Section 8: Muscular dystrophies and home ventilation

Figures & data

Table 1. Congenital muscular dystrophies (FVC: Forced vital capacity).

Class of muscular dystrophy	Common name	Clinical features	Age of required ventilatory support	Other respiratory findings	References
Congenital muscular dystrophy Type 1A (MDC1A),	Merosin Deficient CMD	Severe form with lack of ambulation and neonatal onset. Complete absence merosin	Nocturnal Ventilation typically first or second decade of life	Approximately 20% need ventilation by age 5	14
		Milder form characterized with partial absence of merosin	Rarely ventilator support and not until fifth decade of life
Collagen VI-related myopathies	Ulrich muscular dystrophy		Ventilator support first to second decade of life	Decreasing FVC with age with annual loss of FVC ∼2.6%	15–18
	Intermediate collagen VI related myopathy		Early third decade of life	Need for ventilation may precede loss of ambulation.
	Bethlem myopathy		Rarely before fifth decade of life
A-Dystroglycan deficiency CMD	Walker-Warburg Syndrome, Muscle-eye brain disease, Fukuyama congenital muscular dystrophy (FCMD), Limb girdle muscular dystrophy	Varied presentation	As early as neonatal period May never need ventilator supports	In large cohort, 12% of 115 patients required ventilator supports ranging from neonatal period to 20 years of age.	19
Rigid Spine CMD	Rigid Spine CMD	Axial weakness by 2 years of age with maintained ambulation		Nocturnal ventilation predates loss of ambulation	20
Facioscapulohumeral muscular dystrophy			Rarely need ventilation before fourth to fifth decade of life		21,22

Table 2. Outcomes of ventilatory support in muscular dystrophies.

Author (year)	Study type	Intervention	Age at initiation: Years (range)	Sample size	Outcome: Mortality	Outcome: Other
Raphael (1994)^26	RCT	Initiation of NIV if: • FVC >20% • pO2 >60 mmHg • pCO2 <45 mmHg	15.5 (11–33)	70 DMD	Increased mortality in the treatment arm (8/35 vs 2/35)	No change in pulmonary function or gas exchange
Ward (2005)^29	RCT	Initiation of NIV if nocturnal TcCO2 > 6.5 kPa and normal daytime PaCO2	18 (7–51)	25 Various neuromuscular disease	No change in mortality; 9 out of 10 in control group started NIV during follow up	Improved baseline nocturnal saturations and percentage of time with elevated nocturnal CO2 in treatment group
Vianello (1994)^11	Case control	Initiation of NIV with evidence of daytime hypercapnia (pCO2 > 45mmHg)	20.1 (13–27)	10	Decreased mortality in treatment arm (0/5 vs 4/5)	Plateau in FVC decline after 6 months of therapy (+0.03 L vs −0.23 L)
Rall (2012)^33	Case control	Ventilation – reasons for offering not specified	N/A		Improved survival in group with ventilation: 27.0 vs 19.0 years
Simonds (1998)^36	Observational	NIV for symptomatic diurnal hypercapnia	20.0 (13–28)	23	5 year survival 73%	Improved daytime oxygenation and ventilation
Jeppesen (2003)^58	Retrospective chart review	NIV and change to tracheostomy when 24/7 need; indication for initiation not clear		41	Increased survival compared to historical cohort
Mellies (2003)^34	Observational	NIV for symptomatic SDB (> 10 events/hour) or ventilator insufficiency (> 50mmHg >50% of night)	12.3 (6–19)	30	100%	Significant improvement in daytime and night time CO2 and O2 measurements; no significant impact on vital capacity
Mohr (1990)^59	Observational	NIV for DMD patients with diurnal hypoventilation	22 (16–27)	8	5/8	Improved daytime pCO2 (63 to 45) with 8 hours/night of NIV use
Kohler (2009)^60	Observational	Ventilation for DMD Patients – indication not clear (19 NIV and 3 IMV)	15.3 (SD – 5.2)	22 out of 43 started ventilation during follow-up period	Median survival: 35 years
Eagle (2002)^30	Historical cohort	NIV routinely offered since 1990s; indication: FVC <1.25 L with Ab normal oximetry or symptomatic		No NIV: n = 134 NIV: n = 24	Improved survival with NIV from 19.29 years (n = 134) to 25.3 year (n = 24)
Ishikawa (2010)^31	Historical cohort	Group 1: <1984: no intervention Group 2: 1984–1991: tracheostomy for CO2 narcosis or intubation Group 3: > 1992: NIV for symptomatic hypercapnia, MAC for peak flow <270 L/min, cardioprotective	Group 1: N/A Group 2: N/A Group 3: 18.9 ± 3.3 years	Group 1: (n = 56) Group 2: (n = 35) Group 3: (n = 96)	Improving 50% mortality Group 1: 18.6 years Group 2: 28.1 years Group 3: 39.6 years	* 11 patients in group 2 and 8 in group 3 died from predominately cardiac causes before regular ventilation was initiated
Passamano (2012)^32		Type of ventilation and indication not clearly indicated		n = 516	Improved respiratory mortality in patients on NIV: 17.7 years (11.6–27.5) vs 27.9 (23.6–38.6)

RCT = Randomized controlled trial.

