Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, 1992
ABSTRACT:The purpose of this investigation was to compare three methods of assessing the excitabi... more ABSTRACT:The purpose of this investigation was to compare three methods of assessing the excitability of lower motoneurones—TA-reflex, H-reflex and F-wave—in 120 patients with spastic hemiparesis following a stroke. The H-reflex was recorded from the soleus muscle after submaximal electrostimulation of the tibial nerve. The T-Achilles (TA) reflex was recorded from the soleus muscle after percussion of the Achilles tendon. The F-wave was recorded in the distal limb muscles after supramaximal electrostimulation of the median, ulnar, fibular and tibial nerves. The patient’s healthy side was used as a control. The TA-reflex, H-reflex and F-wave showed increased amplitudes on the spastic side. All amplitude ratios: TA/M, H/M, Fmax/M and Fmean/M were increased. The H-reflex thresholds were decreased. The F-wave duration, persistence and number of phases were also increased on the spastic side. Despite clinically decreased muscle tone, there were no changes in TA or H-reflex parameters aft...
Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, 1995
ABSTRACT:Writer’s cramp is frequently associated with hand tremor and with other focal dystonias.... more ABSTRACT:Writer’s cramp is frequently associated with hand tremor and with other focal dystonias. Sometimes brain infarction, haemorrhage, arterio-venous malformations or tumors are found to cause symptomatic focal dystonias. A 44-year-old man came to our attention due to writer’s cramp of his right hand and postural 6-8 Hz tremor. About three months after the onset of the disease the tremor and dystonia disappeared, while a right hemiparesis gradually appeared. Cranial computed tomography showed a hypodense nonhomogeneous lesion in the left cerebral hemisphere parietally, that was assumed to represent a cystic tumor. The patient underwent craniotomy and the histological diagnosis revealed an astrocytoma (Grade II-III). In conclusion our findings confirm the common anatomical basis of symptomatic focal dystonia and tremor. Both can appear after disruption of the pathways within and adjacent to the basal ganglia.
It is well known that during the withdrawal period after chronic alcohol intake, tremor is one of... more It is well known that during the withdrawal period after chronic alcohol intake, tremor is one of the symptoms that disturb patients. Alcohol withdrawal tremor might be a variant of enhanced physiological tremor, most often caused by anxiety or emotional stress. The aim of this investigation was to establish the EMG pattern of alcoholic tremor and to compare it with the well known pattern of enhanced physiological tremor caused by anxiety or emotional stress. Forty patients 20-43 years old were investigated by a neurologist and psychiatrist 1-10 days after acute alcohol withdrawal. They all met the criteria for chronic alcoholism. Thirty three patients 26-43 years old with the complaint of tremor and anxiety or emotional stress were also investigated. An electromyographic investigation was performed to evaluate the pattern, frequency and amplitude of tremor. Results revealed that both groups of patients had 8-12 Hz low amplitude postural tremor with synchronous activity in antagonis...
The nosology of scapuloperoneal syndrome remains controversial. Is it a variant of Charcot-Marie-... more The nosology of scapuloperoneal syndrome remains controversial. Is it a variant of Charcot-Marie-Tooth's disease, a form of myopathy, or of spinal muscular atrophy is still unknown. A family with a scapuloperoneal syndrome caused by anterior horn cell involvement is described. Data for sensory involvement were also found. In addition one member of the family had motor nerves and corticospinal tract involvement. The distribution of weakness and muscle wasting was unusual--only lower limbs were involved. However, electromyographic data for both upper and lower limbs involvement were evident. The combination of scapuloperoneal syndrome with sensory loss has been described by Davidenkow, but was not proved by neurographic investigation. Later only one case with proved sensory disturbances was reported. Patients with motor nerves involvement in addition were reported, but not received satisfactory explanation. Probably in some patients the disease could be manifested only with anteri...
A statement of the Central and East European (CEE) MS Expert Group 355 1 3 enzymes, and ophthalmo... more A statement of the Central and East European (CEE) MS Expert Group 355 1 3 enzymes, and ophthalmologic changes. Recommendations on the use of fingolimod including safety aspects are given in this article.
