Nodal-paranodal antibodies in HIV-immune mediated radiculo-neuropathies: Clinical phenotypes and relevance.

BACKGROUND: The frequency of nodal-paranodal antibodies in HIV-infected patients with chronic immune-mediated radiculo-neuropathies (IMRN) has not been previously described. METHODS: HIV-infected patients who met the inclusion criteria for chronic IMRN were screened for immunoglobulin G (IgG) antibodies directed against nodal (neurofascin (NF)186) and paranodal (NF155, contactin-1 (CNTN1) and contactin-associated protein(Caspr1)) cell adhesion molecules, using a live, cell-based assay. To explore potential pathogenicity, binding of human IgG to myelinated co-cultures was assessed by incubation with patients' sera positive for nodal or paranodal antibodies. Normal human serum was added as a source of complement to assess for complement activation as a mechanism for myelin injury. RESULTS: Twenty-four HIV-infected patients with IMRN were included in the study, 15 with chronic inflammatory demyelinating polyneuropathy (CIDP), 4 with ventral root radiculopathies (VRR), and 5 with dorsal root ganglionopathies (DRG). Five patients with CIDP had combined central and peripheral demyelination (CCPD). Three patients (12.7%) tested positive for neurofascin IgG1 antibodies in the following categories: 1 patient with VRR was NF186 positive, and 2 patients were NF155 positive with DRG and mixed sensory-motor demyelinating neuropathy with optic neuritis, respectively. CONCLUSION: The frequency of nodal-paranodal antibodies is similar among IMRN regardless of HIV status. Interpretation of the results in the context of HIV is challenging as there is uncertainty regarding pathogenicity of the antibodies, especially at low titres. Larger prospective immune studies are required to delineate pathogenicity in the context of HIV, and to establish a panel of antibodies to predict for a particular clinical phenotype.

Molecular deletion patterns in Duchenne and Becker muscular dystrophy patients from KwaZulu Natal.

There exists much phenotypic heterogeneity in Duchenne muscular dystrophy and its allelic variant, Becker muscular dystrophy. The molecular findings on 53 patients with Duchenne and 15 patients with Becker type muscular dystrophy in KwaZulu Natal, South Africa are reported. Multiplex PCR was performed using primers targeting 18 hot-spot exons throughout the dystrophin gene. Analysis of the multiplex PCR data revealed that 39/68 (57.0%) patients included in the study showed a deletion (33 DMD and 6 BMD patients). Twenty-five patients were Black, 4 were White and 10 were Indian. Using the Chamberlain and Beggs multiplex PCR assays, the region of the genome most frequently affected by a deletion includes exons 47-51. The distal region of the dystrophin gene was most frequently affected by the deletion in both Black and Indian patients. There were too few White patients for conclusions to be drawn concerning the most frequently affected part of the gene. Although the numbers are insufficient to determine whether ethnic differences are present, the Chamberlain and Beggs multiplex PCR assays detect deletions with the same frequency in South African DMD/BMD patients as that reported in the literature.

Ischemic stroke in young HIV-positive patients in Kwazulu-Natal, South Africa.

Cerebrovascular disease occurs in HIV-positive individuals, but no relationship between the two has been established. The authors reviewed a cohort of patients aged 15 to 44 years to evaluate stroke in HIV-positive and negative subjects. Patients who were HIV-positive with no other identifiable etiology were compared to age- and race-matched HIV-negative patients. HIV-positive and HIV-negative groups did not differ in angiographic, cardiac, or serologic tests. A positive HIV test does not provide causal information or diagnosis.

Oral trimethoprim-sulfamethoxazole in the treatment of cerebral toxoplasmosis in AIDS patients--a prospective study.

Toxoplasma encephalitis is the commonest cause of intracranial mass lesions in AIDS patients. Effective therapy includes pyrimethamine plus sulfadiazine, clindamycin with pyrimethamine, and co-trimoxazole. This study examines the efficacy of oral co-trimoxazole in 20 AIDS patients with toxoplasmosis and seeks to confirm the experience of Torre et al.

