Association of high-sensitivity C-reactive protein with susceptibility to Schizophrenia in Tunisian population.

The pathogenic mechanisms underlying Schizophrenia (SZ), one of the most frequent mental disorders, are complex and poorly understood. Several evidences suggest that inflammatory processes may underpin some of its neurobiological correlates. The aim of this study was: (i) to analyze the potential association between circulating levels of the C-reactive protein (CRP), a crucial inflammatory marker, and Schizophrenia in Tunisian patients and healthy controls (HC) cohorts; (ii) to investigate the genetic diversity of three CRP variants (rs1417938, rs1130864 and rs1205) and; (iii) to analyze a potential relationship between expression and genetic data and clinical and socio demographical characteristics. CRP polymorphisms were exanimated for 155 patients and 203 HC by taqMan5'-nuclease. High-sensitivity CRP (hs-CRP) serum level was measured in 128 clinically stable out-patient SZ patients and 63 HC subjects via an automated biochemical analyzer. We found that hs-CRP levels were significantly higher in SZ patients as compared to HC. No significant differences were found when the proportions of CRP variants were compared in patients and HC. Further analysis according to clinical and socio demographical characteristics revealed a positive association with age and hypertension. Our data on an original Tunisian sample confirm the previous finding in others population groups.

Wilson's disease: appreciable improvement of sub-cortical white matter abnormalities after copper chelating treatment: five years follow-up.

Severe sub-cortical white matter abnormalities are unusual features in Wilson's disease and are reported to be poorly or not responsive to copper chelating therapy or to be worsened by it. We report on a 12-year-old boy with Wilson's disease and extensive sub-cortical white matter involvement. After five years of copper chelating therapy, an appreciable improvement of these lesions was obtained. The physiopathology of these unusual cerebral white matter abnormalities is discussed.

L-2-hydroxyglutaric aciduria: clinical and molecular study in three Tunisian families. Identification of a new mutation and inter-familial phenotype variability.

We report clinical and molecular studies in three unrelated Tunisian families containing seven patients with L2HGA. Although the age of onset is similar in all these patients at nearly 6 years, they progressively developed peculiar clinical phenotypes different from family to family. The three patients of family 1 showed mental retardation, epilepsy, cerebellar ataxia and pyramidal and pseudobulbar syndromes. The two patients of family 2 showed mental retardation and parkinsonism especially extrapyramidal stiffness, dystonia and myoclonus. The two patients of family 3 showed an intermediate phenotype; they share some clinical signs of the patients of family 1 (epilepsy, pyramidal and extrapyramidal syndromes) and some clinical signs of the patients of family 2 (extrapyramidal stiffness and dystonia). Molecular study identified a novel homozygous c.185C>A, p.A62D mutation on the L2HGDH gene in families 1 and 3 and the already known homozygous c.241A>G, p.K81E mutation in family 2. We suppose that the type of mutation in the L2HGDH gene does not play a complete role in the inter-familial phenotype variability. Disturbance of other unknown metabolic pathways related to L2HGA may contribute to this phenomenon.

Osteoma of the calvaria in L-2-hydroxyglutaric aciduria.

L-2-Hydroxyglutaric aciduria (L-2-OHGA) is a rare autosomal recessive neurometabolic disease linked to chromosome 14q21.1 and is caused by mutations in the gene that most likely encodes L: -2-hydroxyglutarate dehydrogenase, which normally catalyses L: -2-hydroxyglutarate to alpha-ketoglutarate. It is characterized by progressive mental deterioration, pyramidal and cerebellar syndromes, macrocephaly and marked polycystic white-matter degeneration mainly involving frontal lobes. Brain tumours of variable nature have frequently been observed in L-2-OHGA. We report a patient affected by this disease who at the age of 20 years developed a bone tumour involving the right frontal region of the calvaria. He had first presented at the age of 10 years with psychomotor delay, clumsy gait and moderate mental impairment. Examination showed macrocephaly, cerebellar ataxia and quadripyramidal syndrome. Brain MRI showed low signal intensities on T1-weighted images and high signal intensities on T2-weighted images in cerebral subcortical white matter. Serum and urinary amino acid assay was normal. Urinary 2-hydroxyglutaric acid was 1418 mmol/mol creatinine (controls <25). Analysis of the L-2-hydroxyglutarate dehydrogenase gene revealed a homozygous mutation in exon 2 (A320G). At the age of 20 years, an osteoma of the right frontal bone was diagnosed. This finding reinforces the opinion concerning the association of L-2-OHGA and tumorigenesis and prompted us to verify the possible responsibility of some overproduced substances in this disease for the development of tumours and to look for any correlation between the type of mutation in the L-2-OHGA gene and the tumorigenic potential observed in some patients affected by this disease.

