Quite a number of patients with neuromuscular disorders (NMDs) also develop affection of the respiratory muscles during the disease course (table 1). [1] [2] Development of respiratory failure may be slow or fast. [3] In case of slow progression the body has sufficient time to adapt and to compensate for the muscular respiratory failure. One consequence of respiratory failure may be hypercapnia and metabolic alkalosis. [4] Recovery from extremely elevated pCO2 values in a patient with NMD has not been reported.

The patient is a 66-year-old HIV-negative, Caucasian male, height 190 cm, weight 62 kg with a history of nicotine abuse (last months 5 - 6 cigarettes/day) without indication of chronic lung disease, previous alcohol abuse (sober since ~2 years), osteoporosis, a trauma with commotio cerebri and a lesion of the left tympanum and vestibular nerve at age 36 year of age, previous arterial hypertension, coronary heart disease, suspected liver cirrhosis and recurrent diarrhoea due to non-specific colitis since nine months prior to admission. Since the age of 65 years he developed slowly progressive weakness of the lower limbs resulting in recurrent falls, associated with weight-reduction of 20 kg, initially being attributed to axonal polyneuropathy. At follow-up general wasting, brisk biceps, triceps and patella tendon reflexes, and neurogenic EMGs without giant motor unit action potentials from the limb muscles were found. Amyotrophic lateral sclerosis (ALS) was suspected.

Clinical neurologic examination four months prior to admission revealed dysarthria, weakness of the left intrinsic hand muscles (M5-) left brady-diadocho-kinesia, weakness of foot extension (M4 right, M2-3 left), weakness of foot flexion on the left side (M4), wasting of the lower limb muscles, and symmetric, stocking type pall-hypaesthesia. There was slight anaemia and hyper-eosinophilia. The vital capacity was 24%. The pCO2 was 58 mmHg but asymptomatic and resolved spontaneously. Based on the clinical presentation and a neurogenic EMG from the paraspinal muscles (positive sharp waves, abundant fasciculations, pseudomyotonic discharges in the cervical, thoracic and lumbar sections) probable ALS was diagnosed and a therapy with riluzole was initiated, without effect. He additionally took acetyl-salicylic acid, vitamin B and calcium. An MRI of the brain three months prior to admission revealed diffuse atrophy, bilateral leucaraiosis, spot-like hyperintensities subcortically and in the basal ganglia, and a diffuse hyper-signal of the pons. An MRI of the cervical spine showed osteochondrosis exclusively confined to C5-C7.

Three months later he was admitted for impaired consciousness, exsiccosis, cachexia, partial respiratory insufficiency, and a body temperature of 35°C. Blood gas analysis showed a pH of 6.9 and a pCO2 of 235 mmHg (table 2, figure 1). The patient required intubation and mechanical ventilation initially with a Bilevel positive airway pressure (BPAP mode. Under this therapy hypercapnia resolved within six hours. Muscle enzymes were elevated, there was slight anaemia, thrombocytopenia and hyper-eosinophilia but coagulation parameters were normal (table 2). Creatine-kinase and alpha-amylase increased during hospitalisation (table 2). There was low fT3/fT4 syndrome with a ratio fT3:fT4 of 1.318. X-ray of the lung revealed pneumonic infiltration of the right basal segments. On admission blood pressure was normal and the ECG showed sinus-rhythm. Echocardiography revealed thickening of the left ventricular myocardium (posterior wall and septum: 15 mm) but was otherwise normal (figure 2). Ultra-sonography of the liver was normal. pCO2 reached its nadir at 38 mmHg, eight hours after admission, but again increased 25 h after admission (table 2, figure 1). Two days after admission the ventilation mode was changed to continuous positive airway pressure-assisted spontaneous breathing (CPAP-ASB) after discontinuation of sedo-analgesia and the patient actively extubated himself. Mobilisation was started, initially with success. After another day, however, respiratory insufficiency recurred but this time the patient was not intubated again. He died three days after admission.

