김종민서울대학교의과대학분당서울대학교병원신경과 Tremor Jong-Min Kim, MD, PhD Department of Neurology, Seoul National University Bundang Hospital, Seoul National University College of Medicine 의분류 1. 현상에따른분류 : 두개의큰카테고리 1) Rest tremor 정의 : 중력에대하여힘을주지않도록받치고있거나 active muscle contraction 이없는상태에서나타나며, 의식적인동작중에는없어지거나그정도가감소함. 2) Action tremor 정의 : active muscle contraction 을하는상태, 의식적인동작중에나타남. Action tremor 는다시다음네가지로분류 ; Postural tremor, Kinetic tremor, Task-specific or position-specific tremor, Isometric tremor. 1. Postural tremor: 팔을앞으로뻗는다든지하는 anti-gravity posture 에서나타난다. 참고 ) re-emergent tremor: 일부의파킨슨병환자들은팔을들고나서수초후 rest tremor와동일한진동수의 postural tremor를보인다. 그리고이 re-emergent tremor는도파민치료에반응한다. 이러한점들에서이 re-emergent tremor 는 rest tremor가자세를취한후 reset 되어나타나는것으로추측. 2. Kinetic tremor: 의식적인동작중에나타남. 세가지로분류함. Jong-Min Kim, MD, PhD Department of Neurology, Seoul National University Bundang Hospital, Bundang Gumi Seongnam 463-707 TEL: 82-31-787-7465 FAX: 82-31-787-4059 E-mail: jongmin1@snu.ac.kr Initial tremor: 동작을시작할때나타남. Dynamic tremor: 움직임중간에나타남. Terminal tremor: intention tremor라고도부름. 목표물가까이갈때나타남. Finger-to-nose test할때잘볼수있음. 3. Task-specific or position-specific tremor Task-specific tremor: 글씨쓰기, 노래하기등과같이특정행위를할때에만나타나거나, 하지않을때보다훨씬더심하게악화되는. 예 ) primary writing tremor, voice tremor position-specific tremor: 특정자세에서만나타나는. 예 ) wing-beating tremor, 수저가입가까이왔을때만나타나는 4. Isometric tremor: 움직임은없이근육수축만있을때에나타나는. 예 ) 주먹을꼭쥐고있을때나오는, 서있을때나오는 orthostatic tremor 2. 진동수에따른분류가장흔한 physiologic tremor, parkinsonian rest tremor, essential tremor의 postural tremor 등은대개 4-10 Hz의진동수. 3Hz 이하의 slow tremor 는 cerebellum 혹은 brain stem의병변으로인한경우가많다. 11-20 Hz의 fast tremor는 orthostatic tremor나다른 tremor의 harmonic oscillation으로나온다. 의검사 Arm extension test, Spiral drawing test, Water pouring test. 2015 년대한신경과학회전공의통합교육 51
김종민 검사실검사로 EMG나 accelerometry로진동수, 진폭을정량화. 그외에연구목적으로고안된각종 scale, questionnaire 들이있다. 의기전 1. physiologic tremor 의기전을 peripheral mechanism, central mechanism 의 2 component 로나누어보면, 1) Peripheral mechanism : peripheral beta-2 adrenoreceptor를매개로하는 mechanical-reflex component. Tremor의 frequency를 f라하면 : f=(k/i) 1/2 [I : inertia, K : stiffness of the joint]. 이공식에따르는 mechanical-reflex component 로서, 팔꿈치의 tremor는 3-5 Hz, 손목의 tremor 는 7-10 Hz, metacarpophalangeal joint의 tremor는 17-30 Hz의진동수를보인다. Inertia 는무게를뜻한다. 따라서무게가바뀌면 tremor의진동수도영향을받는다. 무거워지면진동수가떨어져느려지는것이다. enhanced physiologic tremor란? : mechanical-reflex component에대한 stretch reflex response 가 fatigue, anxiety, 약물등에의하여증가되어나타나는것. 위진동수공식의지배를받는다. 2) Central mechanism : central network나 cell group의 oscillatory activity에서기원. central network of cell group의 oscillatory activity 가 motor-unit activity를조절 (modulation) 하고있음. 그결과동작에참여하는 motor-unit들은 mean frequency of discharge 에상관없이대개가 8-12 Hz 근방의진동수 (peak: 10 Hz) 로 entrained 됨. 이 central mechanism에의한 tremor frequency : not f=(k/i) 1/2. oscillatory activity를보이는 network의위치 : olivo-cerebello-rubral loop, thalamocortical rhythmicity 의두가지가있음. => physiologic tremor에서는 peripheral mechanism이주로작용함. 