Parkinson病

脳神経

Parkinson病の病態

Parkinson病の病態は「大脳皮質→大脳基底核→視床→大脳皮質」という流れで構成される「大脳皮質ー大脳基底核ループ」という神経回路を用いて説明されることが多い。

大脳皮質からは随意運動指令を伝達する錐体路と呼ばれる神経伝導路に加えて、不随意運動を調整する指令を伝達する錐体外路と呼ばれる神経伝導路が出ている。

ちなみに錐体外路とは錐体路以外の運動に関与する神経伝導路の総称である。具体的には「大脳皮質ー大脳基底核ループ」自体とその構成物のいずれかから出る運動に関与する神経伝導路全体を指し、不随意運動と随意運動の調整を行なっている。

大脳皮質や大脳基底核から出て不随意運動を調整している錐体外路と大脳皮質ー大脳基底核ループを構成して錐体路による随意運動の調整を行う錐体外路が存在するということである。

錐体外路のどこかが障害されると錐体外路症状(パーキンソニズムを含む)が生じる。つまり、錐体外路症状とは「大脳皮質→大脳基底核→視床→大脳皮質のループ回路」のどこかに異常が生じた結果として出現する運動系の障害の総称だと理解できる。

「大脳皮質ー大脳基底核ループ」が運動に関してどのような役割を果たしているのかを説明する。

運動指令を出していない非運動時には淡蒼球内節が視床を抑制して大脳皮質を興奮させないようにしている。

非運動時から運動するにあたっては大脳皮質を興奮させる必要が生じる。

そこで、運動時には黒質に存在するドパミン神経が線条体(被殻+尾状核)にドパミンを送って、ドパミンを受け取った線条体が淡蒼球を抑制することによって視床を脱抑制させて大脳皮質を興奮させる。

要するにドパミンは非運動時には抑制されている大脳皮質を運動時に興奮させるために必要な物質ということである。

「大脳皮質ー大脳基底核ループ」という神経回路は運動指令を行う大脳皮質を抑制したり脱抑制させることで、運動を止めたり開始するといった指令の調整を可能にしてスムーズな運動を行うことを可能にしているのである。

Parkinson病はこの「大脳皮質ー大脳基底核ループ」が中脳黒質に存在するドパミン神経細胞の変性によるドパミン産生量低下によって上手く機能しなくなった結果として起こる疾患である。

ドパミン神経細胞の変性は神経毒性を持つα-シヌクレインの凝集体であるLewy小体によって引き起こされるのだが、この機序はLewy小体型認知症と同じでありParkinson病とLewy小体型認知症を同一のスペクトラムで捉えるLewy小体病という考え方もある。

Parkinson病の症状

パーキンソニズム(運動症状)

ドパミン不足によって、運動を開始しようとしても淡蒼球内節に抑制されている視床を脱抑制させて大脳皮質を興奮させるということができない。淡蒼球内節を抑制する働きをする線条体がドパミンが不足すると作動しないからである。

このため、随意運動を開始しようとしても大脳皮質を興奮させることができないので動くことができずに随意運動減少となる。また、不随意運動を調整する役割を果たす錐体外路も機能しなくなるので不随意運動が出現してしまう。

随意運動減少と不随意運動出現による症状をパーキンソニズムと呼ぶ。

具体的には安静時振戦(静止時振戦)と無動・寡動(動作緩慢)と筋強剛:rigidity(筋固縮)と姿勢反射障害を指す。

パーキンソニズムは「大脳皮質ー大脳基底核ループ」が障害される他の疾患でも生じる。

筋固縮、無動・寡動(動作緩慢)、姿勢反射障害はパーキンソン病に特異的な症状ではなく、安静時振戦(静止時振戦)はパーキンソン病に比較的特異的な症状であるとされる。

また、顔面筋の動きが乏しくなることによって仮面を被っているかのように表情の変化が少なくなるのが特徴的で仮面様顔貌と呼ばれる。

非運動症状

非運動症状はパーキンソニズム(運動症状)の前駆症状として出現することが多い。

自律神経症状

神経毒性を持つα-シヌクレインは中脳黒質のドパミン神経細胞のみならず、中枢自律神経や末梢自律神経にも凝集するためParkinson病患者は自律神経障害を呈する。

自律神経症状として便秘や起立性低血圧や排尿障害や脂漏性顔貌などの症状が起こる。排尿障害は過活動膀胱による尿意切迫症候群が主な症状となる。脂漏性顔貌とは自律神経の障害によって脂腺から皮脂の分泌量が増加して脂ぎった顔貌となることを指す。

