Motor neuron disease presenting with respiratory failure

JOURNAL

OF THE

NEUROLOGICAL SCIENCES ELSEVIER

Journalof theNeurologicalSciences139(Suppl.)(1996)117-122

Motor neuron disease presenting with respiratory failure M. de Carvalho a7* , T. Matias b, F. Coelho ‘, T. Evangelista a, A. Pinto ‘, M.L. Sales Luis a a Department of Neurology, EMG Laboratory, Hospital de Santa Maria, Au. ProjI Egas Moniz, 1600 Lisbon, Portugal b Department of Medical Rehabilitation, Hospital de Santa Maria, Lisbon, Portugal ’ Department of Neurology, Hospital Egos Moniz, Lisbon, Portugal

Abstract Respiratory failure accountsfor the majority of deathsin amyotrophic lateral sclerosis(ALS) but only rarely is ALS diagnosedon the basis of respiratory insufficiency. We report four ALS patients presenting with acute respiratory failure. In three patients we have performed EMG needle examination of both hemidiaphragms which showed severe denervation. We reviewed 25 patients previously describedpresenting with respiratory failure. Almost all patients showed upper limbs weaknessand diaphragm involvement; few patients had bulbar dysfunction. The prognosis of these patients is not always a permanentventilator dependence.Rapidly progressiveventilatory failure may be a striking initial sign of ALS; the main reasonis a weakeneddiaphragm. There are possibilities of significant improvement after a period of rest with ventilatory assistance.In the initial phaseof the disease,bulbar dysfunction is not the more common reasonof acute respiratory failure. Keywords:

Amyotrophiclateralsclerosis;Respiratoryfailure, onset;Diaphragm;Upperlimb atrophy,onset;Electromyography

1. Introduction Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of the upper and lower motor neurons, with consequent widespread atrophy and weakness, which also involves the respiratory muscles. ALS patients progress to respiratory insufficiency and death as a result of weakness and fatigue of respiratory muscles. Weak gag reflex, cough reflex dysfunction, reduced pulmonary compliance and incoordination of respiratory efforts are important problems that can cause or precipitate respiratory impairment (Rosen, 1986; Braun, 1987; Oppenheimer, 1993). Exacerbation of respiratory failure often occurs in the context of lying infection (Rosen, 1986; Braun, 1987; Oppenheimer, 1993). The close correlation between ventilatory function and outcome in ALS is well established, and is well known that ALS patients may be unaware of respiratory problems even in the face of an important ventilatory impairment (Fallat et al., 1979; Fallat et al., 1987). The most important cause of respiratory failure and alveolar hypoventilation is the loss of negative intrathoracic pressure, normally carried out by the diaphragm, as consequence of cervical ventral * Correspondingauthor. Tel.: f351 (1) 797-7782;Fax: +351 (1) 795-7474.

horns cell death (Parhad et al., 1978; Meyrignac et al., 1985; Rosen, 1986; Howard et al., 1989; Gay et al., 1991; Sherman and Paz, 1994; Evangelista et al., 1995). Respiratory failure may be the only initial manifestation of ALS (Miller et al., 1957; Paul and Appenzeller, 1962; Fromm et al., 1977; Parhad et al., 1978; Sivak and Streib, 1980; Nightingale et al., 1982; Hill et al., 1983; Daras et al., 1984; Meyrignac et al., 1985; Al-Shaikh et al., 1986; Carre et al., 1988; Howard et al., 1989; Hoshino et al., 1991). Motor neuron degeneration in the cervical cord corresponding to the phrenic nerve nuclei is the most probable cause of early respiratory impairment (Serpick et al., 1965; Parhad et al., 1978; Nightingale et al., 1982; Hill et al., 1983; Daras et al., 1984; Meyrignac et al., 1985; Al-Shaikh et al., 1986; Carre et al., 1988; Howard et al., 1989). Nevertheless only in a single case was electromyography (EMG) of the diaphragm performed in ALS patients presenting with respiratory failure (Carre et al., 19881, and revealed severe neurogenic abnormalities on one side. We report four ALS patients presenting with acute respiratory failure. In three patients we have performed EMG needle examination of both hemidiaphragms which showed severe denervation. Two patients with an advanced disease but without respiratory impairment were used as controls.

