Alzheimer CSF biomarkers in routine clinical setting.

OBJECTIVES: Our work was aimed to evaluate Alzheimer's disease diagnosis improvement using cerebrospinal fluid biomarkers (CSF) in neurological daily practice. MATERIALS AND METHODS: For this purpose, 150 patients clinically and neurochemically classified as having AD or cognitive impairment with or without other dementia type were included in the study. The following CSF peptides were studied, blindly to the clinical diagnosis: beta-amyloid(1-42) peptide (Aß(1-42)), Tau (T-tau), threonine-181 hyperphosphorylated tau protein (P-tau(181)), and beta-amyloid(1-40) peptide (Aß(1-40)). From these measurements, Innotest® Amyloid Tau Index (IATI) was calculated for each patient. RESULTS: This assessment allowed to separate 83 biochemical profiles of AD and 67 non-Alzheimer's disease (non-AD), both AD and non-AD categories match with clinical data amounting to 73% and 90%, respectively. Among mild cognitive impairment (MCI) patients, CSF biomarkers led to discriminate those who are likely to be AD. We devoted a special section to Aß(1-40) which is not a routine parameter but can help to confirm a pathological amyloid process as Aß(1-42)/Aß(1-40) ratio underlining the real decline of the Aß(1-42). CONCLUSIONS: The interest of biomarkers and their ability to solve awkward cases were carefully noticed all the more when a discrepancy between clinical and CSF biological data was involved. The final proposed algorithm allowed to identify pathogenic forms of AD according to the prevailing role of hyperphosphorylated tau or amyloid beta peptide.

Glutamate dehydrogenase and aspartate aminotransferase in leukocytes of patients with motor neuron disease.

We report the results of glutamate dehydrogenase (GDH) and aspartate aminotransferase (AAT) activities in leukocytes of 24 patients with motor neuron disease (MND) and 20 matched control subjects. In 62.5% of patients suffering from MND, we detected a leukocyte GDH deficiency (+/- 2 SD) as compared with the mean value obtained in controls. By contrast, there was no difference in leukocyte AAT activities in affected and nonaffected subjects. Abnormal cellular glutamate metabolism might be involved in the pathogenesis of MND.

Acute or subacute alcoholic neuropathy mimicking Guillain-Barré syndrome.

Over the last 10 years we have encountered 8 patients with chronic alcoholism who presented with severe symmetrical polyneuropathy, primarily proximal in 6, which evolved over a period of 24 h to 3 weeks. In 3 cases, artificial ventilation was required. Sensory symptoms were in all instances intense, and tendon reflexes absent. CSF protein levels were normal. The course was one of gradual improvement, often incomplete with residual motor and distal sensory deficits. Three patients died within 2 months to 2 years with multiple and severe pathologies attributable to chronic alcoholism. There was no evidence for disorders other than the alcoholism and malnutrition. Electrophysiological findings were consistent with predominantly axonal lesions and nerve biopsy specimens confirmed acute and severe axonal lesions. Several of these patients had been referred to us with a possible diagnosis of Guillain-Barré syndrome due to the severity of the neuropathy and the rapidity of its onset (Landry syndrome). Acute alcoholic neuropathy is distinguishable, however, on clinical, electrophysiological and morphological grounds.

Improvement in motor evoked potentials and clinical course post-steroid therapy in multiple sclerosis.

Motor evoked potentials (MEP) were recorded in 23 patients with definite relapsing multiple sclerosis before and after treatment with a short course of high dose of methylprednisolone. MEP were performed together with clinical examination just before treatment, and 6 and 60 days later. The following results were observed: (1) a statistically significant relationship between the corticospinal deficit and the alteration in MEP, (2) a significant improvement in latency of MEP by day 6, (3) a significant correlation between the change in the Kurtzke disability scale rating and the improvement in MEP. The results provide further evidence for the possible effectiveness of short courses of high dose corticosteroids in the treatment of relapses of multiple sclerosis and the usefulness of MEP in its assessment.

Sleep-wake cycle in human African trypanosomiasis.

