Monoclonal antibody-defined immunoregulatory cells in multiple sclerosis cerebrospinal fluid.

To determine if previously reported peripheral blood suppressor cell defects are also found in the central nervous system (CNS) of patients with multiple sclerosis (MS), we studied cerebrospinal fluid (CSF) and peripheral blood lymphocytes from 40 MS patients and 15 patients with other neurological diseases. With an indirect immunofluorescence technique using the OKT series of monoclonal antibodies (OKT4, marking helper/inducer cells, OKT5 and OKT8 marking suppressor/cytotoxic cells, and OKT3 marking all peripheral T cells) we found that MS patients tested in the first 2 wk of exacerbation had invariably diminished CSF suppressor/cytotoxic cells, which was followed by an elevation of these cells in the 3rd wk of exacerbation. Repeat studies of three patients showed that perturbations of CSF suppressor/cytotoxic cells were dependent on clinical status. These observations add to the accumulating data that suggest altered immunity in the pathogenesis of MS.

Combined influences of Gm and HLA phenotypes upon multiple sclerosis susceptibility and severity.

In some Caucasian populations, multiple sclerosis (MS) susceptibility has been independently related to given alleles of HLA or Gm systems that respectively code for major histocompatibility complex class I and II antigens or immunoglobulin G heavy chains. Whether given combinations of alleles at both series of loci simultaneously influence MS susceptibility and/or severity was investigated by comparing 147 French MS patients and 226 geographically-matched healthy controls. The G2m(-23)/HLA-B35 phenotype and G1m(-1)/HLA-B7(-)/HLA-DR2 phenotype were respectively associated with significant protection against (relative risk = 0.05) and susceptibility to (relative risk = 4.3) MS. When considering MS severity, the presence of HLA-B7 antigen correlated with a more severe disease in Gm1/Gm3 heterozygous patients, but not in Gm3/Gm3 homozygous patients. Conversely, an HLA-B12-associated milder disease was restricted to Gm3/Gm3 homozygotes. These results demonstrate the combined influence on MS of genetic loci that are unlinked but immune response-associated. Combined Gm and HLA typing is very likely able to serve as a prognostic indicator in this disease.

Thalamic stimulation and proximal tremor. A specific target in the nucleus ventrointermedius thalami.

The severe proximal cerebellar postural tremor (also called action or intention or hyperkinetic tremor) is barely influenced by thalamotomy or stimulation of the thalamus at the classic target in the lower part of the nucleus ventrointermedius thalami (VIM). In four patients with a severe postural distal and proximal tremor, an electrode fitted with four points of contact was introduced within the entire height of the VIM. In each patient, stimulation of the lower part of the VIM was most effective in the distal component of the tremor, whereas its proximal component was specifically reduced by stimulation of its upper part. These results indicate that (1) proximal postural tremors can be as much affected by stimulation of the VIM as distal tremors, (2) there is a somatotopy in the VIM that is similar to that in the nucleus ventralis posterolateralis thalami, and (3) it is possible with this technique to adjust the VIM stimulation site so as to obtain the maximum efficacy according to the locale of the tremor.

Asterixis in focal brain lesions.

Asterixis was observed in 20 cases of focal brain lesions. Metabolic or toxic factors were excluded. An electromyogram study of asterixis was carried out in nine cases to establish the diagnosis. The site of the focal lesion was either parietal or mesencephalic and was always contralateral to the asterixis. "Focal asterixis" could result from a dysfunction of the sensorimotor integration in the parietal lobe and the midbrain.

Cerebrospinal myelin basic protein in multiple sclerosis. Identification of two groups of patients with acute exacerbation.

The myelin basic protein concentration in the cerebrospinal fluid (CSF) of 125 patients with multiple sclerosis was measured using a radioimmunoassay technique with a detection level of 200 pg/mL and was correlated with the clinical course of the disease. Myelin basic protein was detected in the CSF of some patients with an active progressive form of the disease and in the CSF obtained during exacerbations with the presence of signs or symptoms not previously experienced by the patient (26 of 29 cases were positive during the period of maximal symptoms). Myelin basic protein was not detected in any patient with an inactive or slowly progressive form of the disease, nor in any patient during exacerbations with only recurrence of old signs or symptoms. These results are consistent with the hypothesis that the two clinical forms of exacerbation defined above may be associated respectively with the absence or presence of an acute demyelination.

Early and delayed SPECT using N-isopropyl p-iodoamphetamine iodine 123 in cerebral ischemia. A prognostic index for clinical recovery.

