PERLAS DE PARKINSON

The  D1 dopamine receptor is predominantly expressed on the STIATONIGRAL NEURONS, while the D2 receptors are primarily found on the STRAITOPALLIDAL NEURONS.

Evidence suggests that in the striatum the D1 and D2 receptors have, respectively, an EXCITATORY ( STRIATONIGRAL) and INHIBITORY action( STRIATOPALIDO)

Activation of the D1 receptors appears to be important in mediating DYSTONIC MOVEMENTS,whereas activation of the D2 receptors may result in CHOREA.

The dopaminergic deafferentation produces an imbalance in the stratal activity, with HYPOACTIVITY OF THE STRAITONIGRAL PATHWAY, and HYPERACTIVITY OF THE STRIATOPALLIDAL PATHWAYS.

The final effect of Dopamine deficiency is poverty or slowness of movements( HYPOKINESIA)

POWER POINT PARKINSON

Fisiopatología Enfermedades de la mielina, neurona motora, enfermedad muscular y neuropatía.

Semana 7 y 8

23 de Febrero al 6 de Marzo

4.       Fisiopatología Enfermedades de la mielina, neurona motora, enfermedad muscular y   neuropatía.

4.1.     Esclerosis Múltiple

4.2.     Enfermedad del Nervio Periférico

4.3.     Plexopatía.

4.4      Paraplejia

4.4.     Lesión del Nervio Periférico y de raíz.

·       Neuropatía diabética

·       Guillain Barré

·       Poliradiculoneuropatía inflamatoria

Fisiopatología de la enfermedades de la mielina

Objetivos de Aprendizaje

• Describa la clasificación General de las principales categorías de neuropatías y miopatias.
  
• Describe la estructura y el funcionamiento normal de un nervio periférico y de un músculo
  
• Describe el concepto de la unidad motora
  
• Describe el diagnostico diferencia de la debilidad neuromuscular
  
• Describir el cuadro clínico de una polineuropatía inflamatoria, miastenia gravis y poliimiositis
  
• Describe como se indican estudios de gabinete y laboratorio en neuropatías y miopatias y
  cuales son los principales hallazgos
  
• Describir las principales diferencias clínicas de la debilidad de una neurópata y una miopatia
  
  
  
  Contenidos

• Anatomía y fisiología de los nervios periféricos y músculos
  
• Incidencia y prevalencía
  
• Fisiopatologia de nervios periféricos unión mioneural y músculo
  
• Conceptos y definiciones Enf de neuronas motoras, radiculopatias, neuropatías,
  enfermedades de unión mioneural miopatias
  
• Clasificación de las enfermedades neuromusculares de acuerdo a su distribución en la
  unidad motora
  
• Bases genéticas , bioquímicas y moleculares de las enfermedades neuromusculares
  
• Estudios de laboratorio, enzimas musculares
  
• Aplicaciones de la electomiografía y velocidad de conducción
  
• Biopsia de músculo indicaciones
  
• Principio de tratamiento inmunosupresion plasmaferesis gammaglobulina
  rehabilitación en polineurpatias miastenia gravis y poliimiositis
  
• Esquema general de manejo en miopatias y neuropatías
  
  Preguntas para favorecer la discusión
  
  ¿Cuál es el abordaje clínico de un paciente con neuropatía? ¿Cuál es el abordaje clínico de un paciente con miastenia?
  ¿Cuál es el abordaje clínico de un paciente con miopatia?
  ¿Cuál es el diagnostico diferencial de la debilidad central y periférica?
  ¿Cuál es el diagnostico diferencial de una miopatia neuropatía y miastenia gravis?
  ¿Qué es una prueba de tensilon?
  ¿Cuál es la calificación clínica de la debilidad de acuerdo al sistema ingles en una escala de 5? ¿Cuáles son las características de una prueba de estimulación repetitiva?
  

¿Cuáles son las características normales de la velocidad de conducción y las alteraciones de velocidad de conducción en neuropatías?
¿Cuáles son las características normales de una electromiografía y sus alteraciones en una mipatia, en una denervacion aguda y en la enfermedad de neuronas motoras
¿Cual es el tratamiento mas indicado en una denervación aguda y en la enfermedad de neuronas motoras?

----------------------------------------------------------------------------------------------------------------------------------Objetivos de Aprendizaje

• Conocer la fisiopatología de la formación de la placa de desmielinización.
  
• Describir los principales síntomas y signos.
  
