Disorders of Movement, Sensation, and Mental Function Chapter 21 Dr. Gary Mumaugh and Dr. Bruce Simet University of Northwestern St. Paul

Context for Assessment of Dysfunction Autonomic Nervous System (ANS) regulates homeostatic, reactive, and sensory functions Efferent nerves traveling out of CNS 2 Divisions: Parasympathetic Sympathetic Brain Stem regulates breathing and alertness and directs nerve connections Midbrain, Pons, and Medulla (see Table 21.2 for functions)

Cranial Nerves have sensory and motor functions 12 nerves (see Table 21.3 for functions) Motor Neurons control voluntary movement See Table 21.5 for Assessing Disorders of Movement See Table 21.6 for Muscle Tissue Disorders

Disease Categories in Neurology Myopathy – muscle diseases Myelopathy – cord compression diseases Neuropathy – nerve diseases Radiculopathy – nerve root compression Plexopathy – nerve plexus compression Encephalopathy – brain diseases

Disorders of Neuromuscular Junction Myasthenia Gravis (MG) Lambert-Eaton myasthenic syndrome (LEMS)

Myasthenia Gravis (MG) Characterized by skeletal muscle weakness and malaise Caused by an autoimmune disorder Antibodies are produced against acetylcholine (Ach) receptors. Antibodies bind to the receptor and are not easily released. Bound antibodies stimulate phagocytosis of endplate muscle membrane Bound antibodies induce degradation of receptor channels Symptoms include Myasthenic crisis – acute muscle weakness resulting in inability to swallow, clear secretions, or breathe well.

Lambert-Eaton Myasthenic Syndrome (LEMS) Similar to MG, but weakness improves with exertion Caused by impaired release of Ach Symptoms: Muscle weakness, dry mouth, decreased sweating, constipation 60% of patients have lung carcinomas prior to diagnosis

Peripheral Nerve Disorders Diffuse Polyneuropathies Guillain-Barre Syndrome Entrapment Syndromes Charcot-Marie-Tooth Disease (Peroneal Muscular Atrophy)

Diffuse Polyneuropathies Characterized by peripheral nerve lesions Caused by a variety of metabolic, toxic, and nutritional conditions Symptoms include Glove-and-stocking anesthesia Characterized by loss of sensation in the hands and feet; loss of larger fibers leads to impaired proprioception

Neuropathy Affects distal nerves in a glove like pattern Paresthesias, weakness, sensory loss Common in diabetes, RA, alcoholic abuse and B12 deficiency

Guillain-Barre Syndrome Characterized by immune-mediated attack on sheaths of well-myelinated fibers Typically occurs after an upper respiratory tract or flu viral infection. Idiopathic. Symptoms: Varying degrees of weakness and tingling sensation in the legs leads to complete paralysis. 85% make complete recovery within 4 - 6 months

Entrapment Syndromes Characterized by focal slowing and loss of intensity of motor and sensory signals Causes of Peripheral nerve lesions: Local compression and trauma (Ex. Saturday night palsy or tardy ulnar palsy) Overuse, repetitive motion injury (Ex. Pronator terres syndrome) Combination of overuse and genetic predisposition (Ex. Carpal tunnel syndrome) Symptoms: Muscle wasting, eventually irreversible fibrosis

Charcot-Marie-Tooth Disease (Peroneal Muscular Atrophy) Heritable, autosomal dominant Characterized by atrophy of peripheral motor and sensory neurons Characterized by onset in late adolescence Symptoms: Weakness and atrophy in distal muscles of the legs

Disorders of the Spinal Cord Syringomyelia Subacute Combined Degeneration of the Cord (Lichtheim’s disease) Amyotrophic Lateral Sclerosis (ALS) Spinal Muscular Atrophies of Infancy and Childhood Friedreick’s Ataxia

Syringomyelia A rare condition that produces a syrinx (fluid filled cavity) in the central spinal cord. Syrinx caused by spinal cord trauma Cause is idiopathic Symptoms include Shawl anesthesia - pain and temperature insensitivity in arms and upper trunk

Subacute Combined Degeneration of the Cord (Lichtheim’s disease) Characterized by a generalized lesion of the posterior half of the spinal cord Usually caused by chronic alcohol abuse

Amyotrophic Lateral Sclerosis (ALS) Also called Lou Gerhig’s disease and Motor Neuron disease Characterized by lower motor neuron lesion and lateral scarring because of upper motor neuron lesion Fatal; 80% of people die within 3 years of diagnosis; no effective treatments Caused by: Environmental toxins, slow viruses Symptom: Excitotoxicity (destructive response of neurons to excessive stimulation)

ALS – Amyotrophic Lateral Sclerosis Degenerative disease of UMN & LMN lesions Unknown cause autoimmune disorder Usually fatal in 1-2 years S & S Weakness of hands, loss of grip, tripping, falling Disease begins distally and works proximally No sensation loss, no pain, no mental loss Difficulty speaking and swallowing, drooling Death in 1-3 years from respiratory failure Diagnosis History and muscle biopsy

Amyotrophic lateral sclerosis (ALS) Classic ALS—“Lou Gehrig disease” Diffusely affects upper and lower motor neurons of the cerebral cortex, brain stem, and spinal cord (corticospinal tracts and anterior roots) Disease leads to progressive weakness leading to respiratory failure and death Patient has normal intellectual and sensory function until death