Sleeping sickness patients are classically described as sleepy by day and restless by night. Prior to this study, we had objectively confirmed this description by recording 24-h sleep patterns in a patient with human African trypanosomiasis. We report 24-h polysomnographic recordings (EEG, electrooculogram, electromyogram, electrocardiogram, and nasal, buccal, and thoracic respiratory traces) performed on two eight-channel electroencephalographs in eight patients with untreated sleeping sickness at an early stage of meningoencephalitis. As in our previously reported patient, there was no hypersomnia. The patients presented mainly a disorganization of the circadian alternation of sleeping and waking, with no or little alteration in the states of vigilance at this early stage of the disease. The disorganization was proportional to the degree of severity of the clinical symptoms. It may be due to an alteration in biological clock mechanisms.

Electroencephalographic and polygraphic features of 24-hour recordings in sleeping sickness and healthy African subjects.

Electroencephalographic (EEG) and polygraphic features were analysed in six healthy control subjects and eight patients suffering from sleeping sickness meningoencephalitis in order to determine possible functional relationships. One patient was disqualified because of intermittent metabolic disease. Twenty-four h polygraphic recordings-EEG, electrooculography (EOG), electromyography (EMG), nasal and buccal air flow, chest respiratory movements-were performed continuously both on paper and on cassette tapes. Tapes were played back on paper (paper speed: 15 mm/s). Traces were analyzed for normal and pathologic features, and transient activation phases and paroxysmal hypnopompic hypersynchrony events were counted. During wakefulness, slow theta and delta waves occurred in four patients, but alpha reactivity was present. During sleep, normal features were seen. However, transient activation phases were decreased in the patients. During slow-wave sleep, four patients presented predominantly monophasic frontal delta bursts along with paroxysmal hypnopompic hypersynchrony events. In conclusion, in sleeping sickness patients, although dampened, the waking process remains responsive and slows down only during the late stage of meningoencephalitis.

Monitoring of the motor pathway during spinal surgery.

Paraplegia caused by irreversible lesions of the spinal cord is one of the major possible complications after scoliosis surgery. Several monitoring methods have been proposed but none are completely satisfactory. Since 1986 the authors assessed motor pathways during scoliosis surgery, using electrical stimulation of the motor cortex and lower limb muscle recordings (tibialis anterior muscle). Twenty-seven patients were included in this study: 25 with idiopathic scoliosis and 2 with dorsal kyphosis. Recordings in anesthetized patients with hypothermia were performed before and after spinal derotation during the surgical procedure. Magnetic cortical stimulation was carried out in ten awake patients before and after surgery. Reproducible responses were obtained in 22 patients under anesthesia. In eight patients no difference of the latency of the muscle response was detected before and after the correction of the spinal angulation. In 14 patients the increase of latency ranged from 0.4 ms to 5.2 ms. No correlation was found between the slowing of motor conduction and the magnitude of spine correction. No central neurologic complications were seen after surgery. The authors concluded that their study demonstrated that motor pathway assessment in anesthetized patients can be performed at different times during the surgical procedure. This technique should help in the future monitoring spinal function during scoliosis surgery.

Atypical electrophysiologic findings in chronic inflammatory demyelinating polyneuropathy (CIDP)--diagnosis confirmed by nerve biopsy.

