[Cerebrotendinous xanthomatosis: a multicentric retrospective study of 15 adults, clinical and paraclinical typical and atypical aspects]. / Étude rétrospective multicentrique de 15 cas adultes de xanthomatose cérébrotendineuse : aspects cliniques et paracliniques typiques et atypiques.

INTRODUCTION: Cerebrotendinous xanthomatosis, a metabolic leukodystrophy with an autosomal recessive inheritance, is secondary to deficiency of sterol 27-hydroxylase, an enzyme involved in cholesterol catabolism. Classical symptoms include clinical or infraclinical xanthomas affecting the skin and tendons, early cataracts, neurological signs and diarrhea. Brain imaging reveals involvement of the dentate nuclei and periventricular white matter hyperintensities. The diagnosis is based on an increased cholestanol level in serum, confirmed by the presence of a mutation in the CYP27A1 gene. Treatment is based on chenodeoxycholic acid. METHOD: We report a retrospective multicentric study of 15 cases of cerebrotendinous xanthomatosis diagnosed in French adults. Clinical, molecular and MRI findings were recorded in all patients. RESULTS: The average age at diagnosis was 39years (range 27-65). Disease onset occurred in childhood in 73% of patients and in adulthood in 27%. All patients with a pediatric onset were diagnosed during adulthood (age range 28-65years). Clinical symptoms variably associated cerebellar syndrome, pyramidal syndrome, cognitive decline, epilepsy, neuropathy (sought in 10 of our patients, present in forms in 8), psychiatric disorders, cataract and xanthomas. One patient had an atypical presentation: monoparesis associated with xanthomas. Brain MRI was abnormal in all: findings consisted in T2-weighted hyperintensity of the dentate nuclei (47%), periventricular leuoencephalopathy (73%) which preferentially involved the posterior cerebral part (60%), leucoencephalopathy with a vascular pattern (7%), hyperintensity of the cortico-spinal tracts (53%), globi pallidi, corpus callosum and cerebral atrophy (33%). Serum cholestanol was elevated in 93% of patients. The most frequent mutation was 1183C>T (n=5/15). Under treatment with chenodeoxycholic acid, eight patients improved initially, followed by stabilization in five of them, and worsening in the others. Four patients died. CONCLUSION: Patients with the xanthoma-neurological disorder association should be tested for cerebrotendinous xanthomatosis. The disease often begins in childhood with a diagnostic delay but also in adulthood. Involvement of the dentate nuclei is specific but not sensitive and the supratentorial leucoencephalopathy is not specific but with an antero-posterior gradient. A vascular distribution and involvement of the corpus callosum are possible. Serum cholestanol assay is very reliable: an elevated level provides the diagnosis, which must nevertheless be confirmed by molecular biology.

Validation of the French version of the MSA health-related Quality of Life scale (MSA-QoL).

INTRODUCTION: Multiple system atrophy (MSA) has considerable impact on health-related quality of life. The MSA health-related Quality of Life scale (MSA-QoL) is a patient-reported questionnaire, which has been recently designed to evaluate the quality of life in MSA. The objective of the present study was to validate the French version of the MSA-QoL questionnaire. METHODS: One hundred and thirty-six consecutive MSA patients were included in the study. Four patients with more than 10% missing responses were excluded from the final analysis. Data quality, scaling assumptions, acceptability, reliability and validity were assessed similar to the original validation of the English version. RESULTS: Missing responses were low, item and subscale scores were evenly distributed and floor and ceiling effects were negligible. Item-total correlations were higher than the recommended greater than 0.30 and internal consistency was high for all subscales. Test-retest reliability was good for all subscales. Validity was supported by moderate interscale correlations between the subscales and the predicted correlations with other scales assessing motor disability, activities of daily living, quality of life and mood. DISCUSSION: The French version of the MSA-QoL displays robust psychometric properties similar to the English version. CONCLUSION: The French version of MSA-QoL seems suitable for assessing quality of life in French speaking MSA patients.

[Guillain-Barré syndrome in a child with normal tendon reflexes]. / Un cas pédiatrique de syndrome de Guillain-Barré à réflexes conservés.

We describe the case of a 10-year-old child with the acute motor axonal neuropathy (AMAN) form of Guillain-Barré syndrome (GBS) with preserved tendon reflexes, 6 days after a bout of gastroenteritis. The child quickly showed weakness of the distal muscles of his four limbs, with preserved tendon reflexes and a raised CSF protein concentration with no cells. Nerve conduction studies showing motor axonal degeneration confirmed the diagnosis of GBS in spite of preserved tendon reflexes. The serum was positive for IgG antibodies to gangliosides GM1 and GD1b. The child received intravenous immunoglobulins, which resulted in a favorable progression. This case proves that GBS with normal tendon reflexes exists. The other cases of SGB with preserved tendon reflexes already described in the literature were the AMANs form with antibodies to gangliosides in the serum and only adults were affected.

Both L-DOPA and HFS-STN restore the enhanced group II spinal reflex excitation to a normal level in patients with Parkinson's disease.

