Total locked-in syndrome in a severe course of acute polyradiculoneuritis

This is an unauthorised machine translation into English made using the DeepL Translate Pro translator. The editors do not guarantee that the content of the article corresponds fully to the original language version.

Dear Editor,

The locked-in syndrome is characterized by quadriplegia and therefore communication with the patient is possible only by vertical eye movement or eyelids. It is a binary communication -⁠ movement of the eyeball in one direction means yes and in the opposite direction means no. If no more free movements are possible, then it is a total locked-in syndrome. However, in these patients there is no disorder of consciousness, on the contrary, communication with them is possible. A number of possible communication methods have been reported -⁠ e.g. using functional MRI, and based on the principle of binary communication [1]. In most patients with locked-in syndrome, the cause is ischemia in the brainstem region, often with thrombosis of the a. basilaris. Other causes include Guillain-Barré syndrome (GBS) [2]. In these patients there is no brainstem disorder but severe lesions of the roots and peripheral nerves, including the cranial nerves. Adequate function of the brain -⁠ the cerebral cortex -⁠ can be inferred from EEG monitoring and the brainstem can be tested by brainstem auditory evoked potentials (BAEP). A patient with severe GBS and total locked-in syndrome was admitted to our intensive care unit (ICU).

A 66-year-old man was transferred from the catchment hospital to the neurological ICU with the presentation of flaccid paraparesis with auditory disturbance 3 days earlier, first in the lower limb (LH) acre, then with ascending spread of paresis and auditory disturbance, and on the day of transfer he was already developing respiratory insufficiency (saturation 82%), severe quadriparesis, dysarthria and dysphagia. According to the documentation, it was a demyelinating type of acute polyradiculoneuritis with liquor findings (protein 0.9 g/ l and leukocytes 20/ 3, and according to the Topelex workup, mild pleocytosis with lipovatous reaction and serous inflammatory activation in the lymphocytic series and with ascending spread were present).

Our patient had been treated for 10 years for type 2 diabetes mellitus and had been on a combination of oral antidiabetic agents with insulin (dapaglifozine 10 mg 1×1, insulin degludec 28 j. 1-0-0) for 3 years. He was also treated for arterial hypertension (perindopril 2 mg) and hypercholesterolemia (atorvastatin 20 mg 0-0-1).

On admission, he was dysarthric, silent and intelligible speech, isochoric, no oculomotor disturbance, decreased corneal reflexes, flatter facial expressions on the left, and briefly raised his head above the mat, only very limited palatal arches raised bilaterally, no elevation of upper limbs (HK) above the mat, grip only hinted at, DK only hinted at hip joint movement, RR C5-8, L2-S2 extinguished, with diffuse reading impairment of HK and DK. Blood pressure 120/ 100, heart rate 120/ min, saturation 82-84%.

Ultrasound examination of the heart showed normal left ventricular function with ejection fraction 75%, no signs of dilatation and diastolic dysfunction grade 2. X-ray of the lungs and heart was without signs of congestion.

Laboratory showed fluctuating glycaemia (4.10-9.90 mmol/l). According to Astrup -⁠ pH 7.351, pCO2 7.73 kPa, pO2 8.53 kPa, ABE 3.9 mmol/ l. There was evidence of anti-GD1b in the serum (weakly positive values), but no evidence in the liquor.

Head MRI was performed with the following sequences: axial plane T2 weighted images, fluid attenuated inversion recovery (FLAIR), susceptibility weighted images (SWI) and diffusion weighted images (DWI); sagittal plane T1 weighted images; coronal plane FLAIR images. The findings were age-appropriate except for inflammatory changes in the lateral nasal and mastoid sinuses, with no focal involvement or other signal acute changes (Figure 1).

On MRI of C section were spacious: spinal canal, degenerative changes C4-7, no signs of myelopathy

On brain CT and CTA -⁠ findings were normal, including vertebrobasilar duct.