OBJECTIVES: Numerous sets of electrophysiological criteria of chronic inflammatory demyelinating polyneuropathy (CIDP) have been proposed, among which the criteria established by an ad hoc subcommittee of the American Academy of Neurology (AAN) in 1991 (Neurology 41 (1991) 617) are the most widely used. As they seemed rather restrictive, the Inflammatory Neuropathy Cause and Treatment (INCAT) group (Ann. Neurol. 50 (2001) 195) proposed modifications of these electrophysiological criteria. However, even using these criteria, some cases of CIDP may not be recognized. In such cases, nerve biopsy has proven useful for confirmation of the diagnosis by demonstrating specific abnormalities. The objective of the study was to determine the profile of electrophysiological abnormalities in patients with atypical electrophysiologic criteria of CIDP and the diagnostic value of multiple A waves and a low median to sural amplitude ratio. PATIENTS AND METHODS: Over a period of 3 years, we classified 44 patients into two categories: those presenting the strict AAN and/or INCAT criteria and those who we regarded as cases of CIDP not meeting these criteria. All patients benefited from one or more clinical and electrophysiological examination. Extensive biological workup and genetic study when appropriate excluded other causes of neuropathy. Nerve biopsies were taken from all patients and samples were included in paraffin and epon for systematic light, teasing and electron microscopic examination. RESULTS AND CONCLUSION: Out of 44 patients, 36 fulfilled the INCAT or AAN criteria. In eight other patients, the diagnosis of CIDP was suspected on clinical and EMG examinations and confirmed by nerve biopsy. In these cases, the electrophysiological exploration showed some abnormalities such as multiple A waves in four out of eight patients or an abnormal pattern of the sensory responses of the median and sural nerves in four out of eight patients that were more indicative of an initial demyelinating process. Six of our patients received immunomodulatory treatment, and five responded favorably.

Central motor conduction and glutamate deshydrogenase: activity in olivo-ponto-cerebellar atrophy.

Central motor conduction was investigated by way of magneto-electric cortico-spinal stimulation in 6 patients with sporadic olivo-ponto-cerebellar atrophy. Two patients were found to have reduced leucocyte GDH activity. Only the 3 patients with corticospinal deficits displayed increased central conduction rates, which were predominant in the lower limbs. The duration of the disease is statistically longer in patients with corticospinal deficit compared to patients with no corticospinal deficit. In OPCA, evoked motor potentials are useful in assessing the corticospinal deficit which does not appear to be linked to reduced leucocyte GDH activity.

[Ventricular tachycardia by branch to branch re-entry. Familial case with Steinert's disease]. / Tachycardie ventriculaire par réentrée de branche à branche. Cas familial avec maladie de Steinert.

Ventricular tachycardia by branch to branch reentry is a rare arrhythmia. It occurs in cardiomyopathies associated with conduction defects. During tachycardia a His potential precedes each QRS complex which usually has a left bundle branch block appearance. The authors report two familial cases of ventricular branch to branch tachycardia (son and mother) without cardiomyopathy. The diagnosis of Steinert's disease was made post-mortem in these two patients. In cases of branch to branch ventricular tachycardia, the diagnosis of myotonic dystrophy should be excluded. Conversely, endocavitary electrophysiological investigation with ventricular stimulation should be proposed for symptomatic patients (dizzy spells, syncope) to diagnose branch to branch ventricular tachycardia, even in cases with conduction defects which could also explain the symptoms.

[Chronic inflammatory demyelinating neuropathies and their variants] / Polyradiculonévrites chroniques et leurs frontières.

The Chronic Inflammatory Demyelinating Polyradiculoneuropathies (CIDP) constitute a syndrome whose incidence is difficult to evaluate, and is probably underestimated. In the course of this presentation, we deliberately restricted discussion to issues raised in recent years concerning the extent of this syndrome. We discuss diagnostic criteria, especially electrophysiological ones. As the criteria proposed by the ad hoc committee of the American Academy of Neurology in 1991 have been questioned due to lack of sensitivity, new ones have been proposed recently. We briefly discuss the different types of chronic dysimmune demyelinating neuropathy: not only the CIDP, but also the Lewis and Sumner syndrome or multifocal inflammatory demyelinating neuropathy and the multiple conduction block neuropathies. At last, we point out the consistent finding of axonal involvement in the course of a chronic demyelinating neuropathy; over time, it can become predominant, which may make diagnosis difficult by suggesting a chronic axonal neuropathy that may be assumed to be primary. Consideration of these points may help clinicians recognize more chronic dysimmune neuropathies, for which immunosuppressive therapy has been found to be effective.

[Chronic polyradiculoneuritis and its frontiers]. / Polyradiculonévrites chroniques et leurs frontières.

