Neurology Part 2 Student 2024 PDF

Neurology: Part 2 “Resolve to be tender with the young, compassionate with the aged, sympathetic with the striving, and tolerant of the weak and the wrong. Sometime in life you will have been all of these.” George Washington Carver  Nomenclature Anterior = Ventral Posterior = Dorsal Afferent...

Neurology: Part 2 “Resolve to be tender with the young, compassionate with the aged, sympathetic with the striving, and tolerant of the weak and the wrong. Sometime in life you will have been all of these.” George Washington Carver  Nomenclature Anterior = Ventral Posterior = Dorsal Afferent = going to the brain (sensory neurons) Efferent = coming from the brain (motor neurons) Ganglion = group of cell bodies AP = action potential Transduction: conversion of stimulus to electrical impulse Transmission: propagation from the periphery to the CNS Perception: interpretation of impulse Neurological Lesion Localization A condition of the: Is referred to as: Brain Brainstem Cerebellum Spinal cord Myelopathy Nerve root Radiculopathy Nerve Neuropathy Neuromuscular junction Muscle Myopathy  Structure of the Spine Chapter: chapter 2 Back Book: Netter's Clinical Anatomy Author: John Hansen Publisher: Elsevier Date: 2023  Structure of the spinal cord Chapter: chapter 2 Back Book: Netter's Clinical Anatomy Author: John Hansen Publisher: Elsevier Date: 2023 Structure of spinal cord Chapter: chapter 2 Back Book: Netter's Clinical Anatomy Author: John Hansen Publisher: Elsevier Date: 2023  Describe the general structure of the spinal cord, the specialized enlargements at cervical and lumbar levels, and the locations of sensory neurons and pathways Trace the sequence of action potential generation and propagation for sensory neurons, and compare it to that of nonsensory neurons Identify the relay pathways of the dorsal column/medial lemniscus system and the spinothalamic tract. How many neurons are involved in conveying sensory information from the periphery to the cortex, Objectives: where conscious recognition of a sensation occurs? Part 1 What are the mediators that signal tissue damage and bring nociceptors to threshold for action potential generation? Explain the neuroanatomy and neurophysiology of altered pain perceptions due to sensitization (increased pain sensation such as allodynia and hyperalgesia), and pain modulation (decreased pain sensation due to activation of local spinal circuits and descending pathways from the brainstem) Identify the major steps in the special senses of vision and hearing, focusing on the initiation of sensation and its transmission by neuroanatomical pathways. Sensory Function Afferent neurons Bringing information to the CNS Respond to stimuli: touch, vibration, Sensing region temperature, and pain of nerve APs from (peripheral sensing region Signal enters the APs are generated in response to this axon) located in are relayed to CNS stimuli and then relayed to the CNS skin, muscle, or the cell body a joint Sensory relay occurs in the dorsal horn of the cord Ascending Tracks Sensory Pathway Dorsal Column: Large fiber, heavily myelinated nerves that are responsible for sensing light touch, vibration, and position sense Quick AP propagation Doral root ganglion-–first order neuron Enter dorsal column, moves upward to the brainstem sensory nuclei— second order neuron Second order neurons move up ward to the thalamus—third order neuron Sensory Exam: decreased light touch, vibration, and change in position sense Sensory Pathway Spinothalamic tract: Small fiber nerves with length dependent involvement. Responsible for pain sensing Enter lateral dorsal root and synapse in the dorsal horn Ascend to brainstem via spinothalamic tract Sensory exam: decreased pin prick and temp Thalamic neurons that receive sensory input project into the somatosensory cortex Question 1 A clinician asks a client to close their eyes and then touches the right forearm with the tip of a cotton applicator. The client indicates a dull sensation on the right forearm. What does this indicate? a. Ability to correctly discriminate location of sensory stimulus by the dorsal column/medial lemniscus system b. Inability to discriminate quality of sensory stimulus by thalamic neurons c. Ability to detect vibration by the sensory cortex d. Ability to correctly discriminate quality and location of sensory stimulus by the spinothalamic system Sensory Pathophysiology Neuropathy: result of damage to peripheral nerves Small fiber: length depended on involvement of the spinothalamic tract Large fiber: Distal > Proximal; Involvement of the dorsal column Mixed: pansensory Clinical Vignette 1 72-year-old female PMHx: T2DM x 10 years Hem. A1C: 8 CC: Increasing falls Exam: Ankle jerk absent bilaterally, decreased vibration and pinprick bilaterally D>P. Romberg positive Where is the pathology?​ Why is her Romberg positve?  