On admission to ICU, intubation was performed, sedation (sufenta and propofol), intravenous immunoglobulin injection (total 200 g over 5 days). After 7 days, sedation was withdrawn, but the patient was still without signs of motor activity. A new lumbar puncture was performed -⁠ protein 3.8 g/ l (norm 0.2-0.45), lactate 2.25 mmol/ l (norm 0.4-2), leukocytes 31/ 3. EEG was performed twice. The graph was dominated by diffuse activity from the alpha to theta band bilaterally, quite often intermittently interrupted by waves from the delta band, without lateralization. We judged this finding to be consistent with encephalopathy of moderate severity or locked-in syndrome. On neurophysiological examination, motor and sensory neurography were unresponsive (n. medianus and n. ulnaris left, n. peroneus and n. tibialis left, n. facialis left). Blink reflex without response. BAEP showed lower wave amplitudes and normal I-V wave latencies (Figure 2).

Due to repeated infections with febrile illnesses (pulmonary, urinary tract), he was repeatedly treated with combinations of antibiotics.

After 19 days of admission, the patient's condition began to improve. Photoreactions appeared, he was motorically responsive to suction, he was twisting his head, and he was trying to articulate with his lips when repeatedly challenged. In the following days, febrile and gradually septic state with renal insufficiency developed again. The patient was transferred to ARO. The patient did not undergo the recommended follow-up EMG and MRI of the C section and plexus with gadolinium administration. After 47 days of admission to our hospital, the patient died in the ARO department due to recurrent septic conditions.

The most common cause of locked-in syndrome is trunk ischemia in the pontomesencephalic region and there is a significant possibility of involvement of the ascending reticular formation with development of impaired consciousness. However, if the roots and nerves (both cranial and spinal) are affected, then the trunk is intact and a poor quadriplegia is present. The only preserved afferent system is hearing -⁠ the auditory nerve is not violated in acute polyradiculitis. And by using hearing, it is possible to work out the mechanisms of binary communication (e.g. by functional MRI or functional infrared spectroscopy) [3]. In patients with total locked-in syndrome, cortical activity is intact, whereas the vegetative state is characterized by an unchanging delta rhythm during the day [4]. EEG is useful for long-term monitoring of these patients [5]. In our patient, we demonstrated good activation of the cerebral cortex underlying BAEP. On repeated EEG examinations, alternating alpha, delta and theta rhythms were noted, consistent with an encephalopathy of moderate severity, locked-in syndrome. The findings were not suggestive of coma vigile or persistent vegetative state.

Patients with locked-in syndrome have a high mortality rate. In patients with trunk ischemia (e.g., thrombosis of the a. basilaris), there is widespread ischemia and involvement of the reticular formation in the trunk and other centers. In patients with root and nerve involvement -⁠ in acute polyradiculoneuritis -⁠ complications of this serious condition occur. In acute polyradiculoneuritis, disturbances of autonomic functions (arterial hypotension, hyponatremia, disturbances of intestinal motility), frequent inflammatory complications (respiratory tract, urinary infections) and nutritional problems are very common [6]. About 70% of these patients die of complications already in the resolution phase of acute polyradiculoneuritis. Northon et al [1] described two patients. The first died after 6 weeks and the second after 3 weeks following a period of artificial ventilation with discontinuation of sedation, when contact was possible by functional MRI. After this period, the first motor signs of contact began to appear, but both died of inflammatory complications of severe condition. Pfefferkorn et al [7] published a case report of a man who developed severe acute polyradiculoneuritis, including total locked-in syndrome, following COVID-19 infection. However, the course of the disease was favourable -⁠ quadriplegia and oculomotor impairment gradually regressed and he was subsequently transferred to a rehabilitation clinic. ALS patients also have complete locked-in syndrome and communication is possible only by auditory stimuli [8]. Our patient started to wake up after 3 weeks with total locked-in syndrome. But then he developed inflammatory complications from which the patient died 57 days after intubation.

In the differential diagnosis of the causes of locked-in syndrome, trunk CMP is the most common, especially with thrombosis of the a. basilaris and its branches. Other known causes include tumors in the trunk and posterior fossa, inflammation, demyelinating lesions (RS, neuromyelitis optica, anti-MOG), infection or intoxication [9].

The case report of acute polyradiculoneuritis with development of total locked-in syndrome is important information. The patient is unable to make any movement. Yet he has good function of both the brainstem and the cortex, which can be demonstrated quite easily by BAEP and EEG. Communication with the patient is possible thanks to sophisticated neurophysiological methods -⁠ e.g. functional MRI. Although the prognosis for most of these patients is serious, some of them will gradually improve. These patients then undergo long-term rehabilitation of residual flaccid quadriparesis.