Tumefactive multiple sclerosis


Tumefactive multiple sclerosis is a condition in which the central nervous system of a person has multiple demyelinating lesions with atypical characteristics for those of standard multiple sclerosis. It is called tumefactive as the lesions are "tumor-like" and they mimic tumors clinically, radiologically and sometimes pathologically.
These atypical lesion characteristics include a large intracranial lesion of size greater than 2.0 cm with a mass effect, edema and an open ring enhancement. A mass effect is the effect of a mass on its surroundings, for example, exerting pressure on the surrounding brain matter. Edema is the build-up of fluid within the brain tissue. Usually, the ring enhancement is directed toward the cortical surface. The tumefactive lesion may mimic a malignant glioma or cerebral abscess causing complications during the diagnosis of tumefactive MS. T2-hypointense rim and incomplete ring enhancement of the lesions on post-gadolinium T1- weighted imaging on brain MRI enable accurate diagnosis of TDL
Normally a tumefactive demyelinating lesion appears together with smaller disseminated lesions separated in time and space, yielding a diagnosis of Multiple Sclerosis. Hence the name "tumefactive multiple sclerosis". When the demyelinating lesion appears alone it has been termed solitary sclerosis. These cases belong to a multiple sclerosis borderline and there is currently no universal agreement on how they should be considered.
Tumefactive multiple sclerosis is a demyelinating and inflammatory disease. Myelination of the axons are highly important for signalling as this improves the speed of conduction of action potentials from one axon to the next. This is done through the formation of high-resistance, low-conductance myelin sheaths around the axons by specific cells called oligodendrocytes. As such, the demyelination process affects the communication between neurons and this consequently affects the neural pathways they control. Depending on where the demyelination takes place and its severity, patients with tumefactive MS have different clinical symptoms.

Signs and symptoms

Symptoms of standard MS consist of both sensory and motor symptoms. The more common symptoms include spasticity, visual loss, difficulty in walking and paresthesia which is a feeling of tickling or numbness of the skin. but symptoms of tumefactive MS are not so clear. They often mimic a variety of other diseases including ischemic stroke, peroneal nerve palsy and intracranial neurologic disease.
Subjects have been reported to suffer from a decreased motor control resulting in a 'foot drop', or significantly reduced leg movement. In other cases closer mimicking strokes, subjects may suffer from confusion, dizziness, and weakness in one side of the face. Symptoms also can mimic a neoplasm with symptoms such as headaches, aphasia, and/ or seizures.
There are some differences with normal MS symptoms.
Spasticity is not as prevalent in tumefactive cases, because in standard MS it is caused by demyelination or inflammation in the motor areas of the brain or the spinal cord. This upper motor neuron syndrome appears when motor control of skeletal muscles is affected due to damage to the efferent motor pathways. Spasticity is an involuntary muscle movement like an exaggerated stretch reflex, which is when a muscle overcompensates and contracts too much in response to the muscle being stretched. It is believed that spasticity is the result of the lack of inhibitory control on the muscles, an effect of neuronal damage.
Visual loss or disturbances are also different. In standard MS, they are a result of inflammation of the optic nerve, known as optic neuritis. The effects of optic neuritis can be loss of color perception and worsening vision. Vision loss usually starts off centrally in one eye and may lead to complete loss of vision after a period of time.
The possible cognitive dysfunction is also rare in tumefactive cases. MS patients may show signs of cognitive impairment where there is a reduction in the speed of information processing, a weaker short-term memory and a difficulty in learning new concepts. This cognitive impairment is associated with the loss of brain tissue, known as brain atrophy which is a result of the demyelination process in MS.
About fatigue: most MS patients experience fatigue and this could be a direct result of the disease, depression or sleep disturbances due to MS. It is not clearly understood how MS results in physical fatigue but it is known that the repetitive usage of the same neural pathways results in nerve fiber fatigue that could cause neurological symptoms. Such repeated usage of neural pathways include continuous reading which may result in temporary vision failure.