Problems in the optimal management of myasthenia gravis patients--a prospective clinical survey at Kalafong Hospital.

OBJECTIVES: This study forms part of a clinical survey of problems in the optimal management of patients with inherited neuromuscular diseases seen at Kalafong Hospital in Pretoria. Our objectives were to determine the problems associated with providing patients with optimal management until true remission (cure), and to apply the findings to ongoing improvement of optimal management. This is the first report of the series. METHODS: Twenty-six patients were studied prospectively from 1986 to 1998. Early sternal-splitting thymectomy on class II-V patients as well as anticholinesterases, corticosteroids, azathioprine, plasma exchange, intensive care and various combinations of these constituted part of the optimal management. An assessment of the total monthly income and distance from hospital was done for each patient. RESULTS: Five of the 15 thymectomised patients (33.3%) were lost to follow-up after reaching remission. Of the remaining 10 patients, 6 (40%) are in true remission and the remaining 4 (26.7%) are in pharmacological remission. Four of the 11 patients (36%) treated non-surgically were lost to follow-up. Of the remaining patients, 1 (9.1%) is in true remission and the remaining 6 (54.5%) are in pharmacological remission. The average monthly income of patients lost to follow-up in the thymectomised group was lower than that of patients who continued follow-up, and their homes were further away from hospital. In the non-surgical group the average monthly income of patients lost to follow-up was higher than that of patients who continued follow-up and their homes were nearer to the hospital. CONCLUSION: Early thymectomy (the aggressive approach) resulted in 40% cures, 26.7% pharmacological remissions, no mortality, minimal morbidity, and early discharge. Loss to follow-up was one of the biggest problems in providing optimal management for these patients. We modified optimal management in response to our patients' concerns without sacrificing excellence, and found that poverty and poor access to tertiary hospitals were possible contributory factors to loss to follow-up. Suggestions are made with regard to tackling the problems. Myasthenia gravis (MG) is a disorder of neuromuscular function resulting from an immunologically based premature destruction of acetylcholine receptors.

Spectrum of myelopathies in HIV seropositive South African patients.

The authors determined the cause of myelopathies in 33 HIV seropositive individuals in KwaZulu/Natal, South Africa. The main associations were with human T-cell lymphotrophic virus-I, tuberculosis, herpes zoster, and syphilis. A novel association with probable bilharziasis was noted. Only one case of vacuolar myelopathy was identified. Opportunistic infections will probably persist until routine antiretroviral therapy becomes widely available in South Africa.

Sequence of the env gene of some KwaZulu-Natal, South African strains of HTLV type I.

Phylogenetic analysis of HTLV-I suggests three main subtypes, namely, cosmopolitan, Central African, and Australo-Melanesian. HTLV-I is endemic in KwaZulu-Natal, South Africa. However, sequence data on the local strains are limited to the LTR region. The env gene of the local strain was amplified and sequenced from the peripheral blood of five seropositive individuals. Four had HTLV-I-associated myelopathy and one had infective eczema. The sequence analysis of the env gene showed a greater then 99% homology of the local strains. They were closely related to the North American strains (99.3%), followed by the Japanese strains (98.3-98.9%). Phylogenetic studies linked the local strains to the cosmopolitan subtype. This study provides new sequence data on the env gene of the local HTLV-I strain.

Multiple sclerosis in black South Africans and Zimbabweans.

Multiple sclerosis is rare among the indigenous black people of Africa. The first account of a black patient with multiple sclerosis in South Africa was published as late as 1987. Since then a search to find black patients with multiple sclerosis in Southern Africa has continued. Seven black patients have now been traced in South Africa and five in Zimbabwe in whom a diagnosis of multiple sclerosis can be accepted. Six of the 12 patients became blind, or nearly so, from severe optic neuritis. Multiple sclerosis in these few black patients more often resembled the disorder as it occurs in oriental people than among white people in southern Africa or the black people of North America or the Caribbean.

Electroencephalogram and computerised cerebral tomography findings in eclampsia.

