Laboratory observations of slow earthquakes and the spectrum of tectonic fault slip modes.

Slow earthquakes represent an important conundrum in earthquake physics. While regular earthquakes are catastrophic events with rupture velocities governed by elastic wave speed, the processes that underlie slow fault slip phenomena, including recent discoveries of tremor, slow-slip and low-frequency earthquakes, are less understood. Theoretical models and sparse laboratory observations have provided insights, but the physics of slow fault rupture remain enigmatic. Here we report on laboratory observations that illuminate the mechanics of slow-slip phenomena. We show that a spectrum of slow-slip behaviours arises near the threshold between stable and unstable failure, and is governed by frictional dynamics via the interplay of fault frictional properties, effective normal stress and the elastic stiffness of the surrounding material. This generalizable frictional mechanism may act in concert with other hypothesized processes that damp dynamic ruptures, and is consistent with the broad range of geologic environments where slow earthquakes are observed.

Abnormal copper metabolism: another "non-Wilson's" case.

We describe a patient with extrapyramidal neurologic disease and an abnormal copper profile with hepatic copper accumulation, but no cirrhosis histologically, thus excluding a diagnosis of Wilson's disease (WD). We compared and highlighted the differences between similar previously reported cases of abnormal copper metabolism and true WD and suggest a spectrum of disease due to abnormal copper metabolism resulting in varied histochemical expression.

New-onset seizures associated with HIV infection.

The authors studied new-onset seizures in 60 heterosexual black South African HIV-infected patients who had not used IV drugs. An intracranial space-occupying lesion was identified in 53% of patients, meningitis in 22%, and no additional cause in 25%. Of the patients with an identifiable cause, 64% had probable tuberculosis (tuberculoma or tuberculous meningitis). The majority of patients had late-stage HIV infection (CD4 counts <200/mm(3)).

Dual infective pathology in patients with cryptococcal meningitis.

Coinfection of the nervous system by two distinct nonviral organisms is uncommon and often undiagnosed. Medical teaching emphasizes that a single pathologic process should be sought; however, in the presence of severe immunocompromise this approach may not hold true. We describe seven HIV-1 seropositive patients with cryptococcal meningitis, three of whom had a proven nervous system infection with a second organism: concurrent tuberculous meningitis, a tuberculoma, and the first documented case of cryptococcal meningitis and neurosyphilis.

The sunflower syndrome. A new look at "self-induced" photosensitive epilepsy.

The stereotyped, episodic abnormal behaviour manifested by a child and her mother on exposure to a particular sort of sunlight is described in detail. The child is the first fully documented patient with this so-called "self-induced" form of photosensitive epilepsy in whom for several years no electroencephalographic sensitivity to flickering light could be demonstrated. The probability that the cingulate circuit may be the anatomical substrate involved in the pathogenesis of these patients' unusual response to sunlight is discussed. Both patients also exhibited remarkably persistent habit rhythmias--the one common to both being that of circling.

Meningitis in a community with a high prevalence of tuberculosis and HIV infection.

OBJECTIVES: To evaluate the spectrum of aetiologies, and distinguishing clinical and laboratory features, of meningeal infection in a community with a high prevalence of tuberculosis (TB) and HIV infection. SETTING: A hospital serving mineworkers, originating from rural areas of Southern Africa. DESIGN: Prospective cohort of 60 consecutive lumbar punctures (LPs), performed for suspected meningitis. MEASUREMENTS: Clinical history and examination; concurrent cerebrospinal fluid (CSF) and blood samples; mortality status six months after entry to study. RESULTS: 38 of 57 patients (66.7%) were HIV-1 positive, 59.5% of whom had a CD4 count <200 cells/mm3. Nine patients had tuberculous meningitis (TBM) and two had tuberculomas; four developed disease while on TB therapy. There was one case of multidrug, and two of isoniazid-resistant TBM. There were nine episodes of cryptococcal meningitis (seven patients), nine of aseptic meningitis, two of neurosyphilis and 20 normal LPs, including four with AIDS dementia complex (ADC). Ten patients with meningococcal infection, part of a larger outbreak, were significantly younger (p=0.004). All patients with tuberculous, cryptococcal (most immune-suppressed p<0.001) and aseptic meningitis were HIV-1 positive. Within six months, 19 patients had died. Death was associated with HIV positivity (p=0.004), low CD4 count (p<0.001) and a diagnosis of cryptococcal meningitis, CNS TB or ADC. CONCLUSION: HIV has a major impact on the burden of disease and mortality, with a predominance of opportunistic chronic meningitides, despite a meningococcal outbreak, in this community. Of concern is the development of TBM despite therapy, and the emergence of drug-resistant strains.