嗅覚低下

においを司る嗅球は病理学的に最初に障害される部位の一つであることが明らかになっている。

REM睡眠行動障害

Lewy小体病(Parkinson病・Lewy小体型認知症)ではREM睡眠時に夢内容を行動化させないための運動指令の調節が上手く働かないため、睡眠中に異常行動がみられる。

抑うつ

パーキンソン病という難病に罹患してしまったことで不安を感じるようになり抑うつが引き起こされる。Parkinson病の病態自体が関わる神経学的な基盤が原因となることもある。

Parkinson病でみられる歩行障害

Parkinson病患者は前傾前屈姿勢を呈して、歩き始めの一歩が踏み出せない「すくみ足」となる。

そして、歩き始めても歩くときに歩幅が狭くなる「小刻み歩行」となる。

この際に床にテープなどで横線を引いて視覚的手がかりを作ることが歩行障害に有効となる。

また、歩いていると段々スピードが増して止まれなくなる「加速歩行(突進歩行)」を呈する。

Lewy小体病(Parkinson病・Lewy小体型認知症)の検査

Lewy小体病(Parkinson病・Lewy小体型認知症)では大脳基底核変性と自律神経変性が生じる
ため、これらの神経変性をシンチグラフィ検査による画像で可視化して診断に用いる。

シンチグラフィとは放射線同位元素で標識された物質を投与後に、放出されるガンマ線を画像化することで分布を把握する検査自体を指す。

SPECTとは断層撮影によってシンチグラフィの画像化を行う方法を指す。SPECTでは身体の断面の画像(断層画像)で確認できる。

ドパミントランスポーターシンチグラフィ

ドパミントランスポーターシンチグラフィによって大脳基底核におけるイオフルパン(123I-ioflupane)の取り込み低下をSPECT画像で確認できる。これは大脳基底核変性を反映する。

ドパミン神経終末に発現しており、シナプス間隙のドパミンを再取り込みする役割を果たすドパミントランスポーター(DAT)はドパミン神経の変性とともに減少する。

このドパミントランスポーターに親和性のある(結合する)イオフルパンを用いてシンチグラフィを行なって「イオフルパンの大脳基底核取り込み低下=ドパミントランスポーターの発現量低下=ドパミン神経変性」を画像化する方法がドパミントランスポーターSPECTである。

MIBG心筋シンチグラフィ

MIBG心筋シンチグラフィによって心筋(心臓交感神経)における123I-mataiodobenzylguanidine(MIBG)の取り込み低下を画像で確認できる。具体的には心臓の部分に集積せず白く見えるようになる。これは心臓交感神経の障害を反映する。

MIBGはノルアドレナリンと構造が類似しているため交感神経に取り込まれる物質である。

交感神経機能を反映することに加えて、交感神経由来の腫瘍である褐色細胞腫にも集積することから褐色細胞腫の診断にも用いられる。

抗Parkinson病薬

パーキンソン病では線条体におけるドパミン作用を増強させる治療が求められる。

そこで、ドパミン自体を体内に投与したら良いように思えるが、ドパミン自体は血液脳関門(Blood Brain Barrier:BBB)を通過することができない。

それなので、血液脳関門を通過できるドパミンの前駆物質となるレボドパ(L-dopa)・ドパミン放出促進薬(アマンタジン塩酸塩)・ドパミン受容体作動薬を投与する。

レボドパ(L-dopa)は体内に投与した後に脳内に到達するまでの間に末梢で幾らかがドパ脱炭酸酵素とカテコール-O-メチル基転移酵素(COMT)によって代謝されてしまう。

