Bickerstaff Brainstem Encephalitis with a Decorticate-like Posture, Involuntary Movements, Impaired Visual Acuity, and Prolonged Motor Disability

Abstract

The acute immune-mediated disorder, Bickerstaff brainstem encephalitis (BBE), is characterized by consciousness disturbance, external ophthalmoplegia, and ataxia. BBE is usually readily diagnosed and patients recover well, but rare features may sometimes obscure the diagnosis, and some patients develop prolonged weakness. We herein describe a Japanese patient with BBE who presented with uncharacteristic features of a decorticate-like posture, involuntary movements, and impaired visual acuity, entered a coma requiring intubation, and later required orthosis-assisted ambulation for 10 months. Despite these uncharacteristic features, the typical triad and other BBE characteristic features can be valuable for making an early diagnosis. BBE with a coma or intubation may therefore occasionally lead to prolonged weakness.

Introduction

Bickerstaff brainstem encephalitis (BBE) is an acute immune-mediated disorder characterized by the typical triad of consciousness disturbances, external ophthalmoplegia, and ataxia (1-3). In addition to this triad, antecedent infectious symptoms, oropharyngeal palsy, either absent or decreased tendon reflexes, and sensory disturbances at the distal extremities are often observed and regarded as characteristic features of BBE (4). In laboratory tests, serum IgG anti-GQ1b antibodies, which are present in more than two-thirds of all BBE patients at diagnosis, serve as objective evidence of BBE and together with the typical triad, are required to make a diagnosis of definite BBE (3-5).

Although the diagnosis of BBE is usually straightforward when a typical triad is present, diagnostic certainty may be questioned in BBE patients who exhibit rare features early in the course, especially before antibody confirmation, since uncharacteristic features of BBE are still not well recognized (6-12). Moreover, although most patients with BBE have a monophasic remitting course with a good recovery, a subset of patients experience limb weakness lasting more than six months; the characteristics of these patients remain unclear (3,4,13-17).

We herein report the case of an adult male with BBE who presented with the uncharacteristic features of a decorticate-like posture, involuntary movements, and impaired visual acuity and subsequently developed prolonged foot drop, which required orthotic support for 10 months.

Case Report

A previously healthy 33-year-old Japanese man was admitted to our hospital with a rapidly progressive consciousness disturbance, external ophthalmoplegia, ataxia, and dysarthria. He had developed a sore throat and hoarseness 4 days earlier, consistent with an upper respiratory tract infection. The day before his presentation, he complained of numbness in his distal limbs and difficulty in walking. The following morning, dysarthria and generalized weakness developed.

On arrival at our hospital (Day 1), his body temperature was 39.5°C. He appeared drowsy and had a Glasgow Coma Scale score of E3V4M5, which made it difficult to reliably evaluate his distinct muscle strength. He had limitations in the abduction of both eyes, but no ptosis or nystagmus. Slurring of speech and appendicular ataxia were observed in all limbs. His deep tendon reflexes were generally reduced and no pathological reflexes were observed. No signs of meningeal irritation were observed.

The results of blood tests on admission were unremarkable, except for mild leukocytosis (9,800 /μL) and a mildly elevated C-reactive protein level (0.36 mg/dL). The tests included measurements of thyroglobulin, thyroid peroxidase, thyroid-stimulating hormone, soluble interleukin-2 receptor, β-D-glucan, and T-SPOT.TB and autoantibodies (antinuclear antibody, Sjögren's syndrome A antigen, Sjögren's syndrome B antigen, single-stranded DNA, double-stranded DNA, proteinase 3-anti-neutrophil cytoplasmic antibody, myeloperoxidase-anti-neutrophil cytoplasmic antibody, glutamic acid decarboxylase, aquaporin-4, and myelin oligodendrocyte glycoprotein). A cerebrospinal fluid (CSF) examination revealed 12 cells/μL (mononuclear/polymorphonuclear=9/3), a protein concentration of 35 mg/dL, and a CSF:serum glucose ratio of 0.58. Magnetic resonance imaging (MRI) of the brain revealed no abnormalities. Since the CSF:serum glucose ratio did not decrease, viral encephalitis and autoimmune encephalitis were primarily suspected in this immunocompetent patient. Intravenous acyclovir was administered until a subsequent polymerase chain reaction test of the patient's CSF was negative for herpes simplex virus-1 and varicella-zoster virus. The patient was then admitted for further evaluation.

