Plasmin deficiency in Alzheimer's disease brains: causal or casual?

Substantial recent evidence suggests that defects in amyloid peptide degradation can be at the base of cases of sporadic Alzheimer's disease (AD). Among the discovered brain enzymes with the capacity to degrade amyloid peptide, the serine protease plasmin acquires special physiological relevance because of its low levels in areas of AD human brains with a high susceptibility to amyloid plaque accumulation. In this article we comment on a series of observations supporting the fact that plasmin paucity in the brain is not simply a secondary event in the disease but rather a primary defect in certain cases of sporadic AD. We also refer to recent data pointing to alterations in raft membrane domains and diminished membrane cholesterol as the underlying cause. Finally, we discuss the possibility that plasmin deficiency in the brain could lead to AD symptomatology because of amyloid aggregation and the triggering of cell death signaling cascades.     

Right parietal contributions to verbal working memory: spatial or executive?

The left inferior parietal cortex has been claimed to be the site of the verbal short-term store, yet imaging studies report activity of a homologous right-hemisphere region in verbal working memory tasks as well. In spite of its prevalent activity, right parietal contributions to verbal working memory are poorly understood. To clarify its role in verbal working memory performance, we tested a patient with a lesion in the right parietal lobe on verbal and spatial versions of the N-back task. The patient was impaired in all the spatial conditions regardless of load (0-, 1-, and 2-back), whereas in the verbal N-back he was impaired only in the conditions with a memory demand (1- and 2-back). Given that we had presented stimuli at multiple locations in the verbal N-back, however, it remained possible that the lesion impaired spatial representation rather than verbal working memory per se. With central stimulus presentation, his performance dramatically improved indicating that his difficulty with the N-back task was largely due to his poor visuospatial abilities.     

Lumbar puncture and dural sinus thrombosis--a causal or casual association?

BACKGROUND: A few cases of cerebral venous thrombosis (CVT) were reported after a lumbar puncture (LP), suggesting a causal association. The purpose of our study was to document that LP might predispose to CVT by decreasing blood flow velocities (BFV) in veins or dural sinus. METHODS: We performed a transcranial Doppler ultrasound study to register the mean BFV of the straight sinus (SS) before, during and after LP. RESULTS: Thirteen patients were studied. LP induced a decrease of 47% of mean BFV in the SS. The mean decrease of BFV was significant immediately at the end (p = 0.003), 30 min after (p = 0.015) and more than 6 h after LP (p = 0.008). CONCLUSIONS: LP induced a sustained decrease of mean BFV in the SS. The decrease of venous blood flow is a possible mechanism contributing to the occurrence of CVT.     

Psychiatry: mindless or brainless, both or neither?

After a period marked by one-sided emphasis on psychodynamics and social issues, or what could be called "brainless" psychiatry on account of its relative neglect of cerebral processes, we are witnessing an opposite trend towards extreme biologism or "mindless" psychiatry. The pendulum has swung periodically from one to the other of these reductionistic positions throughout the history of psychiatry. The author argues that neither brainless nor mindless psychiatry can do justice to the complexity of mental illness and to the treatment of patients. Psychiatry's distinguishing feature as a clinical discipline is its equal concern with subjective experience, or the mind, and with the body, including brain function, which together constitute a person, a psychiatrist's proper focus of inquiry and intervention. Moreover, a person, viewed as a mindbody complex, is in constant interaction with the environment. It follows that both study of mental illness and clinical practice need to take into account the psychological, the biological and the social aspects. These three aspects are not mutually reducible and are indispensable for the understanding and treatment of the individual patient. Such a comprehensive, biopsychosocial approach provides an antithesis to the reductionistic viewpoints and, in the writer's opinion, is both practically and theoretically most satisfying.     

Limbic encephalitis with anti‐GAD antibodies and Thomsen myotonia: a casual or causal association?

The association between hereditary myotonic disorders and epilepsy is seldom described in the literature. To date, few reports have dealt with dystrophic myotonias, whereas a single case demonstrating an association between sporadic congenital myotonia and epilepsy was recently reported in a patient carrying a de novo mutation of the CLCN1 gene. Additional evidence for a role of CLCN1 in the pathogenesis of epilepsy is derived from large‐scale exome analysis of ion channel variants and expression studies. Here, we describe the first case of association between familial Thomsen myotonia and epilepsy. All the affected members of a two‐generation family presented myotonia and disclosed a pathogenic mutation in CLCN1. In addition, one individual experienced epileptic seizures due to limbic encephalitis (LE) with anti‐GAD antibodies. The occurrence of the two diseases in this patient could be a chance association, however, CLCN1 mutation, as a susceptibility factor for epilepsy through dysfunction of GABA_a inhibitory signalling, cannot be ruled out as a possible influence.     

Tardive dyskinesia: eliminated, forgotten, or overshadowed?

PURPOSE OF REVIEW: The present review focuses on atypical antipsychotics and tardive dyskinesia. RECENT FINDINGS: We have known for many years that clozapine has a diminished risk of tardive dyskinesia compared with typical antipsychotics. The last decade has seen the introduction of a number of other atypical antipsychotics, allowing us to begin evaluating whether they too share this attribute. In addition, the opportunity to use these drugs as first-line treatment permits a more precise means of establishing risk. While longer-term data are required, the limited evidence available clearly indicates that the atypical antipsychotics have a decreased liability of tardive dyskinesia, approximately 1% compared with 5% for typical agents annually. Like clozapine, the other atypical antipsychotics also demonstrate antidyskinetic properties in individuals with preexisting tardive dyskinesia. The underlying mechanisms remain unclear, and without such information it is not possible to say what clinical conditions, if any, might diminish or even eliminate these advantages. SUMMARY: An update is provided regarding the atypical antipsychotics and tardive dyskinesia. This information is critical in our decision-making regarding choice of antipsychotic and optimal use in the clinical setting.     

COVID-19 and Parkinson’s disease: a casual association or a possible second hit in neurodegeneration?

Journal of Neurology -     

Depression sub-typing: unitary, binary or arbitrary?

The strongest statistical support for the binary view of depression has been provided by factor (principal components) analytic studies which delineate a bipolar factor with features interpreted as reflecting "endogenous depression" and "neurotic depression" at opposing poles. We review the seminal studies to suggest instead that the bipolar factor has generally polarised depression and anxiety, and that no such entity or symptom complex of "neurotic depression" has been isolated. Instead "neurotic depression" has been defined principally by features of anxiety and personality style. We argue that the suggested entity is, in fact, a pseudo-entity, being no more than a residual group of non-depressive features without any significant intrinsic depressive characteristics. We support our interpretation by showing comparable solutions in published studies of depressives alone, contrasted with separate analyses of anxious and depressed patients. We also report two studies in which the "neurotic depressive" pole is made to appear and disappear by the inclusion and exclusion of anxiety items. As factor analytic studies have defined the "residual" pole so variably, we argue that some features held to distinguish neurotic depression are of no utility and that such a diagnosis is meaningless. We suggest that the clinician should not proceed (after excluding endogenous depression) to conclude that the default option is necessarily an entity "neurotic depression" and that instead a heterogeneous group of options (e.g. anxiety, personality disorder) require review. If the "neurotic depressive" type of the multivariate analytic studies is a pseudo-entity, then a modified unitary view of depression may be valid.