ESSENTIAL TREMORReferat 6 / Tahun IIIOleh: Meilia M. SuriadiPembimbing: dr. Djadjang Suhana, SpS(K)

TREMOR Osilasi ritmis involunter bagian tubuh tertentu dalam dataran tertentuKontraksi otot agonis & antagonis Simultan atau alternansPola sinyal berasal dari osilator sentral

ESSENTIAL TREMORGangguan gerak Sering terjadi pada dewasaPengaruh terhadap tampilan aktivitas fungsional & sosial.Diferensiasi terhadap sindroma tremor lain penting edukasi & terapi

Essential Tremor

EPIDEMIOLOGIPrevalensi: 0,3-5,6% populasi umum0,5-11,1%: pertolongan medisPria = wanita usiaUsia awitan: Bimodal (15-20 th & 50-70 th)Rata-rata: 35-45 th

EPIDEMIOLOGIAmplitudo tremor: usiaFrekuensi tremor: usiaDewasa muda: 8-12 HzLanjut usia: 6-8 HzDisabilitas 85%: perubahan signifikan dalam kehidupan sosial15%: disabilitas serius akibat ET

Essential Tremor2 bentuk ET:Familial ETSporadic ETKlinis: tak ada perbedaanUsia awitan:Familial ET: dekade 2 / 3Sporadic ET: dekade 6 / 7

ETIOLOGIEsensial: bawaan / diturunkanFamilial ET: 50-70% kasusAutosomal dominanGen: kromosom 3q (FET1) & 2p (ETM)Sporadic ET: etiologi ?

PATOFISIOLOGILesi struktural spesifik belum diidentifikasiMekanisme patofisiologi belum jelasPencitraan Metabolik: kerusakan neuronal serebelumFungsional: keterlibatan Nc olivarius inferior & serebelum dalam generasi dan propagasi aktivitas osilasi abnormal perifer: tremor

Perubahan konsentrasi penanda biokimia sentral & perifer GABA, glisin, serin LCS ringan glutamat LCS Abnormalitas reseptor GABAA thalamus epinefrin pada daerah spesifik otakLocus ceruleus 5x, nc dentatus 130x, korteks serebelum 2x

GAMBARAN KLINISTremor 1 extremitas superior sisi lainGerakan: fleksi-ekstensi pergelangan tanganAsimetri ringanIntermiten (saat aktivasi emosional) persistenAmplitudo : aktivitas emosional: aktivitas manual terampilHilang saat tidur

Essential TremorMonosymptomatic Abnormalitas langkah & keseimbanganTremor postural & kinetik, frekuensi 4-12 HzTremor hilang saat relaksasi bagian tubuhTonus & refleks normal

Essential TremorTremor kepalaPola horizontal atau vertikalTremor suara, lidah, palatumDisartria Palatum: clicking dalam telinga

Kriteria Diagnostik ET

Inclusion criteria:Bilateral, largely symmetric postural or kinetic tremor involving hands and forearms that is visible and persistentPossible additional or isolated tremor in head but absence of abnormal posturing Exclusion criteria:Other abnormal neurologic signs, especially dystonia The presence of known causes of enhanced physiologic tremor, including current or recent exposure to drugs that are known to cause tremor or a drug-withdrawal stateHistoric or clinical evidence of psychogenic tremor Convincing evidence of sudden onset or evidence of stepwise deteriorationPrimary orthostatic tremorIsolated voice tremorIsolated position-specific or task-specific tremors, including occupational tremors and primary writing tremorIsolated tongue or chin tremorIsolated leg tremor

WHIGET Tremor Rating Scale

ScoreDefinition0Absolutely no visible tremor 1Mild tremor, intermittent or continuous; similar to normal or enhanced physiologic tremor 2Obvious tremor that is expected in patients with essential tremor. Must meet all the following criteria:Moderate amplitudeUsually presentClearly oscillatory (hand not just a little shaky or unsteady but clearly oscillates between 2 extremes) 3Large-amplitude, jerky tremor. Examples include:When handling liquids (pouring, drinking, using a spoon), patient spills but is able to complete the task without spilling all the liquid.When touching finger to nose, patient has difficulty hitting examiners finger and circles around it many times.When drawing a spiral, large-amplitude wavy tremor present, but patient able to draw spiral. 4Extremely large-amplitude, jerky tremor. Examples include:When handling liquids (pouring, drinking, using a spoon), patient unable to attempt the task or to perform the task without spilling all the liquid.When touching figner to nose, patient has difficulty hitting examiners finger and circles around it many times; patient reluctant to touch own face for fear of self-injury.When drawing a spiral, patient unable to make or maintain pen to paper contact; unable to draw a spiral.