On Day 2, the patient's condition deteriorated. The patient lapsed into a coma and exhibited a decorticate-like posture in response to noxious stimuli. He lost the corneal and eyelash reflexes, had dilated pupils that were sluggishly reactive to light, and showed an absent gag reflex. The patient developed aspiration pneumonia, and as his oxygenation deteriorated, endotracheal intubation was performed. Although BBE was suspected, the presence of a rare, uncharacteristic feature of a decorticate-like posture made the diagnosis uncertain. Other forms of autoimmune encephalitis were also considered, and intravenous methylprednisolone pulse therapy (1,000 mg/day for 3 days) was administered (Figure).

Figure.

The clinical course of the patient, a 33-year-old male, who demonstrated independent ambulation without orthoses at the time of admission. ACV: acyclovir, IVIg: intravenous immunoglobulin, IVMP: intravenous methylprednisolone, PE: plasma exchange

Due to the fact that the patient showed no improvement, plasma exchange was initiated on Day 4. However, no clinical response was observed after three sessions. Because of adverse effects suspected to be related to plasma exchange, including a marked decrease in his fibrinogen levels and the development of a skin rash, intravenous immunoglobulin (0.4 g/kg/day for 5 days) was initiated on Day 11. On Day 13, a high level of serum IgG anti-GQ1b antibodies was detected in the patient's pre-treatment serum. Therefore, he was diagnosed with definite BBE based on the diagnostic criteria for BBE (4). Among other anti-ganglioside IgG antibodies, IgG anti-GD1a, GT1a, and GT1b antibodies were also positive.

On Day 16, although the patient's consciousness disturbance persisted, he began to show spontaneous movements such as head shaking, arm flexion and extension, ballistic movements, and oral dyskinesias that continued until Day 23. On Day 20, the patient was able to follow simple instructions such as opening and closing his eyes and grasping the examiner's hands several times. Over the next several days, he gradually expressed his intentions, responding to closed questions with nodding or head-shaking. On Day 28, he expressed his intentions by mouth movements, and on Day 38, he was able to communicate verbally through a speaking cannula; he was also aware of his impaired visual acuity and photophobia. Although a comprehensive ophthalmologic assessment could not be performed due to the patient's poor general condition, his visual acuity was limited to finger counting at 1 meter at that time, and his visual symptoms gradually improved without any additional treatment.

Once the patient was able to communicate verbally, he complained of numbness and hyperalgesia in his limbs, and was unable to dorsiflex either foot. His muscle weakness was symmetrical and flaccid, and he tested positive for antiganglioside IgG antibodies. Based on previous reports regarding BBE, the limb weakness in this patient was attributed to BBE (3,4). Other causes of weakness, such as critical illness neuropathy or compressive peroneal neuropathy, were deemed unlikely because the patient had numbness and hyperalgesia in his limbs, with a Medical Research Council sum score of 48/60, and he was therefore regularly repositioned every four hours. Nerve conduction studies were performed, but were limited to the patient's right side due to severe pain. In the peroneal nerve, no compound muscle action potential was elicited when recording the extensor digitorum longus. When recording from the tibialis anterior, the compound muscle action potential was reduced to 1.46 mV, whereas the distal motor latency and motor conduction velocity were within the normal limits. The other nerves, including the median, tibial, superficial peroneal, and sural nerves, were normal.

Despite undergoing rehabilitation, the patient's limb weakness persisted, and he was unable to walk independently. The patient was transferred to a rehabilitation hospital on Day 55. After transfer, lower-limb orthoses were prescribed, and the patient continued rehabilitation. On Day 132, the patient was able to ambulate independently without the use of orthoses. He resumed work as a system engineer at 6 months, regained independent ambulation without orthoses at 10 months, and at 2 years and 6 months, his only residual symptom was numbness in the toes.