A double-blind controlled clinical trial of oxcarbazepine versus phenytoin in adults with previously untreated epilepsy.

In the last 5 years oxcarbazepine (OXC) has been registered in many countries for use as first-line and add-on treatment for partial seizures with or without secondarily generalized seizures (PS) and generalized tonic-clonic seizures without partial onset (GTCS). Its use as monotherapy in adults with newly diagnosed epilepsy was investigated in this double-blind, randomized, parallel-group comparison with phenytoin (PHT). A total of 287 adult patients, with either PS or GTCS, were randomized. After retrospective baseline assessment, patients were randomized to OXC or PHT in a 1:1 ratio. The double-blind treatment phase was divided into two periods: a flexible titration period of 8 weeks, followed by 48 weeks of maintenance treatment. In the efficacy analyses, no statistically significant differences were found between the treatment groups. Seventy patients (59.3%) in the OXC group and 69 (58.0%) in the PHT group were seizure-free during the maintenance period. A total of 56 of the patients in the OXC group discontinued treatment prematurely (five because of tolerability reasons) compared to 61 in the PHT group (16 for tolerability reasons). The number of premature discontinuations due to adverse experiences showed a statistically significant difference in favour of OXC. There was no statistically significant difference between the groups with respect to the total number of premature discontinuations. This trial provides further support for the efficacy and safety of OXC as first-line treatment in adults with PS and GTCS. In addition, the results show that OXC has significant advantages over PHT in terms of tolerability.

Vitelliform macular degeneration associated with mitochondrial myopathy.

A patient with mitochondrial myopathy is described. Examination of his fundus revealed bilateral vitelliform degeneration of the maculae. This lesion is a focal abnormality of the retinal pigment epithelium and may be a manifestation of the underlying mitochondrial disease.

Frusemide: a safe diuretic during lithium therapy?

This paper reports the effect of frusemide given in therapeutic doses for hypertension in patients receiving prophylactic lithium for affective disorders. It was found that frusemide had no significant effect on plasma lithium concentration in these patients who were studied over a 12-week period. It was concluded that frusemide is a safe diuretic to administer to patients receiving lithium therapy.

Hemiplegia and the billowing mitral leaflet syndrome.

Four young patients presenting with major neurological episodes and with coexisting prolapsing mitral valve are described. An attempt at correlating the two entities is made. The neurological complications of prolapsing mitral valve are stressed.

Huntington's chorea in a black family: a report of 2 cases.

Two cases of Huntington's chorea occurring in a Black family are presented. One patient had, in addition, an arteriovenous anomaly of the cerebral circulation. The genealogy of the family is described and the probability of mixed descent is noted. The impression gained from the literature that Huntington's chorea rarely occurs in Blacks is strengthened.

Optic neuritis in an urban black African community.

PURPOSE: To describe the clinical profile of idiopathic optic neuritis in South African blacks. METHODS: South African black patients with acute isolated idiopathic optic neuritis, treated and followed for at least 3 months at a large medical centre, were studied. Exclusion criteria were other causes of optic neuropathy (such as ischaemic optic neuropathy, toxins or Leber's hereditary optic neuropathy); all causes of optic neuritis (such as HIV, neurosyphilis, sarcoid or connective tissue disease); neurological disease outside of the optic nerves; and any race other than South African black. Patients underwent extensive ophthalmic, neurological, radiological, cerebrospinal fluid and blood assessment. RESULTS: Eighteen eyes of 10 patients were studied. The mean age was 35.7 years and 9 patients were female. Only 2 patients had truly unilateral optic neuritis, the other 8 having either bilaterally simultaneous or consecutive disease. Presenting visual acuity (VA) was less than 6/60 in 17 of 18 eyes, with severe dyschromatopsia in all eyes. Fifteen eyes had optic disc swelling. All patients were treated with corticosteroids. After at least 3 months follow-up only 6 eyes recovered VA of 6/12 or better, with only 3 eyes recovering colour vision of 10/13 or better on Ishihara plate testing. No patient had multiple sclerosis (MS) on presentation, nor developed MS on follow-up. CONCLUSION: Idiopathic optic neuritis in black South Africans differs from that in whites. The higher prevalence of bilateral cases and of optic disc swelling, the weaker association with MS and the extremely poor visual outcome distinguish optic neuritis in black South Africans.

Cerebral cysticercosis. A case report and review of the literature.

