nervous system

Vegetative dysfunctions - general symptomatology, vegetative dystonias, postural/orthostatic and regional disorders

- Condition in which the autonomic nervous system does not work properly. This may affect the functioning of the heart, bladder, intestines, sweat glands, pupils, and blood vessels. - General symptomatology: 1. Psychical disorders- phobias, anxiety, aggression, tiredness, decrease of intellectual output, sleep disorders. 2. Circulatory disorders- ● Microcirculation: sudden redness or paleness of skin (flush), cyanosis or edematous manifestation without organic reasons. ● Systemic circulation: orthostatic hypotension, collapse, hypertension, paroxysmal cardiac arrhythmia (tachycardia, bradycardia, extra systole), angina pain. ● Cerebral circulation: vasomotor headache, vertigo, syncope, migraine. 3. Respiratory disturbances- respiratory dysrhythmias, hyperpnoea, tachypnoea, dysphonia, bronchospasms, neurogenic asthma. 4. Gastrointestinal disorders- dysphagia, hypomotility or hypermotility of bowels, spasms in stomach, neurogenic diarrhea, constipation, meteorism, insufficiency or spasms of sphincters (cardia, pylorus, rectum). 5. Urinary disorders- polyuria, anuria, urinary urgency, painful spasms of urinary sphincters. 6. Genital disorders- sy. of erectile dysfunction, menstruation disorders. 7. Secretory disorders- hyper/anhidrosis, hypo/hypersalivation, lactation disorders, change in composition of sweat, saliva or mucus in respiratory airways. 8. Disorders of regulation of body temperature- hyperthermia, feeling of cold, subfebrility. 9. Metabolism disturbance- cachexia, anorexia nervosa, acute hypoglycemic or hypoglycemic attacks. 10. Endocrine disorders- sexual hormonal dysfunction, thyroid & parathyroid disorders, disbalance in adrenal functions, pheochromocytoma. 11. Trophic disorders- atrophy and keratosis of skin, skin pigmentation disorders, loss of hair, demineralisation of skeleton. Disorders of blood and immune cells- disorders of thrombocyte aggregation, macrophage dysfunctions Common autonomic disorders: 2. Syndrome of orthostatic (postural) hypotension- ● Characteristics: fall of BP > 20/10 mmHg during sudden change of body position from sitting or lying position to standing position ,transient rise of HR > 30/min. ● Occurrence: both in women and men 20 - 50 y. ● Mechanism: failure of Sympatico tonic postural baroreflex. Orthostatic hypotension is caused primarily by gravity-induced blood pooling in the lower extremities, which in turn compromises venous return, resulting in decreased cardiac output and subsequent lowering of arterial pressure. Still, the blood pressure does not normally fall very much, because it immediately triggers a vasoconstriction (baroreceptor reflex), pressing the blood up into the body again. Therefore, a secondary factor that causes a greater than normal fall in blood pressure is often required (failure of postural baroreflex). ● Signs: sudden fainting or fall, paleness in face, vertigo and titubations - loss of balance, headache, tiredness. ● Etiology: ○ Hereditary- congenital.(shy drager syndrome). ○ Metabolic defects in catecholamine synthesis. ○ Vascular alpha-adrenergic receptor hyposensitivity. 2. Shy drager syndrome= familial orthostatic hypotension- ● Characteristics: fall of BP > 20/10 mmHg during sudden change of body position from sitting or lying position to standing position ,transient rise of HR > 30/min. ● Etiology: progressive degeneration and atrophy of cortex and other regions in CNS. ● Mechanism: progressive disappearance of autonomic functions. ● Signs: - Attacks of severe postural hypotension - syncope. - Parkinsonism, cerebellar ataxia, central sleep apnoea, tremors, slow movement. - Other autonomic dysfunction (anhidrosis, erectile dysfunction, dysuria, disorders of peristalsis). 3. Syndrome of postural tachycardia (POTS- postural orthostatic tachycardia syndrome)- ● Characteristics: without postural hypotension- change of BP < 20/10 mmHg. Rise of HR > 30/min and plasmatic level of norepinephrine 600 pg/ml during longer standing. ● Occurrence: young women < 35. (F: M = 4:1). ● Mechanism: permanently increased basal sympathicotonia. ● Etiology: - Preceding viral infection. - Cardiac beta-adrenergic receptor hypersensitivity. - Loss of cardiac baroreflex sensitivity. - Autoimmune: Ab against alpha-3 nicotinic receptor in ganglia. ● Signs: palpitations, weakness, fainting, redness and swelling of lower extremities, scotomas, tremor, headache, tiredness during long duration standing.

Dementia syndrome - causes, classification

- Syndrome in which there is deterioration in memory, thinking, behavior and the ability to perform everyday activities. - Causes of dementia = classification based on cause: 1. Neurodegenerative disease: ● Familial Alzheimer's disease. ● Lewy body disease: ○ Dementia with lewy bodies. ○ Dementia in parkinson's disease. ● Frontotemporal degeneration: (Plaques : Tau , TPD-43 , FUS) ○ Frontotemporal dementia. ○ Huntington disease. ○ Pick's disease. 2. Infections: ● Human prion diseases. ○ Creutzfeldt jakob disease. ○ Fatal familial insomnia. ○ Gerstmann-Sträussler-Scheinker syndrome. ● HIV. ● Syphilis. ● Herpes encephalitis. 3. Metabolic diseases: ● Thyroid disorders. ● Wilson's disease (genetic- copper build up in the body). ● Hepatic failure. ● Renal failure. ● Chronic hypovitaminosis (B1,B3,B6,B12). 4. Trauma: ● Repeated head trauma. 5. Toxic: ● Wernicke-korsakoff syndrome- B1 deficiency + alcohol abuse. ● Heavy metals. 6. Cerebrovascular diseases: ● Binswanger's disease- caused by widespread, microscopic areas of damage to the deep layers of white matter in the brain. The damage is the result of the thickening and narrowing (atherosclerosis) of arteries that feed the subcortical areas of the brain. ● Amyloid angiopathy- amyloid deposits form in the walls of the blood vessels of the central nervous system.

Disorders of higher neural functions - agnosia,

Agnosia: - Inability to process sensory information. Often there is a loss of ability to recognize objects, persons, sounds, shapes, or smells while the specific sense is not defective nor is there any significant memory loss. 1. Tactile (astereognosia) - false identification of things by touch, damaged Parietal association cortex. ● Amorphognosia - shape, surface ● Ahylognosia - matter substance (wood, metal, liquid etc.). 2. Visual - misidentifications of objects by vision (not blindness !). ● Global- identification by touch, hearing and smelling preserved. Damaged temporal-occipital-parietal lobe borderline zone. ● Colors - loss of color concept (different from color blindness). Damaged Corpus callosum, occipital lobe. 3. Auditory - misidentification of meaningful sounds (not deafness!). Damages temporal-parietal borderline zone. ● Verbal - inability to recognize sounds of speech from other sounds. ● Amusia - inability to recognize melodies, music from other sounds. 4. Asomatognosia- loss of recognition or awareness of part of the body. Damage to parietal lobe. ● Autotopagnosia - wrong determination of different parts of the own body. (when asked to point on their eyes, point on other place). ● Acoenesthesia - misidentification of the own body. ● Prosopagnosia - wrong identification of human faces ● Anosognosia- unawareness of own illness or the deficits resulting from illness. 5. Sy. of sensory extinction - moderate form of combined tactile and visual agnosia (ignoring of perceptions from impaired part of the body). 6. Neglect syndrome - the one with the clock drawing - spatial neglect. (sensory extinction, autotopagnosia, visual agnosia).

