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seorang penari. Gerakan itu tidak berirama, sifatnya kuat, cepat dan tersentak-sentak dan arah
geraknya cepat berubah. Gerakan khoreatik yang melanda tangan-lengan yang sedang
melakukan gerakan voluntary membuat gerakan voluntar itu berlebihan dan canggung.
Gerakan choreatik ditangan-lengan seringkali disertai gerakan meringis-ringis pada wajah
dan suara mengeram atau suara-suara lain yang tidak mengandung arti. Kalau timbulnya
sekali-sekali maka sifat yang terlukis diatas tampak dengan jelas, tetapi apabila timbulnya
gencar, maka gerakan choreatiknya menyerupai atetosis. Chorea dalam bentuk yang khas
ditemukan pada chorea syndenham dan chorea gravidarum. Pada chorea Huntington ia timbul
dengan gencar sehingga lebih tepat dinamakan koreoatetosis Huntington. Chorea dapat
bangkit juga secara iatrogenik yakni akibat penggunaan obat-obat anti psikosis (seperti
haloperidol, dan phenothiazine).
Dengan kata lain chorea adalah gerakan tak terkenali yang berupa sentakan berskala
besar dan berulang-ulang, seperti berdansa, yang dimulai pada salah satu bagian tubuh dan
menjalar kebagian tubuh yang lainnya secara tiba-tiba dan tak terduga. Gerak chorea dapat
dibuat nyata bila pasien disuruh melakukan dua macam gerakan sekaligus, misalnya ia
disuruh menaikkan lengannya keatas sambil menjulurkan lidah. Gerakan chorea didapatkan
dalam keadaan istirahat dan menjadi lebih hebat bila ada aktivitas dan ketegangan. Chorea
menghilang bila penderitanya tidur.
MEKANISME DOPAMINERGIK
Pada khorea Huntington, komposisi dari striatal dopamin normal, mengindikasikan
bahwa kelainan utama yang mengancam jiwa, tetapi sudah terkena penyakit, ukuran
menengah, pada striatal saraf-saraf dopaminergik. Zat-zat farmakologik yang dapat
menurunkan kadar dopamin (seperti reserpine, tetrabenazine) atau memblok reseptor
dopamin (seperti obat-obat neuroleptik) dapat menimbulkan khorea. Sejak obat-obatan yang
menurunkan komposisi dopamin striatal dapat menimbulkan khorea, meningkatkan jumlah
dopamin akan menambah buruk keadaan seperti pada khorea yang diinduksi levodopa yang
terlihat pada penyakit Parkinson.
MEKANISME KOLINERGIK
Konsep dari mekanisme ini yaitu menyeimbangkan antara asetilkolin dan dopamin yang
merupakan hal penting bagi fungsi striatum yang normal memberikan hal penting untuk
memahami penyakit parkinson. Pada fase awal penyakit parkinson, obat-obat anti kolinergik
digunakan umum, khususnya saat tremor sebagai gejala predominan. Gejala-gejala parkinson
lain seperti bradikinesia dan rigiditas juga dapat terjadi.
Perkembangan khorea pada pasien yang diberikan obat-obat kolinergik seperti
triheksipenidil merupakan pengamatan klinis yang umum. Lebih lanjut obat visostigmin intra
vena (antikoliesterase sentral) dapat mengurangi khorea untuk sementara.dengan cara yng
sama khorea yang diinduksi antikolinergik dapat menjadi lebih berat dengan pemberian
visostigmin.
Dalam ganglia basalis pasien dengan penyakit huntington terjadi pengurangan kolin
asetil transferase, yaitu enzim yang mengkatalisator sintesis asetil kolin. Berkurangnya
reseptor kolinergik muskarinik juga telah ditemukan. Dua pengamatan ini dapat menjelaskan
bermacam-macam respon terhadap visostigmin dan efek terbatas dari prekursor asetilkolin,
seperti kolin dan lesitin.
MEKANISME SEROTONERGIK
Manipulasi dari sriatal serotonin dapat berperan dalam pembentukan dari berbagai
macam pergerakan abnormal. Penghambatan pengambilan kembali serotonin seperti
fluoksetin dapat menimbulkan parkinsonisme, akinesia, mioklonus, atau tremor.
Peranan serotonin (5-hidroksi triptamin) dalam pergerakan khorea kurang jelas. Striatum
mempunyai konsentrasi serotonin yang relatif tinggi. Penatalaksanaan farmakologik tuuntuk
merangsang atau menghambat reseptor serotonin pada khorea huntington tidak menunjukkan
efek, mengindikasikan kontribusi terbatas serotonin dalam patogenesis khorea.
