Medical Nemesis 50 years on Lees, Andrew J
Lancet neurology,
12/2023, Letnik:
22, Številka:
12
Journal Article
Recenzirano
The book begins: “Within the last decade medical professional practice has become a major threat to health.” Since Illich wrote his book, medicine is driven by profit, with astronomical sums being ...wasted on low value intervention. Listening attentively, observing, and examining a patient are considered cost ineffective and barely reimbursable by health insurance.
IMPORTANCE: Clinical subtyping of Parkinson disease at diagnosis is useful in estimating disease course and survival. Severity and rate of progression of neuropathologies are important determinants ...of clinical Parkinson subtypes. OBJECTIVE: To provide longitudinal clinical disease-course data and neuropathologic correlation for newly proposed Parkinson disease subtypes. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of consecutive patients with autopsy-confirmed Parkinson disease who were regularly seen throughout their disease course by hospital specialists in the United Kingdom and donated their brain at death to the Queen Square Brain Bank between January 2009 and December 2017. Patients with additional neuropathologic diagnoses, monogenic forms of parkinsonism, or insufficiently detailed clinical information were excluded. Based on severity of motor symptoms, rapid eye movement sleep behavior disorder, and autonomic and cognitive function at diagnosis, patients were classified adapting a subtyping classification into mild-motor predominant, intermediate, or diffuse malignant subtypes. MAIN OUTCOMES AND MEASURES: Time from diagnosis to disease milestones (recurrent falls, wheelchair dependence, dementia, and care home placement) and death were compared between subtypes, and their risk was estimated using Cox hazard regression models. Severity and distribution of Lewy pathology and Alzheimer disease–related pathology were assessed using staging systems. RESULTS: From a total of 146 patients, 111 patients were included (67 men 60.4%; mean SD age at diagnosis, 62.5 11.5 years). The diffuse malignant subtype had earlier development of milestones and reduced survival. Cox proportional hazard regression showed an increased adjusted risk of any disease milestone (hazard ratio, 10.90; 95% CI, 5.51-21.58; P < .001) and death (hazard ratio, 3.65; 95% CI, 1.98-6.75; P < .001) in the diffuse malignant group. Age at diagnosis was the only additional variable with statistical significance (adjusted hazard ratio for death, 1.14; 95% CI, 1.11-1.17; P <.001). Staging of Lewy pathology and Alzheimer disease–related pathology did not differ between subtypes, although they showed different rates of progression, and the latter was associated with age at death. CONCLUSIONS AND RELEVANCE: Parkinson clinical subtypes at diagnosis may estimate disease course and survival, which may be useful in providing a more accurate prognosis in individual patients in clinical practice and helping to stratify subgroups in clinical trials. Different severity and progression of neuropathologies are important determinants of Parkinson subtypes, and age at diagnosis should be included in future subtype classifications.
The evasive strategy of ordering further diagnostic tests inevitably leads to worsening of the condition. The condition is as deserved of study as functional neurological disorder or chronic fatigue ...syndrome, in the hope that new explorations in search of its root cause will lead to the development of efficacious evidence-based treatments. A Body Made of Glass: A History of Hypochondria Caroline Crampton Granta Books, 2024 pp 304; £16.99 ISBN 9781783789054
Summary Progressive supranuclear palsy (PSP) is a clinical syndrome comprising supranuclear palsy, postural instability, and mild dementia. Neuropathologically, PSP is defined by the accumulation of ...neurofibrillary tangles. Since the first description of PSP in 1963, several distinct clinical syndromes have been described that are associated with PSP; this discovery challenges the traditional clinicopathological definition and complicates diagnosis in the absence of a reliable, disease-specific biomarker. We review the emerging nosology in this field and contrast the clinical and pathological characteristics of the different disease subgroups. These new insights emphasise that the pathological events and processes that lead to the accumulation of phosphorylated tau protein in the brain are best considered as dynamic processes that can develop at different rates, leading to different clinical phenomena. Moreover, for patients for whom the diagnosis is unclear, clinicians must continue to describe accurately the clinical picture of each individual, rather than label them with inaccurate diagnostic categories, such as atypical parkinsonism or PSP mimics. In this way, the development of the clinical features can be informative in assigning less common nosological categories that give clues to the underlying pathology and an understanding of the expected clinical course.
