Clinicopathological aspects of the neuropathy of neurogastrointestinal encephalomyopathy (MNGIE) in four patients including two with a Charcot-Marie-Tooth presentation.

We report on four patients with severe polyneuropathy associated with intestinal pseudoobstruction (MNGIE). Three patients presented characteristic supranuclear ophthalmoplegia, and hyperdense signals on T2 weighted cerebral MRI and dystrophic mitochondria in Schwann cells and in endothelial cells in nerve biopsy specimens. Two of these patients had a Charcot-Marie-Tooth (CMT) presentation. All three were heterozygous for a recessively transmitted double substitution in the TP gene: Glu286Lys/Glu289Ala, Asp156Gly/Leu177Pro and Glu289Ala/Gly387Asp. The fourth patient, who was the only patient of this series with an affected sib, had no oculomotor manifestations, nor T2 hyperdense signals on brain MRI, and no TP gene mutation and or morphological abnormalities of mitochondria on electron microscopic examination. He was the only patient of this series with an affected sib. The three patients with the full MNGIE syndrome died before the age of 30 years. Detailed results of nerve pathology show that severe axonal degeneration is associated with segmental abnormalities of the myelin sheath in this syndrome which appears genetically heterogeneous. Our findings suggest that only ophthalmoplegia and hyperdense signals on cerebral MRI are directly related to the mitochondriopathy.

'Fou rire prodromique' as the heralding symptom of lenticular infarction, caused by dissection of the internal carotid artery in a 12-year-old boy.

A 12-year-old, right-handed boy experienced a pathological fit of laughter before a sudden right hemiplegia. Magnetic resonance imaging showed a left basal ganglia infarction, induced by a left internal carotid dissection. Arteriography revealed an underlying fibromuscular dysplasia. This case study demonstrates that cerebral artery dissection can occur in children and that a basal ganglia infarction may be preceded by pathological laughter called 'fou rire prodromique'. The clinical and anatomical relationship of this paroxysmal event are discussed.

Incidence of multiple sclerosis in Dijon, France: a population-based ascertainment.

Incidence of multiple sclerosis (MS) was prospectively determined within the population of the city of Dijon (94,000 inhabitants under 60 years old) at 47 degrees northern latitude, in Burgundy, France. All the incident cases were diagnosed according to the criteria of Poser, associated to the study of cerebrospinal fluid, evoked potentials and cerebral magnetic resonance imaging. Diagnosis was assessed in all the cases by a neurologist working either in the University Hospital (four neurologists) or in private offices (seven neurologists). The ascertainment was performed on a full 5-year period, from 1993 to 1997. Twenty-one cases were diagnosed in the population of 94,000 inhabitants, with an incidence of 6.1/100,000/year in women, 3.3/100,000/year in men and 4.3/100,000/year in both sexes. The sex-ratio female/male was 2.5. Our data are similar to those of the literature, in particular in countries around the Burgundy area. Our data allow evaluation of the burden of MS in our area and allow evaluation of the changes of incidence in the future.

[Ischemic cerebrovascular stroke of arterial origin in the child]. / Les accidents vasculaires cérébraux ischémiques d'origine artérielle chez l'enfant.

Comparing stroke in children with stroke in adults can provide interesting information because age and cerebral plasticity induce specific clinical features and outcome. Arterial ischemic strokes are the most frequent in childhood although the problem is not one of arteriosclerosis. Arterial dissection, Moya-Moya syndrome, and cardioembolic and thrombogenic events induced by hemoglobin diseases and hyperhomocyteinemia must be detected at the first event. In some cases, onset is marked by head trauma or an infectious syndrome. The important feature is that outcome is better than in adults and is marked by onset of hemidystonia, partial epilepsy. Aphasia is benign if stroke arises before the child has learned to write.

[Contribution of magnetic resonance imaging in sclerotic combined degeneration of the spinal cord due to vitamin B12 deficiency]. / Intérêt de l'imagerie par résonance magnétique dans la sclérose combinée de la moelle par carence en vitamine B12.

Subacute combined degeneration (SCD) of the spinal cord is known to present histopathologically degenerative lesions in the spinal cord, but few studies on the neuroradiological findings have so far been reported. We present the interest of initial and follow-up MR findings in three cases of SCD. In the three cases, a causal event precipitated the onset of neurological symptoms: general anesthesia for the first and the third one and folic acid treatment for the second one. Clinical evolution was favorable after specific treatment with nearly total recovery. The initial MR study disclosed lesions predominantly involving the posterior columns of the spinal cord: high intensity on T2 weighted image was seen in the initial MR study and disappeared three months after treatment in correlation with good recovery, but with a delay. The recognition of this MR pattern suggests that MRI may be used in conjunction with clinical assessment to confirm the diagnosis and to monitor the efficacity of treatment in SCD.

[Statins and stroke]. / Statines et accidents vasculaires cérébraux.

The role of cholesterol in the pathogenesis of stroke, the role of the treatment of hypercholesterolemia in the prevention of stroke have been controversed. The explanation was based on the heterogenous characteristics of stroke, on the relationship between several risk factors, and on the role of the age, in the evaluation of these 2 questions. The discovery of statins induced major therapeutic trials whose aim was the impact on coronary events. These trials demonstrated that statins were accompanied with a major reduction of cholesterol levels and stroke events similar to the one observed with coronary events. Even prospective, placebo controlled, randomized specific trials for stroke are necessary, we can state that cholesterol reduction is the most important mechanism accounting for a decrease in stroke occurrence with statins.

