After the discovery of a series of autoantibodies against neuronal cell surface antigens (NSAs) of the CNS in the past 10 years, the concept of encephalitis has changed dramatically. Accordingly, a practical, syndrome-based diagnostic approach to autoimmune encephalitis was proposed in 2016. These autoantibodies have also been identified in a subset of overlapping encephalitis and demyelinating syndrome, epilepsy, first episode psychosis, movement disorders, post-herpes simplex encephalitis, progressive dementia, postpartum psychosis, stiff-person spectrum disorders, or non-REM/REM sleep behavior disorder. Although not all neuronal antibody tests are available in Japan, we have entered a new era that we have to make a correct diagnosis and start appropriate immunotherapy based on initial neurological assessment and conventional tests, without being constrained by conventional fixed ideas or normal-appearing brain MRIs while waiting for neuronal antibody test results. Although many issues need to be resolved in Japan in terms of diagnosis and treatment in autoimmune encephalitis, this review focusses on recent progress in autoimmune encephalitis and its related disorders closely related to clinical practice, including Hashimoto encephalopathy and new-onset refractory status epilepticus (NORSE).
A 77-year-old woman with lung adenocarcinoma noticed bilateral ptosis 7 weeks after a first pembrolizumab infusion. Her symptoms rapidly progressed to generalized manifestations including limb and neck weakness, dyspnea, and dysphasia within the following two weeks. We diagnosed him with pembrolizumab-related myasthenia gravis and myositis based on clinical symptoms, elevation of muscle enzymes and anti-acetylcholine receptor antibodies, repetitive nerve stimulation and muscle biopsy. We commenced combination immunotherapy, including intravenous and oral steroid therapy, immune absorption therapy and plasma exchange therapy with noninvasive positive-pressure ventilation and tracheotomy positive pressure ventilation. She had gradual symptoms improvement and discharged after 209 days in a hospital. In this case, anti-titin antibodies, one of anti-striational antibodies, was positive and correlated with severity of myasthenia gravis. With the development of immune checkpoint inhibitors for various malignancies, clinicians should closely monitor patients for important immune-related adverse events and coordinate on early treatment.
This is a case of a 71 years old man. Hemichorea appeared in the left half of his body in the middle of November, 2014. Minute hyperintense areas in the white matter near the posterior horn of the right lateral ventricle and in the right parasagittal frontal cortex was shown in MRI diffusion weighted image. Severe stenosis was seen in the right internal carotid artery, and reduction in cerebral blood flow of the right cerebral hemisphere including the basal ganglia was shown in single photon emission computed tomography (SPECT). After having carotid endarterectomy of the right internal carotid artery in January, 2015, hemichorea disappeared, and the cerebral blood flow of the right cerebral hemisphere improved. It is known that hemichorea is caused by the infarction of the basal ganglia. In recent years, some hemichorea cases are reported around East Asia caused by internal carotid artery stenosis with reduction in cerebral blood flow.
A 48-year-old man was admitted to our department with generalized convulsive seizures followed by recurrent partial clonic convulsions in the left face and arm. Convulsions stopped temporarily after administration of diazepam, fosphenytoin, and levetiracetam. However, frequent partial seizures occurred repeatedly and general anesthesia was required to control seizures. Diffusion-weighted and T2-weighted images revealed a high-intensity lesion in the right frontal lobe. A tumor-like area in the white matter showed high intensity on T2-weighted images with ring enhancement on gadolinium-enhanced T1-weighted images. An area of frontal cortex near the tumor was also enhanced. Brain surgery was performed for the purposes of diagnosis, seizure control and tumor resection. Histological findings demonstrated oligodendroglioma in the ring-enhancing area, but not in the frontal cortex. This fact indicated that contrast enhancement of the frontal cortex was caused by status epilepticus. It is important to recognize that status epilepticus could cause contrast enhancement on magnetic resonance imaging.
A 93-year-old man was admitted to our hospital with disturbance of consciousness. Brain magnetic resonance imaging (MRI) showed hyperintensity of the subarachnoid space in the left frontal and parietal lobes on diffusion weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR). Gadolinium-enhancement of the pia mater was also observed. We did not perform biopsy because of a high risk of perioperative complication. Although physical examination found no evidence of the rheumatoid arthritis, rheumatoid factors and anti-cyclic citrullinated peptides antibodies were elevated. He was suspected to have rheumatoid meningitis. We treated him with intravenous methylprednisolone (0.5 g/day) for 3 days. Rheumatoid meningitis often shows hyperintensity of the subarachnoid space on the DWI and FLAIR, and steroid therapy is effective.
