Ian Bone

Improving the Assessment of Outcomes in Stroke Use of a Structured Interview to Assign Grades on the Modified Rankin Scale

Background and Purpose— The modified Rankin Scale is widely used to assess changes in activity and lifestyle after stroke, but it has been criticized for its subjectivity. The purpose of the present study was to compare conventional assessment on the modified Rankin Scale with assessment through a structured interview. Methods— Sixty-three patients with stroke 6 to 24 months previously were interviewed and graded independently on the modified Rankin Scale by 2 observers. These observers then underwent training in use of a structured interview for the scale that covered 5 areas of everyday function. Eight weeks after the first assessment, the same observers reassessed 58 of these patients using the structured interview. Results— Interrater reliability was measured with the &kgr; statistic (weighted with quadratic weights). For the scale applied conventionally, overall agreement between the 2 raters was 57% (&kgr;w=0.78); 1 rater assigned significantly lower grades than the other (P =0.048). On the structured interview, the overall agreement between raters was 78% (&kgr;w=0.93), and there was no overall difference between raters in grades assigned (P =0.17). Rankin grades from the conventional assessment and the structured interview were highly correlated, but there was significantly less disagreement between raters when the structured interview was used (P =0.004). Conclusions— Variability and bias between raters in assigning patients to Rankin grades may be reduced by use of a structured interview. Use of a structured interview for the scale could potentially improve the quality of results from clinical studies in stroke.

Reliability of the Modified Rankin Scale Across Multiple Raters Benefits of a Structured Interview

Background and Purpose— The modified Rankin Scale (mRS) is widely used to assess global outcome after stroke. The aim of the study was to examine rater variability in assessing functional outcomes using the conventional mRS, and to investigate whether use of a structured interview (mRS-SI) reduced this variability. Methods— Inter-rater agreement was studied among raters from 3 stroke centers. Fifteen raters were recruited who were experienced in stroke care but came from a variety of professional backgrounds. Patients at least 6 months after stroke were first assessed using conventional mRS definitions. After completion of initial mRS assessments, raters underwent training in the use of a structured interview, and patients were re-assessed. In a separate component of the study, intrarater variability was studied using 2 raters who performed repeat assessments using the mRS and the mRS-SI. The design of the latter part of the study also allowed investigation of possible improvement in rater agreement caused by repetition of the assessments. Agreement was measured using the &kgr; statistic (unweighted and weighted using quadratic weights). Results— Inter-rater reliability: Pairs of raters assessed a total of 113 patients on the mRS and mRS-SI. For the mRS, overall agreement between raters was 43% (&kgr;=0.25, &kgr;w=0.71), and for the structured interview overall agreement was 81% (&kgr;=0.74, &kgr;w=0.91). Agreement between raters was significantly greater on the mRS-SI than the mRS (P<0.001). Intrarater reliability: Repeatability of both the mRS and mRS-SI was excellent (&kgr;=0.81, &kgr;w ≥0.94). Conclusions— Although individual raters are consistent in their use of the mRS, inter-rater variability is nonetheless substantial. Rater variability on the mRS is thus particularly problematic for studies involving multiple raters. There was no evidence that improvement in inter-rater agreement occurred simply with repetition of the assessment. Use of a structured interview improves agreement between raters in the assessment of global outcome after stroke.

Suboptimal medication adherence in Parkinson's disease.