Visual disturbances - overview: refractory disorders, defects of visual field; glaucoma, cataract

Alterations in vision can result from disorders of: - Eyelids and optic globe (conjunctivitis, cornea damage, uveitis) - Intraocular pressure (glaucoma) - Lens (cataract) - Vitreous humor and retina (retinopathy and macular degeneration) - Optic pathways and visual cortex - Extraocular muscles and eye movement Disorders of refractionRefraction = ability to focus an object on the retina, depends on size and shape of eyeball, cornea and focusing ability of the lens Individual differences in formation and growth of eyeball and cornea: - Eyeball too short -> focus point posterior to retina -> hyperopia (farsightedness) - Eyeball too long -> focus point anterior to retina -> myopia (nearsightedness) - Asymmetric bowing of cornea (or other defects) -> astigmatism Glaucoma - Mechanical obstruction of aqueous outflow - Primary: without evidence of preexisting ocular or systemic disease - Secondary: inflammation of eye, tumors, blood cells of hemorrhage - Degenerative changes, corneal edema, opacification -> impaired vision - Open-angle glaucoma: o Abnormality of trabecular meshwork that controls flow of aqueous humor o Risk: hypertension, type 2 DM, hyperthyroidism, corticosteroid drugso Usually chronic -> progressive optic nerve damage - Angle-closure glaucoma: o Occlusion of anterior chamber by iris o Cause: inherited anatomic defecto o Sudden, intermittent increase in intraocular pressure -> ocular pain, blurred vision (corneal edema), mydriasis, nausea and vomiting - Congenital and infantile glaucoma: anterior chamber retains fetal configuration, familial origin or sporadic - Lens opacity, impaired transmission of light to retina - Most common cause of age-related visual loss - Risks: age, genetics, diabetes, UVB radiation, heavy smoking, corticosteroid drugs, miotic ophthalmic drugs - Traumatic cataract: foreign body injury -> aqueous and vitreous humor enter lens -> cataract formation; exposure to heat; ionizing radiation - Congenital cataract: genetic defects, toxins, virus (rubella); mostly not progressive - Senile Cataract: bilateral, age-depending enlargement of lens -> compression and dehydration of old tissue -> lens proteins become more insoluble (increase of calcium, sodium, potassium) -> pigment accumulates in lens fibers -> loss of lens transparency - Clinical: depends on extent of opacity, if lesion is uni- or bilateral o Increasingly blurred vision, visual distortion o Decrease of visual acuity o Glare or abnormal presence of light in visual field Visual field defects - Result from damage to retina, optic pathways or visual cortex - Determination of location by visual field testing:

in. vascular dementia; Alzheimer's disease)

Alzheimer's disease: osmosis - Degenerative disease of cortex. - Most common cause of dementia. - Causes: ● Not completely known. Probably genetic + lifestyle + environmental. ● Most cases (95%) are sporadically and seen in elderly. - Risk factors: ● Genetics: few mutation that are associated with Alzheimer's disease: ○ ε4 allele of apolipoprotein E. ○ Presenilins 1 and 2 (transmembrane proteins)- in familial cases. ○ APP gene (amyloid precursor protein). ○ Down's syndrome- development of disease in ~40. ● Age- increase incidence with increased age (>85 ~ 50% will have dementia). ● Gender- Women>men. ● Family history. ● Low degree of education. ● Trauma. ● Depression. ● Estrogen. - Clinical features: ● Slow-onset memory loss (begins with short-term memory loss and progresses to long-term memory loss) and progressive disorientation. ● Loss of learned motor skills and language. ● Changes in behavior and personality. ● Patients become mute and bedridden; infection is a common cause of death. - Morphologic features: 1. Beta-amyloid plaques= senile plaques- ● Beta secretase cleaves the amyloid precursor protein (APP) instead of alpha secretase and form→ amyloid beta monomer→ monomers join together to form beta-amyloid plaques. ● Outside of neurons→ disrupt signaling and induce inflammation. ● Amyloid may also deposit around vessels, increasing the risk of hemorrhage. 2.. Neurofibrillary tangles- ● Tau protein is part of microtubules in cytoskeleton of neurons. ● Activation of kinase (unknown cause) lead to phosphorylation of Tau protein→ change shape→ stop supporting microtubules→ clumps with other Tau protein to form tangles. ● Intracellular aggregations!. These above changes lead to neuronal dysfunction and apoptosis→ brain atrophy with narrowing of gyri, widening of sulci and dilation of ventricles. Vascular dementia: - 2nd most common cause of dementia. - Multifocal infarction and injury due to: ● Hypertension. ● Atherosclerosis. ● Vasculitis. ● Cerebrovascular diseases- e.g. Binswanger's disease. - Vascular dementia results from conditions that damage your brain's blood vessels, reducing their ability to supply your brain with the amounts of nutrition and oxygen it needs to perform thought processes effectively. Pick's disease: - Degenerative disease of the frontal and temporal cortex. - Characterized by round aggregates of tau protein (Pick bodies) in neurons of the cortex. - Behavioral and language symptoms arise early; eventually progresses to dementia. - Unknown cause.

cerebri anterior, media, posterior syndrome

Anterior cerebral artery syndrome: condition whereby the blood supply from the anterior cerebral artery (ACA) is restricted, leading to a reduction of the function of the portions of the brain supplied by that vessel: the medial aspects of the frontal and parietal lobes, basal ganglia, anterior fornix and anterior corpus callosum. Symptoms: ● Hemiparesis or hemiplegia contralaterally - lower limb. ● Sensory deficits contralaterally - lower limb. ● Apraxia. ● Anosmia. Middle cerebral artery syndrome: same, damage to: the lateral aspects of frontal, temporal and parietal lobes, the corona radiata, globus pallidus, caudate and putamen.. Symptoms: ● Hemiparesis or hemiplegia contralaterally- face, upper and lower extremities. ● Sensory deficits contralaterally- face, upper and lower extremities. ● Ataxia- contralateral extremities. ● Broca's, wernicke's or global aphasia. ● Hemispatial neglect, apraxia, anosognosia. Posterior cerebral artery syndrome: damage to occipital lobe, the inferomedial temporal lobe, a large portion of the thalamus, and the upper brainstem and midbrain. Symptoms: ● Visual agnosia. ● Prosopagnosia. ● Contralateral hemiplegia. ● Oculomotor nerve palsy. ● Chorea, tremor, hemiballismus.

Speech disturbances:

Aphasia- an impairment of language, affecting the production or comprehension of speech and the ability to read or write. always due to injury to the brain (typically stroke). Main types: a. Expressive, nonfluent, motor, Broca's aphasia - partial loss of the ability to produce language although comprehension generally remains intact. ● Damage to Broca's area- posterior-inferior frontal lobe. ● Speech fragmented- slow labored speech. ● Word finding difficulty- seeking for common words, names, terms. ● Comprehension intact.- الفهم سليم ● Reading & writing skills little impaired. b. Receptive, sensory, Wernicke's aphasia - difficulty understanding written and spoken language. ● Damage to Wernicke's area- posterior-superior temporal lobe. ● Fluent speech but full of agrammatisms & neologisms- no meaning. ● Impaired comprehension of speech.. ● Reading & writing impaired. ● Anosognosia (do not realize the defect). ● Repeating words impaired. c. Global sensoric-motor - ● Frontal & temporal lobes (occlusion middle cerebral artery, internal carotid artery). ● Most severe. ● No fluent speech, no comprehension, can't repeat words, ● No reading and writing. d. Auditory sensoric- ● Temporal lobe damage along the paths between primary and secondary auditory cortex. ● speech is fluent الكلام بطلاقة, understanding is impaired. ● Similar to Wernicke's- but here repeating of words intact. e. Conductive- ● Damage to parietal lobe. ● Speech is fluent, comprehension intact.- ● Poor speech repetition. f. Anomia - ● Damage to superior temporal gyrus or angular gyrus. ● Mild form. ● Speech is fluent, problems with isolated usage of names, terms.

Neurodegenerative diseases - classification; genetic basis; inclusions diseases (taopaties, amyloidosis, and the like.)

