Epidemic of acute inflammatory myopathy in Karnataka, South India: 30 cases Nagaraja D, Taly AB, Suresh TG, Gourie-Devi M, Sarala Das, Rao BSS. Epidemic of acute inflammatory myopathy in Karnataka, South India: 30 cases. Acta Neurol Scand 1992: 86: 230-236.
Thirty patients of acute inflammatory myopathy were seen over a short period of I 1 months (February to December 1986) at NIMHANS, Bangalore, South India. The characteristic features were: short febrile illness followed a few days later by myalgia, edema of extremities, severe motor weakness and involvement of multiple other systems. Their mean age was 32.3 years and M:F ratio was 4: 1. CK levels were increased in all. EMG done in 23 patients showed spontaneous activity in 13 and myopathic pattern in all. Nerve conduction studies revealed abnormalities in 12 cases. Muscle biopsy done in 2 1 patients showed varying degree of myophagocytosis and inflammatory infiltrates. All patients received steroids for only 6-8 weeks. Twenty-two patients recovered, one developed residual disability and 7 patients died during the acute phase. None of the survivors has developed relapse so far. Such cases with monophasic illness in clusters have not been reported earlier.
Inflammatory myopathies form a heterogenous group of disorders and have a wide clinical spectra and varying etiologies (1-4). The disease may run an acute fulminant course or a chronic course simulating muscular dystrophy. It may manifest as focal process and remain so or may have diffuse involvement of muscles and other systems (3-10). Often the disease involves an individual sporadically. However, familial and epidemic occurrences have also been reported, the latter being attributed to viral infections (8-1 1). Thirty patients of acute myositis seen in cluster over a short period of 11 months (February to December 1986) at National Institute of Mental Health and Neuro Sciences, (NIMHANS), Bangalore, South India with distinct clinical features form the basis of this report. Similar cases were never seen by us before February 1986 and have not been encountered after December 1986 till date. Material and methods
National Institute of Mental Health and Neuro Sciences (NIMHANS) is a major neurological centre in South India. On an average 2-3 patients of subacute or chronic polymyositis were seen in a year at this centre from the year 1959 to 1985. In contrast, 30 patients of acute myopathy with distinct clinical fea-
230
’,
’,
D. Nagaraja A. B. Taly T. G. Suresh M. Gourie-Devil, Sarala Das’, B. S. S.Rao3
’,
’
Departments of Neurology, Neuropathology, Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore, India
Key words: acute inflammatory myopathy; epidemic; subclinical neuropathy D. Nagaraja, Additional Professor of Neurology, NIMHANS, Bangalore - 560 029, India Accepted for publication December 19, 199 1
tures were seen in the year 1986. All these patients underwent a detailed clinical and laboratory evaluation during the acute phase. Special attention was paid to record the place of residence, places visited in the previous 3 months, similar illness in the neighbourhood, past health and evolution of symptoms. Hemogram, urine analysis (routine, microscopy and for myoglobin), serological tests for syphilis, blood sugar and urea, serum creatine phosphokinase (CK), serum protein electrophoresis, SGOT, SGPT, bilirubin and alkaline phosphatase, Rheumatoid factor, LE Cell phenomenon, X-ray chest and EKG were done in all the patients. Electromyography was done in 23 patients and motor and sensory nerve conduction studies were conducted in right common peroneal and sural nerves respectively in 21 patients. Muscle biopsies from quadriceps were collected during acute phase for histological and enzyme histochemical studies from 2 1 patients. Four fragments were examined in each of the muscle biopsies. Electron microscopic study was done on 11 biopsies. Enzyme histochemical study included ATPase (PH 9.5, 4.5 and 4.3) SDH and NADH-TR reactions. All the 23 survivors were reassessed periodically to determine the recovery pattern. Serial CK and ESR were done. Fourteen patients underwent repeat EMG during follow up. Three of the 7 patients who died were autopsied.
Epidemic of acute inflammatory myopathy in Karnataka, South India: 30 cases Results Clinical features
Of the thirty patients, 22 presented during the month of June, July and August. Eighteen patients were from the city of Bangalore, 10 were from other districts of Karnataka, of whom 3 had visited Bangalore within 8 weeks prior to the onset of the illness, and 2 were from neighbouring states. None of the patients had symptoms of neuromuscular disease in the past. There were 24 men and 6 women in the age range of 3.5 to 62 years (mean 32.3 years). The onset was acute and the initial symptoms were fever, myalgia, swelling of limbs, skin rash and muscle weakness. Fever was without chills, ranged between 100102°F and occurred in 19 cases. Myalgia was severe in all and did not respond to analgesics and nonsteroidal anti-inflammatory agents. Global and nonpitting severe swelling of limbs was seen in 87% of cases (Fig. 1). Swelling of the face (n = 10) and trunk (n = 3) was also noted in few. Erythematous nonitching diffuse macular rashes were seen in 18 patients (face 10, trunk 8, neck 7 and limbs 12). Muscle weakness was universal and evolved over 1 to 15 days (mean 8.1 days) after the onset of fever and myalgia. It progressed for 1-40 days (mean 19.4 days) to reach its peak. All the patients had proximal muscle weakness (28 in upper limbs, 29 in lower limbs) and 23 in addition had distal weakness. It was more severe in proximal muscles than distal muscles and ranged between mild in 1/3 to moderately severe in 2/3rd (Table l), sixteen patients had truncal and neck flexor weakness and 5 had facial weakness. Six patients had dysphagia, necessitating nasogastric feeding. Three cases had respiratory muscle paralysis and required ventilatory assistance but none had oculomotor weakness. All the deep
tendon reflexes were normal in 7, absent in 2 and sluggish in 10 patients. In the remaining 11 patients, ankle jerks were preserved in 10 while the other reflexes were either sluggish (9 cases) or absent (1 case). In Case 26 only the ankle jerks were diminished while other reflexes were normal. Mild distal sensory impairment for touch and pin prick was observed in 2 patients. Two patients had generalised tonic-clonic seizures, at the onset and at the peak of illness respectively. None had cognitive, pyramidal, cerebellar or extrapyramidal deficits. Fifteen patients had involvement of other systems, either clinically or on investigations. Hypertension was noticed in 9; it was mild to moderate in 6 and severe in 3. None of these patients had prior history of hypertension. Systolic murmur mainly over pulmonary area was present in four patients. Polyarthralgia (2), oliguria (3), hematuria (2) and retinal haemorrhage (2) were other associated features. Laboratory parameters
The results of investigations were as follows. Hemoglobin of less than 12 gm% (8), leukocytosis (4), ESR of more than 20mm l s t h (13) (ranging between 5 mm to 61 mm), positive test for rheumatoid factor (2), elevated creatine kinase level in all less than 1000 IU = 5, 1000 to 5000 IU = 13 and more than 5000 IU = 12, (n = 170 IU), raised levels of SGOT and SGPT with normal bilirubin and alkaline phosphatase (20), hypocalcemia (2), hypokalemia (l), hyperkalemia (2), raised urea or creatinine (7), urinary abnormality (10) (hematuria - 4, proteinuria - 10, Casts - 3), radiological evidence of cardiomegaly (2) and pulmonary infiltrate (3) and electrocardiographic abnormalities ( 10) (nonspecific ST-T changes = 7, atrial arrhythmia = 2). Serum protein electrophoresis, LE cell phenomenon and HBs Ag, urine for myoglobinuria done in all and EEGs in 4 patients revealed normal or negative results. Electrophysiology (n=23)
Fig. 1. Shows (a) swelling of upper and lower extremities in acute phase and (b) complete resolution of swelling after 4 weeks (Patient - 25).