Background: Ibudilast is a phosphodiesterase inhibitor influencing inflammation and neurodegenera... more Background: Ibudilast is a phosphodiesterase inhibitor influencing inflammation and neurodegeneration in multiple sclerosis (MS). This study evaluated the safety, tolerability, and effects on MRI parameters of 2 different doses of ibudilast in relapsing forms of MS. Methods: In this multicenter, double-blind, phase 2 trial, patients with relapsing MS and gadolinium-enhancing lesions were randomly assigned 1:1:1 to receive 30 or 60 mg ibudilast or placebo every day for 12 months. The primary endpoint was the cumulative number of newly active lesions on bimonthly brain MRI over 12 months. Secondary endpoints included relapse rate, change in Expanded Disability Status Scale (EDSS) score, T2-hyperintense and T1hypointense lesion volumes, and percent brain volume change (PBVC). Results: A total of 297 patients were randomized in 19 centers. During the first 12 months, the mean number of active lesions and relapse rate did not differ between treatment arms. A reduction in PBVC (p ϭ 0.04) was found in the 60-mg group (0.8%) compared with placebo (1.2%). Post hoc analysis showed a reduction in the proportion active lesions that evolved into persistent black holes for the 60-mg (0.14; p ϭ 0.004) and 30-mg (0.17; p ϭ 0.036) groups compared with the placebo group (0.24). Over 2 years, there were fewer patients (p ϭ 0.026) with confirmed progression on the EDSS. Treatment with ibudilast was generally safe and well tolerated. Conclusion: Ibudilast showed no beneficial effect on the rate of newly active lesions and relapses. However, preliminary evidence suggests that ibudilast seems to act in a neuroprotective fashion as measured by 2 independent MRI outcomes, with a possible beneficial clinical effect on disability progression. Classification of evidence: This interventional study provides Class III evidence on the effect of ibudilast on disease activity. Neurology ® 2010;74:1-1 GLOSSARY AE ϭ adverse event; CI ϭ confidence interval; DTPA ϭ diethylenetriaminepentaacetic acid; EAE ϭ experimental autoimmune encephalomyelitis; EDSS ϭ Expanded Disability Status Scale; Gd ϭ gadolinium; IAC ϭ Image Analysis Center; IFN ϭ interferon; IL ϭ interleukin; ITT ϭ intent-to-treat; mRNA ϭ messenger RNA; MS ϭ multiple sclerosis; PBH ϭ persistent black hole; PBVC ϭ percent brain volume change; PDEI ϭ phosphodiesterase inhibitor; RR ϭ relative risk; TNF ϭ tumor necrosis factor. Phosphodiesterase inhibitors (PDEIs) have been considered as possible treatment for multiple sclerosis (MS), given their anti-inflammatory effects. Ibudilast mainly inhibits phosphodiesterase types 3, 4, 10, and 11 1,2 and inhibits leukotrienes and nitric oxide synthesis mechanisms which are involved in MS. 3 Ibudilast is used in Japan and Korea to treat bronchial asthma and cerebrovascular disorders. 4,5 Ibudilast exerts a number of beneficial effects in the brain, 6 e.g., the inhibition of tumor necrosis factor (TNF)-␣ release from the astrocytes and microglial cells, 2,3 reducing neuronal degeneration. In chronic cerebral ischemia, treatment with ibudilast reduced white matter lesions and microglia activation. 7 Ibudilast protects astrocytes against apoptosis 8 and, in the animal model of Krabbe disease, inhibits oligodendrocyte apoptosis and demyelination. 9
Background: The ExtaviJect ® 30G autoinjector was developed to facilitate parenteral selfadminist... more Background: The ExtaviJect ® 30G autoinjector was developed to facilitate parenteral selfadministration of interferon beta-1b (Extavia ®), a first-line disease-modifying therapy in patients with multiple sclerosis. Our aim was to assess patient compliance with treatment when using the autoinjector, patients' and nurses' experiences of using the device, its tolerability, and patient satisfaction. Methods: This was a 12-week, real-world, prospective, observational, noninterventional study conducted in nine European countries. Questionnaires were used to measure patient compliance and to assess patients' and nurses' experiences. All adverse events were recorded by severity, including injection site reactions or pain. Patient satisfaction and health-related quality of life were assessed using the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) and EuroQol-5 Dimension (EQ-5D) instruments, respectively. Results: Of 582 patients enrolled, 568 (98%) received at least one injection and attended the first follow-up visit at 6 weeks, and 542 (93%) attended the second follow-up visit at 12 weeks. For the whole study, 548 of 568 (97%) patients were compliant with treatment. Among the various questions assessing whether the device was easy and quick to use accurately, without fear of the needle, 56%-98% of patients and 59%-98% of nurses were in agreement. There were nine serious adverse events (four disease-related) reported among the 227 (39%) patients reporting adverse events. Scores increased in the TSQM-9 convenience domain between weeks 6 and 12 (P=0.0009), and in the EQ-5D visual analog scale between baseline and week 12 (P,0.0001), indicating improvement in health-related quality of life. Conclusion: ExtaviJect 30G was convenient to use and was associated with high levels of compliance.
