MOVEMENT DISORDERS .pptx

movement disoders types and description

1. MOVEMENT DISORDERS

2. Basal ganglia disorders. Subclassified as hypokinetic and hyperkinetic disorders. Rigidity due to pyramidal tract involvement and ataxia due to cerebellar involvement are some times included under umbrella of movement disorders.

3. BASAL GANGLIA DISORDERS HYPOKINETIC HYPERKINETIC AKINESIA RIGIDITY TREMOR CHOREA ATHETOSIS TICS PARKINSON’S DISEASE HUTINGTON DISEASE TOURETTES SYNDROME DYSTONIA MANNERISMS STEREOTYPES MYOCLONUS

4. HYPERKINETIC MOVEMENT DISORDERS RHYTHMIC NONRHYTHMIC TREMOR SUSTAINED SLOW FAST DYSTONIA ATHETOSIS SUPPRESSIBLE NON-SUPPRESSIBLE TICS ATHETOSIS CHOREA BALLISMUS DYSKINESIA MYOCLONUS

5. TREMOR Tremor is defined as rhythmic sinusoidal oscillation of a body part, usually due to alternating activation of agonist and antagonist muscles. Tremor seen when body part is at rest is called rest tremor. Tremor triggered by movement is called a kinetic tremor. Postural tremor seen in certain postures i.e out stretching of hands and action tremor, seen during movement are types of kinetic tremor. To study tremor in a patient first look for tremor when limbs are at rest then ask the patient to stretch out their limbs and lastly make them do alternating action like finger-nose-finger movements.

6. TREMOR

7. DYSTONIA Dystonia is defined as an involuntary movement that produces muscle spasms leading to twisting movements or abnormal sustained posture of the affected body part or region. Dystonia is a manifestation of co-contraction of agonist and antagonist muscles Certain posture or positions of body part can alleviate dystonia.

8. DYSTONIA TREATMENT Medical (a) Trihexyphenidyl, benzodiazepines and tetrabenazine (b) Botulinum Toxin: for focal dystonias Surgical: Deep brain stimulation of globus pallidus internus In all patients with young onset primary dystonias, a trial with L-Dopa for 3 months is essential, before classifying the dystonia as L-dopa non-responsive. Usually a dose of 300 to 600 mg/day of levodopa is required.

9. CHOREA Chorea is defined as brief quasi purposeless involuntary movements that flit and flow from one body part to another Chorea is often generalised but can remain focal, e.g. face or one side of the body (hemi-chorea). In clinical practice the terms chorea and choreoathetosis are often used interchangeably. Athetoid movements are slow, distal.

10. BALLISMUS Severe proximal chorea resulting in wild flinging movement of limbs is known as ballism. Hemiballism refers to ballism restricted to one side of the body. Vascular injury involving the subthalamic nucleus is the commonest cause for hemiballism.

11. TICS Brief involuntary stereotypic movements or vocalisations An important characteristic of tics is patient’s ability to suppress them for short periods Patients feel a sense of subjective discomfort during suppression of tics .

12. TICS Simple motor tic: Eye blinking, eyebrow raising, winking, forehead raising, pouting, nose wrinkling, shoulder raising. Complex motor tic: Head shaking, touching self, touching others, kicking, jumping, hopping. Simple vocal tic: Grunting, sniffing, coughing, humming,whistling. Complex vocal tic: Saying words or parts of words, echolalia, pallilalia.

13. TICS The most important tic disorder is Tourette’s syndrome. It affects 14 % of population under the age of 18 years. Beyond 18 years,symptoms wane reducing its prevalence in adult life. Diagnosisof Tourette’s syndrome requires presence of multiple motorand vocal tics, and these tics for one year and in a person under18 years of age. Tics in Tourette’s syndrome and tics can be treated with tetrabenazine, clonazepam, clonidine and botulium toxin

14. MYOCLONUS Myoclonus is a brief electric shock like jerk. Physiological myoclonus is experienced by all as hiccups or jerks while falling asleep (hypnic jerk). Myoclonus results from brief activation of a group of muscles. This activation can be from the cortex, subcortical structures like brainstem; spinal cord or nerve, root and plexii.

15. MYOCLONUS Clinically it may be possible to localise the origin of myoclonus. Cortical origin manifests as small amptitude distal limb jerk and is often focal. It may be stimulus sensitive, i.e gently tapping the affected body part triggers the myoclonic jerk Subcortical myoclonus is large amplitude and generalised.

