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Phosphorylase kinase (PhK) deficiency is the underlying cause of variable clinical symptoms depending on the tissues involved. Until today, only a few cases of myopathy associated with muscle PhK deficiency caused by a mutation in the gene encoding the alpha subunit of phosphorylase kinase (PHKA1) have been reported. We describe a male patient with myopathy and absent muscle PhK activity caused by a frameshift mutation in the gene encoding the alpha subunit of PhK on chromosome Xq12-q13., ((c) 2005 Wiley-Liss, Inc.)

We present the case of a 29-year-old woman with Down syndrome who developed bilateral frontal ischemic stroke. Cerebral angiography demonstrated an occlusion of the both supraclinoid internal carotid arteries associated with dilated collateral vessels, consistent with moyamoya disease. We review the clinical and radiological features of moyamoya disease associated with Down syndrome and discuss a few major physiopathologic hypotheses to explain this association.

Glycogen-storage diseases type I (GSD type I) are due to a deficiency in glucose-6-phosphatase, an enzymatic system present in the endoplasmic reticulum that plays a crucial role in blood glucose homeostasis. Unlike GSD type Ia, types Ib and Ic are not due to mutations in the phosphohydrolase gene and are clinically characterized by the presence of associated neutropenia and neutrophil dysfunction. Biochemical evidence indicates the presence of a defect in glucose-6-phosphate (GSD type Ib) or inorganic phosphate (Pi) (GSD type Ic) transport in the microsomes. We have recently cloned a cDNA encoding a putative glucose-6-phosphate translocase. We have now localized the corresponding gene on chromosome 11q23, the region where GSD types Ib and Ic have been mapped. Using SSCP analysis and sequencing, we have screened this gene, for mutations in genomic DNA, from patients from 22 different families who have GSD types Ib and Ic. Of 20 mutations found, 11 result in truncated proteins that are probably nonfunctional. Most other mutations result in substitutions of conserved or semiconserved residues. The two most common mutations (Gly339Cys and 1211-1212 delCT) together constitute approximately 40% of the disease alleles. The fact that the same mutations are found in GSD types Ib and Ic could indicate either that Pi and glucose-6-phosphate are transported in microsomes by the same transporter or that the biochemical assays used to differentiate Pi and glucose-6-phosphate transport defects are not reliable.

A 36-year-old man, treated for epilepsy since early childhood, was hospitalized for nocturnal paroxysmal disorders. The EEG-EKG-video monitoring revealed complex partial seizures with bradycardia secondary to a sino-auricular block. The occurrence of autonomic disturbances during seizures is well known, mostly described in temporal epilepsy. Ictal bradycardia, with asystole, has been unfrequently reported, while tachycardia appears more common. A systematic investigation of cardiac data synchronized with EEG recordings, especially in case of aspecific fainting, could give a more accurate diagnosis and treatment, and so reducing sudden unexplained death in epileptic patients.

A 44-year-old maniacodepressive woman developed acute encephalopathy due to the association of lithium carbonate and haloperidol. She was treated with lithium salts for many years and the serum level of lithium was within the therapeutic range. The encephalopathy was worsened by hyperthermia, dehydration, and reintroduction of haloperidol, 5 days after the first discontinuation of the neuroleptic. The clinical features were characterized by a persistent cerebellar syndrome, more than one year after the interruption of these medications.

The molecular abnormality of a phosphoglycerate kinase variant which was associated with severe tissue enzyme deficiency and episodes of muscle contractions and myoglobinuria was examined. Analysis of the patient's DNA showed the existence of a nucleotide transversion A/T - C/G in exon 7. No other nucleotide change was detected in the coding region of the variant gene. The mutation should produce a single amino acid substitution Glu - Ala at protein position 251 counting from the NH2-terminal acetyl serine residue. The protein abnormality caused by the amino acid substitution cannot explain the enzyme deficiency. Northern blot hybridization indicated that the PGK mRNA content of the patient's lymphoblastoid cells was only about 10% of that of normal. Nucleotide sequence analysis revealed the existence of two PGK mRNA components in the patient's cells. The major component corresponds to the normal PGK mRNA except for A - C change at nucleotide position 755 counting from adenine of the chain initiation codon. The minor component contains 5' region (52 bases) of intron 7 between exon 7 and exon 8. An inframe chain termination codon exists in the minor mRNA component, and the COOH-terminal half is expected to be deleted in the translation product. These results indicate that the low PGK activity in the patient's tissues is mainly due to retarded and aberrant pre-mRNA splicings caused by the change of the consensus 5' splice sequence AGgt to a nonconsensus sequence CGgt at the junction between exon 7 and intron 7 of the variant gene.

Deficiency of carnitine palmitoyltransferase type II (CPT II) is a clinically heterogeneous autosomal recessive disorder of lipid metabolism. The most common mutation in the CPT II gene is the S113L mutation, which substitutes leucine for serine at amino acid position 113. We studied an inbred family with three affected cousins with CPT II deficiency and found the S113L mutation to be present in a homozygous state in all three patients. Pedigree analysis traced the S113L mutation back to one common ancestor. Although the patients in this family have an identical genotype at the CPT II locus, their clinical picture ranges from asymptomatic to lethal.

