Evaluation of the application of the European guidelines for the diagnosis and clinical care of amyotrophic lateral sclerosis (ALS) patients in six French ALS centres.

BACKGROUND AND PURPOSE: Our objective was to evaluate the extent to which the 2005 recommendations of the European Federation of Neurological Sciences (EFNS) on the multidisciplinary management of amyotrophic lateral sclerosis (ALS) are followed in clinical practice. METHODS: This was a multicentre observational study involving six French ALS referral centres receiving prevalent and incident cases. Recommendations were translated into ad hoc questions referring to key aspects of management, and their application was evaluated by a clinical research assistant who independently examined the medical charts (MCs). When necessary, an independent board-certified neurologist answered the questions based on examination of the MC and interview of the caring neurologist. Questions regarding diagnosis and communication were put to patients in a self-administered questionnaire. RESULTS: In all, 376 patients [176 incident, 200 prevalent cases; median age at diagnosis 62.8 years (interquartile range 55.7-72.3); sex ratio 1.37; 27.3% bulbar onset] were included. All the topics covered in the recommendations were evaluated: diagnostic delay (e.g. mean 13.6 months, associated with age and onset); breaking the news (e.g. criteria for communication quality were satisfactory in more than 90%); multidisciplinary and sustained support (e.g. clinic visits were scheduled every 2-3 months in 90%). Also considered were whether riluzole had been offered, symptom management, genetic testing, ventilation, communication defects, enteral nutrition, palliative and end-of-life care. Characteristics associated with poor compliance with some guidelines (schedule of visits, delayed riluzole initiation) were also identified. CONCLUSION: This is the first evaluation of the application of the EFNS recommendations for the management of ALS in a nationwide sample. The results allow us to highlight areas for improvement.

Eczematous dermatosis and thrombocytosis induced by efalizumab: two new side effects.

Efalizumab was authorized to be put on the market in France starting July 21, 2005. Its efficacy and tolerance profile in plaque psoriasis at a dose of 1 mg kg(-1) weekly in a subcutaneous injection have been studied in phase III trials. At the current moment, more than 3,500 patients have been included in clinical trials. Flu-like symptoms (fever, chills, headaches, nausea, vomiting, myalgia) are the most frequent adverse events. On the skin, a localized papular rash or the aggravation of the psoriasis in an edematous or even pustular form are the two most regularly observed complications. At the biological level, hyperlymphocytosis and a temporary increase in alkaline phosphatases without clinical consequences are the most frequent anomalies. We report 2 adverse events under efalizumab that to our knowledge have never been described: a case of an eczematous rash and a case of thrombocytosis.

[Bowen's disease and squamous cell carcinoma in Haber's syndrome: two cases]. / Maladie de Bowen et carcinome épidermoïde au cours d'un syndrome de Haber: deux cas.

BACKGROUND: Haber's syndrome is a rare form of autosomal dominant genodermatosis. Clinically, it is associated with rosaceiform dermatosis of the face that begins in childhood, and profuse keratotic lesions resembling seborrheic keratoses, seen predominantly on the trunk, the tops of the limbs and the scalp. We report two cases of Bowen's disease and cutaneous epidermoid carcinoma in Haber's syndrome patients. OBSERVATIONS: A 67 year-old woman with Haber's syndrome and with a familial history consulted for a budding lesion on the abdomen, histological examination of which confirmed epidermoid carcinoma. A 77 year-old woman presented a clinical picture consistent with Haber's syndrome, with three infiltrated erythematosquamous abdominal lesions. Histological examination of a biopsy sample confirmed the clinical diagnosis of Bowen's disease. The patient was successfully treated with imiquimod. DISCUSSION: These two cases appear to indicate the existence of an association between Haber's syndrome and the presence of cutaneous carcinomatous lesions. We propose the hypothesis of transformation of the keratoses seen in seborrheic keratosis. These lesions may be considered as pre-cancerous. Association with skin carcinomas requires regular monitoring of these patients. The use of imiquimod to treat lesions in patients with Bowen's disease resulted in complete cure.

Primary Gougerot-Sjögren syndrome: a dermatological approach.

Gougerot-Sjögren syndrome (GSS) is a chronic heterogeneous non-organ-specific autoimmune disease, encompassing a wide spectrum of clinical manifestations. It is characterized by a lymphocytic infiltration of the exocrine glands, also called epitheliitis, resulting in xerostomia and keratoconjunctivitis sicca. The skin can also be involved; for example, xerosis is a consequence of epitheliitis. Dermatological consequences of polyclonal reactivity are vasculitis and manifestations of B-cell proliferation vary from plasma cell infiltrates to B-cell lymphoma.

[Guillain-Barré syndrome secondary to cranial surgery: direct or fortuitous relationship?]. / Syndrome de Guillain-Barré secondaire à une craniectomie: association fortuite ou relation directe?

The Guillain-Barré syndrome, an acute polyradiculonevritis (PRN), usually appears after a post-infectious immuno-allergic reaction. We report a case of acute PRN following cranial surgery. Post-surgical Guillain-barré syndrome is rarely described. We reviewed the pathophysiological mechanisms possibly involved in this disease that have to be evoked in patients with abnormal post-surgical neurological symptoms.

Selective regulation of current densities underlies spontaneous changes in the activity of cultured neurons.

We study the electrical activity patterns and the expression of conductances in adult stomatogastric ganglion (STG) neurons as a function of time in primary cell culture. When first plated in culture, these neurons had few active properties. After 1 d in culture they produced small action potentials that rapidly inactivated during maintained depolarization. After 2 d in culture they fired large action potentials tonically when depolarized, and their properties resembled very closely the properties of STG neurons pharmacologically isolated in the ganglion. After 3-4 d in culture, however, their electrical properties changed and they fired in bursts when depolarized. We characterized the currents expressed by these neurons in culture. They included two TTX-sensitive sodium currents, a calcium current, a delayed-rectifier-like current, a calcium-dependent potassium current, and two A-type currents. The changes in firing properties with time in culture were accompanied by an increase in inward and decrease in outward current densities. A single-compartment conductance-based model of an STG neuron was constructed by fitting the currents measured in the biological neurons. When the current densities in the model neuron were matched to those measured for the biological neurons in each activity state, the model neuron closely reproduced each state, indicating that the changes in current densities are sufficient to account for the changes in intrinsic properties. These data indicate that STG neurons isolated in culture change their intrinsic electrical properties by selectively adjusting the magnitudes of their ionic conductances.

Rhythmogenesis, amplitude modulation, and multiplexing in a cortical architecture.

In a network of excitatory and inhibitory neurons, hyperpolarization-activated inward currents can help to produce population rhythms in which individual cells participate sparsely and randomly. A shift in the activation curve of such a current changes the fraction of the cells participating in any given cycle of the population rhythm, thus changing the amplitude of the field potential. Furthermore, the frequency of the population rhythm remains relatively fixed over a substantial range of amplitudes, allowing the population rhythm to play a separate processing role from that of the individual components.

Activity-dependent regulation of conductances in model neurons.

Neurons maintain their electrical activity patterns despite channel turnover, cell growth, and variable extracellular conditions. A model is presented in which maximal conductances of ionic currents depend on the intracellular concentration of calcium ions and so, indirectly, on activity. Model neurons with activity-dependent maximal conductances modify their conductances to maintain a given behavior when perturbed. Moreover, neurons that are described by identical sets of equations can develop different properties in response to different patterns of presynaptic activity.