A clinical study of kuru patients with long incubation periods at the end of the epidemic in Papua New Guinea

Kuru is so far the principal human epidemic prion disease. While its incidence has steadily declined since the cessation of its route of transmission, endocannibalism, in Papua New Guinea in the 1950s, the arrival of variant Creutzfeldt–Jakob disease (vCJD), also thought to be transmitted by dietary prion exposure, has given kuru a new global relevance. We investigated all suspected cases of kuru from July 1996 to June 2004 and identified 11 kuru patients. There were four females and seven males, with an age range of 46–63 years at the onset of disease, in marked contrast to the age and sex distribution when kuru was first investigated 50 years ago. We obtained detailed histories of residence and exposure to mortuary feasts and performed serial neurological examination and genetic studies where possible. All patients were born a significant period before the mortuary practice of transumption ceased and their estimated incubation periods in some cases exceeded 50 years. The principal clinical features of kuru in the studied patients showed the same progressive cerebellar syndrome that had been previously described. Two patients showed marked cognitive impairment well before preterminal stages, in contrast to earlier clinical descriptions. In these patients, the mean clinical duration of 17 months was longer than the overall average in kuru but similar to that previously reported for the same age group, and this may relate to the effects of both patient age and PRNP codon 129 genotype. Importantly, no evidence for lymphoreticular colonization with prions, seen uniformly in vCJD, was observed in a patient with kuru at tonsil biopsy

Management evaluation of metastasis in the brain (MEMBRAIN)—a United Kingdom and Ireland prospective, multicenter observational study

Background: In recent years an increasing number of patients with cerebral metastasis (CM) have been referred to the neuro-oncology multidisciplinary team (NMDT). Our aim was to obtain a national picture of CM referrals to assess referral volume and quality and factors affecting NMDT decision making. Methods: A prospective multicenter cohort study including all adult patients referred to NMDT with 1 or more CM was conducted. Data were collected in neurosurgical units from November 2017 to February 2018. Demographics, primary disease, KPS, imaging, and treatment recommendation were entered into an online database. Results: A total of 1048 patients were analyzed from 24 neurosurgical units. Median age was 65 years (range, 21-93 years) with a median number of 3 referrals (range, 1-17 referrals) per NMDT. The most common primary malignancies were lung (36.5%, n = 383), breast (18.4%, n = 193), and melanoma (12.0%, n = 126). A total of 51.6% (n = 541) of the referrals were for a solitary metastasis and resulted in specialist intervention being offered in 67.5% (n = 365) of cases. A total of 38.2% (n = 186) of patients being referred with multiple CMs were offered specialist treatment. NMDT decision making was associated with number of CMs, age, KPS, primary disease status, and extent of extracranial disease (univariate logistic regression, P < .001) as well as sentinel location and tumor histology (P < .05). A delay in reaching an NMDT decision was identified in 18.6% (n = 195) of cases. Conclusions: This study demonstrates a changing landscape of metastasis management in the United Kingdom and Ireland, including a trend away from adjuvant whole-brain radiotherapy and specialist intervention being offered to a significant proportion of patients with multiple CMs. Poor quality or incomplete referrals cause delay in NMDT decision making