Predictors of Care Home Admission and Survival Rate in Patients With Syndromes Associated With Frontotemporal Lobar Degeneration in Europe.

BACKGROUND AND OBJECTIVES: Data on care home admission and survival rates of patients with syndromes associated with frontotemporal lobar degeneration (FTLD) are limited. However, their estimation is essential to plan trials and assess the efficacy of intervention. Population-based registers provide unique samples for this estimate. The aim of this study was to assess care home admission rate, survival rate, and their predictors in incident patients with FTLD-associated syndromes from the European FRONTIERS register-based study. METHODS: We conducted a prospective longitudinal multinational observational registry study, considering incident patients with FTLD-associated syndromes diagnosed between June 1, 2018, and May 31, 2019, and followed for up to 5 years till May 31, 2023. We enrolled patients fulfilling diagnosis of the behavioral variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA), progressive supranuclear palsy (PSP) or corticobasal syndrome (CBS), and FTD with motor neuron disease (FTD-MND). Kaplan-Meier analysis and Cox multivariable regression models were used to assess care home admission and survival rates. The survival probability score (SPS) was computed based on independent predictors of survivorship. RESULTS: A total of 266 incident patients with FTLD were included (mean age ± SD = 66.7 ± 9.0; female = 41.4%). The median care home admission rate was 97 months (95% CIs 86-98) from disease onset and 57 months (95% CIs 56-58) from diagnosis. The median survival was 90 months (95% CIs 77-97) from disease onset and 49 months (95% CIs 44-58) from diagnosis. Survival from diagnosis was shorter in FTD-MND (hazard ratio [HR] 4.59, 95% CIs 2.49-8.76, p < 0.001) and PSP/CBS (HR 1.56, 95% CIs 1.01-2.42, p = 0.044) compared with bvFTD; no differences between PPA and bvFTD were found. The SPS proved high accuracy in predicting 1-year survival probability (area under the receiver operating characteristic curve = 0.789, 95% CIs 0.69-0.87), when defined by age, European area of residency, extrapyramidal symptoms, and MND at diagnosis. DISCUSSION: In FTLD-associated syndromes, survival rates differ according to clinical features and geography. The SPS was able to predict prognosis at individual patient level with an accuracy of ∼80% and may help to improve patient stratification in clinical trials. Future confirmatory studies considering different populations are needed.

Incidence and Trends of Progressive Supranuclear Palsy and Corticobasal Syndrome: A Population-Based Study.

BACKGROUND: Few studies have investigated the incidence of PSP and CBS in the population. OBJECTIVE: To examine the incidence of and trends in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) in a population-based cohort of residents of Olmsted County, MN. METHODS: We used the 1991-2005 population-based, Olmsted County Parkinsonism-cohort study, defined via the Rochester Epidemiology Project. A movement-disorder specialist reviewed medical records, to confirm PSP and CBS diagnoses. RESULTS: We identified 21 patients with these diagnoses 1991-2005 : 18 (85.7%), PSP; 3 (14.3%), CBS. The median diagnosis age was 78 (range: 66-88). 13/21 (62.0%) were male. MRI was performed pre-diagnosis in 11 patients (8 PSP and 3 CBD); 10 showed atrophy consistent with clinical diagnoses. We observed concordance between clinical and pathological diagnoses in two PSP patients who underwent autopsy. Combined incidence for PSP and CBS in Olmsted County was 3.1 per 100,000 person-years (2.6 per 100,000 person-years, PSP; 0.4 per 100,000 person-years, CBS). Incidence was higher in men (4.5, 95% CI, 2.0-7.0) than women (1.8, 95% CI, 0.5-2.9). A combined, significant trend of increasing incidence was observed between 1991 and 2005 (B=0.69, 95% CI 0.42, 0.96, p<0.001). Median time from symptom onset to death among both groups was 6 years (range PSP, 1-10 years; range CBS, 3-8 years). CONCLUSIONS: The combined incidence for PSP and CBS was 3.1 per 100,000 person-years, higher in men than women. We observed a significant increase in both PSP and CBS, likely due to advancing imaging technology and improved diagnostic ability among physicians.

Post authorization safety study comparing quetiapine to risperidone and olanzapine.

