Martin A. Samuels

The Brain–Heart Connection

Neurocardiology has many dimensions, but it may be conceptualized as divided into 3 major categories: the heart’s effects on the brain (eg, cardiac source embolic stroke), the brain’s effects on the heart (eg, neurogenic heart disease), and neurocardiac syndromes (eg, Friedreich disease). The present review deals with the nervous system’s capacity to injure the heart. This subject is inherently important but also represents an example of a much more widespread and conceptually fascinating area of neurovisceral damage in general. In 1942, at the culmination of his distinguished career as Professor of Physiology at Harvard Medical School, Walter B. Cannon published a remarkable paper entitled “‘Voodoo’ Death,”1 in which he recounted anecdotal experiences, largely from the anthropology literature, of death from fright. These often remote events, drawn from widely disparate parts of the world, had several features in common. They were all induced by an absolute belief that an external force, such as a wizard or medicine man, could, at will, cause demise and that the victim himself had no power to alter this course. This perceived lack of control over a powerful external force is the sine qua non for all the cases recounted by Cannon, who postulated that death was caused “by a lasting and intense action of the sympathico-adrenal system.” Cannon believed that this phenomenon was limited to societies in which the people were “so superstitious, so ignorant, that they feel themselves bewildered strangers in a hostile world. Instead of knowledge, they have fertile and unrestricted imaginations which fill their environment with all manner of evil spirits capable of affecting their lives disastrously.” Over the years since Cannon’s observations, evidence has accumulated to support his concept that “voodoo” death is, in fact, a real phenomenon but, far from being limited to ancient peoples, may be a basic …

Neurogenic heart disease: A unifying hypothesis

Electrocardiographic abnormalities have been known to occur in the context of neurologic disease for a long time. These changes fall into 2 categories: arrhythmias and repolarization abnormalities. However, until relatively recently these changes were believed to represent purely electrophysiologic alterations and not real heart disease. It is now clear that some patients with neurogenic electrocardiographic changes show cardiac enzyme release and myofibrillar degeneration at autopsy. There are 4 major methods for producing myofibrillar degeneration (i.e., contraction band necrosis or coagulative myocytolysis): catecholamine infusion, stress-steroid, nervous system stimulation and reperfusion. The common thread connecting these 4 methods is the opening of receptor-operated calcium channels, resulting in intense contraction of cardiac muscle. Thus, neurogenic influence over cardiac function may represent a continuum. In the mild reversible circumstance, only the electrocardiographic change will be seen, whereas in the severe, irreversible situation, myofibrillar degeneration will ensue with release of cardiac enzymes. Cardiac cell death may be caused by oxygen free radicals produced by metabolism of catecholamines or reperfusion or both, after variable periods of ischemia. This concept represents a unifying hypothesis, tying together the clinical, physiologic, biochemical and pathologic findings in neurogenic heart disease.

How Neurologists Think A Cognitive Psychology Perspective on Missed Diagnoses

Physicians use heuristics or shortcuts in their decision making to help them sort through complex clinical information and formulate diagnoses efficiently. Practice would come to a halt without them. However, there are pitfalls to the use of certain heuristics, the same ones to which humans are prone in everyday life. It may be possible to improve clinical decision making through techniques that minimize biases inherent in heuristics. Five common clinical heuristics or other sources of cognitive error are illustrated through neurological cases with missed diagnoses, and literature from cognitive psychology and medicine are presented to support the occurrence of these errors in diagnostic reasoning as general phenomena. Articulation of the errors inherent in certain common heuristics alerts clinicians to their weaknesses as diagnosticians and should be beneficial to practice. Analysis of cases with missed diagnoses in teaching conferences might proceed along formal lines that identify the type of heuristic used and of inherent potential cognitive errors. Addressing these cognitive errors by becoming conscious of them is a useful tool in neurologic education and should facilitate a career‐long process of continuous self‐improvement. ANN NEUROL 2010;67:425–433

Uremic Encephalopathy and Other Brain Disorders Associated with Renal Failure

Kidney failure is one of the leading causes of disability and death and one of the most disabling features of kidney failure and dialysis is encephalopathy. This is probably caused by the accumulation of uremic toxins. Other important causes are related to the underlying disorders that cause kidney failure, particularly hypertension. The clinical manifestations of uremic encephalopathy include mild confusional states to deep coma, often with associated movement disorders, such as asterixis. Most nephrologists consider cognitive impairment to be a major indication for the initiation of renal replacement therapy with dialysis with or without subsequent transplantation. Sleep disorders, including Ekboms syndrome (restless legs syndrome) are also common in patients with kidney failure. Renal replacement therapies are also associated with particular neurologic complications including acute dialysis encephalopathy and chronic dialysis encephalopathy, formerly known as dialysis dementia. The treatments and prevention of each are discussed.