0022-510X/96/$15.00Copyright0 1996ElsevierScienceB.V. All rights reserved. PII SOO22-5 10X(96)00089-5

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2. Patients, methods and case reports Four patients presenting with respiratory failure and not aware of previous neurological impairment were seen in the General Intensive Care Unit or the Pulmonary Department Intensive Care Unit of the Santa Maria Hospital during 1994- 1995. Clinical information was obtained from direct observation and chart review. We evaluated the clinical presentation, respiratory investigations, neurological examination and EMG studies. Two other ALS patients with an advanced disease but without respiratory complaints were also submitted to diaphragm EMG, after informed consent. Needle electromyography of the diaphragm was performed as described previously (Saadeh et al., 1993). The two control patients were also investigated for phrenic nerve conduction as reported elsewhere (Evangelista et al., 1995).

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Fig. 1. Case 2. Right diaphragm, full inspiration. One polyphasic motor unit, unstable, with increased recruitment rate.

2.1. Case I A 5 l-year-old male was admitted on 1l/1/94 with acute respiratory failure. For two weeks he had complained of progressive dyspnoea and had exhibited disturbed behaviour. On admission he was lethargic and cyanotic. Arterial blood had a pH of 7.1, pC0, of 103 mmHg and a p0, of 43 mmHg. He had paradoxical abdominal movement. Chest X-ray showed only an elevation of both diaphragms. An endotracheal tube was placed and the patient was treated with a volume-controlled ventilator. Fiberbronchoscopic findings were normal. Neurological examination on admission was normal but two weeks later he was found to have mild atrophy of first dorsal interosseus muscles of both hands. The diagnosis of ALS was confirmed by clinical evolution and EMG. No diaphragmatic investigation was performed. The patient was discharged 6 months later and is living with mechanical ventilation at home. He initially required ventilatory support at night and during a few hours of the day (he learned to use the accessory inspiratory muscles), but now he requires 24 h continual ventilatory assistance. 2.2. Case 2 A 65year-old male. He was admitted on 31/08/94 with acute respiratory failure. He had symptoms of respiratory distress during the preceding 4 weeks. On admission he was in coma and cyanotic. An endotracheal tube was placed and the patient was treated with a volume-controlled ventilator. No arterial blood analysis was performed before ventilation. Chest X-ray and fiberbronchoscopic findings were normal. Neurological examination showed bilateral pyramidal signs, moderate atrophy of first dorsal interosseus muscles of both hands, right deltoid and tongue which had sparse fasciculation. The EMG examination demonstrated widespread denervation, normal conduction

velocities and no conduction block. The EMG of both hemidiaphragms revealed profuse fibrillation and sharp waves; on full inspiration a reduced pattern with predominance of polyphasic potentials with increased recruitment rate was observed. After 9 months on a respirator, the patient fulfilled definitive ‘EL Escorial’ criteria, and had mild ophthalmoparesis. A second EMG of both hemidiaphragms performed at that time revealed no spontaneous activity; on the full inspiration we recorded two polyphasic motor units on the left side, one with larger amplitude and moderately unstable when analysed by high-pass filter band, and one single polyphasic motor unit on the right side (Fig. 1). After several trials to wean the patient from the ventilator, the patient is still at the Intensive Care Unit with mechanical ventilation for 24 h. 2.3. Case 3 A 79-year-old male was admitted in 12/03/94 with acute respiratory failure. He had a previous history of chronic bronchitis and his family described a severe deterioration of respiratory function during the last month. On admission he was confused and cyanotic. Arterial blood had a pH of 7.2, pC0, of 106 mmHg and p0, of 56 mmHg. He had paradoxical abdominal movements. Chest X-ray showed only an elevation of both diaphragms. An endotracheal tube was placed and the patient was treated with a volume-controlled ventilator. Fiberbronchoscopic findings were normal. Neurological examination revealed bilateral pyramidal signs, mild atrophy of first dorsal interosseus muscles of both hands, and widespread fasciculations on upper limbs. The EMG examination demonstrated widespread denervation, normal conduction velocities and no conduction block. Diaphragmatic EMG on the right side showed fibrillation and on full inspiration a single polyphasic motor unit; on the left side we observed sparse

M. de Carvalho et al. /Journal

of the Neurological

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Fig. 2. Case 3. Left diaphragm, full inspiration. One polyphasic motor unit; using a high-pass filter we observed moderate instability.

