The role in clinical practice of nuclear medicine imaging such as cerebral blood flow SPECT, DAT SPECT, and MIBG scintigraphy is to contribute to the improvement of accuracy in differential diagnosis of neurodegenerative diseases, although these methods have cost and radiation exposure problems. In this review, these three imaging methods are outlined, and typical case series are introduced. Expectations for nuclear medicine in an aging society are larger than the present situation, and further development is required in the future.
Superficial hemosiderosis is a rare neurodegenerative disorders associated with accumulation of hemosiderin on the surface of the brain and spinal cord. The Japanese guideline for the diagnosis and classification of superficial hemosiderosis divided it into three entities, according to the distribution of iron deposition and the clinical symptoms : “classical”, “localized” and “atypical” types. Individuals having classical type are supported by government in terms of medical expenses. Classical type of superficial hemosiderosis shows slowly progressive and irreversible cerebellar ataxia, sensorineural hearing loss, and/or myelopathy. MRI T2*WI or SWI demonstrates characteristic linear low intensity signals along the surface of the brain and spinal cord. In classical cases, it is important to confirm the bleeding lesions including duropathy. However, the appropriate treatment of the lesions does not always produce good clinical recoveries. In individuals of localized type, some of them are associated with cerebral amyloid angiopathy. Pathologically, severe hemosiderin deposits and tissue necrosis are present at the level of cerebellum in classical type. Hemosiderin deposits are also seen at the base of cerebrum, brainstem and spinal cord. The pharmacological treatments including hemostatics, steroids and iron chelators need to be evaluated further.
Superficial hemosiderosis (SHS) is a rare, neurodegenerative disease caused by toxic accumulation of hemosiderin on the surface of the brain and the spinal cord. With the Japanese guideline for the diagnosis and classification of SHS has been divided into three entities, according to the distribution of iron deposition and the clinical symptoms : “classical” type, “localized” type and “atypical” type. In “classical” type SHS. With our questionnaire survey to 792 medical institutes of the Japanese Society of Neurology, to collect information about SHS, estimated total number of patients with SHS in 2017 was 128 at 55 institutes. Among 122 patients with available data, 63% of patients had “classical” type (c–SHS), 24% had “localized” type (l–SHS), and 10% had “atypical” type (a–SHS). In this article, more detailed features of epidemiological findings about patients with SHS in Japan.
Superficial siderosis (SS) is a rare condition in which hemosiderin is deposited on the pial surface of the brain and/or spinal cord. It is supposed that hemosiderin deposition is a result of recurrent or persistent hemorrhage in the subarachnoid space. There are two types of SS. One is a “classical type”, in which low intensity of MRI is diffuse and symmetrical in brainstem and cerebellum. Patients with classical SS usually reveal slowly progressive and irreversible cerebellar ataxia, sensorineural hearing loss, myelopathy and/or cognitive decline due to involvement of the acoustic nerve, cerebellum, spinal cord and/or cerebral cortex. The other is a “localized (cortical) type”, in which low intensity of MRI is localized in cerebral cortex without infratentorial involvement. The most common causes of hemorrhage in “localized type” are cerebral amyloid angiopathy and/or Alzheimer's disease.
Superficial siderosis (SS) of the central nervous system shows some characteristic imaging features including prominent hypointensity over the brain on T2*–weighted or susceptibility–weighted images. In “classic SS” the lesions are distributed predominantly in the cerebellum and brainstem in the posterior fossa and further more prominent in the vermis than hemispheres in the cerebellum. MRI of the total spinal cord is essential in the evaluation of spinal duropathy which is one of the most important etiologies of classic SS. In “localized SS” are various imaging findings associated with hemorrhagic cerebrovascular disorders, trauma such as traumatic subarachnoid hemorrhage, and neoplasms with intratumoral hemorrhage. Cerebral amyloid angiopathy is a common and important cause of localized SS and often associated with cortical subarachnoid hemorrhage and cerebral microbleedings.
Superficial siderosis is a radiological or pathological diagnosis of hemosiderin deposition in the brain and spinal cord that is caused by chronic subarachnoid hemorrhage. The classic triad of symptoms are bilateral sensorineural hearing loss, ataxia, and myelopathy, which typically leads to progressive and irreversible neurological dysfunction. The most common causes of the chronic subarachnoid hemorrhage that lead to superficial siderosis include CNS tumors, head and neck trauma, and arteriovenous malformations, although an occult source remains unidentified in some cases.
