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Respiratory failure in nemaline myopathy
ELSEVIER
notable respiratory failure at birth and die in early infancy. Although the moderate congenital form has been described as a benign and nonprogressive to slowly progressive disease [2,3], some patients evidence apparent progression leading to respiratory failure and death [4-81. We report 4 patients who had marked respiratory failure and the results of polysomnographic studies of 1 patient with the severe neonatal form and 1 of 3 patients with the moderate congenital form.
Susaki M, Takeda M, Kobayashi K. Nonaka I. Respiratory failure in nemaline myopathy. Pediatr Neural I994; 16: 344346.
Nemaline myopathy was first described by Shy et al. [ 11 as one of the nonprogressive congenital myopathics. The disease has been classified into three subtypes based on the clinical presentation, i.e., the severe neonatal, moderate congenital (classic) and adult onset forms 121. Although the prognosis differs from form to form, respiratoiy infection or failure is the most common cause o1 atieilts with the scvcrc neonatal form usually have
Fw~ the DiviGon\ of ‘“Child Neurology and ‘Laboratory Mcdicinc; National Center Hospital for Ment,d, Nervous and Muscular Disorders; National Center of Neurology and Psychiatry; Kodaira. Tokyo, Japan.
344
PEDIATRIC
NEUROLOGY
Vol.
I6 No. 4
Pdrnt 1. The muscle pathologic findings in early childhood of this l6-ye‘ar-old girl have been described previously 191. She had severe hypotonia and respiratory difficulty at birth and wrls placed on a respirator for 2 days. From the clinical and muscle biopsy findings. she was d agnosed as having the severe neonatal form of nemaline myopathy. She has survived despite many episodes-at least IO-of severe respiratory infection requiring mechanical ventilation. Her face was long and narrow with no emotional expression, due to marked facial muscle involvement. She had a high-arched palate. Her skeletal muscles were markedly wasted. She could move her neck, shoulders, irdex fingers, or ankles at minimal magnitude. Muscle stretching reflexes were absent. She has needed nasal intermittent positive pressure ventilation (NIPPV) during sleep for the past 3 years. She has shown paradoxical movement of the abdomen with inspiration. She can drive her electric wheel chair by her neck muscles. Her vital capzlcity was only 100 ml. Arterial blood gas analy& revealed high pC0, (60 to 80 mm Hg) and low ~0~ (SO to 70 mm Hg) during the day. Ptr!iarr/ 2. A IS-year-old boy was horn to healthy parents after an uncvcntful pregnancy. Hc showed slightly delnycd motor development. I lc \l;\rtc*tl IO walh ilI IO ~u~nth\ of a!:~, At 3 )%!ill3 Ol’ ilgc. I'rom the IllllkCI~ pillllOl~~giC findings. IIC Wilb diagnohcd ilb having rlclllillinc my(~pathy. AI H ycarh of age. hc sutidcn:y dc~cl~~l~cd acute respiratory msufl’icicncy w it h hypcrcapnia 01’ pC0, grcntcr than IO0 mm Hg and was placed on a ventilator. Thereafter, he required mechanical ventilation during sleep [4j. He had manifested an abdominal squeeze at the end of expiration. From I4 years of age, he was placed on a respirator for the entire day but was still able to walk. In the next year, he lost the ability to walk. However. he could sit and use his upper extremities for eating and writing. He died of severe respiratory rnfection at I.5 years of age. Postmortem examination was performed except for the CNS. Purirru 3. A l4-year-old girl was born uneventfully at term. Her parcnth wcrc healthy and nonconsanguineous. Her younger brother also manifested nernaline myopathy and died of respiratory infection. She showed slight delay in motor development and ~11,s slight!:: 5yvotonic from birth. She began to walk at 20 months of age. At 2 years of age. she suddenly developed hypercapnic acute respiratory insufficiency (pC0, greater than 100 mm Hg) and rccluired a req~irator. She underwent a muscle biopsy. which rcvealcd ~IIC morphologic characteris,t,c:~ of nemaline myopathy 151. Thereafter. she rcquircd mechanical ventilation all day. although she could sit alone and could n~rrvc her cxtrcmitics against
Communications should be addressed to: Dr. Sasaki; Division of Child Neurology; National Center Hospital for Mental, Nervous and Muscular Disorder<: NCNP.4-I-I Ogawahigashicho. Koduira. Tokyo 187, Japan. Received September I I, 1996; accepted January 7, 1997.
