Recent advances in the mangement of extra pyramidal basal ganglia disorders
RECENT ADVANCES IN THEMANGEMENT OF EXTRA PYRAMIDAL- (BASAL GANGLIA) DISORDERSProf. A.V. SRINIVASAN, MD, DM, Ph.D, F.A.A.N, F.I.A.N, EMERITUS PROFESSOR TAMILNADU DR.M.G.R MEDICAL UNIVERSITY CHENNAI FORMER PROFESSOR AND HEAD INSTITUTE OF NEUROLOGY MADRAS MEDICAL COLLEGE 17th MAY 2009
Sir William OslerTo study the phenomenon of diseasewithout books is to sail an uncharted sea,while to study books, without patients isnot to go to sea at all. Sir William Osler Aphorisms
DEFINITIONMovement disorders can be defined asneurologic syndromes in which there iseither an excess of movement or paucity ofvoluntary and automatic movements,unrelated to weakness or spasticity.
MOVEMENT DISORERSDESCRIBEDStarted on 1567 to 2008 – 111 conditions
CATEGORIES OF MOVEMENTS1. Automatic2. Voluntary3. Semivoluntary4. Involuntary
DEDICATED TO PROF C.D.MARSDEN- A GENIUS IN MOVEMENT DISORDERS•P- PARKINSONISM•R- RESTLESS LEG SYNDROME•O- OROFACIAL DYSKINESIA•F- FIBRILLATION AND FASCICULATIONS• C –CHOREA INCLUDING HEMIBALISM• D- DYSTONIA• M- MYOCLONUS,MYOKYMIA,MYORHYTHMIA,MTAF• A-ATAXIA,AKATHESIA,ATHETOSIS,ABD.DYS• R-RETT SYNDROME,• S-STEREOTYPY,SPASM(HEMIFACIAL),JUMPY STUMPS• D-DYSKINESIA(PAROXYSMAL)• E-ESSENTIAL TREMOR, EKPLEXIA(HYPER)• N-NEUROLEPTIC INDUCED -TARDIVE DYSKINESIA
CHOREARandom, quick Huntington disease unsustained Neurocanthocytosis purposeless movements that have Postinfectious an unpredictable chorea flowing pattern Drug-induced chorea Vascular chorea Autoimmune chorea Chorea gravidarum
Ballismus, Chorea, Athotosis and DystoniaThese should NOT be thought of asseparate entities amenable to specificdefinition but rather as a SPECTRUM ofmovements that blend into one-anotherWHY?
Because……..• They often co-exist• Even neurologists may often not be able to agree as to how a particular movement should be classified!• They often ( with some notable exceptions ) have the same significance in terms of aetiology.
The spectrumBallismus Chorea Athetosis Dystonia Movements become - Less violent / explosive / jerky - Smoother and more flowing - More sustained They differ from tics in that they cannot be suppressed by voluntary control
Ballismus• Violent “flinging” movement of entire limb• Almost always unilateral and therefore use term “ HEMIBALLISMUS”• Involves proximal musculature and is sometimes thought of as a “ proximal unilateral chorea ”• Usually due to a CVA in contralateral subthalamic nucleus
Secondary to medical disorders (A SHEEP)• Anoxic brain damage ( post – CPR )• Systemic lupus erythematosis• Hepatic failure• Endocrine - Thyrotoxicosis - Addisons• Electrolyte - Low Ca, Mg, - High Na• Polycythemia rubra vera
Chorea ( “dance” in Greek)• Rapid irregular muscle jerks• May affect limbs, head, face and tongue• In the limbs chorea refers more to distal movements ( as proximal movements usually called ballismus)• Patients often attempt to conceal involuntary movements by superimposing voluntary movements onto them e.g. an involuntary movement of arm towards face may be adapted to look-like an attempt to look at watch
Sydenham’s chorea• Mainly children / adolescents• Complication of previous group A streptococcal infection• Usually no recent history of infection• Acute / subacute onset• May have behavioural problems• Usually remits spontaneously
Chorea gravidarum• Chorea of any cause that begins in pregnancy• May represent recurrence of Sydenham’s chorea.• Most commonly associated with anti- phospholipid syndrome +/- SLE• Usually resolves spontaneously
Athetosis “ changeable” in Greek• Slow, flowing, often twisting movements• Occurs mainly distally ( hands, fingers)• Can also affect face and tongue• Often use term “ choreoathetosis ” due to overlap between syndromes ( chorea referring to less smooth , more jerky movements)
TREATMENT OF MYOCLONUS Drug Initial Adult DoseClonazepam 0.5 mg / dayLevetiracetam 250 mg / dayPiracetam 400 mg 3 times a dayPrimidone 25 mg / dayValporate 125 mg 2 times a day
TREATMENT OF MYOCLONUS Indication Usual Effective Dose Posthypoxic myoclonus Spinal 2 mg/day divided myoclonus Progressive myoclonic 3 times a day epilepsy Essential myoclonus 1000-1500 mg/day Posthypoxic myoclous Cortical myoclonus Spinal myoclous 1200-16,000 mg/day divided 3 Posthypoxic myoclonus Cortical times a day myoclonus Progressive myoclonic epilepsy Essential myoclonus 500-750 mg/day Cortical myoclonus 750-1000 mg/day divided 2 Most forms of myoclonus times a day
TREMORRepetitive oscillation Essential tremor of a body part Physiologic tremor Parkinson tremor Crebellar tremor
