A history of the path towards imaging of the brain: From skull radiography through cerebral angiography.

This publication reviews the steps in the path towards obtaining a complete image of the brain. Up to the 1920s, plain X-ray films could demonstrate only calcified tumors, shifts in midline position of a calcified pineal gland due to a mass in the cranium, or foreign metallic objects within the skull. Walter Dandy reported in 1918 that he visualized cerebral ventricles by introducing air as a contrast agent through a trocar into one of the occipital lobes or the right frontal horn of the ventricular system. Dandy localized lesions that distorted or shifted the ventricles. In 1920, Dandy placed air by lumbar puncture into the spinal subarachnoid space that could visualize the brain and entire ventricles. Antonio Egas Moniz with the assistance of his neurosurgeon colleague, Almeida Lima, obtained X-ray images of cerebral arteries of dogs and decapitated human heads from corpses after injecting strontium bromide into their carotid arteries. Satisfied by these experiments, Moniz injected strontium bromide directly into carotid arteries of five patients which failed to show intracranial vessels. In the sixth patient, intracranial arteries were outlined but that patient died of cerebral thrombosis presumably due to the hyper-osmolality of that contrast agent. Finally, on June 18, 1927, Moniz injected 22% sodium iodine into a 20-year-old man and obtained clear visualization of his carotid artery and intracerebral branches after temporarily occluding the artery with a ligature. Direct percutaneous puncture of the cervical carotid artery remained the primary technique unto the 1960s to visualize intracranial blood vessels until Seldinger's technique was introduced in 1953. Computerized axial tomography (CAT) and magnetic resonance imaging (MRI) replaced cerebral arteriography for localizing tumors and epidural or subdural hemorrhage. However, angiography is used currently for embolization of aneurysms and removal of thrombi or emboli in patients with acute stroke.

Alice in Wonderland Syndrome: A Historical and Medical Review.

Alice in Wonderland syndrome is a disorienting neurological condition that affects human perception to the senses of vision, hearing, touch, sensation, and the phenomenon of time. Individuals affected with Alice in Wonderland syndrome can experience alterations in their perception of the size of objects or their own body parts, known as metamorphopsias. It is known to occur in conditions including migraine, epilepsy, and certain intoxicants and infectious diseases. The name refers to Lewis Carrol's well-known children's book Alice's Adventures in Wonderland, in which the title character experiences alterations of sensation in which she felt that her body had grown too tall or too small, or parts of her body were changing shape, size, or relationship to the rest of her body. The syndrome was described in 1952 by Caro Lippman, and given its name in 1955 by John Todd. The metamorphopsias characteristic of this condition are also sometimes referred to as Lilliputian hallucinations, a reference to the fictional island of Lilliput in the novel Gulliver's Travels, written by Jonathan Swift in 1726. As such, many literary and medical publications have roots in the description of this syndrome. The purpose of this review is to summarize the literary and historical significance of Alice in Wonderland syndrome, as well as to provide the reader with a medical overview of the condition.

What's in the Literature?

In this edition of this column, we review new studies concerning the pathophysiology, treatment, and outcomes of patients with necrotizing myopathy, genetic testing in congenital myopathies, and limb girdle muscular dystrophies, and the incidence of polyneuropathy in the myotonic dystrophies. Various studies in myasthenia gravis, including those concerning antibody testing, clinical features, and quality of life are also reviewed as are recent findings in congenital myasthenic syndromes. Finally, 2 studies concerning polyneuropathy are discussed, including one on the association of polyneuropathy in patients with the metabolic syndrome and one on laboratory testing in patients with otherwise idiopathic small fiber polyneuropathy.

Adolf Beck: a forgotten pioneer in electroencephalography.

Adolf Beck, born in 1863 at Cracow (Poland), joined the Department of Physiology of the Jagiellonian University in 1880 to work directly under the supervision of the prominent physiology professor, Napoleon Cybulski. Following his suggestion, Beck started experimental studies on the electrical brain activity of animals, especially in response to sensory stimulation. Beck placed electrodes directly on the surface of brain to localize brain potentials that were evoked by sensory stimuli. He observed spontaneous fluctuations in the electrical brain activity and noted that these oscillations ceased after sensory stimulation. He published these findings concerning the electrical brain activity, such as spontaneous fluctuations, evoked potentials, and desynchronization of brain waves, in 1890 in the German language Centralblatt für Physiologie. Moreover, an intense polemic arose between physiologists of that era on the question of who should claim being the founder of electroencephalography. Ultimately, Richard Caton from Liverpool showed that he had performed similar experiments in monkeys years earlier. Nevertheless, Beck added new elements to the nature of electrical brain activity. In retrospect, next to Richard Caton, Adolf Beck can be regarded, together with Hans Berger who later introduced the method to humans, as one of the founders of electroencephalography. Soon after his success, Beck got a chair at the Department of Physiology of the University at Lemberg, now Lviv National Medical University.

