Inflammatory Demyelinizing Disease
Short Summary

28-year old female had a sudden visus decrease. Her brain MRI showed several myelin lesions and she was diagnosed with Inflammatory Demyelinizing Disease. Because of her Hodgkin’s lymphoma history it is recommended to implement preventive therapy only if another episode consistent with MS will occur.

Patient's Questions
1)           How can you obtain a differential diagnosis among the various types of demyelinizing diseases? How long has to pass from a MRI to the following check ones?

2)         Does a preventive therapy for the MS (Multiple Sclerosis) exist? When is it correct to start the therapy for the MS? Which are the side effects of the MS therapies?

3)         Apart from the stress, which are the situations and/or the behaviours that must be avoided to prevent the pathology course from worsening and/or accelerating? Do you think that working on the computer for 8 hours a day could negatively affect the left eye problems? Are there MS cases that do not degenerate?

4)         In the future will the patient be able to have babies without problems? 
Medical Background

Expert's Opinion

Patient's History
Age: 28, Sex: Female
Diagnosis : Inflammatory Demyelinizing Disease
Hodgkin’s lymphoma type NS since May 1999 started with mediastinal and laterocervical lymphadenopathies with associated systemic symptomatology (stage II B). A polychemotherapy treatment was performed according to the ABVD protocol (4 cycles) followed by radiotherapeutic treatment on mantle (3600 r) ended in January 2000 with the complete remission of the disease. Subsequently, the patient has undergone periodic controls which have always confirmed the obtained answer; the latest complete restaging is in March 2006.
Case history:
In the month of April 2008 the patient had a sudden and severe visus decrease in the left eye, for this reason she had her eyes examined by a specialist, professor Frosini, who highlighted, in the left eye, a moderate increase of the blind eyespot and a reduction of central sensitivity with no presence of the classic centrocecal scotosis; the VEP (Visual Evoked Potentials), in particular the P100, slightly increased in the right eye and clearly increased in the left eye -regular ocular fundus and visus in the left eye of 3-4/10. Suspecting, for this reason, a neurologic cause, more detailed diagnosis were performed (visual field and VEP) that led to a diagnosis of optic neuritis.
A brain MRI scan was further performed with contrast medium on 03/2008 with presence of some small hyperintense foci in the long TR sequence at the white matter level of both cerebral hemispheres, numerically prevalent in the left side; one, at least , affects the middle part of the corpus callosum. In contrastographic phase one of these lesions shows a slight enhancement, at the level of the right semioval center. The conclusions of the examination gave evidence for: “compatibly with the clinical-anamnestic reference (optic neuritis left eye), the described findings show a suspected demyelinizing disease, to be correlated with clinical and laboratory data”.
The patient was, therefore, invited to the neurology department of Careggi hospital to meet Professor Massacesi where, on the base of the clinical and instrumental picture, the diagnosis of inflammatory demyelinizing disease was confirmed and, at the same time, she was put on cortisone therapy with Solumedrol 100 mg in 250 intravenous saline solution for 5 days. Moreover, a DH (Day Hospital) was expected for further tests to be performed. After this therapy the visus improved even if she didn’t have a complete recovery of the sight.
During the DH on 05/2008 the performed examinations and, in particular, the liquor examination, were found to be suggestive of CIS (Clinically Isolated Syndrome) in the field of an inflammatory demyelinizing disease of the central nervous system, for this reason, at this moment, no therapy is expected.
A follow-up neurological visit was furthermore performed on 07/2008 at an interval of 3 months from the first one with the following medical report: “examination compared to the previous one performed, elsewhere, on 032008 where, even if we consider the limits connected with the imperfect matching of the scanning planes in relation to the various technical parameters that have been used, it seems that the appearance of a punctiform focal lesion, in correspondence to the left frontal subcortical white matter, is appreciable. Further demyelinizing foci, previously described in the bihemispheric white matter, are substantially unmodified. At today’s check two limited focal lesions, located , respectively, in pontine and right paramedian field of the medulla oblongata, are more appreciated. A further, more doubtful and less distinct focal lesion, is recognizable on the right thalamic side. Ventricular system in situ, within the norm. Regular width of the CSF subarachnoid spaces. After intravenous contrast medium treatment none of the described foci shows contrastographic captation".
A follow-up neurological visit was further performed with doctor Repice who explained the patient that, as she didn't show other symptoms besides the optic neuritis, she wouldn’t have been treated with any therapy as per health protocol. In other words the patient was told that she had to wait for another episode or event before starting a treatment.
Moreover, the neurologist explained to Ms. X that, as a consequence of the Hodgking’s lymphoma in 1999, as described in the anamnesis, in the future not every available therapy could be compatible with her clinical condition.
 
Expert's Answer
1.     The patient is reported as having a clinically isolated syndrome (CIS), namely optic neuritis (ON). Typical cases of which have not only reduced visual acuity but also a central scotoma, which was absent in this case. Also, it is unclear why the patient had
enlarged blindspot, since papillitis has not been reported.  
Therefore the ophthalmologic findings are still unclear.
 
2.    The brain MRI showed several myelin lesions. However, the typical demyelinating lesions, perpendicular to the ventricle, are not reported.
The corpus callosium lesion should raise suspicion of Susac syndrome, but there are no clinical details supporting this diagnosis.
The bilaterally prolonged VEP are consistent with multiple sclerosis (MS) but also raise the possibility of neuromyelitis optica (NMO).
In addition, a large number of disorders could affect the optic nerves.
The required tests include CSF study which has been done but not reported, in particular regarding the existence of oligoclonal bands and other inflammatory markers; blood studies including qCRP, rheumatological screen, ACE for sarcoidosis, and anti AQ4 antibodies for NMO.
 
3.     If MS is confirmed or other disorders excluded, it is possible to suggest preventive therapies with either b-interferons or glatiremar acetate (GA). Because of the Hodgkin history, care should be executed since these drugs affect the immune system. The least likely to cause adverse events is GA. However, it might be prudent to halt therapy and see the natural course of the disease, and implement preventive
therapy after another episode consistent with MS (if it ever occurs), and of course based on results of the above tests.
 
4.     Stress is the only relevant factor. It would also be advisable to avoid heat stress. The computer work described is not relevant.
 
5.     MS patients can have babies, and actually during the pregnancy period relapses are less likely to occur (although this is offset in the postpartum year). None of the drugs mentioned above has been proved safe in terms of teratogenicity, but the risks seem to be small if they ever exist.
 

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