pediagenosis: Nervous
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Showing posts with label Nervous. Show all posts
Showing posts with label Nervous. Show all posts

Wednesday, May 12, 2021

Neurochemical Disorders Affective Disorders

Neurochemical Disorders Affective Disorders


Neurochemical Disorders I: Affective Disorders
‘Affect’ refers to mood and affective disorders comprise of both a pathological lowering (depression) and elevation (mania) of mood. Bipolar affective disorder (manic-depression) refers to an oscillation between depression and mania. These conditions are not simply characterized by mood changes, however, and depression may comprise a number of characteristic features.
Both depression and mania may be accompanied by features of psychosis (delusions and hallucinations; see Chapter 58). The nature of the psychosis tends to be mood-congruent: in depression, the patient may believe that he or she is guilty of something or hear voices that are critical and unpleasant. Mania may be accompanied by grandiose delusions.

Neurochemical basis of depression

Depression
Aetiology
This is a common and mania disorder with a lifetime prevalence that has been estimated to be as high as 15%, with women affected more than men (approximately 2:1). It can occur in response to adverse circumstances (reactive depression), as well as for no apparent circumstantial reason (endogenous depression), although often the distinction between these two different types of depression is not that clear-cut. In both cases the depression probably arises through a combination of genetic and environmental factors.
Neurochemical Disorders Schizophrenia

Neurochemical Disorders Schizophrenia


Neurochemical Disorders II: Schizophrenia
Schizophrenia is a syndrome characterized by specific psychological manifestations, including auditory hallucinations, delusions, thought disorders and behavioural disturbances. It is a common disorder with a lifetime prevalence of 1% and an incidence of 2–4 new cases per year per 10 000 population. It is more common in men and typically presents early in life. Like all psychiatric disorders there is no diagnostic test for this condition, which is defined by the existence of key symptoms.
·       Positive symptoms:
      delusions: abnormal or irrational beliefs, held with great conviction and out of keeping with an individual’s sociocultural background;
      hallucinations: perceptions in the absence of stimuli.
·       Negative symptoms:
      blunting of mood, apparent apathy, lack of spontaneous speech and action;
      disordered speech.

Neurochemical Disorders II: Schizophrenia, delusions, hallucinations, The dopamine hypothesis of schizophrenia,

Aetiology
A distinction used to be made between type 1 and 2 schizophrenia but this has fallen out of fashion as it may relate more to the length of time that the individual has had the condition. The cause of schizophrenia is unknown but a number of aetiological factors have been suggested:

Monday, May 10, 2021

Neurochemical Disorders Anxiety

Neurochemical Disorders Anxiety


Neurochemical Disorders Anxiety
Anxiety is a normal emotional reaction to threatening or potentially threatening situations, and is accompanied by sympathetic overactivity. In anxiety disorders the patient experiences anxiety that is disproportionate to the stimulus, and sometimes in the absence of any obvious stimulus. There is no organic basis for anxiety disorders, the symptoms resulting from overactivity of the brain areas involved in ‘normal’ anxiety. Psychiatric disorders that occur without any known brain pathology are called neuroses.
Anxiety disorders are subdivided into four main types: generalized anxiety disorder, panic disorder, stress reactions and phobias. Many transmitters seem to be involved in the neural mechanisms of anxiety, the evidence being especially strong for γ-aminobutyric acid (GABA) and 5-hydroxytryptamine (5-HT). Because intravenous injections of cholecystokinin (CCK4) into humans cause the symptoms of panic it has been suggested that abnormalities in different transmitter systems might be involved in particular types of anxiety disorder. This remains to be seen.
Neurochemical Disorders III: Anxiety, Anxiety disorders,

There is some evidence for decreased GABA binding in the left temporal pole, an area concerned with experiencing and controlling fear and anxiety.
Neurodegenerative Disorders

Neurodegenerative Disorders


Neurodegenerative Disorders
Neurodegenerative disorders are those conditions in which the primary pathological event is a progressive loss of populations of CNS neurones over time. However, it is increasingly being recognized that most neurodegenerative disorders have an inflammatory component to them, and that inflammatory diseases of the central nervous system (CNS) (such as multiple sclerosis, see Chapter 62) will cause neuronal loss and degeneration.
Aetiology
There are a number of theories on the aetiology of neurodegenerative disorders, which may not be mutually exclusive. Of late there has been much work looking at the genetic risk factors for developing these disorders (see Chapter 63), and some common sets of genes are being found for them, e.g. genes involved with inflammation and immunity.