MEKANISME GABAergik
Lesi yang paling konsisten pada khorea huntington terlihat dengan hilangnya saraf-saraf
dalam ganglia basalis yang mensintesis dan mengandung GABA. Arti dari semua ini tidak
diketahui. Bermacam-macam tehnik farmakologi untuk meningkatkan GABA didalam sistem
saraf pusat telah dicoba, bagaimanapun tidak ada manfaat yang diperoleh.
SUBSTANSI P DAN SOMATOSTATIN
Substansi P telah diketahui berkurang pada penyakit huntington, sementara itu
somatostatin meningkat. Arti dari semua ini belum diketahui.
Introduction
Movement disorders are a recognised complication of stroke. Many different
types of hyperkinetic and hypokinetic movement disorders have been reported
and can be seen after ischaemic and haemorrhagic stroke. [1] Dystonia,[2, 35, 68, 911, 12
14]
chorea with or without hemiballismus,[12, 1417, 18, 19, 20, 21] tremor[13, 14, 23, 24, 25, 26, 27
29]
parkinsonism,[12, 20, 30, 31, 3234] segmental or focal myoclonus,[1, 14, 20, 21] athetosis,
pseudoathetosis[14, 35] and asterixis[1, 21, 36] have all been described and occur at
presentation of the stroke,[20, 21, 37] in the delayed setting[2, 5, 14, 21, 37] or as a progressive
condition.[2, 14] Transient dyskinesias or 'limb shaking' spells have been described
as a symptom of transient ischaemic attacks.[1, 38, 39]
Current knowledge is based on individual case reports, small case series and
extracts from stroke registries. This article reviews the different types of abnormal
movements with anatomical correlation, epidemiology, treatment and prognosis.
Definitions
Hemichoreaunilateral, rapid involuntary motions of flexion and extension,
rotation or crossing, which may involve all body parts, but predominantly distal
parts.[1, 41]
Hemiballismus (hemiballism)severe, violent, arrhythmic and large amplitude
excursion of a limb from a proximal joint with an element of rotation. [1, 41]
Temporal Relationship
The time scale to develop a movement disorder varies considerably from the day
of onset to several years after the stroke and also depends on the type of
movement disorder[5, 14, 20, 21] Chorea presented earlier (mean 4.3 days post-stroke)
in one series and parkinsonism much later (mean 117.5 days post-stroke).
[20]
However, there is a wide variability within each movement disorder; the delay
in developing dystonia after stroke can be anything from 1 day to 5 years. [5]
The delay between the stroke and the onset of the abnormal movement may
reflect time required for the partial recovery of motor function and development of
pathological circuitry.[14]
to the cortex. The cortex sends excitatory inputs to the striatum; the striatum
inhibits the pallidum which in turn inhibits the thalamus. [43] The net effect of cortical
activity is to trigger the striatum to release the thalamus from pallidal inhibition,
thus allowing thalamic outputs to excite the cortex. [43] These direct pathways are
modulated by other loops from the substantia nigra (dopaminergic) and
subthalamic nucleus. At rest, neurones in the striatum are quiescent and those in
the pallidum are active, thereby inhibiting the thalamic excitation of the motor
cortex. Before and during a movement, the striatum becomes active and inhibits
the pallidum, allowing more excitation of the motor thalamic nuclei and cortex.
[43]
Interruption of direct or indirect pathways by focal lesions may lead to
movement disorders. However, there are no specific sites or arterial territories for
any given dyskinesia and lesions in different parts of the motor pathways may be
responsible for the same movement disorder.[1, 21] Figure 2 shows a drawing of a
horizontal section of the cerebrum at the level of the insula showing the major
grey and white matter structures and their blood supply.[43, 44]
(Enlarge Image)
Figure 1.
Schematic, simplified diagram of the connections of the basal ganglia. Stimulatory pathways are
shown in unbroken lines and inhibitory pathways in broken lines.
(Enlarge Image)
Figure 2.
A drawing of a horizontal section of the cerebrum at the level of the insula showing the major
grey and white matter structures and their blood supply. ACA: anterior cerebral artery
(leptomeningeal branches);MCA: middle cerebral artery (lenticulostriate branches); ICA: internal
carotid artery (perforating branches); PCoA: posterior communicating artery (perforating
branches); AChA: anterior choroidal artery;thalamogeniculate and thalamoperforate arteries:
branches of the posterior cerebral artery; PChA: posterior choroidal artery; PCA: posterior
cerebral artery (modified with permission from figure 29.8 in [44], p. 392).
