Re: 추체외로 탐구!! 파킨슨 증상의 이해를 위해...

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Neuroanatomy, Extrapyramidal System

Jane Lee; Maria Rosaria Muzio.

Author Information and Affiliations

Last Update: November 9, 2022.

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Introduction

The extrapyramidal system (EPS) is an anatomical concept first developed by Johann Prus in 1898 when he discovered that the disturbance in pyramidal tracts failed to prevent epileptic motor activity. Prus postulated that, apart from pyramidal tracts, there must be alternative pathways, called the "extrapyramidal tracts," that "delivered epileptic activity" from the cerebral cortex to the spinal cord.[1][2] Clinically, the term "extrapyramidal" was thus adopted to distinguish between the clinical effects produced by damage involving the basal ganglia and those of damage to the classic "pyramidal" pathway. Despite this distinction, however, the two systems have important anatomical and functional relationships.

The EPS serves an essential function in maintaining posture and regulating involuntary motor functions. In particular, the EPS provides:

• Postural tone adjustment

• Preparation of predisposing tonic attitudes for involuntary movements

• Performing movements that make voluntary movements more natural and correct

• Control of automatic modifications of tone and movements

• Control of the reflexes that accompany the responses to affective and attentive situations (reactions)

• Control of the movements that are originally voluntary but then become automatic through exercise and learning (e.g., in writing)

• Inhibition of involuntary movements (hyperkinesias), which are particularly evident in extrapyramidal diseases.

소개

추체외로계(EPS)는

1898년 요한 프루스가 피라미드 관의 교란이

간질 운동 활동을 예방하지 못한다는 사실을 발견하면서

처음 개발한 해부학적 개념입니다.

프루스는 피라미드 관 외에 대뇌 피질에서 척수로 “간질 활동을 전달하는” “피라미드 외 관”이라는 대체 경로가 있을 것이라고 가정했습니다.[1][2] 

따라서

임상적으로

기저핵과 관련된 손상으로 인한

임상 효과와 전통적인 “피라미드” 경로의 손상으로 인한 효과를 구별하기 위해

“피라미드 외”라는 용어가 채택되었습니다.

그러나

이러한 구분에도 불구하고

두 시스템은 중요한 해부학적 및 기능적 관계를 가지고 있습니다.

EPS는 자세를 유지하고 불수의적 운동 기능을 조절하는 데 필수적인 기능을 합니다. 특히 EPS는 다음을 제공합니다:

• 자세 톤 조정
• 불수의적 움직임을 위한 predisposing tonic attitudes 준비
• 자발적인 움직임을 보다 자연스럽고 정확하게 만드는 동작 수행
• 톤과 움직임의 자동 수정 제어
• 정서적이고 세심한 상황에 대한 반응 (반응)에 수반되는 반사 신경 제어
• 원래는 자발적이지만 운동과 학습(예: 글쓰기)을 통해 자동적으로 되는 움직임의 제어
• 추체외로 질환에서 특히 두드러지는 불수의적 움직임(과다 운동증)의 억제.

• Inhibition of involuntary movements (hyperkinesias), which are particularly evident in extrapyramidal diseases.

The EPS, therefore, controls the automatic activities but also influences voluntary motility through a tonic function. These regulation mechanisms involve the processing of centers located in multiple brain regions, such as parts of the cerebral cortex, the cerebellum, the thalamus, the reticular substance, and several basal ganglia. The term basal ganglia or basal nuclei refers to a group of subcortical nuclei. Among these nuclei, the caudate nucleus and the putamen nuclei, which together constitute the neostriatum, plus the substantia nigra (SN), red nucleus (RN), and the subthalamic nucleus of Luys compose the nuclei of the EPS. From all these centers, numerous subcortical tracts, or the extrapyramidal tracts, stem out and terminate in the spinal cord. However, the majority of tracts travel through the basal ganglia.

Thus, anatomically, the EPS can be defined as a set of nuclei and fiber tracts that receive projections from the cerebral cortex and send projections to the brainstem and spinal cord and, functionally, works as a complex motor-modulation system.

