[Chorea-acanthocytosis without acanthocytes]. / Choréo-acanthocytose sans acanthocytes.

INTRODUCTION: Chorea-acanthocytosis (ChAc) is one of the neuroacanthocytosis syndromes which form a group of disorders characterized by the association of neurological abnormalities and spiculated red blood cells called acanthocytes. ChAc patients exhibit involuntary movements, psychiatric abnormalities and progressive cognitive deterioration. We report a case of ChAc in which blood smears failed to demonstrate acanthocytes. CASE REPORT: A 26-year-old man presented since two years with hyperkinetic movements. The family history was non contributive, parents were consanguineous. Neurological examination revealed choreatic hyperkinesia and dystonia, predominant in the orofacial region. Mild cognitive decline and behavior abnormalities were noted with repetitive activities. Brain MRI showed striatal atrophy. Molecular testing for Huntington's disease was negative. Routine biological screening was normal except for elevated CPK and LDH. Copper and ceruloplasmin blood levels were normal, as well as purine metabolism and lipoproteins. Further screening for metabolic diseases showed no significant abnormality. Expression of Kell antigens was normal. In several blood smears no acanthocytes were seen. Electromyographic studies showed slight neuropathic changes. Despite the absence of acanthocytes, chorein western blot was performed on blood samples which revealed an absent or markedly reduced level of chorein in erythrocyte membranes. A mutation of the ChAc gene was thus likely so the diagnosis of ChAc was retained. Genetic studies for VPS13A are pending. DISCUSSION: ChAc is an autosomal recessive disorder due to mutations of the VPS13A gene coding for chorein. Absence or late appearance of acanthocytes in ChAc has been described in a few case reports. In conclusion ChAc is a rare disorder in which the presence of acanthocytes is not mandatory. In case of doubt, chorein western blot can be useful.

[Late cerebellar ataxia associated with fragile X premutation]. / Ataxie cérébelleuse tardive due à la prémutation de l'X fragile.

INTRODUCTION: The fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder that affects carriers, principally males after 50 years of age, of premutation alleles of the fragile X mental retardation 1 (FMR1) gene. Clinical features of FXTAS are an intention tremor and/or a cerebellar ataxia, with or without parkinsonism, cognitive disorders, neuropathy and autonomic dysfunction. MRI shows symmetrical signal abnormalities in the middle cerebellar peduncles and deep cerebellar white matter, typically sparing the dentate nucleus, associated with generalized atrophy. We report a case of FXTAS with isolated cerebellar ataxia. CASE REPORT: We report the case of a 60-year-old right-handed man with an uneventful personal and familial history. Since 2002, he progressively developed gait ataxia associated with paresthesia in the lower limbs. The physical examination revealed static and kinetic cerebellar ataxia with dysarthria. Exhaustive screening tests (inflammatory, immunological, metabolic, infectious and neoplasic) and the cerebrospinal fluid analysis were normal. The brain MRI T2-weighted sequences showed diffuse increased signal in both cerebellar white matter and middle peduncles suggestive of FXTAS. Functional explorations (evoked somesthesic and visual potentials, electromyogram, and cerebral scintigraphy) confirmed the isolated cerebellar involvement. The FXTAS was suggested and the genotype was explored. Southern Blot revealed an expansion of trinucleotide CGG with 107 repetitions, confirming the diagnosis of FXTAS. DISCUSSION: In patients with a fragile X premutation, FMR1 protein levels are gradually reduced with increased repeat number, despite elevated FMR1 transcripts levels. Neuropathologic examination reveals eosinophilic intranuclear inclusions in neurons and astrocytes throughout the cortex, subcortical regions, and brain stem. The pathogenic hypothesis would be related to a gain of function with toxic effects of FMR1 messenger RNA on cellular metabolism. Cerebellar ataxia, which may be isolated or not, is the most frequent neurologic manifestation, like many studies showed. CONCLUSION: FXTAS should be suspected in patients with unexplained late-onset cerebellar ataxia. Typical presentation includes a male in his fifties with progressive ataxia and tremor. Brain MRI with symmetrical cerebellar abnormalities is very suggestive of this diagnosis. Genetic screening and advice for the patient and his family must be proposed in order to detect the fragile X syndrome.

Auto-immune cerebellar ataxia with anti-GAD antibodies accompanied by de novo late-onset type 1 diabetes mellitus.

UNLABELLED: Autoantibodies to glutamic acid decarboxylase (GAD-Ab) have been described in stiff-man syndrome, type 1 diabetes mellitus and in patients with auto-immune polyglandular failure. In addition, a few patients with progressive cerebellar ataxia show high titres of GAD-Ab, suggesting an auto-immune origin. AIM: This is a report of a patient presenting with cerebellar ataxia associated to late-onset type 1 diabetes and polyendocrine auto-immunity. CASE REPORT: A 47-year-old woman with a past medical history of vitiligo and Graves' disease presented with late-onset type 1 diabetes. For two years, she had complained of progressive gait instability and oscillopsia. Neurological examination revealed multidirectional, horizontal rotatory fixation and gaze nystagmus, gait ataxia and mild limb ataxia in the left upper arm. METHODS: Imaging studies, electrophysiological studies, routine biological and detailed immunological screening as well as a study of cerebrospinal fluid (CSF) were performed. RESULTS: Brain magnetic resonance imaging showed cerebellar atrophy. Routine biological screening was normal. Immunological screening showed positivity for numerous antibodies (Ab), including GAD-Ab, thyroid peroxidase-Ab, thyroglobulin-Ab, 21-hydroxylase (adrenal)-Ab, gastric parietal cell-Ab and GM1 ganglioside IgG-Ab. CSF was normal, with no oligoclonal bands detected. GAD-Ab were positive in CSF, suggesting an auto-immune origin of the cerebellar ataxia. Treatment with intravenous immunoglobulin led to a slight improvement in nystagmus and gait instability. CONCLUSION: Auto-immune cerebellar ataxia related to GAD-Ab is a rare condition that typically affects women with late-onset type 1 diabetes or other auto-immune disorders, including auto-immune polyendocrinopathy. Immunomodulatory treatment may be effective.

