56 results in The Cerebellum and its Disorders
2 - Neuroanatomy of the cerebellum
- from PART I - INTRODUCTION
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- By Fernand Colin, formerly, Department of Neurophysiology, Free University of Brussels, Belgium, Laurence Ris, Laboratory of Neurosciences, University of Mons-Hainaut, Belgium, Emile Godaux, Laboratory of Neurosciences, University of Mons-Hainaut, Belgium
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Summary
Introduction
In humans, the cerebellum overlies the posterior parts of the pons and medulla, occupying a large part of the posterior fossa. Structurally, the cerebellum consists of four pairs of deep nuclei, embedded in white matter, and is surrounded by a cortical mantle of gray matter. Unlike in the cerebral cortex, the cytoarchitecture of the cerebellum is remarkably uniform. This chapter reviews the fundamental aspects of the macroscopic and microscopic anatomy of the cerebellum, with emphasis on aspects of functional importance.
Evolution
Cartilaginous fish have a transversal eminence at the level of the octavo-lateral line system (Schnitzlein and Faucette, 1969). Even in the lower species, the afferent pathway is not limited to the VIIIth nerve. Trigeminal somesthetic projections and a genuine spinocerebellar tract are present. The cytoarchitecture of the cerebellum has evolved with few refinements.
In most teleosts and amphibians the cerebellum is a single leaf with lateral auricles (Fig. 2.1). In reptiles and birds, this original leaf duplicates in the rostral direction as a foliated fan-like structure, named the vermis because of its worm-like appearance. The posterior portions (the flocculus and paraflocculus) and their lateral expansions (the auricles) are the oldest phylogenetic part, making up the vestibulocerebellum. From birds to primates the number of folia increases significantly (22 in pigeons and 260 in humans). In parallel with this rostro-caudal expansion and the development of the cerebral cortex, there has been a continuous medio-lateral expansion of the hemispheres. The area of transition between the vermis and the hemispheres is called the intermediate region.
9 - The role of the cerebellum in affect and psychosis
- from PART III - CLINICAL SIGNS AND PATHOPHYSIOLOGICAL CORRELATIONS
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- By Jeremy D. Schmahmann, Cognitive/Behavioral Neurology Unit, Massachusetts General Hospital, Boston, USA
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Summary
Introduction
Contemporary investigations provide substantial clinical and experimental support for the hypothesis generated in the early part of the twentieth century that the cerebellum participates in a multitude of nervous system functions beyond that of motor control. Executive functions such as strategy formation, self-monitoring, reasoning, and working memory; visual–spatial learning and analysis; and linguistic processing, among other cognitive paradigms, have all been shown to require a cerebellar contribution both in normal subjects and in patients with acquired cerebellar lesions. The role of the cerebellum in the modulation of emotion also appears to be critically important in both health and disease states. The focus of this chapter, therefore, is directed toward the cerebellar contribution to behaviors associated with the experience and expression of emotion. It summarizes anatomic investigations demonstrating substrates that could sustain a cerebellar contribution to nonmotor as well as motor behaviors, and describes contemporary clinical studies that report changes in behavior, personality, and affect following lesions of the cerebellum. It includes data from morphologic and functional neuroimaging experiments that support a wider role of the cerebellum in nervous system function, and specifically that suggest an important contribution of the cerebellum to the regulation of affect and to psychosis. The chapter concludes with an examination of the dysmetria of thought hypothesis, and discusses how this theory harmonizes with models of cerebellar function proposed by other contemporary theorists.
34 - Dentatorubral-pallidoluysian atrophy
- from PART VIII - DOMINANTLY INHERITED PROGRESSIVE ATAXIAS
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- By Shoji Tsuji, Department of Neurology, Brain Research Institute, Niigata University, Japan
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Summary
Introduction
Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare, autosomal dominant, neurodegenerative disorder clinically characterized by various combinations of cerebellar ataxia, choreoathetosis, myoclonus, epilepsy, dementia, and psychiatric symptoms (MIM# 125370) (Naito and Oyanagi, 1982). The term DRPLA was originally used by Smith et al. to describe a neuropathological condition associated with severe neuronal loss, particularly in the dentatorubral and pallidoluysian systems of the central nervous system, in a sporadic case without a family history (Smith et al., 1958; Smith, 1975). The hereditary form of DRPLA was first described in 1972 by Naito and his colleagues. Since then, several reports on Japanese pedigrees with similar clinical presentations have been published (Oyanagi and Naito, 1977; Tanaka et al., 1977; Hirayama et al., 1981; Iizuka et al., 1984; Suzuki et al., 1985; Iizuka and Hirayama, 1986; Akashi et al., 1987; Iwabuchi, 1987; Iwabuchi et al., 1987; Naito et al., 1987), and DRPLA has been established as a distinct disease entity.
