Neurolgy II Movement Disorders PDF

NEUROLOGY II: LE 6 | TRANS 3 Movement Disorders: Disorders of the Basal Ganglia; Chorea, Athetosis, Ballismus, Tremors, Dystonia, Tics DOMINIQUE Q. PEREZ MD, FPNA | 04/23/2024 c...

NEUROLOGY II: LE 6 | TRANS 3 Movement Disorders: Disorders of the Basal Ganglia; Chorea, Athetosis, Ballismus, Tremors, Dystonia, Tics DOMINIQUE Q. PEREZ MD, FPNA | 04/23/2024 c Subthalamic nucleus and the substantia nigra OUTLINE → Included in the basal ganglia due to close connections with the I. Anatomy of the Basal VII. Involuntary Movements caudate and lentiform nuclei Ganglia A. Chorea Claustrum and amygdaloid nuclear complex II. Basal Ganglia Circuitry B. Athetosis → Different connections and functions III. Physiology of the Basal C. Ballismus → Sometimes included but do not participate directly in the Ganglia D. Dystonia modulation of movement IV. Motor Syndromes E. Tremors A. Hypokinetic F. Asterixis B. MOTOR SYSTEMS B. Hyperkinetic G. Myoclonus V. Neurotransmitters in the H. Startle Syndrome Basal Ganglia I. Tics and Habit Spasms VI. Symptoms of Basal J. Akathisia Ganglia Disease VIII. Synchronous Case A. Hypokinesia IX. Review Questions B. Bradykinesia X. References C. Disorders of Postural XI. Appendix Figure 2. Motor Systems[Lecturer’s PPT] Fixation, Equilibrium and Pyramidal systems (discussed in a separate chapter) Righting → Corticospinal and Corticobulbar tracts D. Rigidity and Alterations Extrapyramidal system (discussed in the next sections) in Muscle Tone → Basal ganglia circuitry / Striatopallidonigral Parapyramidal system SUMMARY OF ABBREVIATIONS → Some physiologists have expanded the list of basal ganglionic DTR Deep Tendon Reflex structures to include the red nucleus, the intralaminar thalamic 📣 ❗️ 📣 📖 📋 Must know Lecturer Book Previous Trans nuclei, and the reticular formations of the upper brain stem → Rubrospinal, reticulospinal, vestibulospinal & tectospinal tracts → Receive direct cortical projections giving rise and running LEARNING OBJECTIVES parallel to the corticospinal ones ✔ No learning objectives were given by the lecturer → Structurally independent of the major extrapyramidal circuits I. ANATOMY OF THE BASAL GANGLIA Prepyramidal cortex (STRIATOPALLIDONIGRAL SYSTEM) → Premotor and supplementary motor cortices ultimately project to the motor cortex ⚠️ ⚠️ A. BASAL GANGLIA MUST KNOW Anatomy of the Basal Ganglia (Striatopallidonigral System) → Neostriatum ▪ Caudate Nucleus ▪ Putamen → Palleostriatum ▪ Globus pallidus − Internal/medial segment − External/lateral segment → Subthalamic Nucleus → Substantia Nigra ▪ Pars Compacta Figure 1. The Basal Ganglia[Lecturer’s PPT] ▪ Pars Reticulata Principally composed of Caudate Nucleus and Lentiform Motor Systems Nucleus → Pyramidal systems → Lentiform Nucleus is subdivided into Putamen and Pallidum ▪ Corticospinal tract and corticobulbar tract (Globus Pallidus) → Extrapyramidal systems ▪ On the lateral aspect of the internal capsule ▪ Striatopallidonigral tract Medial to the internal capsule is the caudate nucleus, thalamus, → Parapyramidal systems subthalamic nucleus, and substantia nigra ▪ Vestibulospinal, reticulospinal, rubrospinal, and Caudate and putamen are continuous structures separated tectospinal tracts incompletely by fibers of the internal capsule → Preparamydal systems ▪ Premotor cortex and supplementary motor cortex ✏️ ✏️ → Cytologically and functionally discrete from the pallidum → Thus it is more meaningful to divide these nuclear masses into: CONCEPT CHECKPOINT ▪ Neostriatum 1. T or F. The caudate and putamen are essentially − Caudate Nucleus independent structures, almost entirely distinct from the − Putamen pallidum, with only minimal interconnections via fibers of ▪ Palleostriatum the internal capsule. − Globus pallidus 2. All are identified as parapyramidal systems EXCEPT: o Internal/medial segment a. Rubrospinal tract o External/lateral segment b. Reticulospinal tract ▪ Subthalamic Nucleus c. Corticospinal tract ▪ Substantia Nigra − Pars Compacta − Pars Reticulata LE 6 TRANS 3 TG-B9: *T. Malaluan, J. Maligsay, N. Manuel TE: G. Garcia, J. Ochoco, & T. Olaivar AVPAA: I. Nayal Page 1 of 16 TG-B10: A. Marcos, *M.Morales,K. Murray  ANS: 1. FALSE Caudate and putamen are a continuous structure separated III. PHYSIOLOGY OF THE BASAL GANGLIA only incompletely by fibers of the internal capsule and are Brake or Switch Function cytologically and functionally discrete from the pallidum → “Brake” 2. C Corticospinal tract is included in Pyramidal systems ▪ Tonic inhibitory action preventing target structures from generating unwanted motor activity II. BASAL GANGLIA CIRCUITRY → “Switch” Striatum (mainly putamen) ▪ Capacity to select which of many available motor programs → Receptive part of the basal ganglia will be active at a given time → Receives input from the cerebral cortex and substantia nigra Motor programming pars compacta → Initiation, sequencing, and modulation of motor activity Internal pallidum and substantia nigra pars reticulata Constant priming of the motor system → Main output nuclei of the basal ganglia → Enables rapid execution of motor acts without premeditation A. DIRECT PATHWAY Glutamic projections from the cortex Dopaminergic projections from the SNpc (D1 receptors) Net effect is facilitation of movement Figure 3. Basal Ganglia Circuitry[Lecturer’s PPT] Two main efferent projections from the putamen Figure 4. Direct Pathway[Lecturer’s PPT] (1) Direct efferent system Physiologic evidence reflects this balanced architecture, one ▪ Putamen → internal globus pallidus → substantia nigra pars excitatory and the other inhibitory within the individual circuit reticulata → Excitatory (2) Indirect efferent system ▪ Cortex ▪ Putamen → traverses the external globus pallidus → ▪ Substantia Nigra pars compacta (SNpc) D1-like receptors subthalamic nucleus which has