Twenty-three patients aged from 26 to 75 years ( mean=52.8 years ) were treated with high doses of Biotin from 2 to 36 months ( mean treatment׳s duration=9.2 months ).
Fourteen patients suffered from primary progressive multiple sclerosis and 9 from secondary progressive multiple sclerosis.
Four patients ( 1–4 ) had permanent visual loss following optic nerve involvement; one patient ( patient 5 ) had progressive lateral hemianopia caused by involvement of optic radiations and 18 patients ( patients 6–23 ) had progressive paraparesis or tetraparesis related to spinal cord involvement.
Patients with prominent optic nerve involvement
The 4 patients with chronic visual loss related to involvement of optic nerves exhibited improvement of visual acuity after a delay of 3 months following treatment׳s onset.
The 8 diseased eyes improved by a mean of 0.18 decimal units ( sd=0.11 ) a threshold considered beyond a possible test–retest effect ( Rosser et al., 2003 ).
In all cases, improvement was observed with the dose of 300 mg/day.
Improvement was maintained over time except in patient 2 who exhibited worsening after a multiple sclerosis relapse.
Improvement of visual acuity was associated with improvement of Goldmann perimetry in patients 2–4.
In addition, VEP ( visual evoked potentials ) were performed in patients 1 and 4. In both cases, P100 waves, although not recordable or very delayed at baseline were clearly observable after 9 months of treatment with normalization of latencies in patient 2.
H-MRS was performed every 3 months from treatment׳s onset in patient 1. A progressive normalization of the Choline / Creatine ratio, a myelin marker, was observed over time. After 9 months of treatment, this ratio had returned to normal values.
Patient with homonymous hemianopia
Patient 5 had progressive left homonymous hemianopia worsening over 4 years, related to a lesion involving optic radiations.
Humphrey perimetry was observed to continuously improve from M2 ( 2 months after treatment׳s initiation ) up to M16 ( last follow-up ).
This was confirmed by Visual field defect׳s quantification showing better mean deviation ( MD ) values reached after 7 months of treatment compared to those obtained during the 4 years of the pre-treatment follow-up.
Despite functional improvement, no change in the size or aspect of the right occipital white matter lesion was noted on brain MRIs performed after treatment׳s onset.
Patients with spinal cord involvement
Eighteen patients had prominent involvement of the spinal cord with progressive tetraparesis ( 11 cases ) or paraparesis ( 7 cases ).
Sixteen out of 18 patients ( 89% ) displayed clinical improvement after a delay ranging from 2 to 8 months.
Seven patients ( 6, 7, 8, 13, 14, 15, 16 ) started to improve with 100 mg/day of Biotin; 5 of them ( 6, 8, 14, 15, 16 ) improved even more after increasing the dosage to 300 mg/day.
In the 9 remaining patients, improvement started at the dose of 200 mg ( patients 21 and 22 ) or 300 mg/day ( patients 9, 11, 17, 18, 19, 20, 23 ).
In 9 cases ( 50% ), improvement was documented by blinded review of videotaped clinical examinations.
In all cases, the blinded examiner recognized that the latest video ( after the longest period of treatment ) corresponded to the best examination.
In the sub-group of 11 patients with tetraparesis, 9 patients improved after a delay of 2–8 months. The longest period of observation in this group was 12 months ( patient 6 ).
Two patients ( 10 and 12 ) did not respond at all to treatment despite increasing the dosage to 300 mg/day.
In patient 21, treatment׳s withdrawal for 15 days was followed by a marked worsening leading to the reintroduction of the treatment.
In the sub-group of 7 patients with paraparesis, all patients improved after a delay ranging from 2 to 5 months. The TW25 test was performed in 5/7 cases and best improvement compared to baseline ranged from 17.6% to 33.8%, which can be considered as clinically relevant ( Goodman et al., 2009, Schwid et al., 2002 ). In patients 7 and 20, although some improvement was observed after 3 months of treatment, the positive effect was not maintained overtime. Worsening occurred following a multiple sclerosis relapse in patient 7 and without any explanation in patient 20.
Other symptoms improvement
Neurologists considered that the following symptoms and signs also improved: fatigue ( 5 cases ), swallowing difficulties ( 4 cases ), dysarthria ( 3 cases ), sensory signs ( 2 cases ), gait ataxia ( 2 cases ), urinary dysfunction ( 2 cases ), cognition ( 1 case ), psychiatric signs ( 1 case ), oscillopia ( 1 case ) motor coordination ( 1 case ) and Uhthoff׳s phenomenon ( 1 case ).
Overall, the EDSS score significantly improved in 4/23 patients ( 22% ) with a decrease of at least 1 point ( for initial EDSS between 4 and 5.5 ) or of at least 0.5 ( for initial EDSS between 6 and 8.5 ).
Effect on relapses
Four patients ( 2, 3, 7 and 10 ) out of 23 ( 13% ) receiving high doses of Biotin experienced at least one multiple sclerosis relapse. This frequency was similar to that observed before treatment in these patients.
No adverse effects were reported in 20 cases. Transient diarrhea was noted in 2 patients.
Patient 1 died from cardiac failure 36 months after treatment׳s onset. Mild aortic valvulopathy with dilatation of the ascending aorta together with a first-degree atrio-ventricular block was discovered during the patient׳s follow-up. No relation was established between treatment׳s onset, mild cardiac abnormalities and death: no change in ECG or cardiac ultrasonography could be noted in this patient.
Patient 15 died one year after treatment׳s onset from a pneumopathy few days after sigmoid volvulus surgery. No relation could be established between death and treatment. ( Xagena )
Sedel F et al, Mult Scler Relat Disord 2015; 4 : 159–169