Evolution

Some reports indicate that an initial tumefactive lesion can evolve to various pathological entities: multiple sclerosis, Balo's concentric sclerosis, Schilder's disease and acute disseminated encephalomyelitis

Course

Usually tumefactive demyelination is monophasic, but cases with recurrence have been reported

Cause

The pathology of the tumefactive demyelinating lesion is heterogeneous. Several conditions can produce tumefactive lesions. This is known because in some special cases the etiology can be identified. For example, there are some cases of NMO, misidentified as MS and treated with interferon-beta by mistake. Some of these patients developed tumefactive lesions. Anyway, it is important to have into account that NMO itself can also produce them
Some other cases have been found related to viral infection, some others related to NMOSD, others could be paraneoplastic, Also some cases could be related to hormonal treatments
Other possible cause are immunomodulatory combinations. In particular, it has been found that switching from standard MS therapies to fingolimod can trigger tumefactive lesions in some MS patients
While standard multiple sclerosis process has an autoimmune response after the breach of the blood–brain barrier, in tumefactive MS things do not process in the same way, and demyelinating lesions do not always show antibody damage. Subjects with tumefactive multiple sclerosis display elevated levels of choline /creatine ratio and increased lactate which is associated with demyelinating diseases. Cases also display oligoclonal bands in the cerebrospinal fluid.
The disease is heterogeneous and the lesions do not always comply with the requirements for multiple sclerosis diagnosis. In these cases it is only possible to speak about tumefactive demyelination.
In general, it is accepted that the two main causes of pseudo-tumoral lesions are Marburg multiple sclerosis and acute disseminated encephalomyelitis. Tumefactive demyelination of the spinal cord is rare but it has been reported
Damage is not confined to the demyelinating area. Wallerian degeneration outside the lesions has been reported.
In general, during the acute phase, the plaques of lesions were characterized by massive demyelination with relatively axonal preservation associated with reactive astrocytosis and infiltration of macrophages. In plaques of chronic lesions, demyelinated lesions with relative axonal preservation and sharply defined margins were major findings. And myelin-laden macrophages accumulate at the edges of plaques and stay inactive

Diagnosis

Diagnosis of tumefactive MS is commonly carried out using magnetic resonance imaging and proton MR spectroscopy. Diagnosis is difficult as tumefactive MS may mimic the clinical and MRI characteristics of a glioma or a cerebral abscess. However, as compared to tumors and abscesses, tumefactive lesions have an open-ring enhancement as opposed to a complete ring enhancement. Even with this information, multiple imaging technologies have to be used together with biochemical tests for accurate diagnosis of tumefactive MS.
Tumefactive demyelination is distinguished from tumor by the presence of multiple lesions, absence of cortical involvement, and decrease in lesion size or detection of new lesions on serial imaging Tumefactive lesions can appear in the spinal cord, making the diagnosis even more difficult.

Magnetic resonance imaging

MRI diagnosis is based on lesions that are disseminated in time and space, meaning that there are multiple episodes and consisting of more than one area. There are two kinds of MRI used in the diagnosis of tumefactive MS, T1-weighted imaging and T2-weighted imaging. Using T1-weighted imaging, the lesions are displayed with low signal intensity, meaning that the lesions appear darker than the rest of the brain. Using T2-weighted imaging, the lesions appear with high signal intensity, meaning that the lesions appear white and brighter than the rest of the brain. When T1-weighted imaging is contrast-enhanced through the addition of gadolinium, the open ring enhancement can be viewed as a white ring around the lesion. A more specific MRI, Fluid attenuation inversion recovery MRI show the signal intensity of the brain. Subjects with tumefactive multiple sclerosis may see a reduction of diffusion of the white matter in the affected area of the brain.

Proton MR spectroscopy

Proton MR spectroscopy identifies biochemical changes in the brain such as the quantity of metabolic products of neural tissue including choline, creatine, N-acetylaspartate, mobile lipids and lactic acid.
When demyelination is occurring, there is breakdown of cell membranes resulting in an increase in the level of choline. NAA is specific to neurons and thus, a reduction in NAA concentration indicates neuronal or axonal dysfunction. As such, the levels of choline and NAA can be measured to determine if there is demyelination activity and inflammation in the brain.
Usually, the ratio of choline to NAA is used as biomarker being higher in gliomas than in TDLs or MS lesions