Concentric needle EMG of right quadriceps revealed increased insertional activity in 9 and mild to profuse spontaneous activity in 13 patients (fibrillations in 12, positive sharp waves in 9 and complex repetitive discharges in 4). Brief duration motor unit potentials (MUPs) were observed in 12 cases, but low amplitude MUPs were seen only in six patients. Fifteen patients had frequent brief duration polyphasic potentials. Four patients also had few high amplitude MUPs. A complete recruitment pattern was noted at minimal to moderate effort in 16 patients (Table 2). Motor conduction study in common peroneal nerve revealed distal motor latency in normal
231
Nagaraja et al. Table 1. Clinical features in 30 patients with acute myositis
06 07 08 09 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
Case
01 02 03 04 05
Month, onset Age, years Sex Duration, days Fever Rash Swelling Muscle Tenderness Weakness Bulbar Neck Limbs Trunk Respiration Deep Tendon Reflexes Ankle Jerks Systemic involvement
06 06 06 06 02 06 06 44 40 36 37 3.5 10 40 M M F M M F M 13 09 30 35 40 07 07
Outcome
t Present
t t t t
t t t
t t t t
t t
- - - t - - t t t -
t t t t t t - - -
D N
N N
A A
I
E
I
- Absent
07 25 M 34
06 07 08 08 08 08 06 06 06 06 08 07 08 09 12 12 10 12 12 07 09 19 34 25 48 36 38 14 36 42 30 47 60 25 05 23 22 45 62 57 26 35 M F M M M M M F M M M M M M M M M F M M F 42 14 10 06 11 44 20 35 13 15 21 20 24 04 11 30 25 55 05 120 38
08 40 M 15
- t t t - t - - t - - t - t t - t t t t - - - t t t t - t t - t t - t - t - t t t t - t t - - - t t - t t - + t t t t t t t - t t t t t t t t t t t - t t t t - t t t t t t t - - t t - t t t - t t t t t t - t
-
- -
- - t t t - - -
+ t t t t
t -
t t t -
+ - - -t t - t t t t t t t t t - t - t + - - - -
-
-
A N
D D
N N D D N D N N N N N D
I
I
I
N Normal
I
I
D Diminished
I
I
A Absent
I
D D
I
D N
I
D D
I
I Improved
range in all. Amplitude of evoked motor response was reduced in one and the conduction velocity was mildly reduced in 7 cases. Apart from one patient in whom no f wave could be elicited, all others had normal minimal f wave latency. Sural sensory conduction study revealed mild reduction in velocity in six cases and moderate reduction in 5 patients. Amplitude of sensory nerve action potential was reduced in only one of these cases. Two additional patients had reduced amplitude of SNAP and in one no SNAP could be obtained. In all, six patients had abnormalities of motor as well as sensory conduction velocity while one had only motor conduction abnormality and 5 had only sensory conduction abnormality (Table 3). Thus, besides myopathy there was additional evidence of demyelinating as well as axonal neuropathy. Histopathological features
Of the 30 patients, biopsy from quadriceps muscle in acute phase was available for examination in 21 cases (Table 4). Widespread degeneration and poly-
232
29 30
I
t -
t t - - t t - t t t - t t t t - t t t t t t t t t t t t - t t t t t - t + - - - + - + +
D D
D N
D D
D D
D N
I
I
I
I
E
P Partially improved
A A
D N
E
D N
I
N N
E
N N
E
N N
I
I
t -
t t t -
t t t -
t -
t t t t t-
N D
D A
D D
D D
D D
I
E
P
E
E Expired
focal necrosis of muscle fibres were consistently seen. Single muscle fibres or clusters of muscle fibres were seen in varying stages of necrosis and active phagocytosis (Fig. 2). Endomysial and perivenous infiltration by mononuclear cells were also seen although interfasicular collection of a large number of chronic inflammatory cells was not a feature. Necrotic single fibres, distributed amidst normal looking fibres with or without myophagocytosis, were observed in one case. Endomysial oedema was seen in a few cases. Regenerating activity of muscle fibres was not a conspicuous feature in most of the biopsies. Enzyme histochemical preparations revealed no preferential involvement of type 1 or type 2 fibres while degenerative changes of myofibres could be better appreciated in the sections stained for SDH and NADH-TR activities. At the ultrastructural level, none of the biopsies examined revealed virus like inclusions. Tubulo reticular inclusions in the vascular endothelial cell were also not identified by electron microscopy. Morphological features were suggestive of necrotising inflammatory myopathy.
Epidemic of acute inflammatory myopathy in Karnataka, South India: 30 cases
Fig. 2. a. Casc 7. Transversely cut skeletal muscle fibres showing necrosis. Well-preserved fibres are also seen. Inflammatory reaction is sparse in this area. Cryostat section (H & E x 400). b. Same as “a” (another area) loss of enzyme activity of varying degree in the necrotic fibres can be seen with relatively well-preserved myofibres in the same field (NADA-TR, x 400). c. Case 4. Muscle biopsy shows myonecrosis, phagocytosis and endomysial inflammatory cellular infiltration. Cryostat section (H & E x 400). d. Same case (“C” showing evidence of vasculitis (an uncommon feature in this series) and endomysial inflammation. Paraffin section (H & E x 400).
