Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study.

BACKGROUND: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS). OBJECTIVE: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion. METHODS: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14). Patients were randomized 10:10:1:1 to autoinjector or PFS in the abdomen, or autoinjector or PFS in the thigh, respectively. Bioequivalence was determined by area under the curve (AUCτ) and maximum plasma concentration (Cmax) for Weeks 8-12. B-cell depletion and safety/tolerability were assessed. RESULTS: A total of 256 patients contributed to the bioequivalence analyses (autoinjector-abdomen, n = 128; PFS-abdomen, n = 128). Abdominal ofatumumab pharmacokinetic exposure was bioequivalent for autoinjector and PFS (geometric mean AUCτ, 487.7 vs 474.1 h × µg/mL (ratio 1.03); Cmax, 1.409 vs 1.409 µg/mL (ratio 1.00)). B-cell counts (median cells/µL) depleted rapidly in all groups from 214.0 (baseline) to 2.0 (Day 14). Ofatumumab was well tolerated. CONCLUSION: Ofatumumab 20 mg q4w self-administered subcutaneously via autoinjector is bioequivalent to PFS administration and provides rapid B-cell depletion.

Pre-pregnancy counseling for women with epilepsy: Can we do better?

OBJECTIVE: For many women with epilepsy (WWE), decision making about pregnancy is difficult, due mainly to the potential teratogenic risks of anti-seizure medications (ASMs). Pre-pregnancy counseling is essential to minimize these risks. This study was conducted to assess the rate and effectiveness of pre-pregnancy counseling for women treated with valproate (VPA) in Estonia. METHODS: We used outpatient prescription data from the national health insurance provider to identify all women treated with VPA during 2011-2018 in Estonia. The personal medical documentation of women who became pregnant while on VPA treatment was reviewed. Pre-pregnancy counseling history and VPA-treatment indications were analyzed. RESULTS: Data from 141 women who became pregnant while on VPA treatment during 2011-2018 time period were analyzed. Of these patients, 77% had epilepsy and 19% psychiatric diagnoses. Pre-pregnancy counseling was recorded for 13% (n = 19) of women who later became pregnant. VPA monotherapy and the lack of VPA treatment indication were associated with the lack of counseling before pregnancy. CONCLUSIONS: This study revealed a significant deficit in pre-pregnancy counseling for WWE treated with VPA in Estonia. Awareness of the need for such counseling should be increased among medical specialists.

Valproic acid prescription trends among females of childbearing age in Estonia: A 14-year nationwide prescription database study.

PURPOSE: Valproic acid (VPA) is a widely used anticonvulsant that is effective against most seizure types. Due to its teratogenic effects, its use should be avoided among females of childbearing age, unless other treatments are ineffective or not tolerated. This study aimed to determine the prevalence of VPA use in 2005-2018 in Estonia, with special attention to females of childbearing age. METHODS: In this retrospective nationwide population-based cohort study, outpatient prescription data from the national health insurance provider were used. Annual sex- and age-specific prevalence rates were calculated, and changes therein during the study period were evaluated. RESULTS: The annual rates of VPA use among females of childbearing age increased significantly in 2005-2014. After 2014, the increasing trend stopped; in 2014-2018, the prevalence rates declined slightly [prevalence rate ratio (PRR), 0.94; P = 0.136]. In males of the same age, the increasing trend continued (PRR, 1.08: P = 0.028). Among neurologists, the rate of VPA prescription to females aged <15 and 15-44 years decreased during 2014-2018 (PRR, 0.74; P < 0.001 and PRR 0.72; P < 0.001, respectively); no change in prescription frequency was seen among psychiatrists during this period. CONCLUSIONS: The increasing trend in VPA usage among females of childbearing age in Estonia stopped after 2014, when the European Medicines Agency's strengthened restrictions on VPA use in females were communicated extensively in Estonia. The level of awareness of VPA's harmful effects during pregnancy is lower in the psychiatric community.

Cognitive profile of patients with manganese-methcathinone encephalopathy.

