Steroid-responsive myeloneuropathy in a man dually infected with HIV-1 and HTLV-I

Two human retroviruses, HIV-1 and HTLV-I, have been associated with myelopathies in addition to other neurologic disorders. We report an American dually infected with HIV-1 and HTLV-I who developed steroid-responsive myeloneuropathy. This 28-year-old bisexual man developed interstitial pneumonitis and a transient midthoracic sensory level followed by the evolution of a slowly progressive spastic paraparesis and sensorimotor neuropathy. Serologic studies demonstrated coinfection with both HIV-1 and HTLV-I. Peripheral blood absolute CD4 count was persistently within the normal range. Cranial MRI was normal and spinal MRI showed T3-T10 atrophy. Serial CSF analyses demonstrated marked intrathecal synthesis of anti-HTLV-I IgG, lymphocytic pleocytosis, elevated protein and immunoglobulin G, and oligoclonal bands. HIV-1 was isolated from CSF but not from peripheral nerve. Lymphoproliferative studies confirmed spontaneous proliferation in both blood and CSF. Soluble interleukin 2 receptor and soluble CD8 were greatly elevated in blood and CSF when compared with patients with HIV-related vacuolar myelopathy and seronegative patients with other causes of myelopathy. Nerve biopsy showed epi- and endoneurial CD8+ lymphocytic infiltration without vasculitis; muscle biopsy showed features of acute and chronic denervation. A 6-week course of prednisone produced sustained improvement in leg strength and walking times. We speculate that the myeloneuropathy was caused by HTLV-I in the setting of coinfection with HIV-1.     

Isolation of HTLV-II from a patient with chronic,progressive neurological disease clinically indistinguishable from HTLV-I-associated myelopathy/tropical spastic paraparesis

An increasing spectrum of diseases has been shown to be associated with the human T-cell lymphotropic virus type I (HTLV-I), most notably a chronic, progressive myelopathy termed HTLV-I-associated myelopathy/tropical spastic paraparesis and adult T-cell leukemia. HTLV-II is a close relative of HTLV-I and is structurally similar but molecularly distinct. This virus is endemic in Amerindian populations and a high seroprevalence rate has been observed in intravenous drug abusers. Here, for the first time, we have identified a patient with a chronic, progressive neurological disease clinically indistinguishable from HTLV-I-associated myelopathy/tropical spastic paraparesis from whom we have isolated and characterized HTLV-II in the absence of any other detectable human retrovirus. Antibodies to HTLV were deteced in both serum and cerebrospinal fluid, with typical HTLV-II banding patterns on Western blots. HTLV-II viral sequences were detected in high copy number from peripheral lymphocytes by polymerase chain reaction techniques, and cloning and sequencing of the virus revealed a 99.5% homology with prototype HTLV-II. These results serve to alert the medical community to the possibility that in addition to HTLV-I, HTLV-II may be associated with a neurological disorder.     

Tropical spastic paraparesis: a neuroepidemiological study in Colombia

A geographic isolate of tropical spastic paraparesis (TSP) in Tumaco, Colombia, is described. Fifty confirmed cases were identified (29 men, 21 women) with an estimated prevalence ratio of 98 cases per 100,000 population. Patients with identified cases ranged in age from 24 to 75 years (mean, 46.5). TSP begins with burning feet, leg stiffness, spastic bladder, and, in men, impotence. Patients exhibited leg weakness, spasticity, hyperreflexia, and scissoring gait. Babinski, Chaddock, and Hoffmann signs could be elicited. Ankle reflexes and vibratory sensation of the feet were decreased. Intellectual function, coordination, and cranial nerves remained normal. TSP is a slowly progressive disorder but so far there have been no deaths from it. Forty cases in this report began between 1971 and 1980; the earliest documented case began in 1952. Living conditions and occupations of the patients were typical for the region. Yaws had occurred in 74% of confirmed cases. No likely etiological neurotoxic or nutritional factors were identified. TSP also has been described in India, Africa, the Seychelles, and Jamaica.     