Discussion

We describe the case of a patient with BBE who presented with the uncharacteristic features of a decorticate-like posture, involuntary movements, impaired visual acuity, and the subsequent development of prolonged foot drop requiring orthotic support for 10 months. When considered together with previous reports, this case suggests two important clinical implications: (i) despite uncharacteristic features, the typical triad (consciousness disturbance, external ophthalmoplegia, and ataxia) and other characteristic findings can be valuable for making an early diagnosis, and (ii) among BBE patients with a severe disturbance of consciousness or requiring intubation, a subset may experience prolonged limb weakness.

Our patient exhibited features that were not characteristic of BBE: namely, a decorticate-like posture, involuntary movements, and impaired visual acuity. The uncharacteristic decorticate-like posture reduced diagnostic certainty in the early phase, which was attained only after IgG anti-GQ1b antibody positivity provided objective confirmation. Nevertheless, the patient also showed the typical triad, as well as characteristic features such as antecedent infectious symptoms, decreased tendon reflexes, and sensory disturbances in the distal extremities. It is well established that BBE is characterized by a triad of disturbances of consciousness, external ophthalmoplegia, and ataxia. In representative clinical studies, each component of this triad was observed in 90-100% of patients, while the other characteristic features were frequently observed (3-5).

Table 1 summarizes the reported cases of BBE with a decorticate-like posture, involuntary movements, and impaired visual acuity (6-12). These reports showed that eight (88.9%) of the nine patients, including the present patient, had a consciousness disturbance, all nine patients had external ophthalmoplegia, all six evaluable patients had ataxia, and eight (88.9%) had other characteristic BBE features beyond the typical triad. In our patient, a decorticate-like posture was observed before diagnostic confirmation. Previous case reports have shown that involuntary movements and impaired visual acuity can develop before diagnostic confirmation (6,10,11). Taken together, even in the presence of uncharacteristic features, the typical triad and other BBE-characteristic features may be observed at frequencies similar to those reported in previous studies, and the recognition of these features can still support an early diagnosis.

Table 1.

Clinical Features of the Present and Reported BBE Patients with Uncharacteristic Features.

Age/sex	Uncharacteristic features	Consciousness disturbance	External ophthal-moplegia	Ataxia	Other characteristic features*	GQ1b antibody	Ref.
33 M	Decorticate-like posture, facial, neck and limb involuntary movements, impaired visual acuity	+	+	+	Antecedent infectious symptoms, decreased tendon reflex, sensory disturbance	+	This case
17 M	Decorticate-like posture, facial and limb involuntary movements	+	+	n.a.**	Antecedent infectious symptoms	n.a.	(6)
72 F	Decorticate-like posture, impaired visual acuity	+	+	n.a.**	Antecedent infectious symptoms	+	(7)
25 M	Decorticate-like posture	+	+	+	Antecedent infectious symptoms, decreased tendon reflex, sensory disturbance	+	(8)
29 F	Facial and limb involuntary movements	+	+	+	Decreased tendon reflex	+	(9)
20 F	Facial, neck, and limb involuntary movements	+	+	n.a.**	-	+	(10)
54 M	Impaired visual acuity	+	+	+	Antecedent infectious symptoms, oropharyngeal palsy, sensory disturbance	+	(11)
57 F	Impaired visual acuity	+	+	+	Antecedent infectious symptoms, oropharyngeal palsy, decreased tendon reflex, sensory disturbance	+	(12)
67 F	Impaired visual acuity	-	+	+	Decreased tendon reflex, sensory disturbance	+	(12)

*Characteristic features include antecedent infectious symptoms, oropharyngeal palsy, absent or decreased tendon reflex, and sensory disturbance.

**Ataxia could not be evaluated because of consciousness disturbance. BBE: Bickerstaff brainstem encephalitis, n.a.: not applicable, Ref.: reference

Several mechanisms may be considered with regard to the pathophysiology of uncharacteristic neurological manifestations. An impairment of consciousness in BBE has generally been attributed to the dysfunction of the ascending reticular activating system in the midbrain and upper pons (18). Although no lesions were detected on MRI in our patient, a similar functional disturbance was possible. Decorticate-like posturing can occur with diffuse cerebral dysfunction, and some reports have noted that it may occasionally be associated with midbrain involvement (7,19). Hyperkinetic movements, such as ballistic movements and oral dyskinesias, are considered manifestations of an abnormal output from the basal ganglia-thalamo-cortical motor circuits (20). Collectively, these findings suggest that a transient and functionally widespread disturbance involving the brainstem arousal pathways and adjacent motor networks likely occurred in this patient. The patient exhibited impaired visual acuity and photophobia, but a detailed ophthalmologic examination could not be performed. Therefore, the precise lesion could not be determined. Previous reports have suggested that IgG anti-GQ1b antibodies could affect the optic nerve, and a similar mechanism might have contributed to his transient visual symptoms (7,11).

