Evolution of brain glucose metabolism with age in epileptic infants, children and adolescents.

During the first years of life, the human brain undergoes repetitive modifications in its anatomical, functional, and synaptic construction to reach the complex functional organization of the adult central nervous system. As an attempt to gain further insight in those maturation processes, the evolution of cerebral metabolic activity was investigated as a function of age in epileptic infants, children and adolescents. The regional cerebral metabolic rates for glucose (rCMRGlc) were measured with positron emission tomography (PET) in 60 patients aged from 6 weeks to 19 years, who were affected by complex partial epilepsy. They were scanned at rest, without premedication, in similar conditions to 20 epileptic adults and in 49 adult controls. The distribution of brain metabolic activity successively extended from sensorimotor areas and thalamus in epileptic newborns to temporo-parietal and frontal cortices and reached the adult pattern after 1 year of age. The measured rCMRGlc in the cerebral cortex, excluding the epileptic lesions, increased from low values in infants to a maximum between 4 and 12 years, before it declined to stabilize at the end of the second decade of life. Similar age-related changes in glucose metabolic rates were not observed in the adult groups. Despite the use of medications, the observed variations of rCMRGlc with age in young epileptic humans confirm those previously described in pediatric subjects. These metabolic changes are in full agreement with the current knowledge of the synaptic density evolution in the human brain.

Demyelinating hereditary neuropathies in children: a morphometric and ultrastructural study.

Twenty-three cases of hereditary demyelinating neuropathies are reported, 13 with different types of hereditary motor and sensory neuropathy (HMSN) and 9 with globoid cell or meta-chromatic leucodystrophies. Ultrastructural and morpho-metric studies showed some critical pathological features emphasizing: 1) the variability of the recessive forms of HMSN; 2) the morphological distinction between HMSN type I and type III; and 3) differences between these types of HMSN and other "onion bulb" neuropathies such as those found in leucodystrophies, which account for distinct underlying mechanisms.

Brain glucose utilisation in acquired childhood aphasia associated with a sylvian arachnoid cyst: recovery after shunting as demonstrated by PET.

Regional brain glucose utilisation was investigated with PET and fluorodeoxyglucose (FDG) in a case of epileptic aphasia (Landau-Kleffner syndrome) associated with a left sylvian arachnoid cyst. CT and MRI had failed to disclose any mass effect of the cyst on surrounding brain structures. Sequential metabolic measurements showed a comparable pronounced hypometabolism in cortical regions around the cyst, involving speech areas, and suggested mild but chronic compression of the developing brain. After placement of a cyst-peritoneal shunt system, significant metabolic improvement occurred in all cortical regions, especially the inferior frontal gyrus and the perisylvian area, with predominant residual deficit in the left superior temporal gyrus. These findings were correlated with a pronounced increase in word fluency and slower progress in verbal auditory comprehension. This report suggests that PET is able to evaluate the functional disturbances associated with expanding arachnoid cysts, and to follow the neurological improvement after drainage.

Effects of body position on sleep related disordered breathing in a patient with Steinert's disease.

Sudden changes in respiratory patterns observed during polysomnographic studies may suggest a positional form of SAHS (sleep apnea-hypopnea syndrome). We report the case of a 37-year-old patient with Steinert's disease with this form of SAHS. Breathing during sleep could be regularized by a simple positional control.

Nonprogressive type II hereditary sensory autonomic neuropathy: a homogeneous clinicopathologic entity.

Two different clinical subtypes were previously identified within hereditary sensory autonomic neuropathy (HSAN) type II: a stable congenital form and a progressive one. This paper discusses two clinicopathologic cases of nonprogressive HSAN type II with morphometric correlations. In addition, a retrospective literature search was carried out to locate other cases where an accurate histologic examination, including ultrastructural features, was available in order to relate clinical and pathologic aspects of the disease. The combined data support the individualization of this neuropathic form as a homogeneous disease, as has been suggested during the last century and underline the clinical importance of this concept for the prognosis and investigation of sensory, auditory, autonomic, and motor functions in children with sensory neuropathies.

A disorder of axonal development, necrotizing myopathy, cardiomyopathy, and cataracts: a new familial disease.

We report severe congenital encephalopathy and profound hypotonia associated with necrotizing myopathy, cardiomyopathy, and cataracts in 3 infants, including 2 sisters. Brain scans suggested agenesis of the corpus callosum. Neuropathological findings consisted of severe atrophy of the corpus callosum (not the usual agenesis with longitudinal callosal bundles), atrophy of the white matter, and absence of pyramidal tracts in the medulla. Multiple axonal swellings were present in the white matter and in Purkinje cells. Except for the corpus subthalamicum, gray matter structures were preserved. These findings are considered to be the expression of a primary disorder of axonal development leading to a reduction in interneuronal synaptic contacts. It is suggested that the anomaly may be due to an extension of the normal phenomenon of axonal elimination, related to a primary defect of the axonal cytoskeleton. The concept of a primary axonal disorder may also apply to other, mostly familial, conditions with progressive atrophy of the cerebral white matter and corpus callosum.

