Abstract: INTRODUCTION: No guideline is available for the long-term therapeutic management of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). STATE OF THE ART: Efficacy of corticosteroids, intravenous immunoglobulins and plasma exchanges has been shown in trials conducted on short periods. Only experts'recommendations are available for management of patients after initiation of these treatments. For corticosteroids, decrease must be very slow on one or two years. With intravenous immunoglobulins, dose per cure must be diminished and then delay between cures extended. Other immunomodulators or immunosuppressors have been tested in CIDP in case of failure of standard treatment and if treatment dependence appears (cyclophosphamide, cyclosporine, azathioprine, mycophenolate, beta-1a interferon, rituximab, tacrolimus, etc.), but no controlled trials are yet available. Treatment of CIDP in the long term is very complex because this entity brings together very different patients. Thereby, in clinical and electophysiological series of the literature, therapeutic prognostic may depend on the delay between first symptoms and treatment, course of the disease, demyelinating pattern on EMG and development of axonal lesions. PERSPECTIVES/CONCLUSIONS: Progress in the long-term treatment of CIDP depend on best diagnosis of the disease, fundamental research on pathophysiology to propose appropriate chemical molecules, and pursuit of trials with standard treatments on longer period and with others rhythm and way of administration. More recent treatments have to been tested in controlled trials too, in monotherapy or bi-therapy. Global cost in a patient treated for CIDP must be evaluated for each treatment. Multicentric approach of these questions will be recommended because of rarity of CIDP.

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Abstract: The classic paraneoplastic neurological syndromes include Lambert-Eaton myasthenic syndrome, limbic encephalitis, sensory neuronopathy, intestinal pseudo-obstruction, subacute cerebellar degeneration, encephalomyelitis, and dermatomyositis. Approximately ten onconeural antibodies that recognize cancer and the nervous system have been described in paraneoplastic neurological syndromes. These antibodies appear to be important diagnostic tools, even though they may not always be present. Deciding whether a given neurological picture is definitely or possibly paraneoplastic depends on the clinical syndrome, any association with onconeural antibodies, and the time elapsed between onset of neurological symptoms and the discovery of the cancer. Diagnosis of a classic paraneoplastic neurological syndrome or the discovery of onconeural antibodies mandates an active and persistent search for cancer, using new techniques such as fluorodeoxyglucose positron emission tomography. In patients with one of these syndromes, the best treatment of the neurological disease is often the diagnosis and early treatment of the cancer.

Abstract: OBJECTIVE: To assess the recovery in muscle strength and functional capacities in subjects with Guillain-Barré syndrome (GBS) for 18 months after onset. DESIGN: Six GBS patients were treated and transferred to our rehabilitation center within the first week of recovery. RESULTS: Isometric and isokinetic strength increased significantly during the first 6 months (P < 0.01). Between 6 and 18 months, muscle strength increased less rapidly (P < 0.05). We showed a significant negative correlation between plateau period duration and knee extensors, elbow flexors muscles strength recovery (rho = -0.82; P = 0.05). At 6 months, manual muscle testing and functional independence motor total scores were close to normal levels. At 18 months, all patients satisfied the criteria for a full recovery. However, they felt difficulties after prolonged exercise. CONCLUSIONS: Until 18 months of recovery, dynamometric measures still showed significant strength improvement. This underscores the need for a minimal 24 months of clinical follow-up with an individualized rehabilitation management program.

Abstract: Involvement of the peripheral nervous system (PNS) is common in patients with cancer and any part, including motor neurons, sensory ganglia, nerve roots, plexuses, cranial and peripheral nerves, and neuromuscular junctions, can be affected. Different mechanisms can initiate damage associated with cancer-related PNS disorders. These include tumour infiltration, toxicity of treatments, metabolic and nutritional perturbations, cachexia, virus infections, and paraneoplastic neurological syndromes. The type of cancer, lymphoma, or solid tumour is a further determinant of a PNS disorder. In this Review we discuss the different causes and mechanisms of disorders of the PNS in patients with cancer and we will focus on their assessment and diagnosis.

