論文の公開元へ

書き出し

Refer/BibIX

RIS

BibTeX

TSV

Clinical Features of Female Carriers and Prodromal Male Patients With Spinal and Bulbar Muscular Atrophy

鳥居, 良太名古屋大学

2023.07.05

概要

主論文の要旨

Clinical Features of Female Carriers and
Prodromal Male Patients With Spinal and
Bulbar Muscular Atrophy
球脊髄性筋萎縮症の女性保因者と発症早期の
男性患者における臨床的特徴

名古屋大学大学院医学系研究科
脳神経病態制御学講座

総合医学専攻

神経内科学分野

（指導：勝野雅央
鳥居良太

教授）

【緒言】
球脊髄性筋萎縮症(Spinal and bulbar muscular atrophy; SBMA)は、成人男性のみに発
症すると考えられている遺伝性神経筋疾患で、緩徐進行性の筋力低下・筋萎縮、嚥下
障害を主徴とする。通常 30 歳から 60 歳の間に四肢の筋力低下などで発症し緩徐に進
行するが、その 10 年以上前から、手指振戦や有痛性筋痙攣などの前駆的症状を認める
ことも知られている。神経学的診察では、筋力低下に加えて、四肢腱反射の低下、下
肢遠位部を中心とした振動覚低下、筋肉を収縮させたときに線維束性収縮が増強する
contraction fasciculation も特徴的である。血液検査では、血清クレアチンキナーゼ高値、
血清クレアチニン低値、軽度の脂肪肝を示唆するトランスアミナーゼの上昇、脂質異
常症、耐糖能異常なども伴う。血清クレアチニンの低下や血清クレアチンキナーゼ高
値も、筋力低下の出現に先行して認められることが多い。1991 年、米国国立衛生研究
所のグループは、SBMA の原因が X 染色体上のアンドロゲン受容体(Androgen receptor:
AR)遺伝子第 1 エクソン内の CAG 繰り返し配列の異常延長にあることを同定した。
名古屋大学神経内科では、CAG リピート数を 97 に延長させたヒト全長 AR を発現す
る SBMA トランスジェニックマウスを作成し、このマウスの解析を進めることで、
SBMA の病態に男性ホルモンであるテストステロンが深く関与することを解明した。
このことは、テストステロンの抑制が、SBMA の治療につながる可能性を示唆するも
のであり、それらの基礎的検討結果に基づいて、名古屋大学を中心に医師主導治験等
が実施され、テストステロンの分泌を抑制するリュープロレリン酢酸塩が、2017 年 8
月に、「球脊髄性筋萎縮症の進行抑制」を効能に薬事承認を受けている。
SBMA は、臨床的には X 連鎖潜性の遺伝形式をとると考えられているが、責任遺伝
子をホモ接合体として保有する女性にも明確な症状が見られないことから、厳密には
X 連鎖潜性遺伝病ということはできない。これまで検討では、責任遺伝子をヘテロ接
合体として保有する SBMA 女性保因者(保因者)にも、軽度な筋力低下があることが指
摘されており、保因者の症状や病態を詳細に検討することが、SBMA の早期病態の解
明につながることが示唆されている。また、SBMA は、運動ニューロン病に分類され
ることが多いが、その筋病理を確認すると、神経原性変化に加えて筋原性変化も関与
していると考えられている。これらの状況を踏まえ、我々は、主に SBMA の早期病態
を探ることを目的に、保因者・SBMA 男性早期患者(早期患者)を男女の健常者と比較
検討する研究を立案した。
【対象及び方法】
研究対象者は、保因者、早期患者、および男女健常者とした。保因者は、遺伝子学
的に SBMA と確定診断された男性患者の母親または娘とし、出産希望がある場合は対
象から除外した。また、早期患者は、改訂筋萎縮性側索硬化症運動機能スケール(the
revised ALS functional rating scale; ALSFRS-R)スコアが 48 点満点であることを条件と
した。運動機能評価には、 SBMA 運動機能スケール (SBMA functional rating scale;
SBMAFRS)、ALSFRS-R、握力、舌圧、徒手筋力テスト(Manual Muscle Testing; MMT)、