[Lateral gaze palsy and progressive scoliosis in 4 Tunisian families]. / Paralysie du regard latéral et scoliose progressive: à propos de 4 familles tunisiennes.

In 1975, Sharpe and Silversides described a neurological entity in a Chinese family. Clinical picture was characterized by paralysis of horizontal gaze, pendular nystagmus and progressive scoliosis. To date, 43 cases have been reported. The pathogenesis remains unclear. The Authors report four Tunisian families with 12 affected individuals. The age of patients ranges from 6 to 34 Years. All examined patients have complete lateral gaze palsy, pendular nystagmus and progressive scoliosis. Blood routine tests, cerebrospinal fluid (CSF), evoked potentials, electromyography (EMG), muscle biopsy, CT scan and cerebral MRI were normal. Autosomal recessive (AR) mode of inheritance is the most probable pattern.

Nasu-Hakola disease in two Tunisian siblings: new radiological findings.

We report radiological features of a biopsy-proven early infantile form of Nasu-Hakoka disease in two Tunisian sisters with new bony and cerebral findings.

Localization of alpha-tocopherol transfer protein in the brains of patients with ataxia with vitamin E deficiency and other oxidative stress related neurodegenerative disorders.

Vitamin E (alpha-tocopherol) is an essential nutrient and an important antioxidant. Its plasma levels are dependent upon oral intake, absorption and transfer of the vitamin to a circulating lipoprotein. The latter step is controlled by alpha-tocopherol transfer protein (alpha-TTP), which is a 278 amino acid protein encoded on chromosome 8, known to be synthesized in the liver. Mutations in alpha-TTP are associated with a neurological syndrome of spinocerebellar ataxia, called ataxia with vitamin E deficiency (AVED). Earlier studies suggested that alpha-TTP is found only in the liver. In order to establish whether alpha-TTP is expressed in the human brain, and what relationship this has to AVED, we studied immunohistochemically the presence of alpha-TTP in the brains of a patient with AVED, normal subjects, and patients with Alzheimer's disease (AD), Down's syndrome (DS), cholestatic liver disease (CLD) and abetalipoproteinemia (ABL). The neuropathology of both AD and DS is thought to be related in part to oxidative stress. The diseases of AVED, of cholestatic liver disease, and of abetalipoproteinemia are thought to be due to lack of circulating tocopherol, leading to inadequate protection against oxidative damage. We demonstrate the presence of alpha-TTP in cerebellar Purkinje cells in patients having vitamin E deficiency states or diseases associated with oxidative stress.

Prognostic factors in congenital hemiplegia in full-term and preterm children.

OBJECTIVES: To determine whether the cerebral CT scan patterns, the type of E.E.G recording, the gestational age, the etiological factors and the side of hemiplegia would influence the functional prognosis in congenital hemiplegia. MATERIAL AND METHODS: 53 children (35 males, 18 females) suffering from congenital hemiplegia were included in the study. They were divided into prematures (16 cases) and full-term children (37 cases). All of them were evaluated for I.Q level, motor performance and language ability. CT scan was performed in all cases and E.E.G recording in the majority of them. RESULTS: Full-term gestational age, cortical and subcortical lesions in term children, irritative E.E.G recording and hemispheric atrophy in both gestational age groups were found to be bad prognostic indicators for functional status in congenital cerebral hemiplegia.

Methylmalonic acidaemia with bilateral globus pallidus involvement: a neuropathological study.