そこで、ドパ脱炭酸酵素阻害薬(カルビドパ)とCOMT阻害薬(エンタカポン)もレボドパと一緒に投与することでレボドパ(L-dopa)の効果を増強させる。

また、ドパミンは脳内でモノアミンオキシダーゼ-B(MAO-B)という酵素によって分解される。

モノアミンオキシダーゼ-B阻害薬(MAO-B阻害薬)も脳内におけるドパミン量を増やすことにつながるのでレボドパと共に投与される。

Wearing-off現象

レボドパ(L-dopa)はドパミンの前駆物質となるため、ドパミン作用を増強する上で直接的であり最も強力な抗Parkinson病薬となるが、長期間使用すると薬効持続時間が短くなってしまいwearing-off現象が起こる。

Wearing-off現象とはレボドパ服用後に次のレボドパ服用まで薬効が持続しないためにParkinson症状が生じてしまう現象を指す。

レボドパの服用回数を細かく分割することで対応する。

また、代謝酵素阻害薬や放出促進薬や受容体作動薬を用いてドパミン作用を増強させることで対応する。

抗Parkinson病薬の副作用

抗Parkinson病は遅発性ジスキネジアや幻覚といった副作用を生じさせることがある。

副作用が出現した場合はまず現在の薬物を減量する。

そして、幻覚に対しては非定型抗精神病薬が有効となり得るがパーキンソニズムを悪化させる可能性があることに注意する必要がある。

直ちに全量の投与を中止すると悪性症候群を引き起こす危険性がある。

遅発性ジスキネジア

遅発性ジスキネジアとは抗精神病薬や抗Parkinson病薬や抗うつ薬や抗てんかん薬の副作用として生じるジスキネジアを指す。

ジスキネジアとはジストニアや舞踏運動などの様々な不随意運動が組み合わさって生じる奇妙な運動を総称する言葉である。ジスキネジアにジストニアや不随意運動が含まれているというイメージで差し支えないと考えられる。

ジスキネジアという言葉は基本的に遅発性ジスキネジアを指すことが多い。

上述したような脳内神経系に作用する薬剤は副作用として様々な種類の不随意運動を引き起こすため、例えばハンチントン病が舞踏運動を引き起こすとかいうように一対一で不随意運動を指す言葉を対応させることができない。遅発性ジスキネジアを呈している患者さんではジストニアと舞踏運動が混ざっていてどっちともいえないというような感じになってしまうことがあるからである。

そこで、脳内神経系に作用する薬剤の副作用として生じた不随意運動はとりあえず遅発性ジスキネジアという言葉で総称して、その遅発性ジスキネジアはジストニアとか舞踏運動など詳細はどの不随意運動で構成されているのかというように考えるのである。

遅発性ジスキネジアの特徴として、

①夜間睡眠時には消失する。

②精神的ストレスがかかると症状は憎悪する。

③症状を止めようと意識すると一時的に軽減するものの、すぐに症状は再開するため完全に止めることはできない。

といったことが挙げられる。

口舌ジスキネジア

無意識に口をもぐもぐさせたり舌を突き出したりするものを指す。

患者は「勝手に口が動いてしまうんです」と訴える。

ジストニア

ジストニアとは身体の一部または全身に持続性の筋収縮をきたす不随意運動を指す。

ジストニアは単独で特発性(原因不明)に生じることも多い。

遅発性ジスキネジアとして生じるだけではなく、原因不明に他の症状なしにジストニアのみを呈することがあることに注意する。

眼瞼けいれん

眼輪筋の筋収縮が持続して目が開かなくなる。

痙性斜頸

頸部の筋収縮が持続して首が傾いた異常な姿勢となった状態が続く。

書痙

何か文字を書こうとするときに指の筋収縮が持続してしまい字が上手く書けなくなる。原因不明に生じることも多い。

参考文献

パーキンソン病治療薬ドパミン系薬剤の副作用(幻覚・妄想)の治療:https://www.jstage.jst.go.jp/article/faruawpsj/52/12/52_1141/_pdf

ジストニア:https://www.nanbyou.or.jp/wp-content/uploads/kenkyuhan_pdf2013/s-sitei11.pdf

3.薬物誘発性不随意運動:https://www.nanbyou.or.jp/wp-content/uploads/kenkyuhan_pdf2013/s-sitei11.pdf

