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Morning report is an important clinical learning activity in many neurological institutions. A long experience of these meetings allows identification of several components to enhance its success. Meetings are best if brief (one or two cases) and held regularly, preferably daily and early in the working day, with full in-person team engagement. A senior clinician should lead the meeting and commit to a single interpretation, without fear of being wrong. Although the environment is relaxed (refreshments typically provided), it is a working meeting and with the essential focus on the patient rather than the learners. The rich learning experience is greatly enhanced by a subsequent confidential email summary and interpretation of the case(s) sent to all participants.

We present two historic cases of severe encephalopathy associated with antithyroid antibodies. The first was published by Lord Brain of Eynsham, and the second was from our department’s archives. Although both cases are from archival sources, they continue to inform current clinical care. We briefly review the poorly defined entity, Hashimoto’s encephalopathy, and discuss diagnostic advances for autoimmune encephalopathy and for Creutzfeldt-Jakob disease. We advocate for giving a trial of corticosteroids to patients with ‘encephalopathy, not otherwise specified’ while awaiting antibody results or more definitive testing. Our case, initially diagnosed as having Creutzfeldt-Jakob disease, responded remarkably (with video evidence) to a trial of corticosteroids.

This article reviews the latest evidence pertaining to childhood sleep disordered breathing (SDB), which is associated with negative neurobehavioural, cardiovascular and growth outcomes. Polysomnography is the accepted gold standard for diagnosing SDB but is expensive and limited to specialist centres. Simpler tests such as cardiorespiratory polygraphy and pulse oximetry are probably sufficient for diagnosing obstructive sleep apnoea (OSA) in typically developing children, and new data-processing techniques may improve their accuracy. Adenotonsillectomy is the first-line treatment for OSA, with recent evidence showing that intracapsular tonsillectomy results in lower rates of adverse events than traditional techniques. Anti-inflammatory medication and positive airway pressure respiratory support are not always suitable or successful, although weight loss and hypoglossal nerve stimulation may help in select comorbid conditions.Educational aimsTo understand the clinical impact of childhood sleep disordered breathing (SDB).To understand that, while sleep laboratory polysomnography has been the gold standard for diagnosis of SDB, other diagnostic techniques exist with their own benefits and limitations.To recognise that adenotonsillectomy and positive pressure respiratory support are the mainstays of treating childhood SDB, but different approaches may be indicated in certain patient groups.

Acute idiopathic hyperammonemia in an adult patient is a life-threatening condition often resulting in a rapid progression to irreversible cerebral edema and death. While ammonia-scavenging therapies lower blood ammonia levels, in comparison, clearance of waste nitrogen from the brain may be delayed. Therefore, we used magnetic resonance spectroscopy (MRS) to monitor cerebral glutamine levels, the major reservoir of ammonia, in a gastric bypass patient with hyperammonemic coma undergoing therapy with N-carbamoyl glutamate and the ammonia-scavenging agents, sodium phenylacetate and sodium benzoate. Improvement in mental status mirrored brain glutamine levels, as coma persisted for 48h after plasma ammonia normalized. We hypothesize that the slower clearance for brain glutamine levels accounts for the delay in improvement following initiation of treatment in cases of chronic hyperammonemia. We propose MRS to monitor brain glutamine as a noninvasive approach to be utilized for diagnostic and therapeutic monitoring purposes in adult patients presenting with idiopathic hyperammonemia.

This final chapter looks in detail at systemic inflammatory diseases that frequently affect both the central and peripheral nervous systems and can begin with neurological symptoms. These diseases cross traditional boundaries between neurology and rheumatology, and diagnosis and treatment require familiarity with the spectrum of neurological involvement with interdisciplinary communication. The chapter reviews some of the more common neurological manifestations of selected autoimmune diseases such as systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, scleroderma, sarcoidosis, primary angiitis of the central nervous system, systemic vasculitis syndromes, and antiphospholipid syndrome.

A 62-year-old man with sarcoidosis was admitted to this hospital because of diplopia and weakness. Examination of the CSF revealed elevated opening pressure and leukocytosis. The patient’s condition deteriorated rapidly. He died 10 days later. A diagnosis was made.

Structural and functional elements of biological systems are highly conserved across vertebrates. Many neurological and psychiatric conditions affect both humans and animals. A cross-species approach to the study of brain and behaviour can advance our understanding of human disorders via the identification of unrecognized natural models of spontaneous disorders, thus revealing novel factors that increase vulnerability or resilience, and via the assessment of potential therapies. Moreover, diagnostic and therapeutic advances in human neurology and psychiatry can often be adapted for veterinary patients. However, clinical and research collaborations between physicians and veterinarians remain limited, leaving this wealth of comparative information largely untapped. Here, we review pain, cognitive decline syndromes, epilepsy, anxiety and compulsions, autoimmune and infectious encephalitides and mismatch disorders across a range of animal species, looking for novel insights with translational potential. This comparative perspective can help generate novel hypotheses, expand and improve clinical trials and identify natural animal models of disease resistance and vulnerability.