a strong reciprocal ▪ Subthalamic nucleus connection → Inhibitory ▪ Contains an internal loop ▪ Striatum − Projections from the subthalamic nucleus → internal ▪ Globus pallidus externa segment of the pallidum and pars reticulata of the ▪ Globus pallidus interna substantia nigra Activation of this direct pathway (see Simplified version from TEs) ▪ Offshoot of the indirect pathway → Inhibits the internal pallidum, which, in turn, disinhibits the − Projections from the external pallidum to the internal ventrolateral and ventroanterior nuclei of the thalamus pallidonigral output nuclei. ▪ Thalamocortical drive is enhanced and cortically initiated From the internal pallidum, two fiber bundles reach the thalamus movements are facilitated → Ansa lenticularis & Fasciculus lenticularis Explanation of Figure 4 → Both of these fiber bundles join the thalamic fasciculus, which → Cortex has excitatory projections that excite the striatum which also contain other projections to the thalamus. is inhibitory by activity A major projection of the ventral thalamic nuclei of the thalamus to → Striatum exerts an inhibitory effect on the GPi which is the premotor cortex completes the large inhibitory by activity cortical-striatal-pallidal-thalamic-cortical motor loop. → Inhibited GPi cannot inhibit the thalamus thus there is more To these, another has been added: thalamocortical drive (3) Hyperdirect pathway → Thalamocortical drive facilitates movement ▪ Activates the subthalamic nucleus directly from the motor cortex, without the necessity of the intervening striatum B. INDIRECT PATHWAY Striatum ⚠️ MUST KNOW ⚠️ → Receptive part of the basal ganglia → Receives input from the cerebral cortex and substantia nigra pars compacta Internal pallidum and substantia nigra pars reticulata → Main output nuclei of the basal ganglia Efferent projections from the Putamen → Direct efferent system → Indirect efferent system Figure 5. Indirect Pathway[Lecturer’s PPT] → hyperdirect pathway 1. ✏️CONCEPT CHECKPOINT✏️ What pathway originates from the putamen, proceeds to D2-like receptors of substantia nigra cors compacta are involved in the Indirect pathway → Arises from the putaminal neurons that contain GABAergic and the internal globus pallidus, and then reaches the smaller amounts of enkephalin substantia nigra pars reticularis? → These projections have an inhibitory effect on the external a. Direct efferent system pallidum which in turn disinhibits the subthalamic nucleus b. Indirect efferent system through GABA release providing more drive to the internal c. Hyperdirect pathway pallidum and substantia nigra pars reticulata ANS: → More drive to the GPi will increase its activity which is 1. A Direct efferent pathway = putamen ⇢ globus pallidus (internal) ⇢ inhibition, it will inhibit more the thalamus substantia nigra pars reticulata NEUROLOGY II Movement Disorders: Disorders of the Basal ganglia; Chorea, Athetosis, Ballismus, Tremors, Dystonia, Tics Page 2 of 16  → Thus, there is a reduction in the thalamocortical input to the cortex and impedes voluntarily movement → Hyperkinetic Basal Ganglionic Syndrome ▪ Involuntary movements (e.g. choreoathetosis, dystonia ) 📣 → Net effect: inhibition of movement Explanation of Figure 5: → Cortex excites the striatum which is inhibitory by activity → Cerebellar Syndrome ▪ Incoordination (or ataxia ) 📣 Current view: enhanced conduction through the indirect pathway → Striatum inhibits the GPe which is inhibitory by activity leads to hypokinesia by increasing pallidothalamic inhibition → Inhibited GPe cannot inhibit the STN which is excitatory by whereas enhanced conduction through the direct pathway results activity in hyperkinesia by decreasing pallidothalamic inhibition → Active STN excites the GPi which is inhibitory Table 1. Clinical Differences between Corticospinal and → Active GPi inhibits the Thalamus (VA/VL) Extrapyramidal Syndromes → Inhibited thalamus means no thalamocortical drive and no movement Corticospinal Extrapyramidal Plastic, equal throughout C. HYPERDIRECT PATHWAY Character in Clasp-knife effect the passive movement the alteration of (spasticity) (rigidity) or intermittent muscle tone (cogwheel rigidity) Generalized but Distribution of Flexors of arms, predominates in flexors of hypertonus extensors of legs limbs and of trunk Involuntary Presence of tremor, chorea, Absent movements athetosis, dystonia Tendon Increased Normal or slightly increased Figure 6. Hyperdirect Pathway[Lecturer’s PPT] Reflexes Provides a fast divergent excitation of its output neurons Babinski Sign Present Absent → From the cortex it provides excitatory output to the subthalamic (UMN lesion) nucleus Paralysis of → Increasing the subthalamic drive to the internal pallidum volitional Present Absent or slight ▪ STN activates GPi (inhibitory by activity) movement → Activated GPi inhibits the ventroanterior and ventrolateral Dopamine released by the pars reticulata of the substantia nigra nuclei of the thalamus helps maintain the normal balance between direct and indirect → Net effect: inhibition of movement pathways Allows for more specific top-down control by the cortex Direct Pathway ⚠️ MUST KNOW ⚠️ → Glutamic projections from the cortex → Dopaminergic projections from the SNpc (D1 receptors) → Net effect is facilitation of movement Indirect Pathway → GABAergic projections from the putamen → Dopaminergic projections from the SNpc (D2 receptors) → Net effect is inhibition of movement Hyperdirect Pathway → Provides a fast divergent excitation of its output neurons → Net effect is inhibition of movement → Allows for more specific top-down control by the cortex 1. ✏️CONCEPT CHECKPOINT✏️ T or F. When excited by the cortex, the striatum exerts an Figure 8 Figure 8. Parkinson Disease (hypokinetic) [Lecturer’s PPT] → This is a prototype of a hypokinetic basal ganglionic syndrome