ジスキネジア:https://www.mhlw.go.jp/topics/2006/11/dl/tp1122-1c22.pdf

不随意運動の診かた:https://www.jstage.jst.go.jp/article/jscn/43/4/43_122/_pdf/-char/ja

不随意運動:https://www.igaku-shoin.co.jp/misc/pdf/1402107652.pdf

重症副作用疾患別対応マニュアル ジスキネジア:https://www.mhlw.go.jp/topics/2006/11/dl/tp1122-1c21.pdf

大脳基底核の機能;パーキンソン病との関連において:http://physiology.jp/wp-content/uploads/2014/01/065040113.pdf

パーキンソン病の自律神経症状:http://physiology.jp/wp-content/uploads/2014/01/065040113.pdf

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  61. The barbell bent-over row is the obvious alternative as a substitution for the Smith machine row.
    It emphasizes the very same primary muscle teams as the Smith machine row.
    This helps strengthen the again muscles, particularly the latissimus dorsi (lats),
    rhomboids, and trapezius muscles (traps). Look for an train that enables an identical lengthy vary of movement to completely
    stretch and contract the again muscles. In Addition To that, if you’re thinking about strengthening
    higher body muscular tissues, the treadmill is most likely going not
    what you’re looking for. That implies that the pull-up bar will not
    really offer you very big benefits when it comes to trying to enhance cardiovascular health, strengthening leg muscular tissues, etc.
    To do this train you want a pull-up bar which is basically a sturdy horizontal bar.

    It’s additionally useful if you have a
    large belly that stops you doing the common two-handed row via a full range of
    motion. Because the pad supports your weight, you presumably can focus on training
    your again with out decrease again fatigue forcing you to chop the
    set short. An train doesn’t need to involve an precise twist to
    work the twisting muscular tissues. By actively preventing your torso from twisting,
    those same muscles are nonetheless being trained.
    Not solely does it bolster unilateral again power but additionally improves overall
    core power.
    That’s why we take the time to select our different workout routines
    rigorously to verify they do the identical thing as
    the unique move. Similar to the inverted row, you can do a TRX row and
    make the train as easy or as hard as you want.
    Instead of performing a full rep, on the best way down you’ll pause on the half method mark,
    bring the load back up, after which deliver the burden all the best way down. So,
    in addition to working your upper again, scapular wall slides
    additionally present your chest with a useful stretch.
    As its name implies, this muscle is located on the again of your shoulder.

    The rear delt is usually underdeveloped and desires plenty
    of direct coaching to ensure that it doesn’t lag behind the opposite two deltoids.
    This also is dependent upon your health objectives however, as a general rule,
    sure you would.
    The variable resistance of the band makes this a late section loaded exercise, where it
    gets more durable as you pull. This allows for a very forceful contraction on the finish of the rowing in movement.
    All you need is something like a TRX suspension trainer, some gymnastic
    rings, or only a waist-high bar that’s robust enough to hold your body weight.
    This rowing train is straightforward on your lower back and
    engages your glutes and core, making it very functional and time-efficient.

    He has competed at a high degree in numerous sports activities, together with rugby, triathlon, mountain climbing, trampolining, powerlifting, and, most recently, stand
    up paddleboarding. When not lecturing, coaching, researching,
    or writing, Patrick is busy having fun with the sunny climate of Cyprus, where he has lived for the last
    20-years. Middle trapezius and rhomboids – situated across and between the scapulae, the mid-traps and rhomboids work collectively to retract your shoulder blades.
    Creating these muscular tissues will give your higher again thickness and could enhance your posture.

    What’s extra, as a end result of all of the resistance comes
    from one aspect, varied muscle tissue in your torso need to
    work harder than regular to keep your physique secure.
    Nevertheless, certainly one of its main downsides is that the power of
    the muscular tissues in your lower back can be a
    limiting factor, especially if you’ve carried out squats or deadlifts earlier
    in the workout. This variation reduces stress on the lower again by positioning you susceptible on an inclined bench.
    Performing unilateral workout routines can help ensure that
    both sides of your body are equally sturdy and muscular.
    Since you are seated on a machine, you may have
    more assist that may in any other case be the responsibility of the stabilizer muscles.