OBJECTIVES: To compare rates of specific adverse outcomes between patients starting quetiapine, olanzapine, or risperidone use in the Netherlands. METHODS: Observational study using the PHARMO Database Network, including patients starting quetiapine (4658), olanzapine (5856), or risperidone (7229) in 2000-2009, comparing rates of all-cause mortality, failed suicide attempts, extrapyrimidal symptoms (EPS), diabetes mellitus (DM), hypothyroidism, and acute myocardial infarction (AMI). KEY FINDINGS: Median follow-up until discontinuation/end of follow-up was 0.6 years. Prescribed doses were generally lower than the approved defined daily doses, especially for quetiapine. Quetiapine was significantly associated with lower EPS rates (HR 0.18; 95% CI 0.13-0.24), but higher failed suicide attempt rates (HR 2.07; 95% CI 1.35-3.16) compared to risperidone. Quetiapine was significantly associated with lower EPS rates (HR 0.59; 95% CI 0.42-0.84) and DM rates (HR 0.66; 95% CI 0.44-0.97) compared to olanzapine. Rates for all-cause mortality, hypothyroidism, and stroke were similar between groups. AMI events were too infrequent to draw conclusions. CONCLUSIONS: Quetiapine was associated with lower EPS, but higher failed suicide attempt rates compared to risperidone. Quetiapine was associated with lower EPS and DM rates compared to olanzapine. The results should be interpreted with caution because of possible channelling and residual confounding. Copyright © 2016 John Wiley & Sons, Ltd.

Diagnostic criteria for corticobasal syndrome: a comparative study.

INTRODUCTION: There are no well-established criteria for patients with corticobasal syndrome. The authors have attempted to clarify this area by comparing and applying three sets of well-known criteria (from Toronto, the Mayo Clinic and Cambridge). PATIENT AND METHODS: The authors first compared the three criteria for overlap and differences, and then applied them to a group of 40 consecutive patients (22 men, mean age 67 years) with focal cortical syndrome characterised by apraxia and Parkinsonism, at both the early stages and later in their illness. RESULTS: Despite an overall similarity, there were major differences in the criteria which affect their applicability. Cognitive impairment was ubiquitous even at presentation, with speech and language impairment the commonest feature. Some classic features, alien limb and myoclonus, were present in a minority only even late in their course. The three criteria were equally applicable to patients with advanced disease (Toronto 92.5%, Cambridge 90% and Mayo 87.5%). Thirty patients (75%) satisfied all three criteria. Using this group as a 'gold standard', 73.3% fulfilled the Cambridge criteria at presentation compared with 46.7% and 36.7% for the Toronto and Mayo Clinic criteria, respectively. Concordance between criteria was poor. CONCLUSION: Cognitive impairment, especially language impairment, was prominent from onset of disease. The Cambridge criteria apply to a higher proportion of cases at an early stage of corticobasal syndrome. The authors suggest a minor modification to capture the high prevalence of aphasia.

Clinical features and mortality in patients with early-onset Alzheimer's disease.

In a population-based study of 198 patients with probable early-onset Alzheimer's disease (AD), we studied the occurrence of extrapyramidal signs (tremors and rigidity), myoclonus, psychosis and seizures, as well as their predictive value for mortality. The presence of tremors was significantly associated with the presence of rigidity. The occurrence of myoclonus was significantly associated with the occurrence of seizures. Psychosis and seizures in AD patients were not associated with mortality. The occurrence of extrapyramidal signs and myoclonus at any point in time during the course of AD increased the risk of mortality significantly. When evaluating their relative importance, extrapyramidal signs appeared to be the most important predictor of mortality.

Serial CT scanning in childhood tuberculous meningitis: prognostic features in 198 cases.

Serial cranial computed tomographic (CT) scanning and intracranial pressure monitoring were performed on 198 children with stage II and III tuberculous meningitis. The aims of the study were to document the course of tuberculous hydrocephalus during medical and surgical treatment, as well as the prognostic significance of parenchymal changes in the brain as demonstrated by CT. Lumbar cerebrospinal fluid pressure was monitored continuously for a 1-hour period in all patients on admission and at weekly intervals in patients with communicating hydrocephalus for the 1st month of treatment. Cranial CT scanning was done on admission and repeated in survivors after 1 month and again after 6 months of antituberculous therapy. The raised intracranial pressure of 112 children with communicating hydrocephalus, as demonstrated by air-encephalography, was treated medically (with daily acetazolamide and furosemide) for 1 month. Thirty-one children with noncommunicating hydrocephalus were referred for immediate ventriculoperitoneal shunting. No significant difference was found in the eventual ventricular size or clinical outcome between the two treatment groups. Lumbar cerebrospinal fluid pressure changes in the children with communicating hydrocephalus closely followed changes in the degree of hydrocephalus during the course of treatment. The main cause of permanent neurologic disability was basal ganglia infarction, which occurred unilaterally in 21% and bilaterally in 10% of patients on admission and developed in a further 22% of children during treatment. A prominent subarachnoid space, which was seen on the CT scan of 36% of patients after the 1st month of treatment and which reverted to normal, probably relates to the poor nutritional state of these patients on admission.(ABSTRACT TRUNCATED AT 250 WORDS)

Low-grade glial tumors in basal ganglia and thalamus: natural history and biological reappraisal.

