricular infusion of pentosan polysulphate (PPS) in seven patients at different clinical centres in the UK. RESULTS: Complications of intraventricular catheterization were frequent. PPS was well-tolerated over a wide dose range (11-110 microg/kg/day) during the 6-month study. Four patients were assessed for the entire study period: one remained stable, two showed minimal deterioration and one progressed significantly. CONCLUSION: Mean survival of all patients was longer than reported values for natural history of specific prion disorders. Possible reasons for these findings are explored.

Blunt cervical spine trauma as a cause of spinal cord injury and delayed cortical blindness.

STUDY DESIGN: Case report. OBJECTIVE: To present and discuss the case of a patient who sustained a significant flexion compression injury of the cervical spine with resulting tetraplegia and development of cortical blindness. SETTING: National Spinal Injuries Unit and Institute of Neurological Sciences, Southern General Hospital, Glasgow, Scotland, UK. METHODS: Clinical and radiological follow-up of the patient. RESULTS: Cortical blindness resulted from vertebral artery dissection associated with blunt cervical spine trauma. The patient is registered blind and is ventilator dependent. CONCLUSION: The potential complications of blunt vertebral artery injury remain poorly recognised. Screening is routinely not performed. Advances in noninvasive radiological techniques may result in recognition of asymptomatic disease and the potential for therapeutic intervention.

Measuring therapy adherence in Parkinson's disease: a comparison of methods.

UNLABELLED: The objective of this study was to assess different methods of measuring therapy adherence in Parkinson's disease (PD). In a single centre observational study, 112 patients with idiopathic PD were randomised to a crossover trial of active monitoring (n = 69, simple tablet count and electronic monitoring), or to no monitoring (n = 43, control group). All patients completed a self report and visual analogue scale (VAS) indicating therapy intake. In the active monitoring group, 56 (81% of cases) used > or = 80% of their medication, and 13 (19% of cases) used <80%, based on electronic monitoring. Median adherence for self report was 100% (interquartile range (IQR) 100 to 100) and for VAS was 100% (IQR 95 to 100), in both active and control groups. Patients taking > or = 80% of prescribed medication had a median total adherence of 98% (IQR 93 to 101) by electronic monitoring, which was similar to that from other METHODS: self report 100%, IQR 100 to 100; VAS 100%, IQR 95 to 100; simple tablet count 98%, IQR 89 to 100. Median total adherence in patients taking <80% of medication was significantly lower by electronic monitoring (69%, IQR 44 to 74) than by other methods: self report 100%, IQR 100 to 100; VAS 100%, IQR 95 to 100; and simple tablet count 90%, IQR 78 to 100 (all p<0.0001). Sensitivities of self report (10%), VAS (17%), and simple tablet count (50%) were all low for detecting suboptimal medicine intake. Self report, VAS, and simple tablet counts are insensitive as predictors of suboptimal medicine usage in PD. How patients take their medicines influences interpretation of the therapy response and consequent management decisions, with implications for clinical trial analysis and clinical practice.

Is inadequate family history a barrier to diagnosis in CADASIL?

OBJECTIVES: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) has typical clinical features that include stroke, migraine, mood disturbances and cognitive decline. However, misdiagnosis is common. We hypothesized that family history is poorly elicited in individuals presenting with features of CADASIL and that enquiry into family history of all four cardinal manifestations of CADASIL is superior to elicitation of family history of premature stroke alone in raising the diagnostic possibility of CADASIL. MATERIALS AND METHODS: Retrospective review of family histories at presentation in 40 individuals with confirmed CADASIL was performed through structured interview in a Neurovascular Genetics clinic (182 first-degree and 242 second-degree relatives identified). Family history obtained from structured interview was compared to family history initially documented at presentation. RESULTS: At initial presentation, 30% of individuals were inaccurately documented to have no family history of significant neurological illness. Thirty-five per cent of patients had an initial alternative diagnosis. Initial inaccurate documentation of negative family history was more frequent in individuals with an initial alternative diagnosis. After structured interviews, 34% of 182 first-degree and 35% of 242 second-degree relatives of CADASIL patients had history of stroke (16% of first-degree relatives had stroke before the age of 50 years). Forty-three per cent of first-degree and 28% of second-degree relatives had migraine, mood disturbance or cognitive decline. CONCLUSIONS: A false-negative family history was commonly documented in individuals presenting with features of CADASIL and was associated with initial misdiagnosis. Restriction of family history to premature stroke alone is probably inadequate to identify affected CADASIL pedigrees.