TREATMENT OF ESSENTIAL TREMOR Drug Initial Adult Usual Effective Dose Dose Propranolol 20 mg/day 80-240 mg/day Primidone 12.5-25mg 50-300 mg/day at bed time divided Bio or at bedtime Topiramate 12.5=25mg/day 400 mg/day maximum dose divided Bio
TICStereotyped, Tourette syndrome automatic Celebral palsy or purposeless developmental delay movements and syndromes vocalizations Autism Huntington disease
PRIMARY TIC DISORDERS DIAGNOSTIC CRITERIADISORDER Presence of multiple motor andTourette syndrome vocal tics Age at onset <21 y Tics must occur many times daily, nearly every day, over a period of >1y Disturbance causes marked distress or significant impairment in daily functioning Condition cannot be ascribed to known neurological disorder (symptomatic or secondary tic disorder) Duration of tic disorder <1 yTransient tic disorder
Primary tic disorders Diagnostic CriteriaDisorder Chronic motor or chronic vocalChronic tic disorder tics (but not both of >1y Chronic single motor or chronic single vocal ticChronic single tic Tic order that begins > age 21 disorder Two temporal patterns: - De novo adult-onset tic - Recurrent childhood tic – a ticAdult-onset tic discorder disorder than goes into remission and recurs during adulthood
DIFFERENTIAL DIANOSIS OF TICSlassificationC Diffenential DiagnosisSimple Motor TicsClonic Myoclonus Chorea SeizuresDystonia Dystonia AthetasisTonic Muscle spasms and crampsComplex Motor Tcs Mannerisms Stereotypies Restless legs syndrome SeizurePhenomenologyAbrupt Myoclonus Chorea Hyperekplexia Paraxysmal dyskinesia SeizuresSensory phenomenon Akathisia-stereotypy(urge relief) Restless legs syndrome
Classification Diffenential DiagnosisPerceived as voluntary AkasthisiaSuppressibility All hyperkinesias but less than ticsDecrease with distraction Akasthisia Psychogenic movementsIncrease with stress Most hyperkinesiasIncrease with relaxation Parkinsonian tremor (after a period of stressA)Multifocal migrate Chorea MyoclonusFluctuate spontaneously Paraxysmal dykinesias SeizuresPresent during sleep Myoclonus (segmental) Periodic movements Painfullegs / moving toes Other hyperkinesias SEizures
General guidelines for treatingtardive syndromes• Taper and slowly eliminate causative medications, if clinically possible. Avid sudden cessation of these drugs, which can exacerbate symptoms• If treatment of tardive movements is necessary, the drugs of first choice are the dopamine-depleting drugs reserpine, tetrabenazine, and a- methylparatyrosine. Monitor for the development of depression, hypotension sedation, and parkinsonism.• If dopamine-depleting agents are ineffective, consider a trial of clozpine or quetiapine.• Dopamine receptor-blocking agents can be used as medications of last resort for patients with tardive syndromes despite the risk of worsening the syndrome over the long term.• Consider globus pallidus stimulation if pharmacotherapy is ineffective.
NEUROLEPTIC INDUCED MOVEMENT DISORDERS1. Acute reaction a. Acute dystonia b. Acute (Subacute) akathisia2. Toxicity state (over dosage) a. Drug-induced parkinsonism3. Neuroleptic malignant syndrome (NMS)4. Tardive stbdrines a. Withdrawal emergent syndrome b.Classic fardive dyskinesia c. Tardive dystonia d. Tardive akathisia e. Tardive myoclonus f. Tardive tremor g. Tardive tics h. Tardive Chorea i. (?) Tardive parkinsonism
TERMINOLOGY OF THE TARDIVE SYNDROMESDescription Equivalent CommonNamesTardive syndromes Tardive syndromeas a group Tardive dykinesiaRepetitive, rhythmic Classic tardiveMovements, usually in dyskinesiaThe oral-buccal-lingual Tardive setreotypyRegion Rhythemic choreaDystonic movementsand posturesrestlessness and the Tardive akasthisiamovement that occuras resultMyoclonus Tardive myoclonusTremor Tardive tremorTucs Tardive tics Tardive tourettismChorea Withdrawal emergent syndrome Tardive choreaOculogyria Tardive oculogyric crisisParkinsonism Tardive Parkinsonism (if it exists)
NATURE HISTORY OFTOURETTE SYNDROME• Excerbation Remission ?• Obsessive-compulsive behavior• Vocal tics (simple complex)• Motor tics (rostrocaudalprogession)• Attention deficit with hyperactivity
Summary• Movement disorders are often difficult to define precisely, but have similar differential diagnoses.• They are often a manifestation of a more widespread neurological or internal medical problem.• Other than the specific treatments mentioned, most details of therapy are beyond the scope of this course.• In some cases treatment includes treatment of underlying cause e.g. Wilson’s disease
Dedicated to my family formaking everything worthwhile
READ not to contradict or confute Nor to Believe and Take for Granted but TO WEIGH AND CONSIDER THANK YOU My sincere thanks to Faculty of MadrasInstitute of Neurology and Madras MedicalCollege for giving this opportunity to speak in the CME Program