Small vessel disease, with small deep infarcts, was the most common sub-type of
stroke leading to abnormal movements.[20, 21] In Alarcon's study, patients with deep
lesions in the basal ganglia, thalamus and brain stem, who developed abnormal
movements, had significantly more haemorrhages compared to controls. [20] Large
and medium vessel atherothrombosis and cardiac embolism are other potential
causes of strokes leading to abnormal movements. [14, 20] A case-control study of 35
patients with delayed onset dyskinesias after thalamic stroke found that 62.9% of
patients had haemorrhagic strokes[14] while a cohort study of 27 patients with
hemiballismus found that all the patients had infarcts. [45]
Table 1 summarises the principle abnormal movements, associated lesions and
drug treatments (see treatment below).
Several broad conclusions can be drawn: lenticular lesions are the most common
lesions that result in dystonia[2, 7, 12, 20, 35, 46] and chorea hemiballism.[15] Lesions in
the posterior thalamus or lesions disrupting the dentatorubrothalamic pathway
are the most common causes of tremor.[24, 25]Parkinsonism after stroke is
associated with lesions in the basal ganglia (mainly striatum or lentiform nucleus)
which can be unilateral or bilateral.[20, 33, 34, 47]
Treatment
This section describes the treatment of each movement disorder. The drugs used
in each condition are shown in Table 1. Few large-scale studies have been
possible due to small numbers of patients and there are therefore no firm
guidelines for the management of these conditions.
Dystonia
Treatment options may be used alone or in combination. Botulinium toxin
injections have been a major breakthrough in the management of dystonia.
[58]
Muscle contraction is reduced by direct injection into the overactive muscle,
which blocks the release of acetylcholine.
Other treatments include benzodiazepines, baclofen, anti-cholinergic drugs and
dopamine-depleting/blocking agents.[2] Clonazepam and diazepam treat focal,
segmental and generalised dystonias. Higher doses are limited by drowsiness.
Like botulinium toxin, the anti-cholinergic drugs block the action of the
neurotransmitter acetylcholine thereby deactivating the muscle contractions.
Trihexyphenidyl (benzhexol) is the most common drug in this class, but may be
more useful in younger patients due to the side-effects of confusion and
constipation in the elderly.[2, 59]
Tetrabenazine can be helpful, but may paradoxically cause dystonia. Combining
benzhexol and tetrabenazine can be very effective in younger patients. [60]
Tremor
Tremor is particularly refractory to drug treatment. Rubral and palatal tremor may
respond to clonazepam and sodium valproate.[61] Dystonic tremor is treated as
dystonia (see above). Adding weight to the affected limb (e.g. wrist weights) can
dampen tremor.[61] Propranolol is traditionally used in essential and thyrotoxic
tremor but may help dampen tremor from all causes. In severe cases, functional
neurosurgery (see below) may be the only useful treatment option.
Myoclonus
The two most commonly used treatments are the GABA ergic drugs, clonazepam
and sodium valproate. Other tried treatments include levetiracetam, piracetam,
Parkinsonism
Patients with true vascular parkinsonism rarely respond to conventional
dopaminergic therapy.[31]Supportive therapy by the physiotherapists and
occupational therapists should be arranged. Treatment for the risk factors for
atherosclerotic diseases to arrest progression is recommended and includes antiplatelet agents, statins and anti-hypertensives.
The caveat to this is that parkinsonism and idiopathic Parkinson's disease can
co-exist, and a controlled trial of levodopa gradually increased up to a maximum
of 600 mg/day (rarely up to 1,000 mg) for a minimum of 1 month should be given
in order not to miss any dopaminergic responsiveness. [63] Just as important in the
apparent non-responders is to wean off the levodopa to confirm that no response,
in fact, occurred and to stop unnecessary medication.
Prognosis
Conclusion
Although rare, many different varieties of abnormal movement can be found after
a stroke either acutely or as a delayed sequel. They can be hyperkinetic (most
commonly hemichoreahemiballismus) or hypokinetic (most commonly vascular
parkinsonism). Most are caused by lesions in the basal ganglia or thalamus but
can occur with strokes at many different locations in the motor circuit. Many are
self-limiting but treatment may be required for symptom control.
References
2. Chuang C, Fahn S, Frucht SJ. The natural history and treatment of acquired hemidystonia:
report of 33 cases and review of the literature. J Neurol Neurosurg Psychiatry (2002) 72:5967.