Course
All patients received steroids (40-60 mg of oral prednisolone or equivalent of parentral dexamethasone) after a mean period of 25.1 days from the onset of motor weakness. The response was dramatic. Myalgia responded first, followed by edema and motor weakness. Full dosages were continued for 3 - 4 weeks and then tapered and stopped over 3 - 4 weeks. Survivors improved within one to eight weeks (mean 13 days) after the peak weakness was attained. CK levels returned to normal within 7 - 12 weeks period. Follow up at 4 months revealed that 22 patients recovered and had no residual signs. One patient was left with weakness and wasting of hand muscles. Clinical and laboratory indicators of systemic involvement also reverted to normal. Seven patients (6 men and 1 woman) died during the acute phase. The duration of illness at the time of death ranged from 7 to 55 days (mean 22.3 days). All these patients had severe weakness and with one exception (Case 30) multiple system involvement. The course was complicated by status epilepticus and carditis in one, electrolyte disturbances in two, cardiac arrhythmia and failure in one and pneumonitis
in 3. All the 3 patients who needed ventilatory support did not survive. Follow-up data
The survivors were initially reviewed at a mean interval of 7.8 months from the onset of illness. None of the patients had relapse of symptoms. Neurological examination did not reveal any deficits and creatine kinase levels were also normal. EMG was repeated in 14 patients (Table 2). Electromyography of quadriceps revealed occasional fibrillation potentials in only one patient. Mean amplitude and duration of MUPs were normal in all. Six patients had a few high amplitude normal duration MUPs. Recruitment pattern was full at moderate effort. Four of the eight patients with initial abnormal motor conduction studies in common peroneal nerve continued to have reduced motor NCV. No SNAP could be recorded from sural nerve in 2 cases. 3 cases had reduced sensory conduction velocity and 2 had reduced amplitude of SNAP (Table 3). Muscle biopsy was not repeated. During long term follow up ranging from 18-44 months none of the patients reported relapse of symptoms.
233
Nagaraja et al. Table 2. Electromyography in 23 patients with acute myositis, in acute phase and recovery phase MUP
Polyphasic
Spontaneous activity
Amp (mv)
Duration (msec)
Amp (mv)
01 02
-
6.5 5.3
3.8
t
2.5 1 .o
03
tt
0.6
5.0
0.6
Case
Duration (msec)
Polyphasic
MUP
Recruitment
Interval from first EMG, Wks
C
32
C
Expired
C
28
Spontaneous activity
Amp (mv)
Duration (msec)
Amp (mv)
3.1
6.2
3.8
4.0
5.8
3.2
ttt -
2.5
1.6
11.6
C
9.4
C C
tt 10.1
tt tttt
Recruitment
tt
11.2
tt 04
Duration (msec)
1.5
t 5.4
-1
36
1.6
9.0
1.3
12.6
9.7
C C
56
0.6
6.1
-
C
Not done
C
36
2.4
6.2
-
tt 05 06
-
-
0.87 0.7
3.1 5.6
1.0
07
-
1.5
2.7
1.5
-
t 6.7
ttt
oa
-
2.4
2.3
2.7
C
t 4.5
C
32
8.8
C
Not done
6.1
-1
40
2.2
6.1
2.0
2.8
7.5
2.7
15.4
C
12.6
C
16.4
C
11.8
C
12.6
C
10.2
C
12.0
C
13.5
C
tt 09
tt
2.7
4.3
2.7
tt 10
tttt
0.5
5.7
0.4
t
ttt 11
tt
2.1
4.6
2.5
t 3.9
C
36
2.1
7.5
1.6
ttt 12
tt
1.7
3.4
2.7
t 4.6
C
32
5.0
-3
Not done
7.8
C
28
5.1
C
Not done
7.1
C
32
2.1
8.7
2.4
0.9
8.0
1.3
2.1
6.5
1.8
t 13
ttt -
14
1.5
2.8
0.45
t 1.2
4.3
0.85
t
tt -
15
3.5
4.0
2.6
ttt 16
tt
1.3
4.0
1.3
t
ttt 17 20
-
0.6 0.8
4.9 3.6
1.1
t
22
-
2.9
2.8
1.6
-
tt 9.9
4.7
9.4
4.9
24
4.3
7.2
2.7
12
3.6
6.7
32
-1 -2
Expired
8.8
C
5.8
-1
t
t
tt 25
tt
2.5
3.3
2.5
-
C
tt 27
ttt
Not done
Not done
10
6.5
C
Expired
6.6
C
Not done
Not done
1.9
4.5
1.1
7.2
-3
tt 28
tt
1.7
3.2
3.4
t 29
-
2.0
4.9
5.6
t Mild, t t Moderate, t t t Gross, t t t t Profuse, C-Complete, - 1 Mildly reduced, -2 Moderately reduced, -3 Grossly reduced.
