Focal myositis – A neurogenic phenomenon?

We report four cases of focal myositis. The patients, three men and one woman, had painful muscle hypertrophy, affecting four different sites. MRI confirmed the muscle enlargement and oedema. Electromyography revealed evidence of acute and chronic denervation in all four cases. Muscle biopsy was available in three and confirmed features suggestive of focal myositis. Based on our patient material, we suggest that chronic nerve irritation, such as compression, can lead to muscle hypertrophy which, when prolonged, provokes fibre necrosis and secondary inflammation. Our finding in four patients having hypertrophy involving four different sites, leads us further to suggest that this may be the common mechanism behind focal myositis.     

Hyperphosphatasia With Neurologic Deficit: A Pyridoxine-Responsive Seizure Disorder?

This report describes the case of a 4 1/2-year-old female with developmental delay and tonic-clonic seizures, persistently elevated serum alkaline phosphatase activity, and low serum pyridoxal 5'-phosphate. Born at term to consanguineous parents, she was dysmorphic and delayed at 5 months. At 11 months, seizures and microcephaly were evident but skeletal and cerebral imaging, karyotyping, and genetic metabolic tests were unremarkable. Serum alkaline phosphatase activity, however, was elevated (1.3 +/- 0.6 times greater than the upper limit of normal) on seven occasions between 5 months and 4(1/2) years of age. Hyperphosphatasia with neurologic deficit (MIM #239300), a rare autosomal recessive disorder, was diagnosed. The low serum levels of pyridoxal 5'-phosphate (6 nmol/L; normal >20 nmol/L) prompted a pyridoxine challenge. A clinically significant but paradoxical response was observed. On electroencephalography, diffuse delta slow waves (1-2 Hz) were observed, suggestive of stage 3 or 4 slow-wave sleep. With daily administration of 100 mg pyridoxine and withdrawal of phenobarbital, seizures were not evident. We suggest that serum alkaline phosphatase should be measured in cases of seizures with paradoxical electroencephalographic response to pyridoxine. Conversely, pyridoxine challenge should be considered in cases of hyperphosphatasia with seizures and neurologic deficit.     

To Detain or Not to Detain: A Question of Public Duty?

This article examines case law and legislation in order to address the question as to whether psychiatrists owe a duty of care to members of the public to detain individuals with mental illnesses and who are at risk of harming others. It explores a hypothetical scenario in which a victim, or his or her estate or family, wishes to sue a psychiatrist for negligent failure to detain an individual with a mental illness who has harmed that victim in some way. The article suggests that current law indicates that a duty of care does not exist to unidentifiable third parties and, further, there are sound policy reasons why the law should take a cautious approach to imposing a duty to detain on psychiatrists in such circumstances.     

Deficits of entropy modulation of the EEG: A biomarker for altered function in schizophrenia and bipolar disorder?

BackgroundThe synchronized activity of distributed neural assemblies — reflected in the electroencephalogram (EEG) — underpins mental function. In schizophrenia, modulation deficits of EEG spectral content during a P300 task have been replicated. The effects of treatment, chronicity and specificity in these deficits and their possible relationship with anatomic connectivity remain to be explored.MethodsWe assessed spectral entropy modulation of the EEG during a P300 task in 79 patients with schizophrenia (of those, 31 were in their first episode), 29 patients with bipolar disorder and 48 healthy controls. Spectral entropy values summarize EEG characteristics by quantifying the irregularity of spectral content. In a subsample, we calculated the network architecture of structural connectivity using diffusion tensor imaging and graph-theory parameters.ResultsWe found significant spectral entropy modulation deficits with task performance in patients with chronic or first-episode schizophrenia and in patients with bipolar disorder, without significant pre-stimulus spectral entropy differences. The deficits were unrelated to treatment doses, and spectral entropy modulation did not differ between patients taking or not taking antipsychotics, lithium, benzodiazepines or antidepressants. Structural connectivity values were unrelated to spectral entropy modulation. In patients with schizophrenia, spectral entropy modulation was inversely related to negative symptoms and directly related to verbal memory.LimitationsAll patients were taking medication. Patients with bipolar disorder were euthymic and chronic. The cross-sectional nature of this study prevented a more thorough analysis of state versus trait criteria for spectral entropy changes.ConclusionSpectral entropy modulation with task performance is decreased in patients with schizophrenia and bipolar disorder. This deficit was not an effect of psychopharmacological treatment or structural connectivity and might reflect a deficit in the synchronization of the neural assemblies that underlie cognitive activity.     