inhibitory effect on the globus pallidus interna, which → There is a loss of dopaminergic input from the substantia nigra inhibits the thalamus, leading to decreased → There is a diminished activity of the direct pathway thalamocortical drive facilitating movement. → These increases the activity in the indirect pathway ANS: ▪ The net effect of indirect pathway is to increase inhibition of 2. FALSE Globus pallidus interna disinhibits the thalamus, leading to an the thalamic nuclei and reduce excitation of the cortical increase in thalamocortical drive, thus facilitating movement. motor system 3. ANSWER & RATIONALE III. MOTOR SYNDROMES Figure 7. Motor Syndromes[Lecturer’s PPT] Activities of the basal ganglia and the cerebellum are blended with and modulate the corticospinal system → Postural influence of the extrapyramidal system is indispensable to corticospinal movement Close association basal ganglia and the corticospinal systems become evident in the course of many forms of neurologic disease Division between pyramidal and extrapyramidal motor system remain useful in distinguishing several motor syndromes: (Figure 7) Figure 9. Huntington Disease (hyperkinetic) [Lecturer’s PPT] → Corticospinal Syndrome ▪ Loss of volitional movement (paralysis or paresis ▪ Spasticity ) 📣 Figure 9 → There is degeneration of the striatum → Direct pathway: overall a net inhibition of the globus pallidus → Hypokinetic Basal Ganglionic Syndrome ▪ Bradykinesia (or hypokinesia ▪ Rigidity (or altered muscle tone )📣📣 ) interna due to the decrease inhibition from the striatum, increased inhibition from the globus pallidus externa, and ▪ Tremor without loss of paralysis deceased excitation from the subthalamic nucleus NEUROLOGY II Movement Disorders: Disorders of the Basal ganglia; Chorea, Athetosis, Ballismus, Tremors, Dystonia, Tics Page 3 of 16  → Indirect pathway: less inhibition of the globus pallidus externa ▪ Tremor without loss of paralysis → more inhibition of the subthalamic nucleus, less excitation of → Hyperkinetic Basal Ganglionic Syndrome the globus pallidus interna ▪ Involuntary movements (e.g. choreoathetosis, dystonia) → In some there is less inhibition of the thalamus and increased → Cerebellar Syndrome excitation of the cortex, leading to hyperkinetic or involuntary ▪ Incoordination mov ements Corticospinal vs Extrapyramidal Syndromes: Brake or Switch Function Corticospinal Extrapyramidal Table 2. Clinicopathologic Correlations of Extrapyramidal Movement Plastic, equal throughout Disorders Character in Clasp-knife effect the passive movement PRINCIPAL LOCATION OF the alteration of SYMPTOMS (spasticity) (rigidity) or intermittent MORBID ANATOMY muscle tone (cogwheel rigidity) Unilateral plastic Contralateral substantia nigra plus Generalized; predominates rigidity with rest tremor (?) other mesencephalic structures Distribution of Flexors of arms, in flexors of limbs and of (Parkinson disease) hypertonus extensors of legs trunk Unilateral Contralateral subthalamic nucleus of Involuntary Presence of tremor, chorea, hemiballismus and Luys or luysial-pallidal connections Absent movements athetosis, dystonia hemichorea Tendon Chronic chorea of Caudate nucleus and putamen Increased Normal or slightly increased Reflexes Huntington type Babinski Sign Athetosis and dystonia Contralateral striatum (pathology of Present Absent (UMN lesion) dystonia musculorum deformans Paralysis of unknown) volitional Present Absent or slight Cerebellar Ipsilateral cerebellar hemisphere; movement incoordination, ipsilateral middle or inferior intention tremor, and cerebellar peduncle; brachium Refer to Table 2 for the Clinicopathologic Correlations of hypotonia conjunctivum (ipsilateral if below Extrapyramidal Movement Disorders decussation, contralateral if above) Extrapyramidal Syndrome Decerebrate rigidity, i.e., extension of arms Usually bilateral in the tegmentum of the upper brainstem at the level of → Wilson Disease ❗️ → Was first delineated by Wilson ▪ Hepatolenticular degeneration describing the abnormality and legs, opisthotonos red nucleus or between red and of bilaterally symmetrical degeneration of the putamen vestibular nuclei → Clinicopathologic studies of Huntington chorea related the Palatal and facial Ipsilateral central tegmental tract excessive movements and rigidity characteristic of the myoclonus (rhythmic) with denervation of the inferior disease to a loss of nerve cells in the striatum olivary nucleus and nucleus → Trétiakoff demonstrated the underlying cell loss of the ambiguus substantia nigra in cases of paralysis agitans which is now Diffuse myoclonus Neuronal degeneration, usually known as Parkinson Disease diffuse or predominating in cerebral → Observations related hemiballismus to lesions in the or cerebellar cortex and dentate subthalamic nucleus of Luy’s and its immediate connections Extrapyramidal Syndrome 📣 nuclei → Was first delineated on clinical grounds by Wilson in 1912 with → None of the relationships between anatomic loci and movement disorders are exclusive and the same movement disorder can result from lesions at one of several sites → Wilson Disease ❗️ the disease-bearing his name ▪ He called it hepatolenticular degeneration to describe the → Symptoms mentioned are mostly found in the location indicated in the corresponding column but it is not consistent or always due to lesions in these locations striking abnormality degeneration of the putamen of bilaterally symmetrical ✏️ CONCEPT CHECKPOINT ✏️ 1. T/F. In parkinson’s disease, there is diminished activity of → Clinicopathologic studies of Huntington chorea related the excessive movements and rigidity characteristic of the the direct pathway which contributes to hyperkinetic disease to a loss of nerve cells in the striatum movements → It was not until 1919 that Trétiakoff demonstrated the 2. What is the principal