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Sinusitis is a common condition, but only very rarely accompanied by isolated cranial nerve palsies. We describe a case of a 64-year-old male with a two-day history of left-sided ptosis associated with one week of nasal congestion and frontal sinus pain. Examination revealed ptosis with left pupil mydriasis. Uncontrasted computed tomography and angiography of the head demonstrated neither intracranial vascular abnormalities nor acute lesions; however, it did show mucosal thickening in the left frontal sinus, ethmoid air cells and left maxillary sinus, indicating potential obstruction of the left ostiomeatal complex. The sinusitis was treated with intranasal steroids, xylomethazoline and nasal douching. The patient reported resolution of all symptoms, including left ptosis, within one week of therapy. This rare case of sinusitis causing ptosis is presented due to its infrequent nature, such that awareness of the differential diagnosis of cranial nerve palsy and complications of sinusitis may be improved.

Vogt-Koyanagi-Harada disease is a rare, multisystem, autoimmune disorder with numerous clinical manifestations, mediated through a T-helper 1 response against melanocytes in the eye, inner ear, central nervous system, hair and skin. We describe a 20-year-old British–Honduran man with recent worsening headache and photophobia, vomiting and visual blurring. On examination, his pupils reacted sluggishly and visual acuities were bilaterally reduced. Optical coherence tomography showed gross retinal swelling and neurosensory detachments. MR scan of the brain was normal, but cerebrospinal fluid showed a reactive picture with 258 ×109 lymphocytes./L (normal ≤5×109/L). Following treatment with immunosuppression (prednisolone, tacrolimus, mycophenolate mofetil, adalimumab), he made a full recovery. Clinicians should consider Vogt-Koyanagi-Harada disease in patients presenting with headache with acute profound visual loss. A prompt diagnosis and immunosuppressive therapy can lead to complete resolution.

Introduction: In addition to tau pathology and neuronal loss, neuroinflammation occurs in progressive supranuclear palsy (PSP). However, the prognostic value of the in vivo imaging markers for these processes in PSP remains unclear. We test the primary hypothesis that baseline in vivo imaging assessment of neuroinflammation in subcortical regions predicts clinical progression in patients with PSP. Methods: Seventeen patients with PSP–Richardson’s syndrome underwent a baseline multimodal imaging assessment, including [11C]PK11195 positron emission tomography (PET) to index microglial activation, [18F]AV-1451 PET for tau pathology and structural MRI. Disease severity was measured at baseline and serially up to 4 years with the Progressive Supranuclear Palsy Rating Scale (PSPRS) (average interval of 5 months). Regional grey-matter volumes and PET ligand binding potentials were summarised by three principal component analyses (PCAs). A linear mixed-effects model was applied to the longitudinal PSPRS scores. Single-modality imaging predictors were regressed against the individuals’ estimated rate of progression to identify the prognostic value of baseline imaging markers. Results: PCA components reflecting neuroinflammation and tau burden in the brainstem and cerebellum correlated with the subsequent annual rate of change in the PSPRS. PCA-derived PET markers of neuroinflammation and tau pathology correlated with regional brain volume in the same regions. However, MRI volumes alone did not predict the rate of clinical progression. Conclusions: Molecular imaging with PET for microglial activation and tau pathology can predict clinical progression in PSP. These data encourage the evaluation of immunomodulatory approaches to disease-modifying therapies in PSP and the potential for PET to stratify patients in early phase clinical trials.

Background: Prodromal Parkinsons Disease is well described but prodromal Progressive Supranuclear Palsy (PSP) is much less understood. The diagnosis of PSP is typically delayed by an average of three years after symptom onset. Understanding the changes that occur in the prodromal and prediagnostic period will aid earlier diagnosis, clarify the natural history, and aid the design of early disease modifying therapy trials. Objectives: To determine motor and cognitive markers of prodromal PSP, with Parkinsons disease as a comparator condition, in a large prospective cohort. Methods: Baseline UK Biobank data from 502,504 individuals were collected between 2006 and 2010. Subsequent PSP and Parkinsons disease cases were identified from primary and secondary care electronic health records diagnostic coding data and death registry, with 5,404 matched controls. Results: 176 PSP cases (mean [SD] time to diagnosis 7.8 [2.8] years) and 2,526 Parkinsons disease cases (time to diagnosis 7.8 [2.9] years) were identified. At baseline, those later diagnosed with PSP had slower reaction times, weaker hand grip, lower fluid intelligence, poorer prospective memory, worse self rated health score and lower digit recall than controls. They had higher mortality than both Parkinsons disease and control groups. Conclusions: Motor slowing, cognitive dysfunction, and postural instability are clinical diagnostic features of PSP and are typically symptomatic three years before diagnosis. However, objective markers of these features are evident over seven years before diagnosis. This suggests a long prodromal course in PSP with subtle changes in motor and cognitive function.