Diabetic Neuropathy Chapter: Section 6 Peripheral Neuropathies Book: The Netter Collection of Medical Illustrations: Nervous System, Volume 7, Part II - Spinal Cord and Peripheral Motor and Sensory Systems Author: H. Royden Jones,Ted Burns,Michael J. Aminoff,Scott Pomeroy Publisher: Elsevier Date: 2013 Pain  Nociceptors (peripheral): Two groups of fibers: Aδ Myelinated axons; conduct at a rate of 5 to 30 m/sec Mechanosensitive nociceptors: respond to intense mechanical stimuli Mechanothermal nociceptors: respond to intense thermal stimuli C-fiber unmyelinated axons Unmyelinated axons; conduct at a much slower rate of 2 m/sec Polymodal nociceptors: respond to thermal, mechanical, and chemical stimuli Release glutamate at their synaptic targets Glutamate produces rapid synaptic excitation of second-order neurons May release substance P Substance P produces slower and longer- lasting excitation. Ascending Pain Pathway: Pain Modulation Primary Activation Direct activity of inflammatory mediators on the nociceptor Secondary Activation Release of substance P and the recruitment of the immune response Inflammatory mediators involved: Bradykinin Histamine Serotonin Arachidonic acid Nerve growth factor Neurophysiology of Pain: Nociception Nociceptors (first-order neurons): Peripheral sensory neurons, activated by tissue- damaging stimuli Make excitatory synaptic contacts with spinothalamic tract neurons. Spinothalamic tract neurons (second-order neurons): Located in the spinal cord dorsal horn Axons that project to the thalamus and brainstem reticular formation. Thalamocortical relay neurons (third-order neurons): Project to somatosensory cortex Recognition and localization of the painful input. Parallel pathways for the emotional and physical response Spinothalamic Tract Neurons: Recap Ascend to the brainstem and thalamus Ascend Transmit pain signals to the midbrain, pons, and medulla Brainstem relay neurons Activates the limbic structures: amygdala, insular cortex, and anterior cingulate cortex Cognitive -evaluative processing Brainstem and thalamic neurons Unique to the ascending pain pathway Third-order neurons project into the somatosensory cortex Terminate Recognition and localization of pain signal Question 2 Which of the following is not a stimulus to pain-detecting sensory endings (nociceptors)? a. Acetylcholine b. Bradykinin c. Histamine d. Prostaglandin Pain Pathway: Pain Modulation Periaqueductal gray (PAG) When activated produces analgesia Contains endogenous opioids (enkephalins, endorphins, and dynorphins) Inhibitory Reducing substance P and glutamate release Neurons project to the medulla and specifically target neurons containing norepinephrine or serotonin Serotonin and norepinephrine are released at the synapse in the dorsal horn Inhibits further APs Gate Theory of Pain Activation of low-threshold touch or mechanoreceptors associated with the Aß axons Nociceptive information through the spinal cord is moderated by simultaneous activation of low- threshold touch receptors For example, if you stub a toe, the natural and effective response is to rub the site of injury and the pain improves  Placebo Effect The placebo effect is a physiological response after the administration of a pharmacologically inert therapy Despite receiving an inactive therapy, the participants reported pain relief Analysis of the fMRI data showed that when the placebo was administered, parts of the brain involved in opioid transmission were activated: dorsolateral prefrontal cortex rostral cingulate cortex Hypothalamus PAG rostral ventral medulla Analgesia decreased after administration of naloxone indicating that our own endogenous opioids are responsible for this pain modulation Sensitization Peripheral: Local inflammatory mediators increasing the APs Hyperalgesia: severe pain from only slightly painful stimuli Centrally: Due to substance P and glutamate Excitability of the neurons in the dorsal horn following high levels of activity Enables subthreshold nociceptors to generate APs Allodynia occurs Pain from non-painful stimuli due to the overexcitability of second-order neurons This Photo by Unknown author is licensed under CC BY. Referred Pain Visceral pain signals reach the cord at the level associated with organ innervation Once signal reaches the cord, the pain is reflected as somatic pain Question 3 When a child bumps their head, the parent tells the child to “rub it.” This is an example of which of the following? a. Central sensitization b. Placebo effect c. Allodynia d. Gate theory of pain Pharmacological Modulation of Pain NSAIDS Inhibit the cyclooxygenase enzyme (COX), impairing the transformation of arachidonic acid into prostaglandins Opioids Modulate pain when bound to receptors Directly in the anterior horn—reducing substance P and nociceptive transmission PAG—descending modulatory inputs Nucleus accumbens—reward center Binding is thought to lead to tolerance, dependency, and substance use disorders Nonpharmacologic: Exercise, psychological therapies, mindfulness, multi-disciplinary rehab  Ascending Tracts Track Origin Fiber Size Function Crossing Termination Dorsal Column Sensory receptor Large Light touch, Ipsilateral Somatosensory proprioception, cortex vibration and two point discrimination Spinothalamic Sensory Receptor Small Pain and Contralateral: Somatosensory temperature inner arms and cortex sensing outer legs Parallel pathway that terminates in the limbic system  A 44-year-old female presents to clinic complaining of severe pain in her left side. She notes that the pain has been on and off for a few day but woke her up this morning Clinical due to extreme discomfort. She notes a minimal rash that "looks like heat." She denies any other symptoms Vignette 2 PMHx: Multiple sclerosis on fingolimod. Vaccines up-to- date except for shingles. Exam: Vesicular erythematic rash following the T-10 dermatome and does not cross midline.  