Nervous System Pathology – Diseases & Treatments of CNS

In Pathology of the Nervous System – All pathological processes in the nervous system leading to the disorder of its activity begin with damage to the tissue elements of the nervous system, first of all – neurons (membranes, receptors, ion channels, second mediators, genetic apparatus). It is also important for the state of interneuronal relationships (structural and functional connections), developing both within individual nerve formations (nuclei, neural networks), and between them.

 

GENERAL ETIOLOGY – PATHOLOGY OF THE NERVOUS SYSTEM

According to Nervous System Pathology, The causes of damage to elements of the nervous system can be exogenous and endogenous.

  • Exogenous causes can be physical, chemical, biological, or psychogenic (eg, traumatic situations, fearful images, sounds, sensations).
  • Endogenous factors: impaired circulation of blood and cerebrospinal fluid in the brain, imbalance of biologically active substances or their effects (hormones, cytokines, neurotransmitters), hypoxia, excessive activation of SPOL, endocrine diseases, impaired thermal and water-electrolyte homeostasis of the body.

Risk factors of Etiology of Nervous System Pathology: intensity, duration, frequency, and frequency of exposure to the causative factor, as well as the state of the nervous system (determined by its genetic characteristics and previous structural and functional damage) and the blood-brain barrier (pathological permeability) at the time of the action of the pathogenic agent.

 

GENERAL PATHOGENESIS OF NERVOUS SYSTEM PATHOLOGY

The main links in the pathogenesis of most forms of pathology of the nervous system are damage to neurons, impaired interneuronal interactions, a disorder of the integrative activity of the nervous system.

Damage to neurons in Nervous System Pathology 

The mechanisms of neuronal damage can be specific and non-specific. 

  1. Nonspecific mechanisms are discussed in detail in Chapter 4 Cell Pathology. These include impaired energy supply, apoptosis of neurons, disorders of protein biosynthesis, autolysis of neuronal components, imbalance of ions and fluid, damage to membranes.
  2. Specific mechanisms. The pathogenetic basis of most forms of disorders of nervous activity is formed by separate or combined disorders of the metabolic processes of various neurotransmitters specific to the neuron. Specific mechanisms of neuronal damage include the following:
    1. disorders of the synthesis of neurotransmitters;
    2. disorders of axonal transport of neurotransmitters;
    3. disorders of neurotransmitter secretion;
    4. violations of the removal of the neurotransmitter;
    5. disorders of the interaction of a neurotransmitter with its receptors –Disorders of interneuronal interactions
    6. These violations are realized through the following mechanisms:
    7. Disorders of the physicochemical processes of intercellular interactions (disorders of electrogenesis, disorders of perception of excitation by neurons, disorders of axonal transport).
    8. Disorders of the forms of functional interaction of neurons: violation of the ratio of rigidly determined and stochastic (probabilistic-statistical) forms of response to stimulation.

Disorders of the integrative activity In Nervous System Pathology 

According to Pathology, Disorders of the integrative activity of the nervous system imply a disruption in the functioning of one or more links of the nervous system: afferent, central, and efferent. This leads to disturbances in the activity of the functional and physiological systems of the body, and in severe injuries – to their decay.


TYPICAL PATHOLOGICAL FORMS OF PATHOLOGY OF NERVOUS SYSTEM

All the variety of typical forms of disorders of the nervous system in Nervous System Pathology, function are subdivided according to three criteria:

  • According to the change in the intensity of influences, pathological enhancement and pathological weakening of neurogenic effects on tissues and organs are distinguished.
  • According to the violation of the adequacy of the response of the nervous system to the stimulus, one speaks of the development of phase states.
  • Disorders of movements, sensitivity, the tropism of target tissues, as well as disturbances of VND are distinguished according to the predominantly disturbed type of nervous activity.

 

According to Nervous System Pathology, The pathological decrease in nerve influences

The pathological weakening of nervous control on tissues and organs occurs when there are violations of the central or efferent links of the nervous system.