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p0, of 50 mmHg. Chest X-ray and fiberbronchoscopy were normal. Neurological examination disclosed bilateral pyramidal signs, moderate atrophy of hand muscles and proximal upper limb muscles, and widespread fasciculations. The EMG examination demonstrated diffuse denervation, normal conduction velocities and no conduction block. Diaphragmatic EMG on the right side showed spontaneous repetitive discharges and two polyphasic motor units during full inspiration; on the left side we observed profuse fibrillation and on full inspiration one very polyphasic motor unit with a high repetitive rate (Fig. 3). At another hospital, the patient was slowly weaned from the ventilator and supported with Bipap only from April till July 1995. In July he contracted severe pneumonia and was again submitted to a volume-controlled ventilator. The patient is still at an Intensive Care Unit of another hospital, under mechanical ventilation. 2.5. Case controls

fibrillation, and on full inspiration one polyphasic motor unit that showed instability of some components if led through a high-pass filter (Fig. 2). Since one year after admission, the patient has been able to be off the ventilator for a few hours during the day but is still confined to the Intensive Care Unit. The patient has nowadays slightly less muscle strength and more diffuse atrophy than at presentation, but he still has no bulbar symptoms. 2.4. Case 4 A 74-year-old male was admitted on 24/03/95 with acute respiratory failure. He had a previous history of emphysema associated with a heavy smoking habit. He had experienced progressive respiratory difficulties for 3 months. On admission he was confused and cyanotic. Arterial blood had a pH of 7.2, pC0, of 104 mmHg and

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(1) A 50-year-old male presented in January 1993 with progressive dysarthria. The neurological examination showed pyramidal tract signs and the EMG investigation confirmed diffuse denervation, suggesting a diagnosis of ALS. Eighteen months later he developed anarthria, swallowing difficulties, weakness and diffuse wasting. He had no respiratory symptoms; a spirometric study revealed a forced vital capacity of 80% of predicted value and he had normal arterial blood gases. A phrenic nerve conduction study revealed normal results on both sides (latency < 10 ms and amplitude > 0.1 mV>. The EMG of diaphragm showed no spontaneous activity and on full inspiration an interference pattern was observed on both sides. (2) A 67-year-old male presented in June 1991 with progressive right upper limb weakness. The neurological examination disclosed pyramidal tract signs, weakness and atrophy of both upper limbs and diffuse fasciculations. The EMG showed widespread denervation and excluded motor neuropathy. The diagnosis of ALS was made. Three years later he had diffuse severe wasting and weakness with pyramidal signs and moderate dysarthria. He had no respiratory symptoms. A spirometric study revealed a forced vital capacity of 76% of predicted value, and he had normal arterial blood gases. A phrenic nerve conduction study revealed normal results. The EMG of diaphragm was also normal on both sides.

3. Discussion

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Fig. 3. Case 4. Left diaphragm, full inspiration. One very polyphasic motor unit with a high repetitive rate.

Although respiratory failure in ALS is a frequent endstage complication and the main cause of death, only rarely is ALS diagnosed on the basis of respiratory insufficiency. To our knowledge only 25 patients with motor neuron disease presenting with respiratory problems have been

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Table 1 Patients presenting with respiratory hypoventilation 1

2

3

4

5

6

7

8

9

10

11

Age Sex Pulmonary disease Neurological examination at presentation

66 m no UL

71 m

49 m no UL B

57 m no UL LL P yes ? Yes ? NL
55 m no UL LL P ? ?

65 m no UL LL P yes ? yes yes

67 m no UL LL

54 f

yes yes

49 m no UL LL P ? ? yes no no no

63 m

Orthopnea Paradoxical abdominal motion Supine-decreased vital capacity Radiology - diaphragm paresis Decreased transdiaphragmatic pressure Phrenic conduction Death (acute event) Mechanical ventilation (MV) Other ventilatory support (after acute event)

60 m no UL LL P yes 3 no yes no

yes no no no

n0

UL P yes ? yes -left -

? ? no no no no

ll0

no no

yes no no no CVN

no yes no

n0

UL LL P/B yes ? no no yes no

ll0

Yes yes ?