The HIV-1 transgenic rat as a model for HIV-1 infected individuals on HAART

HIV-1 viral replication is limited in patients given highly active anti-retroviral therapy (HAART); however, HIV-1 viral proteins are still present. We demonstrate that the developing HIV-1Tg rat, which expresses all of the HIV-1 viral genes except the gag–pol replication genes, maintains lower body weight compared with the F344 control rat. Although HIV-1Tg rats eat and drink less than the control animals, they are not anorexic and show no evidence of anhedonia. At 19 months (mo) of age, HIV-1Tg rats begin to show clinical signs of wasting that progress to death. Using real-time RT-PCR, we compared the expression of the HIV viral proteins Tat, gp120, nef, and vif, in the HIV-1Tg rats at 2–3 mo of age with those at 10–11 mo of age. RNA levels of viral protein in the spleens of younger rats were significantly greater than those in the older rats (P < 0.01). Conversely, viral protein mRNA levels in the spinal cord, cerebellum, and striatum were significantly greater in the older rats than in the younger animals (P < 0.01). In the prefrontal cortex, Tat and nef expression was significantly greater at 2–3 mo of age than at 10–11 mo of age (P < 0.05). These findings indicate that there may be age-dependent differential expression of various HIV viral proteins, with a switch from peripheral immune organs to the CNS, even when the animals are still pre-symptomatic. Our study also demonstrates that this non-infectious rat can be a useful model simulating HIV-1 infected individuals that are on HAART.     

Cognitive deficits and emotional disorders in HIV-1 infected individuals

The associations between cognitive functioning, depression questionnaire results, and diagnosed psychiatric disorders were examined among 85 HIV-1 infected patients at different stages of systemic infection and 39 seronegative controls. An affective scale and a somatic scale of the Beck Depression Inventory (BDI) were used to measure depression. Psychiatric disorders before or after the diagnosis of seropositivity were evaluated. The patients with symptomatic HIV-1 infection (AIDS related complex, AIDS) reported more somatic symptoms of depression than the subjects with asymptomatic infection or the controls, whereas psychological depression and psychiatric disorders were unrelated to the severity of HIV-1 disease. Psychiatric disorders diagnosed during HIV-1 disease were slightly associated with poor verbal memory only among symptomatic patients. Impaired visual memory showed an association with depressive mood and with psychiatric disorders preceding the diagnosis of seropositivity which suggests that factors other than HIV-1 may explain these subjects' poor visual memory.     

Stavudine and the peripheral nerve in HIV-1 infected patients

Stavudine (2′,3′-didehydro-3′deoxythymidine) is a pyrimidine analogue that may be of great value in combination antiretroviral therapy (ART) for treating patients infected with human immunodeficiency virus type 1 (HIV-1). We assessed potential neurotoxic side effects by comparing peripheral nerve function in patients receiving ART including stavudine (n = 107) with that of patients receiving ART with zidovudine (n = 103). A cross-sectional analysis of electroneurographic data revealed no significant differences. In a follow-up examination of 31 patients newly started on ART with stavudine we observed no significant effects of the drug on electrophysiological measures. At a daily dose of 1.0 mg/kg the incidence of peripheral nervous system disease in our patients was about 10%. Repeated follow-up analysis of 13 patients on stavudine showed a significant reduction in sural nerve amplitude. Quantitative sensory testing in 13 patients revealed no systematic effect of stavudine on small nerve fibers. Peripheral nerve function in HIV-1 seropositive patients on ART with stavudine did not differ significantly from that in patients on ART with zidovudine. Therefore stavudine at a daily dose of 1.0 mg/kg is an alternative for patients who do not tolerate, or who have become resistant to zidovudine and can be recommended as a first-line drug in combination ART. Received: 31 March 1998 Received in revised form: 9 July 1998 Accepted: 19 August 1998     

Early neurodevelopmental markers predictive of mortality in infants infected with HIV-1

One-hundred and fifty-seven vertically infected HIV-1 positive infants (85 males, 72 females) underwent longitudinal assessment to determine whether early neurodevelopmental markers are useful predictors of mortality in those infants who survive to at least 4 months of age. Survival analysis methods were used to estimate time to death for quartiles of 4-month scores (baseline) on the Bayley Scales of Infant Development (BSID). Cox proportional hazards progression was used to estimate relative hazard (RH, 95% CI) of death for BSID scores and potential confounders. Thirty infants with BSID scores at 4 months of age died during follow-up. Survival analysis revealed greater mortality rates in infants with BSID (Mental Developmental Index and Psychomotor Developmental Index) scores in the lower quartile (p=0.004, p=0.036). Unadjusted univariate analyses revealed increased mortality associated with baseline CD4+ 29%, gestational age <37 weeks, smaller head circumference, advanced HIV and higher plasma viral load. BSID scores independently predicted mortality after adjusting for treatment, clinical category, gestational age, plasma viral load and CD4+ percentage.     