16. STEREOTYPY Stereotypy is a continuous, repetitive, coordinated movement that may be associated with a variety of disorders and rarely occurs as an isolated, idiopathic movement disorder.

17. ‹#› PARKINSON’S DISEASE

18. Second most common age-related neurodegenerative disease, exceeded only by Alzheimer’s. Mean age of onset of PD is about 60 years , and the lifetime risk is ~2% for men and 1.3% for women. Frequency of PD increases with aging, but cases can be seen in individuals in their twenties and even younger, particularly in association with a gene mutation.

19. Rest tremor Rigidity (stiffness) Bradykinesia (slowing) Gait dysfunction with postural instability CARDINAL FEATURES

20. Freezing of gait Speech difficulty Swallowing impairment Autonomic disturbances Sensory alterations Mood disorders Sleep dysfunction Cognitive impairment Dementia ADDITIONAL CLINICAL FEATURES

21. Pathologically, the hallmark features of PD Degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) Reduced striatal dopamine Intraneuronal proteinaceous inclusions known as Lewy bodies and Lewy neurites that primarily contain the protein α-synuclein

22. Neuronal degeneration with inclusion body formation can also affect Cholinergic neurons of the nucleus basalis of Meynert (NBM) Norepinephrine neurons of the locus coeruleus (LC) Serotonin neurons in the raphe nuclei of the brainstem Neurons of the olfactory system, cerebral hemispheres, spinal cord, and peripheral autonomic nervous system.

23. ATYPICAL, SECONDARY AND OTHER FORMS OF PARKINSONISM ATYPICAL PD: Refers to a group of neurodegenerative conditions that usually are associated with more widespread pathology than found in PD . Include Multiple System Atrophy (MSA), Progressive Supranuclear Palsy (PSP), and Corticobasal syndrome (CBS). As a group, they present with parkinsonism (rigidity and bradykinesia) but manifest clinical differences from PD reflecting the differences in their underlying pathology. In comparison to PD, the atypical parkinsonisms are characterized clinically by early involvement of speech and gait, absence of rest tremor, lack of motor asymmetry, poor or no response to levodopa, and a more aggressive clinical course .

24. SECONDARY PARKINSONISMS: Occur as a result of a variety of primary conditions including that can cause damage to specific regions of the basal ganglia. Dopamine-blocking agents such as neuroleptics are the most common cause of secondary parkinsonism. Other drugs that can cause secondary parkinsonism include tetrabenazine, calcium channel blockers (flunarizine, cinnarizine), amiodarone, and lithium .

25. TREATMENT LEVODOPA DOPAMINE AGONISTS MAO-B INHIBITORS COMT INHIBITORS OTHER MEDICAL THERAPIES SURGICAL TREATMENT

26. LEVODOPA Levodopa is routinely administered in combination with a peripheral decarboxylase inhibitor to prevent its peripheral metabolism to dopamine and the development of nausea, vomiting, and orthostatic hypotension due to activation of dopamine receptors in the area postrema that are not protected by the BBB.

27. LEVODOPA

28. LEVODOPA Levodopa remains the most effective symptomatic treatment for PD and the gold standard against which new therapies are compared. Levodopa benefits the classic motor features of PD, prolongs independence and employability, improves quality of life, and increases life span. Almost all PD patients experience improvement, and failure to respond to an adequate trial of levodopa should cause the diagnosis to be questioned.

29. LEVODOPA There are important limitations of levodopa therapy. Acute dopaminergic side effects include nausea, vomiting, and orthostatic hypotension. These are usually transient and can generally be avoided by starting with low doses and gradual titration. Levodopa-induced motor complications consist of fluctuations in motor response (“on” episodes when the drug is working and “off” episodes when parkinsonian features return) and involuntary movements known as dyskinesias which typically complicate “on” periods

30. LEVODOPA Behavioral complications can also be encountered in levodopa-treated patients. A dopamine dysregulation syndrome has been described where patients have a craving for levodopa and take frequent and unnecessary doses of the drug in an addictive manner.

31. DOPAMINE AGONISTS Act directly on dopamine receptors Do not require metabolic conversion to an active product and do not undergo oxidative metabolism Initial dopamine agonists were ergot derivatives ( bromocriptine, pergolide, cabergoline) and were associated with potentially serious ergot-related side effects such as cardiac valvular damage and pulmonary fibrosis. Second generation of non ergot dopamine agonists (e.g., pramipexole, ropinirole, rotigotin)

32. DOPAMINE AGONISTS Ropinirole and pramipexole are available as orally administered immediate and extended-release formulations. Rotigotine is administered as a once-daily transdermal patch . Apomorphine must be administered parenterally as it is rapidly and extensively metabolized if taken orally.