• Comprender el uso de los criterios clínicos en la esclerosis múltiple.
  
• Conocer los hallazgos de imagen el la desmielinización
  
• Conocer los principios terapéuticos Contenidos
  

• Clasificación de la enfermedad desmielinizante
  
• Epidemiología de la esclerosis múltiple
  
• Fisiopatologia de la desmielinización
  
• Formas clínicas
  
• Criterios diagnósticos
  
• Hallazgos en la imagen LCR y potenciales evocados
  
• Inmunosupresión e inmunomodulación
  
  Preguntas para favorecer la discusión
  ¿ En que sitio ubicas la lesión ¿
  ¿Qué significa diseminación espacial y temporal?
  ¿Qué es un brote agudo?
  ¿Cuál es el criterio de Poser?
  ¿Cuales son las formas clínicas de la enfermedad?
  ¿Qué significa inmunosupresión e inmunomodulación?
  ¿Cuándo se establece el diagnostico diferencial de la perdida de visión monocular? 
  

SABIAS QUE ? EN RELACION AL PARKINSON

In Parkinson’s, the circuitry in a tiny region of the brain called the basal ganglia becomes dysfunctional. Along with the cerebellum, the basal ganglia normally acts as a kind of adviser that helps people learn adaptive skills by classic conditioning — rewarding good results with dopaminebursts and punishing errors by withholding the chemical. Babies rely on the basal ganglia to learn how to deploy their muscles to reach, grab, babble and crawl, and later to accomplish many complex tasks without thinking. For example, when a tennis player practices a stroke over and over again, the basal ganglia circuitry both rewards and “learns” the correct sequence of activities to produce, say, a good backhand drive automatically.

But this brain circuit has a vulnerability: It depends on dopamine. When the production of dopamine is interrupted, as it is with Parkinson’s, the signals passing through the basal ganglia are garbled, and it ends up giving poor advice. Corrupted signals pass to other brain regions such as the thalamus (which relays sensory and motor data) and the cortex (which is responsible for many higher functions such as language and consciousness). These bad signals disrupt communication between the brain and the muscles. This is one reason people with Parkinson’s have trouble picking up small objects and moving around fluently: Their motions are too hesitant, too small, too slow, too rigid, too shaky, too feeble and badly timed. These are symptoms of a brain in conflict with itself.

Having Parkinson’s feels a bit like going on vacation in another country and having to drive on the “wrong” side of the road. Driving is one of those activities that we outsource, in large part, to the basal ganglia. When an American, who has spent thousands of hours driving on the right side of the street, tries to drive in England, his learned habits are a liability. To compensate, he must invoke the deliberate and goal-directed part of his brain — the cortex — to override the basal ganglia. The driving will be difficult, partly because the conscious brain is now doing all the work, but mainly because it’s having to compensate for signals from the basal ganglia that are inappropriate for the situation at hand.

Having Parkinson’s feels a bit like going on vacation in another country and having to drive on the “wrong” side of the road. Driving is one of those activities that we outsource, in large part, to the basal ganglia. When an American, who has spent thousands of hours driving on the right side of the street, tries to drive in England, his learned habits are a liability. To compensate, he must invoke the deliberate and goal-directed part of his brain — the cortex — to override the basal ganglia. The driving will be difficult, partly because the conscious brain is now doing all the work, but mainly because it’s having to compensate for signals from the basal ganglia that are inappropriate for the situation at hand.

But why is the production of dopamine interrupted in the first place?

That may come down to the behavior of a common protein called alpha-synuclein. This molecule’s importance for Parkinson’s was discovered over 20 years ago, when the New Jersey neuroscientist Lawrence Golbestumbled across two patients who were descendants of an extended family originally from the Italian village of Contursi. This family was cursed with a very rare genetic form of Parkinson’s; family members had a 50 percent chance of inheriting the disease. Subsequent research found that those affected carried a mutated gene on Chromosome 4 that coded for alpha-synuclein.

While Parkinson’s disease is not usually inherited like this, the discovery provided a vital clue about the way Parkinson’s typically worked. Most patients do not have this mutation, but they do, it turned out, have sticky deposits of alpha-synuclein inside their brains, found when they were examined post-mortem. This protein seems to be an integral part of the disease that affects all Parkinson’s patients.

