Guillain-Barre syndrome (GBS)

Findings

When compared with pre-contrast T1 weighted sagittal images (Figure 3), post-gadolinium sagittal T1-weighted images demonstrate enhancement and thickening of the cauda equina (Figure 4).


Guillain-Barre syndrome (GBS)


Guillain Barre syndrome (GBS) is an acute inflammatory demyelinating polyneuropathy (AIDP). It is an autoimmune disease affecting the peripheral nervous system, usually triggered by an acute infectious process. It is frequently severe and usually presents as an ascending paralysis beginning as weakness in the legs that spreads to the upper limbs and the face along with complete loss of deep tendon reflexes. Hypo- or areflexia, autonomic dysfunction and cranial nerve involvement is commonly associated. It is generally preceded by an antecedent bacterial or viral infection. Nearly 40% of patients are seropositive for Campylobacter jejuni. Diagnosis is based on clincial signs and symptoms, lumbar puncture and electrophysiologic crtieria. CSF findings include elevated protein level without pleocytosis. Nerve conduction findings suggestive of GBS include nerve conduction slowing, conduction block, prolonged distal latency, and prolonged or absent F waves. Therapeutic options include supportive measures, plasmapharesis, and immunoglobulin.
Although ascending paralysis is the most common form of spread in GBS, other variants also exist. Miller Fisher syndrome (MFS) is a rare variant of GBS and manifests as a descending paralysis, proceeding in the reverse order of the more common form of GBS. It usually affects the ocular muscles first and presents as opthalmoplegia, ataxia and areflexia. Anti-GQ1b antibodies are found in 90% of cases. Acute motor axonal neuropathy (AMAN), also known as Chinese Paralytic Syndrome, attacks motor nodes of Ranvier and is prevalent in China and Mexico. The disease can be seasonal and recovery can be rapid. Anti-GD1a antibodies are often present. Acute motor sensory neuropathy (AMSAN) is similar to AMAN but also affects sensory nerves with severe axonal damage. Recovery can be incomplete.

Radiologic studies are typically performed in order to exclude other causes. MR of the spine is performed to define infiltrative etiologies such as tranverse myelitis and compressive causes of polyradiculopathy. In cases of equivocal CSF or nerve conduction findings or atypical clinical findings, MRI of the spine can confirm or exclude the diagnosis. Findings usually include thickening and enhancement of the nerve roots that surround the medullary cone and extend along the length of the cauda equina. In GBS, there is lymphocytic and macrophagic infiltration around endoneural vessels with associated demyelination of the affected nerves. The abnormal enhancement of the intrathecal nerve roots is suggestive of blood brain barrier breakdown. Differential diagnosis of abnormal intrathecal nerve root enhancement includes AIDS-related polyradiculopathy in patients affected by CMV, arachnoiditis, sarcoidosis, and metastatic disease, The most common site of enhancement in GBS may be anterior nerve roots rather than posterior nerve roots. MRI is a sensitive but non-specific examination. Motor weakness and sensory change are correlated with patterns of nerve root enhancement and nerve conduction findings.

Acute disseminated encephalomyelitis (ADEM)

Findings

There is patchy T2 prolongation involving the thalami, basal ganglia, and scattered areas of white matter and cortex. There was no diffusion restriction or abnormal contrast enhancement.

Differential diagnosis
- Demyelinating disease (including ADEM or multiple sclerosis)
- Progressive multifocal leukoencephalopathy
- Toxic or metabolic etiologies
- Creutzfeldt-Jakob disease
- Lymphoma


Diagnosis: Acute disseminated encephalomyelitis (ADEM)


Discussion

Acute disseminated encephalomyelitis (ADEM) is an acute, monophasic demyelinating disease. It is similar to multiple sclerosis in its clinical and pathologic features. It is most commonly seen in children, but can be seen at any age. It is likely of autoimmune etiology and typically follows vaccination or viral infection. ADEM occurs most commonly from October to March. Pathogenesis likely involves T helper cells sensitized to auto antigens, such as myelin protein. Symptoms include fever, headache, and meningeal signs. Seizures, focal neurologic deficits, stupor, and coma may develop. ADEM is often clinically distinct from MS in its association with viral exposure, presence of constitutional symptoms, presence of cortical signs, and lack of posterior column abnormalities. CSF analysis is crucial to the diagnosis.

Treatment includes steroids and full recovery is possibly if treated early. Mortality was as high as 10% to 20% although this data was obtained prior to modern ICU technology.

