Comorbidities and factors associated with central nervous system infections and death in non-perinatal listeriosis: a clinical case series.

BACKGROUND: Listeriosis is a rare disease caused by the bacterium Listeria monocytogenes and mainly affects at risk people. Listeriosis can lead to sepsis, central nervous system (CNS) infections and death. The objectives of this study were to describe and quantify comorbidities and neurological sequelae underlying non-perinatal listeriosis cases and to describe the factors associated with death and CNS infections in non-perinatal listeriosis. METHODS: We retrospectively collected clinical data through computerized, paper or microfilmed medical records in two Belgian university hospitals. Logistic regression models and likelihood ratio tests allowed identifying factors associated with death and CNS infections. RESULTS: Sixty-four cases of non-perinatal listeriosis were included in the clinical case series and 84 % were affected by at least one comorbid condition. The main comorbidities were cancer, renal and severe cardio-vascular diseases. Twenty-nine patients (45 %) suffered from a CNS infection and 14 patients (22 %) died during hospitalization, among whom six (43 %) had a CNS involvement. Among surviving patients, eleven suffered from neurological sequelae (22 %) at hospital discharge; all had CNS infection. Five of these patients (45 %) still suffered of their neurological sequelae after a median follow-up of one year (range: 0.08-19). The factor associated with death during the hospitalization was the presence of a severe cardiovascular disease (OR = 4.72, p = 0.015). Two factors inversely related with CNS infections were antibiotic monotherapy (OR = 0.28, p = 0.04) and the presence of renal disease (OR = 0.18, p = 0.02). CONCLUSIONS: In a public health context these results could be a starting point for future burden of listeriosis studies taking into account comorbidity.

[Management of Parkinson's disease in 2009]. / Traitement de la maladie de Parkinson en 2009.

The cause of Parkinson's disease remains unknown and no cure or prevention exists so far. Levodopa remains by far the most potent symptomatic therapy, but induces side-effects such as motor fluctuations and abnormal movements, which can somewhat be counterbalanced by optimizing levodopa plasma levels or acting at receptors level with long half-life dopamine agonists. In severe cases, functional surgery with deep brain stimulation can be offered. Some non-dopaminergic symptoms like dementia, freezing, postural instability or dysautonomia do not respond to dopaminergic drugs and need special care.

[Rhabdomyolysis and hypothyroidism]. / Le cas clinique du mois. Rhabdomyolyse et hypothyroïdie.

We describe the case of a 29 year old patient who presented severe myalgias and asthenia for 3 months. First biological assessment revealed muscular lysis and raised transaminases. The following complementary screening showed major hypothyroidism with the presence of anti-microsomes antibodies, a carpian canal syndrome and a left ventricular systolic dysfunction. A diagnosis of hypothyroidic rhabdomyolysis consecutive to a Hashimoto disease was then mash. Patient was treated by hormonal thyroid substitution with a progressive improvement of muscular symptoms to complete recovery, and a concomitant normalization of cardiac and thyroid functions.

General principles for clinical use of repetitive transcranial magnetic stimulation (rTMS).

Repetitive transcranial magnetic stimulation (rTMS), a non-invasive technique allowing stimulating neurons in the cerebral cortex, is able to modify durably local as well as distant neuronal activity. Results obtained by stimulation of the primary motor cortex and measurements of induced muscle responses suggest that effects on cortical excitability depend on stimulation frequency and intensity, as well as of pulse-train duration. Such data, as well as results of animal studies have brought a physiological basis for the use of rTMS for treatment of various neurological and psychiatric disorders, and particularly depression. Nevertheless, as long as large randomized studies have not been conducted, rTMS should not replace other existing and validated therapies.

Induction of long-lasting changes of visual cortex excitability by five daily sessions of repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers and migraine patients.

We have shown that in healthy volunteers (HV) one session of 1 Hz repetitive transcranial magnetic stimulation (rTMS) over the visual cortex induces dishabituation of visual evoked potentials (VEPs) on average for 30 min, while in migraineurs one session of 10 Hz rTMS replaces the abnormal VEP potentiation by a normal habituation for 9 min. In the present study, we investigated whether repeated rTMS sessions (1 Hz in eight HV; 10 Hz in eight migraineurs) on 5 consecutive days can modify VEPs for longer periods. In all eight HV, the 1 Hz rTMS-induced dishabituation increased in duration over consecutive sessions and persisted between several hours (n=4) and several weeks (n=4) after the fifth session. In six out eight migraineurs, the normalization of VEP habituation by 10 Hz rTMS lasted longer after each daily stimulation but did not exceed several hours after the last session, except in two patients, where it persisted for 2 days and 1 week. Daily rTMS can thus induce long-lasting changes in cortical excitability and VEP habituation pattern. Whether this effect may be useful in preventative migraine therapy remains to be determined.