Patients take less medication than prescribed in many disease areas but evidence for suboptimal therapy adherence in Parkinsons disease (PD) is limited. A single‐center observational study of antiparkinsonian medication was undertaken using electronic monitoring (MEMS; Aardex, Zug, Switzerland) over 3 months. Of 68 patients approached, 6 declined and 8 dropped out, leaving 54 patients (taking 117 preparations) with available data. Poorer compliance was associated significantly with younger age, with taking more antiparkinsonian tablets per day, with higher depression scores, and with poorer quality of life. Of the 54 evaluable patients, 11 (20%) had average total compliance of under 80% (underusers) and 43 (80%) had average total compliance of over 80% (satisfactory adherence). Underusers had median total compliance of 65% (interquartile range, 37–74) versus 98% (interquartile range, 93–102) in the satisfactory adherence group. Timing compliance (number of doses taken in the correct time interval) was poor in both underusers (median, 11%; interquartile range, 2–20) and those with satisfactory adherence (median, 25%; interquartile range, 11–73). In conclusion, poorer compliance is associated with younger age, depression, and more tablets per day, and one‐fifth of PD patients underuse medication. Consideration of drug therapy adherence has implications in the management of PD.

The Apolipoprotein E ε4 Allele and Outcome in Cerebrovascular Disease

Background and Purpose —Polymorphism of the apolipoprotein E gene ( APOE ) may influence outcome after traumatic brain injury and intracerebral hemorrhage, with the e4 allele being associated with poorer prognosis. We investigated APOE allele distribution in acute stroke and the effect of the e4 allele on outcome. Methods — APOE genotypes were determined in 714 stroke patients: 640 ischemic stroke and 74 intracerebral hemorrhage patients. The survival effect of the e4 allele was assessed with the use of a stratified log-rank test. A Cox proportional hazards regression model was used to estimate the independent effect of e4 dose (0, 1, or 2) on survival, and logistic regression was used to determine the effect on 3-month outcome (good if alive at home, poor if in care or dead). Results —Allele distribution matched the general population with no difference between the ischemic and hemorrhagic groups. Survival in the entire cohort was unaffected by e4 dose. Improved survival with increasing e4 dose was found in the ischemic group (relative hazard=0.76 per allele; P =0.04). If transient ischemic attacks were excluded, a trend for improved survival persisted ( P =0.06). With intracerebral hemorrhage, a trend was seen toward reduced survival with e4 ( P =0.07, log-rank test). Three-month outcome in the ischemic group was unaffected by e4 dose, and a trend toward poorer outcome with e4 was seen for intracerebral hemorrhage ( P =0.10). Conclusions —The APOE e4 allele had divergent effects on survival and outcome in ischemic and hemorrhagic strokes in this population. The reported adverse effect on patients with intracerebral hemorrhage was supported. The favorable survival effect on ischemic stroke patients requires further study.

Ictal/postictal SPECT in the pre-surgical localisation of complex partial seizures.

Single photon emission computed tomography (SPECT) used in conjunction with HM-PAO (Ceretec-Amersham International) was used to image regional cerebral blood flow (rCBF) in 28 patients with medically intractable complex partial seizures during or soon after a seizure, and interictally. Changes from interictal rCBF were seen in 26/28 (93%) patients. The main findings were; 1) During the seizure--hyperperfusion of the whole temporal lobe; 2) Up to 2m postically--hyperperfusion of the hippocampus with hypoperfusion of lateral temporal structures; 3) From 2-15m postically--hypoperfusion of the whole temporal lobe. When compared with EEG and MRI data, correct localisation to one temporal lobe was obtained in 23 patients. In one further patient bilateral temporal foci, and in a further two patients frontal foci, were correctly identified. There were no disagreements between EEG and SPECT localisation. Temporal lobe surgery was successful (by the criterion of at least 90% reduction in seizure frequency) in all but one of the 23 patients operated on. It is concluded that ictal/postictal SPECT is a reliable technique for the presurgical localisation of complex partial seizures. The data indicate a likely sequence of changes in rCBF during and after complex partial seizures of temporal lobe origin.

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.