0 1997 by Elsevier Science PI1 SO887-8994(97)00032-5
Inc. All rights reserved. @0887-8994/97/$17.00
The biopsy findings for the respiratory muscles from Patient 2 were reported previously respiratory muscles obtained at p were basically the same as those including marked variation in fib fibrosis, core/targetoid structure The overall findings progressed i
FP F C P 0 cz EOG Ment Thora ECG -.----
-.-.
-.
-
-___________-.~__-_-_--_____----4-----.----..A-
e---------G=;
-
---
.I
_-_
.7
\rlllflfl
.-
/I
-
---,
/I/./
-
-_;;;J,=..
gravity.
She could
eat and write
deteriorated. Patient 4. A female nasogastric unassisted
infant
by herself.
Her
was markedly
motor
ability
hypotonic
has not
and requilcd
;t
tube at birth. She could swallow food at 6 months, sit at I2 months, and wall\ alone at I8 months of age. At 5 years
of age, from
the muscle
biopsy
findings,
she was diagnosed
as having
nemaline myopathy. Her face was long and narrow. She had a higharched palate. At 9 years of age. she began having a headache in the early morning. Now, at I3 years of age, she can walk skills have not deteriorated recently. Arterial blood elevated
pC0,
of SO to 70 mm
A polysolnnographic EEG.
Patients 2 and 3 suddenly developed hypercapnia with loss of consciousness, while they were still ambulant with mild muscle weakness in the extremities. Patient 4 also had hypercapnia, although she could walk alone. several studies of acute respiratory insufficiency in patients with the moderate congenital form [4,5,7,8], a discrepancy between gross motor ability and respiratory function has been reported to be common in nemaline myopathy. Therefore, we should always be aware of respiratory failure, even in ambulant patients with minimal limb muscle weakness. Accordingly, the onset of re tory failure in nemaline myopathy diffe progressive muscle dystrophies, including
an clcctromyogram
study
alone and her motor gas analysis revealed
Hg in the morning.
was performed
t I’M<;)
on Patients
at mcntalis
mu~lc.
I and 3. An
;III clcctrooculo-
myopathy, we performed polysomnogr of the 4 patients. Apnea or irregular th occurred only during pOz and pC0, monitor stud nia occurred only during Therefore, the wors believed to result fr incffcctivc hrcathing. Conhcyuc
(KKJ wcrc f.Jrilfll (IXX;). thoracic Ill0W!1lIClltb. ,~Illd ill1 cl~clrocitrclic,grurll rccordcd. 7'lWl~CUt~lil~OU~ pc'0, and pO, wcrc continuou4y rccordc*d
with
iI triln~cutancou~
pO,/l~(‘()~
monitor
Apnea was defined as no thoracic seconds. Samples of the diaphragm and
J;~pan).
obtained
from
Patient
2 at pk)stmortcm
t I
Mcd~c;~l,
‘l’ohy().
movcmcnth for more than IO biceps bra&ii nw~lcs wcrc
examination.
Sleep
stage
9:oo
6:00
8.00 ----
REM
-- _-." I
Apnea or irregular thoracic movements occurred only during rapid eye movement (REM) sleep in both 1 and 4. Thoracic movements became irregular for 20 to 60 seconds when rapid eye movements occurred repeatedly. Just after these irregular thoracic movements, the heart and respiratory rates increased (Fig 1). In other sleep stages, no apnea or irregular thoracic movements were tient 1, contraction of the sternocleidomas-
II III
----l--f
‘- -.--I _____ _^"_-- .-----
IV PCOZkw~ -.
Pf.h,!~,~ -
__
90 -. 8o ______ . 70 @.
_
-- .-. .--
50 ---- --
-. ----
_, ;--
. ..
-
--
.;
1.-.s.m Ly&.-
,__.
&a-
-
_ ,' - .__
-
100 P./---pi
during the apnea (data not Serial transcutaneous pOz and pC0, moni onstrated that hypercapnia transiently occurr EM sleep in both patients (Fig 2). P stages, the pOz and pCOz eveIs were ahnost stable.