PEMERIKSAAN PENUNJANGDiagnosis ET: klinisTak ada penanda biologisCT scan & MRI normalPemeriksaan laboratorium & pencitraan: bila riwayat keluarga & pemeriksaan ETEMG / akselerometri: bukan pemeriksaan rutin

DIAGNOSIS BANDINGMultiple sclerosisPenyakit WilsonChorea HuntingtonPenyakit degeneratif serebelumTremor dipresipitasi obat & toksnTremor dipresipitasi penyakit sistemik

PENATALAKSANAANTujuan: Minimalisasi disabilitas fungsionalMengurangi hambatan sosialMeningkatkan kualitas hidup penderitaJenis:FisioterapiIntervensi tingkah laku & psikologisPerubahan gaya hidupFarmakoterapiTindakan bedah

Pemilihan jenis kebutuhan & keadaan penderitaKeparahan tremorPenyakit koeksistenTerapi obat saat iniRespons terhadap terapi sebelumnyaTidak perlu penatalaksanaan bila tak ada keluhan disabilitas fungsional / psikososialTerapi farmakologisMengurangi amplitudo tremor & disabilitasTerapi simptomatikJangan berharap eradikasi tremor menyeluruhTidak mengobati, mencegah, memperlambat progresi penyakit

Fisioterapi & Intervensi Tingkah LakuTeknik pembelajaran adaptifET ringanMinimalisasi disabilitas fungsional, social embarrassment, & jejas personalContoh:Gunting ujung tumpulSerbet di bawah cangkir

FarmakoterapiET ringan:Minimalisasi paparan stres emosional & makanan-minuman tremorogenikReassurance-blocker / alkohol; intermitenET mengganggu aktivitas harian:Farmakoterapi jangka panjangPilihan kondisi komorbid, keamanan, efikasiPenilaian efektivitas obat: menulis, menuang, minum

-blockerTerapi lini pertamaPropranolol: Terpilih efikasi telah terbuktiMekanisme belum diketahuiDiduga: via hambatan reseptor 2 perifer dalam serabut / gelendong ototDosis: 120-240 mg/hariDurasi efek 4 jamPropranolol lepas lambatMetoprolol, timolol, atenolol, sotalol

-blockerEfek samping: BronchospasmeDepresi, insomniaDisfungsi ereksiKontraindikasi relatif:Gagal jantung berat, blok konduksi jantungBronchospasmePenderita DM tipe II

PrimidonStruktur analog fenobarbitalMetabolit utama: PEMA & fenobarbitalMekanisme kerja: belum diketahuiEfektivitas propranololObat lini pertamaDosis < 250 mg/hariDurasi 24 jam

PrimidonEfek samping:Terutama saat awal terapiNausea, malaiseAtaxia, dizziness, sedasi, bingungKontraindikasi:Kehamilan, menyusui, porfiria

GabapentinMekanisme kerja: belum diketahuiDiduga: peranan tonus GABAergik sentralTerapi jangka pendek 1200-1800 mg/hari pada lanjut usiaDapat ditoleransi sebagai terapi jangka panjang pada dewasa mudaTerapi alternatif untuk ET Efek samping: Ataxia, iritabilitas, sedasi, kenaikan berat badan

AlkoholEfek tremorolitik temporerPET: alkohol hiperaktivitas serebelum, mungkin dimediasi mekanisme GABAergik

BenzodiazepinMekanisme kerja: belum diketahuiDiduga augmentasi GABAergikEfek ansiolitik penderita cemasHati-hati: lanjut usia efek samping sentralAlprazolamEfektivitas primidonDosis 0,75 mg/hariKlonazepam: 1-6 mg/hariLorazepam: 0,25-0,5 mg prn

Botulinum toxin ATremor kepala & suara yang resisten terhadap obat-obatan oralTerbatas untuk tremor ekstremitas superiorKontraindikasi:Miastenia gravis, sindroma Eaton-LambertPenyakit motor neuron, sindroma pascapolioAntibiotika aminoglikosidaKehamilan

Intervensi bedahPenderita dengan disabling tremorTeknik:Thalamotomi stereotaktikChronic thalamic deep brain stimulation (DBS)Kontraindikasi:Keadaan umum burukGangguan kognisiDapat bersifat kuratif

Thalamotomi stereotaktikThermokoagulasi Nc. Ventralis intermedius (Vim) thalamusDisrupsi aktivitas tremorogenik abnormal di sirkuit serebelum-thalamusUnilateral, kontralateral tremor extremitasEfikasi tinggiMorbiditas persisten & berat < 2%