Multiple sclerosis (MS) is a chronic and potentially highly disabling disorder with considerable ... more Multiple sclerosis (MS) is a chronic and potentially highly disabling disorder with considerable social impact and economic consequences. It is the major cause of nontraumatic disability in young adults. The social costs associated with MS are high because of its long duration, the early loss of productivity, the need for assistance in activities of daily living and the use of immunomodulatory treatments and multidisciplinary health care. Available MS epidemiological estimates are aimed at providing a measure of the disease burden in Europe. The total estimated prevalence rate of MS for the past three decades is 83 per 100 000 with higher rates in northern countries and a female:male ratio around 2.0. Prevalence rates are higher for women for all countries considered. The highest prevalence rates have been estimated for the age group 35-64 years for both sexes and for all countries. The estimated European mean annual MS incidence rate is 4.3 cases per 100 000. The mean distribution by disease course and by disability is also reported. Despite the wealth of epidemiological data on MS, comparing epidemiological indices among European countries is a hard task and often leads only to approximate estimates. This represents a major methodological concern when evaluating the MS burden in Europe and when implementing specific cost-ofillness studies.
the BHT-3009 Study Group Objective: To evaluate the efficacy and safety of BHT-3009 in relapsing-... more the BHT-3009 Study Group Objective: To evaluate the efficacy and safety of BHT-3009 in relapsing-remitting multiple sclerosis (MS) and to confirm that BHT-3009 causes immune tolerance. Methods: BHT-3009 is a tolerizing DNA vaccine for MS, encoding full-length human myelin basic protein. Relapsingremitting MS patients were randomized 1:1:1 into three groups: placebo, 0.5mg BHT-3009, or 1.5mg BHT-3009, given intramuscularly at weeks 0, 2, 4, and every 4 weeks thereafter until week 44. The primary end point was the 4-week rate of occurrence of new gadolinium-enhancing lesions on brain magnetic resonance images from weeks 28 to 48. Protein microarrays were used to measure levels of anti-myelin autoantibodies. Results: Compared with placebo, in the 267 patient analysis population the median 4-week rate of new enhancing lesions during weeks 28 to 48 was 50% lower with 0.5mg BHT-3009 (p ϭ 0.07) and during weeks 8 to 48 was 61% lower with 0.5mg BHT-3009 (p ϭ 0.05). The mean volume of enhancing lesions at week 48 was 51% lower on 0.5mg BHT-3009 compared with placebo (p ϭ 0.02). No significant improvement in magnetic resonance imaging lesion parameters was observed with 1.5mg BHT-3009. Dramatic reductions in 23 myelin-specific autoantibodies in the 0.5mg BHT-3009 arm were observed, but not with placebo or 1.5mg BHT-3009. Conclusions: In relapsing-remitting MS patients, treatment with the lower dose (0.5mg) of BHT-3009 for 44 weeks nearly attained the primary end point for reduction of the rate of new enhancing magnetic resonance imaging lesions (p ϭ 0.07) and achieved several secondary end points including a reduction of the rate of enhancing magnetic resonance imaging lesions from weeks 8 to 48 (p ϭ 0.05). Immunological data in a preselected subgroup of patients also indicated that treatment with 0.5mg induced antigen-specific immune tolerance. The greater dose was ineffective.