    I hope at least certainly one of these Barbell Row alternate options I’ve listed right here is an efficient
    match for you and your exercise routine.
    It requires lots of grip energy, and you’ll find your grip power improving with each set.
    If you can’t lift lots of weight, you’d be better off performing common dumbbell rows.
    The T-bar row is a bent-over row alternative focusing on the upper-back muscle tissue for
    bodybuilders and strongmen. It’s one of many best bent-over row machines to use with proper type, even for newbies.
    Some bent-over row options are much less likely to injure
    the decrease again.
    If your torso stays more upright, this reduces tension on these muscles and places more of the burden load on your higher back muscles.
    If you feel an excessive amount of engagement of your biceps as you pull the load in the path of your torso you will not be retracting your shoulder
    blades enough. If you perform the t-bar row with your knees
    locked out it will very doubtless influence your technique.

    Both that, or you discover yourself rounding your
    backbone, doubtlessly exposing yourself to an elevated danger
    of harm. Every substitute presents its personal advantages, such as diminished stress on the lower again and enhanced stability along with
    better muscle activation. Your back is an especially necessary a half of your physique for
    posture, strength, physique steadiness, and overall function. Poor posture may cause shoulder, neck, and again pain, along
    with extra critical conditions like exhaustion, hypertension, and decreased mood.

    I merely cannot have a listing of back workouts without including Chin-ups or Pull-ups.
    I’m choosing Chin-ups right here as a result of the narrower,
    underhand grip extra carefully mimics a Chest Supported
    Row, however you can’t go wrong (ever) with a Pull-up both.
    Attempt to restrict rotating the torso as a lot as potential when doing Renegade Rows.
    It’s pure to wish to open the torso toward the aspect of the
    arm you’re rowing with – try to battle towards this and keep as sq.
    as attainable. The preliminary setup and stance for
    Barbell Bent Over Rows ought to be particular
    to the lifter’s deadlifting and/or Olympic lifting targets.
    Having equivalent setups and grips might be great for the lifts to hold over to the compound movements.
    You’ll typically see people lower the bar too rapidly, using momentum and their
    posterior chain to power the load up out of
    the bottom portion of the raise.
    Option one is the inverted row, where you employ the burden of your individual physique, somewhat than a barbell or dumbbell, to offer resistance.

    However in the course of the lat pulldown, the spinal
    erectors aren’t trained to the same extent as they are in the course of the barbell row.
    Like many exercises, the barbell row actually has
    the potential to be dangerous for your again should you don’t do it correctly,
    however it’s not bad for your again per se.

    Rear delt rows may be carried out with dumbbells, barbells, cables, or resistance bands.
    Unlike the standard barbell row, the pendlay row begins from the ground.
    The bent over row is an train that strengthens the muscle tissue of your center again. This carry
    additionally has the further benefit of working your latissimus dorsi, or lower again, and the muscle
    tissue in your arms. Incorporating this lift into your weekly exercise routines will strengthen your again and improve your posture.

    Oftentimes, a standard lat pulldown bar with a shoulder-width grip is used for a
    lat pulldown. If you’re seeking to achieve extra energy, explosiveness,
    and energy whereas lowering the stress positioned on your lower again,
    then the pendlay row is a good barbell row alternative! A pendlay row is similar to a barbell row; nevertheless, the barbell begins on the floor and comes to a complete cease between each rep.
    The T-bar row is a superb bent-over barbell row for
    somebody that has been doing bent-over barbell rows for a while and has hit a plateau.

    Here are some nice alternate options that’ll work your legs, core,
    and again as nicely as getting your coronary heart rate
    up. In simple words, you’ll be able to describe lawnmower
    pulls as a one-handed bent-over row with an additional twist
    at the high of the movement. Get in a position where your
    legs are barely bent, your back straight
    at a few 45-degree angle or more to a vertical line, and your arms
    stretched. To do that exercise you begin standing up over the
    bar which is between your legs along with your again to the
    bottom anchor point. Decide the weight off the ground through
    the use of your legs while preserving your back straight.
    The name of this exercise comes from the shape this bar has because of the
    horizontal deal with at the end of the bar.
    You may need something like a heavy weighted
    vest to make the movement difficult enough.
    We have been training weighted calisthenics for years, and we have been in plenty
    of competitions around Europe. We are not right here
    to demonize any train, and bluntly changing them with a safer various isn’t all the
    time the best way to cope with the scenario. Changing
    the train would possibly help you dodge the ache, nevertheless it doesnt tackle the underlying issue.
    She holds a BSc in Exercise and Sport Sciences and a Grasp of Research in Well Being and Wellbeing
    from the University of Exeter. She is on a mission to help folks live a fulfilling,
    impactful life through fitness and way of life.