Lack of false recognition in schizophrenia: a consequence of poor memory?

The tendency to falsely recognize items as ones previously presented is increased in patients with frontal lesions and in older participants, whereas patients with medial temporal lobe damage may display such poor memory that they are not especially susceptible to false recognition. Since patients with schizophrenia are often compared to these groups neurocognitively, we explored the extent to which they are more susceptible to false memory. Participants were presented with word lists along a semantic theme, such as "bread". After list presentation, recognition tasks were administered which contained both the studied words as well as unstudied words. Some of the unstudied words were related to the theme of the previously studied words, but never actually presented (e.g. semantic "lures"). In a separate test, free recall of these lists of words was assessed. Interestingly, it was control participants who made more errors at recall, and were especially susceptible to intrusions of the semantic lures. Patients with schizophrenia did not make more false recognition errors in general, and surprisingly they made disproportionately fewer false recognition errors to semantic lures specifically. We conclude that despite poor memory, patients with schizophrenia are not especially susceptible to interference from previous tasks and are not particularly prone to false recollections.     

Prevention of apoptotic neuronal death by controlling procaspases? A point of view

In various animal models of neurodegenerative diseases the long-lasting control of cell death by anti-apoptotic therapies is not successful. We present here our view on the control of procaspase expression in a model of cerebral stroke. We have investigated how Hu-Bcl-2 overexpression modifies cell death protein activation in a model of cerebral ischemia induced by permanent middle cerebral artery occlusion (MCAO). In wild type mice MCAO induced release of cytochrome c from the mitochondria, and activation of caspases 9 and 3. In parallel with caspases activation, procaspase 9 and procaspase 3 were, respectively, increased and decreased. In Hu-Bcl-2 transgenic mice cytochrome c release and caspases 9 and 3 activation were blocked. However procaspase 9 increased, like in wt mice, but procaspase 3 remained unchanged. By 2 weeks after MCAO caspases were no longer blocked in Hu-Bcl-2 transgenic mice. Procaspase 9 increase could represent a time bomb in Hu-Bcl-2 mice where caspase 9 activation is blocked. Indeed, cellular accumulation of procaspase 9 is a potentially harmful event able to overcome anti-apoptotic protection by Bcl-2 and threaten cells with rapid destruction. Through understanding of the upstream regulation of procaspase 9, early targets for the pharmacological control of apoptotic cell death may be revealed.     

Are Some Memory Deficits Unique to Lesions of the Mammillary Bodies?

The role of the mammillary bodies in human memory is still in debate. A recent model of human amnesia proposes similar functions for the mammillary bodies and the hippocampus. But the main evidence for this model comes from animal studies using the delayed non-matching to sample paradigm. We describe a patient who developed a severe memory impairment after surgical removal of a germinoma. Postsurgical high resolution MRI revealed bilaterally shrunken mammillary bodies and an infarct of the left mammillary body. There were no other relevant lesions. Neuropsychological testing showed mildly impaired frontal lobe functions (executive functions, working memory and word fluency), almost intact learning and recognition, but severely impaired free and delayed recall. Experimental investigations revealed a reduced but preserved release of proactive interference and a pronounced impairment of recency and source judgments. We conclude that the mammillary bodies do play a prominent role in human memory, although the role differs slightly from that of the hippocampus.     