Basic principles: ● Characterized by loss of neurons within the gray matter; often due to accumulation of protein which resist degradation and damages neurons ○ Protein aggregates may arise because of mutations that either ■ Alter the protein's conformation - misfolded proteins: eg. alpha-synuclein(parkinson's), Tau, beta-amyloid (alzheimer's), prions. ■ Disrupt the pathways involved clearance of the proteins: eg. Polyglutamine chains (huntington). ○ Regardless of how they arise, the protein aggregates typically are resistant to degradation, show aberrant localization within neurons, and elicit a stress response from the cell; in addition, they are often directly toxic to neurons. ● Degeneration of the cortex leads to dementia. ● Degeneration of the brainstem and basal ganglia leads to movement disorders. ● These diseases can be grouped by clinical presentation into: dementias, hypokinetic movement disorders (including forms of parkinsonism), hyperkinetic movement disorders, cerebellar ataxias, and motor neuron diseases. Genetic Basis: Many are caused by genetic mutations. In many of the different diseases, the mutated gene has a common feature: a repeat of the CAG nucleotide triplet. CAG encodes for the amino acid glutamine. A repeat of CAG results in a polyglutamine tract. Tauopathies - Tau proteins are proteins that stabilize microtubules. They are abundant in neurons of the central nervous system; Pathologies and dementias of the nervous system such as Alzheimer's disease and Parkinson's disease are associated with tau proteins that have become defective and no longer stabilize microtubules properly → Tau proteins are hyperphosphorylation → Tau Tangles → causing the protein to dissociate from microtubules and form aggregates in an insoluble form. Amyloidosis is a group of diseases in which abnormal protein, known as amyloid fibrils, builds up in tissue. Symptoms depend on the type and are often variable. Amyloid Beta (Aβ) - the main component of the amyloid plaques found in the brains of Alzheimer patients. The peptides derive from the amyloid precursor protein (APP), which is cleaved by beta secretase and gamma secretase to yield Aβ Alzheimer's disease - Amyloid-beta (extracellular Amyloid plaques)- Hyperphopshorylated Tau (Neurofibrillary tangles) Huntington's disease - Huntingtin (Neuronal inclusions) Parkinsons disease - α-synuclein (Lewy bodies)

Lesions of the spinal cord - transverse lesion (incl. spinal shock); Brown - Séquard hemisection syndrome Classification, by:

Classification, by: Level of injury (tetraplegia(quadriplegia), paraplegia) Complete injury (loss of motor and sensory nerves) or Incomplete injury (anterior cord, posterior cord, etc.) Acute or Progressive Etiology: Accidents, sports, violence, tumor, ischemia, congenital, demyelination:) Transverse lesions (level of injury) 1. C1-C4: Life threatening; "C3 C4 C5 keep the diaphragm alive" → acute respiratory failure 2. Lower cervical: a. Diaphragm maintained, inspiration affected; normocapnia; b. Tetraplegia(quadriplegia) c. Vegetative disability: disability of peripheral vasoconstriction, postural hypotension/slow response for hypotension conditions, triggers for reflexes are inhibited (like urinary bladder tension); loss of defecation and micturition. 3. Thoracic, Lumbar, Sacral: a. Ventilation maintained b. Paraplegia c. Impaired defecation and micturition Decreased bowel motility

Cerebrovascular stroke - classification, etiopathogenesis; Manifestation

Definition: the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. Classification + etiology: 1. Ischemic stroke osmosis - Regional ischemia to the brain that results in focal neurologic deficits lasting > 24 hours. ● If symptoms last < 24 hours, the event is termed a transient ischemic attack (TIA). - Types: 1. Thrombotic stroke: ● Due to rupture of an atherosclerotic plaque. ● Atherosclerosis usually develops at branch points (e.g. bifurcation of internal carotid and middle cerebral artery in the circle of Willis). 2. Embolic stroke: ● Due to thromboembolism. ● Most common source of embolism is the left sided heart (atrial fibrillation, foramen ovale), but can also originate from dislodged thrombus from ruptured atherosclerotic plaque. ● Usually involves the middle cerebral artery. 3. Lacunar stroke: ● Secondary to hyaline arteriosclerosis (proteins deposits in arterial wall), a complication of hypertension. ● Small cystic areas of infarction (looks like lacuna). - Pathogenesis: Blockage of blood supply→ no oxygen, no glucose→ buildup of sodium and calcium in the cell. Sodium→ draw water into the cell→ swell (=cytotoxic edema). Calcium→ reactive oxygen radicals→ damage lipids in mitochondria and lysosomes→ release of apoptosis inducing factors and degradative enzymes. - The damaged blood vessels results in break of blood brain barrier due to inflammation→ cerebral edema→ increased ICP→further hypoxic damage and Herniation. - Manifestations: depend on the damaged area of brain: ● Anterior/middle cerebral artery stroke- Numbness, sudden muscle weakness. ● Posterior cerebral artery- vision disturbances. ● Broca's/wernicke areas. ● Confusion, dizziness, weakness is usually in half of the body (contralateral to affected hemisphere). ● F- face- facial drooping, numbness, weakness, usually asymmetric. ● A- arms- one arm drift downward- weakness. ● S- speech- slurred, trouble speaking/comprehend speech. 2. Hemorrhagic stroke: - When artery is ruptured and bleed into the brain. - Types according bleeding site: 1. Intracerebral hemorrhagic stroke- ● Bleeding into brain parenchyma. ● Etiopathogenesis: hemorrhage→ less flow downstream + compression on nearby blood vessels, skull and brain tissue. - Hypertension that can lead to: ● Hyaline arteriosclerosis (deposition of proteins in the arterial wall and weakening them). ● Microaneurysms called charcot- bouchard of the lenticulostriate vessels from the anterior circle of willis that reach basal ganglia. - Arteriovenous malformations- can rupture. - Vasculitis. - Vascular tumors- hemangioma. - Amyloid angiopathy. ● Complications- increased ICP, hypoxia, herniation. ● Manifestation: same as ischemic. 2. Subarachnoid hemorrhagic stroke- discussed in previous topic. ● Hemorrhage→ less flow downstream + compression on nearby blood vessels, skull and brain tissue. ● Complications- hydrocephalus (blood irritate the meninges→ inflammation and scarring→ obstruction to CSF outflow→ accumulation in the ventricles).

Disorders of higher neural functions - dyspraxia,

Dyspraxia=apraxia - Disordered execution of motor programs. - Dyspraxia is a neurological disorder that impacts an individual's ability to plan and process motor tasks. General dyspraxias 1. Ideational apraxia ● In diffuse cortical damage. ● Purpose of movement is unrecognized. ● Plan and execution of movement are correct. ● Individual is unable to plan movements related to interaction with objects, because he has lost the perception of the object's purpose, the patient appears to have lost the knowledge or thought of what an object represents. ● E.g The patient would make errors such as combing their hair with the wrong side of the comb. 2. Ideomotor apraxia- ● In damage to inferior parietal lobule + superior temporal gyrus + frontal lobe. ● Purpose of movement is recognized. ● Plan of movement is missing (Difficult in planning separate activities and their order). ● E.g. Ideomotor apraxia impinges on one's ability to carry out common, familiar actions on command, such as waving goodbye. 3. Constructive apraxia- ● Damage to premotor area - frontal lobe. ● Intention, purpose and plan of movement are correct. Execution of movement is impaired. ● People are unable to perform tasks or movements even though they understand the task, are willing to complete it, and have the physical ability to perform the movements. ● E.g inability to correctly copy or draw an image. Specific dyspraxias: 1. Speech dyspraxia (motor program of voice muscles). 2. Mimic dyspraxia (disorder of articulation and facial mimic). 3. Gait apraxia (frontal ataxia). 4. Dyspraxia of corpus callosum (cross - coordination of limbs).

