Grinker's myelinopathy, also known as anoxic leukoencephalopathy, is a rare disease of the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

. The disease is characterized by a delayed

leukoencephalopathy Leukoencephalopathy ( leukodystrophy-like diseases) is a term that describes all of the brain white matter diseases, whether their molecular cause is known or unknown. It can refer specifically to any of these diseases: * Progressive multifocal le ...

after a hypoxic episode. It is typically, though not necessarily, related to

carbon monoxide poisoning Carbon monoxide poisoning typically occurs from breathing in carbon monoxide (CO) at excessive levels. Symptoms are often described as " flu-like" and commonly include headache, dizziness, weakness, vomiting, chest pain, and confusion. Large ...

heroin overdose An opioid overdose is toxicity due to excessive consumption of opioids, such as morphine, codeine, heroin, fentanyl, tramadol, and methadone. This preventable pathology can be fatal if it leads to Hypoventilation, respiratory depression, a let ...

. It occurs in roughly 2.8% of those who experience an acute hypoxic/

anoxic Anoxia means a total depletion in the level of oxygen, an extreme form of hypoxia or "low oxygen". The terms anoxia and hypoxia are used in various contexts: * Anoxic waters, sea water, fresh water or groundwater that are depleted of dissolved ox ...

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 White matter refers to areas of the central nervous system that are mainly made up of myelinated axons, also called Nerve tract, tracts. Long thought to be passive tissue, white matter affects learning and brain functions, modulating the distr ...

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 Dementia is a syndrome associated with many neurodegenerative diseases, characterized by a general decline in cognitive abilities that affects a person's ability to perform activities of daily living, everyday activities. This typically invo ...

Parkinsonism Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia (slowed movements), Rigidity (neurology), rigidity, and balance disorder, postural instability. Both hypokinetic features (bradykinesia and akinesia) and hyperkinetic f ...

, agitation,

urinary incontinence Urinary incontinence (UI), also known as involuntary urination, is any uncontrolled leakage of urine. It is a common and distressing problem, which may have a significant effect on quality of life. Urinary incontinence is common in older women ...

, and

pseudobulbar palsy Pseudobulbar palsy is a medical condition characterized by the inability to control facial movements (such as chewing and speaking) and caused by a variety of neurological disorders. Patients experience difficulty chewing and swallowing, have i ...

, among many other neuropsychiatric symptoms. Microscopically, extensive hemispheric demyelination and the degeneration of

basal ganglia The basal ganglia (BG) or basal nuclei are a group of subcortical Nucleus (neuroanatomy), nuclei found in the brains of vertebrates. In humans and other primates, differences exist, primarily in the division of the globus pallidus into externa ...

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

. 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 Edema (American English), also spelled oedema (British English), and also known as fluid retention, swelling, dropsy and hydropsy, is the build-up of fluid in the body's tissue (biology), tissue. Most commonly, the legs or arms are affected. S ...

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

often leads to

cerebral ischemia Brain ischemia is a condition in which there is insufficient bloodflow to the brain to meet metabolic demand. This leads to poor oxygen supply in the brain and may be temporary such as in transient ischemic attack or permanent in which there is ...

, a condition where the brain does not receive enough oxygen to satisfy its needs. This results in lesions to a great deal of

subcortical The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. It is the largest site of neural integration in the central nervous system, and plays a key ...

cerebral

but leaves

axons An axon (from Greek ἄξων ''áxōn'', axis) or nerve fiber (or nerve fibre: see spelling differences) is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action pot ...

, 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

Cerebral edema

Cerebral edema Cerebral edema is excess accumulation of fluid ( edema) in the intracellular or extracellular spaces of the brain. This typically causes impaired nerve function, increased pressure within the skull, and can eventually lead to direct compres ...

, or unusual swelling of the brain, is commonly caused by

episodes. If it is severe enough, it is known to cause preferential damage to cerebral

due to excessive swelling of

glial cells Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (the brain and the spinal cord) and in the peripheral nervous system that do not produce electrical impulses. The neuroglia make up ...

while leaving many other tissues unharmed. This theory suggests that hypoxia and carbon monoxide induce a form of

resulting in white matter

necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. The term "necrosis" came about in the mid-19th century and is commonly attributed to German pathologist Rudolf Virchow, who i ...

