Cochransalas2272

Establishing the etiology of CDI with MRI in combination with clinical and biochemical assessment facilitates appropriate targeted treatment. This chapter illustrates the wide variety of causes and imaging correlates of CDI on neuroimaging, discusses the optimal imaging protocols, and revises the detailed neuroanatomy required to interpret these studies.Once central diabetes insipidus (CDI) has been diagnosed, every effort should be made to reveal its underlying cause. Autoimmune CDI should be considered in the differential diagnosis of idiopathic CDI and also of mass lesions of the sella region. An autoimmune etiology of CDI was first suggested in 1983 by the detection of autoantibodies to hypothalamic vasopressin-producing cells (AVPcAb) in adults and also in children with the disease, using the indirect immunofluorescence test. The major autoantigen for autoimmune CDI has now been recognized as rabphilin-3A, a protein of secretory vesicles of the neurohypophyseal system. The detection of autoantibodies to rabphilin-3A by Western blotting or of AVPcAb provides strong evidence for the diagnosis of autoimmune CDI. Autoimmune CDI is recognized mostly in patients who had also been diagnosed with endocrine autoimmune disorders. The radiological and morphological correlate with autoimmune DI is lymphocytic infundibuloneurohypophysitis (LINH) as detected by magnetic resonance imaging and biopsies that show massive infiltration of the posterior pituitary and the infundibulum with lymphocytes and some plasma cells, and fibrosis in the later stages of the disease. LINH may be associated with lymphocytic anterior hypophysitis. Both may either appear spontaneously or on treatment with immune checkpoint inhibitors.Traumatic brain injury (TBI), a growing public health problem worldwide, has recently been recognized as one of the leading causes of hypopituitarism. The main causes of TBI-induced pituitary dysfunction are car accidents, falls, violence, sports-related brain injury, and war accidents, including blast-related brain injuries. Car accidents and falls are the most common causes of TBI and pituitary dysfunction among the younger generation and elderly population, respectively. The prevalence of hypopituitarism after TBI is about 30%. GH is the most common hormone lost. The mechanisms underlying hypopituitarism are still unclear; however, recent studies have demonstrated that hypoxic insult, increased intracranial pressure, axonal injury, genetic predisposition, neuroinflammation, and autoimmunity may be responsible for the development of pituitary dysfunction. Neuroendocrine abnormalities are recently described in athletes dealing with contact sports, including boxing and kickboxing, which are characterized by chronic repetitive head trauma. Mild TBI and concussion are accepted in boxing and kickboxing. The positivity of antipituitary and antihypothalamic antibodies is also a significant risk factor in the development of neuroendocrine abnormalities. Autoimmune reaction may also be responsible for the reduction in pituitary volume in boxers with hypopituitarism. In this chapter, the role of autoimmunity in the occurrence of pituitary dysfunction among boxers is discussed.Neuromyelitis optica (NMO) is an autoimmune disorder of the central nervous system that preferentially affects the optic nerve and the spinal cord. In around 80% of NMO patients, autoantibodies binding to aquaporin-4 (AQP4) are detected. AQP4-IgG unifies a spectrum of disorders (NMOSD) that include not only optic neuritis, longitudinally extensive transverse myelitis but also syndromes caused by lesion of the diencephalic region and the circumventricular organs (CVOs). The distinctive immunopathological characteristics of NMOSD lesions, occurring in regions where AQP4 is highly expressed, supports a central role for AQP4-IgG in disease pathogenesis. AQP4 expression is concentrated in CVOs and in the hypothalamus, mainly in the dorsal hypothalamic area, dorsomedial hypothalamic nucleus and suprachiasmatic nucleus. LY303366 order Several neuroendocrine disorders caused by inflammatory lesions involving the diencephalic region have been described in patients with NMOSD, including syndrome of inappropriate antidiuresis, sleep disorders, and other endocrinopathies caused by hypothalamic injury. Focus of this chapter is the involvement of hypothalamus and CVOs in AQP4 autoimmunity.Narcolepsy Type 1 (NT1) is hypothesized to be an autoimmune disease targeting the hypocretin/orexin neurons in the lateral hypothalamus. Ample genetic and epidemiologic evidence point in the direction of a pathogenesis involving the immune system. Many autoantibodies have been detected in blood samples from NT1 patients, but none in a consistent manner. Importantly, T cells directed toward hypocretin/orexin neurons have been detected in samples from NT1 patients. However, it remains to be seen if these potentially autoreactive T cells are also present in the hypothalamus and if they are pathogenic. For this reason, NT1 does still not fully meet the criteria for being classified as a genuine autoimmune disease, even though more and more results are pointing in that direction as will be described in this chapter. The autoimmune hypothesis has led to many attempts at slowing or stopping disease progression with immunomodulatory treatment, but so far the overall results have not been very encouraging. It is clear that more research into the pathogenesis of NT1 is needed to establish the precise role of the immune system in disease development.Hypothalamitis is a rare inflammatory disorder involving the hypothalamus and classified as primary, or isolated, and secondary hypothalamitis. Secondary hypothalamitis although very rare is more common than the primary one and may occur in patients affected by autoimmune diseases such as autoimmune hypophysitis, systemic autoimmune diseases, infective diseases in patients affected by immune-deficit, paraneoplastic encephalitis, or in patients treated with immune checkpoint inhibitors. In accordance with the rarity of this disease, diagnosis and management of hypothalamitis prove to be challenging. The diagnosis requires a high index of clinical suspicion. The main symptoms may be various degrees of hypopituitarism, neuropsychiatric and behavioral disorders, and disturbances of autonomic and metabolic regulation. Magnetic resonance images play a crucial role in the diagnosis of hypothalamitis and in the exclusion of a neoplastic lesion. Therapeutic management should be oriented according to the disease etiology.