Multiple sclerosis (MS) is a neurological disorder characterized by inflammatory demyelination an... more Multiple sclerosis (MS) is a neurological disorder characterized by inflammatory demyelination and neurodegeneration in the central nervous system. Until recently, diseasemodifying treatment was based on agents requiring parenteral delivery, thus limiting long-term compliance. Basic treatments such as beta-interferon provide only moderate efficacy, and although therapies for second-line treatment and highly active MS are more effective, they are associated with potentially severe side effects. Fingolimod (Gilenya ®) is the first oral treatment of MS and has recently been approved as single disease-modifying therapy in highly active relapsing-remitting multiple sclerosis (RRMS) for adult patients with high disease activity despite basic treatment (beta-interferon) and for treatment-naïve patients with rapidly evolving severe RRMS. At a scientific meeting that took place in Vienna on November 18th, 2011, experts from ten Central and Eastern European countries discussed the clinical benefits and potential risks of fingolimod for MS, suggested how the new therapy fits within the current treatment algorithm and provided expert opinion for the selection and management of patients.
Background: According to the majority of epidemiological studies for primary torsion dystonia (PT... more Background: According to the majority of epidemiological studies for primary torsion dystonia (PTD), it is a rare disease, although there are some controversial data, showing much higher figures. Because the need of clarification in this field, the aim of this study is to estimate the frequency of primary torsion dystonia in the Bulgarian population. Materials and Methods: We made an official inquiry to the National Center for Health Information, and to the National Health-Insurance Fund for the total count of all the patients, registered with the diagnose of PTD for a period of a year. Simultaneously we examined the archive of the University Multidisciplinary Hospital for Active Treatment of Neurology and Psychiatry - UMHATNP “St. Naum” in Sofia, with a specialized department of Movement Disorders, for the period of 01.01.2008-01.01.2012. Results: Crude annual prevalence of primary torsion dystonia estimated in this study is significantly lower than most reported epidemiological fi...
Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, 1992
ABSTRACT:The purpose of this investigation was to compare three methods of assessing the excitabi... more ABSTRACT:The purpose of this investigation was to compare three methods of assessing the excitability of lower motoneurones—TA-reflex, H-reflex and F-wave—in 120 patients with spastic hemiparesis following a stroke. The H-reflex was recorded from the soleus muscle after submaximal electrostimulation of the tibial nerve. The T-Achilles (TA) reflex was recorded from the soleus muscle after percussion of the Achilles tendon. The F-wave was recorded in the distal limb muscles after supramaximal electrostimulation of the median, ulnar, fibular and tibial nerves. The patient’s healthy side was used as a control. The TA-reflex, H-reflex and F-wave showed increased amplitudes on the spastic side. All amplitude ratios: TA/M, H/M, Fmax/M and Fmean/M were increased. The H-reflex thresholds were decreased. The F-wave duration, persistence and number of phases were also increased on the spastic side. Despite clinically decreased muscle tone, there were no changes in TA or H-reflex parameters aft...
Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, 1995
ABSTRACT:Writer’s cramp is frequently associated with hand tremor and with other focal dystonias.... more ABSTRACT:Writer’s cramp is frequently associated with hand tremor and with other focal dystonias. Sometimes brain infarction, haemorrhage, arterio-venous malformations or tumors are found to cause symptomatic focal dystonias. A 44-year-old man came to our attention due to writer’s cramp of his right hand and postural 6-8 Hz tremor. About three months after the onset of the disease the tremor and dystonia disappeared, while a right hemiparesis gradually appeared. Cranial computed tomography showed a hypodense nonhomogeneous lesion in the left cerebral hemisphere parietally, that was assumed to represent a cystic tumor. The patient underwent craniotomy and the histological diagnosis revealed an astrocytoma (Grade II-III). In conclusion our findings confirm the common anatomical basis of symptomatic focal dystonia and tremor. Both can appear after disruption of the pathways within and adjacent to the basal ganglia.