Alterations affecting the various circuits play a crucial role in the pathogenesis of extrapyramidal motor disorders. Classic examples of injury to the EPS are Parkinson disease (PD), Huntington chorea (HC) caused by degenerative processes in the striatum, Sydenham chorea, multiple systemic atrophy (MSA), and progressive supranuclear palsy. In 1995, the World Health Organization's International Classification of Diseases released a classification for extrapyramidal and movement disorders. This chapter encompasses PD, secondary parkinsonism, other degenerative diseases of the basal ganglia, and several clinical conditions featuring dystonia, dyskinesia, and tremors (e.g., essential tremor). The clinical aspects of these clinical conditions are manifold and are not only the effect of alterations of voluntary movements. Because EPS probably establishes connections with the motor cortex by regulating the process of movement from the first ideational stages, voluntary movement can also become impaired in extrapyramidal pathology. For instance, slowing of voluntary movements such as walking is usually observed.

Moreover, the alterations that lead to these extrapyramidal pathologies mainly concern neurodegenerative processes. Thus, depending on the specific disease, the main symptoms are alterations of involuntary movements such as tremors, spasms, impairment of voluntary movements as well as a decline in cognitive functions involving mainly memory tasks, and affective sphere disorders such as depression. Postural alterations are also detected. For instance, the so-called Pisa syndrome, which is an abnormal posture in which the body appears to be leaning to one side like the Tower of Pisa, is an atypical feature of MSA. Finally, autonomic alterations and several non-motor symptoms, such as pain, can be part of the clinical picture of these pathologies.

따라서

EPS는

자동 활동을 제어할 뿐만 아니라

tonic 기능을 통해

자발적 운동성에도 영향을 미칩니다.

이러한 조절 메커니즘은

대뇌 피질의 일부, 소뇌, 시상, 망상 물질 및 여러 기저핵과 같은

여러 뇌 영역에 위치한 중추의 처리를 포함합니다.

basal ganglia 또는 기저핵이라는 용어는 피질하 핵의 그룹을 의미합니다.

이 핵들 중

꼬리핵과 푸타멘핵은 함께 신교질을 구성하며,

여기에 흑질핵(SN), 적핵(RN), 루이스 시상하핵이 더해져 EPS의 핵을 구성합니다.

Among these nuclei, the caudate nucleus and the putamen nuclei, which together constitute the neostriatum, plus the substantia nigra (SN), red nucleus (RN), and the subthalamic nucleus of Luys compose the nuclei of the EPS.

이 모든 중추에서

수많은 피질하 관 또는 피라미드 외관이 나와

척수에서 종결됩니다.

그러나

대부분의 관은

기저핵을 통해 이동합니다.

따라서 해부학적으로 EPS는 대뇌 피질에서 돌기를 받아 뇌간과 척수로 돌기를 보내는 일련의 핵과 섬유 관으로 정의할 수 있으며, 기능적으로는 복잡한 운동 조절 시스템으로 작동합니다.

Thus, anatomically, the EPS can be defined as a set of nuclei and fiber tracts that receive projections from the cerebral cortex and send projections to the brainstem and spinal cord and, functionally, works as a complex motor-modulation system.

다양한 회로에 영향을 미치는 변화는

피라미드 외 운동 장애의 발병에 중요한 역할을 합니다.

EPS 손상의 대표적인 예로는

파킨슨병(PD),

선조체의 퇴행성 과정으로 인한 헌팅턴 무도병(HC),

시덴햄 무도병,

다발성 전신 위축증(MSA),

진행성 핵상 마비 등이 있습니다.

1995년 세계보건기구의 국제질병분류는

추체외로 및 운동 장애에 대한 분류를

발표했습니다.

이 장에서는

PD,

이차성 파킨슨병,

기저핵의 기타 퇴행성 질환,

근긴장 이상증, 진전증(예: 본태성 진전)을 특징으로 하는

여러 임상 질환을 포괄합니다.