We herein experienced one patient with typical branch atheromatous disease (BAD) type infarction. Digital subtraction angiography (DSA) and MRI fusion imaging revealed the relationship between atheromatous plaque and perforating branches. A 66-year-old male presented acute onset of dysarthria, the left side hemiparesis and sensory disturbance. Diffusion-weighted MR imaging (DWI) showed the right pontine acute infarction. We started to treat with dual antiplatelet therapy. However, the left-side hemiparesis was worsening on 4 days after admission. DWI showed infarct growth and plaque imaging revealed the atheromatous plaque in the basilar artery. We fused DSA and MRI T2 weighted imaging (DSA-MR fusion imaging) to illustrate the relationship between the atheromatous plaque and the perforating branches. DSA-MR fusion imaging showed that the paramedian artery and the short circumferential artery ran around and into the pontine infarct lesion. Additionally, one of the paramedian arteries was occluded. Those neuroradiological findings coincided with the pathological concept of BAD. DSA-MR fusion imaging can prove the pathological concept of BAD.
A 41-year-old woman experienced back pain upon waking up. Immediately afterward, she experienced a continual orthostatic headache. Thereafter, right ear fullness and dizziness also occurred. One month later, she became aware of repeated numbness that started in the right hand and spread to the right half of the body and lower limbs and continued for repeated periods of approximately 20–30 min. Neurological examination revealed no abnormal findings except for orthostatic headache. Electroencephalography showed no epileptic discharge. Head MRI revealed left convexal subarachnoid hemorrhage (cSAH) restricted to the prefrontal sulcus, left frontal cerebral venous thrombosis, diffuse dural thickening with gadolinium enhancement, and subdural hematoma in the posterior cranial fossa. Spinal MRI revealed epidural fluid accumulation around the thoracic spine. CT myelography revealed cerebrospinal fluid leakages at the cervical, thoracic, and lumbar vertebrae levels. The patient was diagnosed with spontaneous intracranial hypotension (SIH), which was treated effectively with a blood patch. In this case, cSAH may have resulted from rupturing of the vessel wall as a result of cortical venous thrombosis induced by SIH. The repeated transient neurologic symptoms suggesting migraine aura may have originated from cSAH, which in turn led to cortical spreading depression. The diagnosis and management of SIH can be often difficult; therefore, repeated migraine-aura-like symptoms are a critical sign of complication with cSAH and cortical venous thrombosis.
A 42-year-old woman diagnosed with multiple sclerosis (MS) at the age of 37 was initially treated with interferon-β IM. The frequency of clinical relapses was twice in 4 years. At the age of 41, due to difficulty in administering muscle injections, an oral medication fingolimod was started. However, it was discontinued after a month due to decreased lymphocyte count, following which natalizumab was administered. The number of relapses increased 3 times in eleven months, and the number of T2 lesions on the MRI increased from 12 to 23. Natalizumab was discontinued because the test for the anti-natalizumab antibody was positive. It was suspected that both, the rebound syndrome caused by fingolimod cessation and the drug neutralization by anti-natalizumab antibodies, were associated with the exacerbation of disease activity. Thus, careful attention should be paid to potential occurrence of these events post switching between disease-modifying drugs for treating MS with high activity.
We present a case of tuberculous meningitis (TBM), wherein pleural effusion developed as a manifestation of paradoxical reaction during anti-tuberculosis therapy. An 87-year-old diabetic man was referred to our clinic for fever and impaired consciousness. He did not obey vocal commands. No ocular motor deficit, facial palsy, or limb weakness was observed. He had hyponatremia due to inappropriate antidiuresis. Examination of the cerebrospinal fluid revealed lymphocytosis and high adenosine deaminase (ADA) activity, suggestive of TBM. He was treated with isoniazid, rifampicin, and pyrazinamide, after which his symptoms quickly resolved. Lymphocyte count, ADA activity, and protein concentration in the cerebrospinal fluid decreased. However, approximately 30 days after the initiation of therapy, he developed mild hypoxemia. A chest CT scan revealed pleural effusion. The pleural fluid was exudate with elevated ADA activity, which was consistent with tuberculous pleural effusion. Shortly after the use of a herbal medicine, Goreisan extract, hyponatremia and hypoproteinemia improved, and the pleural effusion was reduced. Approximately one-third of patients with TBM are reported to develop a paradoxical reaction, such as tuberculoma, hydrocephalus, and optochiasmatic and spinal arachnoiditis. The present case suggests that extra-central nervous system manifestations, including pleural effusion, should be considered when treating TBM.