Distal infantile spinal muscular atrophy associated with paralysis of the diaphragm: a variant of infantile spinal muscular atrophy.

We report the clinical, electrophysiological, and morphological observations of five infants with an unusual form of spinal muscular atrophy (SMA). In these infants muscular weakness and atrophy were initially restricted to the distal limbs and this pattern was associated with paralysis of the diaphragm. The difference between the clinical manifestations of this syndrome and the classical form of infantile spinal muscular atrophy (SMA type 1) as well as other congenital hereditary neuropathies is discussed.

Familial dysautonomia in a non-Jewish girl, with histological evidence of progression in the sural nerve.

A case of typical familial dysautonomia (HSN, type III) in a non-Jewish girl is reported. The number of unmyelinated fibres was found to be reduced and sural nerve biopsy showed evidence of past axonal degeneration. There was also marked endoneurial fibrosis and a lack of the largest myelinated fibres. Signs of histological progression not yet described in the sural nerve and other clinical and morphological features could be explained by different penetrance degrees of the disease.

Morphometric studies of normal sural nerves in children.

Quantitative histologic studies of biopsies of normal sural nerves were performed on nine children aged 4 days to 17 years. Stereologic computerized procedures were used to determine total endoneurial area, size distribution and number of myelinated, unmyelinated fibers and Schwann cell nuclei per nerve and per square millimeter, and the ratio of myelin thickness to axonal diameter. There was an inverse linear relationship between the number of myelinated fibers per square millimeter and increasing age. A stronger correlation was found between the number of Schwann cell nuclei per nerve (P less than 0.01) and per square millimeter (P less than 0.001) and the logarithm of age. The slope of myelin thickness/axon diameter regression lines (P less than 0.001) changed with age in linear relationship (correlation coefficient: P less than 0.001). There were no age-dependent changes in the number and density of unmyelinated fibers, but the number of unmyelinated axons per Schwann cell subunit decreased with age. Size distribution histograms for myelinated fibers showed a unimodal profile in the newborn. A second peak at 6-7 micron appeared at age 3 months, shifting progressively to 9-11 micron at 14 years. The distribution of unmyelinated fibers was unimodal, with a peak around 0.8 micron, irrespective of age. There were marked individual variations in endoneurial area.

Congenital neuropathy with prevailing axonal changes. A clinical and histological report.

A case of congenital neuropathy associated with an unclassified chronic brain disorder is described. Morphological findings differ from the reported congenital neuropathies where primary myelin change have been usually found. In contrast, sural nerve biopsy showed marked signs of active or past axonal degeneration; at the teasing and morphometric analysis there was also some evidence of segmental demyelination. Atypical onion bulb formations (Evans and Murray type) and a very poor demyelination activity stressed the prevailing axonal involvement with possibly secondary segmental demyelination.

Hereditary motor and sensory neuropathies (HMSN). Retinal involvement and ERG alterations.

Hereditary motor and sensory neuropathies (HMSN) is a complex group of diseases, mainly of unknown etiology. In 1975, Dyck proposed a classification based essentially on the type of hereditary transmission, nerve conduction velocity and histologic aspect of small nerve biopsies. Hagberg & Westerberg (1983) proposed a new classification. The association between HMSN and retinitis pigmentosa or optic atrophy is sometimes described. Analysing the reported cases, it became evident that the neurologic disease was not clearly defined and the ophthalmologic examination rarely made. In most cases, ERG data were lacking. The authors studied the ocular involvement with ERG in nine patients. The ERG was low in only one patient. Their study suggests that ERG may be a useful approach for the differential diagnosis in some forms of HMSN.

Abnormalities of muscle fibers in maple syrup urine disease.

Muscle fiber abnormalities are described in three cases of neonatal maple syrup disease. There were important variations in fiber diameters. Lesions consisted in focal or diffuse destruction of myofibrils. In view of recent biochemical and clinical data, a direct relation between elevated branched-chain amino acid levels and the muscular abnormalities seems improbable.

[Sultopride, treatment of choice for psychomotor agitation in severe encephalopathy. 33 cases in a neuropediatric milieu]. / Le sultopride, traitement de choix de l'agitation psycho-motrice chez l'encéphalopathe profond. A propos de 33 cas en milieu neuropédiatrique.

