The Japanese Society of Neurology decided to aim to convert neurology, which is currently a subspecialty of internal medicine, to a basic specialty in the Japanese medical specialty system at the special general meeting of corporate members in January 2018. Because the details of new specialty system in Japan remain unstable, the committee to promote achievement of neurology as a basic specialty planned to hold a special symposium regarding the specialty system at the 60th annual meeting of the Japanese Society of Neurology in May 2019. This article compiles the abstracts of speakers in this symposium. Speakers were from Ministry of Health, Labour and Welfare, the Japan Medical Association, and our society members. We discussed the reason why neurology should be a basic specialty, the consideration indispensable for the regional health care as a basic specialty, how to reach our goal, and problems to overcome. Based on the decision at the special general meeting of corporate members mentioned above and such discussion, we will continue making best efforts to achieve neurology as a basic specialty through negotiation with relevant players including the Japanese Society of Internal Medicine.
A 46 year-old man with schizophrenia had taken several anti-psychotic drugs since 25 years of age. From ~35 years of age, he noticed occasional neck torsion to the left, and later an ataxic gait; both symptoms gradually worsened. On admission, the patient was taking olanzapine (5 mg/day) and biperiden hydrochloride (1 mg/day) because his schizophrenia was well controlled. His parents were not consanguineous, and there was no family history of neuropsychiatric diseases. On neurological examination, he showed mild cognitive impairment, saccadic eye pursuit with horizontal gaze nystagmus, mild dysarthria, dystonic posture and movement of the neck, incoordination of both hands, and an ataxic gait. Deep tendon reflexes were normal except for the patellar tendon reflex, which was exaggerated bilaterally. Pathological reflexes were negative and there was no sign of rigidity, sensory disturbance or autonomic dysfunction. Ophthalmological examinations detected thinning of the outer macula lutea in both eyes, indicative of macular dystrophy. After admission, all anti-psychotic drugs were ceased, but his dystonia was unchanged. Levodopa and trihexyphenidyl hydrochloride were not effective. General blood, urine and cerebrospinal fluid examinations showed no abnormalities. Brain MRI showed cerebellar atrophy and bilateral symmetrical thalamic lesions without brainstem atrophy or abnormal signals in the basal ganglia. I123-IMP SPECT also revealed a decreased blood flow in the cerebellum. Genetic screening, including whole exome sequencing conducted by the Initiative on Rare and Undiagnosed Disease identified no possible disease-causing variants. The patient’s dystonia worsened and choreic movements manifested on his right hand and foot. We suspected dystonia with marked cerebellar atrophy (DYTCA), but could not exclude drug-induced dystonia. Macular dystrophy and bilateral thalamic lesions on brain MRI have not been previously described in DYTCA. Whether these features might be primarily associated with dystonia or cerebellar ataxia now remains to be determined.
We describe herein a case with left-side ptosis induced by pure midbrain infarction in a 49-year-old woman. She also presented with diplopia and right-side cerebellar ataxia. MRI demonstrated new ischemic stroke of the left ventral paramedian midbrain. In this case, ischemia of the left oculomotor fascicles caused the left-side ptosis and diplopia, and ischemia of the left decussation of the superior cerebellar peduncle caused the right-side cerebellar ataxia. These symptoms resulted from inner superior medial mesencephalic branch infraction. This case offers an educational example that can be explained by models proposed in the past and requires knowledge of neuroanatomy and cerebrovasculature.
A 41-year-old man noticed numbness of the fingers and toes, and gradually developed limb weakness and sensory impairment. The patient was diagnosed with typical chronic inflammatory demyelinating polyradiculoneuropathy. Over the course of clinical diagnosis, the limb and trunk ataxia, and finger tremor became prominent, and the presence anti-neurofascin-155 antibody was examined and confirmed positive. The effects of corticosteroids, intravenous immunoglobulin, and plasma apheresis were limited, and the disease progressed slowly and noticeably. Therefore, cyclosporine was introduced as treatment, and the patient’s weakness and ataxia significantly improved. Rituximab treatment is expected to be effective in patients with the same antibody and immunosuppressant treatment may be useful in intractable cases.
A 78-year-old woman with bilateral fungal sinusitis, which resulted in right orbital apex syndrome, underwent endoscopic sinus surgery and optic nerve decompression. Two months after the operation, she complained of anxiety and insomnia. Head CT showed subdural hematoma-like effusion and burr hole drainage was conducted. The collected fluid was not hematoma, but bloody, xanthochromic effusion with no pathogenic bacteria. Ten days later, she underwent drainage and dural biopsy after craniotomy because of relapse of subdural hygroma and progression of hypertrophic pachymeningitis associated with aggravation of psychiatric symptoms. A sample of the dura mater showed dense fibrosis with thickening, and Pseudomonas aeruginosa (P. aeruginosa) was detected by culture. Although otitis or sinusitis secondary to P. aeruginosa infection has been reported as a leading cause of infectious pachymeningitis, psychiatric symptoms alone and concomitant refractory subdural hygroma are atypical and unreported manifestations. In patients with pachymeningitis and a history of transnasal endoscopic surgery, P. aeruginosa infection should be considered, irrespective of an atypical clinical course and negative blood or fluid culture. Additionally, dural biopsy might help in detection of pathogenic bacteria.