The prevalence of cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) in the west of Scotland.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is caused by mutations of the Notch3 gene on 19p13. Varying phenotypic expression leads to under recognition and misdiagnosis. Prevalence therefore remains uncertain. We sought to estimate the prevalence of CADASIL in the west of Scotland. METHODS: A register for CADASIL was established at a regional neurosciences centre in 2002. All patients with genetically (exons 3, 4, 5, and 6) or histologically confirmed CADASIL residing in two defined administrative health areas were identified. Pedigree members at varying risk of carrying the mutation were also identified and the number of probable Notch3 mutation carriers in the defined population was predicted. Prevalence was calculated for definite CADASIL cases, with and without probable carrier numbers, based upon adult population figures from the 2002 national census. RESULTS: Twenty two individuals from seven pedigrees with confirmed CADASIL and resident in the defined geographical area were identified, yielding a prevalence of 1.98 (95% confidence interval 1.24-3.00) per 100 000 adults. An additional 37 individuals were predicted to be carriers of the Notch3 mutation, yielding a probable mutation prevalence of 4.14 (3.04-5.53) per 100,000 adults. CONCLUSIONS: The prevalence of genetically proven CADASIL was 1.98 per 100,000 adults in the defined population. This figure underestimates disease burden.

Clinical features associated with medically unexplained stroke-like symptoms presenting to an acute stroke unit.

In many areas of secondary care, symptoms unexplained by disease account for around one-third of all patients seen. We sought to investigate patients presenting with medically unexplained stroke-like symptoms to identify distinguishing features which may help to identify a non-organic aetiology. Patients given a discharge diagnosis of medically unexplained stroke-like symptoms over the preceding 11 years were identified retrospectively from a prospectively completed stroke unit database. Age- and sex-matched controls with ischaemic or haemorrhagic stroke or transient ischaemic attack were also identified. Clinical features on presentation, ischaemic risk factors, alcohol history, marital status and history of depression or anxiety were examined. Previous or subsequent admissions with medically unexplained syndromes were also examined via record linkage with hospital discharge records. A medically unexplained syndrome was assumed to be present if an International Classification of Diseases 9 discharge code for one or more of the thirteen conditions forming recognized functional syndromes was given. Logistic regression was applied to determine predictors of non-organicity. One hundred and five patients and controls, 1.6% of all stroke unit admissions were identified, 62% (65 patients) were females. Mean age was 50.3 +/- 14.9. Compared with age- and sex-matched controls patients with medically unexplained stroke-like symptoms were significantly more probable to have a headache at presentation (47% vs. 26%, P = 0.0004), have a diagnosis of one or more additional medically unexplained syndromes (24% vs. 11%, P = 0.007) but significantly less probable to present with symptoms of vertebrobasilar dysfunction (32% vs. 61%, P < 0.0001). A history of anxiety or depression, as recorded in the notes, was not found to be associated with a medically unexplained presentation. Medically unexplained stroke-like presentations are common (1.6% of all stroke presentations), they are most strongly predicted by the presence of other functional somatic syndromes, headache and the absence of symptoms of vertebrobasilar dysfunction.

The investigation of acute severe headache suggestive of probable subarachnoid haemorrhage: a hospital-based study.

We reviewed the diagnostic approach to patients presenting with headache suggestive of subarachnoid haemorrhage (SAH) and normal cranial imaging, both locally and using a questionnaire, in other units throughout the United Kingdom. We emphasize the correct timing of cranial imaging and lumbar puncture (LP), the importance of proceeding to LP and utilizing spectrophotometry in patients with normal cranial imaging, and the appropriate use of angiography.

Apolipoprotein E genotype, coagulation, and survival following acute stroke.

The authors hypothesized that divergent influences of the APOE epsilon4 allele on ischemic and hemorrhagic stroke survival might result from differences in coagulation profiles. In 49 hemorrhagic stroke patients, epsilon4 carriers had higher partial thromboplastin time ratios (p < 0.01) than non-epsilon4 carriers. Among 529 ischemic stroke patients, increasing epsilon4 allele dose was associated with improved survival (p = 0.03) after adjusting for baseline NIH stroke scale (p = 0.00001) and partial thromboplastin time ratio (p = 0.01). Relative anticoagulation does not fully explain the survival advantage in epsilon4-carrying ischemic stroke patients.