location of morbid anatomy of underlying cell loss of the substantia nigra in cases of what athetosis and dystonia? was then called paralysis agitans and is now known as a. Caudate nucleus and putamen Parkinson Disease b. Contralateral striatum → Finally, a series of observations related hemiballismus to c. Ipsilateral cerebellar hemisphere lesions in the subthalamic nucleus of Luy’s and its ANS: immediate connections 1. F. There is diminished activity of the direct pathway which contributes → While these observations have been invaluable, it has become to HYPOkinetic movements apparent from clinical work that none of the relationships 2. B Caudate nucleus and putamen = chronic chorea of Huntington type. between anatomic loci and movement disorders are Ipsilateral cerebellar hemisphere = cerebellar incoordination, intention tremor, and hypotonia. exclusive and the same movement disorder can result from lesions at one of several sites IV. NEUROTRANSMITTERS IN THE BASAL GANGLIA 📣 → Symptoms mentioned here are mostly found in the location Most important neurotransmitter substances from the point of view indicated in the corresponding column but it is not consistent of basal ganglionic function are: or always due to lesions in these locations ⚠️ ⚠️ → Glutamate → Acetylcholine MUST KNOW → GABA → Serotonin Close association basal ganglia and the corticospinal systems → Dopamine ❗️ become evident in the course of many forms of neurologic dx A. GLUTAMATE Division between pyramidal and extrapyramidal motor system Primary excitatory neurotransmitter of the brain distinguishes several motor syndromes: Released by the excitatory neurons from the cortex and → Corticospinal Syndrome ▪ Loss of volitional movement (paralysis or paresis ▪ Spasticity ) 📣 subthalamic nucleus B. GAMMA-AMINO BUTYRIC ACID (GABA) → Hypokinetic Basal Ganglionic Syndrome Main inhibitory neurotransmitter in the brain, ▪ Bradykinesia ▪ Rigidity reticulata projection neurons ❗️ Released by the striatal, pallidal, and substantia nigra pars NEUROLOGY II Movement Disorders: Disorders of the Basal ganglia; Chorea, Athetosis, Ballismus, Tremors, Dystonia, Tics Page 4 of 16  C. DOPAMINE ▪ Released by the excitatory neurons from the cortex and compacta ❗️ Main source in the basal ganglia is the substantia nigra pars Action is determined by the type of receptor where it binds: subthalamic nucleus → GABA ▪ Main inhibitory nt → D1-like (D1 and D5) ▪ Striatal, pallidal, and substantia nigra pars reticulata ▪ Net excitatory projection neurons ▪ Involved in direct pathway → Dopamine → D2-like (D2, D3, and D4) ▪ Net inhibitory ▪ Involved in the indirect pathway ▪ Main source: substantia nigra pars compacta ▪ Table 3. Post Synaptic Dopamine Receptors 📣 PHARMACO ANATOMIC PATHWAY TYPE LOGIC DISTRIBUTION INVOLVEMENT ACTION D1 Highly D1-like(e) Direct D2 concentrated in D2-like(i) Indirect the striatum D3 Nucleus D2-like(i) Indirect accumbens D4 Frontal cortex D2-like(i) Indirect Certain limbic structures D5 Hippocampus D1-like(e) Direct Limbic system * (e) = excitatory; (i) = inhibitory Figure 10. No need to memorize: Properties and localization of → Acetylcholine dopamine receptors [Lecturer’s PPT] ▪ Produced by: − Local interneurons in the striatum (modulatory effect) Five known types of postsynaptic dopamine receptors, each with D1 and D2 receptors ❗️ a particular anatomic distribution and pharmacologic action 📣 − Projection neurons of the pedunculopontine nucleus (for locomotion) ▪ Table 4. Receptor and Net Effect → Are the ones most implicated in diseases of the basal ganglia Table 3. Post Synaptic Dopamine Receptors 📣 Muscarinic RECEPTOR M1 NET EFFECT Net excitatory PATHWAY M2 and M4 Net inhibitory ANATOMIC PHARMACOLOGIC TYPE INVOLVE Nicotinic Net excitatory DISTRIBUTION ACTION MENT → Norepinephrine D1 Highly D1-like(e) Direct ▪ Produced by projection neurons of the locus coeruleus D2 concentrated in D2-like(i) Indirect (modulatory effect) the striatum → Serotonin D3 Nucleus D2-like(i) Indirect ▪ Produced by serotonergic neurons of the median raphe accumbens nuclei (modulatory effect) D4 Frontal cortex D2-like(i) Indirect → Adenosine Certain limbic ▪ Endogenous molecule structures ▪ A2A receptors D5 Hippocampus D1-like(e) Direct − Colocalized with dopamine D2 receptors in the Limbic system striatum *(e) = excitatory; (i) = inhibitory ✏️ CONCEPT CHECKPOINT 1. What is the net effect of a Nicotinic Receptor ✏️ D. ACETYLCHOLINE ❗️ Produced by: a. Excitatory → Local interneurons in the striatum b. Inhibitory ❗️ ▪ Modulatory effect c. Any of the above → Projection neurons of the pedunculopontine nucleus 2. Which of the following is the primary excitatory ▪ For locomotion neurotransmitter of the brain? Net effect depends on the receptor where it binds a. GABA b. Glutamate Table 4. Receptor and Net Effect c. Adenosine RECEPTOR NET EFFECT 3. Norepinephrine is produced by? M1 Net excitatory a. Projection neurons of the median raphe nuclei Muscarinic M2 and M4 Net inhibitory b. Projection neurons of the pedunculopontine nucleus Nicotinic Net excitatory c. Projection neurons of the locus coeruleus E. NOREPINEPHRINE ANS: 1. A Refer to Table X. Produced by projection neurons of the locus coeruleus 2. B GABA is the main inhibitory neurotransmitter in the brain while (modulatory effect) adenosine is an endogenous molecule in the brain. F. SEROTONIN 3. C Serotonin is produced by serotonergic neurons of the median raphe nuclei. Acetylcholine produced by projection neurons of the Produced by serotonergic neurons of the median raphe nuclei pedunculopontine nucleus (modulatory effect) VI. SYMPTOMS OF BASAL GANGLIA DISEASE G. ADENOSINE Table 5. Symptoms of Basal Ganglia A2A receptors ❗️ Endogenous molecule in the brain → Colocalized with dopamine D2 receptors in the striatum Negative Symptoms Hypokinesia Positive Symptoms Tremor ⚠️ MUST