-1-

改訂重症筋無力症定量(the modified quantitative Myasthenia Gravis; mQMG)スコア、15
フィート歩行テスト、rise from bed テストを用いた。電気生理学的検査として運動単
位数の推定のための MUNE(Motor Unit Number Estimation)、針筋電図検査を実施した、
その他、血液検査、二重エネルギーX 線吸収測定法(dual energy X‐ray absorptiometry：
DEXA)による全身筋量検査を行った。
【結果】
研究対象者は、保因者 21 例、早期男性患者 11 例、健常女性 17 例、健常男性 14 例
であった。保因者には、SBMA の前駆症状として知られている有痛性けいれんを経験
している割合が有意に高く(保因者: 71%、健常女性: 12%、p < 0.001)、また振戦の割合
も高い傾向があった(保因者:19%、健常女性: 0%、p = 0.057)(Table 1）。また、各筋の
筋力を詳細に調べたところ、特に頸部屈筋を中心に低下していた(Table 1)。電気生理
学的検査では、保因者において有意に MUNE は低下しており、下位運動ニューロンの
数が減っていることが示唆された(保因者：210.5±69、健常女性：270.8±70、p < 0.016)
(Figure 1)。針筋電図検査では、高振幅波、多相波といった慢性脱神経所見を示唆する
所見があり(Table 2)、保因者にも神経原性変化を認めることが分かった。また、保因
者では、明確な血清クレアチンキナーゼ上昇はなく、筋量の低下も認められなかった
のに対し、早期男性患者では、血清クレアチンキナーゼ値の上昇、血清クレアチニン
値の低下、筋量測定における筋量低下を認め、SBMA の早期病態には、神経原性変化
に加えて、筋原性変化も併せて存在する可能性が示唆された(Figure 2)。
【考察】
本研究では、臨床的に無症状と考えられていたSBMAの女性保因者にも、頸部屈筋
力の低下や有痛性けいれんといった軽微な臨床症状があること、電気生理学的検査で
は、慢性脱神経所見を認めるとともに、運動ニューロン数が減少していることが判明
し、保因者にも神経原性変化を認めることが示唆された。一方、早期男性患者は、血
清クレアチンキナーゼ高値、筋肉量低下など、筋原性変化の特徴を持ち合わせること
が分かり、SBMA患者は筋原性変化と神経原性変化を併せ持つことが推察された。保
因者と早期患者の相違点の1つに、血清テストステロンレベルがあることから、この違
いが保因者と早期患者の病態の差になっている可能性がある。具体的には、神経原性
変化と筋原性変化を引き起こすテストステロン値に、閾値の差があり、特定のレベル
を超えると神経原性変化に加えて筋原性変化を引き起こすことが想定できる。その場
合、保因者の病態は、男性患者において男性ホルモン値が高くなる前、すなわち、思
春期前の病態に類似していることになる。
【結語】
従来無症状と考えられてきたSBMA女性保因者にも軽度な臨床症状があり、この症
状は神経原性変化に基づくものであると考えらる。これは男性患者において血清テス

-2-

トステロン値が高くなる前、つまり、思春期前の病態に類似している可能性がある。
SBMA患者に加え、保因者の病態をより詳細に検討することで、SBMAの病態の全体像
を明らかにすることが期待できる。

-3-

Table 1 Comparison of the early-stage signs and the motor functions between female carriers and
healthy controls
Female carriers

Healthy females

n = 21

n = 17

Hand tremors (number)

4

0

0.057a

Muscle cramps (number)

15

2

<0.001a

Neck flexion

4.6 ± 0.5

5.0 ± 0.0

0.002b

Upper limbs

29.0 ± 1.5

29.8 ± 0.8

0.072b

Lower limbs

29.0 ± 1.3

29.8 ± 0.8

0.090b

Head lifted

0.67 ± 0.66

0.24 ± 0.44

0.021b

Arm outstretched

0.24 ± 0.63

0.0 ± 0.0

0.096b

Leg outstretched

0.38 ± 0.81

0.12 ± 0.49

0.222b

p-value

Early-stage signs

Motor functions
MMT

mQMG score

Data are shown as the mean ± standard deviation
aChi-square test, bStudent t-test
MMT, manual muscle testing; mQMG score, the modified quantitative myasthenia gravis score

