运动障碍疾病 Movement Disorders Neurology Department The Second Affiliated Hospital Harbin Meical University

Extrapyramidal Disorders General Conception: The dysfunction of basal ganglia putamen globus pallidus lentiform nucleus caudate nucleus subthalamus corpus striatum substantia nigra basal ganglia

General Conception Two types of symptoms Muscular hypotonus associated with hyperkinesia(F1) Muscular hypertonus characterized with hypokinesia(F2)

Parkinson’s disease---conception Also called paralysis agitans. a common degeneration disease in nervous system becomes increasingly common with advancing age characterized by rest tremor, bradykinesia, rigidity, abnormal gait and posture

Parkinson’s disease---Etiology Aging: over middle aged persons Environmental toxin: MPTP(l-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine) in astrocyte oxidated MPP+ mitochondrion in substantia nigra neuronal death Genetic factor: alpha-synuclein gene -----susceptibility

Parkinson’s disease---Pathology loss of pigmentation and cells in the substantia nigra Lewy body in the basal gangalia, sympathetic ganglia and brainstem.

Parkinson’s disease---Biochemistry L- tyrosine (blood) TH L-Dopa DDC DA MAO and COMT HVA Nigrostriatal pathway is the most important. dopamine depletion dopaminergic nigrostriatal system Extrapyramidal Pathway

dopamine acetylcholine

Parkinson disease’s---Clinical findings Over middle aged & insidious onset and gradual progression. Tremor: often appear as the first sign. Characters: 4~6Hz, conspicuous at rest, increase at times of emotional stress, improves during voluntary activity, stop during sleep, begin from hand , “N” progression.

Parkinson disease’s---Clinical findings Rigidity(F1/F2): lead pipe / cogwheel phenomenon. Minimal rigidity: move the contralateral limb, head dropping test, road mark sign

Parkinson disease’s--Clinical findings Bradykinesia: slowness and reduction of voluntary movement, difficult to initiate, masked face, hypophonia, micrographia. Abnormal gait and posture: flexed posture; difficult to get up, start walking, turn or stop. Shuffling gait and absence of the arm swing. Festinating gait(late sign).

Parkinson disease’s--Clinical findings Other features: Myerson’s sign, oily face, intractable constipation, postural hypotension, cognitive disturbance, hallucination, depression

Parkinson’s disease---Differential diagnosis Parkinsonism: postencephalitic parkinsonism, drug or toxin-induced parkinsonism(CO, Mn), arteriosclerotic parkinsonism. Depression: a trial of antidepressant drug treatment may be helpful.

Parkinson’s disease---Differential diagnosis Essential(benign, familial) tremor: family history, early onset, nod or head shake. Parkinsonism associated with other neurologic diseases: Diffus Lewy body disease(hallucination), Wilson disease, Huntington chorea, multiple system atrophy(MSA), PSP, cortical basal ganglionic degeneration(CBGD).

Parkinson’s disease---Treatment Begin from low dose and individualized. Anticholinergic drugs: helpful in alleviating tremor and rigidity. Artane(1~2mg, tid). Amantadine: for mild parkinsonism. 50mg, bid~tid. Levodopa: L-Dopa/DCI(4:1)---compound; side effects: nausea, hypotension(peripheral) dyskinesia and motor fluction(central) wearing off or on-off phenomenon

Parkinson’s disease---Treatment DA-R agonist: bromocriptine MAOB/COMT inhibitor Surgery: pallidotomy and deep brain stimulation(high frequency thalamic stimulation) Physical therapy and aids for daily living Prognosis dead from complications

Sydenham Chorea--- Conception Also called rheumatic chorea. A usual manifestation of rheumatic fever in nervous system. Presents in childhood or young adult life. Clinical findings involuntary chorea dystonia weakness automatic action disturbance emotional changes

Sydenham Chorea--- Etiology Related with the infection of Hemolytic Streptococcus A. Anti-neuron antibodies can react with the neurons in caudate or subthalamic nucleus. Maybe relate with endocrine changes.

Sydenham Chorea--- Clinical findings 5~15ys. G/B=3:1 Subacute or insidious onset Early symptom: irritability, inattention, unsteady gait, easily dropping objects, et al.

Sydenham Chorea--- Clinical findings Chorea: rapid, irregular, involuntarily, unpredictably obvious on face( facial grimacing and tongue movements) prominent when nervous and disappeared during sleep.

Sydenham Chorea--- Clinical findings Muscle tone and power: reduced. Triad: limb weakness, chorea and ataxia. milkmaid grasp, wax-waning sign, dancing gait. Psychiatric symptom: agitation, hallucination Rheumatic fever findings. Self-limitation

Sydenham Chorea--- Testing 1.Serum test: rapid erythrocyte sedimentation, increased wbc. 2. EEG: unspecific. 3. Image test: 29~85% patients present low density focus in caudate nucleus on CT.

Sydenham Chorea--- Diagnosis&Differential diagnosis Onset age, triad , rheumatic fever findings 1. Habit spasm: stereotyped action on the same muscle 2. Congenital chorea: earlier onset 3. Tourette syndrome: tics on face accompanied by strange voice and dirty words.

Sydenham Chorea--- Diagnosis&Differential diagnosis 4.Huntington Chorea: onset after middle age, dementia, familial history 5. Torsion spasm: continuous, hypermyotonia when torsion happens

Sydenham Chorea--- Treatment & Prognosis rest, keep quiet, avoid stimulation penicillin or other antibiotics(10~14 days) and deltacortone(until the symptoms disapper) apozepam(5mg, bid/tid), haloperidol(0.5~1mg, bid/tid). side effects of extrapyramidal system Self-limited 3~6 months after the onset

Wiloson Disease--- Conception & Etiology Also called hepatolenticular degeneration(HLD) A kind of inherited disease extrapyramidal sign Autosomal recessive cirrhosis inheritance disease psychiatric symptom of copper metabolism kidney impairment disturbance---Etiology K-F circle on cornea

Wiloson Disease--- Clinical findings childhood/young adult life reflect the disproportionate involvement of the caudate nucleus, putamen, cerebral cortex and cerebellum. resting/postural tremor, rigidity, facial grimacing, ataxia, choreiform movements of limbs, disorders of affect , behavior , personality or psychology

Wiloson Disease--- Clinical findings May progress rapaidly(younger); often gradually progress with periods of remission and exacerbation Nonneurologic findings: ocular and hepatic abnormalities

Wiloson Disease--- Differential diagnosis multiple sclerosis juvenile-onset Huntington disease

Wiloson Disease--- Investigative studies Serum copper and ceruloplasmin(CP) are low, and 24h urinary copper excretion is generally increased. Abnormal liver function blood test and aminoaciduria Image test show cerebrocortical atrophy and abnormalities in the basal ganglia.

Wiloson Disease--- Treatment D-Penicillamine(1~1.5g/d): allergic test Restriction of dietary copper zinc sulfate(200mg/d) decrease absorbance Treatment must be continued for life. Early treatment can give a better recovery.