The amyotrophic lateral sclerosis (ALS) patient perspective on misdiagnosis and its repercussions.

We studied the rate of initial "misdiagnosis', along with factors than might distinguish such patients, in 64 patients with amyotrophic lateral sclerosis (ALS) who completed a survey of 34 questions. Announcement of the survey was made by electronic newsletter and users group bulletin board directed at ALS patients. The questionnaire was distributed to interested ALS patients via electronic mail (e-mail), and 64 ALS patients (81% from the USA) returned their completed questionnaires via reply e-mail or postal mail. Seventeen patients (27% of total group) indicated at least 1 prior misdiagnosis, most commonly spinal stenosis/radiculopathy; 5 listed unnecessary and costly surgical treatments (laminectomy, endarterectomy). Misdiagnosis appeared to be more common in patients above age 60 and may be more common in patients originating in cities versus smaller communities. Mean time from onset of first symptom until definitive diagnosis of ALS was prolonged in patients with initial misdiagnosis (19 months) compared with non-misdiagnosed patients (10 months). Such a previous misdiagnosis may decrease a patient's chance of acceptance into multicenter ALS drug trials.

Pulmonary function at diagnosis of amyotrophic lateral sclerosis. Rate of deterioration.

The purpose of this study was to determine the degree of respiratory muscle impairment in patients with newly diagnosed amyotrophic lateral sclerosis (ALS) and the subsequent rate of decline of respiratory function. Thirty-one of 36 patients had respiratory muscle weakness at presentation, although only 7 complained of any respiratory symptoms. Vital capacity (percent predicted) was significantly lower in the symptomatic group (55.9 +/- 20.3) compared with the asymptomatic group (76.4 +/- 21.0). Respiratory muscle impairment as measured by vital capacity (percent predicted) was related to stage of disease at presentation. Rate of decline of respiratory muscle strength as measured by VC (-3.5 percent/month), negative inspiratory pressure (NIF) (+2.9 cm H2O/month), and positive expiratory pressure (PEP) (-3.4 cm H2O/month) tended to be linear with a great deal of interpatient variability. It is concluded that early measurement of respiratory muscle strength in ALS with subsequent follow-up studies may be useful in determining overall prognosis and in decision making.

Upper airway dysfunction in olivopontocerebellar atrophy.

We report the findings in a patient known to have olivopontocerebellar atrophy who developed respiratory distress, inspiratory stridor, and maximum inspiratory and expiratory flow volume loops. Treatment with carbidopa-levodopa gave symptomatic relief.

Misdiagnosis in patients with amyotrophic lateral sclerosis.

To confirm our impression that a high percentage of patients with amyotrophic lateral sclerosis are initially misdiagnosed, we reviewed records of 33 patients with a definitive diagnosis of amyotrophic lateral sclerosis seen over 10 years. Fourteen patients (43%) were initially misdiagnosed. Mean time to correct diagnosis was significantly greater for the misdiagnosed group (16.0 +/- 9.3 months) than for the rest of the patients (7.6 +/- 4.1 months). Two of three patients with an initial symptom of dyspnea were misdiagnosed. Three patients underwent laminectomies because of misdiagnosis. Age, stage of disease, and unusual presenting symptoms were not identified as causes of misdiagnosis. Most likely causes were physicians' failure to consider the diagnosis and lack of familiarity with the common clinical presentations of amyotrophic lateral sclerosis. Earlier diagnosis of amyotrophic lateral sclerosis may help prevent medical mismanagement and may benefit patients both medically and psychologically.

Effect of inspiratory resistance and theophylline on respiratory muscle strength in patients with amyotrophic lateral sclerosis.

The effect of breathing through inspiratory flow resistive loads ranging between 4.5 and 27.0 cm H2O/L/s was assessed in eight patients with amyotrophic lateral sclerosis (ALS) and in eight control subjects. ALS patients developed respiratory muscle fatigue manifested by significant declines in negative inspiratory pressure (18.3%), vital capacity (7.2%), and peak inspiratory flow rate (5.5%). Control subjects did not fatigue with these resistances. In ALS patients, theophylline increased respiratory muscle strength after resistive breathing as manifested by an increase in negative inspiratory pressure (28.2%), vital capacity (10%), and peak inspiratory flow rate (11.8%). It is concluded that in patients with ALS, the already weakened respiratory muscles are easily fatigued. Furthermore, theophylline can strengthen loaded respiratory muscles in patients with ALS.