FISIOPATOLOGIA DEL PARKINSON

La lesión primaria en la EP es la degeneración de las neuronas que contienen neuromelanina en el tallo cerebral, en especial las de la pars compacta de la sustancia nigra, que se observa macroscópicamente pálida por la pérdida del pigmento. Al microscopio los núcleos normalmente pigmentados muestran una marcada pérdida de células y reemplazo por gliosis. Las neuronas que permanecen suelen contener los llamados cuerpos de Lewy ( característica patológica de la EP) , los cuales so cuerpos de inclusión eosinófilos localizados dentro del citoplasma neuronal. El principal constituyente de los cuerpos de Lewy es una proteína filamentosa, llamada alfa sinucleína. Es importante mencionar que los cuerpos de Lewy se encuentran en otras enfermedades degenerativas, llamadas genéricamente sinucleopatías, que incluye a demencia por cuerpos de Lewy, entre otras.
La afección inicial en el tallo cerebral progresa de una manera caudorostral, es decir, ascendente, con posterior afección del diencéfalo, los ganglios basales, las estructuras mediales de lóbulo temporal y finalmente la corteza cerebral.

La patogénesis en el desarrollo de la EP tiene que ver con complejos mecanismos moleculares que se presentan , que incluyen los siguientes:

• Estrés oxidativo
• Disfunción del sistema ubiquitina-proteosoma
• Disfunción mitocondrial
• Excitocidad
• Inflamación

Todos los mecanismos anteriores tienen como vía final en común el desarrollo de apoptosis. 

Parkinson

TRASTORNOS DEL MOVIMIENTO

Objetivos de Aprendizaje

El alumno entenderá la funcion de los ganglios basales, su correlacion con distintos neurotransmisores, así como las implicaciones patológicas que tienen en distintas entidades clinicas.
El alumno entendera la fisiopatologia de la enfermedad de Parkinson, poniendo en practica sus conocimientos de anatomia y patologia, llegando a poder hacer un diagnostico sindromatico de la enfermedad, y logrando establecer los distintos grados de avance de la misma.Establecerá metodos de abordaje diagnostico y se verá en forma general y en base a la fisiopatologia las distintas modalidades de tratamiento.
Se estudiaran los distintos tipos de movimientos extrapiramidales.
Se veran las distintas formas de ataxia, tanto de origen cerebeloso como de origen espinal. Contenidos
• Clasificación de los desordenes del movimiento o Enfermedad de ganglios basales
o Disnquinesias tardias
o Hemibalismo
o Atetosis
o Corea de Huntington y Sydenham o Ataxia Cerebelosas
o Ataxias Espinales

• Epidemiología de la enfermedad de la enfermedad de parkinson
  
• Bases genéticas y moleculares de la enfermedad de parkinson
  
• Manifestaciones clínicas
  
• Diagnóstico diferencial
  
• Bases del tratamiento
  Preguntas para favorecer la discusión
  ¿Qué es un temblor y como se clasifica?
  ¿ Como se clasifican las alteraciones del movimiento?
  ¿ Mecanismo fisiopatológico por el cual se producen cada una de las alteraciones del movimiento? ¿Cuál es le diagnostico diferencial?
  ¿Cuales son los principales signos que se deben de buscar en el examen neurológico?
  ¿Cuales son los signos cardinales y los asociados en la enfermedad de parkinson?
  ¿Cómo se clasifica la enfermedad de parkinson? 
  

STROKE

http://stroke.ahajournals.org/content/early/2013/05/07/STR.0b013e318296aeca.full.pdf+html

Table 1. Definition of Stroke
The term “stroke” should be broadly used to include all of the following: Definition of CNS infarction: CNS infarction is brain, spinal cord, or retinal
cell death attributable to ischemia, based on
1. pathological, imaging, or other objective evidence of cerebral, spinal cord,
or retinal focal ischemic injury in a defined vascular distribution; or 2. clinical evidence of cerebral, spinal cord, or retinal focal ischemic
injury based on symptoms persisting ≥24 hours or until death, and other etiologies excluded. (Note: CNS infarction includes hemorrhagic infarctions, types I and II; see “Hemorrhagic Infarction.”)

Definition of ischemic stroke: An episode of neurological dysfunction caused by focal cerebral, spinal, or retinal infarction. (Note: Evidence of CNS infarction is defined above.)

Definition of silent CNS infarction: Imaging or neuropathological evidence of CNS infarction, without a history of acute neurological dysfunction attributable to the lesion.