Epilepsy and other neurological conditions associated with seizures (generalized, focal) - etiopathogenesis

Epilepsy ● Recurring and unpredictable seizures of neurons synchronously active; sudden excitatory signals over and over = paroxysmal; ● Occur either from Too much excitation: NMDA are receptors for the excitatory neurotransmitter Glutamate (which normally, once bound to NMDA → Calcium influx); fast or long lasting activation of these receptors may lead to epilepsy. Too little inhibition: GABA receptors for inhibitory neurotransmitter GABA (which normally bound → Chloride influx); epilepsy patients have dysfunctional GABA receptors which are unable to cause inhibition. ● The seizures can be noticeable or subjective (unnoticeable) depending on type of nerves affected. ● Status Epilepticus - If seizures last over 5 minutes - medical emergency! ● Aura: sensation that occurs immediately before seizures, a strange sensation and dizziness ● Prodorma: Hours/days before seizure attack - headache and depression ● Focal and Generalized Seizures: ○ Focal (partial) Seizures typically affect only 1 local area of the brain - eg. 1 hemisphere - and divided into: ■ Seizures without impaired awareness (usually affecting a small area of the brain), and ■ Seizures with impaired awareness ○ Generalized Seizures involve both hemispheres; and include several subtypes: ■ Tonic seizures: Stiff muscle and flexed; falling backward ■ Atonic seizures: Relaxed/Floppy; falling forward ■ Clonic seizures: Convolutions ■ Tonic-Clonic seizures: Most common; Initiates with Tonic phase followed by Clonic phase ■ Myoclonic seizures: Short muscle twitches ■ Absence seizures:=petit mal "Spaced out" look; impaired awareness; unresponsive

Extrapyramidal disorders - hyperkinetic: classification, characteristics (incl. Huntington's disease)

Extrapyramidal Disorders = Disorders relating to Basal Ganglia (Caudate, putamen and globus pallidus) and Subthalamic Nucleus. Divided to: - Hyperkinetic-Hypotonic Disorders: Tremor, Dystonia, Myoclonus, Tic, Chorea, Hemiballismus a. Characteristics: Irregular, involuntary movements; Diminished muscle tone at rest; dyskinesias b. Dopamine > Ach (Dopamine initiates movements) Hypokinetic-Hypertonic Disorders (next topic): Parkinsonism, Stiff man syndrome, Psychomotor retardation a. Characteristics: muscle rigidity and an inability to produce movement b. Dopamine Huntington Disease (Hyperkinetic) ● Degeneration of GABAergic neurons in the caudate nucleus of the basal ganglia (normally inhibit movement) ○ Autosomal dominant disorder (chromosome 4) characterized by expanded trinucleotide repeats (CAG → codes for glutamine) in the Huntington gene (HTT); Long chains of Glutamine aggregate( >36CAG repeats)→ cause overexication → which increased Calcium Influx → cell Degeneration → death. ○ Further expansion of repeats during spermatogenesis leads to anticipation (earlier symptoms onset with each generation). ● Presents with chorea and athetosis that can progress to dementia and depression; average age at presentation is 40 years. *All previous symptoms are related to degeneration of neurons in the brain, and loss of brain tissue especially at the dorsal striatum (caudate & putamen). (eventually leading to enlargement of the lateral ventricles) ● Suicide is a common cause of death. - Dystonia * Hereditary/acquired * Cholinergic excess in striatum * - sustained irregular, involuntary contractures - Writer's cramp Generalized torsi spasm (mani) -Athetosis * Cerebral palsy, pregnancy * Loss of cholinergic & abundance of dopaminergic effects in striatum * irregular, twisting, turbulent, extra-movements of extremities Walking - interrupted -Hemiballism * Stroke in subthalami nucleus * Cortical escape from basal ganglia control *sudden, violent, purposeless, excessive, throwing movements ('Throwing a ball')

Hereditary Ataxias:

Friedreich's ataxia - Gene mutation causing abnormal GAA repeats in gene coding for 'frataxin' -> mitochondrial iron overload and impaired function. -Autosomal recessive - Gait unsteadiness beginning from 5-15 years - Followed by upper-extremity ataxia, dysarthria, paresis of lower extremities. - Decline of mental functions - Reflexes and vibration/position senses lost - Typical clubfoot, scoliosis and progressive cardiomyopathy. Spinocerebellar ataxias (SCAs) - Group of genetic disorders frequently caused by trinucleotide repeat expansions - Autosomal dominant - Varies among group - Most common: SCA type 3 (Machado-Joseph disease) Ataxia, parkinsonism, possibly dystonia, facial twitching, ophthalmoplegia Ataxia-Telangiectasia - Mutation in gene encoding protein kinase ATM responsible for DNA repair - Autosomal recessive - - Progressive neurological impairment - Cerebellar ataxia - Variable immunodeficiencies - X-Ray hypersensitivity - Ocular and cutaneous telangiectasia (vascular lesions) Predisposition to malignancies

Motor disorders - general neuropathophysiology; terminology, symptomatology

General Neuropathophysiology: A Motor process comprises of Phasic activity: and episodic contraction with energy demand;showing with EMG(Electromyography) change;mostly flexors Isotonic - Muscle tension/tone is stable, but length of muscle changes. Tonic Activity: sustained muscle resistance ; no showing EMG change; mostly extensors Isometric - Muscle tension/tone is changed, and muscle length is kept (Isometric vs Isotonic Image) Terminology ● Paralysis - loss of movement ability; also palsy ● Paresis - partial paralysis; weakened movement ○ Hemiparesis - of 1 side of the body ○ Quadriparesis - all 4 limbs ○ Monoparesis - weak limb ○ Paraparesis - of 2 lower limbs ● Hypokinesia - decreased muscle Contraction; Bradykinesia (seen in parkinson) ● Hyperkinesia - increased muscle Contraction activity; Dyskinesia (Chorea, athetosis, tic التشنجات اللاإرادية, ballism, tremor...) ● Hypotonic - low muscle Tone; Flaccidity ● Hypertonia - high muscle Tone; Spasticity; Rigidity- ● Ataxia/Dystaxia - lack of coordination of voluntary muscle movements ● Dyskinesia: disorders of involuntary muscle movements (Chorea, Tics, Athetosis, Ballism etc...) Symptomatology ● Tremor: rhythmical, involuntary and predictable twitching of body part ○ Resting tremor: when skeletal muscle is at rest; parkinsonism ○ Action Tremor: When in process of voluntary contraction of muscle ○ Postural Tremor: When skeletal muscle hold in position vs gravity ● Rigidity: an increase in muscle tone → resistance to passive movement ● Dystonia: twisting and repetitive movements or abnormal posture (due to repetitive muscle contractions) ● Chorea: Random, purposeless movements spreading from 1 body part to another ● Athetosis: Random, twisting, turbulent extra moments of extremities ● Ballism: High amplitude flailing of the limbs; throwing movements of entire limb ● Tics: stereotypic or patterned movements that is frequently preceded by an urge to move

Demyelinating disorders - classification, etiopathogenesis; Multiple sclerosis - forms, manifestations