Sixteen patients with stroke, five patients with permanent regressive ischemic neurologic deficit, and three patients with transient ischemic attacks were studied by single photon emission computed tomography performed within the first hour (early scan) and four hours (delayed scan) after injection of N-isopropyl-p-iodoamphetamine-iodine-123 (IMP). These patients were classified into three groups according to their clinical improvement three months later, and results of single photon emission computed tomography were compared with computed tomographic scan results and correlated to the clinical outcome. Regional brain hypoactivity of IMP differed in some cases between early and delayed IMP scans, showing in those cases a "redistribution" activity. The amplitude of this redistribution was significantly correlated with the clinical outcome of patients with stroke, whereas the value of hypoactivity on early IMP scan did not show such a correlation. The higher the redistribution amplitude was, the better was the clinical outcome. Comparative regional brain hypoactivity of IMP on early and delayed scans could represent a prognostic index of clinical recovery inasmuch as it gives information concerning viability of ischemic brain tissue.

Disruption of residual reading capacity in a pure alexic patient after a mirror-image right-hemispheric lesion.

A 74-year-old woman became a letter-by-letter reader after the occurrence of a left occipito-temporal hematoma. Seven months later, she suffered a second, mirror-image hematoma in the right hemisphere. After this second lesion, her residual reading capacity deteriorated dramatically in terms of both accuracy and reading latencies for words and isolated letters. Our findings support the hypothesis that the right hemisphere contributes to the residual reading capacities of pure alexic patients.

Peripheral neuropathies after arthropod stings not due to Lyme disease: a report of five cases and review of the literature.

Five patients developed neurologic symptoms a few hours to 2 months after being stung by a non-hooking arthropod with immediate cutaneous reaction. The patients had no clinical or serologic evidence for Lyme borreliosis and rickettsial disease. Clinical and electrophysiologic findings were consistent with a mixed axonal and demyelinating mononeuropathy, a monomelic multiple mononeuropathy, a mononeuropathy multiplex, a radiculoneuritis, and a distal symmetric polyneuropathy. Muscle and nerve biopsies showed lymphoplasmacytic small-vessel vasculitis in all patients, and wallerian degeneration in three. These patients, and 17 others from the literature, indicate a spectrum of peripheral neuropathies occurring after insect and spider stings.

Somatosensory cortical activations are suppressed in patients with tactile extinction: a PET study.

OBJECTIVE: To investigate whether tactile extinction alters the cortical somatosensory activations induced by hand vibration. BACKGROUND: Tactile extinction occurs mainly after right-brain lesions and consists of the inability to perceive a contralesional cutaneous stimulation when a similar stimulus is applied to the mirror region of the ipsilesional hemibody. The pathophysiology of tactile extinction is poorly understood, but it is considered to be a deficit of selective attention of somatosensory stimuli. Although other theories have been proposed, our understanding of the pathophysiology of tactile extinction may benefit from functional imaging studies. METHODS: We selected three patients with pure tactile extinction and a mainly subcortical right-brain lesion that spared the primary sensorimotor cortex (SM1). We used PET to investigate the responses to unilateral and bilateral hand vibration in SM1 and the secondary somatosensory cortical area (SII). RESULTS: During bilateral hand vibration, activation was normal in the left SM1, suppressed in the right SM1, and markedly decreased in both SII, which was consistent with the extinction of the left-hand stimulus. During unilateral left-hand vibration, the activation of the right SM1 was still markedly impaired, but the activation of both SII was normal. CONCLUSIONS: We found marked changes in the activation of cortical somatosensory areas induced by hand vibration in patients with tactile extinction. The role of selective attention in cortical activation is also examined.

Right-side neglect in Alzheimer's disease.

Unilateral neglect--the inability to pay attention to events occurring on one side of space--usually occurs for left-side events after focal right-hemisphere damage. We report a 73-year-old woman with probable AD and no evidence of focal brain lesions who showed signs of right-side neglect and extinction. Neglect was more severe after 1 year. Neuroimaging techniques demonstrated an asymmetry of cortical involvement, with cortical atrophy and hypoperfusion predominant in the left posterior regions. Unilateral neglect should be assessed systematically in AD.

Retest effects and cognitive decline in longitudinal follow-up of patients with early HD.

