-
PloS One 2016Spastic gait is a key feature in patients with hereditary spastic paraparesis, but the gait characterization and the relationship between the gait impairment and...
BACKGROUND
Spastic gait is a key feature in patients with hereditary spastic paraparesis, but the gait characterization and the relationship between the gait impairment and clinical characteristics have not been investigated.
OBJECTIVES
To describe the gait patterns in hereditary spastic paraparesis and to identify subgroups of patients according to specific kinematic features of walking.
METHODS
We evaluated fifty patients by computerized gait analysis and compared them to healthy participants. We computed time-distance parameters of walking and the range of angular motion at hip, knee, and ankle joints, and at the trunk and pelvis. Lower limb joint moments and muscle co-activation values were also evaluated.
RESULTS
We identified three distinct subgroups of patients based on the range of motion values. Subgroup one was characterized by reduced hip, knee, and ankle joint range of motion. These patients were the most severely affected from a clinical standpoint, had the highest spasticity, and walked at the slowest speed. Subgroup three was characterized by an increased hip joint range of motion, but knee and ankle joint range of motion values close to control values. These patients were the most mildly affected and had the highest walking speed. Finally, subgroup two showed reduced knee and ankle joint range of motion, and hip range of motion values close to control values. Disease severity and gait speed in subgroup two were between those of subgroups one and three.
CONCLUSIONS
We identified three distinctive gait patterns in patients with hereditary spastic paraparesis that correlated robustly with clinical data. Distinguishing specific features in the gait patterns of these patients may help tailor pharmacological and rehabilitative treatments and may help evaluate therapeutic effects over time.
Topics: Adult; Ankle Joint; Biomechanical Phenomena; Electromyography; Female; Gait; Gait Disorders, Neurologic; Hip Joint; Humans; Knee Joint; Male; Middle Aged; Muscle Spasticity; Muscle, Skeletal; Paraparesis, Spastic; Range of Motion, Articular; Walking
PubMed: 27732632
DOI: 10.1371/journal.pone.0164623 -
Pathogens (Basel, Switzerland) Jan 2022, a metastrongyloid nematode, parasitizes in meningeal vessels in the thoracolumbar spinal cord of cats in South America and causes progressive paraparesis. Recently,...
, a metastrongyloid nematode, parasitizes in meningeal vessels in the thoracolumbar spinal cord of cats in South America and causes progressive paraparesis. Recently, the first report outside of South America described gurltiosis in a cat in Spain. As this parasitic disease has so far been largely neglected, especially outside of South America, the aim of the present case study was to add knowledge to the histologic and immunohistochemical characterization of central nervous lesions. To this purpose, formalin-fixed and paraffin-embedded (FFPE) tissue samples from the spinal cord and brain of five cats affected by clinical signs caused by and of three control cats without CNS lesions were histopathologically examined using hematoxylin and eosin stain (HE), Elastica van Gieson stain, as well as periodic acid-Schiff (PAS) reaction. Moreover, immuno- histochemistry for alpha smooth muscle actin and Factor VIII-related antigen were performed to characterize vascular lesions. Lesions were consistent with previous descriptions and were mainly located in the spinal cord and consisted of chronic suppurative or lymphoplasmahistiocytic meningi tis as well as suppurative vasculitis, congestion and varicosis of meningeal veins. In view of the recent detection of this parasite in Europe and the increasing inner-European transport of rescued domestic cats, veterinarians in Europe should be aware of the clinical and pathomorphological presentation of this disease.
PubMed: 35056036
DOI: 10.3390/pathogens11010088 -
Neurology Apr 2020To identify the etiology of an outbreak of spastic paraparesis among women and children in the Western Province of Zambia suspected to be konzo.
OBJECTIVE
To identify the etiology of an outbreak of spastic paraparesis among women and children in the Western Province of Zambia suspected to be konzo.