OBJECTIVE: To define more clearly the neuropathophysiology of eclampsia. DESIGN: A prospective study relating to computerised cerebral tomography (CAT) scan and electroencephalogram (EEG) findings in eclampsia. SETTING: A large referral centre in a developing society. SUBJECTS: Thirty-two women with eclampsia. MAIN OUTCOME MEASURES: Abnormalities in EEG and CAT scan findings. RESULTS: Approximately 45% of the women studied had CAT scan abnormalities, while 90% had EEG abnormalities. A burst suppression pattern on EEG examination was found in four women suggesting a temporary dissolution of cerebral function to the midbrain level as the cause of seizures. CONCLUSIONS: EEGs are probably more sensitive than CAT scans in detecting the extent of the pathology in the brain in women with eclampsia.

Prevalence and transmission of HTLV-I infection in Natal/KwaZulu.

A community-based seroprevalence survey for human T-cell lymphotropic virus type I (HTLV-I) was undertaken in the Ngwelezane district of Natal/KwaZulu. A total of 1,018 individuals was interviewed for risk factors and had blood drawn for serological examination. To exclude antibody cross-reactivity between anti-HTLV-I and anti-HTLV-II all Western blot HTLV-I-positive samples were further subjected to a Select HTLV test. For comparison, anonymous HIV testing was done. The areas of residence of patients with myelopathy associated with HTLV-I were also ascertained. The seroprevalence of HTLV-I was 2.6% (95% confidence interval (CI) 1.62-3.58). An age-related rise in HTLV-I seropositivity from 1.3% in the 15-24-year age group to 6.1% in the over 55-year-old group was noted. There was no significant association between HTLV-I antibody positivity and marital status, occupation, history of blood transfusion, scarification, age at first sexual experience and number of sexual partners. Anti-HIV-1 antibody testing revealed a positivity of 3.5% (95% CI 2.4-4.68) and the relative risk for co-infection with both HTLV-I and HIV-1 in the 15-24-year group was 1.16 (95% CI 1.08-1.24). The study also identified the first HTLV-II-seropositive case in the Natal/KwaZulu region. Up to December 1991, 90 cases of HTLV-I-associated myelopathy/tropical spastic paraparesis were seen at the Neurology Unit, Wentworth Hospital. The patients came from all parts of Natal, from Pongola in the north to Transkei in the south. The Natal/KwaZulu region is, therefore, an endemic HTLV-I area.

Peripheral nerve lesions in HTLV-I associated myelopathy (HAM/TSP).

Peripheral nerve dysfunction (PND) was found in as many as 43% of our patients with human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM/TSP). To evaluate the PND further we biopsied the sural nerve in 6 patients. The histological features were varying degrees of demyelination, remyelination, axonal atrophy and degeneration, and perineurial fibrosis. "Globule" or "sausage" formation was prominent in two of the specimens. Inflammatory infiltrates were absent. No deposits of IgG, IgM, IgA, or complement were detected in the biopsies. No viral antigen or proviral DNA was detected. It is proposed that the PND and the histological findings noted are part of HTLV-I-associated disease and not an unrelated disorder. The pathogenesis of the PND remains unclear. There was no evidence of direct viral infection. The histological findings could represent primary changes induced by viral-triggered release of soluble factors, such as cytokines or secondary changes to more proximal disease, e.g., root involvement.

The clinicoradiological profile of cerebral venous thrombosis.

The clinical presentation, diagnostic and radiological aspects and the probable aetiology in 20 consecutively studied patients with cerebral venous thrombosis (CVT) are described. In this retrospective analysis patients were evaluated extensively according to a stroke investigative protocol. Computed tomography signs for CVT may be identified in the majority of cases and frequently obviate the need for angiography. In those patients in whom no satisfactory precipitating factor was recognised further haematological tests revealed abnormalities that are known causes of thrombosis in 7 patients. Eighty-five per cent of the patients made an excellent recovery. It is concluded that CVT can often be diagnosed non-invasively, the presumptive cause can be found in the majority of patients and the prognosis is excellent.