We report a case of herpetic brainstem encephalitis (HBE) retrospectively diagnosed in adult patient. Clinical and neuroimaging features were reviewed and the treatment and outcomes of the neurologic syndromes evaluated. External ophthalmoplegia is a rare clinical presentation of classical brainstem encephalitis and is usually transient. Brain CT showed brain swelling, predominantly in the posterior fossa, and bilateral subdural effusion. On the 9th hospital day, he suddenly developed respiratory arrest, and his consciousness state deteriorated to coma. This is the first case reporting a recurrence of ocular symptoms in an anti-GQ1b antibody negative patient with BBE. The brains of the mice inoculated with the clinical isolate showed brainstem and cerebellar demyelination.
However, after the discontinuation of acyclovir therapy, peripheral facial palsy occurred on the left side. Ashley), Children’s Hospital, University of Washington, Seattle, WA; and Rose Medical Center (Dr. She was discharged without any neurologic sequelae. A complete remission was achieved 3 days after the treatment. Conclusions. Neurological symptoms gradually improved on the therapy of aciclovir and adrenal cortico-steroid. We will discuss the symptoms and treatment of reported pediatric cases of anti-GQ1b antibody negative cases of MFS and the variation between cases representing a spectrum of illness.
She underwent an uneventful recovery and returned to baseline and did not have seizure recurrence until 6 years later. Most commonly, this syndrome is associated with anti-GQ1b antibodies [4–6]. As there was no evidence of extrahepatic manifestation we decided to perform a transarterial chemoembolization (TACE) of the hepatic lesions. There have been rare episodes described of negative anti-GQ1b antibody cases of MFS, with no recurrences of symptoms reported. In this report, we describe the first anti-GQ1b antibody negative case with recurrent symptoms. These symptoms were quickly followed by wheezing and dyspnea, diagnosed as an episode of bronchial asthma. On examination, he showed an alert mental state and, except for a high fever, vital signs within normal limits.
Atypical brainstem encephalitis caused by herpes simplex virus 2. MRI brain showed only minor atrophic changes (fig 1). In this communication, we report the clinical spectrum of these patients seen during the post-monsoon period in 1998 in a JE endemic area. He had a prior six-month history of weekly headaches located in the frontal region that lasted for up to 30 minutes at a time and were responsive to therapy with ibuprofen and cold compresses. Of the remaining 8 patients, 1 presented with a neurologic relapse following HSVE, and 7 had a partial phenotype (cases 39–46; 2 male; age range 1–18 years, median 11 years; see ). Bilateral knee and ankle jerks were sluggish with bilateral extensor plantar. A review of systems demonstrated no obvious weakness, sensory changes, dysarthria, or dysphagia.
He had no systemic symptoms on presentation: cough, rash, joint pains, or night sweats. An optometry exam 6 months prior to admission was normal. He was not taking any medication on a daily basis. On initial examination he was alert and cooperative. He was afebrile with normal vital signs. His pupils were equal and reactive, his visual fields were normal, and normal visual acuity was documented. Examination of the extraocular movements revealed slight left-sided esotropia.
He had dysmetria bilaterally with the finger-to-nose test. He was ataxic, with poor balance, and unable to perform a tandem gait. The rest of the neurological and general examinations were unremarkable. Initial investigations, which included complete blood count, electrolytes, and CT brain scan, were normal. Over the next 24 hours his clinical status continued to evolve; he developed a severe holocephalic throbbing headache and had dysconjugate eye movements in all directions, followed by a decrease in level of consciousness. On upward gaze, downbeat vertical nystagmus was elicited and horizontal diplopia noted on bidirectional lateral eye movements. Deep tendon reflexes remained normal.
Ophthalmological evaluation showed visual acuities of 20/50 OD and 20/30 OS, as well as convergence retraction nystagmus. Fundoscopy was normal. Thereafter, she had with progressive improvement of fever and seizures, but cognitive deterioration and new onset left hemiparesis persisted. A lumbar puncture was completed 48 hours after presentation. Cerebrospinal fluid analysis (CSF) revealed 1 RBC, 0 WBC, glucose 3.0 mmol/L (normal range 2.2–3.9 mmol/L), and protein 0.14 mmol/L (normal range 0.15–0.45 g/L). CSF bacterial culture was negative. CSF viral PCR studies completed for herpes simplex virus, varicella zoster virus, enterovirus, and parechovirus were all negative.