The gene for DRPLA was discovered by two independent Japanese groups in 1994, and an unstable CAG trinucleotide repeat expansion in the protein-coding region of this gene was found to be the causative mutation for DRPLA (Koide et al., 1994; Nagafuchi et al., 1994a).
7 - Clinical signs of cerebellar disorders
- from PART III - CLINICAL SIGNS AND PATHOPHYSIOLOGICAL CORRELATIONS
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- By Mario-Ubaldo Manto, Cerebellar Ataxias Unit, Free University of Brussels, Belgium
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Summary
Clinically relevant anatomy
The reader is referred to Chapter 2 of Part I for a detailed description of the anatomy of the cerebellum. Basically, the cerebellum is divided into ten lobules, which are shown in Fig. 7.1a. Two major fissures subdivide the cerebellum into three lobes: the anterior and posterior lobes are demarcated by a primary fissure, and a postero-lateral fissure separates the posterior lobe and the flocculonodular lobe (Fig. 7.1b; Gilman et al., 1981). This latter lobe is also called the vestibulocerebellum.
Mainly on the basis of phylogenetic studies, the cerebellum has been divided into archicerebellum, paleocerebellum and neocerebellum (Fig. 7.1c). There is an approximate relationship between this nomenclature and the projections of afferent pathways towards the cerebellum (Brodal, 1981). The term spinocerebellum is also used to designate paleocerebellum, because important projections are directed from the spinal cord towards the paleocerebellum, whereas the terms neocerebellum and pontocerebellum are used equally to designate this most recent part of cerebellum.
In clinical practice, there are basically three sagittal areas, including cortical and subcortical structures (Fig. 7.1d): a vermal zone in relation to the fastigial nucleus; a paravermal or intermediate zone associated with the interpositus nucleus; and a lateral zone whose Purkinje cells project to the dentate nucleus (Fig. 7.1d). Midline zone includes the vermis and flocculo-nodular lobe. Table 7.1 indicates main afferent and efferent pathways for each of these three sagittal zones. The three sagittal zones described here should not be confused with the sagittal bands of the cerebellum (see Chapter 2).
24 - Cerebellar grafts
- from PART VI - ADVANCES IN GRAFTS
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- By Lazaros C. Triarhou, Formerly, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, USA
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Summary
Introduction
The complex organization of the adult cerebellar network is a product of precisely timed and spatially coordinated developmental events (Miale and Sidman, 1961; Fujita, 1967; Larramendi, 1969; Altman, 1982; Goffinet, 1983; Altman and Bayer, 1985a,1985b). Cerebellar Purkinje cells are generated in the cerebellar primordium around embryonic day (E) 12 and migrate to the surface before birth in the mouse (Miale and Sidman, 1961). Around postnatal day (P) 3, Purkinje cells start to disperse in a monolayer and soon afterwards they receive synaptic contacts from afferent axons. The advent of the interaction with migrating granule cells accelerates a profuse synaptogenesis with Purkinje cell dendrites, which grow into the characteristic Purkinje dendritic trees by P12 (Larramendi, 1969; Altman, 1982). Neurons of the deep cerebellar nuclei are generated about a day before Purkinje cells, Golgi cells toward the end of gestation, whereas stellate and basket cells are produced during the first postnatal week, and granule cells during the first two weeks of postnatal life (Miale and Sidman, 1961; Fujita, 1967; Altman, 1982).
Normally, only Purkinje cells project axons outside the cerebellar cortex toward the deep cerebellar nuclei (Eccles et al., 1967; Ito, 1984). All of the remaining cortical neurons are interneurons, functioning to modulate Purkinje cell activity. Purkinje cells are also modulated by afferent olivocerebellar climbing fibers (see also Chapter 2). Mossy fibers indirectly affect Purkinje cell activity through the mediation of the granule cell parallel fibers, which establish synapses on Purkinje dendrites. The axons of the deep nuclei neurons transmit impulses outside the cerebellum, toward postcerebellar targets that include the ventrolateral nucleus of the thalamus, the red nucleus, and the vestibular nuclei (Thach et al., 1992).