General principles ● Myelin insulates axons, improving the speed and efficiency of conduction. ○ Oligodendrocytes myelinate the CNS. ○ Schwann cells myelinate the PNS. Demyelinating disorders are characterized by destruction of myelin or oligodendrocytes; axons are generally preserved Classification: 1. Hereditary/Congenital - Dysmyelination; examples: a. Krabbe disease (AR) - deficiency of galactosylceramidase → buildup of unmetabolized lipids → affects the growth of the nerve's myelin sheath b. Pelizaeus-merzbacher disease - mutation that causes hypomyelination 2. Degradation of Myelin - Demyelination; examples: a. Multiple Sclerosis - affects CNS Nerves b. Guillain-Barre - affects Peripheral nerves c. Waller Degeneration - when a nerve fiber is cut or crushed and the part of the axon distal to the injury degenerates Multiple Sclerosis (Hypersensitivity type lV) ● Autoimmune destruction of CNS myelin and oligodendrocytes (cells that produce the myelin) ○ Most common chronic CNS disease of young adults (20-30 years of age); more commonly seen in women ○ Associated with HLA-DR2 ● Mechanism: ○ T-cells cross the BBB → T-cells get activated by myelin → increased inflammatory response → letting more immune cells (eg. B-cells) to cross the BBB + mediators + auto-antibodies (from B-cells) damage directly the oligodendrocytes. ○ After some damage → T regulatory cells cease the autoimmune response → letting remyelination happen → every time this happens it forms plaque and sclerosis, not 100% healed → eventually after many times the damage will be irreversible. ● Forms: 1. Relapsing-Remitting MS (RRMS): most common 2. Secondary-Progressive MS (SPMS) 3. Primary-Progressive MS (PPMS) 4. Progressive-Relapsing MS (PRMS) ● Manifestations (depending on location of plaques): 1. Charcot's Neurologic Triad: a. Dysarthria - abnormal speech and vertigo (Brainstem plaques) b. Nystagmus & blurring- (optic nerve plaques) c. Intention Tremor: muscle weakness, spasms, tremor, ataxia) (muscle pathways plaques) 2. Internuclear ophthalmoplegia (medial longitudinal fasciculus) 3. Hemiparesis or unilateral loss of sensation (cerebral white matter, usually periventricular) 4. Bowel, bladder, and sexual dysfunction (autonomic nervous system) ● Diagnosis is made by MRI (reveals plaques) and lumbar puncture (reveals increased inflammation cells).

Auditory disorders - overview: perceptive and conductive disorders, tinnitus

Hearing is a special sensory function that incorporates 1. the sound-transmitting properties of the external ear canal 2. the eardrum that separates external and middle ear 3. the bony ossicles of the middle ear 4. the sensory receptors of the cochlea in the inner ear 5. the neural pathways of the vestibulocochlear and auditory nerve 6. the primary auditory and auditory association cortices Hearing loss can be caused by * Conductive disorders (auditory stimuli are not transmitted through the structures of outer/middle ears to sensory receptors in inner ear) * Perceptive disorders (affecting the inner ear, auditory nerve, or auditory pathways * Combination of conductive and sensorineural disorders Conductive Hearing loss: - Occurs when auditory stimuli are not adequately transmitted through the auditory canal, tympanic membrane, middle ear, or ossicle chain to the inner ear * Temporary causes: Impacted cerumen in outer ear or fluid in middle ear, foreign bodies like insects or cotton pieces * More permanent causes: Thickening of the bony structures (ossicles and oval window) of middle ear due to otosclerosis or Paget disease Perceptive hearing loss: - Sound waves are conducted to the inner ear, but abnormalities of cochlear apparatus, auditory nerve or central auditory pathways decrease or distort the transfer of information to the brain --> Commonly irreversible disorder Causes: * Genetic (mostly monogenetic AR), prelingual (hearing loss occurs before speech development) or postlingual (after speech development), can be part of a syndrome * Trauma/Tumours in inner ear (Acoustic neuromas - affecting 8th CN) * Vascular disorders with haemorrhage, or thrombosis of vessels supplying the inner ear * Infections (bacterial meningitis in children, untreated Otitis media) * Drugs * Environmentally induced - Exposure to excessively intense sound (> 120 dB) -> damage to organ of Corti Tinnitus: - the perception of abnormal ear or head noises, not produced by an external stimulus. - Tinnitus may be constant/intermittent, unilateral/bilateral Occurs when auditory stimuli are not adequately transmitted through the auditory canal, tympanic membrane, middle ear, or ossicle chain to the inner ear Sound waves are conducted to the inner ear, but abnormalities of cochlear apparatus, auditory nerve or central auditory pathways decrease or distort the transfer of information to the brain Commonly irreversible disorder - Objective tinnitus: sound is detected or potentially detectable by another observer (vascular abnormalities or neuromuscular disorders) - Subjective tinnitus: noise perception without noise stimulation of cochlea (abnormal firing of auditory receptors, cochlear neurotransmitter dysfunction, ionic dysbalance, central miss- processing Etiology: - Earwax, Medications (aspirin, also nicotine, caffeine) -> Transient tinnitus - Noise-induced hearing loss, Presbycusis (perceptive hearing loss occurring with age), hypertension, atherosclerosis, head injury, cochlear infection -> more persistent tinnitus

Extrapyramidal disorders - hypertonic: dystonia; parkinsonism (incl. Parkinson's disease)

Hypokinetic-Hypertonic Disorders : Parkinsonism, Stiff man syndrome, Psychomotor retardation Characteristics: muscle rigidity and an inability to produce movement Ach > Dopamine Parkinson Disease ● Degenerative loss of dopaminergic neurons in the substantia nigra (pars compacta) of the basal ganglia ○ Nigrostriatal pathway of basal ganglia uses dopamine to initiate movement. ● Common disorder related to aging; seen in 2% of older adults seen in 1% of people over >60 years old ● Unknown etiology; sometimes can be related to genetic abnormalities in ; PINK1 , PARKIN , ALPHA SYNUCLEIN genes . Rarely it can be caused by toxic impurity by MPTP (found in some drugs). ● Clinical features ('TRAP') ○ 1. Tremor: tremor at rest; disappears with movement ○ 2. Rigidity: cogwheel rigidity in the extremities ○ 3. Akinesia/bradykinesia: slowing of voluntary movement; expressionless face ○ 4. Postural instability and shuffling gait ● Histology reveals loss of pigmented neurons in the substantia nigra and round, eosinophilic inclusions of α-synuclein - Lewy bodies - in affected neurons. ● Dementia is a common feature of late disease. ○ Early-onset dementia is suggestive of Lewy body dementia - which is characterized by dementia, hallucinations and parkinsonian features; histology reveals cortical Lewy bodies. Stiff Man Syndrome: disorder of unclear cause, a disabling autoimmune CNS disorder characterized by progressive muscle rigidity and gait impairment with superimposed painful spasms that involve axial and limb musculature, triggered by heightened sensitivity to external stimuli. Treatment: Anticholinergics, botulinum toxin injection

Impaired intellect

Intellect= complex of psychic functions defining the person's abilities to dominate in certain area; inborn and acquired mental comprehensions, knowledge, solutions, experiences + usage of this knowledge (memory, abstract thought, analysis and synthesis, creativity, motivation, judgment, vocabulary) Intelligence - hereditary basis of intellect (individual abilities) 2 disorders: Mental retardation: ● Inconsistent or incomplete development of intellect. ● Characteristics: incomplete psychomotor development of speech, abstract thoughts, cogitation, reasoning, memories, learning disabilities incl motor skills.. ● Etiology: - Hereditary (phenylketonuria, fragile X chromosome). - Inborn - congenital (Down sy., Klinefelter sy., Turner sy.). - Perinatal (labor injury). - Postnatal (infection, intoxication). ● Grades: - Mental retardation - moronأحمق - IQ 70-80. - Mental deficiency (hypophrenia): ■ Light (debility) IQ 50-70 (mainly abstraction). ■ Mild (imbecility) IQ 35-49 (speech). ■ Severe (idiotism) IQ 20-34 (most qualities). ● Mental degeneration (dementia ● Characteristics: extinction of mental abilities (memory), practical skills, verbal communication, social habits, retrieval of new knowledge. ● Develops over time. ● Partial dementia vs. total demencia: - Heller' infantile dementia (dementia occurring in childhood). - Pseudodemencia - mental suppression -e.g. stressful part of life (violence). ● Causes: diffuse organic (structural), biochemical brain changes→ gray matter atrophy, frontal-parietal area. ● Manifestation: disorder of intellect + memory + emotion + action. 1. Disorders of attention→ learning, retention of data. 2. Disorientation in time and space, delayed thinking, loss of criticism confabulations, depressive mood, dysphoria, psychomotor apraxia. 3. Wasting of self-care practise, ethical limitations, abusiveness, irresponsibility, anosognosia. ● Disorders: dementia syndromes, korsakoff syndrome.