The present patient was characterized by prolonged limb weakness due to BBE. The reported frequency of limb weakness among BBE cases is 50-60%, and earlier investigations indicated that some patients with BBE show prolonged limb weakness, with a persistent inability to walk independently (3-5,13). Nevertheless, the clinical characteristics of patients with BBEs who experience long-term motor disability have not been fully clarified. Based on reports of adult BBE patients with limb weakness lasting more than 6 months, together with the present case, four (80%) of the five patients developed coma, and all five required intubation after admission, as shown in Table 2 (14-17). In contrast, it has been estimated that 20-30% of BBE patients experience coma, and 15-35% require intubation (3-5,21). Among the BBE patients with a severe consciousness disturbance or those requiring intubation, a subset can experience prolonged limb weakness.

Table 2.

Clinical Features of BBE Patients with Prolonged Limb Weakness.

Age/sex	Disability	Coma	Intubation	IgG GQ1b antibodies	Other IgG antibodies	Treatment	Ref.
33 M	Bilateral foot drop until 10 mo after onset	+	+	+	GD1a, GT1a, GT1b	IVMP, IVIg, PE	This case
37 M	Assisted ventilation 4 mo after onset, and limb weakness and wheelchair-dependent 12 mo after onset	+	+	+	GT1a	PE	(14)
61 M	All limb weakness with 2-3/5 in MRC scale at 2 mo after onset, and right upper limb weakness with 3-4/5 in MRC scale at 8 mo after onset	+	+	+	-	IVIg	(15)
65 M	Limb weakness with wheelchair dependence at 5 mo after onset, and bilateral foot drop with a walking frame at 15 mo after onset	+	+	+	-	IVIg	(16)
71 F	Severe muscle atrophy and limb weakness at 17 mo after onset and death at 22 mo after onset	-	+	+	-	IVMP	(17)

BBE: Bickerstaff brainstem encephalitis, IVIg: intravenous immunoglobulin, IVMP: intravenous methylprednisolone pulse therapy, MRC: Medical Research Council, mo: months, PE: plasma exchange, Ref.: reference

All five BBE patients with prolonged limb weakness were IgG anti-GQ1b antibody-positive (Table 2). No evidence has shown that the presence of anti-GQ1b antibodies alone is associated with a poor prognosis. Antibodies against ganglioside complexes have been linked to certain clinical phenotypes (22,23). Notably, one case of Guillain-Barré syndrome, a condition that forms a continuous spectrum disorder with BBE, with anti-GQ1b/GD1b antibodies reportedly had a poor clinical course (24,25). Although the prolonged motor disability in these five patients could be related to such antibodies, ganglioside complex antibodies were not assessed in any of these cases; therefore, their involvement remains uncertain. Our patient tested positive for IgG anti-GD1a antibodies, which have been reported to be associated with poor outcomes in Guillain-Barré syndrome (26). In addition, BBE patients with limb weakness have been reported to show a higher frequency of IgG anti-GD1a antibody positivity than those without limb weakness (3), thus raising the possibility that IgG anti-GD1a antibodies might contribute to prolonged limb weakness.

A subset of patients with BBE show prolonged limb weakness, leading to a delayed resumption of daily and occupational activities. However, there is insufficient evidence to determine whether early initiation and specific immunotherapy modalities contribute to improved outcomes in these patients. To address the lack of evidence on treatment efficacy in this subset, it is necessary to improve early diagnostic certainty and better characterize BBE patients with prolonged limb weakness.

In conclusion, while the diagnostic importance of the typical triad and other BBE characteristic features is already well recognized, this case demonstrates that these features can still be valuable for making an early diagnosis, even in the presence of uncharacteristic features. Among BBE patients with a severe disturbance of consciousness or those requiring intubation, a subset may experience prolonged limb weakness.

The authors state that they have no Conflict of Interest (COI).