PART IV - SPORADIC DISEASES
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26 - Spinocerebellar ataxia type 1
- from PART VIII - DOMINANTLY INHERITED PROGRESSIVE ATAXIAS
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- By Xi Lin, Departments of Pediatrics, Neurology, Neuroscience, and Molecular and Human Genetics, Howard Hughes Medical Institute, Baylor College ofMedicine, Houston, Texas, USA, Harry T. Orr, Institute of Human Genetics, University of Minnesota, Minneapolis, USA, Huda Y. Zoghbi, Departments of Pediatrics, Neurology, Neuroscience, and Molecular and Human Genetics, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas, USA
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Introduction
Spinocerebellar ataxia type 1 (SCA1) is one of a complex group of autosomal dominant ataxias, which were first recognized as distinct from the recessive Friedreich's ataxia in 1893 by Marie. The clinicopathological presentations of these ataxias are extremely heterogeneous, with variable degrees of neurodegeneration in the cerebellum, spinal tracts, and brainstem. Thus, the classification of SCAs remained difficult and controversial until the 1990s, when the identification of distinct genes for several dominant ataxias allowed unequivocal genetic, if not clinical, differentiation (Orr and Zoghbi, 1996). SCA1 was one of the first neurogenetic diseases to be mapped to an autosome using classical linkage studies (Yakura et al., 1974; Jackson et al., 1977). The cloning of the SCA1 gene, the elucidation of a dynamic CAG trinucleotide repeat expansion as the mutational mechanism, and the establishment of cellular and animal models for this disorder have greatly advanced our understanding of the molecular and cellular mechanisms underlying SCA1 pathogenesis. These studies will undoubtedly provide the basis for developing effective therapeutics.
Clinical features
SCA1 usually strikes during the third or fourth decade of life, typically progressing over 10 to 15 years. In SCA1 families, the affected individuals in successive generations tend to have an earlier onset and more severe manifestations of the disease, a phenomenom referred to as anticipitation. Early onset in the first decade has been documented in such families (Schut, 1950; Zoghbi et al., 1988). The most salient clinical features of SCA1 include ataxia, dysarthria, and bulbar palsies. Other neurological abnormalities, such as extrapyramidal signs and peripheral neuropathy, often show extensive interfamilial and intrafamilial variability (Subramony and Vig, 1998; Zoghbi and Orr, 2000).
Preface
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- By Mario-Ubaldo Manto, Brussels, Massimo Pandolfo, Brussels
- Edited by Mario-Ubaldo Manto, University of Brussels, Massimo Pandolfo, Université de Montréal
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Summary
Our knowledge of cerebellar functions has increased exponentially during the last two decades. Powerful new neuroimaging techniques and the spectacular development of molecular biology are probably the most striking examples of developments that have completely changed the field.
We started the project that led to this book because we were convinced that the time was ripe for an updated, comprehensive text attempting to summarize this new knowledge and present it in a coherent, systematic fashion. In preparing this book, our aim was to present the current perspective on the functional roles of the cerebellum as well as on the clinical and pathophysiological aspects of cerebellar diseases. We wanted to provide a comprehensive review of the major advances of these last years.
The Cerebellum and its Disorders is divided into nine parts, each giving an overview of a particular area. In each chapter the latest discoveries are presented in the context of their clinical relevance. In Part I, the fundamental aspects of cerebellar structure and functions are covered. This part serves as the basis for those that follow. Part II addresses the main models of cerebellar function that have been proposed so far. Part III includes an overview of cerebellar symptoms and their pathophysiology, including the emerging concepts on the cognitive roles of the cerebellum and their clinical implications. Part IV addresses the broad spectrum of sporadic cerebellar disorders. Part V deals with the effect of toxic agents on the cerebellum. Part VI covers the growing area of cerebellar grafts. Part VII summarizes the neuropathology of cerebellar disorders. Parts VIII and IX are dedicated to the genetics of dominant and recessive cerebellar ataxias, respectively.