A 16-month-old boy was hospitalized because of a 1-day history of severe ketoacidosis with lethargy, hypotonia, vomiting, and important dyspnoea. Organic acid assay by gas chromatography-mass spectrometry confirmed the diagnosis of methylmalonic acidaemia (MMA). On the sixteenth day, he developed an acute extrapyramidal disorder. The CT scan of the brain disclosed bilaterally symmetric lucency of basal ganglia. He died at 17 months of age. Post-mortem neuropathological examination, showed severe necrosis with spongiosis, cystic cavitation and numerous lipid-laden macrophages of the globi pallidi, and mild spongiosis of subthalamic nuclei, mammillary bodies, portion of internal capsule adjacent to globus pallidus, superior cerebellar peduncles and tegmentum of brainstem. Pallidal infarction, a focal ischaemic lesion, demonstrates that ischaemia/energy depletion may be important in the etiology of the neuropathology of MMA.

Dihydropteridine reductase deficiency in a large consanguineous Tunisian family: clinical, biochemical, and neuropathologic findings.

We report the case of a large consanguineous Tunisian family of seven siblings suffering from dihydropteridine reductase deficiency with either typical clinical, biochemical, or autopsy findings. Two cousins also were reported to have the same symptoms. This metabolic disorder is characterized by severe microcephaly, psychomotor regression, and progressive basal ganglia calcifications. Dihydropteridine reductase assay on samples collected from the two brothers still alive did not show measurable activity. The sister and four brothers died between the ages of 3 years and 7 years. A neuropathology study done on the sister showed diffuse demyelination throughout the white matter and spongy vacuolation in the subthalamic nuclei, the superior cerebellar peduncles and the tegmentum tracts of the brain stem. The anterointernal part of the putamen was completely necrotic with nearly total nerve cell loss. Abnormal vascular proliferation and calcification of the walls of small, medium, and large arteries and veins, as well as diffusely scattered pericapillary and isolated calcospherites, were seen in this necrotic region. We think that folate deficiency may be involved in the pathogenesis of the basal ganglia calcification.

Electrophysiology and nerve biopsy: comparative study in Friedreich's ataxia and Friedreich's ataxia phenotype with vitamin E deficiency.

The authors report a comparative study of peripheral nerve conductions and nerve biopsy and somatosensory evoked potentials between 15 patients with Friedreich's ataxia and 15 patients with Friedreich's ataxia phenotype with selective vitamin E deficiency. The patients in the two groups are of similar age, age of onset, and clinical phenotype. Peripheral motor nerve action potential amplitude, and conduction velocities are within normal ranges in the two groups. In the Friedreich's ataxia group there is an early and severe peripheral sensory axonal neuronopathy, characterised by an important reduction of the amplitude of sensory action potential, and important loss of myelinated fibres with complete disappearance of large myelinated fibres without any regenerative process. In the Friedreich's ataxia phenotype with selective vitamin E deficiency group there is slight-to-moderate axonal sensory neuropathy with normal to moderate decrease of large myelinated fibre density and important regeneration in nerve biopsy. Somatosensory evoked potentials are markedly involved in the two groups asserting a severe involvement of somatosensory pathway in lumbar, thoracic and cervical spinal cord. These findings suggest that the pathological mechanism involved in the two diseases are different: central peripheral axonopathy in Friedreich's ataxia and central distal axonopathy in Friedreich's ataxia phenotype with selective vitamin E deficiency.

Atypical ataxia telangiectasia with early childhood lower motor neuron degeneration: a clinicopathological observation in three siblings.

We report three brothers belonging to a consanguineous family and suffering from ataxia telangiectasia with severe early neurogenic amyotrophy. Pathological examination of the brain and spinal cord in one of them showed Purkinje cell loss with empty baskets and numerous axonal spheroids, dorsal column demyelination with astrocytic proliferation and severe anterior horn cell degeneration. We consider these pathological findings to be related to Louis-Bar disease. Anterior horn cell changes may be one of the early pathological features in ataxia telangiectasia.

Juvenile form of dihydropteridine reductase deficiency in 2 Tunisian patients.

Two brothers are described who had juvenile-onset DHPR deficiency. Both were considered normal until six years of age when they developed a fluctuating and progressive encephalopathy combining mental retardation, epilepsy, pyramidal, cerebellar and extrapyramidal signs.

