Acupuncture in the treatment of HTLV-I-associated myelopathy / tropical spastic Paraparesis.

We investigate the possible effects of acupuncture on the improvement of neurological problems in HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP)disease. Twenty patients with HAM/TSP were studied in this pre and post-test clinical trial. Urinary incontinence, global motor disability, spasticity, and pain severity were evaluated before, one month, and three-month after the intervention. Analyses demonstrated a significant reduction of urinary symptoms one month after acupuncture (P = 0.023). A significant improvement was observed in patients' pain and the spasticity at the upper extremity joints, one and three-month after the intervention (P < 0.05). This study suggests that body acupuncture can be used as a complementary treatment to improve HAM/TSP neurological symptoms.

Clinical features of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in northeast Iran.

This study aimed to introduce clinical manifestations of patients in northeast Iran with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and describe the epidemiological features, as well as risk factors for HTLV-1 infection. This is a cross-sectional study of HTLV-1 infected cases and HAM/TSP patients referred by outpatient neurology clinics as well as Mashhad Blood Transfusion Center from 2005 to 2010. The study comprises 513 cases, including 358 healthy carriers (HCs) and 145 HAM/TSP patients. The majority of carriers were male (73.5%), whereas 67.6% of HAM/TSP sufferers were female (P < 0.001). The mean age of HAM/TSP patients and HCs was 45.9 ± 13.6 and 39.5 ± 11.58 years, respectively (P < 0.001). The history of transfusion, surgery, hospitalization and cupping was observed in a significant greater number of HAM/TSP patients than the HCs (P < 0.001, P < 0.001, P < 0.001 and P = 0.029, respectively). Gait disturbance was the most common complaint in HAM/TSP patients (72.4%). This research develops an HTLV-1 data registry in an endemic area such as Mashhad which can serve useful purposes, including evaluation of clinical and laboratory characteristics of HAM/TSP patients and epidemiological data of HTLV-1-infected cases.

Paraparesia espástica progresiva asociada a HTLV-I en Chile: estudio y seguimiento de 121 pacientes por diez años / Progresive spastic paraparesis associated to HTLV-I in Chile

Revision is made to 121 Chilean patients with progressive adult spastic paraparesis (PSPs) associated to HTLV-I. Epidemiologic, clinical, diagnosis and associated illnesses aspects are analyzed as well as the pathogenesis. The follow-up of patients during several years allowed defining the evolutional profile, establishing the causes of death and studying the virus' behavior. Pathogenesis hypothesis arose from the neuropathological search to define the mechanisms of damage supported on immunohystochemical studies. It was confirmed that the CNS illness is a degenerative process linked to a central axonopathy which expresses flaws in the axoplasmic transport, particularly affecting the corticospinal tracts, although there is a more extended myeloencephalic involvement. Furthermore, the virus is capable of producing a multisystemic illness that may simultaneously involve the nervous system; the hematological system; the exocrine glands; the hepatic, lung, muscular and bone parenchymas.

Se revisan las paraparesias espásticas progresivas del adulto (PEPAs) producidas por el HTLV-I, en 121 pacientes chilenos. Se analizan los aspectos epidemiológicos, clínicos, diagnósticos, las enfermedades asociadas, y la patogenia. El seguimiento de los pacientes durante varios años permitió definir el perfil evolutivo, establecer las causas de muerte y estudiar el comportamiento del virus. De los casos con anatomía patológica surgieron hipótesis, que han permitido definir mecanismos de daño, sustentados en estudios inmunohistoquímicos. Se pudo confirmar que la enfermedad del SNC es un proceso degenerativo, vinculado a una axonopatía central que expresa fallas del transporte axoplásmico, que afecta particularmente la vía corticoespinal, aunque existe un compromiso más extenso mielo-encefálico. Además, el virus es capaz de producir una enfermedad multisistémica, que puede comprometer simultáneamente el sistema nervioso, el sistema hematológico, las glándulas exocrinas, el parénquima hepático, pulmonar, muscular y óseo.

[Immunopathogenesis and treatment of the myelopathy associated to the HTLV-I virus]. / Inmunopatogenesis y tratamiento de la mielopatia asociada al virus linfotropico humano de celulas T (HTLV-I).

