A 76-year-old man, who received atezolizumab for the treatment for small cell lung cancer, acutely developed limb weakness with sensory disturbance after the third course of the treatment. Nerve conduction studies were consistent with demyelinating polyneuropathy and acute demyelinating polyneuropathy caused by atezolizumab was suggested. Atezolizumab was immediately withdrawn, and intravenous immunoglobulin (IVIg) and methylprednisolone pulse therapies with subsequent oral administration of prednisolone were initiated, after which neurological deficits steadily improved. Although Guillain–Barré syndrome-like neuropathy caused by immune checkpoint inhibitor (ICI) was occasionally reported, this is the first case of acute demyelinating polyneuropathy triggered by atezolizumab, monoclonal antibody targeting programmed death-ligand 1. This case suggests that combined treatments with IVIg and corticosteroids are effective for neuropathy induced by atezolizumab as same as those by other ICI.
A 76-year-old man with renal cell carcinoma exhibited consciousness disturbance and high fever after two cycles of combination therapy with ipilimumab and nivolumab. His cerebrospinal fluid (CSF) showed a protein concentration of 385 mg/dl, a cell count of 147/mm3, an interleukin-6 concentration of 1,280 pg/ml, and an adenosine deaminase concentration of 24.8 U/l. Contrast-enhanced FLAIR images were notable for diffuse meningeal enhancement. He was diagnosed with meningoencephalitis caused by an immune-related adverse event from immune checkpoint inhibitors (ICIs). His symptoms improved after repeated intravenous methylprednisolone pulse therapy and oral prednisolone. The meningeal enhancement disappeared, and the CSF findings became almost normal. As consciousness levels improved, we observed quadriplegia and peripheral neuropathy with antiganglioside antibodies, which led to a diagnosis of polyradiculoneuropathy. This is a rare case of a patient with overlapping meningoencephalitis and polyradiculoneuropathy induced by ICIs.
Laminopathy, caused by mutations in the LMNA gene, include a variety of diseases, such as Emery–Dreifuss muscular dystrophy. A Japanese woman developed progressive muscle weakness, muscle atrophy and joint contractures of upper and lower limbs after the age of two years old. She had restrictive respiratory dysfunction, and developed both supraventricular and ventricular arrhythmias after the fourth decade of life. At 55 years old, she had tracheostomy, required mechanical ventilation and was implanted with the implantable cardioverter defibrillator. The serum level of creatine kinase was within normal range. Electromyography showed polyphasic or large motor unit potentials and reduced interference pattern, while relatively normal recruitment. The exome analysis of disease-related genes revealed a heterozygous pathogenic variant c.1072G>A (p.E358K) in the LMNA gene, which contributed to the diagnosis of laminopathy.
An 86-year-old man was admitted for the abrupt onset of right hemiparesis and aphasia. DWI revealed the high intensity legion in the left insular cortex, and MRA demonstrated the left middle cerebral artery occlusion. Recanalization of the artery was not achieved after mechanical thrombectomy. The diagnosis of infective endocarditis was made as Enterococcus faecalis was cultured from the blood, and mobile vegetation was detected at the aortic valve by transthoracic echocardiography. The patient died from multiple organ failure at 19 days. Autopsy findings revealed fibrin-rich thrombus in the left middle cerebral artery containing neutrophils and bacteria. At the occluded site, neutrophils had intensively infiltrated into the vessel wall, and endothelial cells had partially disappeared. Moreover, disrupted internal elastic lamina was discovered. These findings could indicate that the thrombus had adhered to the vessel wall. The adhesion of the thrombus and vessel wall could be associated with unsuccessful recanalization after endovascular thrombectomy in patients with ischemic stroke due to infective endocarditis.