 

The reasons for typical Pathology of Nervous System

  • Organic damage to the central nervous system in Nervous System Pathology 
    • Mechanical trauma to the brain or spinal cord, as well as organ and tissue nerve formations.
    • Inflammatory processes (eg encephalitis, meningitis).
    • Tumors of the brain and spinal cord or their membranes.
    • Degenerative processes (for example, in amyotrophic lateral sclerosis, in Alzheimer’s disease, etc.).
    • Circulatory disorders (ischemia, venous hyperemia, stasis).
  • Functional disorders of nervous activity in Nervous System Pathology:
    • Reducing the intensity of the excitatory process (for example, during anesthesia).
    • Hyperactivation of the nuclei of the central nervous system, which has an inhibitory effect on other structures of the nervous system.
  • Disturbances in the efferent link of the nervous control system in Nervous System Pathology:
    • Traumatic interruption (partial or complete) of signal conduction.
    • Disorders of impulse conduction along axons or axonal transport.
    • Disorders of perception of nerve influences by target cells (for example, under conditions of hypoxia, ion imbalance, changes in the number and affinity of receptors for neurotransmitters).

 

Manifestations, The complex of the metabolic, neurotransmitter, and structural-functional changes in postsynaptic neurons, tissues, and organs arising with a significant decrease or loss of nervous control are called “denervation syndrome”.

 

Pathological intensification of nervous influences Causes – Nervous System Pathology 

Pathological amplification of neural influences on effector structures develops as a result of primary and secondary excessive increases in the level or duration of neuronal excitation.

  • The reasons for the primary excessive excitation of neurons in Nervous System Pathology:
    • An increase in the influx of excitatory afferentation (for example, under stress, painful irritation).
    • Prolongation of the action of excitatory neurotransmitters (for example, with an increased release of a neurotransmitter into the synaptic cleft, a decrease in the processes of its destruction or removal).
    • Increased sensitivity of neurons to excitatory signals (for example, as a result of an increase in the content of K + in the interstitium).
  • Reasons for a secondary excessive increase in the intensity or duration of excitation of neurons that were already in a state of increased activity in the Nervous System Pathology:
    • Deafferentation of nerve structures.
    • Decreased secretion of inhibitory neurotransmitters. The inhibitory mechanisms of the nervous system are very sensitive to pathogenic influences. In this regard, the “phenomenon of disinhibition” is one of the main mechanisms for the development of many disorders of nervous activity.

Manifestations, Hyperactivation of nerve structures can lead to the formation of “stagnant foci of excitation.” Their functioning is manifested by various neuropathological syndromes (for example, thalamic pain syndrome, phantom pain). The formation of such foci (for example, in the centers of the hypothalamus) can lead to severe disorders – arterial hypertension, polyphagia, gastric hypersecretion, cardiac arrhythmias, and others.

 

Phase states of Nervous system pathology

According to the Pathology of Nervous System, Phase states are responses inadequate in intensity or character (“quality”) to the parameters of the stimulus and the needs of the organism.

  • Reasons for the development of phase states:

    • Genetically determined pathological changes in the nervous system.
    • Acquired disorders of the structure and function of the nervous system (for example, in conditions of ischemia, tumor growth, encephalitis, intoxication).
  • Effects:

    • Loss of normal interneuronal relationships, functional assemblies of neurons or systems (functional decay of the nervous system).
    • Formation of pathological functional connections between neurons (“pathological integration”), new functional sets of neurons, and systems (formation of a “pathological system”).
  • Manifestations. The following main types of phase states are distinguished:

    • Equalizing – It is characterized by the same responses of nervous structures to influences of different intensities.
    • Medium irritants – It manifests itself as a response only to stimuli of medium intensity.
    • Paradoxical – It is characterized by a weak reaction or its absence to a strong stimulus, the preservation or strengthening of a reaction to weak stimuli.
    • Narcotic – It is manifested by a consistent loss of reactions to weak, and then to strong stimuli.
    • Brake – It is characterized by a lack of response to any stimulus.
    • Ultra paradoxical – It is manifested by a qualitative change in the ratio between the nature of the stimulus and the reaction it causes. In this state, negative reactions develop in response to positive stimuli and vice versa.