It is well known that during the withdrawal period after chronic alcohol intake, tremor is one of... more It is well known that during the withdrawal period after chronic alcohol intake, tremor is one of the symptoms that disturb patients. Alcohol withdrawal tremor might be a variant of enhanced physiological tremor, most often caused by anxiety or emotional stress. The aim of this investigation was to establish the EMG pattern of alcoholic tremor and to compare it with the well known pattern of enhanced physiological tremor caused by anxiety or emotional stress. Forty patients 20-43 years old were investigated by a neurologist and psychiatrist 1-10 days after acute alcohol withdrawal. They all met the criteria for chronic alcoholism. Thirty three patients 26-43 years old with the complaint of tremor and anxiety or emotional stress were also investigated. An electromyographic investigation was performed to evaluate the pattern, frequency and amplitude of tremor. Results revealed that both groups of patients had 8-12 Hz low amplitude postural tremor with synchronous activity in antagonis...
The nosology of scapuloperoneal syndrome remains controversial. Is it a variant of Charcot-Marie-... more The nosology of scapuloperoneal syndrome remains controversial. Is it a variant of Charcot-Marie-Tooth's disease, a form of myopathy, or of spinal muscular atrophy is still unknown. A family with a scapuloperoneal syndrome caused by anterior horn cell involvement is described. Data for sensory involvement were also found. In addition one member of the family had motor nerves and corticospinal tract involvement. The distribution of weakness and muscle wasting was unusual--only lower limbs were involved. However, electromyographic data for both upper and lower limbs involvement were evident. The combination of scapuloperoneal syndrome with sensory loss has been described by Davidenkow, but was not proved by neurographic investigation. Later only one case with proved sensory disturbances was reported. Patients with motor nerves involvement in addition were reported, but not received satisfactory explanation. Probably in some patients the disease could be manifested only with anteri...
A statement of the Central and East European (CEE) MS Expert Group 355 1 3 enzymes, and ophthalmo... more A statement of the Central and East European (CEE) MS Expert Group 355 1 3 enzymes, and ophthalmologic changes. Recommendations on the use of fingolimod including safety aspects are given in this article.
Background: Ibudilast is a phosphodiesterase inhibitor influencing inflammation and neurodegenera... more Background: Ibudilast is a phosphodiesterase inhibitor influencing inflammation and neurodegeneration in multiple sclerosis (MS). This study evaluated the safety, tolerability, and effects on MRI parameters of 2 different doses of ibudilast in relapsing forms of MS. Methods: In this multicenter, double-blind, phase 2 trial, patients with relapsing MS and gadolinium-enhancing lesions were randomly assigned 1:1:1 to receive 30 or 60 mg ibudilast or placebo every day for 12 months. The primary endpoint was the cumulative number of newly active lesions on bimonthly brain MRI over 12 months. Secondary endpoints included relapse rate, change in Expanded Disability Status Scale (EDSS) score, T2-hyperintense and T1hypointense lesion volumes, and percent brain volume change (PBVC). Results: A total of 297 patients were randomized in 19 centers. During the first 12 months, the mean number of active lesions and relapse rate did not differ between treatment arms. A reduction in PBVC (p ϭ 0.04) was found in the 60-mg group (0.8%) compared with placebo (1.2%). Post hoc analysis showed a reduction in the proportion active lesions that evolved into persistent black holes for the 60-mg (0.14; p ϭ 0.004) and 30-mg (0.17; p ϭ 0.036) groups compared with the placebo group (0.24). Over 2 years, there were fewer patients (p ϭ 0.026) with confirmed progression on the EDSS. Treatment with ibudilast was generally safe and well tolerated. Conclusion: Ibudilast showed no beneficial effect on the rate of newly active lesions and relapses. However, preliminary evidence suggests that ibudilast seems to act in a neuroprotective fashion as measured by 2 independent MRI outcomes, with a possible beneficial clinical effect on disability progression. Classification of evidence: This interventional study provides Class III evidence on the effect of ibudilast on disease activity. Neurology ® 2010;74:1-1 GLOSSARY AE ϭ adverse event; CI ϭ confidence interval; DTPA ϭ diethylenetriaminepentaacetic acid; EAE ϭ experimental