An infective disorder
Neuronal death with a glial reaction (gliosis) is commonly seen in infective disorders (typically viral) with inflammation in the CNS. However, in neurodegenerative disorders such a reaction is not seen, although the observation that human immunodeficiency virus (HIV) infection can cause a dementia has raised the possibility that some neurodegenerative disorders may be caused by a retroviral infection. Furthermore, the development of dementia with spongiform changes throughout the brain in response to the proliferation of abnormal prion proteins as occurs in Creutzfeldt–Jakob disease has further fuelled the debate on an infective aetiology in some neurodegenerative disorders (eg α-synuclein in PD).

Neurodegenerative Disorders, autoimmune process

An autoimmune process
Autoantibodies have been described in some neurodegenerative conditions, e.g. antibodies to calcium channels in motor neurone disease (MND). However, the absence of an inflammatory response would argue against this hypothesis, although neuronal degeneration with a minimal inflammatory infiltrate can be seen in the paraneoplastic syndromes (see Chapter 62) as well as the more recently described autoimmune disorders targeting ion channels and receptors.
Neurophysiological Disorders Epilepsy

Neurophysiological Disorders Epilepsy


Neurophysiological Disorders: Epilepsy
Definition and classification of epilepsy
Epilepsy represents a transitory disturbance of the functions of the brain that develops suddenly, ceases spontaneously and can be induced by a number of different provocations. It is the most prevalent serious neurological conditions, with a peak incidence in early childhood and in the elderly.
Patients may be classified according to whether:
·    the fit is generalized or partial (focal), i.e. remains within one small CNS site, e.g. temporal lobe;
·       there is an impairment of consciousness (if there is then it is termed complex);
·       the partial seizure causes secondary generalization.
Overall, 60–70% of all epileptics have no obvious cause for their seizures, and abouttwo-thirds of all patients stop having seizures within 2–5 years of their onset, usually in the context of taking medication.

Neurophysiological Disorders: Epilepsy, Definition and classification of epilepsy, Pathogenesis of epilepsy, Treatment of epilepsy, Mechanisms of action of anticonvulsants,

Pathogenesis of epilepsy
The aetiology of epilepsy is largely unknown, but much of the therapy used to treat this condition works by modifying either the balance between the inhibitory γ-aminobutyric acid (GABA) and excitatory glutamatergic networks within the brain or the repetitive firing potential of neurones.
Neuroimmunological Disorders

Neuroimmunological Disorders


Neuroimmunological Disorders
Central nervous system immunological network
The central nervous system (CNS) has relative immunological privilege compared with the peripheral nervous system (PNS) and most other parts of the body. The reasons for this are as follows:
Neuroimmunological Disorders, Acute disseminated encephalomyelitis, Other immunological diseases,
·   The blood–brain barrier (BBB) normally prevents most lymphocytes, macrophages and antibodies from entering the CNS (see Chapters 5 and 13).
    It has a very poorly developed lymphatic drainage system.
        There is only low level expression of major histocompatibility complex (MHC) antigens.
        There are no antigen presenting cells.

Wednesday, April 28, 2021

Neurogenetic Disorders

Neurogenetic Disorders


Neurogenetic Disorders
A large number of genetic disorders involve the nervous system, and some of these have pathology confined solely to this system. Recent advances in molecular genetics have meant that many diseases of the nervous system are being redefined by their underlying genetic defect.
Three major new developments have revolutionized the role of genetic factors in the evolution of neurological disease. First, genes encoded in the maternally inherited mitochondrial genome can cause neurological disorder; Second, a number of inherited neurological disorders have as their basis an expanded trinucleotide repeat (triplet repeat disorders); Third, the ability to use sophisticated genotyping of individual cases (exome sequencing) to find novel mutations is starting to yield new insights into diseases of the nervous system.

Neurogenetic Disorders

Disorders with gene deletions
Many different disorders within the nervous system result from the loss of a single gene or part thereof. For example, hereditary neuropathy with a liability to pressure palsies, in which the patient has a tendency to develop recurrent focal entrapment neuropathies in association with a large deletion on chromosome 17, which includes the gene coding for the peripheral myelin protein 22 (PMP 22).
Cerebrovascular Disease

Cerebrovascular Disease


Cerebrovascular Disease
Definition of stroke
A stroke or cerebrovascular accident (CVA) is typically an event of sudden onset (although it can occur over hours in some patients where a major vessel is slowly thrombosing). It is due to an interruption of blood supply to an area of the central nervous system (CNS) that causes irreversible loss of tissue at the core with a penumbra of compromised tissue around the area that may still be salvageable. If the disturbance in blood flow is temporary it causes a transient ischaemic attack or TIA. This is often a harbinger of a stroke. Stroke is common and its consequences depend on the vessel that has been occluded.