UL LL B yes yes? 7

no no CVN

yes no no CVN

Case references: 1-3 (Miller et al., 1957); 4 (Paul and Appenzeller, 1962); 5 (Serpick et al., 1965); 6 (Sivak and Streib, 1980); 7-9 (Nightingale et al., 1982); 10, 11 (Howard et al., 1989). m, male; f, female; UL, upper limb weakness and/or atrophy; LL, lower limb weakness and/or atrophy; P, pyramidal lesion signs; B, bulbar involvement; NL, normal latencies; < A, small amplitudes; MVN, mechanical ventilation at night; CV, ventilation with a cuirass at night. Supine-decreased vital capacity is considered when supine position provokes severely diminished ventilatory capacity as comapared with upright position. Radiology - diaphragm paresis means absent or paradoxical diaphragm excursion as assessed by chest X-ray or fluoroscopy.

described previously. Eleven patients had a history of alveolar hypoventilation without severe acute respiratory failure (see Table 1) (Miller et al., 1957; Paul and Appenzeller, 1962; Serpick et al., 1965; Sivak and Streib, 1980; Nightingale et al., 1982; Howard et al., 1989). Fourteen

patients had a history of acute severe ventilatory insufficiency requiring invasive ventilation after a variable period of progressive dyspnoea (see Table 2) (Fromm et al., 1977; Parhad et al., 1978; Sivak et al., 1982; Hill et al., 1983; Daras et al., 1984; Meyrignac et al., 1985; Al-Shaikh et al.,

Table 2 Patients presenting with acute respiratory failure 1

2

3

4

5

6

Age Sex Pulmonary disease Duration of dyspnoea before the acute event Neurological examination at presentation

68 m no 2M N

70 m no ? UL LL

63 f copd 1M UL LL

? ? yes

68 f no 3M UL? LL? B? ? ? yes

46 f copd ?M N

Orthopnea Paradoxical abdominal motion Radiology - diaphragm paresis

69 m copd 3W UL? LL? P? ? ? yes

? ? yes

Decreased transdiaphragmatic pressure Diaphragm EMG Death (acute event) Mechanical ventilation (MV) Ventilatory support (after acute event)

-

yes yes

no yes RBc

no yes RB =

yes yes

7

52 m copd 8M? UL LL B ? ? ? ? yes ? ? no yes left a no no no yes yes yes TO, ‘none? ’ MVN

8

9

10

11

12

13

14

60 m no 4M UL? LL? P? ? ? yes left -

59 m no 3M UL LL P-B ? ? yes

59 m no 2M UL

65 m no 6M N

? ? ?

yes yes ?

68 m no 15M UL LL P-B yes yes yes

71 m no 2M UL LL B yes yes ?

76 m no 1M UL LL P ? ? ?

no yes MV

yes no no yes yes none CV ’

yes b no yes MVN

no yes MV

yes no yes none

no Yes MV

Case references: 1, 2 (Fromm et al., 1977); 3, 4 (Parhad et al., 1978); 5 (Sivak et al., 1982); 6, 7 (Hill et al., 1983); 8, 9 (Daras et al., 1984); 10 (Meyrignac et al., 1985); 11 (Al-Shaikh et al., 1986); 12 (Carre et al., 1988); 13 (Howard et al., 1989); 14 (Hoshino et al., 1991). m, male; f, female; copd, previous history of chronic pulmonary disease; M, months: W, weeks; N, normal neurological examination; UL, upper limb weakness and/or atrophy; LL, lower limb weakness and/or atrophy; P, pyramidal lesion signs; B, bulbar involvement; RB, rocking bed: T, tracheostomy; 0,) oxygen; MVN, mechanical ventilation at night; CV, ventilation with a cuirass. a Diaphragmatic EMG through oesophagus - poor information; b diaphragmatic EMG on the right side showing denervation; ’ respiratory failure causing death after the first acute event. Supine-decreased vital capacity is considered when supine position provokes severely diminished ventilatory capacity as comapared with upright position. Radiology - diaphragm paresis means absent or paradoxical diaphragm excursion as assessed by chest X-ray or fluoroscopy.

M. de Carvalho et al. /Journal

of the Neurological

Table 3 New cases presenting with acute respiratory failure 1

2

3

4

Age Sex Pulmonary disease Duration of dyspnoea before the acute event Neurological examination at presentation

51 m “0 2W N

79 m copd days UL P

14 m copd 3M UL P

Orthopnea Paradoxical abdominal motion

yes yes

65 m “0 4W UL P B ? ?

yes yes

? ?