The Autism Diagnostic Observation Schedule—Generic: A Standard Measure of Social and Communication Deficits Associated with the Spectrum of Autism

The Autism Diagnostic Observation Schedule—Generic (ADOS-G) is a semistructured, standardized assessment of social interaction, communication, play, and imaginative use of materials for individuals suspected of having autism spectrum disorders. The observational schedule consists of four 30-minute modules, each designed to be administered to different individuals according to their level of expressive language. Psychometric data are presented for 223 children and adults with Autistic Disorder (autism), Pervasive Developmental Disorder Not Otherwise Specified (PDDNOS) or nonspectrum diagnoses. Within each module, diagnostic groups were equivalent on expressive language level. Results indicate substantial interrater and test—retest reliability for individual items, excellent interrater reliability within domains and excellent internal consistency. Comparisons of means indicated consistent differentiation of autism and PDDNOS from nonspectrum individuals, with some, but less consistent, differentiation of autism from PDDNOS. A priori operationalization of DSM-IV/ICD-10 criteria, factor analyses, and ROC curves were used to generate diagnostic algorithms with thresholds set for autism and broader autism spectrum/PDD. Algorithm sensitivities and specificities for autism and PDDNOS relative to nonspectrum disorders were excellent, with moderate differentiation of autism from PDDNOS.     

Parenchymal “Damage” in Transient Ischemic Attacks (Tias) and Prolonged Reversible Ischemic Neurologic Deficits (Prinds):—The Role of Cranial CT and EEG

Over a period of 6 years (1985–1990) we reviewed records of patients with one or more TIAs or PRINDs (196 TIAs, 63 PRINDs) 111 patients (42.9%) suffered from TIAs/PRINDs of the anterior circulation. In all cranial CT scanning (CCT) was performed, whereas only in 79 EEG was recorded after recovery from the symptoms. 25 patients (22.5%) out of the 111 showed low density areas of recent onset in CCT made responsible for the attack. Among the EEGs of the 79 patients 35 (44.3%) revealed corresponding electrical abnormalities. Out of the 79 patients investigated by both methods in 14 (17.7%) a lesion was demonstrated in CCT and focal abnormality in EEG. In 11 (13.9%) EEG was normal despite a lesion manifested in CCT. Vice versa 21 patients (26.6%) showed normal CCTs but focal abnormalities in EEG. By far most cases (43%) had normal CCTs and EEGs.

These results may contribute to a redefinition of TIA and PRIND as clinically defined syndroms in prae-CT-area.     

Lack of glutathione peroxidase-1 exacerbates Aβ-mediated neurotoxicity in cortical neurons

Summary. The aetiologies of Alzheimer’s disease (AD) are complex and multifactorial. Current therapies are largely ineffective, as the pathophysiological pathways are poorly understood. Observations in AD autopsies, as well as in vivo and in vitro observations in transgenic mice, have implicated oxidative stress as pathogenic in AD. This study used the Glutathione Peroxidase-1 knockout mouse (Gpx1−/−) model to investigate the role of antioxidant disparity in neuropathologies. Cultured neurons from control and Gpx1−/− embryos were treated with AD-related peptides and the degree of cell loss compared. Results show that antioxidant disparity makes Gpx1−/− cells more susceptible to Aβ toxicity. Surrogate replacement of Gpx1 with the reactive oxygen species scavenger N-acetyl cysteine and the Gpx1 mimetic ebselen, reverses the Gpx1−/− increased susceptibility to Aβ toxicity. Such results support a role for oxidative stress in AD-related neuronal loss. This study is the first to report such findings using the Gpx1−/− model, and supports a role for oxidative stress as one of the contributing factors, in development of AD-like pathologies.     

Are some cases of psychosis caused by microbial agents? A review of the evidence

The infectious theory of psychosis, prominent early in the twentieth century, has recently received renewed scientific support. Evidence has accumulated that schizophrenia and bipolar disorder are complex diseases in which many predisposing genes interact with one or more environmental agents to cause symptoms. The protozoan Toxoplasma gondii and cytomegalovirus are discussed as examples of infectious agents that have been linked to schizophrenia and in which genes and infectious agents interact. Such infections may occur early in life and are thus consistent with neurodevelopmental as well as genetic theories of psychosis. The outstanding questions regarding infectious theories concern timing and causality. Attempts are underway to address the former by examining sera of individuals prior to the onset of illness and to address the latter by using antiinfective medications to treat individuals with psychosis. The identification of infectious agents associated with the etiopathogenesis of schizophrenia might lead to new methods for the diagnosis, treatment and prevention of this disorder.