Abstract: PURPOSE: To identify the role of fatigue, its evaluation and its causes in the pathophysiology context of acquired or hereditary neuromuscular diseases of the spinal anterior horn cell, peripheral nerve, neuromuscular junction and muscle. MATERIAL AND METHODS: A literature review has been done on Medline with the following keywords: neuromuscular disease, peripheral neuropathy, myopathy, fatigue assessment, exercise intolerance, force assessment, fatigue scale and questionnaire, then with the terms: Fatigue Severity Scale, Chalder Fatigue Scale, Fatigue Questionnaire, Piper Fatigue Scale, electromyography and the combination of the word Fatigue with the following terms: Amyotrophic Lateral Sclerosis (ALS), Post-Polio Syndrome (PPS), Guillain-Barre Syndrome, Immune Neuropathy, Charcot-Marie-Tooth Disease, Myasthenia Gravis (MG), Metabolic Myopathy, Mitochondrial Myopathy, Muscular Dystrophy, Facioscapulohumeral Dystrophy, Myotonic Dystrophy. RESULTS: Fatigue is a symptom very frequently reported by patients. Fatigue is mainly evaluated by strength loss after an exercise, by change in electromyographic activity during a given exercise and by questionnaires that takes into account the subjective (psychological) part of fatigue. Due to the large diversity of motor disorders, there are multiple clinical expressions of fatigue that differ in their presentation, consequences and therapeutic approach. CONCLUSION: This review shows that fatigue has to be taken into account in patients with neuromuscular diseases. In this context, pathophysiology of fatigue often implies the motor component but the disease evolution and the physical obligates of daily life also induce an important psychological component.

Abstract: OBJECTIVE: To study the utility of electroneuromyography in analysis of upper limb pain as a function of the existence of a diagnostic hypothesis. METHODS: We retrospectively compared the consecutive electroneuromyographic examinations performed between 1 January and 30 September 2004. All recordings were performed by the same examiner in the neurophysiology clinic in the department of neurology of Saint-Etienne university hospital UHC at the request of hospital specialists or surgeon and private general practitioners. In each examination, at a minimum and regardless of the specific situation, motor conduction speed, F waves, and sensory conduction speed were recorded for the median nerve and the ulnar nerve on the right and left. For the arm in question, needle electromyography explored the muscles depending on the C5-T1 roots. RESULTS: In all, 76 patients had ENMG examinations, 38 for whom the physician had a diagnostic hypothesis and 38 patients without. In the case of a diagnosis based on clinical suspicions, examination was normal in 73.7% of cases compared with 23.7% when there was a clinically based hypothesis (p<0.01). These findings did not vary significantly according to the specialization of the referring physician. CONCLUSION: Electromyography and nerve conduction studies are useful to confirm a diagnosis based on patient reports and clinical data, it is not useful when no diagnosis has been suggested.

Abstract: Anti-CV2 antibodies (AB) react with the developmentally regulated neural proteins CRMPs and particularly with CRMP5. They occur with small cell lung cancer (SCLC) and thymoma. SCLCs universally express CRMP5. We investigated the expression of CRMPs in thymoma and thymus. In thymoma, none of the CRMPs were detected by immunohistochemistry in tumorous epithelial cells with specific antibodies including CRMP5 but an antibody reacting with a peptide common to the CRMPs labeled a 66-kDa protein in Western blot of rat brain, thymus, and thymoma extracts. Thus, the normal CRMP5 is probably not expressed by tumorous epithelial cells. These results indicate that the mechanisms leading to CRMP5 autoimmunization are different in SCLC and thymoma.

Abstract: INTRODUCTION: Extrapontine myelinolysis is a well-known complication of hyponatremia and its treatment. It rarely occurs without central pontine myelinolysis, usually after overly rapid correction of hyponatremia. Its prognosis is considered poor. EXEGESIS: We report the case of a patient with autoimmune polyglandular syndrome with subacute adrenal failure responsible of severe hyponatremia. Despite a well-conducted treatment, the patient developed acute anxiety, catatonia, dysphagia and parkinsonism revealing extrapontine myelinolysis demonstrated on MRI. Outcome was favorable. CONCLUSION: Extrapontine myelinolysis may occur in the absence of central pontine myelinolysis despite a treatment of hyponatremia conducted according to published guidelines. Treatment should be extremely cautious when hyponatremia has been lasting for more than 48 hours.