1 - Embryology of the cerebellum
- from PART I - INTRODUCTION
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- By Mario-Ubaldo Manto, Cerebellar Ataxias Unit, Free University of Brussels, Belgium
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Summary
The development of the cerebellum
Although cerebellum differentiates early during embryogenesis, it only reaches its final configuration several months after birth (Koop et al., 1986 ; Lechtenberg, 1993). The neural tube is initially composed of a pair of neural folds which will fuse in the midline dorsally. The embryonic neural groove closes to become the neural tube at four weeks of gestation. The fusion proceeds from the most rostral region to the most caudal. When the rostral neuropore closes, three brain vesicles can be identified: the forebrain, the midbrain, and the hindbrain (three-vesicle stage). The hindbrain is also called rhombencephalon. At five weeks, the forebrain and the hindbrain both subdivide (five-vesicle stage). The hindbrain is generating the metencephalon rostrally and the myelencephalon caudally. Metencephalon and myelencephalon are separated by the pontine flexure of rhombencephalon. Cerebellum was thought to originate exclusively from metencephalon, but it has been shown that caudal mesencephalon also participates in the genesis of the rostral parts of cerebellum. The superior vermis begins to be formed at about seven to eight weeks of gestation, and the fusion of the inferior vermis continues up to about 18 weeks. The superior rhombic lip and the adjacent parts proliferate to generate the rudiment of the cerebellum (Fig. 1.1A). The central cavity of rhombencephalon becomes the fourth ventricle. In the following weeks, cerebellar development is characterized macroscopically by an expansion in four directions: rostrally, caudally, dorsally, and laterally.
6 - Models of cerebellar function
- from PART II - THEORIES OF CEREBELLAR CONTROL
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- By Steve G. Massaquoi, Department of Electrical Engineering and Computer Science and Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, USA, Helge Topka, Department of Neurology, University of Tübingen, Germany
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Summary
Introduction
Especially because the circuitry of the cerebellum is strikingly uniform and has been relatively well characterized anatomically and physiologically, many investigators have been prompted to devise theories to explain its function. Over the centuries, many conceptions of cerebellar function have been put forward, and it still cannot be said that a consensus view has been achieved. However, despite their seeming diversity, theories of cerebellar function have converged significantly. Useful summaries and reviews of the more historical ideas can be found in several places (Llinas, 1981; Pellionisz, 1985; Thach et al., 1992). In order to afford better quantitative analysis and to take advantage of our growing computer simulation capabilities, models of cerebellar function have been formulated increasingly in mathematical terms. This chapter focuses on these models and attempts to introduce them from a qualitative engineering perspective, with a bare mimimum of mathematical detail. Specifically, it reviews the basic character of cerebellar function, describing it as an adaptive modulator or ‘controller’ of movement, rather than as a principal driver of movement. It then describes the types of signal processing that are thought to occur in the cerebellum and the essential features of the neuronal architecture that would implement these proposed types of computation. The central theoretical principles of controller design that are used to understand and evaluate cerebellar models are then outlined. Specifically, feedforward, feedback, internal model-based, and discontinuous control strategies are discussed. Finally, several specific mathematical models have been selected to highlight important concepts in the evolution of the quantitative thinking about the cerebellum.
20 - Endocrine disorders: clinical aspects
- from PART IV - SPORADIC DISEASES
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- By Mario-Ubaldo Manto, Cerebellar Ataxias Unit, Free University of Brussels, Belgium, Henry Zulewski, Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Harvard Medical School, Boston, USA
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Introduction
The main endocrine cause of cerebellar ataxia is hypothyroidism. The incidence of the sporadic congenital form of hypothyroidism is about 1 per 4000 births (Delange, 1996), but the percentage of patients presenting cerebellar defi- cits associated with congenital hypothyroidism has not been determined. In adults, the reported percentages of hypothyroid patients with ataxic gait vary according to series (Kudrjavcev, 1978), varying from 0.3% to 5%.
