47-year-old female with a diagnosis of Multiple Sclerosis ,who suffers from progressive tetraparesis, more pronounced in the lower extremities. Her treatment included mitoxantrone and Interferon-beta treatment, both were discontinued because of side effects. Her movement difficulties, due to the left lower limb rigidity, are increasing progressively.
1) What is the best treatment?
2) Any alternative treatment and/ or treatments under trial?
3) In particular, do you think that autotransplantation of cells taken from the spinal cord can be used with success in this case?
female, 47 years old
Diagnosis: Demyelinizing Disease
At the age of 16 road accident causing a frontal extracranial hematoma;
At the age of 18 appendectomy;
At the age of 25 and 30 hospitalized following adnexitis;
At the age of 26 hospitalization in the urology ward due to cystitis with hydronephrosis with no results;
At the age of 25, after the second delivery, she suffered from depression treated with psychotherapy.
At the age of 32 hemorrhoidectomy.
In 2004 acute backache with radiation to both lower limbs pharmacologically treated with NSAIDs and steroids. Since then, periodic re-acutization of this symptomatology mostly radiated to the posterior face of the left lower limb. Therefore, she carried out a lumbosacral NMR in January 2005 with evidence of L5-S1 disc herniation, more evident towards the right side. Since then she has performed postural gymnastics with good results.
Since summer 2006 motor clumsiness and slight coordination of the left lower limb movements with limitation in running or walking fast and going down the stairs, for instance. Perhaps, the patient was already suffering from this disorder, in a milder form, from 1–2 years, but she had traced it to lumbosciatic pain. Therefore, she underwent medical neurological examination for suspected demyelinizing disease and the neurologist advised a brain NMR that the patient carried out on 2.2007 showing an allergic reaction to Gadolinium (appearance of diffused urticarioid skin eruptions, slight illness, nausea, vomiting and hypotension regressed by means of intravenous steroid injection in E.R.). The NMR report related as follows: “some areas of lengthened relaxation time in the temporal periventricular white matter deep bilaterally: finding consistent with demyelinizing disease.”
A NMR of the cervical spine without contrast medium was also carried out on 02/2007 with the following report: “in the marrow, beginning from C2 until the first dorsal vertebrae, evidences of several hyperintense images in the T2-weighed sequences with a maximum diameter of about 10-15 mm; the lesions marked are consistent with demyelinizing disease and are most evident in the left lateral and midline dorsal region of the spinal cord.
Spinal tap carried out in February 2007: cells 2 – glucose 63 – proteins 31 - IgG index = 0.8. Tourtellotte’s formula 5.9. Later blood tests have revealed a hypothyroidism condition due to thyroiditis, therefore the patient underwent treatment with Eutorox.
Since summer 2007 the patient has noticed that sometimes things slipped out of her right hand; the motor dysfunction of the her left lower limb still persisted.
A further brain and cervical cord NMR carried out on 08. 2007 highlighted the appearance on a new left frontal lesion and an accentuation of the lesions at the spinal cord level.
She received two cycles of mitoxantrone soon discontinued for leukopenia supervened; Following a specialist examination performed by Dr. L. “the clinical diagnosis of multiple sclerosis following a progressive course was confirmed (the repeated NMRs of 02/2007, 08/2007 and 02/2008 have documented an increase in the lesion load), therefore the patient underwent Interferon-beta treatment also discontinued as it caused her intense articular pain and muscular rigidity. From what her husband reports, there are proofs that the movement difficulties, due to the left lower limb rigidity, are increasing progressively and this is clear from the fact that the number of walks, for instance to the beach, is reducing more and more.
The patient underwent several neurological specialist examinations. After many specialist examinations and as Dr. B. did not make a therapeutic decision, the patient decided to go to Padua in order to consult Prof. G., a world-famous researcher”, who suggested her to join a group of patients treated with a new drug, of which her husband does not remember the name, already in Phase II that had already obtained excellent results. Unfortunately, as a result of the medical tests performed in order to take part to this clinical trial, the patient did not have the necessary requirements for being enrolled in the group and, therefore, she remained outside the aforementioned clinical trial.
At present the patient is carrying out again all the follow-up examinations in order to begin a new treatment with Cyclophosphamide, an immunosuppressor with anti-inflammatory effect.
This is a 47 year- old female with a diagnosis of Multiple Sclerosis , who suffers from progressive tetraparesis, more pronounced in the lower extremities. This indicates that her illness involves ,mainly, the spinal cord.
Little detail is provided to me in the attached material. I feel that I am lacking sufficient information about her disease course- is it a pure progressive course or is it a relapsing- progressive course ( relapses superimposed on progression of leg weakness) ? Was the right hand weakness in the summer of 2007 a relapse/ acute exacerbation of her illness?
If it is a purely progressive disease, what is the slope of progression- is it a rapidly progressive disease or is it a slowly progressive one ?
I do not have any data about ocular involvement ( visual acuity, fundoscopic and VER testing ).This data is essential because in the differential diagnosis of MS , there is a unique variant called Neuromyelitis Optica, a disease that involves both the spinal cord and the optic nerves and its diagnosis is based upon, apart of the clinics, detection of antibodies against aquaporin 4 in the serum.
Concerning treatments – was she ever treated with steroids, either orally or intra- venous ? If the answer is positive, how did she respond to this treatment?
Lacking all the above mentioned information, I am making an assumption that the patient has a progressive course of MS. Unfortunately, if the disease course is mainly progressive, it is poorly, if any, responsive to immunomodulatory medications , such as Interferon beta or Copaxone.
In my opinion, chemotherapy, for example Mitoxantrone or Cyclophospamide may cause severe side effects that greatly overweighs their transient and mild clinical efficacy. I believe that such toxic medications should be reserved for "malignant" cases of MS , where the disease is very rapidly progressive.
I recommend testing of levels of vitamin B12 in the serum. Many patients with MS suffer from vitamin B12 deficiency, and this may aggravate their gait disability. Vitamin D testing in the blood is also important (low levels may have negative effects in MS ).
I recommend to give the patient pulse therapy with intra venous high dose steroids- 1 gram of methylprednisolne per day for 5 consecutive days , followed by 10 days of tapering with oral prednisone. Then, I would suggest that she will receive monthly pulses of 1 gram of methylprednisolone per day for 2-3 consecutive days per month for 6 months. (serum glucose and blood pressure should be monitored ). Bone densitometry and intra ocular pressure should be measured before treatment, and intra ocular pressure should be measured during treatment.
Treatment with Baclofen or Tizanidine may alleviate the leg spasticity. A low dose of 5 mg of Bacolfen twice daily should be started , with gradual increment of the dosage.
Physiotherapy and Occupatinal therapy are an essential part of the treatment and should be included in the daily schedule. Swimming/ hydrotherapy and Pilatis are especially recommended to MS patients.
Participation in a clinical trial is certainly an alternative that should be taking into account. Usually, patients in trials are carefully watched and get special medical attention. There are some ongoing trials in MS, but most of them are designed for relapsing- remitting patients. Autologous bone marrow transplantation is yet a hazardous procedure, and her efficacy on patients' clinical status is mild to moderate. Many medications on trial ,and bone marrow transplantation included amongst them , demonstrated overwhelming affect on MRI parametes, but this improvement in the imaging was not always reflected in impressive improvement in the patients status.