Cerebrovascular Disease

Investigation of stroke
·       History and examination
·       Computed tomography (CT)/magnetic resonance imaging (MRI)
·     Blood tests including full blood count, erythrocyte sedimentation rate, renal function, glucose and lipids
·   Electrocardiogram (ECG) which may be repeated and prolonged if a cardiac source for the stroke is suspected
Other investigation may include an ECHO cardiogram and imaging of the blood vessels and/or a CSF examination and this depends on the type of stroke (see Table 64.1).
Neuroradiological Anatomy

Neuroradiological Anatomy


Neuroradiological Anatomy
The ability to better delineate the anatomy of the central nervous system (CNS) in everyday neurological practice using modern imaging techniques has increased with improvements in technology and its widespread adoption in hospitals throughout the world. The major methods for imaging the nervous system are discussed in Chapter 53, but in general magnetic resonance imaging (MRI) is the best way to look at anatomical structure and its capacity to do this is dependent on the strength of the magnetic field that can be generated with the scanner. Most hospitals use a 1.5 Tesla (T) machine, but increasingly 3T machines are being used and for research purposes 7T scanners have been developed for human use. While the introduction of more sophisticated MRI and computed tomography (CT) sequences has enabled us to better define the vasculature of the brain, the gold standard is still formal angiography and indeed is the only way to visualize the blood vessels in the spine if this is needed, which is rare.
Neuroradiological Anatomy

MRI of the cerebral hemispheres
MRI of the cerebral hemispheres clearly reveals a large number of structures which are illustrated in Figures 65.1 to 65.5. In particular:
·    The different lobes of the brain can be clearly seen although the central sulcus in the human brain lies more posteriorly than one would imagine.
·     The basal ganglia structures can be seen in terms of the caudate, putamen and globus pallidum. The subthalamic nucleus and substantia nigra are harder to see, although the latter is becoming easier to recognize with newer MRI scanners.
·       The thalamus and the integrity of the ventricular system.
·       The major pathways running in the internal capsule and the corpus callosum.
·     The visual pathways can also be clearly seen up to the optic tracts. The optic radiations cannot be seen using standard imaging paradigms. Getting clear pictures of the optic pathway can be difficult and sometimes special sequences are needed to look at it in detail if there is a high suspicion of pathology.
·     Limbic system structures are much harder to see, given their location on the medial aspects of the temporal lobe. The hippocampi can usually be seen, although if volumetric loss in this structure is being sought (e.g. in cases of possible Alzheimer’s disease) then special imaging protocols should be used as it is easy to mistakenly see atrophy in this structure using standard scan sequences.
     The pituitary and its relationship to the visual pathways and hypothalamus can also be seen.
NEURONAL STRUCTURE

NEURONAL STRUCTURE


NEURONAL STRUCTURE
Neuronal structure reflects the functional characteristics of the individual neuron. Incoming information is projected to a neuron mainly through axonal terminations on the cell body and dendrites. These synapses are isolated and are protected by astrocytic processes. The dendrites usually make up the greatest surface area of the neuron. Some protrusions from dendritic branches (dendritic spines) are sites of specific axodendritic synapses. 
NEURONAL STRUCTURE

Each specific neuronal type has a characteristic dendritic branching pattern called the dendritic tree, or dendritic arborizations. The neuronal cell body varies from a few micrometers (µm) in diameter to more than 100 µm. The neuronal cytoplasm contains extensive rough endoplasmic reticulum (rough ER), reflecting the massive amount of protein synthesis necessary to maintain the neuron and its processes. The Golgi apparatus is involved in packaging potential signal molecules for transport and release. Large numbers of mitochondria are necessary to meet the huge energy demands of neurons, particularly those related to the maintenance of ion pumps and membrane potentials. Each neuron has a single (or occasionally no) axon, usually emerging from the cell body or occasionally from a dendrite (e.g., some hip- pocampal CA neurons). The cell body tapers to the axon at the axon hillock, followed by the initial segment of the axon, which contains the Na+ channels, the first site where action potentials are initiated. The axon extends for a variable distance from the cell body (up to 1 m or more). An axon larger than 1 to 2 µm in diameter is insulated by a sheath of myelin provided by oligodendroglia in the central nervous system (CNS) or Schwann cells in the peripheral nervous system (PNS). An axon may branch into more than 500,000 axon terminals, and may terminate in a highly localized and circumscribed zone (e.g., primary somatosensory axon projections used for fine discriminative touch) or may branch to many disparate regions of the brain (e.g., noradrenergic axonal projections of the locus coeruleus). A neuron whose axon terminates at a distance from its cell body and dendritic tree is called a macroneuron or a Golgi type I neuron; a neuron whose axon terminates locally, close to its cell body and dendritic tree, is called a microneuron, a Golgi type II neuron, a local circuit neuron, or an interneuron. There is no typical neuron because each type of neuron has its own specialization. However, pyramidal cells and lower motor neurons are commonly used to portray a so-called typical neuron.
TYPES OF SYNAPSES