33. DOPAMINE AGONISTS Acute side effects are primarily dopaminergic and include nausea, vomiting, and orthostatic hypotension. Side effects associated with chronic use include hallucinations and cognitive impairment Sedation with sudden unintended episodes of falling asleep

34. MAO-B INHIBITORS Inhibitors of monoamine oxidase type B (MAO-B) block central dopamine metabolism and increase synaptic concentrations of the neurotransmitter Selegiline and rasagiline are relatively selective inhibitors of the MAO-B isoform of the enzyme. Provide antiparkinsonian benefits when used as monotherapy in early disease stages and reduced “off” time when used as an adjunct to levodopa in patients with motor fluctuations. Generally safe and well tolerated.

35. MAO-B INHIBITORS May increase dyskinesia in levodopa-treated patients, but this can usually be controlled by down-titrating the dose of levodopa. Inhibition of the MAO-A isoform prevents metabolism of tyramine in the gut, leading to a potentially fatal hypertensive reaction known as a “cheese effect” because it can be precipitated by foods rich in tyramine such as some cheeses, aged meats, and red wine Selegiline and rasagiline do not functionally inhibit MAO-A and are not associated with a cheese effect with doses used in clinical practice

36. MAO-B INHIBITORS Safinamide is a reversible MAO-B inhibitor that has recently been approved as an adjunct to levodopa in advanced PD patients with motor fluctuations. Also acts to block activated sodium channels and inhibit glutamate release, and is currently being studied as a possible antidyskinetic agent.

37. COMT INHIBITORS When levodopa is administered with a decarboxylase inhibitor, it is primarily metabolized in the periphery by the catechol-O-methyl transferase (COMT) enzyme . Inhibitors of COMT increase the elimination half-life of levodopa and enhance itsits brain availability. Combining levodopa with a COMT inhibitor reduces “off” time and prolongs “on” time in fluctuating patients while enhancing motor scores .

38. COMT INHIBITORS Two COMT inhibitors, tolcapone and entacapone , have been approved for use. More recently, opicapone (a long-acting, once daily COMT inhibitor) has been approved. Side effects of COMT inhibitors are primarily dopaminergic (nausea, vomiting, increased dyskinesia) and can usually be controlled by down-titrating the dose of levodopa by 20–30%.

39. COMT INHIBITORS Severe diarrhea has been described with tolcapone, and to a lesser degree with entacapone, and necessitates stopping the medication in 5–10% of individuals. Cases of fatal hepatic toxicity have been reported with tolcapone. Discoloration of urine can be seen with COMT inhibitors due to accumulation of a metabolite, but it is of no clinical concern.

40. OTHER MEDICAL THERAPIES Centrally acting anticholinergic drugs such as trihexyphenidyl and benztropine were used historically for the treatment of PD, their major clinical effect is on tremor, although it is not certain that this benefit is superior to what can be obtained with agents such as levodopa and dopamine agonists.

41. OTHER MEDICAL THERAPIES Amantadine was originally introduced as an antiviral agent, but was appreciated to also have antiparkinsonian effects that are thought to be due to N-methyl-d-aspartate (NMDA) receptor antagonism. It is the only oral agent that has been demonstrated in controlled studies to reduce dyskinesia without worsening parkinsonian features, although benefits may be relatively transient .

42. SURGICAL TREATMENT Most surgical procedures for PD performed today use deep brain stimulation (DBS). Here, an electrode is placed into the target area and connected to a stimulator inserted subcutaneously over the chest wall. DBS simulates the effects of a lesion without necessitating making a brain lesion. The precise mechanism whereby DBS works is not fully resolved but may act by disrupting the abnormal neurophysiological signals associated with PD and motor complications.

43. SURGICAL TREATMENT DBS for PD primarily targets the STN or the Gpi. It provides dramatic results, particularly with respect to tremor and reducing both “off” time and dyskinesias, but does not provide superior clinical benefits or improve features that do not respond to levodopa such as freezing, falling, and dementia.

44. MANAGEMENT OF THE NONMOTOR AND NONDOPAMINERGIC FEATURES OF PD NONPHARMACOLOGIC THERAPY