A clinicopathological observation of Nyssen-van Bogaert syndrome with second motor neuron degeneration: two distinct clinical entities.

OBJECTIVES: To report a novel clinicopathological observation of Nyssen-van Bogaert syndrome. To compare this observation with those previously reported. To discuss the nosological entity of this syndrome. To define the exact etiopathogenic mechanism of the neurogenic amyotrophy occurring at the late stage of the disease. MATERIALS AND METHODS: The patient was a 16-year-old girl who developed loss of vision and deafness at the age of 8. Ataxia with slight cerebellar signs were present by the age of 14. Over the next 2 years, she developed distal weakness and wasting of the legs with depressed ankle reflexes. She died at the age of 16. Deparaffinized sections of the brain, the brain stem, the cerebellum and the spinal cord were stained with haematoxylin & eosin (H&E), Nissl, Woelcke, Bodian, periodic acid-schiff (PAS), Sudan Black and Kluver Barera. Antibodies anti-GFAP, anti-MPB and anti-neurofilaments were used for immunohistochemical stainings following the avidin-biotin-peroxydase complex (ABC) methods. RESULTS: The clinical pictures in our patient are similar to those previously reported in juvenile patients with optico-cochleo-dentate syndrome. Pathological study of the nervous system confirmed the diagnosis of Nyssen-van Bogaert syndrome and also showed a severe anterior horn, posterior horn and Clarke's column nerve cell degeneration with anterior root atrophy. CONCLUSION: From these clinical and pathological data, the authors suggest to include Nyssen-van Bogaert syndrome among the group of multiple system atrophy, propose to divide this syndrome into 2 forms (an early infantile form and a juvenile form) and consider that the neurogenic amyotrophy occurring at the late stage of the disease in juvenile and adult patients is mainly caused by the second motor neuron involvement.

Friedreich's ataxia with isolated vitamin E deficiency: a neuropathological study of a Tunisian patient.

The neuropathological findings in a Tunisian patient with Friedreich's ataxia with vitamin E deficiency are reported. The main histological changes are: (1) spinal sensory system demyelination with neuronal atrophy, axonal spheroids and corpora amylacea; (2) neuronal lipofuscin accumulation in the third cortical layer of the cerebral cortex, thalamus, lateral geniculate body, twelfth and ambiguus nuclei, spinal horns and posterior root ganglia. Ultrastructurally, the lipopigments were of uniform granularity without lipid droplets.

[Congenital fibrolipoma of the mesencephalic protuberation area]. / Fibrolipome congénital de la région mésencéphaloprotubérantielle.

BACKGROUND: Congenital origin of brain fibrolipoma is still debated. A case of such a tumor is presented. CASE REPORT: A female newborn presented with severe hypotonia and macrocephaly that were seen since birth. She died at the age of 2 days. Post-mortem examination showed hydrocephaly due to a tumor located in the mesencephalo-protuberantial region. Histological features of this tumor were those of a fibrolipoma. CONCLUSION: The presence of this brainstem tumor at birth confirms its congenital origin.

Clinical and pathological study of three Tunisian siblings with L-2-hydroxyglutaric aciduria.

This report describes three brothers belonging to a consanguineous family suffering from a progressive neurological disorder associated with L-2-hydroxyglutaric aciduria. Clinically this disorder is characterized by childhood onset, pyramidal signs, cerebellar and pseudobulbar syndromes and epilepsy. Pathological examination of the brain in the oldest patient, who died at the age of 30 years, showed bilateral and diffuse spongiosis with notable cystic cavitations of the cerebral white matter without abnormal storage in neurons and glial cells. We consider that these findings are related to L-2 hydroxyglutaric aciduria. To our knowledge this present case represents the first to be reported with neuropathological examination.

[Amebic brain abscess. Apropos of a case]. / Abcès cérébral amibien. A propos d'un cas.

We report a case of double primary amoebic brain abscess in a 22 year old man, with signs of intracranial hypertension and deficit. Computed tomography found two hypodense lesions, not suggestive of pyogenic abscesses. Aspiration of one of the two abscesses, revealed the organism, and the two abscesses regressed in response to medical treatment. The authors insist on the rarity of these abscesses, their gravity, and the difficulty of the diagnosis.