KNOW Neurotransmitters in the Basal Ganglia ⚠️ Bradykinesia Loss of normal postural Rigidity Involuntary movements reflexes (e.g., chorea, athetosis, → Glutamate ballismus, dystonia) ▪ Primary excitatory nt NEUROLOGY II Movement Disorders: Disorders of the Basal ganglia; Chorea, Athetosis, Ballismus, Tremors, Dystonia, Tics Page 5 of 16  All motor disorders consist of: Rigidity → Negative Symptoms → Muscles are continuously or intermittently firm and tense ▪ Functional deficits → Involves both flexor (more prominent) and extensor muscles, → Positive Symptoms greater on large muscle groups ▪ Excessive motor activity → Even or uniform quality throughout the range of movement of ▪ Release or disinhibition of the activity of the undamaged the limb, or “lead-pipe” rigidity part of the motory system → Not velocity dependent → Present during most of the waking state A. HYPOKINESIA → Tendon reflexes are not enhanced Reduction in the spontaneous movements of an affected part ▪ When released the limb does not assume its original Failure to engage freely in the natural actions of the body Frequent automatic, habitual movements observed in the normal individual are absent or greatly reduced → Cogwheel Phenomenon ❗️ position it maintains its position. ▪ When the hand is dorsiflexed, one encounters a rhythmically → For example, putting hands on the face, folding the arms or interrupted, ratchet-like resistance crossing the legs, looking to one side while the eyes move but → Distinct types of variable resistance to passive movement is not the head, in arising from a chair, one in which patient is unable to relax muscle group on request → Failure to make the usual small preliminary adjustments, ▪ Paratonic Rigidity or Oppositional resistance: when blinking is infrequent, saliva is swallowed less frequently muscle is passively stretched, the patient appears actively (drooling), the face lacks expressive mobility (masked facies), resisting the movement speech is rapid, mumbling, monotonic, and the voice is mostly → May indicate impairment of connections between the basal soft ganglia and the frontal lobes Strength is not significantly diminished ▪ Must be distinguished from waxy flexibility seen in psychotic Most clearly expressed in a parkinsonian patient where it takes the catatonic patients form of extreme underactivity (‘“poverty’) of movement. − Flexibility cerea: When a limb placed in a suspended Akinesia is the extreme form of hypokinesia position is maintained for minutes in the identical posture [Adams] B. BRADYKINESIA Slowness of movement Velocity of movement, or the time of onset to completion of movement, is slower than normal C. DISORDERS OF POSTURAL FIXATION, EQUILIBRIUM, AND RIGHTING Figure 14. Spasticity[Lecturer’s PPT] Spasticity → Not preceded by an initial “free interval” and has an even or uniform quality throughout → “Clasp-knife” movement in which there is a give at the end of the movement → Velocity dependent → DTRs are enhanced ⚠️ ⚠️ Figure 11. Postural Fixation[Lecturer’s PPT] Involuntary flexion of the trunk, limbs, and neck as seen in Figure MUST KNOW 11. Symptoms of Basal Ganglia Anticipatory and compensatory righting and reflexes are impaired → Negative Symptoms or Functional Deficits Inability to make appropriate postural adjustments to tilting or ▪ Hypokinesia falling ▪ Bradykinesia Inability to move from the reclining to standing position ▪ Loss of normal postural reflexes → Positive Symptoms or Excessive motor activity ▪ Tremor ▪ Rigidity ▪ Involuntary movements (e.g. chorea, athetosis, ballismus, dystonia) Hypokinesia → Reduction in the spontaneous movements of an affected part Figure 12. Impairment of anticipatory, and compensatory righting and → Failure to engage freely in the natural actions of the body reflexes[Lecturer’s PPT] → Frequent automatic, habitual movements observed in the See Figure 12. normal individual are absent or greatly reduced → First patient (Left) was able to prevent himself from falling after → Akinesia is extreme form of hypokinesia the pull test Bradykinesia → Second patient (Right) continuously fell backward, unable to → Slowness of movement correct his posture → The velocity of movement, or the time of onset to completion Not attributable to weakness or defects in proprioceptive, of movement, is slower than normal labyrinthine, or visual function Disorders of postural fixation, equilibrium, and righting → Principal forces that control the normal posture of the head and → Involuntary flexion of the trunk, limbs, and neck trunk → Anticipatory, and compensatory righting reflexes are D. RIGIDITY AND ALTERATIONS IN MUSCLE TONE impaired → Inability to make appropriate postural adjustments to tilting or falling → Inability to move from the reclining to standing position Rigidity and alterations in muscle tone → Rigidity ▪ Muscles are continuously or intermittently firm and tense ▪ Involves both flexor (more prominent) and extensor Figure 13. Rigidity[Lecturer’s PPT] muscles, greater on large muscle groups NEUROLOGY II Movement Disorders: Disorders of the Basal ganglia; Chorea, Athetosis, Ballismus, Tremors, Dystonia, Tics Page 6 of 16  ▪ Even or uniform quality throughout the range of → Hemichorea movement of the limb, or “lead-pipe” rigidity ▪ Limited to one side of the body ▪ Not velocity dependent ▪ Seen in stroke or vascular malformations ▪ Present during most of waking states ▪ Tendon reflexes are not enhanced ▪ Cogwheel Phenomenon − When the hand is dorsiflexed, one encounters a rhythmically interrupted, ratchet-like resistance ▪ Distinct types of variable resistance to passive movement is one in which patient is unable to relax [Lecturer’s PPT] muscle group on request Figure 15. Chorea − Paratonic Rigidity: when muscle are passively stretched, the patient appears actively resisting the movement B. ATHETOSIS Derived from the