We describe an additional patient with spastic paraplegia 48 (SPG48). A 52-year-old woman with gradually increasing gait disturbance was admitted to our hospital. When she was 47 years old, acquaintances noted a shuffling gait. Gait worsening was evident at 48 years. Spastic gait was apparent at 50, and she required a walking stick at 54. Her elder brother had similar gait disturbance. No consanguinity was known. Neurologic examination at 52 disclosed spasticity and moderate weakness in the lower limbs. Spasticity and brisk reflexes in all limbs. Laboratory studies including HTLV-1 titer detected no abnormalities. MRI demonstrated mild corpus callosum narrowing and prominent anterior periventricular hyperintensities in fluid attenuation inversion recovery images. In limb muscles, electromyography (EMG) showed a chronic neurogenic pattern including reduced interference. Gene analysis identified compound homozygosity in exon 7 of adaptor-related protein complex 5 subunit zeta 1 (AP5Z1), including a novel frameshift mutation, c.1662_1672del;p.Glu554Hfs*15 in the patient, and a heterozygous missense mutation in asymptomatic family members, including her mother, two siblings, and a daughter. The frameshift mutation is considered a pathogenic variant according to American College of Medical Genetics and Genomics standards and guidelines. Based on clinical features, imaging findings and genetic abnormalities, we diagnosed this patient with SPG48. Mutations in AP5Z1, which encodes the ζ subunit of AP-5, underlie SPG48. The AP-5 adaptor protein complex, which is mutated in SPG48, binds to both spastizin and spatacsin. While hereditary spastic paraplegias generally are clinically and genetically heterogenous, SPG48, SPG11, and SPG15 are clinically similar.
A 39-year-old man presented with an 8-month history of pain and paresthesia of the right foot sole and difficulty in the right toe dorsiflexion. A neurological examination revealed weakness in performing both the ankle and right foot toe dorsiflexion, reduced right planta pedis sensation, and absent right Achilles tendon reflex. Tinel’s sign was present on the right popliteal fossa and medial part of the right ankle. MRI of the right knee showed multiple cystic lesions in his right tibial nerve. The cystic lesions extended from the popliteal fossa and were thought to be intraneural ganglion cysts. On MRI performed 4 months later, most of the cystic lesions spontaneously vanished. Therefore, intraneural ganglia should be considered when atypical mononeuropathy, such as tibial nerve palsy, is present.
A 42-year-old man with a history of two previous coronary embolisms was referred to our hospital. He had been experiencing muscle weakness since he was around 40 years old. He had muscle atrophy of the scapula, upper arm, and lower extremities, and electromyography revealed myogenic changes in the limb muscles. Histopathological analysis of the muscle biopsy specimen revealed a complete deficiency of emerin protein, and genetic examination revealed a mutation in the emerin (EMD) gene, resulting in a diagnosis of Emery-Dreifuss muscular dystrophy (EDMD). EDMD is a muscular disorder with three symptoms: joint contracture at early onset, muscle weakness and atrophy, and cardiac dysfunction. Although this patient showed no obvious joint contracture, the course and clinical symptoms vary among patients. Therefore, in patients in whom clinical diagnosis is difficult, muscle biopsy and genetic testing should be performed for EDMD in order to prevent sudden death due to this disease.
A 66-year-old woman with small-cell lung cancer and cancer-associated retinopathy with anti-recoverin antibodies presented with subacute paraplegia associated with recurrence of lung cancer. Although a spinal cord MRI did not show any visible lesion, the neurological symptoms and cerebrospinal fluid findings indicated myelitis. Anti-CV2/CRMP5 antibodies were also positive and the patient was diagnosed with paraneoplastic myelopathy. After medication with prednisolone, her neurological symptoms improved and she survived over three years without recurrence of neurological symptoms. In general, paraneoplastic myelopathy is refractory against immunotherapy but in this case, immunotherapy was successful and resulted in long-term survival. We recommend examining anti-neuronal antibodies and choose and continue the appropriate immunotherapy.
A 49-year-old woman was admitted to our hospital with suspected hypertensive encephalopathy. On the basis of MRI showing leptomeningeal enhancement and Class V cytology of the CSF, she was diagnosed as having leptomeningeal carcinomatosis. Although no primary site was detected, a few melanin granules were observed at the third CSF examination. The atypical cells in the CSF demonstrated immunoreactivity for HMB-45 and S-100, which are specific markers of malignant melanoma. There have been few reports of meningeal melanomatosis in Japan. This case illustrates that immunostaining is diagnostically useful in patients with leptomeningeal carcinomatosis from neoplasms with unknown primary sites.