Chronic ataxic neuropathies associated with anti-GD1b IgM antibodies: response to IVIg therapy.

OBJECTIVE: To determine the responses to treatment of patients with chronic sensory ataxic neuropathy associated with anti-GD1b IgM antibodies. METHODS: Patients with chronic sensory ataxic neuropathy associated with anti-GD1b IgM antibodies followed in our department for at least 12 months between 2001 and 2008 were identified and studied retrospectively. Patients were tested at regular intervals using the INCAT disability score. Patients whose disability scores improved by at least one point were taken to have responded to the treatment. Intravenous immunoglobulin (IVIg; 2 g/kg) was administered for 3 to 5 days once every 6 weeks or corticosteroids at an initial daily dose of 1 mg/kg. RESULTS: 13 patients treated during the 8-year period of interest were included in this study. Seven of 13 patients displayed IgM anti-GQ1b, GT1b and GD3 antibodies suggesting reactivity against disialosyl epitope. IgM gammopathy was detected in four of six of serum with anti-disialosyl antibodies and two of the seven other sera. Nine of the 13 patients improved in response to IVIg. Oral corticosteroid treatment was attempted on four patients prior to IVIg treatment, and partial recovery occurred in one, who became steroid-dependent and showed little benefit in the long term. CONCLUSIONS: Screening for anti-GD1b IgM antibodies should be carried out on all patients with chronic ataxic sensory neuropathies. In 69% of the cases studied, the patients' condition improved in response to IVIg. This study shows the short-term efficiency of this treatment. Sustained responses were obtained in the long term by continuing the infusions.

[Seronegative myasthenia and myasthenia gravis with anti-MuSK antibody: a retrospective study of 20 cases]. / Myasthénie séronégative et myasthénie avec anticorps anti-MuSK : une série rétrospective de 20 cas.

INTRODUCTION: Despite the fact that anti-muscle specific tyrosine kinase (MuSK) antibodies have been discovered for seven years, only a few studies have, until now, focused on myasthenia without acetylcholine-receptors antibodies (ab) (formerly known as "seronegative myasthenia"), and among them, anti-MuSK-antibody-positive and -negative patients. METHOD: We retrospectively studied 20 patients with "seronegative" myasthenia gravis, eight of them being anti-MuSK-ab positive, the remaining twelve being negative. We searched for clinical, neurophysiological, and therapeutic differences between the two groups (anti-MuSK-ab positive: anti-MuSK+ versus anti-MuSK-ab negative: anti-MuSK-). RESULTS: Anti-MuSK+ patients had more predominantly bulbar involvement and had more severe disease (these patients required referral to intensive care more frequently). There was no difference between the two groups concerning treatment efficiency and tolerance. Most of our patients were treated with acetylcholinesterase-inhibitors, and immunomodulatory or immunosuppressive drugs that could indirectly reflect greater severity. However, there was no difference in treatments for anti-MuSK+ versus anti-MuSK- patients. CONCLUSION: These results both confirm and complete the preexisting data on RACh-negative myasthenia, and especially on myasthenia associated with MuSK antibodies.

Dehydroepiandrosterone for myotonic dystrophy type 1.

BACKGROUND: Myotonic dystrophy type 1 may be associated with low circulating dehydroepiandrosterone (DHEA) levels. This study was aimed at investigating the efficacy and safety of DHEA in myotonic dystrophy type 1 patients. METHODS: This was a prospective, multicenter, randomized, double-blind, placebo-controlled trial conducted from February 2005 to January 2006 at 10 university-affiliated neuromuscular disease centers in France. Seventy-five ambulatory adults with myotonic dystrophy type 1 received an oral replacement dose (100 mg/d) or a pharmacologic dose (400 mg/d) of DHEA, or placebo. The primary endpoint was the relative change in the manual muscle testing (MMT) score from baseline to week 12. Secondary outcome measures included changes from baseline to week 12 in quantitative muscle testing and timed functional testing, respiratory and cardiac function, and quality of life. This study was registered with ClinicalTrials.gov identifier NCT00167609. RESULTS: The median (1st, 3rd quartile) relative changes in MMT score from baseline to week 12 after randomization were 3.1 (-0.9, 6.7), 1.9 (-2.7, 3.5), and 2.2 (0, 7.9), in the DHEA 100 mg, DHEA 400 mg, and placebo groups, respectively. There were no differences between placebo and combined DHEA groups (p = 0.34), placebo and DHEA 100 mg (p = 0.86), or placebo and DHEA 400 mg (p = 0.15). There were also no evidence for a difference between groups for the changes from baseline to week 12 in any secondary outcome. CONCLUSIONS: There is no evidence that a 12-week treatment with replacement or pharmacologic doses of dehydroepiandrosterone improves muscle strength in ambulatory myotonic dystrophy type 1 patients.

