Transcript Diapositiva 1 - Sociedad de Neurología del Uruguay

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ETIOPATOGENIA
EXISTE BASE GENETICA?
PORQUE RESPONDE AL OH?
QUE ESTRUCTURAS CAUSAN EL TEMBLOR?
CUAL ES EL NT MAS IMPORTANTE?
EXISTE DETERIORO COGNITIVO?
MORTALIDAD ESTA AUMENTADA?
CUAL ES LA BASE NEUROPATOLOGICA?
INFLUYEN FACTORES DIETETICOS-METABOLICOS?
OVERLAP CON OTRAS ENTIDADES
EXPERIMENTACION ANIMAL
NEUROIMAGEN FUNCIONAL
NEUROCIRUGIA FUNCIONAL
¿EXISTE BASE GENETICA?
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50 % AF – AD (65 %) POLIGENICA. PENETRANCIA COMPLETA A LOS 65.
DETECCION EN FAMILIAS DE GENES INVOLUCRADOS :
Cr. 4P;
3Q13 (ETM 1); (D3)
2P22-25(ETM2)
6p23
ASOCIACIONES: EP – D – M- CMT
¿QUE ESTRUCTURA CAUSA EL
TEMBLOR?
PET
Hemisferios Cerebelosos
Via dento-rubro-talamica- cortical
Oscilador talámico
Oscilador olivar
Aceleración ritmo descarga MNI
Oscilador central origina; periferia modula; influencia somatosensitiva.
*Hiperfunción
c/OH
via cerebelo talamica (Glutamato), reversible
Estudios de Coherencia (sincronía EMG – NI áreas cer.): varios osciladores según
topografía del temblor.
NEUROCIRUGIA FUNCIONAL: NVI
NEUROPATOLOGÍA: celulas torpedo (Pk), CL, atrofia dentado.
ESTIMULACION MAGNETICA TRANSCRANEANA CEREBELO
TEMBLOR EN LAS HEREDOATAXIAS
DISFUNCIONES OME EN TE
A positron emission tomography study of essential
tremor: Evidence for overactivity of cerebellar
connections
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Dr. I. H. Jenkins, MRCP 1 *, P. G. Bain, MRCP 2, J. G. Colebatch, FRACP 1, P. D. Thompson, PhD. 2, L. J.
Findley, MD 2, R. S. J. Frackowiak, MD 1, C. D. Marsden, DSc 2, D. J. Brooks, MD 1
1Medical Research Council (MRC) Cyclotron Unit, Hammersmith Hospital, London, United Kingdom
2MRC Human Movement and Balance Unit, National Hospital for Neurology and Neurosurgery, London,
United Kingdom
*Correspondence to I. H. Jenkins, MRC Cyclotron Unit, Hammersmith Hospital, DuCane Road, London
W12 OHS, UK
ABSTRACT
The origin of essential tremor is unknown. Animal models have suggested that the inferior olivary
nucleus may act as a tremor generator. We used positron emission tomography to study changes in
regional cerebral blood flow associated with involuntary postural tremor and passive wrist oscillation in
patients with essential tremor. Activation due to voluntary wrist oscillation and arm extension without
tremor was studied in normal control subjects. The essential tremor group had bilaterally increased
cerebellar blood flow at rest (without tremor) compared with the control group. Involuntary postural
tremor was associated with further bilateral cerebellar activation, and also contralateral striatal,
thalamic, and sensorimotor cortex activation. Voluntary wrist oscillation, maintained arm extension
without tremor, and passive wrist oscillation were all associated with significant ipsilateral rather than
bilateral cerebellar activation. We conclude that essential tremor is associated with increased bilateral
cerebellar activity both at rest and during tremor.
Received: 24 August 1992; Revised: 27 January 1993; Accepted: 11 February 1993
Lesión o (+) NVI tálamo (eferencia
cerebelosa) mejora temblor: normaliza
oscilación celular anómala en
Hemisferios Cerebelosos
Figure 1 Section of cerebellar folium from a patient with essential tremor, showing two
torpedoes (arrows)
Permission obtained from American Medical Association © Louis ED et al. (2006) Arch Neurol 63: 1189–1193.