Midbrain syndromes of Benedikt, Claude, and Nothnagel Setting the record straight

Current neuro-ophthalmology textbooks vary considerably in their definitions of the eponymic oculomotor fascicular syndromes-Benedikt’s, Claude’s, and N~thnagel’sl-~ (table, first three columns). By contrast, Weber’s syndrome is universally accepted as ipsilateral oculomotor palsy and contralateral hemiparesis due to a peduncular 1esi0n.l.~ Because eponyms have both historical and humanistic value, unified descriptions for these syndromes are necessary to preserve their integrity and usefulness. Therefore, we studied Benedikt’s, Claude’s, and Nothnagel’s original descriptions in an attempt to clarify the syndromes attributed to them.

Sensory form of acute polyneuritis

A patient presented with severe sensory loss and ataxia with total arreflexia, and elevation of CSF protein with pleocytosis. At autopsy there was extensive lymphocytic infiltration of nerves and posterior roots, sparing the anterior roots. Teased fiber preparation of nerve showed a demyelinating lesion. There were no abnormalities in the CNS. The condition appears to be an acute sensory polyneuritis bearing a close relationship to acute Guillain-Barré syndrome.

Hashimoto’s encephalopathy mimicking Creutzfeldt-Jakob disease: brain biopsy findings

A previous report in this journal described seven cases of Hashimoto’s encephalopathy (HE) clinically resembling Creutzfeldt-Jakob disease (CJD).1 Brain biopsies in such cases are rare and have suggested “vasculitis”.2 We contribute a report of rapidly progressive dementia in a patient undergoing brain biopsy before the diagnosis of HE was established, showing features suggesting early spongiform change but with inflammation. A 57 year old woman was taken to a local hospital following a generalised seizure. She was discharged that night after negative cranial computed tomography and cerebrospinal fluid (CSF) analysis. Within a few days she was noted by family members to be acting strangely and hallucinating. Her doctor found her to be somnolent and rigid without focal neurological findings. Magnetic resonance imaging of the brain showed a questionable increase in gadolinium contrast uptake in a 7 mm area of the left medial frontal cortex. An electroencephalogram (EEG) showed bihemispheric slowing without epileptiform activity. Despite an extensive inpatient evaluation (including biochemical, haematological, endocrine, infectious, autoimmune, and toxic analyses), no cause for the encephalopathy could be found. The patient was then referred to our institution for brain biopsy and further care. Samples of left frontal cortex showed light microscopic evidence of rare vacuoles abutting neurones, suggesting early spongiform change (fig 1). Glial fibrillary acid protein staining showed moderate gliosis. A few perivascular lymphoid cells and macrophages were present, with microglia scattered …

Lymphocyte transformation in response to phytohaemagglutinin in primary biliary cirrhosis: The search for a plasma inhibitory factor

The aim of this study was to determine the importance of plasma inhibitory factors in producing the impaired phytohaemagglutinin (PHA)-induced lymphocyte transformation that is seen in some patients with primary biliary cirrhosis. Twenty-six normal subjects and 12 patients with primary biliary cirrhosis were studied. The lymphocytes from each subject were cultured in the presence of autologous plasma and also in the presence of homologous plasma from a normal subject or from a patient with primary biliary cirrhosis. The results confirm that a proportion of patients with primary biliary cirrhosis are anergic and that the impaired lymphocyte transformation to PHA in vitro can be partially accounted for by the presence of inhibitory factors in the plasma. However, these factors are unlikely to account completely for the impaired transformation, it being probable that there are also abnormalities of the T lymphocytes themselves.

Structure and mechanism of the UvrA–UvrB DNA damage sensor

Nucleotide excision repair (NER) is used by all organisms to eliminate DNA lesions. We determined the structure of the Geobacillus stearothermophilus UvrA–UvrB complex, the damage-sensor in bacterial NER and a new structure of UvrA. We observe that the DNA binding surface of UvrA, previously found in an open shape that binds damaged DNA, also exists in a closed groove shape compatible with native DNA only. The sensor contains two UvrB molecules that flank the UvrA dimer along the predicted path for DNA, ~80 Å from the lesion. We show that the conserved signature domain II of UvrA mediates a nexus of contacts among UvrA, UvrB and DNA. Further, in our new structure of UvrA, this domain adopts an altered conformation while an adjacent nucleotide binding site is vacant. Our findings raise unanticipated questions about NER and also suggest a revised picture of its early stages.

Case 15-1988

Presentation of Case A 26-year-old woman was admitted to the hospital because of a question of dilated cardiomyopathy and a stroke. She was well until six days earlier, when she went out with frien...