Chapter: Section 8 Pain Clinical Vignette: 2 Book: The Netter Collection of Medical Illustrations: Nervous System, Volume 7, Part II - Spinal Cord and Peripheral Motor and Sensory Systems​​ Author: H. Royden Jones,Ted Burns,Michael J. Aminoff,Scott Pomeroy​​ Publisher: Elsevier​​ Date: 2013​ Primary infection varicella zoster virus (VZV) initially infects lymphoid tissue and CD4 T cells viral progeny infect sensory nerve endings in epithelium virus migrates up neural axons to establish latency in sensory ganglia Latent infection in ganglia kept under control in large part by VZV-specific T-cell immunity Immune Response importance of T-cell immunity for prevention of varicella zoster virus (VZV) reactivation evinced by multiple clinical observations herpes zoster incidence increases with age-related decline in cell-mediated immunity or reductions in immunity related to immunosuppression persons with T-cell immune deficiencies may have more severe disease antibodies to VZV can be detected throughout life, but do not protect against herpes zoster infection Special Senses Chapter: 5 Cranial Nerve II Optic Nerve and Visual System Book: Netter's Neurology Author: Geetha K. Athappilly,Ippolit C.A. Matjucha Publisher: Elsevier Date: 2020 Visual System Cranial Nerve II (optic nerve) Visual acuity Evaluation of intracranial pressure via direct inspection of optic nerve Cranial Nerves III, IV, and VI (oculomotor, trochlear, and abducens) Responsible for extraocular movement Evaluate for diplopia, nystagmus, and ptosis Chapter: 5 Cranial Nerve II Optic Nerve and Visual System Book: Netter's Neurology Author: Geetha K. Athappilly,Ippolit C.A. Matjucha Publisher: Elsevier Date: 2020 Visual Pathway Each retina is divided by anatomical location Nasal retina Temporal retina The left visual field projects to the nasal retina of the left eye and the temporal retina of the right eye The right visual field projects to the temporal retina of the left eye and the nasal retina of the right eye This is due to the refraction of light through the biconvex lens Chapter: 5 Cranial Nerve II Optic Nerve and Visual System Book: Netter's Neurology Author: Geetha K. Athappilly,Ippolit C.A. Matjucha Publisher: Elsevier Date: 2020 Visual Pathway The optic nerves carry the signal posteriorly and cross at the optic chiasm After the chiasm, signals are carried on the optic tracts to the lateral geniculate bodies The neurons of the lateral geniculate bodies, via the optic radiations, project into the visual cortex in the occipital lobe Visual Field Deficits  A 80-year-old male with a history of hypertension comes to the ED with the complaint of vision loss and left sided Clinical numbness that began two hours earlier On exam you note a homonymous hemianopsia of the left Vignette 3 visual field 1. Where is the lesion?  Clinical Vignette 3 1. Where is the lesion? Right occipital and thalamic stroke Vascular territory: Posterior Cerebral Artery (PCA) Case courtesy of Dr Bruno Di Muzio, Radiopaedia.org, rID: 41812 Auditory cortex Auditory system Outer Ear Funnels sound waves Middle Ear Tympanic membrane picks up vibration Creates movements of the three ear bones—the malleus, incus, and stapes Inner Ear The vibrations are detected by the hair cells of the cochlea Hair cells depolarize releasing glutamate and creating APs Greater bilateral distribution of sound compared to vision Question 4 Which of the following shows a correct pairing of visual pathway pathology and patient presentation? a. Optic nerve— bipolar hemianopsia b. Optic chiasm— right nasal hemianopsia c. left optic track— total blindness of left eye d. Right visual cortex (all optic radiations) – left homonymous hemianopsia  Identify the components of neuromuscular innervation leading to muscle contraction, including the location of motor neurons, their axons, and details of the neuromuscular junction Define the term “lower motor neuron lesion” and give examples of disorders that result in lower motor neuron lesions Describe and draw the circuitry involved in the muscle stretch reflex, and give examples of pathological changes that increase and decrease reflex excitability Compare and contrast the origins, tract locations, terminations, and functions of the medial and lateral pathways from the brainstem influence motor activity Objectives: Identify the anatomical locations and physiological functions of the motor neuron pools preferentially innervated by medial versus lateral brainstem pathways Part 2 Identify the functions of the corticospinal tract (CST) Describe and sketch the pathway of the CST from neurons in the motor cortex, through the brainstem and in the spinal cord Explain the clinical presentation of the upper motor neuron lesion and the lower motor neuron lesion clarifying the mechanisms linking the initial lesion with the subsequent changes in control of movement. Give examples of each type of lesion. Characterize the clinical findings associated with Parkinson disease and compare them with typical findings in upper or lower motor neuron lesions Identify the major functions of the cerebellum, characterize the clinical findings associated with cerebellar disease, and compare them with typical findings in upper or