Definition of intracerebral hemorrhage: A focal collection of blood within the brain parenchyma or ventricular system that is not caused by trauma.
(Note: Intracerebral hemorrhage includes parenchymal hemorrhages after CNS infarction, types I and II—see “Hemorrhagic Infarction.”)

Definition of stroke caused by intracerebral hemorrhage: Rapidly developing clinical signs of neurological dysfunction attributable to a focal collection of blood within the brain parenchyma or ventricular system that is not caused by trauma.

Definition of silent cerebral hemorrhage: A focal collection of chronic blood products within the brain parenchyma, subarachnoid space, or ventricular system on neuroimaging or neuropathological examination that is not caused by trauma and without a history of acute neurological dysfunction attributable to the lesion.

Definition of subarachnoid hemorrhage: Bleeding into the subarachnoid space (the space between the arachnoid membrane and the pia mater of the brain or spinal cord).

Definition of stroke caused by subarachnoid hemorrhage: Rapidly developing signs of neurological dysfunction and/or headache because of bleeding into the subarachnoid space (the space between the arachnoid membrane and the pia mater of the brain or spinal cord), which is not caused by trauma.

Definition of stroke caused by cerebral venous thrombosis: Infarction or hemorrhage in the brain, spinal cord, or retina because of thrombosis of a cerebral venous structure. Symptoms or signs caused by reversible edema without infarction or hemorrhage do not qualify as stroke.

Definition of stroke, not otherwise specified: An episode of acute neurological dysfunction presumed to be caused by ischemia or hemorrhage, persisting ≥24 hours or until death, but without sufficient evidence to be classified as one of the above. 

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Stroke is classically characterized as a neurological deficit attributed to an acute focal injury of the central nervous system (CNS) by a vascular cause, including cerebral infarction, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH), and is a major cause of disability and death worldwide. 


The current World Health Organization definition of stroke (introduced in 1970 and still used) is “rapidly developing clinical signs of focal (or global) disturbance of cerebral function, lasting more than 24 hours or leading to death, with no apparent cause other than that of vascular origin.”  


In 2009, an expert committee of the AHA/ASA published a scientific statement defining TIA and recommending evaluation. The definition proposed was “transient ischemic attack (TIA): a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia without acute infarction.” 


Based on advances including modern brain imaging, the 24-hour inclusion criterion for cerebral infarction is inaccurate and misleading, because permanent injury can occur much sooner.  

However, the location and extent of infarction is one variable to consider when choosing treatment. 

The word “transient” indicates a lack of permanence.    

Modern brain imaging has shown that many patients in whom symptoms and signs of brain ischemia are clinically transient have evidence of brain infarction. If the ischemia caused death of the tissue, it is misleading to designate the ischemia as transient. Similarly, ischemia may produce symptoms and signs that are prolonged (and so qualify in older definitions as strokes), and yet no permanent brain infarction has occurred. 


Knowledge of neuroanatomy and vascular anatomy is important for the clinical diagnosis of stroke and transient CNS ischemia. Brain injuries attributable to vascular causes are nearly always focal, unless they lead to increases in intracranial pressure that cause global cerebral hypoperfusion, as in SAH, or massive infarcts and ICHs.  

During clinical diagnosis, 3 questions require an answer: (1) Is the process vascular or a stroke-like mimic? If a vascular process, then (2) where in the CNS is the abnormality, and which blood vessels supply that area? and (3) What is the disease mechanism (e.g., ischemia or hemorrhage)? 



Retinal infarction is a clinical diagnosis in a patient with acute painless visual loss, typically associated with ischemic whitening of the retina observed on funduscopic examination. A “cherry red spot” may be evident in the macula in patients with central retinal artery occlusion. Retinal infarction rarely requires additional testing to confirm the diagnosis, although occasionally fluorescein angiography is used in atypical cases. 

Radiographic Diagnosis    


Traditional ideas that a strict brain time window exists for acute stroke differ from modern imaging findings obtained by methods such as MRI diffusion-weighted imaging (DWI), which highlights tissue changes after several minutes to days after transient or permanent ischemic events.12,13 A recent Cochrane review of CT and MRI for the diagnosis of acute cerebral infarction within 12 hours of symptom onset showed that the pooled estimates for CT sensitivity and DWI MRI sensitivity were 0.39 and 0.99, respectively, using a clinical diagnosis as the reference standard.