Thirty-three patients showing a definite group of symptoms including chiefly agitation or self-mutilation often dramatic have been treated with sultopride at doses ranging from 7 to 50 mg/kg/day at the Institut Médico-Pédagogique de l'Enfant-Jésus at Ciney. Forty-eight per cent showing this particular symptoms have been cured or greatly improved with sultopride. In 36% the response was incomplete in that it appeared to be identical with sultopride solely or with the previous medications. An opposite result has been noted in 16% only. Side-effects consisted in extra-pyramidal symptoms, drowsiness and digestive disorders. This study leads to the conclusion that sultopride can be considered as the most efficient therapeutical approach to the management of agitation or self-mutilation in severe encephalopathy.

Congenital hypomyelination polyneuropathy. Pathological findings compared with polyneuropathies starting later in life.

Biopsies from patients with congenital hypomyelination polyneuropathy (Group I) and with late infantile (Group II) and juvenile (Group III) forms of hereditary motor and sensory neuropathy (HMSN) type III were compared, using morphometric methods and ultrastructural analysis. In congenital polyneuropathies (Group I), myelin sheaths were practically absent and onion bulbs, essentially made of multiple laminae of double layered basement membrane, surrounded every axon in the size range of normal myelinated axons. The number of these axons was markedly reduced. Serial sectioning of an isolated fibre showed that the territory of successive clusters of Schwann cell nuclei was considerably reduced when compared with the biopsies in Groups II and III and with normal controls. Fibres without myelin surrounded by multiple layers of basement membrane represented between 25 and 50 per cent of the entire population of fibres in the size range of myelinated fibres in Group II and were practically absent in Group III. The number of "myelinated' fibres (that is, fibres with myelin, and amyelinate or demyelinated fibres) was normal in Groups II and III. Although there is no indication that congenital hypomyelination onion bulb polyneuropathy is a separate entity, it can be considered as a subtype of Dejerine-Sottas disease (HMSN type III). In this disease there is a gradient of severity both in clinical expression and in the disorder of Schwann cells. In the severe congenital form, all Schwann cells are affected and are incapable of forming myelin. The diminution of the number of nerve fibres in the "myelinated' fibre size range, whether or not related to a prenatal involvement of Schwann cells, is another expression of the gravity of this form. The proportion of amyelinate fibres, i.e. with Schwann cells incapable of forming myelin, becomes less in the more benign late infantile and juvenile forms of the disease in which a process of demyelination and remyelination takes place. The literature on the congenital neuropathies, a heterogeneous assembly of diseases, is reviewed.

[Mononeuritis multiplex in a case of primary macroglobulinemia (author's transl)]. / Mononévrite multiple dans un cas de macroglobulinémie de Waldenström.

A case of Waldenström's disease with peripheral nerve involvement resembling mononeuritis multiplex is described. The various etiopathogenic mechanisms generally cited in connection with peripheral neuropathies observed in cases of macroglobulinemia, most often of the polyneuritic type, are discussed in turn : nerve infiltration by lymphocytes, intervention of an immunologic mechanism through the agency of paraprotein links with amyloidosis. However, the reported case differs from habitual cases on account of the asymmetry of the nerve involvement and the discovery of vasculitic lesions on muscle biopsy. The hypothesis of ischemic neuropathy associated with serum hyperviscosity is proposed and confirmed by the clinical improvement and reduction of macroglobulin obtained by repeated plasma exchanges and administration of Chlorambucil.

Aqueductal stenosis in X-linked hydrocephalus: a secondary phenomenon?

Two cases of x-linked hydrocephalus are reported. One underwent postmortem examination: serial sections of the brain stem failed to show stenosis of the aqueduct, the mean and minimal cross-sectional areas of which were normal. However, there were some morphological changes which were compatible with a mechanical compression of the brain stem. It is postulated that in the Bickers and Adams syndrome of x-linked hereditary hydrocephalus the primary defect is a communicating hydrocephalus leading usually, but not always, to aqueductal stenosis. The importance of electrophysiological investigations for the correct diagnosis of the characteristic clasped-thumb deformity is also indicated.

Uncommon case of type II glycogenosis.

The authors report an uncommon case of type II glycogenosis. An 8-year-old boy developed a slow progressive myopathy. Biopsy of skeletal muscle showed scarce lesions under the optic microscope but in 50% of the fibers the presence of vacuoles filled with glycogen under the electron microscope. Ultrastructural analysis of fibroblasts in culture showed numerous vacuoles filled with glycogen, characteristic of type II glycogenosis. Enzymatic analysis revealed that acid-alpha-glucosidase activity was normal in muscle tissues but deeply deficient in leukocytes and fibroblasts in culture. This is, as far as we know, the first case with such a discrepancy in the distribution of the enzymatic activity, and it underlines the necessity of investigating several tissues in atypical cases.