The Alice in Wonderland syndrome.

The Alice in Wonderland syndrome is a term applied to altered bizarre perceptions of size and shapes of a patient's body and illusions of changes in the forms, dimensions, and motions of objects that a patient with this syndrome encounters. These metamorphopsias arise during complex partial seizures, migraine headaches, infections, and intoxications. The illusions and hallucinations resemble the strange phenomena that Alice experienced in Lewis Carroll's Alice's Adventures in Wonderland. Charles Lutwidge Dodgson, whose nom de plume was Lewis Carroll, experienced metamorphopsias. He described them in the story that he wrote for Alice Liddell and her two sisters after he spun a tale about a long and strange dream that the fictional Alice had on a warm summer day. The author of this chapter suggests that Dodgson suffered from migraine headaches and used these experiences to weave an amusing tale for Alice Liddell. The chapter also discusses the neurology of mercury poisoning affecting the behavior of Mad Hatter character. The author suggests that the ever-somnolent Dormouse suffered from excessive daytime sleepiness due to obstructive sleep apnea.

Association of common variants in the human eyes shut ortholog (EYS) with statin-induced myopathy: evidence for additional functions of EYS.

INTRODUCTION: Of the nearly 38 million people in the USA who receive statin therapy, 0.1-0.5% experience severe or life-threatening myopathic side effects. METHODS: We performed a genome-wide association study (GWAS) in a group of patients with severe statin myopathy versus a statin-tolerant group to identify genetic susceptibility loci. RESULTS: Replication studies in independent groups of severe statin myopathy (n = 190) and statin-tolerant controls (n = 130) resulted in the identification of three single-nucleotide polymorphisms (SNPs), rs9342288, rs1337512, and rs3857532, in the eyes shut homolog (EYS) on chromosome 6 suggestive of an association with risk for severe statin myopathy (P = 0.0003-0.0008). Analysis of EYS cDNA demonstrated that EYS gene products are complex and expressed with relative abundance in the spinal cord as well as in the retina. CONCLUSION: Structural similarities of these EYS gene products to members of the Notch signaling pathway and to agrin suggest a possible functional role in the maintenance and regeneration of the structural integrity of skeletal muscle.

Neurognostics question. Gordon Morgan Holmes.

Gordon Morgan Holmes, MD, MRCP was an Irish born neurologist who received his medical education at Trinity College, Dublin, Ireland. He was trained in neuroanatomy and neuropathology at the Senckenberg Institute, Frankfort-Am-Main by Ludwig Edinger. He then returned to serve as a Registrar (House Officer) mentored by Richard Gowers and John Hughlings Jackson at the National Hospital, Queen Square, London. He collaborated with Thomas Granger Stewart in describing the loss of recoil in patients with cerebellar hemispheric tumors in 1904. Volunteering in 1914 for frontline hospital duty, he examined soldiers who had injuries to their occipital area causing hypotonia, dysmetria, staggering gait, and falling to the side ipsilateral to their injured cerebellar hemisphere. Holmes discovered that increasing the pace of the finger-nose manuever and applying slight resistance to a moving limb attenuated the dysmetria. Continuing observation of these patients afforded him to describe the evolution of their injuries to include increasing tremor and decreasing hypotonia. Holmes first attached levers to the limbs of hispatients to record their movements on a moving smoked paper kymograph. In 1939 he published photograh tracings made by low mass minature light bulbs attached to ataxic limbs that showed thehpometira and hypometria of their movements ipsilateral to their damaged cerebellar lobes. Holmes made sigficant contributions to understanding of the physiology of the human cerebellum.

Hyaline inclusion myopathy: unmasked by statin therapy.

We report a case of a patient with history of alcohol abuse, treatment for hepatitis C and repeated strenuous physical activity who developed severe muscle pain and weakness during statin therapy. The symptoms persisted after discontinuation of the drug. The diagnosis of myopathy was made clinically and by electromyography. As his symptoms persisted a muscle biopsy was performed which showed inclusions consistent with hyaline inclusions. Hyaline inclusion myopathy is discussed in the context of this case with review of the literature.