Contribution of PET studies in diagnosis of corticobasal degeneration.

Five patients with clinical features of corticobasal degeneration (CBD) were studied with PET imaging. The main clinical findings included a unilateral extrapyramidal motor disorder, without significant response to levodopa, as well as clumsiness, dysarthria, apraxia and a clear asymmetry of neurological signs. PET studies with (18)F-labeled 2-deoxy-2-fluoro-D-glucose disclosed mainly a significant hypometabolism in the thalamus and motor cortex controlateral to the more affected limbs. Additional relationships between individual clinical signs and PET data were also found. We concluded that PET findings supported the clinical diagnosis of CBD, although the specific pattern related to this condition needs to be more precisely defined. Further studies are especially needed to correlate clinical data and PET results with pathological examination.

A retrospective study of Creutzfeldt-Jakob disease in Belgium.

Using data from Belgian neuropathological archives, completed with the results of a comprehensive study of available medical records, we found 100 patients who fulfilled diagnostic criteria for probable or definite Creutzfeldt-Jakob d1551isease (CJD). Mean age at death was 63 years. The median disease duration was 9 months. Progressive mental deterioration was present in all cases, whereas signs of cerebellar dysfunction and myoclonus were found in approximately 80% of the patients. In 50% of the population, the EEG revealed characteristic abnormalities. Ninety-six patients suffered from the sporadic type of CJD, while 4 suffered from a hereditary form. In our series, we could find no evidence for the new variant, neither for an iatrogenic cause.

Sporadic Creutzfeldt-Jakob disease. A clinico-neuropathological analysis of nine definite cases.

The authors have analyzed clinico-neuropathologically nine cases of the definite sporadic form of Creutzfeldt-Jakob disease (CJD). All cases were female, with mean age of 62.7 years. Eighty-nine percent of the patients exhibited prodromal and initial psychiatric symptoms; definite signs of dementia, and myoclonus were present in 100% of cases. The EEG was abnormal in all cases and pseudoperiodic paroxysms were present in 56% of the patients. Their evolution time ranged from 3 to 19 months. Neuropathologically, brain and cerebellar atrophy, spongiosis, astrocytosis and neuronal loss were present in 100% of the patients. In 5 (56%) of these 9 cases, prion protein (PrP) amyloid plaques were detected in the cerebellum, by optical- and electronmicroscopy. There was a positive correlation between the number of plaques and the evolution time. The authors outline the similarities of their cases in the elderly with the new variant of CJD described in young people.

The anti-Hu syndrome: a clinical and immunological study of 7 cases.

The authors describe the clinical and biological data of seven patients with anti-Hu antibodies. Six of them displayed a small cell lung carcinoma (SCLC), but no cancer was detected in the 7th patient in spite of an extensive workup. The clinical heterogeneity of the anti-Hu syndrome is emphasized. The major symptoms were linked to a severe sensory neuropathy in three cases, to cerebellitis in two cases, to dysautonomia in one case, and to gastro-intestinal pseudo-obstruction in one case. One patient also displayed EMG abnormalities characteristic of the Lambert-Eaton myasthenic syndrome. Two patients developed opsoclonus or ocular flutter associated with severe confusion in the late stage of their disease. In four patients, the neurological signs and symptoms preceded the discovery of the SCLC, and in two cases the initial detection of anti-Hu antibodies prompted the successful search for this tumor. Immunopathological events injuring the peripheral and central nervous system are briefly discussed.

Persisting perfusion defect in transient ischemic attacks: a new clinically useful subgroup?

BACKGROUND AND PURPOSE: Cerebral infarction and prolonged regional hypoperfusion have been described in patients with transient ischemic attacks (TIAs). The aim of this study was to compare the sensitivity of single-photon emission CT (SPECT) with that of brain CT and to evaluate the clinical significance of differentiation of TIA patients with or without focal hypoperfusion. METHODS: From a hospital-based population, we studied the SPECT and CT findings in 76 consecutive patients, without a stroke history, who presented with TIA in the carotid artery territory. The recorded variables were the time of SPECT, imaging (<36 or > or = 36 hours), clinical presentation, history of previous TIA(s), duration of the presenting attack (<2 or > or = 2 hours), vascular risk factors, and etiology. We used both visual and semiquantitative analyses for the SPECT evaluation. Acetazolamide challenge was not performed. RESULTS: The overall SPECT sensitivity was 36% (27/76). When brain CT and SPECT were performed in the same patients, the SPECT sensitivity was significantly higher than that of CT (19/59 [32%] versus 8/59 [14%]; P=.007). The SPECT sensitivity was not dependent on the time of investigation, duration of attacks, history of TIA(s), or the clinical presentation. The vascular risk and etiologic factors were not significantly different between the patients with or without prolonged focal hypoperfusion. Logistic regression did not identify any variable to discriminate the two groups. CONCLUSIONS: Despite its better sensitivity compared with CT, SPECT performed without the acetazolamide test provides no additional clinically useful information on the vascular risk factors and etiology in TIA patients.