Moyamoya disease in children. A review of the clinical and radiological features and current treatment.

Two cases of moyamoya disease observed in two children are reported. The two cases recall the frequency of ischemic strokes, transient ischemic attacks, and seizures revealing the disease. Diagnosis is made by cerebral arteriography showing carotid stenosis and the dense deep arterial collateral as seen in these two cases. Magnetic resonance imaging makes it possible to identify this vascular disease as it reveals vascular varicosities in the basal ganglia, as in case 1. Strokes can sometimes be prevented by constructing an anastomosis between the superficial temporal artery and the middle cerebral artery, as demonstrated in case 1. Thus, the diagnosis of moyamoya disease has been improved by magnetic resonance imaging and there is now a surgical treatment to prevent ischemic stroke.

Headache in hypothyroidism. Prevalence and outcome under thyroid hormone therapy.

OBJECTIVE: To evaluate the frequency of headache in patients with hypothyroidism. DESIGN: A prospective study of a cohort of patients with hypothyroidism. SETTING: Outpatients or inpatients in a headache clinic and endocrinological clinic. PATIENTS: 102 adults, ages 35 to 78 (83F, 19M) experiencing clinical and biological hypothyroidism. RESULTS: Thirty-one patients with hypothyroidism of 102 (30%) presented with headache 1 to 2 months after the first symptoms of hypothyroidism. The headache was slight, nonpulsatile, continuous, bilateral, and salicylate responsive and disappeared with thyroid hormone therapy. CONCLUSION: The authors believe there is a prevalence of nonspecific headache in hypothyroidism and that it has a particular response to thyroid hormone therapy. Hypothyroidism is another cephalalgia with an endocrinological cause after menstrual cephalalgia. We suspect a metabolic or vascular pathophysiological process.

Stroke in children under 16 years of age. Clinical and etiological difference with adults.

OBJECTIVES: The aim of this study was to re-evaluate the clinical features of stroke in children, their outcome and the place of the different mechanisms, in the light of CT-scan and magnetic resonance imaging. METHODS: A 10-year review of the Dijon Childhood Neurology Clinic experience (1985-1995) identified 54 patients with arterial stroke. Diagnosis was established by CT-scan and angiography and by magnetic resonance imaging from 1987. When an hemorrhagic stroke was identified, a cerebral arteriogram and an investigation of the coagulation factors were performed. When an ischemic stroke was identified, the following tests were performed: an ultrasound examination of the cervical arteries, a cerebral arteriogram, a lumbar puncture, an investigation of the coagulation factors and lipid status, a measurement of homocystine in the plasma and the urine, an electrocardiogram, a Holter procedure and a cardiac echography. RESULTS: During the 11 full calendar years of this study, we observed 54 stroke patients. There were 31 cases of ischemic stroke, representing some 57% of the total, as well as 23 cases of hemorrhagic stroke, representing 43% of the total. Of the 31 cases with ischemic stroke, 4 had no known predisposing condition, 6 occurred in children with pre-existing heart disease, 2 had moya-moya disease, 2 had leukemia, 2 had a carotid dissection, 1 had an hemolytic-uremic syndrome, and 14 were observed in patients with other associated conditions, such as infections (7 cases) or slight cranial trauma (7 cases). On CT-scan, a basal ganglia infarction was identified in 14 cases. Among the 23 hemorrhagic strokes, 9 were due to arteriovenous malformations, 2 to arterial aneurysm and 5 to cavernomas. Two cases occurred in hemophilia, 2 in idiopathic thrombocytopenic purpura, and 2 after throat infections. One case had no etiologic factor. Clinical course was marked by a low mortality rate even in hemorrhagic stroke, long-lasting seizures, and hemidystonia. CONCLUSION: This neuro-imaging survey focused on the real place of hemorrhage and basal ganglia infarctions in children under 16 years of age, compared to adulthood. Follow-up demonstrated good or complete resolution of neurological deficits despite the frequent late hemidystonia and late epilepsy.

Neurological phenotype in Waardenburg syndrome type 4 correlates with novel SOX10 truncating mutations and expression in developing brain.

Waardenburg syndrome type 4 (WS4), also called Shah-Waardenburg syndrome, is a rare neurocristopathy that results from the absence of melanocytes and intrinsic ganglion cells of the terminal hindgut. WS4 is inherited as an autosomal recessive trait attributable to EDN3 or EDNRB mutations. It is inherited as an autosomal dominant condition when SOX10 mutations are involved. We report on three unrelated WS4 patients with growth retardation and an as-yet-unreported neurological phenotype with impairment of both the central and autonomous nervous systems and occasionally neonatal hypotonia and arthrogryposis. Each of the three patients was heterozygous for a SOX10 truncating mutation (Y313X in two patients and S251X [corrected] in one patient). The extended spectrum of the WS4 phenotype is relevant to the brain expression of SOX10 during human embryonic and fetal development. Indeed, the expression of SOX10 in human embryo was not restricted to neural-crest-derived cells but also involved fetal brain cells, most likely of glial origin. These data emphasize the important role of SOX10 in early development of both neural-crest-derived tissues, namely melanocytes, autonomic and enteric nervous systems, and glial cells of the central nervous system.