Benito-León J and Louis ED (2006) Essential tremor: emerging views of a common disorder
Nat Clin Pract Neurol 2: 666–678 10.1038/ncpneuro0347
Figure 2 Section of the dentate nucleus from an individual with essential tremor, showing
neuronal loss
Permission obtained from American Medical Association © Louis ED et al. (2006) Arch Neurol 63: 1189–1193.
Benito- León J and Louis ED (2006) Essential tremor: emerging views of a common disorder
Nat Clin Pract Neurol 2: 666–678 10.1038/ncpneuro0347
Figure 3 Multiple Lewy bodies (arrows) are seen in a section of the locus ceruleus from a
patient with essential tremor
Permission obtained from AAN Enterprises, Inc. © Louis ED et al. (2006) Neurology 66: 1756–1759.
Benito-León J and Louis ED (2006) Essential tremor: emerging views of a common disorder
Nat Clin Pract Neurol 2: 666–678 10.1038/ncpneuro0347
OH 50 %
¿POR QUÉ?
ETANOL MODULA (-) GLUTAMATO A
TRAVES DE RECEPTOR NMDA, VIA
HIPERACTIVADA EN EL TEMBLOR
ESENCIAL.
Eur J Neurol.
2008 Jul;15(7):697-705. Epub 2008 May 15. Links
A possible mechanism for the beneficial
effect of ethanol in essential tremor.
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Manto M, Laute MA.
Laboratoire de Neurologie Expérimentale, ULB-Erasme, Bruxelles, Belgium. [email protected]
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BACKGROUND: Essential tremor is one of the most common movement disorders in elderly people. The hypothesis
of a disregulation of N-methyl-D-aspartate (NMDA) pathways has been suggested. It was shown
experimentally that infusion of NMDA in cerebellar nuclei down-regulates glutamate release. METHODS: We assessed
the effects of intranuclear administration of harmaline on the NMDA-mediated regulation of glutamate in rats using
reverse dialysis. We hypothesized that ethanol, which improves essential tremor in the clinic, antagonizes the effect of
harmaline upon glutamatergic transmission. We tested the interaction of ethanol and harmaline upon glycerol (a
marker of membrane turn-over), lactate, and pyruvate concentrations. RESULTS: Harmaline increased the
concentrations of glutamate and impaired the NMDA-mediated regulation of glutamate. Ethanol decreased the
concentrations of glutamate during NMDA stimulation in case of pre-administration with
harmaline. Concentrations of glycerol rose with harmaline. Glycerol levels markedly decreased during NMDA
infusion when inhibitors of nitric oxide synthase, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate antagonists
or NMDA antagonists were administered. Harmaline increased lactate/pyruvate ratios during NMDA infusion but these
ratios returned to normal values in presence of ethanol. DISCUSSION: We provide a possible mechanism for the
beneficial effect of ethanol on essential tremor. The concept of glutamatergic disregulation underlying
essential tremor is highlighted. Consequences for our understanding of essential tremor are discussed.
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PMID: 18445025 [PubMed - indexed for MEDLINE]
Neurology 2006;66;69-74
Ann Neurol. 1985 Apr;17(4):329-33.
Association between essential tremor and
Parkinson's disease.
Geraghty JJ, Jankovic J, Zetusky WJ.
To examine a possible relationship of essential tremor to Parkinson's disease (PD),
130 patients with essential tremor were studied. Twenty-five patients had both
essential tremor and PD. These 25 patients were matched for age and duration of
PD symptoms with 25 patients who had idiopathic PD. Bradykinesia, postural
instability, and gait difficulty were more severe in the patients with idiopathic PD.
Degree of tremor, rigidity, and functional disability did not differ in the two groups.
The prevalence of PD in the population with essential tremor was 24 times greater
than expected. This
study suggests that some patients
with essential tremor have a genetically increased
risk for PD.
PMID: 4004153 [PubMed - indexed for MEDLINE]
Muscle Nerve. 1993 Sep;16(9):904-10. Links
Hereditary motor-sensory neuropathy and
movement disorders.
Cardoso FE, Jankovic J.
Department of Neurology, Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of Medicine, Houston, Texas 77030.