Neuropathology of superficial siderosis is characterized by deposition of hemosiderin into the subarachnoid space with resultant hemosiderin deposition mainly in astrocytes and microglia of the subpial layers, especially in infratentorial structures, cerebellum, brainstem and spinal cord. Olfactory bulbs and cranial nerves, especially VIII, are also vulnerable to hemosiderin deposition.
Cerebral amyloid angiopathy (CAA), which results from amyloid deposition in the small and medium–sized blood vessels of the leptomeninges and central nervous system, is one of the cardinal causes of superficial siderosis (SS). Several amyloid precursor proteins are known to cause CAA. Aβ type CAA is the most frequently found in elderly people or patients with Alzheimer's disease (AD). Cystatin C, prion protein, ABri/ADan, transthyretin (TTR), and gelsolin, are all associated with hereditary CAA. Hereditary ATTR (ATTRv) amyloidosis is an autosomal dominant disease caused by mutations in TTR gene. In several specific TTR mutations including L12P, D18G, A25T, V30G, A36P, T49P, G53E, G53A, G53R, F64S, T69H, and Y114C, leptomeningeal vessels are severely involved by amyloid deposits. On the other hand, in TTR V30M, which is the most common variant type in Japanese hereditary ATTR amyloidosis, CAA was not so noticeable except for homozygous V30M patients. However, with improvement of the prognosis by liver transplantation or disease modifying drugs, CAA has recently become a major problem even in heterozygous V30M patients. These patients developed transient ischemic attack (TIA)–like episodes, stroke, and intracranial hemorrhages, causing SS.
Superficial siderosis (SS) has distinctive clinical features, including chronic progressive sensorineural hearing disturbance, cerebellar ataxia, and myelopathy, which are associated with hemosiderin deposition on the surface of the brain and spinal cord. The treatment strategy for SS consists of two kinds of procedures : elimination of chronic minor bleeding, and reduction of neurodegenerative processes caused by oxidative stress due to the deposited hemosiderin. First, to eliminate hemorrhage in the subarachnoid space―which causes the hemosiderin deposition in the central nervous system (CNS)―an early appropriate inspection of bleeding sources and subsequent surgical treatments, including fistula closure, are required. Recent imaging technologies, including constructive interference into steady state (CISS)/fast imaging employing steady–state acquisition (FIESTA) and dynamic CT myelography, have improved the ability to search for bleeding sources, such as dural defects, enabling early surgical treatment. Unfortunately, most patients require additional treatment to reduce hemosiderin neurotoxicity as neurological symptoms of patients undergoing such surgical treatments continue to deteriorate. To date, no effective treatment methods against hemosiderin neurotoxicity have been reported. Therapeutic efficacy for clinical and radiological features and safety in administration of deferiprone, a lipid–soluble iron chelator that can penetrate through the blood–brain barrier and chelate free iron in the CNS, have been reported. The clinical trial of the administration of deferiprone revealed quantitative clinical and radiological recovery in several postoperative patients with SS, where an early and long–term administration of deferiprone led to better outcomes, indicating a potential promising treatment. An earlier cochlear implantation was also reported to be beneficial for sensorineural hearing loss, which might depend on the site of the lesion and the degree of cochlear nerve functionality. In conclusion, the combination therapy of surgical elimination of a chronic bleeding source and administration of the iron chelator is probably the best treatment strategy for SS, and optionally, a cochlear implantation for patients manifesting hearing loss should be considered as well.
当院の小児科・内科移行カンファレンスを経て移行した22例の診療録とカンファレンス記録を後方視的に調査し，移行後の診療における重要点，移行の利点と問題点，ならびに望ましい移行のありかたを検討した．原疾患は，脳性麻痺17例，Lennox–Gastaut症候群2例，先天奇形症候群，ダウン症候群，自閉スペクトラム症各1例であった．診断の見直し，抗てんかん薬の調整，摂食嚥下機能評価・指導など医療を最適化し，患者・家族への疾患理解や今後の療養方針を考えるべく患者教育を行った．そして，医療ソーシャルワーカー（medical social worker：MSW）と在宅訪問支援看護師の協力を得て地域医療連携を推進し，適切な福祉サービス利用のために社会資源利用の見直しを行った．移行には個別対応が必要で，時間がかかる点が問題であった．小児科医，成人診療科医とMSW，在宅訪問看護師などの多職種による関わりが，移行をより良いものにできる．