Discussion
The salient features of the present series were: occurrence of cases in cluster over a short period quite in contrast to the hospital statistics of the previous 27 years, acute onset, male preponderance, characteristic clinical profile of fever, myalgia, skin rash and muscle weakness evolving over a brief period, high incidence of bulbar and respiratory muscle involvement, multiple systemic manifestations (50%), very high CK levels, subclinical sensory motor neuropathy (40%), dramatic response to short course of steroids, high mortality (23.3 %), negligible morbid-
ity (3.3%), rapid return of muscle power, CK and EMG to normal and absence of relapse during long term follow up even after stopping of steroid within a few weeks of the therapeutic response. All these cases fulfilled Bohan’s criteria of “definite” idiopathic inflammatory myopathies ( 12). However, idiopathic inflammatory myopathy unlike the cases in present series usually has a subacute or chronic course occurs sporadically, involves women more often than men, responds variably to steroids and may relapse after withdrawal of steroids. The monophasic illness in the present series appeared similar to acute viral myositis. The clinical
Epidemic of acute inflammatory myopathy in Karnataka, South India: 30 cases Table 3. Nerve conduction studies in 21 patients with acute myositis -Acute and recovery phase FOIIOW-UP
Acute phase Common peroneal (motor)
Case
No. 1 2 3 4 5 7 8 9 10 11 12 13 14 15 16 17 20 22 25 27 28 Control value (n=30)
Common peroneal (motor)
Sural Interval from 1st week
Distal latency
MNCV (misec)
SNAP (amp pv)
SNCV) (misec)
32
3.6
41.5
17
45.6
3.8 3.2 4.0 3.5 4.9
52.1 45.0 50.0 47.8 46.8
13 18 35
46.8 45.0 50.0
4.2 3.5 2.9
Distal latency (m. sec)
MNCV (misec)
SNAP (amp pv)
SNCV (misec)
3.9 5.3 3.7 4.1
46.8 42.6 55.0 50.0
45 32 30 35
43.4 35.8 39.3 45.6
3.1 3.9 3.2 3.5 3.1 2.9 3.2 3.0 3.2 3.0 3.5 3.1 3.3 3.5 4.3 4.5
52.1 47.0 49.3 56.0 50.0 47.2 48.4 51.7 47.5 46.7 50.0 37.5 53.7 48.4 39.2 41.7
35 18 17 25 30 30 12.5 22 50 20 165 10 12 20
58.0 37.7 48.5 45.1 50.0 41.2 46.6 44.3 43.5 40.6 41.6 39.4 50.0 41.9
No snap
No snap
24 12 10
18
46.0
Expired
5.3k0.6
5 l.Ok3.7
18.5k3.6
48.0k3.8
Not done
symptoms in the latter vary from localised self limiting myositis like the post-influenza1 myositis or epidemic pleurodynia (3,4, 10) to severe rhabdomyolysis with necrotising myositis (6, 12). Viral myositis may occur sporadically or in epidemic form and is often age dependent affecting mainly children (3, 10). Reports of acute rhabdomyolysis have been sporadic and various agents like influenza virus, coxsackie B5 virus, echo virus 9, adeno virus 21, herpes simplex and Epstein Barr virus and mycoplasma pneumoniae have been implicated, though virus isolation has not been generally unsuccessful (3, 6, 7, 12). Occasionally virus like particles have been identified on electron microscopy (7, 11). Acute nephritis and myocarditis have also been reported with coxsackie infection. However, multiple organ involvement like central nervous system, kidneys, heart and skin as evident in the present report is rare (12- 14). Yet another feature of interest was evidence of sub-clinical neuropathy. The nature of neuropathy was probably mixed i.e. demyelinating as well as axonal. Subclinical neuropathy in idiopathic polymyositis in the absence of dyscollagenosis or malignancy is rare and has not been documented in acute viral myositis. The histopathological observations suggested in-
Sural
Expired
28 36 36 32
No snap
20
39.8
48.4 54.0 47.2
20 22 10
40.0 45.8 50.0
3.7
56.5
15
43.6
3.6 3.7
37.6 52.0
9 17
43.7 48.0
3.4 3.7 6.3
50.0 50.0 34.6
50 42
48.6 46.6 -
Not done
40 36 32 Not done
28 Not done
32 32 Expired
No snap
flammatory nature of the disease however, changes were variable and did not correlate with the severity of muscle weakness and rise in creatine kinase level. This could be because the changes in polymyositis are multifocal and biopsy site may not truly reflect the disease process. It is also likely that severe weakness, rise in the enzyme level and abnormal electromyography were due to dysfunction rather than destruction of muscle fibre as evidenced by the absence of inflammatory infiltration in 8 out of 21 biopsies studied and almost all the survivors except one made near total recovery. Alternatively absence of inflammatory infiltration in 8 and absence of any specific changes in 3 patients may be due to the patchy nature of the lesion and the biopsy slides not including such areas, as these cases did not differ from others and CK was markedly elevated in them. Few atrophic fibres probably indicated associated neurogenic lesion as was also evident by electrophysiological studies. Electronmicroscopic study did not reveal inclusion bodies or viral particles in any of the biopsy. This however, does not exclude viral etiology. While the clinical features suggest the novelty of this syndrome, the etiopathogenesis is speculative. Involvement of multiple organs indicate a diffuse
235
Nagaraja et al. Table 4. Histopathological observations in quadriceps muscle biopsy in 21 patients with acute myositis
SI. No. ~~
Day of biopsy
Weakness grade (MRC)
Preserved architecture
4 3 3 3 4 3 3 4 4 3 3 4 4 2 2 2 3 4 4 4 4
P P P
Myonecrosis
Myophago cytosis
Hyalini zation
Regeneration
Atrophic fibres
Perifascicular atrophy
Interstitial infiltration
Perivascular infiltration
~~
01 02 03 04 05 07 10 13 15 16 17 18
19 20 21 23 25 26 27 28 30
20 14 36 42 30 7 52 45 14 27 40 17 10 26 12 15 24 20 42 7 27
L P P P P P P P P
P P P P P L
L P L
t ttt ttt ttt t
-
tt t t tt ttt t t tt t
-
t tt tt
-
tt
P=preserved except areas of necrosis, L=lost, -=absent, t =mild. t t =moderate, t t t =severe.
process like vasculitis. However, histopathological study did not substantiate the same. A generalised membrane abnormality of mitochondria1 cytopathy could account for simultaneous involvement of different systems. Clustering of cases points toward toxic or infective etiology however detailed enquiry failed to disclose any toxic factor. Although electron microscopic study of muscles did not show any inclusion bodies or viral particles, reports of serum anti-viral antibody titre in a few patients suggested coxsackie B , infection. Acknowledgements The authors gratefully acknowledge the secretarial assistance of Mr. M.V. Srinivasan and the staff of the department of electrodiagnosis (Neurology) and medical illustration.
References 1. BOHAN A, PETERJB. Polymyositis and dermatomyositis. 2. N Engl J Med 1975: 292: 403-407. 2. BOHAN A, PETERJB. Polymyositis and dermatomyositis. 1. N Engl J Med 1975: 292: 344-347. 3. MASTAGLIA FL, OJEDAVJ. Inflammatory myopathies: Part 1. Ann Neurol 1985: 17: 215-227.