 

Neurogenic movement disorders or Pathology of the nervous system 

Neurogenic movement disorders are characterized by pathological changes in the number of movements, their pace, and coordination.

The following classes of neurogenic movement disorders are distinguished:

  1. Hypokinesia – limitation of the volume, number, and speed of voluntary movements.
  2. Hyperkinesia – an increase in the volume and number of involuntary movements.
  3. Hypodynamia – decreased physical activity and muscle strength.
  4. Ataxia – impaired coordination of movements.

 

Hypokinesia

Limits on the volume, number, and speed of voluntary movements are classified according to several criteria.

  • Depending on the severity of movement disorders, paresis and paralysis are distinguished.
    • Paresis – a decrease in the amplitude, speed, strength, and number of voluntary movements.
    • Paralysis (plegia) – the complete absence of voluntary movements.
  • Depending on the prevalence (scale) of movement disorders, different variants of plegia or paresis are distinguished.
    • Monoplegia (-paresis) – paralysis or paresis of one limb.
    • Paraplegia (-paresis) – paralysis or paresis of both arms or both legs.
    • Hemiplegia (-paresis) – paralysis or paresis of one half of the body.
    • Triplegia (-paresis) – paralysis or paresis of three limbs.
    • Tetraplegia (-paresis) – paralysis or paresis of all limbs.
  • Depending on the change in muscle tone, spastic, rigid, and flaccid forms of hypokinesia are distinguished.
    • Spastic – Increased muscle tone, usually of one group. It is observed with central paralysis and paresis.
    • Rigid – The tone of one or more antagonist muscle groups has been increased for a long time. It is observed when the extrapyramidal system is affected.
    • Lethargic – Decreased tone of paralyzed muscles. It develops with peripheral paresis and paralysis.
  • Depending on the predominantly affected nerve structures, central, peripheral, extrapyramidal, and myasthenic forms of hypokinesia are distinguished.
    • Central paralysis and paresis are caused by damage to the pyramidal neurons of the motor analyzer and their axons. Manifestations: hyperreflexia, muscle hypertension, pathological reflexes, clonuses, synkinesis.
    • Peripheral paralysis and paresis are caused by lesions of peripheral motor neurons and their axons. Manifestations: muscle hypotension, hypo or areflexia, hypo, or muscle atrophy.
    • Extrapyramidal paralysis and paresis develop when the extrapyramidal system is affected. Manifestations: muscle hypertension, muscle stiffness, postural reflexes, catalepsy.
    • Myasthenic hypokinesia is caused by impaired synaptic transmission in the neuromuscular synapses. Manifestations: muscle weakness (myasthenia gravis), rapid muscle fatigue.

 

Hyperkinesia

Increases in the volume and number of involuntary movements develop as a result of damage to neurons in various structures of the brain (extrapyramidal system, thalamus, subthalamic nucleus, the dentate nucleus of the cerebellum, red nucleus, cortex, and their communication systems). There are fast (convulsions, chorea, tremor, and tics) and slow hyperkinesis (athetosis and spastic torticollis).

 

Convulsions

Convulsions are sudden, paroxysmal, or constant involuntary muscle contractions of varying intensity, duration, and prevalence.

There are clonic, tonic, and mixed convulsions.

  • Clonic seizures – short-term and irregular contractions of individual muscle groups, following each other at relatively short intervals.
  • Tonic cramps are prolonged (up to several tens of seconds) muscle contractions, as a result of which the body or limbs “freeze” in various forced positions.

 

Ataxias

Ataxias are locomotor disorders characterized by impaired spatial and temporal coordination of voluntary movements. Ataxia develops when various structures are affected: the cerebellum, spinal cord, frontal cortex, midbrain, thalamus, labyrinth.

 

Sensitivity disorders of Nervous System Pathology

Neurogenic disturbances insensitivity, both “simple” (tactile, temperature, proprioceptive, painful) and complex (feelings of localization, discrimination, stereognosis) are caused by damage to the somatosensory analyzer.