Impact of disease-modifying treatments in North African migrants with multiple sclerosis in France.

BACKGROUND: Multiple Sclerosis in North African migrants (MS-NA) is more aggressive with mostly primary progressive forms and cerebellar symptoms. Despite an earlier onset in NA patients, the disease progresses more rapidly, with a higher proportion showing incomplete recovery from the first relapse, a shorter time between the first two relapses, a higher number of relapses in the first 5 years, and a shorter time to reach an EDSS of 4.0 and 6.0. We collected data and studied the impact of disease-modifying therapies (DMT) in NA patients with MS, among the 4144 MS patients treated in our MS clinics. METHODS: We performed a descriptive population-based study of MS-NA patients. Data were crossed with expected age- and gender-matched characteristics available in our EDMUS databases for the period 1995-2007. RESULTS: A total of 133 patients, representing 66% of the MS-NA patients included in the database were identified: mean age at the first documented symptom: 29.7 years; mean time from diagnosis to the beginning of DMT: 1.2 years. 40% of MS-NA patients had an EDSS >3 at the beginning of treatment (vs. 25%; P=0.002). A majority of patients were treated initially with immunomodulatory drugs (MS-NA: 48% vs. CT: 51%, P=0.8). NA patients were treated earlier after diagnosis (1.3 years vs. 4.5 years, P=0.003), with the frequent use of immunosuppressive drugs: for remitting forms, mitoxantrone (18.5% vs. 7.8%, P=0.0001) and for progressive forms, cyclophosphamide (38% vs. 28%, P=0.003). CONCLUSIONS: Considering EDSS follow-up during DMT, MS-NA patients appear as responsive as other MS patients to treatment, despite the earlier treatment prescription and the more frequent use of immunosuppressors.

[Dopamine dysregulation syndrome in Parkinson's disease]. / Syndrome de dysrégulation dopaminergique dans la maladie de Parkinson.

Dopamine replacement therapy in Parkinson's disease ameliorates motor symptoms. However, it has recently been recognized that a small subgroup of patients suffer motor and behavioral disturbances attributable to taking quantities of medication well beyond the dose required to treat their motor disabilities. Dopamine dysregulation syndrome can be regarded as a pattern of compulsive medication use leading to disabling motor and behavioral features. The major theories of psychostimulant addiction may help explain some of the phenomena seen in the dopamine dysregulation syndrome. In contrast to the predictable pattern of severe degeneration of ventrolateral nigral dopaminergic cells, there is a smaller and more variable loss of dopamine neurons within the ventral tegmental areas. Sensitization of ventral striatal networks to antiparkinsonian therapy and appetitive behaviors may be analogous to the neuroplastic changes in the dorsal striatum thought to contribute to the motor complications of treatment such as dyskinesias. This syndrome greatly affects patients, their families and society. Treatment is difficult; deep brain stimulation of the subthalamic nucleus may therefore prove useful in some cases.

[Subthalamic nucleus stimulation using a Fisher ZD stereotactic frame, MR-CT fusion guidance and peroperative orthogonal radiographs, in Parkinson disease]. / Evaluation de la stimulation du noyau sous-thalamique utilisant un cadre de Fischer adapté, un guidage par fusion IRM-scanner et un contrôle radiographique stéréotaxique peropératoire, dans la maladie de Parkinson.

BACKGROUND: We present the method and results of an original technique to implant electrodes in the subthalamic nucleus (STN) to treat Parkinson's disease, based on adaptations of the Fisher ZD stereotactic frame. METHODS: Targets coordinates were calculated after fusion of stereotactic CT-scan and MRI images. STN was localized by its theoretical coordinates according to AC-PC and by its direct visualization on T2 images. Electrodes were implanted after local anesthesia, using peroperative multicanal microrecordings and test stimulation. Electrodes location was checked by peroperative perpendicular radiographs. To avoid projection of the frame arm on the area of interest on anteroposterior and lateral radiographs, the arm was fixed at 45 degrees from the usual 90 degrees position. This original fixation needed a trigonometric transformation of the X and Y stereotactic coordinates. Radiopaque markers, fixed on the frame, were identified on the radiographs, allowing the calculation of the stereotactic coordinates of the electrode tip, which were then entered in the stereotactic MRI, to check its location from the defined target. RESULTS: No problem due to adaptations of the frame occurred in the 60 patients. In all cases, peroperative radiographs allowed to confirm the correct location of electrodes. Six months after surgery, UPDRS III score without medication was decreased by 52% with stimulation "on". UPDRS IV items 32, 33 and 39 scores were decreased by 75,7, 79,5 and 72%. Daily dopa-equivalent dose was decreased by 71%. One asymptomatic thalamic hematoma and two wound infections occurred. CONCLUSION: This method was efficient and safe to implant deep electrodes.