The natural history of 70 patients affected by low-grade astrocytomas was recorded after the histological diagnosis was obtained by serial stereotactic biopsy. Forty-three percent of these patients died within 3 years. The value of cell kinetics assessment at the time of stereotactic biopsy was investigated, and the labeling index percent may be considered the most accurate prognostic factor in these histologically homogeneous astrocytomas. It has been confirmed that the young age of patients predicts a more favorable course, but the value of this also seems to be linked to and dependent on cell kinetics. These data are discussed in view of the opportunity to perform more aggressive "cytoreductive" treatments in deep brain tumors when these indices support an expected poor prognosis.

Bilateral striatal lesions in childhood.

From 1983 to 1991, 13 patients were identified with a clinical radiologic association characterized by acute or persistent neurologic dysfunction and bilateral lesions in the basal ganglia region demonstrated by ultrasound, computed tomography, or magnetic resonance imaging. Initial clinical manifestations of this group of patients were characterized by extrapyramidal signs (i.e., dystonia 9, hypotonia 2, athetosis 1, rigidity 1), altered state of consciousness in 5, and seizures in 3. The outcomes of most of these patients were poor: 10 had motor sequelae, 9 cognitive impairment, and 4 died. The outcomes of 2 patients, however, were much better than what was expected from the initial presentation. Based on current and previous reports, the diagnostic approach and classification of patients with neurologic dysfunction and bilateral striatal lesions are presented.

[Prediction of outcome in putaminal hemorrhage].

We obtained information on patients with putaminal hemorrhage (3,638 medically treated cases and 3,372 surgically treated cases). With these data, we have developed easily applicable and clinically useful prediction models for both mortality and activities of daily living (ADL) at three months after admission. We derived these models by Hayashi's discriminant technique for categorical data. Before their derivation, variables generally available on the initial day of hospitalization and possibly related to outcome were examined individually with tests of homogeneity. Neurological grading (NG), age, deformity of cisterns around midbrain, midline shift, hematoma volume, and motor paralysis were identified as candidate predictors of both mortality and ADL. CT classification was also added to the predictors of ADL. Initially, all these factors were included in tentative models, and then those which were found not to contribute substantially to the prediction were deleted. Ultimately, we proposed two models, one for mortality and the other for ADL. The mortality model used NG, hematoma volume, and deformity of cisterns around midbrain as predictors, and the ADL model used age, NG, CT classification, hematoma volume, and motor paralysis. Average correct classification rates were 87% (medical) and 69% (surgical) for mortality, and 64% (medical) and 60% (surgical) for ADL. With these models, we evaluated indications of both kinds of treatment by comparing each predicted ADL of the medically treated cases with that of the surgically treated cases.

The prognostic value of ventricular rupture in cerebral hemorrhage.

Analysis of 41 cerebral hemorrhage cases associated or not with intraparenchymatous hematoma and ventricular rupture shows the role played by these associated phenomena in the evaluation and prognosis of these patients. The death rate was 56.25% in simple cerebral hemorrhage, 100% in hemorrhage associated with hematoma, 30.76% in hemorrhage associated with ventricular rupture and 80% in hemorrhage associated with hematoma and ventricular rupture. The authors point out that the mere presence of ventricular rupture is not a really aggravating factor. A particular severity resulting from association of hemorrhage with hematoma seems to be due to the extension of the cerebral lesion produced by the two conditions associated.

Neuroleptic-induced extrapyramidal symptoms with fever. Heterogeneity of the 'neuroleptic malignant syndrome'.

From 39 reported cases of the "neuroleptic malignant syndrome," three groups were identified: those with concurrent medical problems that could cause fever that accompanied the extrapyramidal symptoms; those with medical problems less clearly related to fever; and those without other medical disorders. Dehydration, infection, pulmonary embolus, and rhabdomyolysis were the common complications of untreated extrapyramidal symptoms. Three patients died, all with medical complications. In 14 cases, no medical cause of fever was identified. Hypotheses about mechanisms for fever include psychiatric illness, disruption of dopaminergic aspects of thermoregulation, and peripheral and central effects on muscle contraction leading to excess heat production. Neuroleptic-induced rigidity should be treated vigorously, with prompt discontinuation of neuroleptic therapy and administration of dopamine agonists in severe cases with or without fever. The cases of extrapyramidal symptoms with fever are too heterogeneous to justify the assumption of a unitary and "malignant" syndrome.