80 b0 40
Sasaki
CI al: Nemaline
Gotnori ~ricitrom~ yfaitr; I*‘iqlrr-c 3. Muncie pcrtltoiogp of rile diaphragtn and biceps brachii ~t~lrscks at postmortem cratnination in Patiettt 2 (modified rv~jyt~oi tttrr,sttiFc.tttiott ~320). Mat-ked variation in jiber si:e. dense interstitial fibrosis, core/targrtotd vtmctures. aud nrtnaline bodies bt’ere ohet?led in tilt* dictptrragtn (a); tttiid ~uriatiotr itt fiber size rrnd tluttterous tretnaiine bodies were observed in the biceps brachii tntrscie (1~).
[ 101 reported that the respiratory center dces not react to hypercapnia. The abnormal thoracic movements are probably caused by respiratory muscle weakness, which is aggravated only during REM sleep because the supportive respiratory muscles, including the sternocleidomastoid and trapezius muscles, may not work effectively. In other sleep stages, the pOz and pC0, levels were almost stable. The histologic findings revealed that respiratory muscles were more markedly involved than other skeletal muscles [41. Acid phosphatase activity was much greater in the diuphragm than in other &&al muscles, indicating that an active autophagic process ensued after the myofibGII;ir dcgcneration 1I I 1. This prcfcrentinl diaphragm involvement well explains the discrepancy between motor ilkility and respiratory involvement it1 patients with Ild’lllilline Illy~~~Xllhy, l!SlN!Ciillly in thrlsc With tlPC I~~OClL’rilk! congenital form.
review
of clinical
presentation
Neurol
1987;29:8
15-20.
[3]
in relation
WA&L-en-Pettersson
ical forlow-up
study
C. Congenital
of tweive
[4] Sasaki M, Yoneyama ment in ncmaline myopathy.
[S] infantile
[7)
nemaline
J Neural
Med
myopathy.
Sci
1989;89:
H, Nonaka 1. Respiratory muscle Pediatr Neurol 199C;6:425-7.
Child a ,ciin-
I-14. involve-
T, Miyao M. Momoi M, Kamoshita S. Nonaka I. An case of nemalme myopathy with severe respiratory f:lilure (in No To Hattatsu
Karpati
childhood Fardeau
patients.
Dev
Ishibashi
Japanese).
[6]
to prognosis.
G,
nemaline
Kulakowski M.
anatomiclucs,
(Tokyo)
Carpenter myopathy.
Documents
Flament-D cliniques.
conccrnant
uric
par insuffisance
S,
respiratorie.
1985; 17:X5-70.
S, Andermann F. A new concept Arch Neurol I97 I ;24:29 l-304. J. Malaisse histologiclues.
nouvclle Arch
L
observation,
Fr Pediatr
of
F. Chevallay ultrastructuraux devolution
M. ct
mortellle
1973;30:505-26.
181 Yam;mloto T. Kamiya N, Hachiya M. et al. A cast of nemaline myol>athy with scvcrc respiratory a11d cardiac failure (in Japancsc). No ‘I‘0 I Iiittillhll
(‘I’OkyO)
IO&l;
10:-37-53.
191 N(mak~~ I. ‘I’o.jo M, Suglta ncmalinc my(~pitIlly. Neuropcdiatrics
Ilw I~IUIIIC~
iley
IIJ,
rchpiratory
Santiago drive
‘I’V,
I I. I+tal mu~lc 1083: 14:47-52. IIaniclc
in congenital
RI’.
characteristic!,
Scllall
myopathy.
13. lidcln~an
A111 J Med
in NII.
1977;63~
459~66. [ 11 il NW
121
1%
Shy GM,
Somcr\ .:I:. Wank(j COlltd’llll~ll llly~~~~~~tlly. Bruin 1003;Hh:793-8
Msrtinez
PEDIATRIC
t”ngel BA.
WK.
Lake
NEUROLOGY
BD.
Childhood
Vol.
‘I’. Ncmalinc IO. nemalinc
I6 No. 4
my(~l~athy.
[ 1I ]
Fdomtka 1. Ishiura
T, Ii K. Pl.ogression myopathy:
A
lOd9;78:484-9
I.
S. Arahata
in nemaline
K, Ishibashi-Ueda
myopathy.
