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Three young children with the Schilder variant of multiple sclerosis were seen within a 3-year period at our hospital. The diagnosis was made on the basis of the typical (but not pathognomonic) clinical and magnetic resonance imaging (MRI) findings after eliminating other demyelinating and post-infectious disorders of the central nervous system. All three patients were treated with prednisone (2 mg/kg/day), which resulted in complete recovery in one patient and mild and moderate residual hemiparesis in the two other patients, respectively. Corticosteroid therapy was continued until the patients' neurologic condition normalized or no further clinical improvement occurred. No relapses were seen after discontinuation of corticosteroid treatment. Computed tomographic (CT) scan and MRI findings after completion of corticosteroid therapy were equally dramatic and corresponded with the clinical improvement. A strongly positive tuberculin skin test and a positive history of contact with adult tuberculosis in two of our patients raise the possibility of a connection between tuberculosis and Schilder's disease.

A previously healthy and normally developed 17-year-old young female presented with a sudden onset of focal motor seizure status that proved to be refractory to anticonvulsive treatment. Severe encephalopathy with visual impairment leading to blindness, mental deterioration, and predominantly left spastic tetraparesis developed progressively. Hepatic disease evolved 4 months after onset of the first symptoms and led to death in hepatic failure 1 month later. Diagnostic studies revealed an elevated protein and lactate in the cerebrospinal fluid, slow-wave and intermittently continuous spike-wave activity in the EEG, and a complex i.v. (cytochrome-C oxidase) deficiency in the muscle biopsy. MRI scans revealed signal abnormalities in the occipital lobe, thalamus, and basal ganglia only after 3 months. Histopathological findings in liver biopsy and in postmortem brain examination displaying widespread predominantly right cortical spongiosis, neuronal loss and astrocytosis were consistent with the clinically suspected diagnosis of progressive neuronal degeneration of childhood with liver disease (PNDC) or Alpers Huttenlocher disease. This rare disorder of unknown origin is usually seen in infants and young children and is rarely reported in adolescence.

Introduction: Lesions in the hippocampus of some epileptic patients were first described one hundred and seventy years ago. Since then our knowledge of the relationship between epileptic seizures and temporal lobe lesions has greatly improved., Development: The aim of this paper is to systematize the symptomatology of the hippocampus and amygdala seizures. These seizures may have a great number of different clinical features: special 'loss' or 'impairment of consciousness', epileptic automatisms and autonomic changes. Moreover, at the beginning of seizures some patients have reported experiences having subjective qualities similar to those experienced in everyday life. P Gloor named them 'experiential phenomena' and subdivided them into affective (eg: fear), perceptual (eg: visual hallucinations) and mnemonic (eg: 'déjà vu' illusion)., Conclusion: It is very important to know the contribution of the hippocampus and the amygdala to the symptomatology of temporal lobe seizures due to the progress of MRI diagnostic possibilities that are improving the surgical outcome.

Objective: To review the main anatomical, histological, physiopathological and aetiological data characteristic of the mesial temporal sclerosis syndrome (ETM). Development. The typical histological findings in ETM are: 1) A specific pattern of loss of neurone density which includes so-called endfolium sclerosis (considered to be a specific pathological entity always found in ETM), and which is usually accompanied by neurone loss in other hippocampal and extra-hippocampal regions. The CA2 region is never affected. 2) Phenomenon of 'mossy fibers sprouting' which are granulosa cells which form two types of synapses: with the the 'basket cells' which are inhibitory interneurones and with the dendrites of granulosa or pyramidal cells of the CA1, CA2 and CA3 Ammon horn cells which are excitatory cells., Conclusions: Probably these organic changes are both the cause and effect of repeated convulsions. Participation in this self-perpetuating circuit may be due to recognised risk factors of ETM (head injury, CNS infections, febrile convulsions in early stages of development) which cause, first of all, death of neurones of the dentate gyrus cells followed by reduced inhibitory activity of the 'basket' cells and therefore sustained hyper-excitability of the pyramidal cells (especially in the CA3 regions), which are responsible for complex partial seizures and massive liberation of glutamic acid. Glutamic acid can cause death of neurones of the granulosa cells of the dentate gyrus, thus closing the circuit. This hypothesis explains the progressive nature of the ETM syndrome. When there is pathology of the cortical structure there is another access via to this circuit--by means of cortical discharges of the so-called perforant pathway which stimulates activity of the pyramidal cells and sets off the chain of events described above. This hypothesis explains the so-called 'dual pathology'.