Acute hemorrhagic leukoencephalitis is a severe variant of ADEM that is often fatal. Pathologically, there is perivascular hemorrhagic necrosis, primarily in the centrum semiovale. The major imaging feature is a rapid progression of white matter lesions over the course of a few days.


Radiologic overview of the diagnosis

CT scan is relatively insensitive, but may show scattered low density areas. T2WI and FLAIR usually show multiple regions of hyper intensity at the gray-white junction, in the brainstem, cerebellum, and basal ganglia. Optic neuritis is also common. Solid or ring enhancement can be seen. There can be variable diffusion restriction. There can be high signal on ADC maps in regions of demyelination. Spectroscopy can show low NAA. Imaging findings can lag behind clinical condition during both onset and resolution. The lesions regress with successful treatment, correlating with clinical improvement. Imaging findings are rarely pathognomonic.


Key points

ADEM is a monophasic demyelinating disease that has similarities to MS.
Imaging findings are rarely pathognomonic. CSF analysis is key to diagnosis.
MRI shows scattered areas of T2 prolongation predominantly in white matter, but may also affect gray matter.

Tumefactive demyelination

Findings

Figure 1, Figure 2, Figure 3, and Figure 4 demonstrate a hypointense T1, hyperintense T2 weighted expansile mass involving the splenium of the corpus callosum. The mass has well defined borders and partially effaces the atrium (trigone) of the left lateral ventricle. There is mild patchy enhancement (Figure 4). DWI images demonstrate increased signal throughout, but only the even more hyperintense rim (Figure 5) demonstrates true restricted diffusion on ADC images (Figure 6). The remainder of the mass is increased signal on ADC images, indicating increased diffusivitiy.


Diagnosis: Tumefactive demyelination


A noncomprehensive list of lesions involving the corpus callosum includes the following: masses such as lipomas, lymphoma, glioblastoma and astrocytoma, and metastases; demyelinating diseases such as multiple sclerosis, progressive multifocal leukoencephalopathy, and Marchiafava-Bignami disease; vascular lesions such as infarctions, vascular malformations; and trauma. More focal lesions with restricted diffusion involving the splenium can also be seen in patients with epilepsy receiving antiepileptic drugs and in the setting of hypoglycemia. Narrowing the differential possibilities to a few relevant entities requires clinical history and detailed analysis of the imaging characteristics. Many of the disease processes mentioned have some unique characteristics that may help favor a particular diagnosis. However, in spite of a full clinical history and an arsenal of imaging tools, a biopsy may ultimately be necessary, as was the case with this patient.

The diagnosis in this case was tumefactive demyelination, which may be thought of as a solitary demyelinating lesion measuring greater than 2 cm and with characteristics that mimic neoplasm. Because of this, tumefactive demyelinating lesions are commonly diagnosed as such only after biopsy. Several imaging characteristics suggestive of such a lesion have been described. These include a large lesion with circumscribed borders and little or no mass effect or surrounding edema. Demyelinating lesions in general also tend to demonstrate an incomplete ring of enhancement, with the nonenhancing component facing the gray matter. The enhancing rim is felt to represent the leading edge of demyelination, and therefore usually faces the white matter. Some foci also have been shown to have decreased perfusion in some studies, which would help distinguish them from glioblastoma and lymphomas.

The abnormality in our case does illustrate a few of these characteristics, such as a circumscribed border and lack of surrounding edema. The lesion did demonstrate increased diffusivity on DWI/ADC maps, which would argue against a highly cellular tumor like lymphoma and a high grade glioma. Active foci of demyelination may demonstrate restricted diffusion. In our case, the thin peripheral rim of restricted diffusion may represent an active edge of demyelination. The mass effect on the atrium of the left lateral ventricle is a confounding factor that can be associated with tumefactive demyelination or neoplasms. Metastases usually elicit a large amount of edema which was noticeably absent in this case. Infarction is also unlikely given the patient’s age and based on the imaging characteristics of the abnormality. Infarctions involving the corpus callosum are uncommon because of the ample blood supply from the anterior and posterior circulation. Unfortunately, none of these features is specific enough to warrant watchful waiting, and therefore a biopsy was performed.

Multiple sclerosis (MS)

Findings

34 yo) Figure 1: Sagittal FLAIR image delineates septo-callosal interface hyperintensities, perpendicular periventricular hyperintensities extending into the deep white matter, and a juxtacortical lesion.
Figure 2: Coronal fat saturated T1 post gadolinium demonstrates enhancement of the left optic nerve.