    If you’ve entry to a Lat Pulldown machine, Shut Grip Lat Pulldowns can work as a stable Single Arm Dumbbell Row various.
    If you don’t have an in depth grip attachment,
    use a decent underhand grip on the straight bar. You can sit or stand, have your chest supported and row ridiculously
    heavy weight. If you’ve access to one of these machines they’ll serve as a wonderful sub for
    Dumbbell One Arm Rows.
    The inverted row may be performed with a barbell and squat rack,
    smith machine, or even rings. You can carry out this train anytime throughout a again or
    upper body workout. As the name implies this train mainly focuses
    on your latissimus dorsi also known as your lats.
    However, that is going to put lots of rigidity on the neck and higher again muscular tissues.
    You might also use this motion as a again finisher for when the muscular tissues have been fatigued with other, tougher back workouts.

    By altering hand positions and adopting either
    a large grip or narrow grip this may even work the back muscle tissue a little in another way.
    So, if you want to address any power imbalances or increase muscle mass to sure elements of
    your back, altering your starting position can help you do this as it’s such
    a flexible exercise. Muscle and recovery is a internet site dedicated to
    serving to you train and reach your train targets ache
    free and as efficiently as attainable.
    Then, facing the head forwards, bracing the core,
    pulling the shoulders down and leaning the torso slightly back, the lifter pulls the bands to the perimeters of their torso.

    To perform a repetition of the Pendlay row, the lifter will first set a loaded barbell on the floor
    instantly over their mid-foot, as if establishing for a deadlift.
    On the other end of the spectrum to the Yates row, the Pendlay row features a
    far more horizontal torso orientation in order to maximise back muscle contraction and vary
    of motion. In comparison to bent over rows, Yates rows
    excel at loading capability, engagement of the biceps brachii
    and diffusing strain away from the lower back. The exercise engages your
    shoulder joint and also involves scapular retraction. Whereas you’re doing the motion, numerous neutralizing muscles hold your body in place.

    Even so, it is probably safer to get a cheap resistance band
    anchor to keep away from any problems. Resistance bands
    are versatile items of fitness equipment which may be principally elastic cords.
    One potential draw back is that you just need an elliptical machine to do that exercise.
    That means both investing in your individual elliptical machine or becoming
    a member of a health club. Both hammer Strength machines and free weights have
    their pros and cons. The trapezius, typically generally recognized as the
    traps, is a kite-shaped muscle that covers the highest half
    of your mid again.
    Apart From that, it is among the best corrective workouts that assist compensate for poor posture and shoulder dysfunction. The inverted row
    is an extremely versatile train that can vary in issue as
    you’re more upright or perpendicular to the ground. Additionally, You can use
    momentum on this train to get extra weight on the bar as properly.
    By letting the weight pull you forward barely
    you have to use your whole physique to pull the
    load in the course of your naval. Sadly, the trade
    off is extra targeting of the erectors and stabilizers than the t-bar row which is normally a deal breaker if you’re affected by low again pain.
    To carry out a repetition of Yates row, the lifter will pull a loaded barbell
    off the floor with the arms set shoulder-width aside using both an underhand or overhand grip.
    The T-bar row is most frequently employed as a bent over row different in instances the
    place a pronated grip, insufficient lat ROM or insufficient loading capacity are a problem.
    Nonetheless, when you do find that the usual barbell bent over row causes problems for you,
    any of the seven bent over row options will provide
    a great substitute. Posterior deltoids – whereas barbell
    bent-over rows are most definitely a back exercise, your
    shoulders are additionally concerned. Of the three deltoids, the posterior or rear head is most
    energetic throughout this train.

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