[Clinical applications of repetitive transcranial magnetic stimulation]. / Applications cliniques de la stimulation magnétique transcrânienne répétitive.

Transcranial magnetic stimulation (TMS), when delivered in trains of pulses is able to induce long-lasting changes of excitability of neuronal networks, not only in the vicinity of the stimulating coil, but also at distant sites. Results of stimulation experiments over the motor cortex indicate that the effects (excitatory or inhibitory) depend on the frequency of stimulation. These data have prompted researchers to use repetitive transcranial magnetic stimulation (rTMS) as a therapeutic tool in various brain disorders, most notably depression. However, as long as large randomized trials have not been conducted, rTMS cannot be recommended as an alternative to validated conventional therapies of such disorders.

Effects of repetitive transcranial magnetic stimulation on visual evoked potentials in migraine.

Between attacks, migraine patients are characterized by potentiation instead of habituation of stimulation-evoked cortical responses. It is debated whether this is due to increased or decreased cortical excitability. We have studied the changes in visual cortex excitability by recording pattern-reversal visual evoked potentials (PR-VEP) after low- and high-frequency repetitive transcranial magnetic stimulation (rTMS), known respectively for their inhibitory and excitatory effect on the cortex. In 30 patients (20 migraine without, 10 with aura) and 24 healthy volunteers, rTMS of the occipital cortex was performed with a focal figure-of-eight magnetic coil (Magstim). Nine hundred pulses were delivered randomly at 1 or 10 Hz in two separate sessions. Stimulus intensity was set to the phosphene threshold or to 110% of the motor threshold if no phosphenes were elicited. Before and after rTMS, PR-VEP were averaged sequentially in six blocks of 100zztieresponses during uninterrupted 3.1 Hz stimulation. In healthy volunteers, PR-VEP amplitude was significantly decreased in the first block after 1 Hz rTMS and the habituation normally found in successive blocks after sustained stimulation was significantly attenuated. In migraine patients, 10 Hz rTMS was followed by a significant increase of first block PR-VEP amplitude and by a reversal to normal habituation of the potentiation (or dishabituation) characteristic of the disorder. This effect was similar in both forms of migraine and lasted for at least 9 min. There were no significant changes of PR-VEP amplitudes after 1 Hz rTMS in migraineurs and after 10 Hz rTMS in healthy volunteers, nor after sham stimulation. The recovery of a normal PR-VEP habituation pattern after high-frequency rTMS is probably due to activation of the visual cortex and the dishabituation in healthy volunteers to cortical inhibition. We conclude, therefore, that the deficient interictal PR-VEP habituation in migraine is due to a reduced, and not to an increased, pre-activation excitability level of the visual cortex.

Motor and phosphene thresholds to transcranial magnetic stimuli: a reproducibility study.

OBJECTIVES: As repetitive transcranial magnetic stimulation (rTMS) is often applied on different days, it is of interest to know whether motor (MT) and phosphene (PT) thresholds are reproducible across time and whether the intensity determined on the first day can be used in subsequent sessions. METHODS: We studied MT and PT over 5 separate recordings in 10 healthy volunteers using a focal coil and a Magstim(Rapid stimulator. After the initial recording (session 1), the others (2 to 5) were performed respectively after 1 day, 7 days, 1 month and 4 months. RESULTS: Mean MT at rest were 65.30 +/- 5.54%, 65.7 +/- 7.18%, 60.4 +/- 4.27%, 61.8 +/- 4.34%, and 63 +/- 9.1% at sessions 1 to 5. Mean PT were 71.43 +/- 6.68%, 66.29 +/- 10.67%, 60.71 +/- 8.64%, 60.57 +/- 8.08%, and 68.71 +/- 15.48% at sessions 1 to 5. MT and PT were reproducible (ANOVA analysis), however, as shown by coefficients of variation, variability between the first 3 sessions exceeded 10% for MT in 3 subjects and in 4 subjects for PT. CONCLUSIONS: It seems preferable to determine thresholds and adapt output intensity of the stimulator at each rTMS session.

Reduced excitability of the motor cortex in untreated patients with de novo idiopathic "grand mal" seizures.