Comparative correlations of HMPAO SPECT indices, neurological score, and stroke subtypes with clinical outcome in acute carotid infarcts.

BACKGROUND AND PURPOSE: The prognostic value of single-photon emission computed tomography (SPECT) remains controversial. The aim of this study was to compare the prognostic value of stroke severity, stroke subtypes, and SPECT indices and to determine which predictive factors have an independent effect on clinical outcome. METHODS: We studied 55 consecutive patients with acute (< 12 hours) carotid infarct within 36 hours of symptom onset with SPECT. Clinical presentation was assessed by the Canadian Neurological Scale and stroke subtypes. SPECT indices were the degree and size of hypoperfusion and crossed cerebellar diaschisis as assessed by a semiquantitative analysis. Outcome was evaluated by the functional status and mortality (Rankin Scale score at 1 month). RESULTS: The Rankin Scale score correlated with the degree (r = .580; P < .00001) and size (r = .616; P < .00001) of hypoperfusion. The mean degree and size of hypoperfusion were significantly higher in patients with poor outcome. Crossed cerebellar diaschisis had no significant predictive value. Statistical analysis determined threshold values for the Canadian Neurological Scale score and the degree and size of hypoperfusion for the functional status and mortality. The degree and size of hypoperfusion had no higher performance than the Canadian Neurological Scale score. The negative predictive value was excellent for both clinical and SPECT indices. Multivariate analysis selected only the size of hypoperfusion as an independent predictor for the functional status (P = .004) and the Canadian Neurological Scale score for mortality (P = .009). CONCLUSIONS: SPECT performed within 36 hours of onset predicts clinical outcome, but different clinical and SPECT indices with threshold values should be chosen according to the relevant outcome end point.

Brain tumor imaging with PET and 2-[carbon-11]thymidine.

METHODS: To assess the potential of thymidine for imaging brain tumors, 20 patients with untreated (n = 14) and recurrent (n = 6) supratentorial intracranial tumors were studied with PET by using 2-[11C]thymidine (Tdr), and the results were compared with [18F]fluorodeoxyglucose (FDG) PET data. RESULTS: Blood analysis consistently revealed a rapid clearance of the intact Tdr together with the appearance of CO2/HCO3- that, with time, accounted for approximately 70% of the total blood activity. As soon as 10 min after tracer injection, brain images showed a low and homogeneous Tdr distribution over the normal brain structures (cortex-to-blood ratio approximately 1). Visual and quantitative analysis revealed increased Tdr uptake (tumor-to-cortex ratio > or = 1.2) in 11 of 14 untreated tumors and in 5 of 6 recurrent tumors. No correlation was found between Tdr uptake and tumor grade. In 12 of the 14 untreated tumors, FDG uptake was low (tumor-to-cortex ratio: 0.83 +/- 0.79), but a FDG hot spot was visualized in 8 of 10 high-grade and in none of the 4 low-grade tumors. FDG uptake was consistently low in recurrent tumors (tumor-to-cortex ratio: 0.49 +/- 0.19), and PET-FDG was negative in 3 of the 6 cases. CONCLUSION: These data indicate the feasibility of brain tumor imaging with Tdr and suggest the potential clinical usefulness of the method in the detection of tumor recurrences. The specificity of the method remains, however, to be investigated.

Brain glucose metabolism in postanoxic syndrome due to cardiac arrest.