Manganese-methcathinone encephalopathy (MME) is a rare parkinsonian syndrome described in drug addicts who have self-injected a home-made mixture containing methcathinone and manganese. We assessed 14 patients with MME and compared their results with 14 matched control subjects. The patients had a parkinsonian syndrome with symmetrical bradykinesia, dystonias, and postural, gait and speech impairment, with moderate restrictions in activities of daily living. Their cognitive status was assessed with the Russian version of the Wechsler Adult Intelligence Scale (WAIS) and with tests of attention (Trail Making Test, Bourdon-Wiersma Dot Cancellation Test), memory (Auditory Verbal Learning Test, Rey-Osterrieth Complex Figure), motor skills (Grooved Pegboard), visuospatial skills (Money Road Map Test, Benton Judgment of Line Orientation), and executive abilities (Verbal Fluency, 5-Point Test, Wisconsin Card Sorting Test). Only a few significant differences emerged. After controlling for multiple comparisons, the results in the WAIS Object Assembly subtest, the Grooved Pegboard test (dominant and nondominant hand) and the Verbal Fluency test remained significant.

Creutzfeldt-Jakob Disease Presenting as Nonconvulsive Status Epilepticus.

Creutzfeldt-Jakob disease is a rare, rapidly progressive spongiform encephalopathy in humans. EEG plays an important role in diagnosing this disease. In some patients, epileptic activity and encephalopathy from various aetiologies may share morphological features on EEG. This similarity could create difficulties in EEG interpretation, especially if the patient presents with disturbed consciousness. In this case report, a 74-year-old female with Creutzfeldt-Jakob disease presented initially with rapidly progressive impairment of consciousness and focal epileptiform activity on EEG. An EEG performed 25 days later showed periodic sharp-wave complexes with triphasic morphology at a rate of 0.5 Hz, compatible with a diagnosis of Creutzfeldt-Jakob disease. Based on these results, we recommend that a diagnosis of Creutzfeldt-Jakob disease be considered in patients presenting with a rapid deterioration of consciousness and a clinical presentation of nonconvulsive status epilepticus. Monitoring these patients with serial EEGs could be useful to establish an accurate diagnosis.

Metabolic syndrome and anticonvulsants: A comparative study of valproic acid and carbamazepine.

PURPOSE: The aim of this study was to compare the risk of metabolic syndrome (MS) and evaluate related factors for MS among people with epilepsy treated with valproate (VPA) or carbamazepine (CBZ). METHODS: A total of 213 adult patients with epilepsy treated with VPA (n=118) or CBZ (n=95) monotherapy were included in the study. Participants were evaluated for the presence of MS, diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS: In the multiple logistic regression analysis, the risk of MS in CBZ- and VPA-treated patients was similar (odds ratio [OR]=0.99; 95% confidence interval [CI], 0.43-2.26; P=0.979). A lower proportion of CBZ-treated patients had abnormally low levels of high-density lipoprotein cholesterol (OR=0.10; 95% CI, 0.02-0.42; P=0.002), whereas a lower proportion of VPA-treated patients had abnormally high concentrations of fasting blood glucose (OR=0.30; 95% CI, 0.13-0.69; P=0.004). Females treated with VPA tended to have a higher risk of MS (OR=1.48; 95% CI, 0.50-4.41; P=0.485) compared to males (OR=0.74; 95% CI, 0.28-1.96; P=0.551), although this difference was not statistically significant. CONCLUSION: Although the overall risk of MS was similar in patients with epilepsy who were treated with VPA or CBZ, the distribution of MS components differed between treatment groups. Patients treated with CBZ or VPA less frequently had decreased high-density lipoprotein cholesterol levels or increased blood glucose concentrations, respectively. Females on VPA treatment could be at higher risk of MS than males.

Structured education can improve primary-care management of headache: the first empirical evidence, from a controlled interventional study.