236
FL, OJEDAVJ. Inflammatory myopathies: Part 4. MASTAGLIA 2. Ann Neurol 1985: 17: 317-323. 5. BLUMBERGS PC, BYRNEE, KAKULAS BA. Polymyositis presenting with respiratory failure. J Neurol Sci 1984: 65: 221-229. 6. JEHNUW, FINKMK. Myositis, myoglobinemia and myoglobinuria, associated with enterovirus echo 9 infection. Arch Neurol 1980: 37: 457-458. Y, ANDOT, YOKOTAJ. Acute fulminant myo7. FUKUYAMA globinuric polymyositis with picornavirus like crystals. J Neurol Neurosurg Psychiatry 1977: 40: 775-781. IA, MITCHELLI. Transient acute myositis in 8. MCKINLAY childhood. Arch Dis Child 1976: 51: 135-137. 9. RUFF RL, SECRISTD. Viral studies in benign acute childhood myositis. Arch Neurol 1982: 39: 261-263. MK, PARTINJC, BOVEKE. Epidemic influenza 10. FARRELL myopathy in Cincinnati in 1977. J Paed 1980: 96: 545-551. PW, KASHGARIAN M. Postviral 11. GRECOTP, ASKANASE myositis myxovirus like structures in affected muscle. Ann Int Med 1977: 86: 193-194. G, HODGES GR. Adenovirus type 12. WRIGHTJ, CONCHONNAI 21 infection concurrence with pneumonia, rhabdomyolysis and myoglobinuria in an adult. JAMA 1979: 241: 2120-2121. CP, LYNNKL, BAILEYRR. Acute renal failure 13. SWAINSON and polymyositis: case report. NZJ Med 1984: 97: 288-289. GM. The heart and cardiac con14. HAUPTHM, HUTCHINS duction system in polymyositis. Dermatomyositis: a clinicopathology study of 16 autopsied patients. Am J Cardiol 1982: 50: 998-1000.
Thirty patients of acute inflammatory myopathy were seen over a short period of I 1 months (February to December 1986) at NIMHANS, Bangalore, South India. The characteristic features were: short febrile illness followed a few days later by myalgia, edema of extremities, severe motor weakness and involvement of multiple other systems. Their mean age was 32.3 years and M:F ratio was 4: 1. CK levels were increased in all. EMG done in 23 patients showed spontaneous activity in 13 and myopathic pattern in all. Nerve conduction studies revealed abnormalities in 12 cases. Muscle biopsy done in 2 1 patients showed varying degree of myophagocytosis and inflammatory infiltrates. All patients received steroids for only 6-8 weeks. Twenty-two patients recovered, one developed residual disability and 7 patients died during the acute phase. None of the survivors has developed relapse so far. Such cases with monophasic illness in clusters have not been reported earlier.
Inflammatory myopathies form a heterogenous group of disorders and have a wide clinical spectra and varying etiologies (1-4). The disease may run an acute fulminant course or a chronic course simulating muscular dystrophy. It may manifest as focal process and remain so or may have diffuse involvement of muscles and other systems (3-10). Often the disease involves an individual sporadically. However, familial and epidemic occurrences have also been reported, the latter being attributed to viral infections (8-1 1). Thirty patients of acute myositis seen in cluster over a short period of 11 months (February to December 1986) at National Institute of Mental Health and Neuro Sciences, (NIMHANS), Bangalore, South India with distinct clinical features form the basis of this report. Similar cases were never seen by us before February 1986 and have not been encountered after December 1986 till date. Material and methods
National Institute of Mental Health and Neuro Sciences (NIMHANS) is a major neurological centre in South India. On an average 2-3 patients of subacute or chronic polymyositis were seen in a year at this centre from the year 1959 to 1985. In contrast, 30 patients of acute myopathy with distinct clinical fea-
230
’,
’,
D. Nagaraja A. B. Taly T. G. Suresh M. Gourie-Devil, Sarala Das’, B. S. S.Rao3
’,
’
Departments of Neurology, Neuropathology, Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore, India
Key words: acute inflammatory myopathy; epidemic; subclinical neuropathy D. Nagaraja, Additional Professor of Neurology, NIMHANS, Bangalore - 560 029, India Accepted for publication December 19, 199 1
tures were seen in the year 1986. All these patients underwent a detailed clinical and laboratory evaluation during the acute phase. Special attention was paid to record the place of residence, places visited in the previous 3 months, similar illness in the neighbourhood, past health and evolution of symptoms. Hemogram, urine analysis (routine, microscopy and for myoglobin), serological tests for syphilis, blood sugar and urea, serum creatine phosphokinase (CK), serum protein electrophoresis, SGOT, SGPT, bilirubin and alkaline phosphatase, Rheumatoid factor, LE Cell phenomenon, X-ray chest and EKG were done in all the patients. Electromyography was done in 23 patients and motor and sensory nerve conduction studies were conducted in right common peroneal and sural nerves respectively in 21 patients. Muscle biopsies from quadriceps were collected during acute phase for histological and enzyme histochemical studies from 2 1 patients. Four fragments were examined in each of the muscle biopsies. Electron microscopic study was done on 11 biopsies. Enzyme histochemical study included ATPase (PH 9.5, 4.5 and 4.3) SDH and NADH-TR reactions. All the 23 survivors were reassessed periodically to determine the recovery pattern. Serial CK and ESR were done. Fourteen patients underwent repeat EMG during follow up. Three of the 7 patients who died were autopsied.