Pelizaeus-Merzbacher disease (PMD) is a degenerative leukodystrophy of the central nervous system resulting in progressive spasticity and neurologic deterioration. Seitelberger (13) divided this rare disease into six types. Five patients with the type 1 and two patients with the type II form of PMD have been treated at the Children's Hospital of Eastern Ontario. Our study sought to identify the orthopaedic manifestations of PMD and to develop a common orthopaedic profile for these patients. All children with types I and II PMD developed spastic quadriparesis, truncal hypotonia, thoracolumbar scoliosis, soft-tissue contractures of the adductors and hamstrings, osteopenia, bilateral coxa valga, and associated hip dislocation.

We report here a family with leukodystrophy clinical features of which are characterized as adult onset, probably autosomal dominant inheritance, hyperreflexia, cerebellar ataxia, autonomic dysfunction and no peripheral nerve involvement. T2-weighted brain MRI revealed diffuse high signal areas in the cerebral white matter. The disorder in our subjects can be distinguished from most leukodystrophies in terms of genetic inheritance, clinical manifestations and laboratory data. Our family is quite similar to the kindred which Eldridge et al. described in 1984 as "hereditary adult-onset leukodystrophy simulating chronic progressive multiple sclerosis". Our family is the third report of this type of leukodystrophy and the first among non-Irish/Scottish family.

Two unrelated and previously healthy girls, aged 17 and 18, presented with a subacute encephalopathy, visual and sensory symptoms and signs, and prominent seizures that were difficult to control. Brain MRI showed lesions (high signal on T2 weighted images) in the occipital lobes and thalamus; EEG showed slow wave activity with superimposed polyspikes. Inexorable downhill progression led to death in hepatic failure within eight months of onset. Histopathological findings in both patients ((a) chronic hepatitis with prominent bile duct proliferation, fatty change, and fibrosis; (b) in the brain a patchy destruction of the cerebral cortex, predominantly involving striate cortex) were characteristic of progressive neuronal degeneration of childhood with liver disease--Alpers-Huttenlocher syndrome--a rare autosomal recessive disorder usually seen in infants and young children.

The surgical treatment of chronic epilepsies is increasing rapidly. A review of 279 surgical specimens of patients with chronic pharmaco-resistant epilepsies from the University of Bonn Medical Centre revealed specific histopathological findings in 89% of all well-preserved specimens. The most frequent focal lesions were low-grade brain tumours such as gangliogliomas, pilocytic astrocytomas and dysembryoplastic neuroepithelial tumours. Other common findings were glioneuronal and vascular malformations and Ammon's horn sclerosis. This suggests that chronic intractable epilepsies are frequently caused by structural alterations.

A rare case of myelinoclastic diffuse sclerosis (MDS), occasionally referred to as Schilder's disease, is reported in a child with Turner's syndrome. The child originally presented with a 3-week history of nausea, vomiting and frontal headaches. Magnetic resonance imaging showed a large, contrast-enhancing, right frontal lobe mass which was ultimately resected uneventfully. Complete laboratory investigations and pathological evaluation of the resected specimen verified the case to be MDS. The clinical presentation, laboratory evaluation, imaging characteristics and diagnosis are discussed in this review of the disease. The importance of including demyelinating diseases in the differential diagnosis for newly discovered mass lesions in the pediatric population is underscored by this case.

