Grinker's myelinopathy, also known as anoxic leukoencephalopathy, is a rare disease of the central nervous system. The disease is characterized by a delayed leukoencephalopathy after a hypoxic episode. It is typically, though not necessarily, related to carbon monoxide poisoning or heroin overdose. It occurs in roughly 2.8% of those who experience an acute hypoxic/anoxic episode. Because of the wide range of symptoms and the delay in onset, it is often misdiagnosed as other neuropathologies. Grinker's myelinopathy was originally characterized by Roy R. Grinker in 1925 or 1926, depending on the source.
Categorization Following an apparent rehabilitation from a severe episode of prolonged cerebral oxygen deprivation, patients with Grinker's myelinopathy begin to experience massive white matter death that leads to a wide range of neurological dysfunctions ranging from confusion and apathy to Parkinson-like symptoms.
Symptoms The symptoms have been known to include apathy, dementia, Parkinsonism, agitation, urinary incontinence, and pseudobulbar palsy, among many other neuropsychiatric symptoms. Microscopically, extensive hemispheric demyelination and the degeneration of basal ganglia are observed.
Onset The onset of the symptoms usually occurs several weeks after the initial hypoxic episode. The hypoxic episode is necessarily severe, usually with an arterial oxygen partial pressure less than 40mmHg. Following the severe hypoxia, the patient typically falls unconscious or into a coma, with the exception of cases of carbon monoxide poisoning. If the patient recovers from this unconscious state, usually within 24 hours, it is typically followed by a successful recovery over a few days (generally 4 to 5). After the short recovery, a lucid period is observed, lasting anywhere from 1 to 4 weeks, in which the patient exhibits no symptoms related to the anoxic episode. It is after this period that the degenerative symptoms begin to appear and rapidly grow in severity.
Causes The main cause of the neurological disorders is believed to be demyelination of the cerebral hemispheres, though there is currently no widely accepted consensus on why. The most commonly accepted theories for the cause of demyelination include hypoxia and cerebral edema due to carbon monoxide toxicity, drug overdose, or cerebral blood vessel damage, and a disruption of myelin-producing pathways.
Carbon monoxide toxicity Because carbon monoxide binds to hemoglobin more efficiently than oxygen and lower systemic blood pressure brought upon by an acute anoxic episode in conjunction with carbon monoxide poisoning often leads to cerebral ischemia, a condition where the brain does not receive enough oxygen to satisfy its needs. This results in lesions to a great deal of subcortical cerebral white matter but leaves axons, U-fibers, and perivascular myelin mostly untouched. Support against this theory stems from the ability to replicate these lesions by using nitrogen-induced hypoxia and hypotension in cats and the onset of this disease in individuals who experienced acute hypoxia without carbon monoxide poisoning
Cerebral edema Cerebral edema, or unusual swelling of the brain, is commonly caused by anoxic episodes. If it is severe enough, it is known to cause preferential damage to cerebral white matter due to excessive swelling of glial cells while leaving many other tissues unharmed. This theory suggests that hypoxia and carbon monoxide induce a form of edema resulting in white matter necrosis. Evidence for this theory comes from the observation of pathological lesions mimicking those of carbon monoxide poisoning where hypoxia and dehydration along with too-rapid rehydration have taken place without carbon monoxide present.
Disruption of myelin-creating pathways The anoxic event is likely to cause damage to cytoplasmic ATP-dependent enzymes in oligodendrocytes. Because many of these enzymes play essential roles in myelin turnover, damage to these enzymes is thought to adversely affect the ability of the body to sustain myelin in white matter, leading to the demyelination of those areas of the brain. The inability to regenerate and remove myelin on certain cells is thought to be responsible for the delay in onset of the disease and for the specificity of the white matter death.
Diagnosis Grinker's myelinopathy is diagnosed by establishing a clinical history of carbon monoxide poisoning, narcotic overdose, myocardial infarction, or other global cerebral hypoxic events. This diagnosis can then be supported by neuroimaging confirmation of broadcast cerebral hemisphere demyelination sparing cerebellar and brainstem tracts. The neuroimaging evidence can also be used to diagnose Grinker's myelinopathy through an elevation in the concentrations of a myelin basic protein in the cerebrospinal fluid . Because this disease shares many of the symptoms with various forms of dementia or hysteria, these possibilities must be eliminated before a diagnosis for Grinker's myelinopathy can be made.
Neuroimaging While there are no standard criteria for the diagnosis of Grinker's myelinopathy, neuroimaging can be an important diagnostic tool in ruling out other diagnoses. Magnetic resonance imaging (MRI) or computed tomography (CT) scans can be used to demonstrate a decrease in white matter density in the patient's cerebral hemispheres, with the typical exception of overlying cortices. Unexplained, uniform demyelination of white matter can indicate acute onset Grinker's myelinopathy.
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