2. pathologic tremor 를일으키는 4 component 1) Peripheral mechanism : mechanical-reflex component 2) Central mechanism : central-neurogenic oscillation 3) Feed-forward loop dysfunction : cerebellum에서기원하여 reflex, tonic, ballistic component의 3 movement component를조절하는 feed-forward loop의기능이상 4) Long latency reflex dysfunction : voluntary action시 25-100 msec의 latency 동안 transcortical loop을경유하여 segmental circuitry로내려가는 descending control system 의이상이네가지요소를들수있음. => Parkinson disease 의경우 1) mechanical-reflex component의역할 : smaller 2) central-neurogenic oscillation의영향 : larger 3) feed-forward loop : alteration in the control of one of the reflex, tonic, or ballistic components 4) long latency reflex (long-loop reflex) : increased latency => essential tremor의경우 : 역시 mechanical-reflex component의역할보다 central-neurogenic oscillation의영향이훨씬더크다. => enhanced physiologic tremor 와 essential tremor의구별에도움이되는 test : mass loading. enhanced physiologic tremor 는팔을뻗고무거운물건, 예를들어 1리터생수병을올려놓으면진동수감소. Essential tremor 는거의영향을받지않음. Rest tremor 의감별진단 (Table 1) Issue 1. 이심한 essential tremor 환자가 rest tremor 를보이는경우는? 다음세가지가능성이있다. 첫째, 이 essential tremor 환자는 Parkinson disease 도함께있을가능성, 그래서세월이흐르면서 Parkinson disease 의다른특징들이서서히나타날가능성. 둘째, 심한 postural/kinetic tremor 로인하여 rest tremor 가사실은없지만마치있는것처럼보이는경우. 셋째, 실제로 essential tremor 의한양상으로 rest tremor 가나타날가능성. 이문제는아직해결되지않고있다. Issue 2. Holmes tremor vs. thalamic stroke vs. myorhythmia vs. palatal tremor or myoclonus - Holmes tremor의정의 : 1) rest tremor 와 intention tremor (+) (postural tremor 도많은경우에동반됨 ). 의양상은약간 jerky movement 가섞여서불규칙해보이는면이있음. 2) 4 Hz 이하의진동수. 3) stroke 후 tremor 시작까지 2 주에서 2년까지도보고가있음. - Holmes tremor의기전 : Cerebello-rubro-thalamic system과 nigrostriatal dopaminergic system의병변으로인함. Voluntary action과동반된 cerebellar signal이 impaired ni- 52 2015 년대한신경과학회전공의통합교육
grostriatal dopaminergic system에서일으키는 rest tremor 를억제해주어야하는데, cerebello-rubro-thalamic system도병변이생겨서 rest tremor 를억제하지못하고그결과로 rest tremor의 rhythm이 voluntary action에침투하여낮은진동수의 intention tremor 를일으킨다고봄. - thalamic stroke 후 tremor: 1) 4 Hz 이하의진동수로 rest tremor와 postural tremor가나오고 myorhythmia 라고도한다. 2) Thalamic tremor : lateral posterior thalamic stroke Table 1. Parkinson disease Parkinson-plus syndromes 1) Multiple-system atrophy 2) Progressive supranuclear palsy 3) Cortico-basal-ganglionic degeneration 4) Diffuse Lewy body disease Hereditary degenerative disorders 1) Wilson disease 2) Huntington disease 3) Neuroacanthocytosis 4) Hallervorden-Spatz disease 5) Gerstmann-Strausler-Scheinker disease Secondary parkinsonism 1) Toxic : CO, Mn, methanol, cyanide, CS2, MPTP 2) Drug-induced : dopamine-blockers, neuroleptics, lithium, flunarizine 3) Vascular : multi-infarct, lower-body parkinsonism 4) Trauma : midbrain injury 5) Tumor, Paraneoplastic 6) Infection : postencephalitic parkinsonism, AIDS, SSPE, Creutzfeldt-Jakob disease 7) Metabolic : hepatolenticular degeneration, hypoparathyroidism 8) Normal pressure hydrocephalus Essential tremor, severe Holmes tremor (midbrain tremor, rubral tremor, Benedikt s syndrome) Myorhythmia, thalamic stroke Tardive tremor Spasmus nutans 후 action tremor와함께 dystonia, athetosis, chorea, sensory loss가함께나오는경우. 