Meta-analysis and systematic review of population-based epidemiological studies in idiopathic intracranial hypertension.

Idiopathic intracranial hypertension (IIH) is positively associated with obesity, mostly in young women. The global increase in obesity may influence the burden of IIH. Using the PubMed, Embase, MEDLINE and Web of Science databases, a meta-analysis and systematic review of epidemiological studies of IIH were performed up to June 2017. Temporal changes in IIH incidence were measured, and incidence rates of IIH were correlated with country-specific World Health Organization obesity rates. Prevalence data and shunting rates of IIH were recorded. The quality of epidemiological studies was assessed using the Standards of Reporting of Neurological Disorders (STROND) criteria. In 15 identified studies, there were 889 patients (87% women), mean age 29.8 years. The incidence of IIH ranged from 0.03 to 2.36 per 100 000 per year. The pooled incidence of IIH was 1.20 per 100 000 per year although there was very high heterogeneity (I2 98%). The incidence rates of IIH were correlated with country-specific prevalence of obesity (Spearman's correlation 0.82, P < 0.01). The prevalence of IIH was rarely recorded. A shunting procedure was reported in 8% of patients. STROND criteria were variably reported, median of 26.5 of 43 (range 16-35). IIH is a public health concern as increased obesity prevalence is associated with increased incidence of IIH. A better quality of epidemiological studies is required to improve understanding of IIH and inform health policy for IIH management.

Impact of social prescribing on general practice workload and polypharmacy.

OBJECTIVES: Social prescribing has emerged as a useful tool for helping patients overcome some of the social and behavioural determinants of poor health. There has been little research on the impact of social prescribing on use of primary healthcare resources. This study sought to determine whether social prescribing activities influenced patient-general practitioner (GP) contacts and polypharmacy. STUDY DESIGN: Quality-improvement design with social prescribing activity interventions from an urban general practice in Northern Ireland. METHODS: Patients over 65 years of age with a chronic condition who attended their GP frequently or had multiple medications were offered a social prescribing activity. Participants' contacts with GP and the new repeat prescriptions before and during the social prescribing activity were measured. The total number of repeat prescriptions per patient was compared at the time of referral and 6-12 months later. Indications for referral, primary diagnoses and reasons for declining participation in a social prescribing activity after referral were prospectively recorded. RESULTS: Sixty-eight patients agreed to participate but only 28 (41%) engaged in a prescribed social activity. There was no statistically significant difference in GP contacts (visits to GP, home visits or telephone calls) or number of new repeat prescriptions between referral and completion of 12 weeks of social prescribing activity. Similarly there was no statistically significant difference in the total number of repeat prescriptions between referral and 6-12 months after social prescribing activity in either intention to treat or per protocol analyses. Social prescribing participants had similar demographic factors. Mental health issues (anxiety and/or depression) were more common among participants than those who were referred but declined participation in a social prescribing activity (P = 0.022). CONCLUSIONS: While social prescribing may help patients' self-esteem and well-being, it may not decrease GP workload. Further research is required to optimise social prescribing benefits.

Superficial siderosis of the central nervous system many years after neurosurgical procedures.

Recurrent haemorrhage into the subarachnoid space causes superficial siderosis, which clinically manifests as cerebellar ataxia, sensorineural hearing loss, and myelopathy. Two patients developed clinical, radiological, and biochemical evidence of superficial siderosis many years after surgery. One had two posterior fossa operations, a left temporal craniectomy, and radiotherapy for a presumed brain tumour before developing clinical evidence of superficial sidersosis 37 years later. The other had small bilateral subdural collections from recurrent shunt revisions following posterior fossa surgery for a Chiari malformation, and then developed deafness and ataxia. The first patient currently has the longest recorded delay between presumed subarachnoid bleeding and clinical manifestations of superficial siderosis. Both patients provide further evidence that superficial siderosis of the central nervous system, a progressive neurodegenerative vascular condition, may be a delayed complication of neurosurgical procedures.

APOE gene polymorphism as a risk factor for cerebral amyloid angiopathy-related hemorrhage.

Cerebral amyloid angiopathy (CAA) due to the accumulation of amyloid beta-protein (Abeta) occurs in up to half of elderly individuals and in most cases of Alzheimer's disease (AD). Following identification of the apolipoprotein E (APOE) epsilon4 allele as a risk factor for AD, APOE epsilon4 was also found to be associated with asymptomatic CAA. The major clinical manifestation of CAA is stroke due to a lobar hemorrhage. A complex relationship between APOE epsilon4, APOE epsilon2 and hemorrhage associated with CAA (CAAH) is emerging. Pathological studies have demonstrated that APOE epsilon2 is over-represented among patients with CAAH. This remains the case for patients with co-existing Alzheimer's disease, who otherwise have a very low epsilon2 allele frequency. Other forms of intracranial hemorrhage do not share the same association, indicating that APOE epsilon2 has a specific association with CAAH. Patients with the epsilon2 allele and CAAH are more likely to have taken anticoagulant or antiplatelet medication, had hypertension or had minor head trauma than non-epsilon2 carriers. In addition, the epsilon2 allele is specifically associated with CAA-associated microangiopathic changes such as fibrinoid necrosis and concentric splitting of the vessel wall.