Intracranial pressure and herniation syndromes

Intracranial pressure: - The brain is enclosed in the rigid confines of the skull, or cranium, making it particularly susceptible to increases in ICP. - Increased ICP is a common pathway for brain injury from different types of insults and agents. Etiopathogenesis: - The cranial cavity contains: blood (10%), brain tissue (80%) and CSF ( 10%). - Each of these three volumes contributes to the ICP. (normally 8-15 mm Hg in the lateral ventricles). ● Increase in tissue volume- e.g. brain tumor, brain edema, bleeding into brain tissue. ● Increase in blood volume- e.g. vasodilation of cerebral vessels or obstruction of venous outflow (heart failure, venous sinus thrombosis). Increase in CSF volume- e.g. excess production (choroid plexus tumor, meningitis), decreased absorption or obstructed CSF circulation - Monro-Kellie hypothesis- The volumes of each of these components can vary slightly without causing marked changes in ICP. This is because small increases in the volume of one component can be compensated for by a decrease in the volume of one or both of the other two components. The tissue volume is relative restricted in ability to undergo change. - In the case of intracranial volumes and pressure, an increase in intracranial volume will have little, or no, effect on ICP as long as compliance is high. Factors that influence compliance include the amount of volume increase, the time frame for accommodation, and the size of the intracranial compartments. For example, small volume increments over long periods of time can be accommodated more easily than a comparable amount introduced over a short time. Consequences + complications: ● Hypoxia of brain tissue and infarction- ○ The cerebral perfusion pressure (CPP), which represents the difference between the mean arterial pressure (MAP) and the ICP (CPP = MAP − ICP), is the pressure gradient driving blood flow to the brain. ○ ↑ ICP→ ↓ CPP→ No driving force that drives the blood to flow into brain and supply it→ inadequate tissue perfusion→ hypoxia→ neuronal death. ●Herniation of the brain Symptoms: ● Decreased consciousness- one of the earliest signs. ● The continued cellular hypoxia leads to general neurologic deterioration. The level of consciousness may deteriorate from alertness through confusion, lethargy, obtundation, stupor, and coma. ● Headache, vomiting without nausea, ocular palsies, altered level of consciousness, back pain and papilledema. Herniation: - Displacement of brain tissue due to mass effect or increased intracranial pressure. - Types and possible consequences: ● Tonsillar herniation involves displacement of the cerebellar tonsils into the foramen magnum. ○ Compression انضغاط of the brain stem leads to cardiopulmonary arrest. ● Subfalcine herniation involves displacement of the cingulate gyrus under the falx cerebri. ○ Compression of the anterior cerebral artery leads to infarction. ● Uncal/transtentorial herniation involves displacement of the temporal lobe uncus under the tentorium cerebelli. ○ Compression of cranial nerve III leads to the eye moving "down and out" and a dilated pupil. ○ Compression of posterior cerebral artery leads to infarction of occipital lobe. ○ Rupture of the paramedian artery leads to Duret (brainstem) hemorrhage.

lesion and irritation sy.; dissociative syndromes;

Irritation syndromes: Hyperesthesia - high physical sensitivity - a non-noxious stimulus causes the sensation of pain Hyperalgesia - increased sensitivity to pain Paresthesia - feeling of tingling, pins and needles, of swelling of limb Dissociative syndrome - Dissociated sensory loss is a pattern of neurological damage caused by a lesion to a single tract in the spinal cord which involves selective loss of fine touch and proprioception without loss of pain and temperature, or vice versa. We include: Brown-squared Syndrome (will be discussed later), Tabetic Dissociation and Syringomyelia Dissociation 1. Tabetic Dissociation- Syndrome of posterior columns - Slow degeneration (specifically, demyelination) of the Dorsal Fasciculus (Gracilis + Cuneatus) - impaired touch and proprioception is ipsilateral - heat, pressure and pain is preserved - deep and discriminative sensitivity is impaired 2. Syringomyelia dissociation- Syndrome of anterolateral spinal fasciculus - A cyst or cavity forms within the spinal cord affecting Spinothalamic tract in Ventrolateral Fascicle - - impaired touch and proprioception is colateral - heat, pressure and pain is impaired - deep and discriminative sensitivity is preserved Irritation syndromes: • Hyperesthesia - heightened perception of touch (touch threshold decrease) • Hyperalgesia - allegedly increased sensitivity to painful stimuli (pain threshold increase) • Paresthesias - feeling of tingling, pins and needles, of swelling of limb, tight bands tied around the body as "water was tickling over the skin" -> disrupted pathways of finer and discriminative sensation (due to polyneuropathy, transient ischaemia of sensory cortex)

Disorders of higher nervous functions - memory disturbances,

Memory disturbances: - Memory is the ability to store and retrieve past data, events and images. ● Modified by: ● Consciousness (general and selective attentiveness, alertness) ● Interest (motivation, mood, reward, etc.). - Disorders of memory: 1. Amnesia: ● Classification: ○ Retrograde ( loss of memory-access to events that occurred, or information that was learned, before an injury or the onset of a disease). ○ Anterograde- loss of the ability to create new memories after the event that caused the amnesia, leading to a partial or complete inability to recall the recent past, while long-term memories from before the event remain intact. ○ Total- e.g. trauma. ○ Partial- e,g delirium. ● Causes: ○ Trauma (bilateral temporal damage, prefrontal lesions). ○ Hypoxia, ischaemia. ○ Avitaminosis B1 (Wernicke-Korsakoff sy.). ○ Epilepsia. ○ Malnutrition. ○ CO poisoning. ○ Commotio, contusion. ○ Degenerative brain diseases. 1. Specific disorders: a. Hypermnesia- condition of having an unusually vivid or elevated memory recall. ( ↑recall + ↑ sureness <-> ↓accuracy + ↓storage) In: mania, delirium, schizophrenia, paranoid- b. Hypomnesia- impaired memory. (↓recall + ↓sureness <-> ↑ storage) In: Drunkenness, brain trauma (commotio). c. Dysmnesia I. Paramnesia - impaired timing of memory traces. ● Ekmnesia (e.g. recent event recalled as far past event). ● Duplicity (e.g. division of one event into 2 different events/joining of two different events into 1 event). II. Allomnesia - distorted sureness (certainty) of memory traces. ● Cryptomnesia (hidden memory) - a forgotten memory returns without it being recognized as such by the subject, who believes it is something new and original. ● Illusions of memory - sureness that certain pictures, sounds or events happened before (illusiones deja vu); people remember events that never happened. III. Confabulations (false memories) - fantasy that has unconsciously replaced real facts in memory (e.g.abduction by aliens). IV. Memory hallucination- experience of memories to something that never existed. V. Pseudologia phantastica - the form of falsifying reality (not ordinary lying).

motor behavior during sleep

Motor behavior during sleep: Non-REM sleep (stages 1-4)- eye movement exist, motor movement- moderate activity REM sleep (20-25% of sleep)- associated with rapid eye movements, loss of muscle movements, and vivid dreaming. Motor systems that control body movements are inhibited, there is a loss of muscle movement and muscle tone. The result is an extraordinary set of paradoxes, in which people see things in their dreams, but cannot move. The mechanism is under debate.