Epidemic of acute inflammatory myopathy in Karnataka, South India: 30 cases Results Clinical features
Of the thirty patients, 22 presented during the month of June, July and August. Eighteen patients were from the city of Bangalore, 10 were from other districts of Karnataka, of whom 3 had visited Bangalore within 8 weeks prior to the onset of the illness, and 2 were from neighbouring states. None of the patients had symptoms of neuromuscular disease in the past. There were 24 men and 6 women in the age range of 3.5 to 62 years (mean 32.3 years). The onset was acute and the initial symptoms were fever, myalgia, swelling of limbs, skin rash and muscle weakness. Fever was without chills, ranged between 100102°F and occurred in 19 cases. Myalgia was severe in all and did not respond to analgesics and nonsteroidal anti-inflammatory agents. Global and nonpitting severe swelling of limbs was seen in 87% of cases (Fig. 1). Swelling of the face (n = 10) and trunk (n = 3) was also noted in few. Erythematous nonitching diffuse macular rashes were seen in 18 patients (face 10, trunk 8, neck 7 and limbs 12). Muscle weakness was universal and evolved over 1 to 15 days (mean 8.1 days) after the onset of fever and myalgia. It progressed for 1-40 days (mean 19.4 days) to reach its peak. All the patients had proximal muscle weakness (28 in upper limbs, 29 in lower limbs) and 23 in addition had distal weakness. It was more severe in proximal muscles than distal muscles and ranged between mild in 1/3 to moderately severe in 2/3rd (Table l), sixteen patients had truncal and neck flexor weakness and 5 had facial weakness. Six patients had dysphagia, necessitating nasogastric feeding. Three cases had respiratory muscle paralysis and required ventilatory assistance but none had oculomotor weakness. All the deep
tendon reflexes were normal in 7, absent in 2 and sluggish in 10 patients. In the remaining 11 patients, ankle jerks were preserved in 10 while the other reflexes were either sluggish (9 cases) or absent (1 case). In Case 26 only the ankle jerks were diminished while other reflexes were normal. Mild distal sensory impairment for touch and pin prick was observed in 2 patients. Two patients had generalised tonic-clonic seizures, at the onset and at the peak of illness respectively. None had cognitive, pyramidal, cerebellar or extrapyramidal deficits. Fifteen patients had involvement of other systems, either clinically or on investigations. Hypertension was noticed in 9; it was mild to moderate in 6 and severe in 3. None of these patients had prior history of hypertension. Systolic murmur mainly over pulmonary area was present in four patients. Polyarthralgia (2), oliguria (3), hematuria (2) and retinal haemorrhage (2) were other associated features. Laboratory parameters
The results of investigations were as follows. Hemoglobin of less than 12 gm% (8), leukocytosis (4), ESR of more than 20mm l s t h (13) (ranging between 5 mm to 61 mm), positive test for rheumatoid factor (2), elevated creatine kinase level in all less than 1000 IU = 5, 1000 to 5000 IU = 13 and more than 5000 IU = 12, (n = 170 IU), raised levels of SGOT and SGPT with normal bilirubin and alkaline phosphatase (20), hypocalcemia (2), hypokalemia (l), hyperkalemia (2), raised urea or creatinine (7), urinary abnormality (10) (hematuria - 4, proteinuria - 10, Casts - 3), radiological evidence of cardiomegaly (2) and pulmonary infiltrate (3) and electrocardiographic abnormalities ( 10) (nonspecific ST-T changes = 7, atrial arrhythmia = 2). Serum protein electrophoresis, LE cell phenomenon and HBs Ag, urine for myoglobinuria done in all and EEGs in 4 patients revealed normal or negative results. Electrophysiology (n=23)
Fig. 1. Shows (a) swelling of upper and lower extremities in acute phase and (b) complete resolution of swelling after 4 weeks (Patient - 25).
Concentric needle EMG of right quadriceps revealed increased insertional activity in 9 and mild to profuse spontaneous activity in 13 patients (fibrillations in 12, positive sharp waves in 9 and complex repetitive discharges in 4). Brief duration motor unit potentials (MUPs) were observed in 12 cases, but low amplitude MUPs were seen only in six patients. Fifteen patients had frequent brief duration polyphasic potentials. Four patients also had few high amplitude MUPs. A complete recruitment pattern was noted at minimal to moderate effort in 16 patients (Table 2). Motor conduction study in common peroneal nerve revealed distal motor latency in normal
231
Nagaraja et al. Table 1. Clinical features in 30 patients with acute myositis
06 07 08 09 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
Case
01 02 03 04 05
Month, onset Age, years Sex Duration, days Fever Rash Swelling Muscle Tenderness Weakness Bulbar Neck Limbs Trunk Respiration Deep Tendon Reflexes Ankle Jerks Systemic involvement
06 06 06 06 02 06 06 44 40 36 37 3.5 10 40 M M F M M F M 13 09 30 35 40 07 07
Outcome
t Present
t t t t
t t t
t t t t
t t
- - - t - - t t t -
t t t t t t - - -
D N
N N
A A
I
E
I
- Absent
07 25 M 34
06 07 08 08 08 08 06 06 06 06 08 07 08 09 12 12 10 12 12 07 09 19 34 25 48 36 38 14 36 42 30 47 60 25 05 23 22 45 62 57 26 35 M F M M M M M F M M M M M M M M M F M M F 42 14 10 06 11 44 20 35 13 15 21 20 24 04 11 30 25 55 05 120 38
08 40 M 15
- t t t - t - - t - - t - t t - t t t t - - - t t t t - t t - t t - t - t - t t t t - t t - - - t t - t t - + t t t t t t t - t t t t t t t t t t t - t t t t - t t t t t t t - - t t - t t t - t t t t t t - t
-
- -
- - t t t - - -
+ t t t t
t -
t t t -
+ - - -t t - t t t t t t t t t - t - t + - - - -
-
-
A N
D D
N N D D N D N N N N N D
I
I
I
N Normal
I
I
D Diminished
I
I
A Absent
I
D D
I
D N
I
D D
I
I Improved
range in all. Amplitude of evoked motor response was reduced in one and the conduction velocity was mildly reduced in 7 cases. Apart from one patient in whom no f wave could be elicited, all others had normal minimal f wave latency. Sural sensory conduction study revealed mild reduction in velocity in six cases and moderate reduction in 5 patients. Amplitude of sensory nerve action potential was reduced in only one of these cases. Two additional patients had reduced amplitude of SNAP and in one no SNAP could be obtained. In all, six patients had abnormalities of motor as well as sensory conduction velocity while one had only motor conduction abnormality and 5 had only sensory conduction abnormality (Table 3). Thus, besides myopathy there was additional evidence of demyelinating as well as axonal neuropathy. Histopathological features
Of the 30 patients, biopsy from quadriceps muscle in acute phase was available for examination in 21 cases (Table 4). Widespread degeneration and poly-
232
29 30
I
t -
t t - - t t - t t t - t t t t - t t t t t t t t t t t t - t t t t t - t + - - - + - + +
D D
D N
D D
D D
D N
I
I
I
I
E
P Partially improved
A A
D N
E
D N
I
N N
E
N N
E
N N
I
I
t -
t t t -
t t t -
t -
t t t t t-
N D
D A
D D
D D
D D
I
E
P
E
E Expired
focal necrosis of muscle fibres were consistently seen. Single muscle fibres or clusters of muscle fibres were seen in varying stages of necrosis and active phagocytosis (Fig. 2). Endomysial and perivenous infiltration by mononuclear cells were also seen although interfasicular collection of a large number of chronic inflammatory cells was not a feature. Necrotic single fibres, distributed amidst normal looking fibres with or without myophagocytosis, were observed in one case. Endomysial oedema was seen in a few cases. Regenerating activity of muscle fibres was not a conspicuous feature in most of the biopsies. Enzyme histochemical preparations revealed no preferential involvement of type 1 or type 2 fibres while degenerative changes of myofibres could be better appreciated in the sections stained for SDH and NADH-TR activities. At the ultrastructural level, none of the biopsies examined revealed virus like inclusions. Tubulo reticular inclusions in the vascular endothelial cell were also not identified by electron microscopy. Morphological features were suggestive of necrotising inflammatory myopathy.