BACKGROUND: Headache disorders are under-recognized and under-diagnosed. A principal factor in their suboptimal management is lack of headache-related training among health-care providers, especially in primary care. In Estonia, general practitioners (GPs) refer many headache patients to neurological specialist services, mostly unnecessarily. GPs request "diagnostic" investigations, which are usually unhelpful and therefore wasteful. GP-made headache diagnoses are often arcane and non-specific, and treatments based on these are inappropriate. The aim of this study was to develop, implement and test an educational model intended to improve headache-related primary health care in Estonia. METHODS: This was a controlled study consisting of baseline observation, intervention and follow-up observation using the same measures of effect. It involved six GPs in Põlva and the surrounding region in Southern Estonia, together with their future patients presenting consecutively with headache as their main complaint, all with their consent. The primary outcome measure was referral rate (RR) to neurological specialist services. Secondary measures included number of GP-requested investigations, GP-made headache diagnoses and how these conformed to standard terminology (ICD-10), and GP-recommended or initiated treatments. RESULTS: RR at baseline (n = 490) was 39.5 %, falling to 34.7 % in the post-intervention group (n = 295) (overall reduction 4.8 %; p = 0.21). In the large subgroup of patients (88 %) for whom GPs made clearly headache-related ICD-10 diagnoses, RR fell by one fifth (from 40 to 32 %; p = 0.08), but the only diagnosis-related RR that showed a statistically significant reduction was (pericranial) myalgia (19 to 3 %; p = 0.03). There was a significant increase towards use of more specific diagnoses. Use of investigations in diagnosing headache reduced from 26 to 4 % (p < 0.0001). Initiation of treatment by GPs increased from 58 to 81 % (p < 0.0001). CONCLUSIONS: These were modest changes in GPs' entrenched behaviour. Nevertheless they were empirical evidence that GPs' practice in the field of headache could be improved by structured education. Furthermore, the changes were likely to be cost-saving. To our knowledge this study is the first to produce such evidence.

Changes in the Peripheral Blood Gene Expression Profile Induced by 3 Months of Valproate Treatment in Patients with Newly Diagnosed Epilepsy.

Valproic acid (VPA) is a widely used antiepileptic drug with a broad range of effects and broad clinical efficacy. As a well-known histone deacetylase (HDAC) inhibitor, VPA regulates epigenetic programming by altering the expression of many genes. The aim of study was to analyze differences in gene expression profiles before and after the start of VPA treatment in patients with newly diagnosed epilepsy. RNA sequencing was used to compare whole-genome gene expression patterns of peripheral blood from nine patients with epilepsy before and 3 months after the start of treatment with VPA. Of the 23,099 analyzed genes, only 11 showed statistically significant differential expression with false discovery rate-adjusted p-values below 0.1. Functional annotation and network analyses showed activation of only one genetic network (enrichment score = 30), which included genes for cardiovascular system development and function, cell morphology, and hematological system development and function. The finding of such a small number of differently expressed genes between before and after the start of treatment suggests a lack of HDAC inhibition in these patients, which could be explained by the relatively low doses of VPA that were used. In conclusion, VPA at standard therapeutic dosages modulates the expression of a small number of genes. Therefore, to minimize the potential side effects of HDAC inhibition, it is recommended that the lowest effective dose of VPA be used for treating epilepsy.

Valproate modulates glucose metabolism in patients with epilepsy after first exposure.

Valproate (VPA) treatment has been reported to be associated with weight gain and metabolic changes, such as hyperinsulinemia. The question of whether hyperinsulinemia and other metabolic changes are consequences of increased weight, or are instead direct results of VPA treatment, remains a matter of debate. The aim of the current study was to explore the influence of VPA treatment on glucose and insulin levels during the oral glucose tolerance test (OGTT) directly following the first intravenous (IV) administration. Sixteen patients (18-46 years old) with newly diagnosed epilepsy underwent an OGTT with 75 g glucose prior to the start of VPA treatment, as well as directly following the first IV VPA administration. We observed that plasma glucose levels during the 120 min of OGTT session following infusion of VPA were significantly lower than those measured during OGTT without VPA treatment (mean ± standard deviation [SD] 4.28 ± 0.94 mmol/l vs. 4.75 ± 1.09 mmol/l respectively, p = 0.038). However, blood concentrations of insulin and C-peptide did not differ significantly between the two measurements. This is the first study to show a potential acute glucose-lowering effect of VPA during OGTT in patients with newly diagnosed epilepsy.

Comparison of the metabolic syndrome risk in valproate-treated patients with epilepsy and the general population in Estonia.

