Research Update
Impairment and Disability
Profiles of
Neuromuscular Diseases:


G.T. Carter, M.D.
R.T. Abresch, M.S.
W.M. Fowler, Jr., M.D.
E.R. Johnson, M.D.
D.D. Kilmer, M.D.
C.M. McDonald, M.D.

RTC/Neuromuscular Diseases
Department of Physical Medicine & Rehabilitation
University of California, Davis
National Inst. on Disability & Rehabilitation Research
Grant H133B30026
August 1995

There are many types of spinal muscular atrophy (SMA), acquired and hereditary; all involve selective destruction of anterior horn cells in the spinal cord. The most common types are usually referred to as type I, II, III and all three are inherited, usually autosomal recessive traits. SMA I, also known as Werdnig-Hoffman disease (WHD) or acute infantile-onset SMA, is a severe disorder that routinely results in death before age 2 years. SMA II, also referred to as early onset, intermediate SMA or chronic WHD, is a less severe disorder, yet still associated with significant morbidity and mortality. This type of SMA usually becomes apparent in the first 6 to 18 months of life. SMA III, also known as Kugelberg-Welander disease (KWD), is a chronic, later onset disorder, associated with significantly less morbidity. SMA III may become apparent between ages 5 to 15 years. Prevalence rates for SMA types II and III range from as high as 40 per million among children to around 12 per million in the general population.

The purpose of this 10 year study was to develop impairment and disability profiles for SMA II and III. Impairment was evaluated by measurements of strength, contractures, spine deformity, cardiac and pulmonary function, and intellectual capacity. Disability evaluations consisted of mobility and upper extremity function, cardiac and pulmonary disease, and psychosocial adjustment.

Forty-five individuals with SMA followed in a regional Neuromuscular Disease Clinic, 1982-1992, were reviewed: 32 SMA II and 13 SMA III. For those with SMA II, mean age was 17 +/- 14 years and mean disease duration 16 +/- 13 years. All had symptoms in the first three years of life, and most (78%) had onset of symptoms in the first year. Twenty-nine (91%) were non-ambulatory. In the 13 subjects with SMA III, the mean age was 40 +/- 20 years, the mean disease duration 17 +/- 10 years, and the mean age of onset 23 +/- 19 years. Six (50%) were non-ambulatory. For both types of SMA, seven (15%) individuals were known to have died during the 10 year study period with a mean age of death 21 +/- 18 years. Most were SMA II.

All participants from the clinic did not receive all measurements, so the individuals in each of the impairment or disability profiles would be considered as samples of the larger clinic population. The effect of age and disease duration was evaluated by both one time event (cross sectional) and longitudinal analysis. In the former, the first measurement obtained on every subject was plotted against years of age and/or disease duration. In the latter, each measurement for each individual for a three year or more period of time was analyzed for any age and/or disease duration effect. Due to the small sample and/or the marked weakness in most individuals, anthropometric, quantitative strength and exercise cardiopulmonary measurements were not obtained.

Muscle Weakness Profile - Manual Muscle Tests (MMT): MMTs were obtained in a sample of 18 SMA type II and 13 type III subjects. On the MMT scale, 5 is normal strength. The muscle is capable of transient resistance but collapses abruptly with a 3.3 MMT grade, and with a 2 grade, the muscle can move only when gravity is eliminated.

			Mean Strength			Strength Loss Per Year
			(MMT Mean +/- S.D.)		(MMT Unit Decline)
Upper extremity		2.8 +/- 0.6	4 +/- 1		ns	ns 
Lower extremity		1.9 +/- 0.8	3 +/- 0.9	-0.03	ns
Proximal muscles	2.0 +/- 0.8	3.5 +/- 0.8	-0.041	ns
Distal muscles		2.9 +/- 0.6	4.1 +/- 1.0	ns	ns
Flexor muscles		2.5 +/- 0.6	3.8 +/- 0.8	ns	ns
Extensor muscles	2.1 +/- 0.8	3.7 +/- 0.8  	ns	ns
All muscle groups 
  combined 		2.3 +/- 0.6	3.8 +/- 0.7	-0.024	ns