METHODS
We conducted an outbreak investigation of individuals from Mongu District, Western Province, Zambia, who previously developed lower extremity weakness. Cases were classified with the World Health Organization definition of konzo. Active case finding was conducted through door-to-door evaluation in affected villages and sensitization at local health clinics. Demographic, medical, and dietary history was used to identify common exposures in all cases. Urine and blood specimens were taken to evaluate for konzo and alternative etiologies.
RESULTS
We identified 32 cases of konzo exclusively affecting children 6 to 14 years of age and predominantly females >14 years of age. Fourteen of 15 (93%) cases ≥15 years of age were female, 11 (73%) of whom were breastfeeding at the time of symptom onset. Cassava was the most commonly consumed food (median [range] 14 [4-21] times per week), while protein-rich foods were consumed <1 time per week for all cases. Of the 30 patients providing urine specimens, median thiocyanate level was 281 (interquartile range 149-522) μmol/L, and 73% of urine samples had thiocyanate levels >136 μmol/L, the 95th percentile of the US population in 2013 to 2014.
CONCLUSION
This investigation revealed the first documented cases of konzo in Zambia, occurring in poor communities with diets high in cassava and low in protein, consistent with previous descriptions from neighboring countries.
Topics: Adolescent; Age Factors; Breast Feeding; Child; Cyanides; Diet; Disease Outbreaks; Female; Humans; Male; Manihot; Muscle Weakness; Paraparesis, Spastic; Protein Deficiency; Rain; Seasons; Thiocyanates; Young Adult; Zambia
PubMed: 32127386
DOI: 10.1212/WNL.0000000000009017 -
Frontiers in Neurology 2023As a rare genetic disease, adrenomyeloneuropathy (AMN) is the most common adult phenotype of X-linked adrenoleukodystrophy (X-ALD). Mutations in the ABCD1 gene have been...
BACKGROUND
As a rare genetic disease, adrenomyeloneuropathy (AMN) is the most common adult phenotype of X-linked adrenoleukodystrophy (X-ALD). Mutations in the ABCD1 gene have been identified to cause AMN.
METHODS
We applied clinical evaluation, laboratory tests, and neuroimaging on three patients with progressive spastic paraparesis. In genetic analysis, we investigated ABCD1 gene mutations by whole-exome sequencing and Sanger sequencing. Bioinformatics tools were used to predict the effects of identified ABCD1 mutations on the protein.
RESULTS
All three patients were men with adult-onset disease, mainly characterized by progressive spastic paraparesis. Among them, two patients had peripheral neuropathy and one patient had signs of adrenal insufficiency. All three patients showed cerebral involvement on brain MRI, while two patients were found with diffuse cord atrophy on spinal MRI. High-VLCFA levels in plasma, as well as C24:0/C22:0 and C26:0/C22:0 ratios, were found in all three patients. In addition, three different ABCD1 mutations were identified in three unrelated Chinese families, including one known mutation (c.1415_1416delAG) and two novel mutations (c.217C>T and c.160_170delACGCAGGAGGC). Based on the clinical assessment, radiographic, biochemical, and genetic testing, the final diagnosis was AMN in these patients with spastic paraparesis.
CONCLUSION
This study reported three patients with AMN and identified two novel mutations in the ABCD1 in the Chinese population. Our finding emphasized that X-ALD is an important cause of adult-onset spastic paraplegia. Thus, neuroimaging, VLCFA testing, and especially the detection of the ABCD1 gene have important implications for the etiological diagnosis of adult patients with spastic paraplegia.