Acta
H. Maruyama
Neuropathol
(Berl)
notable respiratory failure at birth and die in early infancy. Although the moderate congenital form has been described as a benign and nonprogressive to slowly progressive disease [2,3], some patients evidence apparent progression leading to respiratory failure and death [4-81. We report 4 patients who had marked respiratory failure and the results of polysomnographic studies of 1 patient with the severe neonatal form and 1 of 3 patients with the moderate congenital form.
Susaki M, Takeda M, Kobayashi K. Nonaka I. Respiratory failure in nemaline myopathy. Pediatr Neural I994; 16: 344346.
Nemaline myopathy was first described by Shy et al. [ 11 as one of the nonprogressive congenital myopathics. The disease has been classified into three subtypes based on the clinical presentation, i.e., the severe neonatal, moderate congenital (classic) and adult onset forms 121. Although the prognosis differs from form to form, respiratoiy infection or failure is the most common cause o1 atieilts with the scvcrc neonatal form usually have
Fw~ the DiviGon\ of ‘“Child Neurology and ‘Laboratory Mcdicinc; National Center Hospital for Ment,d, Nervous and Muscular Disorders; National Center of Neurology and Psychiatry; Kodaira. Tokyo, Japan.
344
PEDIATRIC
NEUROLOGY
Vol.
I6 No. 4
Pdrnt 1. The muscle pathologic findings in early childhood of this l6-ye‘ar-old girl have been described previously 191. She had severe hypotonia and respiratory difficulty at birth and wrls placed on a respirator for 2 days. From the clinical and muscle biopsy findings. she was d agnosed as having the severe neonatal form of nemaline myopathy. She has survived despite many episodes-at least IO-of severe respiratory infection requiring mechanical ventilation. Her face was long and narrow with no emotional expression, due to marked facial muscle involvement. She had a high-arched palate. Her skeletal muscles were markedly wasted. She could move her neck, shoulders, irdex fingers, or ankles at minimal magnitude. Muscle stretching reflexes were absent. She has needed nasal intermittent positive pressure ventilation (NIPPV) during sleep for the past 3 years. She has shown paradoxical movement of the abdomen with inspiration. She can drive her electric wheel chair by her neck muscles. Her vital capzlcity was only 100 ml. Arterial blood gas analy& revealed high pC0, (60 to 80 mm Hg) and low ~0~ (SO to 70 mm Hg) during the day. Ptr!iarr/ 2. A IS-year-old boy was horn to healthy parents after an uncvcntful pregnancy. Hc showed slightly delnycd motor development. I lc \l;\rtc*tl IO walh ilI IO ~u~nth\ of a!:~, At 3 )%!ill3 Ol’ ilgc. I'rom the IllllkCI~ pillllOl~~giC findings. IIC Wilb diagnohcd ilb having rlclllillinc my(~pathy. AI H ycarh of age. hc sutidcn:y dc~cl~~l~cd acute respiratory msufl’icicncy w it h hypcrcapnia 01’ pC0, grcntcr than IO0 mm Hg and was placed on a ventilator. Thereafter, he required mechanical ventilation during sleep [4j. He had manifested an abdominal squeeze at the end of expiration. From I4 years of age, he was placed on a respirator for the entire day but was still able to walk. In the next year, he lost the ability to walk. However. he could sit and use his upper extremities for eating and writing. He died of severe respiratory rnfection at I.5 years of age. Postmortem examination was performed except for the CNS. Purirru 3. A l4-year-old girl was born uneventfully at term. Her parcnth wcrc healthy and nonconsanguineous. Her younger brother also manifested nernaline myopathy and died of respiratory infection. She showed slight delay in motor development and ~11,s slight!:: 5yvotonic from birth. She began to walk at 20 months of age. At 2 years of age. she suddenly developed hypercapnic acute respiratory insufficiency (pC0, greater than 100 mm Hg) and rccluired a req~irator. She underwent a muscle biopsy. which rcvealcd ~IIC morphologic characteris,t,c:~ of nemaline myopathy 151. Thereafter. she rcquircd mechanical ventilation all day. although she could sit alone and could n~rrvc her cxtrcmitics against
Communications should be addressed to: Dr. Sasaki; Division of Child Neurology; National Center Hospital for Mental, Nervous and Muscular Disorder<: NCNP.4-I-I Ogawahigashicho. Koduira. Tokyo 187, Japan. Received September I I, 1996; accepted January 7, 1997.