Absence of cystatin C mutation in sporadic cerebral amyloid angiopathy-related hemorrhage.

In Icelandic pedigrees a cystatin C mutation, glutamine 68 (L68Q), causes autosomal dominant cerebral amyloid angiopathy-related hemorrhage (CAAH). We examined 33 patients with sporadic CAAH for this mutation. None carried L68Q and, including this report, only one of 52 published cases of sporadic CAAH has had the cystatin C mutation. Despite vascular colocalization of cystatin C with amyloid beta-protein, cystatin C L68Q is rare in sporadic CAAH.

Cerebral amyloid angiopathy-related hemorrhage. Interaction of APOE epsilon2 with putative clinical risk factors.

BACKGROUND AND PURPOSE: Current evidence suggests that the apolipoprotein E (APOE for gene; apoE for protein) epsilon4 allele predisposes to cerebral amyloid angiopathy (CAA) whereas epsilon2 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 taking antiplatelet medication, and a similar number were demented. Nine patients were hypertensive, and 4 had a history of recent minor head trauma. The relative frequency of each of these clinical features was similar to that in previous reports. Forty-four percent (16 of 36) possessed an epsilon2 allele. Antiplatelet or anticoagulant medication, hypertension, or minor head trauma were significantly more frequent antecedents of CAAH in epsilon2 carriers than in non-epsilon2 carriers (81% versus 35%, P=0.008), antiplatelet/anticoagulant medication in particular (P=0.038). CONCLUSIONS: Our findings suggest that antiplatelet or anticoagulant medication, hypertension, or minor head trauma are most likely to precipitate cerebral hemorrhage in patients with CAA who are also epsilon2 carriers. This may result from isoform-specific effects of apoE on the structure of amyloid-laden blood vessel walls.

The apolipoprotein E epsilon2 allele and the pathological features in cerebral amyloid angiopathy-related hemorrhage.

Cerebral amyloid angiopathy (CAA) is associated with apolipoprotein E (APOE gene, apoE protein) polymorphism: current evidence suggests that the epsilon4 allele is a risk factor for the development of CAA and the epsilon2 allele predisposes to hemorrhage. We sought to determine the relationship between the APOE epsilon2 allele and both the immunoreactivity profiles and vascular complications of CAA. We performed immunohistochemistry for amyloid beta-protein (A beta), apoE, cystatin C, and activated microglia, and examined the morphology of cortical and leptomeningeal vessels in 37 CAA-related hemorrhage (CAAH), 26 Alzheimer disease (AD) patients, and 20 controls. The extent of immunostaining of vessels for A beta, apoE, cystatin C, and perivascular activated microglia increased from controls through AD to a maximum in CAAH patients. Among cases with CAA (37 CAAH, 19 AD, and 6 controls, n = 62) vascular apoE (p < 5 x 10(-4)), cystatin C (p < 10(-4)), activated microglia (p < 10(-4)), vessels with a high ratio of wall thickness to lumen diameter (p < 0.003) as well as dilated/microaneurysmal vessels (p < 0.01) were present more frequently in patients with hemorrhage than without; however, these features were not associated with the APOE epsilon2 allele. Fibrinoid necrosis alone was associated with the APOE epsilon2 allele (p < 0.04) and we suggest that over-representation of APOE epsilon2 in CAAH may result from its association with fibrinoid necrosis.

Surgical intervention, biopsy and APOE genotype in cerebral amyloid angiopathy-related haemorrhage.

Twelve patients who had surgical removal of a cerebral haematoma had a biopsy or autopsy diagnosis of cerebral amyloid angiopathy-related haemorrhage (CAAH). Ten had a cortical biopsy at the time of surgery and eight reports of these were interpreted as showing CAA to be the cause of the haemorrhage. The diagnosis in the remaining two was made at autopsy. Six patients had a biopsy and autopsy, resulting in a 67% (four of six) biopsy sensitivity. Amyloid beta-protein (A beta) immunohistochemistry was more sensitive than tinctorial stains in detecting CAA. As previously reported in CAAH there was an excess of patients with the APOE epsilon 2 allele (33% versus 16% in a control group). Four patients (33%) were alive at 3 months. Despite surgical intervention, CAAH has a poor outcome in patients with impaired consciousness. Clinical awareness of CAAH and use of A beta immunostaining may increase the diagnostic yield from cerebral biopsy.