[Treatment's initiation in chronic inflammatory demyelinating polyradiculopathy (CIDP)]. / Initier le traitement de la PRNC.

Treatment's initiation in chronic inflammatory demyelinating polyradiculopathy (CIDP) remains a difficult medical decision. Only plasma exchanges, intravenous immunoglobulins (IVIg) and corticosteroids are proven effective treatments. Immunosuppressors are actually not first-line treatments in CIDP. Particular CIDP forms are associated with different response to treatments: pure motor CIDP should be treated by IVIg, and corticosteroids should only carefully be used in Lewis-Sumner syndrome. Otherwise, IVIg are first-line treatment in diabetic patients. Patients must be informed of side's effects and expected clinical effects. Early treatment was actually not proved to prevent axonal damages in CIDP patients, and waiting seems to be the best therapeutic option in poorly symptomatic patients. Recently, clinical guidelines were proposed to help clinician in this treatment choice, but there is no consensus about the best dose, duration or administration way to CIDP treatments. Further studies should be performed to clarify these points and to determine immunosuppressor agents place in treatment strategy.

[Long-term follow-up of multifocal motor neuropathy with conduction block under intravenous immunoglobulin]. / Neuropathies motrices multifocales avec blocs de conduction, profil évolutif sous immunoglobulines intraveineuses.

INTRODUCTION: Multifocal motor neuropathy with conduction block is an immune-mediated motor neuropathy, which usually responds to intravenous immunoglobulin. However, efficacy of long-term intravenous immunoglobulin is controversial. Our aim was to establish the long-term effects of intravenous immunoglobulin therapy on clinical and neurophysiological outcome measures and to determine the criteria predicting a good response to long-term intravenous immunoglobulin treatment. METHODS: We retrospectively included all multifocal motor neuropathy with conduction blocks patients followed for at least 4 years who received intravenous immunoglobulin therapy. We compared clinical data, MRC sumscores and electrophysiological data between the first and the last examination in the department. RESULTS: Seventeen patients were followed for an average of 8 years (range 4 to 18 years). At last examination, weakness remained asymmetric, predominant in the upper limbs, with a peripheral nerve distribution. At last examination, 3 patterns of evolution was seen: 6/17 patients had muscle strength improvement and need no more intravenous immunoglobulin therapy, 6/17 had initial improvement but became intravenous immunoglobulin dependent and 5/17 did not respond to intravenous immunoglobulin. MRC sumscores, number of conduction blocks and distal compound muscle action potential amplitudes were comparable between the first and the last examination (p>0.05). Improvement of MRC sumscores was not correlated with the clinical, biological and electrophysiological data that we analysed: age, gender, duration of disease, time from onset to intravenous immunoglobulin therapy, number of involved nerves, number of affected limbs, presence of muscle atrophy, MRC sumscores at diagnosis, number of conduction blocks, mean amplitude of the motor evoked potentials, presence of anti-GM1 antibodies, titers and IgM or IgG type of anti-GM1 antibodies. CONCLUSIONS: In this study, one third of multifocal motor neuropathy with conduction blocks patients have clinical improvement at last examination and need no more treatment, one third are intravenous immunoglobulin dependent and one third have never responded to intravenous immunoglobulin. Electrophysiological data are comparable between the first and the last examination. No predictive factor has been disclosed for long-term response to intravenous immunoglobulin.

[Idiopathic chronic dysautonomia: when should the diagnosis be made?]. / Dysautonomie chronique idiopathique: quand porter le diagnostic?

INTRODUCTION: Chronic autonomic disorders may complicate a wide range of conditions which can be divided into secondary, due to specific diseases, and primary, in which no cause has been determined. CASE REPORT: We report the case of a 43-year-old woman, who presented a chronic autonomic failure, which had begun by symptomatic orthostatic hypotension. Progressively, syncopes became daily, causing considerable discomfort associated with other signs of sympathic dysfunction: unilateral Horner's syndrome, diarrhea and hypohidrosis. The autonomic involvement was confirmed by study of the cardiovascular responses to tilt-up and electrophysiological autonomic testing. Etiologic search for a chronic acquired neuropathy (diabetes, amyloidis, paraneoplastic) or an inherited neuropathy was not conclusive. After five years, dysautonomic symptoms increased, but remained isolated. The physical examination did not show other clinical abnormalities such as cerebellar, pyramidal or extrapyramidal failure in favor of a multiple system atrophy or Parkinson's disease. All these data suggest the diagnosis of a primary autonomic failure. CONCLUSION: The diagnosis of primary autonomic failure is difficult to make because it requires that all the investigations in search of an etiology are negative and a long follow-up to be sure that dysautonomic symptoms persist isolated after many years of progression.