TYPES OF SYNAPSES


TYPES OF SYNAPSES
A synapse is a site where an arriving action potential, through excitation-secretion coupling involving Ca2+ influx, triggers the release of one or more neurotransmitters into the synaptic cleft (typically 20 µm across). 
TYPES OF SYNAPSES
The neurotransmitter acts on receptors on the target neuronal membrane, altering the membrane potential  from  its  resting state. These  postsynaptic potentials are called graded potentials. Most synapses carrying information toward a target neuron terminate as axodendritic or axosomatic synapses. Specialized synapses, such as reciprocal synapses or complex arrays of synaptic interactions, provide specific regulatory control over the excitability of their target neurons. Dendrodendritic synapses aid in the coordinated firing of groups of related neurons such as the phrenic nucleus neurons that cause contraction of the diaphragm.
NEURONAL CELL TYPES

NEURONAL CELL TYPES


NEURONAL CELL TYPES
Local interneurons and projection neurons demonstrate characteristic size, dendritic arborizations, and axonal projections. In the CNS (denoted by dashed lines), glial cells (astrocytes, microglia, oligodendroglia) provide support, protection, and maintenance of neurons. Schwann cells and satellite cells provide these functions in the PNS. 
NEURONAL CELL TYPES
The primary sensory neurons (blue) provide sensory transduction of incoming energy or stimuli into electrical signals that are carried into the CNS. The neuronal outflow from the CNS is motor (red) to skeletal muscle fibers via neuromuscular junctions, or is autonomic preganglionic (red) to autonomic ganglia, whose neurons innervate cardiac muscle, smooth muscle, secretory glands, metabolic cells, or cells of the immune system. Neurons other than primary sensory neurons, LMNs, and preganglionic autonomic neurons are located in the CNS in the brain (enclosed by upper dashed lines) or spinal cord (enclosed by lower dashed lines). Neurons and glia are not drawn to scale.

Wednesday, April 14, 2021

3D NEURONAL STRUCTURE AND NEUROHISTOLOGY

3D NEURONAL STRUCTURE AND NEUROHISTOLOGY


3D NEURONAL STRUCTURE AND NEUROHISTOLOGY
3D NEURONAL STRUCTURE AND NEUROHISTOLOGY
        A. Spinal cord lower motor neuron. Nissl substance (rough endoplasmic reticulum) stains purple. The nucleolus is stained in the clear nucleus. Cresyl violet stain.
B.Cerebellar Purkinje neurons. Large dendrites branch from the cell body. Intraneuronal neurofibrils and background neural processes (neuropil) stain densely. Silver stain.
GLIAL CELL TYPES

GLIAL CELL TYPES


GLIAL CELL TYPES
Astrocytes provide structural isolation of neurons and their synapses and provide ionic (K+) sequestration, trophic support, and support for growth and signaling functions to neurons. Oligodendroglia (oligodendrocytes) provide myelination of axons in the CNS.
ASTROCYTE BIOLOGY

ASTROCYTE BIOLOGY


ASTROCYTE BIOLOGY
Astrocytes are the most abundant glial cells in the CNS. They arise from neuroectoderm and are intimately associated with neural processes, synapses, vasculature, and the pial-glial membrane investing the CNS. Astrocytes in gray matter are called protoplasmic astrocytes, and in white matter they are called fibrous astrocytes.
MICROGLIAL BIOLOGY

MICROGLIAL BIOLOGY


MICROGLIAL BIOLOGY
MICROGLIAL BIOLOGY
Microglial cells are mesenchymal cells derived from yolk sac that come to reside in the CNS. They are a unique resident population with the capacity for self-renewal. Microglia provide constant surveillance of the local microenvironment, moving back and forth up to 1.5 µm/min. Microglial processes can grow and shrink up to 2-3 µm/min. They have a territory 15-30 µm wide, with little overlap with each other. Resting microglia have soma of 5-6 µm diameter, and activated microglia are ameboid in appearance, with soma of approximately 10 µm diameter.

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