Using positron emission tomography (PET), thirteen studies of regional brain glucose utilization were performed in 12 patients with postanoxic syndrome due to cardiac arrest. Investigations were carried out at least one month after brain anoxia. Seven subjects were in a persistent vegetative state. The others had regained normal consciousness with various residual neurological signs. When compared with normal values obtained in 16 normal, age-matched subjects, mean cerebral glucose metabolism was drastically decreased (+/- 50%) in vegetative cases, and to a lesser degree (+/- 25%) in conscious subjects. The most consistent regional alterations were observed in the parieto-occipital cortex (9 cases), the frontier between vertebral and carotid arterial territories. Other selective anomalies were found in the frontomesial junction (5 cases), the striatum (3 cases with dystonia), and the visual cortex (2 cases with cortical blindness). This study suggests that cerebral anoxia results in a global brain hypometabolism, which appears related to the vigilance state, as well as in regional disturbances preferentially located in arterial border zones. Although our findings remain to be confirmed in larger series, they suggest that PET provides a useful index of residual brain tissue function after anoxia and may assist in the monitoring of postanoxic encephalopathies.

Highly sensitive detection of beta-2 transferrin in rhinorrhea and otorrhea as a marker for cerebrospinal fluid (C.S.F.) leakage.

As beta-2 transferrin is almost specific to the cerebrospinal fluid, its detection in rhinorrhea or otorrhea fluids demonstrates the occurrence of CSF fistula. We describe a highly sensitive method based on immunoaffinity-mediated capillary blotting for the detection of this cathodic isoform of transferrin in minute amounts (3 microliters) of rhinorrhea or otorrhea fluids. Application of this method in a series of 10 patients with CSF fistula is reported.

Neuralgic amyotrophy with involvement of cranial nerves IX, X, XI and XII.

We report a patient who presented with involvement of multiple cranial nerves associated with otherwise typical neuralgic amyotrophy. This syndrome of unknown etiology is not limited to the brachial plexus. Simultaneous involvement of cranial nerves IX, X, XI, and XII is a unique presentation. The electrophysiological data indicate the presence of a multifocal neuropathy.

Herpes simplex virus type 2 meningitis without genital lesions: an immunoblot study.

Two sexually active female patients presented with acute meningitis. The CSF abnormalities were severe and persistent. In spite of the absence of genital lesions, serological studies revealed a primary infection by herpes simplex virus type 2. An immunoblot study revealed intrathecal synthesis of anti-herpes antibodies early in the course of the disease.

Intrathecal synthesis of anti-mycobacterial antibodies in patients with tuberculous meningitis. An immunoblotting study.

Cerebrospinal fluid (CSF) and serum samples from eight patients with bacteriologically proven (6) or clinically suspected (2) tuberculous meningitis were tested for the presence of anti-mycobacterial IgG antibodies by an affinity-mediated immunoblot technique. This technique is based on agarose gel isoelectric focusing of paired CSF and serum samples diluted to the same IgG concentration, and transfer of the specific IgG antibodies onto mycobacterial antigen-loaded nitrocellulose sheets. An intrathecal synthesis of anti-mycobacterial oligoclonal IgG antibodies, often superimposed on diffuse polyclonal production was shown in all patients but not in patients with tension headache or other neurological disorders. Similar results were obtained when a purified mycobacterial antigen, A60, was used for coating the nitrocellulose sheets in place of a whole mycobacterial homogenate, indicating that A60 was a major immunogen. The number of anti-mycobacterial oligoclonal IgG bands increased with time, and persisted for years even in clinically cured patients. Some IgG bands had no detectable anti-mycobacterial activity, at least with the antigens preparations used in this study. The demonstration of such anti-mycobacterial IgG bands in the CSF could be a useful adjunct for the diagnosis of tuberculous meningitis, especially in the case of negative cultures.

Brain glucose metabolism in postanoxic syndrome. Positron emission tomographic study.

Thirteen positron emission tomographic studies of cerebral glucose utilization were carried out in 12 patients with postanoxic syndrome due to cardiac arrest. Seven subjects were in a persistent vegetative state. The 5 other subjects were normally conscious, but disclosed focal neurological signs. When compared with normal values, mean cerebral glucose metabolism was drastically decreased (+/- 50%) in vegetative subjects, and to a lesser degree (+/- 25%) in conscious patients. The most consistent regional alterations were found in the parieto-occipital cortex (9 cases), the frontier between vertebral and carotid arterial territories, followed by the frontomesial junction (5 cases), the striatum (3 cases with dystonia), thalamus (2 cases), and visual cortex (2 cases with cortical blindness). These data suggest that brain anoxia can result in global brain hypometabolism, which appears related to the vigilance state, as well as in regional alterations preferentially located in arterial border zones.

[Neurological involvement as manifestation of Behçet's disease. 4 clinical case reports]. / Atteintes neurologiques révélatrices d'une maladie de Behçet. Quatre observations cliniques.