Radiology - diaphragm paresis Diaphragm EMG Death (acute event)

yes no

no D no

yes D

no D

“0

“0

Mechanical ventilation (MV)

yes

yes

yes

yes

Ventilatory support (after acute event)

MVN

MVN

MVN

Bipap

m, male: f, female; copd, previous history of chronic pulmonary disease; M, months; W, weeks; UL, upper limb weakness and/or atrophy; LL, lower limb weakness and/or atrophy; P, pyramidal lesion signs; B, bulbar involvement; MVN, mechanical ventilation at night: D, diaphragm EMG showing severe neurogenic changes. Supine-decreased vital capacity is considered when supine position provokes severely diminished ventilatory capacity as comapared with upright position. Radiology - diaphragm paresis means absent or paradoxical diaphragm excursion as assessed by chest X-ray or fluoroscopy.

1986; Carre et al., 1988; Howard et al., 1989; Hoshino et al., 199 11. We added our four patients to this late group (Table 3). Although the presenting complaint was that of respiratory insufficiency, only three patients had normal neurological examination (case 1 of Fromm et al., 1977, case 2 of Parhad et al., 1978; Al-Shaikh et al., 1986) as was the case in our first patient. The patients show the expected age distribution for ALS, but it is surprising to verify that only four women were described. From the group of patients with acute respiratory failure, four had a previous history of chronic obstructive pulmonary disease, as in two out of our four patients. This probably signifies that these patients are more prone to respiratory failure once the inspiratory muscles are weakened. At least 22 out of 29 patients had weakness and/or wasting of the upper limbs, meaning a more severe neuronal loss at the cervical spinal cord. On the other hand at least 15 had lower limb weakness and/or wasting, and only seven had clear bulbar involvement. From the above we can conclude that the main reason for respiratory failure in these patients is not a weak gag reflex leading to aspiration, but probably a weak diaphragm. This conclusion is warranted by verifying that 27 out of 29 patients showed some evidence of diaphragmatic dysfunction. Two cases underwent autopsy; one showed a severe atrophic diaphragm (Parhad et al., 1978 - Table 2, case 3) and other patient had a predominant neuronal depletion of

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ventral horns from C, to C, (Meyrignac et al., 1985 Table 2, case 10). Three of our cases showing a severe denervation of the diaphragm ascertain that these cases are closely correlated to a severe weakness and fatigability of the diaphragm. Our controls cases excluded that severe diaphragm denervation could frequently occur in very handicapped patients but with otherwise normal ventilatory function. All these findings confirm previous evidence of a clear correlation between respiratory function and diaphragm performance in this disease (Gay et al., 1991; Evangelista et al., 1995). These patients are not always permanently ventilatordependent. The 11 patients with hypoventilation derived benefit from invasive ventilation when more symptomatic, less than half requiring any support after the critical event (three used cuirass ventilation at night, and one invasive ventilation at night). The 18 patients with more severe acute ventilatoty failure required invasive ventilation during the critical phase, nevertheless only two died in this phase. Afterwards five required 24 h invasive ventilation, five mechanical ventilation at night, two rocking beds, one cuirass ventilators, one benefited from tracheostomy plus oxygen, one was helped with Bipap (in accordance with our experience - Pinto et al., 19951, and finally three patients were free of any respiratory support. These results imply that those motivated patients presenting with respiratory symptoms have a capacity to improve once the critical phase is over. We believe that the relief of any respiratory load, the kinesitherapy, the rest period afforded, and the training of the accessory muscles are the main reasons for improvement. There are theoretical reasons to believe that a respiratory central drive dysfunction can also affect the ALS patients; nevertheless a central drive lesion was never proved (Meyrignac et al., 1985). Sleep studies performed in ALS showed some evidence of central apnoea in 12 patients so far (Sivak and Streib, 1980; Howard et al., 1989; Hoshino et al., 1991; Gay et al., 19911, but most patients had obstructive breathing events. Alveolar hypoventilation appears earlier during sleep than in the waking state, probably due to the loss of compensation by the central control of breathing during sleep (Lissoni et al., 1990). On the other hand, we should not exclude the blunting of the respiratory drive due to increased bicarbonate from hypercapnia, which can mimic a central drive dysfunction (Heineman et al., 1974). Rapidly progressive ventilatory failure may be a striking initial sign of ALS; the main reason is a weakened diaphragm. Selective vulnerability of certain motor cell groups is a feature of the disease that can explain this unusual presentation @wash, 1980; Swash et al., 1986). There are possibilities of significant improvement after a period of rest with ventilatory assistance. In the initial phase of the disease, bulbar dysfunction is not the more common reason of acute respiratory failure.

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