lower motor neuron lesions Motor activity Spinal motor neurons and interneurons: Responsive to sensory feedback from muscles, tendons, and pain sensors Motor cortex with corticospinal output: Voluntary movement Brainstem pathways: regulate muscle tone and unconscious adjustments in muscle activity Lower Motor Neurons Cell bodies are in the ventral horn of the spinal cord gray matter Descending motor pathway are found in the white matter Ventral and lateral Motor neurons are efferent Brining information from the CNS to the periphery Lower Motor Neurons At the cervical and lumbar enlargements specific target muscle groups are clustered together The most medial neurons control the axial muscles Gridle muscles are controlled by the neurons lateral to the axial group Limb muscle are controlled by neurons lateral to the gridle muscles Flexors (lateral) Extensors (medial) Neuromuscular Junction (NMJ) Synapse between the motor neuron and target muscles Postsynaptic membrane is enriched with nicotinic acetylcholine receptors The binding of acetylcholine to the nicotinic receptor allows Na+ to move into the muscle, depolarizing the membrane This opens voltage-gated Ca++ channels, allowing for crossbridge formation Myasthenia Gravis is an autoimmune reaction to the nicotinic acetylcholine receptors Lower Motor Neuron Lesions Motor neurons in the brainstem and spinal cord Motor neurons in the motor cortex are upper motor neurons Final element in skeletal muscle contraction If pathology occurs electromyography (EMG) shows disorganized low-level electrical activity (fibrillation), rather than action potential activity  Motor Neuron Disease: Signs and Symptoms Sign Upper Motor Neuron Lower Motor Neuron Weakness Yes Yes Atrophy No Yes Fasciculations No Yes Reflexes Increased Decreased Tone Increased Decreased Reflex Circuit Muscle Spindle Sensory Fiber (Ia fiber) Proprioceptor AP activity is proportional to the length and velocity of stretch Heavily myelinated fiber Releases glutamate on the motor neuron increasing the APs The motor neuron will release acetylcholine at the NMJ, creating the stretch reflex. Golgi Tendon Organ (Ib fiber) Stretch GTO releases GABA on the motor neuron The relationship between the two, tune movement  32 YO female presents to clinic complaining of changes in her walking. She denies any acute injuries. She notes that her hands seem clumsy but otherwise denies any changes. Clinical PMHx: negative Exam : Hyper-reflexive throughout, sensation intact, 4/5 Vignette 4 strength throughout gait- spastic. 1. Where is the pathology?​ Clinical Vignette Upper motor neuron lesion due to cervical myelopathy at C6-7 Descending Tracts Vestibulospinal Tract Signal begins in the vestibular nerve Signal travels to the vestibular nuclei Superior portion sends signals to control eye movement Medial portion controls head and neck Lateral portion controls trunk and limbs Control extensor muscles Helps maintain proper posture and balance Found in the ventral white matter of the cord Chapter: Section 2 Book: The Netter Collection of Medical Illustrations: Nervous System, Volume 7, Part II - Spinal Cord and Peripheral Motor and Sensory Systems​​ Author: H. Royden Jones,Ted Burns,Michael J. Aminoff,Scott Pomeroy​​ Publisher: Elsevier​​ Date: 2013​ Reticulospinal Tract Gets signals from the ascending tracks Control extensor muscles Supports the Vestibulospinal Track Found in the ventral white matter Chapter: Section 2 Book: The Netter Collection of Medical Illustrations: Nervous System, Volume 7, Part II - Spinal Cord and Peripheral Motor and Sensory Systems​​ Author: H. Royden Jones,Ted Burns,Michael J. Aminoff,Scott Pomeroy​​ Publisher: Elsevier​​ Date: 2013​  Corticospinal Tract (CST) Signal begins in the primary motor cortex (PMC), synapse occurs in the ventral horn, and the signal is carried to the skeletal muscle The PMC receives input from the basal ganglia and cerebellum to refine movement The cerebellum sends the final plan for movement back to the PMC Lateral Fine, precise distal limb movement Found in the lateral white matter Anterior (ventral) Gross, large, proximal and axial movement Found in the anterior white matter Chapter: Section 2 Book: The Netter Collection of Medical Illustrations: Nervous System, Volume 7, Part II - Spinal Cord and Peripheral Motor and Sensory Systems​​ Author: H. Royden Jones,Ted Burns,Michael J. Aminoff,Scott Pomeroy​​ Publisher: Elsevier​​ Date: 2013​ Pathology of the Corticospinal Tract Upper Motor Neuron Lesions: Initial flaccid paralysis and areflexia, followed by spastic paralysis and hyperactive reflexes. Brainstem lesions cause paralysis contralateral to the lesion, accompanied by ipsilateral or contralateral cranial nerve deficits, depending on the level of the lesion. Spinal cord damage to the tract is usually accompanied by alterations in the autonomic and sensory systems Symptoms depend on the size of the lesion and the somatopic location  Pathology of the CST Chapter: 15 Ischemic Stroke​ Book: Netter's Neurology​ Author: Barbara Voetsch,Matthew E. Tilem ,Michael Adix,Ian Kaminsky​ Publisher: Elsevier​ Date: 2020  Rubrospinal Tract (RuST) Supports the CST Signal begins in the PMC Receives input from the cerebellum Major role in activating flexor muscle groups Upper limbs Keeps distal limbs in check Local control of afferent input to