To explore the relationship between hereditary motor and sensory neuropathy (HMSN) and movement disorders, we examined 7 patients
with HMSN referred to our Movement Disorders Clinic and surveyed members of the Charcot-Marie-Tooth association. The following
movement disorders were observed in the index patients: postural tremor in 6, rest tremor in 3, and Parkinsonism and dystonia in 2.
Tremor, present in 40% of the 201 patients who responded to the survey, was first noted at a mean age of 36 years, and mostly involved
the hands. Family history of tremor was more frequent in the tremor group (P < 0.005), which also had a significantly worse writing score
The overlap in clinical features between
HMSN-associated tremor and essential tremor (ET), the
high frequency of family history of tremor, and the lack of
a relationship between the severity of tremor and of
peripheral neuropathy suggest that the tremor in HMSN is
pathogenically related to ET.
than the nontremor group (P < 0.001).
PMID: 8355721 [PubMed - indexed for MEDLINE]
NEUROLOGY 2005;65:391-396
© 2005 American Academy of Neurology
Blood harmane concentrations and dietary protein consumption in essential
tremor
E. D. Louis, MD, MS, W. Zheng, PhD, L. Applegate, BA, L. Shi, MS and P. Factor-Litvak, PhD
Conclusions: The similarity between patients and controls in daily animal protein consumption and the absence of the normal
correlation between daily animal protein consumption and logHA in patients suggests that another factor (e.g., a metabolic defect)
may be increasing blood harmane concentration in patients.
Mov Disord. 2005 Mar;20(3):298-305. Links
Harmaline-induced tremor as a potential preclinical screening method for essential tremor medications.
Martin FC, Thu Le A, Handforth A.
Research Service, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California 90073, USA.
[email protected]
No preclinical method to evaluate potential new medications for essential tremor (ET) is available currently.
E. D. Louis, W. Zheng, X. Mao, and D. C. Shungu
Blood harmane is correlated with cerebellar
metabolism in essential tremor: A pilot study
Neurology, August 7, 2007; 69(6): 515 - 520.
TRATAMIENTO
Benito- León J and Louis ED (2006) Essential tremor: emerging views of a common disorder
Nat Clin Pract Neurol 2: 666–678 10.1038/ncpneuro0347
Figure 4 Archimedean spirals drawn by individuals with and without essential tremor
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IDENTIFICAR CAUSAS: INTERROGAR - TSH
EXPLICAR Q NO PADECE EP
NO TRATAR SI NO INTERF. FUNCIONALIDAD
IDENTIFICAR y FAVORECER CONDUCTAS (-)
EL TRATAMIENTO ES SINTOMATICO
LARGO PLAZO
A MENUDO MAL TOLERADO
CONTRAINDICACIONES
CAUSAS DE TEMBLOR
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EMOCIONES: ANSIEDAD STRESS MIEDO
FATIGA
HIPOGLICEMIA
HIPERTIROIDISMO
FEOCROMOCITOMA
FARMACOS
ALCOHOL
• NIVEL de EVIDENCIA II-B
• 1 – 2 TRAGOS ALCOHOL ETILICO
• REDUCE 75 % el TEMBLOR EN 50-90 % de los
PACIENTES
• TRANSITORIO: 45 – 60 MINUTOS
• PUEDE DESARROLLARSE TOLERANCIA
• ADVERTIR EVITAR ABUSO
• EL RIESGO DE ADICCION ES BAJO
ALPRAZOLAM
0,25 – 1 mgs. v/o
HORAS ANTES
DE UN EVENTO
Neurology 2005;64;2008-2020; originally published online Jun 22, 2005;
This information is current as of August 20, 2008
Abstract—Background:
Essential tremor (ET) is one of the most common tremor disorders in adults and is
characterized by kinetic and postural tremor. To develop this practice parameter, the authors reviewed available evidence regarding
initiation of pharmacologic and surgical therapies, duration of their effect, their relative benefits and risks, and the
strength of evidence supporting their use. Methods: A literature review using MEDLINE, EMBASE, Science Citation
Index, and CINAHL was performed to identify clinical trials in patients with ET published between 1966 and August
2004. Articles were classified according to a four-tiered level of evidence scheme and recommendations were based on the
Results and Conclusions: Propranolol and primidone reduce limb tremor
(Level A). Alprazolam, atenolol,gabapentin (monotherapy), sotalol, and topiramate are
probably effective in reducing limb tremor (Level B). Limitedstudies suggest that
propranolol reduces head tremor (Level B). Clonazepam, clozapine, nadolol, and
nimodipine possibly reduce limb tremor (Level C). Botulinum toxin A may reduce hand
tremor but is associated with dose-dependent hand weakness (Level C). Botulinum toxin
A may reduce head tremor (Level C) and voice tremor (Level C), but breathiness,
hoarseness, and swallowing difficulties may occur in the treatment of voice tremor.