Objective:
To evaluate the association between diagnosis of Parkinson disease (PD) and risk factors or early symptoms amenable to population‐based screening.
Methods:
A systematic review and ...meta‐analysis of risk factors for PD.
Results:
The strongest associations with later diagnosis of PD were found for having a first‐degree or any relative with PD (odds ratio OR, 3.23; 95% confidence interval CI, 2.65–3.93 and OR, 4.45; 95% CI, 3.39–5.83) or any relative with tremor (OR, 2.74; 95% CI, 2.10–3.57), constipation (relative risk RR, 2.34; 95% CI, 1.55–3.53), or lack of smoking history (current vs never: RR, 0.44; 95% CI, 0.39–0.50), each at least doubling the risk of PD. Further positive significant associations were found for history of anxiety or depression, pesticide exposure, head injury, rural living, beta‐blockers, farming occupation, and well‐water drinking, and negative significant associations were found for coffee drinking, hypertension, nonsteroidal anti‐inflammatory drugs, calcium channel blockers, and alcohol, but not for diabetes mellitus, cancer, oral contraceptive pill use, surgical menopause, hormone replacement therapy, statins, acetaminophen/paracetamol, aspirin, tea drinking, history of general anesthesia, or gastric ulcers. In the systematic review, additional associations included negative associations with raised serum urate, and single studies or studies with conflicting results.
Interpretation:
The strongest risk factors associated with later PD diagnosis are having a family history of PD or tremor, a history of constipation, and lack of smoking history. Further factors also but less strongly contribute to risk of PD diagnosis or, as some premotor symptoms, require further standardized studies to demonstrate the magnitude of risk associated with them. ANN NEUROL 2012
In search of Charcot's second sight Lees, Andrew J
Lancet neurology,
June 2021, 2021-06-00, 20210601, Letnik:
20, Številka:
6
Journal Article
Recenzirano
At the age of 37, he achieved his wish when he was appointed chef de service at La Salpêtrière: “The clinical types available for study are represented by numerous examples, which enable us to study ...categorical disease during its entire course, so to speak, since the vacancies that occur in any specific disease are quickly filled in the course of time. After a loaded pause, he might ask a question about the family history or command the patient to make a movement. Charcot was aware of his gift of seeing things in a flash and, to assist his audience, he always amplified his astute observations with memorable, verbal descriptions. An example of his ability to recount clearly what he had heard or seen is provided in this account of the speech of a patient with multiple sclerosis: “There is a symptom more frequently found than nystagmus…and this is a peculiar difficulty in enunciation…
Both positive and negative associations between higher body mass index (BMI) and Parkinson disease (PD) have been reported in observational studies, but it has been difficult to establish causality ...because of the possibility of residual confounding or reverse causation. To our knowledge, Mendelian randomisation (MR)-the use of genetic instrumental variables (IVs) to explore causal effects-has not previously been used to test the effect of BMI on PD.
Two-sample MR was undertaken using genome-wide association (GWA) study data. The associations between the genetic instruments and BMI were obtained from the GIANT consortium and consisted of the per-allele difference in mean BMI for 77 independent variants that reached genome-wide significance. The per-allele difference in log-odds of PD for each of these variants was estimated from a recent meta-analysis, which included 13,708 cases of PD and 95,282 controls. The inverse-variance weighted method was used to estimate a pooled odds ratio (OR) for the effect of a 5-kg/m2 higher BMI on PD. Evidence of directional pleiotropy averaged across all variants was sought using MR-Egger regression. Frailty simulations were used to assess whether causal associations were affected by mortality selection. A combined genetic IV expected to confer a lifetime exposure of 5-kg/m2 higher BMI was associated with a lower risk of PD (OR 0.82, 95% CI 0.69-0.98). MR-Egger regression gave similar results, suggesting that directional pleiotropy was unlikely to be biasing the result (intercept 0.002; p = 0.654). However, the apparent protective influence of higher BMI could be at least partially induced by survival bias in the PD GWA study, as demonstrated by frailty simulations. Other important limitations of this application of MR include the inability to analyse non-linear associations, to undertake subgroup analyses, and to gain mechanistic insights.
In this large study using two-sample MR, we found that variants known to influence BMI had effects on PD in a manner consistent with higher BMI leading to lower risk of PD. The mechanism underlying this apparent protective effect warrants further study.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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