Table 3. Modes of ventilation.

Author (year)	Study type	Sample size	Age: Years ± SD	Outcome
McKim (2013)^41	Cohort retrospective	n = 12 DMD	19.8 ± 3.4	Mean survival of 5.7 years on 24 hour NIV (10/12 still alive)
Soudon (2005)^44	Case control	N = 42 DMD IMV N = 26 NIV	32.7 ± 5.1 27.0 ± 5.7	Increased secretions and chest infections in the IMV group. Improved weight in the IMV group. Similar reasons for death.
Bach (1993^40	Observational	N = 257 (43 DMD)	DMD patients 18.4 ± 4.1	23/43 DMD patients utilized MPV including 10 for >10 years. Death rates were similar to those who converted to IMV
Toussaint (2006)^42	Observational	N= 42 DMD	23.5 ± 4.7 at time of initiation of MPV	50% survival at age 31 with NIV/MPV; stabilization of respiratory scores; stabilization of vital capacity decline

Need to specify that results are presented as mean ± SD; IMV = invasive mechanical ventilation via tracheostomy; MPV = mouth piece ventilation.

Table 4. Predictors of nocturnal hypoventilation/SDB.

Author (Year)	Population	Outcome	Predictive measure
Lyager (1995)^49	DMD n = 14; age: 19.2 (15.4–30.4)	Ventilation need (Daytime symptoms and daytime hypercapnia)	For DMD: FVC <30% 7 of 7 patients needing nocturnal ventilation
Laub (2006)^48	DMD n = 48; age: 20 (15–25)	Ventilation need (daytime symptoms, blood gas abnormalities)	For DMD needing ventilation: Mean VC: 26% predicted with SD of 13%
Mellies (2003)^53	Total n = 49; SMA, other dystrophies/myopathies); age: 11.3 ± 4.4 DMD n = 7; age: 14.6 ± 4.0	SDB (polysomnography) Nocturnal hypercapnia	SDB Inspiratory VC <60% had 97% sensitivity Peak Inspiratory (PIP) Pressure <41 cm H2O sensitivity of 87% Nocturnal Hypercapnia: Inspiratory VC <40%, 96% sensitivity for PIP <25 cm H2O 72% predicted 1 DMD with IVC of 63%, had obstructive nighttime episodes
Hukins (2000)^54	DMD n = 19; 18.6 ± 3.9 years	TST <90% (proportion of total sleep time <90% SaO2)	FEV1 <40% was 91% sensitive (50% specific) for a TST <90% of 2%. Arterial Blood Gas: PaCO2 ≥45, 91% sensitive and 75% specific Base Excess ≥4 100% specific, 55% sensitive
Toussaint (2007)^47	DMD n = 114	Nocturnal hypercapnia Diurnal hypercapnia	Vital capacity of ≤1820 mL sensitivity/specificity: 97%/51% MIP ≤39 cm H2O; sensitivity/specificity: 71%/54% Vital Capacity of <680 mL sensitivity/specificity of 90%/95%
Ragette (2002)^52	N = 42; 10 DMD, 10 CMD, 7 limb girdle dystrophy; mean age: 28.7 (14–63)	Sleep disordered breath (Polysomnography – REM related hyponeas) Continuous nocturnal hypoventilation	Vital Capacity <60%; sensitivity/specificity: 91%/89% MIP <45 cmH2O; sensitivity/specificity: 82%/89% Vital Capacity <40%; sensitivity/Specificity: 94%/79% MIP cmH2O; sensitivity/specificity: 95%/65%
Canny (1989)^50	DMD n = 143	Daytime hypercapnia	7 of 143 patients had daytime hypercapnia. Vital capacities of (9, 10, 24, 40, 40 and 47)% predicted
Bersanini (2012)^51	N = 52 (20 DMD); age: 14.9 (10.1–16.1)	Nocturnal hypoxemia (≥2% of night with <90% saturation) and nocturnal hypercapnia (PCO2 > 50 mmHg for ≥2% of night) Polysomnography in 27 patients	No correlation with pulmonary function or blood gas anomalies. No PFT/blood gas marker predicted Apnea Hypopnea Index >5
Katz (2010)^46	n = 39; congenital muscular dystrophy n = 6	Nocturnal hypoventilation on polysomnography: Elevation of CO2 by 10 mmHg and/or drop in saturation by at least 5% for 10 minutes	FVC <70% predicted; sensitivity/specificity of 71.5%/64.1% FEV1<65% predicted; sensitivity/specificity of 71.4%/79.5% Scoliosis correlated with nocturnal hypoventilation:sensitivity/specificity of 88.9%/80.4%

Ages given in years ± SD or (range).

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