Chronic deep brain stimulation (DBS) (Level C) and thalamotomy (Level C) are highly
efficacious in reducing tremor. Each procedure carries a small risk of major
complications. Some adverse events from DBS may resolve with time or with adjustment
of stimulator settings. There is insufficient evidence regarding the surgical treatment of
head and voice tremor and the use of gamma knife thalamotomy (Level U). Additional
prospective, double-blind, placebo-controlled trials are needed to better determine the
efficacy and side effects of pharmacologic and surgical treatments of ET.
NEUROLOGY 2005;64:2008–2020
level of evidence.
B-BLOQUEANTES
• PROPANOLOL (OTROS: TIMOLOL NADOLOL
SOTALOL METOPROLOL)
• NIVEL DE EVIDENCIA I-A (DE ELECCION)
• (-) REC. B2 PERIFERICOS, TB. PROBABLE CENTRAL
B1
• CONTRAINDICACIONES: INS. CARD (II-III); DM,
ASMA, EPOC, AOC, BAV 2-3.
• EFECTOS SECUNDARIOS: FATIGA, IMPOTENCIA,
DEPRESION, HIPOTENSION, ARRITMIAS.
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PROPANOLOL
DOSIS INDIVIDUALIZADA
EFECTO NO ES DOSIS DEPENDIENTE
40 mg 1 VEZ AL DIA POR 3 DIAS
AUMENTAR 40 mg CADA 3 DIAS HASTA 120 (EN 3
TOMAS O PREPARADOS DE ACCION PROLONGADA)
• SI NO HAY RESPUESTA AUMENTAR A 160 mg/dia.
SI NO RESPONDE RETIRAR GRADUALMENTE
(AUNQUE HASTA 320 PUEDE HABER RESPUESTA)
• CONTROLA EL TEMBLOR EN UN 50%, S/T MANOS,
EN 50 – 70% DE LOS PACIENTES, ALGUNOS
RESPUESTA NOTABLE, OTROS NO RESPONDEN
PRIMIDONA
• REDUCE 40- 50 % TEMBLOR EN 50 – 70 % DE LOS
PACIENTES, S/T MANOS. EVIDENCIA I-A
• BARBITURICO METABOLIZA A FENOBARBITAL, PERO SU
ACCION ANTITEMBLOR ES INDEPENDIENTE,
PROBABLEMENTE CENTRAL
• INICIAR EN DOSIS BAJAS 62,5 mg. (1/4 comp. 250) *NO
HAY COMP DE 50 o 60*. DE NOCHE. CADA 3 DIAS PASAR A
½ COMP., LUEGO ¾, LUEGO 1. SI NO BASTA DOSIS UNICA
NOCTURNA DE 250 mg, AGREGAR 1 o 2 tomas mas de ½
COMP (125) EN LA M y la T.
• FRECUENTE INTOLERANCIA 25 % (VARIABLE,
FARMACOGENETICA): HIPERSOMNIA, MAREOS,
VERTIGOS, NAUSEAS, OBNUBILACION, COMA, RASH. 24 –
72 % SE ALIVIA.
Zesiewicz, T. A. et al. Neurology 2005;64:2008-2020
Table 1 Pharmacological agents for the treatment of essential tremor
Benito- León J and Louis ED (2006) Essential tremor: emerging views of a common disorder
Nat Clin Pract Neurol 2: 666–678 10.1038/ncpneuro0347
Zesiewicz, T. A. et al. Neurology 2005;64:2008-2020