0 1997 by Elsevier Science PI1 SO887-8994(97)00032-5
Inc. All rights reserved. @0887-8994/97/$17.00
The biopsy findings for the respiratory muscles from Patient 2 were reported previously respiratory muscles obtained at p were basically the same as those including marked variation in fib fibrosis, core/targetoid structure The overall findings progressed i
FP F C P 0 cz EOG Ment Thora ECG -.----
-.-.
-.
-
-___________-.~__-_-_--_____----4-----.----..A-
e---------G=;
-
---
.I
_-_
.7
\rlllflfl
.-
/I
-
---,
/I/./
-
-_;;;J,=..
gravity.
She could
eat and write
deteriorated. Patient 4. A female nasogastric unassisted
infant
by herself.
Her
was markedly
motor
ability
hypotonic
has not
and requilcd
;t
tube at birth. She could swallow food at 6 months, sit at I2 months, and wall\ alone at I8 months of age. At 5 years
of age, from
the muscle
biopsy
findings,
she was diagnosed
as having
nemaline myopathy. Her face was long and narrow. She had a higharched palate. At 9 years of age. she began having a headache in the early morning. Now, at I3 years of age, she can walk skills have not deteriorated recently. Arterial blood elevated
pC0,
of SO to 70 mm
A polysolnnographic EEG.
Patients 2 and 3 suddenly developed hypercapnia with loss of consciousness, while they were still ambulant with mild muscle weakness in the extremities. Patient 4 also had hypercapnia, although she could walk alone. several studies of acute respiratory insufficiency in patients with the moderate congenital form [4,5,7,8], a discrepancy between gross motor ability and respiratory function has been reported to be common in nemaline myopathy. Therefore, we should always be aware of respiratory failure, even in ambulant patients with minimal limb muscle weakness. Accordingly, the onset of re tory failure in nemaline myopathy diffe progressive muscle dystrophies, including
an clcctromyogram
study
alone and her motor gas analysis revealed
Hg in the morning.
was performed
t I’M<;)
on Patients
at mcntalis
mu~lc.
I and 3. An
;III clcctrooculo-
myopathy, we performed polysomnogr of the 4 patients. Apnea or irregular th occurred only during pOz and pC0, monitor stud nia occurred only during Therefore, the wors believed to result fr incffcctivc hrcathing. Conhcyuc
(KKJ wcrc f.Jrilfll (IXX;). thoracic Ill0W!1lIClltb. ,~Illd ill1 cl~clrocitrclic,grurll rccordcd. 7'lWl~CUt~lil~OU~ pc'0, and pO, wcrc continuou4y rccordc*d
with
iI triln~cutancou~
pO,/l~(‘()~
monitor
Apnea was defined as no thoracic seconds. Samples of the diaphragm and
J;~pan).
obtained
from
Patient
2 at pk)stmortcm
t I
Mcd~c;~l,
‘l’ohy().
movcmcnth for more than IO biceps bra&ii nw~lcs wcrc
examination.
Sleep
stage
9:oo
6:00
8.00 ----
REM
-- _-." I
Apnea or irregular thoracic movements occurred only during rapid eye movement (REM) sleep in both 1 and 4. Thoracic movements became irregular for 20 to 60 seconds when rapid eye movements occurred repeatedly. Just after these irregular thoracic movements, the heart and respiratory rates increased (Fig 1). In other sleep stages, no apnea or irregular thoracic movements were tient 1, contraction of the sternocleidomas-
II III
----l--f
‘- -.--I _____ _^"_-- .-----
IV PCOZkw~ -.
Pf.h,!~,~ -
__
90 -. 8o ______ . 70 @.
_
-- .-. .--
50 ---- --
-. ----
_, ;--
. ..
-
--
.;
1.-.s.m Ly&.-
,__.
&a-
-
_ ,' - .__
-
100 P./---pi
during the apnea (data not Serial transcutaneous pOz and pC0, moni onstrated that hypercapnia transiently occurr EM sleep in both patients (Fig 2). P stages, the pOz and pCOz eveIs were ahnost stable.