Musculopathies - classification, symptoms (incl. Duchenne's dis.); Neuromuscular plate disorders (in. Myasthenia gravis)

Myopathies - disorders of the muscle fibers themselves Muscular Dystrophy - group of Hereditary muscle diseases characterized by progressive skeletal muscle weakness (and not disorder of the nerve supplying it) ● General signs and symptoms: Progressive muscular weakness, poor balance, walking difficulty, frequent falls, calf pain, limited range of motion, drooping eyelids, scoliosis. X-Linked Muscular Dystrophies (recessive) (OSMOSIS) ● Degenerative disorder characterized by muscle wasting and replacement of skeletal muscle by adipose tissue ● Due to mutations of dystrophin (DMD gene at chromosome 21): ○ Dystrophin is important for anchoring the muscle cytoskeleton to the extracellular matrix. ○ Mutations are often spontaneous; large gene size predisposes to high rate of mutation. ● Duchenne muscular dystrophy is due to deletion of dystrophin (nonsense mutation or frameshift;) ○ Presents as proximal muscle weakness at 1 year of age; rapidly progresses to involve distal muscles; ■ Calf pseudohypertrophy is a characteristic finding. ■ Serum creatinine kinase is elevated. ■ Clinically evident by age of 5, wheelchair bound by teenager age, death by early adulthood ○ Death results from cardiac or respiratory failure; myocardium is commonly involved. ● Becker muscular dystrophy is due to mutated dystrophin - misshapen مشوه protein; clinically results in milder disease (in 10-15 years of age) *Gower's sign: the child patient uses his/her hands to asses standing up Neuromuscular junction disorders Disorders of neuromuscular junction are usually caused by functional abnormalities (not morphological) Myasthenia Gravis (OSMOSIS) ● Type 2 hypersensetivety reaction, causing B cells to secrete Autoantibodies against the postsynaptic acetylcholine receptor at the neuromuscular junction (Type ll Hypersensitivity) → block Ach binding → no action potential. ○ These antibodies also trigger complement system involvement → inflammation → muscle destruction and lowering number of Ach receptors ● More commonly seen in women (20-30 years old) ,or in older men (60-70 Y.O) ● Clinical features ○ Muscle weakness that worsens with use and improves with rest; ○ Facies Myasthenia: ■ Ptosis: drooping of eyelids ■ Diplopia: double vision ■ Dysphagia: harder to swallow ■ Dysarthria: impaired speech ○ Affects breathing muscles - dyspnea ○ Symptoms improve with anticholinesterase agents. Lambert-Eaton Myasthenia Gravis ● Antibodies against presynaptic Voltage-gated calcium channels of the neuromuscular junction ● Arises as a paraneoplastic syndrome, most commonly due to small cell carcinoma of the lung ● Leads to impaired acetylcholine release ○ Firing of presynaptic calcium channels is required for acetylcholine release. ● Clinical features ○ Proximal muscle weakness that improves with use; eyes are usually spared. ○ Dry mouth, impotence; reduced or absent reflexes ○ Anticholinesterase agents do not improve symptoms. ○ Resolves with resection of the cancer

Paralysis, palsy - Upper and lower motor neuron sy. - etiopathogenesis; manifestations

Paralysis is defined as complete loss of strength in an affected muscle or muscle group - mostly due to nerve damage • Monoplegia (one limb), diplegia (same body region on both sides), hemiplegia (one side), paraplegia (both legs and trunk), quadriplegia (all four limbs and trunk)• Ascending paralysis: Guillain-Barre syndrome, descending paralysis: botulism • Spastic paralysis: hypertonia, flaccid paralysis: hypotoniaPalsy is a complete or partial muscle paralysis, often accompanied by loss of sensation and uncontrollable body movements or tremors o Bell's palsy: paralysis or severe weakness of facial muscles on one side o Cerebral palsy: group of neurological disorders appearing in childhood Upper motor neuron sy. Location: Corticospinal (bulbar) + subcorticospinal tract Etiology: Damage to motor cortex and along the pyramidal pathway (capsula interna, brainstem, spinal cord) Symptoms:Contralateral to site of damage Muscles:Normal Tonus: Hypertonia (spasticity) in groups of muscles - mostly late sign Reflexes:Hyperreflexia (brisk reflexes) Pathological reflexes: • Babinski• Chadock• Oppenheim • Gordon Lower motor neuron sy. Location: Motorneurons and axons Etiology: Damage to the nerve, plexus Damage to the anterior horn or ventral roots Trauma, ischemia Symptoms:Homolateral to site of damage General: • Weakness (palsy) in one or more muscles, groups Muscles:Atrophic Tonus:Hypotonia, atonia (flaccidity) Reflexes:Hyporeflexia, areflexia

Sleep disorders - classification; dyssomnia

Sleep= a condition of body and mind which typically recurs for several hours every night, in which the nervous system is inactive, the eyes closed, the postural muscles relaxed, and consciousness practically suspended. During sleep the brain in humans and other mammals undergoes a characteristic cycle of brain-wave activity that includes intervals of dreaming. Classification of sleep disorders: 1.Primary sleep disorders: Dyssomnias: عسر النوم: - Problems with sleep length, depth, quantity and quality of sleep. 1. Insomnia: ● Problems in falling asleep and/or maintaining sleep. ● 30 - 40% of adults. ● Can be acute/chronic, primary/secondary(fatal familial insomnia-prion!). ● Complications: lower performance, lower reaction time (vehicle collision), depression, poor immunity, hypertension, diabetes. 2. Hypersomnia: ● Oversleeping. ● Can be Idiopathic, Recurrent- Kleine-Levin syndrome (are sleep disorder characterized by persistent episodic hypersomnia and cognitive or mood changes- patients sleep 15 to 21 hours a day during episodes, jaws!) , Posttraumatic. 3. Narcolepsy: ● Excessive daytime attacks of sleepiness. ● Characterized also by: ○ Cataplexy (decrease or loss of muscle tone). ○ Sleep paralysis. 4. Respiratory dyssomnia: ● Sleep apnea. ○ Obstructive- complete or partial obstructions of the upper airway. ○ Central- the effort to breathe is diminished or absent and is usually associated with a reduction in blood oxygen saturation. Usually due to an instability in the body's feedback mechanisms that control respiration- In pure central sleep apnea, the brain's respiratory control centers are imbalanced during sleep and fail to give the signal to inhale, causing the individual to miss one or more cycles of breathing. ○ Mixed. 5. Circadian dyssomnia: ● Extrinsic type ○ Jet lag اختلاف التوقيت which affects people who travel across several time zones. ○ Shift work sleep disorder which affects people who work nights or rotating shifts. ● Intrinsic type ○ Delayed sleep phase disorder (DSPD)- characterized by a much later than normal timing of sleep onset and offset and a period of peak alertness in the middle of the night. ○ Advanced sleep phase disorder (ASPS)- characterized by difficulty staying awake in the evening and difficulty staying asleep in the morning. ○ Non-24-hour sleep-wake syndrome (Non-24), in which the affected individual's sleep occurs later and later each day, with the period of peak alertness also continuously moving around the clock from day to day. Parasomnias:

Somatosensitive disorders - neurophysiology

Somatosensory neurophysiology: ● Relays information about four major modalities: Touch, Temperature, Body position and Pain; Transmission of information over three types of neurons: 1. First-order neurons: from sensory receptors to dorsal horn neurons 2. Second-order neurons: transmitting information to the thalamus 3. Third-order neurons: Forward information from thalamus to sensory cortex ● Afferent pathways (fibers) ○ Alpha-delta fibers: thicker (myelinated); Faster (first-pain); mechanical and thermal stimuli; sharp localized pain ○ C-Fibers: Unmyelinated, slower (second pain) primary chemical stimulus (but also mechanical and thermal) deep pain ● Pain threshold: the point at which stimulus is perceived as pain ● Perceptual Dominance: intense pain at 1 location may cause an increase in the pain threshold ("hurts less") in another location ● Pain tolerance: how long enduring the pain until responding to it (tends to increase with age) ○ Decreased with repeated exposure, fatigue, and sleep deprivation ○ Increased with alcohol consumption, meds, hypnosis, warmth, distractions, faith ● Localization of pain: ● Noxa - The factor that causes pain ● Nociceptors - pain receptors, free nerve endings ● Stimuli: Mediators (Histamine, bradykinin, Prostaglandin); pH (acidosis); Changes in ion balance (Calcium, Potassium) ● Pain types: ○ Nociceptive: Nociceptive pain is a medical term used to describe the pain from physical damage or potential damage to the body.(stimulation of peripheral nerve) **There's no damage to the nerve itself** ■ Radicular: irritation of spinal roots (eg. herniation) ○ Neuropathic: damage or disease affecting any nerve-system related (dysfunction of nerves) ■ Causalgia: Causalgia is a chronic pain condition seen after the section (damage, cutting) of a nerve. It is characterized by a chronic burning pain and hypersensitivity in the area supplied by that nerve. ■ Neuralgia: Neuralgia is defined as an intense burning or stabbing pain caused by irritation of or damage to a nerve. The pain is usually brief but may be severe. It often feels as if it is shooting along the course of the affected nerve. ○ Phantom Pain: sensation of pain in amputated part of body