Cerebral Amyloid Angiopathy–Related Hemorrhage: Interaction of APOE ε2 With Putative Clinical Risk Factors

Background and Purpose—Current evidence suggests that the apolipoprotein E (APOE for gene; apoE for protein) e4 allele predisposes to cerebral amyloid angiopathy (CAA) whereas e2 is associated with CAA-related hemorrhage (CAAH). The clinical risk factors for other forms of intracranial hemorrhage are a less-frequent feature of CAAH. In this study we examined potential clinical risk factors in patients with CAAH and assessed these with respect to APOE genotype. Methods—Thirty-six patients were identified with a pathological diagnosis of CAAH. Clinical notes were reviewed to document age of hemorrhage onset, history of dementia, antiplatelet/anticoagulant medication, hypertension, minor head trauma, or transient neurological events. In a review of reported cases of CAAH, the frequency of these clinical features was also recorded. APOE genotypes were determined with use of polymerase chain reaction techniques. Results—There were 24 women and 12 men; the mean age was 70.3 years. One third (n=12) had been taki...

CT, MR and SPECT imaging in temporal lobe epilepsy.

Cranial computed tomography (CT) with modified temporal lobe technique, 0.15T magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) were carried out on 30 patients with intractable temporal lobe epilepsy. Lateralising abnormalities were detected in 21/30 patients overall. Specific lesions were detected by CT in one patient and by MRI in seven patients (in one case bilateral). In addition CT detected asymmetry of the sylvian fissures or temporal horns in 10 patients, and MRI in eight patients. SPECT detected lateralising abnormalities in 19 patients (in five cases bilateral). It is concluded that low field MRI is superior to modified CT in demonstrating subtle structural lesions of the temporal lobe. Functional scanning with SPECT supports the evidence of origin of an epileptic focus in a substantial proportion of cases and may improve the selection of patients for surgery.

Detection of intracranial emboli in patients with carotid disease

Transcranial Doppler emboli signal detection has been reported in several patient groups, including patients with symptomatic internal carotid artery stenosis. The potential of this technique in assessing embolic risk and selecting patients for surgery was examined in this study. Selected patients with symptomatic internal carotid artery stenosis underwent combined extracranial and transcranial Doppler study in the Vascular Surgery and Neurovascular Unit. Patients and normal controls were monitored with transcranial Doppler over both middle cerebral arteries. Severity of carotid disease was diagnosed with colour Duplex ultrasound examination or angiography. Selected patients underwent cranial computed tomography and transthoracic echocardiography. Patients undergoing carotid endarterectomy were re-examined one month after surgery. Fifty symptomatic patients, six asymptomatic patients and 30 normal controls were examined. Carotid disease was unilateral in 34 and bilateral in 22 cases. Emboli signals were detected in 94% of patients. The emboli signal count in patients with unilateral carotid stenosis was significantly higher in the middle cerebral artery distal to the stenosed internal carotid compared to the contralateral middle cerebral artery [14 (10-22) versus 2 (0-7) signals per hour, median and 95% confidence intervals, p < 0.001] and in symptomatic compared to asymptomatic cerebral hemispheres [15 (11-21) versus 4 (2-9) signals per hour, p < 0.001]. Emboli were detected in the contralateral middle cerebral artery in 40% of patients with unilateral carotid disease, in 85% of whom an additional embolic source was identified. No emboli signals were detected after carotid endarterectomy distal to the operated internal carotid, or in any of the normal controls. In conclusion, intracranial emboli signals are common in patients with carotid stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Human cranial CSF volumes measured by MRI: Sex and age influences

Accurate measurements of CSF volumes would assist in the diagnosis of several important neurological conditions. Using Magnetic Resonance Imaging (MRI) we have devised a method to measure both total intracranial CSF volume and ventricular volume. This initial study, in normal humans, provides an answer to two longstanding questions: first, do these volumes differ between the sexes; second, do both total and ventricular CSF volumes increase with normal aging? We found that the total cranial CSF volume and skull size of males were significantly greater than those of females, but that there was not a statistically significant difference between the ventricular volumes of the sexes. Total cranial CSF volume increased steeply with age in both sexes but although there was an increase in ventricular volume with age in males, no significant increase with age could be demonstrated in females.