INTRODUCTION: Human T-cell lymphotropic virus type-I (HTLV-I) causes tropical spastic paraparesis/HTLV-I associated myelopathy (TSP/HAM). Immunopathogenesis and available treatments for TSP/HAM are reviewed. DEVELOPMENT: At least 20 million people are infected worldwide and 0.3-4% will develop TSP/HAM. Incidence in endemic areas is around 2 cases/ 100,000 inhabitants and year. The 50% of TSP/HAM patients suffer from clinical progression during their first ten years. Progression is associated with high proviral load and ager than 50 years at onset. HTLV-I proviral DNA and m-RNA load are significantly raised in TSP/HAM patients compared to asymptomatic carriers. This antigenic load activates T cells CD8+ specific for Tax-protein, which up-regulate pro-inflammatory cytokines. Corticoids, plasma-exchange, intravenous immunoglobulins, danazol, pentoxifilline, green-tea polyphenols, lactobacillus fermented milk, zidovudine, lamivudine, monoclonal antibodies (daclizumab), interferon, and valproic acid have been used in open trials in a small number of patients. Nevertheless, their clinical efficacy is limited. Interferon alpha and beta-1a have cytostatic properties and may cause a reduction in HTLV-I proviral load. CONCLUSIONS: High HTLV-I proviral load and an exaggerated pro-inflammatory cellular response are involved in the pathogenesis of TSP/HAM. No therapy has been conclusively shown to alter long-term disability associated with TSP/HAM. Multicentric clinical trials are necessary to assess long-term efficacy of interferon in TSP/HAM.

Profound biotinidase deficiency in a child with predominantly spinal cord disease.

Biotinidase deficiency is an autosomal recessively inherited disorder that manifests during childhood with various cutaneous and neurological symptoms particularly seizures, hypotonia, and developmental delay. Spinal cord disease has been reported rarely. We describe a 3-year-old boy with profound biotinidase deficiency who presented with progressive spastic paraparesis and ascending weakness in the absence of the usual characteristic neurological manifestations. Supplementation with biotin resulted in resolution of paraparesis with persistent mild spasticity in the lower limbs. DNA mutation analysis revealed that he was homozygous for a novel missense mutation (C>T1339;H447Y) in the BTD gene. This case indicates that biotinidase deficiency should be included in the differential diagnosis of subacute myelopathy and emphasizes the importance of a prompt diagnosis to prevent irreversible neurological damage.

Vestibular-evoked myogenic potential (VEMP) to evaluate cervical myelopathy in human T-cell lymphotropic virus type I infection.

STUDY DESIGN: Cross-seccional analysis. OBJECTIVE: To define the clinical usefulness of vestibular-evoked myogenic potential (VEMP) in detecting cervical medullar involvement related to human T-cell lymphotropic virus type 1 (HTLV-1) associated myelopathy/tropical spastic paraparesis (HAM/TSP). SUMMARY OF BACKGROUND DATA: VEMP is generated by acoustic or galvanic stimuli, passing through the vestibulo-spinal motor tract, the spinal nerves and recorded by means of surface electrodes on the sternocleidomastoid muscle. HAM/TSP is a progressive inflammatory myelopathy with predominant lesions at the thoracic spinal cord level, although the cervical spine can be affected. VEMP may be of value to investigate cervical myelopathy. METHODS: Seventy-two individuals were evaluated of whom 30 HTLV-1 were seronegative and 42 HTLV-1 seropositive (22 asymptomatic, 10 with complaints of walking difficulty without definite HAM/TSP and 10 with definite HAM/TSP). VEMP was recorded using monaural delivered short tone burst (linear rise-fall 1 millisecond, plateau 2 milliseconds, 1 KHz) 118 dB NA, stimulation rate of 5 Hz, analysis time of 60 milliseconds, 200 stimuli, band pass filtered between 10 and 1.500 Hz. RESULTS: VEMP was normal in the seronegative group (30 controls). In the seropositive, abnormal VEMP was seen in 11 of 22 (50%) of the HTLV-1 asymptomatic carriers, in 7 of 10 (70%) of those with complaints of walking difficulty and in 8 of 10 (80%) of the HAM/TSP patients. In this last group, the pattern of response was different. No VEMP response was more frequent when compared with the HTLV-1 asymptomatic group (2-tailed P-value = 0.001). CONCLUSION: VEMP may possibly be useful to identify patients with cervical myelopathy and to distinguish variable degrees of functional damage. Minor injury would be related to latency prolongation and major injury to no potential-evoked response.

Intermittent high-dose vitamin C therapy in patients with HTLV-I associated myelopathy.

The efficacy of intermittent high-dose vitamin C therapy was evaluated in seven patients with HTLV-I-associated myelopathy (HAM). All HAM patients responded well to this therapy without serious side effects. Grade of disability score improved at 9.7 (SD 5.8) months after the therapy from 7.1 (3.3) to 3.6 (2.0) (p < 0.01). Serum immunosuppressive acidic protein was elevated before and decreased after the therapy from 747 (316) to 398 (86) micrograms/ml (p < 0.05), suggesting favourable immunomodulatory action of vitamin C therapy in HAM patients.

Excessive muscular fatigue in patients with spastic paraparesis.

We used intermittent tetanic contractions and 31P magnetic resonance spectroscopy to investigate human tibialis anterior muscle metabolism and fatigability in a group of patients with spastic paraparesis and in normal controls. During intermittent tetanic stimulation, the decline in tension was significantly greater in patients than in controls, and the half-relaxation time of the tetanus was more prolonged. Moreover, the decline in phosphocreatine and intracellular pH was significantly greater in patients than in controls. These observations suggest that biochemical changes in the muscles of patients with upper motor neuron lesions may contribute to their excessive fatigability.