An 18-year-old man without familial history of neuropathy developed motor and sensory disturbance of bilateral upper limbs after maintaining shoulder abduction/external rotation and elbow flection position of both upper limbs for an hour during military training. Neurological examination and electromyography studies suggested left brachial plexopathy, although a nerve conduction study (NCS) showed mild demyelination of bilateral median nerve and right ulnar nerve. Thoracic outlet syndrome (TOS) was firstly suspected because symptoms were induced by the specific position which narrows, costoclavicular and retropectoralis minor space and cause compression of the brachial plexus; however, no findings suggesting TOS were observed on computed tomography and magnetic resonance imaging. Hence, we suspected a diagnosis of hereditary neuropathy with liability to pressure palsies (HNPP) due to having episodes of bilateral acute brachial plexopathy and mild demyelination on NCS. The diagnosis of HNPP was confirmed by the deletion of the PMP22 gene deletion.
A 35-year-old pregnant woman with mild migraine experienced thunderclap headache at 37 weeks of gestation. Her cerebral MRA showed arterial segmental narrowing of right middle cerebral artery and bilateral posterior cerebral artery. When admitted, she had no sign of eclampsia/preeclampsia. After 4 days, she had premature rupture of the membrane and gave birth by caesarean section. Caesarean section immediately resolved the headache. The postpartum course of the patient and her baby was uneventfull. One month after her onset, her cerebral MRA showed improvement in arterial segmental narrowing of cerebral artery. We diagnosed reversible cerebral vasoconstriction syndrome (RCVS) assoiated with pregnancy. Pregnancy-related RCVS develops primarily during the puerperal period, but our case was a rare case that developed just before delivery and was successful with aggressive intervention. When antepartum RCVS develops, early cesarean section with epidural anesthesia in parallel with active treatment for headache may lead to good outcomes for both mother and child.
A 77-year-old woman developed acute onset of orthostatic hypotension, urinary retention, and constipation. Neurological examination on admission showed severe orthostatic hypotension accompanied by syncope, mydriatic pupils, and attenuation of light reflexes with no abnormalities in other neurological systems. Autonomic testing revealed denervation hypersensitivity in norepinephrine (NE) intravenous infusion test and 0.125% pilocarpine instillation test, low NE in the serum, and decreased amount of sweating in quantitative sudomotor axon reflex test. These findings indicated dysfunction of postganglionic autonomic nerves. Autoimmune autonomic ganglionopathy (AAG) was diagnosed due to the presence of anti-ganglionic acetylcholine receptors. The patient was given intravenous high-dose immunoglobulin therapy (IVIg), improving orthostatic hypotension, urinary retention, and constipation. Previous reports indicated that the response to IVIg varied from case to case. Thus, this case suggests that IVIg is effective in acute-onset AAG cases.
Blau syndrome (BS) is a rare granulomatous inflammatory disease presenting in early childhood as dermatitis, arthritis, and uveitis. Here, we describe a case of hydrocephalus in a patient with sporadic BS. A 36-year-old female, with mutations in the NOD2 gene on chromosome 16, who had been diagnosed with BS at the age of 19 years, had visual impairment and required support when walking for a long time. She was admitted to our hospital due to deterioration in her walking ability and an inability to stand by herself. We diagnosed an obstructive hydrocephalus based on head MRI. The aqueductal stenosis and obstructive hydrocephalus associated with granulomatous lesions were considered in this case. After third ventricle fenestration, her standing movement and walking improved immediately.
A 74-year-old man visited our hospital with a 1-month history of awareness of wobbling while walking. Head MRI revealed fresh cerebral infarction in the territory of the right middle cerebral artery, and cervical carotid ultrasonography revealed severe stenosis at the origin of the right internal carotid artery. No left internal carotid artery could be confirmed, and no carotid canal was evident on CT of the head, suggesting congenital agenesis of the left internal carotid artery. Carotid artery stenting was performed for the stenosed right internal carotid artery that was refractory to medical treatment, obtaining a good outcome. Patients with congenital internal carotid artery agenesis show unique hemodynamics and anatomical features. Particularly in cases with cerebral infarction, an understanding of the etiology and complicated classification of disease types is needed, in addition to familiarity with comorbidities.