이러한 임상 질환의 임상 양상은 다양하며 자발적 움직임의 변화로 인한 영향만이 아닙니다. EPS는 아마도 첫 번째 관념 단계부터 운동 과정을 조절하여 운동 피질과의 연결을 설정하기 때문에 피라미드 외 병리에서도 자발적 움직임이 손상될 수 있습니다.

예를 들어, 걷기와 같은 자발적 움직임의 둔화가 일반적으로 관찰됩니다.

또한,

이러한 추체 외로 병리를 유발하는 변화는

주로 신경 퇴행성 과정과 관련이 있습니다.

따라서

특정 질환에 따라

떨림, 경련, 자발적 움직임의 손상과 같은 불수의적 움직임의 변화와

주로 기억 작업과 관련된 인지 기능의 저하,

우울증과 같은 정서 영역 장애가 주요 증상입니다.

자세 변화도 감지됩니다.

예를 들어,

피사의 사탑처럼 몸이 한쪽으로 기울어지는 비정상적인 자세인

이른바 '피사 증후군'은

multiple systemic atrophy 의 비정형적인 특징입니다.

마지막으로,

자율신경계 변화와 통증과 같은

여러 비운동성 증상이

이러한 병리의 임상 양상의 일부가 될 수 있습니다.

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Structure and Function

The EPS is polysynaptic in nature and composed of several tracts and nuclei. The tracts include the reticulospinal, vestibulospinal, rubrospinal, and tectospinal tracts.[3] See Illustration. Tracts of the Spinal Cord.

Reticulospinal Tract

This tract transmits motor commands from the reticular formation. The medial (pontine) reticulospinal tract originates in the pontine reticular formation and projects down to the ventromedial spinal cord via the ipsilateral anterior funiculus, which contains alpha and gamma motor neurons of the extensor muscles. The ascending spinothalamic tracts also stimulate the medial reticulospinal tract. The lateral (medullary) reticulospinal tract ordinates in the medullary reticular formation and projects to motor neurons in the spinal cord via the bilateral lateral funiculus.[4][5]

Vestibulospinal Tract

The medial vestibulospinal tract originates in the medial vestibular nuclei, or Schwalbe's nucleus, in the medulla and terminates in the limb motor neurons. They are responsible for innervating upper-body musculature, especially muscles of the neck and forelimbs. The lateral vestibulospinal tract originates in the lateral vestibular nuclei, or Deiter's nucleus of the pons, and ipsilaterally courses down to the Rexed's laminae VII and VIII. These laminae contain premotor interneurons and other alpha and gamma motor neurons that are responsible for innervating the extensor muscles that oppose gravity as well as inhibiting the flexor muscles. The vestibulospinal tract plays a crucial role in maintaining an erect posture.[6][7] 

Rubrospinal tract

The rubrospinal tract originates from the red nucleus of the midbrain tegmentum. It crosses the midline in ventral tegmental decussation located in the caudal midbrain (see Image. The Midbrain or Mesencephalon). The tract forms a contralateral tract in the dorsolateral part of the lateral funiculus and lies in the ventrolateral part of the spinal cord. The rubrospinal tract mainly transmits signals into the red nucleus from the motor cortex and cerebellum to the spinal cord and ventral horn lamina V, VI, and VII.[8] In these laminae, the rubrospinal tract synapses with alpha and gamma motor neurons that stimulate the flexor muscles. The importance of the tract lies in the maintenance of muscle tone and in the regulation of rudimentary motor skills that are refined by corticospinal control.[9] With the corticospinal tract, the rubrospinal tract controls hand and finger movements in addition to flexor muscles. 