autoimmune encephalomyelitis; EDSS ϭ Expanded Disability Status Scale; Gd ϭ gadolinium; IAC ϭ Image Analysis Center; IFN ϭ interferon; IL ϭ interleukin; ITT ϭ intent-to-treat; mRNA ϭ messenger RNA; MS ϭ multiple sclerosis; PBH ϭ persistent black hole; PBVC ϭ percent brain volume change; PDEI ϭ phosphodiesterase inhibitor; RR ϭ relative risk; TNF ϭ tumor necrosis factor. Phosphodiesterase inhibitors (PDEIs) have been considered as possible treatment for multiple sclerosis (MS), given their anti-inflammatory effects. Ibudilast mainly inhibits phosphodiesterase types 3, 4, 10, and 11 1,2 and inhibits leukotrienes and nitric oxide synthesis mechanisms which are involved in MS. 3 Ibudilast is used in Japan and Korea to treat bronchial asthma and cerebrovascular disorders. 4,5 Ibudilast exerts a number of beneficial effects in the brain, 6 e.g., the inhibition of tumor necrosis factor (TNF)-␣ release from the astrocytes and microglial cells, 2,3 reducing neuronal degeneration. In chronic cerebral ischemia, treatment with ibudilast reduced white matter lesions and microglia activation. 7 Ibudilast protects astrocytes against apoptosis 8 and, in the animal model of Krabbe disease, inhibits oligodendrocyte apoptosis and demyelination. 9
Background: The ExtaviJect ® 30G autoinjector was developed to facilitate parenteral selfadminist... more Background: The ExtaviJect ® 30G autoinjector was developed to facilitate parenteral selfadministration of interferon beta-1b (Extavia ®), a first-line disease-modifying therapy in patients with multiple sclerosis. Our aim was to assess patient compliance with treatment when using the autoinjector, patients' and nurses' experiences of using the device, its tolerability, and patient satisfaction. Methods: This was a 12-week, real-world, prospective, observational, noninterventional study conducted in nine European countries. Questionnaires were used to measure patient compliance and to assess patients' and nurses' experiences. All adverse events were recorded by severity, including injection site reactions or pain. Patient satisfaction and health-related quality of life were assessed using the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) and EuroQol-5 Dimension (EQ-5D) instruments, respectively. Results: Of 582 patients enrolled, 568 (98%) received at least one injection and attended the first follow-up visit at 6 weeks, and 542 (93%) attended the second follow-up visit at 12 weeks. For the whole study, 548 of 568 (97%) patients were compliant with treatment. Among the various questions assessing whether the device was easy and quick to use accurately, without fear of the needle, 56%-98% of patients and 59%-98% of nurses were in agreement. There were nine serious adverse events (four disease-related) reported among the 227 (39%) patients reporting adverse events. Scores increased in the TSQM-9 convenience domain between weeks 6 and 12 (P=0.0009), and in the EQ-5D visual analog scale between baseline and week 12 (P,0.0001), indicating improvement in health-related quality of life. Conclusion: ExtaviJect 30G was convenient to use and was associated with high levels of compliance.
Multiple sclerosis (MS) is a chronic and potentially highly disabling disorder with considerable ... more Multiple sclerosis (MS) is a chronic and potentially highly disabling disorder with considerable social impact and economic consequences. It is the major cause of nontraumatic disability in young adults. The social costs associated with MS are high because of its long duration, the early loss of productivity, the need for assistance in activities of daily living and the use of immunomodulatory treatments and multidisciplinary health care. Available MS epidemiological estimates are aimed at providing a measure of the disease burden in Europe. The total estimated prevalence rate of MS for the past three decades is 83 per 100 000 with higher rates in northern countries and a female:male ratio around 2.0. Prevalence rates are higher for women for all countries considered. The highest prevalence rates have been estimated for the age group 35-64 years for both sexes and for all countries. The estimated European mean annual MS incidence rate is 4.3 cases per 100 000. The mean distribution by disease course and by disability is also reported. Despite the wealth of epidemiological data on MS, comparing epidemiological indices among European countries is a hard task and often leads only to approximate estimates. This represents a major methodological concern when evaluating the MS burden in Europe and when implementing specific cost-ofillness studies.