Abstract: PURPOSE: There is evidence that myasthenia gravis is substantially underdiagnosed in older people, for which diagnosis and treatment may be difficult. METHOD: We report on a series of 23 cases of myasthenia gravis diagnosed after the age of 65. Diagnosis was ascertained by compatible symptoms, associated with electrophysiological evidence and/or presence of antibodies to the acetylcholine receptor (AchRAb) and/or positive prostigmine test. RESULTS: Twelve female and 11 male patients were identified, with a mean age of 77 (range: 66-89). Initial symptoms were ocular in 8 cases (35%), bulbar and ocular in 9 cases (39%), generalized in 6 cases (26%). Diagnosis was delayed in many patients (mean delay 31+/-47 months). Prostigmine test was positive in 16 cases (100%), AchRAb were positive in 19/23 cases (83%). Only one thymoma was found. Other diagnoses than myasthenia gravis, mainly stroke, were often considered. Treatment with anticholinesterase drugs, prescribed in all cases, has been able to control symptoms in only 3 cases. Corticosteroids were used in 10 cases, azathioprine or mycophenolate mofetil in 14 cases, intravenous immunoglobulins in 8 cases, and plasma exchanges in 2 cases. Thymectomy was performed on one patient with thymoma. Three patients were hospitalized in intensive care units for several weeks, and 3 patients died from their myasthenia. CONCLUSION: Diagnosis of myasthenia gravis is often missed or delayed in the elderly, because of a broad differential diagnosis in older people, and because the high incidence of the disease in middle and old age is often overlooked. The outcome of myasthenia gravis in older people is far from simple, and immunomodulation proves to be necessary in most cases. However, quality of life of surviving patients appears good.

Abstract: A total of 29 patients with cancer and neuropathies of unknown origin that were possibly paraneoplastic were tested for antiganglioside antibodies by immunodot blot and ELISA. None of the patients had onconeural antibodies. They were compared with 41 normal subjects and 187 patients with metabolic or idiopathic neuropathies. Antiganglioside antibodies, mainly IgM anti-GM1, were more frequently found in the patients with cancer than in the control groups. However, the levels of antibodies were not different from those of the controls. There was no correlation with the pattern of the neuropathy. These results do not support the hypothesis that antiganglioside antibodies are frequent and major immunological targets in paraneoplastic neuropathies.

Abstract: Paraneoplastic peripheral neuropathies constitute a heterogeneous group of conditions. A link between the tumor and the neuropathy has been demonstrated in a subgroup only. Definite paraneoplastic neuropathies correspond to neuropathies associated with antibodies reacting with antigens common to the peripheral nervous system and the cancer. Neuropathies associated with anti-Hu antibodies are the most frequent and consist mainly in subacute sensory neuronopathy. Sensory or sensory-motor neuropathies with anti-CV2 antibodies are less frequent. The link between the cancer and the neuropathy is less clear in the other forms. The frequency of cancer in this group varies from 1 to 18 p.cent.These neuropathies include inflammatory demyelinating neuropathies, neuropathy and vasculitis, lower motor neurone diseases, and autonomic neuropathies. Occasionally, the neuropathy improves with treatment of the tumor. Recent data suggest that gangliosides may be the target of the immune process in neuropathies associated with melanoma.

Abstract: A patient with myasthenia gravis and thymoma developed neuromyelitis optica (NMO) and necrotizing myositis 4 months after treatment of the tumor. Antibodies reacting with the CNS and thymic epithelial cells were detected in the serum during the acute phase of NMO, suggesting that the NMO was linked to the thymoma.

Abstract: OBJECTIVE: To evaluate the feasibility and the interest of isokinetic measures tests in subjects with inflammatory demyelinating polyradiculoneuropathy or Guillain-Barré syndromes (GBS). METHODS: Nine patients with GBS are tested at the beginning and after 6 months of recovery stage. They benefit from (1) isokinetic assessment of muscular strength of knee, elbow, ankle: flexion/extension and shoulder abduction/adduction ranging 30 per s at 180 per s angular velocity; (2) isometric assessment of the same muscular groups; (3) manual muscle testing; (4) functional independence measure. RESULTS: Isokinetic tests were tolerated at 60 and 120 per s. Fatigability appears since the third second of isometric test. The relationships between isokinetic, manual tests and isometric tests are variables (0.29 < r < 0.97). The evaluation after 6 months of recovery showed a good sensibility of isokinetic test. CONCLUSION: The continuation of this motor isokinetic evaluation, in a large population, will permit to establish longitudinal and evolutive profile of each patient and will facilitate to chose the rehabilitation program.

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Abstract: We present a patient with a superficial siderosis and a white matter involvement on MRI and a demyelinating pattern on visual evoked potentials. White matter involvement is supposed to be secondary to vascular modifications induced by superficial siderosis.