Tectospinal Tract

The tectospinal tract originates from the superior colliculus of the midbrain and receives stimulation from the retina and cortical visual association areas, courses ventromedial to the periaqueductal gray (PAG) matter, and terminates in the contralateral anterior gray horn lamina VI, VII, and VIII of cervical and upper thoracic segments of the spinal cord (see Illustration. Tectospinal Tract). It serves a critical function in the orientation of the head, neck, eyes, and upper extremities in response to sudden movement, loud noises, and bright lights.[10][11]

구조와 기능

EPS는 본질적으로 다시냅스이며 여러 관로와 핵으로 구성되어 있습니다. 이러한 관에는 망상 척수관, 전정 척수관, 윤상 척수관 및 구조 척수관이 포함됩니다.[3] 그림 참조. 척수의 관

망상 척수관
이 관은 망상 형성에서 운동 명령을 전달합니다. 내측(폰틴) 망상 척수는 폰틴 망상 형성에서 시작하여 신근의 알파 및 감마 운동 뉴런을 포함하는 동측 전방 굴곡을 통해 복내측 척수로 돌출됩니다. 상행 척수관은 또한 내측 망상 척수를 자극합니다. 외측(골수성) 망상 척수관은 골수성 망상 형성에서 정렬되어 양측 외측 신경절을 통해 척수의 운동 신경세포로 돌출됩니다.[4][5][6]

전정 척수
내측 전정척수관은 수질의 내측 전정핵 또는 슈발베핵에서 시작하여 사지 운동 뉴런에서 종결됩니다. 이들은 상체 근육, 특히 목과 팔다리 근육에 신경을 전달하는 역할을 합니다. 외측 전정신경은 외측 전정핵 또는 폰의 데이터핵에서 시작하여 동측으로 렉세드 7번 및 8번 층으로 내려갑니다. 이 층에는 중력에 대항하는 신근을 자극하고 굴근을 억제하는 역할을 하는 전운동 신경세포와 기타 알파 및 감마 운동 신경세포가 포함되어 있습니다. 전정 척추는 직립 자세를 유지하는 데 중요한 역할을 합니다[6][7].

윤상 척수
윤상 척수는 중뇌 소뇌의 붉은 핵에서 시작됩니다. 이 관은 꼬리 중뇌에 위치한 복측 중뇌 분절의 중앙선을 가로지릅니다( 이미지 참조 . 중뇌 또는 중뇌). 이 관은 외측 연골의 등측 부분에 대측 관을 형성하고 척수의 복측 부분에 위치합니다. 루브로척수관은 주로 운동 피질과 소뇌에서 척수와 배쪽 뿔 층 V, VI, VII로 신호를 전달합니다.[8] 이 층에서 루브로척수관은 굴곡근을 자극하는 알파 및 감마 운동 뉴런과 시냅스를 형성합니다. 이 관의 중요성은 근육 긴장도 유지와 피질척수 제어에 의해 개선되는 기초적인 운동 기술의 조절에 있습니다.[9] 피질척수 관과 함께 윤상 척수는 굴근뿐만 아니라 손과 손가락의 움직임도 제어합니다.

구조 척수
척수 척수는 중뇌의 상부 꼬리뼈에서 시작하여 망막과 피질 시각 연관 영역으로부터 자극을 받고, 복내측으로 진행하여 뇌관 주위 회백질(PAG) 물질에 도달하며, 척수의 경추 및 상흉부 분절의 반대측 전회각 층 VI, VII 및 VIII에서 종결됩니다( 그림 참조 . 척수 척수). 갑작스러운 움직임, 시끄러운 소음, 밝은 빛에 반응하여 머리, 목, 눈, 상지의 방향에 중요한 기능을 합니다.[10][11]

Embryology

The central nervous system (CNS) derives from a subspecialized ectoderm called the neuroectoderm. Over two to eight weeks of embryological development, notochord causes the evolution of the neural plate. The neural plate eventually differentiates into the neural tube via neurulation, which eventually forms the central nervous system. The brain forms from the cranial two-thirds, and the spinal cord forms from the caudal one-third of the neural tube.[12]

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Blood Supply and Lymphatics

Blood Supply to the Brain

The main blood supply to the brain includes the internal carotid arteries (anterior circulation) and the vertebral arteries (posterior circulation). The internal carotid arteries arise at the bifurcation of the common carotid arteries and branch into the anterior and middle cerebral arteries. The anterior and middle cerebral arteries are the anterior circulation of the brain and contribute to the blood circulation of the forebrain. These blood supplies further branch into numerous arteries, such as the lenticulostriate arteries that pass through the white matter and deeper structures, such as basal ganglia and thalamus. The posterior circulation of the brain includes posterior cerebral, basilar, and vertebral arteries. The two vertebral arteries join at the level of the pons and form the basilar artery at the midline of the brainstem. The circle of Willis is the name given to the anastomosing vessels that connect the anterior and posterior circulation of the brain. 