Multifocal motor neuropathy with and without conduction block: a single entity?

OBJECTIVE: To assess if multifocal motor neuropathy (MMN) with and MMN without conduction block (CB) are similar or distinct diseases. METHODS: The authors reviewed the clinical features and responses to IV immunoglobulin (IVIg) treatment of patients with MMN with and without CB at diagnosis, after 4 years of follow-up and at the last examination. They included all patients showing clinical features of MMN who had been followed for at least 4 years: All had asymmetric purely motor weakness with a peripheral nerve distribution, without any sensory, bulbar, or respiratory signs and without any upper motor neuron involvement. RESULTS: Twenty patients had CB and 13 had no CB. Median follow-up time was 7 years. There were no differences between the two groups in term of age, sex, time from onset to diagnosis, anti-GM1 antibody titers, or CSF data. Nerve distribution, number of affected limb regions, predominant weakness in distal upper extremities, asymmetric weakness, cramps, fasciculations, and Medical Research Council sum-scores in upper and lower limbs were comparable at diagnosis, 4 years of follow-up, and last examination. Few significant differences were observed. Involvement of median nerve was less frequent at 4 years of follow-up (14/20 vs 4/13; p = 0.027) and at the last examination (17/20 vs 5/13; p = 0.009) in patients without CB. Proximal weakness was less frequent in patients with MMN without CB at the last examination (7/20 vs 0/13; p = 0.027). Fewer nerves were involved in patients without CB at the last examination (4.5 vs 2; p = 0.04). Efficacy of IVIg was similar in MNN patients without CB (8/13) and with CB (14/20; p > 0.05). CONCLUSION: After a median follow-up time of 7 years, patients with and without conduction block showed similar clinical features and a similar response to IV immunoglobulin treatment.

[Multiple sclerosis associated with neurofibromatosis type I]. / Association neurofibromatose de type I et sclérose en plaques.

Association between neurofibromatosis type 1 (NF-1) and multiple sclerosis (MS) has been very rarely described. We report the case of a 40-year-old woman presenting familial NF-1 who had café au lait spots and cutaneous neurofibromatosis since childhood. Five years earlier, she experienced a first episode of unilateral optic neuritis, recurrent sensory and motor disturbances, then gait ataxia and pyramidal tract dysfunction with progressive walking impairment. Altered evoked potentials, CSF analysis and cerebral MRI findings were consistent with the diagnosis of MS (secondary progressive form after relapsing-remitting phase). We review major demographic, clinical and laboratory data of MS associated with NF-1 and discuss about the potential pathophisiological mechanisms implied.

[Hashimoto's encephalitis and sleep disorders]. / Encéphalite d'Hashimoto et troubles du sommeil.

Hashimoto's encephalitis is a rare cause of encephalitis which is improved by corticosteroid treatment. We report the case of a 42-year-old woman who developed progressive dementia associated with episodes of recurrent discorders of consciousness which rapidly improved with corticosteroids. During these episodes, no sleep activity was recorded on the holter EEG. These discorders were reversible with treatment and a normal EEG sleep pattern reappeared. At physical examination, Hashimoto's encephalitis can mimic Creutzfeld-Jakob disease. Systematic sleep-EEG recordings can be helpful for diagnosis of sleep disorders related Hashimoto's encephalitis. This case illustrates the importance of searching for antithyroid antibodies in patients with unexplained encephalitis.

[Chorea-acanthocytosis: report of a new family]. / Chorée-acanthocytose: une nouvelle famille.

Chorea-acanthocytosis is a rare cause of chorea. The genetic origin of the disease was proven with the isolation of the gene on chromosome 9q21. We report the case of two sisters who had two different expressions of this disease. The first sister developed secondary epilepsy associated with abnormal movement of the face. The second presented abnormal movements of the face and apathy. Both improved with serotoninergic treatment. Diagnosis was suggested on the basis of clinical findings and confirmed by identification of acanthocyes and integrity of the Kell blood antigen. Search for acanthocytes should be performed in all patients with chorea. Chorea associated with acanthocytosis has a better prognosis than chorea arising from other causes. Other neurological manifestations or complications may be present or mot; long-term follow-up in a specialized center iq needed for prevention.