Table 2 Electromyography findings in female carriers
Tongue
Subject number

Denervation
potentials#

Biceps

High amplitude
motor unit

Polyphasic

potentials

Denervation

Quadriceps

High amplitude

potentials#

motor unit

Polyphasic

potentials

Denervation
potentials#

High amplitude
motor unit

Polyphasic

potentials

1

-

+

-

-

-

-

-

+

-

2

-

-

+

-

-

-

-

-

-

3

-

+

+

-

-

-

-

-

-

4

-

-

+

-

-

-

-

-

-

5

-

+

+

-

-

-

-

+

-

6

-

-

+

-

-

-

-

-

-

7

-

-

+

-

-

-

-

+

+

8

-

-

+

-

-

-

-

+

+

9

-

-

+

-

-

-

-

+

-

10

-

-

-

-

-

-

-

+

-

11

-

-

-

-

-

-

-

+

-

12

-

-

-

-

-

-

-

-

+

#Denervation

potentials: any of fibrillation, positive sharp waves, or fasciculation was observed

-4-

Figure 1 Decreased MUNE in female carriers
MUNE was performed on the ulnar nerve of the dominant (A) and non-dominant hand (B) of female carriers (n = 17)
and healthy female controls (n = 17). MUNE values calculated by either amplitude or area were significantly decreased
in female carriers. The maximum CMAP of female carriers was equivalent to controls, but their average SMUP was
larger than controls.
Circles in each figure indicate outliers of box-and-whisker plot. *p < 0.05; CMAP, compound muscle action potential;
MUNE, motor unit number estimation; SMUP, single motor unit potential

Figure 2 Differences in serum markers and muscle mass among the groups
(A) CK levels were slightly, but significantly, higher in female carriers (123 ± 72 IU/L) than in healthy female controls
(83 ± 40 IU/L), but the average values in the carriers were within the normal range. Male early stage SBMA subjects
had significantly higher serum CK levels than healthy male controls. (B, C) Muscle mass markers such as creatinine
and ALST mass were not significantly different between female carriers and their controls, but male early stage subjects
had substantial alterations. (D) Testosterone levels were physiologically lower in females than in males, with no
significant difference in female carriers. SBMA subjects had significantly higher serum testosterone levels than healthy
male controls.
Circles in each figure indicate outliers of box-and-whisker plot. *p < 0.05; **p < 0.005; ALST, appendicular lean soft
tissue; CK, creatine kinase; HC(F), healthy female controls; HC(M), healthy male controls; SBMA, spinal and bulbar
muscular atrophy

-5-

論文の公開元へ

この論文で使われている画像

参考文献

Kennedy WR, Alter M, Sung JH. Progressive proximal spinal and bulbar muscular

atrophy of late onset: a sex-linked recessive trait. Neurology. 1968; 18:671–680.

Hashizume A, Fischbeck KH, Pennuto M, Fratta P, Katsuno M. Disease

mechanism, biomarker and therapeutics for spinal and bulbar muscular atrophy

(SBMA). J Neurol Neurosurg Psychiatry. 2020; 91:1085–1091.

La Spada AR, Wilson EM, Lubahn DB, Harding AE, Fischbecket KH. Androgen

receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature.

1991; 352:77–79.

Hijikata Y, Hashizume A, Yamada S, et al. Biomarker- Based analysis of preclinical

progression in spinal and bulbar muscular atrophy. Neurology. 2018; 90:1501–

1509.

Atsuta N, Watanabe H, Ito M, et al. Natural history of spinal and bulbar muscular

atrophy (SBMA): a study of 223 Japanese patients. Brain. 2006; 129:1446–1455.

Liberman A, Shakkottai V, Albin R. Polyglutamine Repeats in Neurodegenerative

Disease. Annu Rev Pathol. 2019; 24:1–27.

Suzuki K, Katsuno M, Banno H, et al. CAG repeat size correlates to

electrophysiological motor and sensory phenotypes in SBMA. Brain. 2008;

131:229–239.

Suzuki K, Katsuno M, Banno H, et al. The profile of motor unit number estimation

(MUNE) in spinal and bulbar muscular atrophy. J Neurol Neurosurg Psychiatry.

2010; 81:567–571.

Yamada S, Hashizume A, Hijikata Y, et al. Decreased peak expiratory flow

associated with muscle fiber- type switching in spinal and bulbar muscular atrophy.

PLoS One. 2016;11: e0168846.