38 yo)Figure 3: Sagittal FLAIR (3a) and axial FLAIR (3b) images demonstrate confluent periventricular and juxtacortical oval plaque-like hyperintense lesions perpendicular to the ventricular axis known as “Dawson’s fingers”.

44 yo) Figure 4: Axial FLAIR shows hyperintense plaques with one extending to a juxtacortical location. Figure 5: Sagittal T2 shows hyperintense plaques within the brainstem and upper cervical spinal cord. Figure 6: Sagittal FLAIR demonstrates periventricular and subcortical hyperintensities.


Diagnosis: Multiple sclerosis


Multiple Sclerosis (MS) is a demyelinating inflammatory CNS disorder of unclear etiology. It specifically affects oligodendrocytes, thus eliminating their supportive function to the neurons they serve. Women are affected twice as frequently as men, usually between the ages of 20 and 40 years. MS is a clinical diagnosis based on history, neurological examination, and paraclinical studies including MR imaging, evoked potentials and CSF studies. The hallmark of this disease is its dissemination in space and time. Diagnosis of MS separates it from clinically isolated syndromes (CIS). MS has different subtypes, the most common being the relapsing-remitting type. Other subtypes include primary progressive, progressive relapsing, and malignant/Marburg. Related demyelinating processes such as Schilder’s diffuse sclerosis and Balo’s concentric sclerosis may be considered MS subtypes. However, recurrent optic neuritis and neuromyelitis optica (Devic’s disease) have been shown to be distinctly separate entities.

Specific MR imaging characteristics include the presence of T2 hyperintensity at the septo-callosal interface and ovoid lesions perpendicular to the ventricles, known as Dawson fingers. These occur along the deep medullary veins. Active lesions may enhance avidly or poorly depending on the degree of acuity and severity. Lesions may also involve the cortex, juxtacortical white matter, brainstem, and spinal cord. These lesions, given their protean distribution and overall presentation, have an extensive differential diagnosis and therefore multiple criteria schemes have been developed to aid in the diagnosis of MS. The differential diagnosis of MS includes acute disseminated encephalomyelitis and its possible subtypes of neuromyelitis optica (Devic disease), acute optic neuritis, and acute transverse myelitis; microvascular white matter ischemic changes; progressive multifocal leukodystrophy; neurosarcoidosis; hypertensive encephalopathy; vasculitis; and encephalitis.

The 2001 International Panel on the Diagnosis of Multiple Sclerosis (IPDMS) (McDonald et al.) “McDonald Criteria” require objective evidence of CNS lesions disseminated in space and time in order to diagnose MS. Spatial criterion is defined by the Barkhof-Tintore MR imaging criteria, which require three of the following four findings: 1) at least one gadolinium-enhancing lesion or 9 T-2 hyperintense lesions; 2) at least one infratentorial lesion; 3) at least one juxtacortical lesion; 4) at least 3 periventricular lesions. Lesions should be greater than 3-mm in cross-section. A spinal cord lesion may substitute for a brain lesion, and in the setting of oligoclonal IgG bands or elevated IgG/Albumin ratio in the CSF, only 2 instead of 9 T2 lesions are needed to satisfy the criteria. Temporal criterion is satisfied by follow up imaging 3 or more months after the onset of the clinical event. The 2005 IPDMS (Polman et al.) suggested revisions to the 2001 McDonald criteria based on several research studies which followed. These modifications were made to allow for the following: 1) multiple spinal lesions may be used to substitute for brain and infratentorial lesion criteria, provided that they are more than 3mm in size, the length is less than 2 vertebral body heights, and the lesion occupies only a portion of the cord cross section, 2) an enhancing spinal cord lesion may be substituted for an enhancing brain lesion, and 3) for dissemination in time, a new T2 lesion discovery interval may be reduced from 3 months to 1 month. Polman also suggested that CSF studies are no longer needed in order to consider a diagnosis of primary progressive MS.


The 2001 IPDMS (McDonald et al.) “McDonald Criteria”

Dissemination in Space: 3 of the following 4
- At least 1 gadolinium-enhancing lesion or 9 T2-weighted hyperintense lesions*
- At least 1 infratentorial lesion
- At least 1 juxtacortical lesion
- At least 3 periventricular lesions

* + oligoclonal IgG bands or elevated IgG/Albumin ratio in the CSF, only 2 T2 lesions are needed


Dissemination in Time: One of the following
- A new enhancing lesion at least 3 months after the initial clinical event in a new clinically relevant area
- A new T2 lesion identified on a new MRI study at least 3 months after the initial scan


The 2005 IPDMS modified “McDonald Criteria”, (Polman et al.)