Types of sensitivity disorders

Sensitivity disorders are classified according to several criteria.

  • Depending on the type of impaired sensitivity and the location of the sensitive nerve endings:
    • Contact types (for example, disorders of tactile, pain, temperature sensitivity).
    • Distant views (for example, disorders of the peripheral part of the visual, auditory, olfactory analyzers).
    • Violation of exteroceptor sensitivity (for example, due to damage to the receptors of the skin and mucous membranes).
    • Disorder of interoceptor sensitivity (for example, as a result of damage to visceroceptors).
  • Depending on the disturbance in the perception of the intensity of sensation:
    • Hypesthesia and anesthesia – decrease and complete loss of sensitivity or some of its varieties, respectively.
    • Hyperesthesia – increased sensitivity to stimulus.
    • Dysesthesia is a violation of the adequacy of sensation to the stimulus that caused it.

General mechanisms of sensitivity disorders

  • Receptor:
    • change in the threshold of receptor sensitivity: hypo- and hypersensitization of receptors;
    • change in the number of receptors (decreased, increased).
  • Conductor – inhibition or blockade of the impulse conduction.
  • Central – change in the sensitivity threshold of neurons and impairment of sensation formation.

 

PAIN – Nervous System Pathology

Pain is a special type of sensitivity that forms under the influence of a pathogenic stimulus. It is characterized by subjectively unpleasant sensations, as well as significant changes in the body, up to disturbances in its vital functions and even death.

The meaning of pain

Any pain has a signaling and pathogenic meaning.

  • The signal value of pain. The sensation of pain is caused by a variety of agents, but they are united by a common property – a real or potential danger of damaging the body. In this regard, the pain signal provides mobilization of the body for protection against the pathogenic agent and protective limitation of the function of the organ affected by the pain.
  • The pathogenic significance of pain. Pain is often a cause or a component of the pathogenesis of various diseases and painful conditions (for example, pain as a result of trauma can cause shock and potentiate its development; pain with inflammation of the nerve trunks causes an increase or decrease in blood pressure, impaired heart, and kidney function).

Distinguish between mechanisms of pain formation (nociceptive system) and mechanisms of pain control (antinociceptive system).

Clinical syndromes

There are several major neuropathic pain syndromes: thalamic pain, phantom pain, and causalgia. Neuropathic pain should be distinguished from somatic pain arising from damage to the skin, muscles, internal organs, and joints.

  • Thalamic pain (thalamic syndrome) develops when the nuclei of the thalamus are damaged or foci of pathological excitement are formed in them. Manifestations: transient episodes of severe polytopic pain; pain is accompanied by autonomic, motor, and psycho-emotional disorders.
  • Phantom pain develops when the central ends of nerves cut during amputation are irritated. Manifestations: pain in a missing part of the body; the intensity of painful sensations ranges from severe itching and burning to excruciating, intolerable sensations.
  • Causalgia is caused by a pathological increase in the sensitivity of nociceptors and the formation of a focus of increased excitation in different areas of the pain impulse. Manifestations: burning pain in the area of ​​damaged nerve trunks, which is provoked or intensified by various influences (touch, heat, cold).

 

Neurogenic trophic disorders

Within the framework of the concept of neurotrophic control, several possible mechanisms of its implementation are considered:

  • Changes in impulse activity in axons (AP frequency, intervals between them). It is assumed that the type of impulses has informational value.
  • Formation of specialized neurotrophic factors transported along with the processes of nerve cells, secreted into the synaptic cleft, and interacting with postsynaptic partners.
  • Changes in the level of functioning of the postsynaptic partner (the old idea of ​​organ atrophy from disuse).
  • Maintaining constant synaptic transmission – the state of innervation. The development of denervation syndrome after nerve damage or blockade of axonal transport is a serious consequence of a violation of this mechanism.

 

Neurodystrophic process

Violation of the trophic function of the nervous system is the pathogenetic basis of the neurodystrophic process.

The neurodystrophic process can occur both in peripheral organs and tissues and in the nervous system itself.