Abstract: Although paraneoplastic subacute sensory neuronopathy is the most frequent presentation of peripheral neuropathy in patients with anti-Hu antibodies, other neuropathies have been reported. In order to investigate the clinical and electrophysiological manifestations of neuropathies associated with anti-Hu antibodies, we conducted a retrospective study of 20 patients. For the electrophysiological study, each nerve was classified as normal, demyelinating, axonal/neuronal or axonal/demyelinating. Peripheral neuropathy was the presenting symptom in 95% of patients. CNS and autonomic neuropathy were present in 40% and 30% of patients, respectively. The course of the neuropathy was acute, mimicking Guillain-Barré syndrome in one patient (5%), and subacute (55%) or progressive (40%) in the others. Clinically, the neuropathy was sensory (70%), sensorimotor (25%) or motor (5%). At onset, symptoms were symmetrical (65%), asymmetrical (25%) or multifocal (10%). Pain was a predominant manifestation (80%). Amyotrophia and fasciculations were rare. The median Rankin's score was 2, three patients having an indolent form. Electrophysiology showed the axonal/neuronal pattern to be the most frequent (46.9% of studied nerves); an axonal/demyelinating or demyelinating pattern being seen in 18.3% and 4.9% of nerves, respectively. The axonal/neuronal pattern was more frequent in sensory nerves and the mixed axonal/demyelinating pattern more frequent in motor nerves (P < 0.01). A higher proportion of abnormal nerves correlated with a progressive course (P < 0.05) or a Rankin's score between 3 and 5 (P < 0.01). In patients with sensory neuropathy, 88.5% of sensory nerves were abnormal, mostly with an axonal/neuronal pattern. In addition, 47% of motor nerves were abnormal so that only four out of 14 patients with a clinically pure sensory neuropathy (28.6%) had an electrophysiological pattern typical of sensory neuronopathy. In patients with a sensorimotor neuropathy, 96.6% of sensory and 71% of motor nerves were abnormal. The only statistical difference between sensory and sensorimotor neuropathies was that patients with sensorimotor neuropathy had more frequent motor nerve involvement (P < 0.05) without differences concerning the distribution of the abnormal patterns. Needle neuromyography showed only limited evidence of motor neurone degeneration in both sensory and sensorimotor neuropathy. The present work shows that the typical clinical and electrophysiological pattern of subacute sensory neuronopathy is rarely encountered in patients with anti-Hu antibody and that motor nerve involvement is frequently seen, even in the absence of a motor deficit. In addition to their potential pathophysiological involvement in the mechanism of the paraneoplastic neuropathy, these findings have practical consequences for the diagnosis of the disorder.

Abstract: Subacute sensory neuronopathy with anti-Hu antibodies is the best-characterized paraneoplastic peripheral neuropathy associated with carcinoma. Anti-CV2 antibodies, another group of paraneoplastic antibodies, react with a 66-kd brain protein belonging to the family of Ulip/CRMP proteins. The manifestations associated with anti-CV2 antibodies include cerebellar degeneration, uveitis, and peripheral neuropathy. Some of these patients also have anti-Hu antibodies. We have compared the clinical, electrophysiological, and pathological characteristics of the peripheral neuropathy in 9 patients with anti-CV2 antibodies (3 of whom also had anti-Hu antibodies) and 12 patients with only anti-Hu antibodies. Data for patients with anti-Hu antibodies alone indicated subacute sensory neuronopathy. Patients with anti-CV2 antibodies had a mixed axonal and demyelinating sensory motor neuropathy that was sometimes superimposed on subacute sensory neuronopathy when both anti-CV2 and anti-Hu antibodies were present. Unlike anti-Hu antibodies, anti-CV2 antibodies reacted with peripheral nerve antigens, as shown by their ability to bind to a 66-kd protein in human and rat nerve on Western blot analysis and to immunolabel peripheral nerve axons and sensory neurons on immunohistochemical study.

Abstract: The diagnosis of cancer is often difficult in patients with paraneoplastic neurological syndrome and anti-Hu antibodies. Fluorodeoxyglucose 18 positron emission tomography scanning is a highly sensitive and specific method to detect lung tumors. We investigated 15 patients with paraneoplastic neurological syndrome and anti-Hu antibodies. Radiological methods led to the diagnosis of cancer in 12 patients, and test results were negative in 3. Whole-body [18F]fluorodeoxyglucose positron emission tomography showed abnormal uptake in the mediastinum in these 3 patients in accordance with the expected location of the malignancy.

Abstract: Manifestations of dementia occurred in two young patients with disseminated lupus erythematosus who had no signs of focalized neurological deficit. In case 1 followed for 8 years, a probably autonomous and familial psychiatric syndrome was complicated during a lupus flare-up by a prolonged dementia syndrome which regressed to a large extent. In the second patient with moderate dementia and familial hearing loss, severe mental deterioration suddenly occurred with long-term degradation of the cognitive capacity. In both of these cases with neurolupus, the frontal clinical signs, the neuropsychological deficits evidenced at testing, and the lesions demonstrated at CT scan and magnetic resonance imaging favored a frontal and/or frontobasal type dementia. Treatment with cyclophosphamide was effective in case 1 after failure of corticosteroid therapy.