6. Fahn S. Concept and classification of dystonia. In: Advances in Neurology, Dystonia 2.Fahn
S, Marsden CD, Calne DB, eds. (1988) New York: Raven Press. 58.
7. Pettigrew LC, Jankovic J. Hemidystonia: a report of 22 patients and review of the literature. J
Neurol Neurosurg Psychiatry (1985) 48:65057.
8. Krystkowiak P, Martinat P, Defebvre L, et al. Dystonia after striatopallidal and thalamic stroke:
clinicoradiological correlations and pathophysiological mechanisms. J Neurol Neurosurg
Psychiatry (1998) 65:7038.
12. Bhatia KP, Marsden CD. The behavioural and motor consequences of focal lesions of the basal
ganglia in man. Brain (1994) 117:85976.
13. Lehricy S, Grand S, Pollak P, et al. Clinical characteristics and topography of lesions in
movement disorders due to thalamic lesions. Neurology (2001) 57:105566.
14. Kim JS. Delayed onset mixed involuntary movements after thalamic stroke. Clinical,
radiological and pathophysiological findings. Brain (2001) 124:299309.
15. Chung SJ, Im JH, Lee MC, Kim JS. Hemichorea after stroke: clinical-radiological correlation. J
Neurol (2004) 251:7259.
17. Krauss JK, Pohle T, Borremans JJ. Hemichorea and hemiballism associated with contralateral
hemiparesis and ipsilateral basal ganglia lesions. Mov Disord (1999) 14:497501.
20. Alarcon F, Zijlmans JC, Duenas G, Cevallos N. Post-stroke movement disorders: report of 56
patients. J Neurol Neurosurg Psychiatry (2004) 75:156874.
25. Miwa H, Hatori K, Kondo T, Imai H, Mizuno Y. Thalamic tremor: case reports and implications
of the tremor generating mechanism. Neurology (1996) 46:759.
26. Ferbert A, Gerwig M. Tremor due to stroke. Mov Disord (2004) 8:17982.
31. Fitzgerald PM, Jankovic J. Lower body Parkinsonism: evidence for a vascular aetiology. Mov
Disord (1989) 4:24960.
35. Lee MS, Kim YD, Kim JT, Lyoo CH. Abrupt onset of transient pseudochoreoathetosis
associated with proprioceptive sensory loss as a result of a thalamic infarction. Mov Disord (1998)
13:1846.
36. Kim JS. Asterixis after unilateral stroke: lesion location of 30 patients. Neurology (2001)
56:5336.
38. Baquis GD, Pessin MS, Scott RM. Limb shaking. A carotid TIA. Stroke (1985) 16:4448.
39. Tatemichi TK, Young WL, Prohovnik I, et al. Perfusion insufficiency in limb-shaking transient
ischemic attacks. Stroke (1990) 21:3417.
41. Fahn S. Phenomenology of movement disorders. In: 7th Annual Course: A Comprehensive
Review of Movement Disorders for the Clinical PractitionerFahn S, Marsden, Jankovic J, eds.
(1997) New York: Columbia University. 361.
43. Kiernan JA, ed. Barr's The Human Nervous System: an Anatomical Viewpoint (2005) 8th
edition. Philadelphia: Lipincott, Williams & Wilkins. 193222.
47. Winikates J, Jankovic J. Clinical correlates of vascular Parkinsonism. Arch Neurol (1999)
56:989.
48. Kim JS. Involuntary movements after anterior cerebral artery territory infarction. Stroke (2001)
32:25861.
54. Bashir K. Clozapine for the control of hemiballismus. Clin Neuropharmacol (1994) 17:47780.
56. Klawans HL, Moses H, Nausieda PA, et al. Treatment and prognosis of hemiballismus. N Engl
J Med (1976) 295:134850.
57. Cardoso F. Outcome after stereotactic thalamotomy for dystonia and hemiballismus.
Neurosurgery (1995) 36:5017.
60. Jankovic J, Orman J. Tetrabenazine therapy of dystonia, chorea, tics and other dyskinesias.
Neurology (1988) 38:3914.
61. Sawle G, ed. Movement Disorders in Clinical Practice (1999) Oxford: Isis Medical Media.
(The very long list of references supporting this review has meant that only the most important are
listed here and are represented by bold type throughout the text. The full list of references is
available at Age and Ageing online.)
Disclosures
Age Ageing. 2009;38(3):260-266.