BACKGROUND: No study has explored the risk of metabolic syndrome (MS) in patients with epilepsy treated with valproate (VPA) at the population level. The aim of this study was to compare the risk of MS in VPA-treated patients in Estonia to the risk in the general population. METHODS: This study involved 118 patients with epilepsy (63 men, 55 women) who received VPA monotherapy. MS was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III criteria. Data were compared with the results of a population-based study of the prevalence of MS in the same geographic region (N = 493; 213 men, 280 women). RESULTS: In the multiple logistic regression analysis, after adjustment for age and sex, the risk of MS in VPA-treated patients was not increased compared to the control subjects (odds ratio [OR] = 1.00; 95% confidence interval [CI], 0.59-1.68). VPA-treated patients had higher serum insulin concentrations than control subjects, independent of body mass index (BMI). A positive association was found between MS development and BMI (OR = 1.47; 95% CI, 1.25-1.73) in VPA-treated patients, but there were no associations with the VPA dosage or the homeostasis model assessment-estimated insulin resistance (HOMA-IR) index. In control subjects, BMI and HOMA-IR had similar predictive abilities for MS occurrence. In VPA-treated patients, the predictive ability of the HOMA-IR index was significantly lower than that of BMI, with areas under the receiver operating characteristic curves of 0.808 and 0.897 (P = 0.05), respectively. CONCLUSIONS: The risk of MS is not increased among VPA-treated patients with epilepsy in Estonia compared to the general population. The HOMA-IR index likely has a lower predictive ability for MS in VPA-treated patients compared to its predictive ability in the general population.

123I-ADAM SPET imaging of serotonin transporter in patients with epilepsy and comorbid depression.

BACKGROUND: Purpose of the study was to investigate alterations in midbrain serotonin transporter (SERT) binding in patients with epilepsy and symptoms of depression compared to patients with epilepsy with no symptoms of depression. METHODS: We studied 12 patients with epilepsy (7 patients had focal and 5 had generalized epilepsy syndromes). The presence of self-reported symptoms of depression was assessed using Beck Depression Inventory (BDI) and the Emotional State Questionnaire (EST-Q). The binding potential of the SERT was assessed by performing brain single photon emission tomography (SPET) using the SERT radioligand 2-((2-((dimethylamino)methyl)phenyl)thio)-5-(123)iodophenylamine (123I-ADAM). RESULTS: Seven patients had BDI and EST-Q subscale scores greater than 11 points, which was interpreted as the presence of symptoms of depression. We found that 123I-ADAM binding was not significantly different between patients with epilepsy with and without symptoms of depression. In addition, 123I-ADAM binding did not show a significant correlation to either BDI or EST-Q depression subscale scores and did not differ between patients with focal vs. generalized epilepsy. CONCLUSION: The results of our study failed to demonstrate alterations of SERT binding properties in patients with epilepsy with or without symptoms of depression.

Cognitive profile and depressive symptoms in patients with epilepsy.

BACKGROUND AND OBJECTIVE: The aim of the present study was to describe the cognitive profile of patients with focal and generalized epilepsy syndrome in comparison with healthy control subjects and to investigate whether depression was related to neuropsychological functioning in these patients. MATERIAL AND METHODS: A total of 36 patients with focal epilepsy and 26 patients with generalized epilepsy were compared with the control group of healthy volunteers (n=53). A battery of neuropsychological tests assessing verbal and visual spatial memory and executive functioning was carried out in addition to the completion of the Beck Depression Inventory (BDI). RESULTS: The results indicated that patients with epilepsy performed significantly worse than controls on all verbal memory subscales and verbal fluency domains. The patients with focal epilepsy scored significantly worse than the patients with generalized epilepsy. The BDI scores were significantly correlated with several scores of the cognitive test in both patients' groups but not in the control group. CONCLUSIONS: Our results suggest that patients with epilepsy, especially with focal-onset epilepsy, show cognitive disturbances predominantly in the verbal memory domain. In addition, depression was found to have a negative effect on cognitive functioning in patients with epilepsy.

Current status of epilepsy health care for adult patients from central and eastern European Union countries--a survey of members of the Central Europe Epilepsy Experts Working Group.

