Movement Disorders. Eric Kraus, MD! Neurology!
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1 Movement Disorders Eric Kraus, MD! Neurology!
2 Classify Bradykinesia! Tic! Myoclonus! Tremor! Dystonia! Athetosis! Chorea! Ballismus!
3 Case 1 This 64 year-old female has had progression of a tremor over the last two years. It affects her writing, eating and sewing.!
4 Tremor: Definition Involuntary! Rhythmic! Sinusoidal movement!
5 General types Action!» Kinetic!» Postural!» Intention (cerebellar)! Resting!
6 Essential tremor Most common movement d/o! Postural and kinetic! Slowly progressive! Prevalence increases with age!» Mean age of presentation 35-45!» Adolescence onset!» 0.5-5% population!» F:M 1:1! Genetic - AD!» FH (+) 50-60%! Distribution!» Hands (symmetric)!» (30%) head, voice, jaw, face!» Legs!» Trunk! Worsened by:!» Emotion!» Hunger!» Fatigue!» Temperature!» Drugs/toxins!
7 Drugs/toxins Steroids! Thyroid hormone! Lithium! Valproic acid! Cyclosporine! Tricyclics! Beta agonists! Theophyline! Neuroleptics! SSRIs! Caffeine! Nicotine! Arsenic! Lead! Cocaine/amphetamines! Alcohol withdrawal! Benzo withdrawal! Other drug withdrawal!
8 Tremor work-up None if c/w essential tremor! Resting tremor is the first distinction to make! Review medications! Ask about alcohol, illicit drugs! Labs!» M7, LFTs, TSH, B12!» Ceruloplasmin and serum Cu!» Urine tox screen!» Rare: Vit E, heavy metals! MRI! Review psychiatric history!
9 Case 2 This 58 year-old male has a left hand tremor at rest and some trouble walking. His hand writing has become smaller, and he no longer smiles.!
10 PD: Clinical Slow progressive course! 4 cardinal features!» Resting tremor!» Bradykinesia!» Rigidity (cogwheel)!» Postural reflex impairment! Other: dementia, depression, autonomic!
11 PD: Levodopa Sinemet = carbidopa/levodopa! Most potent drug for PD! Preferred treatment age > 75! Side effects!» GI!» Dyskinesias!» Dementia, hallucinations!» Orthostatic hypotension! Start 25/100 QD, increase q 3d up 3 tid as needed!
12 PD: Dopamine Agonist Act directly on dopamine receptors! Synergy with levodopa! Longer T1/2! Reduced dyskinesias! Same side effects as levodopa! Initial treatment age < 65! 3rd generation options(pramipexole, Ropinirole)!
13 PD: MAO-B Inhibitors Rasagiline and Selegiline! Reduction of motor fluctuations! May have neuroprotective effects!» Consider in early onset disease!
14 PD: COMT inhibitors Block COMT metabolism of levodopa! Dopaminergic SEs!» Reduce levodopa by 30%! Entacapone (Comtan)! Combination drug!» Carbidopa/levodopa/entacapone!
15 Treatment Flow Chart Levodopa Levodopa COMT AADC AADC COMT 3-OMD Dopamine Dopamine 3-OMD MAO-B COMT 3,4-DHPA 3-MT COMT = catechol-o-methyltransferase AADC = amino acid decarboxylase MAO = monoamine oxidase OMD = O-methyldopa DHPA = dihydroxyphenylacetic acid MT = methoxytyramine COMT Homovanillic acid MAO-B
16 Case 3 This 58 year-old male is having trouble walking in that he can't seem to keep up with his wife. Several falls have occurred. His hand writing has become smaller, and his wife wonders if he hasn't had a stroke because he no longer smiles. No tremor is present. Sinemet does not help.!
17 Parkinsonism Parkinson s Disease! Neuroleptic side effect! Post-encephalitic! Toxins (Mn, CO, MPTP)! Dementia! Wilson s disease! Basal ganglia calcifications! Parkinson-plus syndromes!» Progressive supranuclear palsy!» Corticobasoganglionic degeneration!» Multisystem atrophy! Autonomic! Cerebellar!» Diffuse Lewy body disease!
18 Case 4 This 47 year-old woman who has trouble sitting still in the evenings. Her legs ache. Walking will temporarily relieve the problem.!
19 Restless Leg Syndrome Characterized by an irresistible urge to move the legs, accompanied by uncomfortable sensations that often occur in the evening or when at rest.!» Creeping, crawling, tingling, aching, burning, pulling, itching, cramping, electric current-like!
20 RLS Prevalence Very common!» Estimated that 2-15% of the population may have RLS symptoms.!» Age of onset varies widely, but onset of symptoms typically presents before age 50. Severity increases with age.!» Greater in women than men!
21 RLS Etiology Primary: Thought to be a CNS disorder, but exact mechanism unknown.!» Familial cases indicate potential genetic component.! Secondary: Iron deficiency, neurologic lesions, pregnancy, uremia, drug induced, diabetes mellitus, venous insufficiency.!
22 RLS - Diagnosis Key diagnostic criteria! Supportive Features! Urge to move legs usually with uncomfortable leg sensations.! Sleep disturbances! Temporary relief with movement partial or total relief by walking or stretching.! Onset or worsening with inactivity! Involuntary leg movements during sleep! Family history! Worsening or onset of sx in the evening or at night.! Positive response to dopaminergic tx.!
23 RLS - Treatment Non-Pharmacologic:!» Stretching/massage!» Long compressive socks in bed!» Hot/Cold compresses!» Hot bath before bed!» Avoid caffeine and alcohol before bed!» Daily exercise!» Mentally alerting activities! Pharmacologic tx:!» Dopamine agonists: pramipexole, ropinerole!» Carbidopa-levodopa!» Clonazepam!» Gabapentin, Carbamazepine.!» Iron: indicated in all pts (if anemic), esp. pregnant women.!» Opioids!
24 Case 5 This 42 year-old female complains of a progressive inability to keep her arms and legs still. She has had depression for 10 years. Her father had the same movements starting at the age of 63.!
25 Huntington Disease Genetics!» CAG repeat!» AD!» Chrom 4! Pathology!» Loss of GABA neurons in striatum!» Diffuse atrophy! Clinical!» Chorea!» Dementia!» Psychiatric! Treatment!» Neuroleptics!» Clonazepam!» Tetrabenazine!» Antidepressants!
26 Case 6 This 35 year-old woman has trouble writing more than one sentence. It started 2 years ago and progressed. No weakness or sensory loss. She can play the piano and eat fine.!
27 Focal dystonias Writer s cramp! Spasmodic torticollis! Blepharospasm! Spasmodic dysphonia! Treatment!» Physical therapy!» Botox!» Levodopa!» Anticholinergics!» Baclofen!» Surgery!
28 Case 7 This 19 year-old male complains of excessive blinking and the need to clear his throat. Onset was at the age of 8. In school he was always in trouble for not paying attention and making abnormal sounds.!
29 Tourette Syndrome Clinical!» Tics: motor and vocal!» Involuntary but suppressible!» Daily > 1 year!» Onset before age 21 (median age = 7)!» Lifelong, decline with age!» OCD!» ADHD! Prevalence 40/100k! Genetics!» 4:1 M:F!» AD with incomplete penetrance!» MZ twins 80%!
30 Tourette Syndrome Treatment!» Counseling!» Neuroleptics!» Clonidine!» Topiramate!» Leviteracetam!» Clonazepam!» Dopamine agonists!» Clomipramine!» SSRIs!» Nicotine patch/gum!
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