80 b0 40
Sasaki
CI al: Nemaline
Gotnori ~ricitrom~ yfaitr; I*‘iqlrr-c 3. Muncie pcrtltoiogp of rile diaphragtn and biceps brachii ~t~lrscks at postmortem cratnination in Patiettt 2 (modified rv~jyt~oi tttrr,sttiFc.tttiott ~320). Mat-ked variation in jiber si:e. dense interstitial fibrosis, core/targrtotd vtmctures. aud nrtnaline bodies bt’ere ohet?led in tilt* dictptrragtn (a); tttiid ~uriatiotr itt fiber size rrnd tluttterous tretnaiine bodies were observed in the biceps brachii tntrscie (1~).
[ 101 reported that the respiratory center dces not react to hypercapnia. The abnormal thoracic movements are probably caused by respiratory muscle weakness, which is aggravated only during REM sleep because the supportive respiratory muscles, including the sternocleidomastoid and trapezius muscles, may not work effectively. In other sleep stages, the pOz and pC0, levels were almost stable. The histologic findings revealed that respiratory muscles were more markedly involved than other skeletal muscles [41. Acid phosphatase activity was much greater in the diuphragm than in other &&al muscles, indicating that an active autophagic process ensued after the myofibGII;ir dcgcneration 1I I 1. This prcfcrentinl diaphragm involvement well explains the discrepancy between motor ilkility and respiratory involvement it1 patients with Ild’lllilline Illy~~~Xllhy, l!SlN!Ciillly in thrlsc With tlPC I~~OClL’rilk! congenital form.
review
of clinical
presentation
Neurol
1987;29:8
15-20.
[3]
in relation
WA&L-en-Pettersson
ical forlow-up
study
C. Congenital
of tweive
[4] Sasaki M, Yoneyama ment in ncmaline myopathy.
[S] infantile
[7)
nemaline
J Neural
Med
myopathy.
Sci
1989;89:
H, Nonaka 1. Respiratory muscle Pediatr Neurol 199C;6:425-7.
Child a ,ciin-
I-14. involve-
T, Miyao M. Momoi M, Kamoshita S. Nonaka I. An case of nemalme myopathy with severe respiratory f:lilure (in No To Hattatsu
Karpati
childhood Fardeau
patients.
Dev
Ishibashi
Japanese).
[6]
to prognosis.
G,
nemaline
Kulakowski M.
anatomiclucs,
(Tokyo)
Carpenter myopathy.
Documents
Flament-D cliniques.
conccrnant
uric
par insuffisance
S,
respiratorie.
1985; 17:X5-70.
S, Andermann F. A new concept Arch Neurol I97 I ;24:29 l-304. J. Malaisse histologiclues.
nouvclle Arch
L
observation,
Fr Pediatr
of
F. Chevallay ultrastructuraux devolution
M. ct
mortellle
1973;30:505-26.
181 Yam;mloto T. Kamiya N, Hachiya M. et al. A cast of nemaline myol>athy with scvcrc respiratory a11d cardiac failure (in Japancsc). No ‘I‘0 I Iiittillhll
(‘I’OkyO)
IO&l;
10:-37-53.
191 N(mak~~ I. ‘I’o.jo M, Suglta ncmalinc my(~pitIlly. Neuropcdiatrics
Ilw I~IUIIIC~
iley
IIJ,
rchpiratory
Santiago drive
‘I’V,
I I. I+tal mu~lc 1083: 14:47-52. IIaniclc
in congenital
RI’.
characteristic!,
Scllall
myopathy.
13. lidcln~an
A111 J Med
in NII.
1977;63~
459~66. [ 11 il NW
121
1%
Shy GM,
Somcr\ .:I:. Wank(j COlltd’llll~ll llly~~~~~~tlly. Bruin 1003;Hh:793-8
Msrtinez
PEDIATRIC
t”ngel BA.
WK.
Lake
NEUROLOGY
BD.
Childhood
Vol.
‘I’. Ncmalinc IO. nemalinc
I6 No. 4
my(~l~athy.
[ 1I ]
Fdomtka 1. Ishiura
T, Ii K. Pl.ogression myopathy:
A
lOd9;78:484-9
I.
S. Arahata
in nemaline
K, Ishibashi-Ueda
myopathy.
Acta
H. Maruyama
Neuropathol
(Berl)