Acetylcholine receptor antibody testing was negative. Thus, brain MRI could not detect abnormalities in more than two-third of the patients with Bickerstaff’s brainstem encephalitis. An electroencephalogram (EEG) was normal for age. Examination findings were considerably improved with minor gait ataxia and slight gaze evoked nystagmus bilaterally. Epileptiform activity was present in 1 patient only. The patient was unable to tolerate further testing including more proximal NCS testing (e.g., face) or EMG testing. Patients who were treated late (n = 2) or untreated (n = 1) had either a poorer outcome or persistence of symptoms.
Review of the literature showed aseptic meningitis as most reported neurological complication in Kikuchi-Fujimoto disease. Aseptic lymphocytic meningitis was described in 9.8% cases in Japan. Following this workup it was felt that BBE was the most likely diagnosis. Due to his complete ophthalmoplegia, treatment with intravenous immunoglobulin (IVIG) for a 5-day treatment period (total dose 2 grams/kg of body weight) was commenced. After his 5-day treatment course with IVIG, the patient’s headaches and level of mentation improved and so he was discharged. At the time of discharge, he had small amplitude vertical gaze bilaterally but still had severe ophthalmoplegia. On follow-up at two weeks, he had progressive improvement of his symptoms; however he had a reoccurrence of diplopia one month after his initial presentation. He had residual deficit of abduction in left gaze and moderately large comitant esotropia (40 prism diopters in near fixation and 45 prism diopters for distance fixation).
He was treated with a 5-week tapering dose of prednisone (40 mg initial dose tapering over 5 weeks). During this time, his ocular motility improved significantly. His long-term follow-up needs included prophylaxis therapy with amitriptyline for migraine headaches. Complete external ophthalmoplegia without ptosis is rarely described in pediatric neurology. The causes of this phenomenon are varied and may involve the neuromuscular junction (e.g., myasthenia gravis), the oculomotor nerves (e.g., MFS, Guillain-Barré syndrome), or the brainstem (BBE, Wernicke’s syndrome) [6, 7]. In the context of this patient, other disorders that were considered included viral encephalitis, ophthalmoplegic migraines, and acquired nonaccommodative esotropia of childhood. Both BBE and MFS have been associated with anti-GQ1b antibodies and Campylobacter jejuni gastroenteritis [3–6].
BBE is described in patients presenting with progressive, symmetric ophthalmoplegia and ataxia, as well as a disturbance of consciousness [5, 8]. Patients with MFS have ophthalmoplegia, ataxia, and areflexia [3, 8]. Additionally, patients with these findings and hypersomnolence have BBE [3, 8]. EEG slow wave activity and hyperintense foci on T2 weighted MRI images have been reported in BBE . Regarding pathology findings in the brain tissue, microscope appearance of HSVE differs between the acute to chronic phase. The levels of antibodies are typically at their peak when neurological symptoms are most profound and then decrease over time . The exact pathophysiology behind anti-GQ1b antibody syndromes remains unknown; however it is postulated that infectious organisms such as Campylobacter jejuni have structurally homologous antigens to human gangliosides which have been found to concentrate in the neuromuscular junction and glial cells [2, 6, 9].
Through molecular mimicry, the cellular immune system identifies both the gangliosides and the infectious agent as foreign antigens. The host immunoglobulins bind to the detected “foreign” antigens resulting in the activation of the membrane attack complex and may lead to injury of nerve terminals and the destruction of Schwann cells . In a case of anti-GQ1b negative MFS or BBE, there may be another antibody against gangliosides that is causing the development of symptoms; however these antibodies have not yet been identified . A case of recurrent Bickerstaff’s Brainstem Encephalitis with an overlap of Guillain-Barre syndrome. Some features were typical of MFS, including the acute onset of ataxia and ophthalmoplegia; however, reflexes were present, and the presence of headache and drowsiness were prominent features suggestive of BBE (however, the MRI and EEG were normal). This extends the recommendations of Fodor et al6 who recommended checking PCR in cases where examination was non-focal and CT negative.