. Evidence for this theory comes from the observation of pathological lesions mimicking those of

where hypoxia and dehydration along with too-rapid rehydration have taken place without

carbon monoxide Carbon monoxide (chemical formula CO) is a poisonous, flammable gas that is colorless, odorless, tasteless, and slightly less dense than air. Carbon monoxide consists of one carbon atom and one oxygen atom connected by a triple bond. It is the si ...

present.

Disruption of myelin-creating pathways

The

event is likely to cause damage to cytoplasmic ATP-dependent enzymes in

oligodendrocytes Oligodendrocytes (), also known as oligodendroglia, are a type of neuroglia whose main function is to provide the myelin sheath to neuronal axons in the central nervous system (CNS). Myelination gives metabolic support to, and insulates the axon ...

. Because many of these

enzymes An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as pro ...

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 A demyelinating disease refers to any disease affecting the nervous system where the myelin sheath surrounding neurons is damaged. This damage disrupts the transmission of signals through the affected nerves, resulting in a decrease in their con ...

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

, narcotic overdose,

myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...

, or other global cerebral hypoxic events. This diagnosis can then be supported by neuroimaging confirmation of broadcast

cerebral hemisphere The vertebrate cerebrum (brain) is formed by two cerebral hemispheres that are separated by a groove, the longitudinal fissure. The brain can thus be described as being divided into left and right cerebral hemispheres. Each of these hemispheres ...

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 Cerebrospinal fluid (CSF) is a clear, colorless Extracellular fluid#Transcellular fluid, transcellular body fluid found within the meninges, meningeal tissue that surrounds the vertebrate brain and spinal cord, and in the ventricular system, ven ...

. Because this disease shares many of the symptoms with various forms of

hysteria Hysteria is a term used to mean ungovernable emotional excess and can refer to a temporary state of mind or emotion. In the nineteenth century, female hysteria was considered a diagnosable physical illness in women. It is assumed that the bas ...

, 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.

Treatment

Treatment of Grinker's myelinopathy is still in the experimental stages and is very individualized. Some suggested treatments are early supportive care, rehabilitation therapies, oxygen treatments, and bed rest. Some episodes of Grinker's myelinopathy that progress to comas have no known treatment to reverse the course. Early supportive care is the anchor of treatment during the first two weeks. Rehabilitation is an important part of the care process and it is important to start the rehabilitation as soon as the patient is able to participate in therapy. Types of therapy include: physical therapy, occupational therapy, speech therapy, and respiratory therapy. These therapies are used to assess the patient's functional status and to develop treatment goals. Each goal is individualized to target the specific neurological impairments to improve the patient's functional abilities. One way to prevent the likelihood of Grinker's myelinopathy occurring is standard or

hyperbaric oxygen Hyperbaric medicine is medical treatment in which an increase in barometric pressure of typically air or oxygen is used. The immediate effects include reducing the size of gas emboli and raising the partial pressures of the gases present. Initial ...

after

. The hyperbaric oxygen treatment eliminates carbon dioxide from the brain, while the standard oxygen treatment normalizes carboxyhemoglobin levels. Another preventative measure one can take is to be on bed rest and abstain from stressful and strenuous procedures for the first 10 days after an extended hypoxic event. Expectation and recognition will also lead to an earlier and more accurate and appropriate use of health care services.

Prognosis

Those patients who survive initial hospitalization are likely to recover from Grinker's Myelinopathy, but may take up to a year or longer. Age seems to be a factor in the time for recovery, as one study indicated that the mean age of patients who recovered within one year was 10 years younger than that of patients who did not. For most patients, a recovery time of 3–6 months is typical. Even after recovering, however, some symptoms may persist, including cognitive deficits or Parkinsonian symptoms that can be treated separately.

References

{{reflist Central nervous system disorders Anatomical pathology