the spinal cord from Golgi tendon organs and cutaneous receptors Found in the lateral white matter Chapter: Section 2 Book: The Netter Collection of Medical Illustrations: Nervous System, Volume 7, Part II - Spinal Cord and Peripheral Motor and Sensory Systems​​ Author: H. Royden Jones,Ted Burns,Michael J. Aminoff,Scott Pomeroy​​ Publisher: Elsevier​​ Date: 2013  Descending Tracts: Pons and Medulla Track Origin Function Crossing Termination Vestibulospinal Vestibular nuclei Controls neck and Ipsilateral limbs Lower motor neuron Track within in the arm extensors; medulla and pons antigravity muscles Bilateral neck Reticulospinal Track Pontine reticular Activates limb Ipsilateral Lower motor neuron formation within the extension Pons ( anterior) Medullary reticular Inhibits limb Bilateral formation within the extension Medullar (lateral)  Descending Tracts: Cortex Track Origin Function Crossing Termination Corticospinal Tract Motor Cortex Contralateral Lower motor Lateral Distal muscle neuron activation Anterior Proximal and axial muscle activation Rubrospinal Tract Red nucleus of the Upper limp flexion Contralateral Lower motor midbrain neuron Question 5 Which of the following is most likely to be observed after a stroke of the motor cortex? a. Absent muscle stretch reflexes b. Impaired rapidly alternating movements c. Weakness and lack of coordination of the contralateral hand d. Resting tremor  Initiates and refines movement Multistep process that begins in the premotor cortex Glutamate neurons in the motor cortex project to striatal acetylcholine interneurons. The striatal interneurons excite GABA neurons projecting from the striatum to the globus pallidus Substantia nigra dopamine neurons oppose the Basal Ganglia excitatory actions of acetylcholine and inhibit the GABA output from the striatum Two pathways: Direct: initiates movement Indirect: prevents unwanted movement  Basal Striatum Ganglia Chapter: Section 7 Basal Ganglia and Movement Disorders Book: The Netter Collection of Medical Illustrations: Nervous System, Volume 7, Part 1 - Brain Author: H. Royden Jones Publisher: Elsevier Date: 2013  Neurodegenerative disorder characterized by loss of dopamine-producing neurons in the substantia nigra Causes overactivity of excitatory acetylcholine transmission in the striatum Associated with: Akinesia Bradykinesia Parkinson's Increased muscle tone (rigidity) Cause is generally unknown, although up to 10% may be Disease linked to specific gene mutations Treatment focuses on restoring dopamine and inhibiting dopamine degrading enzymes Additional, treatment can focus on blocking acetylcholine receptors or stimulating dopamine receptors Deep brain stimulation can help with the movement symptoms associated with PD  Clinical Manifestations of PD Motor Symptoms: Nonmotor Symptoms: T – tremor (although not required for Depression/Apathy diagnosis) Anxiety R – rigidity Constipation A – Akinesia or bradykinesia Urinary dysfunction P – postural instability Insomnia Masked facies, hypophonia, micrographia, Orthostatic hypotension anosmia Cognitive decline  PARKINSONISM IDIOPATHIC ATYPICAL DRUG-INDUCED STRUCTURAL PARKINSON’S PARKINSONISM PARKINSONISM CAUSE DISEASE (PARKINSON’S PLUS) LEWY BODY MULTIPLE PROGRESSIVE CORTICOBASAL DEMENTIA SYSTEM SUPRANUCLEAR DEGENERATION ATROPHY PALSY  Clinical An 80-year-old male with Parkinson's disease presents to clinic for increasing falls. Vignette 5 His gait is worsening, and he is "off" more than he is "on". CEREBELLUM The function of the cerebellum is quality control Assists in the creation of the movement plan inputs the information to the motor cortex This is achieved through proprioception Cerebellar pathology can be due to: Vascular causes Masses Congenital  Cerebellar Pathology Clinical Manifestations: Ataxia- uncoordinated movement Dysmetria- fluctuation between over and undershooting a target Dysdiadochokinesia- inability to conduct rapid alternating movement Intention tremor- worsens near target Chapter: Section 8 Cerebellum and Ataxia Book: The Netter Collection of Medical Illustrations: Nervous System, Volume 7, Part 1 - Brain Author: H. Royden Jones Publisher: Elsevier Date: 2013  Summary of Motor Disorders Motor Disorder Muscle Strength Muscle Tone Muscle Atrophy Reflex Tone Gait Posture and Balance Weakness, may be proximal and Neuromuscular asymmetrical, may junction disease affect only cranial Focal decrease in Depends on site of Depends on site of Mild Often preserved nerve distribution, affected areas involvement involvement (myasthenia gravis) with difficulty in speech and swallowing Lower motor neuron lesion Maintained within Decreased or Foot drop, unilateral Decreased Decreased Severe constraints of absent loss of strength (polio, peripheral weakness nerve trauma)  Summary of Motor Disorders Posture and Motor Disorder Muscle Strength Muscle Tone Muscle Atrophy Reflex Tone Gait Balance Upper motor Hemiparetic—arm Maintained neuron lesion flexed, leg Decreased Spasticity None Increased within constraints extended, of weakness (stroke) circumduction gait Slow initiation and Increased, with May be Postural instability, Parkinson disease Decreased None freezing, small steps, tremor or rigidity increased falls are common absent arm swing Difficulty Uncoordinated, Uncoordinated Cerebellar disease Normal None Normal maintaining