OBJECTIVES: Transcranial magnetic stimulation (TMS) was used to investigate motor cortex excitability, intracortical excitatory, and inhibitory pathways in 18 patients having experienced a first "grand mal" seizure within 48 hours of the electrophysiological test. All had normal brain MRI, and were free of any treatment, drug, or alcohol misuse. Results were compared with those of 35 age matched normal volunteers. METHODS: The following parameters of responses to TMS were measured: motor thresholds at rest and with voluntary contraction, amplitudes of responses, cortical silent periods, and responses to paired pulse stimulation with interstimulus intervals of 1 to 20 ms. RESULTS: In patients, there were significantly increased motor thresholds with normal amplitudes of motor evoked potentials (MEPs), suggesting decreased cortical excitability. Cortical silent periods were not significantly different from those of normal subjects. Paired TMS with short interstimulus intervals (1-5 ms) induced normal inhibition of test MEPs, suggesting preserved function of GABAergic intracortical inhibitory interneurons. On the contrary, the subsequent period of MEP facilitation found in normal subjects (ISIs of 6-20 ms) was markedly reduced in patients. This suggests the existence of abnormally prolonged intracortical inhibition or deficient intracortical excitation. In nine patients retested 2 to 4 weeks after the initial seizure, these abnormalities persisted, although to a lesser extent. CONCLUSION: The present findings together with abnormally high motor thresholds could represent protective mechanisms against the spread or recurrence of seizures.

Ipsilateral motor responses to focal transcranial magnetic stimulation in healthy subjects and acute-stroke patients.

BACKGROUND AND PURPOSE: Prevalence and characteristics of ipsilateral upper limb motor-evoked potentials (MEPs) elicited by focal transcranial magnetic stimulation (TMS) were compared in healthy subjects and patients with acute stroke. METHODS: Sixteen healthy subjects and 25 patients with acute stroke underwent focal TMS at maximum stimulator output over motor and premotor cortices. If present, MEPs evoked in muscles ipsilateral to TMS were analyzed for latency, amplitude, shape, and center of gravity (ie, preferential coil location to elicit them). In stroke patients, possible relationships between early ipsilateral responses and functional outcome at 6 months were sought. RESULTS: With relaxed or slightly contracting target muscle, maximal TMS over the motor cortex failed to elicit ipsilateral MEPs in the first dorsal interosseous (FDI) or biceps of any of 16 normal subjects. In 5 of 8 healthy subjects tested, ipsilateral MEPs with latencies longer than contralateral MEPs were evoked in FDI muscle (in biceps, 6 of 8 subjects) during strong (>50% maximum) contraction of the target muscle. In 15 of 25 stroke patients, ipsilateral MEPs in the unaffected relaxed FDI (in biceps, 6 of 25 stroke patients) were evoked by stimulation of premotor areas of the affected hemisphere. Their latencies were shorter than those that MEPs evoked in the same muscle by stimulation of the motor cortex of the contralateral unaffected hemisphere. Such responses were never obtained in normal subjects and were mostly observed in patients with subcortical infarcts. Patients harboring these responses had slightly better bimanual dexterity after 6 months. CONCLUSIONS: Ipsilateral MEPs obtained in healthy individuals and stroke patients have different characteristics and probably different origins. In the former, they are probably conveyed via corticoreticulospinal or corticopropriospinal pathways, whereas in the latter, early ipsilateral MEPs could originate in hyperexcitable premotor areas.

Neuromuscular transmission in migraine: a single-fiber EMG study in clinical subgroups.

OBJECTIVE: To search for impairment of neuromuscular transmission by single-fiber electromyography (SFEMG) in patients with common forms of migraine. BACKGROUND: P/Q Ca(2+) channels are genetically abnormal in most cases of familial hemiplegic migraine (International Headache Society [IHS] code 1.2.3) and may be involved in other types of migraine. Besides in the brain, these channels are found in motor nerve endings, where they control stimulation-induced acetylcholine release. If they are functionally abnormal, the neuromuscular transmission might be impaired. METHODS: Sixty-two migraineurs (18 without aura, IHS code 1.1; 19 with typical aura, IHS code 1.2.1; 10 with prolonged aura, IHS code 1.2.2; 15 with and without aura) and 16 healthy control subjects underwent stimulation SFEMG. Results were expressed as the mean value of consecutive differences (MCD) and percentage of single-fiber abnormalities (abnormal jitter or impulse blocking). RESULTS: Average MCD was comparable in control subjects and migraineurs (17.1 +/- 2.6 versus 17.5 +/- 4.7 microsec). By contrast, single-fiber abnormalities were found in 17 patients but in none of the control subjects (p = 0.036). Most of these patients had unilateral sensorimotor symptoms and/or aphasia and/or loss of balance during the aura. SFEMG abnormalities were significantly correlated with the occurrence of these clinical features and with a diagnosis of migraine with prolonged aura. CONCLUSIONS: Stimulation SFEMG shows mild abnormalities of neuromuscular transmission in a subgroup of migraineurs with aura, characterized by clinical features frequently found in human P/Q Ca(2+) channelopathies. These abnormalities might thus be due to genetically modified P/Q Ca(2+) channels.