Progressive supranuclear palsy causes diverse clinical presentations, including classical Richardson’s syndrome and several variant phenotypes. Clinical trials of disease-modifying therapies have recently been completed, with more planned for the next 2 years. However, many people with progressive supranuclear palsy do not meet eligibility criteria for these clinical trials. Understanding clinical progression with different phenotypes would improve trial design and enhance the accuracy of risk–benefit and cost–benefit assessments of new treatments for progressive supranuclear palsy. We set out to determine rates of motor and cognitive progression of possible, probable and definite progressive supranuclear palsy, with different phenotypes, from a representative cohort in a regional UK healthcare service. Longitudinal clinical data from people with Richardson’s syndrome and variant phenotypes were analysed using linear mixed-modelling, using both the full and modified versions of the Progressive Supranuclear Palsy Rating Scale, Mini-Mental State Examination and the revised Addenbrooke’s Cognitive Examination. Subgroup analyses considered patients meeting recent Phase II trial entry criteria and patients with neuropathological confirmation. Two hundred and twenty-seven patients [male = 59%, mean age (±standard deviation), 71.8 (±7.0) years] were followed for a mean 21.6 (±15.6) months. One hundred and seventy-four (77%) had Richardson’s syndrome at the outset, 25 had cortical variant presentations (13%, frontal, corticobasal, speech and language variants) and 28 had subcortical variant presentations (14%, parkinsonism, postural instability and gait freezing variants). Across all participants, annual progression in Richardson’s syndrome was faster than variant phenotypes on the Mini-Mental State Examination (−1.8 versus −0.9/year, P = 0.005) and revised Addenbrooke’s Cognitive Examination (−5.3 versus −3.0/year, P = 0.01) but not the Progressive Supranuclear Palsy Rating Scale (9.0 versus 7.1/year, P = 0.2) nor the modified Progressive Supranuclear Palsy Rating Scale (2.7 versus 2.3/year, P = 0.4). However, for those with more than 1 years’ follow-up, a significant difference was observed between Richardson’s syndrome and variant phenotypes in Progressive Supranuclear Palsy Rating Scale (8.7 versus 6.3/year, P = 0.04). Survival was longer in variant phenotypes than Richardson’s syndrome [7.3 (±3.9) versus 5.6 (±2.0) years, P = 0.02]. Pathologically confirmed cases (n = 49) supported these findings. Patients meeting basic trial-eligibility criteria (n = 129) progressed faster on the Progressive Supranuclear Palsy Rating Scale than trial-not-eligible patients (10.1 versus 6.1/year, P = 0.001). In conclusion, phenotypes other than Richardson’s syndrome show slower progression and longer survival. Trial criteria do not select representative progressive supranuclear palsy cases. This has implications for trial design, and application of trial results to clinically more diverse patient populations., Street et al. show that progression and survival with progressive supranuclear palsy vary according to people’s symptoms and clinical trial eligibility. Common clinical trial criteria exclude many patients. Their exclusion may limit the relevance of clinical trials and affect the relative risks and benefits of future treatments for many people., Graphical Abstract Graphical Abstract

IntroductionIn addition to tau pathology and neuronal loss, neuroinflammation occurs in progressive supranuclear palsy (PSP). However, the prognostic value of the in vivo imaging markers for these processes in PSP remains unclear. We test the primary hypothesis that baseline in vivo imaging assessment of neuroinflammation in subcortical regions predicts clinical progression in patients with PSP.MethodsSeventeen patients with PSP–Richardson’s syndrome underwent a baseline multimodal imaging assessment, including [11C]PK11195 positron emission tomography (PET) to index microglial activation, [18F]AV-1451 PET for tau pathology and structural MRI. Disease severity was measured at baseline and serially up to 4 years with the Progressive Supranuclear Palsy Rating Scale (PSPRS) (average interval of 5 months). Regional grey-matter volumes and PET ligand binding potentials were summarised by three principal component analyses (PCAs). A linear mixed-effects model was applied to the longitudinal PSPRS scores. Single-modality imaging predictors were regressed against the individuals’ estimated rate of progression to identify the prognostic value of baseline imaging markers.ResultsPCA components reflecting neuroinflammation and tau burden in the brainstem and cerebellum correlated with the subsequent annual rate of change in the PSPRS. PCA-derived PET markers of neuroinflammation and tau pathology correlated with regional brain volume in the same regions. However, MRI volumes alone did not predict the rate of clinical progression.ConclusionsMolecular imaging with PET for microglial activation and tau pathology can predict clinical progression in PSP. These data encourage the evaluation of immunomodulatory approaches to disease-modifying therapies in PSP and the potential for PET to stratify patients in early phase clinical trials.

Human infection with the trematode Fasciola occurs with a worldwide prevalence of up to 17 million. Sheep and cattle are the normal host. Infection typically results in hepatobiliary disease, but extrahepatic manifestations are occasionally reported. Here, we present the case of a previously healthy 31-year-old Kurdish woman, admitted to hospital with a subarachnoid hemorrhage, eosinophilic meningitis, and lung and liver disease. A diagnosis of Fasciola infection was made based on strongly positive serology in blood and cerebrospinal fluid. The patient improved following treatment with triclabendazole and prednisolone.