OBJECTIVE: To assess the natural progression of cognitive impairment in Huntington's disease (HD) and to reveal factors that may mask this progression. BACKGROUND: Although numerous cross-sectional studies reported cognitive deterioration at different stages of the disease, progressive cognitive deterioration has been, up to now, difficult to demonstrate in neuropsychological longitudinal studies. METHODS: The authors assessed 22 patients in early stages of HD at yearly intervals for 2 to 4 years (average, 31.2 +/- 10 months), using a comprehensive neuropsychological battery based on the Core Assessment Program for Intracerebral Transplantation in Huntington's Disease (CAPIT-HD). RESULTS: The authors observed a significant decline in different cognitive functions over time: these involved primarily attention and executive functions but also involved language comprehension, and visuospatial immediate memory. Episodic memory impairment that was already present at the time of enrollment did not show significant decline. The authors found a significant retest effect at the second assessment in many tasks. CONCLUSION: Many attention and executive tasks adequately assess the progression of the disease at an early stage. For other functions, the overlapping of retest effects and disease progression may confuse the results. High interindividual and intraindividual variability seem to be hallmarks of the disease.

Multiple-domain dissociation between impaired visual perception and preserved mental imagery in a patient with bilateral extrastriate lesions.

A brain-damaged patient is described whose pattern of performance provides insight into both the functional mechanisms and the neural structures involved in visual mental imagery. The patient became severely agnosic, alexic, achromatopsic and prosopagnosic following bilateral brain lesions in the temporo-occipital cortex. However, her mental imagery for the same visual entities that she could not perceive was perfectly preserved. This clear-cut dissociation held across all the major domains of high-level vision: object recognition, reading, colour and face processing. Our findings, together with other reports on domain-specific dissociations and functional brain imaging studies, provide evidence to support the view that visual perception and visual mental imagery are subserved by independent functional mechanisms, which do not share the same cortical implementation. In particular, our results suggest that mental imagery abilities need not be mediated by early visual cortices.

T cell subsets in multiple sclerosis. A longitudinal study of exacerbating-remitting cases.

Twenty-four untreated MS patients with exacerbating-remitting disease were longitudinally studied for T-cell subset distribution within peripheral blood, using monoclonal antibodies OKT3, OKT4 and OKT8. A decreased percentage of OKT8 reactive cells, with a correlative increase of the OKT4/OKT8 ratio, was detected in relapsing MS patients, in most cases within 2 weeks before and 1 week after the onset of relapse. Longitudinal analysis of individual fluctuations allowed to detect during relapse an increase of OKT4/OKT8 ratio over the value recorded during remission in 78% of MS patients. Only 50% of patients however exhibited an OKT4/OKT8 ratio exceeding the 5% confidence upper limit of healthy control values. Relapse was more often associated with T-cell subset abnormalities in patients who suffered several attacks during the period of study. MS patients in remission, when considered as a group did not show significant abnormalities of the T-cell subset balance, although some individuals did present with wider T-cell subset fluctuations than healthy controls.

Peripheral injections of Freund's adjuvant in mice provoke leakage of serum proteins through the blood-brain barrier without inducing reactive gliosis.

Breakdown of the blood-brain barrier (BBB) and ensuing gliosis are common events following physical trauma to the central nervous system (CNS) or during autoimmune diseases such as experimental allergic encephalomyelitis (EAE). Some studies of EAE in rodents report that peripheral injections of complete Freund's adjuvant (CFA), which contains heat-inactivated Mycobacterium to provoke peripheral inflammation without adversely affecting the CNS, can itself lead to increased BBB permeability to small tracer molecules and certain serum proteins. To study the equivocal relationship between serum protein extravasation and reactive gliosis, we injected C57BL/6 mice with CFA and histologically assessed the permeability of various serum proteins and the reactivity of proximal microglia and astrocytes in the uninjured brainstem and spinal cord enlargements after 1-4 weeks. Our results confirm that CFA injections induce progressive increases in the perivascular extravasation of serum IgG, albumin, IgM, and exogenous horseradish peroxidase, all to varying degrees, most prominently in the brainstem and cervical spinal cord after 2-3 weeks. More importantly, neither microglial cells nor astrocytes in regions of focal serum protein leakage appeared morphologically reactive based on immunoreactivity for CR3 receptors (Mac-1) or glial fibrillary acidic protein (GFAP), respectively. Because we found no evidence of T cell infiltration accompanying the exudates, our results indicate that in the absence of physical trauma or inflammatory cells resident CNS neuroglia remain quiescent upon exposure to extravasated serum proteins.

Muscle mitochondrial DNA in encephalomyopathy and ragged red fibres: a Southern blot analysis and literature review.