PubMed: 36925939
DOI: 10.3389/fneur.2023.1126729 -
Nihon Rinsho Men'eki Gakkai Kaishi =... 2016A small percentage of those infected with human T-lymphotropic virus type 1 (HTLV-1) develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a... (Review)
Review
A small percentage of those infected with human T-lymphotropic virus type 1 (HTLV-1) develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a debilitating neurodegenerative disease. This disease impacts essential bodily functions, and since currently available treatments are considered to be poorly effective, there is a dire need to develop a truly effective treatment to suppress disease progression. Recently, the authors and others have determined that HTLV-1 in HAM/TSP patients primarily infects T cells expressing the chemokine receptor CCR4. The authors postulated that HTLV-1 causes these T cells to develop Th1-like functions that are critical for the pathogenesis of HAM/TSP. They described an inflammatory positive feedback loop in which cross-talk between these abnormal Th1-like cells and astrocytes produce and maintain spinal cord lesions in HAM/TSP patients. When an anti-CCR4 antibody was tested against cells from HAM/TSP patients, the antibody instigated the destruction of the CCR4-positive cells, reducing the number of infected cells and the amount of inflammatory activity. Thus, the anti-CCR4 antibody is expected to become a fundamentally new treatment for HAM/TSP that directly targets infected cells. The treatment is currently being tested in clinical trials.
Topics: Antibodies, Monoclonal; Astrocytes; Chemokine CXCL10; Clinical Trials as Topic; Feedback, Physiological; Humans; Molecular Targeted Therapy; Paraparesis, Tropical Spastic; Receptor Cross-Talk; Receptors, CCR4; Receptors, CXCR3; T-Lymphocytes; Th1 Cells
PubMed: 27320936
DOI: 10.2177/jsci.39.207 -
Annals of Physical and Rehabilitation... Dec 2016People with hereditary and spontaneous spastic paraparesis (HSSP) report that their legs are stiffer and walking is slower when their legs are cold.
BACKGROUND
People with hereditary and spontaneous spastic paraparesis (HSSP) report that their legs are stiffer and walking is slower when their legs are cold.
OBJECTIVES
This study explored the effects of prolonged superficial cooling and warming of the lower leg on walking speed and local measures of neuromuscular impairments.
METHODS
This was a randomised pre- and post-intervention study of 22 HSSP participants and 19 matched healthy controls. On 2 separate occasions, one lower leg was cooled or warmed. Measurements included walking speed and measures of lower limb impairment: ankle movement, passive muscle stiffness, spasticity (stretch reflex size), amplitude and rate of force generation in dorsi- and plantarflexors and central and peripheral nerve conduction time/velocity.
RESULTS
For both participants and controls, cooling decreased walking speed, especially for HSSP participants. For both groups, cooling decreased the dorsiflexor rate and amplitude of force generation and peripheral nerve conduction velocity and increased spasticity. Warming increased dorsiflexor rate of force generation and nerve conduction velocity and decreased spasticity.
CONCLUSIONS
Superficial cooling significantly reduced walking speed for people with HSSP. Temperature changes were associated with changes in neuromuscular impairments for both people with spastic paraparesis and controls. This study does not support the use of localised cooling in rehabilitation for people with spastic paraparesis as reported in other neurological conditions. Rehabilitation interventions that help prevent heat loss (insulation) or improve limb temperature via passive or active means, particularly when the legs and/or environment are cool, may benefit people with spastic paraparesis.
Topics: Adult; Aged; Aged, 80 and over; Ankle; Case-Control Studies; Cryotherapy; Female; Humans; Leg; Male; Middle Aged; Muscle Spasticity; Muscle, Skeletal; Neural Conduction; Paraparesis, Spastic; Physical Therapy Modalities; Random Allocation; Rewarming; Walking Speed; Young Adult
PubMed: 27262978
DOI: 10.1016/j.rehab.2016.04.006 -
International Journal of Infectious... Aug 2024Infective dermatitis associated with human T-cell lymphotropic virus type-1 (HTLV-1) (IDH) is a severe form of chronically infected eczema occurring in early childhood,... (Review)
Review
Infective dermatitis associated with human T-cell lymphotropic virus type-1 (HTLV-1) (IDH) is a severe form of chronically infected eczema occurring in early childhood, although very rarely cases have been reported in adults. Most of the cases are from Jamaica and Brazil and occur in individuals with low socioeconomic status. IDH is always associated with refractory Staphylococcus aureus or beta-hemolytic Streptococcus infection of the skin and nasal vestibules. Patients with IDH may develop other even more severe HTLV-1-associated diseases, such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) of early or late appearance and adult T-cell leukemia/lymphoma. In the context of the Brazilian experience, it has been observed that 54% of IDH patients exhibit the juvenile form of HAM/TSP while the estimated incidence of adult HAM/TSP is 3%. As there are no curative treatments for HTLV-1 infection (or vaccines) or most of its associated diseases, prevention of infection is fundamental, mainly by vertical transmission, as it is responsible for the development of IDH, infantojuvenile HAM/TSP, and ATL. Public measures to reduce this transmission must be implemented urgently. Furthermore, it is recommended, mainly in HTLV-1 endemic areas, to search for HTLV-1 infection in all patients with infected eczema, even in adults.