Arterial oxygen saturation during Nd:YAG laser photoresection of endobronchial tumors under local anesthesia. Use of intermittent supplemental oxygen with pulse oximetry guidance.

Although Nd:YAG laser photoresection of endobronchial lung tumor can result in significant arterial oxygen desaturation, oxygen supplementation during procedures is often limited due to fear of intrabronchial combustion. We gave intermittent pulse supplemental oxygen to ten patients during 26 laser procedures performed under local anesthesia using SaO2 measured by a pulse oximeter as a guide. In four procedures (15.4 percent), severe oxygen desaturation contraindicated performing or completing laser phototherapy. In the remaining 22 procedures (84.6 percent), laser photoresection was safely and successfully performed without incident. Thus, pulse oximetry is a valuable tool and intermittent oxygen supplementation with pulse oximeter guidance an effective technique for maintaining adequate oxygenation during laser photoresection.

Apnea testing in brain death.

A standardized protocol was followed in 33 apneic oxygenation tests on 20 patients suspected of being brain dead. Spontaneous respiratory movements developed in just one patient; this patient was the only one who did not show electrocerebral silence on electroencephalography. Significant hypoxemia, hypotension, or cardiac arrhythmias were not encountered despite lung disease in 14 of our 20 patients. The apnea test protocol employed proved to be safe and sensitive. With a starting partial arterial carbon dioxide pressure greater than or equal to 36 mm Hg and a disconnection time from the ventilator of ten minutes in a normothermic patient (greater than or equal to 36.1 degrees C [greater than or equal to 97 degrees F]), the pressure threshold of 60 mm Hg should be reached in all patients.

Sleep, sleep apnea and the fibromyalgia syndrome.

A patient who presented with primary fibromyalgia syndrome (PFS) was found to have sleep apnea. Since frequent wakening and nonrestorative sleep are prominent clinical complaints in both disorders, we hypothesized an etiologic relationship. A subsequent clinical survey of 11 additional sleep apneics revealed that 3 (27%) fulfilled proposed criteria for PFS. This was significantly greater than local and literature reported studies of nonrheumatologic patients and was comparable to reported prevalence of fibromyalgia in rheumatologic referral populations. A blinded sleep physiology study of 7 patients with PFS revealed a significantly increased percentage of transitional sleep and increased frequency of miniarousals/h, but no significant evidence of occult sleep apnea compared to matched normal controls. The frequent arousals of sleep apnea may be associated with fibromyalgia in some patients but do not explain the sleep disorder of PFS.

A "saw-tooth" pattern in Parkinson's disease.

A patient with severe Parkinson's disease had a maximum inspiratory and expiratory flow-volume loop showing a "saw-tooth" pattern. It is concluded that this sign is not specific for the sleep apnea syndrome.

A computer program for the interpretation of hemodynamic pressures.

A computer program for the interpretation of data obtained during hemodynamic monitoring suitable for running on many commonly available microcomputers is presented. Potential modifications of the program are discussed.

Effect of naloxone on ventilatory control in parents of victims of sudden infant death syndrome.

To determine whether the decreased responses to CO2, hypoxia, and flow resistive loads in parents of sudden infant death syndrome (SIDS) victims are due to an effect of endogenous opioids, we tested response to these stimuli in 10 parents (5 couples) of such children after injection of saline placebo and after injection of naloxone hydrochloride (3 mg). The responses after saline were comparable to those of our previous study, i.e., lower than normal. Ventilatory response to CO2 and hypoxia, as well as airway occlusion pressure responses to flow resistive loading, were not significantly different after naloxone compared with saline. We concluded that increased endogenous opioids do not play a significant role in these subjects' reduced ventilatory drive.

Sleep deprivation decreases ventilatory response to CO2 but not load compensation.

Because sleep is known to reduce ventilatory drive, and sleep deprivation is a common accompaniment to ventilatory failure, we tested ventilatory response to carbon dioxide (delta V1/delta PCO2) and response to an inspiratory flow resistive load (change in delta P100/delta PCO2 with load) after both a normal night of sleep and after 24 hours of sleep deprivation in 13 healthy volunteers. Sleep deprivation was associated with a significant decrease in delta V1/delta PCO2 from 2.51 +/- .36 to 2.09 +/- .34 L/min/mm Hg (p less than 0.02). However, load compensation was preserved during sleep deprivation. Since many acutely-ill patients are sleep deprived, an associated reduction of ventilatory drive may play a role in progressive respiratory insufficiency.