Thalamic Deep Brain Stimulation (DBS)Penderita dengan disabling tremor tak terkontrol adekuat dengan farmakoterapiNonablatif & dapat disesuaikanUnilateral atau bilateralMorbiditas permanen rendahMekanisme kerja: belum diketahuiDiduga: supresi tremor ec chronic artificial neural noise disrupsi aktivitas siklik sirkuit motorik

Thalamic Deep Brain Stimulation (DBS)Efikasi thalamotomiTremor extremitas, kepala & suaraEfek samping: (jarang)Penurunan kognitif, disartria, paresis facialGait imbalance, ataxia lenganKekurangan:BiayaRisiko respons inflamasi & infeksi

Practice ParameterAmerican Academy of NeurologyPropranolol & primidon mengurangi tremor extremitasBotulinum toxin A mungkin mengurangi tremor kepala & suaraChronic DBS & thalamotomi memberikan efikasi tinggi dalam mengurangi tremor

ESSENTIAL TREMOREducation & SupportFunctional impairmentSocial embarrassmentYesPrimidone orGabapentinNoPropranololCombination therapy Thalamotomy or Vim DBS for upper extremityBotulinum toxin for disabling head & voice tremormonitorYesNoContraindications to -blockers?

THANK YOU

Samuel Adams American Revolutionist 1722-180340 yo

71 yo

Deep brain stimulation (DBS) electrode implanted intracranially with wires connecting to pulse generators in the intraclavicular region. DBS electrode has four platinum/ridum contacts. Sagittal MRI shows electrode implanted in subthalamic nucleus of patient with Parkinsons disease.

Figure 2. A deep brain stimulator electrode is placed in the desired structure of the brain. The electrode is connected to a battery implanted under the skin below the collarbone. The patient is able to turn the generator off and on with a handheld control magnet Figure 3. A stereotactic head frame is attached to the patient's head with four pins. A localizer cage is placed on top of the frame during the MRI scan.

Figure 4. An electrode is precisely positioned in the desired brain area with the aid of a stereotactic head frame. Once the exact nerve cells are located, the surgeon can pass a heating current to destroy those cells or insert a stimulator to regulate those cells

DBS of the VIM nucleus relieves tremor for PD and also patients suffering from essential tremor. DBS of one or both STN nuclei provides excellent control of all PD symptoms, including L-dopa related dyskinesia. The Procedure Stereotactic frame placement under local anaesthesia. MR targetting. Calculation of co-ordinates of the target. Burr-hole under local anaesthesia. Insertion of electrode to the target, guided by macro-stimulation and or micro-electrode recordings. The patient stays awake and interacts continuously with the neurologist and neurosurgeon to find the best location (within 1 or 2 mm) to achieve maximum benefit. Under general anaesthesia, the electrode is connected to the programmable pulse generator placed under the skin of the chest wall. The movement disorder team will activate the generators and determine the correct settings to obtain the maximum clinical benefit with minimal side effects. Once the optimal settings have been determined, the patients can turn stimulation on and off with a small magnet. For example, some patients may turn the generator off at bedtime. Risks of DBS is small in experienced hands for suitably selected patients. There is a 2% risk of serious bleeding inside the brain, and a small chance of infection plus other possible remote risks of burr-hole and anaesthesia.

In 1997, the FDA approved the marketing of the implanted device to suppress tremor in people with essential tremor and Parkinson's disease. This system includes an insulated wire lead that is surgically implanted deep within the thalamus. The lead is connected by an extension wire passed under the skin to a pulse generator implanted near the collarbone. Patients control the stimulation by passing a hand-held magnet over the implanted pulse generator to turn it on or off, or to increase or decrease stimulation depending on their tremor suppression needs. To achieve maximum tremor suppression, physicians program the generator to deliver the precise stimulation needed for each individual patient. In clinical studies, more than 80 percent of essential tremor and Parkinson's patients had total or significant suppression o f their disabling tremor and significant reduction in disability. Patients in clinical studies have resumed daily life activities that were previously difficult or impossible, such as writing, pouring liquids, feeding and dressing themselves. Tremor medications often can be reduced or discontinued. Tremor control therapy is indicated for patients whose drugs are ineffective in controlling their disabling tremor. The most common potential side-effects of stimulation include paresthesia, paresis, dysarthria and disequilibrium, but these generally are reduced or disappear when stimulation is decreased or stopped. Risk typically associate with this surgery includes loss of effect and intracranial hemorrhage.