Topics: Humans; HTLV-I Infections; Human T-lymphotropic virus 1; Brazil; Paraparesis, Tropical Spastic; Adult; Dermatitis
PubMed: 38697604
DOI: 10.1016/j.ijid.2024.107058 -
Pharmacology & Therapeutics Feb 2021Human T-cell leukemia virus type I (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a rare inflammatory disease causing unremitting and... (Review)
Review
Human T-cell leukemia virus type I (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a rare inflammatory disease causing unremitting and progressive neurological disorders, such as spastic paraparesis, neurogenic bladder, and sensory disturbance of the lower extremities. Although there is no cure, immune-modulating agents such as corticosteroids are most widely used to slow disease progression. Biomarkers for the clinical assessment of HAM/TSP should be identified because the prediction of functional prognosis and the assessment of treatment efficacy are challenging due to the slowly progressive nature of the disease. The lack of surrogate biomarkers also hampers clinical trials of new drugs. This review summarizes biomarker candidates for the clinical assessment of patients with HAM/TSP. Most of the reported biomarker candidates are associated with viral components or inflammatory mediators because immune dysregulation provoked by HTLV-1 infection is thought to cause chronic inflammation and damage the spinal cord of patients with HAM/TSP. Although information on the diagnostic accuracy of most of the reported biomarkers is insufficient, several molecules, including inflammatory mediators such as CXCL10 and neopterin in the cerebrospinal fluid, have been suggested as potential biomarkers of functional prognosis and treatment response. Several clinical trials for HAM/TSP are currently underway, and we expect that these studies will provide not only evidence pertaining to treatment, but also novel findings regarding the utility of biomarkers in this disease. The establishment of clinical biomarkers will improve patient care and promote the development of therapies for HAM/TSP.
Topics: Biomarkers; Clinical Trials as Topic; Human T-lymphotropic virus 1; Humans; Inflammation Mediators; Laboratories; Paraparesis, Tropical Spastic; Spinal Cord Diseases
PubMed: 32835825
DOI: 10.1016/j.pharmthera.2020.107669 -
Journal of Vascular Surgery Sep 2021The outcomes after open repair of thoracoabdominal aneurysms (TAAAs) have been definitively demonstrated to worsen as the TAAA extent increases. However, the effect of... (Comparative Study)
Comparative Study Observational Study
OBJECTIVE
The outcomes after open repair of thoracoabdominal aneurysms (TAAAs) have been definitively demonstrated to worsen as the TAAA extent increases. However, the effect of TAAA extent on fenestrated/branched endovascular aneurysm repair (F/BEVAR) outcomes is unclear. We investigated the differences in outcomes of F/BEVAR according to the TAAA extent.
METHODS
We reviewed a single-institution, prospectively maintained database of all F/BEVAR procedures performed in an institutional review board-approved registry and/or physician-sponsored Food and Drug Administration investigational device exemption trial (trial no. G130210). The patients were stratified into two groups: group 1, extensive (extent 1-3) TAAAs; and group 2, nonextensive (juxtarenal, pararenal, and extent 4-5) TAAAs. The perioperative outcomes were compared using the χ test. Kaplan-Meier analysis of 3-year survival, target artery patency, reintervention, type I or III endoleak, and branch instability (type Ic or III endoleak, loss of branch patency, target vessel stenosis >50%) was performed. Cox proportional hazards modeling was used to assess the independent effect of extensive TAAA on 1-year mortality.