Today, attention is focused on multisequence use of rapid MRI as a biomarker for acute identification of permanent tissue injury as well as viable tissue at risk, widely known as the penumbra.15 Multimodal magnetic resonance angiography, DWI, fluid-attenuated inversion recovery (FLAIR), and perfusion-weighted MRI are used to detect “mismatch,” which identifies the area of potentially reversible injury.  


The use of all of these imaging studies is based on the underlying hypothesis that if the blood supply is not restored, the penumbra will succumb to permanent injury eventually and result in a negative clinical outcome.  

Pathology   


The histopathological criteria for recognizing acute irreversible ischemic neuronal injury (necrosis) have been recognized for decades: An affected neuron loses its basophilic cytoplasm (the result of Nissl substance, or rough endoplasmic reticulum) and prominently nucleolated nucleus, which are replaced by a neuronal cell body showing brightly eosinophilic neuronal cytoplasm lacking identifiable substructure, and a pyknotic or collapsed nucleus; the tinctorial change in the cytoplasm may precede nuclear change (Figure 1).  

A, Subacute cerebral infarction involving left cerebral hemisphere (indicated by arrowheads) that had occurred ≈3 to 4 days before death. Note the pronounced cerebral edema with left-to-right shift of midline structures, including subfalcine herniation of the cingulate gyrus, and marked central diencephalic herniation. 

C, Old cystic cerebral infarcts (observed at autopsy) in 2 different patients. Brain at left shows appearance of left cerebral hemisphere immediately after calvarium has been removed. Arrowheads indicate a large cavity in the middle cerebral artery territory. Brain (coronal section) at right shows a large right MCA territory infarct (indicated by arrowheads) in a patient who had experienced stroke many years previously.  

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The timing of the neuroimaging in relation to the onset of ischemia may impact whether imaging evidence of stroke is seen, since signs of ischemia on noncontrast head CT are seen within the first few hours of CNS infarction in 31% to 60% of cases.45–48 Therefore, within the first 12 hours of an acute stroke, a tissue-based diagnosis of CNS infarction is not possible with the use of routine noncontrast head CT alone but could be if MRI were widely used. Because noncontrast head CT remains the most commonly used imaging modality in the acute setting,49 a patient may have a clear clinical vascular syndrome supporting a diagnosis of CNS infarction but not meet a tissue-based definition of CNS infarction if only CT is used. 

Although the duration of ischemia is important in both focal and global ischemia, focal ischemia is acutely treated with reperfusion strategies to improve flow in an artery. In distinct contrast, global ischemia is acutely treated by correcting the systemic disorder that is the underlying cause of hypo perfusion   


The evaluation of patients with focal and global ischemia also differs. Focal ischemia typically requires assessment of the cervical and cerebral arteries, investigation of a possible cardiac source of emboli, and evaluation of risk factors for atherosclerosis, whereas the evaluation of global ischemia is focused on identifying the underlying cause of hypo perfusion. 


Patients with focal ischemia present with neurological deficits that are localizable to a particular vascular distribution and rarely have a depressed level of consciousness.

However, patients with global ischemia    most commonly present with diffuse nonfocal neurological symptoms, particularly diminished consciousness. The prognosis also differs between focal and global ischemia, because mortality for focal ischemia is ≈12%,56 while for global ischemia >80% of patients do not survive hospitalization, with two thirds of the deaths attributable to neurological injury.

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The brain, spinal cord, and retina derive from neural tube tissue and therefore constitute the CNS, while the cranial and peripheral nerves derive from neural crest tissue.62 There are differences in the mechanisms of ischemia, treatment, and recovery between CNS and peripheral nervous system (PNS) ischemia that warrant limitation of the definition of infarction to the CNS.  


CNS ischemia, as previously described, results from stenosis or occlusion of both large vessels and small vessels attributable to local thrombosis or embolization from other vascular regions or from critical hypoperfusion in border-zone regions. PNS ischemia typically results from small-vessel occlusion of the vasa nervorum presenting as mononeuropathies, most commonly related to vasculitis or diabetes mellitus. 


For CNS ischemia, the treatment is focused on establishing reperfusion in the acute setting and then secondary prevention of ischemia. For PNS ischemia, treatments are focused on the underlying condition (ie, steroids for vasculitis or glucose control for diabetes mellitus), and acute reperfusion treatments are not available. The CNS and PNS also differ with respect to potential for recovery after ischemic injury. The PNS has a greater regenerative capacity than the CNS because of innate differences between the neurons and supportive cells in these locations, allowing for PNS axonal regeneration after injury.