Greek word meaning “unfixed” [Adam’s] 📖 ▪ May indicate impairment of connections between the basal ganglia and frontal lobes of the body in one position ❗️ Inability to sustain fingers and toes, tongue, or any other part → Abnormal movements are most pronounced in the digits and → Spasticity ▪ Not preceded by an initial “free interval” and has an even or uniform quality throughout hand, face, tongue, and throat ▪ But no group of muscles is spared ❗️ Maintained posture is interrupted by relatively slow, writhing, or ▪ “Clasp-knife” movement in which there is a give at the twisting, purposeless movements that tend to flow into one end of the movement another ▪ Velocity dependent Combination of athetosis and chorea of all four limbs is a cardinal ▪ DTRs are enhanced ✏️CONCEPT CHECKPOINT 2. What is the extreme form of hypokinesia? ✏️ feature of: → Huntington's disease → Double athetosis – form of cerebral palsy that begins in a. Rigidity childhood. b. Spasticity Athetosis appearing in the first years of life c. Bradykinesia → Result of congenital or postnatal hypoxia or kernicterus d. Akinesia 3. It is a type of rigidity in which when muscles are passively In adults, may occur as an episodic or persistent disorder in stretched, the patient appears actively resisting the hepatic encephalopathy, as a manifestation of chronic intoxication movement. with phenothiazines or haloperidol and as a feature of certain a. Cogwheel Phenomenon degenerative diseases, most notably Huntington chorea but also b. Spasticity Wilson's disease c. Paratonic Rigidity May occur as an effect of excess L-dopa in the treatment of d. Flexibility Crea Parkinson’s disease → Decrease in the activity of the subthalamic nucleus and the ANS: internal segment of the globus pallidus 4. D. Akinesia is the extreme form of hypokinesia 5. C. Paratonic Rigidity or Oppositional Resistance Diseases characterized by athetosis: → Huntington disease → Wilson disease VII. INVOLUNTARY MOVEMENTS → Cerebral palsy → Kernicterus A. CHOREA Derived from the Greek word meaning “dance” 📖 [Adam’s] → Hepatic Encephalopathy → Drug-induced (phenothiazines, haloperidol, L-dopa) type ❗️ Involuntary arrhythmic movements of a forcible rapid, jerky → Movements may be simple or quite elaborate and of variable distribution → When superimposed on voluntary actions or reflex movement, they may assume an exaggerated and bizarre character Diseases characterized by chorea: → Inherited disorders ▪ Huntington disease: Figure 16. Athetosis [Lecturer’s PPT] − Chorea is a major feature − Choreoathetotic: movements are more typically to be a C. BALLISMUS merging of choreiform and athetosis motions ▪ Neuroacanthocytosis movement of an entire limb ❗️ Uncontrollable, large amplitude, poorly patterned flinging → Usually unilateral, may be continuous or intermittent, and may ▪ Wilson disease → Immune-mediated chorea be regarded as hysterical in nature ▪ Sydenham chorea Conceptualized as big chorea and is closely related to athetosis − Linked to streptococcal infection → Frequent coexistence of these movement abnormalities ▪ Chorea gravidarum → Tendency to blend into a less-obtrusive choreoathetosis of the − Linked to pregnancy as it may expose the patient to distal parts of the affected limb lupus-related chorea Result of a lesion of or near the contralateral subthalamic → Lupus erythematosus nucleus → Antiphospholipid antibodies Bilateral hemiballismus may be due to metabolic disturbance → Paraneoplastic ▪ In few cases with lung cancer → Drug-induced chorea ▪ Neuroleptics, OCPs, phenytoin, excess L-Dopa and dopamine agonists, cocaine → Chorea symptomatic of systemic disease ▪ Transitory - occurs during an acute metabolic derangement ▪ Resolves along with metabolic derangement ▪ Symptom of systemic disease : thyrotoxicosis, polycythemia Figure 17. Ballismus [Lecturer’s PPT] vera, toxoplasmosis and AIDS NEUROLOGY II Movement Disorders: Disorders of the Basal ganglia; Chorea, Athetosis, Ballismus, Tremors, Dystonia, Tics Page 7 of 16  D. DYSTONIA Unnatural spasmodic movement or posture that puts the limb in a twisted position → Intermittent, brief, or prolonged spasms or contractions of a group of adjacent muscles that place the body part in a forced and unnatural position Figure 20. Spasmodic Torticollis [Lecturer’s PPT] → Often patterned, repetitive, and tremulous → Can be initiated or worsened by attempted movement BLEPHAROSPASM → Involuntary and cannot be inhibited Causes of generalized dystonia and involuntarily forced closure of the eyes Occurs in mid and late adult life, F>M ❗️ Spasm of the orbicularis oculi muscles → excessive blinking → Dystonia musculorum deformans: associated with a mutation in the DYT gene → Idiopathic dystonia: familial and autosomal dominant → Rapid-onset dystonia-parkinsonism: onset in adolescence or early adulthood, rapid progression (hours or days) → Neuroleptic drugs: retrocollis, arching of the back, internal rotation of the arms, extension of the elbows and wrists (Opisthontonos) Diseases characterized by dystonia → Hereditary and degenerative dystonia Figure 21. Blepharospasm [Lecturer’s PPT] ▪ Huntington chorea ▪ Dystonia musculorum deformans LINGUAL, FACIAL, AND OROMANDIBULAR SPASMS ▪ Focal dystonias and occupational spasms (MEIGE SYNDROME) ▪ Parkinson disease ▪ Progressive supranuclear palsy the platysma, and protrusion of the tongue ❗️ Forceful opening of the jaw, retraction of the lips, spasm of → Or the jaw may be clamped shut, and the lips may purse → Drug-induced dystonias ▪ Phenothiazine, haloperidol, metoclopramide, neuroleptic Occurs in the 6th decade of life, F>M intoxication, excess L-dopa → Symptomatic (secondary) dystonias → Idiopathic/focal dystonias ▪ Spasmodic Torticollis ❗️ ▪ Wilson disease, kernicterus, AIDS, multiple sclerosis ▪ Blepharospasm ▪ Hemifacial spasm Figure 22. Meige Syndrome [Lecturer’s