We performed a retrospective study on 7 children in whom the auditory brainstem responses (ABR) showed absence or significantly poor formation of waves II-V. Two patients had degenerative diseases that affected the brains diffusely. In the remaining 5 patients, the symptoms consisted of action tremor (3 patients) or pyramidal signs (2 patients). There were neither clinical signs nor neuroimaging findings suggesting brainstem involvements. The evolutional changes of the ABRs had a good correlation with the clinical course. Absence or significantly poor formation of waves II-V of ABR occurs in various diseases and may not necessarily reflect severe organic brain lesions.

Objective: To study the clinical and pathological features of a kindred with an adult-onset autosomal dominant leukodystrophy., Patients: Five symptomatic and nine asymptomatic at-risk members of the kindred., Interventions: Subjects underwent detailed histories and general and neurologic examinations. Further evaluation included electroencephalography, evoked potentials, electromyography, autonomic testing, and analysis of serum, urine, and cerebrospinal fluid. One patient underwent sural nerve biopsy and analysis. Another, previously studied patient, underwent a limited autopsy., Results: Cerebellar and pyramidal dysfunction began in the fourth and fifth decades of life; subtle autonomic symptoms were often present years earlier. Frontal lobe dysfunction and abnormalities of the central visual pathways were mild and of late onset. Sensorineural hearing loss was common. The peripheral nervous system was spared. Autopsy results of one patient revealed severe degeneration of the white matter at all levels of the neuraxis, but most prominent in the frontoparietal and cerebellar regions, with sparing of the subcortical U fibers. Histological and ultrastructural examinations failed to show evidence of a specific pathogenetic mechanism or etiology., Conclusion: This disorder seems to be a distinct type of hereditary leukodystrophy, but its exact nature remains unknown.

Congenital muscular dystrophies (CMD) are heterogenous in clinical and pathologic manifestations. The "pure" classical form includes cases without severe impairment of intellectual development (Type 1), and cases with normal or subnormal IQ which show white matter hypodensity on CT scan examination. This latter group is sometimes called the "occidental type cerebro-muscular dystrophy" (OCMD). In this study we report clinical and pathologic findings in 38 cases with pure CMD. Eighteen of them were classified as Type 1 and 20 as OCMD, following the neuroradiological work-up. Statistical analysis between the two groups were done for: age range, consanguinity, multiple joint contractures, maximal motor capacity, facial involvement, high CK, endomysial fibrosis, adiposis, fiber atrophy and necrosis. CK was significantly higher in the OCMD group. Though not statistically significant, multiple joint contractures and muscle fiber necrosis were seen in more OCMD patients. These parameters denoted severity. The results of electrophysiological tests did not show any statistical differences. In pure CMDs there is evidence for overlap between the two sub-groups. OCMD cases may tend to run a more severe course in the presence of significantly higher CK levels.

Four unrelated children were thought to have valproate-associated hepatotoxicity. They presented with recurrent partial secondarily generalized status epilepticus and epilepsia partialis continua followed by mental and motor regression. Despite treatment with multiple antiepileptic medications, they continued to have seizures. After initiation of valproic acid (VPA), all 4 manifested liver failure within 3 months. Two of these children each had 1 sibling who was not exposed to VPA, but who developed the same clinical picture including liver failure. At the time of autopsy, all 6 children had similar neuropathological findings with focal areas of spongiosis and neuronal loss, diffuse gliosis, and Alzheimer type II cells. One VPA-treated patient underwent a successful liver transplantation only to die from relentlessly progressive neurological deterioration. We propose that many of the reported patients with VPA-associated hepatotoxicity represent undiagnosed patients with early childhood hepatocerebral degeneration, the Huttenlocher variant of Alpers' syndrome. This disease manifests by obstinate partial seizures, recurrent partial secondarily generalized status epilepticus, epilepsia partialis continua, psychomotor deterioration, and hepatic dysfunction that is exacerbated by VPA administration. The accelerated demise from liver failure in the nontransplanted patients before the central nervous system pathology fully evolves makes the diagnosis of this rare condition difficult. The occurrence of disease in the unexposed siblings suggests recessive inheritance.