Two cases of histologically proven cerebral cysticercosis are presented. In both cases subcutaneous tissue nodules, a rare feature, were present. Several disease patterns are apparent--meningeal, parenchymatous and ventricular, spinal cord lesions and mixed patterns. Epilepsy is by far the major presenting symptom of cysticercosis, which in turn plays a significant role in the causation of adult-onset epilepsy in Blacks. Despite its drawbacks, the haemagglutination inhibition test remains the most satisfactory serological method at present available for the diagnosis of cysticercosis; it is positive in up to 85% of cases of proven cysticercosis. With the advent of computed tomography many cases of unsuspected cysticercosis (symptomatic or asymptomatic) are being discovered.

Carbohydrate metabolism in motor neurone disease.

Eight patients with classical motor neurone disease, and eight control patients with neurological disease and matched for degree of wasting, were studied. Both groups had abnormal glucose tolerance, but the patients with motor neurone disease had a significantly lower insulin response both to oral glucose loading and to intravenous tolbutamide. These results suggest that in patients with motor neurone disease there is an impaired synthesis or release of insulin due to islet cell damage. Blood pyruvate and lactate, and cerebrospinal fluid pyruvate, lactate, and citrate, did not differ significantly from the control group. Blood citrate levels were significantly higher in patients with motor neurone disease compared with the controls. Triglyceride levels were raised in patients with motor neurone disease compared to the control patients. This may be secondary to the increased citrate levels.

Demyelinating disorder of the central nervous system occurring in black South Africans.

OBJECTIVES: To investigate the nature and cause in eight black South African patients of a recurrent (multiphasic), remitting, and relapsing demyelinating disease of the CNS. METHODS: The clinical and laboratory investigations and radiological manifestations of these patients were documented. RESULTS: Each patient had two or more acute attacks of demyelinating disease affecting the CNS. The clinical presentations of the patients were predominantly those of multiphasic neuromyelitis optica (NMO). Brain MRI in these patients showed features consistent with those described for acute disseminated encephalomyelitis (ADEM), as well as lesions that are described in multiple sclerosis. There was involvement of the corpus callosum in addition to typical ADEM lesions. Laboratory investigations excluded all other known causes of multiphasic CNS demyelination. Oligoclonal antibodies were not detected in these patients at any time. The patients were all from a population with a low risk for MS (black South Africans). CONCLUSION: The patients described here represent a new phenotypic expression of a recurrent (multiphasic), steroid sensitive, inflammatory demyelinating disorder of the CNS occurring in black South Africans. The disorder is either a distinct inflammatory demyelinating disorder of the CNS of as yet unknown aetiology, or a varied form of MS (ADEM/NMO) occurring in a population with a low risk (where the genetic trait and environmental risk factors for MS do not exist) for MS.

The diagnosis and significance of isolated third nerve palsy in the African.

The clinical spectrum of forty-one cases of isolated third nerve palsy in the African (Negro) population is presented. A high proportion (58%) was due to cerebral aneurysm. Other causes were syphilis (15.5%) diabetes mellitus (11%), and ophthalmoplegic migraine (11%). It is evident from this study that, contrary to accepted thinking on this subject, there are no clinical features which reliably distinguish between these groups. Early cerebral angiography is therefore mandatory.

Crural hypertrophy associated with centronuclear myopathy.

A case of centronuclear myopathy of adult onset with striking hypertrophy of lower limb muscles in a black South African man is described with details of the light microscopic, histochemical, and ultrastructural features. The association of hypertrophied muscles with centronuclear myopathy has not to our knowledge been reported previously and it is felt that this may be a variant of the condition.

The clinical and genetic characteristics of spinocerebellar ataxia type 7 (SCA 7) in three Black South African families.

OBJECTIVES: Spinocerebellar ataxia type 7 is a rare autosomal dominant neurodegenerative disorder characterized by progressive cerebellar and retinal degeneration, described in various population groups in the literature. This is the first description from South Africa. The objective was to document the clinical and genetic characteristics of our patients and to determine concordance with other described cases. PATIENTS AND METHODS: The index cases were identified clinically on the basis of the typically described features of progressive ataxia with visual failure due to progressive cerebellar and retinal/macular degeneration. Associated neurological disturbances were documented. Where possible, and available, family members were assessed and pedigrees were delineated. Molecular tests for SCA expansions were determined in the index cases. RESULTS: Three pedigrees of SCA 7 were identified. The patients were all Black South Africans. The genetic and clinical characteristics are typical for SCA 7. CONCLUSION: SCA 7 is a rare distinct neurodegenerative disorder characterized by trinucleotide expansion.