PPT] TASK-SPECIFIC DYSTONIA MUSICIAN’S SPASM Occurs when the patient is performing a specific task Delicate motor skill, perfected by years of practice and performed almost automatically, suddenly requires a conscious and labored effort for its execution [Lecturer’s PPT] Figure 18. Dystonia Spasm of the finger occurs while playing the instrument FOCAL DYSTONIAS Restricted or fragmented forms of dystonia ❗️ → Spasmodic Torticollis (Idiopathic Cervical Dystonia) → Blepharospasm → Lingual, Facial, and Oromandibular Spasms (Meige Syndrome) → Task-specific dystonias ▪ Writer's Cramp and Musician's Spasm → Drug-induced tardive (delayed) dyskinesia Figure 23. Musician’s Spasm. [Lecturer’s PPT] WRITER’S CRAMP Upon attempting to write, all the muscles in the thumb and ❗️ fingers either go into spasm or are inhibited by a feeling of stiffness and pain [Lecturer’s PPT] Figure 19. Focal Dystonia SPASMODIC TORTICOLLIS Most common ❗️ (IDIOPATHIC CERVICAL DYSTONIA) Usually begins as a subtle tilting or turning of the head that tends to worsen slowly Peak incidence in the 5th decade, F>M Figure 24. Writer’s cramp [Lecturer’s PPT] DYT1 gene abnormality Localized to the neck and cervical muscles TREATMENT → Most prominently affected muscles are the Treatment varies depending on the type of dystonia sternocleidomastoid, levator scapulae, and trapezius Focal Dystonia Worse upon standing or walking and reduced or abolished by → Periodic Botox injections contractual stimulus Generalized Dystonia: More difficult to treat Muscles undergo hypertrophy → Medications: Anticholinergic agents, Trihexyphenidyl, → In late stage, pain of the contracting muscle is common benztropine, and ethopropazine NEUROLOGY II Movement Disorders: Disorders of the Basal ganglia; Chorea, Athetosis, Ballismus, Tremors, Dystonia, Tics Page 8 of 16  → Invasive procedures: Deep brain stimulation targets the Identifying feature: appears or enhances with attempts to Pallidum and Ventrolateral Thalamus maintain a static limb posture or to produce a smooth trajectory of Drug-induced Dystonia: movement → Stop the offending drug, which requires identifying the Worsened by emotion, exercise, and fatigue triggering drug first One infrequent type of essential tremor is faster and of the same → Tetrabenazine and reserpine, centrally active monoamine frequency (6 to 8 Hz) as enhanced physiologic tremor depleting agents May increase in severity to a point where the patient’s handwriting becomes illegible and he cannot bring a spoon or glass to his lips without spilling its contents → Eventually, all tasks that require manual dexterity become difficult or impossible Autosomal dominant inheritance pattern with high penetrance. → Typical essential tremor occurs in several members of a family, hereditary essential tremor 📖 for which reason it has been called familial, genetic, or → Idiopathic and familial types cannot be distinguished on the basis of their physiologic and pharmacologic properties ▪ Should not be considered as separate entities. Figure 25. Treatment options for dystonia [Lecturer’s PPT] Tremor frequency diminishes slightly with age while its amplitude increases. E. TREMORS Tremor usually begins in the hands and is symmetrical Involuntary rhythmic oscillatory movement Lower limbs are usually spared or only minimally affected → Produced by alternating or irregularly synchronous contractions Treatment: Primidone, Beta-blockers, Botox injections of reciprocally innervated muscles → Rhythmic quality ▪ Distinguishes tremor from the other involuntary movements → Oscillatory nature ▪ Distinguishes tremor from myoclonus and asterixis Tremors are classified either resting or action tremors → Action tremors ▪ Evident during the use of the affected body part ▪ Accentuated as greater precision of movement is demanded Figure 27. Essential tremor [Lecturer’s PPT] ▪ Tremors are absent when the limbs are relaxed ▪ Can be roughly divided into two categories: 📖 − Goal-directed action tremor of the ataxic type related to CEREBELLAR TREMOR Also called intention, ataxic, or goal-directed action tremor Salient feature: Requires the performance of an exacting, cerebellar disorders precise, projected movement − Postural tremors, which are either the enhanced Tremor is absent when the limbs are inactive and during the first physiologic variety or essential (genetic) tremor part of a voluntary movement → Resting tremors → As the action and fine adjustments continue, an irregular ▪ Occurs while at rest interruption of forward progression appears ▪ Parkinsonian tremors Oscillations occur in more than one plane − Frequency: 3-5 Hz → Mainly horizontal and perpendicular − Coarse, rhythmic tremor, localized in one or both hands Tremor and ataxia may seriously interfere with the patient’s and forearms (usually asymmetric) performance of skilled acts − Occurs when the limb is in an attitude of repose and is → In some patients there is a rhythmic oscillation of the head on suppressed or diminished by willed movement the trunk (titubation), or of the trunk itself, at approximately the − Characterized by bursts of activity that alternate between same rate opposing muscle groups This type of tremor points to disease of the cerebellum or its − “Alternating” in the sense that it takes the form of outflow connections flexion–extension or abduction–adduction of the fingers → Certain peripheral nerve diseases may simulate it. forearm is also a common presentation − Pill rolling tremor 📖 or the hand; pronation–supination of the hand and A lesion of the nucleus interpositus or dentate nucleus causes an ipsilateral tremor of ataxic type, associated with other manifestations of cerebellar ataxia. o Flexion–extension of the fingers in combination with → In addition, such a lesion gives rise to a “simple tremor” 📖 adduction–abduction of the thumb yields this