The case of Alexander's fibrinoidal leucodystrophy that was presented below is an exemplar of extremely rare degenerative disease of the CNS. On the grounds of the clinical course of the disease it seems that our case can be reckoned as an early childhood form of Alexander's disease. An interesting difference that pays attention is the marked hydrocephalus. In the most cases of Alexander's disease the volume of ventricular system is normal however most of authors expresses that it sometimes can be slightly and insignificantly enlarged.

We report a case of rapidly progressive cerebral demyelinating disease in a previously healthy 40-year-old woman. This case satisfies the diagnostic criteria for myelinoclastic diffuse sclerosis (MDS), but is unusual in the age of onset. This is the 1st case of MDS in an adult with full documentation of clinical, biochemical, radiographic, and pathologic features.

Adrenoleukodystrophy, a sex-linked peroxisomal disorder that results in the impaired oxidation of long-chain saturated fatty acids and causes neurologic impairment, is a rare cause of Addison's disease in children. Adrenomyeloneuropathy is the name given to a biochemically identical but milder and more slowly progressive variant of adrenoleukodystrophy that affects young adults, in whom adrenal insufficiency may long precede nervous system dysfunction. The transmission of adrenomyeloneuropathy, like that of most cases of adrenoleukodystrophy, is sex-linked. Because of a preponderance of male patients among a group of patients with the onset of adrenal failure in childhood, we questioned whether this condition might be the initial manifestation of adrenomyeloneuropathy. We therefore measured the plasma concentrations of very-long-chain saturated fatty acids in eight patients with adrenal insufficiency; of these, five had elevated plasma hexacosanoic acid concentrations (range, 2.42 to 6.43 mumol per liter; mean normal level [+/- SD], 0.83 +/- 0.45), confirming the presence of adrenomyeloneuropathy. Magnetic resonance imaging showed clear evidence of brain involvement in all five patients. Reexploration of the family histories revealed additional missed cases. We conclude that the possibility of adrenomyeloneuropathy should be considered in any boy with Addison's disease.

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLO-SL) is a rare hereditary disease affecting both brain and bones. Skeletal symptoms begin in early adulthood and neuropsychiatric symptoms at approximately age 30. Progressive dementia associated with an accentuated frontal lobe syndrome handicaps the patients. The author describes inadequate psychosocial reactions of the spouses of 21 Finnish PLO-SL patients. The reactions included rejection and divorce in 8 cases and rejection without divorce in 1 case. Jealousy, violence, and alcoholism were common in male spouses. The author suggests that some of the spouses' negative psychosocial reactions may be lessened if the family is informed early about the nature of the disorder.

Cerebral sclerosis and Addison disease were observed at age 14 years in a previously healthy sister of an affected boy. Clinical findings and family history established the diagnosis of X-linked adrenoleukodystrophy, which is normallly confined to males. The affected female has a normal karyotype; both X chromosomes are morphologically inconspicuous. Thus, this patient may be the first documented example of clinically manifest adrenoleukodystrophy in a heterozygote, which supports our previous conclusion that this X-linked locus is subject to inactivation.

A sporadic case of sudanophilic leukodystrophy of the simple form (Peiffer) was reported. The patient was three-year-old girl who had suffered from progressive developmental retardation and neurological disorders such as ataxia, cortical blindness and spastic paralysis of the extremities for eighteen months after she had showed normal development till one and a half years old and died from respiratory insufficiency. On admission, computerized tomogram scan demonstrated diffuse low density lesions of the cerebral white matter extending subsequently to the subcortical white matter. Examination of cerebrospinal fluid revealed only slight increase of protein. Lysosomal enzyme activities such as arylsulfatase and beta-galactosidase in the white blood cells were normal except for distinctly low activity of a-mannosidase without any clinical symptoms suggesting a-mannosidase deficiency. Amino acids in blood were normal. The brain weighed 900 gm. On the coronal sections most part of the cerebral white matter was so strongly degenerated and disappeared that the lateral ventricular structure was not discernible. Histologically, a diffuse and symmetrical demylination, loss of axons including U fibers and moderate gliosis were observed in the residual white matter in the cerebrum and pons. There was no inflammatory cells and metachromatic substances. Large amount of sudanophilic droplets showing polarizing cross and needle like crystals were found in the intra- and/or extracytoplasm of macrophages. Demyelinated lesions with little tissue reaction were also found in the cerebellum, medulla oblongata and in pyramidal tracts through midbrain to cervical spinal cord. There were slight loss of neurons and moderate astrocytosis in the cerebral cortex and basal ganglia. There were no Rosenthal fibers and no sparing of islets of myelin.(ABSTRACT TRUNCATED AT 250 WORDS)