The Chronic Inflammatory Demyelinating Polyradiculoneuropathies (CIDP) constitute a syndrome whose incidence is difficult to evaluate, and is probably underestimated. In the course of this presentation, we deliberately restricted discussion to issues raised in recent years concerning the extent of this syndrome. We discuss diagnostic criteria, especially electrophysiological ones. As the criteria proposed by the ad hoc committee of the American Academy of Neurology in 1991 have been questioned due to lack of sensitivity, new ones have been proposed recently. We briefly discuss the different types of chronic dysimmune demyelinating neuropathy: not only the CIDP, but also the Lewis and Sumner syndrome or multifocal inflammatory demyelinating neuropathy and the multiple conduction block neuropathies. At last, we point out the consistent finding of axonal involvement in the course of a chronic demyelinating neuropathy; over time, it can become pre-dominant, which may make diagnosis difficult by suggesting a chronic axonal neuropathy that may be assumed to be primary. Consideration of these points may help clinicians recognize more chronic dysimmune neuropathies, for which immunosuppressive therapy has been found to be effective.

[4 cases of Guillain-Barré syndrome with axonal lesions]. / Quatre cas de syndrome de Guillain-Barré avec lésions axonales.

We report the neurological features observed in 4 patients who developed a clinically typical Guillain-Barré syndrome. Electrophysiological and histological data displayed an unusual number of axonal lesions, although these were always associated with demyelination. These cases must be distinguished from the rare cases of Guillain-Barré syndrome with pure axonal lesions. Three patients had a poor functional recovery. This confirms the more severe prognosis of Guillain-Barré syndrome with major axonal degenerative changes.

[Motor evoked potentials. Technic and results in the normal subject]. / Potentiels évoqués moteurs. Technique, résultats chez le sujet normal.

The transcranial stimulation of the motor cortex and spinal cord was introduced in clinical neurology by Merton and Morton (1980). This reproducible and non invasive technique gives the possibility to elicit unilaterally or bilaterally evoked motor potentials. It is possible to define a Total Conduction Time (TCT) from cortex to muscle and a Peripheral Conduction Time (PCT) from spinal cord to muscle. The central conduction time is given by the latency difference between TCT and PCT. This delay represents the duration of the descending corticospinal volley plus the delay necessary to depolarize spinal motor neurons. For central pathways supplying the upper limbs TCT is 4.3 milliseconds and for central pathways supplying the lower limbs TCT is 9.3 milliseconds. This technique of central motorpathway assessment can be used to define the magnitude of a central motor deficit in neurological diseases affecting the corticospinal tract, during surgical procedures involving the spinal cord and in comatose patients. The new magnetic stimulation is painless and will probably widen the utilization of this method.

[Epidemiology of amyotrophic lateral sclerosis in the Limousin area]. / Epidémiologie de la sclérose latérale amyotrophique en Limousin.

Several epidemiologic studies of amyotrophic lateral sclerosis have shown a uniform repartition over the world. We report the results of a retrospective study and the preliminary results of a prospective study carried out in the Limousin area. The mean incidence per/year is 0.97/100,000 in the retrospective study and 1.3/100,000 in the prospective study. Such data are similar to those previously reported. The two major findings are the high frequency of bulbar palsy and the high mean age of the patients. This can be associated with the high mean age of the population in the Limousin area as compared to other regions.

[Study of central motor pathways using cortical magnetic stimulation and spinal electrical stimulation: results in 20 normal subjects]. / Etude de la voie motrice centrale par stimulation magnétique corticale et électrique spinale: résultats chez 20 sujets normaux.

Evoked motor potentials can be elicited by magnetic cortical or electric spinal stimulations. The central conduction time (CCT) corresponds to the difference in latencies between the total conduction time (from cortex to muscle) and the peripheral conduction time (from spinal cord to muscle). CCT is the sum of the conduction time in the cortico-spinal fibers, of the spinal synaptic delay, and of the conduction time in the proximal part of the motor roots. CCT values (mean + standard deviation) were determined in 20 healthy subjects ranging from 21 to 56 years of age (mean 31.2). Results of magnetic cortical stimulation were compared to the results of electrical stimulation of the cortex. CCTs after magnetic cortical stimulation were longer than CCTs after electric cortical stimulation. This could be explained by the fact that electrical stimulation elicits a direct response in the cortico-spinal tract whereas magnetic cortical stimulation has indirect effects on the pyramidal cells of the motor cortex through excitatory interneurons. Compared with electrical stimulation, the magnetic stimulation has the great advantage of being painless and allows a safe evaluation of the central motor pathways in man.