Absence of response to early transcranial magnetic stimulation in ischemic stroke patients: prognostic value for hand motor recovery.

BACKGROUND AND PURPOSE: Transcranial magnetic stimulation (TMS) has been proposed as a prognostic tool in stroke patients. Most of the previous studies agree in considering the presence of motor-evoked potentials (MEPs) in the first days after a stroke as an indicator of good outcome. In the present study, we have assessed the prognostic value of the absence of response to early TMS on hand motor recovery in stroke patients with complete hand palsy at onset due to ischemia in the area of the middle cerebral artery. METHODS: Fifteen patients submitted to TMS within 48 hours of stroke onset (defined as day 1) and again after 1 year. They were also evaluated clinically on day 1 by a scale derived from the Medical Research Council (MRC) and by the National Institutes of Health (NIH) stroke scale; they were reevaluated by the same scales and by Barthel Index on day 365. RESULTS: On day 1, all the patients had complete hand palsy and no response to TMS; their NIH scores showed great variability. After 1 year, 6 of 15 patients regained small and prolonged MEPs, together with a very poor and not functionally useful motor recovery. NIH scores were significantly improved. Barthel Index scores showed large interindividual differences and were not correlated with MRC scores. CONCLUSIONS: We conclude that in patients with complete hand palsy, the absence of response to TMS in the first hours is predictive of absent or very poor, not useful, hand motor recovery.

Interictal cortical excitability in migraine: a study using transcranial magnetic stimulation of motor and visual cortices.

We performed transcranial magnetic stimulations of the motor and visual cortices in healthy controls (n = 27) and in patients suffering from migraine without (n = 33) or with (n = 25) aura between attacks. By using a 13-cm circular coil placed over the vertex and recordings of the first dorsal interosseus muscle, we measured thresholds (at rest and during contraction), amplitudes of motor evoked potentials and cortical silent periods. Paired stimulations with short (1-20 msec) interstimulus intervals were performed to assess intracortical inhibition. The visual cortex was stimulated with the same coil placed over the occipital scalp (7 cm above the inion) and the prevalence and threshold of phosphene production was determined. In patients with migraine with aura, motor thresholds during isometric contraction were significantly higher, whereas the prevalence of stimulation-induced phosphene production was lower compared with healthy controls. These changes were not correlated with attack frequency or disease duration. No differences were found between subject groups in thresholds at rest, motor evoked potential amplitudes, cortical silent periods, or response curves after paired stimuli. These results are in favor of cortical hypoexcitability rather than hyperexcitability in patients with migraine with aura between attacks.

[Applications of cortical magnetic stimulation]. / Applications de la stimulation magnétique corticale.

In the last decade, a new electrophysiological tool has become available since the development of painless magnetic stimulators able to activate the primary motor cortex and the motor roots in conscious man. Therefore, it became possible to measure the conduction time within fast-conducting central motor pathways by substracting from the total latency of muscle responses elicited by cortical stimuli the conduction time in peripheral nerves. This technique proved sensitive enough to illustrate early abnormalities of central motor conduction in various neurological diseases such as multiple sclerosis, amyotrophic lateral sclerosis, cervical spondylotic myelopathy, degenerative ataxias or hereditary spastic paraplegias. When recorded early after stroke, motor evoked potentials are also a valuable tool to predict functional outcome. They can also illustrate subtle pathophysiological disturbances in diseases where there is no direct involvement of central motor pathways such as Parkinson's disease, dystonia or epilepsy. Magnetic cortical stimulation also offers unique opportunities to explore intracerebral inhibitory and excitatory circuits and mechanisms of brain plasticity. The recent development of rapid rate stimulators also enables functional studies of non-motor cerebral regions such as visual or frontal cortices. Moreover, rapid rate stimulation seems useful in the treatment of drug-resistant depression but the safety of this procedure, particularly with regard to the production of seizures or kindling, remains to be fully documented.