Novel mutations widen the phenotypic spectrum of slow skeletal/ß-cardiac myosin (MYH7) distal myopathy.

Laing early onset distal myopathy and myosin storage myopathy are caused by mutations of slow skeletal/ß-cardiac myosin heavy chain encoded by the gene MYH7, as is a common form of familial hypertrophic/dilated cardiomyopathy. The mechanisms by which different phenotypes are produced by mutations in MYH7, even in the same region of the gene, are not known. To explore the clinical spectrum and pathobiology, we screened the MYH7 gene in 88 patients from 21 previously unpublished families presenting with distal or generalized skeletal muscle weakness, with or without cardiac involvement. Twelve novel mutations have been identified in thirteen families. In one of these families, the father of the proband was found to be a mosaic for the MYH7 mutation. In eight cases, de novo mutation appeared to have occurred, which was proven in four. The presenting complaint was footdrop, sometimes leading to delayed walking or tripping, in members of 17 families (81%), with other presentations including cardiomyopathy in infancy, generalized floppiness, and scoliosis. Cardiac involvement as well as skeletal muscle weakness was identified in nine of 21 families. Spinal involvement such as scoliosis or rigidity was identified in 12 (57%). This report widens the clinical and pathological phenotypes, and the genetics of MYH7 mutations leading to skeletal muscle diseases.

A novel mutation in the SCN4A responsible for cold-induced myotonia with normal electromyography findings on room temperature.

One family is described with a novel SCN4A mutation, causing cold-aggravated myotonia without weakness. One affected family member had a normal needle electromyography at room temperature. Myotonic discharges were only discovered after cooling of the tested muscles.

Late onset painful cold-aggravated myotonia: three families with SCN4A L1436P mutation.

We describe three Belgian families with a L1436P mutation in the SCN4A gene, causing a sodium channel myotonia with an atypical clinical presentation, characterized by late onset painful cold-aggravated myotonia. These families represent a distinct phenotype within the spectrum of sodium channel myotonia.

Malignant ventricular arrhythmia in a case of adult onset of spinal muscular atrophy (Kugelberg-Welander disease).

We present a case of a 43-year-old male patient with adult onset of spinal muscular atrophy (SMA). The patient first came to our attention with atrioventricular (AV) block. A dual-chamber pacemaker (DDD-PM) was implanted. Four years later, the PM data log showed occurrence of frequent episodes of nonsustained ventricular tachycardia (NSVT). The episodes progressed in duration and frequency. An electrophysiological study revealed prolonged His-ventricular (HV) interval duration and induction of sustained ventricular tachycardia. The patient was successfully upgraded to a prophylactic dual-chamber cardioverter defibrillator. Our case is the first description of a patient with adult-onset SMA (Kugelberg-Welander disease [KWD]) and malignant ventricular arrhythmias.

Fatigue as the presenting symptom of chronic inflammatory demyelinating polyneuropathy.

Different clinical presentations of chronic inflammatory demyelinating polyneuropathy (CIDP) have been described. Fatigue is generally considered to be a secondary sign and is not mentioned as a warning sign for the diagnosis. We present a patient with CIDP in whom fatigue remained the only symptom, hereby stressing the importance of adding this disease to the differential diagnosis of fatigue. Immunomodulatory treatment did not change the clinical course of the patient, but electrodiagnostic features improved substantially.

Impact of reimbursement restrictions on the choice of antiepileptic drugs: Belgian Study on Epilepsy Treatment (BESET).

BACKGROUND: In Belgium, new and costly antiepileptic drugs (AEDs) are only reimbursed as second-line treatment, after documented treatment with conventional and cheaper AEDs has failed. The objective of this study was to describe the treatment of epilepsy in Belgium and to analyze the impact of the reimbursement restrictions on the choice of AEDs. METHODS: Between May and June 2003, a sample of 100 neurologists, representative of the entire neurological community in teaching, academic, and regional hospitals in Belgium, were personally interviewed on the basis of a structured questionnaire (modified Rand method). The questionnaire contained questions on treatment choices and strategies in adult epilepsy. RESULTS: Unanimously, initial monotherapy was the preferred treatment strategy in all types of epilepsy. In the opinion of most neurologists, valproate was the first choice for idiopathic generalized and focal epilepsy with/without secondary generalization. Carbamazepine as their first choice for the treatment of focal epilepsy. New AEDs were most often prescribed as second-line therapy. Lamotrigine was the most frequently prescribed new AED and used for both generalized and focal epilepsy. It was followed by levetiracetam, topiramate and oxcarbazepine for focal epilepsy. In the absence of reimbursement restrictions, two new AEDs would be significantly more often prescribed as a first-line therapy: lamotrigine for idiopathic generalized epilepsy and oxcarbazepine for focal epilepsy. CONCLUSIONS: The neurologists reached a high level of consensus on many of the key treatment questions. Monotherapy with valproate and carbamazepine was the standard treatment strategy in Belgium. Lamotrigine and less so levetiracetam, topiramate and oxcarbazepine were commonly prescribed as second-line AEDs. In the absence of reimbursement restrictions, lamotrigine and oxcarbazepine would be more frequently prescribed.

Standards of care for non-convulsive status epilepticus: Belgian consensus recommendations.