This article presents the clinical and pathological history of a 10-year-old boy with adrenoleukodystrophy as well as a tabular survey of 17 additional cases of which the necropsy records were published in the literature. So far as the case of adrenoleukodystrophy directly observed by the authors themselves is concerned, commencement of the disease was in the seventh year of life, with symptoms of Addison's disease and diffuse inflammatory cerebral sclerosis being observed at about the same time. The cerebral disease manifested itself as a progressive pseudobulbar and pyramidal tract symptomatology and as a progressive cerebral psychosyndrome reminiscent of an endocrinal psychosyndrome. Morphologically, the adrenoleukodystrophy was characterized by severe dystrophy of the cortex of the suprarenal gland and the brain are considered the points of action of a still unknown noxa.e suprarenal gland as well as by extensive sudanophilic processes of decomposition in the cerebromedullary substance, putamen, pallidum, and thalamus. Striated cells and cytoplasmic filamentous inclusions observed in the brain and suprarenal glands in a number of cases reported in the literature were not found by the present authors. The cortex of th

The case of a 14-year-old boy with "diffuse cerebral sclerosis", preceded by signs of primary adrenal cortical insufficiency for 7 years with familiar antecedents is reported. This disorder, named adrenoleukodystrophy, has a sex-lin(ed recessive inheritance. The clinical picture is characterized by mental deterioration, gait disturbances, visual impairment, associated with primary adrenal cortical insufficiency. Confirming the data from literature, in our case the pathological study showed myelin degeneration and diffuse gliosis in the cerebral white matter, with no involvement of subcortical fibers. Inflammatory cells are common, and have a perivascular distribution. In the fasciculata and reticular zones of the adrenal gland, "baloon-shaped" cells are evident, most of them presenting a vacuolized and striated cytoplasm. Similar lipidic inclusions have been found in the Schwann cells of the periheral nerves and testis. The findings are compared with twenty cases from the literature.

A 51-year-old woman became blind from involvement of both occipital lobes with a confluent lesion demonstrated by computed tomographic scan. Biopsy showed demyelination consistent with Schilder's 1912 variant of diffuse sclerosis. No cytoplasmic inclusions were found on electron microscopy.

A case of a complete Kearns-Sayre syndrome, of early onset, associated with cerebral and cerebellar leukodystrophy and basal ganglia calcification is reported. The clinical, neurophysiological and morphological findings suggest multisystem involvement.

We report on a case of a 30-month-old child who presented with a clinical syndrome compatible with leucodystrophy and in whom neuropathological features of both Pelizaeus-Merzbacher disease and subacute necrotizing encephalopathy were shown. The significance of the neuropathological findings is discussed in the light of a possible coexistence of both diseases which has not previously been reported.

After 5 years of cyclic vomiting an 8 year old boy was presented with coma and hyponatremia. ACTH and renin plasma concentrations were elevated, cortisol concentrations did not rise after ACTH-stimulation. Behavioural abnormalities including secondary enuresis and dysarthria drew attention to the possibility of an association of adrenal insufficiency with leucodystrophy. NMR tomography of the brain showed symmetrical demyelinated areas in the parieto-occipital regions. Very long chain fatty acids were elevated. The mother showed discrete neurological symptoms and elevated long chain fatty acids. Cyclic vomiting might suggest adrenoleukodystrophy.