Dissemination in Space: 3 of the following 4
- At least 1 gadolinium-enhancing lesion (spinal cord, brainstem, and brain) or 9 T2-weighted hyperintense lesions (spinal cord, brainstem, and brain)*
- At least 1 infratentorial lesion (spinal cord, brainstem, and cerebellum)
- At least 1 juxtacortical lesion
- At least 3 periventricular lesions

* +oligoclonal IgG bands or elevated IgG/Albumin ratio in the CSF, only 2 T2 lesions are needed


Dissemination in Time: One of the following
- A new enhancing lesion at least 3 months after the initial clinical event in a new clinically relevant area
- A new T2 lesion identified on a new MRI study at least 1 month (30 days) after the initial scan


Conclusion

Diagnostic criteria for MS and its variants are continually revised as more data becomes available and MR imaging technology improves. Notwithstanding, attention to detail with precise temporospatial descriptions of lesions is essential for the diagnosis of MS and may also have prognostic value.

Extrapontine myelinolysis (osmotic demyelination syndrome)

Findings

Figure 1: Sagittal T1 image taken parasagitally at the level of the dentate nucleus. There are T1 hypointensities within the subcortical white matter and in the brachium pontis.
Figure 2: Axial T2 at the level of the cerebral subcortical white matter. There is T2-hyperintensity in the centrum semiovale bilaterally. The signal abnormality is fairly symmetrical.
Figure 3: Axial T2 at the level of the splenium of the corpus callosum. There are T2-hyperintensities within the splenium of the corpus callosum and asymmetrical T2-hyperintensities along the corticospinal tracks within the posterior limbs of internal capsules.
Figure 4: Axial T2 at the level of the middle cerebellar peduncles. There is T2-hyperintensity within the brachium pontis bilaterally. Note that the signal abnormality is symmetrical. Also note that the signal within the pons was normal.
Figure 5: Axial FLAIR at the level of the splenium of the corpus callosum. There are FLAIR-hyperintensities within the splenium of the corpus callosum and asymmetrical FLAIR -hyperintensities along the corticospinal tracks within the posterior limbs of internal capsules.
Figure 6 and Figure 7: Axial diffusion weighted and ADC map images at the level of the middle cerebellar peduncles. There is increased signal in both DWI and in the ADC map, consistent with the subacute stage of myelinolysis (four weeks after onset of symptoms). The DWI and ADC maps at the level of the centrum semiovale and splenium (not shown) demonstrated similar findings.


Diagnosis: Extrapontine myelinolysis (osmotic demyelination syndrome)


Central pontine myelinolysis (CPM), was first described in 1959 in patients with a history of alcoholism and malnutrition. Extrapontine myelinolysis (EPM) is the extrapontine manifestation of osmotic myelinolysis and can occur with or without central pontine myelinolysis. In one autopsy series, myelinolysis was found to be confined to the pons (CPM) in about 50% of cases, combined CPM and EPM occurred in about 30 % of cases, and exclusive EPM occurred in about 20% of cases7.

CPM and EPM are characterized by symmetrical loss of myelin with relative preservation of axons and neuronal cell bodies. Pathologically, there is dissolution of the myelin sheaths of fibers. There is however, no evidence of inflammation. The myelinolysis occurs with relative sparing of the nerve cells and axon cylinders.

Although initial reports were largely confined to chronic alcoholics, osmotic myelinolysis has also been seen in patients with electrolyte disturbances, particularly hyponatremia that has been rapidly corrected (more then 10mmol/l/day), and in liver transplant patients being immune-suppressed with cyclosporine. Alcohol continues to be a particularly frequent etiology (up to 40% of cases)7.

Osmotic myelinolysis can affect a variety of sites resulting in a variety of symptoms. The MRI appearance is characteristic with lesions being symmetrical. However, the timing of the appearance of lesions on MRI may be significantly delayed. If there is a strong clinical suspicion of the diagnosis, repeat imaging at 1 to 2 weeks may reveal lesions that were not initially apparent. Diffusion weighted imaging (DWI) might have the capability of detecting lesions undetectable on conventional MRI earlier, with one case report in the literature showing an altered DWI in a patient within 24 hours of symptoms at a time when conventional MRI findings were inconspicuous.