ALS Lou Gehrig's Disease

Spinal Muscular Atrophies of Infancy and Childhood Rare, heritable motor disorders that leave sensory capacities intact Werdnig-Hoffman disease (floppy baby syndome) Onset in infancy, rapidly progresses Symptoms: Motor degeneration, but normal intelligence and development

Friedreick’s Ataxia Fatal motor-sensory disorder Chronic, average course of 15-20 years Half of patients diagnosed develop cardiomyopathies Caused by autosomal recessive disorder affecting production of frataxin Results in mitochondrial dysfunction and free radical toxicity Symptoms: Spinal cord is small and nerve fibers are depleted

Disorders Arising in the Basal Ganglia Parkinson’s Disease Huntington’s Disease

Parkinson Disease Severe degeneration of the basal ganglia (corpus striatum) involving the dopaminergic nigrostriatal pathway Parkinsonian tremor Parkinsonian rigidity Parkinsonian bradykinesia Postural disturbances Autonomic and neuroendocrine symptoms Cognitive-affective symptoms

Parkinson’s Disease Slow, degenerative CNS disorder Course of disease lasts 10-20 years Affects twice as many men as women Caused by damage to the substantia negra Normally provides outflow pathway from basal ganglia to the cortex and a feedback loop to the caudate and putamen

Typically idiopathic Symptoms Impairs flow of motor programs from the basal ganglia Causes bradykinesia (slow movement) and difficulty initiating movement Loss of feedback loop expresses itself as resting tremor Gradual loss of dopamine-producing cells Typically idiopathic Known to result from lesion by toxins Symptoms Muscle rigidity, bradykinesia, palsy (resting tremor), tiredness and weakness, poor balance, dementia

Degenerative disorder of the basal ganglia Usually in men over 50 One million cases in USA S & S Four classic symptoms: Resting muscle tremor Slowness of voluntary movement – bradykinesia Impaired postural reflexes – simian posture Inability to maintain balance when being shoved or bumped Other symptoms: Increased muscle tone or rigidity Small “steppage” gaits Frozen facial expression – “masked face” Handwriting changes - micrographia

Diagnosis Treatment No classic diagnostic tests or lab studies Dopamine is used for the first five years Anticholinergic drugs, MAO inhibitors, Symmetryl The meds do not stop the progression, they only provide symptomatic relief Surgical treatment is currently experimental Implanting cadaver or fetal basal ganglion cells Progress and Promise in Parkinson's Disease

Huntington’s Disease Characterized by dominant genetic defect on chromosome 4 Dementia consists of progressive loss of cognitive function Massive cellular loss from caudate and putamen Course of disease is about 15 years Symptoms: rapid, writhing contortions of hands, arms, face, trunk and profound dementia

Huntington Disease Also known as “chorea” Autosomal dominant hereditary-degenerative disorder Severe degeneration of the basal ganglia (caudate nucleus) and frontal cerebral atrophy Depletion of gamma-aminobutyric acid (GABA)

Cerebral Palsy General term that applies to disabilities that derive from perinatal brain injury Movement problems, sensory and cognitive impairment CP is commonly classified based on the area of the body most affected Quadriplegic CP – all 4 limbs affected Diplegic CP – lower limbs affected more than upper Monoplegic CP – only 1 limb affected Diplegic/Paraplegic

Multiple Sclerosis (MS) Possibly caused by an interaction between a viral illness in teen years and a genetic predisposition Arises through a single mechanism of lesion Focal, chronic, progressive Areas of demyelination are called plaques Confined to white matter Optic neuritis is often the first symptom Chronic exacerbation and remission Triggers: infection, medication, stress, fatigue

Demyelinating Disorders Multiple sclerosis (MS) MS is a progressive, inflammatory, demyelinating disorder of the CNS Types Mixed (general) Spinal Cerebellar

Common symptoms: Visual impairment or blindness Hyperreflexia Difficulty urinating Difficulty swallowing Extreme intolerance of heat Emotional outbursts Depression or euphoria

Alzheimer’s Disease Dementia is the loss of ordered neural function Main characteristic of Alzheimer’s is a slow progression of dementia, 5 years Initially only short-term storage and retrieval is affected Gradually well-consolidated memories are affected Patient experiences restlessness and wandering Eventually patient is mute and paralyzed Death usually comes from infection of a weakened, dehydrated patient

Atrophy Pyramidal cells die along with axons → loss of white matter → Gyri shrink → ventricles expand Severity and progression of disease due to Neurofibrillary tangles Neurotic plaques Made up of Amyloid (starchlike) proteins Amyloid beta protein Directly toxic to neural tissue Triggers inflammatory response

Dementia Progressive failure of cerebral functions that is not caused by an impaired level of consciousness Classifications Cortical Subcortical Cortical and subcortical

Alzheimer Disease (AD) Familial, early and late onset Nonhereditary (sporadic, late onset) Theories Mutation for encoding amyloid precursor protein Alteration in apolipoprotein E Loss of neurotransmitter stimulation of choline acetyltransferase

Alzheimer Disease (AD) Neurofibrillary tangles Senile plaques Clinical manifestations Forgetfulness, emotional upset, disorientation, confusion, lack of concentration, decline in abstraction, problem solving, and judgment Diagnosis is made by ruling out other causes of dementia