rather than weak ataxic gait balance Question 6 Which basal ganglia neurotransmitter must be present at correct levels relative to dopamine for normal motor function? a. Acetylcholine b. Glutamate c. Norepinephrine d. Serotonin Higher Functions of the Nervous System  Describe the neuroanatomy of higher executive functions and some of the tasks that are used to assess some of these functions Identify the major brain pathways, neurotransmitters, and output systems involved in psychological, endocrine, and autonomic responses to acute stress Objectives: Describe the evidence for altered brain characteristics in depression, and the biological basis of antidepressant drug Part 3 action Compare and contrast the brain systems responding to stress and those thought to be responsible for anxiety Discuss the possible role of the dopamine input to nucleus accumbens in substance use disorders, and the evidence for endogenous opioid and cannabinoid-like substances in brain function. Anatomy of Cognition and Behavior Prefrontal cortex (PFC) is made up of: Dorsolateral PFC: is used in short-term working memory Dorsomedial: sense of self, social impressions, fear, morality Orbitofrontal cortex (OFC): holistic sense of the environment Closely linked to the limbic system and motor cortex  Brain Mechanism of Stress Brainstem structures activate the output of stress effector systems. Sympathetic nervous system sympathetically controlled adrenal medulla hypothalamic-pituitary-adrenal (HPA) axis. The central neurotransmitters initiating the stress response include: norepinephrine from the locus ceruleus corticotropin-releasing hormone from the paraventricular nucleus of the hypothalamus and limbic region Activation increases heart rate and blood pressure, mobilizes fuels such as glucose and fatty acids, and suppresses systems such as growth, gastrointestinal function, and sexual function Brain Circuit Flip Question 7 What is the mechanism by which stressful stimuli increase anxiety and sharpen perception of stressful challenges? a. Activation of norepinephrine neurons in the locus ceruleus b. Activation of basal forebrain acetylcholine cells c. Activation of glutamate neurons in the hippocampus d. Activation of sympathetic cardiovascular neurons Neurobiology of Depression Major Depressive Disorder is the most common mental health condition Abnormalities of HPA axis regulation may contribute to MDD Daily cortisol levels are above average indicating a failure of the normal negative feedback, which is mediated by the hippocampus Blood flow is decreased to the PFC and increased to the Amygdala This could reflect a tendency toward negative thoughts accompanied by apathy, loss of pleasure, and slower thought processing  Postpartum Depression 85% of females are affected, with 10-15% of cases being severe Symptoms can occur within the first 4 weeks after delivery Females remain at very high risk for affective illness during the first 3 months after delivery remain at heightened risk up to 1 year after childbirth Chapter: Section 4 Psychiatry Book: The Netter Collection of Medical Illustrations: Nervous System, Volume 7, Part 1 - Brain Author: H. Royden Jones Publisher: Elsevier Date: 2013  Common mental health disorder with high annual prevalence Neurobiology Neurobiological studies implicate the amygdala and hippocampus, and cortical regions—insula, anterior of Anxiety cingulate, and ventromedial PFC Activity is reduced in dorsolateral PFC and related emotion- regulation areas Substance Use Disorders Increase dopamine release from the VTA neurons that project to the nucleus accumbens, the brain’s pleasure and reward center Individuals with substance use disorders exhibit compulsive patterns: Tolerance Cravings Withdrawal Chapter: Section 4 Psychiatry Book: The Netter Collection of Medical Illustrations: Nervous System, Volume 7, Part 1 - Brain Substance Use Disorder Author: H. Royden Jones Publisher: Elsevier Date: 2013 Question 8 Describe the hypothesized functional neuroanatomy of opioid use disorder and the role of risk factors for opioid use. a. The release of dopamine in the nucleus accumbens is reinforcing b. GABA neurons activate the reward center c. Decreased blood flow to the PFC increases tolerance d. Excitation of the acetylcholine neurons in the basal forebrain reinforcing desire  Briefly describe brain development and the key stages in that development Define the terms seizure and epilepsy and describe the relationship between these two terms. Objectives: Give examples of different types of seizures and epilepsy, Part 4 and some characteristics of these types Compare the major types of headaches and the hypotheses of headache mechanisms What is thought to be optimal care for concussion, with respect to assessment and management? Brain Development Begins in the third week of development Neurons rapidly multiply in gestational weeks 4-12 During this time neuron numbers total about twice the levels of adults Apoptosis begins about week 16 Myelination begins before birth Peak activity will occur several years after birth Sensory Motor Critical for neurodevelopmental milestones Chapter: Section 1 Normal and Abnormal Development Brain Development Book: The Netter Collection of Medical Illustrations: Nervous System, Volume 7, Part 1 - Brain Author: H. Royden Jones Publisher: Elsevier