10. Sorarù G, C. D'Ascenzo, A. Polo, et al. Spinal and bulbar muscular atrophy:

Skeletal muscle pathology in male patients and heterozygous females. J Neurol Sci.

2008; 264:100–105.

11. Manzano R, Soraru G, Grunseich C, et al. Beyond motor neurons: expanding the

clinical spectrum in Kennedy’s disease. J Neurol Neurosurg Psychiatry. 2018;

89:808–812.

12. Sahashi K, Katsuno M, Hung G, et al. Silencing neuronal mutant androgen receptor

in a mouse model of spinal and bulbar muscular atrophy. Hum Mol Genet. 2015;

24:5985–5994.

13. Lieberman AP, Yu Z, Murray S, et al. Peripheral androgen receptor gene

suppression rescues disease in mouse models of spinal and bulbar muscular

atrophy. Cell Rep. 2014; 7:774–784.

14. Katsuno M, Adachi H, Kume A, et al. Testosterone reduction prevents phenotypic

expression in a transgenic mouse model of spinal and bulbar muscular atrophy.

Neuron. 2002; 35:843–854.

15. Grunseich C, Fischbeck KH. Molecular pathogenesis of spinal and bulbar muscular

atrophy (Kennedy’s disease) and avenues for treatment. Curr Opin Neurol. 2020;

33:629–634.

16. Schmidt BJ, Greenberg CR, Allingham-Hawkins DJ, Spriggs EL. Expression of Xlinked bulbospinal muscular atrophy (Kennedy disease) in two homozygous

women. Neurology. 2002; 59:770–772.

17. Mariotti C, Castellotti B, Pareyson D, et al. Phenotypic manifestations associated

with CAG-repeat expansion in the androgen receptor gene in male patients and

heterozygous females: a clinical and molecular study of 30 families. Neuromuscul

Disord. 2000; 10:391–397.

18. Hattori M, Tsuboi T, Yokoi K, et al. Subjects at risk of Parkinson’s disease in health

checkup examinees: cross-sectional analysis of baseline data of the Nat-PROBE

study. J Neurol. 2020; 267:1516–1526.

19. Hashizume A, Katsuno M, Suzuki K, et al. A functional scale for spinal and bulbar

muscular atrophy: cross-sectional and longitudinal study. Neuromuscul Disord.

2015; 25:554–562.

20. Yamada S, Hashizume A, Hijikata Y, et al. Ration of urinary N-terminal titin

fragment to urinary creatinine is a novel biomarker for amyotrophic lateral

sclerosis. J Neurol Neurosurg Psychiatry. 2021; 92:1072–1079.

21. Mano T, Katsuno M, Banno H, et al. Tongue pressure as a novel biomarker of

spinal and bulbar muscular atrophy. Neurology. 2014; 82:255–262.

22. Besinger UA, Toyka KV, Homberg M, Heininger K, Hohlfeld R, Fateh-Moghadam

A. Myasthenia gravis: long-term correlation of binding and bungarotoxin blocking

antibodies against acetylcholine receptors with changes in disease severity.

Neurology. 1983; 33:1316–1321.

23. Brinkmann JR, Andres P, Mendoza M, et al. Guidelines for the use and

performance of quantitative outcome measures in ALS clinical trials. J Neurol Sci.

1997; 147:97–111.

24. Hijikata Y, Katsuno M, Suzuki K, et al. Treatment with creatine monohydrate in

spinal and bulbar muscular atrophy: protocol for a randomized, double-blind,

placebo-controlled trial. JMIR Res Protoc. 2018;7: e69.

25. Shefner JM, Cudkowicz ME, Zhang H, Schoenfeld D, Jillapalli D, Northeast ALS

Consortium. The use of statistical MUNE in a multicenter clinical trial. Muscle

Nerve. 2004; 30:463–469.

26. Lehky TJ, Chen CJ, Di Prospero NA, Rhodes LE, Fischbeck H, Floeter MK.

Standard and modified statistical MUNE evaluations in spinal-bulbar muscular

atrophy. Muscle Nerve. 2009; 40:809–814.

27. Hijikata Y, Katsuno M, Suzuki K, et al. Impaired muscle uptake of creatine in

spinal and bulbar muscular atrophy. Ann Clin Transl Neurol. 2016; 3:537–546.