Subclinical hypothyroidism has a high prevalence in the general population, reaching a level of 5–10% (Cooper, 1991 Wiersinga, 1995 Samuels, 1998). Elderly women are particularly at risk (Samuels, 1998). The incidence of progression to clinical hypothyroidism has been estimated to be 5–15% per year. For subclinical hyperthyroidism, the prevalence is estimated to be 0.7–6.0% (Ross, 1996). Studies on the natural history of endogenous subclinical hyperthyroidism are limited to patients presenting autonomously functioning adenomas. Between 8.8% and 18% of patients develop thyrotoxicosis over a follow-up period of six to seven years. There are no epidemiological data concerning the incidence of cerebellar ataxia in subclinical hypothyroidism and subclinical hyperthyroidism. Recently, there have been several descriptions of cerebellar ataxia associated with Hashimoto's thyroiditis, but its incidence is also undetermined, partly because assessment of the prevalence of Hashimoto's thyroiditis is diffi- cult. Indeed, laboratory signs are found in 5–11% of the general population, but are not necessarily associated with clinical signs of thyroid dysfunction (Flynn et al., 1988 Kothbauer-Margreiter et al., 1996). In addition, studies reporting this association have included only small numbers of patients.
PART IX - RECESSIVE ATAXIAS
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23 - Other cerebellotoxic agents
- from PART V - TOXIC AGENTS
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- By Mario-Ubaldo Manto, Cerebellar Ataxias Unit, Jean Jacquy, Department of Neurology, Free University of Brussels, Belgium
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Summary
DRUGS
Anticonvulsants
Phenytoin
Clinical findings
Phenytoin is the anticonvulsant drug which is the most frequently implicated in drug-induced cerebellar ataxia. Toxicity develops either during chronic treatment or as a consequence of an acute overdose. Patients exhibit cerebellar signs ranging from a mild vestibulo-ocular cerebellar syndrome including nystagmus and ataxic gait, to a marked pancerebellar syndrome comprising nystagmus, ocular dysmetria, slurred speech, limb ataxia, and broadbased ataxic gait (Utterbock, 1958; Selhorst et al., 1972). In the case of chronic administration for epilepsy, the delay between initiation of treatment and onset of ataxic signs varies from several days to several years. The cerebellar syndrome may be completely reversible after reduction of doses or withdrawal of the drug, or can be irreversible. Most clinicians agree that patients exhibiting irreversible signs have a higher phenytoin serum level and a longer history of epilepsy than those with reversible signs (Munoz-Garcia et al., 1982). In addition, these patients were usually taking a greater number of drugs. In rare conditions, phenytoin-induced cerebellar ataxia may be associated with a peripheral neuropathy or a slight cognitive deterioration.
In the case of overt or silent cerebellar disease, patients are at risk of developing marked ataxia when phenytoin is administered. For instance, in hereditary myoclonus epilepsy, phenytoin worsens myoclonic jerks and generates severe ataxia.
Phenytoin is also toxic during the prenatal period. Indeed, pontocerebellar hypoplasia has been described following intrauterine exposure in humans (Gadisseaux et al., 1984; Squier et al., 1990).
21 - Alcohol toxicity in the cerebellum: fundamental aspects
- from PART V - TOXIC AGENTS
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- By Roberta Pentney, Department of Anatomy and Cell Biology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, USA
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Summary
Introduction
Abuse of alcohol and alcoholism are associated with a risk of toxic damage to the central nervous system (CNS), frequently accompanied by modified behavioral patterns, such as ataxia of the lower extremities associated with alcohol-induced cerebellar degeneration in humans. Most of what is known about alcohol toxicity has been inferred from the study of autopsied human tissues and of in-vitro and in-vivo tissue and animal models. A major advantage of well-characterized animal models is that in them the progress of particular diseases and associated behavioral dysfunction can be documented. The discussion in this chapter focuses primarily on the toxic actions of ethanol in an animal model and on our current understanding of the functional consequences of those actions.
The rodent cerebellum is illustrated schematically in Fig. 21.1. Basic similarities in the organization and synaptic circuitry of the cerebellum in all mammals make nonprimate mammalian species, especially rodents, excellent subjects for experimental studies of cerebellar structure and function. Toxic effects of ethanol on cerebellar structure and function have been studied extensively in rodents, and results from studies not considered here have been reviewed previously (see Hunt and Nixon, 1993).
Neuronal targets of ethanol
As illustrated in Fig. 21.1C–F, there are five major types of resident cerebellar neurons, but only two of these have figured prominently in studies of the effects of ethanol: the granule neurons, the most numerous neurons in the cerebellum, and the Purkinje neurons, the most spectacular neurons in the cerebellum. The discussion that follows focuses on these two cell types. The experimental effects of alcohol on the morphometry and function of these cerebellar cortical cells are summarized in Table 21.1.