Diminished libido, impotence and infertility have been detected in 5 of 6 men with adreno-leukodystrophy, a universally fatal disease. The importance of the clinical recognition of these patients and their separation from others with relatively innocuous causes of testicular dysfunction are discussed.

Five cases of Schilder's disease with adrenal insufficiency are reported (adrenoleucodystrophy) one of whom has a first cousin with Addison's disease. The principle clinical features of the disorder are outlined and particularly the great variability in the severity of the adrenal insufficiency. The current understanding of this disorder is reviewed.

The results of neurochemical examination of brain tissue derived from 2 cases of adreno-leukodystrophy have been presented. Both white and grey matter contained suadanophilic material. Although free fatty acid was also present, cholesteryl ester accounted for the bulk of the sudanophilic material. Total cholesterol, galactolipid and phospholipid content was reduced in both white and grey matter. The lipid loss was particularly severe from white matter indicative of considerable demyelination. Cholesterol was found to be the only major sterol present in white or grey matter. Subcellular fractionation of the diseased white matter resulted in myelin and two related fractions, one of which was very fatty and was rich in steryl ester. Morphological examination of myelin indicated loosely-packed lamellae. All of 3 fractions had adenosine 2',6'-cyclic nucleotide-3'-phosphohydrolase activity. Myein and the fraction not rich in cholesteryl ester had discernable basic protein bands when examined by polyacrylamide gel electrophoresis. Analysis of the fatty acid composition of choline and ethanolamine glycerophospholipids indicated a general increase of saturated fatty acids, relative to control values and a decrease in long-chain fatty acids. Examination of sphingomyelin fatty acids also demonstrated a loss of long-chain fatty acids. The fatty acid composition of the cholesteryl esters from white and grey matter differed. The findings indicate generalized damage to the brain, both of white and grey matter, with the damage to the white matter being much more severe. No abnormal sterol or other lipid was isolated.

Adrenoleukodystrophy (Schilder-Addison's disease) is a sex-linked recessive syndrome usually observed in children, associating neurological disorders and Addison's disease. Its outcome is death after a few years. The authors report the case of a man in whom a spastic paraparesis and a mental deterioration appeared at the age of 30 years. A biological adrenal deficiency was found: plasma cortisol and urinary 17-hydroxy-steroids and 17-ketosteroids failed to increase after synacthen stimulation; plasma ACTH level was above normal. Since two nephews of the patient suffered from adrenoleukodystrophy, the same disease is likely in the reported patient.

An unusual case of neuraxonal dystrophy in a 24-year-old man has been described. The condition started at the age of 10 years with motoric disturbances, later the patient developed spastic quadruparesis and deep dementia in last two years. The disease appears to be of genetic origin. The morphology is characterized by the generalized presence of spheroids in the central nervous system. Additional findings of status pigmentosus and dysmyelinisatus do not exclude the case from being labelled neuraxonal dystrophy.

The patients with mesofrontal epilepsy (ME) were under this study. Idiopathic atrophic events in the cerebral cortex are the major etiology factors. ME seizures develop as a sequence of epileptic discharges in the supplementary motor zone (SMZ) and have some characteristic features as tonic convulsions in one or both hands with concomitant adversive spells, short seizures with prompt after-seizure orientation and the proprioceptive afferent signals being capable of provoking the spells. Such peculiarities of ME manifestations depend on both structural-functional SMZ organization and the state of epileptic focus trigger channel. The whole brain functional state is also of major importance.

The results of a larger study of psychopathological disorders in relation to pre-operative and post-operative examined heart surgery patients, where the heart-lung machine was used, will be shown, to begin with, on 20 patients. Pre-operative examination showed quite clearly, among other things, that patients suppress obvious operation risks. General mental disorders were seen post-operative in 4 patients, and these were diagnosed as organic psychosis. A comparison between psychotic and other patients shows, among other things, that somatic predictors such as cerebral sclerosis and atrophy, or a cerebral trauma tend to promote post-operative psychosis. A releasing cause could be a cerebral hypoxia brought about by the extracorporeal blood circulation. In our opinion psychological factors can only be found in the contents of psychosis.