the BHT-3009 Study Group Objective: To evaluate the efficacy and safety of BHT-3009 in relapsing-... more the BHT-3009 Study Group Objective: To evaluate the efficacy and safety of BHT-3009 in relapsing-remitting multiple sclerosis (MS) and to confirm that BHT-3009 causes immune tolerance. Methods: BHT-3009 is a tolerizing DNA vaccine for MS, encoding full-length human myelin basic protein. Relapsingremitting MS patients were randomized 1:1:1 into three groups: placebo, 0.5mg BHT-3009, or 1.5mg BHT-3009, given intramuscularly at weeks 0, 2, 4, and every 4 weeks thereafter until week 44. The primary end point was the 4-week rate of occurrence of new gadolinium-enhancing lesions on brain magnetic resonance images from weeks 28 to 48. Protein microarrays were used to measure levels of anti-myelin autoantibodies. Results: Compared with placebo, in the 267 patient analysis population the median 4-week rate of new enhancing lesions during weeks 28 to 48 was 50% lower with 0.5mg BHT-3009 (p ϭ 0.07) and during weeks 8 to 48 was 61% lower with 0.5mg BHT-3009 (p ϭ 0.05). The mean volume of enhancing lesions at week 48 was 51% lower on 0.5mg BHT-3009 compared with placebo (p ϭ 0.02). No significant improvement in magnetic resonance imaging lesion parameters was observed with 1.5mg BHT-3009. Dramatic reductions in 23 myelin-specific autoantibodies in the 0.5mg BHT-3009 arm were observed, but not with placebo or 1.5mg BHT-3009. Conclusions: In relapsing-remitting MS patients, treatment with the lower dose (0.5mg) of BHT-3009 for 44 weeks nearly attained the primary end point for reduction of the rate of new enhancing magnetic resonance imaging lesions (p ϭ 0.07) and achieved several secondary end points including a reduction of the rate of enhancing magnetic resonance imaging lesions from weeks 8 to 48 (p ϭ 0.05). Immunological data in a preselected subgroup of patients also indicated that treatment with 0.5mg induced antigen-specific immune tolerance. The greater dose was ineffective.
Multiple sclerosis (MS) is a neurological disorder characterized by inflammatory demyelination an... more Multiple sclerosis (MS) is a neurological disorder characterized by inflammatory demyelination and neurodegeneration in the central nervous system. Until recently, diseasemodifying treatment was based on agents requiring parenteral delivery, thus limiting long-term compliance. Basic treatments such as beta-interferon provide only moderate efficacy, and although therapies for second-line treatment and highly active MS are more effective, they are associated with potentially severe side effects. Fingolimod (Gilenya ®) is the first oral treatment of MS and has recently been approved as single disease-modifying therapy in highly active relapsing-remitting multiple sclerosis (RRMS) for adult patients with high disease activity despite basic treatment (beta-interferon) and for treatment-naïve patients with rapidly evolving severe RRMS. At a scientific meeting that took place in Vienna on November 18th, 2011, experts from ten Central and Eastern European countries discussed the clinical benefits and potential risks of fingolimod for MS, suggested how the new therapy fits within the current treatment algorithm and provided expert opinion for the selection and management of patients.
Background: According to the majority of epidemiological studies for primary torsion dystonia (PT... more Background: According to the majority of epidemiological studies for primary torsion dystonia (PTD), it is a rare disease, although there are some controversial data, showing much higher figures. Because the need of clarification in this field, the aim of this study is to estimate the frequency of primary torsion dystonia in the Bulgarian population. Materials and Methods: We made an official inquiry to the National Center for Health Information, and to the National Health-Insurance Fund for the total count of all the patients, registered with the diagnose of PTD for a period of a year. Simultaneously we examined the archive of the University Multidisciplinary Hospital for Active Treatment of Neurology and Psychiatry - UMHATNP “St. Naum” in Sofia, with a specialized department of Movement Disorders, for the period of 01.01.2008-01.01.2012. Results: Crude annual prevalence of primary torsion dystonia estimated in this study is significantly lower than most reported epidemiological fi...
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