OBJECTIVE: To investigate the contribution of group II spinal pathways in Parkinsonian upper limb rigidity and the modulation of spinal excitability of group I and group II pathways by L-DOPA and subthalamic nucleus-high-frequency stimulation (STN-HFS). METHODS: The effect of ulnar nerve electrical stimulation on Flexor Carpi Radialis Electromyogram (FCR EMG) was investigated in two groups of patients: patients receiving medication (MED group) and chronically surgically implanted patients (DBS group). Results were compared in patients ON and OFF treatment, and between patients and control subjects. RESULTS: The resulting long-lasting facilitation in FCR EMG had similar characteristics in all groups, and surface area was assessed in analysis windows corresponding to the parts supposed to be mediated by non-monosynaptic spinal pathways to FCR motoneurones, fed by hand muscle group I and group II afferents (Lourenço et al., 2006). In both the MED and DBS groups, the group I excitation was not altered but the group II excitation was particularly enhanced when OFF treatment, compared to controls, and both L-DOPA and STN-HFS restored the group II spinal excitation to normal level. CONCLUSION: Both L-DOPA and STN-HFS influence the metabolism of monoamines in the midbrain, and restore the descending neuromodulation on group II spinal reflex. SIGNIFICANCE: These results further support a group II contribution to the enhanced long latency response (LLR) to muscle stretch observed in wrist muscles of rigid Parkinson's disease (PD) patients.

Levodopa raises objective pain threshold in Parkinson's disease: a RIII reflex study.

BACKGROUND: Patients suffering from Parkinson's disease (PD) describe painful sensations that could be related to neuropathic pain. Experimental data have indicated the involvement of basal ganglia and dopaminergic pathways in central nociceptive processing. AIM: The objective of this study was to assess and compare the effect of levodopa on the objective pain threshold in patients with PD and healthy subjects. METHODS: The objective pain threshold was assessed by the nociceptive flexion reflex (RIII) in 13 PD patients and 10 healthy subjects. Patients and healthy subjects were evaluated under two randomised conditions: with levodopa (ON) and without (OFF). RESULTS: Levodopa significantly increased the RIII threshold of PD patients (6.9 (1.2) mA in the OFF condition vs 8 (1.1) mA in the ON position; p = 0.02). RIII threshold was significantly lower in PD patients than in healthy subjects in the OFF condition (6.9 (1.2) mA vs 9.7 (3.4) mA; p = 0.02). RIII threshold did not change after levodopa administration in healthy subjects. CONCLUSION: These results provide evidence of a dopaminergic modulation of objective pain threshold in PD patients. In addition, the decrease in RIII threshold in PD patients, in the OFF condition, compared with controls, confirms the existence of an objective pain perception disturbance in PD.

Cortical tremor (FCMTE: familial cortical myoclonic tremor with epilepsy).

For 15 years, 50 Japanese and European families with cortical myoclonic tremor and epilepsy were reported in the literature under various names. More recently, the acronym familial cortical myoclonic tremor with epilepsy (FCMTE) has been proposed for this new clinical entity based on both clinical and electrophysiological criteria: irregular postural myoclonic tremor of the distal limbs, familial history of epilepsy, autosomal dominant inheritance, and a rather benign outcome. The diagnosis is confirmed by electrophysiological features favoring cortical reflex myoclonus (enhanced C reflex at rest, giant somatosensory evoked potentials (SEPs), premyoclonus cortical spikes detected by the jerk-locked back-averaging method), and a good response to antiepileptic drugs. The genetic analysis of these families shows heterogeneity with a linkage to chromosome 8q24 for Japanese families, a linkage to chromosome 2p for Italian families, the exclusion of 8q24 locus for a Spanish family, and the exclusion of both loci for a Dutch family. The similarities of this syndrome with the group of myoclonic epilepsy suggest an abnormality of a gene encoding ion channels.

Chronic administration of selective serotonin reuptake inhibitor (SSRI) paroxetine modulates human motor cortex excitability in healthy subjects.

The aim of the study was to investigate the effect of chronic administration of paroxetine (selective serotonin reuptake inhibitor: SSRI) on motor cortex excitability in healthy subjects by means of transcranial magnetic stimulation (TMS), functional magnetic resonance imaging (fMRI) and behavioral motor tests. In a randomized, double-blind, crossover study, twenty-one right-handed subjects received 20 mg daily of either paroxetine or a placebo over a period of 30 days separated by a period of 3 months wash-out. The TMS study is presented here correlated with some results of the motor behavior study (finger tapping test) and the fMRI study (primary sensorimotor cortex (S1M1) volume of activation). TMS was used to test motor threshold (MT), motor evoked potential recruitment curve (RC), cortical silent period (CSP) and paired-pulse intracortical inhibition and facilitation (ICI, ICF). Chronic administration of paroxetine did not modulate ICI or CSP but induced a significant enhancement of mean ICF (ANOVA P=0.04), which significantly correlated with increase of speed in a finger tapping test (P=0.02). This suggests a modulation of cortical interneuronal excitatory pathways without changes in the excitability of cortical inhibitory GABAergic interneurons. A decrease of RC (ANOVA P=0.05) was also observed after 30 days intake of paroxetine in comparison with placebo and was associated with changes of fMRI activation intensity (left S1M1 hypoactivation, ), without changes of S1M1 activation volume. Finally, the different modulation of RC and ICF after chronic administration of paroxetine compared to single dose (opposite effects) emphasizes the different pharmacological action of the drug at cortical level depending on its acute or long-term administration.