RESULTS
During the study period, 299 F/BEVAR procedures were performed for 87 extensive TAAAs (29%) and 212 nonextensive TAAAs (71%). Most repairs had used company-manufactured, custom-made devices (n = 241; 81%). Between the two groups, no perioperative differences were observed in myocardial infarction, stroke, acute kidney injury, dialysis, target artery occlusion, access site complication, or type I or III endoleak (P > .05 for all). The incidence of perioperative paraparesis was greater in the extensive TAAA group (8.1% vs 0.5%; P = .001). However, the incidence of long-term paralysis was equivalent (2.3% vs 0.5%; P = .20), with nearly all patients with paraparesis regaining ambulatory function. On Kaplan-Meier analysis, no differences in survival, target artery patency, or freedom from reintervention were observed at 3 years (P > .05 for all). Freedom from type I or III endoleak (P < .01) and freedom from branch instability (P < .01) were significantly worse in the extensive TAAA group. Cox proportional hazards modeling demonstrated that F/BEVAR for extensive TAAA was not associated with 1-year mortality (hazard ratio, 1.71; 95% confidence interval, 0.91-3.52; P = .13).
CONCLUSIONS
Unlike open TAAA repair, the F/BEVAR outcomes were similar for extensive and nonextensive TAAAs. The differences in perioperative paraparesis, branch instability, and type I or III endoleak likely resulted from the increasing length of aortic coverage and number of target arteries involved. These findings suggest that high-volume centers performing F/BEVAR should expect comparable outcomes for extensive and nonextensive TAAA repair.
Topics: Aged; Aged, 80 and over; Aortic Aneurysm, Thoracic; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Endoleak; Endovascular Procedures; Female; Graft Occlusion, Vascular; Humans; Male; Middle Aged; Paraparesis; Prosthesis Design; Registries; Retrospective Studies; Risk Assessment; Risk Factors; Stents; Time Factors; Treatment Outcome; Vascular Patency
PubMed: 33617981
DOI: 10.1016/j.jvs.2021.01.062 -
Journal of Comparative Pathology Jul 2022Marek's disease (MD) is caused by virulent strains of Gallid alphaherpesvirus type 2 (MD virus serotype 1; MDV 1) and frequently causes a lymphoproliferative disorder in...
Marek's disease (MD) is caused by virulent strains of Gallid alphaherpesvirus type 2 (MD virus serotype 1; MDV 1) and frequently causes a lymphoproliferative disorder in poultry and other galliform birds worldwide. However, within the peafowl (Phasianinae) subfamily, there are only rare confirmed reports of MD. Here we report MD in an Indian peafowl (Pavo cristatus), which clinically presented with hindlimb paraparesis and intraocular swelling of the right eye. Soft, off-white to tan masses within the right eye, sciatic nerves and coelomic cavity were identified at post-mortem examination which effaced the cranial pole of the kidneys and diffusely effaced the testes. Lymphoid neoplasia was identified histologically at all of these sites and there was extensive hepatic lymphoid cell infiltration, which had not been grossly evident. The T-cell origin of the lymphoid cells was confirmed by immunohistochemistry for CD3 antigen. A virulent strain of MDV 1 was detected by real-time polymerase chain reaction in DNA samples extracted from the kidney and testes. As MD is rare in peafowl it should be considered as a differential diagnosis for intraocular and coelomic masses with associated clinical signs.
Topics: Animals; Chickens; Eye Diseases; Herpesvirus 2, Gallid; Marek Disease; Paraparesis; Poultry Diseases
PubMed: 35817540
DOI: 10.1016/j.jcpa.2022.04.003