[Early diagnosis of Guillain-Barré syndrome by electric stimulations of the nerve roots]. / Diagnostic précoce du syndrome de Guillain-Barré par stimulations électriques radicularies.

Ulnar nerve electrical stimulations from motor roots to wrist were used in the early Guillain-Barré syndrome (GBS), to improve the electrophysiological diagnosis yield. 22 patients with a GBS were investigated with this technique between 3 to 17 days after the onset. Conventional electrophysiological examination was sufficient to diagnose an Acute Inflammatory Demyelinating Polyneuropathy in 12 cases. In 10 other patients, standard examination remained negative or not conclusive, and vertebral electrical stimulations were decisive for the diagnosis, showing conduction bloks. This method could be routinely performed for an early diagnosis, in association with conventional motor conduction measurements. This study confirms the possibility of a pure proximal demyelinating impairment of the peripheral nervous system in the early GBS.

[Glycogenesis due to adult phosphorylase kinase deficiency]. / Glycogénose par déficit en phosphorylase kinase chez un adulte.

A 42-year-old man presented exercise-induced muscle pain without myogloburia since the age of 12 years. Histochemistry and electronmicroscopy of a muscle biopsy revealed subsarcolemmal and inter-myofibrillar accumulation of glycogen. Exercise on a bicycle ergometer produced a normal raise of lactate. Biochemical study showed a partial defect in phosphorylase activity.

[Circadian analysis of sleep, rectal temperature and immunological and endocrinological variables in sleeping sickness: preliminary study]. / Analyse circadienne du sommeil, de la température rectale et de variables immunologiques et endocrinologiques dans la maladie du sommeil: etude préliminaire.

A multidisciplinary study was conducted in 8 patients with neurological Human African Trypanosomiasis. The sleep-wake cycle followed an ultradian pattern which was more pronounced in patients with more severe symptoms. The EEG trace was consistently interrupted by numerous cyclic activation patterns with K complexes, rapid low amplitude elements and slow high voltage elements. Circadian rhythmicity was also disturbed in other physiological (rectal temperature), immunological (interleukins) or hormonal (cortisol, prolactin) variables, the disturbance being greater in severely hit patients.

[The distribution of sleep and wakefulness in human African trypanosomiasis]. / Distribution du sommeil et de la veille dans la trypanosomose humaine africaine.

Last century, patients with human African trypanosomiasis were described as sleepy by day and restless by night, and physicians referred to this condition as sleeping sickness. Such a description could have evoked a disturbance of circadian rhythms. However, it is only in 1989 that the first 24-hour recording was performed by our team in Niamey (Niger) in a patient with sleeping sickness. The patient was a Niger-born farm worker who had contracted the disease near Gagnoa (Côte d'Ivoire). Polysomnographic recordings (electroencephalogram, EEG, electrooculogram, electromyogram, electrocardiogram, buccal and nasal airflow, and chest respiratory movements) showed a disappearance of the circadian distribution of sleep and wakefulness, which tended to occur evenly throughout day and night, with a sleep-wake alternation of approximately 80 minutes. Two investigations were conducted thereafter. The first one was done at Daloa (Côte d'Ivoire) in 8 patients who were recorded during two 24-hour periods, with and without hourly blood samples; the second at Brazzaville (Congo) in 10 patients recorded for 24 hours before and after treatment with melarsoprol. All patients were at the stage of early meningoencephalitis. At Daloa, polysomnographic recordings were taken on two 8-channel EEG machines (Alvar Minihuit, and T3-ECEM), as well as on a portable Oxford Medilog 9000 system from the same electrodes. Sleep and wake structure was altered in the most severely sick patient, the EEG trace being loaded with slow waves. Stages 1 and 2, and stages 3 and 4 could not be distinguished from one another. In the other patients, all sleep stages were easily scored. No difference was seen between recordings, regarding blood collection.(ABSTRACT TRUNCATED AT 250 WORDS)