PURPOSE: The aim of this survey was to review and compare the current approaches to epilepsy management in central and eastern EU (CEEU) countries. METHOD: The questionnaire was sent to ten invited experts from Bulgaria, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Slovakia, and Slovenia. It focused on the treatment of adults. RESULTS: The number of neurologists and epilepsy reference centers is highly variable in CEEU countries. None of the analyzed states has a formal specialization in epileptology. No universal state-approved criteria for reference centers exist in Czech Republic, Estonia, Hungary, Latvia, and Slovenia. Generally, the protocols for epilepsy treatment in CEEU countries, including drug-resistant epilepsy, are in accordance with international guidelines; however, most countries have their own national standards of care and some have local clinical guidelines. Also, the reimbursement systems for antiepileptic drugs in CEEU countries are highly variable. Seven countries have epilepsy surgery centers. The costs of epilepsy surgeries are fully reimbursed, procedures performed abroad may also be covered. The length of time spent on waiting lists for surgery following the completion of preoperative investigations varies from two weeks to three years. The fraction of patients who qualified and were operated on within 12 months ranges from 20% to 100%. CONCLUSION: The lack of unified procedures pertaining to the evaluation and therapy of epilepsy is reflected by marked differences in access to treatment modalities for patients from CEEU countries.

Epileptic laughter: 2 case reports.

Two cases of gelastic epilepsy in a 6-year-old girl with attacks of mirthful laughter and a 38-year-old male patient with episodes of laughter without any positive emotions are presented. Temporal lobe epilepsy was diagnosed in the first case and possible frontal lobe epilepsy in the second case. It is concluded that that this rare form of epilepsy can be difficult to diagnose and treat, and can clinically be accompanied by urinary incontinence.

Fulminant inflammatory neuropathy mimicking cerebral death.

We report a case of a 44-year-old woman who developed rapidly progressive tetraparesis followed by respiratory failure and abolition of brainstem reflexes. Electrodiagnostic studies excluded the possibility of cerebral death and confirmed the diagnosis of acute motor-sensory axonal neuropathy. The initial fulminant course of the disease was followed by slow recovery to independence in daily activities.

Manganese-Induced Parkinsonism due to Ephedrone Abuse.

During recent years, a syndrome of hypokinesia, dysarthria, dystonia, and postural impairment, related to intravenous use of a "designer" psychostimulant derived from pseudoephedrine using potassium permanganate as the oxidant, has been observed in drug addicts in several countries in Eastern Europe with some cases also in Western countries. A levodopa unresponsive Parkinsonian syndrome occurs within a few months of abusing the homemade drug mixture containing ephedrone (methcathinone) and manganese. The development of this neurological syndrome has been attributed to toxic effects of manganese, but the role of the psychostimulant ephedrone is unclear. This paper describes the clinical syndrome, results of neuroimaging, and therapeutic attempts.

Peripheral blood RNA expression profiling in illicit methcathinone users reveals effect on immune system.

Methcathinone (ephedrone) is relatively easily accessible for abuse. Its users develop an extrapyramidal syndrome and it is not known if this is caused by methcathinone itself, by side-ingredients (manganese), or both. In the present study we aimed to clarify molecular mechanisms underlying this condition. We used microarrays to analyze whole-genome gene expression patterns of peripheral blood from 20 methcathinone users and 20 matched controls. Gene expression profile data were analyzed by Bayesian modeling and functional annotation. Of 28,869 genes on the microarrays, 326 showed statistically significant differential expression with FDR adjusted p-values below 0.05. Quantitative real-time PCR confirmed differential expression for the most of the genes selected for validation. Functional annotation and network analysis indicated activation of a gene network that included immunological disease, cellular movement, and cardiovascular disease functions (enrichment score 42). As HIV and HCV infections were confounding factors, we performed additional stratification of subjects. A similar functional activation of the "immunological disease" category was evident when we compared subjects according to injection status (past versus current users, balanced for HIV and HCV infection). However, this difference was not large therefore the major effect was related to the HIV status of the subjects. Mn-methcathinone abusers have blood RNA expression patterns that mostly reflect their HIV and HCV infections.

Unique spectrum of SPAST variants in Estonian HSP patients: presence of benign missense changes but lack of exonic rearrangements.