Sensory neuropathies:

Some abnormalities of sensation: • Hypoesthesia (Anesthesia) - general loss of sensory experiences • Synesthesia - location of sensation evoked by one stimulus to two different parts of body • Autotopagnosia - disordered location of stimuli on surface of body • Dermoalexia - inability to recognize numbers, letters or figures "written" on skin • Alloesthesia - instability of location of applied sensory stimuli in the body regions • Stereoagnosia - inability to recognize various objects by hand without direct visual inspection • Akinesthesia - inability to recognize movements of limbs or body segments; loss of sensory perception from dynamic kinaesthetic receptors or proprioceptors in joints, tendons. • Acoenesthesia - loss of self-identification of body as a whole Irritation syndromes: • Hyperesthesia - heightened perception of touch (touch threshold decrease) • Hyperalgesia - allegedly increased sensitivity to painful stimuli (pain threshold increase) • Paresthesias - feeling of tingling, pins and needles, of swelling of limb, tight bands tied around the body as "water was tickling over the skin" -> disrupted pathways of finer and discriminative sensation (due to polyneuropathy, transient ischaemia of sensory cortex)

Spinal shockand Brown - Séquard hemisection syndrome

Spinal Shock Injury (SCI) ● A sudden transversal damage of the spinal cord causing loss of sensation accompanied by motor paralysis with initial loss but gradual recovery of reflexes. (Peripheral neurons become temporarily unresponsive to brain stimuli) ● Immediately following SCI: Flaccid paralysis, temporary loss of reflexes, sensitivity perception and GIT impaired functions. ● Spinal shock lasts from days to weeks until recovery ● Recovery is from caudal to cranial way (going up) ● First reflex to recover: Bulbocavernosus reflex - Anal Sphincter reflex Neurogenic shock ● Can result from severe central nervous system damage (brain injury, cervical or high thoracic spinal cord) ● Results in decreased of sympathetic activity → imbalance of autonomic system --> increased parasympathetic activity (which not opposed by sympathetic) → Vasodilation, bradycardia and hypotension --> dangerous! Brown - Séquard hemisection syndrome ● Definition: Damage to ½ of the spinal cord, resulting in paralysis and loss of proprioception on the ipsilateral side of the injury and loss of pain and temperature sensations on the contralateral side of injury ● *Damages : -Descending Corticospinal tract , = motor paralysis , loss of proprioception (ipsilateral side) -Ascending Dorsal column tract , = impaired position, vibration and touch sensation (ipsilateral side) - Spinothalamic tract = loss of pain & temperature sensation(contralateral side) ● Causes: tumor, trauma, ischemia, infection, inflammatory diseases (TB, MS) ● Deficit of Pain and temperature: Contralateral ● Weakness and Deficit of vibration and Position: Ipsilateral

Subdural and subarachnoidal bleeding

Subdural hemorrhage: - Blood gathers between the inner layer of the dura mater and the arachnoid mater. - Usually resulting from tears in bridging veins which cross the subdural space. - Causes: trauma, Patients on anticoagulants (warfarin) or antiplatelets (aspirin). - Can be: ● Acute- most lethal→ increased intracranial pressure. ● Subacute. ● Chronic- more common in alcoholism and elderly (because brain atrophy causes the brain to shrink away from the dura and stretch fragile bridging veins). - Symptoms: ● Headache. ● Confusion. ● Change in behavior. ● Dizziness. ● Nausea and vomiting. ● Lethargy or excessive drowsiness. ● Weakness. ● Variable changes of consciousness. - Treatment: small→ monitoring, bigger→ catheterization and drainage, craniotomy (opening of skull and drainage). Subarachnoid hemorrhage: - Bleeding into the subarachnoid space (between the arachnoid membrane and the pia mater). - Causes: ● Most frequently (85%) due to rupture of a berry aneurysm. ○ Berry aneurysms are thin-walled saccular outpouchings that lack a media layer - increasing the risk for rupture. ○ Most frequently located in the anterior circle of Willis at branch points of the anterior communicating artery. ○ Associated with Marfan syndrome and autosomal dominant polycystic kidney disease. ● Trauma. ● Anticoagulated states- e.g. medications. ● Arteriovenous malformations. - Symptoms: ● Presents as a sudden headache with nuchal rigidity (neck stiffness). ● Vomiting. ● Decreased level of consciousness. ● Fever. ● Seizures. - Lumbar puncture shows xanthochromia (yellow hue due to bilirubin breakdown).

Spinal cord lesions - lateral and posterior columns sy.; Dissociation sy.; Amyotrophic lateral sclerosis;

Types and Classification of Spinal cord injury: 1. Tetraplegia (sometimes - referred as quadriplegia)-> loss of motor or sensory function (or both) after damage to cervical part -> - Resulting impairment of function in arms, trunk, legs and pelvic organs 2. Paraplegia -> loss of motor or sensory function (or both) after damage to thoracic, lumbar or sacral part -> arm functioning is preserved, but, depending on injury level, impaired functioning trunk, legs, pelvic organs 1. Complete injury = complete destruction of neural tissue and resulting UMN and LMN paralysis, no motor or sensory function preserved in sacral segments S4-S6 2. Incomplete injury = partial preservation of residual motor or sensory function below level of injury, better prognosis for return of function 1. Tabetic Dissociation- Syndrome of posterior columns - Slow degeneration (specifically, demyelination) of the Dorsal Fasciculus (Gracilis + Cuneatus) - impaired touch and proprioception is ipsilateral - heat, pressure and pain is preserved - deep and discriminative sensitivity is impaired 2. Syringomyelia dissociation- Syndrome of anterolateral spinal fasciculus - A cyst or cavity forms within the spinal cord affecting Spinothalamic tract in Ventrolateral Fascicle - - impaired touch and proprioception is colateral - heat, pressure and pain is impaired - deep and discriminative sensitivity is preserved Dissociative syndrome - Dissociated sensory loss is a pattern of neurological damage caused by a lesion to a single tract in the spinal cord which involves selective loss of fine touch and proprioception without loss of pain and temperature, or vice versa. We include: Brown-sequard Syndrome (will be discussed later), Tabic Dissociation and Syringomyelia Dissociation. Amyotrophic lateral sclerosis (ALS) ● Degenerative disorder of upper and lower motor neurons of the corticospinal tract ● Pathomechanism: motor neurons develop protein-rich inclusions (TPD-43, FUS) in their cell bodies and axons; probably due to defects in protein degradation. ○ Anterior motor horn degeneration leads to Lower Motor Neuron Syndrome: flaccid paralysis with muscle atrophy, fasciculation, weakness with decreased muscle tone, impaired reflexes, and negative Babinski sign. ○ Lateral corticospinal tract degeneration leads to Upper Motor Neuron Syndrome: spastic paralysis with hyperreflexia, increased muscle tone, and positive Babinski sign. ● Atrophy and weakness of hands is an early sign. ○ Lack of sensory impairment distinguishes ALS from syringomyelia. ● Most cases are sporadic, arising in middle age adults.