주로근위부를침범함. - myorhythmia의정의 : 4 Hz 이하의진동수로 rest시혹은 action시모두, continuous 혹은 intermittent하게, 비교적 rhythmic하게나타나는 movement. Supination-pronation (pill-rolling) pattern의 Parkinson disease의 rest tremor와달리 flexion-extension하는양상. Brain stem 구조, 특히 substantia nigra와 inferior olive, 그리고 cerebellum 의병변으로발생. 예를들면 brainstem stroke, cerebellar degenerations, Wilson disease, Whipple disease. 잠이들면없어지고, palatal myoclonus와동반되기도함. - palatal myoclonus란?: Palatal tremor라고도하는데, agonist-antagonist의 synchronous or alternating contraction 으로나오는 tremor와달리여기서는 palatal movement 가 agonist의 rhythmic contraction 으로나오기때문에 myoclonus 가더정확한표현임. Guillain-Mollaret triangle (dentate nucleus-red nucleus-central tegmental tract-inferior olivary nucleus) 의병변으로발생 (Table 2). Action tremor 중 postural tremor 의감별진단 (Table 3) Action tremor 중 Kinetic tremor, Task- or position-specific tremor, Isometric tremor 의감별진단 (Table 4) Issue 1. Titubation이란?: Axial muscle 의 hypotonia로인한머리와몸통의 rhythmic oscillation. Cerebellum 이나 cerebellar outflow 의병변으로인한 kinetic tremor와함께 postural tremor와 titubation이동반하는경우가많다. Table 2. Essential palatal myoclonus 잠들면없어짐 Tensor veli palatini 수축 (trigeminal nerve) 전체 soft palate 움직임 Ear-clicking sound Symptomatic palatal myoclonus 잘때도지속 Levator veli palatini 수축 (facial nucleus, nucleus ambiguous) Soft palate 변두리만움직임 Inferior olive hypertrophy 2015 년대한신경과학회전공의통합교육 53
김종민 Table 3. Physiologic tremor Enhanced physiologic tremor 1) Stress-induced : emotion, anxiety, fatigue, exercise, fever 2) Endocrine : thyrotoxicosis, hypoglycemia, adrenocorticosteroids, pheochromocytoma 3) Drugs : beta-agonist (e.g., theophylline, epinephrine), CNS stimulants (amphetamines), psychiatric drugs (neuroleptics, tricyclic antidepressant, lithium), methylxanthines (coffee, tea), valproic acid, dopaminergic drugs (levodopa, dopamine agonists) 4) Toxic : alcohol withdrawal, Hg, Pb, As, Bi, Br Essential tremor Postural tremor associated with 1) Parkinson disease, Parkinsonism 2) Dystonia 3) Myoclonus 4) Neuropathic tremor : motor neuron disease, peripheral neuropathy, peripheral nerve injury, reflex sympathetic dystrophy, Hereditary motor-sensory neuropathy (Roussy-Levy syndrome) 5) Kennedy syndrome (X-linked spinobulbar atrophy) Holmes tremor (midbrain tremor, rubral tremor, Benedikt s syndrome) Tardive tremor Cerebellar hypotonic tremor (titubation) Table 4. Kinetic tremor (dynamic and intention tremor) a. Cerebellar or cerebellar outflow lesions : stroke, trauma, multiple sclerosis, Wilson disease, drugs, toxins b. Midbrain lesion : stroke, trauma, multiple sclerosis, Wilson disease, drugs, toxins Task- or position-specific tremor a. Writing b. Other task-specific tremors Isometric tremor a. Orthostatic tremor b. Muscle contraction during sustained exertion c. Miscellaneous tremors and other rhythmic movements 1) Mixed with myoclonus : palatal myoclonus, oscillatory myoclonus, asterixis (negative myoclonus) 2) Dystonic tremors 3) Cortical tremors 4) Epilepsia partialis continua 5) Nystagmus 6) Clonus 7) Fasciculation 8) Shivering 9) Head bobbing due to third ventricular cysts 54 2015 년대한신경과학회전공의통합교육
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