Date: 2013 Spinal Muscular Atrophy Second most common genetic disorder Mutation of the SMN1 gene Most common type is SMA type 1 (autosomal recessive) Survival is around 2 years. Symptoms: 1. Atonia 2. weakness of muscles used for sucking breathing 3. failing to reach motor developmental milestones Pathogenesis: death of the spinal motor neuron—cause LMNL Treatment: Nusinersen and onasemnogene abeparvovec-xioi Consider social determinates of health from state-to-state  Spinal Muscular Atrophy Chapter: Section 10 Motor Neuron and Its Disorders Book: The Netter Collection of Medical Illustrations: Nervous System, Volume 7, Part II - Spinal Cord and Peripheral Motor and Sensory Systems Author: H. Royden Jones,Ted Burns,Michael J. Aminoff,Scott Pomeroy Publisher: Elsevier Date: 2013  Consider differences in etiology for pediatric and adult seizure types. Common causes: 1. Hypoxic ischemic encephalopathy 2. Strokes 3. Intracranial hemorrhage (more common in preterm infants) Neonatal 4. Inborn errors of metabolism 5. Other metabolic disturbances Seizures 6. Genetic disorders, 7. Intracranial infection 8. Malformation syndromes Pathogenesis: Incomplete development of inhibitory receptors coupled with predominance of excitatory receptors, fewer potassium channels, and immature neurotransmitter systems. Pediatric Febrile Seizures Associated with fevers No evidence of intracranial infection Usual ages: 6 months – 6 years Generalized seizure Simple < 15 minutes; Complex >15 minutes No postictal neurological deficit Causes much parental angst Autism: Autism spectrum disorder is a condition that appears very early in childhood development, varies in severity, and is characterized by impaired social skills, communication problems, and repetitive behaviors. Difficulty understanding and using non-verbal social cues such as eye contact, facial expressions, gestures, and body language. Development Downs Syndrome: Down syndrome is a chromosomal condition that is associated with and intellectual disability, a characteristic facial appearance, and weak muscle tone (hypotonia) in infancy. Intellectual disability Most cases of Down syndrome result from trisomy 21. Fragile X syndrome: Fragile X syndrome is a genetic condition that causes a range of developmental problems. M Nearly all cases of fragile X syndrome are caused by a mutation in which a DNA segment, known as the CGG triplet repeat, is expanded within the FMR1 gene  Must have two of the following: headache lasting 4- 72 hours, unilateral location, pulsating quality, moderate to severe pain, and/or aggravated by routine activities. Additionally, one of following must be present: Dx Criteria for nausea and/or vomiting, photophobia and/or phonophobia. Migraine The patient should have 5 or more attacks that meet this criteria. Aura can be associated but is not needed for diagnosis. ICHD-3. Cephalalagia 2018.  Must have two attacks fulfilling the following criteria: One or more of the following aura symptoms: visual, sensory, speech and/or language, motor, brainstem, retinal Dx Criteria for Migraine At least three of the following six characteristics: at least one aura symptoms that spreads gradually over 5 minutes, two or more aura symptoms that occur in succession, each w/Aura symptom last 5-60 minutes, at least one aura symptom is unilateral, at least one aura symptom is positive, the aura is accompanied or followed by headache, Not better accounted for by another ICHD-3 diagnosis ICHD-3. Cephalalagia 2018.  Migraine Clinical Subtype Presentation Migraine Migraine with Brainstem aura Symptoms originating (previously Basilar Migraine) from the brainstem, no with Aura: motor weakness Hemiplegic Migraine Migraine with aura Subtypes including motor weakness (50) SNNOOP10: Red P P Pattern change Positional headache and Orange P P Precipitated by sneezing, coughing or exercise Papilledema Flags in P Progressive headache Headache P Pregnancy or puerperium P Painful eye with autonomic features P Posttraumatic onset P Pathology of the immune system P Painkiller overuse Episodic syndromes associated with Migraine Recurrent gastrointestinal Benign paroxysmal Benign paroxysmal disturbance vertigo torticollis ICHD-3. Cephalalgia 2018. Lifestyle Modifications Acute Migraine Treatment Treatment Preventative Migraine Treatment Considerations Contraceptive use in the migraine population Antidepressants and triptans  TBI induced by biomechanical forces Pathophysiological changes are complex and attributed to trauma Potassium accumulation, depolarization, and glutamate release --> Excitotoxity Sports Cell injury to the axon Common Features of Concussion: Related Sport-related concussion may be caused by a direct blow to the head, face, neck. Concussion Rapid onset of impaired neurological function that often resolves quickly. Sport-related concussion may result in neuropathological changes. It results in a range of clinical signs and symptoms that may or may not involve loss of consciousness. The clinical signs and symptoms cannot be explained by drug, alcohol, or medication use. Treatment: Physical and cognitive rest with a stepwise return to sports and other activities. Sports Related Concussion  Sports Related Concussion Chapter: 19 Trauma to the Brain Book: Netter's Neurology Author: Khaled Eissa,Carlos A. David,Jeffrey E. Arle Publisher: Elsevier Date: 2020 Question 9 What is a consequence of frequent use of abortive medications to treat migraine headaches? a. There is an increase in cortical spreading depression b. There is a reduction in the incidence of migraine aura c. There is a sustained state of cerebral vasodilation, perpetuating the migraine d. There is increased incidence of headaches  Describe normal brain changes with aging and distinguish between these and pathological aging due to a variety of Objectives: diseases. Part 5 Describe and draw cerebral circulation How is the brain globally affected by a stroke, and what are the effects of strokes of different brain regions? Neurodegenerative disorders Neuronal networks are progressively impaired. Pathologic changes in AD: Buildup of β-amyloid (Aβ) protein (plaques) between neurons Presence of tau protein within axons (neurofibrillary tangles)  Acute Stroke Principles: Achieve timely recanalization of the occluded artery and Achieve reperfusion of the ischemic tissue Optimize Optimize collateral flow Avoid Avoid secondary brain injury. Stroke Epidemiology Stroke has dropped to the 5th leading cause of death in the US Annual incidence 795,000 strokes 610,000 first/new strokes 185,000 recurrent Leading cause of long-term disability in the US NIH Stroke Scale (NIHSS) 15 exam components Helps ”talk” to other providers in an objective manner Two Pairs of M.C.A Arterial A.C.A Supply P.C.A Basilar a. Vertebral A. Internal Carotid A. This Photo by Unknown author is licensed under CC BY-SA. Cerebral Blood Circulation Meet HAL INTRACRANIAL CIRCULATION WILLIS! Question 10 Which of the following shows a correct pairing of vasculature, cortical territory, and patient presentation after ischemic stroke? a. Anterior cerebral artery – lateral frontal cortex – weakness of arm and face b. Anterior cerebral artery – medial frontal cortex – weakness of foot and leg c. Middle cerebral artery – medial frontal cortex – weakness of foot and leg d. Middle cerebral artery – medial occipital cortex – visual disturbances, cortical blindness Artery Cerebral Cortex Affected Signs & Symptoms Anterior Circulation ICA Can be frontal lobe, posterior frontal lobe, anterior Contralateral paralysis of face, arm, leg temporal lobe Sensory deficits in face, arm, leg Aphasia (when dominant hemisphere affected) Can also have subcortical infarcts Apraxia, agnosia, and unilateral neglect (when nondominant hemisphere affected) (affected cerebral cortex depends on whether ACA or Homonymous hemianopia MCA, or both, are involved) ACA With distal branch involvement, medial aspect of Contralateral leg and foot paralysis ipsilateral frontal lobe is affected Contralateral sensory impairment of leg, foot, and toes Gait impairment Slowed performance of tasks, slowed response Flat affect, limited or lack of interest in environment Impaired memory Artery Cerebral Cortex Affected Signs & Symptoms Anterior Circulation MCA If M1 branch is occluded, then a Contralateral paralysis of face large MCA territory infarct and arm occurs, affecting most of that Sensory deficits in face and hemisphere arm Aphasia (global aphasia when dominant hemisphere affected) Apraxia, agnosia, and unilateral neglect (when nondominant hemisphere affected) Homonymous hemianopia Posterior Circulation Artery​ Cerebral Cortex Affected​ Signs & Symptoms Dizziness Nystagmus Dysarthria Vertebral artery involvement can be devastating, Dysphagia VA depending on whether one or both VAs are Facial, eye, nasal pain involved Ipsilateral facial weakness and numbness Ataxia Gait instability Paralysis of all four extremities Paralysis of nearly all voluntary muscles, such that Vertebrobasilar territories include thalamus, patient is in a pseudocoma or locked-in (i.e., patient is BA medulla, cerebellum, pons, midbrain, and occipital awake, but unable to communicate because of lobes paralysis) Paresis of facial, tongue, and swallowing muscles Artery Cerebral Cortex Signs & Symptoms Affected Peripheral branch involvement (superficial Homonymous hemianopia​ cortex affecting visual function)​ Cortical blindness​ PCA​ Deep cortical branch Cognitive deficits: memory involvement (cerebellar recall and retention of new peduncle, thalamus, memory​ brainstem)​  Chapter: 15 Ischemic Stroke Book: Netter's Neurology Posterior Circulation Author: Barbara Voetsch,Matthew E. Tilem,Michael Adix,Ian Kaminsky Publisher: Elsevier Date: 2020  A 56-year-old female presents to the Emergency Department (ED) after developing acute-onset continual dizziness, gait disturbance, and near syncope this morning while cleaning her home. The patient denied any recent trauma, precipitating symptoms or aura. The dizziness has Clinical been continuous throughout the morning and she denies encountering symptoms like this before. Vignette The patient has a past medical history of episodic migraine and hypertension (HTN). She denies any recent surgeries. She takes lisinopril 10mg for her HTN, nortriptyline 75mg for migraine prevention and rizatriptan 10mg PRN for her acute migraine attacks. She denies illicit drug use, smoking or drinking. Clinical Vignette Exam: Head Impulse Nystagmus Test of Skew (HINTS) was performed. HINTS testing revealed no corrective saccade on head impulse testing (HIT), bi-directional nystagmus and negative test of skew using the cover-uncover technique