The prognosis of the osmotic demyelination syndrome is variable. In a reported series, about 6 % of patients died, about 32 % survived but were left dependent, about 32% had some deficits but were independent, and about 30% recovered completely. Initial clinical features are not predictive of outcome and a recent case series found conventional MRI findings were not prognostic but the prognostic role of diffusion-weighted imaging is still unclear 3,4,8.

In conclusion, CPM and EPM are the same disease, sharing the same pathology, associations, and time course but differing in clinical manifestations due to differences in the affected structures. Both diseases have lesions that are strikingly symmetrical.

Acute disseminated encephalomyelitis (ADEM)

Additionale clinical history: A 23-month-old male with 2 weeks of viral symptoms presenting with progressive weakness and inability to walk.


Findings

Figure 1, Figure 2, and Figure 3: Axial FLAIR images demonstrate increased signal intensity in the centrum semiovale (Figure 3), putamen (Figure 2) and thalamus (Figure 2) as well as the dentate nuclei (Figure 1).
Figure 4: T1 weighted post gadolinium axial image demonstrates no evidence of enhancement.


Diagnosis: Acute Disseminated Encephalomyelitis (ADEM)


ADEM is thought to be a postviral leukoencephalopathy of children and young adults mediated by an allergic or autoimmune cross-reaction with an antigen. The patient typically presents with confusion, headaches, seizures and/or focal neurological symptoms occurring within 2 or 3 weeks of a recent viral infection, vaccination, respiratory infection or exanthematous disease of childhood. Epstein-Barr virus, cytomegalovirus and Mycoplasma pneumoniae are the most common pathogens associated with ADEM. The diagnosis can be made by clinical history and CSF analysis. CSF analysis may demonstrate an increase in white cells with lymphocyte predominance and an increase in myelin basic protein.

On MR, ADEM demonstrates multiple foci of high signal intensity on FLAIR and T2 weighted images in the white matter, especially subcortically. The cortical gray matter is usually spared though deep gray matter lesions are occasionally observed. Gadolinium T1 weighted images may demonstrate enhancement in a nodular or ring like pattern. ADEM can also affect the spinal cord or brain stem. The main differential to consider is multiple sclerosis as the imaging characteristics and clinical presentation may overlap. Because ADEM is generally considered a monophasic disease, a follow-up MR 6 months after the start of the disease should not reveal any new lesions. Although patients with ADEM are at a slight increased risk for recurrence, if new lesions are found multiple sclerosis should be strongly considered.

The treatment of ADEM is the administration of corticosteroids. The resolution of neurological deficits is often seen within one month of onset of the disease (80-90%), however, permanent neurological damage may occur (10-20%).

Balo's concentric sclerosis

Findings

Figure 1: T1-weighted image shows low density in both the posterior and the left anterior periventricular region.
Figure 2: T2-weighted image shows high signal in the periventricular lesions with suggestion of concentric rings of hyperintensity and isointensity.
Figure 3: FLAIR image reveals edema in the periventricular lesions.
Figure 4 and Figure 5: The postcontrast T1-weighted images show enhancement in a concentric ring like fashion and hold the key to the diagnosis.


Diagnosis: Balo's concentric sclerosis


Balo’s concentric Sclerosis (BCS) is a rare demyelinating disorder considered to be a variant of multiple sclerosis (MS).Histologically it is characterized by alternating rings of myelin preservation or remyelination and demyelination involving the cerebral hemispheres, brain stem, spinal cord, and optic chiasm. The clinical course of BCS is considered variable with the current treatment modalities.

The MR imaging findings show hypointense and isointense concentric bands on T1 weighted images, concentric hyperintense and isointense bands on T2 weighted images. The hyperintense bands on T2 weighted images correspond to concentric bands of demyelination with gliosis and perivascular lymphocytic infiltration. The isointense bands represent the white matter which has been spared or has had remyelination. On the post contrast T1 weighted images all the lesions showed concentric rings of enhancement, indicating rings of active inflamed and spared white matter.

It has been noted that with treatment and over a period of time, the contrast enhancement decreases and so does the size of the lesions. The characteristic concentric pattern may not be observed if the MR imaging is not performed early in the disease. Our patient is still in the hospital being treated with high dose steroids.

Differential for the imaging findings would include Marburg variety of multiple sclerosis, ADEM (Acute disseminated encephalomyelitis) and lymphoma. ADEM also has multiple lesions which enhance after gadolinium administration. The age of the patient does not favor that and the patient did not have history of any viral illness. Lymphoma should have more mass effect and more enhancement. The patient did not have any history of immunosuppresion.