28. Ito D, Hashizume A, Hijikata Y, et al. Elevated serum creatine kinase in the early

stage of sporadic amyotrophic lateral sclerosis. J Neurol. 2019; 266:2952–2961.

29. Baumgartner R, Koehler K, Gallagher D, et al. Epidemiology of sarcopenia among

the elderly in New Mexico. Am J Epidemiol. 1998;147:755–763.

30. Hashizume A, Katsuno M, Banno H, et al. Longitudinal changes of outcome

measures in spinal and bulbar muscular atrophy. Brain. 2012; 135:2838–2848.

31. Lombardi V, Querin G, Ziff OJ, et al. Muscle and not neuronal biomarkers correlate

with severity in spinal and bulbar muscular atrophy. Neurology. 2019;92:e1205–

1211.

32. Bridel C, van Wieringen WN, Zetterberg H, et al. Diagnostic Value of

Cerebrospinal Fluid Neurofilament Light Protein in Neurology: A Systematic

Review and Meta-analysis. JAMA Neurol. 2019; 76:1035–1048.

33. Fukami Y, Iijima M, Koike H, et al. Association of neurofilament light chain levels

with clinicopathology of chronic inflammatory demyelinating polyneuropathy,

including NF155 reactive patients. J Neurol. 2021; 268:3835–3844.

34. Kuhle J, Barro C, Andreasson U, et al. Comparison of three analytical platforms for

quantification of the neurofilament light chain in blood samples: ELISA,

electrochemiluminescence immunoassay and Simoa. Clin Chem Lab Med. 2016;

54:1655–1661.

35. Tanaka F, Sobue G, Doyu M, et al. Differential pattern in tissue-specific somatic

mosaicism of expanded CAG trinucleotide repeats in dentatorubral-pallidoluysian

atrophy, Machado-Joseph disease, and X-linked recessive spinal and bulbar

muscular atrophy. J Neurol Sci. 1996; 135:43–50.

36. Dejager S, Bry-Gauillard H, Bruckert E, et al. A comprehensive endocrine

description of Kennedy’s disease revealing androgen insensitivity linked to CAG

repeat length. J Clin Endocrinol Metab. 2002; 87:3893–3901.

37. Ishihara H, Kanda F, Nishio H, et al. Clinical features and skewed X-chromosome

inactivation in female carriers of X-linked recessive spinal and bulbar muscular

atrophy. J Neurol. 2001; 248:856–860.

38. Kadi F, Bonnerud P, Thornell AEL. The expression of androgen receptors in human

neck and limb muscles: effects of training and self-administration of androgenicanabolic steroids. Histochem Cell Biol. 2000; 113:25–29.

39. Sobue G, Doyu M, Kachi T, et al. Subclinical phenotypic expressions in

heterozygous females of X-linked recessive bulbospinal neuronopathy. J Neurol

Sci. 1993; 117:74–78.

40. Xu Y, Halievski K, Katsuno M, et al. Pre-clinical symptoms of SBMA may not be

androgen-dependent: implications from two SBMA mouse models. Hum Mol

Genet. 2018; 27:2425–2442.

41. Darras BT, Crawford TO, Finkel RS, et al., Neurofilament as a potential biomarker

for spinal muscular atrophy. Ann Clin Transl Neurol. 2019; 6:932–944.

Figure Legends

Figure 1. Correlation of expanded CAG repeat number with motor function in

female carriers

(A–F) In female carriers, CAG repeat size in the androgen receptor gene was correlated

with the SBMAFRS score (B), total score of the upper (D) and lower limbs (E) in the

MMT, and the timed walk test (F), but not with the ALSFRS-R (A) or mQMG score

(C). Pearson correlation coefficient (r) and the p-value are shown in each panel.

ALSFRS-R, revised Amyotrophic Lateral Sclerosis Functional Rating Scale; MMT,

Manual Muscle Test; mQMG, modified Quantitative Myasthenia Gravis; SBMAFRS,

Spinal and Bulbar Muscular Atrophy Functional Rating Scale

Figure 2. Differences in serum markers and muscle mass among the groups

(A) CK levels were slightly, but significantly, higher in female carriers (123 ± 72 IU/L)

than in healthy female controls (83 ± 40 IU/L), but the average values in the carriers

were within the normal range. Male early stage SBMA subjects had significantly higher

serum CK levels than healthy male controls. (B, C, D) Muscle mass markers such as

creatinine, ALST mass, and SMI were not significantly different between female

carriers and their controls, but male early stage subjects had substantial alterations. (E)

Testosterone levels were physiologically lower in females than in males, with no

significant difference in female carriers. SBMA subjects had significantly higher serum

testosterone levels than healthy male controls. (F) Serum NfL levels were not

significantly different between female carriers and their controls, but SBMA subjects

had slightly, but significantly, higher serum NfL levels than healthy male controls.