38 - Ataxia telangiectasia and variants
- from PART IX - RECESSIVE ATAXIAS
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- By Susan Perlman, Department of Neurology, Jacques-Olivier Bay, Centre Jean Perrin, Department d'Oncologie Moléculaire, Clermont-Ferrand, France, Nancy Uhrhammer, Centre Jean Perrin, Department d'Oncologie Moléculaire, Clermont-Ferrand, France, Richard A. Gatti, Department of Pathology, VCLA School of Medicine, Los Angeles, California, USA
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Introduction
Ataxia-telangiectasia (A-T) is an autosomal recessive, multisystem disorder with early-onset cerebellar ataxia as its most common defining neurologic feature. The constellation of accompanying extraneural features aids in its clinical diagnosis and includes conjunctival and cutaneous telangiectases, elevated levels of serum alphafetoprotein (AFP), chromosome aberrations, immunodeficiency with recurrent sinopulmonary infection, cancer susceptibility, and radiation hypersensitivity. Since identification of the causative gene, ATM (for ataxia-telangiectasia mutated), on chromosome 11q22-q23 (Gatti et al., 1988;Uhrhammer et al., 1995; Lange et al., 1995; Savitsky et al., 1995), the molecular basis of certain aspects of the disease have become clearer, although others remain to be elucidated (Gatti et al., 1991; Gatti, 2001).
Clinicopathologic syndrome
The earliest reports of an early-onset, familial, progressive choreoathetosis with ocular telangiectases (Syllaba and Henner, 1926) and of an early-onset, progressive cerebellar degeneration with cutaneous telangiectasia (thought to be a variant neurocutaneous syndrome) (Louis-Bar, 1941) did not recognize this as a distinct entity until the seminal clinicopathological studies of Boder and Sedgwick (1957) and of Biemond (1957), calling attention to the absence of the thymus gland and the prominence of severe recurrent sinopulmonary infections, the main cause of death (47% in one series: Sedgwick and Boder, 1991). A rapid succession of case reports confirmed the clinical syndrome of ‘ataxia-telangiectasia’ and also the presence of lymphoreticular malignancy as the second most frequent cause of death (22% malignancy alone, 26% malignancy with infection) (Boder and Sedgwick, 1963). It has proven to be the most common recessively inherited cerebellar ataxia in children under five years of age, with a prevalence of 1/40000–1/100000 live births (Swift, 1985; Swift et al., 1986).
19 - Thyroid hormone and cerebellar development
- from PART IV - SPORADIC DISEASES
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- By Noriyuki Koibuchi, Department of Physiology, Gunma University School of Medicine, Maebashi, Japan
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Summary
The important role of thyroid hormone (l-triiodothyronine, T3 l-tetraiodothyronine, T4) in the growth and differentiation of many organs, including the central nervous system, is well known (Legrand, 1986 Oppenheimer and Schwartz, 1997). In particular, the development of the rodent cerebellum is severely affected by perinatal hypothyroidism (Legrand, 1979 Koibuchi and Chin, 1999). Although the mechanism of thyroid hormone action on cerebellar development is not fully understood, recent studies have provided new insights into its molecular mechanisms in this process.
Molecular mechanisms of thyroid hormone action: a general overview
Thyroid hormone exerts its major effect by binding to the nuclear thyroid hormone receptor, a ligand-regulated transcription factor (Chin and Yen, 1997), although thyroid hormone action at non-genomic sites such as mitochondria, plasma membrane, and cytoplasm has also been reported (Davis and Davis, 1997). Figure 19.1 shows the mechanism of thyroid hormone action at the nuclear level. Thyroid hormone receptor is bound to specific DNA sequences known as thyroid hormone-response elements. When thyroid hormone receptor binds to thyroid hormone response element, it interacts with retinoid X receptors to form heterodimers, which, in turn, bind to a number of coregulators such as corepressors and coactivators. The liganded thyroid hormone receptor/retinoid X receptor/ coregulator complex ultimately determines nuclear thyroid hormone action (Chin and Yen, 1997).
Nuclear thyroid hormone receptors are encoded by two genomic loci (alpha and beta). Each thyroid hormone receptor gene produces two variants as a result of alternative splicing and different promoter usage (Lazar, 1993). Thyroid hormone receptor alpha gene produces thyroid hormone receptor alpha1 and c-erbA alpha2, whereas thyroid hormone receptor beta gene produces thyroid hormone receptor beta1, and beta2 (Fig. 19.2).