BACKGROUND: Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous disorder that can be an autosomal-dominant, autosomal-recessive, or X-linked disease. The most common autosomal-dominant form of the disease derives from mutations in the SPAST gene. METHODS: The aim of this study was to analyze 49 patients diagnosed with HSP from the Estonian population for sequence variants of the SPAST gene and to describe the associated phenotypes. Healthy control individuals (n = 100) with no family history of HSP were also analyzed. All patient samples were screened using denaturing high performance liquid chromatography (DHPLC) and multiplex ligation-dependent probe amplification (MLPA) assay. Samples with abnormal DHPLC and MLPA profiles were sequenced, with the same regions sequenced in control samples. RESULTS: Sequence variants of SPAST were identified in 19/49 HSP patients (38.8%), twelve among them had pathogenic mutations. Within the latter group there was one sporadic case. Eight patients had pure, and four - complex HSP. The twelve variants were identified: seven pathogenic (c.1174-1G>C, c.1185delA, c.1276C>T, c.1352_1356delGAGAA, c.1378C>A, c.1518_1519insTC, c.1841_1842insA) and five non-pathogenic (c.131C>T, c.484G>A, c.685A>G, c.1245+202delG, c.1245+215G>C). Only 2 of these mutations had previously been described (c.131C>T, c.1245+202delG). Three mutations, c.1174-1G>C, c.1276 C>T, c.1378C>A, showed intrafamilial segregation. CONCLUSION: This study identified new variants of the SPAST gene which included benign missense variants and short insertions/deletions. No large rearrangements were found. Based on these data, 7 new pathogenic variants of HSP are associated with clinical phenotypes.

Bladder dysfunction in hereditary spastic paraplegia: what to expect?

BACKGROUND: Hereditary spastic paraplegia (HSP) comprises a group of rare neurodegenerative disorders characterised by progressive spasticity and hyperreflexia of the legs. Neurogenic bladder dysfunction is a well recognised problem in patients with HSP but it has not yet been described systematically in the literature. The aim of this study was to provide an evidential overview of the ways in which urinary dysfunction presents in HSP. METHODS: 49 patients with HSP were included and underwent evaluation. A history was followed by a semi-structured interview and, in those patients who consented, measurement of residual volume of urine (PVR) and urodynamic evaluation. RESULTS: 38 subjects (77.6%) reported some type of urinary symptom. Subjective complaints of bladder problems showed a correlation with verified urinary dysfunction. There were no significant differences in the occurrence of urinary disturbances between the pure and complex forms of HSP. The most frequent symptoms were incontinence (69.4%), hesitancy (59.2%), increased frequency of micturition (55.1%) and urgency (51.0%). Incomplete bladder emptying was the rarest (36.7%). The most common combination of symptoms was to have all of them (14.3%). Incomplete bladder emptying as a complaint was associated with an increased risk of PVR. Women had a higher risk of increased voiding frequency. CONCLUSIONS: To our knowledge, this work is the first systematic and disease oriented overview of neurogenic bladder disturbances in patients with HSP. Our results may be useful to the clinicians who work with HSP patients, allowing them to make appropriate screening and management decisions.

Functional assessment of lower extremities in hereditary spastic paraplegia.

OBJECTIVES: To characterize the spasticity and range of motion (ROM) in patients with hereditary spastic paraplegia (HSP) and to correlate these parameters with walking speed. DESIGN: An observational population-based cohort study. SETTING: Patient data were acquired from a population-based epidemiologic study performed earlier in Estonia. PARTICIPANTS: Persons (N=46) (mean age, 50.1y) with clinically confirmed HSP diagnosis (mean duration, 20.9y) participated in the study. INTERVENTIONS: Active and passive ROMs were measured with a plastic 360 degrees goniometer. Spasticity was evaluated by using the modified Ashworth scale (MAS). The time it took a patient to walk 10m was recorded. MAIN OUTCOME MEASURES: Measurements included testing of active and passive ROM as a marker for mobility, the MAS for spasticity, and time to complete a 10-m walk. RESULTS: A higher degree of spasticity in hip muscles was associated with lower values of active ROM and slower walking. Walking speed was negatively correlated to disease duration and participant age. CONCLUSIONS: The present study provides analysis of the contributions of spasticity and ROM to walking speed in HSP, both factors negatively influence gait in persons with HSP.