Genetic disorder associated with idiopathic hypogonadotrophic hypogonadism (IHH) and progressive cerebellar ataxia.
Gordon Holmes Spinocerebellar Ataxia; Cerebellar Ataxia Hypogonadotropic Hypogonadism Syndrome; Deficiency of Luteinizing Hormone-Releasing Hormone Ataxia Syndrome.
Sir Gordon Morgan Holmes (1876-1965), a British neurologist, described this autosomal-recessive transmitted syndrome almost 100 years ago. He was born as the son of a Louth farmer 40 miles north of Dublin and was educated at Dundalk Educational Institution (now Dundalk Grammar School) and Trinity College, Dublin, where he graduated in medicine in 1897. He is best known for carrying out pioneering research into the cerebellum and the visual cortex.
Incidence and genetic inheritance
Only a few case reports exist in the literature.
The underlying pathophysiology is not completely clear. There are conflicting reports in the literature as to whether the primary neuroendocrine defect is of hypothalamic gonadotropin-releasing hormone (GnRH) secretion, as with most causes of IHH, or of pituitary resistance to GnRH action.
The first symptoms are that of hypogonadotropic hypogonadism, although there seems to be a broad clinical spectrum of this disease as patients with hypergonadotropic hypogonadism have been described as well. A defect in the production or the release of gonadotropins in the pituitary gland is responsible for the hypogonadotropic state. Most often, plasma concentrations of luteinizing hormone and follicle-stimulating hormone fail to rise after repetitive stimulation with gonadotropin-releasing hormone, which is consistent with a primary pituitary defect. However, a small number of patients do respond to exogenous GnRH, suggesting a primary hypothalamic disturbance. Usually, in the third to fourth decade of life, progressive cerebellar ataxia and profound dementia develop, resulting in patients who are bedridden with no purposeful movements and finally death secondary to aspiration pneumonia. CT and/or MRI scans may reveal marked cerebellar and, to a lesser degree, cortical atrophy, as well as hypodensities in the cerebral white matter. Spasticity and nystagmus are not features of this disorder.
Although no case reports on this disease in association with anesthesia exist, it is probably best to apply the same precautions as in ☞Friedreich Ataxia with regard to muscle relaxants (however, cardiomyopathy has not been described in Gordon Holmes Syndrome). The use of a peripheral nerve stimulator during induction is essential to titrate the relaxants to effect and to closely monitor recovery. Because different muscle groups are affected, the clinical manifestation and the anesthesia management intra- and post-operatively can vary significantly with the disease. It is highly recommended to monitor carefully for residual paralysis in more than one site (group muscle) on the patient.
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