13 - Cerebellar stroke
- from PART IV - SPORADIC DISEASES
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- By Serge Blecic, Service de Neurologie, l'Hôpital Erasme, Free University of Brussels, Belgium, Julien Bogousslavsky, Service de Neurologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
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Summary
Introduction
Before the advent of computed tomography (CT) and magnetic resonance imaging (MRI), descriptions of cerebellar infarctions were mainly based upon necropsy findings and neurosurgical reports (Amarenco, 1995). CT and MRI techniques have led to a comprehensive description of the clinical features and distribution of cerebellar strokes, allowing clinicians to make precise clinico-anatomic correlations before the death of the patient.
The cerebellum is supplied by three main arteries arising from the vertebrobasilar system: the two vertebral arteries and the basilar artery. The complex formed by the cerebellum, brainstem, and brain occipital areas receives about one-third of the cardiac output (Mettler, 1948). Because the cerebellum and brainstem are supplied by the same arteries, they are frequently damaged together when artery occlusion occurs. Stroke in the territory of cerebellar arteries may be life threatening. However, edematous stroke in the cerebellum may have a relatively good functional outcome if emergency surgery is performed. Therefore, early recognition of the clinical pictures of cerebellar stroke is of the utmost importance.
Vascularization of cerebellum
Vertebrobasilar system
The vertebral artery is divided into four segments. The first segment (V1) courses directly from its origin (the subclavian artery) to the transverse foramen of C6. The second segment (V2) is within the transverse foramen from C6 to C2–C1. Usually, the third segment (V3) begins at the transverse foramen of C2 and emerges on the surface of the costo-transverse foramen of the atlas. It passes behind the posterior arch of C1 and is then located between the atlas and the occiput.
Frontmatter
- Edited by Mario-Ubaldo Manto, University of Brussels, Massimo Pandolfo, Université de Montréal
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- Book:
- The Cerebellum and its Disorders
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- 06 July 2010
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- 15 November 2001, pp i-iv
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PART VIII - DOMINANTLY INHERITED PROGRESSIVE ATAXIAS
- Edited by Mario-Ubaldo Manto, University of Brussels, Massimo Pandolfo, Université de Montréal
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- Book:
- The Cerebellum and its Disorders
- Published online:
- 06 July 2010
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- 15 November 2001, pp 407-408
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36 - Friedreich's ataxia
- from PART IX - RECESSIVE ATAXIAS
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- By Massimo Pandolfo, Service de Neurologie, l'Hôpital Erasme, Free University of Brussels, Belgium
- Edited by Mario-Ubaldo Manto, University of Brussels, Massimo Pandolfo, Université de Montréal
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- Book:
- The Cerebellum and its Disorders
- Published online:
- 06 July 2010
- Print publication:
- 15 November 2001, pp 505-518
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Summary
Introduction
In 1863, Nicholaus Friedreich, Professor of Medicine in Heidelberg, Germany, wrote three articles about a ‘degenerative atrophy of the posterior columns of the spinal cord’ causing progressive ataxia, sensory loss, and muscle weakness (Friedreich, 1863a, 1863b, 1863c). It could strike several siblings with normal, unaffected parents. Friedreich reported additional cases in 1876 and 1877. Charcot suspected for some time that Friedreich had described a form of tabes, but eventually he recognized that it was a new disease entity. Brousse (1882) was the first to use the name ‘Friedreich ataxia.’ After a few years, Ladame (1890) reported more than 100 cases. In the years that followed, more and more descriptions of inherited degenerative diseases causing ataxia were published. Many of these cases were noted to have some characteristics resembling Friedreich's ataxia, eventually blurring the definition of the disease (Bell and Carmichael, 1939). Only in the late 1970s did landmark studies establish the autosomal recessive pattern of inheritance (Geoffroy et al., 1976; Harding, 1981; Harding and Zilkha, 1981) and define rigorous diagnostic criteria (Geoffroy et al., 1976; Harding, 1981). It was realized that the disease shows variability in the clinical picture, sometimes with atypical presentations coexisting in the same family with typical cases (Winter et al., 1981; Filla et al., 1990, 1991; Muller-Felber et al., 1993). Specific variants, such as the so-called Acadian ataxia (Barbeau et al., 1984; Richter et al., 1996), were recognized in some ethnic groups.
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