Non-convulsive status epilepticus (NCSE) makes up around one-third of all cases of SE, affecting approximately 1,000 to 4,000 individuals per year in Belgium. Compared with convulsive SE, NCSE has received considerably less attention, is underdiagnosed and undertreated. However, if recognised, NCSE can however be treated successfully. A workshop was convened by neurologists from major Belgian centres to review the latest information on NCSE and to make recommendations on diagnosis and treatment. These recommendations are not only intended for neurologists, but also for primary care physicians and physicians in intensive care units. NCSE should be suspected whenever cases of fluctuating consciousness or abrupt cognitive or behavioural changes are noted. Confirmation of diagnosis by EEG should be obtained wherever possible. In view of the often subtle clinical signs, EEG is also vital for monitoring treatment outcome. Non-comatose patients should generally be treated in a neurology ward since referral to an ICU is unnecessary. First-line treatment should be an intravenous benzodiazepine. For many patients who fail to respond to benzodiazepines, intravenous valproate will successfully abrogate seizure activity. Intravenous phenytoin can be used in patients with focal NCSE in whom valproate is contraindicated or ineffective. Time and care should be spent in identifying an appropriate and effective antiepileptic drug regimen without recourse to anaesthesia. For comatose patients, treatment intensity should be graded according to epilepsy history, general medical state and prognosis. In some patients, intensive remedial measures may allow rapid resolution of NSCE, whereas in more vulnerable patients, such treatment may be counterproductive.

Standards of care for adults with convulsive status epilepticus: Belgian consensus recommendations.

Status epilepticus (SE) is a significant health problem, affecting approximately 1,000 to 4,000 individuals per year in Belgium. A workshop was convened by a panel of neurologists from major Belgian centers to review the latest information relating to the definition, diagnosis and treatment of convulsive SE. The panelists sought to make recommendations for practising neurologists, but also primary care physicians and physicians in intensive care units when initiating emergency measures for patients with convulsive SE. As there is an association between prolonged seizures and a poor outcome, the importance of early (within the first 5 minutes of seizure onset) and aggressive treatment is to be stressed. In addition to general systemic support (airway, circulation), intravenous administration of the benzodiazepines lorazepam or diazepam is recommended as first-line therapy. Intramuscular midazolam may also be used. If SE persists, second-line drugs include phenytoin or valproate, and third-line drugs the barbiturate phenobarbital, the benzodiazepine midazolam, or the anaesthetics thiopental or propofol, or eventually ketamine. If the patient does not recover after therapy, monitoring of seizures should involve an electroencephalogram to avoid overlooking persistence of clinically silent SE. As a general rule, the intensity of the treatment should reflect the risk to the patient from SE, and drugs likely to depress respiration and blood pressure should initially be avoided. If initial treatment with a benzodiazepine fails to control seizures, the patient must be referred to the emergency unit and a neurologist should be contacted immediately.

Epilepsy and driving in Belgium: proposals and justification.

Proposals about the regulations and medical criteria concerning epilepsy and driving, originally drawn up by the Commission on Epilepsy and Risk from the Belgian League against Epilepsy were discussed and amended by a panel of representatives of several scientific societies and of all Belgian universities in order to establish a broad consensus among Belgian epileptologists. The history of driving licencing in Belgium is discussed and some background information given to put the regulations in perspective. A proposal is made for an acceptable level of risk. Subsequently, a quantification of risk for different situations concerning seizures is attempted. The proposals will be discussed and some further practical advice given. Individual assessment of the ability to drive remains indispensable.

Ropivacaine 3.75 mg/ml, 5 mg/ml, or 7.5 mg/ml for cervical plexus block during carotid endarterectomy.

OBJECTIVE: To examine the effect of 225 mg (7.5 mg/mL), 150 mg (5 mg/mL), and 112.5 mg (3.75 mg/mL) ropivacaine on quality of cervical plexus block during carotid endarterectomy. METHODS: Patients (n = 93) scheduled for carotid endarterectomy were randomized to receive a cervical plexus block with deep infiltration of 10 mL and superficial infiltration of 20-mL volumes of ropivacaine 7.5, 5.0, or 3.75 mg/mL. Pain, coughing, hemodynamic consequences of the block, postoperative visual analog scores, and pain satisfaction index were recorded. If necessary, anesthesia supplements with aliquots of 3 mL lidocaine 1% were given during surgery. RESULTS: Incidences of coughing and hoarseness were similar in all groups. More local anesthetic infiltrations were required in the ropivacaine 3.75-mg/mL and 5-mg/mL groups. Postoperatively, no intragroup differences were observed. A trend toward better pain satisfaction was observed in the ropivacaine 7.5-mg/mL group. CONCLUSION: The best quality of cervical plexus block associated with the smallest incidence of pain for patients undergoing carotid endarterectomy was obtained with 30 mL of 225 mg and 150 mg of ropivacaine, respectively.

Mutations in the small GTP-ase late endosomal protein RAB7 cause Charcot-Marie-Tooth type 2B neuropathy.

Charcot-Marie-Tooth type 2B (CMT2B) is clinically characterized by marked distal muscle weakness and wasting and a high frequency of foot ulcers, infections, and amputations of the toes because of recurrent infections. CMT2B maps to chromosome 3q13-q22. We refined the CMT2B locus to a 2.5-cM region and report two missense mutations (Leu129Phe and Val162Met) in the small GTP-ase late endosomal protein RAB7 which causes the CMT2B phenotype in three extended families and in three patients with a positive family history. The alignment of RAB7 orthologs shows that both missense mutations target highly conserved amino acid residues. RAB7 is ubiquitously expressed, and we found expression in sensory and motor neurons.