Epidemic of acute inflammatory myopathy in Karnataka, South India: 30 cases
Fig. 2. a. Casc 7. Transversely cut skeletal muscle fibres showing necrosis. Well-preserved fibres are also seen. Inflammatory reaction is sparse in this area. Cryostat section (H & E x 400). b. Same as “a” (another area) loss of enzyme activity of varying degree in the necrotic fibres can be seen with relatively well-preserved myofibres in the same field (NADA-TR, x 400). c. Case 4. Muscle biopsy shows myonecrosis, phagocytosis and endomysial inflammatory cellular infiltration. Cryostat section (H & E x 400). d. Same case (“C” showing evidence of vasculitis (an uncommon feature in this series) and endomysial inflammation. Paraffin section (H & E x 400).
Course
All patients received steroids (40-60 mg of oral prednisolone or equivalent of parentral dexamethasone) after a mean period of 25.1 days from the onset of motor weakness. The response was dramatic. Myalgia responded first, followed by edema and motor weakness. Full dosages were continued for 3 - 4 weeks and then tapered and stopped over 3 - 4 weeks. Survivors improved within one to eight weeks (mean 13 days) after the peak weakness was attained. CK levels returned to normal within 7 - 12 weeks period. Follow up at 4 months revealed that 22 patients recovered and had no residual signs. One patient was left with weakness and wasting of hand muscles. Clinical and laboratory indicators of systemic involvement also reverted to normal. Seven patients (6 men and 1 woman) died during the acute phase. The duration of illness at the time of death ranged from 7 to 55 days (mean 22.3 days). All these patients had severe weakness and with one exception (Case 30) multiple system involvement. The course was complicated by status epilepticus and carditis in one, electrolyte disturbances in two, cardiac arrhythmia and failure in one and pneumonitis
in 3. All the 3 patients who needed ventilatory support did not survive. Follow-up data
The survivors were initially reviewed at a mean interval of 7.8 months from the onset of illness. None of the patients had relapse of symptoms. Neurological examination did not reveal any deficits and creatine kinase levels were also normal. EMG was repeated in 14 patients (Table 2). Electromyography of quadriceps revealed occasional fibrillation potentials in only one patient. Mean amplitude and duration of MUPs were normal in all. Six patients had a few high amplitude normal duration MUPs. Recruitment pattern was full at moderate effort. Four of the eight patients with initial abnormal motor conduction studies in common peroneal nerve continued to have reduced motor NCV. No SNAP could be recorded from sural nerve in 2 cases. 3 cases had reduced sensory conduction velocity and 2 had reduced amplitude of SNAP (Table 3). Muscle biopsy was not repeated. During long term follow up ranging from 18-44 months none of the patients reported relapse of symptoms.
233
Nagaraja et al. Table 2. Electromyography in 23 patients with acute myositis, in acute phase and recovery phase MUP
Polyphasic
Spontaneous activity
Amp (mv)
Duration (msec)
Amp (mv)
01 02
-
6.5 5.3
3.8
t
2.5 1 .o
03
tt
0.6
5.0
0.6
Case
Duration (msec)
Polyphasic
MUP
Recruitment
Interval from first EMG, Wks
C
32
C
Expired
C
28
Spontaneous activity
Amp (mv)
Duration (msec)
Amp (mv)
3.1
6.2
3.8
4.0
5.8
3.2
ttt -
2.5
1.6
11.6
C
9.4
C C
tt 10.1
tt tttt
Recruitment
tt
11.2
tt 04
Duration (msec)
1.5
t 5.4
-1
36
1.6
9.0
1.3
12.6
9.7
C C
56
0.6
6.1
-
C
Not done
C
36
2.4
6.2
-
tt 05 06
-
-
0.87 0.7
3.1 5.6
1.0
07
-
1.5
2.7
1.5
-
t 6.7
ttt
oa
-
2.4
2.3
2.7
C
t 4.5
C
32
8.8
C
Not done
6.1
-1
40
2.2
6.1
2.0
2.8
7.5
2.7
15.4
C
12.6
C
16.4
C
11.8
C
12.6
C
10.2
C
12.0
C
13.5
C
tt 09
tt
2.7
4.3
2.7
tt 10
tttt
0.5
5.7
0.4
t
ttt 11
tt
2.1
4.6
2.5
t 3.9
C
36
2.1
7.5
1.6
ttt 12
tt
1.7
3.4
2.7
t 4.6
C
32
5.0
-3
Not done
7.8
C
28
5.1
C
Not done
7.1
C
32
2.1
8.7
2.4
0.9
8.0
1.3
2.1
6.5
1.8
t 13
ttt -
14
1.5
2.8
0.45
t 1.2
4.3
0.85
t
tt -
15
3.5
4.0
2.6
ttt 16
tt
1.3
4.0
1.3
t
ttt 17 20
-
0.6 0.8
4.9 3.6
1.1
t
22
-
2.9
2.8
1.6
-
tt 9.9
4.7
9.4
4.9
24
4.3
7.2
2.7
12
3.6
6.7
32
-1 -2
Expired
8.8
C
5.8
-1
t
t
tt 25
tt
2.5
3.3
2.5
-
C
tt 27
ttt
Not done
Not done
10
6.5
C
Expired
6.6
C
Not done
Not done
1.9
4.5
1.1
7.2
-3
tt 28
tt
1.7
3.2
3.4
t 29
-
2.0
4.9
5.6
t Mild, t t Moderate, t t t Gross, t t t t Profuse, C-Complete, - 1 Mildly reduced, -2 Moderately reduced, -3 Grossly reduced.