Blood Supply to the Spinal Cord

The main blood supplies to the spinal cord arise from the vertebral arteries, which originate from the subclavian artery, and from ten to twelve medullary arteries, which arise from the segmental branches of the aorta. The anterior spinal artery is responsible for vascular supply to the ventral portion of the spinal cord, and it originates from the vertebral artery at the level of the medulla. From the vertebral artery at the level of the medulla, medullary arteries form and combine to become the anterior spinal artery. The posterior spinal artery is responsible for supplying the dorsal portion of the spinal cord, and it originates from the vertebral artery as paired arteries that course along the posterior surface of the spinal cord. 

The anterior spinal artery branches into multiple sulcal arteries that supply the ventral two-thirds of the spinal cord. The posterior spinal artery is responsible for supplying the majority of dorsal horns and dorsal columns. The anastomosing arteries that connect the anterior and posterior spinal arteries are called the vasocorona. The vasocorona supplies the white matter in a ring-like fashion by surrounding the spinal cord peripherally.

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Clinical Significance

A large number of causes can induce syndromes and clinical manifestations of extrapyramidal damage. Most of the EPS alterations have a degenerative cause. A genetic component underlies some disorders, while injury processes, and those due to perfusive damage, are also possible. Extrapyramidal syndromes can also be associated with drugs such as antipsychotic drugs and reserpine, as well as toxic substances such as carbon monoxide, cyanide, and paraquat, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Manganese can occupationally induce secondary parkinsonism through serious neurotoxicity involving the basal ganglia.[13][14]

General Clinical Features

The alterations of the extrapyramidal system can be grouped into hypokinesias and hyperkinesias.

Hypokinesias

Unlike pyramidal pathology, extrapyramidal involvement does not lead to paralysis but instead to scarcity or absence of movements which are termed hypokinesia and akinesia, respectively. Both conditions can express voluntary and involuntary movements. Several voluntary acts, such as walking, writing, and speaking, will slow down. Concerning involuntary movements, a reduction, or loss, of the associated movements of pendulation of the upper limbs during walking or mimic and expressive movements can be observed. Furthermore, slowness in the execution of voluntary movements, especially at the beginning of the movement or when this is about to complete, can be present. This condition is termed bradykinesia.

Hyperkinesias

These concern abnormal involuntary movements that can present in extrapyramidal diseases. These movements become distinguished by:

• Choreic movements: sudden, irregular, incomplete, aimless, variable movements

• Athetotic movements: arrhythmic, slow, exaggerated, tentacular movements

• Hemiballism: the movements are similar to choreic movements but much more intense and persist during sleep

• Rapid muscle contractions, which reproduce a stereotyped movement, repeated obsessively; they can become voluntarily inhibited, even if with effort

• Tremors: the extrapyramidal tremor (e.g., the typical tremor of PD) is rhythmic, at a slow pace (4 to 5 oscillations per second), not very wide, uniform, more pronounced at rest, and attenuates during voluntary and passive movements - for instance, it disappears during sleep

• Spasms: involuntary movements of a tonic type (intense and lasting contraction, but transient) or clonic (series of rhythmic contractions of short duration, separated by periods of rest)

• Myoclonus: rapid, sudden contractions involving isolated muscles or bundles of muscle fibers - usually do not cause motor effects

Among hyperkinesias, several discharge phenomena are also included:

• Spastic crying: it is frequently observable in people with pseudobulbar syndrome, where an insignificant cause can trigger spasmodic or spastic crying

• Forced gaze crisis: oculogyric tonic crisis, with a forced deviation of the eyes, sideways or upwards, lasting from a few minutes to a few hours, which repeats periodically, sometimes accompanied by simultaneous homologous rotation of the head

• Torsion spasm: deformation of the lordotic or kyphoscoliosis back-lumbar spine, with contortion movements

• Spastic stiff neck: rhythmic spasms of rotation and inclination of the body towards one side, sometimes accompanied by a lifting of the corresponding shoulder

In extrapyramidal diseases, signs and symptoms of a non-motor nature can occur. For example, disturbances of attention, slowed or monotonous ideation, and poor control of emotion and instincts are such findings.