Two patients with recurrent paroxysmal cardio-vascular symptoms are described. The first, an adult, suffered from syncopal events which did not respond to carbamazepine treatment and had a normal interictal EEG and ECG. The second, a child, presented with attacks of cyanosis, apnoea, and non-responsiveness in clusters, with normal interictal examinations. In both patients, prolonged simultaneous EEG and ECG monitoring demonstrated ictal bradycardia accompanied by paroxysmal discharges in the left temporal area.

Using positron emission tomography (PET), thirteen studies of regional brain glucose utilization were performed in 12 patients with postanoxic syndrome due to cardiac arrest. Investigations were carried out at least one month after brain anoxia. Seven subjects were in a persistent vegetative state. The others had regained normal consciousness with various residual neurological signs. When compared with normal values obtained in 16 normal, age-matched subjects, mean cerebral glucose metabolism was drastically decreased (+/- 50%) in vegetative cases, and to a lesser degree (+/- 25%) in conscious subjects. The most consistent regional alterations were observed in the parieto-occipital cortex (9 cases), the frontier between vertebral and carotid arterial territories. Other selective anomalies were found in the frontomesial junction (5 cases), the striatum (3 cases with dystonia), and the visual cortex (2 cases with cortical blindness). This study suggests that cerebral anoxia results in a global brain hypometabolism, which appears related to the vigilance state, as well as in regional disturbances preferentially located in arterial border zones. Although our findings remain to be confirmed in larger series, they suggest that PET provides a useful index of residual brain tissue function after anoxia and may assist in the monitoring of postanoxic encephalopathies.

We report a late onset form of polysaccharide myopathy with progressive limb girdle muscles weakness, without cardiomyopathy. Muscle biopsy showed a vacuolar myopathy in type 1 fibres. The PAS positive diastase resistant deposits were made of filamentous material at electron microscopy similar to long chain glycogen. Muscle glycogen levels and glycogen metabolism enzymes were normal. Numerous abnormal mitochondrial with paracrystalline inclusions were observed around the storage material. Twelve patients with polysaccharide amylopectin-like storage myopathy have previously been reported. This disease must be distinguished from other diseases with polysaccharide accumulation such as branching enzyme deficiency and some cases of phosphofructokinase deficiency. In other disorders, no deficient enzymes in the glycogen pathway was found. Some of them show systemic storage (Lafora disease, adult polyglucosan body disease). Corpora amylacea, Bielchowsky bodies and basophilic degeneration of the myocardium represent localised depositions. A few inclusions can also be observed in hypothyroid myopathy. In polysaccharide myopathy allosteric inactivation of phosphofructokinase by a mitochondrial dysfunction is considered by analogy with cases of polysaccharide storage related to phosphofructokinase deficiency.

In 1988, 40 experts (physicians, psychologists, social workers, lawyers, family association representatives...) coming from the E.E.C., the United States, Canada and Sweden met in Brussels to derive the guidelines for a minimal assessment of head injured people. This workshop led to a research contract between E.B.I.S. (European Brain Injury Society) and the E.E.C. Directorate for Science regarding a European evaluation document. The aims of the document are both clinical and scientific. Hence the document has to be simple, specific and feasible. The document has two parts: initial state and repeated follow-up. It ends with final comments and action plan. The first statistical data of the validation study concern mainly the link between initial severity of injury and final handicap, cognitive and behavioural troubles, familial and professional aspects of handicap.

Muscular glycogenosis is a disease resulting from genetical abnormalities altering an enzyme which is involved in glycogen metabolism. In addition to disorders of glycogenosis and glycolysis, there are other pathological processes such as alpha-glycosidase deficiency and diseases associated with abnormal polysaccharide structure. A short review of the various diseases with their particular features is reported.

Muscular glycogenosis is a disease resulting from genetic abnormalities altering an enzyme which is involved in glycogen metabolism. In addition to disorders of glycogenolysis and glycolysis, there are other pathological processes such as acid maltase (alpha-glucosidase) deficiency and diseases associated with abnormal glycogen structure. Glycolysis is the only metabolic pathway that can produce ATP in the absence of oxygen. It is then easy to understand that any disturbance in this energy pathway can result in dysfunction of the muscle machine and in a number of symptoms which are common to these abnormalities. An overall review of the various diseases know to exist on the glycogenolytic and glycolytic pathway will enable the reader to acquire a better knowledge of their particular features.

Antiepileptic drugs as well epilepsy itself are known to induce some cognitive impairment. Thirty-six epileptic patients under unchanged and reduced therapy conditions were followed from a clinical (seizures' evaluation, reaction times [RTs], memory tests) and neurophysiological (EEG, BAEPs, ERPs) point of view, weekly as inpatients (mean stay 8.9 weeks) and after 1 and 3 months as outpatients. This study showed on one hand no clear correlation between RTs and ERPs components, and on the other hand an improvement of the most complex RT after reduction of polytherapy or stabilization of seizures by the introduction of carbamazepine-CR in newly treated patients. These data suggest that in epileptic patients there exists a slowing of cognitive processes between the stimulus evaluation time and the motor response and that this step is improved when a reduced but efficient therapy is given.