Purine nucleoside phosphorylase deficiency in a patient with spastic paraplegia and recurrent infections

Purine nucleoside phosphorylase deficiency is a rare autosomal recessive immunodeficiency disease. The characteristic features of the disease include severe T cell immune defects with recurrent infections, a failure to thrive, and progressive neurological findings. To date, 35 cases of purine nucleosidase phosphorylase deficiency have been reported worldwide. A 2-year-old female patient was hospitalized due to recurrent infections starting from 6 months and a fever that had continued for a month. The parents were first cousins. Physical examination showed a failure to thrive, herpetic lesions around the lips, painful lesions on the tongue and the buccal mucosa, lung infection, and spastic paraparesis in the lower extremities. She had motor and mental retardation. Laboratory tests revealed lymphopenia; low CD3, CD4, and CD8 counts; normal immunoglobulin levels; low uric acid; and very low purine nucleoside phosphorylase enzyme activity (1.4 nmol/h/mg; normal range, 490-1530). DNA sequencing of the purine nucleosidase phosphorylase gene revealed a missense homozygous mutation, a G to A transition at exon 4 position 64 (349G>A transition), which led to a substitution of alanine by threonine at codon 117 (Ala117Thr). Both parents were heterozygous for the mutation. This is the second purine nucleosidase phosphorylase deficient case to have been presented and carrying this mutation worldwide. Various antibiotics, antifungal drugs, and intravenous immunoglobulin were used to treat the infections during her 3 months. This form of treatment proved to be unresponsive, resulting in her subsequent death at 26 months of age.     

FES cycling reduces spastic muscle tone in a patient with multiple sclerosis

We report on a multiple sclerosis patient who received functional electrical stimulation to reduce spastic muscle tone of the lower limbs. Stimulation by means of surface electrodes applied to the thigh muscles induced cycling leg movements. Spastic muscle tone was measured clinically using the modified Ashworth scale and semiautomatically by pendulum testing of spasticity. This was done before and directly after stimulation. The patient was able to endure the stimulation for ca. 30 minutes; there was a significant reduction of spasticity after each stimulation session. We conclude, that this type of stimulation could be another potential treatment modality for multiple sclerosis patients, especially those with a high score in the expanded disability Status scale.     

Tropical spastic paraparesis in the Seychelles Islands: a clinical and case-control neuroepidemiologic study

We confirmed the occurrence of endemic tropical spastic paraparesis (TSP) in the Seychelles. Most patients (14/21) were low-income black women. Mean age at onset was 42.8 years (range, 20 to 65). In 62%, onset and progression were slow. Complete paralysis developed in 8/21 (38%) after an evolution of 2 to 15 years. All patients had bilateral pyramidal signs. Loss of vibratory perception occurred in 6/21 (28%). A case-control study of putative risk factors failed to show significant differences. The clinical and epidemiologic features of TSP in the Seychelles appear to be similar to those described in other tropical countries.     

“疾病焦虑障碍”的访谈与治疗

咨客,男性,30岁左右,已婚,育有一子。最近,他对自己的身体健康状况感到越来越焦虑。作为一名动物检疫员,他主要负责家禽或其他动物食品的质量控制。近来,总是认为自己因为在工作中接触动物而患上了感染性疾病,即使经过多家医院就诊后已经排除感染,仍会寻找其他的原因。例如,认为自己通过接触他人使用过的按摩椅或街边的流浪动物而患上某种疾病。这种担心非常强烈,虽然他从未被诊断为狂犬病,也没有被任何动物咬过,但仍多次就诊于医院并接种狂犬疫苗。每天都会仔细检查身体,寻找是否有咬痕或其他污染源。通过本次咨询,他被诊断为疾病焦虑障碍,并开始接受抗焦虑药物治疗。此外,在医生的指导下进行认知行为治疗和正念减压治疗,用于对抗闯入性思维。