Extrapyramidal Syndromes

Concerning the different associations between tone and movement disorders, two fundamental syndromes are distinguishable: pallidal syndrome and striated syndromes.

Pallidal syndrome

This syndrome is characterized by muscle hypertonia, bradykinesia, and sometimes by tremor (hypertonic-hypokinetic syndrome) and is mainly observed in PD. In particular, PD is characterized by generalized extrapyramidal hypertonia, static tremor, and akinesia. The hypertonia is mainly observed at the root of the limbs, is permanent, and is accompanied by an exaggeration of postural reflexes. For example, flexing the hand on the forearm remains for a few moments in this position before reverting. The static tremor predominates in the upper limbs; moreover, it is wide and regular. Akinesia is a loss of the ability to move muscles voluntarily. A typical sign of akinesia is 'freezing.' The patient loses automatic and associated movements, with difficulty regaining balance, and they walk with the center of gravity moved forward or in a stooped posture. Non-motor symptoms such as pain are usually essential features of the disease and can also precede motor disorders.[15][16]

Striated Syndromes

Also termed hyperkinetic-dystonic syndromes include the choreic syndrome characterized by choreic movements and hypotonia; the athetosis syndrome with athetosis movements and hypotonia; the hemiballism syndrome; and the hepatolenticular syndrome, better known as Wilson disease.

Bilateral Injuries At The Brainstem Level

In addition to quadriplegia, two fundamental pictures of hypertonia can be observed, depending on the level of injury: decerebrate rigidity and decorticate rigidity. The EPS plays a key role in both phenomena.

Decorticate Rigidity

Decorticate rigidity occurs when an injury at the superior border of the red nucleus disturbs descending corticospinal and rubrospinal tracts (see Illustration. Decorticate Posturing). This condition leads to the flexion of the upper extremities and extension of the lower extremities with painful stimuli.[17] The injury to the red nucleus causes subsequent overactivation of the rubrospinal tract and medullary reticulospinal tract. Also, the lateral corticospinal tract is disturbed, which causes flexor muscles of the lower extremities to be impaired and allows the pontine reticulospinal and medial and lateral vestibulospinal to induce biased extension.

Decerebrate Rigidity

Decerebrate rigidity occurs when an injury at the superior border of the pons disconnects the posterior aspect of the brainstem and the spinal cord from the rest of the brain (see Illustration. Decerebrate Posturing). With the transection, stroke, or hemorrhage of the brainstem regions, the lateral ventrospinal tract and the reticulospinal tract over-activate extensor motor neurons with restricted inhibition of the cortex and basal ganglia. This, in turn, causes increased activity of alpha motor neurons and gamma motor neuron discharges.[7] As a result, the injury causes the extensor muscles of all limbs and muscles of the neck and trunk to have increased tone (i.e., the extension of elbows in addition to the extension and internal rotation of all extremities).

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Figure

The Midbrain or Mesencephalon. Transverse section of the mid-brain at the level of superior colliculi, optic nerve, cerebral aqueduct, nucleus of oculomotor nerve, medial longitudinal fasciculus, red nucleus, tegmentum, and lemniscus. Henry Vandyke Carter, (more...)

Figure

Tectospinal Tract Contributed by O Chaigasame, MD

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Decorticate Posturing Illustration by K Humphreys

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Decerebrate Posturing Illustration by K Humphreys

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Tracts of the Spinal Cord Polarlys and Mikael Häggström, Public Domain, via Wikimedia Commons