These results show that the mean strength grades for all muscle groups were significantly lower in SMA II than in SMA III. The total mean strength grade for all muscle groups combined was 2.3 +/- 0.6 MMT units for type II and 3.8 +/- 0.7 for type III. Only the SMA type II subjects exhibited a significant decline in total strength, as a function of age or disease duration, measured by examining the linear regression from cross-sectional analysis. In both types of SMA, the proximal muscles were weaker than the distal muscle groups, and the lower extremity muscles weaker than the upper extremity muscles. There was essentially no difference between combined flexor and extensor muscle strength. However, in type II SMA, extensor muscle groups were slightly weaker than flexor muscles in comparisons at the elbow, wrist, hip and knee, while the neck flexors were weaker than the neck extensors. In all other muscle groups there was no difference between flexor and extensor strength. The most impaired muscle groups in SMA II were the trunk, and hip and knee extensors. There was no difference in strength between the dominant and non-dominant sides.

In SMA III, there were no significant declines in strength per year of age in any of the muscle groups on cross sectional analysis, with the exception of the ankle invertors. In SMA II, the proximal musculature showed loss of strength over time, whereas the distal muscles showed no significant decline with age. The lower extremity muscles also showed a decline in strength while the upper extremity muscle groups did not have a significant strength loss. Individual longitudinal measurements over three or more years showed marked individual variations.

Limb Range of Motion (ROM) Profile: ROM was measured in 18 SMA II and 13 SMA III subjects to evaluate contractures using standard goniometry. Measurements included elbow and wrist extension, hip adduction for iliotibial band tightness, hip and knee extension and ankle dorsiflexion. Percent reductions in ROM by 20 degrees or more:

	 		Percent with 20 Degrees Loss ROM

	Elbows		22		 0
	Wrists		44		15
	Hips		38		 8
	Knees		50		 8
	Ankles		22		 0

The frequency of contractures was very high in SMA II and infrequent in type III. In regards to this observation and the high percentage of scoliosis, it should be noted that most of the type II subjects were non-ambulatory for many years. Severity of contractures was also high in type II with a contracture index (CI) of 1.39 for all joints combined and 2.58 at the knees. (CI is a product of the percentage of subjects with contractures times the maximal loss of ROM divided by 1,000. A high CI would be greater than 1.0 and a low CI less than 0.5). By both cross-sectional and longitudinal analysis of the effects of age and disease duration, there was considerable individual variation. However, several SMA II individuals showed significant loss of hip and knee ROM from ages 10-20 years.

Spine Deformity Profile: Descriptive information regarding spine deformity was obtained from 32 subjects with type II SMA and 13 with type III. Twenty-five (78%) of the 32 with type II SMA had clinical evidence of scoliosis; one with hyperlordosis and two with kyphoscoliosis. Thirteen (52%) of these had spinal interventions. Individuals without spine deformity were younger, had a shorter disease duration, and were wheelchair users for a shorter period of time than those with scoliosis. However, there was no difference in the percent of wheelchair users between the two groups. X-rays were obtained on the 12 individuals without spinal interventions. The mean Cobb angle of the primary curve was 62 +/- 37 degrees. There was no correlation between the curve pattern and disease duration. In subjects with longitudinal X-rays for three or more years, there was significant curve progression. Only one of the individuals with SMA III had clinical and radiographic evidence of scoliosis.

Pulmonary Function and Restrictive Lung Disease (RLD) Profile: Pulmonary function tests (PFT) were obtained in 17 type II and 13 type III subjects:

           				Mean Percent of Predicted Values

Forced Vital Capacity			54 +/- 26	84 +/- 22
Forced Expiratory Volume/1 sec	  	59 +/- 34	85 +/- 23
Total Lung Capacity			73 +/- 34	94 +/- 17
Maximum Inspiratory Pressure		100 +/- 58	88 +/- 26
Maximum Expiratory Pressure		79 +/- 23	91 +/- 21

Using the American Medical Association guidelines for RLD, 58% of the individuals with type II SMA had severe or moderate RLD, as compared to only 14% with SMA III. A Forced Vital Capacity (FVC) below 50% predicted is considered to be severe RLD, and between 51-60% to be moderate RLD. Analysis of both one-time event and longitudinal PFTs showed a significant age and disease duration effect only in subjects with SMA II. Consistent with the high level of severe to moderate RLD, 47% of the SMA II individuals had a history of major respiratory complications, such as frequent episodes of pneumonia, as compared to only 14% of those with SMA III. Both disease duration and FVC had an effect on the frequency of pulmonary complications in those with SMA II, but there was no spine deformity effect on either pulmonary function or respiratory complications.