Assembly of bacterial ring-shaped hexameric replicative helicases on single-stranded (ss) DNA requires specialized loading factors. However, mechanisms implemented by these factors during opening and closing of the helicase, which enable and restrict access to an internal chamber, are not known. Here, we investigate these mechanisms in the Escherichia coli DnaB helicase•bacteriophage λ helicase loader (λP) complex. We show that five copies of λP bind at DnaB subunit interfaces and reconfigure the helicase into an open spiral conformation that is intermediate to previously observed closed ring and closed spiral forms; reconfiguration also produces openings large enough to admit ssDNA into the inner chamber. The helicase is also observed in a restrained inactive configuration that poises it to close on activating signal, and transition to the translocation state. Our findings provide insights into helicase opening, delivery to the origin and ssDNA entry, and closing in preparation for translocation.

Susac's syndrome is a rare autoimmune microangiopathy characterized by the clinical triad of encephalopathy, branch retinal artery occlusions, and sensorineural hearing loss. In many cases, the clinical triad is not fully present at the onset of symptoms. MRI studies often show characteristic punched out lesions of the central fibers of the corpus callosum, and leptomeningeal enhancement and deep gray matter lesions may also be seen. Here we present a case of Susac's syndrome in a middle aged man with the unique clinical finding of cauda equina syndrome and spinal MRI showing diffuse lumbosacral nerve root enhancement. Biopsy specimens of the brain, leptomeninges, and skin showed evidence of a pauci-immune endotheliopathy, consistent with pathology described in previous cases of Susac's syndrome. This case is important not only because it expands the clinical features of Susac's syndrome but also because it clarifies the mechanism of a disorder of the endothelium, an important target for many disorders of the nervous system.

A 31-year-old woman was admitted to the hospital after being unable to eat or drink for 1 week. She had had nausea, vomiting, and abdominal discomfort, as well as episodes of crampy epigastric pain with vomiting and intermittent chills and sweats, for 8 months.

An 89-year-old man was brought to the ER by his wife and son for an evaluation of changes in cognition and personality. Six months earlier, he began needing help managing finances and operating his computer. He had poor memory for recent events and difficulty expressing himself.

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.

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 selfimprovement. ANN NEUROL 2010;67:425– 433

The mini-chromosome maintenance (MCM) proteins serve as the replicative helicases in archaea and eukaryotes. Interestingly, an MCM homolog was identified, by BLAST analysis, within a phage integrated in the bacterium Bacillus cereus (Bc). BcMCM is only related to the AAA region of MCM-helicases; the typical amino-terminus is missing and is replaced by a segment with weak homology to primases. We show that BcMCM displays 3'--5' helicase and ssDNA-stimulated ATPase activity, properties that arise from its conserved AAA domain. Isolated BcMCM is a monomer in solution but likely forms the functional oligomer in vivo. We found that the BcMCM amino-terminus can bind ssDNA and harbors a zinc atom, both hallmarks of the typical MCM amino-terminus. No BcMCM-catalyzed primase activity could be detected. We propose that the divergent amino-terminus of BcMCM is a paralog of the corresponding region of MCM-helicases. A divergent amino terminus makes BcMCM a useful model for typical MCM-helicases since it accomplishes the same function using an apparently unrelated structure.

We describe a method for preparing large, linear DNA molecules in amounts that are suitable for structural studies. The procedure employs self-primed DNA amplification on a starting molecule that consists of the sequence of interest flanked by the cohesive end sequences from bacteriophage lambda as well as endonuclease recognition sites. Amplification produces long polymers of DNA, tens of kilobases in length, which harbor many copies of the sequence of interest. Endonuclease digestion of these polymers, followed by chromatographic purification, yields high-quality preparations of the DNA molecule of interest. Reliance on the cohesive end sequences to initiate self-primed amplification effectively enables the synthesis of DNA molecules of interest with minimal restriction on length and sequence.

A 77-year-old man was admitted to the hospital because of difficulty speaking and altered mental status. He had been well until the day before admission, when pain developed in the right side of the face and in the right ear. Several days earlier, he had fallen on the sidewalk and hit his head. On examination, he was lethargic with incomprehensible speech; dried blood was seen in the right ear canal. CT scanning of the head disclosed pneumocephalus and opacification of the right mastoid air cells.

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 …

Multiple sclerosis (MS) can affect cardiovascular function in a variety of ways leading to abnormalities in blood pressure response, heart rate, heart rhythm, left ventricular systolic function, and may cause pulmonary edema or cardiomyopathy. Cardiovascular dysfunction in MS is incompletely understood and likely underrecognized.The clinical presentation and pathophysiology of cardiovascular dysfunction in MS are reviewed, as are the cardiovascular toxicities of MS therapies, fingolimod and mitoxantrone. Cardiovascular dysfunction in MS can be caused by brainstem lesions affecting autonomic pathways in the medulla, overall plaque burden, and clinical severity of the disease.Cardiovascular abnormalities may be clinical or subclinical, and can lead to sudden death in some cases. Neurologists should be aware of the clinical presentation and pathophysiology of cardiovascular dysfunction in MS so as to ameliorate cardiovascular symptoms, prevent cardiovascular complications, and choose therapeutic agents that do not worsen underlying cardiovascular disease.