  • Typically, the neurodystrophic process develops in denervation syndrome. Significantly, denervation reduces the resistance of the denervated organ or tissue to damaging factors: infection, mechanical injury, temperature, and other influences.
  • Deafferentation. Neutrophic disorders develop with damage to the afferent structures of the nervous system. Thus, transection of the sensory nerve can lead to no less pronounced trophic disorders in the organ than its motor denervation.


Violations of HNA

One of the most common forms of pathology of the nervous system is neurosis. The term “neurosis” is used to refer to functional disorders of the nervous system – violations of the HNA. Neuroses are referred to as “diseases of civilization” and associate their widespread prevalence with the growing urbanization of the population, information overload, a decrease in the share of physical labor in the life of a modern person, the impact on him of unfavorable social factors, numerous psycho-traumatic situations.

In the clinical aspect, neurosis is a psychogenic state and acts either as an independent nosological form or as a pre-morbid condition preceding various somatic or mental illnesses.

It is believed that the cause of the neurosis is mental trauma. This leads to both functional disorders in the central nervous system and certain microstructural changes in the brain.

From a pathophysiological point of view, neurosis is a typical form of the pathology of the nervous system. It occurs as a result of overvoltage and breakdown of HNA under the influence of influences to which the nervous system is not able to adequately respond.

The pathogenetic basis of neuroses is constituted by disturbances in strength, mobility, and balance of the main nervous processes – excitation and inhibition.

Neuroses are characterized by:

  • disorders of HNA;
  • development of phase states in the nervous system;
  • neurogenic disorders of autonomic functions, movement, sensitivity, trophism;
  • the decrease in the body’s resistance to various endogenous and exogenous pathogenic agents.

 

Reproduction of neuroses in animals

Experimental reproduction of neuroses is based on a single principle: to set an unbearable task for an animal.

For this purpose, effects are used that cause overstrain and disruption of the processes of excitation or inhibition, as well as the collision of instincts of alternative biological significance. Modern approaches to the methods of experimental reproduction of neuroses in animals are aimed at the maximum approximation to the conditions of their occurrence in humans. These methods include:

  • Restriction of the “reflex-instinct of freedom” (for example, forcible fixation of the animal in the pen).
  • Violation of the natural daily diet or light rhythm associated with the change of day and night.
  • Changes in habitual herd-hierarchical or herd-sex relations (for example, in monkeys).
  • Preliminary authorization of the nervous system (for example, under the influence of chronic noise, ionizing radiation, isolation of the animal from its parents in early childhood).

 

ETIOLOGY OF NEUROSIS IN HUMAN IN MEDICINE

The neurosis is based on neurotic conflict, i.e. such an attitude of the individual to a specific situation, which makes it impossible and “unbearable” to make a rational decision.

  • Cause of neurosis: mental trauma of the person (for example, serious illness or loss of loved ones, work, or “academic” difficulties).
  • Conditions for the development of neurosis:
    • Biological: hereditary predisposition, gender (neurosis rarely occurs in men), age (neurosis often develops in puberty and climacteric periods), constitutional features of a person (asthenic are more prone to neuroses), past and current diseases that reduce the body’s resistance.
    • Social: features of professional activity (for example, information overload, the monotony of work operations), unfavorable marital status, unsatisfactory living conditions, peculiarities of sexual education, etc.
    • Psychogenic: personality traits, mental trauma in childhood.

 

The role of HNA features in the development of neuroses in Medicine

The same mental trauma often causes various disorders of the nervous processes in the higher parts of the nervous system. In this case, the type of HNA is of great importance.

  • Melancholic (a weak type of HNA) is most susceptible to neurotic disorders. Such people are characterized by the rapid exhaustion of the excitatory process, weakness of internal cortical inhibition, and passive reaction to stimulation. This predetermines the onset of neurosis with the development of inhibition and the formation of passive-defensive reactions.
  • Choleric (strong unbalanced type) – This type is distinguished by a strong excitatory process, weak cortical inhibition, and active reactions to stimuli. This leads to the development of an excitatory type of neurosis with the formation of active search reactions.
  • Phlegmatic (strong balanced inert type) – It is characterized by the development of neurosis with pathological mobility of nervous processes.
  • Sanguine (strong balanced mobile type) – The most resistant to the reproduction of neuroses due to its high resistance to various kinds of pathogenic agents.