Circles in each figure indicate outliers of box-and-whisker plot. *p < 0.05; **p < 0.005;

ALST, appendicular lean soft tissue; CK, creatine kinase; HC(F), healthy female

controls; HC(M), healthy male controls; NfL, neurofilament light chain; SBMA, spinal

and bulbar muscular atrophy; SMI, skeletal muscle mass index

Figure 3. Decreased MUNE in female carriers

MUNE was performed on the ulnar nerve of the dominant (A) and non-dominant hand

(B) of female carriers (n = 17) and healthy female controls (n = 17). MUNE values

calculated by either amplitude or area were significantly decreased in female carriers.

The maximum CMAP of female carriers was equivalent to controls, but their average

SMUP was larger than controls.

Circles in each figure indicate outliers of box-and-whisker plot. *p < 0.05; CMAP,

compound muscle action potential; MUNE, motor unit number estimation; SMUP,

single motor unit potentia

Table 1. Baseline characteristics of female carriers, male subjects with SBMA, and healthy controls

Female carriers

Healthy females

n = 21

54.5 ± 14.7

n = 17

52.4 ± 13.7

0.651

Male subjects with

SBMA

n = 11

42.4 ± 13.3

156.8 ± 6.3

p-value

Healthy males

p-value

n = 14

49.1 ± 7.4

0.122

3.5 ± 4.8

49.5 ± 2.9

153.5 ± 5.2

0.094

170.8 ± 8.4

173.6 ± 4.5

0.340

56.8 ± 11.0

53.5 ± 6.4

0.243

65.7 ± 10.0

72.6 ± 8.1

0.069

23.0 ± 3.5

22.7 ± 3.0

0.693

22.5 ± 2.6

24.1 ± 2.6

0.133

Hand tremors (number)

0.057a

<0.001a

Muscle cramps (number)

<0.001a

0.726a

not examined

Age at examination (years)

Disease duration (years)

23.8 ± 3.9/

CAG repeat size in AR

48.3 ± 3.3

Height (cm)

Body weight (kg)

Body mass index (kg/m )

Decreased vibration sense

(number)

Data are shown as the mean ± standard deviation

Chi-square test

AR, androgen receptor; NA, not applicable; SBMA, spinal and bulbar muscular atrophy

Table 2. Clinical features of motor function in female carriers, male subjects with SBMA, and healthy controls

ALSFRS-R score

Female carriers

n = 21

47.2 ± 1.5

Healthy females

n = 17

47.9 ± 0.2

0.044

Male subjects

n = 11

48.0 ± 0.0

Healthy males

n = 14

48.0 ± 0.0

SBMAFRS score

54.9 ± 1.9

55.8 ± 0.5

0.047

54.6 ± 1.3

56.0 ± 0.0

0.006

Grip power, dominant side (kg)

23.7 ± 4.4

25.7 ± 5.4

0.206

31.6 ± 8.6

48.4 ± 5.5

<0.001

Grip power, non-dominant side (kg)

21.4 ± 4.5

23.3 ± 4.5

0.217

29.8 ± 9.0

46.1 ± 7.1

<0.001

Tongue pressure (kPa)

34.2 ± 7.0

36.9 ± 6.8

0.327

23.6 ± 10.0

43.3 ± 8.5

<0.001

p-value

MMT

Neck flexion

4.6 ± 0.5

5.0 ± 0.0

0.002

4.4 ± 0.7

29.0 ± 1.5

29.8 ± 0.8

0.072

29.0 ± 1.3

29.8 ± 0.8

0.090

29.6 ± 0.8

1.3 ± 1.8

0.35 ± 0.79

0.046

1.4 ± 1.3

0.0 ± 0.0

0.006

0.67 ± 0.66

0.24 ± 0.44

0.021

0.7 ± 0.6

0.0 ± 0.0

0.004

0.24 ± 0.63

0.0 ± 0.0

0.096

0.4 ± 0.7

0.0 ± 0.0

0.104

0.38 ± 0.81

0.12 ± 0.49

0.222

0.3 ± 0.47

0.0 ± 0.0

0.082

Timed walk test (s)