Discussion
The salient features of the present series were: occurrence of cases in cluster over a short period quite in contrast to the hospital statistics of the previous 27 years, acute onset, male preponderance, characteristic clinical profile of fever, myalgia, skin rash and muscle weakness evolving over a brief period, high incidence of bulbar and respiratory muscle involvement, multiple systemic manifestations (50%), very high CK levels, subclinical sensory motor neuropathy (40%), dramatic response to short course of steroids, high mortality (23.3 %), negligible morbid-
ity (3.3%), rapid return of muscle power, CK and EMG to normal and absence of relapse during long term follow up even after stopping of steroid within a few weeks of the therapeutic response. All these cases fulfilled Bohan’s criteria of “definite” idiopathic inflammatory myopathies ( 12). However, idiopathic inflammatory myopathy unlike the cases in present series usually has a subacute or chronic course occurs sporadically, involves women more often than men, responds variably to steroids and may relapse after withdrawal of steroids. The monophasic illness in the present series appeared similar to acute viral myositis. The clinical
Epidemic of acute inflammatory myopathy in Karnataka, South India: 30 cases Table 3. Nerve conduction studies in 21 patients with acute myositis -Acute and recovery phase FOIIOW-UP
Acute phase Common peroneal (motor)
Case
No. 1 2 3 4 5 7 8 9 10 11 12 13 14 15 16 17 20 22 25 27 28 Control value (n=30)
Common peroneal (motor)
Sural Interval from 1st week
Distal latency
MNCV (misec)
SNAP (amp pv)
SNCV) (misec)
32
3.6
41.5
17
45.6
3.8 3.2 4.0 3.5 4.9
52.1 45.0 50.0 47.8 46.8
13 18 35
46.8 45.0 50.0
4.2 3.5 2.9
Distal latency (m. sec)
MNCV (misec)
SNAP (amp pv)
SNCV (misec)
3.9 5.3 3.7 4.1
46.8 42.6 55.0 50.0
45 32 30 35
43.4 35.8 39.3 45.6
3.1 3.9 3.2 3.5 3.1 2.9 3.2 3.0 3.2 3.0 3.5 3.1 3.3 3.5 4.3 4.5
52.1 47.0 49.3 56.0 50.0 47.2 48.4 51.7 47.5 46.7 50.0 37.5 53.7 48.4 39.2 41.7
35 18 17 25 30 30 12.5 22 50 20 165 10 12 20
58.0 37.7 48.5 45.1 50.0 41.2 46.6 44.3 43.5 40.6 41.6 39.4 50.0 41.9
No snap
No snap
24 12 10
18
46.0
Expired
5.3k0.6
5 l.Ok3.7
18.5k3.6
48.0k3.8
Not done
symptoms in the latter vary from localised self limiting myositis like the post-influenza1 myositis or epidemic pleurodynia (3,4, 10) to severe rhabdomyolysis with necrotising myositis (6, 12). Viral myositis may occur sporadically or in epidemic form and is often age dependent affecting mainly children (3, 10). Reports of acute rhabdomyolysis have been sporadic and various agents like influenza virus, coxsackie B5 virus, echo virus 9, adeno virus 21, herpes simplex and Epstein Barr virus and mycoplasma pneumoniae have been implicated, though virus isolation has not been generally unsuccessful (3, 6, 7, 12). Occasionally virus like particles have been identified on electron microscopy (7, 11). Acute nephritis and myocarditis have also been reported with coxsackie infection. However, multiple organ involvement like central nervous system, kidneys, heart and skin as evident in the present report is rare (12- 14). Yet another feature of interest was evidence of sub-clinical neuropathy. The nature of neuropathy was probably mixed i.e. demyelinating as well as axonal. Subclinical neuropathy in idiopathic polymyositis in the absence of dyscollagenosis or malignancy is rare and has not been documented in acute viral myositis. The histopathological observations suggested in-
Sural
Expired
28 36 36 32
No snap
20
39.8
48.4 54.0 47.2
20 22 10
40.0 45.8 50.0
3.7
56.5
15
43.6
3.6 3.7
37.6 52.0
9 17
43.7 48.0
3.4 3.7 6.3
50.0 50.0 34.6
50 42
48.6 46.6 -
Not done
40 36 32 Not done
28 Not done
32 32 Expired
No snap
flammatory nature of the disease however, changes were variable and did not correlate with the severity of muscle weakness and rise in creatine kinase level. This could be because the changes in polymyositis are multifocal and biopsy site may not truly reflect the disease process. It is also likely that severe weakness, rise in the enzyme level and abnormal electromyography were due to dysfunction rather than destruction of muscle fibre as evidenced by the absence of inflammatory infiltration in 8 out of 21 biopsies studied and almost all the survivors except one made near total recovery. Alternatively absence of inflammatory infiltration in 8 and absence of any specific changes in 3 patients may be due to the patchy nature of the lesion and the biopsy slides not including such areas, as these cases did not differ from others and CK was markedly elevated in them. Few atrophic fibres probably indicated associated neurogenic lesion as was also evident by electrophysiological studies. Electronmicroscopic study did not reveal inclusion bodies or viral particles in any of the biopsy. This however, does not exclude viral etiology. While the clinical features suggest the novelty of this syndrome, the etiopathogenesis is speculative. Involvement of multiple organs indicate a diffuse
235
Nagaraja et al. Table 4. Histopathological observations in quadriceps muscle biopsy in 21 patients with acute myositis
SI. No. ~~
Day of biopsy
Weakness grade (MRC)
Preserved architecture
4 3 3 3 4 3 3 4 4 3 3 4 4 2 2 2 3 4 4 4 4
P P P
Myonecrosis
Myophago cytosis
Hyalini zation
Regeneration
Atrophic fibres
Perifascicular atrophy
Interstitial infiltration
Perivascular infiltration
~~
01 02 03 04 05 07 10 13 15 16 17 18
19 20 21 23 25 26 27 28 30
20 14 36 42 30 7 52 45 14 27 40 17 10 26 12 15 24 20 42 7 27
L P P P P P P P P
P P P P P L
L P L
t ttt ttt ttt t
-
tt t t tt ttt t t tt t
-
t tt tt
-
tt
P=preserved except areas of necrosis, L=lost, -=absent, t =mild. t t =moderate, t t t =severe.
process like vasculitis. However, histopathological study did not substantiate the same. A generalised membrane abnormality of mitochondria1 cytopathy could account for simultaneous involvement of different systems. Clustering of cases points toward toxic or infective etiology however detailed enquiry failed to disclose any toxic factor. Although electron microscopic study of muscles did not show any inclusion bodies or viral particles, reports of serum anti-viral antibody titre in a few patients suggested coxsackie B , infection. Acknowledgements The authors gratefully acknowledge the secretarial assistance of Mr. M.V. Srinivasan and the staff of the department of electrodiagnosis (Neurology) and medical illustration.
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