 

TYPES OF NEUROSES IN NERVOUS SYSTEM PATHOLOGY

There is currently no generally accepted classification of neuroses. Traditionally, there are three groups of the most common forms of neuroses: obsessive-compulsive disorder, hysteria, neurasthenia.

  • The neurosis of obsessive states – ll types of obsessive states is characterized by a repetitive feeling of fear, fear (phobia) of something or someone: certain objects, activities, situations. Examples of similar disorders:
    • claustrophobia – fear of enclosed spaces;
    • agorophobia – fear of open spaces;
    • carcinophobia – fear of tumor diseases.

 

  • Hysterical neurosis. Hysteria is characterized by very variegated and variable symptoms. The symptoms of hysteria can be reduced to several groups of painful manifestations.
    • Inappropriate behavior – Patients are distinguished by increased effectivity, impressionability, suggestibility and self-hypnosis, instability of mood, forgetfulness.
    • Autonomic disorders (see below).
    • Movement disorders – With hysteria, convulsive seizures (without loss of consciousness), transient paresis, and paralysis may develop.
    • Sensory disturbances – Hysterical neurosis is often accompanied by transient blindness, deafness, loss of smell, taste, paresthesia.
    • Sexual abnormalities – (eg, impotence, decreased libido).
  • Neurasthenia is considered the most common form of neurosis. Manifestations:
    • Autonomic disorders (see below).
    • Increased excitability, fatigue, and exhaustion of the nervous system.
    • Disorders of attention, impaired concentration.
    • Decreased performance, lethargy.
    • Instability of mood, often – depression.
    • Sleep disorders (falling asleep, restless sleep, unpleasant dreams).
    • Sexual dysfunction (eg, decreased sex drive, impotence).

 

GENERAL MANIFESTATIONS OF NEUROSIS IN PATHOGENY

In the process of development of a neurotic state, there is a natural sequence of inclusion in the structure of neurosis of various systems and, as a consequence, the formation of general manifestations:

  • Inadequacy of autonomic reactions to the effect (for example, tachycardia, arrhythmia, shortness of breath, excessive sweating, redness or blanching of the skin and mucous membranes, hypo- and hypertensive reactions, sleep and appetite disturbances, a feeling of pain in the heart arising in response to an effect that the patient gives particular value).
  • Development of pathological sensorimotor reactions (for example, hypersensitivity to various external influences or changes in the body, fussiness, unnecessary movements, gestures, passing paresis and paralysis, facial expressions inadequate to the event).
  • Frequent affective reactions – a violent emotional response to an impact or situation (for example, anxiety, fear of death, emotional stress, sobbing, abuse).
  • Intellectual analysis of the disease state and decision-making on the form of behavior (development of compensation measures). They are aimed at overcoming the current situation and painful sensations.

The specified sequence of the formation of manifestations in the development of neuroses is revealed in most patients. It is essential that in ontogenesis the order of the inclusion of the body’s reactions to various influences has the same sequence: first, vegetative reactions are observed, and then sensorimotor, affective, and ideational reactions are included.

 

CONCEPT ABOUT “VEGETONEUROSIS”

One of the common, permanent, and early components of neurosis are vegetative disorders: various syndromes of dysfunction of internal organs and their physiological systems (blood circulation, respiration, digestion, reproductive, and others). They are the result of centrogenic disorders in the regulation of their activity of neurogenic genesis.

In the clinical literature, these disorders are designated by various terms: “neurocirculatory dystonia”, “vegetative neurosis”, “vegetative dystonia”, “vegetative-vascular dystonia” and many others. Neurotic conditions often precede somatic pathologies: coronary artery disease, hypertension, gastric ulcer, and duodenal ulcer, various endocrinopathies.