3.21 ± 0.68

2.74 ± 0.39

0.037

2.56 ± 0.41

2.21 ± 0.49

0.071

Rise from bed test (s)

2.47 ± 1.37

2.00 ± 0.63

0.165

1.56 ± 0.42

1.56 ± 0.35

0.970

Upper limbs

Lower limbs

mQMG score

Total

Head lifted

Arm outstretchedc

Leg outstretched

Data are shown as the mean ± standard deviation

Upper limbs: shoulder flexion, elbow flexion, and wrist extension, normal score = 30

Lower limbs: hip joint flexion, knee flexion, and ankle extension, normal score = 30

Arm outstretched: total score of both arms, normal score = 0

Leg outstretched: total score of both legs, normal score = 0

ALSFRS-R, revised Amyotrophic Lateral Sclerosis Functional Rating Scale; MMT, Manual Muscle Test; mQMG score, modified Quantitative

Myasthenia Gravis score; NA, not applicable; SBMA, spinal and bulbar muscular atrophy; SBMAFRS, Spinal and Bulbar Muscular Atrophy

Functional

Scale

Rating

Table 3. Electromyography findings in female carriers

Biceps

Tongue

Denervation

potentials#

High

amplitude

motor unit

potentials

Polyphasic

Denervation

potentials#

High

amplitude

motor unit

potentials

Quadriceps

Polyphasic

Denervation

potentials#

High

amplitude

motor unit

potentials

Polyphasic

Subject

number

Denervation potentials: any of fibrillation, positive sharp waves, or fasciculation was observed

Clinical Features of Female Carriers and Prodromal Male Patients With Spinal and

Bulbar Muscular Atrophy

Ryota Torii, Atsushi Hashizume, Shinichiro Yamada, et al.

Neurology published online September 30, 2022

DOI 10.1212/WNL.0000000000201342

This information is current as of September 30, 2022

Updated Information &

Services

including high resolution figures, can be found at:

http://n.neurology.org/content/early/2022/09/30/WNL.0000000000201

342.full

Subspecialty Collections

This article, along with others on similar topics, appears in the

following collection(s):

Autonomic diseases

http://n.neurology.org/cgi/collection/autonomic_diseases

Permissions & Licensing

Information about reproducing this article in parts (figures,tables) or in

its entirety can be found online at:

http://www.neurology.org/about/about_the_journal#permissions

Reprints

Information about ordering reprints can be found online:

http://n.neurology.org/subscribers/advertise

Neurology ® is the official journal of the American Academy of Neurology. Published continuously since

rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.

...

参考文献をもっと見る

分野

大学

学位論文種類・取得年

言語

Clinical Features of Female Carriers and Prodromal Male Patients With Spinal and Bulbar Muscular Atrophy

概要

この論文で使われている画像

関連論文

重症TAFRO症候群2症例に対する運動療法の負荷量の検討(症例報告）

心大血管外科術後患者における亜鉛欠乏と身体機能の関係(症例報告)

Ultrasonographic evaluation reveals thinning of cervical nerve roots and peripheral nerves in spinal and bulbar muscular atrophy

蜂窩織炎を繰り返す下肢リンパ浮腫へ集中排液治療が効果的だった症例(症例報告)

Predictive factors for massive hemorrhage in women with retained products of conception : a prospective study

参考文献

分野

大学

学位論文種類・取得年

言語

コピーが完了しました

URLをコピーしました

Clinical Features of Female Carriers and Prodromal Male Patients With Spinal and Bulbar Muscular Atrophy

概要

この論文で使われている画像

関連論文

重症TAFRO症候群2症例に対する運動療法の負荷量の検討(症例報告）

心大血管外科術後患者における亜鉛欠乏と身体機能の関係(症例報告)

Ultrasonographic evaluation reveals thinning of cervical nerve roots and peripheral nerves in spinal and bulbar muscular atrophy

蜂窩織炎を繰り返す下肢リンパ浮腫へ集中排液治療が効果的だった症例(症例報告)

Predictive factors for massive hemorrhage in women with retained products of conception : a prospective study

参考文献