We report four patients with Behçet's disease characterized by initial and predominant neurological signs and symptoms. In three cases, a clinical picture of relapsing meningoencephalitis preceded the appearance of the classical signs of the disease for several months or years; in the fourth case, an acute febrile aseptic meningitis coincided with the development of bipolar aphthosis and uveitis. Disease activity was linked to a blood inflammatory syndrome and neutrophilic leucocytosis. Acute phases were associated with CSF mixed pleocytosis and high protein content. Brain CT scans and MRI were very effective to detect lesions which are mainly located in the brain stem and basal ganglia. High-dose corticosteroids and, in cases of relapses, immunosuppressive drugs were required to treat these severe forms of Behçet's disease.

Monoclonal IgM gammopathy with anti-myelin associated glycoprotein (MAG) activity and polyneuropathy. A study of three cases.

The authors describe three patients with a chronic sensory-motor polyneuropathy associated with a monoclonal IgM gammopathy. In each case, the M-component was shown to display an antibody activity against the Myelin-Associated Glycoprotein (MAG) in a western blot technique. Sera from the three patients stained specifically the myelin sheaths of normal human peripheral nerves after incubation with rabbit anti-IgM. Motor conduction velocities were very low in each case. Morphological studies of the sural nerve from one patient revealed a moderate loss of myelinated fibres, some onion-bulbs but also a microangiopathy and signs of axonal degeneration.

Decreased glucose utilization in the striatum and frontal lobe in probable striatonigral degeneration.

Nine positron emission tomography studies of regional cerebral glucose metabolism were performed in 7 patients with probable striatonigral degeneration, a disorder characterized by parkinsonian features and absent or poor response to L-dopa. When compared with values obtained in normal volunteers, mean cerebral glucose metabolism was slightly reduced in subjects with striatonigral degeneration who, in addition, had a marked (20.5%, +/- 3 SD) relative hypometabolism in putaminal and caudate nuclei. Significant hypometabolism was also found in motor/premotor as well as in prefrontal cortex. In 2 subjects who were studied twice a deterioration of relative striatal metabolism paralleled clinical evolution. Magnetic resonance imaging disclosed the presence of abnormal iron deposits in the putamen in all cases but showed no cortical anomalies. These results suggest that positron emission tomography with [18F]fluorodeoxyglucose may provide an index of cell and processes degeneration in the striatum in striatonigral degeneration and is able to detect functional deficits in frontal cortex. The presence of striatal hypometabolism might be a predictor of a poor response to L-dopa.

Positron tomography demonstrates frontal lobe hypometabolism in progressive supranuclear palsy.

A regional analysis of cerebral glucose metabolism was carried out in 9 patients with progressive supranuclear palsy by using positron emission tomography with fluorodeoxyglucose as the tracer. A consistent metabolic map of frontal hypometabolism was found in 7 patients. Brain metabolism was normal in 1 subject and diffusely decreased in another. In the 7 patients with selective hypofrontality, motor and premotor areas were severely hypometabolic, while heteromodal association cortex and paralimbic regions were comparatively less affected. Although this pattern of frontal alterations, probably due to disconnection, appeared consistent with the clinical features of the disease, it proved difficult to correlate the metabolic maps with neuropsychological disturbances.

[3H]GBR 12935 binding to dopamine uptake sites: subcellular localization and reduction in Parkinson's disease and progressive supranuclear palsy.

[3H]GBR 12935 bound with high affinity to dopamine uptake sites in rat striatum where a close parallelism was observed between the subcellular localization profiles for [3H]dopamine uptake and [3H]GBR 12935 specific binding. Using the same ligand, we characterized the dopamine uptake sites in human striatum: the mean KD value was 3.2 nM and the specific binding was inhibited by several dopamine uptake blockers but with slightly lower affinities than those observed in the rat. The subcellular localization profile revealed a synaptosomal enrichment of the specific binding in human striatum. [3H]GBR 12935 binding was decreased in the putamen and caudate nucleus of subjects with Parkinson's disease (33 and 46% of control values, respectively) and progressive supranuclear palsy (38 and 57% of control values, respectively). It is very unlikely that the remaining binding sites in both diseases correspond to piperazine acceptor sites that are not involved in dopamine uptake. However, we cannot exclude the possibility that some of these remaining dopamine transporter sites are not functional, since the reduction in [3H]GBR 12935 specific binding was less marked than the decrease in the dopamine content of the same areas.