Cardiac Function and Cardiovascular Disease Profile: Forty-one individuals received electrocardiograms (ECG). Twenty-six (63%) of the initial ECGs for both types of SMA were reported as abnormal, although most had minor findings such as baseline irregularity. Major abnormalities were abnormal Q-waves (31%) and tachycardia (12%). Analysis of one-time and longitudinal tracings indicated that there was no disease duration effect. Only 12% of the subjects had a history of cardiovascular complications such as dyspnea, palpitations, and chest pain, and there was no correlation between ECG abnormalities and cardiac complications.

Intellectual and Cognitive Function Profile: The Wechsler Adult Intelligence Scale (WAIS-R) and selected tests of the Halstead-Reitan Neuropsychological Test Battery (HR) were given to 14 adults with SMA II and III. Full scale WAIS-R IQ was 106+/- 15, verbal IQ 110+/- 16, and performance IQ 101+/- 15 (scaled scores); all within normal limits for intellectual function. The means for each of the sub-tests were in the normal range, with the exception of the digit sub-test, which had a T-score slightly below the published normal range. There was no significant difference between verbal and motor performance IQ indicating that even severe weakness of the upper extremities did not affect IQ. As in most of the other neuromuscular diseases, there were mild, slightly below average range scores on the HR Trials A and B and Speech Sounds Perception mean T-scores. For subjects tested longitudinally for 5 or more years, there was no disease duration effect.

Psychological Adjustment: The Minnesota Personality Inventory (MMPI), Suicide Probability Scale (SPS) and the California Personality Inventory (CPI) were administered to 11 adults with SMA II and III. The means for the MMPI hysteria, depression, schizophrenia, and hypochondriasis sub-scales were more than one standard deviation greater than published MMPI norms. However, the mean values for the CPI and SPS scales were within normal limits. Problems applying the MMPI to a physically disabled population have been previously noted, and the SMA results were not significantly different from individuals with other neuromuscular diseases.

Mobility and Extremity Function Profiles: Upper and lower timed motor performance tests (TMP) and functional evaluation levels (FG) were obtained in 11 individuals with SMA II and 12 with SMA III. Functional grades consisted of 6 levels of function for the upper extremities (UE) and 10 levels for the lower extremities (LE). Grade 1 on both scales is normal function, and a full time wheelchair user would be LE grade 9. TMP tests, measured in seconds, were standing from lying supine, climbing three stairs, running or walking 30 feet, standing from sitting, putting on a T-shirt, and cutting a premarked square. Times were compared with both those of able-bodied controls and a 120 second cutoff limit.

All individuals with SMA II had been using a wheelchair full-time for more than three years (LE FG9), so 100% were unable to complete a LE TMP task within 120 seconds. In the upper extremities, only 36% were able to raise their arms above their head (UE FGs 1 and 2), while the remainder (64%) were at functional grades 3 (can raise a glass to mouth but cannot raise hands above head) or above. The percentage of subjects unable to complete an UE TMP task within 120 seconds ranged from 69%-92% with the exception of cutting a square which was completed by 87% in a prolonged time, compared to controls.

Sixty-four percent of the SMA type III subjects were able to walk and climb stairs, with or without the aid of a railing (LE FGs 1-3). Only 36% were below LE FG 3, and 21% were non-ambulatory. Eighty-three percent were able to raise their arms above their head (UE FGs 1 and 2). The percentage of individuals unable to complete the TMP tasks within 120 seconds varied from 8%-33% depending on the task. Most completed each task in a prolonged time relative to controls. Unlike the subjects with SMA II, there was a significant relationship between MMT strength and TMP tasks.

In both types of SMA, there was no age or disease duration effect on functional evaluations or TMP tests since the age at which functional levels changed was extremely variable.

Summary: SMA II individuals had marked weakness and progressive decline of strength while those with type III had moderate weakness and a very slowly progressive course. There was a high frequency and severity of contractures and scoliosis, and significant restrictive lung disease in type II, while these complications were rare in type III. Timed motor performance and functional evaluations showed that weakness resulted in substantial disability in SMA II. There was no significant cardiovascular impairment, and intellectual and cognitive function were within normal limits as was psychosocial adjustment.

This impairment and disability profile and previous profiles of HMSN, FSHD, LGS, and MMD
are summaries of papers to be published in
the American Journal of Physical Medicine & Rehabilitation, October 1995.

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