The presented patient is interesting for two aspects, the diagnosis of probable ALS and the transient survival of severe hypercapnia. Arguments against the diagnosis of probable ALS are the cerebral MRI findings, axonal polyneuropathy attributed to previous alcohol consumption, despite alcohol abstinence since two years, the presence of unexplained myocardial thickening, osteoporosis, occurrence of tachycardious atrial fibrillation one day before death, hepathopathy with normal ultrasound of the liver despite abstinence from alcohol since at least two years, severe, recurrent diarrhoea from non-specific colitis, severe respiratory muscle failure in the absence of bulbar involvement and upper limb weakness, and the stocking-type sensory abnormalities. Hypertrophic cardiomyopathy, osteoporosis, atrial fibrillation, non-specific colitis, hepatopathy, and sensory abnormalities have not been reported together with ALS. Thickening of the left ventricular myocardium cannot be explained with a previous history of arterial hypertension, since his blood pressure was normal since years, without requiring anti-hypertensive medication. Atrial fibrillation could be attributed to the pulmonary infection but it cannot be excluded that it was due to affection of the cardiac conduction system by another disease. Arguments for ALS are that the family history was negative for NMDs, the EMG findings, and the recurrent respiratory dysfunction. [5] Assuming a causal relation between the NMD and at least some of the abnormalities additionally present, ALS is rather unlikely given the multi-system presentation, which is not sufficiently explained by the previous alcohol abuse, respiratory insufficiency in the absence of bulbar involvement, and the absence of giant potentials on EMG. Hyper-eosinophilic syndrome or tryptophane abuse were excluded since there was only slight hyper-eosinophilia and since the patient had not received tryptophane. Since hypercapnia was most likely acute, given the normal HCO3 on admission, it could have also resulted from excessive metabolisation of glucose from muscle catabolism or glycolysis.

Based on the clinical presentation and the abnormalities additionally found, the patient most likely suffered from a multi-system disorder mimicking ALS, affecting the skeletal muscle, peripheral nerves, central nervous system, liver, myocardium, bones, and the gastrointestinal tract. Conditions mimicking ALS are listed in table 3. [5] Most of them were excluded by history and appropriate investigations but some, such as mercurium, lead, or aluminium intoxication, or metabolic disorder, remain differential diagnoses, which could explain the various abnormalities in the presented patient. Though we admit that all described abnormalities could have occurred independently from each other, it cannot be, on the other hand, excluded that at least some of the abnormalities were due to a common cause. Explanations for recurrent hyper-eosinophilia remain speculative. Contrary to the repeatedly "elevated liver enzymes" being attributed to liver disease, the echogenicity of the liver, however, was normal. Possibly, the so called "liver enzymes" were derived from the skeletal muscle and were misinterpreted as hepatopathy. Assuming that the absent Achilles tendon reflexes, weakness of the distal lower limbs, and the sensory disturbances were due to alcohol polyneuropathy, it has to be stressed that he refrained from alcohol since at least two year prior to admission. Other causes of sensori-motor polyneuropathy were not considered and no investigations into this direction initiated. From which of the various NMDs listed in table 1 the patient actually suffered remains speculative since he died before carrying out a muscle biopsy. Acquired NMDs were excluded by the investigations carried out. Concerning the hereditary forms, congenital NMDs were excluded by history and other forms by the clinical presentation and the disease course.

Whether respiratory insufficiency was due to polyneuropathy, the NMD, the respiratory infection, or the cerebral lesions, remains speculative. Arguments against polyneuropathy are that polyneuropathies hardly manifest in the axial nerves and that polyneuropathy was not so severe to also affect the upper limbs. An argument against the respiratory infection is that serological infection parameters and X-ray of the lungs were normal on admission and that severity of pneumonia in the described patient hardly leads to respiratory failure. Arguments against the pontine glioses or the supratentorial hyperintensities attributable to pontine or extra-pontine myelinolysis are that muscle force was almost normal in the upper limbs and that there was no weakness of the extra-ocular muscles or bulbar dysfunction. The most likely cause of respiratory failure remains a NMD, which predominantly affected the respiratory muscles and the lower limbs. [6] [7] Since metabolic myopathies are the NMDs most frequently mimicking ALS, [8] this type of NMD was regarded as the one most likely responsible for the chronic respiratory failure. That the patient surviving such an excessively high pCO2 level can be attributed to the slowly progressive nature of the respiratory failure and the ability of the body to adapt to such stressful compromising conditions. [9] [10] Already four months prior to admission, hypercapnia was reported, without manifesting clinically at that time. Whether the underlying NMD additionally supported the adaptation to respiratory acidosis by facilitated the compensation of the respiratory acidosis by metabolic adaptation remains speculative. [11]

Severe hypercapnia from weakness of the respiratory muscles may be survived, if respiratory failure develops slowly and if there is sufficient time for the body to adapt. NMDs associated with respiratory insufficiency may mimic ALS. Patients with chronic muscular respiratory failure should be closely monitored not to miss the point when intermittent positive pressure ventilation is required to prevent acute deterioration by triggers such as infections or acidosis.

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