characteristic of Parkinson disease − Increasing rigidity obscures or reduces resting tremor TG Note: See appendix for the table on the main types of tremors ❗️ Figure 28. Cerebellar tremor [Lecturer’s PPT] RUBRAL TREMOR Higher amplitude tremor associated with cerebellar ataxia → Lifting the arm slightly or maintaining a static posture with the arms held out, results in a wide-ranging, rhythmic 2- to 5-Hz Figure 26. Main Types of Tremor [Lecturer’s PPT] “wing-beating” movement ❗️ ESSENTIAL TREMOR → Tremor can throw the patient off balance Most common type of tremor Lesion in the midbrain involving the rostral projections of the Lower frequency (4 to 8 Hz) than physiologic tremor dentatorubrothalamic fibers and the medial part of the ventral → Unassociated with other neurologic changes; thus it is called tegmental reticular nucleus “essential.” → Because of the location of the lesion in the region of the red → Usually at the lower end of this frequency range and of variable nucleus, Holmes originally called this a rubral tremor amplitude NEUROLOGY II Movement Disorders: Disorders of the Basal ganglia; Chorea, Athetosis, Ballismus, Tremors, Dystonia, Tics Page 9 of 16  First observed in patients with hepatic encephalopathy but was later noted to occur with hypercapnia, uremia, and other metabolic and toxic encephalopathies Evoked by holding arms outstretched with hands dorsiflexed, noting flexion movements of the hands Unilateral asterixis occurs in the arm and leg opposite the anterior thalamic lesion Figure 29. Rubral tremor [Lecturer’s PPT] → Other localization may include frontal lobe, midbrain, and cerebellum ORTHOSTATIC TREMOR If this presents as bilateral, this is most likely due to metabolic Rare but striking tremor isolated to the legs encephalopathies Remarkable by its occurrence only during quiet standing and its cessation almost immediately on walking Difficult to classify and more relevant to disorders of gait than it is to tremors of other types → Frequency of the tremor has been recorded as approximately 14 to 16 Hz, making it difficult to observe and more easily palpable An important accompanying feature is the sensation of severe imbalance, which causes the patient to assume a widened stance Figure 32. Asterixis [Lecturer’s PPT] while standing G. MYOCLONUS Helicopter sign ❗️ → These patients are unable to walk a straight line (tandem gait) → Sound resembling a distant helicopter during auscultation over Very rapid, shock-like contractions of a group of muscles, irregular in rhythm and amplitude, and, with few exceptions, asynchronous and asymmetrical in distribution the thigh or calf or during surface EMG of the affected muscles → Segmental myoclonus Treatment: Some cases have responded to the administration of ▪ Phenomenon in which contractions occur singly or are clonazepam, gabapentin, primidone, or sodium valproate alone or repeated in a restricted group of muscles, such as those of in combination but it often proves difficult to treat an arm or leg → Polymyoclonus ▪ Widespread, lightning-like, arrhythmic repeated contractions Muscle contraction is brief (20 to 50 ms) in all forms of myoclonus—that is, faster than that of chorea, with which it may be confused Speed of the myoclonic contraction is the same whether it involves a part of a muscle, a whole muscle, or a group of muscles TG Note: See appendix for Causes of Generalized and Regional Myoclonus Figure 30. Orthostatic tremor [Lecturer’s PPT] PALATAL TREMOR Rare disorder consisting of rapid, rhythmic, involuntary movements of the soft palate Persists during sleep and is sometimes associated with pendular nystagmus that is synchronized with the palatal movements Palatal Myoclonus 📖 → For many years it was thought to be a form of uniphasic Figure 33. Myoclonus [Lecturer’s PPT] 📖 myoclonus (hence the terms palatal myoclonus and palatal nystagmus) FOCAL, SEGMENTAL, AND REGIONAL MYOCLONUS → Because of the persistent rhythmicity, it is now classified as a Localized myoclonic jerk tremor 2 Forms ❗️ → Essential Palatal Tremor Takes the form of an almost continuous arrhythmic jerking of a restricted group of muscles, often on one side of the body Patients with idiopathic epilepsy may complain of a localized ▪ Reflects the rhythmic activation of the tensor veli palatini myoclonic jerk or a short burst of myoclonic jerks, occurring muscles ▪ No known pathologic basis generalized seizure, after which these movements cease 📖 particularly on awakening and on the day or two preceding a major 📖 ▪ Palatal movement may impart a repetitive audible click, which ceases during sleep DIFFUSE MYOCLONUS → Symptomatic Palatal Tremor Polymyoclonus ▪ Caused by a diverse group of brainstem lesions that Described a sporadic instance of idiopathic widespread muscle interrupt the central tegmental tracts jerking in an adult ▪ There is a latency of many months after the focal injury Several disparate disorders give rise to diffuse myoclonus 📖 before the tremor becomes evident → It may occur in pure or “essential” form as a benign, often familial, nonprogressive disease H. STARTLE SYNDROME AKA hyperekplexia Contraction of the orbicularis, neck, spinal musculature, and legs of greater amplitude, in response to minimal stimuli Mutation of inhibitory glycine receptor Figure 31. Palatal tremor [Lecturer’s PPT] Localized in the pontine reticular nuclei with transmission to the lower brainstem and spinal motor neurons via the reticulospinal F. ASTERIXIS tract Consists of arrhythmic lapses of sustained posture that allow Treatment: gravity or the inherent elasticity of muscles to produce a sudden → Clonazepam and Levetiracetam movement, which the patient then corrects, sometimes with ▪ Anti-seizure medications overshoot → Vigevano maneuver ▪ Act of flexing the neck and bringing the arms close to the torso which may reduce the intensity of