Various mitochondrial DNA abnormalities have been described in patients with encephalomyopathies. We performed Southern blot analysis of skeletal muscle mitochondrial DNA in nine adult patients with clinical features and ragged red fibres suggesting mitochondrial dysfunction. Two patients with encephalomyopathy and two with the MERRF syndrome (myoclonus epilepsy with ragged red fibres) had the normal PvuII restriction pattern of muscle mitochondrial DNA. In contrast, mitochondrial DNA deletion was observed in two of six patients with ophthalmoplegia. One suffered from typical Kearns-Sayre syndrome and the other from isolated external ophthalmoplegia. None of these patients had affected relatives. The detection of mitochondrial DNA deletion in external ophthalmoplegia and their site and size support previously reported data.

Extensive form of progressive multifocal leucoencephalopathy associated with laryngeal carcinoma.

A case is reported of the rare association between progressive multifocal leucoencephalopathy and carcinoma. A 66-year-old man underwent a laryngectomy for carcinoma. Four years later he developed a local recurrence. Simultaneously there were behavioural disturbances and a left motor neglect followed by dense hemiplegia and coma. The patient died a further 5 months later. Anergy was demonstrated by skin tests. CT scan showed asymmetrical non-enhancing low-density areas in the hemispheric white matter, brain-stem and cerebellum and neuropathological examination confirmed extensive myelin loss with typical papovavirus inclusions in oligodendrocytes identified by electron microscopy.

Bilateral infarction of the anterior cingulate gyri and of the fornices. Report of a case.

A 70-year-old woman had complex behavioural changes of sudden onset. The symptoms consisted of indifference, docility and inappropriate urination, but predominantly in a lack of attention. She was unable to maintain the attention necessary to perform a goal-directed activity and she was distracted by any stimulus, such as a sound, an object, or a word, which might induce behaviour irrelevant to the preconceived activity. She also exhibited confabulatory-amnestic syndrome. Neuropathological examination of the brain revealed infarcts in th territories of both anterior cerebral arteries. The rostral part of the anterior cingulate gyrus (Acg), small areas of the adjacent medial prefrontal cortex, and the underlying white matter were destroyed bilaterally. Infarction involved the deep territory of the left anterior cerebral artery, with a bilateral lesion of the fornices. This cingulate damage was more restricted than the Acg lesions reported in some cases of akinetic-mutism, which extended more caudally, but was presumably larger than the lesions created in psychosurgery. The impairment of attention was analyzed according to the possible roles of the cingulate and of the fornix lesions as causing a dysfunction between the frontal lobes and the hippocampal formations.

Increased growth of myoblasts from hypertrophic muscles in syringomyelia.

Proliferation and differentiation of myoblasts from hypertrophic muscles were studied "in vitro" in two cases of syringomyelia with muscle hypertrophy (MH). Their myoblast growth was compared with that of muscle cells sampled on the contralateral side in the same patients and in control subjects. The effect of a circulating factor was tested using patient sera in place of fetal calf and horse sera. The results showed that MH cells were morphologically abnormal (giant and granular). MH myoblasts proliferated more rapidly than contralateral and normal myoblasts, their fusion was accelerated and the resulting myotubes synthesized higher levels of protein. MH sera increased these effects. Serum factors are therefore likely to be involved in "in vivo" muscle hypertrophy. These findings suggest that the pathogenesis of muscle hypertrophy in syringomyelia involves acquired abnormalities due to molecules released in response to neural lesions.

Dissociation between distal and proximal left limb agraphia and agraphesthesia in a patient with a callosal disconnection syndrome.

A few neuropsychological studies have suggested the existence of bilateral hemispheric representations for the proximal parts of the limbs in humans. We report the case of a patient who presented with a callosal disconnection syndrome, which at a later stage of disease became restricted to left agraphia, left agraphesthesia and left auditory extinction. The anomic character of the agraphesthesia was demonstrated. Tactile naming was normal, which allows us to conclude that separate callosal pathways related to the left language areas transmit information for graphesthesia and tactile naming. Agraphia and agraphesthesia were not observed when the proximal part of the left upper limb was utilized. These observations support the conclusion that writing and graphesthesia with the proximal part of the limb can be mediated by the ipsilateral cortex.

Inversion superiority in visual agnosia may be common to a variety of orientation polarised objects besides faces.

Selective impairment in recognition of faces (prosopagnosia) resulting from certain localized cortical lesions has been advanced as an argument for a face specific brain module. The argument is claimed to be strengthened by the discovery of an inversion superiority effect in the recognition of faces by a prosopagnosic patient (Farah et al., Vis Res 1995b;35:2089-2093). The present paper reports an inversion superiority effect in the recognition of faces and shoes in a visual agnosic patient. The finding raises the possibility that several classes of orientationally polarized objects, of which shoes and faces are examples, will exhibit inversion superiority.