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Biot's Breathing in a Woman with Fatal Familial Insomnia: Is There a Role for Noninvasive Ventilation?

Published Online:https://doi.org/10.5664/jcsm.28046Cited by:8

ABSTRACT

We present the case of a 48-year-old woman suffering from fatal familial insomnia (FFI)—a rare prion disease—who developed Biot's breathing and secondary respiratory failure during the early stages of the illness. Once hypercapnia was detected a trial of nocturnal noninvasive ventilation (NIV) was offered with important improvement of arterial blood gases (ABG), and subjective good quality of sleep. To our knowledge, this is the first report in the medical literature of the use of NIV in the management approach of this devastating disease. Its impact on the prognosis and survival of these patients, however, is yet to be elucidated.

Citation:

Casas-Mendez LF; Lujan M; Vigil L; Sansa G. Biot's breathing in a woman with fatal familial insomnia: is there a role for noninvasive ventilation?. J Clin Sleep Med 2011;7(1):89-91.

INTRODUCTION

Fatal familial insomnia (FFI) is a rare inherited prion disease described by Lugaresi et al. in 1986.1 It is a consequence of a mis-sense mutation at codon 178 of the prion protein (PrP) gene on chromosome 20,2 which causes severe thalamic damage.

The disease is characterized by a uniformly fatal course. At early stages, the majority of patients complain of vigilance troubles and inability to initiate and maintain sleep associated with dysautonomic disturbances. Progressively, hallucinatory states appear and, finally, patients fall into a persistent stupor and die.3

The duration of the disease, defined from the beginning of insomnia, varies from 8 to 72 months. Some patients die suddenly in full consciousness and others lapse into a vegetative state, with death occurring due to respiratory or systemic infection.3

Non infectious respiratory disturbances in the clinical course of FFI have been described in previous reports.4 Since most patients develop an abnormal pattern of breathing, it has been hypothesized that this could happen when structures other than the thalamus are affected.4 In fact, the majority of these disturbances have been associated with brainstem damage and a worse clinical evolution, which is related to a specific mutation of the PrP gene.5

Biot's breathing and secondary hypercapnic respiratory failure have not been described in the clinical course of FFI. We present a case of a patient who developed hypercapnic respiratory failure attributed to Biot's breathing and received noninvasive ventilation (NIV) during the early course of the disease.

REPORT OF CASE

A 48-year-old female patient with 2 relatives previously diagnosed with FFI was referred to our hospital for a management approach. She had been studied during the previous 12 months due to her inability to initiate sleep, progressive behavioral changes, and associated dysautonomia. The analysis of the PrP gene revealed the codon 178 point mutation and methionine (MET) homozygosity at position 129, confirming the FFI diagnosis.

A complete polysomnographic sleep study (PSG) showed low sleep efficiency (20%), with an absence of stages 3-4 and REM sleep. The nasal pressure showed periods of rapid shallow breathing alternating with apnea periods lasting > 10 seconds during sleep and awake stage. This pattern was equally present in the respiratory effort channels, being compatible with Biot's breathing (Figure 1).

Figure 1
Figure 1

Biot's breathing in a patient with hypercapnic respiratory failure and homozygous methionine mutation of the PrP gene.

A pattern of periodic shallow breathing (nasal pressure, into the dot line square) with equal irregularities in the respiratory effort channels (into the continuous line square) alternating with apnea periods was observed while the patient was awake. The figure shows a conventional EEG epoch of 30 sec/page and 3 channels of the respiratory analysis (nasal pressure, pulse oximetry, and the respiratory effort) during 2 minutes.

During the 2 weeks after the PSG, dysautonomia worsened and the patient fell into a stupor state. She developed severe hypoxemia and hypercapnia (pH: 7.32, PaO2: 43 mm Hg, PaCO2: 62 mm Hg) in absence of respiratory infection. It was decided to initiate NIV, and a few hours later there was an important improvement on the ABG (pH: 7.36, PaO2: 71 mm Hg, PaCO2: 44 mm Hg) with recovery of the level of consciousness. Given these results, the patient received nocturnal NIV during the following weeks. Tolerance was satisfactory, with improvement of daytime hypercapnia and the subjective perception of falling asleep with the NIV.

Two months after NIV was started the patient worsened, with increased requirements of NIV and a progressive inability to eat and communicate. Given the prognosis of the disease, and in accordance with the patient and her relative's wishes, no other procedures were considered. Seventy days after NIV was started, the patient died as a consequence of septic shock of abdominal origin due to acute dilatation of the colon (Ogilvie's syndrome), which was considered another manifestation of dysautonomia.

The pathological findings in autopsy confirmed the diagnosis of FFI. Moreover, an intense neuronal loss with widespread gliosis at the thalamus and brainstem, without spongiform changes, was identified.

DISCUSSION

In our knowledge, this is the first report where NIV has been used as part of the multidisciplinary strategy for FFI management.

Although various respiratory disturbances and sleep disordered breathing (tachypnea, irregular breathing alternating with periods of apnea, etc.) could be expected in the course of FFI due to the compromise of the brainstem—as it has been described in previous series and cases4—Biot's breathing with secondary hypercapnic respiratory failure has not been mentioned in these patients, nor has a specific management approach with ventilatory support. A possible explanation lays in the retrospective character of these series and, perhaps more importantly, the short clinical course in the classic presentation of the disease. This devastating evolution associated with breathing disturbances is, in fact, a clinicopathological phenotype that has been attributed to Met homozygosity in the codon 129 of the PrP gene (such as it was demonstrated in our case), while patients with Met/Valine heterozygosity have shown a more progressive deterioration and prolonged disease.5

In our patient, the respiratory disturbances seen in the PSG registry were observed during sleep and wakefulness and were characterized by an abnormal respiratory pattern where periods of apnea alternated with irregular breathing (both the nasal pressure and the respiratory effort channels showed an equal trace in the PSG) as a consequence of brainstem neuronal loss, which supports the diagnosis of Biot's breathing.6

The experience accumulated in the use of NIV in other respiratory disorders associated to the improvement of the ABG seen in this case, and the subjective good quality of sleep explained by the patient when she was receiving ventilatory support suggest that the main respiratory disturbances were ameliorated by the NIV (unfortunately a PSG registry with NIV could not be performed).

In summary, we believe that a systematic respiratory assessment (including a simple ABG and physical inspection) should be conducted, especially at early stages of the disease and when the Met homozygosity mutation has been demonstrated. In addition, we believe that, once the respiratory failure appears, a trial of nocturnal NIV is justified. Benefits of NIV should be assessed not only on the basis of improvement of ABG; since the impact on quality of life and sleep could be more important. These considerations are relevant for the management of other devastating diseases like advanced amyotrophic lateral sclerosis (ALS). Improvement of survival in ALS patients is documented with early respiratory assessment,7 but it remains to be answered whether this approach might improve the survival in patients with prion diseases.

DISCLOSURE STATEMENT

This was not an industry supported study. The authors have indicated no financial conflicts of interest.

ABBREVIATIONS

FFI

Fatal familial insomnia

PrP

Prion protein

NIV

Noninvasive ventilation

Met

Methionine

PSG

Polysomnography

ABG

Arterial blood gases

ALS

Amyotrophic lateral sclerosis

EEG

Electroencephalogram

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