Multiple Sclerosis_1
Short Summary

21-year-old female with an acute onset of a unilateral sixth cranial nerve deficit. Brain MRI showed at least a dozen white matter lesions, one of them contrast-enhancing. Sensory evoked potentials showed a bilateral increase in latency. Multiple sclerosis was diagnosed, and the patient was treated by corticosteroids, followed by improvement of symptoms. The first follow-up revealed no focal neurological signs with a history of a transitory unilateral lower limb hyposthenia. On the second visit, a horizonto-rotatory nystagmus and irregular paraesthesia in the right toes are documented. Spinal MRI showed a new and contrast enhancing lesion.

Patient's Questions
1)    What are the most useful treatment indications, recommended for the pathology in question?

2)    Centers of excellence in Italy and abroad?

3)    Names of the most qualified Italian or European specialists for this pathology?
 

 

Medical Background

Female , 21 years old
Diagnosis: MULTIPLE SCLEROSIS
 
No significant conditions in past medical history.
Onset of headaches at the end of December 2006 and subsequent visual defect until the appearance of double vision looking to the left. After arriving at the Emergency Room of San Donato Hospital in Arezzo, the patient was therefore hospitalized for tests on December 2006.
Upon admission, the objective neurological exam pointed only to a left sixth cranial nerve deficit.
 
Examinations performed during hospitalization:
-           Cranial CT (December 2006): negative, so in-depth diagnostic study with brain MR was recommended;
-           brain MR (January 2007): ..in left bulbopontine seat hyper-intense focal lesion in long TR sequence of the size of 9 x 5 mm complete with pathological contrast-graphic enhancement. In supratentorial location, focal lesions in the left occipital seat, periventricular, at the callosal-septal interface, right frontal joint, and at the level of the synovial centers for a total of at least a dozen inactive lesions…;
-           CSF test (10/01):
•           Appearance              clear
•           Total proteins (LCR)            25 mg/dL        (15 – 45);
•           Glucose (LCR)                      55 mg/dL        (40 – 60);
•           Cell count                              0.3cells/mcgL (up to 2);
•           Sediment                               no pathological findings

-           Carotid and Vertebral Color Doppler (December 30, 2006): normal.
Auditory evoked potential normal; visual evoked potential normal.
Sensory evoked potential: bilateral increase of the P3a wave latency.
Blood chemistry screen: normal except for total cholesterol 230 mg/dl (vn<200) and triglycerides 152 mg/dl (vn<150).
 
Cortisone therapy was started during hospitalization, with improved symptoms; this treatment was continued at home following discharge on January 2007, according to a diminishing scheme.
In light of the tests performed during hospitalization, Multiple Sclerosis was diagnosed, so the hospital physicians informed the patient that treatment was unnecessary as long as new symptoms connected with the disease did not appear. 
The patient underwent periodic neurological check-ups on a regular basis with Dr. X, whose reports follow:
-           (05/2007): “during today’s check-up the patient had no focal neurological signs, EDSS is 0. Anamnestically recent sense of transitory hyposthenia for a few hours in the right lower limb not to be attributed to the demyelinating disease. The diagnosis of Relapsing-Remitting Multiple Sclerosis is reconfirmed; said diagnosis backed by the positive NMR, the number of plates and owing to recent enhancement evidence of pontine plate consistent with the finding of positive CSF due to the presence of some oligoclonal IgGs. Brain and bone marrow MR check-up with gadolinium in 6 months. Specific treatment is not recommended.”

-           (01/2008): “with today’s check-up, the neurological objectivity shows only spontaneous horizonto-rotatory nystagmus when looking to the right, result of the past pontine lesion. There are no coordination, strength and sensitivity findings (irregular paraesthesia in the fourth and fifth toes of the right foot seem to be of peripheral significance). Neuro-radiological follow-up to be scheduled soon is recommended.”
 
The pathology was stable until the brain-encephalic stem + cervical + dorsal column NMR of March 2008: “Check-up test in patient with diagnosis clinically defined as demyelinating disease. It is impossible to compare with past history due to non-availability of images. No active lesions are seen in today’s check-up. Multiple lesions of the periventricular white matter, right front-parietal joint area, semioval centers, left occipital region and callosal-septal interface are appreciated. Other lesions are found in FCP on the level of the middle left cerebellar brachium and bulbopontine seat. The ventricular system and the thickness of the callosum are normal.
The study of the bone marrow shows no pathological enhancements. Some plates near C2, C4 and D2 are appreciated, doubtful alteration of signal in C6-C7, no medullary atrophy.
 
However, in June the patient started to complain of persistent and continuous tingling in the feet with consequent execution of a cervical + dorsal column NMR on June 19, 2008, with evidence of active injury, the relevant finding of which is provided below: “Check-up of patient with demyelinating disease, compared with previous one of March 2008.
A new lesion close to C3-C4 in the rear portion of the bone marrow is appreciated with contrast-graphic enhancement, indicative of plate activity. The rest of the bone marrow lesion remains unaltered.” 
 
On June 2008 the patient started a cycle of cortisone, the dosage regimen of which is provided:
Urbason 20 mg                                 1 injection for 6 days + ½ vial for 4 days
Limpidex 15 mg (gastroprotective agent) 1 tablet for 30 days.
 
On July 2008 the patient will be examined again by a specialist, and at that time should commence a treatment that at this point has been declared absolutely necessary.

Expert's Opinion

The history as well as the paraclinical findings of this young lady are very well compatible with a diagnosis of MS. The current diagnostic criteria for MS (2005 Revisions of the “McDonald Criteria”) are met.
 
The main treatment goals in MS are to terminate inflammation and to reduce irreversible axonal damage, both often present especially early in the disease process. Therefore, there is now an almost universal consensus among experts that many MS patients will benefit from early therapy and that treatment should be started as soon as possible. These recommendations have recently been extended to the group of pediatric-onset MS patients, this fact being of interest in view of the relatively young age of the patient. Well in-line with these expert opinions, an initiation of a disease-modifying therapy is currently being recommended for the patient by her attending physician.
 
First-line licensed drugs for a basic therapy of MS are the Beta-Interferons and Glatirameracetate. These drugs also appear to be safe and well tolerated in young patients, including children. 
 
Treatment should preferably be initiated and monitored by an experienced clinical MS specialist. However, the medical centre should be situated as close to the place of residence of the patient as possible, in order to allow frequent follow-ups and competent care in acute exacerbations/attacks. There are of course many qualified MS-specialists in Italy. It should be kept in mind that those with the highest scientific reputation are not necessarily those who provide the best clinical care.
 

I am confident that the patient could benefit from a disease-modifying MS therapy and would recommend that such a treatment (which is quite standardized) should be coordinated by a local MS-specialist.                                                                 

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